Cdk6 Inhibitors

Cyclin-dependent kinases (Cdks) are a family of proteins that play a crucial role in regulating the cell cycle, a series of events that leads to cell growth and division. Cdks are a type of serine/threonine kinase, which means they add phosphate groups to specific serine or threonine residues on target proteins, thereby regulating their activity. Cdks are present in all eukaryotic organisms, including humans, and are highly conserved across species. They work in conjunction with another group of proteins called cyclins, which are named after their periodic oscillation in concentration throughout the cell cycle. Cyclins bind to Cdks and activate them by inducing a conformational change that exposes the kinase active site. Cyclin-dependent kinase 6 (Cdk6) inhibitors constitute a diverse class of compounds designed to modulate cell cycle progression, particularly in the context of cancer. These inhibitors act by selectively targeting the kinase activity of Cdk6, a crucial regulator of the G1 to S phase transition in the cell cycle. The primary mechanism involves preventing the phosphorylation of retinoblastoma protein (Rb), a key substrate of Cdk6, which, when phosphorylated, promotes cell cycle progression. Palbociclib, Ribociclib, and Abemaciclib exhibiting specificity towards Cdk6 and effectively arresting cell cycle progression in cancer cells. Broad-spectrum kinase inhibitors such as Flavopiridol and Dinaciclib target multiple Cdks, including Cdk6, showcasing promise in inhibiting aberrant cell proliferation. Compounds like PD0332991 and LY2835219 have demonstrated efficacy by specifically blocking Cdk6.