ArticleCell chemical biology2018
Lessons in PROTAC Design from Selective Degradation with a Promiscuous Warhead.
Article in Cell chemical biology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 425 papers.
What it found
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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
425 citing papers in PubMed, 876 citations in OpenAlex.
- PROTACs in cancer therapy: targeted degradation of GPX4, PARP and epigenetic regulators.Journal of enzyme inhibition and medicinal chemistry · 2026Review
- 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
- Performance of Rilpivirine-Based Hydrophobic Tags and PROTACs Directed Against HIV-1 Reverse Transcriptase.bioRxiv : the preprint server for biology · 2026Article
- Ubiquitin receptor-mediated, ubiquitin-independent targeted protein degradation via 26Science advances · 2026Article
- Proteolysis Targeting Chimera (PROTAC) Linkerology Enhances the CDK-Degradation Selectivity Profile of a Multi-CDK Inhibitor: Discovery of Potent, Anti-Leukemic CDK9 Degraders.ACS pharmacology & translational science · 2026Article
- Discovery and Development of First-in-Class Cereblon-Recruiting RIPK1 Degraders.Journal of medicinal chemistry · 2026Article
- From Ternary Modeling to Predictive PROTAC Design: A Computational Perspective.Journal of chemical information and modeling · 2026Article
- The synthetic landscape of cereblon (CRBN) binders: from thalidomide to emerging chemotypes.Chemical Society reviews · 2026Review
- C-MET tyrosine kinase receptor: mechanisms, clinical applications and future perspectives in cancer therapy.Signal transduction and targeted therapy · 2026Review
- Proteolysis Targeting Chimeric-Based Technology in Myeloma and Lymphoma.Molecular cancer therapeutics · 2026Review
- Review
- COMPASS: A Computational Pipeline to Identify Linkers Predicting Ubiquitinable PROTAC-Induced Ternary Complexes.ChemMedChem · 2026Article
- Mapping Scientific Landscapes and Therapeutic Innovations of Targeted Protein Degradation: A Scientometric Review.Pharmaceutics · 2026Review
- A quantitative approach for defining the degradability landscape of protein degraders.Nature communications · 2026Article
- Article
- Discovery of SMD-6346: A Potent, Selective, and Orally Active SMARCA2 Degrader for Targeting SMARCA4-Deficient Human Cancers.Journal of medicinal chemistry · 2026Article
- A Type II CDK6 Degrader Enables Cellular Targeting beyond the Limits of Type II Inhibition.Journal of the American Chemical Society · 2026Article
- Tumor immune cell targeting chimeras reprogram tumor-associated macrophages.Nature chemical biology · 2026Article
- Molecular glue degraders: Rational design, specificity engineering, and advanced delivery.Acta pharmaceutica Sinica. B · 2026Review
365 more citing papers are in PubMed but not listed here.
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Authors and funding
10 authors at 2 institutions in 1 country.
Funding
Abstract
Inhibiting protein function selectively is a major goal of modern drug discovery. Here, we report a previously understudied benefit of small molecule proteolysis-targeting chimeras (PROTACs) that recruit E3 ubiquitin ligases to target proteins for their ubiquitination and subsequent proteasome-mediated degradation. Using promiscuous CRBN- and VHL-recruiting PROTACs that bind >50 kinases, we show that only a subset of bound targets is degraded. The basis of this selectivity relies on protein-protein interactions between the E3 ubiquitin ligase and the target protein, as illustrated by engaged proteins that are not degraded as a result of unstable ternary complexes with PROTAC-recruited E3 ligases. In contrast, weak PROTAC:target protein affinity can be stabilized by high-affinity target:PROTAC:ligase trimer interactions, leading to efficient degradation. This study highlights design guidelines for generating potent PROTACs as well as possibilities for degrading undruggable proteins immune to traditional small-molecule inhibitors.
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What OpenQuestion holds
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.