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 ERα and ERβ 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 ERα than with ERβ, mimicking 4-hydroxytamoxifen more than raloxifene.