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

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

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.

• Jezik: Angleški jezik
• Ključne besede: the Petasis borono-Mannich reaction, Strecker synthesis, CRBN ligands
• Vrsta gradiva: Članek v reviji
• Tipologija: 1.01 - Izvirni znanstveni članek
• Organizacija: FFA - Fakulteta za farmacijo
• Status publikacije: Objavljeno
• Različica publikacije: Objavljena publikacija
• Datum objave: 01.01.2023
• Leto izida: 2023
• Številčenje: Vol. , iss.
• PID: 20.500.12556/RUL-144171
• UDK: 615.4:54
• ISSN pri članku: 2633-0679
• DOI: 10.1039/D2CB00223J
• COBISS.SI-ID: 136507395
• Datum objave v RUL: 02.02.2023

Gradivo je del revije

• Naslov: RSC chemical biology
• Skrajšan naslov: RSC chem. biol.
• ISSN: 2633-0679
• COBISS.SI-ID: 56276227