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PLX-4720, a 7-azaindole derivative discovered by a structure-guided discovery approach, is a potent inhibitor of B-RafV600E, the most frequent oncogenic protein kinase mutation, with the value of 50% inhibition concentration IC50 of 13 nM. PLX-4720 exhibits selective inhibition against B-RafV600E rather than wild type B-Raf (IC50 = 160 nM) as well as a wide range of other kinases, such as FRK, CSK, SRC, FAK, FGFR, and Aurora A (IC50 > 1000 nM for all). PLX-4720 potently inhibits ERK phosphorylation in tumor cell lines harboring B-RafV600E, induces cell cycle arrest and apoptosis in B-RafV600E-positive melanoma cells and causes tumor growth delays in B-RafV600E-dependent tumor xenograft models through oral administration.

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