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Literature summary extracted from

  • McGuire, J.J.; Haile, W.H.
    Metabolism-blocked antifolates as potential anti-rheumatoid arthritis agents: 4-amino-4-deoxy-5,8,10-trideazapteroyl-D,L-4-methyleneglutamic acid (CH-1504) and its analogs (2009), Biochem. Pharmacol., 77, 1161-1172.
    View publication on PubMed

Inhibitors

EC Number Inhibitors Comment Organism Structure
1.5.1.3 N-(4-[[(2,4-diaminopteridin-6-yl)methyl](methyl)amino]benzoyl)-gamma-glutamyl-gamma-glutamyl-gamma-glutamyl-gamma-glutamylglutamic acid
-
 Homo sapiens
1.5.1.3 N-(4-[[(2,4-diaminopteridin-6-yl)methyl](methyl)amino]benzoyl)-gamma-glutamyl-gamma-glutamylglutamic acid
-
 Homo sapiens
1.5.1.3 N-(4-[[(2,4-diaminopteridin-6-yl)methyl](methyl)amino]benzoyl)glutamic acid
-
 Homo sapiens
1.5.1.3 N-([5-[2-(2,4-diaminoquinazolin-6-yl)ethyl]-2,3-dihydrothiophen-2-yl]carbonyl)-4-methylideneglutamic acid
-
 Homo sapiens
1.5.1.3 N-[4-[2-(2,4-diamino-7H-pyrrolo[2,3-d]pyrimidin-5-yl)ethyl]benzoyl]-4-methylideneglutamic acid
-
 Homo sapiens
1.5.1.3 N-[4-[2-(2,4-diaminopyrido[3,2-d]pyrimidin-6-yl)ethyl]benzoyl]-4-methylideneglutamic acid
-
 Homo sapiens
1.5.1.3 N-[4-[2-(2,4-diaminoquinazolin-6-yl)ethyl]-2-fluorobenzoyl]-4-methylideneglutamic acid
-
 Homo sapiens
1.5.1.3 N-[4-[2-(2,4-diaminoquinazolin-6-yl)ethyl]benzoyl]-4-methylideneglutamic acid
-
 Homo sapiens
1.5.1.3 N-[4-[2-(2-amino-4-methylquinazolin-6-yl)ethyl]benzoyl]-4-methylideneglutamic acid
-
 Homo sapiens
1.5.1.20 N-(4-[[(2,4-diaminopteridin-6-yl)methyl](methyl)amino]benzoyl)-gamma-glutamyl-gamma-glutamyl-gamma-glutamyl-gamma-glutamylglutamic acid
-
 Homo sapiens
1.5.1.20 N-(4-[[(2,4-diaminopteridin-6-yl)methyl](methyl)amino]benzoyl)-gamma-glutamyl-gamma-glutamylglutamic acid
-
 Homo sapiens
1.5.1.20 N-(4-[[(2,4-diaminopteridin-6-yl)methyl](methyl)amino]benzoyl)glutamic acid
-
 Homo sapiens
1.5.1.20 N-([5-[2-(2,4-diaminoquinazolin-6-yl)ethyl]-2,3-dihydrothiophen-2-yl]carbonyl)-4-methylideneglutamic acid
-
 Homo sapiens
1.5.1.20 N-[4-[2-(2,4-diamino-7H-pyrrolo[2,3-d]pyrimidin-5-yl)ethyl]benzoyl]-4-methylideneglutamic acid
-
 Homo sapiens
1.5.1.20 N-[4-[2-(2,4-diaminopyrido[3,2-d]pyrimidin-6-yl)ethyl]benzoyl]-4-methylideneglutamic acid
-
 Homo sapiens
1.5.1.20 N-[4-[2-(2,4-diaminoquinazolin-6-yl)ethyl]-2-fluorobenzoyl]-4-methylideneglutamic acid
-
 Homo sapiens
1.5.1.20 N-[4-[2-(2,4-diaminoquinazolin-6-yl)ethyl]benzoyl]-4-methylideneglutamic acid
-
 Homo sapiens
1.5.1.20 N-[4-[2-(2-amino-4-methylquinazolin-6-yl)ethyl]benzoyl]-4-methylideneglutamic acid
-
 Homo sapiens
2.1.1.45 N-(4-[[(2,4-diaminopteridin-6-yl)methyl](methyl)amino]benzoyl)-gamma-glutamyl-gamma-glutamyl-gamma-glutamyl-gamma-glutamylglutamic acid
-
 Homo sapiens
2.1.1.45 N-(4-[[(2,4-diaminopteridin-6-yl)methyl](methyl)amino]benzoyl)-gamma-glutamyl-gamma-glutamylglutamic acid
