RGB-286638 2HCl

Description: RGB-286638 2HCl, the dihydrochloride salt of RGB-286638, is a multi-targeted cyclin-dependent kinase (CDK) inhibitor. It inhibits the kinase activity of cyclin T1-CDK9, cyclin B1-CDK1, cyclin E-CDK2, cyclin D1-CDK4, cyclin E-CDK3, and p35-CDK5 with IC50 values of 1, 2, 3, 4, 5 and 5 nM, respectively; it also inhibits GSK-3beta, TAK1, Jak2 and MEK1, with IC50 of 3, 5, 50, and 54 nM respectively. RGB-286638 triggers P53-dependent and -independent anti-multiple myeloma (MM) activity through inhibition of transcriptional CDKs. GB-286638 treatment resulted in MM cytotoxicity in vitro associated with inhibition of MM tumor growth and prolonged survival in vivo. RGB-286638 displayed caspase-dependent apoptosis in both wt-p53 and mutant-p53 cells that was closely associated with the downregulation of RNA polymerase II phosphorylation and inhibition of transcription.

References: Leukemia. 2013 Dec; 27(12):2366-75.