Publications by authors named "Pedro Alfonso Torres-Gomez"
Article Synopsis
- Due to rising drug resistance in tuberculosis patients, there is a critical demand for new drugs targeting novel mechanisms to bypass existing resistance.
- Benzofuran has shown potential as a TB treatment by targeting the thioesterase domain of Pks13, but it poses a risk of inhibiting the hERG cardiac ion channel, leading to heart irregularities.
- Although the research team improved the compound's safety profile, they ultimately halted development due to persistent cardiac concerns, yet the study supports Pks13 as a promising target for new TB drugs and encourages exploring different chemical structures.
Screening of a GSK-proprietary library against intracellular identified , a thioalkylbenzoxazole hit. Biological profiling and mutant analysis revealed that this compound is a prodrug that is bioactivated by the mycobacterial enzyme MymA. A hit-expansion program including design, synthesis, and profiling of a defined set of analogues with optimized drug-like properties led to the identification of an emerging lead compound, displaying potency against intracellular bacteria in the low micromolar range, high in vitro solubility and permeability, and excellent microsomal stability.
View Article and Find Full Text PDFIdentification of Novel Anti-mycobacterial Compounds by Screening a Pharmaceutical Small-Molecule Library against Nonreplicating Mycobacterium tuberculosis.
ACS Infect Dis
December 2015
Identification of compounds that target metabolically diverse subpopulations of Mycobacterium tuberculosis (Mtb) may contribute to shortening the course of treatment for tuberculosis. This study screened 270,000 compounds from GlaxoSmithKline's collection against Mtb in a nonreplicating (NR) state imposed in vitro by a combination of four host-relevant stresses. Evaluation of 166 confirmed hits led to detailed characterization of 19 compounds for potency, specificity, cytotoxicity, and stability.
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