lack CDK4 mutations (451Lu, WM35, and WM983) are highly sensitive to SB590885 with IC50 of <1 μM. Increased levels of cyclin D1 resulting from genomic amplification mediate SB590885 resistance in B-Raf V600E-mutated melanomas.[3]...
SB-590885 is a novel triarylimidazole that selectively inhibits Raf kinases with more potency towards B-Raf than c-Raf. SB-590885 stabilizes the oncogenic B-Raf kinase domain in an active configuration, which is distinct from the previously reported mechanism of action of the multi-kinase inhibito...
Malignant cells expressing oncogenic B-Raf show selective inhibition of mitogen-activated protein kinase activation, proliferation, transformation, and tumorigenicity when exposed to SB-590885, whereas other cancer cell lines and normal cells display variable sensitivities or resistance to similar treatment. ...