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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Veröffentlicht in:	Molecules (Basel, Switzerland) Switzerland), 2022-11, Vol.27 (23), p.8119
Hauptverfasser:	Radhakrishnan, Sridhar, Hoff, Oskar, Muellner, Markus K
Format:	Artikel
Sprache:	eng
Schlagworte:	Bioavailability Biodegradation Cancer Chemical properties Degradation Drugs E3 recruiter Ligands (Biochemistry) Machinery Pharmaceutical research Physiological aspects PIC Polyethylene glycol PROTAC Proteasome Endopeptidase Complex - metabolism Proteasomes Proteins Proteolysis proximity-inducing compound Review targeted protein degradation Ubiquitin Ubiquitin - metabolism Ubiquitin-proteasome system Ubiquitin-Protein Ligases - metabolism Ubiquitination
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Beschreibung
Zusammenfassung:	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.
ISSN:	1420-3049 1420-3049
DOI:	10.3390/molecules27238119