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.
