2.1.1.45 (+)tetrahydropteroylglutamate - 109828 2.1.1.45 (2S)-2-[(4-([(2,4-diaminopteridin-6-yl)methyl](methyl)amino)phenyl)formamido]pentanedioic acid i.e, methotrexate, A DHFR inhibitor, binds at the DHFR active site 220748 2.1.1.45 (2S)-2-[([4-[(2-amino-6-methyl-4-oxo-4,7-dihydro-3H-pyrrolo[2,3-d]pyrimidin-5-yl)sulfanyl]phenyl]carbonyl)amino]pentanedioic acid dual inhibitor of thymidylate synthase and dihydrofolate reductase. Comparison with inhibitory effect on human and Toxoplasma gondii enzyme 25616 2.1.1.45 (2S)-2-[([4-[(2-amino-6-methyl-4-oxo-4,7-dihydro-3H-pyrrolo[2,3-d]pyrimidin-5-yl)sulfanyl]phenyl]carbonyl)amino]pentanedioic acid dual inhibitor of thymidylate synthase and dihydrofolate reductase. Comparison with inhibitory effect on Escherichia coli and Toxoplasma gondii enzyme 25616 2.1.1.45 (6R)-tetrahydropteroylglutamate - 109860 2.1.1.45 (S)-2-(5(((1,2-dihydro-3-methyl-1-oxobenzo(f)quinazolin-9-yl)methyl)amino)1-oxo-2-isoindolinyl)glutaric acid BW1843U89, U89, distorts the thymidylate synthase active site 146719 2.1.1.45 (S)-2-(5(((1,2-dihydro-3-methyl-1-oxobenzo[f]quinazolin-9 yl)methyl)amino)1-oxo-2-isoindolinyl)glutaric acid - 39750 2.1.1.45 (S)-2-(5(((1,2-dihydro-3-methyl-1-oxobenzo[f]quinazolin-9-yl)methyl)amino)1-oxo-2-isoindolinyl)glutaric acid - 155280 2.1.1.45 (S)-2-(5-(((1,2-dihydro3-methyl-1-oxobenzo[f]quinazolin-9-yl)methyl)amino)-1-oxo-2-isoindolinyl)glutaric acid BW1843U89 109880 2.1.1.45 1,1-bis-(4-hydroxyphenyl)-1H-naphtho[1,2-c]furan-3-one - 668 2.1.1.45 1,3-propanediphosphonic acid allosteric inhibitor of human thymidylate synthase; stabilizes an inactive conformer of loop 181-197. Mixed inhibitor of dUMP, uncompetitive inhibitor versus methylenetetrahydrofolate below 0.00025 mM, noncompetitive above 0.001 mM, respectively. 1,3-Propanediphosphonic acid shows positive cooperativity with antifolate inhibitor ZD9331. It leads to the formation of enzyme tetramers, but not of higher oligomers 38144 2.1.1.45 1-(2'-deoxyribosyl)8-azapurin-2-one 5'-monophosphate - 109959 2.1.1.45 1-(5-cyano-1,6-dihydro-6-oxo-4-p-tolylpyrimidin-2-yl)-4-phenylthiosemicarbazide - 243479 2.1.1.45 1-(beta-D-2'-deoxyribofuranosyl)1,6-dihydro-8-azapurin-2(3H,6H)-one 5'-monophosphate - 109961 2.1.1.45 1-(beta-D-2'-Deoxyribofuranosyl)8-azapurin-2-one 5'-monophosphate - 90457 2.1.1.45 1-(beta-D-2-deoxyribofuranosyl)-4-hydroxyamino-5-bromopyrimidin-2(1H)-one 5'-monophosphate - 32773 2.1.1.45 1-(beta-D-2-deoxyribofuranosyl)-4-hydroxyamino-5-chloropyrimidin-2(1H)-one 5'-monophosphate - 32774 2.1.1.45 1-(beta-D-2-deoxyribofuranosyl)-4-hydroxyamino-5-fluoropyrimidin-2(1H)-one 5'-monophosphate - 32775 2.1.1.45 1-(beta-D-2-deoxyribofuranosyl)-4-hydroxyamino-5-hydroxymethylpyrimidin-2(1H)-one 5'-monophosphate - 32776 2.1.1.45 1-(beta-D-2-deoxyribofuranosyl)-4-hydroxyamino-5-iodopyrimidin-2(1H)-one 5'-monophosphate - 32777 2.1.1.45 1-(beta-D-2-deoxyribofuranosyl)-4-hydroxyaminopyrimidin-2(1H)-one 5'-monophosphate - 32778 2.1.1.45 1-ethyl-3-dimethylaminopropyl carbodiimide - 109998 2.1.1.45 1-phenyl-3-(3-dimethylaminopropyl) carbodiimide - 109742 2.1.1.45 1-phenyl-3-(3-trimethylaminopropyl) carbodiimide - 109743 2.1.1.45 10-formyl folic acid - 109744 2.1.1.45 10-formyl-5,8-dideazafolate - 1847 2.1.1.45 10-formyl-7,8 dihydrofolate-tetra-gamma-L-glutamate - 110034 2.1.1.45 10-formyldihydropteroylglutamate - 50458 2.1.1.45 10-formyldihydropteroylheptaglutamate - 50459 2.1.1.45 10-formyldihydropteroylpentaglutamate - 50460 2.1.1.45 10-formyltetrahydrofolate - 536 2.1.1.45 10-Formyltetrahydrofolylheptaglutamate - 45049 2.1.1.45 10-Formyltetrahydrofolylmonoglutamate - 45050 2.1.1.45 10-formyltetrahydropteroylheptaglutamate - 110033 2.1.1.45 10-formyltetrahydropteroylmonoglutamate - 50462 2.1.1.45 10-formyltetrahydropteroylpolyglutamate - 49653 2.1.1.45 10-methylfolate - 169699 2.1.1.45 10-propargyl-5,8-dideazafolate - 3137 2.1.1.45 10-propargyl-5,8-dideazafolate PDDF 3137 2.1.1.45 10-propargyl-5,8-dideazafolate PDDF, folate-like TS inhibitor 3137 2.1.1.45 10-propargyl-5,8-dideazafolate i.e. PDDF. Dual inhibitor of thymidylate synthase and dihydrofolate reductase. Comparison with inhibitory effect on human and Toxoplasma gondii enzyme 3137 2.1.1.45 10-propargyl-5,8-dideazafolate i.e. PDDF. Dual inhibitor of thymidylate synthase and dihydrofolate