ARV-771

ARV-771 is a potent, small-molecule proteolysis-targeting chimera (PROTAC) designed to induce the degradation of Bromodomain and Extra-Terminal motif (BET) proteins, including BRD2, BRD3, and BRD4. Developed by Arvinas, the molecule consists of a BET-targeting ligand linked to a ligand for the von Hippel-Lindau (VHL) E3 ubiquitin ligase. By bringing the E3 ligase into close proximity with BET proteins, ARV-771 facilitates their polyubiquitination and subsequent degradation via the 26S proteasome. This mechanism leads to the depletion of BET proteins and the suppression of downstream oncogenic signaling, most notably the down-regulation of c-Myc. ARV-771 has demonstrated significant preclinical efficacy in various cancer models, including prostate cancer and multiple myeloma. Research indicates that resistance to ARV-771 can be mediated by the up-regulation of the drug efflux pump ABCB1 (P-glycoprotein), which reduces intracellular drug concentrations.