Detailed information for compound 608010
Basic information
Technical information
- TDR Targets ID: 608010
- Name: ethyl 4-[(4-ethoxyphenyl)methyl]-3,5-dimethyl -1H-pyrrole-2-carboxylate
- MW: 301.38 | Formula: C18H23NO3
-
H donors: 1
H acceptors: 1
LogP: 4.29
Rotable bonds: 7
Rule of 5 violations (Lipinski): 1 - SMILES: CCOc1ccc(cc1)Cc1c(C)[nH]c(c1C)C(=O)OCC
- InChi: 1S/C18H23NO3/c1-5-21-15-9-7-14(8-10-15)11-16-12(3)17(19-13(16)4)18(20)22-6-2/h7-10,19H,5-6,11H2,1-4H3
- InChiKey: AHTZIFIBNCSFEG-UHFFFAOYSA-N
Network
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Synonyms
- 4-[(4-ethoxyphenyl)methyl]-3,5-dimethyl-1H-pyrrole-2-carboxylic acid ethyl ester
- 4-(4-ethoxybenzyl)-3,5-dimethyl-1H-pyrrole-2-carboxylic acid ethyl ester
- 4-(4-Ethoxy-benzyl)-3,5-dimethyl-1H-pyrrole-2-carboxylic acid ethyl ester
- BAS 00690294
- CBDivE_010586
- Oprea1_172147
- Oprea1_137491
- STOCK2S-03371
- ZINC00198240
Targets
Known targets for this compound
| Species | Target name | Source | Bibliographic reference |
|---|---|---|---|
| Saccharomyces cerevisiae | dihydroorotate dehydrogenase | Starlite/ChEMBL | No references |
| Plasmodium berghei | dihydroorotate dehydrogenase, putative | No references | |
| Plasmodium vivax | dihydroorotate dehydrogenase, mitochondrial precursor, putative | No references | |
| Plasmodium falciparum | dihydroorotate dehydrogenase | Starlite/ChEMBL | No references |
Predicted pathogen targets for this compound
By orthology
By sequence similarity to non orthologous known druggable targets
No druggable targets predicted by sequence similarity
Obtained from network model
Ranking Plot
Putative Targets List
Activities
| Activity type | Activity value | Assay description | Source | Reference |
|---|---|---|---|---|
| Activity (functional) | NOVARTIS: Antimalarial liver stage activity measured as a greater than 50% reduction in Plasmodium yoelii schizont area in HepG2-A16-CD81 cells at 10uM compound concentration, determined by immuno-fluorescence. | ChEMBL. | 22096101 | |
| CC50 (functional) | > 100 uM | Huh7 cytotoxicity for Pf inhibitors | Novartis-GNF Malaria Box. | No reference |
| CC50 | > 100 uM | NOVARTIS: Cytotoxicity against human hepatocellular carcinoma cell line (Huh7) | ChEMBL. | 18579783 |
| EC50 (functional) | = 0.2787 uM | PF proliferation inhibition 3D7 | Novartis-GNF Malaria Box. | No reference |
| EC50 (functional) | = 0.2787 uM | NOVARTIS: Inhibition of Plasmodium falciparum 3D7 (drug-susceptible) proliferation in erythrocyte-based infection assay | ChEMBL. | 18579783 |
| EC50 (functional) | = 0.347 uM | W2 Pf proliferation inhibition | Novartis-GNF Malaria Box. | No reference |
| EC50 (functional) | = 0.347 uM | NOVARTIS: Inhibition of Plasmodium falciparum W2 (drug-resistant) proliferation in erythrocyte-based infection assay | ChEMBL. | 18579783 |
| IC50 (binding) | = 40 nM | Enzymatic Assays | BINDINGDB. | No reference |
| IC50 (binding) | = 60 nM | BindingDB_Patents: Enzymatic Assays. Type 2 DHODH activity was monitored with either the direct assay measuring the formation of orotate or via a chromogen reduction assay using DCIP. Although the extinction coefficient and absorption wavelength are preferable for the chromogen reduction assay, the inorganic electron acceptor DCIP can be utilized by DHODH as the final electron acceptor in lieu of CoQn when the endogenous substrate is at a low concentration. As such, the direct assay was used to measure the binding affinity of pfDHODH to CoQD and L-DHO. The enzymatic reaction was performed by varying the L-DHO concentration (1-400 uM) or CoQD concentration (1-200 uM) while keeping the other substrate constant and in excess. Inhibition of DHODH by small molecules was evaluated using the chromogen based assay with a final substrate concentration of 200 uM L-DHO, 18 uM CoQD, and 100 uM DCIP, unless otherwise noted. | ChEMBL. | No reference |
| IC50 (binding) | = 83 nM | BindingDB_Patents: Enzymatic Assays. Type 2 DHODH activity was monitored with either the direct assay measuring the formation of orotate or via a chromogen reduction assay using DCIP. Although the extinction coefficient and absorption wavelength are preferable for the chromogen reduction assay, the inorganic electron acceptor DCIP can be utilized by DHODH as the final electron acceptor in lieu of CoQn when the endogenous substrate is at a low concentration. As such, the direct assay was used to measure the binding affinity of pfDHODH to CoQD and L-DHO. The enzymatic reaction was performed by varying the L-DHO concentration (1-400 µM) or CoQD concentration (1-200 µM) while keeping the other substrate constant and in excess. Inhibition of DHODH by small molecules was evaluated using the chromogen based assay with a final substrate concentration of 200 µM L-DHO, 18 µM CoQD, and 100 µM DCIP, unless otherwise noted. | ChEMBL. | No reference |
| IC50 (binding) | > 10000 nM | Enzymatic Assays | BINDINGDB. | No reference |
| IC50 (binding) | > 30000 nM | Enzymatic Assays | BINDINGDB. | No reference |
| IFI promiscuity index | = 0.01515 | IFI promiscuity index | Novartis-GNF Malaria Box. | No reference |
Phenotypes
Whole-cell/tissue/organism interactions
| Species name | Source | Reference | Is orphan |
|---|---|---|---|
| Plasmodium falciparum | ChEMBL23 | 18579783 |
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: CHEMBL600689
- Search by Novartis-GNF Malaria Box
Bibliographic References
No literature references available for this target.
If you have references for this compound, please enter them in a user comment (below) or Contact us.