reductase. Comparison with inhibitory effect on Escherichia coli and Toxoplasma gondii enzyme 3137 2.1.1.45 10-propargyl-5,8-dideazafolate i.e. PDDF. Dual inhibitor of thymidylate synthase and dihydrofolate reductase. Comparison with inhibitory effect on human and Escherichia coli enzyme 3137 2.1.1.45 1843U89 i.e. (2R)-2-(5-[[(1-hydroxy-3-methyl-5,10a-dihydrobenzo[f]quinazolin-9-yl)methyl]amino]-1-oxo-1,3-dihydro-2H-isoindol-2-yl)butanedioic acid, folate-based inhibitor 38048 2.1.1.45 2',5-difluoro-ara-UMP slow-binding (time-dependent) inhibitor 77200 2.1.1.45 2'-deoxy-2',2'-difluorouridine 5'-dihydrogen classic inhibitor (no time dependence of inhibition observed) 77199 2.1.1.45 2'-deoxy-5-fluorouridine 5'-phosphate - 155281 2.1.1.45 2'-deoxyuridine - 1705 2.1.1.45 2'-fluoro-ara-UMP classic inhibitor (no time dependence of inhibition observed) 77198 2.1.1.45 2,4-diamino pteridine - 50346 2.1.1.45 2,4-diamino quinazoline antifolate - 50476 2.1.1.45 2,4-dioxo-N-(2-(1-(m-tolyl)-1H-1,2,3-triazol-4-yl)phenyl)-1, 2, 3, 4-tetrahydropyrimidine-5-sulfonamide - 243551 2.1.1.45 2-(2-(4-((2-amino-4-oxo-4,7-dihydro-3H-pyrrolo[2,3-d]pyrimidin-5-yl)methyl)benzamido)-4-cyanophenyl)acetic acid - 243559 2.1.1.45 2-(2-(4-((2-amino-4-oxo-4,7-dihydro-3H-pyrrolo[2,3-d]pyrimidin-5-yl)methyl)benzamido)-4-methoxyphenyl)acetic acid - 243560 2.1.1.45 2-(2-(4-((2-amino-4-oxo-4,7-dihydro-3H-pyrrolo[2,3-d]pyrimidin-5-yl)methyl)benzamido)phenyl) acetic acid - 243561 2.1.1.45 2-(2-(4-hydroxybenzylidene)hydrazinyl)-6-oxo-4-(p-tolyl)-1,6-dihydropyrimidine-5-carbonitrile - 243562 2.1.1.45 2-(4-((2-amino-4-oxo-4,7-dihydro-3H-pyrrolo[2,3-d]pyrimidin-5-yl)methyl)benzamido) terephthalic acid - 243567 2.1.1.45 2-(4-((2-amino-4-oxo-4,7-dihydro-3H-pyrrolo[2,3-d]pyrimidin-5-yl)methyl)benzamido)-4-chloro benzoic acid - 243568 2.1.1.45 2-(4-((2-amino-4-oxo-4,7-dihydro-3H-pyrrolo[2,3-d]pyrimidin-5-yl)methyl)benzamido)-4-cyanobenzoic acid - 243569 2.1.1.45 2-(4-hydroxy[1,1'-biphenyl]-3-yl)-4-methyl-1H-isoindole-1,3(2H)-dione - 243572 2.1.1.45 2-amino-4-hydroxyquinazoline - 110107 2.1.1.45 2-amino-4-hydroxyquinazoline folic acid - 21925 2.1.1.45 2-amino-4-oxo-4,7-dihydro-pyrrolo[2,3-d]pyrimidine-methyl-phenyl-L-glutamic acid inhibitor of Cryptosporidium hominis thymidylate synthase with 5fold selectivity over the human enzyme. Compound also has anti-cryptosporidial activity in cell culture and inhibits dihydrofolate reductase enzyme activity with IC50 values of 0.049 microM 206210 2.1.1.45 2-amino-4-oxo-4,7-dihydro-pyrrolo[2,3-d]pyrimidine-methyl-phenyl-L-glutamic acid potent enzyme inhibitor with anti-cryptosporidial activity in cell culture, chemical synthesis, overview. The inhibitor forms several hydrogen bonds and van der Waals interactions with the DHFR active site residues, binding close to the nicotinamide ring of NADPH. The carbonyl oxygens of the catalytic D32 hydrogen bond with N3 of the inhibitor forming a fork that holds the inhibitor in optimal position bound to the enzyme 206210 2.1.1.45 2-amino-5-[(2,5-dimethoxyphenyl)sulfanyl]-6-ethylthieno[2,3-d]pyrimidin-4(3H)-one - 14850 2.1.1.45 2-amino-5-[(2-chlorophenyl)sulfanyl]-6-ethylthieno[2,3-d]pyrimidin-4(3H)-one - 14859 2.1.1.45 2-amino-5-[(3,4-dichlorophenyl)sulfanyl]-6-methylthieno[2,3-d]pyrimidin-4(3H)-one dual inhibitor of thymidylate synthase and dihydrofolate reductase. Comparison with inhibitory effect on human and Toxoplasma gondii enzyme 6311 2.1.1.45 2-amino-5-[(3,4-dichlorophenyl)sulfanyl]-6-methylthieno[2,3-d]pyrimidin-4(3H)-one dual inhibitor of thymidylate synthase and dihydrofolate reductase. Comparison with inhibitory effect on Escherichia coli and Toxoplasma gondii enzyme 6311 2.1.1.45 2-amino-5-[(3,4-dichlorophenyl)sulfanyl]-6-methylthieno[2,3-d]pyrimidin-4(3H)-one dual inhibitor of thymidylate synthase and dihydrofolate reductase. Comparison with inhibitory effect on human and Escherichia coli enzyme 6311 2.1.1.45 2-amino-5-[(3,4-dichlorophenyl)thio]-6-ethylthieno[2,3-d]pyrimidin-4(3H)-one - 14851 2.1.1.45 2-amino-5-[(3,5-dichlorophenyl)sulfanyl]-6-ethylthieno[2,3-d]-pyrimidin-4(3H)-one - 14852 2.1.1.45 2-amino-5-[(3,5-dimethoxyphenyl)sulfanyl]-6-ethylthieno[2,3-d]pyrimidin-4(3H)-one - 14858 2.1.1.45 2-amino-5-[(3-chlorophenyl)sulfanyl]-6-ethylthieno[2,3-d]pyrimidin-4(3H)-one - 14857 2.1.1.45 