2.1.1.45: thymidylate synthase
This is an abbreviated version!
For detailed information about thymidylate synthase, go to the full flat file.
Word Map on EC 2.1.1.45
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2.1.1.45
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5-fluorouracil
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thymidine
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colorectal
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dihydrofolate
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antifolate
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methotrexate
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dihydropyrimidine
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pyrimidine
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fluoropyrimidine
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phosphorylase
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ribonucleotide
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leucovorin
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pemetrexed
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resect
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fdump
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uracil
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mthfr
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casey
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schedule
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polyglutamates
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non-small
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cisplatin
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folylpolyglutamate
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deoxyuridine
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oxaliplatin
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5-fluoro-2'-deoxyuridine
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antimetabolite
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orotate
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irinotecan
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capecitabine
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5-fu-based
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ccrf-cem
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folate-dependent
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gemcitabine
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folinic
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formyltransferase
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quinazoline
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glycinamide
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dttp
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polyglutamylation
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2'-deoxyuridine
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tegafur
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medicine
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methotrexate-resistant
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deoxycytidylate
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cross-complementing
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drug development
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transformylase
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5-fu-induced
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dutpase
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aminopterin
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deoxythymidine
- 2.1.1.45
- 5-fluorouracil
- thymidine
- colorectal
- dihydrofolate
- antifolate
- methotrexate
- dihydropyrimidine
- pyrimidine
-
fluoropyrimidine
- phosphorylase
- ribonucleotide
