ArticleNature chemical biology2017
Inhibition of RAS function through targeting an allosteric regulatory site.
Article in Nature chemical biology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 191 papers.
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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
191 citing papers in PubMed, 293 citations in OpenAlex.
- Protein Engineering-Enabled Cryo-EM Investigation of Small GTPases.Journal of molecular biology · 2026Article
- Intracellular protein binders for imaging, control and future therapeutics.Nature biomedical engineering · 2026Review
- Targeting the H/KRAS α4-β6-α5 Allosteric Lobe with Macrocyclic Peptides.ACS medicinal chemistry letters · 2026Article
- Disulfide tethering reveals cryptic pockets in oncogenic KRAS.Communications chemistry · 2026Article
- hERG epitope mimic-decoy peptide corrects autoimmune-long QT syndrome in guinea pigs.Communications medicine · 2026Article
- Cell Surface Markers of Mesenchymal Stem Cells: Current Knowledge and Advances in Characterization Technologies.Life (Basel, Switzerland) · 2025Review
- Identification and characterization of binders to a cryptic and functional pocket in KRAS.Nature communications · 2025Article
- Inducible tag-free degradation of endogenous proteins with AlissAID and development of a photoactivable inducer.Communications biology · 2025Article
- A nucleotide-independent, pan-RAS-targeted DARPin elicits anti-tumor activity in a multimodal manner.Molecular oncology · 2025Article
- RAS-membrane interaction and oligomerization: there is more than meets the eye.Biochemical Society transactions · 2025Review
- Lipid nanoparticle-delivered intrabodies for inhibiting necroptosis and pyroptosis.The Biochemical journal · 2025Article
- PANCS-Binders: a rapid, high-throughput binder discovery platform.Nature methods · 2025Article
- From Concepts to Inhibitors: A Blueprint for Targeting Protein-Protein Interactions.Chemical reviews · 2025Review
- Investigation of potential KRASG12D inhibitors: a comparative study between MRTX1133 and natural compounds via computational structural biology approaches.BMC research notes · 2025Article
- Sensitive and Adaptable Turn-On Maturation (ATOM) Fluorescent Biosensors for Detecting Subcellular Localization of Protein Targets in Cells.Bio-protocol · 2025Article
- High-throughput protein binder discovery by rapid in vivo selection.bioRxiv : the preprint server for biology · 2025Article
- Development of potent inhibitors against KRAS, its mutant G12R, allosteric and Switch-I/Switch-II site.In silico pharmacology · 2025Article
- Review
- Development of mirror-image monobodies targeting the oncogenic BCR::ABL1 kinase.Nature communications · 2024Article
- Inhibition and degradation of NRAS with a pan-NRAS monobody.Oncogene · 2024Article
131 more citing papers are in PubMed but not listed here.
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Authors and funding
23 authors at 8 institutions in 2 countries.
Funding
Abstract
RAS GTPases are important mediators of oncogenesis in humans. However, pharmacological inhibition of RAS has proved challenging. Here we describe a functionally critical region, located outside the effector lobe of RAS, that can be targeted for inhibition. We developed NS1, a synthetic binding protein (monobody) that bound with high affinity to both GTP- and GDP-bound states of H-RAS and K-RAS but not N-RAS. NS1 potently inhibited growth factor signaling and oncogenic H-RAS- and K-RAS-mediated signaling and transformation but did not block oncogenic N-RAS, BRAF or MEK1. NS1 bound the α4-β6-α5 region of RAS, which disrupted RAS dimerization and nanoclustering and led to blocking of CRAF-BRAF heterodimerization and activation. These results establish the importance of the α4-β6-α5 interface in RAS-mediated signaling and define a previously unrecognized site in RAS for inhibiting RAS function.
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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.