ly3009120

LY3009120 (DP-4978) is a potent pan-Raf inhibitor with IC50 values of 44 nM for A-raf, 31-47 nM for B-Raf, and 42 nM for C-Raf in A375 cells. Phase 1.

LSN3074753, a derivative of LY3009120, acts as a pan-RAF and Raf dimer inhibitor. This compound exhibits inhibitory activity against tumor cells driven by either BRAF monomers or RAF dimers, particularly in the activation of the MAPK pathway, including colorectal cancers with BRAF or KRAS mutations. When combined with Cetuximab, LSN3074753 demonstrates additive and synergistic effects in colorectal cancer PDX models, especially in those harboring KRAS or BRAF mutations.