ArticleNature communications2023
Affinity and cooperativity modulate ternary complex formation to drive targeted protein degradation.
Article in Nature communications, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 63 papers.
What it found
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Who cites it
63 citing papers in PubMed, 112 citations in OpenAlex.
- PROTACs in cancer therapy: targeted degradation of GPX4, PARP and epigenetic regulators.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
- Generalizable Strategies for the Synthesis of Cereblon-Recruiting PROTAC Prodrugs.Angewandte Chemie (International ed. in English) · 2026Article
- A Versatile DNA-Encoded Library Platform for the Discovery of Highly Cooperative Chemical Inducers of Proximity.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Bridging E3 Ligase Binding and Targeted Degradation Through Fluorescence Polarization.International journal of molecular sciences · 2026Article
- A real-time FRET ubiquitin transfer assay for quantitative characterization of ternary complexes in targeted protein degradation.Cell reports methods · 2026Article
- COMPASS: A Computational Pipeline to Identify Linkers Predicting Ubiquitinable PROTAC-Induced Ternary Complexes.ChemMedChem · 2026Article
- Computational mapping of productive POI-E3 ligase conformations to guide de novo degrader design: application to WEE1 and PKMYT1 PROTACs.Journal of cheminformatics · 2026Article
- On the Scope of DCAF1-Recruiting PROTACs Degrading Protein Kinases.Journal of medicinal chemistry · 2026Article
- Tumor immune cell targeting chimeras reprogram tumor-associated macrophages.Nature chemical biology · 2026Article
- Pyridine-containing antitumor agents: structure-oriented medicinal chemistry, structure-activity relationships, and ADMET liabilities.Medicinal chemistry research : an international journal for rapid communications on design and mechanisms of action of biologically active agents · 2026Review
- Targeted Protein Degradation of NUDT5 Dissociates Catalytic Inhibition from Protein Loss in 6-Thioguanine Response.Nature communications · 2026Article
- Structural basis for selective and potent degradation of IRAK4 by KT-474.Nature communications · 2026Article
- Degradation of G-quadruplex-binding proteins in chromatin using G4-ligand-based proteolysis-targeting chimeras.Nature chemistry · 2026Article
- Pharmacological targeting of IRF4 as a therapeutic strategy for multiple myeloma.Nature chemical biology · 2026Article
- Methods to Study the Molecular Mechanism and Drive the Design of Protein Degraders.Chemical reviews · 2026Review
- Metastable Protein-Protein Interactions as a Design Principle for PROTACs: Insights from the RIPK1-VHL System.JACS Au · 2026Article
- Interface Architecture of a VHL-PROTAC Complex with and without Cullin-2.Journal of the American Chemical Society · 2026Article
- A nanobody-based proteolysis-targeting chimera offers broad-spectrum protection against diverse influenza virus infections.Signal transduction and targeted therapy · 2026Article
- Targeting "undruggable" cancer proteins: pharmacological challenges and emerging strategies.Translational cancer research · 2026Review
3 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
13 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Targeted protein degradation via "hijacking" of the ubiquitin-proteasome system using proteolysis targeting chimeras (PROTACs) has evolved into a novel therapeutic modality. The design of PROTACs is challenging; multiple steps involved in PROTAC-induced degradation make it difficult to establish coherent structure-activity relationships. Herein, we characterize PROTAC-mediated ternary complex formation and degradation by employing von Hippel-Lindau protein (VHL) recruiting PROTACs for two different target proteins, SMARCA2 and BRD4. Ternary-complex attributes and degradation activity parameters are evaluated by varying components of the PROTAC's architecture. Ternary complex binding affinity and cooperativity correlates well with degradation potency and initial rates of degradation. Additionally, we develop a ternary-complex structure modeling workflow to calculate the total buried surface area at the interface, which is in agreement with the measured ternary complex binding affinity. Our findings establish a predictive framework to guide the design of potent degraders.
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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.