Early evaluation of opportunities in oral delivery of PROTACs to overcome their molecular challenges
Wenzhan Yang, Sugandha Saboo, Liping Zhou, Sean Askin, Annette Bak
Abstract
PROteolysis TArgeting Chimeras (PROTACs) offer new opportunities in modern medicine by targeting proteins that are intractable to classic inhibitors. Heterobifunctional in nature, PROTACs are small molecules that offer a unique mechanism of protein degradation by hijacking the ubiquitin-mediated protein degradation pathway, known as the ubiquitin-proteasome system. Herein, we present an analysis on the structural characteristics of this novel chemical modality. Furthermore, we review and discuss the formulation opportunities to overcome the oral delivery challenges of PROTACs in drug discovery.
Topics & Concepts
UbiquitinDrug discoveryProteasomeProtein degradationProteolysisMechanism (biology)Computational biologyChemistryBioinformaticsBiologyCell biologyBiochemistryEnzymeGenePhilosophyEpistemologyProtein Degradation and InhibitorsPeptidase Inhibition and AnalysisUbiquitin and proteasome pathways