PLX-4720 is an orally-available, ATP-competitive, highly selective, azaindole-based inhibitor of B-Raf (V600E) with IC50 value of 13 nM. PLX-4720 has additional activity towards mutant forms of c-Raf-1 (Y340D, Y341D) at an IC50 of 6.7 nM, with modest single micromolar activity versus kinases such as FRK, CSK, SRC, FGFR, KDR< HGK, and Aurora A. [1] PLX-4720 has shown preclinical activity in melanoma and thyroid cancer models. [1, 2]

PLX-4720 preferentiallly inhibits ERK phosphorylation in tumor cell lines bearing the V600E allele. In melanoma models it induces cell cycle arrest and apoptosis exclusively in B-Raf (V600E)-positive cells.

In an orthotopic 8505c human thyroid cancer mice model, PLX-4720 caused significant reduction in tumor growth (>90%) and dramatically decreased lung metastases. [3]