PLX5568

PLX5568 is a selective small molecule inhibitor of Raf kinases, specifically targeting C-Raf (RAF1) and B-Raf (BRAF), developed by Plexxikon in partnership with Roche. Identified using Plexxikon's proprietary Scaffold-Based Drug Discovery platform, the compound was primarily investigated for the treatment of autosomal dominant polycystic kidney disease (ADPKD) and as a non-opioid analgesic. In preclinical studies, PLX5568 demonstrated the ability to reduce cyst proliferation in PKD models by inhibiting the MAPK/ERK signaling pathway. However, its clinical utility was severely limited by findings that the drug promoted renal and hepatic fibrosis in rat models. Although the compound progressed into Phase 1 clinical trials, development for these primary indications was ultimately halted due to these adverse fibrotic effects.