- leucovorin
- pemetrexed
-
resect
- fdump
- uracil
- mthfr
-
casey
-
schedule
- polyglutamates
-
non-small
- cisplatin
- folylpolyglutamate
- deoxyuridine
- oxaliplatin
- 5-fluoro-2'-deoxyuridine
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antimetabolite
- orotate
- irinotecan
- capecitabine
-
5-fu-based
-
ccrf-cem
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folate-dependent
- gemcitabine
-
folinic
-
formyltransferase
- quinazoline
- glycinamide
- dttp
-
polyglutamylation
- 2'-deoxyuridine
-
tegafur
- medicine
-
methotrexate-resistant
- deoxycytidylate
-
cross-complementing
- drug development
-
transformylase
-
5-fu-induced
- dutpase
- aminopterin
- deoxythymidine
Reaction
Synonyms
BgDHFR-TS, bifunctional TS-DHFR, DFR-TS, DHFR-TS, DHFR–TS, dihydrofolate reductase-thymidylate synthase, dTMP synthase, HTS, human TS, LBRM_06_0830, methylenetetrahydrofolate:dUMP C-methyltransferase, More, Thy1, ThyA, thymidylate synthase, thymidylate synthase A, thymidylate synthase-dihydrofolate reductase, thymidylate synthetase, ThyX, TMP synthetase, TMPS, TS, TS-DHFR, TSase, TYMS, Y110A7A.4
ECTree
2.1.1.45 thymidylate synthaseAdvanced search results
results (
results (Inhibitors
Inhibitors on EC 2.1.1.45 - thymidylate synthase
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INHIBITOR 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
IMAGE
(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
(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
(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
(S)-2-(5(((1,2-dihydro-3-methyl-1-oxobenzo[f]quinazolin-9 yl)methyl)amino)1-oxo-2-isoindolinyl)glutaric acid
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(S)-2-(5(((1,2-dihydro-3-methyl-1-oxobenzo[f]quinazolin-9-yl)methyl)amino)1-oxo-2-isoindolinyl)glutaric acid
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(S)-2-(5-(((1,2-dihydro3-methyl-1-oxobenzo[f]quinazolin-9-yl)methyl)amino)-1-oxo-2-isoindolinyl)glutaric acid
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BW1843U89
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
1-(5-cyano-1,6-dihydro-6-oxo-4-p-tolylpyrimidin-2-yl)-4-phenylthiosemicarbazide
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1-(beta-D-2'-deoxyribofuranosyl)1,6-dihydro-8-azapurin-2(3H,6H)-one 5'-monophosphate
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1-(beta-D-2'-Deoxyribofuranosyl)8-azapurin-2-one 5'-monophosphate
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1-(beta-D-2-deoxyribofuranosyl)-4-hydroxyamino-5-bromopyrimidin-2(1H)-one 5'-monophosphate
-
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1-(beta-D-2-deoxyribofuranosyl)-4-hydroxyamino-5-chloropyrimidin-2(1H)-one 5'-monophosphate
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1-(beta-D-2-deoxyribofuranosyl)-4-hydroxyamino-5-fluoropyrimidin-2(1H)-one 5'-monophosphate
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1-(beta-D-2-deoxyribofuranosyl)-4-hydroxyamino-5-hydroxymethylpyrimidin-2(1H)-one 5'-monophosphate
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1-(beta-D-2-deoxyribofuranosyl)-4-hydroxyamino-5-iodopyrimidin-2(1H)-one 5'-monophosphate
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1-(beta-D-2-deoxyribofuranosyl)-4-hydroxyaminopyrimidin-2(1H)-one 5'-monophosphate
-
-
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
2'-deoxy-2',2'-difluorouridine 5'-dihydrogen
classic inhibitor (no time dependence of inhibition observed)
2'-fluoro-ara-UMP
classic inhibitor (no time dependence of inhibition observed)
2,4-dioxo-N-(2-(1-(m-tolyl)-1H-1,2,3-triazol-4-yl)phenyl)-1, 2, 3, 4-tetrahydropyrimidine-5-sulfonamide
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2-(2-(4-((2-amino-4-oxo-4,7-dihydro-3H-pyrrolo[2,3-d]pyrimidin-5-yl)methyl)benzamido)-4-cyanophenyl)acetic acid
