A Reliable and Sustainable Multicomponent Access to Protein Degraders

25 October 2021, Version 2
This content is a preprint and has not undergone peer review at the time of posting.


The use of small molecules to induce targeted protein degradation is increasingly growing in the drug discovery landscape and protein degraders have progressed rapidly through the pipelines. Despite the advances made so far, their synthesis still represents a significant burden and new approaches are urgently demanded. Herein, we report an unprecedented platform that leverages the modular nature of both multicomponent reactions and degraders to enable the preparation of highly decorated PROTACs and hydrophobic tag-mediated degraders. Compared to the existing methods, our approach offers a versatile and cost-effective means to access libraries of protein degraders and increase the chance of identifying successful clinical candidates.


Protein degraders
Multicomponent reactions
Ugi reaction

Supplementary materials

A Reliable and Sustainable Multicomponent Access to Protein Degraders: Supplementary Material
Experimental procedures and spectra data; Copies of 1H and 13C spectra


Comments are not moderated before they are posted, but they can be removed by the site moderators if they are found to be in contravention of our Commenting Policy [opens in a new tab] - please read this policy before you post. Comments should be used for scholarly discussion of the content in question. You can find more information about how to use the commenting feature here [opens in a new tab] .
This site is protected by reCAPTCHA and the Google Privacy Policy [opens in a new tab] and Terms of Service [opens in a new tab] apply.