Sambucetti, L. C., Zhou, W., Calaoagan, J., Kara, L., Liu, X., Sato, B., . . . Laderoute, K. (2013, 6-10 April). SR16388 impairs protein homeostasis and induces autophagy in diverse human cancer cell lines. Paper presented at the Annual Meeting of the American Association for Cancer Research (AACR’13), Washington, DC.
SR16388 is a novel amino steroid that targets estrogen-binding proteins including genomic estrogen receptors (ERs). Preclinical studies have demonstrated that SR16388 is a well-tolerated, orally active compound with compelling properties as an experimental antitumor agent: SR16388 has been demonstrated to 1) inhibit the proliferation and viability of diverse human cancer cell lines in vitro; 2) have antiangiogenic activity in vivo; and 3) reduce the growth of human tumor xenografts in mice. SR16388, which binds to and potently inhibits ERα and ERβ in breast cancer cells, also inhibits the widely expressed orphan nuclear receptor ERRα that has been implicated in the development of various human malignancies. ERRα is thought to regulate tumor cell energy metabolism associated with energy stress within solid tumor microenvironments.