2-amino-5-[(4-bromophenyl)sulfanyl]-6-ethylthieno[2,3-d]pyrimidin-4(3H)-one - 14856 2.1.1.45 2-amino-5-[(4-chlorophenyl)sulfanyl]-6-ethylthieno[2,3-d]pyrimidin-4(3H)-one - 6360 2.1.1.45 2-amino-6-ethyl-5-(2-naphthylthio)thieno[2,3-d]pyrimidin-4(3H)-one - 14853 2.1.1.45 2-amino-6-ethyl-5-(phenylsulfanyl)thieno[2,3-d]pyrimidin-4(3H)-one - 6359 2.1.1.45 2-amino-6-ethyl-5-(pyridin-4-ylsulfanyl)thieno[2,3-d]pyrimidin-4(3H)-one - 14854 2.1.1.45 2-amino-6-ethyl-5-[(4-fluorophenyl)sulfanyl]thieno[2,3-d]pyrimidin-4(3H)-one - 14855 2.1.1.45 2-amino-6-ethyl-5-[(4-nitrophenyl)sulfanyl]thieno[2,3-d]pyrimidin-4(3H)-one - 6361 2.1.1.45 2-amino-6-methyl-5-(2-naphthylsulfanyl)thieno[2,3-d]pyrimidin-4(3H)-one dual inhibitor of thymidylate synthase and dihydrofolate reductase. Comparison with inhibitory effect on human and Toxoplasma gondii enzyme 6312 2.1.1.45 2-amino-6-methyl-5-(2-naphthylsulfanyl)thieno[2,3-d]pyrimidin-4(3H)-one dual inhibitor of thymidylate synthase and dihydrofolate reductase. Comparison with inhibitory effect on Escherichia coli and Toxoplasma gondii enzyme 6312 2.1.1.45 2-amino-6-methyl-5-(2-naphthylsulfanyl)thieno[2,3-d]pyrimidin-4(3H)-one dual inhibitor of thymidylate synthase and dihydrofolate reductase. Comparison with inhibitory effect on human and Escherichia coli enzyme 6312 2.1.1.45 2-amino-6-methyl-5-[(4-nitrophenyl)sulfanyl]thieno[2,3-d]pyrimidin-4(3H)-one dual inhibitor of thymidylate synthase and dihydrofolate reductase. Comparison with inhibitory effect on human and Toxoplasma gondii enzyme 6313 2.1.1.45 2-amino-6-methyl-5-[(4-nitrophenyl)sulfanyl]thieno[2,3-d]pyrimidin-4(3H)-one dual inhibitor of thymidylate synthase and dihydrofolate reductase. Comparison with inhibitory effect on Escherichia coli and Toxoplasma gondii enzyme 6313 2.1.1.45 2-amino-6-methyl-5-[(4-nitrophenyl)sulfanyl]thieno[2,3-d]pyrimidin-4(3H)-one dual inhibitor of thymidylate synthase and dihydrofolate reductase. Comparison with inhibitory effect on human and Escherichia coli enzyme 6313 2.1.1.45 2-chloro-N'-[5-methyl-4-(4-methylphenyl)-6-oxo-1,6-dihydropyrimidin-2-yl]acetohydrazide - 243591 2.1.1.45 2-hydrazinyl-1,6-dihydro-6-oxo-4-p-tolyl pyrimidine-5-carbonitrile - 243595 2.1.1.45 2-hydroxyethyl disulfide - 6426 2.1.1.45 2-mercaptoethanol - 63 2.1.1.45 2-[2-(3-methoxyphenoxy)propyl]-4-methyl-1H-isoindole-1,3(2H)-dione - 243615 2.1.1.45 3,3-bis(4-methoxyphenyl)-1H,3H-benzo[de]isochromen-1-one induces apoptotic cell death in SK-MEL-2 and SK-MEL-28 melanoma cell lines, mediated by downregulation of Bcl-2 protein level and PARP cleavage, and independent of p53 and Bax. Pan-caspases inhibitor Z-VAD-FMK blocks the effect 146242 2.1.1.45 3,3-bis-(3-chloro-4-hydroxyphenyl)-1H,3H-[1,8-c,d]pyran-1-one - 665 2.1.1.45 3-(4-((2-amino-4-oxo-4,7-dihydro-3H-pyrrolo[2,3-d]pyrimidin-5-yl)methyl)benzamido)-4-(carboxymethyl)benzoic acid - 243682 2.1.1.45 3-beta-D-ribofuranosylmaleimide showdomycin 110195 2.1.1.45 3-beta-D-ribofuranosylmaleimide 5'-phosphate showdomycin 5'-phosphate 110196 2.1.1.45 4'-[(4-methyl-1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)methyl][1,1'-biphenyl]-2-carbonitrile - 243714 2.1.1.45 4,5,6,7-tetrachloro-2-[3-(phenylsulfanyl)propyl]-1H-isoindole-1,3(2H)-dione - 243715 2.1.1.45 4-amino-N10-methylfolic acid - 39751 2.1.1.45 4-chloro-N'-(5-cyano-1,6-dihydro-6-oxo-4-p-tolylpyrimidin-2-yl)benzohydrazide - 243755 2.1.1.45 5'-CGCGGTACGGACACCGCGCG-3' targets the TS mRNA translation start site TSS and increases the thymidylate synthase gene transcription in HeLa cell 146723 2.1.1.45 5,10-methenyltetrahydrofolylhexa-gamma-L-glutamate - 110035 2.1.1.45 5,10-methylenetetrahydrofolate - 401 2.1.1.45 5,5'-dithiobis(2-nitrobenzoic acid) - 221 2.1.1.45 5-bromo-2'-deoxyuridylic acid - 110302 2.1.1.45 5-bromo-N4-hydroxy-2'-deoxycytidine - 110303 2.1.1.45 5-bromoacetamido-5'-deoxythymidine - 32747 2.1.1.45 5-chloro-N4-hydroxy-2'-deoxycytidine - 110304 2.1.1.45 5-chloroacetamido-5'-deoxythymidine - 109765 2.1.1.45 5-fluoro-2'-deoxyuridine comparison with inhibitory effect of FdUMP[10] and 5-fluorouraci 3318 2.1.1.45 5-fluoro-2'-deoxyuridine 5'-(p-aminophenyl phosphate) - 50549 2.1.1.45 5-fluoro-2'-deoxyuridine 5'-monophosphate - 6765 2.1.1.45 5-fluoro-2'-deoxyuridine 5'-monophosphate FdUMP 6765 2.1.1.45 5-fluoro-2'-deoxyuridine monophosphate - 169697 2.1.1.45 