CDK9作为癌症研究靶点的概述。
Overview of CDK9 as a target in cancer research.
作者信息
Morales Fatima, Giordano Antonio
机构信息
a Sbarro Institute for Cancer Research and Molecular Medicine, Center for Biotechnology, College of Science and Technology, Temple University , Philadelphia , PA , USA.
b Department of Medicine , Surgery and Neuroscience, University of Siena , Siena , Italy.
出版信息
Cell Cycle. 2016;15(4):519-27. doi: 10.1080/15384101.2016.1138186.
CDK9 is a protein in constant development in cancer therapy. Herein we present an overview of the enzyme as a target for cancer therapy. We provide data on its characteristics and mechanism of action. In recent years, CDK9 inhibitors that have been designed with molecular modeling have demonstrated good antitumoral activity in vitro. Clinical studies of the drugs flavopiridol, dinaciclib, seliciclib, SNS-032 and RGB-286638 used as CDK9 inhibitors are also reviewed, with their additional targets and their relative IC50 values. Unfortunately, treatment with these drugs remains unsuccessful and involves many adverse effects. We could conclude that there are many small molecules that bind to CDK9, but their lack of selectivity against other CDKs do not allow them to get to the clinical use. However, drug designers currently have the tools needed to improve the selectivity of CDK9 inhibitors and to make successful treatment available to patients.
细胞周期蛋白依赖性激酶9（CDK9）是癌症治疗中不断发展的一种蛋白质。在此，我们概述了该酶作为癌症治疗靶点的情况。我们提供了关于其特性和作用机制的数据。近年来，通过分子建模设计的CDK9抑制剂在体外已显示出良好的抗肿瘤活性。还综述了用作CDK9抑制剂的药物氟吡汀、地西他滨、司立西利、SNS - 032和RGB - 286638的临床研究，包括它们的其他靶点及其相对半数抑制浓度（IC50）值。不幸的是，使用这些药物进行治疗仍然未获成功，且涉及许多不良反应。我们可以得出结论，有许多小分子与CDK9结合，但其对其他细胞周期蛋白依赖性激酶缺乏选择性，这使得它们无法用于临床。然而，药物研发人员目前拥有提高CDK9抑制剂选择性并使患者能够获得成功治疗所需的工具。
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