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Design of a Highly Selective and Potent Class of Non-planar Estrogen Receptor Agonists

På svenska

Author

  • Henrik Sunden
  • Jian-Nong Ma
  • Lars K. Hansen
  • Anna-Lena Gustavsson
  • Ethan S. Burstein
  • Roger Olsson

Summary, in English

Selective activation of the estrogen receptor (ER) could be a safe approach to hormone replacement therapy for both women and men, in contrast to the estrogens currently used for women which activate both ER and ER, occasionally causing severe side effects. cis-10-SR, was shown to have an EC50 value of <1nM, potency 100-fold higher than that of AC-131. Even more interestingly, compound trans-10-SS exhibited 1000-fold ER/ER selectivity while still maintaining good potency (approximate to 10nM). In addition, trans-10-SS showed only partial agonist activity (30-60% Eff.) toward ER at 10M. trans-10-SS appears to be the first molecule to take advantage of both conservative amino acid differences found in the - and -faces of the binding cavities of ER and ER beta.

Publishing year

2013

Language

English

Pages

1283-1294

Publication/Series

ChemMedChem

Volume

8

Issue

8

Document type

Journal article

Publisher

Wiley-Blackwell

Topic

  • Pharmaceutical Sciences

Keywords

  • asymmetric synthesis
  • neurological agents
  • estrogen receptors
  • modulators
  • Parkinson's disease

Status

Published

ISBN/ISSN/Other

  • ISSN: 1860-7187