ARV-471

(Rac)-Vepdegestrant is the isomer of Vepdegestrant (HY-138642). Vepdegestrant ((R)-Lavandulol) is an orally active PROTAC estrogen receptor degrader against breast cancer. Vepdegestrant is a hetero-bifunctional molecule that facilitates the interactions between estrogen receptor alpha and an intracellular E3 ligase complex. Vepdegestrant leads to the ubiquitylation and subsequent degradation of estrogen receptors via the proteasome. Vepdegestrant robustly degrades ER in ER-positive breast cancer cell lines with a half-maximal degradation concentration (DC50) of about 2 nM[1].

[1] Lin X, et al. Targeting estrogen receptor α for degradation with PROTACs: A promising approach to overcome endocrine resistance. Eur J Med Chem. 2020;206:112689. DOI:10.1016/j.ejmech.2020.112689
[2] Hermida-Prado F, et al. Endocrine Therapy Synergizes with SMAC Mimetics to Potentiate Antigen Presentation and Tumor Regression in Hormone Receptor-Positive Breast Cancer. Cancer Res. 2023 Oct 2;83(19):3284-3304. DOI:10.1158/0008-5472.CAN-23-1711
[3] JJ Flanagan, et al. Abstract P5-04-18: ARV-471, an oral estrogen receptor PROTAC degrader for breast cancer.