ArticleNature chemical biology2019
Electrophilic PROTACs that degrade nuclear proteins by engaging DCAF16.
Article in Nature chemical biology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 231 papers, 1 of them a synthesis that pooled it.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
231 citing papers in PubMed, 1 synthesis or guideline pooled it, 469 citations in OpenAlex.
- Cellular functions and molecular mechanisms of ubiquitination in osteosarcoma.Frontiers in oncology · 2022Pooled it
- Context matters in PROTAC design: navigating the trade-off between degradation and developability.Journal of enzyme inhibition and medicinal chemistry · 2026Review
- PROTACs in personalized and precision medicine: transforming targeted therapy with advances in selectivity and patient stratification.Cancer chemotherapy and pharmacology · 2026Review
- Dual E3 ligase recruitment by monovalent degraders for tunable SMARCA 2/4 degradation.Nature chemical biology · 2026Article
- Genetic links between multimorbidity and human aging.GeroScience · 2026Article
- A pharmacological modality to sequester homomeric proteins.Nature chemical biology · 2026Article
- High-throughput ligand diversification to discover chemical inducers of proximity.Nature chemical biology · 2026Article
- A New Recruitable E3 Ligase UHRF1 Supporting Targeted Protein Degradation: A Minimal Azide as a Recruitment Ligand.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Proteomics-Driven Strategies for Proximity-Inducing Drug Discovery.Angewandte Chemie (International ed. in English) · 2026Review
- PAX3::FOXO1-Targeting PROTAC Induces Myogenic Differentiation of Fusion-Positive Rhabdomyosarcoma Cells.Cancers · 2026Article
- Mapping Scientific Landscapes and Therapeutic Innovations of Targeted Protein Degradation: A Scientometric Review.Pharmaceutics · 2026Review
- Aryl Aldehyde-Anchored Small Molecules Recruit FBXO22 for Targeted Degradation of NSD2.Journal of medicinal chemistry · 2026Article
- Identification of Clofibric Acid as a Synoviolin (SYVN1) Ligand for Proteolysis-Targeting Chimera (PROTAC) Development.ACS medicinal chemistry letters · 2026Article
- Research Trends and Emerging Frontiers in Proteolysis Targeting Chimeras (PROTACs): A Bibliometric Analysis of 2630 Publications (2001-2025).Pharmaceuticals (Basel, Switzerland) · 2026Article
- Analysis of Confounding Factors in Reactive Cysteine Profiling Reveals Enhanced Chromatin-Protein Association via CDK7 Inhibition by THZ1.ACS chemical biology · 2026Article
- A Global Ligandability Map of Tryptoline Butynamide Stereoprobes Identifies Covalent Inhibitors of the Actin Maturation Protease.Journal of the American Chemical Society · 2026Article
- First Generation Proteolysis Targeting Chimeras (PROTACs) for the Treatment of Progeria.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Covalent Reprogramming of Kinase Binders to Modulate Protein Abundance.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Methods to Study the Molecular Mechanism and Drive the Design of Protein Degraders.Chemical reviews · 2026Review
- Discovery of a KLHL41 Ligand for Muscle Specific Protein Degradation.Nature communications · 2026Article
171 more citing papers are in PubMed but not listed here.
Corrections and comments
- Commented on byStick it to E3s.2019
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
Ligand-dependent protein degradation has emerged as a compelling strategy to pharmacologically control the protein content of cells. So far, however, only a limited number of E3 ligases have been found to support this process. Here, we use a chemical proteomic strategy that leverages broadly reactive, cysteine-directed electrophilic fragments coupled to selective ligands for intracellular proteins (for example, SLF for FKBP12, JQ1 for BRD4) to screen for heterobifunctional degrader compounds (or proteolysis targeting chimeras, PROTACs) that operate by covalent adduction of E3 ligases. This approach identified DCAF16-a poorly characterized substrate recognition component of CUL4-DDB1 E3 ubiquitin ligases-as a target of electrophilic PROTACs that promote the nuclear-restricted degradation of proteins. We find that only a modest fraction (~10-40%) of DCAF16 needs to be modified to support protein degradation, pointing to the potential for electrophilic PROTACs to induce neosubstrate degradation without substantially perturbing the function of the participating E3 ligase.
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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.