-
 Homo sapiens
2.1.1.45 N-(4-[[(2,4-diaminopteridin-6-yl)methyl](methyl)amino]benzoyl)glutamic acid
-
 Homo sapiens
2.1.1.45 N-([5-[2-(2,4-diaminoquinazolin-6-yl)ethyl]-2,3-dihydrothiophen-2-yl]carbonyl)-4-methylideneglutamic acid
-
 Homo sapiens
2.1.1.45 N-[4-[2-(2,4-diamino-7H-pyrrolo[2,3-d]pyrimidin-5-yl)ethyl]benzoyl]-4-methylideneglutamic acid
-
 Homo sapiens
2.1.1.45 N-[4-[2-(2,4-diaminopyrido[3,2-d]pyrimidin-6-yl)ethyl]benzoyl]-4-methylideneglutamic acid
-
 Homo sapiens
2.1.1.45 N-[4-[2-(2,4-diaminoquinazolin-6-yl)ethyl]-2-fluorobenzoyl]-4-methylideneglutamic acid
-
 Homo sapiens
2.1.1.45 N-[4-[2-(2,4-diaminoquinazolin-6-yl)ethyl]benzoyl]-4-methylideneglutamic acid
-
 Homo sapiens
2.1.1.45 N-[4-[2-(2-amino-4-methylquinazolin-6-yl)ethyl]benzoyl]-4-methylideneglutamic acid
-
 Homo sapiens
2.1.2.2 N-(4-[[(2,4-diaminopteridin-6-yl)methyl](methyl)amino]benzoyl)-gamma-glutamyl-gamma-glutamyl-gamma-glutamyl-gamma-glutamylglutamic acid
-
 Homo sapiens
2.1.2.2 N-(4-[[(2,4-diaminopteridin-6-yl)methyl](methyl)amino]benzoyl)-gamma-glutamyl-gamma-glutamylglutamic acid
-
 Homo sapiens
2.1.2.2 N-(4-[[(2,4-diaminopteridin-6-yl)methyl](methyl)amino]benzoyl)glutamic acid
-
 Homo sapiens
2.1.2.2 N-([5-[2-(2,4-diaminoquinazolin-6-yl)ethyl]-2,3-dihydrothiophen-2-yl]carbonyl)-4-methylideneglutamic acid
-
 Homo sapiens
2.1.2.2 N-[4-[2-(2,4-diamino-7H-pyrrolo[2,3-d]pyrimidin-5-yl)ethyl]benzoyl]-4-methylideneglutamic acid
-
 Homo sapiens
2.1.2.2 N-[4-[2-(2,4-diaminopyrido[3,2-d]pyrimidin-6-yl)ethyl]benzoyl]-4-methylideneglutamic acid
-
 Homo sapiens
2.1.2.2 N-[4-[2-(2,4-diaminoquinazolin-6-yl)ethyl]-2-fluorobenzoyl]-4-methylideneglutamic acid
-
 Homo sapiens
2.1.2.2 N-[4-[2-(2,4-diaminoquinazolin-6-yl)ethyl]benzoyl]-4-methylideneglutamic acid
-
 Homo sapiens
2.1.2.2 N-[4-[2-(2-amino-4-methylquinazolin-6-yl)ethyl]benzoyl]-4-methylideneglutamic acid
-
 Homo sapiens
2.1.2.3 2-[[([4-[2-(2,4-diamino-7H-pyrrolo[2,3-d]pyrimidin-5-yl)ethyl]phenyl]carbonyl)amino]methyl]-3-methylidenebutanedioic acid weak inhibition of enzymes of folate metabolism relevant to rheumatoid arthritis therapy such as thymidylate synthase EC 2.1.1.45, two formyltransferases of purine biosynthesis EC 2.1.2.2 and EC 2.1.2.3, and 5,10-methylenetetrahydrofolate reductase EC 1.5.1.20. Potent inhibition of dihydrofolate reductase Homo sapiens
2.1.2.3 2-[[([4-[2-(2,4-diaminopyrido[3,2-d]pyrimidin-6-yl)ethyl]phenyl]carbonyl)amino]methyl]-3-methylidenebutanedioic acid weak inhibition of enzymes of folate metabolism relevant to rheumatoid arthritis therapy such as thymidylate synthase EC 2.1.1.45, two formyltransferases of purine biosynthesis EC 2.1.2.2 and EC 2.1.2.3, and 5,10-methylenetetrahydrofolate reductase EC 1.5.1.20. Potent inhibition of dihydrofolate reductase Homo sapiens
