Therapeutic inhibition of the Janus kinases

Abstract

Since the success of imatinib in the treatment of chronic myeloid leukemia, tyrosine kinaseinhibitors have been shown to be both efficacious and well tolerated despite absolute specificityfor a single kinase. Consequently, multiple tyrosine kinase inhibitors have been approved andmany more are in development. The JAK family of tyrosine kinases consists of 4 cytoplasmicproteins, which are obligatorily required for Type I/II cytokine receptors to signal and activateintracellular signaling pathways. They are critical for the function of over 60 cytokines and aretherefore attractive targets for the generation of new immunomodulatory and oncology drugs.