ArticleACS central science2024
DCAF16-Based Covalent Handle for the Rational Design of Monovalent Degraders.
Article in ACS central science, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 47 papers.
What it found
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The trial behind it
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
47 citing papers in PubMed.
- High-throughput ligand diversification to discover chemical inducers of proximity.Nature chemical biology · 2026Article
- Epidermal Growth Factor Receptor as a Model Drug Target for Scrutinizing the Status Quo in Drug Discovery and Chemical Biology.ACS bio & med chem Au · 2026Review
- FDA Approval of the First-Ever PROTAC: Vepdegestrant (ARV-471) Marks a New Era in Targeted Protein Degradation.Journal of medicinal chemistry · 2026Article
- Eyes Toward the Clinic: Selective Inhibition and Degradation Approaches to Bromodomain-Containing Proteins.Chembiochem : a European journal of chemical biology · 2026Review
- Molecular glue degraders: Rational design, specificity engineering, and advanced delivery.Acta pharmaceutica Sinica. B · 2026Review
- Covalent Reprogramming of Kinase Binders to Modulate Protein Abundance.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Harnessing FBXO31 with Terminal Amide-Functionalized Molecules for Targeted Protein Degradation.Journal of the American Chemical Society · 2026Article
- Small-molecule degraders for oncogenic KRASNature communications · 2026Article
- Understanding the Role of H-Bonds in the Stability of Molecular Glue-Induced Ternary Complexes.Journal of chemical information and modeling · 2026Article
- An Optimized RNF126-Targeting Covalent Handle for Molecular Glue Degraders.bioRxiv : the preprint server for biology · 2026Article
- Induced proximity-based therapeutic modalities.Nature reviews. Drug discovery · 2026Review
- Targeted Protein Degradation in Cancer: PROTACs, New Targets, and Clinical Mechanisms.Biomolecules · 2026Review
- Sub-stoichiometric Degradation is Dispensable for Potent PROTACs: A Case Study for Irreversible Covalent BTK Degraders.bioRxiv : the preprint server for biology · 2026Article
- A Novel Paradigm for Targeting Challenging Targets: Advancing Technologies and Future Directions of Molecular Glue Degraders.Molecules (Basel, Switzerland) · 2026Review
- Clues for glues: from serendipity to nature's blueprints in degrader discovery.Essays in biochemistry · 2025Review
- Discovery of Non-Degradative Covalent Molecular Glues for Transcriptional Reprogramming.bioRxiv : the preprint server for biology · 2025Article
- Covalent Reprogramming of Kinase Binders to Modulate Protein Homeostasis.bioRxiv : the preprint server for biology · 2025Article
- Ketoboronate as a Minimal Covalent-Reversible Tag for Targeted Lysosomal Degradation of Extracellular and Membrane Proteins.Journal of the American Chemical Society · 2025Article
- Rational design of potent small-molecule SMARCA2/A4 degraders acting via the recruitment of FBXO22.Nature communications · 2025Article
- Mode of action of a DCAF16-recruiting targeted glue that can selectively degrade BRD9.Nature communications · 2025Article
Corrections and comments
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Authors and funding
9 authors.
Funding
Abstract
Targeted protein degradation with monovalent molecular glue degraders is a powerful therapeutic modality for eliminating disease causing proteins. However, rational design of molecular glue degraders remains challenging. In this study, we sought to identify a transplantable and linker-less covalent handle that could be appended onto the exit vector of various protein-targeting ligands to induce the degradation of their respective targets. Using the BET family inhibitor JQ1 as a testbed, we synthesized and screened a series of covalent JQ1 analogs and identified a vinylsulfonyl piperazine handle that led to the potent and selective degradation of BRD4 in cells. Through chemoproteomic profiling, we identified DCAF16 as the E3 ligase responsible for BRD4 degradation-an E3 ligase substrate receptor that has been previously covalently targeted for molecular glue-based degradation of BRD4. Interestingly, we demonstrated that this covalent handle can be transplanted across a diverse array of protein-targeting ligands spanning many different protein classes to induce the degradation of CDK4, the androgen receptor, BTK, SMARCA2/4, and BCR-ABL/c-ABL. Our study reveals a DCAF16-based covalent degradative and linker-less chemical handle that can be attached to protein-targeting ligands to induce the degradation of several different classes of protein targets.
Identifiers
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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.