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

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 prototyp...

Full description

Saved in:
Bibliographic Details
Published inRSC chemical biology Vol. 4; no. 3; pp. 229 - 234
Main Authors Kuchta, Robert, Heim, Christopher, Herrmann, Alexander, Maiwald, Samuel, Ng, Yuen Lam Dora, Sosi, Izidor, Keuler, Tim, Krnke, Jan, Gütschow, Michael, Hartmann, Marcus D, Steinebach, Christian
Format Journal Article
LanguageEnglish
Published England RSC 08.03.2023
Subjects
Chemistry
Online AccessGet full text

Cover

More Information
Summary: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. The Petasis borono-Mannich reaction was employed for an entry towards three-branched cereblon ligands. The high-affinity ligands were used to assemble molecular glues and proteolysis targeting chimeras (PROTACs) targeting BRD4 for degradation.
Bibliography:1
13
https://doi.org/10.1039/d2cb00223j
C NMR and MS data. See DOI
Electronic supplementary information (ESI) available: Schemes S1 and S2, Fig. S1-S5; biological, chemical, and physicochemical methods; synthetic procedures; structures
H NMR
ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
content type line 23
These authors contributed equally.
ISSN:2633-0679
2633-0679
DOI:10.1039/d2cb00223j