Development of Potent ERα Inhibitors: Effectively Inhibit the Growth of Breast Cancer Cells

Breast cancer is the highest incidence among female cancers in the world, but the approved clinical drugs have strong side effects, and some even have carcinogenic effects. Lonidamine has attracted much attention due to its stronger inhibitory effect and smaller side effects for breast cancer, but its low bioavailability limits its clinical application. To overcome this challenge, we hope to further enhance its effect of inhibiting cancer cell proliferation and increase its bioavailability by modifying the structure of lonidamine. After continuous efforts, we designed and synthesized two drug molecules 18a (YRL-01) and 18b (YRL-02) with higher inhibitory activity than lonidamine based on the structure-based drug design strategy, with IC50 values of 45 mu M and 53 mu M, respectively. Subsequent molecular docking experiments showed that these two molecules should act by targeting the estrogen receptoralpha (ER alpha). We believe that the research results will provide meaningful guidance for the design and development of innovative drugs against breast cancer in the future.

Automated summary

Breast cancer is the most prevalent cancer among women worldwide. However, currently approved clinical drugs for breast cancer have significant side effects, some of which are even carcinogenic. Lonidamine has been studied due to its potent inhibitory effect with fewer side effects, but its low bioavailability limits its clinical application. In this study, researchers aimed to enhance lonidamine's inhibitory effect on cancer cell proliferation and improve its bioavailability by modifying its structure. Through structure-based drug design strategy, two new drug molecules (18a and 18b) with higher inhibitory activity than lonidamine were synthesized. Subsequent molecular docking experiments suggested that these molecules target the estrogen receptor alpha (ER alpha). These findings are believed to provide valuable guidance for the design and development of innovative drugs against breast cancer in the future.