The many faces of Janus kinase.
Janus kinases have proved to be essential for many immunological processes but there is growing evidence that they also play a critical role in pathogenesis of many diseases including inflammatory diseases and cancer where they promote multiple steps of tumorigenesis. Several companies are in late stage clinical programs for the development of JAK kinase inhibitors and the first small molecule JAK inhibitor, Jakafi® (ruxolitinib) has been just approved for treatment of myeloproliferative neoplasms. Several other molecules are on the rise to treat arthritis, psoriasis and multiple types of cancer. This commentary will provide a review of the JAK kinase field as it pertains to small molecule inhibition for the treatment of cancer and autoimmune diseases with an emphasis on JAK2. The use of experimental and clinical inhibitors of JAK will be discussed for solid tumor and hematological malignancies, lupus, arthritis, colitis, neurological disorders, pain, diabetes and cardiovascular disease. In addition, it will review current paradigms in the field and treatment programs which could be complemented by small molecule inhibitors of Janus kinase.
Cephalon, Inc., Drug Discovery Research, 145 Brandywine Parkway, West Chester, PA 19380, USA. matthew.seavey@gmail.com
Matthew M
MM
Seavey
Pawel
P
Dobrzanski
D000970:Antineoplastic Agents / Q000494:pharmacology; D001172:Arthritis, Rheumatoid / Q000188:drug therapy / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005786:Gene Expression Regulation; D019337:Hematologic Neoplasms / Q000188:drug therapy; D006801:Humans; D015212:Inflammatory Bowel Diseases / Q000188:drug therapy / Q000378:metabolism; D053614:Janus Kinase 2 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D053612:Janus Kinases / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism*; D008180:Lupus Erythematosus, Systemic / Q000188:drug therapy / Q000378:metabolism; D009154:Mutation; D009196:Myeloproliferative Disorders / Q000188:drug therapy / Q000378:metabolism; D009369:Neoplasms / Q000188:drug therapy / Q000276:immunology / Q000378:metabolism*; D050796:STAT3 Transcription Factor / Q000378:metabolism; D050799:STAT5 Transcription Factor / Q000378:metabolism; D015398:Signal Transduction
D000970:Antineoplastic Agents; D016207:Cytokines; D004791:Enzyme Inhibitors; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; D050799:STAT5 Transcription Factor; C507924:JAK2 protein, human; D053614:Janus Kinase 2; D053612:Janus Kinases