ErSO-TFPy

ErSO-TFPy potently inhibits multiple ERα+ breast cancer cell lines, exhibiting nanomolar IC50 values (≈ 5-25 nM). Its mechanism of action involves cation dysregulation, leading to cell swelling and the rapid induction of TRPM4-dependent necrotic cell death via activation of the anticipatory Unfolded Protein Response (a-UPR). Remarkably, a single dose of ErSO-TFPy achieves complete regressions of large tumors in preclinical models with sustained effect, despite its short half-life and transient blood exposure. This single-dose efficacy is coupled with excellent tolerability, demonstrated by high maximum tolerated doses (MTD) in mice (150 mg/kg IV), rats (>50 mg/kg IV), and dogs (>5 mg/kg IV), and a favorable therapeutic index, contrasting with multi-dose requirements of typical chemotherapies.