PDF(Pubmed)
Abstract：
The regulation of the cancer cell cycle heavily relies on cyclin-dependent kinases (CDKs). Targeting CDKs has been identified as a promising approach for effective cancer therapy. In recent years, there has been significant attention paid towards developing small-molecule CDK inhibitors in the field of drug discovery. Notably, five such inhibitors have already received regulatory approval for the treatment of different cancers, including breast tumors, lung malignancies, and hematological malignancies. This review provides an overview of the synthetic routes used to produce 17 representative small-molecule CDK inhibitors that have obtained regulatory approval or are currently being evaluated through clinical trials. It also discusses their clinical applications for treating CDK-related diseases and explores the challenges and limitations associated with their use in a clinical setting, which will stimulate the further development of novel CDK inhibitors. By integrating therapeutic applications, synthetic methodologies, and mechanisms of action observed in various clinical trials involving these CDK inhibitors, this review facilitates a comprehensive understanding of the versatile roles and therapeutic potential offered by interventions targeting CDKs.
摘要：
癌细胞周期的调节严重依赖于细胞周期蛋白依赖性激酶(CDK)。靶向CDK已被确定为有效癌症治疗的有希望的方法。近年来,在药物发现领域中,已经对开发小分子CDK抑制剂给予了极大的关注。值得注意的是,五种这样的抑制剂已经获得了监管部门的批准，用于治疗不同的癌症，包括乳腺肿瘤,肺部恶性肿瘤,和血液恶性肿瘤。这篇综述概述了用于生产17种代表性小分子CDK抑制剂的合成路线，这些抑制剂已获得监管批准或目前正在通过临床试验进行评估。它还讨论了它们在治疗CDK相关疾病中的临床应用，并探讨了与它们在临床环境中使用相关的挑战和局限性。这将刺激新型CDK抑制剂的进一步开发。通过整合治疗应用，合成方法学，以及在涉及这些CDK抑制剂的各种临床试验中观察到的作用机制，这篇综述有助于全面了解针对CDK的干预措施所提供的多功能作用和治疗潜力.
