Janus kinase protein family (JAK protein family)

Janus kinase proteins (JAKs) are a family of intracellular, non-receptor tyrosine kinases that mediate signal transduction from cytokine and growth factor receptors through the JAK-STAT pathway. Each JAK is characterized by two main domains: a kinase domain and a catalytically inactive pseudokinase domain. They are essential for various biological processes, including immune cell development, hematopoiesis, and inflammatory signaling. Abnormal activation or mutation of JAK proteins is implicated in a range of diseases, including autoimmune disorders, cancers, and immunodeficiencies. Multiple small-molecule JAK inhibitors have been developed and approved for therapeutic use in inflammatory and neoplastic diseases, though challenges include adverse effects, drug selectivity, and acquired resistance

Other names

JAKsJust Another KinaseJanus kinasesJAK1JAK2JAK3TYK2

Competitive inhibition of the ATP-binding site of JAK kinases, preventing receptor phosphorylation and downstream STAT activation. Disruption of JAK dimerization or conformational changes (emerging strategies). Irreversible (covalent) inhibitors and reversible inhibitors exist