Current Challenges in Small Molecule Proximity-Inducing Compound Development for Targeted Protein Degradation Using the Ubiquitin Proteasomal System

Bivalent proximity-inducing compounds represent a novel class of small molecule therapeutics with exciting potential and new challenges. The most prominent examples of such compounds are utilized in targeted protein degradation where E3 ligases are hijacked to recruit a substrate protein to the prot...

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Autores principales: Radhakrishnan, Sridhar, Hoff, Oskar, Muellner, Markus K.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Review
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9740444/
https://www.ncbi.nlm.nih.gov/pubmed/36500212
http://dx.doi.org/10.3390/molecules27238119
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author Radhakrishnan, Sridhar
Hoff, Oskar
Muellner, Markus K.
author_facet Radhakrishnan, Sridhar
Hoff, Oskar
Muellner, Markus K.
author_sort Radhakrishnan, Sridhar
collection PubMed
description Bivalent proximity-inducing compounds represent a novel class of small molecule therapeutics with exciting potential and new challenges. The most prominent examples of such compounds are utilized in targeted protein degradation where E3 ligases are hijacked to recruit a substrate protein to the proteasome via ubiquitination. In this review we provide an overview of the current state of E3 ligases used in targeted protein degradation, their respective ligands as well as challenges and opportunities that present themselves with these compounds.
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spelling pubmed-97404442022-12-11 Current Challenges in Small Molecule Proximity-Inducing Compound Development for Targeted Protein Degradation Using the Ubiquitin Proteasomal System Radhakrishnan, Sridhar Hoff, Oskar Muellner, Markus K. Molecules Review Bivalent proximity-inducing compounds represent a novel class of small molecule therapeutics with exciting potential and new challenges. The most prominent examples of such compounds are utilized in targeted protein degradation where E3 ligases are hijacked to recruit a substrate protein to the proteasome via ubiquitination. In this review we provide an overview of the current state of E3 ligases used in targeted protein degradation, their respective ligands as well as challenges and opportunities that present themselves with these compounds. MDPI 2022-11-22 /pmc/articles/PMC9740444/ /pubmed/36500212 http://dx.doi.org/10.3390/molecules27238119 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Review
Radhakrishnan, Sridhar
Hoff, Oskar
Muellner, Markus K.
Current Challenges in Small Molecule Proximity-Inducing Compound Development for Targeted Protein Degradation Using the Ubiquitin Proteasomal System
title Current Challenges in Small Molecule Proximity-Inducing Compound Development for Targeted Protein Degradation Using the Ubiquitin Proteasomal System
title_full Current Challenges in Small Molecule Proximity-Inducing Compound Development for Targeted Protein Degradation Using the Ubiquitin Proteasomal System
title_fullStr Current Challenges in Small Molecule Proximity-Inducing Compound Development for Targeted Protein Degradation Using the Ubiquitin Proteasomal System
title_full_unstemmed Current Challenges in Small Molecule Proximity-Inducing Compound Development for Targeted Protein Degradation Using the Ubiquitin Proteasomal System
title_short Current Challenges in Small Molecule Proximity-Inducing Compound Development for Targeted Protein Degradation Using the Ubiquitin Proteasomal System
title_sort current challenges in small molecule proximity-inducing compound development for targeted protein degradation using the ubiquitin proteasomal system
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9740444/
https://www.ncbi.nlm.nih.gov/pubmed/36500212
http://dx.doi.org/10.3390/molecules27238119
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