Leveraging Ligand Affinity and Properties: Discovery of Novel Benzamide-Type Cereblon Binders for the Design of PROTACs

• Published in: Journal of medicinal chemistry Vol. 66; no. 21; pp. 14513 - 14543
• Main Authors: Steinebach, Christian, Bricelj, Aleša, Murgai, Arunima, Sosič, Izidor, Bischof, Luca, Ng, Yuen Lam Dora, Heim, Christopher, Maiwald, Samuel, Proj, Matic, Voget, Rabea, Feller, Felix, Košmrlj, Janez, Sapozhnikova, Valeriia, Schmidt, Annika, Zuleeg, Maximilian Rudolf, Lemnitzer, Patricia, Mertins, Philipp, Hansen, Finn K., Gütschow, Michael, Krönke, Jan, Hartmann, Marcus D.
• Format: Journal Article
• Language: English
• Published: WASHINGTON American Chemical Society 09.11.2023; Amer Chemical Soc
• Subjects: Chemistry, Medicinal; Life Sciences & Biomedicine; Pharmacology & Pharmacy; Science & Technology; MULTIPLE-MYELOMA; ANTIANGIOGENIC PROPERTIES; RECOGNITION; IMMOBILIZED ARTIFICIAL MEMBRANE; LENALIDOMIDE; DEGRADATION; FLUORINE; BROMODOMAIN; BINDING; HYDROGEN-BONDS

Immunomodulatory imide drugs (IMiDs) such as thalidomide, pomalidomide, and lenalidomide are the most common cereblon (CRBN) recruiters in proteolysis-targeting chimera (PROTAC) design. However, these CRBN ligands induce the degradation of IMiD neosubstrates and are inherently unstable, degrading hy...