The JAK kinases: not just another kinase drug discovery target.
There are four members of the JAK family of protein tyrosine kinases (PTKs) in the human genome. Since their discovery in 1989, great strides have been made in the understanding of their role in normal intracellular signalling. Importantly, their roles in pathologies ranging from cancer to immune deficiencies have placed them front and centre as potential drug targets. The recent discovery of the role of activating mutations in the kinase-like domain (KLD) of JAK2 in the development of polycythemia rubra vera, and the elaboration of KLD mutation as a broader mechanism by which cells might become hyperproliferative has sparked enormous interest in the development of JAK selective drug candidates. I review herein the progress that has been made in the discovery of JAK-targeted inhibitors, and discuss the challenges that face the development of these drugs for use in the clinic.
Wilks
Andrew F
AF
SYN|thesis med chem, PO Box 450, South Yarra, Victoria 3141, Australia. andrew.wilks@synmedchem.com
D000595:Amino Acid Sequence; D055808:Drug Discovery; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D007527:Isoenzymes / Q000737:chemistry / Q000145:classification / Q000235:genetics / Q000378:metabolism*; D053612:Janus Kinases / Q000737:chemistry / Q000145:classification / Q000235:genetics / Q000378:metabolism*; D008958:Models, Molecular; D008969:Molecular Sequence Data; D015394:Molecular Structure; D011487:Protein Conformation; D016415:Sequence Alignment; D015398:Signal Transduction / Q000502:physiology
D004791:Enzyme Inhibitors; D007527:Isoenzymes; D053612:Janus Kinases