NITD-304

NITD-304 is an orally active anti-tuberculosis agent. NITD-304 exerts inhibitory and bactericidal activities gainst Mycobacterium tuberculosis and multidrug-resistant Mycobacterium tuberculosis. NITD-304 inhibits mycobacterial cell wall biosynthesis and demonstrates synergistic or additive growth inhibitory activity with select antibacterial agents. NITD-304 shows low risk of cardiotoxicity and drug-drug interactions, with no inhibition of major cytochrome P-450 enzymes or hERG channel. NITD-304 can be used for the research of tuberculosis and multidrug-resistant tuberculosis^[1][2]. In Vitro:NITD-304 (5 days) potently inhibits growth of virulent Mtb H37Rv with an MIC₅₀ of 0.015 μM after 5 days of incubation^[1].
NITD-304 (10 days) inhibits 99% growth of diverse MDR Mtb clinical isolates at concentrations from <0.04 to 0.08 μM after 10 days of incubation^[1].
NITD-304 (0.04-5.00 μM; 1-6 days) induces concentration- and time-dependent bactericidal activity against Mtb H37Rv^[1].
NITD-304 (0.1-5 μM; 5 days) reduces intracellular Mtb burden in activated THP-1 macrophages in a concentration-dependent manner^[1].
NITD-304 (0-100 μM) induces iniB reporter activity in M. bovis BCG, indicating it inhibits mycobacterial cell wall biosynthesis^[1].
NITD-304 exhibits no significant in vitro cytotoxicity or genotoxicity, low risk of hERG-mediated cardiotoxicity, and no inhibition of major cytochrome P-450 enzymes^[1].
NITD-304 (5 days) has reduced activity against Mtb with mmpL3 gene mutations, increasing its MIC₅₀ to 0.052-0.222 μM^[1]. In Vivo:NITD-304 (12.5-100 mg/kg; p.o.; daily; 4 weeks) dose-dependently reduces Mycobacterium tuberculosis lung burden in an acute mouse tuberculosis model, with a minimum effective dose of 37.5 mg/kg^[1].