(R)-CR8 trihydrochloride

Cyclin-dependent kinases (CDKs) are key regulators of cell cycle progression and are therefore promising targets for cancer therapy.¹ (R)-CR8 is a second-generation analog of (R)-roscovitine that inhibits Cdk1/cyclin B, Cdk2/cyclin A, Cdk2/cyclin E, Cdk5/p25, and Cdk9/cyclin T with IC₅₀ values of 0.09, 0.072, 0.041, 0.11, and 0.18 μM, respectively.^2,3 (R)-CR8 has 2- to 4-fold improved potency for the inhibition of CDKs over (R)-roscovitine and can inhibit the proliferation of various cancer cell lines with ~40-fold more potency than (R)-roscovitine (IC₅₀s ~ 0.39 versus 27.8 μM, respectively).^2,3 (R)-CR8 also inhibits casein kinase 1 (CK1δ/ε) with an IC₅₀ value of 0.40 μM and inhibits GSK3α/β with an IC₅₀ value of 12 μM.²

1.Bettayeb, K., Baunbaek, D., Delehouze, C., et al.CDK inhibitors roscovitine and CR8 trigger Mcl-I down-regulation and apoptotic cell death in neuroblastoma cellsGenes Cancer1(4)369-380(2010) 2.Bettayeb, K., Oumata, N., Echalier, A., et al.CR8, a potent and selective, roscovitine-derived inhibitor of cyclin-dependent kinasesOncogene27(44)5797-5807(2008) 3.Oumata, N., Bettayeb, K., Ferandin, Y., et al.Roscovitine-derived, dual-specificity inhibitors of cyclin-dependent kinases and casein kinases 1J. Med. Chem.51(17)5229-5242(2008)