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However, due to conservation of their ATP\u2010binding sites, development of selective agents has remained elusive. Here, we report imide\u2010based degrader molecules capable of degrading both CDK4\/6, or selectively degrading either CDK4 or CDK6. We were also able to tune the activity of these molecules against Ikaros (IKZF1) and Aiolos (IKZF3), which are well\u2010established targets of imide\u2010based degraders. We found that in mantle cell lymphoma cell lines, combined IKZF1\/3 degradation with dual CDK4\/6 degradation produced enhanced anti\u2010proliferative effects compared to CDK4\/6 inhibition, CDK4\/6 degradation, or IKZF1\/3 degradation. In summary, we report here the first compounds capable of inducing selective degradation of CDK4 and CDK6 as tools to pharmacologically dissect their distinct biological functions.<\/jats:p>","DOI":"10.1002\/anie.201901336","type":"journal-article","created":{"date-parts":[[2019,2,26]],"date-time":"2019-02-26T00:58:00Z","timestamp":1551142680000},"page":"6321-6326","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":264,"title":["Development of Dual and Selective Degraders of Cyclin\u2010Dependent Kinases 4 and 6"],"prefix":"10.1002","volume":"58","author":[{"given":"Baishan","family":"Jiang","sequence":"first","affiliation":[{"name":"Department of Cancer Biology Dana-Farber Cancer Institute  Boston MA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eric S.","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Cancer Biology Dana-Farber Cancer Institute  Boston MA 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