PC190723

PC190723 is a synthetic small-molecule antibacterial agent that has been studied as an inhibitor of FtsZ, the essential bacterial cytoskeletal protein involved in cell division. It was identified in pharmaceutical research as a lead compound targeting bacterial cytokinesis and is named from its development catalog.

Mechanism of action and target: PC190723 binds to a pocket in FtsZ, inhibiting polymerization and reducing GTPase activity. This disruption impairs Z-ring formation at the division site, halting bacterial cytokinesis and leading to growth arrest and cell death. The compound shows potent activity primarily against Gram-positive bacteria, with Staphylococcus aureus including methicillin-resistant strains (MRSA) among the better-characterized targets. Activity against many Gram-negative bacteria is limited, largely due to permeability barriers and efflux mechanisms.

Spectrum and resistance: In vitro studies have demonstrated strong activity against S. aureus strains, while activity against other species varies. Resistance can arise from mutations in FtsZ that decrease binding affinity, and from increased efflux or other mechanisms that reduce intracellular drug concentrations.

Development status and pharmacology: PC190723 has been used as a lead compound in the exploration of FtsZ inhibitors and has shown efficacy in animal models of S. aureus infection. However, challenges such as suboptimal solubility, bioavailability, and broader-spectrum activity have limited progression to clinical use. Research efforts have focused on optimizing pharmacokinetic properties and expanding the antibacterial spectrum while maintaining target specificity.

See also: FtsZ inhibitors, antibacterial agents, MRSA.