Sharma P Sapra, Sharma R, Tyagi R
Department of Chemistry, C.S.S.S. (P. G.) College, Machhra, Meerut, Uttar Pradesh, India.
Curr Cancer Drug Targets. 2008 Feb;8(1):53-75. doi: 10.2174/156800908783497131.
Cancer drug discovery is one of the most rapidly changing areas of pharmaceutical research. Uncontrolled proliferation is a hallmark of cancer cells. Over the past two decades, it has become increasingly clear that in many human cancers, hyperactivity of Cyclin Dependent Kinases (CDKs) is one of the mechanisms underlying the physiological hyper-proliferation. CDKs are serine/threonine protein kinases, which play an important role in cell-cycle regulation. Their sequential activation ensures, the correct timing and ordering of events required for cell cycle progression. Therefore, inhibition of CDKs, through the insertion of small molecules into its ATP binding pocket has emerged as a potential therapy method for cancers. Consequently, a number of small molecules with CDK inhibitory properties have been developed. Many of these have been evaluated as potent inhibitors and some are currently in clinical-trials for various types of cancer. This review reports various CDK inhibitors, natural as well as small molecules, along with their reported activities for various CDKs. It will highlight the potential for the development of novel anti-cancer molecules.
癌症药物研发是制药研究中变化最为迅速的领域之一。不受控制的增殖是癌细胞的一个标志。在过去二十年中，越来越明显的是，在许多人类癌症中，细胞周期蛋白依赖性激酶（CDK）的过度活跃是生理上过度增殖的潜在机制之一。CDK是丝氨酸/苏氨酸蛋白激酶，在细胞周期调控中起重要作用。它们的顺序激活确保了细胞周期进程所需事件的正确时间和顺序。因此，通过将小分子插入其ATP结合口袋来抑制CDK已成为一种潜在的癌症治疗方法。因此，已经开发了许多具有CDK抑制特性的小分子。其中许多已被评估为强效抑制剂，有些目前正在针对各种类型的癌症进行临床试验。本综述报告了各种CDK抑制剂，包括天然的和小分子的，以及它们对各种CDK的报道活性。它将突出新型抗癌分子的开发潜力。
