Accessing three-branched high-affinity cereblon ligands for molecular glue and protein degrader design

Kuchta, Robert (author), Heim, Christopher (author), Herrmann, Alexander (author), Maiwald, Samuel (author), Ng, Yuen Lam Dora (author), Sosič, Izidor (author), Keuler, Tim (author), Krönke, Jan (author), Gütschow, Michael (author), Hartmann, Marcus D. (author), Steinebach, Christian (author)

The Petasis borono-Mannich reaction was employed for an alternative entry towards three-branched cereblon ligands. Such compounds are capabable of making multiple interactions with the protein surface and possess a suitable linker exit vector. The high-affinity ligands were used to assemble prototypic new molecular glues and proteolysis targeting chimeras (PROTACs) targeting BRD4 for degradation. Our results highlight the importance of multicomponent reactions (MCRs) in drug discovery and add new insights into the rapidly growing field of protein degraders.

• Language: English
• Keywords: the Petasis borono-Mannich reaction, Strecker synthesis, CRBN ligands
• Work type: Article
• Typology: 1.01 - Original Scientific Article
• Organization: FFA - Faculty of Pharmacy
• Publication status: Published
• Publication version: Version of Record
• Publication date: 01.01.2023
• Year: 2023
• Numbering: Vol. , iss.
• PID: 20.500.12556/RUL-144171
• UDC: 615.4:54
• ISSN on article: 2633-0679
• DOI: 10.1039/D2CB00223J
• COBISS.SI-ID: 136507395
• Publication date in RUL: 02.02.2023

Record is a part of a journal

• Title: RSC chemical biology
• Shortened title: RSC chem. biol.
• ISSN: 2633-0679
• COBISS.SI-ID: 56276227