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2-(2-(4-((2-amino-4-oxo-4,7-dihydro-3H-pyrrolo[2,3-d]pyrimidin-5-yl)methyl)benzamido)-4-methoxyphenyl)acetic acid
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2-(2-(4-((2-amino-4-oxo-4,7-dihydro-3H-pyrrolo[2,3-d]pyrimidin-5-yl)methyl)benzamido)phenyl) acetic acid
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2-(2-(4-hydroxybenzylidene)hydrazinyl)-6-oxo-4-(p-tolyl)-1,6-dihydropyrimidine-5-carbonitrile
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2-(4-((2-amino-4-oxo-4,7-dihydro-3H-pyrrolo[2,3-d]pyrimidin-5-yl)methyl)benzamido) terephthalic acid
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2-(4-((2-amino-4-oxo-4,7-dihydro-3H-pyrrolo[2,3-d]pyrimidin-5-yl)methyl)benzamido)-4-chloro benzoic acid
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2-(4-((2-amino-4-oxo-4,7-dihydro-3H-pyrrolo[2,3-d]pyrimidin-5-yl)methyl)benzamido)-4-cyanobenzoic acid
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2-(4-hydroxy[1,1'-biphenyl]-3-yl)-4-methyl-1H-isoindole-1,3(2H)-dione
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2-chloro-N'-[5-methyl-4-(4-methylphenyl)-6-oxo-1,6-dihydropyrimidin-2-yl]acetohydrazide
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2-[2-(3-methoxyphenoxy)propyl]-4-methyl-1H-isoindole-1,3(2H)-dione
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3,3-bis(4-methoxyphenyl)-1H,3H-benzo[de]isochromen-1-one
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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
3-(4-((2-amino-4-oxo-4,7-dihydro-3H-pyrrolo[2,3-d]pyrimidin-5-yl)methyl)benzamido)-4-(carboxymethyl)benzoic acid
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3-beta-D-ribofuranosylmaleimide 5'-phosphate
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showdomycin 5'-phosphate
4'-[(4-methyl-1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)methyl][1,1'-biphenyl]-2-carbonitrile
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4,5,6,7-tetrachloro-2-[3-(phenylsulfanyl)propyl]-1H-isoindole-1,3(2H)-dione
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4-chloro-N'-(5-cyano-1,6-dihydro-6-oxo-4-p-tolylpyrimidin-2-yl)benzohydrazide
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5'-CGCGGTACGGACACCGCGCG-3'
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targets the TS mRNA translation start site TSS and increases the thymidylate synthase gene transcription in HeLa cell
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5-fluoro-2'-deoxyuridine
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comparison with inhibitory effect of FdUMP[10] and 5-fluorouraci
5-fluoro-dUMP[10]
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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
6-bromo-3,3-bis(3-chloro-4-hydroxyphenyl)-1H,3H-benzo[de]isochromen-1-one
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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
6-chloro-3,3-bis(4-hydroxyphenyl)-1H,3H-benzo[de]isochromen-1-one
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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
BGC 9331
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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
BGC 945
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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
CQLYQRSG
allosteric peptide inhibitor, binds to the dimer interface and stabilizes the inactive form of the protein
crocetin
binding pattern of crocetin is similar to that of ralitrexed and it poses maximum MolDock score as well as the rerank score
FdUMP[10]
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multimer of 5-fluoro-2'-deoxyuridine 5'-monophosphate, inhibits cell growth with greater potency than 5-fluorouracil and 5-fluoro-2'-deoxyuridine
gefitinib
