PF-04880594

PF-04880594 is a small molecule, potent and selective inhibitor of RAF serine/threonine protein kinases, including B-Raf, the B-RafV599E mutant, and c-Raf. It exhibits sub-nanomolar inhibitory activity (IC50: 0.19 nM for B-Raf, 0.13 nM for B-RafV599E, 0.39 nM for c-Raf) and is designed to block RAF-mediated signaling within the MAPK/ERK pathway, which is involved in cell proliferation and survival. In preclinical models, PF-04880594 significantly reduced cell viability and ERK activity, but also induced ERK phosphorylation and epithelial hyperplasia due to RAF dimerization. Originally developed by Pfizer, PF-04880594 has primarily been studied for antitumor potential, especially in models of BRAF-mutant cancers, and was intended for the treatment of conditions such as melanoma. Development has not progressed beyond preclinical/early clinical phases, and it is not marketed for any indication[1][2][3][4][5][7][9].