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Literature summary extracted from
- Structure-based approach to pharmacophore identification, in silico screening, and three-dimensional quantitative structure-activity relationship studies for inhibitors of Trypanosoma cruzi dihydrofolate reductase function (2008), Proteins, 73, 889-901.
Crystallization (Commentary)
| EC Number | Crystallization (Comment) | Organism |
|---|---|---|
| 1.5.1.3 | structure-based three-dimensional quantitative structure-activity relationship 3D-QSAR approach to predict the biochemical activity for inhibitors of Trypanosoma cruzi dihydrofolate reductase-thymidylate synthase. Crystal structures of complexes of the enzyme with eight different inhibitors of the DHFR activity together with the structure in the substrate-free state have been used to validate and refine docking poses of ligands | Homo sapiens |
| 1.5.1.3 | structure-based three-dimensional quantitative structureactivity relationship 3D-QSAR approach to predict the biochemical activity for inhibitors of Trypanosoma cruzi dihydrofolate reductase-thymidylate synthase. Crystal structures of complexes of the enzymewith eight different inhibitors of the DHFR activity together with the structure in the substrate-free state have been used to validate and refine docking poses of ligands | Trypanosoma cruzi |
Inhibitors
| EC Number | Inhibitors | Comment | Organism | Structure |
|---|---|---|---|---|
| 1.5.1.3 | 2-[(3-[3-[(2,4-diaminopyrimidin-5-yl)methyl]-4-methoxyphenyl]prop-2-yn-1-yl)oxy]benzoic acid | ratio of IC50 values human/Trypanosoma enzyme 47 | Homo sapiens |  |
| 1.5.1.3 | 2-[(3-[3-[(2,4-diaminopyrimidin-5-yl)methyl]-4-methoxyphenyl]prop-2-yn-1-yl)oxy]benzoic acid | ratio of IC50 values human/Trypanosoma enzyme 47 | Trypanosoma cruzi | |
| 1.5.1.3 | 3-((3-[(2,4-diaminopyrimidin-5-yl)methyl]-4-methoxyphenoxy)methyl)benzoic acid | ratio of IC50 values human/Trypanosoma enzyme is 86 | Homo sapiens | |
| 1.5.1.3 | 3-((3-[(2,4-diaminopyrimidin-5-yl)methyl]-4-methoxyphenoxy)methyl)benzoic acid | ratio of IC50 values human/Trypanosoma enzyme is 86 | Trypanosoma cruzi | |
| 1.5.1.3 | 3-[(3-(3-[(2,4-diaminopyrimidin-5-yl)methyl]-4-methoxyphenyl)prop-2-yn-1-yl)oxy]benzoic acid | ratio of IC50 values human/Trypanosoma enzyme is 77 | Homo sapiens | |
| 1.5.1.3 | 3-[(3-[3-[(2,4-diaminopyrimidin-5-yl)methyl]-4-methoxyphenyl]prop-2-yn-1-yl)oxy]benzoic acid | ratio of IC50 values human/Trypanosoma enzyme is 77 | Trypanosoma cruzi | |
| 1.5.1.3 | 4-((5-[(2,4-diaminopyrimidin-5-yl)methyl]-2,3-dimethoxyphenyl)ethynyl)benzoic acid | ratio of IC50 values human/Trypanosoma enzyme is 129 | Homo sapiens | |
| 1.5.1.3 | 4-((5-[(2,4-diaminopyrimidin-5-yl)methyl]-2,3-dimethoxyphenyl)ethynyl)benzoic acid | ratio of IC50 values human/Trypanosoma enzyme is 129 | Trypanosoma cruzi | |
| 1.5.1.3 | 6-[[(2,5-diethoxyphenyl)amino]methyl]-5-methylpyrido[2,3-d]pyrimidine-2,4-diamine | - |
Homo sapiens | |
| 1.5.1.3 | 6-[[(2,5-diethoxyphenyl)amino]methyl]-5-methylpyrido[2,3-d]pyrimidine-2,4-diamine | - |
Trypanosoma cruzi | |
| 1.5.1.3 | 7-[5-[(2,4-diaminopyrimidin-5-yl)methyl]-2,3-dimethoxyphenyl]hept-6-ynoic acid | ratio of IC50 values human/Trypanosoma enzyme is 49 | Homo sapiens | |
| 1.5.1.3 | 7-[5-[(2,4-diaminopyrimidin-5-yl)methyl]-2,3-dimethoxyphenyl]hept-6-ynoic acid | ratio of IC50 values human/Trypanosoma enzyme is 49 | Trypanosoma cruzi | |
| 1.5.1.3 | additional information | structure-based three-dimensional quantitative structure-activity relationship 3D-QSAR approach to predict the biochemical activity for inhibitors of Trypanosoma cruzi dihydrofolate reductase-thymidylate synthase and comparison with human dihydrofolate reductase. Crystal structures of complexes of the enzyme with eight different inhibitors of the DHFR activity together with the structure in the substrate-free state have been used to validate and refine docking poses of ligands, good agreement between experimental and predicted enzyme inhibition data | Homo sapiens | |
