title: Identification of tertiary sulfonamides as RORc inverse agonists.
abstract: Screening a nuclear receptor compound subset in a RORc biochemical binding assay revealed a benzylic tertiary sulfonamide hit. Herein, we describe the identification of compounds with improved RORc biochemical inverse agonist activity and cellular potencies. These improved compounds also possessed appreciable selectivity for RORc over other nuclear receptors.
authors.affiliation: Genentech, Inc., 1 DNA Way, South San Francisco, CA 94080, USA. Electronic address: Fauber.Benjamin@gene.com.
authors.forename: Benjamin P
authors.initials: BP
authors.lastname: Fauber
authors.affiliation: Genentech, Inc., 1 DNA Way, South San Francisco, CA 94080, USA.
authors.forename: Olivier
authors.initials: O
authors.lastname: René
authors.affiliation: Argenta, Units 7-9 Spire Green Centre, Flex Meadow, Harlow, Essex CM19 5TR, UK.
authors.forename: Brenda
authors.initials: B
authors.lastname: Burton
authors.affiliation: Genentech, Inc., 1 DNA Way, South San Francisco, CA 94080, USA.
authors.forename: Christine
authors.initials: C
authors.lastname: Everett
authors.affiliation: Genentech, Inc., 1 DNA Way, South San Francisco, CA 94080, USA.
authors.forename: Alberto
authors.initials: A
authors.lastname: Gobbi
authors.affiliation: Argenta, Units 7-9 Spire Green Centre, Flex Meadow, Harlow, Essex CM19 5TR, UK.
authors.forename: Julie
authors.initials: J
authors.lastname: Hawkins
authors.affiliation: Genentech, Inc., 1 DNA Way, South San Francisco, CA 94080, USA.
authors.forename: Adam R
authors.initials: AR
authors.lastname: Johnson
authors.affiliation: Genentech, Inc., 1 DNA Way, South San Francisco, CA 94080, USA.
authors.forename: Marya
authors.initials: M
authors.lastname: Liimatta
authors.affiliation: Argenta, Units 7-9 Spire Green Centre, Flex Meadow, Harlow, Essex CM19 5TR, UK.
authors.forename: Peter
authors.initials: P
authors.lastname: Lockey
authors.affiliation: Argenta, Units 7-9 Spire Green Centre, Flex Meadow, Harlow, Essex CM19 5TR, UK.
authors.forename: Maxine
authors.initials: M
authors.lastname: Norman
authors.affiliation: Genentech, Inc., 1 DNA Way, South San Francisco, CA 94080, USA.
authors.forename: Harvey
authors.initials: H
authors.lastname: Wong
mesh_terms: D006801:Humans; D008024:Ligands; D062105:Molecular Docking Simulation; D057132:Nuclear Receptor Subfamily 1, Group F, Member 3 / Q000819:agonists* / Q000378:metabolism; D013329:Structure-Activity Relationship; D013449:Sulfonamides / Q000737:chemistry* / Q000494:pharmacology*
chemical_list: D008024:Ligands; D057132:Nuclear Receptor Subfamily 1, Group F, Member 3; C539900:RORC protein, human; D013449:Sulfonamides
keywords: Autoimmune; IL-17; Inflammation; RORc; RORγ