Pharmacological characterization of AC-262536, a novel selective androgen receptor modulator

J Steroid Biochem Mol Biol. 2008 Mar;109(1-2):129-37. doi: 10.1016/j.jsbmb.2007.11.001. Epub 2007 Nov 22.

Abstract

Because of the limitations and liabilities of current testosterone therapies, non-steroidal tissue-selective androgen receptor modulators may provide a clinically meaningful advance in therapy. Using a functional cell-based assay AC-262536 was identified as a potent and selective AR ligand, with partial agonist activity relative to the natural androgen testosterone. A 2-week chronic study in castrated male rats indicated that AC-262536 significantly improves anabolic parameters in these animals, especially in stimulating the growth of the levator ani and in suppressing elevated LH levels. In sharp contrast to testosterone, AC-262536 has weak androgenic effects, as measured by prostate and seminal vesicle weights. Thus, AC-262536 represents a novel class of selective androgen receptor modulators (SARMs) with beneficial anabolic effects.

MeSH terms

  • Anabolic Agents / pharmacology
  • Androgens*
  • Animals
  • Azabicyclo Compounds / pharmacology*
  • Base Sequence
  • Cell Line
  • DNA Primers / genetics
  • Genes, Reporter
  • Humans
  • Ligands
  • Male
  • Muscles / anatomy & histology
  • Muscles / drug effects
  • Naphthalenes / pharmacology*
  • Orchiectomy
  • Organ Specificity
  • Pituitary Gland / drug effects
  • Pituitary Gland / physiology
  • Prostate / anatomy & histology
  • Prostate / drug effects
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, Androgen / genetics
  • Receptors, Androgen / metabolism
  • Seminal Vesicles / anatomy & histology
  • Seminal Vesicles / drug effects
  • Testosterone / pharmacology

Substances

  • AC-262536
  • Anabolic Agents
  • Androgens
  • Azabicyclo Compounds
  • DNA Primers
  • Ligands
  • Naphthalenes
  • Receptors, Androgen
  • Testosterone