Structure-activity relationships for a family of benzothiophene selective estrogen receptor modulators including raloxifene and arzoxifene.

Abstract

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.

• Authors: Cassia R Overk, Kuan-Wei Peng, Rezene T Asghodom, Irida Kastrati, Daniel D Lantvit, Zhihui Qin, Jonna Frasor, Judy L Bolton, Gregory R J Thatcher
• Journal: ChemMedChem (ChemMedChem) Vol. 2 Issue 10 Pg. 1520-6 (Oct 2007) ISSN: 1860-7187 [Electronic] Germany
• PMID: 17654759 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)

Chemical References

• Lipids
• Piperidines
• Receptors, Estrogen
• Selective Estrogen Receptor Modulators
• Thiophenes
• Raloxifene Hydrochloride
• LY 353381

Topics

• Animals
• Female
• Lipids (blood)
• Organ Size (drug effects)
• Piperidines (chemistry, pharmacology)
• Raloxifene Hydrochloride (chemistry, pharmacology)
• Rats
• Rats, Sprague-Dawley
• Receptors, Estrogen (drug effects)
• Selective Estrogen Receptor Modulators (chemistry, pharmacology)
• Structure-Activity Relationship
• Thiophenes (chemistry, pharmacology)
• Uterus (drug effects)