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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
Hydroxyurea
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supresses thymidilate synthase in growing algae, but no effect on purified enzyme
LCQFYVVN
allosteric peptide inhibitor, binds to the dimer interface and stabilizes the inactive form of the protein
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
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
N'-(5-cyano-1,6-dihydro-6-oxo-4-p-tolylpyrimidin-2-yl)-4-nitrobenzohydrazide
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N-(2-(1-(2-chlorophenyl)-1H-1,2,3-triazol-4-yl) phenyl)-2,4-dioxo-1,2,3,4-tetrahydropyrimidine-5-sulfonamide
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N-(2-(1-(3-chlorophenyl)-1H-1,2,3-triazol-4-yl) phenyl)-2,4-dioxo-1, 2,3,4-tetrahydropyrimidine-5-sulfonamide
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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
N-(3-(1-(2-chlorophenyl)-1H-1,2,3-triazol-4-yl) phenyl)-2,4-dioxo-1,2,3,4-tetrahydropyrimidine-5-sulfonamide
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N-(3-(1-(3-chlorophenyl)-1H-1,2,3-triazol-4-yl) phenyl)-2,4-dioxo-1,2,3,4-tetrahydropyrimidine-5-sulfonamide
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N-(3-(1-(4-chlorophenyl)-1H-1,2,3-triazol-4-yl) phenyl)-2,4-dioxo-1,2,3,4-tetrahydropyrimidine-5-sulfonamide
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N-(4-((2-amino-6-methyl-4-oxo-3,4-dihydro-5H-pyrrolo(3,2-d)pyrimidin-5-yl)methyl)benzoyl)-L-glutamic acid
N-(4-((2-amino-6-methyl-4-oxo-3,4-dihydrothieno(2,3-d)pyrimidin-5-yl)sulfanyl)benzoyl)-L-glutamic acid
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N-(4-((2-amino-6-methyl-4-oxo-4,7-dihydro-3H-pyrrolo(2,3-d)pyrimidin-5-yl)thio)benzoyl)-L-glutamic acid
N-(4-(1-(2-chlorophenyl)-1H-1,2,3-triazol-4-yl) phenyl)-2,4-dioxo-1,2,3,4-tetrahydropyrimidine-5-sulfonamide
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N-(4-(1-(3-chlorophenyl)-1H-1,2,3-triazol-4-yl) phenyl)-2,4-dioxo-1,2,3,4-tetrahydropyrimidine-5-sulfonamide
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N-(4-(1-(4-chlorophenyl)-1H-1,2,3-triazol-4-yl) phenyl)-2,4-dioxo-1,2,3,4-tetrahydropyrimidine-5-sulfonamide
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N-(4-[[(2,4-diaminopteridin-6-yl)methyl](methyl)amino]benzoyl)-gamma-glutamyl-gamma-glutamyl-gamma-glutamyl-gamma-glutamylglutamic acid
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N-(4-[[(2,4-diaminopteridin-6-yl)methyl](methyl)amino]benzoyl)-gamma-glutamyl-gamma-glutamylglutamic acid
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N-(4-{[(2-amino-4-oxo-1,4-dihydroquinazolin-6-yl)methyl](prop-2-ynoyl)amino}benzoyl)-L-glutamic acid
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N-([5-[2-(2,4-diaminoquinazolin-6-yl)ethyl]-2,3-dihydrothiophen-2-yl]carbonyl)-4-methylideneglutamic acid
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N-[4-[(2-amino-6-ethyl-4-oxo-3,4-dihydrothieno[2,3-d]pyrimidin-5-yl)thio]benzoyl]-L-glutamic acid
N-[4-[(2-amino-6-methyl-4-oxo-3,4-dihydro-5H-pyrrolo[3,2-d]pyrimidin-5-yl)methyl]benzoyl]-L-glutamic acid
N-[4-[(2-amino-6-methyl-4-oxo-3,4-dihydrothieno[2,3-d]pyrimidin-5-yl)sulfanyl]benzoyl]-L-glutamic acid
N-[4-[2-(2,4-diamino-7H-pyrrolo[2,3-d]pyrimidin-5-yl)ethyl]benzoyl]-4-methylideneglutamic acid
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N-[4-[2-(2,4-diaminopyrido[3,2-d]pyrimidin-6-yl)ethyl]benzoyl]-4-methylideneglutamic acid
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N-[4-[2-(2,4-diaminoquinazolin-6-yl)ethyl]-2-fluorobenzoyl]-4-methylideneglutamic acid
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N-[4-[2-(2,4-diaminoquinazolin-6-yl)ethyl]benzoyl]-4-methylideneglutamic acid
