MSU-44147

MSU-44147 is a small-molecule inhibitor that targets the membrane transport protein MmpL3 in Mycobacterium abscessus; it exhibits selective anti-mycobacterial activity and low cytotoxicity toward eukaryotic cells. By inhibiting MmpL3-mediated lipid transport, MSU-44147 reduces levels of trehalose dibranchate, thereby disrupting cell wall synthesis and biofilm formation, and exhibits bactericidal activity against intracellular bacteria; simultaneously, it produces additive or synergistic effects when used in combination with various antibiotics.

MSU-44147 (80 μM–0.08 nM; 3 days) potently inhibits the growth of Mycobacterium abscessus ATCC 19977 in vitro and exhibits time-dependent bactericidal activity at a concentration of 5× MIC; simultaneously, it potently inhibits Mycobacterium tuberculosis strains, Mycobacterium abscessus, and Mycobacterium chancroidi; it exhibits no activity against nontuberculous mycobacteria at concentrations up to 80 μM; and it demonstrates variable antibacterial activity against clinically isolated multidrug-resistant Mycobacterium abscessus strains.
MSU-44147 (0.18 nM–160 μM; 3 d) disrupts mature Mycobacterium abscessus biofilms, with an EC₅₀ of 1.96 μM; it also reduces bacterial viability within biofilms, with a corresponding EC₅₀ of 0.18 μM.
MSU-44147 (1–160 μM; 3 d) does not kill non-replicating, starved Mycobacterium abscessus ATCC 19977 at concentrations up to 160 μM [1].