TAK-632

TAK-632 is a selective kinase inhibitor targeting pan-RAF inhibition. TAK-632 inhibited phosphorylation of MEK (pMEK) in melanoma A375 cells (BRAFV600E) with an IC50 value of 12 nM. TAK-632 suppresses RAF activity in BRAF wild-type cells with minimal RAF paradoxical activation. TAK-632 induces RAF dimerization but inhibits the kinase activity of the RAF dimer, probably because of its slow dissociation from RAF. TAK-632 demonstrates potent antiproliferative effects both on NRAS-mutated melanoma cells and BRAF-mutated melanoma cells with acquired resistance to BRAF inhibitors through NRAS mutation or BRAF truncation.