(R)​-​CR8

(R)?-?CR8 (CR8), a second-generation analog of Roscovitine, is a potent CDK1/2/5/7/9 inhibitor. (R)?-?CR8 inhibits CDK1/cyclin B (IC₅₀=0.09 μM), CDK2/cyclin A (0.072 μM), CDK2/cyclin E (0.041 μM), CDK5/p25 (0.11 μM), CDK7/cyclin H (1.1 μM), CDK9/cyclin T (0.18 μM) and CK1δ/ε (0.4 μM). (R)?-?CR8 induces apoptosis and has neuroprotective effect^[1][2]. (R)-CR8 acts as a molecular glue degrader that depletes cyclin K^[3]. In Vitro: (R)-CR8 (CR8) (0.1-100 μM; 48 hours) is a potent inducer of apoptotic cell death with an IC₅₀ of 0.49 μM for SH-SY5Y cell line^[1].
(R)-CR8 (0.25-10 μM) induces a dose-dependent induction of poly-(ADP-ribose)polymerase (PARP) cleavage^[1].
The CDK-bound form of (R)-CR8 has a solvent-exposed pyridyl moiety that induces the formation of a complex between CDK12-cyclin K and the CUL4 adaptor protein DDB1, bypassing the requirement for a substrate receptor and presenting cyclin K for ubiquitination and degradation^[3]. In Vivo: (R)-CR8 (5?mg/Kg; i.p.) results in a significant reduction in lesion size at 28 days in histological assessment^[2].