Acolbifene is a selective estrogen receptor modulator (SERM). It inhibits transcriptional activity of estrogen receptor α (ERα) and ERβ induced by estradiol .1 It binds to ERs in cytosol from human breast cancer and non-cancerous uterine cells (Kis = 0.047 and 0.042 nM, respectively) and to ERs in cytosol from rat uterine cells (IC50 = 0.44 nM) but not to progesterone or androgen receptors in cytosol from rat uterine and ventral prostate cells (IC50s = 22,500 and >10,000 nM, respectively).1,2 Acolbifene inhibits E2-stimulated proliferation of T47D, ZR-75-1, and MCF-7 breast cancer cells (IC50s = 0.146, 0.75, and 0.321 nM, respectively) but not basal proliferation.1 Acolbifene (50 μg per day) inhibits tumor growth stimulated by estrone in a ZR-75-1 human breast cancer xenograft model in ovariectomized mice.3 It also inhibits E1-stimulated endometrial epithelium thickening in vivo in ovariectomized mice when administered at a dose of 50 μg per day.
1.Labrie, F., Labrie, C., Bélanger, A., et al.EM-652 (SCH 57068), a third generation SERM acting as pure antiestrogen in the mammary gland and endometriumJ. Steroid Biochem. Mol. Biol.69(1-6)51-84(1999) 2.Martel, C., Provencher, L., Li, X., et al.Binding characteristics of novel nonsteroidal antiestrogens to the rat uterine estrogen receptorsJ. Steroid Biochem. Mol. Biol.64(3-4)199-205(1998) 3.Gutman, M., Couillard, S., Roy, J., et al.Comparison of the effects of EM-652 (SCH57068), tamoxifen, toremifene, droloxifene, idoxifene, GW-5638 and raloxifene on the growth of human ZR-75-1 breast tumors in nude miceInt. J. Cancer99(2)273-278(2002)