OpenSourceTB:OSTB Series 2: Difference between revisions
Matthew Todd (talk | contribs) (→Predicted Target: added chembl predictions) |
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The EBI prediction:<br> | The EBI prediction:<br> | ||
P96222 (HTH-type transcriptional regulator Eth) now http://www.uniprot.org/uniprot/P9WMC1 and https://www.ebi.ac.uk/chembl/target/inspect/CHEMBL1772929 | P96222 (Mtb HTH-type transcriptional regulator Eth) now http://www.uniprot.org/uniprot/P9WMC1 and https://www.ebi.ac.uk/chembl/target/inspect/CHEMBL1772929. The compound shares a lot of structural features found in known actives (activity <=10 μM) for this target in ChEMBL. These features include the thiophene ring, -CF<sub>3</sub>, pyrrole ring and nitrile. | ||
===Synthetic Chemistry=== | ===Synthetic Chemistry=== | ||
Revision as of 15:18, 25 January 2015
Starting Point
GSK2290170A, identified by GSK in a high throughput screen (to be published shortly).
Properties
Inherited data from GSK for GSK2290170A: MIC vs. H37Rv = 10 μM, active against non-replicating TB (>50% inhibition) in 10 experiments out of 13) and with mean PXC50 of 5.2 μM. Toxicity vs. HepG2 was >100 μM. cLogP is 3.1 and (presumably) measured solubility is 72 μg/mL. Chrom LogD (pH 7.4) is 5.21, and molecular weight 385.
Known occurrences
"GSK2290170A" was, when this page was created, absent from Google. Pubchem search leads to a patent.
Predicted Target
A prediction of the target was carried out by Marc Marti-Renom and ChEMBL as part of the original HTS paper identifying the compound.
The compound (GSK2290170A) has four predictions, three from Marc's approach and one from the ChEMBL’s approach. (The details on how the predictions were identified are in the forthcoming manuscript).
Marc's predictions:
1) O06266 (an epoxide hydrolase). Link: GSK2290170A —> 3TH-S38-3ans_A —> S38-O06266 (i.e. the GSK compound is similar to 3TH in PDB, which was co-crystallized with 3ans (a Human soluble epoxide hydrolase in complex with a synthetic inhibitor). In turn, the model of the Tuberculosis epoxide hydrolase (O06266) was based on 3ans template and the binding site was conserved. Thus, the path links GSK2290170A to O06266.
2) A2VJ47 (an epoxide hydrolase ephB), GSK2290170A —> 3TH-S38-3ans_A —> S38-A2VJ47
3) P64411 (Heat shock protein 90, GSK2290170A —> 3TH-PFT-3k99_A —> PFT-P64411
The EBI prediction:
P96222 (Mtb HTH-type transcriptional regulator Eth) now http://www.uniprot.org/uniprot/P9WMC1 and https://www.ebi.ac.uk/chembl/target/inspect/CHEMBL1772929. The compound shares a lot of structural features found in known actives (activity <=10 μM) for this target in ChEMBL. These features include the thiophene ring, -CF3, pyrrole ring and nitrile.
Synthetic Chemistry
The starting compound was resynthesized according to (Jessica insert and link to lit source). (Jessica describe synthesis and insert scheme here).
Strings
GSK2290170A ClC1=C(C(NCC2=CC=CS2)=O)N=C3C(C(F)(F)F)=CC(C#N)=CN31 InChI=1S/C15H8ClF3N4OS/c16-12-11(14(24)21-6-9-2-1-3-25-9)22-13-10(15(17,18)19)4-8(5-20)7-23(12)13/h1-4,7H,6H2,(H,21,24) LWIBMEYBVJUXDE-UHFFFAOYSA-N
Licence
Content is CC-BY-4.0.
Contact
To discuss this project or page, see the contact info on the OSTB Main Page
