Q203是一种中氮杂吡啶酰胺。 在培养基中抑制结核分枝杆菌H37Rv活性的MIC50值为2.7 nM。

Q203 is a novel potent anti-tuberculosis agent targeting cytochrome b subunit qcrB and inhibits M. tuberculosis H37Rv (MIC50: 2.7 nM).

Q203 was active against the reference strain M. tuberculosis H37Rv at a minimum concentration required to inhibit the growth of 50% of organisms (MIC50) of 2.7 nM in culture broth medium and at an MIC50 of 0.28 nM inside macrophages [1]. Verapamil increased the potency of Q203 against Mycobacterium tuberculosis both in vitro and ex vivo [2]. Inhibition of cytochrome bd, a parallel branch of the mycobacterial respiratory chain, by aurachin D invoked bactericidal activity of Q203. Inhibition of respiratory chain activity by Q203 was incomplete, but could be enhanced by inactivation of cytochrome bd, either by genetic knock-out or by inhibition with aurachin D [3].

Q203 had a bioavailability of 90% and a terminal half-life of 23.4 h. The volume of distribution was moderate (5.27 l per kg body weight), and the systemic clearance was low (4.03 ml/min/kg). It promoted a reduction in bacterial load of more than 90% at a dose of 10 mg per kg body weight, an effect comparable to that of bedaquiline or isoniazid [1].

1334719-95-7

C29H28ClF3N4O2

557

IAP6;Telacebec

DMSO:18 mg/mL (32.3 mM)
H2O:Insoluble
Powder: -20°C for 3 years
In solvent: -80°C for 2 years