Antitubercular drugs for an old target: GSK693 as a promising InhA direct inhibitor

Martínez Hoyos, María; Mendoza Losana, Alfonso

Publication:
Antitubercular drugs for an old target: GSK693 as a promising InhA direct inhibitor

dc.contributor.author	Martínez Hoyos, María
dc.contributor.author	Mendoza Losana, Alfonso
dc.date.accessioned	2023-11-10T15:05:28Z
dc.date.available	2023-11-10T15:05:28Z
dc.date.issued	2016-05-08
dc.description.abstract	Despite 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.	en
dc.description.sponsorship	he research leading to these results has received funding from GlaxoSmithKline R&D the Global Alliance for TB Drug Development, and from the European Union's 7th framework program (FP7-2007-2013) under the Orchid grant agreement no. 261378.	en
dc.identifier.bibliographicCitation	Martínez-Hoyos, M.,Mendoza-Losana, A. et al. (2016). Antitubercular drugs for an old target: GSK693 as a promising InhA direct inhibitor. EBioMedicine (Vol. 8), pp. 291-301.	es
dc.identifier.doi	https://doi.org/10.1016/j.ebiom.2016.05.006
dc.identifier.issn	2352-3964
dc.identifier.publicationfirstpage	291	es
dc.identifier.publicationlastpage	301	es
dc.identifier.publicationtitle	EBioMedicine	es
dc.identifier.publicationvolume	8	es
dc.identifier.uri	https://hdl.handle.net/10016/38831
dc.identifier.uxxi	AR/0000030744
dc.language.iso	eng	es
dc.publisher	Elsevier	es
dc.rights	© 2016 The Authors.	es
dc.rights	Atribución-NoComercial-SinDerivadas 3.0 España	*
dc.rights.accessRights	open access	es
dc.rights.uri	http://creativecommons.org/licenses/by-nc-nd/3.0/es/	*
dc.subject.eciencia	Medicina	es
dc.subject.other	Tuberculosis	es
dc.subject.other	Antibiotic	en
dc.subject.other	InhA	en
dc.subject.other	Bactericidal	en
dc.subject.other	Drug discovery	en
dc.subject.other	Single-cell imaging	en
dc.subject.other	Catalase	en
dc.title	Antitubercular drugs for an old target: GSK693 as a promising InhA direct inhibitor	en
dc.type	research article	*
dc.type.hasVersion	VoR	*
dspace.entity.type	Publication