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N-[4-[2-(2-amino-4-methylquinazolin-6-yl)ethyl]benzoyl]-4-methylideneglutamic acid
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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
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
novobiocin
Tequatrovirus T4
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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+
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
propylene diphosphonate
-
mixed competitive-noncompetitive inhibitor with respect to dUMP
QFYVVNSE
allosteric peptide inhibitor, binds to the dimer interface and stabilizes the inactive form of the protein
SELSCQLY
allosteric peptide inhibitor, binds to the dimer interface and stabilizes the inactive form of the protein
VNSELSCQ
allosteric peptide inhibitor, binds to the dimer interface and stabilizes the inactive form of the protein
YVVNSELS
allosteric peptide inhibitor, binds to the dimer interface and stabilizes the inactive form of the protein
ZD9331
antifolate inhibitor, shows positive cooperativity with 1,3-propanediphosphonic acid
(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
(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
1,1-bis-(4-hydroxyphenyl)-1H-naphtho[1,2-c]furan-3-one
-
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1,1-bis-(4-hydroxyphenyl)-1H-naphtho[1,2-c]furan-3-one
-
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1,1-bis-(4-hydroxyphenyl)-1H-naphtho[1,2-c]furan-3-one
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1,1-bis-(4-hydroxyphenyl)-1H-naphtho[1,2-c]furan-3-one
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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
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
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
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
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
2-amino-5-[(2,5-dimethoxyphenyl)sulfanyl]-6-ethylthieno[2,3-d]pyrimidin-4(3H)-one
-
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2-amino-5-[(2,5-dimethoxyphenyl)sulfanyl]-6-ethylthieno[2,3-d]pyrimidin-4(3H)-one
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2-amino-5-[(2,5-dimethoxyphenyl)sulfanyl]-6-ethylthieno[2,3-d]pyrimidin-4(3H)-one
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2-amino-5-[(2-chlorophenyl)sulfanyl]-6-ethylthieno[2,3-d]pyrimidin-4(3H)-one
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2-amino-5-[(2-chlorophenyl)sulfanyl]-6-ethylthieno[2,3-d]pyrimidin-4(3H)-one
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2-amino-5-[(2-chlorophenyl)sulfanyl]-6-ethylthieno[2,3-d]pyrimidin-4(3H)-one
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2-amino-5-[(3,4-dichlorophenyl)sulfanyl]-6-methylthieno[2,3-d]pyrimidin-4(3H)-one
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dual inhibitor of thymidylate synthase and dihydrofolate reductase. Comparison with inhibitory effect on human and Toxoplasma gondii enzyme
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
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
2-amino-5-[(3,4-dichlorophenyl)thio]-6-ethylthieno[2,3-d]pyrimidin-4(3H)-one
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2-amino-5-[(3,4-dichlorophenyl)thio]-6-ethylthieno[2,3-d]pyrimidin-4(3H)-one
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2-amino-5-[(3,4-dichlorophenyl)thio]-6-ethylthieno[2,3-d]pyrimidin-4(3H)-one
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2-amino-5-[(3,5-dichlorophenyl)sulfanyl]-6-ethylthieno[2,3-d]-pyrimidin-4(3H)-one
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2-amino-5-[(3,5-dichlorophenyl)sulfanyl]-6-ethylthieno[2,3-d]-pyrimidin-4(3H)-one
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2-amino-5-[(3,5-dichlorophenyl)sulfanyl]-6-ethylthieno[2,3-d]-pyrimidin-4(3H)-one
