Dabrafenib (GSK2118436)

Dabrafenib is a selective inhibitor of mutant B-RafV600E (IC50 = 0.8 nM), with 4- and 6-fold reduced potency against wild type B-Raf and c-Raf (IC50 = 3.2 and 5 nM, respectively) [1]. Has been in clinical trials in patients with B-RafV600E metastatic melanoma and other solid tumors. Endoplasmic reticulum stress and autophagy are induced in melanoma cells after treatment with dabrafenib and protect cells from dabrafenib toxicity [2]. Induces epithelial differentiation in BRAF-mutant colorectal cancer cells [3].

References:

1) Huang et al. (2013), B-Raf and the inhibitors: from bench to bedside; J.Hematol.Oncol. 6 1

2) Ji et al. (2016), Endoplasmic reticulum stress-induced autophagy determines the susceptibility of melanoma cells to dabrafenib; Drugs Des. Dev. Ther., 10 2491

3) Herr et al. (2015), B-Raf inhibitors induce epithelial differentiation in BRAF-mutant colorectal cancer cells; Cancer Res., 75 216