Current Challenges in Small Molecule Proximity-Inducing Compound Development for Targeted Protein Degradation Using the Ubiquitin Proteasomal System
R. Sridhar, Oskar Hoff, Markus K. Muellner
Abstract
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.
Topics & Concepts
UbiquitinProteasomeSmall moleculeProtein degradationChemistryCell biologyComputational biologyUbiquitin ligaseBiochemistryNanotechnologyBiologyMaterials scienceGeneProtein Degradation and InhibitorsUbiquitin and proteasome pathwaysMultiple Myeloma Research and Treatments