OpenSourceTB:OSTB Series 2: Difference between revisions
Matthew Todd (talk | contribs) m (→Starting Point) |
Matthew Todd (talk | contribs) (→Starting Point: added related series sections) |
||
| Line 16: | Line 16: | ||
ChEMBL flags up that a search on SureChEMBL reveals that the compound has appeared (along with nearest neighbours) on 2 patents of the same patent family: https://www.surechembl.org/document/US-20090176778-A1/ and https://www.surechembl.org/document/US-20120121540-A1/ | ChEMBL flags up that a search on SureChEMBL reveals that the compound has appeared (along with nearest neighbours) on 2 patents of the same patent family: https://www.surechembl.org/document/US-20090176778-A1/ and https://www.surechembl.org/document/US-20120121540-A1/ | ||
===Related Structures=== | |||
[http://www.nature.com/nm/journal/v19/n9/full/nm.3262.html Discovery of Q203, a potent clinical candidate for the treatment of tuberculosis]<br> | |||
[http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0052951 Identification of Novel Imidazo[1,2-a]pyridine Inhibitors Targeting M. tuberculosis QcrB] | |||
===Predicted Target=== | ===Predicted Target=== | ||
Revision as of 05:05, 26 January 2015
Starting Point
GSK2290170A (TCMDC-143693) identified by GSK in a high throughput screen (to be published shortly).
Properties
Inherited data from GSK for TCMDC-143693: 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" and "TCMDC-143693" were, when this page was created, absent from Google. Pubchem search leads to a patent.
ChEMBL flags up that a search on SureChEMBL reveals that the compound has appeared (along with nearest neighbours) on 2 patents of the same patent family: https://www.surechembl.org/document/US-20090176778-A1/ and https://www.surechembl.org/document/US-20120121540-A1/
Related Structures
Discovery of Q203, a potent clinical candidate for the treatment of tuberculosis
Identification of Novel Imidazo[1,2-apyridine Inhibitors Targeting M. tuberculosis QcrB]
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 (TCMDC-143693) 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: TCMDC-143693 —> 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 TCMDC-143693 to O06266.
2) A2VJ47 (an epoxide hydrolase ephB), TCMDC-143693 —> 3TH-S38-3ans_A —> S38-A2VJ47
3) P64411 (Heat shock protein 90, TCMDC-143693 —> 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
