Development of STING degrader with double covalent ligands

In this study, we used a minimal covalent handle recently developed as the ligand portion of an E3 ligase. The engineered STING degrader with a low molecular weight compound covalently binds to STING and E3 ligase. Degrader 2 showed sustained STING degradation activity at lower concentrations (3 µM, 48 h, about 75 % degradation) compared to a reported STING PROTAC, SP23. This discovery holds significance for its potential in treating autoinflammatory and autoimmune diseases, offering promising avenues for developing more efficacious STING-targeted therapies.PMID:38408510 | DOI:10.1016/j.bmcl.2024.129677
Source: Bioorganic and Medicinal Chemistry Letters - Category: Chemistry Authors: Source Type: research