Discovery of ERα-targeting PROTACs with intrinsic fluorescence for precision theranostics of breast cancer

  • RSC Med Chem. 2025 May 22. doi: 10.1039/d5md00281h.
Yihe Wu  1 ,  Junhong Dai  1 ,  Xiaofei Deng  1 ,  Pei He  1 ,  Jinsen Liang  1 ,  Lilan Xin  1 ,  Baohua Xie  1 ,  Shenghong Zhu  2 ,  Chune Dong  1 ,  Hai-Bing Zhou  1  3
Affiliations
  • 1. Department of Hematology, Zhongnan Hospital of Wuhan University, School of Pharmaceutical Sciences, Wuhan University Wuhan 430071 China [email protected] [email protected].
  • 2. Yangtze River Pharmaceutical Group JiangSu Haici Biological Pharmaceutical Co., Ltd. 8 Taizhen Road, Medical New & Hi-tech Industrial Development Zone Taizhou 225321 China.
  • 3. State Key Laboratory of Virology and Biosafety, Frontier Science Center for Immunology and Metabolism, School of Pharmaceutical Sciences, Wuhan University Wuhan 430071 China.
PMID: 40530084 DOI: 10.1039/d5md00281h
Abstract

Real-time monitoring of protein degradation is challenging. Herein, novel ERα-targeted dual-function PROTACs with intrinsic fluorescence were designed and synthesized for precision theranostics of breast Cancer. Among them, W2 showed good antiproliferative activity, selective ERα degradation and imaging capabilities in MCF-7 breast Cancer cell lines. The in vivo safety assay indicated that W2 was well-tolerated up to a dose of 500 mg kg-1 with no acute toxicity. This work demonstrates the great potential of ERα-targeted PROTACs as theranostic agents in breast Cancer treatment.

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