2.1.2.3 2-[[([4-[2-(2,4-diaminoquinazolin-6-yl)ethyl]-2-fluorophenyl]carbonyl)amino]methyl]-3-methylidenebutanedioic acid weak inhibition of enzymes of folate metabolism relevant to rheumatoid arthritis therapy such as thymidylate synthase EC 2.1.1.45, two formyltransferases of purine biosynthesis EC 2.1.2.2 and EC 2.1.2.3, and 5,10-methylenetetrahydrofolate reductase EC 1.5.1.20. Potent inhibition of dihydrofolate reductase Homo sapiens
2.1.2.3 2-[[([4-[2-(2-amino-4-methylquinazolin-6-yl)ethyl]phenyl]carbonyl)amino]methyl]-3-methylidenebutanedioic acid weak inhibition of enzymes of folate metabolism relevant to rheumatoid arthritis therapy such as thymidylate synthase EC 2.1.1.45, two formyltransferases of purine biosynthesis EC 2.1.2.2 and EC 2.1.2.3, and 5,10-methylenetetrahydrofolate reductase EC 1.5.1.20. Potent inhibition of dihydrofolate reductase Homo sapiens
2.1.2.3 2-[[([5-[2-(2,4-diaminoquinazolin-6-yl)ethyl]-2,5-dihydrothiophen-2-yl]carbonyl)amino]methyl]-3-methylidenebutanedioic acid weak inhibition of enzymes of folate metabolism relevant to rheumatoid arthritis therapy such as thymidylate synthase EC 2.1.1.45, two formyltransferases of purine biosynthesis EC 2.1.2.2 and EC 2.1.2.3, and 5,10-methylenetetrahydrofolate reductase EC 1.5.1.20. Potent inhibition of dihydrofolate reductase Homo sapiens
2.1.2.3 4-amino-4-deoxy-5,8,10-trideazapteroyl-D,L-40-methyleneglutamic acid weak inhibition of enzymes of folate metabolism relevant to rheumatoid arthritis therapy such as thymidylate synthase EC 2.1.1.45, two formyltransferases of purine biosynthesis EC 2.1.2.2 and EC 2.1.2.3, and 5,10-methylenetetrahydrofolate reductase EC 1.5.1.20. Potent inhibition of dihydrofolate reductase Homo sapiens
2.1.2.3 N-(4-[[(2,4-diaminopteridin-6-yl)methyl](methyl)amino]benzoyl)-gamma-glutamyl-gamma-glutamyl-gamma-glutamyl-gamma-glutamylglutamic acid
-
 Homo sapiens
2.1.2.3 N-(4-[[(2,4-diaminopteridin-6-yl)methyl](methyl)amino]benzoyl)-gamma-glutamyl-gamma-glutamylglutamic acid
-
 Homo sapiens
2.1.2.3 N-(4-[[(2,4-diaminopteridin-6-yl)methyl](methyl)amino]benzoyl)glutamic acid
-
 Homo sapiens
2.1.2.3 N-([5-[2-(2,4-diaminoquinazolin-6-yl)ethyl]-2,3-dihydrothiophen-2-yl]carbonyl)-4-methylideneglutamic acid
-
 Homo sapiens
2.1.2.3 N-[4-[2-(2,4-diamino-7H-pyrrolo[2,3-d]pyrimidin-5-yl)ethyl]benzoyl]-4-methylideneglutamic acid
-
 Homo sapiens
2.1.2.3 N-[4-[2-(2,4-diaminopyrido[3,2-d]pyrimidin-6-yl)ethyl]benzoyl]-4-methylideneglutamic acid
-
 Homo sapiens
2.1.2.3 N-[4-[2-(2,4-diaminoquinazolin-6-yl)ethyl]-2-fluorobenzoyl]-4-methylideneglutamic acid
-
 Homo sapiens
2.1.2.3 N-[4-[2-(2,4-diaminoquinazolin-6-yl)ethyl]benzoyl]-4-methylideneglutamic acid
-
 Homo sapiens
2.1.2.3 N-[4-[2-(2-amino-4-methylquinazolin-6-yl)ethyl]benzoyl]-4-methylideneglutamic acid
-
 Homo sapiens

