title: Discovery and biological evaluation of benzo[a]carbazole-based small molecule agonists of the thrombopoietin (Tpo) receptor.
abstract: A novel series of benzo[a]carbazole-based small molecule agonists of the thrombopoietin (Tpo) receptor is reported. Starting from a 3.4 microM high throughput screen hit, members of this series have been identified which are full agonists with functional potency <50 nM and oral bioavailability in mice.
authors.affiliation: Genomics Institute of the Novartis Research Foundation (GNF), San Diego, CA 92121, USA.
authors.forename: Phil B
authors.initials: PB
authors.lastname: Alper
authors.forename: Thomas H
authors.initials: TH
authors.lastname: Marsilje
authors.forename: Daniel
authors.initials: D
authors.lastname: Mutnick
authors.forename: Wenshuo
authors.initials: W
authors.lastname: Lu
authors.forename: Arnab
authors.initials: A
authors.lastname: Chatterjee
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Roberts
authors.forename: Yun
authors.initials: Y
authors.lastname: He
authors.forename: Donald S
authors.initials: DS
authors.lastname: Karanewsky
authors.forename: Donald
authors.initials: D
authors.lastname: Chow
authors.forename: Jianmin
authors.initials: J
authors.lastname: Lao
authors.forename: Andrea
authors.initials: A
authors.lastname: Gerken
authors.forename: Tove
authors.initials: T
authors.lastname: Tuntland
authors.forename: Bo
authors.initials: B
authors.lastname: Liu
authors.forename: Jonathan
authors.initials: J
authors.lastname: Chang
authors.forename: Perry
authors.initials: P
authors.lastname: Gordon
authors.forename: H Martin
authors.initials: HM
authors.lastname: Seidel
authors.forename: Shin-Shay
authors.initials: SS
authors.lastname: Tian
mesh_terms: D000284:Administration, Oral; D000818:Animals; D001555:Benzene Derivatives / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D002227:Carbazoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D020650:Combinatorial Chemistry Techniques; D015195:Drug Design; D006801:Humans; D051379:Mice; D015394:Molecular Structure; D019906:Nuclear Magnetic Resonance, Biomolecular; D053628:Receptors, Thrombopoietin / Q000819:agonists* / Q000737:chemistry; D013329:Structure-Activity Relationship; D013926:Thrombopoietin / Q000737:chemistry / Q000378:metabolism
chemical_list: D001555:Benzene Derivatives; D002227:Carbazoles; D053628:Receptors, Thrombopoietin; D013926:Thrombopoietin