CDK6 PROTAC CP-10 is a potent, selective CDK6 degrader (DC50=2.1 nM, U251 cells) generated by linking CDK6 inhibitor palbociclib and E3 ligase CRBN recruiter pomalidomide. CP-10 induces specific degradation of CDK6, with far weaker CDK4 degradation with DC50 of 150-180 nM. CP-10 induces degradation of CDK6 by the ubiquitin-proteasome system. CP-10 shows cell inhibition potential (IC50=10 nM) in multiple myeloma cell MM.lS and mantle cell lymphoma cells (in Mino, IC50=8 nM) or comparable activities in leukemia cells, induces degradation of amplified/mutated forms of CDK6 (D163G mutation).