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2-amino-5-[(3,5-dimethoxyphenyl)sulfanyl]-6-ethylthieno[2,3-d]pyrimidin-4(3H)-one
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2-amino-5-[(3,5-dimethoxyphenyl)sulfanyl]-6-ethylthieno[2,3-d]pyrimidin-4(3H)-one
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2-amino-5-[(3,5-dimethoxyphenyl)sulfanyl]-6-ethylthieno[2,3-d]pyrimidin-4(3H)-one
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2-amino-5-[(3-chlorophenyl)sulfanyl]-6-ethylthieno[2,3-d]pyrimidin-4(3H)-one
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2-amino-5-[(3-chlorophenyl)sulfanyl]-6-ethylthieno[2,3-d]pyrimidin-4(3H)-one
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-
2-amino-5-[(3-chlorophenyl)sulfanyl]-6-ethylthieno[2,3-d]pyrimidin-4(3H)-one
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-
2-amino-5-[(4-bromophenyl)sulfanyl]-6-ethylthieno[2,3-d]pyrimidin-4(3H)-one
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-
2-amino-5-[(4-bromophenyl)sulfanyl]-6-ethylthieno[2,3-d]pyrimidin-4(3H)-one
-
-
2-amino-5-[(4-chlorophenyl)sulfanyl]-6-ethylthieno[2,3-d]pyrimidin-4(3H)-one
-
-
2-amino-5-[(4-chlorophenyl)sulfanyl]-6-ethylthieno[2,3-d]pyrimidin-4(3H)-one
-
-
2-amino-5-[(4-chlorophenyl)sulfanyl]-6-ethylthieno[2,3-d]pyrimidin-4(3H)-one
-
-
2-amino-6-ethyl-5-(pyridin-4-ylsulfanyl)thieno[2,3-d]pyrimidin-4(3H)-one
-
-
2-amino-6-ethyl-5-(pyridin-4-ylsulfanyl)thieno[2,3-d]pyrimidin-4(3H)-one
-
-
2-amino-6-ethyl-5-[(4-fluorophenyl)sulfanyl]thieno[2,3-d]pyrimidin-4(3H)-one
-
-
2-amino-6-ethyl-5-[(4-fluorophenyl)sulfanyl]thieno[2,3-d]pyrimidin-4(3H)-one
-
-
2-amino-6-ethyl-5-[(4-fluorophenyl)sulfanyl]thieno[2,3-d]pyrimidin-4(3H)-one
-
-
2-amino-6-ethyl-5-[(4-nitrophenyl)sulfanyl]thieno[2,3-d]pyrimidin-4(3H)-one
-
-
2-amino-6-ethyl-5-[(4-nitrophenyl)sulfanyl]thieno[2,3-d]pyrimidin-4(3H)-one
-
-
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
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
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
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
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
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
3,3-bis-(3-chloro-4-hydroxyphenyl)-1H,3H-[1,8-c,d]pyran-1-one
-
-
3,3-bis-(3-chloro-4-hydroxyphenyl)-1H,3H-[1,8-c,d]pyran-1-one
-
-
3,3-bis-(3-chloro-4-hydroxyphenyl)-1H,3H-[1,8-c,d]pyran-1-one
-
-
3,3-bis-(3-chloro-4-hydroxyphenyl)-1H,3H-[1,8-c,d]pyran-1-one
-
-
3,3-bis-(3-chloro-4-hydroxyphenyl)-1H,3H-[1,8-c,d]pyran-1-one
-
-
3,3-bis-(3-chloro-4-hydroxyphenyl)-1H,3H-[1,8-c,d]pyran-1-one
-
-
3,3-bis-(3-chloro-4-hydroxyphenyl)-1H,3H-[1,8-c,d]pyran-1-one
-
-
3,3-bis-(3-chloro-4-hydroxyphenyl)-1H,3H-[1,8-c,d]pyran-1-one
-
-
3,3-bis-(3-chloro-4-hydroxyphenyl)-1H,3H-[1,8-c,d]pyran-1-one
-
-
3,3-bis-(3-chloro-4-hydroxyphenyl)-1H,3H-[1,8-c,d]pyran-1-one
-
-
3,3-bis-(3-chloro-4-hydroxyphenyl)-1H,3H-[1,8-c,d]pyran-1-one
-
-
3,3-bis-(3-chloro-4-hydroxyphenyl)-1H,3H-[1,8-c,d]pyran-1-one
-
-
5-fluoro-2'-deoxyuridylic acid
-
very strong inhibition, pseudo-noncompetitive
5-fluoro-2'-deoxyuridylic acid
-
-
5-fluoro-2'-deoxyuridylic acid
-
-
5-fluoro-2'-deoxyuridylic acid
-
-
485359, 485366, 485369, 485375, 485377, 485378, 485379, 485383, 485384, 485385, 485387, 485393, 485397, 485400, 485411, 485419, 485423, 485430
5-fluoro-2'-deoxyuridylic acid
-
-
392255, 485359, 485369, 485375, 485383, 485384, 485387, 485393, 485400, 485402, 485404, 485413, 485427, 485430
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
5-fluorodeoxyuridine
-
forms an inhibitory, ternary covalent complex with the enzyme
5-fluorouracil
-
but a major mechanism of resistance to 5-fluorouracil is overexpression of thymidylate synthase
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
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
