Pyrogallin, an ATP-Competitive Inhibitor of JAK3

摘要

The Janus kinase (JAK) family mediates important cytokine signaling proliferation, growth, hematopoiesis, and immune response in a variety of cells. The JAK family consists of four different tyrosine kinases: TYK2, JAK1, JAK2, and JAK3. Activation of JAK1 and JAK3 induces phosphorylation of STAT (Signal Transducers and Activators of Transcription) proteins. The phosphorylated STAT proteins then dimerize and traffic into the nucleus in which they work as a transcription factor to regulate genes involved in various immune responses, In contrast to other JAK kinases present in a wide range of cell lines, JAK3 is selectively expressed only in matured hematopoietic cells. Thus, specific inhibition of JAK3 would have therapeutic potential in treatment of immune-related diseases including asthma and rheumatoid arthritis via immunosuppression without affecting cells and organ compartments except the immune system.