1.1.1.1 alcohol dehydrogenase pharmacology the alcohol dehydrogenase effectively catalyzes the reductions of various substituted alpha-chloroacetophenones to form the (R)-enantiomer of the corresponding chlorohydrins with excellent ennatiomeric purity. The co-factor NADH can be recycled by the D-glucose dehydrogenase and D-glucose regeneration system or via the simple hydrogen transfer mode using iso-propanol as the hydrogen donor. The applicability of the alcohol-dehydrogenase-catalyzed hydrogen transfer reduction in the synthesis of optically active chlorohydrins is demonstrated by carrying out several reductions on the preparative scale. Thus enzyme is a valuable biocatalyst for the preparation of chiral chlorohydrins of pharmaceutical interest 1.1.1.3 homoserine dehydrogenase pharmacology enzyme is a target for inhibitor design for construction of antimicrobial agents 1.1.1.10 L-xylulose reductase pharmacology enzyme is a target for design and development of potent and specific structure-based inhibitors binding in the active site 1.1.1.17 mannitol-1-phosphate 5-dehydrogenase pharmacology inhibition of AfM1PDH might be a useful target for therapy of Aspergillus fumigatus infections 1.1.1.B18 L-1-amino-2-propanol dehydrogenase pharmacology the enzyme produces double chiral aminoalcohols, which are used as pharmaceuticals. The Rhodococcus expression vector, pRET11100, constructed by removing aadh from the pRET1172 plasmid may be useful for bioconversion 1.1.1.22 UDP-glucose 6-dehydrogenase pharmacology target for inhibitor design 1.1.1.35 3-hydroxyacyl-CoA dehydrogenase pharmacology the short-chain 3-hydroxyacyl-CoA dehydrogenase is a target for intervention in case of Alzheimer's disease and Parkinson's disease 1.1.1.B40 11beta-hydroxysteroid dehydrogenase (NAD+) pharmacology the enzyme is an important therapeutic target for diabetes in humans 1.1.1.44 phosphogluconate dehydrogenase (NADP+-dependent, decarboxylating) pharmacology the enzyme is a target for inhibitor development for usage as drugs against African Trypanosomiasis 1.1.1.B51 3-quinuclidinone reductase (NADPH) pharmacology stereospecific production of (R)-3-quinuclidinol, an important chiral building block for the synthesis of various pharmaceuticals 1.1.1.B52 3-quinuclidinone reductase (NADH) pharmacology stereospecific production of (R)-3-quinuclidinol, an important chiral building block for the synthesis of various pharmaceuticals 1.1.1.B52 3-quinuclidinone reductase (NADH) pharmacology stereospecific production of (R)-3-quinuclidinol, an important chiral building block for the synthesis of various pharmaceuticals, high yield of (R)-3-quinuclidinol up to 916 g/L * d using a bioreduction approach 1.1.1.B52 3-quinuclidinone reductase (NADH) pharmacology stereospecific production of (R)-3-quinuclidinol, an important chiral building block for the synthesis of various pharmaceuticals. The 3-quinuclidinone reductase and Leifsonia sp. alcohol dehydrogenase genes are efficiently expressed in Escherichia coli cells. A number of constructed Echerichia coli biocatalysts (intact or immobilized) are applied to the resting cell reaction and optimized. Under the optimized conditions, (R)-(-)-3-quinuclidinolis synthesized from 3-quinuclidinone (15% w/v, 939 mM) giving a conversion yield of 100% for the immobilized enzyme. The optical purity of the (R)-(-)-3-quinuclidinol produced by the enzymatic reactions is above 99.9% 1.1.1.146 11beta-hydroxysteroid dehydrogenase pharmacology isozyme 11beta-HSD1 is a target in treatment of metabolic diseases such as diabetes mellitus type 2 or obesity 1.1.1.146 11beta-hydroxysteroid dehydrogenase pharmacology the enzyme is an important therapeutic target for diabetes in humans 1.1.1.188 prostaglandin-F synthase pharmacology enzyme is a target for cyclooxygenase-independent antineoplastic actions of nonsteroidal anti-inflammatory drugs 1.1.1.205 IMP dehydrogenase pharmacology the enzyme is a potential target as modulators in MTX chemotherapy of resistant cells, overview 1.1.1.282 quinate/shikimate dehydrogenase [NAD(P)+] pharmacology enzymes of the shikimate pathway has been promoted as a target for the development of antimicrobial agents 1.1.1.300 NADP-retinol dehydrogenase pharmacology enzyme RDH8 is a therapeutic target for controlling bis-retinoid A2E cytotoxicity 1.1.1.326 zerumbone synthase pharmacology zerumbone is a predominating potential multi-anticancer agent 1.1.99.21 D-sorbitol dehydrogenase (acceptor) pharmacology miglitol (N-hydroxyethyl-1-deoxynojirimycin), a type of hypoglycemic drug works by competitively inhibiting alpha-glucosidase activity to control postprandial blood glucose, can be used in the treatment of type II diabetes mellitus. 6-(N-hydroxyethyl)-amino-6-deoxy-alpha-L-sorbofuranose, is a key intermediate for the synthesis of miglitol, is produced from N-2-hydroxyethyl glucamine (NHEG) by biotransformation with resting cells of Gluconobacter oxydans. Balanced co-expression of both the mSLDH and the PQQ synthases is effective for the industrial production of 6-(N-hydroxyethyl)-amino-6-deoxy-L-sorbofuranose 1.1.99.21 D-sorbitol dehydrogenase (acceptor) pharmacology synergistic improvement of PQQ-dependent D-sorbitol dehydrogenase activity from Gluconobacter oxydans for the biosynthesis of miglitol precursor 6-(N-hydroxyethyl)-amino-6-deoxy-alpha-L-sorbofuranose. Miglitol (N-hydroxyethyl-1-deoxynojirimycin) is a pseudomonosaccharide glucosidase inhibitor in the treatment of non-insulin-dependent mellitus 1.2.1.11 aspartate-semialdehyde dehydrogenase pharmacology enzyme is a target for development of antibiotics 1.2.1.11 aspartate-semialdehyde dehydrogenase pharmacology inhibitor design from enzyme three-dimensional structure 1.2.1.12 glyceraldehyde-3-phosphate dehydrogenase (phosphorylating) pharmacology lung-stage schistosomula immunofluorescence reactivity is diminished following antiserum absorption with reconbinant glyceraldehyde 3-phosphate dehydrogenase. Discussion of glyceraldehyde 3-phosphate dehydrogenase as a candidate vaccine antigen 1.2.3.1 aldehyde oxidase pharmacology metabolic inactivation of neonicotinoid insecticide substrates by enzyme system coupled with Drosophila nicotinic acetylcholine receptor 1.3.1.9 enoyl-[acyl-carrier-protein] reductase (NADH) pharmacology the enzyme is a target for developing novel anti-tubercular agents 1.3.1.9 enoyl-[acyl-carrier-protein] reductase (NADH) pharmacology the enzyme is a target for the antitubercular drug isoniazid. InhA inhibitors targeted at the enoyl substrate binding site may be effective against existing isoniazid-resistant strains of Mycobacterium tuberculosis 1.3.1.14 dihydroorotate dehydrogenase (NAD+) pharmacology drug design based upon selective enzyme inhibition 1.3.1.22 3-oxo-5alpha-steroid 4-dehydrogenase (NADP+) pharmacology enzyme is a target for drug developement 1.3.1.24 biliverdin reductase pharmacology critical role for biliverdin reductase A in protecting against lipid accumulation and oxidative stress in hepatocytes which may serve as a future therapeutic target for non-alcoholic fatty liver disease (NAFLD) and its progression to non-alcoholic steatohepatitis (NASH) 1.3.1.24 biliverdin reductase pharmacology transduced fusion protein Tat-biliverdin reductase A (Tat-BLVRA) markedly inhibits cell death, DNA fragmentation, and generation of ROS. Transduced Tat-BLVRA inhibits the apoptosis and mitogen activated protein kinase (MAPK) signaling pathway and it passes through the blood-brain barrier (BBB) and significantly prevents hippocampal cell death in an ischemic model. Tat-BLVRA provides a possibility as a therapeutic molecule for ischemia 1.3.1.70 DELTA14-sterol reductase pharmacology enzyme is a potential antifungal target site, development of antifungal compounds 1.3.1.72 DELTA24-sterol reductase pharmacology 3beta-hydroxysterol DELTA24-reductase on the surface of hepatitis C virus-related hepatocellular carcinoma cells can be a target for molecular targeting therapy 1.3.1.118 meromycolic acid enoyl-[acyl-carrier-protein] reductase pharmacology structural investigations of reactive isoniazid species in order to promote the design of new inhibitors of InhA as potential antituberculous drugs 1.3.1.118 meromycolic acid enoyl-[acyl-carrier-protein] reductase pharmacology the enzyme is a target for developing novel anti-tubercular agents 1.3.1.118 meromycolic acid enoyl-[acyl-carrier-protein] reductase pharmacology the enzyme is a target for the development of new anti-tubercular drugs 1.3.3.12 L-galactonolactone oxidase pharmacology because humans lack the capacity to synthesize ascorbate, the trypanosomal enzymes involved in ascorbate biosynthesis are interesting targets for drug therapy 1.3.5.2 dihydroorotate dehydrogenase (quinone) pharmacology A77 1726 inhibits cell growth in multiple myeloma cell lines at clinically achievable concentrations by induction of apoptosis. Inhibition of cell growth is partly due to inhibition of multiple myeloma cell proliferation. A77 1726 shows synergistic and additive activity together with genotoxic agents melphalan, treosulfan, and doxorubicin 1.3.8.6 glutaryl-CoA dehydrogenase (ETF) pharmacology targeted suppression of GCDH by lentivirus-mediated shRNA and excessive intake of lysine may be a useful cell model of glutaric aciduria type 1, overview 1.3.98.3 coproporphyrinogen dehydrogenase pharmacology the structure of HemN sets the stage for the development of inhibitors with antibacterial function due to the uniquely bacterial occurence of the enzyme 1.3.99.38 menaquinone-9 beta-reductase pharmacology menaquinone synthesis may be a drug target in Mycobacteria 1.3.99.38 menaquinone-9 beta-reductase pharmacology menaquinone synthesis may be a drug target in Mycobacterium tuberculosis 1.4.3.3 D-amino-acid oxidase pharmacology co-administration of the enzyme inhibitor 5-chloro-benzo[d]isoxazol-3-ol significantly enhances the efficacy of D-serine in attenuating prepulse inhibition deficits by administration of dizocilpine, an NMDA receptor antagonist. Therefore, co-administration of D-serine and a DAAO inhibitor has therapeutic potential for the treatment of schizophrenia 1.4.3.3 D-amino-acid oxidase pharmacology diminished DAO activity and elevations in D-serine may serve as an effective therapeutic intervention for the treatment of psychiatric symptoms 1.4.3.14 L-lysine oxidase pharmacology promising enzyme for further investigation as a potential anticancer agent. Antitumor effect against murine tumors and human cancer xenografts 1.4.3.22 diamine oxidase pharmacology formulation of vegetal diamine oxidase as a food supplement for the prevention of food allergy and treatment of enteric dysfunction. Study on the stability of diamine oxidase, purified from Lathyrus sativus seedlings, in various simulated intestinal media is reported. The catalytic activity of different diamine oxidase concentrations is tested in simulated intestinal media with different pH and containing cholic acids, pancreatic bicarbonate, and proteases or exogenous food- and drink-derived items, such as lipids or alcohol, alone or in combination 1.4.3.22 diamine oxidase pharmacology improved food supplements must be developed to help histamine intolerant humans. At least 50 nkat free porcine diamine oxidase are required to convert 75 mg histamine to (imidazol-4-yl)acetaldehyde in an in vitro test system. This results in a reduction of histamine by 90%. The enzyme showes weak stability under simulated intestinal conditions with a half-life period of around 19 min. Therefore, a lot more exogenous diamine oxidase would be required for efficient histamine degradation in the human intestine 1.5.1.33 pteridine reductase pharmacology successful antifolate chemotherapy in Leishmania will have to target simultaneously both pterine reductase 1 and dihydrofolate reductase-thymidylate synthase 1.5.3.13 N1-acetylpolyamine oxidase pharmacology N,N'-butanedienyl butanediamine, i.e. MDL 72527 or CPC-200, a small molecule specific inhibitor of polyamine oxidase, effectively blocks androgen-induced reactive oxygen species production in human prostate cancer cells, as well as significantly delays prostate cancer progression and death in animals developing spontaneous prostate cancer 1.6.5.2 NAD(P)H dehydrogenase (quinone) pharmacology a series of lavendamycin analogues are tested in docking studies employing an X-ray derived NQO1 active site computational model, structure-based analogue design criteria are valid, resulting in the design of two analogues with high substrate specificity and selective toxicity toward NQO1-rich cells 1.7.1.B2 aromatic nitroreductase [NAD(P)H] pharmacology Pseudomonas aeruginosa NfsB and nitro-CBI-DEI is a promising enzyme/prodrug combination for gene directed enzyme prodrug therapy 1.7.3.3 factor-independent urate hydroxylase pharmacology urate oxidase is a potential therapeutic protein in the prevention and treatment of tumor lysis syndrome and hyperuricemia. However, its severe immunogenicity limits its clinical application. Engineering site-specific modifications of keto groups in urate oxidase by using evolved Methanocaldococcus jannaschii aminoacyl-tRNA synthetase(s)/suppressor tRNA pairs reduces its antigenicity. The mutated uricase exhibits decreased antigenic properties, while its catalytic activities remain unchanged 1.8.1.7 glutathione-disulfide reductase pharmacology enzyme is a target for enzyme inhibitor and antimalarial drug development 1.8.1.10 CoA-glutathione reductase pharmacology anti-staphylococcal agent, possible target for the design of selective inhibitors that would interrupt the thiol metabolism of the human pathogen Staphylococcus aureus 1.8.1.12 trypanothione-disulfide reductase pharmacology enzyme is a drug target 1.8.1.12 trypanothione-disulfide reductase pharmacology enzyme is a target for selective drug design 1.8.1.12 trypanothione-disulfide reductase pharmacology trypanothione reductase plays a central role in the trypanosomatid parasite’s defense against oxidative stress, trypanothione reductase is a promising target for antitrypanosomal drugs, 2-iminobenzimidazole class are potent trypanothione reductase inhibitors against Trypanosoma brucei rhodesiense and low cytotoxicity against human cells 1.8.1.12 trypanothione-disulfide reductase pharmacology trypanothione reductase plays a central role in the trypanosomatid parasite’s defense against oxidative stress, trypanothione reductase is a promising target for antitrypanosomal drugs, binding affinity towards trypanothione reductase and glutathione reductase of nitrofuran derivatives is assessed by standard molecular docking procedures and both, energy and structural output analysis, nitrofuran ligands display a slight preference to bind the closely related human glutathione reductase, they should not be considered as drugs with selective inhibition of trypanothione reductase 1.8.1.12 trypanothione-disulfide reductase pharmacology trypanothione reductase plays a central role in the trypanosomatid parasite’s defense against oxidative stress, trypanothione reductase is a promising target for antitrypanosomal drugs, novel inhibitors are identified 1.8.1.12 trypanothione-disulfide reductase pharmacology trypanothione reductase plays a central role in the trypanosomatid parasite’s defense against oxidative stress, trypanothione reductase is a promising target for antitrypanosomal drugs, synthesis of dethiotrypanothione and related trypanothione analogues featuring ring-closing olefin metathesis macrocyclizations is described 1.11.1.7 peroxidase pharmacology the enzyme is used as anticancer agent, which is verified by using three concentration of enzyme (0.010, 0.015, 0.020 mM/ml) which show a significant kill for Mcf-7 cells at (0.015 mg/ml), with cytotoxicity activity reaching (45%) 1.13.11.6 3-hydroxyanthranilate 3,4-dioxygenase pharmacology the enzyme is a target for pharmacological downregulation because it is involved in formation of quinolinic acid, a highly potent excitotoxin implicated in a number of neurodegenerative conditions 1.13.11.34 arachidonate 5-lipoxygenase pharmacology human 5-lipoxygenase is a well-validated target for anti-inflammatory therapy. Development of 5-LOX inhibitors with higher activities is highly required 1.13.11.52 indoleamine 2,3-dioxygenase pharmacology first reaction in the tryptophan catabolic pathway in mammals 1.13.11.52 indoleamine 2,3-dioxygenase pharmacology IDO-1 is a target for pharmacological inhibition in the treatment of cancer 1.13.11.55 sulfur oxygenase/reductase pharmacology sulfur metabolism 1.13.12.5 Renilla-type luciferase pharmacology investigations into regulation and functional roles of kinases 1.13.12.5 Renilla-type luciferase pharmacology used as an assay for assessing potential liver toxicity by measuring GADD45-beta induction as an control for increased DNA damage 1.14.11.11 hyoscyamine (6S)-dioxygenase pharmacology tropane alkaloids including hyoscyamine, anisodamine, scopolamine and anisodine, are used medicinally as anticholinergic agents with increasing market demand, improvement of production by metabolic engineering introduction of genes encoding the branch-controlling enzyme tropinone reductase I and the downstream rate-limiting enzyme hyoscyamine-6beta-hydroxylase 1.14.11.28 proline 3-hydroxylase pharmacology the prolyl 3-hydroxylase P3H2 is a novel targets for epigenetic silencing in breast cancer 1.14.11.28 proline 3-hydroxylase pharmacology the prolyl 3-hydroxylase P3H3 is a novel targets for epigenetic silencing in breast cancer 1.14.11.29 hypoxia-inducible factor-proline dioxygenase pharmacology modulation of PHD2 activity might be considered as a new way to inhibit glioblastoma progression 1.14.11.66 [histone H3]-trimethyl-L-lysine9 demethylase pharmacology KDM4A possesses the potential to act as an oxygen sensor in the context of chromatin modifications, with possible implications for epigenetic regulation in hypoxic disease states 1.14.13.9 kynurenine 3-monooxygenase pharmacology kynurenine represents a branch point of the kynurenine pathway, being converted into the neurotoxin 3-hydroxykynurenine via kynurenine monooxygenase, neuroprotectant kynurenic acid, and anthranilic acid. As a result of this branch point, kynurenine monooxygenase is an attractive drug target for several neurodegenerative and/or neuroinflammatory diseases, especially Huntington's, Alzheimer's, and Parkinson's diseases 1.14.13.9 kynurenine 3-monooxygenase pharmacology the enzyme is a potential drug target for treatment of neurodegenerative disorders such as Huntington's and Alzheimer's diseases 1.14.13.38 anhydrotetracycline 6-monooxygenase pharmacology synthesis of chlortetracycline 1.14.13.39 nitric-oxide synthase (NADPH) pharmacology NO synthase can be used to gain insight into the biological role of endogenous agmatine 1.14.13.64 4-hydroxybenzoate 1-hydroxylase pharmacology construction of a novel artificial pathway for arbutin biosynthesis in Escherichia colid. De novo biosynthesis of arbutin from simple carbon sources is established and a generalizable strategy for the biosynthesis of shikimate pathway derived chemicals is provided. Arbutin is a hydroquinone glucoside compound existing in various plants. It is widely used in pharmaceuticaland cosmetic