molecules of the month

(R)-CR8 is a known CDK inhibitor that was recently discovered to be a molecular glue-type degrader of cyclin K. A crystal structure of an E3 component-CR8-CDK12-cyclin K complex shows that CR8 acts by binding to the active site of a CDK (which binds to cyclin K), and recruiting an E3 component through a solvent-exposed lipophilic moiety on the molecule. This interesting mechanism is something to consider when observing unexpected cellular activities with solvent-exposed motifs in discovery programs!