5-fluoro-2'-deoxyuridine-5'-monophosphate - 42067 2.1.1.45 5-fluoro-2'-deoxyuridylic acid - 798 2.1.1.45 5-fluoro-2'-deoxyuridylic acid very strong inhibition, pseudo-noncompetitive 798 2.1.1.45 5-Fluoro-2-deoxyuridine FUdR 43538 2.1.1.45 5-fluoro-dUMP - 10542 2.1.1.45 5-fluoro-dUMP enzyme forms, in the presence of tetrahydrofolate, a covalently bound 5-fluoro-dUMP-thymidylate synthase complex. The tetrahydrofolate- and time-dependent, covalent binding by thymidylate synthase is accompanied by the enzyme inactivation 10542 2.1.1.45 5-fluoro-dUMP[10] a 10-mer of 5-fluoro-dUMP, a suicide inhibitor of thymidylate synthase, designed to bypass resistance to 5-fluorouracil, acts as a pro-drug of 5-fluoro-dUMP 146721 2.1.1.45 5-fluorodeoxyuridine 5-FUdR, TS-targeting chemotherapeutic agent 3977 2.1.1.45 5-fluorodeoxyuridine - 3977 2.1.1.45 5-fluorodeoxyuridine forms an inhibitory, ternary covalent complex with the enzyme 3977 2.1.1.45 5-fluorodeoxyuridine monophosphate - 220799 2.1.1.45 5-Fluoroorotate - 3183 2.1.1.45 5-fluoropyrimidine-2,4(1H,3H)-dione - 155282 2.1.1.45 5-fluorouracil - 812 2.1.1.45 5-fluorouracil but a major mechanism of resistance to 5-fluorouracil is overexpression of thymidylate synthase 812 2.1.1.45 5-fluorouracil 5-FU 812 2.1.1.45 5-fluorouracil 5-FU, TS-targeting chemotherapeutic agent 812 2.1.1.45 5-fluorouracil WiDr cells: 0.005 mM inhibits growth to 22%, inhibition cannot be potentiated by leucovorin but is rescued by uridine, 0.025 mM inhibits growth to 10%, inhibition can be rescued badly by uridine to an value of 31%, SW-948 and HT-29 cells: 0.005 mM shows an antiproliferative activity that is not affected by leucovorine addition and can be rescued by uridine, 0.1 mM shows a complete inhibition that cannot be rescued by uridine 812 2.1.1.45 5-fluorouracil 0.001 mM inhibits growth to 13%, inhibition can be rescued by uridine, 0.005 mM inhibits growth completely, inhibition cannot be rescued by uridine 812 2.1.1.45 5-fluorouracil transfection with p53 induces resistance to 5-fluorouracil 812 2.1.1.45 5-fluorouracil comparison with inhibitory effect of FdUMP[10] and 5-fluoro-2'-deoxyuridine 812 2.1.1.45 5-fluorouridine - 2938 2.1.1.45 5-Formyl-2'-deoxyuridylic acid - 9074 2.1.1.45 5-haloacetamido-5'-deoxythymidine - 110315 2.1.1.45 5-hydroseleno-2'-deoxyuridylic acid - 110316 2.1.1.45 5-hydroxy-methyl-2'-deoxyuridine 5'-monophosphate - 110319 2.1.1.45 5-iodo-2'-deoxyuridylic acid - 110322 2.1.1.45 5-iodoacetamido-5'-deoxythymidine - 110323 2.1.1.45 5-iodoacetamidomethyl-2'-deoxyuridine 5'-phosphate - 110324 2.1.1.45 5-Mercapto-2'-deoxyuridylic acid - 10544 2.1.1.45 5-Mercapto-2'-deoxyuridylic acid possesses antitumor activity against Ehrlich ascites cells 10544 2.1.1.45 5-Nitro-2'-deoxyuridine 5'-monophosphate - 43562 2.1.1.45 5-nitro-2'-deoxyuridylic acid - 50559 2.1.1.45 5-trifluoromethyl-2'-deoxyuridine 5'-monophosphate - 50560 2.1.1.45 5-trifluoromethyl-2'-deoxyuridylic acid - 50561 2.1.1.45 5F-dUMP mechanism-based inhibitor 247159 2.1.1.45 6-bromo-3,3-bis(3-chloro-4-hydroxyphenyl)-1H,3H-benzo[de]isochromen-1-one induces apoptotic cell death in SK-MEL-2 and SK-MEL-28 melanoma cell lines, mediated by downregulation of Bcl-2 protein level and PARP cleavage, and independent of p53 and Bax. Pan-caspases inhibitor Z-VAD-FMK blocks the effect 146318 2.1.1.45 6-chloro-3,3-bis(4-hydroxyphenyl)-1H,3H-benzo[de]isochromen-1-one induces apoptotic cell death in SK-MEL-2 and SK-MEL-28 melanoma cell lines, mediated by downregulation of Bcl-2 protein level and PARP cleavage, and independent of p53 and Bax. Pan-caspases inhibitor Z-VAD-FMK blocks the effect 146319 2.1.1.45 8-azapurinone deoxyribonucleoside 5'-phosphate - 169700 2.1.1.45 aminofolate - 32850 2.1.1.45 aminopterin - 1003 2.1.1.45 antifolate inhibits activitiy of bifunctional DHFR-TS enzyme 146720 2.1.1.45 antrycide - 13323 2.1.1.45 Arabinouridylate - 92474 2.1.1.45 atherospermidine competitive inhibition 220768 2.1.1.45 ATP - 4 2.1.1.45 benzyloxycarbonylamino-N,O-didansyl-L-tyrosine - 667 2.1.1.45 BGC 9331 treatment results in concentration-dependent increase in thymidine uptake in FR-positive epidermoid KB cells and in increase of membrane-associated equilibrative nucleoside transporter type 1 levels. Tumor [18F]-fluorothymidine accumulation in KB xenografts increases