ArticleNature communications2018
Small molecule inhibitors of RAS-effector protein interactions derived using an intracellular antibody fragment.
Article in Nature communications, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 68 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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
68 citing papers in PubMed, 130 citations in OpenAlex.
- Brønsted-basic small molecules activate GTP hydrolysis in KRAS-Q61 mutants.Nature chemical biology · 2026Article
- Article
- Review
- Identification of KRAS mutants (G12C, G12D, and G12V) inhibitors.Future medicinal chemistry · 2025Article
- The complex journey of targeting RAS in oncology.BMC cancer · 2025Review
- Article
- Evolution of computational techniques against various KRAS mutants in search for therapeutic drugs: a review article.Cancer chemotherapy and pharmacology · 2025Review
- Pharmacological inhibition of RAS overcomes FLT3 inhibitor resistance in FLT3-ITD+ AML through AP-1 and RUNX1.iScience · 2024Article
- Genetically encodable biosensors for Ras activity.RSC chemical biology · 2024Review
- Crystallographic Studies of KRAS in Complex with Small Molecules and RAS-Binding Proteins.Methods in molecular biology (Clifton, N.J.) · 2024Article
- The acidic stretch and the C-terminal nuclear export signal motif of NPM1 mutant: are they druggable in AML?Leukemia · 2023Review
- Discovery of Hit Compounds Targeting the P4 Allosteric Site of K-RAS, Identified through Ensemble-Based Virtual Screening.Journal of chemical information and modeling · 2023Article
- Multiplexed imaging for probing RAS-RAF interactions in living cells.Biochimica et biophysica acta. Biomembranes · 2023Article
- Targeting Ras with protein engineering.Oncotarget · 2023Review
- Targeting small GTPases: emerging grasps on previously untamable targets, pioneered by KRAS.Signal transduction and targeted therapy · 2023Review
- Selected Approaches to Disrupting Protein-Protein Interactions within the MAPK/RAS Pathway.International journal of molecular sciences · 2023Review
- Intracellular Antibodies for Drug Discovery and as Drugs of the Future.Antibodies (Basel, Switzerland) · 2023Review
- In Silico Evaluation of the Thr58-Associated Conserved Water with KRAS Switch-II Pocket Binders.Journal of chemical information and modeling · 2023Article
- Eliminating oncogenic RAS: back to the future at the drawing board.Biochemical Society transactions · 2023Article
- Evolution of nanobodies specific for BCL11A.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
8 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
16 authors at 6 institutions in 2 countries.
Funding
Abstract
Targeting specific protein-protein interactions (PPIs) is an attractive concept for drug development, but hard to implement since intracellular antibodies do not penetrate cells and most small-molecule drugs are considered unsuitable for PPI inhibition. A potential solution to these problems is to select intracellular antibody fragments to block PPIs, use these antibody fragments for target validation in disease models and finally derive small molecules overlapping the antibody-binding site. Here, we explore this strategy using an anti-mutant RAS antibody fragment as a competitor in a small-molecule library screen for identifying RAS-binding compounds. The initial hits are optimized by structure-based design, resulting in potent RAS-binding compounds that interact with RAS inside the cells, prevent RAS-effector interactions and inhibit endogenous RAS-dependent signalling. Our results may aid RAS-dependent cancer drug development and demonstrate a general concept for developing small compounds to replace intracellular antibody fragments, enabling rational drug development to target validated PPIs.
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Identifiers
What OpenQuestion holds
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.