Tuberculosis (TB) is an infectious disease usually caused by Mycobacterium tuberculosis (MTB) bacteria. Besides, Tuberculosis generally affects the lungs, but it can also affect other parts of the body. Importantly, The increased number of multidrug-resistant TB (MDR-TB) and extensively drug-resistant TB (XDR-TB) strains has created a great challenge for the treatment and control of tuberculosis. So, Repurposed antituberculosis drugs as well as new drugs are urgently needed to treat drug-resistant tuberculosis more safely and effectively.

TBI-166 is an orally active anti-tuberculosis agent.

TBI-166 shows antimicrobial activity in vitro. Such as, TBI-166 inhibits M. tuberculosis H37Rv replicates (MIC: 0.063 μg/mL), and is effective against 16 drug-sensitive clinical isolates (Mycobacterial species) with MICs of 0.005-0.15 μg/mL. Besides, TBI-166 (0-1 μg/mL, 3 days) inhibits intracellular M. tuberculosis (Mycobacterium tuberculosis) in M. tuberculosis infecting J774A.1 cells. Moreover, TBI-166 also shows inhibitors for rv0678 mutant and wild-type M. tuberculosis strains. Which shows MIC values of 0.18, 0.19, 0.19, 0.06 µg/mL for BDQ-1 C305T, BDQ-2 292–316 nt deletion, BDQ-3 C403T, H37Rv WT, respectively.

TBI-166 shows antimicrobial activity in vivo. In the acute infection model (BALB/c mice infected with M. tuberculosis H37Rv), TBI-166 (10-80 mg/kg; oral; 20 days) shows dose-dependent antituberculosis activity with the mean lung CFU counts for all doses is 2.2- to 4.2-log units lower than those for the untreated control group. Meanwhile, TBI-166 shows good mice tolerated with the LD50 value of more than 3,000 mg/kg. In addition, TBI-166 (10-80 mg/kg; oral; 8 weeks) shows the time-dependent killing of M. tuberculosis in chronic murine TB infected by low-dose aerosol with M. tuberculosis H37Rv. Moreover, TBI-166 (10, 20, 40, 80 mg/kg; 4 weeks) reduces pigmentation in ears compared to CFZ (20 mg/kg), showing a shorter plasma half-life of about 45 h.

All in all, TBI-166 is a potent and orally active anti-tuberculosis agent. Besides, TBI-166 shows antimicrobial activity in vitro and in vivo.

Reference：

[1] Xu J, et al. Antimicrob Agents Chemother. 2019 Apr 25;63(5):e02155-18.

[2] Zhu H, et al. Antimicrob Agents Chemother. 2021 Mar 18;65(4):e02164-20.