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.
1) Le et al. (2019) Repurposing human kinase inhibitors to create an antibiotic active against drug-resistant Staphylococcus aureus, persisters and biofilms; Nat. Chem. 12 145