Detailed information for compound 300460
Basic information
Technical information
- TDR Targets ID: 300460
- Name: 2-[[4-[(4-oxo-1H-quinazolin-6-yl)methyl-prop- 2-ynylamino]benzoyl]amino]pentanedioic acid
- MW: 462.455 | Formula: C24H22N4O6
-
H donors: 4
H acceptors: 8
LogP: 2.01
Rotable bonds: 11
Rule of 5 violations (Lipinski): 1 - SMILES: C#CCN(c1ccc(cc1)C(=O)NC(C(=O)O)CCC(=O)O)Cc1ccc2c(c1)c(O)ncn2
- InChi: 1S/C24H22N4O6/c1-2-11-28(13-15-3-8-19-18(12-15)23(32)26-14-25-19)17-6-4-16(5-7-17)22(31)27-20(24(33)34)9-10-21(29)30/h1,3-8,12,14,20H,9-11,13H2,(H,27,31)(H,29,30)(H,33,34)(H,25,26,32)
- InChiKey: AOGOUTMDEVCZHA-UHFFFAOYSA-N
Network
Hover on a compound node to display the structore
Synonyms
- 2-[[4-[(4-oxo-1H-quinazolin-6-yl)methyl-prop-2-ynyl-amino]benzoyl]amino]pentanedioic acid
- 2-[[oxo-[4-[(4-oxo-1H-quinazolin-6-yl)methyl-prop-2-ynylamino]phenyl]methyl]amino]pentanedioic acid
- 2-[[4-[(4-oxo-1H-quinazolin-6-yl)methyl-prop-2-ynyl-amino]phenyl]carbonylamino]pentanedioic acid
- 2-[[4-[(4-keto-1H-quinazolin-6-yl)methyl-propargyl-amino]benzoyl]amino]glutaric acid
Targets
Known targets for this compound
| Species | Target name | Source | Bibliographic reference |
|---|---|---|---|
| Homo sapiens | thymidylate synthetase | Starlite/ChEMBL | References |
| Mus musculus | thymidylate synthase | Starlite/ChEMBL | References |
| Lactobacillus casei | Thymidylate synthase | Starlite/ChEMBL | References |
| Lactobacillus casei | Dihydrofolate reductase | Starlite/ChEMBL | References |
| Homo sapiens | dihydrofolate reductase | Starlite/ChEMBL | References |
| Rattus norvegicus | Dihydrofolate reductase | Starlite/ChEMBL | References |
Predicted pathogen targets for this compound
By orthology
By sequence similarity to non orthologous known druggable targets
Obtained from network model
Ranking Plot
Putative Targets List
| Species | Potential target | Raw | Global | Species |
|---|---|---|---|---|
| Mycobacterium tuberculosis | Probable thymidylate synthase ThyA (ts) (TSASE) | 0.0584 | 0.5625 | 0.8875 |
| Chlamydia trachomatis | dihydrofolate reductase | 0.0623 | 0.6338 | 0.5 |
| Mycobacterium leprae | DIHYDROFOLATE REDUCTASE DFRA (DHFR) (TETRAHYDROFOLATE DEHYDROGENASE) | 0.0623 | 0.6338 | 1 |
| Echinococcus multilocularis | dihydrofolate reductase | 0.0623 | 0.6338 | 1 |
| Loa Loa (eye worm) | dihydrofolate reductase | 0.0623 | 0.6338 | 1 |
| Brugia malayi | Dihydrofolate reductase | 0.0623 | 0.6338 | 1 |
| Plasmodium vivax | bifunctional dihydrofolate reductase-thymidylate synthase, putative | 0.0822 | 1 | 0.5 |
| Echinococcus granulosus | dihydrofolate reductase | 0.0623 | 0.6338 | 1 |
| Brugia malayi | thymidylate synthase | 0.0584 | 0.5625 | 0.8875 |
| Toxoplasma gondii | bifunctional dihydrofolate reductase-thymidylate synthase | 0.0822 | 1 | 0.5 |
| Schistosoma mansoni | dihydrofolate reductase | 0.0623 | 0.6338 | 1 |
| Mycobacterium tuberculosis | Dihydrofolate reductase DfrA (DHFR) (tetrahydrofolate dehydrogenase) | 0.0623 | 0.6338 | 1 |
| Mycobacterium ulcerans | dihydrofolate reductase DfrA | 0.0623 | 0.6338 | 1 |
| Plasmodium falciparum | bifunctional dihydrofolate reductase-thymidylate synthase | 0.0822 | 1 | 0.5 |
| Trichomonas vaginalis | conserved hypothetical protein | 0.0278 | 0 | 0.5 |
| Trypanosoma cruzi | dihydrofolate reductase-thymidylate synthase | 0.0822 | 1 | 1 |
| Onchocerca volvulus | 0.0584 | 0.5625 | 0.5 | |
| Trypanosoma brucei | dihydrofolate reductase-thymidylate synthase | 0.0822 | 1 | 0.5 |
| Brugia malayi | dihydrofolate reductase family protein | 0.0623 | 0.6338 | 1 |
Activities
| Activity type | Activity value | Assay description | Source | Reference |
|---|---|---|---|---|
| I50 (binding) | = 0.13 uM | Inhibition of L1210 leukemia thymidylate synthase (TS) enzyme | ChEMBL. | 2704031 |
| I50 (binding) | = 7 uM | Inhibition of human WIL2/dihydrofolate reductase activity | ChEMBL. | 2704031 |
| IC50 (binding) | = 0.13 uM | Inhibition of L1210 leukemia thymidylate synthase (TS) enzyme | ChEMBL. | 2704031 |
| IC50 (binding) | = 0.16 uM | Inhibitory concentration of compound to inhibit Thymidylate synthase (TS) in L1210 cells at conc. of 200 microM | ChEMBL. | 2704030 |
| IC50 (binding) | = 0.16 uM | Inhibitory concentration of compound to inhibit Thymidylate synthase (TS) in L1210 cells at conc. of 200 microM | ChEMBL. | 2704030 |
| IC50 (binding) | = 0.16 uM | The compound was not tested for inhibition of L1210 Thymidylate synthase due to insolubility | ChEMBL. | 2362285 |
| IC50 (functional) | = 0.27 uM | Inhibition of the growth of methotrexate sensitve L1210 leukemia/S cells in culture | ChEMBL. | 2704031 |
