ArticleJournal of the American Chemical Society2023
E3-Specific Degrader Discovery by Dynamic Tracing of Substrate Receptor Abundance.
Article in Journal of the American Chemical Society, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
What it found
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Who cites it
27 citing papers in PubMed, 39 citations in OpenAlex.
- Proteomics-Driven Strategies for Proximity-Inducing Drug Discovery.Angewandte Chemie (International ed. in English) · 2026Review
- Methods to Study the Molecular Mechanism and Drive the Design of Protein Degraders.Chemical reviews · 2026Review
- Cysteine availability tunes ubiquitin signaling via inverse stability of LRRC58 E3 ligase and its substrate CDO1.Nature communications · 2026Article
- From Serendipity to Strategy: Rationalizing Molecular Glue Discovery and Proximity-Induced Pharmacology through Chemical Biology.Journal of the American Chemical Society · 2026Review
- Utilization of Functional Degradation Pathways for the Characterization of Ubiquitin-Proteasome System Tool Compounds.Methods in molecular biology (Clifton, N.J.) · 2026Article
- Exploring Novel E3 Ligases and Neosubstrates for Molecular Glue Degraders and Therapeutic Applications in Cancer.Oncology research · 2026Review
- Systematic Analysis of E3 Ligase-Related Genes Identified UBE2L3 as a Prognostic Biomarker Associated With Drug Resistance in Acute Myeloid Leukemia.International journal of general medicine · 2025Article
- Cullin-Conciliated Regulation of Plant Immune Responses: Implications for Sustainable Crop Protection.Plants (Basel, Switzerland) · 2024Review
- Extrapolating Lessons from Targeted Protein Degradation to Other Proximity-Inducing Drugs.ACS chemical biology · 2024Review
- Principles of paralog-specific targeted protein degradation engaging the C-degron E3 KLHDC2.Nature communications · 2024Article
- Mechanism of degrader-targeted protein ubiquitinability.Science advances · 2024Article
- Pooled endogenous protein tagging and recruitment for systematic profiling of protein function.Cell genomics · 2024Article
- Targeted protein degradation: from mechanisms to clinic.Nature reviews. Molecular cell biology · 2024Review
- Ubiquitin-specific proximity labeling for the identification of E3 ligase substrates.Nature chemical biology · 2024Article
- Article
- Targeted Protein Degradation: Current and Emerging Approaches for E3 Ligase Deconvolution.Journal of medicinal chemistry · 2024Review
- Noncanonical assembly, neddylation and chimeric cullin-RING/RBR ubiquitylation by the 1.8 MDa CUL9 E3 ligase complex.Nature structural & molecular biology · 2024Article
- Alkylamine-tethered molecules recruit FBXO22 for targeted protein degradation.Nature communications · 2024Article
- Paralogue-selective degradation of the lysine acetyltransferase EP300.bioRxiv : the preprint server for biology · 2024Article
- Cullin-RING ligases employ geometrically optimized catalytic partners for substrate targeting.Molecular cell · 2024Article
Corrections and comments
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Authors and funding
11 authors at 2 institutions in 2 countries.
Funding
Abstract
Targeted protein degradation (TPD) is a new pharmacology based on small-molecule degraders that induce proximity between a protein of interest (POI) and an E3 ubiquitin ligase. Of the approximately 600 E3s encoded in the human genome, only around 2% can be co-opted with degraders. This underrepresentation is caused by a paucity of discovery approaches to identify degraders for defined E3s. This hampers a rational expansion of the druggable proteome and stymies critical advancements in the field, such as tissue- and cell-specific degradation. Here, we focus on dynamic NEDD8 conjugation, a post-translational, regulatory circuit that controls the activity of 250 cullin RING E3 ligases (CRLs). Leveraging this regulatory layer enabled us to develop a scalable assay to identify compounds that alter the interactome of an E3 of interest by tracing their abundance after pharmacologically induced auto-degradation. Initial validation studies are performed for CRBN and VHL, but proteomics studies indicate broad applicability for many CRLs. Among amenable ligases, we select CRL
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What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.