PK150 (2165324-62-7) is a Sorafenib analog that displays significant antibacterial activity against several pathogenic strains (S.aureus?NCTC8325, MIC = 0.3 μM; vancomycin -resistant enterococci, MIC = 3 μM; and?M.tuberculosis?MIC = 2 μM). It was inactive against Gram-negative bacteria. It effectively reduced persister cells in ciprofloxacin-treated stationary?S.aureus?cultures and effectively eradicated staphylococcus biofilms. PK150 did not develop antibacterial resistance in an agar-plate-based assay. Its antibacterial properties were attributed to demethylmenaquinone methyltransferase (MenG) inhibition and signal peptidase IB (SpsB) activation. PK150 displayed?in vivo?efficacy in a murine bloodstream infection model against methicillin-sensitive?S. aureus?and a neutropenic mouse thigh model against methicillin-resistant?S. aureus?strain ATCC33591. Inactive against a panel of over 250 human kinases.
