In Vitro: (R)-CR8 (CR8) trihydrochloride (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. ?(R)-CR8 trihydrochloride (0.25-10 μM) induces a dose-dependent induction of poly-(ADP-ribose)polymerase (PARP) cleavage. ?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.