The hallmark of cancer is the continuous proliferative capacity of cancerous cells. In mammalian cells progression is controlled by the cell cycle, where checkpoints are regulated by CDKs. CDK 4 and CDK 6 regulates cell cycle progression at the G1 restriction point, thus are highly considered as anti-cancer drug targets. The cell cycle contains a dimeric enzyme which becomes active and inactive at regular intervals. The dimeric enzyme consists of a catalytic subunit, CDK and a regulatory subunit, cyclin. CDK with cyclin combines to form a cyclin-CDK complex for the regulation of cell cycle. Cyclin-CDK complex gets activated after phosphorylation which results in release of proteins, that leads to cell proliferation.
CDK inhibitors are the proteins that networks with a cyclin-CDK complex to inhibit the kinase activity of the complex, usually during G1 phase. Clinical application of first-generation, non-selective CDK inhibitors are designed to inhibit proliferation of cells, that was initially hindered by the lack of efficacy and high risk of toxicity observed with these agents. The development of a new generation of selective CDK 4/6 inhibitors, including palbociclib, abemaciclib and ribociclib has ability to target CDK 4/6 with fewer adverse effects and improved effectiveness, as they have a vital role in the G1 to S phase cell-cycle transition.
Drug manufacturing companies are constantly involved in the quest to find better and new treatment strategies by targeting CDKs which can be effective in various indications including cancer and Cushing’s disease treatment. Various companies are developing drug candidates using different technologies for the development of effective and better drugs, which is driving the growth of the pipeline.
As of July 2017, the CDK inhibitors therapeutics pipeline comprises of approximately 24 drug candidates in different stages of development.
CDK INHIBITORS DRUG CANDIDATES UNDER DEVELOPMENT (2017)
Some of the key players developing drugs as CDK inhibitors for the treatment of various indications include Eli Lilly and Company, Merck & Co., AstraZeneca plc and others.
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