Cyclin-dependent kinase (CDK)

Cyclin-dependent kinases (CDKs) are a family of serine/threonine protein kinases that require association with regulatory proteins called cyclins to become enzymatically active. Alone, CDKs are inactive; cyclin binding induces conformational changes that activate the kinase function. The primary function of CDKs is to drive cell cycle progression by phosphorylating specific target proteins at key checkpoints, but some also regulate transcription and other cellular events. CDKs have a two-lobed structure typical of protein kinases: an N-terminal β-sheet-rich lobe and a C-terminal α-helical lobe. Activation requires both cyclin binding and phosphorylation at specific residues within the activation loop/T-loop. Activity is tightly regulated by cyclins, phosphorylation/dephosphorylation events, inhibitory proteins, and checkpoint kinases. Dysregulation leads to diseases including cancer, neurodegenerative disorders, and stroke. Several small-molecule inhibitors targeting specific members of this family have shown promise in clinical trials for various cancers due to their central role in proliferation control.

Small-molecule inhibitors targeting specific members of this family.