ArticleJournal of medicinal chemistry2019
Iterative Design and Optimization of Initially Inactive Proteolysis Targeting Chimeras (PROTACs) Identify VZ185 as a Potent, Fast, and Selective von Hippel-Lindau (VHL) Based Dual Degrader Probe of BRD9 and BRD7.
Article in Journal of medicinal chemistry, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 158 papers.
What it found
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Who cites it
158 citing papers in PubMed, 326 citations in OpenAlex.
- Bridging E3 Ligase Binding and Targeted Degradation Through Fluorescence Polarization.International journal of molecular sciences · 2026Article
- The roles of chromatin remodeling and 3D genome organization in cancers: from mechanistic insights to emerging treatment options.Molecular cancer · 2026Review
- Design of Synthesizable PROTACs through Synthesis Constrained Generative Model and Reinforcement Learning.JACS Au · 2026Article
- Eyes Toward the Clinic: Selective Inhibition and Degradation Approaches to Bromodomain-Containing Proteins.Chembiochem : a European journal of chemical biology · 2026Review
- Structural basis for selective and potent degradation of IRAK4 by KT-474.Nature communications · 2026Article
- Methods to Study the Molecular Mechanism and Drive the Design of Protein Degraders.Chemical reviews · 2026Review
- Article
- Review
- Recent Progress and Prospect in Studying Selective Inhibitors Toward Bromodomain Family Members.Molecules (Basel, Switzerland) · 2026Review
- Targeted Protein Degradation in Lung Cancer: The Emerging Role of PROTAC Technology and E3 Ligases.Current medicinal chemistry · 2026Review
- Interpretable PROTAC Degradation Prediction With Structure-Informed Deep Ternary Attention Framework.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- A selective RPL15 PROTAC degrader enhances anti-PD-1 immunotherapy in a murine melanoma tumor model.Oncogene · 2025Article
- Mode of action of a DCAF16-recruiting targeted glue that can selectively degrade BRD9.Nature communications · 2025Article
- Allostery in Disease: Anticancer Drugs, Pockets, and the Tumor Heterogeneity Challenge.Journal of molecular biology · 2025Review
- The Role of Reactive Oxygen Species in Lung Cancer Development: Nanomedicine as a Therapeutic Strategy.Biomolecules · 2025Review
- Characterization of PROTAC specificity and endogenous protein interactomes using ProtacID.Nature communications · 2025Article
- Accurate PROTAC-targeted degradation prediction with DegradeMaster.Bioinformatics (Oxford, England) · 2025Article
- Methods to accelerate PROTAC drug discovery.The Biochemical journal · 2025Review
- Unveiling New Triazoloquinoxaline-Based PROTACs Designed for the Selective Degradation of the ncBAF Chromatin Remodeling Subunit BRD9.Chemistry (Weinheim an der Bergstrasse, Germany) · 2025Article
- Epigenetic reader chromodomain as a potential therapeutic target.RSC chemical biology · 2025Review
98 more citing papers are in PubMed but not listed here.
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Authors and funding
11 authors at 4 institutions in 4 countries.
Funding
Abstract
Developing PROTACs to redirect the ubiquitination activity of E3 ligases and potently degrade a target protein within cells can be a lengthy and unpredictable process, and it remains unclear whether any combination of E3 and target might be productive for degradation. We describe a probe-quality degrader for a ligase-target pair deemed unsuitable: the von Hippel-Lindau (VHL) and BRD9, a bromodomain-containing subunit of the SWI/SNF chromatin remodeling complex BAF. VHL-based degraders could be optimized from suboptimal compounds in two rounds by systematically varying conjugation patterns and linkers and monitoring cellular degradation activities, kinetic profiles, and ubiquitination, as well as ternary complex formation thermodynamics. The emerged structure-activity relationships guided the discovery of VZ185, a potent, fast, and selective degrader of BRD9 and of its close homolog BRD7. Our findings qualify a new chemical tool for BRD7/9 knockdown and provide a roadmap for PROTAC development against seemingly incompatible target-ligase combinations.
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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.