industries owing to its well-known skin-lightening property as well as anti-oxidant, anti-microbial, and anti-inflammatory activities. A 4-hydroxybenzoate 1-hydroxylase gene from Candida parapsilosis CBS604 and a glucosyltransferase (arbutin synthase) gene from Rauvolfia serpentina are introduced into Escherichia coli lead to the production of 54.71 mg/l of arbutin from glucose. Further redirection of carbon flux into arbutin biosynthesis pathway by enhancing shikimate pathway genes enables production of 3.29 g/l arbutin, which is a 60-fold increase compared with the initial strain. Final optimization of glucose concentration added in the culture medium is able to further improve the titer of arbutin to 4.19 g/l in shake flasks experiments, which is around 77-fold higher than that of initial strain 1.14.13.128 7-methylxanthine demethylase pharmacology methylxanthine intermediates of caffeine catabolism obtained by the action of N-demethylases have many applications. In medicine, theobromine and theophylline are used as diuretics, vasodilators, and myocardial stimulants. Monomethylxanthines can be converted to effective caffeine derivatives by chemical derivatization and hence can serve as interesting alternatives to caffeine. Xanthine also finds pharmaceutical application in drugs for treatment of asthma. The biotechnological potential of N-demethylases therefore lies not only in general decaffeination purposes but also in specific product recovery from caffeine 1.14.14.17 squalene monooxygenase pharmacology squalene epoxidase is an attractive potential target for drugs used to inhibit the growth of pathogenic fungi or to lower cholesterol level in humans 1.14.14.83 geraniol 8-hydroxylase pharmacology co-overexpression of geraniol-10-hydroxylase and strictosidine synthase improves anti-cancer drug camptothecin accumulation in Ophiorrhiza pumila 1.14.14.91 trans-cinnamate 4-monooxygenase pharmacology trans-cinnamate 4-monooxygenase plays a key role in the ability of phenylpropanoid metabolism to channel carbon to produce the 4-methoxybenzoyl group on the disaccharide moiety of OSW-1 (3beta,16beta,17alpha-trihydroxycholest-5-en-22-one 16-O-[O-[2-O-(4-methoxybenzoyl)-beta-D-xylopyranosyl]-(1->3)-2-O-acetyl-alpha-L-arabinopyranoside]). OSW-1 is about 10-100 times more cytotoxic than clinically applied anticanceragents such as mitomycin C, adriamycin, cisplatin, camptothecin, and paclitaxel, but has a low toxicity towards normal cells. This potency, in combination with a unique mechanism of action and selectivity toward malignant tumor cells, gives OSW-1 and its analogues great potential as anticancer agents 1.14.14.92 benzoate 4-monooxygenase pharmacology the enzyme is involved in detoxification of benzoate, a key intermediate in aromatic compound metabolism in fungi. Because this enzyme is unique to fungi, it is a promising drug target in fungal pathogens of other eukaryotes. By identifying selected derivatives of cinnamic acid as possible antifungal drugs, and CYP53 family enzymes as their targets, a potential inhibitor-target system for antifungal drugs is developed 1.14.14.154 sterol 14alpha-demethylase pharmacology - 1.14.14.154 sterol 14alpha-demethylase pharmacology target enzyme for azole antifungal agents. These specific inhibitors are of great importance as plant growth regulators, fungicides and herbicides in the agricultural and medical fields 1.14.14.154 sterol 14alpha-demethylase pharmacology all known functional sterols lack a 14alpha-methyl group, and therefore the 14alpha-demethylation reaction has received much attention from the pharmaceutical and agriculture-chemical industry as a possible means to specifically control and inhibit sterol biosynthesis in mammals, fungi, and plant 1.14.14.154 sterol 14alpha-demethylase pharmacology target for cholesterol-lowering drugs 1.14.14.154 sterol 14alpha-demethylase pharmacology target enzyme for the design of phyla-specific sterol 14alpha-demethylase inhibitors 1.14.14.154 sterol 14alpha-demethylase pharmacology CYP51 is a key target for fungal antibiotic therapy 1.14.14.154 sterol 14alpha-demethylase pharmacology Chagas disease is caused by the protozoan parasite Trypanosoma cruzi, which depends on the production of endogenous sterols, and therefore can be blocked by sterol 14alpha-demethylase inhibitors 1.14.14.154 sterol 14alpha-demethylase pharmacology the chemotherapy of leishmaniasis is a serious problem in the field of neglected tropical diseases. Since the biosynthesis of specific sterols is vital for effective survival, normal proliferation and infectivity of Leishmania parasites, the sterol 14alpha-demethylase inhibitors obtained from azole antifungal drug discovery programs can be used in antileishmanial therapy 1.14.14.154 sterol 14alpha-demethylase pharmacology the enzyme constitutes an important biological target for the most popular class of antifungals 1.14.15.19 C-19 steroid 1alpha-hydroxylase pharmacology modification at the C-1 position of a steroid is of pharmaceutical interest. Biotransformation can overcome tedious multistep chemical synthesis 1.14.17.3 peptidylglycine monooxygenase pharmacology enzyme is an attractive target for development of anti-tumor compounds 1.14.18.1 tyrosinase pharmacology (2R,3R)-taxifolin isolated from Benitade may possibly be a of new tyrosinase inhibitor alternative to cosmetic agents such as arbutin and kojic 1.14.18.1 tyrosinase pharmacology kurarinol, kuraridinol, and trifolirhizin are candidates as skin-whitening agents 1.14.18.1 tyrosinase pharmacology results indicate that the polyvinylpyrrolidone (PVP)-wrapped fullerene derivative (Radical Sponge) could be expected for its wide-ranged application as a whitening cosmetic material 1.14.18.1 tyrosinase pharmacology results of low cytotoxicity, high inhibition of melanin synthesis and lack of effect on gene expression suggest that p-hydroxybenzyl alcohol can be a potential agent for skin lightening to be used in cosmetic products 1.14.18.1 tyrosinase pharmacology study of suicide inactivation and irreversible inhibition is important in the functional design of synthetic inactivators for therapeutic applications 1.14.19.1 stearoyl-CoA 9-desaturase pharmacology enhancing SCD1-mediated desaturation of saturated fatty acids and subsequent formation of neutral lipid droplets may become a promising therapeutic target to reduce saturated fatty acid-induced lipotoxicity in the pathogenesis of diabetic nephropathy 1.14.19.1 stearoyl-CoA 9-desaturase pharmacology targeting SCD1 in combination with sorafenib may be another therapeutic strategy against liver cancer. Clinically, SCD1 serves as a good predictive marker for patient responses to sorafenib treatment. Targeting SCD1 synergizes the effect of sorafenib both in vitro and in vivo 1.14.19.17 sphingolipid 4-desaturase pharmacology the cells capacity to biosynthesize dihydroceramides must be taken into account in proautophagic Des1 inhibitors-including therapies 1.14.19.58 tryptophan 5-halogenase pharmacology 5-Br- and 5-Cl-tryptophan could presumably be applied as a pharmacologically attractive precursor of serotonin 1.14.19.64 (S)-stylopine synthase pharmacology a microbial system is established for producing a protoberberine-type alkaloid (stylopine) in Pichia cells 1.14.19.65 (S)-cheilanthifoline synthase pharmacology a microbial system is established for producing a protoberberine-type alkaloid (stylopine) in Pichia cells 1.14.19.70 mycocyclosin synthase pharmacology CYP121 is a potential target for the treatment of Mycobacterium tuberculosis infections 1.14.20.13 6beta-hydroxyhyoscyamine epoxidase pharmacology tropane alkaloids including hyoscyamine, anisodamine, scopolamine and anisodine, are used medicinally as anticholinergic agents with increasing market demand, improvement of production by metabolic engineering introduction of genes encoding the branch-controlling enzyme tropinone reductase I and the downstream rate-limiting enzyme hyoscyamine-6beta-hydroxylase 1.17.3.2 xanthine oxidase pharmacology inhibition of xanthine oxidase is a potential therapeutic approach to diabetic neuropathy and vasculopathy 1.17.3.2 xanthine oxidase pharmacology the enzyme is a target in treatment of heart failure 1.17.4.1 ribonucleoside-diphosphate reductase pharmacology inhibition of RNRs is a proven strategy for combating cancer and some viruses 1.21.3.1 isopenicillin-N synthase pharmacology model system for study of endogenous functions of beta-lactams in bacteria 2.1.1.1 nicotinamide N-methyltransferase pharmacology biomarkers for cardiovascular risk factors 2.1.1.1 nicotinamide N-methyltransferase pharmacology molecular targets for cancer therapy and diagnosis 2.1.1.1 nicotinamide N-methyltransferase pharmacology NNMT as potential biomarker and therapeutic target 2.1.1.1 nicotinamide N-methyltransferase pharmacology the enzyme might be a good molecular target for lung cancer therapy 2.1.1.33 tRNA (guanine46-N7)-methyltransferase pharmacology enzymes NSUN2 and METTL1 are implicated in 5-fluorouracil sensitivity in HeLa cells. Interfering with methylation of tRNAs might provide a promising rationale to improve 5-fluorouracil chemotherapy of cancer 2.1.1.50 loganate O-methyltransferase pharmacology Catharanthus roseus is the sole commercial source for monoterpenoid indole alkaloids vindoline and catharanthine, components of the anticancer dimers vinblastine and vincristine 2.1.1.72 site-specific DNA-methyltransferase (adenine-specific) pharmacology enzyme is a target for antibiotics and antbiotic development 2.1.1.B76 flavone/flavonol 7-O-methyltransferase pharmacology the enzyme reaction product rhmanetin, produced from quercetin, inhibits the formation of beta-amyloid. Rhamnetin holds great promise for use in therapeutic application in neurodegenerative disease, method evaluation, overview 2.1.1.100 protein-S-isoprenylcysteine O-methyltransferase pharmacology the enzyme is a target in anticancer therapy 2.1.1.101 macrocin O-methyltransferase pharmacology tylosin is used in veterinary medicine for treatment of infections caused by gram-positive bacteria and mycoplasma 2.1.1.101 macrocin O-methyltransferase pharmacology tylosin fermentation, antibiotic biosynthesis, enzyme catalyzes conversion of macrocin to tylosin in vivo 2.1.1.102 demethylmacrocin O-methyltransferase pharmacology tylosin fermentation, antibiotic biosynthesis 2.1.1.203 tRNA (cytosine34-C5)-methyltransferase pharmacology enzymes NSUN2 and METTL1 are implicated in 5-fluorouracil sensitivity in HeLa cells. Interfering with methylation of tRNAs might provide a promising rationale to improve 5-fluorouracil chemotherapy of cancer 2.1.1.244 protein N-terminal methyltransferase pharmacology NTMT1 inhibitors can be potential anticancer therapeutics 2.1.2.1 glycine hydroxymethyltransferase pharmacology L-serine is required for pharmaceutical purposes, availability of a sugar-based microbial process for its production is desirable, however, SHMT prevents overproduction of L-serine, control of the essential SHMT activity by a novel physiological approach 2.1.2.11 3-methyl-2-oxobutanoate hydroxymethyltransferase pharmacology enzyme might be an attractive target for inhibitor design 2.1.2.11 3-methyl-2-oxobutanoate hydroxymethyltransferase pharmacology enzyme could serve as target for anti-fungal drugs, since it is not present in mammals 2.2.1.1 transketolase pharmacology benfotiamine treatment activates glucose metabolism in INS-1 cells in high-glucose culture conditions and maximizes the cells' ability to synthesize insulin. Treatment activates glucokinase 2.2.1.6 acetolactate synthase pharmacology AHAS might be a target protein for the development of anti-tuberculosis therapeutics 2.3.1.5 arylamine N-acetyltransferase pharmacology arylamine N-acetyltransferases have a key role in the detoxication and metabolic activation of numerous xenobiotics, including therapeutic drugs and carcinogens 2.3.1.5 arylamine N-acetyltransferase pharmacology NATs play an important role in the detoxication and, or bioactivation of numerous drugs and xenobiotics 2.3.1.6 choline O-acetyltransferase pharmacology Nelumbo nucifera semen extract improves memory in rats with scopolamine-induced dementia through the induction of choline acetyltransferase expression and inhibition of acetylcholinesterase activity 2.3.1.21 carnitine O-palmitoyltransferase pharmacology CPT I, model enzyme for studies of fatty acid-induced apoptosis in cancer therapy 2.3.1.21 carnitine O-palmitoyltransferase pharmacology the data represent proof in principle that a pharmacological agent that stimulates hepatic fatty acid oxidation, perhaps acting on carnitine palmitoyltransferase 1a, could provide a novel approach to treatment of nonalcoholic fatty liver disease 2.3.1.22 2-acylglycerol O-acyltransferase pharmacology [acyl CoA]monoacylglycerol acyltransferase 2 (MGAT2) is of interest as a target for therapeutic treatment of diabetes, obesity and other diseases which together constitute the metabolic syndrome 2.3.1.23 1-acylglycerophosphocholine O-acyltransferase pharmacology the enzyme is a potential therapeutic targets for the regulation of immune and inflammatory disorders 2.3.1.26 sterol O-acyltransferase pharmacology ACAT-1 and ACAT-2 selective inhibitors may prove to have clinical benefit to reduce atherosclerosis via directly reducing the size of the lipid-rich core in the atherosclerotic plaques or the absorption of cholesterol in intestine, respectively 2.3.1.26 sterol O-acyltransferase pharmacology K-604, a potent and selective inhibitor of ACAT-1, suppresses the development of atherosclerosis in an animal model without affecting plasma cholesterol levels, providing direct evidence that pharmacological inhibition of ACAT-1 in the arterial walls leads to suppression of atherosclerosis 2.3.1.26 sterol O-acyltransferase pharmacology the data suggest that antiatherosclerotic activity of licorice in hypercholesterolemic patients might be related with its ACAT inhibitory effects 2.3.1.26 sterol O-acyltransferase pharmacology the results strongly support the idea that CS-505 could be promising as a therapeutic agent for the treatment of atherosclerosis 2.3.1.28 chloramphenicol O-acetyltransferase pharmacology method development for a sensitive model system for analyzing the rapid delivery of active enzymes into various regions of the brain of Rattus norvegicus with therapeutic bioavailability, intranasal delivery of chloramphenicol acetyltransferase from Escherichia coli, a relatively large enzyme, in its active form into different regions of the brain, overview 2.3.1.32 lysine N-acetyltransferase pharmacology cyclic adenosine monophosphate response element-binding binding protein and p300 are lysine acetyltransferases responsible for the regulation of mineralocorticoid receptor providing therapeutic targets for the treatment of hypertension 2.3.1.37 5-aminolevulinate synthase pharmacology enzyme is a target for drug development because of its immunological and inhibitor specificity 2.3.1.41 beta-ketoacyl-[acyl-carrier-protein] synthase I pharmacology synthase III is a target for drug development against multi-drug resistant strains 2.3.1.41 beta-ketoacyl-[acyl-carrier-protein] synthase I pharmacology target for the development of drugs for the treatment of cancer and tuberculosis, involved in biosynthesis of precursors of pharmacological agents 2.3.1.48 histone acetyltransferase pharmacology the GCN5-NF-kB pathway is a potentialmolecular target for stem cell mediated regenerative medicine and the treatment of metabolic bone diseases such as osteoporosis 2.3.1.57 diamine N-acetyltransferase pharmacology compounds capable of potently inducing SSAT and having favorable pharmacological properties in animals are potential anticancer agents 2.3.1.95 trihydroxystilbene synthase pharmacology expression of the stilbene synthase gene from Vitis vinifera in transgenic Populus alba results in high accumulation of the antioxidant resveratrol glucosides 2.3.1.147 glycerophospholipid arachidonoyl-transferase (CoA-independent) pharmacology the enzyme may be a new therapeutic target to regulate inflammatory mediators 2.3.1.163 10-hydroxytaxane O-acetyltransferase pharmacology use in synthesis of taxol for anticnacer treatment 2.3.1.167 10-deacetylbaccatin III 10-O-acetyltransferase pharmacology use in synthesis of taxol for anticnacer treatment 2.3.1.167 10-deacetylbaccatin III 10-O-acetyltransferase pharmacology key enzyme in the biosynthesis of the anticancer drug paclitaxel, which catalyses the formation of baccatin III from 10-deacetylbaccatin III 2.3.1.167 10-deacetylbaccatin III 10-O-acetyltransferase pharmacology paclitaxel is a type of broad-spectrum anticancer drug in short supply. The price of acetyl-CoA, which is the acetyl group donor for the enzymatic synthesis of the intermediate, baccatin III, is the bottleneck of the mass production of paclitaxel. The study reports that N-acetyl-D-glucosamineas an acetyl group donor can substantially reduce the cost of production 2.3.1.176 propanoyl-CoA C-acyltransferase pharmacology although SCP-2 was established as a protein that transfers cholesterol and phospholipids decades ago, recent findings with lipid rafts/caveolae and SCP-2 suggest that they may provide a conceptual link to metabolic processes that might be regulated through the respective signaling pathways 2.3.1.180 beta-ketoacyl-[acyl-carrier-protein] synthase III pharmacology the enzyme is a target for design and development of antibacterial drugs against pathogenic bacteria 2.3.1.180 beta-ketoacyl-[acyl-carrier-protein] synthase III pharmacology the enzyme is a target for development of antibiotics 2.3.1.180 beta-ketoacyl-[acyl-carrier-protein] synthase III pharmacology the enzyme is a target for development of inhibitors for treatment of the multi-drug resistant pathogen Staphylococcus aureus 2.3.1.275 acyl phosphate:glycerol-3-phosphate acyltransferase pharmacology the PlsX/Y pathway defines the most widely distributed pathway for the initiation of phospholipid formation in bacteria and represents a target for the development of antibacterial therapeutics 2.3.2.2 gamma-glutamyltransferase pharmacology bile extracts from diclofenac-dosed rats at 200 mg/kg, show the presence of the gamma-GT-mediated diclofenac-S-acyl-glutathione degradation product diclofenac-N-acyl-cysteinylglycine, where a total of 8 microg is excreted 6 h postadministration. When diclofenac-S-acyl-glutathione is incubated with gamma-GT, the GSH adduct is degraded in a linear time-dependent fashion 2.3.2.2 gamma-glutamyltransferase pharmacology cisplatin administration significantly elevates blood urea nitrogen and serum creatinine in male rats day 5 post-treatment. Inhibition of gamma glutamyltranspeptidase prevents cisplatin nephrotoxicity, but not cellular toxicity in rat proximal tubular cultures 2.3.2.2 gamma-glutamyltransferase pharmacology cisplatin administration significantly elevates blood urea nitrogen and serum creatinine in mice day 4 post-treatment. Inhibition of gamma glutamyltranspeptidase prevents cisplatin nephrotoxicity 2.3.2.2 gamma-glutamyltransferase pharmacology the administration of a single intraperitoneal dose of potassium dichromate decreases the activity of gamma-glutamyl transpeptidase and