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 μM and 53 μM, respectively. Subsequent molecular docking experiments showed that these two molecules should act by targeting the estrogen receptoralpha (ERα). We believe that the research results will provide meaningful guidance for the design and development of innovative drugs against breast cancer in the future.