| IC50 (functional) | = 0.27 uM | Inhibition of the growth of methotrexate sensitve L1210 leukemia/S cells in culture | ChEMBL. | 2704031 |
| IC50 (functional) | = 0.4 uM | Tested for 50% inhibition of L1210 cell growth in vitro | ChEMBL. | 2362285 |
| IC50 (functional) | = 0.4 uM | Tested for 50% inhibition of L1210 cell growth in vitro | ChEMBL. | 2362285 |
| IC50 (binding) | = 7 uM | Inhibition of human WIL2/dihydrofolate reductase activity | ChEMBL. | 2704031 |
| IC50 (functional) | = 75 uM | Inhibition of the growth of methotrexate resistant L1210 leukemia/R 81 cells in culture | ChEMBL. | 2704031 |
| IC50 (functional) | = 75 uM | Inhibition of the growth of methotrexate resistant L1210 leukemia/R 81 cells in culture | ChEMBL. | 2704031 |
| ID50 (functional) | = 0.4 uM | Compound was evaluated for inhibition dose required to inhibit the growth of L1210 cells in culture. | ChEMBL. | 2704030 |
| ID50 (functional) | = 0.4 uM | Compound was evaluated for inhibition dose required to inhibit the growth of L1210 cells in culture. | ChEMBL. | 2704030 |
| Ki (binding) | = 26 nM | Binding affinity of the compound against thymidylate synthase | ChEMBL. | 1995868 |
| Ki (binding) | = 26 nM | Binding affinity of the compound against thymidylate synthase | ChEMBL. | 1995868 |
| Ki (binding) | = 2250 nM | Compound was evaluated for the inhibition of partially purified rat liver Dihydrofolate reductase (DHFR) enzyme. | ChEMBL. | 2704030 |
| Ki (binding) | = 2250 nM | Compound was evaluated for the inhibition of partially purified rat liver Dihydrofolate reductase (DHFR) enzyme. | ChEMBL. | 2704030 |
| Ki (binding) | = 2.5 uM | Binding affinity of the compound against Dihydrofolate reductase | ChEMBL. | 1995868 |
| Ki (binding) | = 2.5 uM | Binding affinity of the compound against Dihydrofolate reductase | ChEMBL. | 1995868 |
| ND (binding) | = 0.16 uM | The compound was not tested for inhibition of L1210 Thymidylate synthase due to insolubility | ChEMBL. | 2362285 |
| Solubility | = 0.043 mg ml-1 | Solubility of the compound at pH 5 | ChEMBL. | 2704030 |
| Solubility | > 107 mg ml-1 | Solubility of the compound at pH 7.4 | ChEMBL. | 2704030 |
| Toxicity (ADMET) | Renal or hepatic toxicities observed in mice after the intravenous administration of 100 mg/kg | ChEMBL. | 1995868 | |
| Toxicity (ADMET) | 0 | Renal or hepatic toxicities observed in mice after the intravenous administration of 100 mg/kg | ChEMBL. | 1995868 |
Phenotypes
Whole-cell/tissue/organism interactions
| Species name | Source | Reference | Is orphan |
|---|---|---|---|
| Mus musculus | ChEMBL23 | 2362285 |
Many chemical entities in TDR Targets come from high-throughput screenings with whole cells or tissue samples, and not all assayed compounds have been tested against a single a single target protein, probably because they get ruled out during screening process. Even if these compounds may have not been of interest in the original screening, they may come as interesting leads for other screening assays. Furthermore, we may be able to propose drug-target associations using chemical similarities and network patterns.
Annotated phenotypes:
We have no manually annotated phenotypes for this drug.
What does this mean? / Care to help?
In TDR Targets, information about phenotypes that are caused by
drugs, or by genetic manipulation of cells (e.g. gene knockouts or
knockdowns) is manually curated from the literature. These
descriptions help to describe the potential of the target for drug
development. If no information is available for this gene or if the
information is incomplete, this may mean that i) the papers
containing this information either appeared after the curation
effort for this organism was carried out or they were inadvertently
missed by curators; or that ii) the curation effort for this
organism has not yet started.
In any case, if you have information about papers containing relevant validation data for this target, please log in using your TDR Targets username and password and send them to us using the corresponding form in this page (only visible to registered users) or contact us.
In any case, if you have information about papers containing relevant validation data for this target, please log in using your TDR Targets username and password and send them to us using the corresponding form in this page (only visible to registered users) or contact us.
External resources for this compound
- ChEMBL: CHEMBL171480
- PubChem: 10073043
Bibliographic References
4 literature references were collected for this gene.
If you have references for this compound, please enter them in a user comment (below) or Contact us.