NITD-349

本公司产品仅用于科研实验，不得用于人体或动物的临床与诊断

NITD-349 是一种新型口服生物可利用的分枝杆菌膜蛋白大 3 (MmpL3) 抑制剂，针对结核分枝杆菌 H37Rv 的 MIC 为 23 nM。

NITD-349 is a novel, orally bioavailable mycobacterial membrane protein Large 3 (MmpL3) inhibitor with MIC of 23 nM against M tuberculosis H37Rv; shows potent activity against both drug-sensitive and multidrug-resistant clinical isolates of Mtb; demonstrates effectivity in treating both acute and chronic Mtb infections in mouse efficacy models.

NITD-349 shows bactericidal activity against in vitro replicating Mycobacterium tuberculosis (Mtb) and also are active against intramacrophage Mtb. Kill kinetic analysis of these compounds showed both concentration- and time-dependent killing of Mtb cells with 3- to 4-log colony-forming unit (CFU) reductionwithin 3 days of treatment. The cidal activity profile of NITD-304 is similar to that of isoniazid for which rapid killing is noticed at concentrations greater than 0.2 μM. The MIC activity of NITD349 against various MDR Mtb strains ranges from 0.04 to 0.08 μM. NITD-349 shows high permeability and moderate in vitro metabolic clearance in mouse and human hepatic microsomes.

In the acute murine efficacy modelNITD-349 shows favorable oral pharmacokinetic (PK) properties in rodents and dogs and are efficacious in mouse models of both acute and chronic Mycobacterium tuberculosis infection. 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.

NITD349

GPCR/G Protein

Antibacterial

Antibacterial

Infection

——

1473450-62-2

306.36

C17H20F2N2O

>98% (HPLC)

DMSO : ≥ 310 mg/mL 1011.91 mM

CC1(CCC(CC1)NC(=O)C2=CC3=C(N2)C=C(C=C3F)F)C

N-(4,4-dimethylcyclohexyl)-4,6-difluoro-1H-indole-2-carboxamide

(-20℃)

With Ice Pack

≥ 2 years