CP-10 is a selective CDK6 degrading PROTAC [1
]. It is a bifunctional molecule that combines the CDK4/6 inhibitor palbociclib
, with the cereblon ligand pomalidomide
. The pomalidomide moiety recruits E3 ubiquitin ligase machinery to the palbociclib-bound kinase protein, which leads to proteasomal degradation of CDK6. Selectivity of CP-10 appears to be cell line dependent, so CDK4 levels should be monitored to detect off-target activity, given palbociclib's selectivity profile for CDK6 and CDK4. CP-10 degrades mutant forms of CDK6 (e.g
) as efficiently as it degrades wild-type kinase protein, and it induces degradation of CDK6 and CDK4 and inhibits the proliferation in palbociclib resistant cell lines.