Activity of a tamoxifen-raloxifene hybrid ligand for estrogen receptors at an AP-1 site

Bioorg Med Chem Lett. 2001 Dec 17;11(24):3129-31. doi: 10.1016/s0960-894x(01)00646-1.

Abstract

To test the effect of ligand flexibility on the selective transcriptional activities of ERalpha and ERbeta from an AP-1 site, an analogue of raloxifene was made that removed the ketone functionality and made the ligand more planar and conformationally more similar to 4-hydroxytamoxifen. Desketoraloxifene was found to be a much stronger activator at an AP-1 site with ERalpha than with ERbeta, mimicking 4-hydroxytamoxifen more than raloxifene.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Estrogen Antagonists / chemistry
  • Estrogen Antagonists / metabolism*
  • Estrogen Receptor alpha
  • Estrogen Receptor beta
  • HeLa Cells
  • Humans
  • Ligands
  • Raloxifene Hydrochloride / chemistry
  • Raloxifene Hydrochloride / metabolism*
  • Receptors, Estrogen / chemistry
  • Receptors, Estrogen / metabolism*
  • Tamoxifen / chemistry
  • Tamoxifen / metabolism*
  • Transcription Factor AP-1 / metabolism*

Substances

  • Estrogen Antagonists
  • Estrogen Receptor alpha
  • Estrogen Receptor beta
  • Ligands
  • Receptors, Estrogen
  • Transcription Factor AP-1
  • Tamoxifen
  • Raloxifene Hydrochloride