title: Fragment-based discovery of JAK-2 inhibitors.
abstract: Fragment-based hit identification coupled with crystallographically enabled structure-based drug design was used to design potent inhibitors of JAK-2. After two iterations from fragment 1, we were able to increase potency by greater than 500-fold to provide sulfonamide 13, a 78-nM JAK-2 inhibitor.
authors.affiliation: Medicinal Chemistry, SGX Pharmaceuticals, Inc, San Diego, CA 92121, USA.
authors.forename: Stephen
authors.initials: S
authors.lastname: Antonysamy
authors.forename: Gavin
authors.initials: G
authors.lastname: Hirst
authors.forename: Frances
authors.initials: F
authors.lastname: Park
authors.forename: Paul
authors.initials: P
authors.lastname: Sprengeler
authors.forename: Frank
authors.initials: F
authors.lastname: Stappenbeck
authors.forename: Ruo
authors.initials: R
authors.lastname: Steensma
authors.forename: Mark
authors.initials: M
authors.lastname: Wilson
authors.forename: Melissa
authors.initials: M
authors.lastname: Wong
mesh_terms: D018360:Crystallography, X-Ray; D015195:Drug Design; D055808:Drug Discovery / Q000379:methods*; D006801:Humans; D053614:Janus Kinase 2 / Q000037:antagonists & inhibitors* / Q000737:chemistry; D008958:Models, Molecular; D047428:Protein Kinase Inhibitors / Q000737:chemistry*; D054852:Small Molecule Libraries; D013329:Structure-Activity Relationship; D013449:Sulfonamides / Q000737:chemistry / Q000494:pharmacology
chemical_list: D047428:Protein Kinase Inhibitors; D054852:Small Molecule Libraries; D013449:Sulfonamides; D053614:Janus Kinase 2