BRD-8000.3, as a specific EfpA inhibitor, is a narrow-spectrum, bactericidal antimycobacterial agent with good wild-type activity[1]. BRD-8000.3 exhibits inhibitory activity against Mycobacterium tuberculosis (Mtb) with an MIC₉₀ value of 800nM[1]. Resistance to BRD-8000.3 could be conferred by mutations in EfpA, including substitutions V319F and A415V[2].
In vitro, BRD-8000.3 has an IC50 value greater than 50μM for HepG2[3].
In vivo, BRD-8000.3, administered orally at 150mg/kg, demonstrated good mouse plasma exposure and low risk for drug–drug interactions, prolongation of the QT interval, or hepatotoxicity[3].
References:
[1] Johnson EO, et al. Large-Scale Chemical-Genetic Strategy Enables the Design of Antimicrobial Combination Chemotherapy in Mycobacteria. ACS Infect Dis. 2020;6(1):56-63.
[2] Khandelwal NK, Gupta M, Gomez JE, et al. Structure and inhibition mechanisms of Mycobacterium tuberculosis essential transporter efflux protein A. Preprint. bioRxiv. 2024;2024.09.04.611325.
[3] Johnson EO, LaVerriere E, Office E, et al. Large-scale chemical-genetics yields new M. tuberculosis inhibitor classes. Nature. 2019;571(7763):72-78.
BRD-8000.3是一种特异性EfpA抑制剂，是一种窄谱杀菌抗真菌剂，具有良好的野生型活性[1]。BRD-8000.3对结核分枝杆菌（Mtb）具有抑制活性，MIC₉₀值为800nM[1]。BRD-8000.3的耐药性可以通过EfpA突变获得，包括V319F和A415V的替换[2]。
体外实验中，BRD-8000.3对HepG2细胞的IC50值大于50μM[3]。
体内实验中，以150mg/kg的剂量口服给药的BRD-8000.3表现出良好的小鼠血浆暴露水平，且药物之间的相互作用风险、QT间期延长风险或肝毒性风险均较低[3]。