The development of novel drug modalities is necessary to overcome the current critical
issues in the treatment of cancer, namely toxicity, insufficient efficacy, and the development …

The rational development of small-molecule degraders (eg, proteolysis targeting chimeras)
remains a challenge as the rate-limiting steps that determine degrader efficiency are largely …

Ubiquitylation is catalyzed by coordinated actions of E3 and E2 enzymes. Molecular
principles governing many important E3-E2 partnerships remain unknown, including those …

A paradigm shift in drug development is the discovery of small molecules that harness the
ubiquitin-proteasomal pathway to eliminate pathogenic proteins. Here we provide a modality …

The Pro/N-degron recognizing C-terminal to LisH (CTLH) complex is an E3 ligase of
emerging interest in the developmental biology field and for targeted protein degradation …

Patients with Skraban‐Deardorff syndrome (SKDEAS), a neurodevelopmental syndrome
associated with a spectrum of developmental and intellectual delays and disabilities, harbor …

The yeast glucose-induced degradation-deficient (GID) E3 ubiquitin ligase forms a suite of
complexes with interchangeable receptors that selectively recruit N-terminal degron motifs of …

Chemically induced proximity-based targeted protein degradation (TPD) has become a
prominent paradigm in drug discovery. With the clinical benefit demonstrated by certain …

The human CTLH/GID (hGID) complex emerged as an important E3 ligase regulating
multiple cellular processes, including cell cycle progression and metabolism. However, the …

Target 2035 is a global initiative that seeks to identify a pharmacological modulator of most
human proteins by the year 2035. As part of an ongoing series of annual updates of this …