CDK6 degrader

CDK6 degraders represent an innovative class of targeted protein degraders (TPD), primarily designed as proteolysis-targeting chimeras (PROTACs), that selectively bind and induce the proteasomal degradation of cyclin-dependent kinase 6 (CDK6). Unlike traditional small-molecule CDK4/6 inhibitors (such as palbociclib, ribociclib, and abemaciclib) which only block enzymatic kinase activity, CDK6 degraders eliminate both the kinase-dependent and kinase-independent (scaffolding) functions of CDK6. This dual mechanism is highly advantageous in hematologic malignancies, such as acute myeloid leukemia (AML) and Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL), where leukemic stem cells exhibit a strong dependency on CDK6. By utilizing heterobifunctional linkers to recruit E3 ubiquitin ligases (such as Cereblon or VHL), these molecules facilitate the ubiquitination and subsequent degradation of CDK6, offering a promising therapeutic strategy to overcome resistance to conventional CDK4/6 inhibitors.

Other names

CDK6 PROTACCDK-6 PROTACCDK 6 PROTACCDK6 degradersCDK-6 degradersCDK 6 degradersCDK6-selective degraderCDK-6-selective degraderCDK 6-selective degraderCDK6-specific degraderCDK-6-specific degraderCDK 6-specific degraderCDK6-targeting PROTACCDK-6-targeting PROTACCDK 6-targeting PROTAC