Application | Comment | Organism |
---|---|---|
medicine | inhibition of TS and DHFR enzymes has found clinical utility as antitumor, antimicrobial and antiprotozoal agents | Homo sapiens |
Crystallization (Comment) | Organism |
---|---|
molecular modeling of complex with inhibitor N-[4-[(2-amino-6-methyl-4-oxo-3,4-dihydrothieno[2,3-d]pyrimidin-5-yl)sulfanyl]benzoyl]-L-glutamic acid. The 6-methyl moiety of of the inhibitor makes important hydrophobic contacts with Trp109 and also serves to lock the 5-position side chain into favorable, low-energy conformations for thymidlyate synthase binding | Escherichia coli |
molecular modeling of complex with inhibitor N-[4-[(2-amino-6-methyl-4-oxo-3,4-dihydrothieno[2,3-d]pyrimidin-5-yl)sulfanyl]benzoyl]-L-glutamic acid. The 6-methyl moiety of of the inhibitor makes important hydrophobic contacts with Trp109 and also serves to lock the 5-position side chain into favorable, low-energy conformations for thymidlyate synthase binding | Toxoplasma gondii |
molecular modeling of complex with inhibitor N-[4-[(2-amino-6-methyl-4-oxo-3,4-dihydrothieno[2,3-d]pyrimidin-5-yl)sulfanyl]benzoyl]-L-glutamic acid. The 6-methyl moiety of of the inhibitor makes important hydrophobic contacts with Trp109 and also serves to lock the 5-position side chain into favorable, low-energy conformations for thymidlyate synthase binding | Homo sapiens |
Inhibitors | Comment | Organism | Structure |
---|---|---|---|
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 | Escherichia coli | |
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 | Homo sapiens | |
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 | Toxoplasma gondii | |
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 | Escherichia coli | |
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 | Homo sapiens | |
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 | Toxoplasma gondii | |
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 | Escherichia coli | |
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 | Homo sapiens | |
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 | Toxoplasma gondii | |
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 | Escherichia coli | |
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 | Homo sapiens | |
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 | Toxoplasma gondii | |
N-(4-((2-amino-6-methyl-4-oxo-3,4-dihydrothieno(2,3-d)pyrimidin-5-yl)sulfanyl)benzoyl)-L-glutamic acid | - |
Homo sapiens | |
N-(4-((2-amino-6-methyl-4-oxo-4,7-dihydro-3H-pyrrolo(2,3-d)pyrimidin-5-yl)thio)benzoyl)-L-glutamic acid | - |
Homo sapiens | |
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 | Escherichia coli | |
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 | Homo sapiens | |
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 | Toxoplasma gondii | |
pemetrexed | dual inhibitor of thymidylate synthase and dihydrofolate reductase. Comparison with inhibitory effect on human and Toxoplasma gondii enzyme | Escherichia coli | |
pemetrexed | dual inhibitor of thymidylate synthase and dihydrofolate reductase. Comparison with inhibitory effect on Escherichia coli and Toxoplasma gondii enzyme | Homo sapiens | |
pemetrexed | dual inhibitor of thymidylate synthase and dihydrofolate reductase. Comparison with inhibitory effect on human and Escherichia coli enzyme | Toxoplasma gondii |
