LSN3074753, an analog of LY3009120 , is a pan- RAF and Raf dimer inhibitor. LSN3074753 demonstrates activity against tumor cells with MAPK pathway activation driven by BRAF monomer or RAF dimers including BRAF- or KRAS-mutant colorectal cancer. LSN3074753 combined with Cetuximab shows additive and synergistic effects for colorectal cancer PDX models, particularly those with KRAS or BRAF mutation.