Cyclin-dependent kinase and Glycogen synthase kinase-3 beta (CDK and GSK-3β)

Cyclin-dependent kinases (CDKs) are a family of serine/threonine kinases that, when complexed with their regulatory cyclin partners, are essential for control of the eukaryotic cell cycle, including regulation of cell division, DNA replication, and cell cycle checkpoints. CDK dysregulation is commonly implicated in cancer and proliferative disorders, making them key cancer therapy targets. Glycogen synthase kinase-3 beta (GSK-3β) is a multifunctional serine/threonine kinase involved in glycogen metabolism, cell signaling, cell proliferation, and apoptosis. GSK-3β phosphorylates a range of substrates, including regulatory cell cycle proteins such as cyclin D1, and is implicated in cancer, neurodegeneration, diabetes, and psychiatric disorders. Both CDKs and GSK-3β are validated drug targets, and a number of small-molecule inhibitors with therapeutic potential have been developed and are in use or in clinical trials. While they share structural similarities and can be targeted simultaneously, they are distinct molecular entities with different, though sometimes intersecting, pathways.

Other names

CDK (Cyclin-dependent kinases)Cyclin-dependent kinase family (including CDK1, CDK2, CDK4, CDK5, CDK6, etc.)Glycogen synthase kinase-3 betaGSK-3 betaGSK3B

ATP-competitive inhibition (most small-molecule inhibitors). Inhibition of substrate phosphorylation (blocks progression of cell cycle for CDKs; blocks downstream signaling for GSK-3β). Modulation of proteasomal degradation of regulatory proteins (e.g., cyclin D1 via GSK-3β phosphorylation). Inhibition of tau hyperphosphorylation (by dual CDK5 and GSK-3β inhibition in neurodegeneration).