title: Selective inhibitors of the Janus kinase Jak3--Are they effective?
abstract: Jak3, together with Jak1, is involved in signal transduction initiated by cytokines signaling through the common gamma chain which are important in immune homeostasis and immune pathologies. Based on genetic evidence Jak3 has been considered to be an attractive target for immunosuppression. The Jak inhibitor tofacitinib (CP-690,550) which is an approved drug for rheumatoid arthritis was originally introduced as a selective Jak3 inhibitor, however, it also inhibits Jak1 and Jak2. The search for new selective Jak3 inhibitors has yielded several compounds whose profiles will be reviewed here. Implications on Jak3 as a therapeutic target are also discussed.
authors.affiliation: Global Discovery Chemistry, Novartis Institutes for Biomedical Research, 4056 Basel, Switzerland. Electronic address: gebhard.thoma@novartis.com.
authors.forename: Gebhard
authors.initials: G
authors.lastname: Thoma
authors.affiliation: Center for Proteomic Chemistry, Screening Sciences, Novartis Institutes for Biomedical Research, 4056 Basel, Switzerland.
authors.forename: Peter
authors.initials: P
authors.lastname: Drückes
authors.affiliation: Autoimmunity, Transplantation and Inflammation Research, Novartis Institutes for Biomedical Research, 4056 Basel, Switzerland. Electronic address: hans-guenter.zerwes@novartis.com.
authors.forename: Hans-Günter
authors.initials: HG
authors.lastname: Zerwes
mesh_terms: D000818:Animals; D006801:Humans; D053616:Janus Kinase 3 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D015394:Molecular Structure; D047428:Protein Kinase Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: D047428:Protein Kinase Inhibitors; D053616:Janus Kinase 3
keywords: Immunosuppression; Jak1; Jak3; Janus kinase inhibitors; Selectivity