ArticleCell chemical biology2017
Ras Binder Induces a Modified Switch-II Pocket in GTP and GDP States.
Article in Cell chemical biology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 74 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
74 citing papers in PubMed, 116 citations in OpenAlex.
- Trial
- Evolution of KRAS molecular glues: from allele-selective to Pan-RAS and protein-protein interaction modulators.Acta pharmacologica Sinica · 2026Review
- An evolutionarily conserved salt bridge stabilizes the active site for GTP hydrolysis in Rho GTPases.The Journal of biological chemistry · 2026Article
- Characterization of rutin bindingto HRAS and MAPK3 and its clinical prognostic relevancein lung cancer: Using in silico and clinical prognostic experimental design.Naunyn-Schmiedeberg's archives of pharmacology · 2026Article
- The Human Omnibus of Targetable Pockets.Journal of cheminformatics · 2025Article
- Targeting KRAS mutations: orchestrating cancer evolution and therapeutic challenges.Signal transduction and targeted therapy · 2025Review
- RAS Pathway Inhibitors Combined with Targeted Agents Are Active in Patient-Derived Spheroids with Oncogenic KRAS Variants from Multiple Cancer Types.Cancer research communications · 2025Article
- An allosteric cyclin E-CDK2 site mapped by paralog hopping with covalent probes.Nature chemical biology · 2025Article
- Recent Advances in Peptide Inhibitors Targeting Wild-Type Ras Protein Interactions in Cancer Therapy.International journal of molecular sciences · 2025Review
- First molecules to reactivate RASBMC cancer · 2025Article
- Covalent Proximity Inducers.Chemical reviews · 2025Review
- Advances and Challenges in RAS Signaling Targeted Therapy in Leukemia.Molecular cancer therapeutics · 2025Review
- Recent progress in human telomerase structure and its therapeutic targeting.Frontiers in molecular biosciences · 2025Review
- A New Dawn for Targeted Cancer Therapy: Small Molecule Covalent Binding Inhibitor Targeting K-Ras (G12C).Current medicinal chemistry · 2025Review
- New insights into protein-protein interaction modulators in drug discovery and therapeutic advance.Signal transduction and targeted therapy · 2024Review
- Article
- Ligand discovery by activity-based protein profiling.Cell chemical biology · 2024Review
- Towards Targeting Endothelial Rap1B to Overcome Vascular Immunosuppression in Cancer.International journal of molecular sciences · 2024Review
- Crystal structure of the GDP-bound human M-RAS protein in two crystal forms.Acta crystallographica. Section F, Structural biology communications · 2024Article
- Immune status and combined immunotherapy progression in Kirsten rat sarcoma viral oncogene homolog (KRAS)-mutant tumors.Chinese journal of cancer research = Chung-kuo yen cheng yen chiu · 2024Article
14 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
8 authors at 3 institutions in 2 countries.
Funding
Abstract
Covalent inhibitors of K-Ras(G12C) have been reported that exclusively recognize the GDP state. Here, we utilize disulfide tethering of a non-natural cysteine (K-Ras(M72C)) to identify a new switch-II pocket (S-IIP) binding ligand (2C07) that engages the active GTP state. Co-crystal structures of 2C07 bound to H-Ras(M72C) reveal binding in a cryptic groove we term S-IIG. In the GppNHp state, 2C07 binding to a modified S-IIP pushes switch I away from the nucleotide, breaking the network of polar contacts essential for adopting the canonical GTP state. Biochemical studies show that 2C07 alters nucleotide preference and inhibits SOS binding and catalyzed nucleotide exchange. 2C07 was converted to irreversible covalent analogs, which target both nucleotide states, inhibit PI3K activation in vitro, and function as occupancy probes to detect reversible engagement in competition assays. Targeting both nucleotide states opens the possibility of inhibiting oncogenic mutants of Ras, which exist predominantly in the GTP state in cells.
Indexed as
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.