NITD-349 是MmpL3的抑制剂，它对毒性结核分枝杆菌 H37Rv 显示出高效的抗分枝杆菌活性，MIC50 为 23 nM。

NITD-349 is an inhibitor of MmpL3. It shows highly potent anti-mycobacterial activity with MIC50 of 23 nM against virulent Mycobacterium tuberculosis H37Rv.

NITD-304 and NITD-349, showed potent activity against both drug-sensitive and multidrug-resistant clinical isolates of Mtb.?Promising pharmacokinetic profiles of both compounds after oral dosing in several species enabled further evaluation for efficacy and safety.?NITD-304 and NITD-349 were efficacious in treating both acute and chronic Mtb infections in mouse efficacy models.?Furthermore, dosing of NITD-304 and NITD-349 for 2 weeks in exploratory rat toxicology studies revealed a promising safety margin.?Finally, neither compound inhibited the activity of major cytochrome P-450 enzymes or the hERG (human ether-a-go-go related gene) channel[1].

In the acute murine efficacy model, treatment of mice with NITD-349 at doses of 12.5 and 50 mg/kg resulted in 0.9- and 3.4-log CFU reduction in lung tissue.?In an established infection mouse model, after 2 weeks of treatment, the efficacy of NITD-349 is comparable to the first-line TB drug rifampicin and is better than ethambutol.?Four weeks of treatment at 100 mg/kg with NITD-349 results in 2.38-log CFU reductions[1].

1473450-62-2

C17H20F2N2O

306.35

NITD-349

DMSO:310 mg/mL (1011.91 mM)
Powder: -20°C for 3 years
In solvent: -80°C for 2 years