Description: Pipendoxifene HCl (ERA923 hydrochloride) is an estrogen antagonist (SERM) with antitumor activity. It inhibits estrogen binding to ER-alpha with IC50 of 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.