Unit of Medicinal Chemistry, Department of Pharmacy, "G. d'Annunzio" University, 66100 Chieti, Italy.
Molecules. 2021 Mar 9;26(5):1488. doi: 10.3390/molecules26051488.
The inhibition of cyclin dependent kinases 4 and 6 plays a role in aromatase inhibitor resistant metastatic breast cancer. Three dual CDK4/6 inhibitors have been approved for the breast cancer treatment that, in combination with the endocrine therapy, dramatically improved the survival outcomes both in first and later line settings. The developments of the last five years in the search for new selective CDK4/6 inhibitors with increased selectivity, treatment efficacy, and reduced adverse effects are reviewed, considering the small-molecule inhibitors and proteolysis-targeting chimeras (PROTACs) approaches, mainly pointing at structure-activity relationships, selectivity against different kinases and antiproliferative activity.
细胞周期蛋白依赖性激酶 4 和 6 的抑制在芳香酶抑制剂耐药转移性乳腺癌中发挥作用。三种双重 CDK4/6 抑制剂已被批准用于乳腺癌治疗，与内分泌治疗联合使用，在一线和二线治疗中均显著改善了生存结果。本文综述了过去五年中为寻找具有更高选择性、治疗效果和降低不良反应的新型选择性 CDK4/6 抑制剂所做的努力，考虑了小分子抑制剂和蛋白水解靶向嵌合体（PROTACs）方法，主要侧重于结构-活性关系、对不同激酶的选择性和抗增殖活性。
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