Issue 3, 2023

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

Abstract

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.

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

Supplementary files

Article information

Article type
Paper
Submitted
31 okt 2022
Accepted
02 jan 2023
First published
03 jan 2023
This article is Open Access
Creative Commons BY-NC license

RSC Chem. Biol., 2023,4, 229-234

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

R. Kuchta, C. Heim, A. Herrmann, S. Maiwald, Y. L. D. Ng, I. Sosič, T. Keuler, J. Krönke, M. Gütschow, M. D. Hartmann and C. Steinebach, RSC Chem. Biol., 2023, 4, 229 DOI: 10.1039/D2CB00223J

This article is licensed under a Creative Commons Attribution-NonCommercial 3.0 Unported Licence. You can use material from this article in other publications, without requesting further permission from the RSC, provided that the correct acknowledgement is given and it is not used for commercial purposes.

To request permission to reproduce material from this article in a commercial publication, please go to the Copyright Clearance Center request page.

If you are an author contributing to an RSC publication, you do not need to request permission provided correct acknowledgement is given.

If you are the author of this article, you do not need to request permission to reproduce figures and diagrams provided correct acknowledgement is given. If you want to reproduce the whole article in a third-party commercial publication (excluding your thesis/dissertation for which permission is not required) please go to the Copyright Clearance Center request page.

Read more about how to correctly acknowledge RSC content.

Social activity

Spotlight

Advertisements