alanine aminopeptidase. Utility of gamma-GT and AAP activities as biomarkers in the evaluation of the Cr-induced nephrotoxicity 2.3.2.5 glutaminyl-peptide cyclotransferase pharmacology Abeta38, Abeta40 and angiogenesis mediators Flt1, Tie2, VEGFD, CAM-1 and ICAM-1 are potential pharmacodynamic markers of glutaminyl cyclase (QC) inhibition, because their levels closely correlate with QC activity in Alzheimer's disease patients. The addition of QC activity to core diagnostic cerebrospinal fluid (CSF) biomarkers may be of specific interest in clinical cases with discordant imaging and biochemical biomarker results. Core CSF diagnostic biomarkers (Abeta42, tau and p-tau) are not part of the diagnostic workup 2.3.2.5 glutaminyl-peptide cyclotransferase pharmacology glutaminyl cyclase is a drug target to diminish pE-Abeta formation 2.3.2.5 glutaminyl-peptide cyclotransferase pharmacology the glutaminyl-peptide cyclotransferase-like protein (QPCTL) is a target to interfere with the CD47 pathway and thereby augment antibody therapy of cancer 2.4.1.5 dextransucrase pharmacology synthesis of chlorogenic acid-4'-O-alpha-D-glucopyranoside, which is a functional component that may be used in the food or pharmaceutical industry. It displays greater physical properties, anti-lipid peroxidation effect, and growth inhibition of colon cancer cell than those of chlorogenic acid 2.4.1.17 glucuronosyltransferase pharmacology based on the in vitro determination of a 25.3 min half-life for 2',4,4'-trihydroxychalcone when incubated with human liver microsomes, the intrinsic clearance of isoliquiritigenin was estimated to be 36.4 ml/min/kg 2.4.1.17 glucuronosyltransferase pharmacology isoform UGT1A8173Ala/277Tyr variant exhibits no detectable glucuronidation activity against the trans isomers of either 4-hydroxytamoxifen or endoxifen. Little or no difference in tamoxifen glucuronidating activity is observed for the UGT1A8173Gly/277Cys or UGT1A10139Lys variants compared with their wild-type counterparts. For active hepatic UGTs, the UGT2B7268Tyr variant exhibits significant 2- and 5fold decreases in activity against the trans isomers of 4-hydroxytamoxifen and endoxifen, respectively, compared with wild-type UGT2B7268His. Functional polymorphisms in tamoxifen-metabolizing UGTs, including UGT2B7 and potentially UGT1A8, may be important in interindividual variability in tamoxifen metabolism and response to tamoxifen therapy 2.4.1.19 cyclomaltodextrin glucanotransferase pharmacology important enzyme in pharmaceutical industry 2.4.1.38 beta-N-acetylglucosaminylglycopeptide beta-1,4-galactosyltransferase pharmacology beta 1,4GalT V inhibitors enhance the therapeutic effect of As2O3 for malignant glioma 2.4.1.80 ceramide glucosyltransferase pharmacology enzyme might be an attractive target for malarial chemotherapy 2.4.1.132 GDP-Man:Man1GlcNAc2-PP-dolichol alpha-1,3-mannosyltransferase pharmacology target for antifungal drug discovery 2.4.1.132 GDP-Man:Man1GlcNAc2-PP-dolichol alpha-1,3-mannosyltransferase pharmacology sreening for alpha-1,3-mannosyltransferase inhibitors and anti-fungal therapeutics 2.4.1.142 chitobiosyldiphosphodolichol beta-mannosyltransferase pharmacology the WD repeat domain 3 (WDR3) and chitobiosyldiphosphodolichol beta-mannosyltransferase (ALG1) genes are target candidates for schizophrenia-related molecules, whose mRNAs are upregulated in the adult (postnatal week seven), but not in the infant (postnatal week one) rats by an indirect dopamine agonist, and phencyclidine, an antagonist of the NMDA receptor 2.4.1.150 N-acetyllactosaminide beta-1,6-N-acetylglucosaminyltransferase pharmacology targeting mucin biosynthesis through GCNT3 may improve drug responsiveness 2.4.1.155 alpha-1,6-mannosyl-glycoprotein 6-beta-N-acetylglucosaminyltransferase pharmacology the work is a step toward intriguing innovative therapeutic strategies for trials currently in consider with glycosyltransferase in neurodegenerative disorders 2.4.1.214 glycoprotein 3-alpha-L-fucosyltransferase pharmacology the enzyme is a target for rational inhibitor design for medication in the treatment of rheumatoid arthritis 2.4.2.1 purine-nucleoside phosphorylase pharmacology substrate 6-mercaptopurine-2'-deoxyriboside is of special interest, because, in contrast to a nucleoside, its parent purine is highly cytotoxic and is known as one of the first compounds applied as anti-cancer drugs 2.4.2.8 hypoxanthine phosphoribosyltransferase pharmacology enzyme is a potential drug target in the treatment of parasite caused disease 2.4.2.8 hypoxanthine phosphoribosyltransferase pharmacology the enzyme is a target for mechanism-based design of specific inhibitors 2.4.2.8 hypoxanthine phosphoribosyltransferase pharmacology inhibitors of EcHPRT may fill a specific niche for the treatment of uropathogenic Escherichia coli infections 2.4.2.9 uracil phosphoribosyltransferase pharmacology potential target for the development of new antibiotics 2.4.2.12 nicotinamide phosphoribosyltransferase pharmacology enzyme is a potential target for development of anticancer drugs 2.4.2.12 nicotinamide phosphoribosyltransferase pharmacology NAMPT inhibition might have therapeutic efficacy in immune-mediated inflammatory diseases through impact on inflammatory cytokine secretion by leukocytes 2.4.2.30 NAD+ ADP-ribosyltransferase pharmacology the enzyme inhibition is a possible tool in cancer therapy both in prophylactic and therapeutic treatment, e.g. by targeting BRCA2 tumors with PARP inhibitors, overview 2.5.1.9 riboflavin synthase pharmacology the enzyme is a target for development of antiinfective drugs 2.5.1.26 alkylglycerone-phosphate synthase pharmacology alkylglycerone phosphate synthase is an oncogene and can be considered as an antitumor drug target. The study designs novel nitrogenous heterocyclic compound improving targetability by computer-aided drug design technology targeting alkylglycerone phosphate synthase. A total of 12 nitrogenous heterocyclic compounds are designed and predicted the absorption, distribution, metabolism and excretion parameters/toxicity. Their activity in terms of proliferation inhibition, cell cycle arrest and apoptosis induction as then measured using an MTS assay and a high-content screening system in U251 cells. The results show that anti-glioma activity is present in several compounds, which is in accordance with the computer prediction. These compounds may be suitable for the development of a glioma therapeutic drug 2.5.1.26 alkylglycerone-phosphate synthase pharmacology the enzyme reduces ether lipid levels in tumor cells and thus decreases cancer pathogenicity. It is considered to be a target of antitumor drugs, with specific inhibitors expected to have marked advantages over traditional chemotherapy methods 2.5.1.29 geranylgeranyl diphosphate synthase pharmacology geranylgeranyl diphosphate biosynthesized by Ginkgo biloba geranylgeranyl diphosphate synthase is an importent key precu´rsor for ginkgolides with pharmaceutical interest 2.5.1.29 geranylgeranyl diphosphate synthase pharmacology geranylgeranyl diphosphate is a key precursor for taxol, one of the most potent antitumor drugs 2.5.1.29 geranylgeranyl diphosphate synthase pharmacology geranylgeranyl diphosphate synthase (GGDPS) inhibitors are of potential therapeutic interest as a consequence of their activity against the bone marrow cancer multiple myeloma 2.5.1.29 geranylgeranyl diphosphate synthase pharmacology the enzyme is a valuable therapeutic target in oncology and more specifically for the treatment of multiple myeloma 2.5.1.29 geranylgeranyl diphosphate synthase pharmacology the enzyme is an antimalarial drug target. Current bisphosphonate drugs that inhibit farnesyl diphosphate synthase and geranylgeranyl diphosphate synthase enzymes by acting as a diphosphate substrate analog show poor bioavailability and selectivity for the bifunctional farnesyl/geranylgeranyl diphosphate synthase in Plasmodium falciparum. The non-bisphosphonate compound, MMV019313, which is highly selective for the bifunctional farnesyl/geranylgeranyl diphosphate synthase shows no activity against human farnesyl diphosphate synthase and geranylgeranyl diphosphate synthase enzymes 2.5.1.30 heptaprenyl diphosphate synthase pharmacology the enzyme is an anti-infective drug target 2.5.1.31 ditrans,polycis-undecaprenyl-diphosphate synthase [(2E,6E)-farnesyl-diphosphate specific] pharmacology target for the development of antibacterials 2.5.1.31 ditrans,polycis-undecaprenyl-diphosphate synthase [(2E,6E)-farnesyl-diphosphate specific] pharmacology the enzyme generate undecaprenyl pyrophosphate. The latter serves as a lipid carrier for peptidoglycan synthesis, thus representing an important target in the antibacterial drug design 2.5.1.31 ditrans,polycis-undecaprenyl-diphosphate synthase [(2E,6E)-farnesyl-diphosphate specific] pharmacology the enzyme is an antibacterial target 2.5.1.31 ditrans,polycis-undecaprenyl-diphosphate synthase [(2E,6E)-farnesyl-diphosphate specific] pharmacology the enzyme is an attractive drug target since it is not used by humans 2.5.1.47 cysteine synthase pharmacology involved in beta-lactam synthesis 2.5.1.58 protein farnesyltransferase pharmacology the enzyme is a promising therapeutic target for the treatment of various Ras-induced cancers and several other kinds of diseases 2.5.1.59 protein geranylgeranyltransferase type I pharmacology the enzyme is a promising therapeutic target for the treatment of various Ras-induced cancers and several other kinds of diseases 2.5.1.61 hydroxymethylbilane synthase pharmacology safety, pharmacokinetics and pharmacodynamics of recombinant human porphobilinogen deaminase P 9808, administered to healthy subjects and asymptomatic porphobilinogen deaminase-deficient subjects with high concentrations of porphobilinogen, the substrate of porphobilinogen deaminase for investigation and establishing of an alternative therapy of acute intermittent porphyria, AIP, overview 2.5.1.63 adenosyl-fluoride synthase pharmacology a two-step radiolabelling protocol of a cancer relevant cRGD peptide is described where the fluorinase enzyme is used to catalyse a transhalogenation reaction to generate [18F]-5'-fluoro-5'-deoxy-2-ethynyladenosine, followed by a click reaction to an azide tethered cRGD peptide. This protocol offers efficient radiolabelling of a biologically relevant peptide construct in water at pH 7.8, 37°C in 2 hours, which is metabolically stable in rats and retains high affinity for alphavbeta3 integrin 2.6.1.39 2-aminoadipate transaminase pharmacology L-alpha-aminoadipate is a component of the precursor to penicillin and cephalosporin 2.6.1.50 glutamine-scyllo-inositol transaminase pharmacology 5'-hydroxystreptomycin production 2.6.1.50 glutamine-scyllo-inositol transaminase pharmacology biosynthesis of aminoglycoside antibiotics 2.6.1.50 glutamine-scyllo-inositol transaminase pharmacology spectinomycin production 2.6.1.50 glutamine-scyllo-inositol transaminase pharmacology 2-deoxystreptamine is a component of numerous clinically important antibiotics such as gentamicin, neomycin, tobramycin, amikacin and hygromycin 2.6.1.62 adenosylmethionine-8-amino-7-oxononanoate transaminase pharmacology enzyme is a potential drug target in tuberculosis treatment 2.6.99.2 pyridoxine 5'-phosphate synthase pharmacology the enzyme is a target for drug development in the treatment of human pathogens being capable, in contrast to the hosts, to synthesize pyridoxine 5'-phosphate 2.7.1.1 hexokinase pharmacology enzyme may constitute an interesting drug target 2.7.1.1 hexokinase pharmacology hexokinase may be an excellent target for the development of a rational chemotherapy against the parasite 2.7.1.1 hexokinase pharmacology enzyme is a target for activator drug design in therapy of type 2 diabetes mellitus 2.7.1.20 adenosine kinase pharmacology enzyme is a target for drug development in tuberculosis treatment of humans due to the structural and substrate specificity differences of human and mycobacterial enzymes, overview 2.7.1.67 1-phosphatidylinositol 4-kinase pharmacology type II phosphatidylinositol 4-kinases are promising targets for therapeutic intervention against viral infections, detailed overview 2.7.1.74 deoxycytidine kinase pharmacology the enzyme is a critical determinant of therapeutic activity for several nucleoside analogue prodrugs 2.7.1.105 6-phosphofructo-2-kinase pharmacology effects of 5-aminoimidazole-4-carboxamide-1-beta-D-ribofuranoside (AICAR) on hepatic glucose metabolism 2.7.1.105 6-phosphofructo-2-kinase pharmacology role of PFKFB3 protein in tumorigenesis, expression studies in human astrocytic gliomas of different malignancy grades 2.7.1.137 phosphatidylinositol 3-kinase pharmacology development of specific isozyme inhibitors may offer therapeutic benefit in a broad range of clinical settings related to cancer, inflammatory and immunological diseases 2.7.1.153 phosphatidylinositol-4,5-bisphosphate 3-kinase pharmacology the PI3Kgamma signaling pathway may represent a suitable target for the development of therapeutic strategies for human diseases characterized by vascular leakage 2.7.3.4 taurocyamine kinase pharmacology the enzyme is a candidate chemotherapeutic target 2.7.7.1 nicotinamide-nucleotide adenylyltransferase pharmacology the amino-terminal insertion of Leishmania NMNATs as a promising pharmacological target for the development of specific control strategies 2.7.7.48 RNA-directed RNA polymerase pharmacology targeting the active sites of polymerase molecules is not likely to be the best antiviral strategy, as inactivated polymerases do not inhibit replication of other viruses in the same cell and can, in fact, be useful in RNA replication complexes, because catalytically inactive polymerases participate productively in functional oligomer formation and catalysis 2.7.7.48 RNA-directed RNA polymerase pharmacology the viral RNA polymerase is an attractive target for inhibition in the treatment of viral infections 2.7.8.27 sphingomyelin synthase pharmacology sphingomyelin synthase 2 (SMS2) is a potential therapeutic target for obesity and insulin resistance 2.7.9.1 pyruvate, phosphate dikinase pharmacology drug design, in silico studies on stereo chemical quality of PPDK protein structure, interaction studies to identify promising ligands to inhibit the function of PPDK, possibility of using proposed ligands as inhibitors for intestinal infections caused by Entamoeba histolytica in humans and for related pathogens, virtual screening of ligands to inhibit PPDK by docking studies using compound input libraries, phylogenetic trees of pathogens as further targets for in silico drug design to inhibit PPDK 2.7.10.1 receptor protein-tyrosine kinase pharmacology ErbB family receptor kinases are targets for anticancer drugs, e.g. gefitinib or erlotinib in the treatment of non-small lung cancer or colorectal cancer, treatment with therapeutic antibodies in case of breast cancer 2.7.10.1 receptor protein-tyrosine kinase pharmacology the enzyme is a target for anticancer drugs, such as STI-571 2.7.10.1 receptor protein-tyrosine kinase pharmacology the receptor protein tyrosine kinases are drug targets in specific treatment of tumor angiogenesis and cancer, e.g. gastrointestinal stromal tumors, drugs are such as gemcitabine, cisplatin, doxorubicin, or erlotinib 2.7.10.2 non-specific protein-tyrosine kinase pharmacology ABL protein tyrosine kinase is a target for treatment of chronic myeloid leukemia with imatinib mesylate, synergistic with AG-490, an inhibitor of JAK2 tyrosine kinase signaling 2.7.10.2 non-specific protein-tyrosine kinase pharmacology non-receptor PTKs are targets for inhibitors as anticancer agents 2.7.10.2 non-specific protein-tyrosine kinase pharmacology PTKS are key targets for anticancer drug discovery 2.7.10.2 non-specific protein-tyrosine kinase pharmacology targeting these Abl-dependent signalling cascades may be of therapeutic value in breast cancers where Src-like function is important 2.7.10.2 non-specific protein-tyrosine kinase pharmacology the enzyme is a pharmaceutical target for inhibitors in therapy of acute inflammatory responses, e.g. acute lung injury, ischemic brain injury, brain injury, spinal cord compression, stroke, and myocardial infarction, detailed overview 2.7.11.1 non-specific serine/threonine protein kinase pharmacology CK2 is a potential therapeutic target and a target for inhibitor design, e.g. in anti-cancer therapy 2.7.11.2 [pyruvate dehydrogenase (acetyl-transferring)] kinase pharmacology target for development of specific inhibitors of PDK isozymes to regulate glucose levels in the blood 2.7.11.10 IkappaB kinase pharmacology enzyme is a target for development of inhibitors of HIV-1 replication, overview 2.7.11.10 IkappaB kinase pharmacology IKK ia a good target for development of anti-rheumatic and anti-inflammatory drugs 2.7.11.10 IkappaB kinase pharmacology IKK is a target for development of therapeutics for treatment of diseases resulting from nuclear transcription factor NFkappaB pathogenesis 2.7.11.10 IkappaB kinase pharmacology IKKbeta/NF-kappaB inhibitors can be useful adjuvants for conventional chemotherapeutic drugs, ionizing radiation, or tumoricidal cytokines, e.g. IFNs or TRAIL 2.7.11.10 IkappaB kinase pharmacology aberrant kinase activity is implicated in many diseases and makes this target class attractive for the pharmaceutical industry 2.7.11.12 cGMP-dependent protein kinase pharmacology enzyme inhibitors are useful in treatment of diverse physiological dysfunctions, overview 2.7.11.12 cGMP-dependent protein kinase pharmacology the enzyme is a target for coccidiostat pyrrole 4-[2-(4-fluorophenyl)-5-(1-methylpiperidine-4-yl)-1H-pyrrol-3-yl]pyridine 2.7.11.20 elongation factor 2 kinase pharmacology the enzyme is a target for development of anticancer drugs 2.7.11.21 polo kinase pharmacology combined inhibition of PLK1 and Bcl2 represent potential Myc-targeting therapeutics 2.7.11.22 cyclin-dependent kinase pharmacology the enzyme is a target for drug development in human malaria treatment 2.7.11.22 cyclin-dependent kinase pharmacology inhibition of the anomalous cdk5/p25 complex is a viable target for treating Alzheimer disease by preventing hyperphosphorylation of tau and neurofibrillary tangle formation 2.7.11.24 mitogen-activated protein kinase pharmacology MAPKs are targets for inhibitors and pharmacological drug development 2.7.11.24 mitogen-activated protein kinase pharmacology protein scaffolds, e.g. of MAP kinases, provide a flexible platform for reprogramming cellular responses and could be exploited to engineer cells with novel therapeutic and biotechnological functions 2.7.11.26 tau-protein kinase pharmacology anti-bodies highly specific for toxic amyloid oligomer subspecies may reduce toxicity via reduction of GSK-3beta amount in Alzheimer's disease therapeutic strategy 2.7.11.30 receptor protein serine/threonine kinase pharmacology enzyme inhibitor (1'R,5'S,6'S)-2-(3',5'-dibromo-1',6'-dihydroxy-4'-oxocyclohex-2'-enyl) acetonitrile is a potential therapeutic agent for fibrotic disease and cancer treatment 2.7.11.31 [hydroxymethylglutaryl-CoA reductase (NADPH)] kinase pharmacology selective AMPK activators are potential therapeutics in type 2 diabetes 