ArticleNature communications2020
A potent KRAS macromolecule degrader specifically targeting tumours with mutant KRAS.
Article in Nature communications, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 86 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
86 citing papers in PubMed, 126 citations in OpenAlex.
- Programmable protein degraders enable selective knockdown of pathogenic β-catenin subpopulations in vitro and in vivo.Science advances · 2026Article
- Intracellular protein binders for imaging, control and future therapeutics.Nature biomedical engineering · 2026Review
- The AUTACE That Degrades KRAS and Engages CD8Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- The NanoBridge system for targeted post-translational modification of challenging proteins.bioRxiv : the preprint server for biology · 2026Article
- Protein-based pan-RAS inhibitor induces tumor regression in female mice via IFNγ and CD8Nature communications · 2026Article
- Emerging biologic modalities for targeted protein degradation.The Journal of biological chemistry · 2026Review
- Article
- The TRIP12's intrinsically disordered region induces chromatin condensates and interferes with nuclear processes.iScience · 2026Article
- Quantitative Degradation Rate Assessment of bioPROTACs Based on Peptide Degrons, E3 Domains, Adapters and Conjugated Small Molecules.ACS chemical biology · 2026Article
- Innovative Therapies for Oncogenic KRAS Mutations: Precision Strategies with PROTACs in Cancer Treatment.Anti-cancer agents in medicinal chemistry · 2026Review
- Article
- Targeting KRAS mutations: orchestrating cancer evolution and therapeutic challenges.Signal transduction and targeted therapy · 2025Review
- Advances in Targeted Therapy for Non-Small-Cell Lung Cancer: Current Progress and Future Directions.International journal of molecular sciences · 2025Review
- Pancreatic cancer in 2025: Have we found a solution?World journal of gastroenterology · 2025Review
- Review
- Mechanistic Foundations of KRAS-Driven Tumor Ecosystems: Integrating Crosstalk among Immune, Metabolic, Microbial, and Stromal Microenvironment.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Review
- Reengineering of a Proteomimetic Pan-Ras Inhibitor into a Ras Degrader.Angewandte Chemie (International ed. in English) · 2025Article
- Recent advances in targeted degradation in the RAS pathway.Future medicinal chemistry · 2025Review
- Protein-Based Degraders: From Chemical Biology Tools to Neo-Therapeutics.Chemical reviews · 2025Review
- From bench to bedside: murine models of inherited and sporadic brain arteriovenous malformations.Angiogenesis · 2025Review
26 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
3 authors at 2 institutions in 2 countries.
Funding
Abstract
Tumour-associated KRAS mutations are the most prevalent in the three RAS-family isoforms and involve many different amino-acids. Therefore, molecules able to interfere with mutant KRAS protein are potentially important for wide-ranging tumour therapy. We describe the engineering of two RAS degraders based on protein macromolecules (macrodrugs) fused to specific E3 ligases. A KRAS-specific DARPin fused to the VHL E3 ligase is compared to a pan-RAS intracellular single domain antibody (iDAb) fused to the UBOX domain of the CHIP E3 ligase. We demonstrate that while the KRAS-specific DARPin degrader induces specific proteolysis of both mutant and wild type KRAS, it only inhibits proliferation of cancer cells expressing mutant KRAS in vitro and in vivo. Pan-RAS protein degradation, however, affects proliferation irrespective of the RAS mutation. These data show that specific KRAS degradation is an important therapeutic strategy to affect tumours expressing any of the range of KRAS mutations.
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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.