PLX4720, Free Base

Soluble in DMSO. PLX4720 is a kinase inhibitor with marked selectivity against B-Raf(V600E), with an IC50 of 13 nM. PLX4720 induced cell cycle arrest and apoptosis exclusively in B-Raf(V600E)-positive cells in melanoma models. In B-Raf(V600E)-dependent tumor xenograft models, PLX4720 caused significant tumor growth delays without evidence of toxicity. Tsai J., et al. 'Discovery of a selective inhibitor of oncogenic B-Raf kinase with potent antimelanoma activity.' Proc. Natl. Acad. Sci. USA 105: 3041-3046 (2008). PLX4720 induced significant tumor regression and reversal of cachexia in an orthotopic mouse model of human anaplastic thyroid cancer that harbored the BRAF(V600E) mutation. Nehs M.A., et al. 'Late intervention with anti-BRAF(V600E) therapy induces tumor regression in an orthotopic mouse model of human anaplastic thyroid cancer.' Endocrinology 153: 985-994 (2012). Resistance to BRAF inhibition by PLX4720 in BRAF-mutant colon cancer can be overcome with PI3K inhibition or demethylating agents in vitro and in vivo. Mao M., et al. 'Resistance to BRAF inhibition in BRAF-mutant colon cancer can be overcome with PI3K inhibition or demethylating agents.' Clin. Cancer Res. 19: 657-667 (2013).