Vepdegestrant (ARV-471)

Vepdegestrant (ARV-471; PF-07850327) is an orally active, heterobifunctional proteolysis-targeting chimera (PROTAC) designed to selectively degrade estrogen receptor alpha (ERα), a key driver of estrogen receptor-positive (ER+) breast cancer. Vepdegestrant functions by simultaneously binding ERα and the E3 ubiquitin ligase cereblon (CRBN), bringing the target protein into proximity with the cellular ubiquitination machinery. This interaction promotes ERα ubiquitination and subsequent degradation by the ubiquitin–proteasome system, reducing ERα protein levels and suppressing estrogen receptor signaling.

Vepdegestrant exhibits potent ER degradation in ER-positive breast cancer cell lines, with a reported half-maximal degradation concentration (DC₅₀) of approximately 2 nM. Its targeted protein degradation mechanism distinguishes it from conventional endocrine therapies that primarily inhibit estrogen receptor activity. Vepdegestrant is being investigated as a targeted therapeutic strategy for ER-positive breast cancer, including settings where resistance to existing endocrine treatments presents a significant challenge.

Product Details

• Product Name: Vepdegestrant

• Synonyms: ARV-471; PF-07850327

• CAS Number: 2229711-68-4

• Molecular Formula: C₄₅H₄₉N₅O₄

• Molecular Weight: 723.90 g/mol

Research Use: For research use only. Not intended for human or veterinary use.