# Bipyraloxifene – a modified raloxifene vector against triple-negative breast cancer

## TL;DR

Researchers developed bipyraloxifene, a modified version of raloxifene, which shows improved effectiveness against aggressive triple-negative breast cancer cells.

## Contribution

The novel hybrid molecule bipyraloxifene was created by combining raloxifene with a 2,2′-bipyridine moiety for enhanced anticancer activity.

## Key findings

- Bipyraloxifene showed significantly higher activity and selectivity against triple-negative breast cancer cells compared to raloxifene.
- The compound induced caspase-mediated apoptosis in cancer cells, maintaining the original drug's mechanism of action.
- Enhanced efficacy was particularly observed in triple-negative stem-like MDA-MB-231 cells.

## Abstract

Raloxifene, a selective oestrogen receptor modulator (SERM), has demonstrated efficacy in the prevention and therapy of oestrogen receptor-positive (ER+) breast cancer, with some degree of effectiveness against triple-negative forms. This suggests the presence of oestrogen receptor-independent pathways in raloxifene-mediated anticancer activity. To enhance the potential of raloxifene against the most aggressive breast cancer cells, hybrid molecules combining the drug with a metal chelator moiety have been developed. In this study, we synthetically modified the structure of raloxifene by incorporating a 2,2′-bipyridine (2,2′-bipy) moiety, resulting in [6-methoxy-2-(4-hydroxyphenyl)benzo[b]thiophen-3-yl]-[4-(2,2′-bipyridin-4′-yl-methoxy)phenyl]methanone (bipyraloxifene). We investigated the cytotoxic activity of both raloxifene and bipyraloxifene against ER+ breast adenocarcinomas, glioblastomas, and a triple-negative breast cancer (TNBC) cell line, elucidating their mode of action against TNBC. Bipyraloxifene maintained a mechanism based on caspase-mediated apoptosis but exhibited significantly higher activity and selectivity compared to the original drug, particularly evident in triple-negative stem-like MDA-MB-231 cells.

The synthetic combination of raloxifene, a selective estrogen receptor modulator, with a 2,2′-bipyridine moiety results in bipyraloxifene, a potential drug with enhanced activity against triple negative breast cancer.