{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T14:35:34Z","timestamp":1789569334186,"version":"build-2803163510"},"reference-count":133,"publisher":"MDPI AG","issue":"24","license":[{"start":{"date-parts":[[2023,12,13]],"date-time":"2023-12-13T00:00:00Z","timestamp":1702425600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81903443"],"award-info":[{"award-number":["81903443"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["24A350003"],"award-info":[{"award-number":["24A350003"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Key Scientific Research Program of the Higher Education Institutions of Henan Province","award":["81903443"],"award-info":[{"award-number":["81903443"]}]},{"name":"Key Scientific Research Program of the Higher Education Institutions of Henan Province","award":["24A350003"],"award-info":[{"award-number":["24A350003"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Cell division in eukaryotes is a highly regulated process that is critical to the life of a cell. Dysregulated cell proliferation, often driven by anomalies in cell Cyclin-dependent kinase (CDK) activation, is a key pathological mechanism in cancer. Recently, selective CDK4\/6 inhibitors have shown clinical success, particularly in treating advanced-stage estrogen receptor (ER)-positive and human epidermal growth factor receptor 2 (HER2)-negative breast cancer. This review provides an in-depth analysis of the action mechanism and recent advancements in CDK4\/6 inhibitors, categorizing them based on their structural characteristics and origins. Furthermore, it explores proteolysis targeting chimers (PROTACs) targeting CDK4\/6. We hope that this review could be of benefit for further research on CDK4\/6 inhibitors and PROTACs.<\/jats:p>","DOI":"10.3390\/molecules28248060","type":"journal-article","created":{"date-parts":[[2023,12,13]],"date-time":"2023-12-13T12:00:37Z","timestamp":1702468837000},"page":"8060","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":28,"title":["Recent Progress in CDK4\/6 Inhibitors and PROTACs"],"prefix":"10.3390","volume":"28","author":[{"given":"Hao","family":"Wang","sequence":"first","affiliation":[{"name":"Key Laboratory of Natural Medicine and Immuno-Engineering of Henan Province, Henan University Jinming Campus, Kaifeng 475004, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianfei","family":"Ba","sequence":"additional","affiliation":[{"name":"Key Laboratory of Natural Medicine and Immuno-Engineering of Henan Province, Henan University Jinming Campus, Kaifeng 475004, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yue","family":"Kang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Natural Medicine and Immuno-Engineering of Henan Province, Henan University Jinming Campus, Kaifeng 475004, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zeqiao","family":"Gong","sequence":"additional","affiliation":[{"name":"Key Laboratory of Natural Medicine and Immuno-Engineering of Henan Province, Henan University Jinming Campus, Kaifeng 475004, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tingting","family":"Liang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Natural Medicine and Immuno-Engineering of Henan Province, Henan University Jinming Campus, Kaifeng 475004, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yahong","family":"Zhang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Natural Medicine and Immuno-Engineering of Henan Province, Henan University Jinming Campus, Kaifeng 475004, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8087-1169","authenticated-orcid":false,"given":"Jianguo","family":"Qi","sequence":"additional","affiliation":[{"name":"Key Laboratory of Natural Medicine and Immuno-Engineering of Henan Province, Henan University Jinming Campus, Kaifeng 475004, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianhong","family":"Wang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Natural Medicine and Immuno-Engineering of Henan Province, Henan University Jinming Campus, Kaifeng 475004, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,12,13]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"263","DOI":"10.1126\/science.abm2010","article-title":"A cell cycle regulator branches out: A key G1 kinase targets transcription to drive cell cycle commitment","volume":"374","author":"Fisher","year":"2021","journal-title":"Science"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"459","DOI":"10.1016\/j.molcel.2020.03.010","article-title":"Cdk1 Controls Global Epigenetic Landscape in Embryonic Stem Cells","volume":"78","author":"Michowski","year":"2020","journal-title":"Mol. 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