Potent and preferential degradation of CDK6 via proteolysis targeting chimera degraders Journal Article
| 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. |
| Article Title: | Potent and preferential degradation of CDK6 via proteolysis targeting chimera degraders |
| 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. Copyright © 2019 American Chemical Society. |
| Journal Title: | Journal of Medicinal Chemistry |
| Volume: | 62 |
| Issue: | 16 |
| ISSN: | 0022-2623 |
| Publisher: | American Chemical Society |
| Date Published: | 2019-08-22 |
| Start Page: | 7575 |
| End Page: | 7582 |
| Language: | English |
| DOI: | 10.1021/acs.jmedchem.9b00871 |
| PUBMED: | 31330105 |
| PROVIDER: | scopus |
| PMCID: | PMC6790125 |
| DOI/URL: | |
| Notes: | Source: Scopus |
