Structure-activity relationships for a family of benzothiophene selective estrogen receptor modulators including raloxifene and arzoxifene.
The search for the "ideal" selective estrogen receptor modulator (SERM) as a substitute for hormone replacement therapy (HRT) or use in cancer chemoprevention has focused on optimization of estrogen receptor (ER) ligand binding. Based on the clinical and preclinical benzothiophene SERMs, raloxifene and arzoxifene, a family of SERMs has been developed to modulate activity and oxidative lability. Antiestrogenic potency measured in human endometrial and breast cancer cells, and ER ligand binding data were correlated and seen to provide a guide to SERM design only when viewed in toto. The in vitro studies were extended to the juvenile rat model, in which the desired antiestrogenic profile and putative cardiovascular benefits of SERMs were observed.
Overk
Cassia R
CR
Department of Medicinal Chemistry & Pharmacognosy, College of Pharmacy, University of Illinois at Chicago, 833 S Wood St, Chicago, IL 60612, USA.
Peng
Kuan-Wei
KW
Asghodom
Rezene T
RT
Kastrati
Irida
I
Lantvit
Daniel D
DD
Qin
Zhihui
Z
Frasor
Jonna
J
Bolton
Judy L
JL
Thatcher
Gregory R J
GR
D000818:Animals; D005260:Female; D008055:Lipids / Q000097:blood; D009929:Organ Size / Q000187:drug effects; D010880:Piperidines / Q000737:chemistry / Q000494:pharmacology*; D020849:Raloxifene Hydrochloride / Q000737:chemistry / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011960:Receptors, Estrogen / Q000187:drug effects; D020845:Selective Estrogen Receptor Modulators / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D013876:Thiophenes / Q000737:chemistry / Q000494:pharmacology*; D014599:Uterus / Q000187:drug effects
D008055:Lipids; D010880:Piperidines; D011960:Receptors, Estrogen; D020845:Selective Estrogen Receptor Modulators; D013876:Thiophenes; D020849:Raloxifene Hydrochloride; C115121:LY 353381