Activity of a tamoxifen-raloxifene hybrid ligand for estrogen receptors at an AP-1 site.
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.
Weatherman
R V
RV
Departments of Pharmaceutical Chemistry and Cellular and Molecular Pharmacology, University of California--San Francisco, CA 94143-0446, USA.
Carroll
D C
DC
Scanlan
T S
TS
D004965:Estrogen Antagonists / Q000737:chemistry / Q000378:metabolism*; D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; D006367:HeLa Cells; D006801:Humans; D008024:Ligands; D020849:Raloxifene Hydrochloride / Q000737:chemistry / Q000378:metabolism*; D011960:Receptors, Estrogen / Q000737:chemistry / Q000378:metabolism*; D013629:Tamoxifen / Q000737:chemistry / Q000378:metabolism*; D018808:Transcription Factor AP-1 / Q000378:metabolism*
D004965:Estrogen Antagonists; D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; D008024:Ligands; D011960:Receptors, Estrogen; D018808:Transcription Factor AP-1; D013629:Tamoxifen; D020849:Raloxifene Hydrochloride