by more than 2fold with maximal levels at 1 to 4 hours and 4 to 24 hours after drug treatment. Quantitiative changes in tumor [18F]-fluorothymidine uptake are associated with increased tumor dUrd levels. BGC 9331 induces accumulation of [18F]-fluorothymidine uptake in the intestine 146722 2.1.1.45 BGC 945 alpha-folate receptor targeted antifolate TS inhibitor; cyclopenta[g]quinazoline-based inhibitor. Treatment results in concentration-dependent increase in thymidine uptake in FR-positive epidermoid KB cells and in increase of membrane-associated equilibrative nucleoside transporter type 1 levels. Tumor [18F]-fluorothymidine accumulation in KB xenografts increases by more than 2fold with maximal levels at 1 to 4 hours and 4 to 24 hours after drug treatment. Quantitiative changes in tumor [18F]-fluorothymidine uptake are associated with increased tumor dUrd levels 71039 2.1.1.45 bromo-2'-deoxyuridine - 50660 2.1.1.45 bromodeoxyuridine - 20169 2.1.1.45 capecitabine prodrug of 5-fluorouracil 38000 2.1.1.45 CB3717 - 32434 2.1.1.45 chloro-2'-deoxyuridine - 50667 2.1.1.45 Chloroacetamide - 10612 2.1.1.45 Cibacron blue - 1138 2.1.1.45 CQLYQRSG allosteric peptide inhibitor, binds to the dimer interface and stabilizes the inactive form of the protein 247151 2.1.1.45 crocetin binding pattern of crocetin is similar to that of ralitrexed and it poses maximum MolDock score as well as the rerank score 41418 2.1.1.45 curcumin - 696 2.1.1.45 cyanide - 118 2.1.1.45 cytosine arabinoside - 2016 2.1.1.45 D1694 - 13332 2.1.1.45 D1694 pentaglutamate - 21955 2.1.1.45 deaza-aminopterin - 50685 2.1.1.45 diglutamate - 110837 2.1.1.45 dihydrofolate - 1351 2.1.1.45 dihydropteroylglutamate - 110847 2.1.1.45 dihydropteroylhexaglutamate - 32625 2.1.1.45 dihydropteroylpentaglutamate - 32446 2.1.1.45 dihydropteroyltriglutamate - 110848 2.1.1.45 dimidium - 13335 2.1.1.45 dithiophosphate - 50698 2.1.1.45 dTMP - 635 2.1.1.45 ethidium - 8400 2.1.1.45 ethyl methanesulfonate - 50715 2.1.1.45 ethylene glycol - 1410 2.1.1.45 FdUMP - 220804 2.1.1.45 FdUMP[10] multimer of 5-fluoro-2'-deoxyuridine 5'-monophosphate, inhibits cell growth with greater potency than 5-fluorouracil and 5-fluoro-2'-deoxyuridine 38143 2.1.1.45 FdUSSO3 - 110914 2.1.1.45 fluorodeoxyuridine monophosphate - 50717 2.1.1.45 fluoroorotic acid - 110932 2.1.1.45 folic acid oligoglutamate - 110934 2.1.1.45 gefitinib inhibits the expression of the transcription factor E2F-1, resulting in a down-regulation of thymidylate synthase at the mRNA and protein level; inhibits the expression of the transcription factor E2F-1, resulting in the down-regulation of thymidylate synthase at the mRNA and protein levels 17786 2.1.1.45 glutamate - 297 2.1.1.45 glyceraldehyde 3-phosphate - 574 2.1.1.45 glycerol - 135 2.1.1.45 GW1843U89 - 18784 2.1.1.45 GW1843U89 direct folate-based inhibitor 18784 2.1.1.45 H2O2 - 22 2.1.1.45 hydroxymethyl-2'-deoxyuridine - 50777 2.1.1.45 Hydroxyurea supresses thymidilate synthase in growing algae, but no effect on purified enzyme 850 2.1.1.45 iodo-2'-deoxyuridine - 50780 2.1.1.45 iodoacetamide - 67 2.1.1.45 iodoacetate - 93 2.1.1.45 Iododeoxyuridine - 44264 2.1.1.45 isomoschatoline competitive inhibition 220767 2.1.1.45 KCl - 79 2.1.1.45 LCQFYVVN allosteric peptide inhibitor, binds to the dimer interface and stabilizes the inactive form of the protein 247148 2.1.1.45 liriodenine competitive inhibition 220770 2.1.1.45 LSCQLYQR octapeptide to specifically target the monomer-monomer interface of the enzyme. A fast-equilibrium mechanism exists that combines trafficking in/out of the cell and degradation pathways within cells 206211 2.1.1.45 LSCQLYQR allosteric peptide inhibitor, binds to the dimer interface and stabilizes the inactive form of the protein 206211 2.1.1.45 melosmine competitive inhibition 220769 2.1.1.45 methasquin - 32676 2.1.1.45 methopterin - 3613 2.1.1.45 methotrexate - 241 2.1.1.45 methotrexate most potent inhibitor of dihydrofolate reductase activity 241 2.1.1.45 methotrexate competitive inhibition 241 2.1.1.45 Mg2+ - 6 2.1.1.45 additional information 5FU-LV, combination of 5-fluorouracil and leucovorin 2 2.1.1.45 additional information combination of 5-FU and leucovorin, enhances the inhibition of thymidylate synthase, 0.001 mM inhibits growth to only 1%, inhibition can be rescued by