Ubiquitination is a key post-translational modification of proteins, affecting the regulation of
multiple cellular processes. Cells are equipped with over 600 ubiquitin orchestrators, called …

Proteolysis-targeting chimeras (PROTACs) describe compounds that bind to and induce
degradation of a target by simultaneously binding to a ubiquitin ligase. More generally …

Small molecules inducing protein degradation are important pharmacological tools to
interrogate complex biology and are rapidly translating into clinical agents. However, to fully …

Highlights•E3 ligase machineries confer specificity to protein ubiquitination.•Multi-subunit
assembly and substrate recognition impact E3 ligase activity.•Molecular glues and …

Inducing macromolecular interactions with small molecules to activate cellular signaling is a
challenging goal. PROTACs (proteolysis-targeting chimeras) are bifunctional molecules that …

Molecular glues enable the degradation of previously “undruggable” proteins via the
recruitment of cereblon (CRBN) to the target. One major challenge in designing CRBN E3 …

Molecular glues, functioning via inducing degradation of the target protein while having
similar molecular weight as traditional small molecule drugs, are emerging as a promising …

Targeted protein degradation is a drug modality represented by compounds that recruit a
target to an E3 ubiquitin ligase to promote target ubiquitination and proteasomal …

Protein misfolding is an emerging field that crosses multiple therapeutic areas and causes
many serious diseases. As the biological pathways of protein misfolding become more …

Conspectus One of the biggest bottlenecks in modern drug discovery efforts is in tackling the
undruggable proteome. Currently, over 85% of the proteome is still considered undruggable …