(R)-CR8 (trihydrochloride)

1786438-30-9

540.92

DMSO : 62.5 mg/mL (115.54 mM; Need ultrasonic)

Apoptosis; Cell Cycle/DNA Damage

(R)-CR8 (CR8) trihydrochloride, a second-generation analog of Roscovitine, is a potent CDK1/2/5/7/9 inhibitor. (R)-CR8 trihydrochloride inhibits CDK1/cyclin B (IC₅₀=0.09 uM), CDK2/cyclin A (0.072 uM), CDK2/cyclin E (0.041 uM), CDK5/p25 (0.11 uM), CDK7/cyclin H (1.1 uM), CDK9/cyclin T (0.18 uM) and CK1delta/epsilon (0.4 uM). (R)-CR8 trihydrochloride induces apoptosis and has neuroprotective effect^[1][2]. (R)-CR8 trihydrochloride acts as a molecular glue degrader that depletes cyclin K^[3]. In Vitro: (R)-CR8 (CR8) trihydrochloride (0.1-100 uM; 48 hours) is a potent inducer of apoptotic cell death with an IC₅₀ of 0.49 uM for SH-SY5Y cell line^[1].
(R)-CR8 trihydrochloride (0.25-10 uM) induces a dose-dependent induction of poly-(ADP-ribose)polymerase (PARP) cleavage^[1].
The CDK-bound form of (R)-CR8 trihydrochloride 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 In Vivo: (R)-CR8 trihydrochloride (5?mg/Kg; i.p.) results in a significant reduction in lesion size at 28 days in histological assessment^[2].