tcsc1641 Dabrafenib Mesylate (GSK-2118436 Mesylate;GSK 2118436B)

Dabrafenib (Mesylate) is a novel, potent, and selective Raf kinase inhibitor, and inhibits the kinase activity of B-Raf^V600Eand c-Raf with IC₅₀ values of 0.6 and 5.0 nM, respectively.

IC50 & Target: IC50: 0.6 nM (BRAF^V600E), 5 nM (CRAF)^[4]

In Vitro: Dabrafenib (GSK2118436, 1 μM) with 0.01 μM GSK1120212 inhibits more than 90% of cell growth in the NRAS mutant clones. GSK2118436 is sufficient to reduce S6P phosphorylation in A375^[1]. Dabrafenib suppresses the PolyP-mediated vascular barrier permeability, upregulation of inflammatory biomarkers, adhesion/migration of leukocytes, and activation and/or production of nuclear factor-κB, tumor necrosis factor-α, and interleukin-6^[2]. Dabrafenib inhibits the release of HMGB1 and downregulates HMGB1-dependent inflammatory responses by enhancing the expressions of cell adhesion molecules (CAMs) in human endothelial cells^[3].

In Vivo: Dabrafenib-treated females have mostly immature reproductive tracts with no evidence of ovulation, similar to age-matched controls; however, DAB-treated females have keratinized and histologically open vaginas^[5].