State Key Laboratory of Natural Medicines and Jiangsu Key Laboratory of Drug Design and Optimization, China Pharmaceutical University, Nanjing, 210009, China.
Department of Medicinal Chemistry, School of Pharmacy, China Pharmaceutical University, Nanjing, 211198, China.
Future Med Chem. 2024 Feb;16(4):369-388. doi: 10.4155/fmc-2023-0259. Epub 2024 Jan 30.
Cyclin-dependent kinases (CDKs) play an important role in the regulation of cell proliferation, and many CDK inhibitors were developed. However, pan-CDK inhibitors failed to be approved due to intolerant toxicity or low efficacy and the use of selective CDK4/6 inhibitors is limited by resistance. Protein degraders have the potential to increase selectivity, efficacy and overcome resistance, which provides a novel strategy for regulating CDKs. In this review, we summarized the function of CDKs in regulating the cell cycle and transcription, and introduced the representative CDK inhibitors. Then we made a detailed introduction about four types of CDKs degraders, including their action mechanisms, research status and application prospects, which could help the development of novel CDKs degraders.
细胞周期蛋白依赖性激酶(CDKs)在细胞增殖的调控中起着重要作用,许多 CDK 抑制剂已被开发出来。然而,由于不耐受毒性或低疗效,泛 CDK 抑制剂未能获得批准,而选择性 CDK4/6 抑制剂的使用受到耐药性的限制。蛋白降解剂具有提高选择性、疗效和克服耐药性的潜力,为调节 CDK 提供了一种新策略。在这篇综述中,我们总结了 CDK 在调节细胞周期和转录中的功能,并介绍了代表性的 CDK 抑制剂。然后,我们详细介绍了四种 CDK 降解剂,包括它们的作用机制、研究现状和应用前景,这有助于新型 CDK 降解剂的开发。