Pipendoxifene

Pipendoxifene, also known as ERA-923, is a new antiestrogen with potential anticancer activity. ERA-923 potently inhibits estrogen binding to ER-alpha (IC50 = 14 nM) . In ER-alpha-positive human MCF-7 breast carcinoma cells, ERA-923 inhibits estrogen-stimulated growth (IC50 = 0.2 nM) associated with cytostasis. In vitro, a MCF-7 variant with inherent resistance to tamoxifen (10-fold) or 4-OH tamoxifen (>1000-fold) retains complete sensitivity to ERA-923 . In preclinical models, ERA-923 has an improved efficacy and safety compared with tamoxifen. In the combination with temsirolimus, ERA-923 showed excellent anticancer activity in preclinical models.