Telacebec

Telacebec (Q203) is a midazopyridine amide compound. Telacebec is active against Mycobacterium tuberculosis H37Rv with an MIC₅₀ of 2.7 nM in culture broth medium. IC50 & Target:MIC50: 2.7 nM (Mycobacterium tuberculosis H37Rv)^[1] In Vitro:Imidazopyridine amide (IPA) compounds block Mycobacterium tuberculosis growth by targeting the respiratory cytochrome bc1 complex. The optimized IPA compound Telacebec (Q203) inhibits the growth of MDR and XDR Mycobacterium tuberculosis clinical isolates in culture broth medium in the low nanomolar range. Telacebec is active against the reference strain Mycobacterium tuberculosis H37Rv with MIC₅₀s of 2.7 nM in culture broth medium and 0.28 nM inside macrophages^[1]. In Vivo:Telacebec (Q203) is efficacious in a mouse model of tuberculosis at a dose less than 1 mg per kg body weight. Telacebec displays pharmacokinetic and safety profiles compatible with once-daily dosing. Telacebec has a bioavailability of 90% and a terminal half-life of 23.4 h. The volume of distribution is moderate (5.27 l per kg body weight), and the systemic clearance is low (4.03 mL/min per kg). After 4 weeks of treatment, reductions of 90%, 99% and 99.9% in M. tuberculosis H37Rv bacterial load is observed in the groups treated with Telacebec at 0.4, 2 and 10 mg per kg body weight, respectively^[1].