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Literature summary for 2.1.1.45 extracted from

  • Gangjee, A.; Li, W.; Yang, J.; Kisliuk, R.L.
    Design, synthesis, and biological evaluation of classical and nonclassical 2-amino-4-oxo-5-substituted-6-methylpyrrolo[3,2-d]pyrimidines as dual thymidylate synthase and dihydrofolate reductase inhibitors (2008), J. Med. Chem., 51, 68-76.
    View publication on PubMedView publication on EuropePMC
Search for more literature for 2.1.1.45

Application

Application Comment Organism
medicine inhibition of thymidylate synthase and DHFR enzymes has found clinical utility as antitumor, antimicrobial and antiprotozoal agents Homo sapiens
medicine inhibition of TS and DHFR enzymes has found clinical utility as antitumor, antimicrobial and antiprotozoal agent Toxoplasma gondii
medicine inhibition of TS and DHFR enzymes has found clinical utility as antitumor, antimicrobial and antiprotozoal agents Escherichia coli

Inhibitors

Inhibitors Comment Organism Structure
(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 Escherichia coli
(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 Homo sapiens
10-propargyl-5,8-dideazafolate PDDF Escherichia coli
10-propargyl-5,8-dideazafolate PDDF Homo sapiens
10-propargyl-5,8-dideazafolate PDDF Toxoplasma gondii
N-(4-((2-amino-6-methyl-4-oxo-3,4-dihydro-5H-pyrrolo(3,2-d)pyrimidin-5-yl)methyl)benzoyl)-L-glutamic acid
-
 Escherichia coli
N-(4-((2-amino-6-methyl-4-oxo-3,4-dihydro-5H-pyrrolo(3,2-d)pyrimidin-5-yl)methyl)benzoyl)-L-glutamic acid
-
 Homo sapiens
N-(4-((2-amino-6-methyl-4-oxo-3,4-dihydro-5H-pyrrolo(3,2-d)pyrimidin-5-yl)methyl)benzoyl)-L-glutamic acid
-
 Toxoplasma gondii
N-(4-((2-amino-6-methyl-4-oxo-4,7-dihydro-3H-pyrrolo(2,3-d)pyrimidin-5-yl)thio)benzoyl)-L-glutamic acid
-
 Escherichia coli
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-4,7-dihydro-3H-pyrrolo(2,3-d)pyrimidin-5-yl)thio)benzoyl)-L-glutamic acid
-
 Toxoplasma gondii
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 Escherichia coli
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 Homo sapiens
pemetrexed
-
 Escherichia coli
pemetrexed
-
 Homo sapiens
pemetrexed
-
 Toxoplasma gondii

Natural Substrates/ Products (Substrates)

Natural Substrates Organism Comment (Nat. Sub.) Natural Products Comment (Nat. Pro.) Rev. Reac.
5,10-methylenetetrahydrofolate + dUMP Escherichia coli
-
 7,8-dihydrofolate + dTMP
-
 ?
5,10-methylenetetrahydrofolate + dUMP Homo sapiens
-
 7,8-dihydrofolate + dTMP
-
 ?
5,10-methylenetetrahydrofolate + dUMP Toxoplasma gondii
-
 7,8-dihydrofolate + dTMP
-
 ?

Organism

Organism UniProt Comment Textmining
Escherichia coli
-
-
-
Homo sapiens
-
-
-
Toxoplasma gondii
-
-
-

Substrates and Products (Substrate)

Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
5,10-methylenetetrahydrofolate + dUMP
-
 Escherichia coli 7,8-dihydrofolate + dTMP
-
 ?
5,10-methylenetetrahydrofolate + dUMP
-
 Homo sapiens 7,8-dihydrofolate + dTMP
-
 ?
5,10-methylenetetrahydrofolate + dUMP
-
 Toxoplasma gondii 7,8-dihydrofolate + dTMP
-
 ?

Synonyms

Synonyms Comment Organism
TS-DHFR
-
 Escherichia coli
TS-DHFR
-
 Homo sapiens
TS-DHFR
-
 Toxoplasma gondii

Cofactor

Cofactor Comment Organism Structure
methenyltetrahydrofolate
-
 Escherichia coli
methenyltetrahydrofolate
-
 Homo sapiens
methenyltetrahydrofolate
-
 Toxoplasma gondii

IC50 Value

IC50 Value IC50 Value Maximum Comment Organism Inhibitor Structure
0.000019
-
-
 Escherichia coli 10-propargyl-5,8-dideazafolate
0.000046
-
-
 Homo sapiens N-[4-[(2-amino-6-methyl-4-oxo-3,4-dihydro-5H-pyrrolo[3,2-d]pyrimidin-5-yl)methyl]benzoyl]-L-glutamic acid
0.000046
-
 potent dual inhibitor of human TS and human DHFR, 2-fold more potent than PDDF and 206-fold more potent than pemetrexed Homo sapiens N-(4-((2-amino-6-methyl-4-oxo-3,4-dihydro-5H-pyrrolo(3,2-d)pyrimidin-5-yl)methyl)benzoyl)-L-glutamic acid
0.000054
-
-
 Homo sapiens (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
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
0.000069
-
-
 Escherichia coli N-[4-[(2-amino-6-methyl-4-oxo-3,4-dihydro-5H-pyrrolo[3,2-d]pyrimidin-5-yl)methyl]benzoyl]-L-glutamic acid
0.000069
-
 potent inhibitor of human TS Escherichia coli N-(4-((2-amino-6-methyl-4-oxo-3,4-dihydro-5H-pyrrolo(3,2-d)pyrimidin-5-yl)methyl)benzoyl)-L-glutamic acid
0.000085
-
-
 Homo sapiens 10-propargyl-5,8-dideazafolate
0.00023
-
-
 Escherichia coli N-[4-[(2-amino-6-methyl-4-oxo-3,4-dihydro-5H-pyrrolo[3,2-d]pyrimidin-5-yl)methyl]benzoyl]-L-glutamic acid
0.00023
-
 moderate inhibitor of human thymidylate synthase Toxoplasma gondii N-(4-((2-amino-6-methyl-4-oxo-3,4-dihydro-5H-pyrrolo(3,2-d)pyrimidin-5-yl)methyl)benzoyl)-L-glutamic acid
0.00027
-
-
 Escherichia coli (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
0.00027
-
 moderate inhibitor of human TS Escherichia coli N-(4-((2-amino-6-methyl-4-oxo-4,7-dihydro-3H-pyrrolo(2,3-d)pyrimidin-5-yl)thio)benzoyl)-L-glutamic acid
0.00043
-
-
 Toxoplasma gondii 10-propargyl-5,8-dideazafolate
0.0028
-
-
 Toxoplasma gondii pemetrexed
0.0095
-
-
 Homo sapiens pemetrexed
0.076
-
-
 Escherichia coli pemetrexed