The Raf kinases activate cellular pathways that lead to cell proliferation and can contribute to certain types of cancer.
1,2 Mutations in the kinase B-
Raf are involved in a wide range of cancers.
3,4 In particular, the mutation B-Raf
V600E occurs in melanomas and thyroid cancer but is poorly targeted by many inhibitors of wild type B-Raf.
5,6 PLX4720 is an orally-
available, highly selective inhibitor of B-Raf
V600E (IC
50 = 13 nM).
6 It is less effective against wild type B-Raf (IC
50 = 160 nM) as well as several other kinases.
6 PLX4720 induces cell cycle arrest and apoptosis in cells and xenografts expressing the mutant of B-Raf.
5,6,7