ArticleNature communications2024
Crystal structures of DCAF1-PROTAC-WDR5 ternary complexes provide insight into DCAF1 substrate specificity.
Article in Nature communications, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed.
- Context matters in PROTAC design: navigating the trade-off between degradation and developability.Journal of enzyme inhibition and medicinal chemistry · 2026Review
- Structural basis of diverse substrate recruitment by the HIV-1 Vpr-hijacked CRL4(VprBP) E3 ligase.PLoS pathogens · 2026Article
- Artificial intelligence empowers targeted protein degradation: Core technological innovations, multi-scenario applications, and translational prospects.Smart molecules : open access · 2026Review
- On the Scope of DCAF1-Recruiting PROTACs Degrading Protein Kinases.Journal of medicinal chemistry · 2026Article
- The role of the WD40-repeat protein family in cancer.Molecular cancer · 2026Review
- Research Trends and Emerging Frontiers in Proteolysis Targeting Chimeras (PROTACs): A Bibliometric Analysis of 2630 Publications (2001-2025).Pharmaceuticals (Basel, Switzerland) · 2026Article
- Understanding and Overcoming Antibody-Drug Conjugate Resistance: Biological Mechanisms and Emerging Analytical Frameworks in Breast Cancer.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Review
- Self-Dimerization Induced Proximity Targeting Chimeras (SDIPTAC) Lead to DCAF1 Loss of Function and Inhibition of HIV Replication.Journal of medicinal chemistry · 2026Article
- VeGA-RX and VeGA-SCX: Controllable SMARTS-Guided Generative Transformers for Precision-DrivenJournal of chemical information and modeling · 2026Article
- Discovery of SKP2-Recruiting PROTACs for Target Protein Degradation.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- PROTAC-based protein degradation: a window of opportunity for melanoma therapy.Journal of biomedical science · 2026Review
- Lessons learned in linking PROTACs from discovery to the clinic.Nature reviews. Chemistry · 2026Review
- Computational Modeling of PROTAC Ternary Complexes as Ensembles Using SILCS-xTAC.Journal of chemical information and modeling · 2026Article
- Insights into WDR5: unveiling its functions, regulation, and impact on skeletal muscle.Epigenetics · 2025Review
- PRosettaC outperforms AlphaFold3 for modeling PROTAC ternary complexes.Scientific reports · 2025Article
- Review
- Design of PROTACs utilizing the E3 ligase GID4 for targeted protein degradation.Nature structural & molecular biology · 2025Article
- OICR-41103 as a chemical probe for the DCAF1 WD40 domain.Communications biology · 2025Article
- Cellular parameters shaping pathways of targeted protein degradation.Communications biology · 2025Review
- PROTACs coupled with oligonucleotides to tackle the undruggable.Bioanalysis · 2025Review
Corrections and comments
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Authors and funding
39 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Proteolysis-targeting chimeras (PROTACs) have been explored for the degradation of drug targets for more than two decades. However, only a handful of E3 ligase substrate receptors have been efficiently used. Downregulation and mutation of these receptors would reduce the effectiveness of such PROTACs. We recently developed potent ligands for DCAF1, a substrate receptor of EDVP and CUL4 E3 ligases. Here, we focus on DCAF1 toward the development of PROTACs for WDR5, a drug target in various cancers. We report four DCAF1-based PROTACs with endogenous and exogenous WDR5 degradation effects and high-resolution crystal structures of the ternary complexes of DCAF1-PROTAC-WDR5. The structures reveal detailed insights into the interaction of DCAF1 with various WDR5-PROTACs, indicating a significant role of DCAF1 loops in providing needed surface plasticity, and reflecting the mechanism by which DCAF1 functions as a substrate receptor for E3 ligases with diverse sets of substrates.
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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.