title: Rethinking JAK2 inhibition: towards novel strategies of more specific and versatile Janus kinase inhibition.
abstract: Janus kinases (JAKs) are required for cytokine receptor signaling. Since the discovery of the highly prevalent JAK2 V617F mutation in myeloproliferative neoplasms (MPNs), JAK2 became a prime target for inhibition. Only one approved JAK2 inhibitor exists, with positive, but not curative effects in MPNs, and promising effects in autoimmune diseases and cancer. On the basis of recent advances in the structural features regulating both normal and mutant JAKs, as well as in small-molecule targeting, we review the current state of JAK2 inhibitor development and present novel avenues of selecting JAK2 inhibitors, with broad and narrow specificities and extend these approaches to other JAKs.
authors.affiliation: Christian de Duve Institute, Ludwig Institute for Cancer Research and Université catholique de Louvain, de Duve Institute, Brussels, Belgium.
authors.forename: E
authors.initials: E
authors.lastname: Leroy
authors.affiliation: Christian de Duve Institute, Ludwig Institute for Cancer Research and Université catholique de Louvain, de Duve Institute, Brussels, Belgium.
authors.forename: S N
authors.initials: SN
authors.lastname: Constantinescu
mesh_terms: D006801:Humans; D053614:Janus Kinase 2 / Q000037:antagonists & inhibitors*; D007938:Leukemia / Q000188:drug therapy; D009196:Myeloproliferative Disorders / Q000188:drug therapy; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use*; D012680:Sensitivity and Specificity
chemical_list: D047428:Protein Kinase Inhibitors; C507924:JAK2 protein, human; D053614:Janus Kinase 2