Inhibitors of Cyclin Dependent Kinases: Useful Targets for Cancer Treatment (An Update)

Cyclin-dependent kinases (CDKs) are serine/threonine protein kinases, which regulate multiple pathways such as the cell division cycle, apoptosis, transcription, and neuronal functions. Their sequential activation ensures the correct timing and ordering of events required for cell cycle progression. 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 CDKs is one of the mechanisms underlying the physiological hyper-proliferation. Therefore, inhibition of CDKs, through the insertion of small molecules into its ATP binding pocket has emerged as a potential therapy method for cancers. For these reasons an intensive search for pharmacological inhibitors of these protein kinases has been carried out during the last decade. 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.

Keywords: Cyclin dependent kinase, CKIs, small molecule inhibitors, anticancer agents, cell cycle, apoptosis.