ArticleJournal of biomolecular screening2010
Identification of a small GTPase inhibitor using a high-throughput flow cytometry bead-based multiplex assay.
Article in Journal of biomolecular screening, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
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Who cites it
33 citing papers in PubMed, 66 citations in OpenAlex.
- A Novel Pharmacologic Activity of Ketorolac for Therapeutic Benefit in Ovarian Cancer Patients.Clinical cancer research : an official journal of the American Association for Cancer Research · 2015Trial
- The role of RAC1 in resistance to targeted therapies in cancer.Small GTPases · 2024Review
- Characterization of Novel Derivatives of MBQ-167, an inhibitor of the GTP-binding proteins Rac/Cdc42.Cancer research communications · 2022Article
- Förster resonance energy transfer biosensors for fluorescence and time-gated luminescence analysis of rac1 activity.Scientific reports · 2022Article
- Article
- Small Molecule Improvement of Trafficking Defects in Models of Neurodegeneration.ACS chemical neuroscience · 2021Article
- Targeting the cytoskeleton against metastatic dissemination.Cancer metastasis reviews · 2021Review
- Creating and screening natural product libraries.Natural product reports · 2020Review
- Homogeneous Dual-Parametric-Coupled Assay for Simultaneous Nucleotide Exchange and KRAS/RAF-RBD Interaction Monitoring.Analytical chemistry · 2020Article
- Transcriptomic Evidence Reveals the Molecular Basis for Functional Differentiation of Hemocytes in a Marine Invertebrate,Frontiers in immunology · 2020Article
- Pep5, a Fragment of Cyclin D2, Shows Antiparasitic Effects in Different Stages of theAntimicrobial agents and chemotherapy · 2019Article
- Druggable targets in the Rho pathway and their promise for therapeutic control of blood pressure.Pharmacology & therapeutics · 2019Review
- Targeting Rac and Cdc42 GTPases in Cancer.Cancer research · 2018Review
- Activation of Rho Family GTPases by Small Molecules.ACS chemical biology · 2018Article
- Rho GTPases, their post-translational modifications, disease-associated mutations and pharmacological inhibitors.Small GTPases · 2018Review
- Article
- Discovery and characterization of small molecule Rac1 inhibitors.Oncotarget · 2017Article
- Flow Cytometry: Impact on Early Drug Discovery.Journal of biomolecular screening · 2015Review
- A Pan-GTPase Inhibitor as a Molecular Probe.PloS one · 2015Article
- Article
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
Small GTPases are key regulators of cellular activity and represent novel targets for the treatment of human diseases using small-molecule inhibitors. The authors describe a multiplex, flow cytometry bead-based assay for the identification and characterization of inhibitors or activators of small GTPases. Six different glutathione-S-transferase (GST)-tagged small GTPases were bound to glutathione beads, each labeled with a different red fluorescence intensity. Subsequently, beads bearing different GTPase were mixed and dispensed into 384-well plates with test compounds, and fluorescent-guanosine triphosphate (GTP) binding was used as the readout. This novel multiplex assay allowed the authors to screen a library of almost 200,000 compounds and identify more than 1200 positive compounds, which were further verified by dose-response analyses, using 6- to 8-plex assays. After the elimination of false-positive and false-negative compounds, several small-molecule families with opposing effects on GTP binding activity were identified. The authors detail the characterization of MLS000532223, a general inhibitor that prevents GTP binding to several GTPases in a dose-dependent manner and is active in biochemical and cell-based secondary assays. Live-cell imaging and confocal microscopy studies revealed the inhibitor-induced actin reorganization and cell morphology changes, characteristic of Rho GTPases inhibition. Thus, high-throughput screening via flow cytometry provides a strategy for identifying novel compounds that are active against small GTPases.
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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.