Benzopyrans are selective estrogen receptor beta agonists with novel activity in models of benign prostatic hyperplasia.
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.
Norman
Bryan H
BH
Discovery Chemistry Research, Bone and Inflammation Research, Lead Optimization Biology, Eli Lilly and Company, Lilly Corporate Center, Indianapolis, Indiana 46285, USA. norman@lilly.com
Dodge
Jeffrey A
JA
Richardson
Timothy I
TI
Borromeo
Peter S
PS
Lugar
Charles W
CW
Jones
Scott A
SA
Chen
Keyue
K
Wang
Yong
Y
Durst
Gregory L
GL
Barr
Robert J
RJ
Montrose-Rafizadeh
Chahrzad
C
Osborne
Harold E
HE
Amos
Robert M
RM
Guo
Sherry
S
Boodhoo
Amechand
A
Krishnan
Venkatesh
V
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
D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; D004967:Estrogens; D005419:Flavonoids; D008024:Ligands; C515130:SERBA-1 compound; D020845:Selective Estrogen Receptor Modulators