Oct 2026· International Journal of Drug Delivery Technology· 0 citations· 49 references
Protein Degradation and Inhibitors
Abstract
The ability to selectively eliminate pathogenic proteins rather than merely inhibit their activity has redefined contemporary drug discovery, positioning targeted protein degradation (TPD) as one of the most significant advances in chemical biology and precision therapeutics. By harnessing endogenous protein quality-control machinery, TPD offers a catalytic and event-driven pharmacological strategy capable of addressing limitations associated with conventional occupancy-driven inhibitors, including poor target selectivity, transient target engagement, acquired resistance, and the inaccessibility of many disease-relevant proteins. Among the expanding repertoire of degrader technologies, proteolysis-targeting chimeras (PROTACs) and molecular glues have emerged as the most mature and clinically advanced platforms, each employing distinct mechanisms to recruit E3 ubiquitin ligases and direct selective protein degradation. Their rapid evolution has been driven by breakthroughs in structural biology, medicinal chemistry, computational modeling
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