title: Selective JAK inhibitors.
abstract: Consisting of four members, JAK1, JAK2, JAK3 and TYK2, the JAK kinases have emerged as important targets for proliferative and immune-inflammatory disorders. Recent progress in the discovery of selective inhibitors has been significant, with selective compounds now reported for each isoform. This article summarizes the current state-of-the-art with a discussion of the most recently described selective compounds. X-ray co-crystal structures reveal the molecular reasons for the observed biochemical selectivity. A concluding analysis of JAK inhibitors in the clinic highlights increased clinical trial activity and diversity of indications. Selective JAK inhibitors, as single agents or in combination regimens, have a very promising future in the treatment of oncology, immune and inflammatory diseases.
authors.affiliation: Department of Pharmacy, National University of Singapore, 18 Science Drive 4, Singapore 117543.
authors.forename: Brian W
authors.initials: BW
authors.lastname: Dymock
authors.forename: Eugene Guorong
authors.initials: EG
authors.lastname: Yang
authors.forename: Yuyi
authors.initials: Y
authors.lastname: Chu-Farseeva
authors.forename: Lianbin
authors.initials: L
authors.lastname: Yao
mesh_terms: D000818:Animals; D004305:Dose-Response Relationship, Drug; D006801:Humans; D053612:Janus Kinases / Q000037:antagonists & inhibitors*; D008958:Models, Molecular; D008968:Molecular Conformation; D047428:Protein Kinase Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D013379:Substrate Specificity
chemical_list: D047428:Protein Kinase Inhibitors; D053612:Janus Kinases