A selective estrogen receptor modulator designed for the treatment of uterine leiomyoma with unique tissue specificity for uterus and ovaries in rats

J Med Chem. 2005 Nov 3;48(22):6772-5. doi: 10.1021/jm050723z.

Abstract

The design of a novel selective estrogen receptor modulator (SERM) for the potential treatment of uterine leiomyoma is described. 16 (LY2066948-HCl) binds with high affinity to estrogen receptors alpha and beta (ERalpha and ERbeta, respectively) and is a potent uterine antagonist with minimal effects on the ovaries as determined by serum biomarkers and histologic evaluation.

MeSH terms

  • Animals
  • Binding Sites
  • Biological Availability
  • Cell Line
  • Cell Proliferation
  • Estradiol / blood
  • Estrogen Receptor alpha / agonists
  • Estrogen Receptor alpha / antagonists & inhibitors*
  • Estrogen Receptor alpha / chemistry
  • Estrogen Receptor beta / agonists
  • Estrogen Receptor beta / antagonists & inhibitors*
  • Female
  • Humans
  • Leiomyoma / drug therapy*
  • Mammary Glands, Animal / cytology
  • Mammary Glands, Animal / drug effects
  • Models, Molecular
  • Naphthalenes / chemical synthesis*
  • Naphthalenes / chemistry
  • Naphthalenes / pharmacology
  • Organ Size / drug effects
  • Ovary / anatomy & histology
  • Ovary / drug effects*
  • Ovary / metabolism
  • Piperidines / chemical synthesis*
  • Piperidines / chemistry
  • Piperidines / pharmacology
  • Rats
  • Rats, Sprague-Dawley
  • Selective Estrogen Receptor Modulators / chemical synthesis*
  • Selective Estrogen Receptor Modulators / chemistry
  • Selective Estrogen Receptor Modulators / pharmacology
  • Structure-Activity Relationship
  • Uterine Neoplasms / drug therapy*
  • Uterus / anatomy & histology
  • Uterus / cytology
  • Uterus / drug effects*
  • Uterus / metabolism

Substances

  • Estrogen Receptor alpha
  • Estrogen Receptor beta
  • LY2066948
  • Naphthalenes
  • Piperidines
  • Selective Estrogen Receptor Modulators
  • Estradiol