Despite nearly four decades of effort, broad inhibition of oncogenic RAS using small-
molecule approaches has proven to be a major challenge. Here we describe the …

Protein-protein interactions (PPIs) are critical for biological processes and predicting the
sites of these interactions is useful for both computational and experimental applications. We …

The druggable genome is limited by structural features that can be targeted by small
molecules in disease-relevant proteins. While orthosteric and allosteric protein modulators …

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 …

Development of novel small molecules that selectively degrade pathogenic proteins would
provide an important advance in targeted therapy. Recently, we have devised a series of …

Manipulation of the ubiquitin-proteasome pathway to achieve targeted silencing of cellular
proteins has emerged as a reliable and customizable strategy for remodeling the …

The design of proteolysis-targeting chimeras (PROTACs) is a powerful small-molecule
approach for inducing protein degradation. PROTACs conjugate a target warhead to an E3 …

Proteolysis-Targeting Chimeras (PROTACs) are bifunctional molecules that bring a target
protein and an E3 ubiquitin ligase into proximity to append ubiquitin, thus directing target …

Protein degradation is an effective native mechanism used in modulating intracellular
information, and thus it plays an essential role in maintaining cellular homeostasis …

New biological tools provide new techniques to probe fundamental biological processes.
Here we describe the burgeoning field of proteolysis-targeting chimeras (PROTACs), which …