Casein Kinase (CK) Inhibitors

Casein kinases I and II (CKI and CKII) are highly conserved, ubiquitous serine/threonine protein kinases that play a significant role in neoplasia and cell survival. CKI can be found in the nucleus and the cytosol and is bound to the cytoskeleton and membranes. The CKI family consists of several isoforms (CKIα, Β, γ1, γ2, γ3, δ, and ε) encoded by seven distinct genes. It plays a significant role in the regulation of circadian rhythm, intracellular trafficking and also acts as a regulator of Wnt signaling, nuclear import, and the progression of Alzheimer’s disease. CKI substrates include transcription factors, cytoskeleton proteins, receptors, tau proteins, presenilin, and b-catenin. CKII has traditionally been classified as a messenger-independent protein serine/threonine kinase and consists of two catalytic and two regulatory subunits. It plays an important role in the progression of the cell cycle and in maintenance of cell viability. It is highly conserved and is known to phosphorylate about 300 different proteins. CKII activity is required at transition points of the cell cycle. Excessive activity of CKII has been linked to oncogenic transformation and the development of primary and metastatic tumors.