title: Benzopyrans are selective estrogen receptor beta agonists with novel activity in models of benign prostatic hyperplasia.
abstract: Benzopyran selective estrogen receptor beta agonist-1 (SERBA-1) shows potent, selective binding and agonist function in estrogen receptor beta (ERbeta) in vitro assays. X-ray crystal structures of SERBA-1 in ERalpha and beta help explain observed beta-selectivity of this ligand. SERBA-1 in vivo demonstrates involution of the ventral prostate in CD-1 mice (ERbeta effect), while having no effect on gonadal hormone levels (ERalpha effect) at 10x the efficacious dose, consistent with in vitro properties of this molecule.
authors.affiliation: Discovery Chemistry Research, Bone and Inflammation Research, Lead Optimization Biology, Eli Lilly and Company, Lilly Corporate Center, Indianapolis, Indiana 46285, USA. norman@lilly.com
authors.forename: Bryan H
authors.initials: BH
authors.lastname: Norman
authors.forename: Jeffrey A
authors.initials: JA
authors.lastname: Dodge
authors.forename: Timothy I
authors.initials: TI
authors.lastname: Richardson
authors.forename: Peter S
authors.initials: PS
authors.lastname: Borromeo
authors.forename: Charles W
authors.initials: CW
authors.lastname: Lugar
authors.forename: Scott A
authors.initials: SA
authors.lastname: Jones
authors.forename: Keyue
authors.initials: K
authors.lastname: Chen
authors.forename: Yong
authors.initials: Y
authors.lastname: Wang
authors.forename: Gregory L
authors.initials: GL
authors.lastname: Durst
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Barr
authors.forename: Chahrzad
authors.initials: C
authors.lastname: Montrose-Rafizadeh
authors.forename: Harold E
authors.initials: HE
authors.lastname: Osborne
authors.forename: Robert M
authors.initials: RM
authors.lastname: Amos
authors.forename: Sherry
authors.initials: S
authors.lastname: Guo
authors.forename: Amechand
authors.initials: A
authors.lastname: Boodhoo
authors.forename: Venkatesh
authors.initials: V
authors.lastname: Krishnan
mesh_terms: D000818:Animals; D001665:Binding Sites; D018360:Crystallography, X-Ray; D047628:Estrogen Receptor alpha / Q000737:chemistry; D047629:Estrogen Receptor beta / Q000819:agonists* / Q000737:chemistry; D004967:Estrogens; D005419:Flavonoids / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D008024:Ligands; D008297:Male; D051379:Mice; D008958:Models, Molecular; D015394:Molecular Structure; D011467:Prostate / Q000187:drug effects / Q000473:pathology; D011470:Prostatic Hyperplasia / Q000188:drug therapy* / Q000473:pathology; D020845:Selective Estrogen Receptor Modulators / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D013329:Structure-Activity Relationship
chemical_list: D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; D004967:Estrogens; D005419:Flavonoids; D008024:Ligands; C515130:SERBA-1 compound; D020845:Selective Estrogen Receptor Modulators