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Panning for snurms: Using cofactor profiling for the rational discovery of selective nuclear receptor modulators

Academic Article
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Overview

authors

  • Kremoser, C.
  • Albers, M.
  • Burris, Thomas
  • Deuschle, U.
  • Koegl, M.

publication date

  • October 2007

journal

  • Drug Discovery Today  Journal

abstract

  • 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.

subject areas

  • Animals
  • Binding Sites
  • Drug Design
  • Gene Expression Profiling
  • Humans
  • Immunoprecipitation
  • Ligands
  • Peptides
  • Protein Conformation
  • Receptors, Cytoplasmic and Nuclear
  • Structure-Activity Relationship
  • Transcription, Genetic
  • Two-Hybrid System Techniques
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Identity

International Standard Serial Number (ISSN)

  • 1359-6446

Digital Object Identifier (DOI)

  • 10.1016/j.drudis.2007.07.025

PubMed ID

  • 17933688
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Additional Document Info

start page

  • 860

end page

  • 869

volume

  • 12

issue

  • 19-20

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