Only around 20% of the human proteome is considered to be druggable with small-molecule
antagonists. This leaves some of the most compelling therapeutic targets outside the reach …

The therapeutic modality of targeted protein degradation promises to overcome limitations of
traditional pharmacology. Small-molecule degraders recruit disease-causing proteins to E3 …

Targeting proteins' enzymatic functions with small molecule inhibitors, as well as functions of
receptor proteins with small-molecule agonists and antagonists, were the major forms of …

The therapeutic approach of targeted protein degradation (TPD) is gaining momentum due
to its potentially superior effects compared with protein inhibition. Recent advancements in …

Degraders have illustrated that compound‐induced proximity to E3 ubiquitin ligases can
prompt the ubiquitination and degradation of disease‐relevant proteins. Hence, this …

Small molecules continue to dominate drug discovery because of their ease of use, lower
cost of manufacturing, and access to intracellular targets. However, despite these …

Targeted protein degradation represents an area of great interest, potentially offering
improvements with respect to dosing, side effects, drug resistance, and reaching …

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 …

Targeted protein degradation has become a reliable tool in the medicinal chemist's toolbox,
as seen with rapid progression of PROTACs (proteolysis targeting chimeras) to clinic …

Targeted protein degradation and stabilization are promising therapeutic modalities due to
their potency and versatility. However, only few E3 ligases and deubiquitinases have been …