Selenium Analogue of LSZ102 as a Highly Potent ER‐α Binder

Abstract

Nowadays, selective estrogen receptor modulators (SERMs) and downregulators (SERDs) are used as the first-line medical treatment for estrogen receptor positive (ER +) tumors. Herein we report synthesis, ER-α binding activity, and cytotoxicity of LSZ102 selenium analogues 11 and 28. TR-FRET competitive ERα binding experiments and cytotoxicity assays have shown that the selenium analogues exhibit closely related activity to LSZ102. Furthermore, the prepared selenium analogues are not toxic in rat cardiomyoblasts (H9C2), indicating that substituted benzo[b]selenophene is a prospective scaffold for the development of ER-α modulators and downregulators for the treatment of ER + cancers.

Selenium analogues of rintodestrant (G1T48) as potent estrogen receptor modulators and downregulators

“…In contrast, the minor differences in the 3D shapes of the potential bioactive molecules due to the slightly different sizes of the chalcogen atoms could serve as a tool for the fine-tuning of target compounds. 22…”