ErSO is a small molecule activator of unfolded protein response (UPR), activates the a-UPR, induces rapid and selective necrosis of ERα-positive breast cancer cell lines in vitro.
ErSO inhibits cell viability of breast cancer cell lines expressing wild-type ERα and the ERαY537S and ERαD538G mutations with IC50 of 11-43 nM (TYS and TDG).
ErSO acts through ERα to elicit strong and sustained cytotoxic activation of the a-UPR.
ErSO does not compete with estrogens for binding to ERα and selectively kills ERα-positive breast cancer cells including those harboring known resistance-mediating ERα mutations.
ErSO kills ERα-positive breast cancer cell lines in vitro induces complete regression in orthotopic cell line xenograft and patient-derived xenograft (PDX) mouse models, regardless of ERα mutational status and without recurrence after cessation of treatment.
ErSO causes complete regression of most tumors in a fulvestrant-resistant, ERα-mutant, PDX mouse model andmetastatic breast cancer mouse models.