Traditional drug discovery focuses on identifying direct inhibitors of target proteins. This
typically relies on a measurable biochemical readout and accessible binding sites whose …

A series of tools for targeted protein degradation are inspiring scientists to develop new
drugs with advantages over traditional small-molecule drugs. Among these tools, proteolysis …

The transformational mechanism of action underpinning targeted protein degradation
strategies, including proteolysis-targeting chimeras (PROTACs), gives potential for potent in …

Traditional drug discovery mainly focuses on direct regulation of protein activity. The
development and application of protein activity modulators, particularly inhibitors, has been …

Targeted protein degradation (TPD) has been established as a viable alternative to
attenuate the function of a specific protein of interest in both biological and clinical contexts …

With the discovery of PROteolysis TArgeting Chimeras (PROTACs) twenty years ago,
targeted protein degradation (TPD) has changed the landscape of drug development …

The majority of currently used therapeutics are small molecule-based and utilize occupancy-
driven pharmacology as the mode of action (MOA), in which the protein function is …

Summary Protein homeostasis, or" proteostasis," is indispensable for a balanced, healthy
environment within the cell. However, when natural proteostasis mechanisms are …

Highlights•Small molecule protein degraders (PROTACs) can target the 'undruggable'
proteome.•Ligands that bind the target anywhere on its surface can be used to make …

Classic small molecule inhibitors that directly target pathogenic proteins typically rely on the
accessible binding sites to achieve prolonged occupancy and influence protein functions …