Panning for SNuRMs: using cofactor profiling for the rational discovery of selective nuclear receptor modulators

Drug Discov Today. 2007 Oct;12(19-20):860-9. doi: 10.1016/j.drudis.2007.07.025. Epub 2007 Sep 19.


Drugs that target nuclear receptors are clinically, as well as commercially, successful. Their widespread use, however, is limited by an inherent propensity of nuclear receptors to trigger beneficial, as well as adverse, pharmacological effects upon drug activation. Hence, selective drugs that display reduced adverse effects, such as the selective estrogen receptor modulator (SERM) Raloxifene, have been developed by guidance through classical cell culture assays and animal trials. Full agonist and selective modulator nuclear receptor drugs, in general, differ by their ability to recruit certain cofactors to the receptor protein. Hence, systematic cofactor profiling is advancing into an approach for the rationally guided identification of selective NR modulators (SNuRMs) with improved therapeutic ratio.

Publication types

  • Review

MeSH terms

  • Animals
  • Binding Sites
  • Drug Design*
  • Gene Expression Profiling / methods
  • Humans
  • Immunoprecipitation
  • Ligands
  • Peptides / metabolism
  • Protein Conformation
  • Receptors, Cytoplasmic and Nuclear / agonists*
  • Receptors, Cytoplasmic and Nuclear / antagonists & inhibitors*
  • Receptors, Cytoplasmic and Nuclear / metabolism
  • Structure-Activity Relationship
  • Transcription, Genetic
  • Two-Hybrid System Techniques


  • Ligands
  • Peptides
  • Receptors, Cytoplasmic and Nuclear