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Review Article

细胞周期蛋白依赖性激酶8抑制剂的发现和发展。

卷 27, 期 32, 2020

页: [5429 - 5443] 页: 15

弟呕挨: 10.2174/0929867326666190402110528

价格: $65

摘要

依赖细胞周期蛋白的激酶8（CDK8）是CDKs家族的一员，由于近年来对其在转录和肿瘤发生中的关键作用的研究而受到广泛关注。 CDK8及其旁系CDK19的选择性抑制为某些癌症的治疗提供了一种新颖的治疗策略。 到目前为止，尽管已经发现了许多针对CDK8的小分子，但由于选择性低和理化性质差，大多数在临床前试验中已被中止。 本文综述了具有不同化学骨架的选择性CDK8抑制剂的设计策略，旨在提高其抑制活性，选择性，代谢稳定性和溶解性。 还审查了它们相应的结构-活性关系（SAR）。 在此综述的讨论基础上，我们希望在不久的将来开发出更有效，更具选择性和类似药物的CDK8抑制剂，并证明其治疗价值。

关键词: CDK8，CDK19，选择性抑制剂，设计，构效关系，代谢稳定性，细胞周期蛋白依赖性激酶，CDK8抑制剂。

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