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Insights Into Vepdegestrant (ARV-471): The First-in-Class Estrogen Receptor Proteolysis-Targeting Chimera Approaching Food and Drug Administration Approval for Breast Cancer
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DOI：10.1002/cmdc.202501111.png)
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Abstract
En 中文
Vepdegestrant (ARV-471) is an orally bioavailable, proteolysis-targeting chimera (PROTAC)-based estrogen receptor (ER) degrader and is among the most clinically advanced ER-targeting PROTAC degraders, identified through a rational medicinal chemistry optimization campaign. It is being developed as an oral small-molecule endocrine therapy for advanced or metastatic ER-positive, human epidermal growth factor receptor 2 (HER2)-negative breast cancer, with particular relevance for tumors harboring ESR1 mutations. On June 6, 2025, Arvinas and Pfizer submitted a New Drug Application (NDA) for vepdegestrant to the U.S. Food and Drug Administration (FDA), representing an important step in the clinical translation of PROTAC technology. This review summarizes the design, synthesis, degradation mechanism, preclinical pharmacology, and clinical development of vepdegestrant and discusses the broader implications and future prospects of oral PROTAC-based ER degraders in breast cancer therapy.
Keywords:
breast cancer
estrogen receptor degrader
proteolysis-targeting chimera
targeted protein degradation
vepdegestrant (ARV-471)
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