Organism

EC Number Organism UniProt Comment Textmining
1.5.1.3 Homo sapiens
-
-
-
1.5.1.20 Homo sapiens
-
-
-
2.1.1.45 Homo sapiens
-
-
-
2.1.2.2 Homo sapiens
-
-
-
2.1.2.3 Homo sapiens
-
-
-

Purification (Commentary)

EC Number Purification (Comment) Organism
1.5.1.3
-
 Homo sapiens
1.5.1.20
-
 Homo sapiens
2.1.1.45
-
 Homo sapiens
2.1.2.2
-
 Homo sapiens
2.1.2.3
-
 Homo sapiens

Source Tissue

EC Number Source Tissue Comment Organism Textmining
1.5.1.3 CCRF-CEM cell
-
 Homo sapiens
-
2.1.1.45 CCRF-CEM cell
-
 Homo sapiens
-
2.1.2.2 CCRF-CEM cell
-
 Homo sapiens
-
2.1.2.3 CCRF-CEM cell
-
 Homo sapiens
-

Substrates and Products (Substrate)

EC Number Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
1.5.1.3 7,8-dihydrofolate + NADPH + H+ assay at 37°C Homo sapiens 5,6,7,8-tetrahydrofolate + NADP+
-
 ?
1.5.1.20 (6R,S)-5,10-methylenetetrahydrofolate + ? assay at 25°C Homo sapiens ?
-
 ?
2.1.2.2 beta-glycinamide ribonucleotide + ATP + formate assay at 25°C Homo sapiens beta-formylglycinamide ribonucleotide + ADP
-
 ?
2.1.2.3 10-formyl-tetrahydrofolic acid + 5'-phosphoribosyl-5-amino-imidazole-carboxamide
-
 Homo sapiens 5,6,7,8-tetrahydrofolic acid + 5'-phosphoribosyl-5-formamido-4-imidazole-4-carboxamide
-
 ?
2.1.2.3 10-formyltetrahydrofolate + 5'-phosphoribosyl-5-amino-imidazole-4-carboxamide
-
 Homo sapiens tetrahdrofolic acid + 5'-phosphoribosyl-5-formamido-4-imidazole-4-carboxamide
-
 ?

Synonyms

EC Number Synonyms Comment Organism
1.5.1.3 DHFR
-
 Homo sapiens
1.5.1.3 dihydrofolate reductase
-
 Homo sapiens
1.5.1.20 5,10-methylenetetrahydrofolate reductase
-
 Homo sapiens
1.5.1.20 MTHFR
-
 Homo sapiens
2.1.1.45 thymidylate synthase
-
 Homo sapiens
2.1.1.45 TMPS
-
 Homo sapiens
2.1.2.2 GAR formyltransferase
-
 Homo sapiens
2.1.2.2 GARFT
-
 Homo sapiens
2.1.2.2 glycinamide ribotide formyltransferase
-
 Homo sapiens
2.1.2.3 5-amino-4-imidazolecarboxamide ribotide formyltransferase
-
 Homo sapiens
2.1.2.3 AICAR formyltransferase
-
 Homo sapiens
2.1.2.3 AICARFT
-
 Homo sapiens

Temperature Optimum [°C]

