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CR8, (S)-Isomer is a cell-permeable (R)-DRF053 (sc-221408) analog that acts as an ATP-binding pocket-targeting CDK/CK1 dual-specific inhibitor (IC50 = 0.09, 0.072, 0.041, 0.11, 1.10, 0.18, and 0.40 μM against Cdc2(CDK1)/cyclin B, CDK2/cyclin A, CDK2/cyclin E, CDK5/p35 (p25), CDK7/cyclin H, CDK9/cyclin T, and casein kinase I δ/ε (CK1δ/ε), respectively). (R)-CR8 inhibits CDK/CK1 more effectively than (R)-Roscovitine, while maintaining similar selectivity profile over other types of kinases (IC50 = 3.6, 3.6, and 12.0 μM against Dyrk1A, ERK 2, and GSK-3α/β, respectively). Both (R)-CR8 and (S)-enantiomers are much more effective than (R)-Roscovitine in apoptosis induction in cell cultures.
1. Bettayeb, K., et al., 2008. CR8, a potent and selective, roscovitine-derived inhibitor of cyclin-dependent kinases. Oncogene. 27(44): 5797-807. PMID: 18574471
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