Cyclin-dependent kinases (CDKs) are a group of multifunctional enzymes consisting of catalytic and regulatory subunits. The regulatory subunit, cyclin, remains dissociated under normal circumstances, and complexation of cyclin with the catalytic subunit of CDK leads to its activation for phosphorylation of protein substrates. The primary role of CDKs is in the regulation of the cell cycle. Retinoblastoma protein (Rb) is one of the widely investigated tumor suppressor protein substrates of CDK, which prevents cells from entering into cell-cycle under normal conditions. Phosphorylation of Rb by CDKs causes its inactivation and ultimately allows cells to enter a new cell cycle. Many cancers are associated with hyperactivation of CDKs as a result of mutation of the CDK genes or CDK inhibitor genes. Therefore, CDK modulators are of great interest to explore as novel therapeutic agents against cancer and led to the discovery of several CDK inhibitors to clinics. This review focuses on the current progress and development of anti-cancer CDK inhibitors from preclinical to clinical and synthetic to natural small molecules.

细胞周期蛋白依赖性激酶（CDK）是一组由催化亚基和调节亚基组成的多功能酶。调节亚基细胞周期蛋白在正常情况下仍保持解离，而细胞周期蛋白与CDK催化亚基的复合作用导致其活化，使蛋白质底物磷酸化。CDK的主要作用是调节细胞周期。视网膜母细胞瘤蛋白（Rb）是CDK中广泛研究的肿瘤抑制蛋白底物之一，它可以阻止细胞在正常条件下进入细胞周期。CDK使Rb磷酸化会使其失活，并最终使细胞进入新的细胞周期。由于CDK基因或CDK抑制剂基因的突变，许多癌症与CDK的过度活化有关。因此，CDK调节剂作为新型抗癌治疗剂而引起人们的极大兴趣，并导致临床上发现了几种CDK抑制剂。这篇综述聚焦于抗癌CDK抑制剂从临床前到临床以及从合成到天然小分子的当前进展和发展。