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LY3009120 is a pan-RAF and RAF dimer inhibitor. It inhibits BRAF WT, CRAF, WT, BRAFV600E, and BRAFV600E+G468A with the IC50 values of 9.1, 15, 5.8, and 17 nM, respectively. [1]

RAF is family of serine/threonine-protein kinase mediates Ras GTPases and the MAPK/ERK cascade. It involves in proliferation, differentiation, apoptosis, survival and oncogenic transformation. [1]

In NRAS mutant SK-Mel2 cells or KRAS mutant HCT116 cells, LY3009120 inhibits the kinase activity of CRAF in a dose-dependent manner and induces BRAF/CRAF heterodimerization. It also blocks Phospho-MEK and -ERK and induces minimal paradoxical activation in RAS mutant Cells. Moreover, treatment of BRAF V600E A375 melanoma cells by LY3009120 for 24 hr predominantly induces a G0/G1 arrest with more than 95% cells in G0/G1 phase. [1]

In nude rats bearing A375 xenograft tumors, oral LY3001920 treatment exerts a dose-dependent inhibition of phospho-MEK and –ERK. 15 or 30 mg/kg LY3009120 shows near complete tumor regression in nude rats bearing PDX tumors.

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