Small-molecule drug discovery has traditionally focused on occupancy of a binding site that
directly affects protein function, and this approach typically precludes targeting proteins that …

Traditional pharmaceutical drug discovery is almost exclusively focused on directly
controlling protein activity to cure diseases. Modulators of protein activity, especially …

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 has exploded over the past several years due to preclinical
and early clinical therapeutic success of numerous compounds, and the emergence of new …

Protein homeostasis networks are highly regulated systems responsible for maintaining the
health and productivity of cells. Whereas therapeutics have been developed to disrupt …

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 (TPD), the ability to control a proteins fate by triggering its
degradation in a highly selective and effective manner, has created tremendous excitement …

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

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

Traditional approaches in the development of small-molecule drugs typically aim to inhibit
the biochemical activity of functional protein domains. In contrast, targeted protein …