EC Number Temperature Optimum [°C] Temperature Optimum Maximum [°C] Comment Organism
1.5.1.3 37
-
 assay at Homo sapiens
1.5.1.20 25
-
 assay at Homo sapiens
2.1.2.2 25
-
 assay at Homo sapiens

IC50 Value

EC Number IC50 Value IC50 Value Maximum Comment Organism Inhibitor Structure
1.5.1.3 0.00000045
-
-
 Homo sapiens N-(4-[[(2,4-diaminopteridin-6-yl)methyl](methyl)amino]benzoyl)glutamic acid
1.5.1.3 0.00000165
-
-
 Homo sapiens N-[4-[2-(2,4-diaminoquinazolin-6-yl)ethyl]-2-fluorobenzoyl]-4-methylideneglutamic acid
1.5.1.3 0.0000018
-
-
 Homo sapiens N-[4-[2-(2,4-diaminopyrido[3,2-d]pyrimidin-6-yl)ethyl]benzoyl]-4-methylideneglutamic acid
1.5.1.3 0.0000027
-
-
 Homo sapiens N-([5-[2-(2,4-diaminoquinazolin-6-yl)ethyl]-2,3-dihydrothiophen-2-yl]carbonyl)-4-methylideneglutamic acid
1.5.1.3 0.0000125
-
-
 Homo sapiens N-[4-[2-(2,4-diamino-7H-pyrrolo[2,3-d]pyrimidin-5-yl)ethyl]benzoyl]-4-methylideneglutamic acid
1.5.1.3 0.000073
-
-
 Homo sapiens N-[4-[2-(2-amino-4-methylquinazolin-6-yl)ethyl]benzoyl]-4-methylideneglutamic acid
1.5.1.20 additional information
-
 value above 0.048 Homo sapiens N-[4-[2-(2,4-diamino-7H-pyrrolo[2,3-d]pyrimidin-5-yl)ethyl]benzoyl]-4-methylideneglutamic acid
1.5.1.20 additional information
-
 value above 0.05 Homo sapiens N-[4-[2-(2-amino-4-methylquinazolin-6-yl)ethyl]benzoyl]-4-methylideneglutamic acid
1.5.1.20 0.0007
-
-
 Homo sapiens N-(4-[[(2,4-diaminopteridin-6-yl)methyl](methyl)amino]benzoyl)-gamma-glutamyl-gamma-glutamyl-gamma-glutamyl-gamma-glutamylglutamic acid
1.5.1.20 0.0012
-
-
 Homo sapiens N-[4-[2-(2,4-diaminoquinazolin-6-yl)ethyl]-2-fluorobenzoyl]-4-methylideneglutamic acid
1.5.1.20 0.0016
-
-
 Homo sapiens N-[4-[2-(2,4-diaminoquinazolin-6-yl)ethyl]benzoyl]-4-methylideneglutamic acid
1.5.1.20 0.0018
-
-
 Homo sapiens N-([5-[2-(2,4-diaminoquinazolin-6-yl)ethyl]-2,3-dihydrothiophen-2-yl]carbonyl)-4-methylideneglutamic acid
1.5.1.20 0.0022
-
-
 Homo sapiens N-(4-[[(2,4-diaminopteridin-6-yl)methyl](methyl)amino]benzoyl)-gamma-glutamyl-gamma-glutamylglutamic acid
1.5.1.20 0.0035
-
-
 Homo sapiens N-[4-[2-(2,4-diaminopyrido[3,2-d]pyrimidin-6-yl)ethyl]benzoyl]-4-methylideneglutamic acid
1.5.1.20 0.033
-
-
 Homo sapiens N-(4-[[(2,4-diaminopteridin-6-yl)methyl](methyl)amino]benzoyl)glutamic acid
2.1.1.45 additional information
-
 value above 0.05 Homo sapiens N-[4-[2-(2-amino-4-methylquinazolin-6-yl)ethyl]benzoyl]-4-methylideneglutamic acid
2.1.1.45 additional information
-
 value above 0.05 Homo sapiens N-[4-[2-(2,4-diamino-7H-pyrrolo[2,3-d]pyrimidin-5-yl)ethyl]benzoyl]-4-methylideneglutamic acid
2.1.1.45 additional information
-
 value above 0.05 Homo sapiens N-[4-[2-(2,4-diaminopyrido[3,2-d]pyrimidin-6-yl)ethyl]benzoyl]-4-methylideneglutamic acid
