Non-ATP competitive inhibitors of cyclin dependent kinases as cancer therapeutics

描述（由申请人提供）：在美国，癌症是导致死亡的主要原因之一，其中一些亚型基本上无法治疗，扩大现有药物靶点将为开发更有效的抗肿瘤药物提供重要的新选择。该项目的主要目标是将一种独特的药物发现策略应用于癌症药物的开发。这将通过将该方法应用于发现和表征与抗癌治疗相关的新药物样小分子疗法的相互作用来实现。基于蛋白质-蛋白质相互作用抑制剂开发药物的改进策略将是有益的，以便克服目前大多数可药物靶标涉及配体-受体和酶-底物相互作用的局限性。我们将把重点放在细胞周期蛋白依赖性激酶底物募集位点作为有效的抗肿瘤药物靶点上。通过这个网站，机会来了

DESCRIPTION (provided by applicant): As cancer is one of the leading causes of death in the United States with some sub-types remaining essentially untreatable, expansion of available drug targets will provide significant new options for the development of more effective antineoplastic agents. The major goal of this project is to apply a unique drug discovery strategy to cancer drug development. This will be accomplished through application of this methodology to the discovery and characterization of new drug-like small molecule therapeutics disrupting interactions relevant to anti-cancer therapy. Improved strategies for developing pharmaceuticals based on inhibitors of protein-protein interactions would be beneficial in order to overcome the limitations of the majority of currently druggable targets to those involving ligand-receptor and enzyme-substrate interactions. We will focus our efforts on the Cyclin Dependent Kinase substrate recruitment site as a validated antitumor drug target. Through this site, the opportunity exists to develop potent and selective inhibitors that are specific to the cell cycle CDKs. Such compounds possessing appropriate drug-like characteristics will potentially be different mechanistically from ATP competitive CDK inhibitors, targeting tumor cells selectively and thereby addressing issues with agents currently being developed.