A Preclinical Candidate Targeting Mycobacterium tuberculosis KasA
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Updated: Dec 25, 2025

A Microscopic Phenotypic Assay for the Quantification of Intracellular Mycobacteria Adapted for High-throughput/High-content Screening
Published on: January 17, 2014
Daigo Inoyama1, Divya Awasthi1, Glenn C Capodagli2
1Department of Pharmacology, Physiology, and Neuroscience, Rutgers University - New Jersey Medical School, Newark, NJ, USA.
Abstract:
Published Mycobacterium tuberculosis β-ketoacyl-ACP synthase KasA inhibitors lack sufficient potency and/or pharmacokinetic properties. A structure-based approach was used to optimize existing KasA inhibitor DG167. This afforded indazole JSF-3285 with a 30-fold increase in mouse plasma exposure. Biochemical, genetic, and X-ray studies confirmed JSF-3285 targets KasA. JSF-3285 offers substantial activity in an acute mouse model of infection and in the corresponding chronic infection model, with efficacious reductions in colony-forming units at doses as low as 5 mg/kg once daily orally and improvement of the efficacy of front-line drugs isoniazid or rifampicin. JSF-3285 is a promising preclinical candidate for tuberculosis.
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