uridine to an almost normal value of 83% 2 2.1.1.45 additional information combination of leucovorin and 5-fluorouracil 5FU-LV, IC50 0.00016 (FM3A/0 cell) 2 2.1.1.45 additional information inhibitory effect of antifolate drugs on enzymatic activity, and inhibitory activity of four aporphine alkaloids from Rollinia pittieri and Pseudomalmea boyacana, and some 2,4-diamino-pyrimidine antifolates, overview 2 2.1.1.45 additional information analysis of enzyme susceptibility to a range of classical inhibitors normally used in the treatment of cancer, bacterial or protozoal infections, in vivo effects in presence of absence of thymidine and/or folate, overview. Modulating certain medium components can affect drug sensitivity, presumably by either competition for uptake and competition for the active site of DHFR-TS. In the case of one human thymidylate synthase inhibitor raltitrexed, the inhibitor is more potent against the intact parasite. Addition of extra glutamic acid residues not only improves retention in the cell, but also increases potency against thymidylate synthase, as it does in human cells. No inhibition by FdUMP 2 2.1.1.45 N',N'-diacetyl-N-(5-cyano-1,6-dihydro-6-oxo-4-p-tolylpyrimidin-2-yl)acetohydrazide compound induces the level of active caspase 3, and elevates the Bax/Bcl2 ratio 44fold in comparison to the control 243972 2.1.1.45 N'-(3-chlorobenzoyl)-2-(2,4-dihydroxypyrimidine-5-sulfonamido)benzoyl hydrazide IC50 value 0.00126 mM for A-549 cells, 0.00208 mM for OVCAR-3 cells, 0.00182 mM for SCG-7901 cells, 0.00442 mM for MDA-MB-231 cells 243975 2.1.1.45 N'-(5-cyano-1,6-dihydro-6-oxo-4-p-tolylpyrimidin-2-yl)-4-nitrobenzohydrazide - 243976 2.1.1.45 N'-(5-cyano-1,6-dihydro-6-oxo-4-p-tolylpyrimidin-2-yl)benzohydrazide - 243977 2.1.1.45 N,O-didansyl-L-tyrosine - 666 2.1.1.45 N-(2-(1-(2-chlorophenyl)-1H-1,2,3-triazol-4-yl) phenyl)-2,4-dioxo-1,2,3,4-tetrahydropyrimidine-5-sulfonamide - 243989 2.1.1.45 N-(2-(1-(3-chlorophenyl)-1H-1,2,3-triazol-4-yl) phenyl)-2,4-dioxo-1, 2,3,4-tetrahydropyrimidine-5-sulfonamide - 243990 2.1.1.45 N-(2-(1-(4-chlorophenyl)-1H-1,2,3-triazol-4-yl) phenyl)-2,4-dioxo-1,2,3,4-tetrahydropyrimidine-5-sulfonamide compound exhibits the most potent activity against A-549 cells (IC50 1.18 microM) and prominent enzyme inhibition. It inhibits A-549 cells proliferation by arresting the cell cycle in the G1/S phase. The inhibitor can downregulate the cycle checkpoint proteins cyclin D1 and cyclin E to inhibit the cell cycle progression, and then induce intrinsic apoptosis by activating caspase-3, and reducing the ratio of bcl-2/bax 243991 2.1.1.45 N-(3-(1-(2-chlorophenyl)-1H-1,2,3-triazol-4-yl) phenyl)-2,4-dioxo-1,2,3,4-tetrahydropyrimidine-5-sulfonamide - 244001 2.1.1.45 N-(3-(1-(3-chlorophenyl)-1H-1,2,3-triazol-4-yl) phenyl)-2,4-dioxo-1,2,3,4-tetrahydropyrimidine-5-sulfonamide - 244002 2.1.1.45 N-(3-(1-(4-chlorophenyl)-1H-1,2,3-triazol-4-yl) phenyl)-2,4-dioxo-1,2,3,4-tetrahydropyrimidine-5-sulfonamide - 244003 2.1.1.45 N-(4-((2-amino-6-methyl-4-oxo-3,4-dihydro-5H-pyrrolo(3,2-d)pyrimidin-5-yl)methyl)benzoyl)-L-glutamic acid - 14434 2.1.1.45 N-(4-((2-amino-6-methyl-4-oxo-3,4-dihydrothieno(2,3-d)pyrimidin-5-yl)sulfanyl)benzoyl)-L-glutamic acid - 71037 2.1.1.45 N-(4-((2-amino-6-methyl-4-oxo-4,7-dihydro-3H-pyrrolo(2,3-d)pyrimidin-5-yl)thio)benzoyl)-L-glutamic acid - 11927 2.1.1.45 N-(4-(1-(2-chlorophenyl)-1H-1,2,3-triazol-4-yl) phenyl)-2,4-dioxo-1,2,3,4-tetrahydropyrimidine-5-sulfonamide - 244010 2.1.1.45 N-(4-(1-(3-chlorophenyl)-1H-1,2,3-triazol-4-yl) phenyl)-2,4-dioxo-1,2,3,4-tetrahydropyrimidine-5-sulfonamide - 244011 2.1.1.45 N-(4-(1-(4-chlorophenyl)-1H-1,2,3-triazol-4-yl) phenyl)-2,4-dioxo-1,2,3,4-tetrahydropyrimidine-5-sulfonamide - 244012 2.1.1.45 N-(4-[[(2,4-diaminopteridin-6-yl)methyl](methyl)amino]benzoyl)-gamma-glutamyl-gamma-glutamyl-gamma-glutamyl-gamma-glutamylglutamic acid - 14813 2.1.1.45 N-(4-[[(2,4-diaminopteridin-6-yl)methyl](methyl)amino]benzoyl)-gamma-glutamyl-gamma-glutamylglutamic acid - 14812 2.1.1.45 N-(4-[[(2,4-diaminopteridin-6-yl)methyl](methyl)amino]benzoyl)glutamic acid - 7833 2.1.1.45 N-(4-{[(2-amino-4-oxo-1,4-dihydroquinazolin-6-yl)methyl](prop-2-ynoyl)amino}benzoyl)-L-glutamic acid - 169698 2.1.1.45 N-([5-[2-(2,4-diaminoquinazolin-6-yl)ethyl]-2,3-dihydrothiophen-2-yl]carbonyl)-4-methylideneglutamic