ArticleCell reports2022
Identification of the nucleotide-free state as a therapeutic vulnerability for inhibition of selected oncogenic RAS mutants.
Article in Cell reports, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed.
- Intracellular protein binders for imaging, control and future therapeutics.Nature biomedical engineering · 2026Review
- Review
- A nucleotide-independent, pan-RAS-targeted DARPin elicits anti-tumor activity in a multimodal manner.Molecular oncology · 2025Article
- From Concepts to Inhibitors: A Blueprint for Targeting Protein-Protein Interactions.Chemical reviews · 2025Review
- A Pan-RAS Inhibitor with a Unique Mechanism of Action Blocks Tumor Growth and Induces Antitumor Immunity in Gastrointestinal Cancer.Cancer research · 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
- Novel druggable space in human KRAS G13D discovered using structural bioinformatics and a P-loop targeting monoclonal antibody.Scientific reports · 2024Article
- Probing RAS Function Using Monobody and NanoBiT Technologies.Methods in molecular biology (Clifton, N.J.) · 2024Article
- Exploring switch II pocket conformation of KRAS(G12D) with mutant-selective monobody inhibitors.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Targeting Ras with protein engineering.Oncotarget · 2023Review
- Targeting the 'Undruggable' Driver Protein, KRAS, in Epithelial Cancers: Current Perspective.Cells · 2023Review
- Secreted frizzled related-protein 2 is prognostic for human pancreatic cancer patient survival and is associated with fibrosis.Cancer biomarkers : section A of Disease markers · 2023Article
- KRAS-specific antibody binds to KRAS protein inside colorectal adenocarcinoma cells and inhibits its localization to the plasma membrane.Frontiers in oncology · 2023Article
- Inhibition of RAS-driven signaling and tumorigenesis with a pan-RAS monobody targeting the Switch I/II pocket.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
Corrections and comments
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Authors and funding
12 authors.
Funding
Abstract
RAS guanosine triphosphatases (GTPases) are mutated in nearly 20% of human tumors, making them an attractive therapeutic target. Following our discovery that nucleotide-free RAS (apo RAS) regulates cell signaling, we selectively target this state as an approach to inhibit RAS function. Here, we describe the R15 monobody that exclusively binds the apo state of all three RAS isoforms in vitro, regardless of the mutation status, and captures RAS in the apo state in cells. R15 inhibits the signaling and transforming activity of a subset of RAS mutants with elevated intrinsic nucleotide exchange rates (i.e., fast exchange mutants). Intracellular expression of R15 reduces the tumor-forming capacity of cancer cell lines driven by select RAS mutants and KRAS(G12D)-mutant patient-derived xenografts (PDXs). Thus, our approach establishes an opportunity to selectively inhibit a subset of RAS mutants by targeting the apo state with drug-like molecules.
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