(R)-ZG197 is a highly selective S. aureus caseinolytic protease P (SaClpP) activator / agonist with EC50 of 1.5 uM and Kd of 58 nM in BLI assays, 20-fold higher activity than that activates HsClpP.
(R)-ZG197 selectively binds to and activates SaClpP but not HsClpP.
(R)-ZG197 activates SaClpP to degrade α-casein and SaFtsZ in vitro. promote the degradation of cellular SaFtsZ protein in cell lysates of S. aureus 8325-4 clpP knockout (ΔclpP) strain with the supplement of the recombinant SaClpP protein, but no SaFtsZ degradation occurred in the presence of the recombinant HsClpP protein.
(R)-ZG197 exhibits antibacterial activity in a SaClpP-dependent manner, significantly suppresses S. aureus with a quantified MIC of 0.5 μg/mL.
(R)-ZG197 displays strong antibacterial activity on a broad spectrum of S. aureus USA300, NRS-1, NRS-70, NRS-100, NRS-108, and NRS-271 MRSA strains.
(R)-ZG197 demonstrates promising antibiotic efficacy in zebrafish and murine skin infection models.