oral ATP-synthase inhibitor
Ph. I candidate for pulmonary tuberculosis
toxicol. risk mitigation from prev. disclosed inhibitor
Bioorg. Med. Chem. Lett.
WuXi AppTec, Shanghai, CN
Context. Sudapyridine (WuXi AppTec) is an oral mycobacterial ATP synthase inhibitor being developed for tuberculosis (TB). Despite the significant success achieved with the discovery of antibiotic drugs in the last several decades, drug resistance, particularly related to agents targeting organisms such as M. tuberculosis, remains a predominant challenge. To make matters worse, potent agents such as Janssen’s first-in-class diarylquinoline, bedaquiline, which was approved in 2012 and sanctioned by the WHO in 2018 for multidrug resistance TB, or the TB Alliance’s pretomanid which is the latest approved TB antibiotic, are associated with serious adverse events such as unexplained mortality and QT prolongation. These challenges highlight the need for continuous development of improved antibacterials targeting M. tuberculosis. Developed from bedaquiline as the…