Cyclin-dependent kinases (CDKs) are a group of multifunctional enzymes consisting of catalytic
and regulatory subunits. The regulatory subunit, cyclin, remains dissociated under normal circumstances,
and complexation of cyclin with the catalytic subunit of CDK leads to its activation for phosphorylation
of protein substrates. The primary role of CDKs is in the regulation of the cell cycle. Retinoblastoma
protein (Rb) is one of the widely investigated tumor suppressor protein substrates of CDK,
which prevents cells from entering into cell-cycle under normal conditions. Phosphorylation of Rb by
CDKs causes its inactivation and ultimately allows cells to enter a new cell cycle. Many cancers are
associated with hyperactivation of CDKs as a result of mutation of the CDK genes or CDK inhibitor
genes. Therefore, CDK modulators are of great interest to explore as novel therapeutic agents against
cancer and led to the discovery of several CDK inhibitors to clinics. This review focuses on the current
progress and development of anti-cancer CDK inhibitors from preclinical to clinical and synthetic to
natural small molecules.
Keywords: Cyclin-dependent kinase, CDK inhibitors, Cell cycle, Clinical trial, Cancer, Natural products.
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