Description: CP-10 (CP10; CP 10), designed from a focused PROTAC library hijacking cancer therapeutic target CDK6, is a novel and potent PROTAC-based protein degrader targeting CDK6 with high selectivity, specificity, and remarkable CDK6 degradation efficiency (DC50=2.1 nM). It inhibits proliferation of several haematopoietic cancer cells with impressive potency including multiple myeloma, and can still degrades mutated and overexpressed CDK6. A design principle as 'match/mismatch' was proposed for understanding the degradation profile differences in these PROTACs. Notably, potent PROTACs with specific and remarkable CDK6 degradation potential were generated by linking CDK6 inhibitor palbociclib and E3 ligase CRBN recruiter pomalidomide. The PROTAC strongly inhibited proliferation of hematopoietic cancer cells including multiple myeloma and robustly degraded copy-amplified/mutated forms of CDK6, indicating future potential clinical applications.