5jfo | pdb_00005jfo
Structure of the M.tuberculosis enoyl-reductase InhA in complex with GSK625
Structural highlights
Publication Abstract from PubMedDespite being one of the first antitubercular agents identified, isoniazid (INH) is still the most prescribed drug for prophylaxis and tuberculosis (TB) treatment and, together with rifampicin, the pillars of current chemotherapy. A high percentage of isoniazid resistance is linked to mutations in the pro-drug activating enzyme KatG, so the discovery of direct inhibitors (DI) of the enoyl-ACP reductase (InhA) has been pursued by many groups leading to the identification of different enzyme inhibitors, active against Mycobacterium tuberculosis (Mtb), but with poor physicochemical properties to be considered as preclinical candidates. Here, we present a series of InhA DI active against multidrug (MDR) and extensively (XDR) drug-resistant clinical isolates as well as in TB murine models when orally dosed that can be a promising foundation for a future treatment. Antitubercular drugs for an old target: GSK693 as a promising InhA direct inhibitor.,Martinez-Hoyos M, Perez-Herran E, Gulten G, Encinas L, Alvarez-Gomez D, Alvarez E, Ferrer-Bazaga S, Garcia-Perez A, Ortega F, Angulo-Barturen I, Rullas-Trincado J, Blanco Ruano D, Torres P, Castaneda P, Huss S, Fernandez Menendez R, Gonzalez Del Valle S, Ballell L, Barros D, Modha S, Dhar N, Signorino-Gelo F, McKinney JD, Garcia-Bustos JF, Lavandera JL, Sacchettini JC, Jimenez MS, Martin-Casabona N, Castro-Pichel J, Mendoza-Losana A EBioMedicine. 2016 Jun;8:291-301. doi: 10.1016/j.ebiom.2016.05.006. Epub 2016 May, 8. PMID:27428438[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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