2.8.1.1 thiosulfate sulfurtransferase pharmacology target for developing a tuberculosis drug 2.8.2.4 estrone sulfotransferase pharmacology reactivation of endogenous SULT1E1 gene expression may represent a novel therapeutic strategy to inhibit estrogen-dependent growth of breast cancer cells 2.8.2.23 [heparan sulfate]-glucosamine 3-sulfotransferase 1 pharmacology use of a chemoenzymatic synthetic approach to synthesize six 3-O-sulfated oligosaccharides, including three hexasaccharides and three octasaccharides. The synthesis is achieved by rearranging the enzymatic modification sequence to accommodate the substrate specificity of 3-O-sulfotransferase 3, analysis of the impact of 3-O-sulfation on the conformation of the pyranose ring of 2-O-sulfated iduronic acid using NMR spectroscopy, and on the correlation between ring conformation and anticoagulant activity. An octasaccharide interacts with antithrombin and displays anti factor Xa activity. The octasaccharide displays a faster clearance rate than fondaparinux, an FDA-approved pentasaccharide drug, in a rat model, making this octasaccharide a potential short-acting anticoagulant drug candidate that could reduce bleeding risk. The presence of the -GlcNS3S6S-IdoA2S- disaccharide unit is required for anticoagulant activity 2.8.2.30 [heparan sulfate]-glucosamine 3-sulfotransferase 3 pharmacology use of a chemoenzymatic synthetic approach to synthesize six 3-O-sulfated oligosaccharides, including three hexasaccharides and three octasaccharides. The synthesis is achieved by rearranging the enzymatic modification sequence to accommodate the substrate specificity of 3-O-sulfotransferase 3, analysis of the impact of 3-O-sulfation on the conformation of the pyranose ring of 2-O-sulfated iduronic acid using NMR spectroscopy, and on the correlation between ring conformation and anticoagulant activity. An octasaccharide interacts with antithrombin and displays anti factor Xa activity. The octasaccharide displays a faster clearance rate than fondaparinux, an FDA-approved pentasaccharide drug, in a rat model, making this octasaccharide a potential short-acting anticoagulant drug candidate that could reduce bleeding risk. The presence of the -GlcNS3S6S-IdoA2S- disaccharide unit is required for anticoagulant activity 3.1.1.1 carboxylesterase pharmacology skin from the minipig back is an appropriate model for preclinical human skin studies, particularly breast skin 3.1.1.1 carboxylesterase pharmacology development and application of hiCE-specific inhibitors designed to selectively modulate drug hydrolysis in vivo 3.1.1.1 carboxylesterase pharmacology enzyme overexpression in colorectal cancer and cancer cell death stemming from its inhibition is an indication of its possible role in cancer progression and a target for chemopreventive agents 3.1.1.4 phospholipase A2 pharmacology development of Lp-PLA2 inhibitors as therapy for atherosclerosis 3.1.1.4 phospholipase A2 pharmacology application of pancreatic phospholipase A2 for treatment of bovine mastitis 3.1.1.4 phospholipase A2 pharmacology bee venom-derived phospholipase A2 can be a promising treatment option for Parkinson's disease. It ameliorates motor dysfunction and modulates microglia activation in Parkinson's disease alpha-synuclein transgenic mice 3.1.1.4 phospholipase A2 pharmacology pharmacological targeting of the enzyme may have important therapeutic benefits in disease mechanisms that involve excessive cell proliferation, in particular, cancer and proliferative glomerulopathies 3.1.1.4 phospholipase A2 pharmacology the enzyme is a potential drug target for developing a selective therapeutic agent for the treatment of psoriasis 3.1.1.4 phospholipase A2 pharmacology the enzyme is an attractive target for the development of anti-inflammatory drugs 3.1.1.7 acetylcholinesterase pharmacology poisoning by organophosphorus compounds (OP) is characterized by inhibition of the key enzyme acetylcholinesterase (AChE) and potentially fatal outcomes in humans. Insufficient efficacy of the standard therapy with atropine and AChE reactivators (oximes) against certain OP initiates synthesis of non-oxime reactivators basing on the common structure 4-amino-2-((diethylamino)methyl)phenol (ADOC). 10 to 34Fold reactivation potency of compound 4-amino-2-[[ethyl(methyl)amino]methyl]phenol compared to 4-amino-2-((diethylamino)methyl)phenol mainly due to improved affinity 3.1.1.8 cholinesterase pharmacology effective use of exogenous human BChE as a bioscavenger for organophosphorus toxicants, e.g. paraoxon. Paraoxon elicites near complete inhibition of liver carboxylesterase at 40 nM 3.1.1.23 acylglycerol lipase pharmacology the enzyme is a therapeutic target 3.1.1.32 phospholipase A1 pharmacology the recombinant protein is allergenic in a biological assay as demonstrated by its capability to induce histamine release of wasp venom-sensitive basophils. The recombinant phospholipase A1 presents a good candidate for wasp venom immunotherapy 3.1.1.73 feruloyl esterase pharmacology feruloyl esterases are enzymes useful in phenolic modifications of pharmaceutical relevance as protectors against several degenerative human diseases 3.1.1.73 feruloyl esterase pharmacology microencapsulated live Lactobacillus fermentum 11976 may augment feruloyl esterase in the gastrointestinal tract. Ferulic acid has many physiological functions in the prevention of chronic disease. 3.1.1.73 feruloyl esterase pharmacology release of phenolic acids 3.1.1.81 quorum-quenching N-acyl-homoserine lactonase pharmacology Ahl-1 lactonase is considered a promising therapeutic agent to inhibit Pseudomonas aeruginosa pathogenicity with no fear of emergence of resistance 3.1.1.81 quorum-quenching N-acyl-homoserine lactonase pharmacology MomL significantly attenuates the virulence of Pseudomonas aeruginosa in a Caenorhabditis elegans infection model, which suggests that MomL has the potential to be used as a therapeutic agent 3.1.1.81 quorum-quenching N-acyl-homoserine lactonase pharmacology the enzyme significantly inhibits the biofilm formation and attenuates extracellular proteolytic activity and pyocyanin production of Pseudomonas aeruginosa PAO1, which indicates the potential application of AiiK as a biocontrol agent or an anti-pathogenic drug 3.1.1.81 quorum-quenching N-acyl-homoserine lactonase pharmacology the pathogen Pseudomonas aeruginosa uses quorum sensing to control virulence and biofilm formation. Enzymatic disruption of quorum sensing is a promising antiinfection therapeutic strategy that does not rely on antibiotics. Aii810, a cold-adapted N-acylhomoserine lactonase can attenuate Pseudomonas aeruginosa virulence factors and biofilm formation. It is an attractive enzyme for use as a therapeutic agent against Pseudomonas aeruginosa infection 3.1.1.81 quorum-quenching N-acyl-homoserine lactonase pharmacology use of purified AiiATSAWB, as hypertonic suspension for inhalation to substitute the action of inactivated host's paraoxonase in treating Pseudomonas aeruginosa infection in cystic fibrosis patients 3.1.1.89 protein phosphatase methylesterase-1 pharmacology RNAi and pharmacologic inhibition of PME-1 in vitro leads to decreased cell proliferation and invasive growth in endometrial cancer cells. Discovery of more potent PME-1 inhibitors may be beneficial for the treatment of endometrial cancer 3.1.2.6 hydroxyacylglutathione hydrolase pharmacology enzyme is a potential anti-cancer and/or anti-protozoal target, rational design of inhibitors 3.1.3.5 5'-nucleotidase pharmacology inhibitors could be used to diminish nucleotide depletion during ischemia/reperfusion 3.1.3.5 5'-nucleotidase pharmacology tool for drug screening 3.1.3.5 5'-nucleotidase pharmacology potential site for pharmacological intervention to protect organs against nucleotide depletion 3.1.3.7 3'(2'),5'-bisphosphate nucleotidase pharmacology the inhibition by lithium suggests the FIG superfamily of enzymes is the target of lithium therapy in manic-depressive illness 3.1.3.25 inositol-phosphate phosphatase pharmacology the enzyme is the putative target of lithium therapy 3.1.3.32 polynucleotide 3'-phosphatase pharmacology PNKP, similar to several other DNA repair proteins, is of increasing clinical interest owing to the identification of small molecule inhibitors of these enzymes that sensitize cells to IR or chemotherapeutic agents 3.1.3.46 fructose-2,6-bisphosphate 2-phosphatase pharmacology a pharmacophore map is generated and validated to identify inhibitors of the F6P–FBPase complex 3.1.3.48 protein-tyrosine-phosphatase pharmacology inhibition of the regulatory interaction in TCPTP is a desirable strategy for TCPTP activation and attenuation of oncogenic receptor tyrosine kinase signalling 3.1.4.1 phosphodiesterase I pharmacology phosphodiesterase plays an important role in regulating cAMP and cGMP, und thus becomes an important site for the pharmacological intervention, i.e. Parkinson's disease, inhibition studies with theinopyrimidine fused quinazolines and pyridopyrimidine fused quinazolinones 3.1.4.1 phosphodiesterase I pharmacology phosphodiesterase plays an important role in regulating cAMP and cGMP, und thus becomes an important site for the pharmacological intervention, i.e. Parkinson's disease, inhibition studies with thienopyrimidine fused quinazolines and pyridopyrimidine fused quinazolinones 3.1.4.3 phospholipase C pharmacology phospholipase C is considered to be one of key enzymes for the design of drug delivery system using the endocytosis route, because PLC can catalyze the membrane fusion between cell membranes and phospholipid vehicles (liposomes) 3.1.4.11 phosphoinositide phospholipase C pharmacology showing that pharmacological inhibition of PLC enhances intestinal Ca2+ transport. This raises the possibility that pharmacological tools targeting PLC can be used to enhance intestinal Ca2+ absorption. Given the prevalence of osteoporosis, which generally comes with negative Ca2+ balance, PLC can be a clinically relevant pharmacological target in the future 3.1.4.12 sphingomyelin phosphodiesterase pharmacology the enzyme is a potential target in the treatment of allergic reactions 3.1.6.2 steryl-sulfatase pharmacology enzyme inhibitors can be used as anti-tumor agents 3.1.6.2 steryl-sulfatase pharmacology inhibition of STS is an important target for the development of new drugs for oncology and immunology 3.1.6.2 steryl-sulfatase pharmacology steroid sulfatase inhibitors could be novel drugs to treat androgen-dependent disorders of the hair follicle such as androgenetic alopecia or hirsutism 3.1.6.2 steryl-sulfatase pharmacology the non-estrogenic STS inhibitor (p-O-sulfamoyl)-N-tetradecanoyl tyramine has anti-cancer activity and should be a potent therapeutic agent for treatment of estrogen-dependent breast cancer 3.1.13.2 exoribonuclease H pharmacology the enzyme is a target for therapeutic antiviral drug development, design, by combinatorial selection, of dsDNA thioaptamers with selected thiophosphate backbone substitutions inhibiting the RNase activity of the reverse transcriptase and the viral replication, overview 3.1.13.2 exoribonuclease H pharmacology the enzyme is targeted by drugs via its RNA-DNA hybrid substrates, overview 3.1.21.1 deoxyribonuclease I pharmacology bacterial biofilm infections are highly prevalent and are a significant cause of morbidity and mortality. With the rapid emergence of resistance to conventional antibiotic therapies and intrinsic biofilm resistance to antibiotic penetration, Pseudomonas aeruginosa biofilm treatment options are limited. Consequently, novel anti-biofilm strategies to prevent biofilm formation and remove existing biofilms are being sought. Glutathione enhances antibiotic efficiency and effectiveness of DNase I in disrupting Pseudomonas aeruginosa biofilms while also inhibiting pyocyanin activity, Thus facilitating restoration of cell enzymatic activity, confluence and viability 3.1.21.1 deoxyribonuclease I pharmacology DNase I has a cytotoxic effect on B16 melanoma cells. DNase I inhibits the migratory activity of melanoma cells in vitro, causing a decrease in the distance of cell front migration and in the area of scratch healing 48 h after the enzyme addition, as well as reducing the rate of cell migration. In mice with B16 metastatic melanoma, intramuscular administration of DNase I in the dose range of 0.12-1.20 mg/kg results in a two- to threefold decrease in the number of surface lung metastases and causes nonspecific antigenic immune stimulation. The pronounced antimetastatic effect of DNase I observed in the in vivo model of metastatic B16 melanoma may be due to both the inhibitory activity of the enzyme on the molecular level (i.e., exDNA degradation) and to its systemic effect on the immune system 3.1.21.2 deoxyribonuclease IV pharmacology this enzyme is absent from mammalian cells, making it an attractive target for anti-tuberculosis drug development 3.1.26.4 ribonuclease H pharmacology the enzyme is a potential target for antileishmanial chemotherapy 3.1.26.5 ribonuclease P pharmacology specific external guide sequences offer a possibility for specific decrease of gene expression by inhibition of RNase P 3.1.26.5 ribonuclease P pharmacology engineered Escherichia coli ribozyme variants are effective in inhibiting HIV infection, the potential of engineering RNase P ribozymes for anti-HIV application 3.1.26.13 retroviral ribonuclease H pharmacology mutations in RNase H can significantly contribute to drug resistance either alone or in combination with nucleoside reverse transcriptase inhibitor-resistance mutations in reverse transcriptase. There exists an equilibrium between nucleoside reverse transcriptase inhibitor incorporation, nucleoside reverse transcriptase inhibitor excision, and resumption of DNA synthesis and degradation of the RNA template by RNase H activity, leading to dissociation of the template-primer and abrogation of HIV-1 replication 3.2.1.1 alpha-amylase pharmacology the enzyme is a target for development of specific inhibitors for diabetes type 2 therapy 3.2.1.14 chitinase pharmacology hAMCase is a potential therapeutic target for anti-inflammatory therapy in Th2-mediated diseases such as asthma 3.2.1.14 chitinase pharmacology since the enzyme exhibits antifungal activity against phytopathogenic and human pathogenic fungi, it can be used as an alternative biofungicide 3.2.1.26 beta-fructofuranosidase pharmacology putative target for antileishmanian drug development 3.2.1.B28 Pyrococcus furiosus beta-glycosidase pharmacology the hyperthermostable beta-glycosidase may be useful for food and pharmaceutical applications 3.2.1.35 hyaluronoglucosaminidase pharmacology isozyme NNH1 is a target for first aid agents from plants in snakebit therapy 3.2.1.37 xylan 1,4-beta-xylosidase pharmacology cooperated transformation of ginsenoside extract to the pharmacologically active ginsenoside 20(S)-Rg3 with a beta-glucosidase. After transforming under optimal condition, the 20 g/l of ginsenoside extract is transformed into 6.28 g/l of Rg3 within 90 min, with a corresponding molar conversion of 95.0% and Rg3 productivity of 1793.49 mg/l/h, respectively 3.2.1.39 glucan endo-1,3-beta-D-glucosidase pharmacology action of endo-beta-1,3-glucanase on the microwave-pretreated paramylon produces soluble beta-1,3-glucans with degrees of polymerisation (DP) ranging from 2-59. The hydrolysis products induce TNFalpha production exhibiting an immunostimulatory effect on murine J774 macrophages 3.2.1.40 alpha-L-rhamnosidase pharmacology alpha-L-rhamnosidase is an important enzyme with applications in the pharmaceutical industries because it can release terminal L-rhamnose residues from various natural products. The D594Q and G827K/D594Q mutant enzymes are more suitable for the industrial processes of isoquercitrin preparation than the wild-type enzyme 3.2.1.59 glucan endo-1,3-alpha-glucosidase pharmacology the enzyme may enhance the efficacy of fungal antibiotics by degrading bacterial exopolysaccharides 3.2.1.76 L-iduronidase pharmacology exploitation of alternative receptor systems that are independent of glycosylation but allow for efficient delivery to the lysosome 3.2.1.76 L-iduronidase pharmacology the enzyme is used in enzyme replacement therapy of mucopolysaccharidosis type I, MPSI, changes in hair morphology of MPSI patients treated with recombinant human enzyme, overview 3.2.1.78 mannan endo-1,4-beta-mannosidase pharmacology tailoring of hydrogel release profiles of potential interest for intestine drug delivery. The rate of hydrolysis of O-acetyl-galactomannan hydrogels modified with alpha-galactosidase increases with decreasing degree of substitution. The addition of alpha-mannanase significantly enhances the release of bovine serum albumin encapsulated in hydrogels with a degree of substitution of 0.36, reaching a maximum of 95% released bovine serum albumin after eight hours compared to 60% without enzyme 3.2.1.83 kappa-carrageenase pharmacology potential use in the future: production of defined phycocolloid oligomers for pharmacy and immunology 3.2.1.104 steryl-beta-glucosidase pharmacology the enzyme may be a promising target for anti-cryptococcal drugs 3.2.1.105 3alpha(S)-strictosidine beta-glucosidase pharmacology Catharanthus roseus produces many pharmaceutically important terpenoid indole alkaloids (TIAs) such as vinblastine, vincristine, ajmalicine, and serpentine. Transcriptional regulator ORCA3 and strictosidine glucosidase (SGD) are both engineered in hairy roots under the control of a glucocorticoid-inducible promoter. Co-overexpression of ORCA3 and SGD result in a significant increase in serpentine by 44%, ajmalicine by 32%, catharanthine by 38%, tabersonine by 40%, lochnericine by 60% and hörhammericine by 56% . The total alkaloid pool is increased significantly by 47%. Combining overexpression of a positive regulator and a pathway gene which is not controlled by this regulator provides a way to enhance alkaloid production 3.2.1.106 mannosyl-oligosaccharide glucosidase pharmacology enzyme is an inhibitor target for antiviral agents that interfere with the formation of essential glycoproteins required in viral assembly, secretion and infectivity 3.2.1.106 mannosyl-oligosaccharide glucosidase pharmacology glucosidase I may be a target for antiviral and antitumor drugs, glucosidase I inhibitors are potentially useful as antiviral, antitumor and antimetastatic agents 3.2.1.108 lactase pharmacology BALB/c mouse LPH cDNA provides a necessary foundation for study of the biological function and regulatory mechanism of the lactose intolerance in mice 3.2.1.113 mannosyl-oligosaccharide 1,2-alpha-mannosidase pharmacology in triple KO (MAN1A1, MAN1A2, and MAN1B1) cells, Man9GlcNAc2 and Man8GlcNAc2 are the major N-glycan structures. The N-glycan structures on recombinant proteins expressed in triple KO cells are simplified and changed from complex types to high-mannose types at the protein level. The triple KO HEK293 cells are suitable for producing recombinant proteins, including lysosomal enzymes with high-mannose-type N-glycans. This approach should accelerate the production of biopharmaceutical proteins with homogenous glycans 3.2.1.114 mannosyl-oligosaccharide 1,3-1,6-alpha-mannosidase