ARV-825

ARV-825 is a hetero-bifunctional small molecule PROteolysis TArgeting Chimera (PROTAC) designed to induce the selective degradation of Bromodomain-containing protein 4 (BRD4). It consists of a BRD4-binding moiety derived from the BET inhibitor OTX015 and a Cereblon (CRBN) E3 ligase ligand, pomalidomide, connected by a flexible linker. By facilitating the formation of a ternary complex between BRD4 and the CRBN E3 ubiquitin ligase, ARV-825 promotes the polyubiquitination and subsequent degradation of BRD4 via the 26S proteasome. This depletion of BRD4 leads to the downstream downregulation of oncogenic factors such as c-Myc. In preclinical studies, ARV-825 has demonstrated potent antitumor activity across various malignancies, including acute myeloid leukemia, lymphoma, and drug-resistant malignant melanoma, where it has been shown to resensitize cells to BRAF inhibitors.