| 1.5.1.3 | additional information | structure-based three-dimensional quantitative structure-activity relationship 3D-QSAR approach to predict the biochemical activity for inhibitors of Trypanosoma cruzi dihydrofolate reductase-thymidylate synthase. Crystal structures of complexes of the enzyme with eight different inhibitors of the DHFR activity together with the structure in the substrate-free state have been used to validate and refine docking poses of ligands, good agreement between experimental and predicted enzyme inhibition data | Trypanosoma cruzi | |
| 1.5.1.3 | trimetrexate | - |
Homo sapiens | |
| 1.5.1.3 | trimetrexate | - |
Trypanosoma cruzi | |
Organism
| EC Number | Organism | UniProt | Comment | Textmining |
|---|---|---|---|---|
| 1.5.1.3 | Homo sapiens | P00374 | - |
- |
| 1.5.1.3 | Trypanosoma cruzi | Q27793 | - |
- |
Substrates and Products (Substrate)
| EC Number | Substrates | Comment Substrates | Organism | Products | Comment (Products) | Rev. | Reac. |
|---|---|---|---|---|---|---|---|
| 1.5.1.3 | 7,8-dihydrofolate + NADPH + H+ | - |
Homo sapiens | 5,6,7,8-tetrahydrofolate + NADP+ | - |
? | |
| 1.5.1.3 | 7,8-dihydrofolate + NADPH + H+ | - |
Trypanosoma cruzi | 5,6,7,8-tetrahydrofolate + NADP+ | - |
? | |
Ki Value [mM]
| EC Number | Ki Value [mM] | Ki Value maximum [mM] | Inhibitor | Comment | Organism | Structure |
|---|---|---|---|---|---|---|
| 1.5.1.3 | 0.0000094 | - |
4-((5-[(2,4-diaminopyrimidin-5-yl)methyl]-2,3-dimethoxyphenyl)ethynyl)benzoic acid | pH 7.0 | Trypanosoma cruzi | |
| 1.5.1.3 | 0.0000122 | - |
7-[5-[(2,4-diaminopyrimidin-5-yl)methyl]-2,3-dimethoxyphenyl]hept-6-ynoic acid | pH 7.0 | Trypanosoma cruzi | |
IC50 Value
| EC Number | IC50 Value | IC50 Value Maximum | Comment | Organism | Inhibitor | Structure |
|---|---|---|---|---|---|---|
| 1.5.1.3 | 0.0000225 | - |
pH 7.0 | Trypanosoma cruzi | 4-((5-[(2,4-diaminopyrimidin-5-yl)methyl]-2,3-dimethoxyphenyl)ethynyl)benzoic acid | |
| 1.5.1.3 | 0.0000256 | - |
pH 7.0 | Trypanosoma cruzi | 7-[5-[(2,4-diaminopyrimidin-5-yl)methyl]-2,3-dimethoxyphenyl]hept-6-ynoic acid | |
| 1.5.1.3 | 0.0000515 | - |
pH 7.0 | Trypanosoma cruzi | 6-[[(2,5-diethoxyphenyl)amino]methyl]-5-methylpyrido[2,3-d]pyrimidine-2,4-diamine | |
| 1.5.1.3 | 0.000131 | - |
pH 7.0 | Trypanosoma cruzi | 2-[(3-[3-[(2,4-diaminopyrimidin-5-yl)methyl]-4-methoxyphenyl]prop-2-yn-1-yl)oxy]benzoic acid | |
| 1.5.1.3 | 0.000183 | - |
pH 7.0 | Trypanosoma cruzi | 3-[(3-[3-[(2,4-diaminopyrimidin-5-yl)methyl]-4-methoxyphenyl]prop-2-yn-1-yl)oxy]benzoic acid | |
| 1.5.1.3 | 0.000222 | - |
pH 7.0 | Trypanosoma cruzi | 3-((3-[(2,4-diaminopyrimidin-5-yl)methyl]-4-methoxyphenoxy)methyl)benzoic acid | |
| 1.5.1.3 | 0.001255 | - |
pH 7.0 | Homo sapiens | 7-[5-[(2,4-diaminopyrimidin-5-yl)methyl]-2,3-dimethoxyphenyl]hept-6-ynoic acid | |
| 1.5.1.3 | 0.0021 | - |
pH 7.0 | Trypanosoma cruzi | trimetrexate | |
| 1.5.1.3 | 0.0023 | - |
pH 7.0 | Homo sapiens | 6-[[(2,5-diethoxyphenyl)amino]methyl]-5-methylpyrido[2,3-d]pyrimidine-2,4-diamine | |
| 1.5.1.3 | 0.002898 | - |
pH 7.0 | Homo sapiens | 4-((5-[(2,4-diaminopyrimidin-5-yl)methyl]-2,3-dimethoxyphenyl)ethynyl)benzoic acid | |
| 1.5.1.3 | 0.0062 | - |
pH 7.0 | Homo sapiens | 2-[(3-[3-[(2,4-diaminopyrimidin-5-yl)methyl]-4-methoxyphenyl]prop-2-yn-1-yl)oxy]benzoic acid | |
| 1.5.1.3 | 0.014 | - |
pH 7.0 | Homo sapiens | 3-[(3-(3-[(2,4-diaminopyrimidin-5-yl)methyl]-4-methoxyphenyl)prop-2-yn-1-yl)oxy]benzoic acid | |
| 1.5.1.3 | 0.019 | - |
pH 7.0 | Homo sapiens | 3-((3-[(2,4-diaminopyrimidin-5-yl)methyl]-4-methoxyphenoxy)methyl)benzoic acid | |
| 1.5.1.3 | 0.248 | - |
pH 7.0 | Homo sapiens | trimetrexate | |
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