title: Improving selective androgen receptor modulator discovery and preclinical evaluation.
abstract: BACKGROUND
  Selective androgen receptor modulators (SARMs) represent a new class of pharmaceuticals that may find wide clinical use. However, selectivity is not understood at the molecular level, which has made the discovery and preclinical evaluation of SARMs difficult.
  
  
  OBJECTIVE
  We review the current state of SARM discovery and preclinical evaluation, as well as our current understanding of the molecular mechanisms controlling AR selectivity. We then discuss how increasing our molecular knowledge of AR selectivity will help create better discovery and evaluation methods and lead to a wider array of safer SARMs.
  
  
  CONCLUSIONS
  The SARM field has advanced rapidly, but without a solid foundation of molecular knowledge to inform discovery and preclinical evaluation methods. The field has also taken a narrow view of selectivity, disregarding many androgen-responsive tissues, which could lead to unforeseen and detrimental side effects with chronic administration of SARMs. An investment in basic research could accelerate the discovery of a new generation of more selective and safer SARMs that could be used to treat an expanded range of clinical conditions.
authors.affiliation: Department of Cellular and Molecular Pharmacology, Genentech Hall Room S576, Box 2280, 600 16th Street, San Francisco, CA 94158-2280, USA +1 415 476 6970 ; +1 415 514 4112 ; jeremy.jones@ucsf.edu.
authors.forename: Jeremy Orion
authors.initials: JO
authors.lastname: Jones