ArticleNature chemical biology2015
Catalytic in vivo protein knockdown by small-molecule PROTACs.
Article in Nature chemical biology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 624 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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
624 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
- PROTACs in personalized and precision medicine: transforming targeted therapy with advances in selectivity and patient stratification.Cancer chemotherapy and pharmacology · 2026Review
- Engineered CTLA-4 targeting chimeras for targeted protein degradation and immune synapse reprogramming.bioRxiv : the preprint server for biology · 2026Article
- Unraveling the secrets of novel PROTACs to improve degradation efficacy.Molecular diversity · 2026Review
- Advancing PROTAC therapeutics through chemistry-guided design of smart delivery systems.Acta pharmacologica Sinica · 2026Review
- Linker Optimization of cMYC RIBOTAC for Efficient cMYC Modulation.ChemMedChem · 2026Article
- Performance of Rilpivirine-Based Hydrophobic Tags and PROTACs Directed Against HIV-1 Reverse Transcriptase.bioRxiv : the preprint server for biology · 2026Article
- Hydrophobic Tag Protein Degraders: An Emerging Therapeutic Strategy for Cancer.Pharmaceuticals (Basel, Switzerland) · 2026Review
- A New Recruitable E3 Ligase UHRF1 Supporting Targeted Protein Degradation: A Minimal Azide as a Recruitment Ligand.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- The synthetic landscape of cereblon (CRBN) binders: from thalidomide to emerging chemotypes.Chemical Society reviews · 2026Review
- Identification and Studies of Highly Potent and Selective Heterobifunctional Galectin‑3 Degraders.ACS medicinal chemistry letters · 2026Article
- C-MET tyrosine kinase receptor: mechanisms, clinical applications and future perspectives in cancer therapy.Signal transduction and targeted therapy · 2026Review
- Optimizing CRBN-ligands for optical targeted protein degradation.RSC medicinal chemistry · 2026Article
- Chemical Scaffolds Driving Modern Anticancer Drug Discovery and Radiotheranostics: Structural Determinants, Translational Opportunities and Future Perspectives.Pharmaceuticals (Basel, Switzerland) · 2026Review
- Tricarbonyl Rhenium-Based PROTACs Degrade the SARS-CoV-2 Mpro Protease.Chemistry (Weinheim an der Bergstrasse, Germany) · 2026Article
- Autonomously Motile Nano-PROTACs Act as Protein-Sweeping Robots to Enhance Targeted Protein Degradation.Advanced materials (Deerfield Beach, Fla.) · 2026Article
- The evolution of cancer therapeutics: from "undruggable" to "drugged".Translational cancer research · 2026Article
- Dual PROTACs Versus Dual Inhibitors in Oncology: A Medicinal Chemistry and Linker Design Perspective.Pharmaceuticals (Basel, Switzerland) · 2026Review
- FDA Approval of the First-Ever PROTAC: Vepdegestrant (ARV-471) Marks a New Era in Targeted Protein Degradation.Journal of medicinal chemistry · 2026Article
- PAX3::FOXO1-Targeting PROTAC Induces Myogenic Differentiation of Fusion-Positive Rhabdomyosarcoma Cells.Cancers · 2026Article
564 more citing papers are in PubMed but not listed here.
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Authors and funding
29 authors.
Funding
Abstract
The current predominant therapeutic paradigm is based on maximizing drug-receptor occupancy to achieve clinical benefit. This strategy, however, generally requires excessive drug concentrations to ensure sufficient occupancy, often leading to adverse side effects. Here, we describe major improvements to the proteolysis targeting chimeras (PROTACs) method, a chemical knockdown strategy in which a heterobifunctional molecule recruits a specific protein target to an E3 ubiquitin ligase, resulting in the target's ubiquitination and degradation. These compounds behave catalytically in their ability to induce the ubiquitination of super-stoichiometric quantities of proteins, providing efficacy that is not limited by equilibrium occupancy. We present two PROTACs that are capable of specifically reducing protein levels by >90% at nanomolar concentrations. In addition, mouse studies indicate that they provide broad tissue distribution and knockdown of the targeted protein in tumor xenografts. Together, these data demonstrate a protein knockdown system combining many of the favorable properties of small-molecule agents with the potent protein knockdown of RNAi and CRISPR.
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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.