title: Identification of the Clinical Candidate (R)-(1-(4-Fluorophenyl)-6-((1-methyl-1H-pyrazol-4-yl)sulfonyl)-4,4a,5,6,7,8-hexahydro-1H-pyrazolo[3,4-g]isoquinolin-4a-yl)(4-(trifluoromethyl)pyridin-2-yl)methanone (CORT125134): A Selective Glucocorticoid Receptor (GR) Antagonist.
abstract: The nonselective glucocorticoid receptor (GR) antagonist mifepristone has been approved in the U.S. for the treatment of selected patients with Cushing's syndrome. While this drug is highly effective, lack of selectivity for GR leads to unwanted side effects in some patients. Optimization of the previously described fused azadecalin series of selective GR antagonists led to the identification of CORT125134, which is currently being evaluated in a phase 2 clinical study in patients with Cushing's syndrome.
authors.affiliation: Corcept Therapeutics , 149 Commonwealth Drive, Menlo Park, California 94025, United States.
authors.forename: Hazel J
authors.identifier: 0000-0002-4316-1301
authors.initials: HJ
authors.lastname: Hunt
authors.affiliation: Corcept Therapeutics , 149 Commonwealth Drive, Menlo Park, California 94025, United States.
authors.forename: Joseph K
authors.initials: JK
authors.lastname: Belanoff
authors.affiliation: Sygnature Discovery , BioCity, Pennyfoot Street, Nottingham, NG1 1GF, U.K.
authors.forename: Iain
authors.initials: I
authors.lastname: Walters
authors.affiliation: Sygnature Discovery , BioCity, Pennyfoot Street, Nottingham, NG1 1GF, U.K.
authors.forename: Benoit
authors.initials: B
authors.lastname: Gourdet
authors.affiliation: Sygnature Discovery , BioCity, Pennyfoot Street, Nottingham, NG1 1GF, U.K.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Thomas
authors.affiliation: Sygnature Discovery , BioCity, Pennyfoot Street, Nottingham, NG1 1GF, U.K.
authors.forename: Naomi
authors.initials: N
authors.lastname: Barton
authors.affiliation: Sygnature Discovery , BioCity, Pennyfoot Street, Nottingham, NG1 1GF, U.K.
authors.forename: John
authors.initials: J
authors.lastname: Unitt
authors.affiliation: Sygnature Discovery , BioCity, Pennyfoot Street, Nottingham, NG1 1GF, U.K.
authors.forename: Timothy
authors.initials: T
authors.lastname: Phillips
authors.affiliation: Sygnature Discovery , BioCity, Pennyfoot Street, Nottingham, NG1 1GF, U.K.
authors.forename: Denise
authors.initials: D
authors.lastname: Swift
authors.affiliation: Sygnature Discovery , BioCity, Pennyfoot Street, Nottingham, NG1 1GF, U.K.
authors.forename: Emily
authors.initials: E
authors.lastname: Eaton
mesh_terms: D000818:Animals; D002853:Chromatography, Liquid; D056945:Hep G2 Cells; D006801:Humans; D013058:Mass Spectrometry; D011965:Receptors, Glucocorticoid / Q000037:antagonists & inhibitors*
chemical_list: D011965:Receptors, Glucocorticoid