LXH254 is a potent C-Raf and B-Raf inhibitor.

LXH254 is an adenosine triphosphate (ATP)-competitive inhibitor of BRAF and CRAF protein kinases. LXH254 is also referred to as a c-RAF (or CRAF) inhibitor or a C-RAF/c-Raf kinase inhibitor. In cell-based assays, LXH254 has demonstrated anti-proliferative activity in cell lines that contain a variety of mutations that activate MAPK signaling. Moreover, LXH254 is a Type 2 ATP -competitive inhibitor of both B-Raf and C-Raf that keeps the kinase pocket in an inactive conformation, thereby reducing the paradoxical activation seen with many B-Raf inhibitors, and blocking mutant RAS-driven signaling and cell proliferation.

LXH254 exhibits efficacy in numerous MAPK-driven human cancer cell lines and in xenograft tumors representing model tumors harboring human lesions in KRAS, NRAS and BRAF oncogenes.Treatment with LXH254 generates tumor regression in several KRAS-mutant models including the NSCLC-derived Calu-6 (KRAS Q61K) and NCI-H358 (KRAS G12C).