acid - 7835 2.1.1.45 N-ethylmaleimide - 49 2.1.1.45 N-[4-[(2,4-diamino-5-methyl-furo[2,3-d]pyrimidin-6-yl)thio]-benzoyl]-L-glutamic acid - 15241 2.1.1.45 N-[4-[(2-amino-6-ethyl-4-oxo-3,4-dihydrothieno[2,3-d]pyrimidin-5-yl)thio]benzoyl]-L-glutamic acid - 14849 2.1.1.45 N-[4-[(2-amino-6-methyl-4-oxo-3,4-dihydro-5H-pyrrolo[3,2-d]pyrimidin-5-yl)methyl]benzoyl]-L-glutamic acid dual inhibitor of thymidylate synthase and dihydrofolate reductase. Comparison with inhibitory effect on human and Escherichia coli enzyme; dual inhibitor of thymidylate synthase and dihydrofolate reductase. Comparison with inhibitory effect on human and Toxoplasma gondii enzyme 14416 2.1.1.45 N-[4-[(2-amino-6-methyl-4-oxo-3,4-dihydro-5H-pyrrolo[3,2-d]pyrimidin-5-yl)methyl]benzoyl]-L-glutamic acid dual inhibitor of thymidylate synthase and dihydrofolate reductase. Comparison with inhibitory effect on Escherichia coli and Toxoplasma gondii enzyme 14416 2.1.1.45 N-[4-[(2-amino-6-methyl-4-oxo-3,4-dihydrothieno[2,3-d]pyrimidin-5-yl)sulfanyl]benzoyl]-L-glutamic acid dual inhibitor of thymidylate synthase and dihydrofolate reductase. Comparison with inhibitory effect on human and Toxoplasma gondii enzyme 6314 2.1.1.45 N-[4-[(2-amino-6-methyl-4-oxo-3,4-dihydrothieno[2,3-d]pyrimidin-5-yl)sulfanyl]benzoyl]-L-glutamic acid dual inhibitor of thymidylate synthase and dihydrofolate reductase. Comparison with inhibitory effect on Escherichia coli and Toxoplasma gondii enzyme 6314 2.1.1.45 N-[4-[(2-amino-6-methyl-4-oxo-3,4-dihydrothieno[2,3-d]pyrimidin-5-yl)sulfanyl]benzoyl]-L-glutamic acid dual inhibitor of thymidylate synthase and dihydrofolate reductase. Comparison with inhibitory effect on human and Escherichia coli enzyme 6314 2.1.1.45 N-[4-[(2-amino-6-methyl-4-oxo-3,4-dihydrothieno[2,3-d]pyrimidin-5-yl)sulfanyl]benzoyl]-L-glutamic acid potent inhibitor of thymidylate synthase 6314 2.1.1.45 N-[4-[2-(2,4-diamino-7H-pyrrolo[2,3-d]pyrimidin-5-yl)ethyl]benzoyl]-4-methylideneglutamic acid - 7836 2.1.1.45 N-[4-[2-(2,4-diaminopyrido[3,2-d]pyrimidin-6-yl)ethyl]benzoyl]-4-methylideneglutamic acid - 7838 2.1.1.45 N-[4-[2-(2,4-diaminoquinazolin-6-yl)ethyl]-2-fluorobenzoyl]-4-methylideneglutamic acid - 7837 2.1.1.45 N-[4-[2-(2,4-diaminoquinazolin-6-yl)ethyl]benzoyl]-4-methylideneglutamic acid - 8822 2.1.1.45 N-[4-[2-(2-amino-4-methylquinazolin-6-yl)ethyl]benzoyl]-4-methylideneglutamic acid - 7834 2.1.1.45 N10-formyltetrahydrofolate - 3218 2.1.1.45 N10-propargyl-5,8-dideazafolate PDDF, a TS folate inhibitor, binds at the TS active site. Residues that are involved in binding the folate analogue PDDF include I402, D513, L516, F520, as well as the nonconserved R603 and conserved M608 located on the C-terminal tail of the TS-domain 220749 2.1.1.45 N4-hydroxy-2'-deoxycytidine - 111514 2.1.1.45 N4-hydroxy-5-methyl-2'-deoxycytidine - 111515 2.1.1.45 N4-hydroxy-dCMP enzyme forms, in the presence of tetrahydrofolate, a covalently bound 5-fluoro-dUMP-thymidylate synthase complex. The tetrahydrofolate- and time-dependent, covalent binding by thymidylate synthase is accompanied by the enzyme inactivation 247145 2.1.1.45 N5-formiminotetrahydropteroyltriglutamate - 109792 2.1.1.45 N5-formyltetrahydropteroyloligoglutamate - 50890 2.1.1.45 NaCl - 42 2.1.1.45 niazimicin - 247153 2.1.1.45 niazirin - 247158 2.1.1.45 nolatrexed transfection with p53 induces resistance to nolatrexed 8763 2.1.1.45 nolatrexed - 8763 2.1.1.45 nolatrexed upon binding, the two insert regions in thymidylate synthase, the functions of which are unclear, undergo positional shifts toward the catalytic center 8763 2.1.1.45 novobiocin coumarin antibiotic produced by Streptomyces nivens, at 10 mM concentration the self-splicing of primary transcripts is inhibited by about 5%, at 40 mM concentration the splicing rate is inhibited by about 50%. The splicing inhibition is strongly dependent on Mg2+ 1758 2.1.1.45 OSI-7904L a liposomal thymidylate synthase inhibitor, a liposomal formulation of OSI-7904 (S)-2-(5-((1,2-dihydro-3-methyl-1-oxobenzo(f)quinazolin-9-yl)methyl)amino-1-oxo-2-isoindolynl)-glutaric acid, administered in combination with oxaliplatin every 21 days in patients with advanced colorectal carcinoma; treatment of patients with advanced colorectal carcinoma, in combination with oxaliplatin. At the highest dose level of