Acolbifene (Synonyms: SCH 57068)

Acolbifene is a selective estrogen receptor modulator (SERM). It inhibits transcriptional activity of estrogen receptor α (ERα) and ERβ induced by estradiol . 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). 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. Acolbifene (50 μg per day) inhibits tumor growth stimulated by estrone in a ZR-75-1 human breast cancer xenograft model in ovariectomized mice. It also inhibits E1-stimulated endometrial epithelium thickening in vivo in ovariectomized mice when administered at a dose of 50 μg per day.

References:
[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 endometrium J. 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 receptors J. 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 mice Int. J. Cancer 99(2), 273-278 (2002).