2.1.1.45 0.0048
-
-
 Homo sapiens N-[4-[2-(2,4-diaminoquinazolin-6-yl)ethyl]-2-fluorobenzoyl]-4-methylideneglutamic acid
2.1.1.45 0.0049
-
-
 Homo sapiens N-([5-[2-(2,4-diaminoquinazolin-6-yl)ethyl]-2,3-dihydrothiophen-2-yl]carbonyl)-4-methylideneglutamic acid
2.1.1.45 0.008
-
-
 Homo sapiens N-[4-[2-(2,4-diaminoquinazolin-6-yl)ethyl]benzoyl]-4-methylideneglutamic acid
2.1.1.45 0.047
-
-
 Homo sapiens N-(4-[[(2,4-diaminopteridin-6-yl)methyl](methyl)amino]benzoyl)glutamic acid
2.1.2.2 additional information
-
 value above 0.05 Homo sapiens N-(4-[[(2,4-diaminopteridin-6-yl)methyl](methyl)amino]benzoyl)glutamic acid
2.1.2.2 additional information
-
 value above 0.05 Homo sapiens N-[4-[2-(2-amino-4-methylquinazolin-6-yl)ethyl]benzoyl]-4-methylideneglutamic acid
2.1.2.2 additional information
-
 value above 0.05 Homo sapiens N-([5-[2-(2,4-diaminoquinazolin-6-yl)ethyl]-2,3-dihydrothiophen-2-yl]carbonyl)-4-methylideneglutamic acid
2.1.2.2 additional information
-
 value above 0.05 Homo sapiens N-[4-[2-(2,4-diamino-7H-pyrrolo[2,3-d]pyrimidin-5-yl)ethyl]benzoyl]-4-methylideneglutamic acid
2.1.2.2 additional information
-
 value above 0.05 Homo sapiens N-[4-[2-(2,4-diaminoquinazolin-6-yl)ethyl]-2-fluorobenzoyl]-4-methylideneglutamic acid
2.1.2.2 additional information
-
 value above 0.05 Homo sapiens N-[4-[2-(2,4-diaminopyrido[3,2-d]pyrimidin-6-yl)ethyl]benzoyl]-4-methylideneglutamic acid
2.1.2.2 additional information
-
 value above 0.05 Homo sapiens N-[4-[2-(2,4-diaminoquinazolin-6-yl)ethyl]benzoyl]-4-methylideneglutamic acid
2.1.2.3 additional information
-
 value above 0.05 Homo sapiens N-(4-[[(2,4-diaminopteridin-6-yl)methyl](methyl)amino]benzoyl)glutamic acid
2.1.2.3 additional information
-
 value above 0.05 Homo sapiens N-[4-[2-(2-amino-4-methylquinazolin-6-yl)ethyl]benzoyl]-4-methylideneglutamic acid
2.1.2.3 additional information
-
 value above 0.05 Homo sapiens N-([5-[2-(2,4-diaminoquinazolin-6-yl)ethyl]-2,3-dihydrothiophen-2-yl]carbonyl)-4-methylideneglutamic acid
2.1.2.3 additional information
-
 value above 0.05 Homo sapiens N-[4-[2-(2,4-diamino-7H-pyrrolo[2,3-d]pyrimidin-5-yl)ethyl]benzoyl]-4-methylideneglutamic acid
2.1.2.3 additional information
-
 value above 0.05 Homo sapiens N-[4-[2-(2,4-diaminoquinazolin-6-yl)ethyl]-2-fluorobenzoyl]-4-methylideneglutamic acid
2.1.2.3 additional information
-
 value above 0.05 Homo sapiens N-[4-[2-(2,4-diaminopyrido[3,2-d]pyrimidin-6-yl)ethyl]benzoyl]-4-methylideneglutamic acid
2.1.2.3 additional information
-
 value above 0.05 Homo sapiens N-[4-[2-(2,4-diaminoquinazolin-6-yl)ethyl]benzoyl]-4-methylideneglutamic acid