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Updated: Oct 3, 2026

High-Throughput Cellular Profiling of Targeted Protein Degradation Compounds Using HiBiT CRISPR Cell Lines
Published on: November 9, 2020
Vepdegestrant: the first FDA-approved oral PROTAC and a milestone in targeted protein degradation
Jeffrey Yang1, Longqin Hu2,3
1Hansoh Bio, LLC, 9900 Medical Center Drive, Suite 200, Rockville, MD, 20850, USA. jeffrey.yang@hansohbio.com.
Abstract:
Vepdegestrant (ARV-471, Veppanu) represents an important milestone in targeted protein degradation (TPD) as the first FDA-approved heterobifunctional proteolysis-targeting chimera (PROTAC). Designed to selectively degrade estrogen receptor α (ERα) through recruitment of the cereblon E3 ubiquitin ligase, vepdegestrant provides an event-driven approach to targeting ERα, including clinically relevant estrogen receptor-1 (ESR1)-mutated forms associated with endocrine therapy resistance. Its oral bioavailability and pharmacological properties enabled clinical development in patients with ER-positive, human epidermal growth factor receptor 2 (HER2)-negative, ESR1-mutated advanced or metastatic breast cancer. In clinical studies, vepdegestrant improved progression-free survival compared with fulvestrant in this patient population, supporting the therapeutic potential of PROTAC-mediated protein degradation. The approval of vepdegestrant provides clinical and regulatory validation of the PROTAC modality and offers important medicinal chemistry lessons for the design and development of next-generation degraders.
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