pharmacology the enzyme is a pharmaceutical target for the design of inhibitors with anti-cancer activity. The QSAR models with the fragmented QM-DFT descriptors may find a useful application in structure-based drug design where pure empirical and forcefield methods reach their limits and where quantum mechanics effects are critical for ligand-receptor interactions. The optimized models will apply in lead optimization processes for alpha-mannosidase II drug developments 3.2.1.125 raucaffricine beta-glucosidase pharmacology the RG product vomilenine is a direct intermediate in ajmaline biosynthesis and utilization of raucaffricine for the ajmaline biosynthestic pathway could be a crucial and rate-limiting step in the formation of the antiarrythmic drug ajmaline 3.2.1.132 chitosanase pharmacology chitosanase from Paenibacillus mucilaginosus TKU032 may have potential applications in production of bioactive chitosan oligosaccharides for the food and pharmaceutical industries 3.2.1.132 chitosanase pharmacology partially acetylated chitosan oligosaccharides have various potential applications in agriculture, biomedicine, and pharmaceutics due to their suitable bioactivities. A more promising approach is enzymatic depolymerization of chitosan using chitinases or chitosanases, as the substrate specificity of the enzyme determines the composition of the oligomeric products 3.2.1.133 glucan 1,4-alpha-maltohydrolase pharmacology increasing interest for pure maltose in the pharmaceutical industry, maltose may be used instead of D-glucose for intravenous feeding 3.2.1.143 poly(ADP-ribose) glycohydrolase pharmacology the enzyme is a promising therapeutic target for the treatment of Chagas' disease 3.2.1.143 poly(ADP-ribose) glycohydrolase pharmacology PARG is a potential interventional target to improve the efficacy of cancer chemotherapy 3.2.1.147 thioglucosidase pharmacology sulforaphane, the reactive isothiocyanate that potently inhibits neoplastic cellular processes and prevents a number of disease states in humans, is difficult to deliver in an enriched and stable form for purposes of direct human consumption. Evaluation of the bioavailability of sulforaphane, either by direct administration of glucoraphanin (a glucosinolate, or beta-thioglucoside-N-hydroxysulfate), or by co-administering glucoraphanin and the enzyme myrosinase to catalyze its conversion to sulforaphane at economic, reproducible and sustainable yields, overview. Following administration of glucoraphanin in a commercially prepared dietary supplement to a small number of human volunteers, the volunteers have equivalent output of sulforaphane metabolites in their urine to that which they produce when given an equimolar dose of glucoraphanin in a simple boiled and lyophilized extract of broccoli sprouts. Furthermore, when either broccoli sprouts or seeds are administered directly to subjects without prior extraction and consequent inactivation of endogenous myrosinase, regardless of the delivery matrix or dose, the sulforaphane in those preparations is 3 to 4fold more bioavailable than sulforaphane from glucoraphanin delivered without active plant myrosinase 3.2.1.166 heparanase pharmacology targeting enzymes that degrade heparan sulfate proteoglycans highlights one approach to maintain normal tissue architecture, inhibit tumor progression, and block metastasis 3.2.2.1 purine nucleosidase pharmacology enzyme inhibitors N-arylmethyl-substituted iminoribitol derivatives as potential chemotherapeutic agents against trypanosomiasis, validation in an in vivo model of African trypanosomiasis 3.2.2.3 uridine nucleosidase pharmacology Saccharomyces cerevisiae enzyme deficient mutant strains expressing protozoan enzymes could be useful tools in drug screening for specific inhibitors against the pathogenic parasites 3.2.2.22 rRNA N-glycosylase pharmacology enables easy immunotoxin creation by coupling target antigen to artificial cysteine residue at non-enzyme-interfering C-terminus of toxin in a predictive way 3.3.2.4 trans-epoxysuccinate hydrolase pharmacology the reaction product L-(+)-butyrylcholine bitartrate may be used as a lecithin substitute 3.3.2.6 leukotriene-A4 hydrolase pharmacology inhibition of LTA4H is a potential therapeutic strategy that can modulate key aspects of asthma 3.3.2.6 leukotriene-A4 hydrolase pharmacology leukotriene 4 hydrolase is a key target for the treatment of cardiovascular disease 3.3.2.10 soluble epoxide hydrolase pharmacology the enzyme is a key target in treatment of acute systemic hypotension 3.3.2.10 soluble epoxide hydrolase pharmacology the enzyme is a target for inhibition in therapy of disorders resulting from hypertension and vascular inflammation 3.3.2.10 soluble epoxide hydrolase pharmacology the enzyme is a target for inhibitor design 3.3.2.10 soluble epoxide hydrolase pharmacology SEH inhibition might have a potential for flow-induced vascular remodeling and neointimal formation 3.3.2.10 soluble epoxide hydrolase pharmacology the enzyme is a promising therapeutic strategy for cardiovascular disease 3.4.11.1 leucyl aminopeptidase pharmacology the enzyme is a target for the antimalarial activity of inhibitor bestatin 3.4.11.1 leucyl aminopeptidase pharmacology potential anti-malarial chemotherapy target 3.4.11.2 membrane alanyl aminopeptidase pharmacology the enzyme is a target for design of inhibitors acting as anti-hypertensive drugs 3.4.11.3 cystinyl aminopeptidase pharmacology enzyme IRAP is a therapeutic target for the treatment of limbic seizures 3.4.11.10 bacterial leucyl aminopeptidase pharmacology the enzyme ia a target for development of drugs in therapy of Lyme disease caused by Borrelia burgdorferi 3.4.11.10 bacterial leucyl aminopeptidase pharmacology the enzyme is a target for development of anti-Helicobacter pylori agents 3.4.14.5 dipeptidyl-peptidase IV pharmacology enzyme is a target for drug design 3.4.14.5 dipeptidyl-peptidase IV pharmacology target for development of selective inhibitors for control of the enzyme's biological function 3.4.17.1 carboxypeptidase A pharmacology construction of synthetic artificial protease with substrate selectivity for CPA as a substrate, designing of the catalyst by use of specific CPA inhibitors, the artificial catalyst can be used as drug with the target being a protein or peptide related to a disease, overview 3.4.17.2 carboxypeptidase B pharmacology carboxypeptidase B is commonly used in the industrial insulin production and as a template for drug design 3.4.17.11 glutamate carboxypeptidase pharmacology the enzyme is used in antibody directed enzyme prodrug therapy to catalyse the formation of an active drug from an inert prodrug. Free carboxypeptidase G2 in the bloodstream must be inhibited before administration of the prodrug in order to avoid a systemic reaction in the patient 3.4.17.20 Carboxypeptidase U pharmacology enzyme inhibitors are valid as enhancer of physiological fibrinolysis in microcirculation and as adjunctive agent to tissue-type plasminogen activator for thromboembolic diseases in humans while maintaining a small effect on primary hemostasis 3.4.17.21 Glutamate carboxypeptidase II pharmacology enzyme inhibitors are used in therapy of neruological disorders, overview 3.4.17.21 Glutamate carboxypeptidase II pharmacology the enzyme is a drug target in neuronal damage and prostate cancer 3.4.17.21 Glutamate carboxypeptidase II pharmacology the enzyme is a target for specific inhibitor design in therapy of neurodegenerative disorders, overview 3.4.17.21 Glutamate carboxypeptidase II pharmacology the enzyme NAALADase is a target for drug treatment in neuropathic pain 3.4.17.21 Glutamate carboxypeptidase II pharmacology effects of PSMA-targeted photodynamic therapy on cytoskeletal networks in prostate cancer cells 3.4.17.21 Glutamate carboxypeptidase II pharmacology PSMA is a target for imaging and therapeutic applications for prostate cancer 3.4.17.21 Glutamate carboxypeptidase II pharmacology usage of the ectodomain of PSMA as target for a retargeted measles virus, that harbors a single-chain antibody specific for the extracellular domain of PSMA (J591) inserted as a C-terminal extension on its viral attachment protein. Live attenuated vaccine strain of measles virus has promising antitumor activity. Fully retargeted MV that infects cells exclusively through the PSMA receptor, which is overexpressed on prostate cancer cells and tumor neovasculature, method, overview. The construct leads to tumor regression 3.4.17.23 angiotensin-converting enzyme 2 pharmacology design and synthesis of first potent and selective enzyme inhibitors may be useful as pharmacological tools to help understanding the biological relevance and potantial role of the enzyme in human disease 3.4.17.23 angiotensin-converting enzyme 2 pharmacology ACE 2 is a potential therapeutic target in the treatment of heart failure 3.4.17.23 angiotensin-converting enzyme 2 pharmacology ACE2 might be a target for treatment of non-small cell lung cancer 3.4.17.23 angiotensin-converting enzyme 2 pharmacology conserved residues at the interface of the spike protein from three strains of coronaviruses NL63, SARS-CoV, and SARS-CoV are identified, which might act as a recognition site for ACE2 receptor. The conserved interaction sites can help in effective targeting of the ACE2 binding site by therapeutics in SARS-CoV as well as SARS-CoV-2 strain 3.4.17.23 angiotensin-converting enzyme 2 pharmacology identification of compounds that bind to either the angiotensin converting enzyme 2 (ACE2) and/or the SARS-CoV-2 spike protein receptor binding domain (SARS-CoV-2 spike protein RBD). All 22 identified compounds provide scaffolds for the development of new chemical entities for the treatment of COVID-19 3.4.17.23 angiotensin-converting enzyme 2 pharmacology the binding of eighteen candidate drugs with ACE2 enzyme and [SARSCoV-2/ACE2] complex is examined by using docking analysis. The docking ranking shows that some of these ligands might have the ability to inhibit SARS-CoV-2. The study shows that Ramipril, Delapril and Lisinopril could bind with ACE2 receptor and [SARSCoV-2/ACE2] complex better than chloroquine and hydroxychloroquine 3.4.19.12 ubiquitinyl hydrolase 1 pharmacology enzyme is a target for the development of antineoplastic agents 3.4.19.12 ubiquitinyl hydrolase 1 pharmacology covalent docking plus MD refinement of a representative set of known SARS-CoV inhibitors into OTUB2, OTUB1, and the PLpro from SARS-CoV-2 to probe their inhibitor binding and rationalize a deubiquitinase selectivity. It is pointed out that the structural differences in cellular deubiquitinases suggest that these enzymes may be different enough to be selectively targeted 3.4.19.13 glutathione gamma-glutamate hydrolase pharmacology the enzyme is involved in a number of physiological and pathological processes through glutathione metabolism and is an attractive pharmaceutical target 3.4.21.6 coagulation factor Xa pharmacology enyme is a potential target for development of antithrombotics, structure-based drug design approach usig the crystal structure of the enzyme-inhibitor complex 3.4.21.6 coagulation factor Xa pharmacology enzyme is a major target for new therapeutics in prevention of blood coagulation 3.4.21.6 coagulation factor Xa pharmacology enzyme is a target for discovery, design of direct inhibitors and development of antithrombotic agents, overview 3.4.21.6 coagulation factor Xa pharmacology enzyme is a target for inhibitor design as anti-thrombotic agents 3.4.21.6 coagulation factor Xa pharmacology factor Xa is a therapeutic target for development of potent and selective direct enzyme inhibitors as antithrombotic compounds for the improved therapy of ischemic heart disease and cerebrovascular disease, no bleeding effect, only modest change in markers of systemic anticoagulation, use of animal models, overview 3.4.21.6 coagulation factor Xa pharmacology the enzyme is a target for development of antithrombotic drug therapy mechanism 3.4.21.6 coagulation factor Xa pharmacology inhibitor N-(5-chloropyridin-2-yl)-N'-[(1S,2R,4S)-4-(N,N-dimethylcarbamoyl)-2-(5-methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridine-2-carboxamido)-cyclohexyl]ethanediamine 4-toluenesulfonate monohydrate dose-dependently inhibits thrombus formation in a rabbit thrombosis model 3.4.21.6 coagulation factor Xa pharmacology inhibitor N-(5-chloropyridin-2-yl)-N'-[(1S,2R,4S)-4-(N,N-dimethylcarbamoyl)-2-(5-methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridine-2-carboxamido)-cyclohexyl]ethanediamine 4-toluenesulfonate monohydrate dose-dependently inhibits thrombus formation in a rat thrombosis model. Bleeding time in rats is not significantly prolonged at an antithrombotic dose 3.4.21.6 coagulation factor Xa pharmacology presence of inhibitor N-(5-chloropyridin-2-yl)-N'-[(1S,2R,4S)-4-(N,N-dimethylcarbamoyl)-2-(5-methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridine-2-carboxamido)-cyclohexyl]ethanediamine 4-toluenesulfonate monohydrate prolongs the activated partial thromboplastin time, prothrombin time and thrombin time in plasma. It does not impair human platelet aggregation induced by ADP or thromboxane A2 receptor agonist U46619. Thrombin-induced platelet aggregation is inhibited with IC50 value of 2.9 microM 3.4.21.6 coagulation factor Xa pharmacology sensitive and specific quantification of inhibitor rivaroxaban in human plasma by high-performance liquid chromatography-tandem mass spectrometry. Concentrations between 0.5 and 500 micrograms per liter can be detected. Inter-assay precision is below 7.4% and inter-assay accuracy is between 96.3% and 102.9% 3.4.21.6 coagulation factor Xa pharmacology study on use of apixaban for prevention of arterial thrombosis in rabbit models of electrically induced carotid artery thrombosis and cuticle bleeding time. Addition of aspirin to apixaban significally reduces the thrombus weight with no significant increase in bleeding time. Addition of aspirin and apixaban to clopidogrel produces a further significant reduction in thrombus weight. Combination of clopidogrel and aspirin with apixaban produces a significant but moderate 2.1fold increase in bleeding time 3.4.21.6 coagulation factor Xa pharmacology treatment of patients undergoing elective total knee replacement post-operatively with betrixaban or enoxiparin for 10-14 days to prevent thromboembolism. Betrixaban shows a dose- and concentration-dependent effect on inhibition of thrombin generation and anti-factor Xa levels. Betrixaban demonstrates antithrombotic activity and is well tolerated in knee replacement patients 3.4.21.7 plasmin pharmacology construction of a deletion mutant of plasminogen lacking the middle portion of the molecule, resulting in kringle I attachment to the serine protease domain. After expression in Escherichia coli and purification, mutant plasminogen is effectively converted to mutant plasmin by tissue plasminogen activator. Mutant plasmin is rapidly inhibited by alpha2-antiplasmin an alpha2-macroglobulin. It demonstrates fibrinolytic potency comparable to human plasma-derived plasmin and is a potentially safe and effective direct thrombolytic agent 3.4.21.7 plasmin pharmacology development of human plasmin product that is rendered inactive by low pH value of 3.0-4.0 until it is delivered directly to the neutral environment of a thrombus by catheter-assisted administration. The product is extremely pure and has a shelf-life of three years at ambient temperature 3.4.21.7 plasmin pharmacology intravitreous injection of plasmin induces partial posterior vitreous detachment in diabetic rats. Combinantion of hyaluronidase and plasmin can induce complete posterior vitreous detachment. It ismore difficult to induce posterior vitreous detachment in diabetic rats than in healthy rats. No obvious toxic reaction was observed in each group 3.4.21.20 cathepsin G pharmacology structure-based drug design 3.4.21.26 prolyl oligopeptidase pharmacology microbial PEPs are studied as potential therapeutics for celiac sprue, an inflammatory disease of the small intestine triggered by proline-rich gluten 3.4.21.26 prolyl oligopeptidase pharmacology the discovery of enzyme inhibitors can revert memory loss caused by amnesic compounds in humans, developing a enzyme inhibitor from carbohydrate based materials 3.4.21.34 plasma kallikrein pharmacology design of specific inhibitors for proteases like plasma kallikrein, but not protein C, to diminish the complement hydrolysis and coagulation during sepsis 3.4.21.42 complement subcomponent C1s pharmacology inhibition of the complement pathway is of great therapeutic interest. The C1 complex is a very attractive target for selective inhibition of the classical complement pathway because it is the only member of the classical pathway that does not participate in the other complement pathways 3.4.21.43 classical-complement-pathway C3/C5 convertase pharmacology pharmacological complement inhibition at the C3 convertase level is a promising approach for attenuation of neuroinflammation and secondary neurodegeneration after head injury 3.4.21.64 peptidase K pharmacology In human variant Creutzfeldt–Jakob disease, up to 90% of total prion protein present in the brain resists degradation with thermolysin, whereas only ?15% of this material resists digestion by proteinase K. Detection of proteinase K-sensitive isoforms of disease-related prion protein using thermolysin should be useful for improving diagnostic sensitivity in human prion diseases 3.4.21.69 Protein C (activated) pharmacology activated protein C is a natural protein with anticoagulant and immunomodulatory effects, and its recombinant version is approved by the U.S. Food and Drug Administration to treat severe sepsis 3.4.21.69 Protein C (activated) pharmacology activated protein C is approved by the Food and Drug Administration as drug for severe sepsis 3.4.21.72 IgA-specific serine endopeptidase pharmacology systemically administered IgA protease is able to reduce the quantity of glomerular IgA immune complexes, both the antigen and antibody components, in a passive mouse model of IgA nephropathy 3.4.21.73 u-Plasminogen activator pharmacology rapid, sensitive and selective method for detection of uPA activator UK-356202 in human plasma using column-switching HPLC and fluorescence detection. The limit of detection is 20 pg/ml, and the method is linear over a 100-fold concentration range 3.4.21.73 u-Plasminogen activator pharmacology Treatment of nude mice bearing subcutaneously or orthotopically implanted human colon cancer cell lines HCT-116 and HT-29 with TX-1877, irradiation or TX-1877 with irradiation results in significant inhibition of matrix metalloproteinase-9 and uPA. Treatments also inhibit the para-aortic lymph node metastasis, however, do not prolong the survival in orthotopic model. In the subcutaneous model, tumors treated with TX-1877 and irradiation show significant reductions in volume 3.4.21.73 u-Plasminogen activator pharmacology uPA blocking antibodies may not be indicated for cancer growth inhibition strategies, but may serve as valuable tools for the implementation of pharmacodelivery strategies against a variety of different tumors 3.4.21.74 venombin A pharmacology Bhaltenin