Compound 8918 is an orally activenon-cytotoxicphosphopantethein (Ppt)-binding pocket-targetingnon-competitive M. tuberculosis (Mtb) Ppt transferase (PptT) inhibitor (IC50 = 2.5 μMEmax 80-90%) th at exhibits mycobactericidal activity (MIC90 = 0.56-3 μM/29 clinical Mtb isolates; MBC99 = 6.25 μM/Mtb3.13 μM/M. smegmatis) with no bactericidal potency against S. aureusE. coliP. aeruginosaStreptomyces or C. albicans. Oral administration is efficacious against H37Rv replication in mouse lung in vivo (by 100%; 100 mg/kg/d4 d/wk for 2 wks). Mutations in MtbH37Rv rv2794c (PptT) or rv279c (Ppt hydrolasePptH) gene confers 8918 resistance.
