ArticleNature communications2021
Selective and noncovalent targeting of RAS mutants for inhibition and degradation.
Article in Nature communications, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 61 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.
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Who cites it
61 citing papers in PubMed, 83 citations in OpenAlex.
- Mapping Mutations and Signaling Network Interactions to Guide Precision Therapy in Gallbladder Cancer.Cancer reports (Hoboken, N.J.) · 2026Review
- 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
- Structural and Energetic Determinants of Monobody Recognition of Oncogenic KRAS Variants.bioRxiv : the preprint server for biology · 2026Article
- RAS Inhibitors: Changing the Paradigm from the Undruggable.Pharmaceutics · 2026Review
- Protein-based pan-RAS inhibitor induces tumor regression in female mice via IFNγ and CD8Nature communications · 2026Article
- De novo design of Ras isoform selective binders.Cell chemical biology · 2026Article
- Systematic and precise interventions for KRAS-mutant cancers.Experimental hematology & oncology · 2026Review
- Emerging biologic modalities for targeted protein degradation.The Journal of biological chemistry · 2026Review
- Cyclized Peptide Inhibitors of the Small G Protein Cdc42 Mimic Binding of Effector Proteins.Biochemistry · 2026Article
- Protein engineering: status report.Protein engineering, design & selection : PEDS · 2026Review
- Unravelling Resistance: Integrating Metabolism, Epigenetics, Immunology, and Proteostasis in Strategies against Kirsten Rat Sarcoma Viral Oncogene Homolog-mutant Colorectal Cancer.International journal of biological sciences · 2026Review
- Targeting KRAS mutations: orchestrating cancer evolution and therapeutic challenges.Signal transduction and targeted therapy · 2025Review
- 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
- Selective targeting of oncogenic hotspot mutations of the HER2 extracellular domain.Nature chemical biology · 2025Article
- Associations of KRAS Point Mutations with Survival of Patients Who Underwent Curative-Intent Resection of Colorectal Liver Metastases.Annals of surgical oncology · 2025Article
- Protein-Based Degraders: From Chemical Biology Tools to Neo-Therapeutics.Chemical reviews · 2025Review
- Advancements in gene therapies targeting mutant KRAS in cancers.Cancer metastasis reviews · 2025Review
- Inhibition and degradation of NRAS with a pan-NRAS monobody.Oncogene · 2024Article
1 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
11 authors at 3 institutions in 1 country.
Funding
Abstract
Activating mutants of RAS are commonly found in human cancers, but to date selective targeting of RAS in the clinic has been limited to KRAS(G12C) through covalent inhibitors. Here, we report a monobody, termed 12VC1, that recognizes the active state of both KRAS(G12V) and KRAS(G12C) up to 400-times more tightly than wild-type KRAS. The crystal structures reveal that 12VC1 recognizes the mutations through a shallow pocket, and 12VC1 competes against RAS-effector interaction. When expressed intracellularly, 12VC1 potently inhibits ERK activation and the proliferation of RAS-driven cancer cell lines in vitro and in mouse xenograft models. 12VC1 fused to VHL selectively degrades the KRAS mutants and provides more extended suppression of mutant RAS activity than inhibition by 12VC1 alone. These results demonstrate the feasibility of selective targeting and degradation of KRAS mutants in the active state with noncovalent reagents and provide a starting point for designing noncovalent therapeutics against oncogenic RAS mutants.
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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.