5-fluorouracil
-
comparison with inhibitory effect of FdUMP[10] and 5-fluoro-2'-deoxyuridine
5-Mercapto-2'-deoxyuridylic acid
-
possesses antitumor activity against Ehrlich ascites cells
benzyloxycarbonylamino-N,O-didansyl-L-tyrosine
-
-
benzyloxycarbonylamino-N,O-didansyl-L-tyrosine
-
-
benzyloxycarbonylamino-N,O-didansyl-L-tyrosine
-
-
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
LSCQLYQR
allosteric peptide inhibitor, binds to the dimer interface and stabilizes the inactive form of the protein
methotrexate
most potent inhibitor of dihydrofolate reductase activity
N-(4-((2-amino-6-methyl-4-oxo-3,4-dihydro-5H-pyrrolo(3,2-d)pyrimidin-5-yl)methyl)benzoyl)-L-glutamic acid
-
-
N-(4-((2-amino-6-methyl-4-oxo-3,4-dihydro-5H-pyrrolo(3,2-d)pyrimidin-5-yl)methyl)benzoyl)-L-glutamic acid
-
-
N-(4-((2-amino-6-methyl-4-oxo-3,4-dihydro-5H-pyrrolo(3,2-d)pyrimidin-5-yl)methyl)benzoyl)-L-glutamic acid
-
-
N-(4-((2-amino-6-methyl-4-oxo-4,7-dihydro-3H-pyrrolo(2,3-d)pyrimidin-5-yl)thio)benzoyl)-L-glutamic acid
-
-
N-(4-((2-amino-6-methyl-4-oxo-4,7-dihydro-3H-pyrrolo(2,3-d)pyrimidin-5-yl)thio)benzoyl)-L-glutamic acid
-
-
N-(4-((2-amino-6-methyl-4-oxo-4,7-dihydro-3H-pyrrolo(2,3-d)pyrimidin-5-yl)thio)benzoyl)-L-glutamic acid
-
N-(4-((2-amino-6-methyl-4-oxo-4,7-dihydro-3H-pyrrolo(2,3-d)pyrimidin-5-yl)thio)benzoyl)-L-glutamic acid
-
-
N-[4-[(2,4-diamino-5-methyl-furo[2,3-d]pyrimidin-6-yl)thio]-benzoyl]-L-glutamic acid
-
-
N-[4-[(2,4-diamino-5-methyl-furo[2,3-d]pyrimidin-6-yl)thio]-benzoyl]-L-glutamic acid
-
-
N-[4-[(2,4-diamino-5-methyl-furo[2,3-d]pyrimidin-6-yl)thio]-benzoyl]-L-glutamic acid
-
-
N-[4-[(2-amino-6-ethyl-4-oxo-3,4-dihydrothieno[2,3-d]pyrimidin-5-yl)thio]benzoyl]-L-glutamic acid
-
-
N-[4-[(2-amino-6-ethyl-4-oxo-3,4-dihydrothieno[2,3-d]pyrimidin-5-yl)thio]benzoyl]-L-glutamic acid
-
-
N-[4-[(2-amino-6-ethyl-4-oxo-3,4-dihydrothieno[2,3-d]pyrimidin-5-yl)thio]benzoyl]-L-glutamic acid
-
-
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
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
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
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
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
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
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
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
nolatrexed
upon binding, the two insert regions in thymidylate synthase, the functions of which are unclear, undergo positional shifts toward the catalytic center
pemetrexed
-
dual inhibitor of thymidylate synthase and dihydrofolate reductase. Comparison with inhibitory effect on human and Toxoplasma gondii enzyme
pemetrexed
dual inhibitor of thymidylate synthase and dihydrofolate reductase. Comparison with inhibitory effect on Escherichia coli and Toxoplasma gondii enzyme
pemetrexed
-
direct folate-based inhibitor; inhibitory to cell growth even in cell lacking thymidylate synthase activity
pemetrexed
-
dual inhibitor of thymidylate synthase and dihydrofolate reductase. Comparison with inhibitory effect on human and Escherichia coli enzyme
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
raltitrexed
upon binding, the two insert regions in thymidylate synthase, the functions of which are unclear, undergo positional shifts toward the catalytic center
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
-
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
-
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
-
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%
-
additional information
-
combination of leucovorin and 5-fluorouracil 5FU-LV, IC50 0.00016 (FM3A/0 cell)
-
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
-
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
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