Inhibitors of cyclin dependent kinases: useful targets for cancer treatment

Abstract

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.