OSI-7904L 9 mg/m2, oxaliplatin 130 mg/m2, one of nine patients experienced dose-limiting toxicity of grade 3 oral mucositis with cycle 1 and five further patients required dose reductions. The toxicity profile of stomatitis, diarrhea, nausea, fatigue, sensory neuropathy and skin rash was consistent with that expected for a thymidylate synthase inhibitor/oxaliplatin combination regimen. High interpatient variability with no detectable interaction between OSI-7904L and oxaliplatin 71038 2.1.1.45 p-chloromercuribenzoate - 43 2.1.1.45 pemetrexed - 1155 2.1.1.45 pemetrexed TS-targeting chemotherapeutic agent 1155 2.1.1.45 pemetrexed dual inhibitor of thymidylate synthase and dihydrofolate reductase. Comparison with inhibitory effect on human and Toxoplasma gondii enzyme 1155 2.1.1.45 pemetrexed dual inhibitor of thymidylate synthase and dihydrofolate reductase. Comparison with inhibitory effect on Escherichia coli and Toxoplasma gondii enzyme 1155 2.1.1.45 pemetrexed dual inhibitor of thymidylate synthase and dihydrofolate reductase. Comparison with inhibitory effect on human and Escherichia coli enzyme 1155 2.1.1.45 pemetrexed transfection with p53 induces resistance to pemetrexed 1155 2.1.1.45 pemetrexed direct folate-based inhibitor; inhibitory to cell growth even in cell lacking thymidylate synthase activity 1155 2.1.1.45 pentalongin - 247155 2.1.1.45 Pentamidine - 2216 2.1.1.45 Phenylglyoxal - 301 2.1.1.45 picrocrocin - 247156 2.1.1.45 piritrexim - 5727 2.1.1.45 plevitrexed - 14821 2.1.1.45 Procion blue - 32951 2.1.1.45 propylene diphosphonate mixed competitive-noncompetitive inhibitor with respect to dUMP 42066 2.1.1.45 prothidium - 13359 2.1.1.45 pteroyldiglutamate - 15939 2.1.1.45 Pteroylheptaglutamate - 12673 2.1.1.45 pteroylhexaglutamate - 13360 2.1.1.45 pteroylmonoglutamate - 12830 2.1.1.45 pteroylpentaglutamate - 4557 2.1.1.45 pteroylpolyglutamate - 31620 2.1.1.45 pteroyltetraglutamate - 20815 2.1.1.45 Pteroyltriglutamate - 6020 2.1.1.45 pyridoxal 5'-phosphate - 32 2.1.1.45 pyrimethamine competitive inhibition 761 2.1.1.45 pyrimethamine - 761 2.1.1.45 QFYVVNSE allosteric peptide inhibitor, binds to the dimer interface and stabilizes the inactive form of the protein 247147 2.1.1.45 quinaspar - 50958 2.1.1.45 Quinazoline - 8184 2.1.1.45 ralitrexed - 247152 2.1.1.45 raltitrexed - 3165 2.1.1.45 raltitrexed RTX, a folate analog that is a specific inhibitor of TS; treatment can stimulate accurate recombination events in human cells. Gene conversions not associated with crossovers are specifically enhanced severalfold. Recombination events provoked by a double-strand break are not impacted by treatment with raltitrexed, nor is error-prone double-strand break repair via nonhomologous end-joining 3165 2.1.1.45 raltitrexed TS-targeting chemotherapeutic agent 3165 2.1.1.45 raltitrexed transfection with p53 induces resistance to raltitrexed 3165 2.1.1.45 raltitrexed direct folate-based inhibitor 3165 2.1.1.45 raltitrexed upon binding, the two insert regions in thymidylate synthase, the functions of which are unclear, undergo positional shifts toward the catalytic center 3165 2.1.1.45 scopoletin - 1357 2.1.1.45 SELSCQLY allosteric peptide inhibitor, binds to the dimer interface and stabilizes the inactive form of the protein 247146 2.1.1.45 SK 28,757 - 49490 2.1.1.45 SK 28,758 - 49489 2.1.1.45 SK 28,815 - 50979 2.1.1.45 suramin - 704 2.1.1.45 tetrahydrohomofolate - 111825 2.1.1.45 tetrahydromethotrexate - 8474 2.1.1.45 thiophosphate - 6027 2.1.1.45 thymidine phosphate product inhibition 2687 2.1.1.45 thymidine phosphate - 2687 2.1.1.45 Thymitaq - 111829 2.1.1.45 TomudexR - 32967 2.1.1.45 trifluoromethyldeoxyuridine 5'-monophosphate - 32970 2.1.1.45 trimethoprim - 503 2.1.1.45 trimethoprim competitive inhibition 503 2.1.1.45 trimetrexate - 3267 2.1.1.45 turmerone - 247154 2.1.1.45 UDP-glucuronate - 226 2.1.1.45 Urea - 116 2.1.1.45 vanoxonin-vanadium - 111886 2.1.1.45 VNSELSCQ allosteric peptide inhibitor, binds to the dimer interface and stabilizes the inactive form of the protein 247150 2.1.1.45 YVVNSELS allosteric peptide inhibitor, binds to the dimer interface and stabilizes the inactive form of the protein 247149 2.1.1.45 ZD1694 - 32433 2.1.1.45 ZD9331 antifolate inhibitor, shows positive cooperativity with 1,3-propanediphosphonic acid 70401