may be of interest as a therapeutic agent in the treatment and prevention of thrombotic disorders 3.4.21.75 Furin pharmacology development of an immunoproapoptotic molecule with antitumor activity: Her2-antigen e23sFv-TD-tBID with a 10-amino acid residue furin cleavage sequence. e23sFv-TD-tBID shows therapeutic value to humans by its cytotoxic effects on primary patient-derived breast tumor cells but not on endothelial cells. It also shows in vivo antitumor activity in female BALB/c athymic mice, overview 3.4.21.79 granzyme B pharmacology granzyme B has antimalarial activity against Plasmodium falciparum strain 3D7A of 1600 nM and can be targeted delivered by a granzyme B-single-chain Fv fusion protein, inhibitory activities on parasite growth of different fusion proteins on two different Plasmodium falciparum strains, overview 3.4.21.79 granzyme B pharmacology antimalarial activity of granzyme B and its targeted delivery by a granzyme B-single-chain Fv fusion protein. Therapeutic efficacies of recombinant antibody-mediated antimalarial immunotherapeutics based on granzyme B, overview 3.4.21.79 granzyme B pharmacology functionalized superparamagnetic iron oxide nanoparticles (SPIONs) have emerged as potential clinical tools for cancer theranostics. GrB-functionalized SPIONs act as a contrast enhancement agent for magnetic resonance imaging and induce specific tumor cell apoptosis. Combinatorial regimens employing stereotactic radiotherapy and/or magnetic targeting are found to further enhance the therapeutic efficacy of GrB-SPIONs in different tumor mouse models. GrB-SPIONs accumulate in the tumor and increase MR contrast enhancement. The therapeutic potential of a systemic administration of GrB-SPIONs is evaluated in o.t. xenograft H1339 lung cancer model with and without brain metastases and U87 glioma mouse models, overview 3.4.21.89 Signal peptidase I pharmacology enzyme is essential for bacterial cell viability, potential molecular target for development of novel antibacterial agents 3.4.21.89 Signal peptidase I pharmacology possible targets for the design of novel antibiotics 3.4.21.89 Signal peptidase I pharmacology signal peptidase structure will be useful in the design of new and improved inhibitors which may be of pharmaceutical importance 3.4.21.89 Signal peptidase I pharmacology the gram positive pathogen plays a significant role in infectious disease, including life threatening methicillin-resistant MRSA infections, the ability to screen for inhibitors of SpsB will represent a significant advance for discovery of antibacterial agents 3.4.21.98 hepacivirin pharmacology the viral protease may be a target for antiviral drugs 3.4.21.118 kallikrein 8 pharmacology enzyme is a drug target in the treatment of epilepsy 3.4.22.1 cathepsin B pharmacology the cathepsin B cleavable spacer Phe-Lys-4-aminobenzyloxycarbonyl, incorporated in an albumin-binding prodrug, is an effective way to increase the therapeutic index of doxorubicin 3.4.22.1 cathepsin B pharmacology use of benzyloxycarbonyl-L-phenylalanyl-alanine-fluoromethylketone for inhibition of cathepsin-B seems a viable therapeutic strategy in TNF-alpha-mediated acute lung damage 3.4.22.1 cathepsin B pharmacology Nicotiana benthamiana has recently emerged as a versatile expression platform for the rapid generation of recombinant biopharmaceuticals, but product yield and quality frequently suffer from unintended proteolysis. Targeted downregulation of cathepsin B can improve the performance of this plant-based expression platform 3.4.22.15 cathepsin L pharmacology chloroquine inhibits the infection with live Nipah virus and Hendra virus at a concentration of 1 microM in vitro. The mechanism for the antiviral action likely is the inhibition of cathepsin L, which is essential for the processing of the viral fusion glycoprotein and the maturation of newly budding virions 3.4.22.15 cathepsin L pharmacology treatment of isolated bovine coronary arteries with cathepsin L markedly attenuates endothelium-dependent vasodilator responses to bradykinin or A23187 by 56% and 69%, respectively. The inhibitory effect of cathepsin L on endothelium-dependent vasodilator responses can be significantly reversed by pre-incubation of the arteries with O2- scavenger, Tiron, or neutralizing anti-endostatin antibody. Cathepsin L dose-dependently increases endostatin production in coronary arteries. Cathepsin L decreases bradykinin- and A23187-induced NO levels in the intact endothelium, but it has no effect on Ca2+ response to these vasodilators. Cathepsin L-induced reduction of NO is restored by the pretreatment of an anti-endostatin antibody. Cathepsin L increases O2- production which can be markedly attenuated by the NAD(P)H oxidase inhibitors, apocynin or anti-endostatin antibody 3.4.22.27 cathepsin S pharmacology the enzyme might be a good target for development of inhibitors in treatment of collagen-induced arthritis and autoimmune myasthenia gravis 3.4.22.32 Stem bromelain pharmacology bromelain is pharmacologically active against B16F10 melanoma cells with complete inhibition of tumor cell proliferation in vitro 3.4.22.32 Stem bromelain pharmacology in vitro anti-cancer activity (anti-proliferation and apoptosis induction) comparison of the freeze-dried and spray-dried bromelain from pineapple stems 3.4.22.33 Fruit bromelain pharmacology use as additive to prevent lymphedema by reducing lymphocongestion, detritus, viscosity of the exsudate and stimulation of phagocytosis of associated leukocytes, use as additive for radiotherapy and surgery due to wound healing effect and reductive effect on inflammation and edema, use as additives for chemotherapy due to inhibitory effects on malignant growth of tumor cells 3.4.22.33 Fruit bromelain pharmacology bromelain is pharmacologically active against B16F10 melanoma cells with complete inhibition of tumor cell proliferation in vitro 3.4.22.37 gingipain R pharmacology enzyme structure is an excellent template for the rational design of drugs with a potential to cure and prevent periodontitis 3.4.22.38 cathepsin K pharmacology cathepsin K is a therapeutic target for bone diseases 3.4.22.38 cathepsin K pharmacology CatK is an established drug target for osteoporosis 3.4.22.38 cathepsin K pharmacology CTSK is a possible therapeutic target in the treatment of obesity 3.4.22.48 staphopain pharmacology studies on development of therapeutic agents directed toward proteolytic virulence factors 3.4.22.51 cruzipain pharmacology induction of RNAi against brucipain of Trypanosoma brucei does not cure mice from infection, however, 50% of these mice survive 60 days longer than uninduced controls. The ability of Trypanosoma brucei to cross an in vitro model of the human blood-brain barrier is also reduced by brucipain RNAi induction 3.4.22.62 caspase-9 pharmacology analysis and improvement of apoptosome inhibitors 3.4.22.62 caspase-9 pharmacology drug development, studies on mechanisms of apoptosis activated in response to marine sponge extracts of Polymastia janeirensis 3.4.22.62 caspase-9 pharmacology in vitro analysis of apoptotic mechanism of isorhamnetin in Lewis lung cancer (LLC) cells, in vivo anti-cancer efficacy 3.4.22.62 caspase-9 pharmacology NaF-induced apoptosis of osteoblasts, in vitro studies, pronounced negative effect of NaF treatment on indices of survival of osteoblasts, decreased proliferation, increased apoptosis and increased caspase-3 and caspase-9 mRNA 3.4.22.62 caspase-9 pharmacology rituximab-induced apoptosis highly dependent on caspase-9 activation, regulated by Bcl-xL expression 3.4.22.62 caspase-9 pharmacology studies on mechanisms of apoptosis induced by high linear energy transfer (LET) radiation 3.4.22.62 caspase-9 pharmacology studies on mechanisms of apoptosis induced by ionizing radiation in human leukaemic cells with a different status of p53 (TP53 tumor suppressor gene) 3.4.22.62 caspase-9 pharmacology studies on molecular mechanisms of caspase-9 activation mediated by reactive oxygen species (ROS) 3.4.22.62 caspase-9 pharmacology studies on the mechanism of cordycepin-induced apoptosis in MA-10 Leydig tumor cells 3.4.22.62 caspase-9 pharmacology the cellular-FLICE inhibitory protein (c-FLIP) analyzed as a potential therapeutic target for breast cancers 3.4.22.62 caspase-9 pharmacology therapeutic usefulness of the herbal drug Hwanggunchungyitang (HGCYT) against cadmium (Cd2+)-induced activation of caspase-9 3.4.22.63 caspase-10 pharmacology tumour necrosis factor-related apoptosis-inducing ligand and SMs effectively kill head and neck squamous cancer cell lines and therefore represent potential targeted therapeutics for head and neck cancer. Distinct molecular mechanisms determine the sensitivity to each agent, with levels of TNF-alpha, caspase-8, Bid and caspase-10 providing important predictive biomarkers of response to these agents 3.4.22.65 peptidase 1 (mite) pharmacology production of recombinant enzymatically and immunologically enzyme for deciphering of immunotherapy mechanisms 3.4.22.B80 SARS-CoV papain-like protease pharmacology covalent docking plus MD refinement of a representative set of known SARS-CoV inhibitors into OTUB2, OTUB1, and the PLpro from SARS-CoV-2 is used to probe their inhibitor binding and rationalize a deubiquitinase selectivity. It is pointed out that the structural differences in cellular deubiquitinases suggest that these enzymes may be different enough to be selectively targeted 3.4.23.15 renin pharmacology the renin-angiotensin system is a potential target for lymphangioleiomyomatosis therapy 3.4.23.15 renin pharmacology after 12 weeks of treatment in patients with hypertension, aliskiren, atenolol and aliskiren/atenolol lower systolic and diastolic blood pressure from baseline by 14.3/11.3, 14.3/13.7 and 17.3/14.1 mmHg, respectively. Systolic blood pressure reductions with aliskiren/atenolol are significantly greater than those with aliskiren or atenolol alone, and diastolic blood pressure reductions are greater than with aliskiren alone. Diastolic blood pressure changes are larger with atenolol than with aliskiren. Aliskiren, atenolol and aliskiren/atenolol reduce geometric mean plasma renin activity from baseline by 65%, 52% and 61%, respectively. In patients with moderate or high baseline plasma renin activity, plasma renin activity is reduced to low levels at week 12 endpoint in a greater proportion of patients receiving aliskiren or aliskiren/atenolol than with atenolol. Aliskiren treatment is associated with numerically lower rates of adverse events and discontinuations due to adverse events compared with atenolol or combination treatment, and unlike atenolol is not associated with bradycardia 3.4.23.15 renin pharmacology aliskiren at the highest approved dose of 300 mg once daily for 7 days and a 4-fold higher dose has no effect on cardiac repolarization or conduction in healthy volunteers 3.4.23.15 renin pharmacology co-administration of aliskiren results in changes below 30% in pharmacokinetic parameters AUC and Cmax of digoxin, atorvastatin, o-hydroxyatorvastatin, and p-hydroxyatorvastatin, indicating no clinically significant interaction with P-glycoprotein or CYP3A4 substrates. Aliskiren AUC is significantly increased by coadministration with atorvastatin or ketoconazole 3.4.23.15 renin pharmacology detailed pharmacodynamic analysis of aliskiren in humans. Development of an integrated pharmacokinetik/pharmacodynamic model for aliskiren, including an empirical submodel to account for additional complexities arising from multiple dosing 3.4.23.15 renin pharmacology renal vasodilation in healthy people with renin inhibitor aliskiren exceeds responses seen with angiotensin-converting enzyme inhibitors and angiotensin receptor blockers. The effects are longer lasting and are associated with significant natriuresis. Aliskiren may provide more complete and more effective blockade of the renin-angiotensin system 3.4.23.15 renin pharmacology study on long-term safety, tolerability, and antihypertensive efficacy on Japanese patients with mild to moderate essential hypertension. Aliskiren alone or in combination with a diuretic or a calcium channel blocker is well tolerated. The incidence of suspected study-related adverse events was 25.3%. The overall responder efficacy was 73.3% at the endpoint. A clinically meaningful reduction of 17.6/12.8 m Hg from baseline was achieved in the mean sitting blood pressure at the endpoint 3.4.23.15 renin pharmacology treatment of Watanabe heritable hyperlipidemic rabbits with aliskiren or aliskiren plus valsartan leads to greater increases in plasma nitric oxide concentration in response to intra-aortic acetylcholine infusion than in control. Aliskiren plus valsartan treatment increases acetylcholine-induced nitric oxide by 6.2 nmol/l, which is significantly higher than with either aliskiren or valsartan alone. Vascular superoxide and peroxynitrite levels are both significantly higher in controls and significantly lower in the aliskiren plus valsartan group than in the aliskiren or valsartan group 3.4.23.16 HIV-1 retropepsin pharmacology the enzyme is a target for drug development active on multidrug-resistant virus 3.4.23.16 HIV-1 retropepsin pharmacology the enzyme is a target for specific inhibitor development 3.4.23.16 HIV-1 retropepsin pharmacology mutations in the gag region NC-p1/TFP-p6/p6pol may influence the selection of darunavir resistance mutations. The I437T/V gag mutation that confers resistance to protease inhibitors reduces the selection of such mutations. Virus with L76V in protease or I437T/V in gag may be already resistant to darunavir 3.4.23.16 HIV-1 retropepsin pharmacology use of suboptimal concentrations of inhibitors atazanavir and lopinavir. Even with high levels of inhibition of viral infectivity, IC90, most of the Gag and Gag-Pol polyproteins are processed, although slight but significant increases in processing intermediates of Gag Are detected. Drug treatments cause a significant increase in the proportion of viruses displaying either immature or aberrant mature morphologies. The aberrant mature particles are characterized by an electron-dense region at the viral periphery and an electron-lucent core structure in the viral center. Drug treatments cause only a slight decrease in overall thermodynamic stability of the viral RNA dimer 3.4.23.B24 signal peptide peptidase pharmacology mechanism of SPP inhibitors in Plasmodium falciparum, overview. PlSPP is an attractive target for the treatment of malaria 3.4.23.45 memapsin 1 pharmacology the enzyme is a potential target for development of inhibitors in Alzheimer's disease therapy and treatment of Down syndrome 3.4.23.46 memapsin 2 pharmacology design of inhibitor drugs for treatment of Alzheimer disease 3.4.23.46 memapsin 2 pharmacology development of inhibitor drugs for the treatment of Alzheimer disease 3.4.23.46 memapsin 2 pharmacology overview about therapeutic strategies by focusing on BACE1 for treatment of Alzheimer disease 3.4.23.46 memapsin 2 pharmacology inhibition of BACE1 may protect neurons from death induced by okadaic acid. Because of increased accumulation of amyloid beta precursor protein in neurons after okadaic acid treatment, more amyloid beta precursor protein turns to be cleaved by beta-secretase, producing neurotoxic beta-C-terminal fragment 3.4.23.46 memapsin 2 pharmacology treatment of London APP transgenic mouse model of Alzheimer's disease that expresses human amyloid precursor protein containing the wild-type beta-secretase site with inhibitors CA074Me or E64d results in substantial improvement in memory deficit assessed by the Morris water maze test. Improved memory function is accompanied by reduced amyloid plaque load, decreased amyloid beta40 and amyloid beta42, and reduced C-terminal beta-secretase fragment derived from amyloid precursor protein by beta-secretase. Inhibitor hHas no effects on any of these parameters in mice expressing the Swedish mutant beta-secretase site of amyloid precursor protein 3.4.23.49 omptin pharmacology studies on treatment of infection by antibiotic-resistant bacteria 3.4.24.3 microbial collagenase pharmacology mechanism of action of collagenase clostridium histolyticum for clinical application 3.4.24.B3 matrix metalloproteinase-11 pharmacology enzyme form with the specific residue A235 is an attractive target for the development of specific inhibitors for use in prevention of cancer progression 3.4.24.B6 matrix metalloproteinase-20 pharmacology enzyme is a potential target for selective inhibition and inhibitor design 3.4.24.7 interstitial collagenase pharmacology MMP-1 is a potential target in therapy of melanoma 3.4.24.11 neprilysin pharmacology inhibitor thiorphan might be effective for reducing elevated A-type natriuretic peptide levels in sepsis. Plasma and lung A-type natriuretic peptide levels in rats treated with lipopolysaccharide are significantly higher than those in the control group, but are significantly decreased by thiorphan administration. Natriuretic peptide receptor-A mRNA levels do not differ significantly among the groups. Natriuretic peptide receptor-C mRNA levels in animals treated with lipopolysaccharide plus thiorphan group are significantly higher than those in the other groups 3.4.24.16 neurolysin pharmacology the ability of Nln to process several neuropeptides suggests that it could potentially serve as a single therapeutic target to modulate the function of multiple targets, the noted neuropeptide systems, critically involved in various mechanisms of brain injury or cerebroprotection/restoration 3.4.24.18 meprin A pharmacology in a mouse model of sepsis induced by cecal ligation puncture that results in elevated levels of serum interleukin 1beta, meprin inhibitor actinonin significantly reduces levels of serum interleukin 1beta 3.4.24.18 meprin A pharmacology ischemic acute kidney injury was induced by occlusion of the left renal artery and vein for 45 min followed by reperfusion, 2 weeks after contralateral nephrectomy. At 24 h after reperfusion, renal function and histology of both males and females showed significant deterioration. The degrees of renal dysfunction and histological damage are much more severe in males than in females. Pre-ischemic treatment with actinonin at 10 or 30 mg/kg i.v., dose-ependently attenuats the ischemia/reperfusion-induced renal injury in male rats, but fails to improve the renal injury in female rats. Verapamil at 1 mg/kg i.v., can efficiently prevent the ischemic acute kidney injury in female rats, as well as male rats 3.4.24.18 meprin A pharmacology regulation of meprin activity by specific inhibition to reduce collagen maturation might be a suitable approach for the treatment of certain pathological conditions 3.4.24.18 meprin A pharmacology meprin alpha is a potential target in treatment of hepatocellular carcinoma (HCC), although meprin alpha has a limited effect on HCC cell proliferation 3.4.24.23 matrilysin pharmacology MMP-7 is an important target for antimetastasis therapy of colorectal cancer because it is a strong proteolytic factor secreted from the cancer cell itself and it induces tumor angiogenesis 3.4.24.23 matrilysin pharmacology in sulindac-treated ApcMin/+ mice, a genetic model of human familial