SB590885 is an effective B-Raf inhibitor (Ki: 0.16 nM, in a cell-free assay). The selectivity of SB590885 for B-Raf is 11-fold greater over c-Raf, no acts to other human kinases.

B-Raf:0.16 nM(Ki), C-Raf:1.72 nM (Ki)

In mice with A375P melanoma xenografts that express the B-Raf(V600E) variant, SB590885 significantly reduces tumor incidence and exhibits a certain inhibitory effect on tumor growth.

SB590885 effectively inhibits ERK phosphorylation (EC50: 28/58/290/58/190 nM) and proliferation (EC50: 0.1/0.87/0.37/0.12/0.15 μM) in Colo205, HT29, A375P, SKMEL28, and MALME-3M cells expressing the carcinogenic B-RafV600E. Compared to c-Raf (Ki: 1.72 nM), SB590885 displays significantly higher selectivity for B-Raf (Ki: 0.16 nM). Unlike the multikinase inhibitor BAY43-9006, SB590885 stabilizes the active conformation of the oncogenic B-Raf kinase domain and shows a high affinity for B-Raf (Kd: 0.3 nM). Melanoma cell lines with the BRAF V600E mutation but without the CDK4 mutation (451Lu, WM983, and WM35) are highly sensitive to SB590885 (IC50 <1 μM).

Cells are treated with increasing concentrations of SB590885 and incubated for 72 hours. Viable cells are quantified using CellTiter-Glo reagent and luminescence detection on a Victor 2V plate reader. Cells are prepared for cell cycle analysis on a Becton Dickinson FACScan. Data is acquired and analyzed using CellQuest v3.3 software.(Only for Reference)