GID4-BRD4 PROTAC

GID4-BRD4 PROTAC is an experimental proteolysis-targeting chimera (PROTAC) designed to induce the selective degradation of Bromodomain-containing protein 4 (BRD4). It functions by recruiting GID4 (the substrate receptor of the CTLH E3 ubiquitin ligase complex) to BRD4, facilitating the ubiquitination and subsequent proteasomal degradation of the target protein. The GID4-binding component was identified using DNA-encoded library (DEL) screening and optimized for high-affinity binding. In preclinical studies, these PROTACs have demonstrated potent biochemical ternary complex formation (EC50 < 1 nM) and effective degradation of BRD4 in various cancer cell lines (DC50 < 1 uM). This molecule serves as a proof-of-concept for utilizing novel, ligandable E3 ligases beyond the standard CRBN and VHL systems to overcome potential resistance and expand the scope of targeted protein degradation (TPD).