ArticleNature2014
Discovery and characterization of small molecules that target the GTPase Ral.
Article in Nature, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 87 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
87 citing papers in PubMed, 147 citations in OpenAlex.
- Article
- M-Sec promotes the production of infectious HIV-1 virus through the exocyst complex in macrophages.PLoS pathogens · 2026Article
- An evolutionarily conserved salt bridge stabilizes the active site for GTP hydrolysis in Rho GTPases.The Journal of biological chemistry · 2026Article
- Cyclized Peptide Inhibitors of the Small G Protein Cdc42 Mimic Binding of Effector Proteins.Biochemistry · 2026Article
- Article
- Trustworthy Inverse Molecular Design via Alignment with Molecular Dynamics.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Small-Molecule KRAS Inhibitors by Tyrosine Covalent Bond Formation.ChemMedChem · 2025Article
- Oncogenic RAS induces a distinctive form of non-canonical autophagy mediated by the P38-ULK1-PI4KB axis.Cell research · 2025Article
- [RGL1 overexpression promotes metastasis of colorectal cancer by upregulating motile focal adhesion assemblyNan fang yi ke da xue xue bao = Journal of Southern Medical University · 2025Article
- Critical role for platelet Ral GTPases in regulating venous thrombosis in mice.Journal of thrombosis and haemostasis : JTH · 2025Article
- The RAL Small G Proteins Are Clinically Relevant Targets in Triple Negative Breast Cancer.Cancers · 2024Article
- A let-7 microRNA-RALB axis links the immune properties of iPSC-derived megakaryocytes with platelet producibility.Nature communications · 2024Article
- Regulation of Ras p21 and RalA GTPases activity by quinine in mammary epithelial cells.Molecular and cellular biochemistry · 2024Article
- A RalA between high-fat diet and mitochondrial shape.Nature metabolism · 2024Article
- Obesity causes mitochondrial fragmentation and dysfunction in white adipocytes due to RalA activation.Nature metabolism · 2024Article
- Mediating kinase activity in Ras-mutant cancer: potential for an individualised approach?Frontiers in pharmacology · 2024Review
- Exploring Covalent Bond Formation at Tyr-82 for Inhibition of Ral GTPase Activation.ChemMedChem · 2023Article
- Identification of Cytochrome P450 2E1 as a Novel Target in Glioma and Development of Its Inhibitor as an Anti-Tumor Agent.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2023Article
- Targeting small GTPases: emerging grasps on previously untamable targets, pioneered by KRAS.Signal transduction and targeted therapy · 2023Review
- Single-cell resolution reveals RalA GTPase expanding hematopoietic stem cells and facilitating of BCR-ABL1-driven leukemogenesis in a CRISPR/Cas9 gene editing mouse model.International journal of biological sciences · 2023Article
27 more citing papers are in PubMed but not listed here.
Corrections and comments
- Commented on by
- Commented on by
Authors and funding
20 authors at 6 institutions in 1 country.
Funding
Abstract
The Ras-like GTPases RalA and RalB are important drivers of tumour growth and metastasis. Chemicals that block Ral function would be valuable as research tools and for cancer therapeutics. Here we used protein structure analysis and virtual screening to identify drug-like molecules that bind to a site on the GDP-bound form of Ral. The compounds RBC6, RBC8 and RBC10 inhibited the binding of Ral to its effector RALBP1, as well as inhibiting Ral-mediated cell spreading of murine embryonic fibroblasts and anchorage-independent growth of human cancer cell lines. The binding of the RBC8 derivative BQU57 to RalB was confirmed by isothermal titration calorimetry, surface plasmon resonance and (1)H-(15)N transverse relaxation-optimized spectroscopy (TROSY) NMR spectroscopy. RBC8 and BQU57 show selectivity for Ral relative to the GTPases Ras and RhoA and inhibit tumour xenograft growth to a similar extent to the depletion of Ral using RNA interference. Our results show the utility of structure-based discovery for the development of therapeutics for Ral-dependent cancers.
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.