Natural Substrates | Organism | Comment (Nat. Sub.) | Natural Products | Comment (Nat. Pro.) | Rev. | Reac. |
---|---|---|---|---|---|---|
5,10-methylenetetrahydrofolate + dUMP | Homo sapiens | inhibition of thymidylate synthase or of DHFR leads to thymineless death of eukaryotic organisms | 7,8-dihydrofolate + dTMP | - |
? |
Organism | UniProt | Comment | Textmining |
---|---|---|---|
Escherichia coli | - |
- |
- |
Homo sapiens | P04818 | - |
- |
Toxoplasma gondii | - |
- |
- |
Substrates | Comment Substrates | Organism | Products | Comment (Products) | Rev. | Reac. |
---|---|---|---|---|---|---|
5,10-methylenetetrahydrofolate + dUMP | - |
Homo sapiens | 7,8-dihydrofolate + dTMP | - |
? | |
5,10-methylenetetrahydrofolate + dUMP | inhibition of thymidylate synthase or of DHFR leads to thymineless death of eukaryotic organisms | Homo sapiens | 7,8-dihydrofolate + dTMP | - |
? |
Synonyms | Comment | Organism |
---|---|---|
TS-DHFR | - |
Homo sapiens |
IC50 Value | IC50 Value Maximum | Comment | Organism | Inhibitor | Structure |
---|---|---|---|---|---|
0.000019 | - |
- |
Escherichia coli | 10-propargyl-5,8-dideazafolate | |
0.000036 | - |
- |
Toxoplasma gondii | N-[4-[(2-amino-6-methyl-4-oxo-3,4-dihydrothieno[2,3-d]pyrimidin-5-yl)sulfanyl]benzoyl]-L-glutamic acid | |
0.00004 | - |
- |
Escherichia coli | N-[4-[(2-amino-6-methyl-4-oxo-3,4-dihydrothieno[2,3-d]pyrimidin-5-yl)sulfanyl]benzoyl]-L-glutamic acid | |
0.00004 | - |
- |
Homo sapiens | N-[4-[(2-amino-6-methyl-4-oxo-3,4-dihydrothieno[2,3-d]pyrimidin-5-yl)sulfanyl]benzoyl]-L-glutamic acid | |
0.00004 | - |
potent inhibitor of human TS and of human DHFR, it is a novel dual TS-DHFR inhibitor, 330-fold more potent than pemetrexed | Homo sapiens | N-(4-((2-amino-6-methyl-4-oxo-3,4-dihydrothieno(2,3-d)pyrimidin-5-yl)sulfanyl)benzoyl)-L-glutamic acid | |
0.000054 | - |
potent inhibitor of human TS and moderate inhibitor of human DHFR | Homo sapiens | N-(4-((2-amino-6-methyl-4-oxo-4,7-dihydro-3H-pyrrolo(2,3-d)pyrimidin-5-yl)thio)benzoyl)-L-glutamic acid | |
0.000085 | - |
- |
Homo sapiens | 10-propargyl-5,8-dideazafolate | |
0.00011 | - |
- |
Homo sapiens | 2-amino-5-[(3,4-dichlorophenyl)sulfanyl]-6-methylthieno[2,3-d]pyrimidin-4(3H)-one | |
0.00011 | - |
- |
Homo sapiens | 2-amino-6-methyl-5-[(4-nitrophenyl)sulfanyl]thieno[2,3-d]pyrimidin-4(3H)-one | |
0.00012 | - |
- |
Homo sapiens | 2-amino-6-methyl-5-(2-naphthylsulfanyl)thieno[2,3-d]pyrimidin-4(3H)-one | |
0.00043 | - |
- |
Toxoplasma gondii | 10-propargyl-5,8-dideazafolate | |
0.0012 | - |
- |
Toxoplasma gondii | 2-amino-5-[(3,4-dichlorophenyl)sulfanyl]-6-methylthieno[2,3-d]pyrimidin-4(3H)-one | |
0.0012 | - |
- |
Toxoplasma gondii | 2-amino-6-methyl-5-(2-naphthylsulfanyl)thieno[2,3-d]pyrimidin-4(3H)-one | |
0.0012 | - |
- |
Escherichia coli | 2-amino-6-methyl-5-[(4-nitrophenyl)sulfanyl]thieno[2,3-d]pyrimidin-4(3H)-one | |
0.0012 | - |
- |
Toxoplasma gondii | 2-amino-6-methyl-5-[(4-nitrophenyl)sulfanyl]thieno[2,3-d]pyrimidin-4(3H)-one | |
0.0023 | - |
- |
Escherichia coli | 2-amino-5-[(3,4-dichlorophenyl)sulfanyl]-6-methylthieno[2,3-d]pyrimidin-4(3H)-one | |
0.0024 | - |
- |
Escherichia coli | 2-amino-6-methyl-5-(2-naphthylsulfanyl)thieno[2,3-d]pyrimidin-4(3H)-one | |
0.0028 | - |
- |
Toxoplasma gondii | pemetrexed | |
0.0095 | - |
- |
Homo sapiens | pemetrexed | |
0.076 | - |
- |
Escherichia coli | pemetrexed |