Deciphering the selective androgen receptor modulators paradigm

Expert Opin Drug Discov. 2013 Feb;8(2):191-218. doi: 10.1517/17460441.2013.741582. Epub 2012 Dec 12.


Introduction: The development and potential clinical use of tissue-selective androgen receptor modulators (SARMs) have advanced tremendously over the past few years. A key aspect of SARMs is the ability to clearly differentiate between the anabolic and androgenic activities. SARMs provide therapeutic opportunities in a variety of diseases, including muscle wasting associated with burns, cancer, end-stage renal disease, osteoporosis, frailty and hypogonadism.

Areas covered: The aim of the present paper is to summarize the current standing of research and development of SARMs and plausible molecular mechanisms underlying the potential for selective modulation of androgen receptor (AR) by different ligands. This paper also provides an update on SARM discovery paradigms for preclinical evaluations.

Expert opinion: Promising results have been obtained in preclinical investigations and initial clinical trials, but long-term safety, tolerability and efficacy studies in patients are still necessary. Preclinically, improving knowledge of tissue selectivity at the molecular level, developing AR selectivity transcription profile, exploring in vitro/in vivo correlation, along with expanding selectivity evaluation among more androgen responsive tissues would accelerate the discovery of a new generation of more selective and safer clinical candidates, minimize false leads and hasten development of effective approaches for an expanded range of clinical conditions.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Clinical Trials as Topic
  • Drug Discovery / methods*
  • Humans
  • Ligands
  • Models, Animal
  • Receptors, Androgen / therapeutic use*


  • Ligands
  • Receptors, Androgen