adenomatous polyposis, collagen genes, viz. Col1a2, Col5a2, Col6a2, and Col6a3, are upregulated, and matrilysin matrix metalloproteases-7 is downregulated. Mmp7 is found in hot spot areas within the tumors of ApcMin/+ mice treated with the vehicle, but is greatly diminished in those mice treated with sulindac 3.4.24.26 pseudolysin pharmacology branched antimicrobial peptide M33 pegylation at the C-terminus of the three lysine-branching core with a Peg4 molecule and the resulting increase in stability to Pseudomonas aeruginosa elastase, peptide resistance to this protease is an important feature for M33-Peg activity against Pseudomonas aeruginosa 3.4.24.36 leishmanolysin pharmacology cationic distearoyl phosphatidylcholine liposomes, used as vaccine adjuvant with the immunodominant 63 kDa glycoprotein of promastigotes, induce significant protection against progressive visceral leishmaniasis in susceptible BALB/c mice. gp63 used without adjuvant elicits partial protection but in association with liposomes exhibits marked resistance in both the livers and spleens of the mice challenged 10 days after the last vaccination. The protective efficacy of liposomal gp63 vaccination is dose dependent, with 2.5 microg of protein showing optimal protection. Mice challenged 12 weeks after immunization are still protected, and a mixed Th1/Th2 response has been induced following immunization 3.4.24.36 leishmanolysin pharmacology immunization of female BALB/c mice with negatively, positively charged or neutral liposomes encapsulated with rgp63, rgp63 in soluble form. The group of mice immunized with recombinant gp63 encapsulated in neutral liposomes shows a significantly smaller footpad swelling upon challenge with Leishmania major compared with positively or negatively charged liposomes. The mice immunized with neutral liposomes show the lowest splenic parasite burden, the highest IgG2a/IgG1 ratio and IFN-gamma production and the lowest IL-4 level compared to the other groups. The results indicate that a Th1 type of immune response is induced in mice immunized with neutral liposomes more efficiently than positively charged liposomes and conversely negatively charged liposomes induce a Th2 type of immune response 3.4.24.63 meprin B pharmacology meprin-beta is strong candidate for a proinflammatory target 3.4.24.63 meprin B pharmacology regulation of meprin activity by specific inhibition to reduce collagen maturation might be a suitable approach for the treatment of certain pathological conditions 3.4.24.65 macrophage elastase pharmacology MMP-12 might be a target for the therapy against allergic bronchial asthma 3.4.24.65 macrophage elastase pharmacology MMP-12 plays a predominant role in the inflammatory process induced by cigarette smoke, and therefore is potentially an important therapeutic target for the treatment of chronic obstructive pulmonary diseases 3.4.24.72 fibrolase pharmacology alfimeprase is a potential therapeutic agents in thrombosis therapy, clinical indications and studies, overview 3.4.24.75 lysostaphin pharmacology lysostaphin is useful for treatment for systemic Staphylococcus aureus infection in a mouse model 3.5.1.1 asparaginase pharmacology L-asparaginase is a cancer chemotherapeutically important enzyme 3.5.1.4 amidase pharmacology nonsteroid anti-inflammatory drugs known as profens, chiral drug 3.5.1.11 penicillin amidase pharmacology both the recombinant protein yield and the specific activity of the enzyme are very high, auguring well for application in the pharmaceutical industry for production of the pharmaceutical intermediates 6-amino penicillanic acid. Penicillin acylases find use in the pharmaceutical industry for the production of semi-synthetic antibiotics 3.5.1.11 penicillin amidase pharmacology penicillin acylases are pharmaceutically important enzymes widely used in the synthesis of semi synthetic beta lactam antibiotics 3.5.1.13 aryl-acylamidase pharmacology the high enzyme activity associated with cobra venom AChE may serve as one of the prominent activity to test the pharmacological effect of AD drugs, as other sources have lower activity 3.5.1.15 aspartoacylase pharmacology the enzyme is the taget for treatment of Canavan disease, enzyme replacement therapy can potentially be used to overcome these defects if a stable enzyme form that can gain access to the appropriate neural cells can be produced. PEGylated form of aspartoacylase are able to traverse the blood-brain barrier and show dramatic enhancement in brain tissue access and distribution, overview. Examination of the effect of enzyme administration on the immunological response 3.5.1.23 ceramidase pharmacology enzyme inhibition may be beneficial in cancer therapy 3.5.1.48 acetylspermidine deacetylase pharmacology HDAC10 isozyme-selective inhibitors will suppress autophagic responses to cancer chemotherapy, thereby rendering cancer cells more susceptible to cytotoxic drugs 3.5.1.60 N-(long-chain-acyl)ethanolamine deacylase pharmacology potential of blocking N-acylethanolamines like palmitoylethanolamide or N-arachidonlyethanolamine (anandamide) from enzymatic degradation via enzyme inhibition as a strategy for pain treatment 3.5.1.60 N-(long-chain-acyl)ethanolamine deacylase pharmacology NAAA inhibitor F215 is a therapeutic agent for osteoarthritis. The therapeutic effects of F215 are blocked by the PPAR-alpha antagonist MK886 3.5.1.70 aculeacin-A deacylase pharmacology useful in preparing deacylated peptides which are used as starting material for semisynthetic antifungal antibiotics, for creating new and more useful antifungal agents 3.5.1.70 aculeacin-A deacylase pharmacology useful in producing peptide nuclei, i.e. deacetylated cyclic hexapeptides, for creating new antifungal agents by introducing different acyl moieties 3.5.1.93 glutaryl-7-aminocephalosporanic-acid acylase pharmacology the product of the reaction 7-aminocephalosporanic acid is a starting material for semisynthetic cephalosporin antibiotics. High thermal stability of the enzyme immobilized on silica gels indicates that it can be successfully used for the production of 7-aminocephalosporanic acid on an industrial scale 3.5.1.97 acyl-homoserine-lactone acylase pharmacology therapeutic efficacy of PvdQ acylase as a quorum quenching agent during Pseudomonas aeruginosa infection (mouse model of pulmonary Pseudomonas aeruginosa infection) 3.5.1.99 fatty acid amide hydrolase pharmacology FAAH is a potential therapeutic target 3.5.1.104 peptidoglycan-N-acetylglucosamine deacetylase pharmacology studies on peptidoglycan modifications by Streptococcus pneumoniae 3.5.1.108 UDP-3-O-acyl-N-acetylglucosamine deacetylase pharmacology the enzyme is a target for antibiotic therapy and structure-based drug design 3.5.1.119 Pup amidohydrolase pharmacology the enzyme provides an ideal target for the development of selective chemotherapies 3.5.2.6 beta-lactamase pharmacology enzyme is a target for design of non-beta-lactam, broad-spectrum peptidomimetic enzyme inhibitors 3.5.3.1 arginase pharmacology enzyme is a target for inhibitor design based on arginine analogues with uncharged, tetrahedral functional groups 3.5.3.4 allantoicase pharmacology possibility to develop metabolism-based strategies for mosquito control 3.5.3.6 arginine deiminase pharmacology ADI has anti-cancer activity by causing depletion of L-arginine, fusion of ADI to 20 kDa PEG improves its pharmaceutical efficiency by increasing the half-life of the enzyme in serum, clinical studies, overview 3.5.3.6 arginine deiminase pharmacology ADI is a potential anti-angiogenic agent and is effective in the treatment of leukemia, ADI in clinical studies, overview 3.5.3.15 protein-arginine deiminase pharmacology PAD1 is a target in skin diseases including psoriasis 3.5.3.15 protein-arginine deiminase pharmacology PAD2 is a target for treatment of glaucoma and multiple sclerosis 3.5.3.15 protein-arginine deiminase pharmacology PAD3 is a target in skin diseases including psoriasis, PAD3-like protein is a target for treatment of certain cancers 3.5.3.15 protein-arginine deiminase pharmacology PAD4 inhibitors F-and Cl-amidine represent potential lead compounds for the treatment of rheumatoid arthritis because a growing body of evidence supports a role for PAD4 in the onset and progression of this chronic autoimmune disorder 3.5.4.1 cytosine deaminase pharmacology exogenous cytosine deaminase gene expression in Bifidobacterium breve I-53-8w for tumor-targeting enzyme/prodrug therapy, overview 3.5.4.1 cytosine deaminase pharmacology the recombinant fusion enzyme HSV-1TKglyCD might be useful in cancer gene therapy 3.5.4.1 cytosine deaminase pharmacology applicability of gene-directed enzyme prodrug therapy (GDEPT), prodrug encapsulation in liposomes, liposomal 5-fluorocytosine (5-FC) achieves high local concentration for suicide therapy 3.5.4.1 cytosine deaminase pharmacology applicability of gene-directed enzyme prodrug therapy using the capability of human adipose tissue-derived mesenchymal stem cells (AT-MSC) as cellular vehicles expressing cytosine deaminase, CDy-AT-MSC/5FC-system, analyzed in cell lines and xenografts 3.5.4.1 cytosine deaminase pharmacology applicability of gene-directed enzyme prodrug therapy, feasibility of using magnetic resonance spectroscopy and optical imaging to measure non-invasively expression and function of cytosine deaminase in a preclinical tumor model 3.5.4.1 cytosine deaminase pharmacology cancer chemotherapy, antibody-directed enzyme-prodrug therapy (GDEPT/ADEPT), biopanning assay 3.5.4.1 cytosine deaminase pharmacology negative selection system for actinobacteria based on cytosine deaminase 3.5.4.4 adenosine deaminase pharmacology Plasmodium falciparum-specific inhibitors of adenosine deaminase have potential for development as antimalarials without inhibition of host enzyme 3.5.4.12 dCMP deaminase pharmacology elevated level of dCMPase in transformed cells and tumors: enzyme may represent another important target for cancer chemotherapy 3.5.4.12 dCMP deaminase pharmacology might have applications in cancer chemotherapy. Enzyme may be an inhibitor target for antitumor agents 3.5.4.12 dCMP deaminase pharmacology enzyme might be a reasonable target for chemotherapeutic agents directed against parasitic as well as neoplastic diseases by limiting the synthesis of dUMP, particularly when used in combination with inhibitors of dTMP synthase or other purine and pyrimidine inhibitors of DNA synthesis 3.5.4.25 GTP cyclohydrolase II pharmacology enzyme is a potential drug target, since numerous pathogenic microorganims are absolutely dependent on endogenous synthesis of riboflavin, target for development of bactericidal inhibitors 3.6.1.5 apyrase pharmacology the enzyme may serve as a therapeutic agent for inhibition of platelet-mediated thrombosis 3.6.1.23 dUTP diphosphatase pharmacology the enzyme is a chemotherapeutic target 3.6.1.23 dUTP diphosphatase pharmacology the enzyme is a potential target for antiviral drug design 3.6.1.27 undecaprenyl-diphosphate phosphatase pharmacology the enzyme is an attractive drug target since it is not used by humans 3.6.2.1 adenylylsulfatase pharmacology biological sulfation process 3.6.4.B7 RadA recombinase pharmacology application potential of archaeal nanobiomotors in drug delivery 3.6.4.13 RNA helicase pharmacology conservation of the NTP-binding pocket among viruses of the family Flaviviridae as potential for development of therapeutics 3.6.4.13 RNA helicase pharmacology peptide inhibitors reproducing the structure of the autoregulatory motif as possibility to develop effective antivirals 3.6.5.2 small monomeric GTPase pharmacology the enzyme is a pharmacological target for the treatment of cardiovascular diseases 3.10.1.1 N-sulfoglucosamine sulfohydrolase pharmacology early treatment of CNS lesions by adeno-associated virus-mediated intraventricular injection of both SGSH and SUMF1 genes may represent a feasible therapy for MPS-IIIA 4.1.1.11 aspartate 1-decarboxylase pharmacology Mycobacterium tuberculosis is the etiological agent of tuberculosis and PanD is a potential drug target 4.1.1.15 glutamate decarboxylase pharmacology the enzyme is a potential important marker for the prediction and diagnosis of type 1 diabetes, and for the development of antigen-specific therapies for the treatment of type 1 diabetes 4.1.1.17 ornithine decarboxylase pharmacology the enzyme is a target in the combination therapy with 2-difluoromethylornithine and a polyamine transport inhibitor MQT 1426, i.e. D-Lys-spermine, against murine squamous cell carcinoma, overview 4.1.1.17 ornithine decarboxylase pharmacology the enzyme ODC is possibly useful in chemotherapy of human malignancies, such as skin cancer 4.1.1.17 ornithine decarboxylase pharmacology ODC is a target for chemoprevention of apoptosis 4.1.1.17 ornithine decarboxylase pharmacology pharmacological inhibition of ODC is a promising therapeutic paradigm for the treatment of visceral and perhaps other forms of leishmaniasis 4.1.1.23 orotidine-5'-phosphate decarboxylase pharmacology human UMP synthase enzyme may be a potential cancer drug target 4.1.1.25 tyrosine decarboxylase pharmacology biosynthesis of pharmaceutically important monoterpenoid indole alkaloids 4.1.1.28 aromatic-L-amino-acid decarboxylase pharmacology biosynthesis of pharmaceutically important monoterpenoid indole alkaloids 4.1.1.32 phosphoenolpyruvate carboxykinase (GTP) pharmacology development of a PEPCK inhibitor may lead to a new therapeutic strategy for the treatment of type II diabetes 4.1.1.32 phosphoenolpyruvate carboxykinase (GTP) pharmacology orally active compounds reversibly inhibiting PEPCK improve glucose homeostasis in type 2 diabetics 4.1.1.33 diphosphomevalonate decarboxylase pharmacology the enzyme is an antibiotic target, since inhibition prevents the production of isopentenyl diphosphate 4.1.1.50 adenosylmethionine decarboxylase pharmacology the enzyme is a target for cancer chemotherapy 4.1.1.50 adenosylmethionine decarboxylase pharmacology potentially important drug target for the chemotherapy of proliferative and parasitic diseases 4.1.1.50 adenosylmethionine decarboxylase pharmacology potentially important target for chemotherapy of filiarial infection 4.1.1.50 adenosylmethionine decarboxylase pharmacology potential target for therapeutic agents against various parasitic diseases and proliferating disorders 4.1.1.53 phenylalanine decarboxylase pharmacology side-effects of pharmacologically active decarboxylation products considered 4.1.2.9 phosphoketolase pharmacology polyketide natural products play an important role in the treatment of a wide range of human physiological disorders 4.1.2.10 (R)-mandelonitrile lyase pharmacology hydroxynitrile lyases are involved in the synthesis of enantiomerically pure cyanohydrins which are important intermediates in the production of pharmaceuticals and agrochemicals. The enzyme synthesizes (R)-mandelonitrile in both, batch reaction and fed-batch reaction and can be effectively used in the synthesis of (R)-mandelonitrile 4.1.2.10 (R)-mandelonitrile lyase pharmacology the enzyme has very high potential for synthesis of cyanohydrins and can be used for the production of enantiopure cyanohydrins. Cyanohydrins are important intermediates in the production of pharmaceuticals and agrochemicals 4.1.2.25 dihydroneopterin aldolase pharmacology the Fas multifunctional enzyme with the activity of the first three enzymes of the folate synthesis pathway: dihydroneopterin aldolase, hydroxymethyldihydropterin pyrophosphokinase and dihydropteroate synthase is an attractive target for chemotherapy, sin 4.1.2.42 D-threonine aldolase pharmacology efficient, environmentally friendly process for the production of (2R,3S)-2-amino-3-hydroxy-3-(pyridin-4-yl)-propanoic acid by a recombinant D-threonine aldolase catalyzed aldol addition of glycine and pyridine 4-carboxaldehyde. (2R,3S)-2-amino-3-hydroxy-3-(pyridin-4-yl)-propanoic acid, is a key intermediate in the synthesis of the (2R,3S)-2-amino-3-hydroxy-3-(pyridin-4-yl)-1-(pyrrolidin-1-yl)propan-1-one, a developmental drug candidate. The aldol addition product directly crystallizes out from the reaction mixture in high purity and high diastereo- and enantioselectivity, contributing to high yield and allowing easy isolation, processing, and downstream utilization 4.1.2.42 D-threonine aldolase pharmacology the enzyme has a considerable potential in biocatalysis for the stereospecific synthesis of various beta-hydroxy amino acids, which are valuable building blocks for the production of pharmaceuticals 4.1.2.47 (S)-hydroxynitrile lyase pharmacology enantiomerically pure cyanohydrins produced by enzyme-catalyzed synthesis are important synthetic intermediates for pharmaceuticals 4.1.2.48 low-specificity L-threonine aldolase pharmacology biotechnological potential for the syntheses of pharmaceutically relevant drug molecules because of the stereospecificity 4.2.1.1 carbonic anhydrase pharmacology extensively investigated enzyme as a target for drug design 4.2.1.46 dTDP-glucose 4,6-dehydratase pharmacology the enzyme is essential to mycobacterial growth and is not found in humans, therefore, it is a potential target for developing new anti-tuberculosis drugs 4.2.1.50 pyrazolylalanine synthase pharmacology production of beta-(pyrazol-1-yl)-L-alanine for pharmacological use by enzyme overexpressed in E. coli 4.2.1.84 nitrile hydratase pharmacology synthesis, biotransformation and biocatalysis of unsaturated/saturated aliphatic, aromatic and heterocyclic nitriles 4.2.2.1 hyaluronate lyase pharmacology enzyme is a target for inhibitor design 4.2.2.1 hyaluronate lyase pharmacology enzyme can be used for production of pharmaceuticals as an alternative to bovine testicular hyaluronidase, BTH, because the production of BTH is stopped due to risk of BSE 4.2.2.1 hyaluronate lyase pharmacology enzyme is a target for development of antimicrobial agents 4.2.2.1 hyaluronate lyase pharmacology the enzyme is a target for structure-based design of selective inhibitors as drugs in bacterial infection therapy 4.2.2.1 hyaluronate lyase pharmacology in vitro microbial hyaluronate lyase is able to split the hyaluronic acid in atherosclerotic plaques under release of calcium deposits and reduces in vivo the development of atherosclerotic lesions in hyperlipidaemic rabbits 4.2.3.24 amorpha-4,11-diene synthase pharmacology amorpha-4,11-diene is a precursor of artemisinin, an important agent in the treatment of malaria, produced via oxidation 4.2.99.18 DNA-(apurinic or apyrimidinic site) lyase pharmacology the enzyme is a potential target in cancer treatment 4.3.1.18 D-Serine ammonia-lyase pharmacology the D-serine dehydratase gene is an excellent marker, especially in the construction of strains for which the use of antibiotic resistance genes as selective markers is not allowed 4.3.1.18 D-Serine ammonia-lyase pharmacology decrease in D-serine content may provide a therapeutic strategy for the treatment of the neurological disorders in which overstimulation of N-methyl-D-aspartate receptors plays a pathological role. D-Serine dehydratase (Dsd1p), which acts dominantly on D-serine, may be a useful D-serine reducing agent. A linear 5-kDa polyethylene glycol (PEG) is conjugated