ArticleSmall GTPases2019
Targeting the α4-α5 interface of RAS results in multiple levels of inhibition.
Article in Small GTPases, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
25 citing papers in PubMed, 34 citations in OpenAlex.
- A Hit Prioritization Strategy for Compound Library Screening Using LiP-MS and Molecular Dynamics Simulations Applied to KRas G12D Inhibitors.Analytical chemistry · 2025Article
- Inhibition and degradation of NRAS with a pan-NRAS monobody.Oncogene · 2024Article
- Towards Targeting Endothelial Rap1B to Overcome Vascular Immunosuppression in Cancer.International journal of molecular sciences · 2024Review
- Structural modifications and kinetic effects ofFrontiers in molecular biosciences · 2024Article
- Review
- Identification of the nucleotide-free state as a therapeutic vulnerability for inhibition of selected oncogenic RAS mutants.Cell reports · 2022Article
- Review
- Targeting the "undruggable" RAS with biologics.Advances in cancer research · 2022Review
- KRAS G12D targeted therapies for pancreatic cancer: Has the fortress been conquered?Frontiers in oncology · 2022Review
- Targeting the KRAS α4-α5 allosteric interface inhibits pancreatic cancer tumorigenesis.Small GTPases · 2022Article
- Review
- Targeting KRAS in pancreatic cancer: new drugs on the horizon.Cancer metastasis reviews · 2021Review
- RAS-inhibiting biologics identify and probe druggable pockets including an SII-α3 allosteric site.Nature communications · 2021Article
- RAS Nanoclusters: Dynamic Signaling Platforms Amenable to Therapeutic Intervention.Biomolecules · 2021Review
- Diffusion-based determination of protein homodimerization on reconstituted membrane surfaces.BMB reports · 2021Review
- Probing RAS Function with Monobodies.Methods in molecular biology (Clifton, N.J.) · 2021Article
- Natural Products Attenuating Biosynthesis, Processing, and Activity of Ras Oncoproteins: State of the Art and Future Perspectives.Biomolecules · 2020Review
- Targeting Endogenous K-RAS for Degradation through the Affinity-Directed Protein Missile System.Cell chemical biology · 2020Article
- RAS Function in cancer cells: translating membrane biology and biochemistry into new therapeutics.The Biochemical journal · 2020Review
- Therapeutic targeting of RAS: New hope for drugging the "undruggable".Biochimica et biophysica acta. Molecular cell research · 2020Review
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
Generation of RAS-targeted therapeutics has long been considered a "holy grail" in cancer research. However, a lack of binding pockets on the surface of RAS and its picomolar affinity for guanine nucleotides have made isolation of inhibitors particularly challenging. We recently described a monobody, termed NS1, that blocks RAS signaling and oncogenic transformation. NS1 binds to the α4-β6-α5 interface of H-RAS and K-RAS thus preventing RAS dimerization and nanoclustering, which in turn prevents RAS-stimulated dimerization and activation of RAF. Interestingly, NS1 reduces interaction of oncogenic K-RAS, but not H-RAS, with RAF and reduces K-RAS plasma membrane localization. Here, we show that these isoform specific effects of NS1 on RAS:RAF are due to the distinct hypervariable regions of RAS isoforms. NS1 inhibited wild type RAS function by reducing RAS GTP levels. These findings reveal that NS1 disrupts RAS signaling through a mechanism that is more complex than simply inhibiting RAS dimerization and nanoclustering.
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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.