Related Experiment Video
Updated: May 14, 2025
Polymalic Acid-based Nano Biopolymers for Targeting of Multiple Tumor Markers: An Opportunity for Personalized Medicine?
Published on: June 13, 2014
Rational Design of Methylene Blue-Raloxifene Conjugates for Efficient Breast Tumor Elimination Triggered by ERα
Yu Zhang1,2, Qiying Yu3, Ziwei Wang2
1Key Laboratory of Plant Resource Conservation and Germplasm Innovation in Mountainous Region (Ministry of Education), College of Life Sciences/Institute of Agro-bioengineering, Guizhou University, Guiyang 550025, Guizhou Province, China.
Abstract:
Small molecules capable of degrading estrogen receptor α (ERα) are of significant interest in breast cancer treatment. Herein, we rationally designed a series of ERα degraders (MR1-MR3) by conjugating methylene blue, a bifunctional photosensitizer, with the raloxifene pharmacophore. The lead compound MR3 exhibited high affinity to ERα, and it can induce a complete depletion of ERα in MCF7 breast cancer cells after 660 nm irradiation (0.4 W/cm2) for 1 min. Owing to the ERα degradation merit, MR3 displayed a 45-fold boosted anticancer activity (IC50 = 0.55 μM) after irradiation. In the breast cancer xenograft mouse model, MR3 induced an obvious tumor regression (tumor growth inhibition = 118%), which was superior to that of the FDA-approved ERα degrader Faslodex. These important features make MR3 extremely intriguing for breast cancer treatment.