to Dsd1p and the effects of PEG-conjugation on its biochemical and pharmacokinetic properties are examined. PEG-Dsd1p retains activity, specificity, and stability of the enzyme. The PEG modification extended the serum half-life of Dsd1p in mice 6fold, from 3.8 h to 22.4 h. PEG-Dsd1p is much less immunogenic compared to the unmodified enzyme. Intraperitoneal administration of PEG-Dsd1p is effective in decreasing the D-serine content in the mouse hippocampus 4.3.1.24 phenylalanine ammonia-lyase pharmacology the ability of PAL to catalyze the conversion of L-Phe into nontoxic compounds in the absence of additional cofactors leads to its use as a therapeutic agent for the treatment of phenylketonuria 4.3.1.24 phenylalanine ammonia-lyase pharmacology enzyme substitution therapy for the treatment of phenylketonuria 4.3.1.24 phenylalanine ammonia-lyase pharmacology enzyme substitution therapy with the phenylalanine ammonia lyase is a new approach to the treatment of patients with phenylketonuria 4.3.1.24 phenylalanine ammonia-lyase pharmacology the enzyme can reduce the level of L-Phe in the blood and is a prospective drug for the treatment of phenylketonuria 4.3.1.24 phenylalanine ammonia-lyase pharmacology the enzyme is specifically advantageous for the production of the hypertension drug 2-chloro-L-phenylalanine 4.3.1.24 phenylalanine ammonia-lyase pharmacology the shift of the pH-optimum from pH 8.5 for the wild-type enzyme to pH 7.5 with 30% higher specific activity than that of the wild-type enzyme, the prolonged half-life of the mutant enzyme at 70°C, the higher resistance to a low pH of 3.5 and protease make the mutant enzyme E75L a candidate for oral medicine of phenylketonuria 4.3.1.25 phenylalanine/tyrosine ammonia-lyase pharmacology enzyme substitution therapy for the treatment of phenylketonuria 4.3.1.25 phenylalanine/tyrosine ammonia-lyase pharmacology the enzyme is a useful biocatalyst for removal of L-phenylalanine from protein hydrolysates, which can be evaluated as potential ingredients in foodstuffs for phenylketonuria patients. The enzyme is also capable to catalyze the deamination of L-tyrosine to p-coumaric acid but at a substantially low reaction rate. Therefore, the final content of L-Tyr in samples treated with L-phenylalanine ammonia-lyase should be analyzed in each case and taken in consideration to avoid its deficiency in phenylketonuria patients 4.3.2.1 argininosuccinate lyase pharmacology argininosuccinate lyase (ASL) is overexpressed in breast cancer and downregulation of argininosuccinate lyase decreases tumor growth by inhibiting cyclin A2 and NO. Administration of ASL shRNA may be a treatment to prevent cancer cell proliferation and induce cancer cell death 4.3.2.10 imidazole glycerol-phosphate synthase pharmacology development of allosteric antibiotics, herbicides, and antifungal compounds because the enzyme is absent in mammals but provides an entry point to fundamental biosynthetic pathways in plants, fungi, and bacteria 4.3.2.10 imidazole glycerol-phosphate synthase pharmacology the enzyme is a potential therapeutic target absent in mammals but present in bacteria, plants, and fungi. Many plant and human pathogens that infect the immunocompromised patient have an IGPS that is highly homologous to the Saccharomyces cerevisiae and Thermotoga maritima enzymes 4.3.3.2 strictosidine synthase pharmacology cooverexpression of geraniol-10-hydroxylase and strictosidine synthase improves anti-cancer drug camptothecin accumulation in Ophiorrhiza pumila 4.3.3.7 4-hydroxy-tetrahydrodipicolinate synthase pharmacology enzyme structure analysis for design of novel therapeutics against bacterial pathogen 4.3.3.7 4-hydroxy-tetrahydrodipicolinate synthase pharmacology enzyme structure guides design of novel therapeutics 4.3.3.7 4-hydroxy-tetrahydrodipicolinate synthase pharmacology structure of the enzyme guides the design of novel therapeutics against the methicillin-resistant pathogen 4.3.3.7 4-hydroxy-tetrahydrodipicolinate synthase pharmacology the enzyme is a promising antibiotic target 4.3.3.7 4-hydroxy-tetrahydrodipicolinate synthase pharmacology the enzyme is a target for antibiotics 4.3.3.7 4-hydroxy-tetrahydrodipicolinate synthase pharmacology the enzyme is an anti-cholera target 4.4.1.4 alliin lyase pharmacology allicin contributes to the prevention of stroke and arteriosclerosis. An acid resistant capsule is filled with pellets of alliin and alliinase. In the intestine, alliin and alliinase are dissolved and alicin is liberated 4.4.1.4 alliin lyase pharmacology a triggered antimicrobial system based on different sulfoxide substrates and alliinase might be superior to the application of conventional fungicides or allicin itself 4.6.1.1 adenylate cyclase pharmacology activation of cardiac adenylyl cyclase isozyme ACVI expression increases the function of the failing ischemic heart in mice, overview. Increased left ventricular ACVI content also markedly reduces mortality and increases left ventricular function after acute myocardial infarction in mice 4.6.1.1 adenylate cyclase pharmacology pharmacological approaches do not allow cell specific manipulation of cyclic nucleotides in tissue and lack precision in space and time, limitations that can be overcome using the light-activated enzyme 4.6.1.2 guanylate cyclase pharmacology activators of sGC may be beneficial in the treatment of a range of diseases including systemic and pulmonary hypertension, heart failure, atherosclerosis, peripheral arterial occlusive disease, thrombosis and renal fibrosis, overview 4.6.1.2 guanylate cyclase pharmacology alternative splicing can regulate endogenous ANP/GC-A signaling, thus, angiotensin II-induced alternative splicing of GC-A may represent a mechanism for reducing the sensitivity to atrial natriuretic peptide 4.6.1.2 guanylate cyclase pharmacology sGC is a target for therapeutic intervention in pulmonary arterial hypertension 4.6.1.2 guanylate cyclase pharmacology pharmacological approaches do not allow cell specific manipulation of cyclic nucleotides in tissue and lack precision in space and time, limitations that can be overcome using the light-activated enzyme 4.6.1.18 pancreatic ribonuclease pharmacology radical-scavenging effects of the ribonuclease inhibitor CPRI may contribute to its function in the cell protection from peroxidative injuries unrelated to inhibition of RNases 4.6.1.18 pancreatic ribonuclease pharmacology inhibitors can be the starting point for the development of compounds that can be used as pharmaceuticals against pathologies associated with ribonuclease A homologues such as human angiogenin, which is implicated in tumor induced neovascularization 4.6.1.18 pancreatic ribonuclease pharmacology human antibody-pancreatic ribonuclease fusion proteins, referred to as immunoRNases, are proposed as an alternative to heterologous immunotoxins, without their immunogenicity and unspecific toxicity issue. But human pancreatic RNase and variants do not prove to be generally suitable as effector component for a therapeutic antibody drug development platform, overview 4.6.1.18 pancreatic ribonuclease pharmacology a recombinant ribonuclease-resistant dimeric variant of human pancreatic ribonuclease is generated which is specifically toxic to cancer cells. Combining dimerization of pancreatic ribonuclease-inhibitor-resistance results in providing potent anti-tumor activity to human pancreatic ribonuclease. The cytotoxic variants of human pancreatic ribonuclease will be useful in designing protein therapeutics with low immunogenicity 5.1.1.1 alanine racemase pharmacology potential candidate for the development of a recombinant vaccine 5.1.1.1 alanine racemase pharmacology Alr of Mycobacterium tuberculosis is a valid drug target and inhibition of Alr alone results in loss of viability in vitro and in vivo 5.1.1.16 protein-serine epimerase pharmacology the enzyme is a candidate for the development of diagnostic tools or therapeutic strategies against the multidrug resistant pathogen related to serious infections mainly affecting immunocompromised individuals 5.1.1.18 serine racemase pharmacology because D-serine affects NMDAR signaling throughout the brain, serine racemase is a promising target for the treatment of disorders related to NMDAR dysfunction 5.1.3.11 cellobiose epimerase pharmacology synthesis of lactulose, which is used as a pharmaceutical against various illnesses, such as chronic constipation 5.1.99.4 alpha-methylacyl-CoA racemase pharmacology the enzyme is partially validated as a potential therapeutic target by siRNA knockdown of the AMACR gene, overview 5.2.1.8 peptidylprolyl isomerase pharmacology Pin1 is a potential therapeutic target in Rel/NF-kappaB-dependent leukemia/lymphomas 5.2.1.8 peptidylprolyl isomerase pharmacology Pin1 is a therapeutic target for reducing aberrant phosphorylation of NF proteins in neurodegenerative disorders such as Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis 5.3.1.8 mannose-6-phosphate isomerase pharmacology absence of mannose-6-phosphate isomerase causes cell lysis and thus the enzyme is a potential target for inhibition and may be a route to antifungal drugs 5.3.1.8 mannose-6-phosphate isomerase pharmacology the enzyme may be a target for anti-Leishmania drug development 5.3.4.1 protein disulfide-isomerase pharmacology protein disulfide isomerase is a potential therapeutic target in amyotrophic lateral sclerosis and (+-)-trans-1,2-bis(mercaptoacetamido)cyclohexane and other molecular mimics of protein disulfide isomerase could be of benefit in amyotrophic lateral sclerosis and other neurodegenerative diseases related to protein misfolding 5.3.99.5 thromboxane-A synthase pharmacology development of a screening assay for the in vitro evaluation of thromboxane A2 synthase inhibitors. Inhibitors of thromboxane synthase are regarded as potentially useful agents in the treatment of cardiovascular diseases and in the prevention of tumor cell metastases 5.3.99.5 thromboxane-A synthase pharmacology the thromboxane A2 synthetase inhibitor 1-[3-(4-benzylhydryl-1-piperazinyl)propyl]-3-(1H-imidazol-1-ylmethyl)-1H-indole-6-carboxylic acid is a candidate anti-asthmatic drug 5.5.1.4 inositol-3-phosphate synthase pharmacology the enzyme is a target for mood stabilizing drugs, and anti-bipolar drugs 5.6.1.3 plus-end-directed kinesin ATPase pharmacology a bias that favors motion toward the minus-end of microtubules might be used to tune transport in healthy cells when properly regulated but contribute to a disease state when misregulated 5.6.1.3 plus-end-directed kinesin ATPase pharmacology a bias that favors motion toward the minus-end of microtubules, cf. EC 3.6.4.5, might be used to tune transport in healthy cells when properly regulated but contribute to a disease state when misregulated 5.6.2.1 DNA topoisomerase pharmacology important cellular target in the treatment of human cancer 5.6.2.1 DNA topoisomerase pharmacology target of a novel class of anticancer drugs the camptothecins 5.6.2.1 DNA topoisomerase pharmacology The structure of the variola topoisomerase IB–DNA cleavage complex, together with the unique biochemical features of the enzyme, provides a starting point for the rational design of antismallpox therapeutics 5.6.2.1 DNA topoisomerase pharmacology Topo I targets for design of antitumor agents 5.6.2.1 DNA topoisomerase pharmacology topoisomerase I is the target for camptothecin-based anticancer drugs that act by increasing levels of topoisomerase I-mediated DNA scission 5.6.2.2 DNA topoisomerase (ATP-hydrolysing) pharmacology important cellular target in the treatment of human cancers 5.6.2.2 DNA topoisomerase (ATP-hydrolysing) pharmacology antitumor effect of inhibitors 5.6.2.2 DNA topoisomerase (ATP-hydrolysing) pharmacology combining topoisomerase II targeting anticancer drug therapy with E1A vector gene therapy might increase the tumor cell sensitivity and thus the therapeutic benefit 5.6.2.2 DNA topoisomerase (ATP-hydrolysing) pharmacology the enzyme induces antitumor activity of alkylating reagent psorospermin and analogues rendering them utilizable for cancer therapy 5.6.2.2 DNA topoisomerase (ATP-hydrolysing) pharmacology the enzyme is a target for anticancer drug development 5.6.2.2 DNA topoisomerase (ATP-hydrolysing) pharmacology the enzyme is a target of numerous anti-tumor drugs 5.6.2.2 DNA topoisomerase (ATP-hydrolysing) pharmacology the enzyme is a therapeutic target for the anti-tumor drug prodigiosin 5.6.2.2 DNA topoisomerase (ATP-hydrolysing) pharmacology Topo II are attractive targets for design of antitumor agents 5.6.2.2 DNA topoisomerase (ATP-hydrolysing) pharmacology Topo II have been attractive targets for design of antitumor agents 6.1.1.1 tyrosine-tRNA ligase pharmacology design of antimicrobial agents against Staphylococcus aureus, largely responsible for hospital-acquired infections, on the basis of knowledge of the crystal structure and the revealed catalytic mechanism 6.1.1.1 tyrosine-tRNA ligase pharmacology design of antimicrobials that target the bacterial enzyme of Bacillus stearothermophilus making use of the differences between the actives sites of the 2 enzymes 6.1.1.6 lysine-tRNA ligase pharmacology Plasmodium falciparum lysyl-tRNA synthetase (PfKRS) as the cellular target for cladosporin activity. Targeting parasitic aminoacyl-tRNA synthetases (aaRSs) can provide an additional component in the present multi-drug cocktail therapy against malaria 6.1.1.10 methionine-tRNA ligase pharmacology the enzyme is an important antibiotic target 6.1.1.12 aspartate-tRNA ligase pharmacology the enzyme is the target of peptide nucleotide antibiotic Microcin C 6.1.1.15 proline-tRNA ligase pharmacology enzyme is a target for design of antibiotics targeting the editing active site since eukaryotic enzyme types are not able to edit misactivated alanine on tRNAPro 6.3.1.2 glutamine synthetase pharmacology since glutamine synthetase is the first metabolic enzyme involved in Trypanosoma cruzi evasion from the parasitophorous vacuole it is a potential target for designing anti-Trypanosoma cruzi drugs 6.3.1.5 NAD+ synthase pharmacology preparation of isotopically labelled [13N]NAD+, a radiopharmaceutical designed for positron emission tomography, by the NAD+ synthetase immobilized on porous glass beads 6.3.1.5 NAD+ synthase pharmacology NadE is a antimycobacterial drug target 6.3.1.8 glutathionylspermidine synthase pharmacology the enzyme would serve as a potential target for antiparasitic chemotherapy 6.3.1.9 trypanothione synthase pharmacology the enzyme would serve as a potential target for antiparasitic chemotherapy 6.3.1.13 L-cysteine:1D-myo-inositol 2-amino-2-deoxy-alpha-D-glucopyranoside ligase pharmacology enzyme is a traget for drug development against actinomycetes 6.3.2.2 glutamate-cysteine ligase pharmacology the enzyme is a potential drug target 6.3.2.2 glutamate-cysteine ligase pharmacology co-treatment by indomethacin and doxorubicin increases the cytotoxicitiy of doxorubicin by decreasing the intracellular contents of glutathione and its conjugates with decreasing expression of gamma-glutamylcysteine synthetase. Indomethacin inhibits the gamma-glutamylcysteine synthetase promoter activity. 6.3.2.2 glutamate-cysteine ligase pharmacology rat model of glutathione depletion using an adenovirus vector with short hairpin RNA against gamma-glutamylcysteine synthetase heavy chain subunit. In the acute 6 or 24 h or subacute 7 days toxicity tests, rats were administered the drugs once or once a day for a week, respectively. Plasma biochemical markers for hepatotoxicity were measured. The 6 and 24 h toxicity test of diclofenac, and the 24 h and 7 days toxicity tests of flutamide show significant serum alanine aminotransferase elevations. The 24 h toxicity test of flutamide shows a slight bilirubin elevation, and histological hepatotoxicity. The 7 days toxicity test of flutamide also demonstrates histological hepatotoxicity 6.3.2.2 glutamate-cysteine ligase pharmacology three days infection of GCSh-shRNA and CYP3A4 simultaneously with H4IIE cells decreases the intracellular GSH level by 50-60% without affecting the expression level of CYP3A4. Using this cell-based system sensitive to the cytotoxicity of reactive metabolites, drugs known for their hepatotoxicity are evaluated. Troglitazone, flutamide, and acetaminophen cause significant decreases of cell viability in CYP3A4/GCSh-shRNA group compared to the other groups such as GFP, CYP3A4, GFP/GCSh-shRNA, indicating that reactive metabolites produced by CYP3A4 and subsequently conjugated by GSH are involved in the cytotoxicity 6.3.2.10 UDP-N-acetylmuramoyl-tripeptide-D-alanyl-D-alanine ligase pharmacology attractive target for development of antibacterial agents 6.3.2.17 tetrahydrofolate synthase pharmacology polymorphism of FPGS rs1544105 might be used as an effective approach for prediction of the treatment out­come of methotrexate (MTX) 6.3.2.49 L-alanine-L-anticapsin ligase pharmacology potential application in industrial protein engineering for the environmentally friendly biological production of useful peptide compounds, such as physiologically active peptides, artificial sweeteners and antibiotics 6.3.3.2 5-formyltetrahydrofolate cyclo-ligase pharmacology the enzyme could be a potentially important enzyme as a target in chemotherapy 6.3.4.3 formate-tetrahydrofolate ligase pharmacology the enzyme might be a target for colorectal cancer therapy 6.3.5.6 asparaginyl-tRNA synthase (glutamine-hydrolysing) pharmacology enzyme may have potential as a species-specific therapeutic drug target 6.4.1.2 acetyl-CoA carboxylase pharmacology pharmacological inhibition of the ACC system is of potential use for treatment of key components of the metabolic syndrome, plasma and hepatic metabolic parameters after fasting and after the hyperinsulinaemic euglycaemic clamp, overview 7.2.2.3 P-type Na+ transporter pharmacology lower concentration of [(dihydroindenyl)oxy]acetic acid should be used for evaluation of the activity of K+-Cl- cotranporter without affecting the activities of coexisting Na+,K+-ATPase and H+,K+-ATPase in cells 7.2.2.10 P-type Ca2+ transporter pharmacology lower concentration of [(dihydroindenyl)oxy]acetic acid should be used for evaluation of the activity of K+-Cl- cotranporter without affecting the activities of coexisting Na+,K+-ATPase and H+,K+-ATPase in cells 7.2.2.16 ABC-type ferric hydroxamate transporter pharmacology analysis of uptake of the antibiotic albomycin into cells of Streptococcus pneumoniae 7.2.2.19 H+/K+-exchanging ATPase pharmacology lower concentration of [(dihydroindenyl)oxy]acetic acid should be used for evaluation of the activity of K+-Cl- cotranporter without affecting the activities of coexisting Na+,K+-ATPase and H+,K+-ATPase in cells 7.4.2.8 protein-secreting ATPase pharmacology the enzyme is a chemotherapeutic target for small-molecule ATPase inhibitors 7.6.2.2 ABC-type xenobiotic transporter pharmacology Cdr1p is a critical factor in the design of therapeutic strategies to combat antifungal resistance 7.6.2.2 ABC-type xenobiotic transporter pharmacology the investigation of the substrate interactions and modulation of multidrug transporters may pave the way for predictive toxicology and pharmacogenomics