Structure-guided synthesis of tamoxifen analogs with improved selectivity for the orphan ERRγ

Esther Y.H. Chao, Jon L. Collins, Stéphanie Gaillard, Aaron B. Miller, Liping Wang, Lisa A. Orband-Miller, Robert T. Nolte, Donald P. McDonnell, Timothy M. Willson, William J. Zuercher

Research output: Contribution to journalArticlepeer-review

Abstract

The design and synthesis of 4-hydroxytamoxifen (4-OHT) derivatives are described. The binding affinities of these compounds toward the orphan estrogen-related receptor γ and the classical estrogen receptor α demonstrate that analogs bearing hydroxyalkyl groups display improved binding selectivity profiles compared with that of 4-OHT. An X-ray crystal structure of one of the designed compounds bound to ERRγ LBD confirms the molecular basis of the selectivity.

Original languageEnglish (US)
Pages (from-to)821-824
Number of pages4
JournalBioorganic and Medicinal Chemistry Letters
Volume16
Issue number4
DOIs
StatePublished - Feb 15 2006
Externally publishedYes

Keywords

  • ERRγ chemical tool
  • Orphan nuclear receptor

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Pharmaceutical Science
  • Drug Discovery
  • Clinical Biochemistry
  • Organic Chemistry

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