Potent and Preferential Degradation of CDK6 via Proteolysis Targeting Chimera Degraders.
Basic Information
ID: ALA4311951
Journal: J Med Chem
Title: Potent and Preferential Degradation of CDK6 via Proteolysis Targeting Chimera Degraders.
Authors: Su S, Yang Z, Gao H, Yang H, Zhu S, An Z, Wang J, Li Q, Chandarlapaty S, Deng H, Wu W, Rao Y.
Abstract: A focused PROTAC library hijacking cancer therapeutic target CDK6 was developed. 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.
CiteXplore: 31330105
DOI: 10.1021/acs.jmedchem.9b00871
Patent ID: ┄