ArticleThe Journal of biological chemistry2012
Characterization of EHop-016, novel small molecule inhibitor of Rac GTPase.
Article in The Journal of biological chemistry, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 147 papers.
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Who cites it
147 citing papers in PubMed, 250 citations in OpenAlex.
- Clinical utility of PDX cohorts to reveal biomarkers of intrinsic resistance and clonal architecture changes underlying acquired resistance to cetuximab in HNSCC.Signal transduction and targeted therapy · 2022Trial
- 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
- Disulfidptosis-based cancer therapy: Opportunity and challenge.Genes & diseases · 2027Review
- Vav2 is a master regulator of repair against bacterial pore-forming toxins.Life science alliance · 2026Article
- A RAC1 SUMOylation switch governs breast cancer metastasis.Signal transduction and targeted therapy · 2026Article
- Rac1 GTPase Regulates the SCFCancers · 2026Article
- Cryo-EM structures of heteromeric Kir4.1/5.1 channel suggest mechanisms of inward rectification and channel blockage.Nature communications · 2026Article
- Rho GTPases in cancer resistance: mechanisms, vulnerabilities, and therapeutic opportunities.Biochemical Society transactions · 2026Review
- Stalling the Enemy: Targeting Nsp13 for Next-Generation SARS-CoV-2 Antivirals.International journal of molecular sciences · 2026Article
- Discovery of a Novel and Potent Kir4.1 Inhibitor as a Safe and Rapid-Onset Antidepressant Agent in Mice.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Rac/Cdc42 inhibitors target pancreatic cancer cells and macrophages in the tumor microenvironment.Cancer treatment and research communications · 2026Article
- The Role of Actin-Binding Proteins in Breast Cancer Progression.Breast cancer (Dove Medical Press) · 2026Review
- Rac1 in gastric cancer: a molecular driver of invasion, EMT, and therapeutic resistance.Journal of translational medicine · 2025Review
- The Cytoskeleton in Adrenal Physiology and Tumours: Functional Roles and Emerging Molecular Targets.International journal of molecular sciences · 2025Review
- A Rac-specific competitive inhibitor of guanine nucleotide binding reduces metastasis in triple-negative breast cancer.Cell reports. Medicine · 2025Article
- Structural Dynamics of Rho GTPases.Journal of molecular biology · 2025Review
- Article
- RAC1 signaling in prostate cancer: VAV GEFs take center stage.Frontiers in cell and developmental biology · 2025Article
- Screening of potential ligands from the ZINC database with RAC1B using molecular docking and dynamics simulation analysis.Bioinformation · 2025Article
- The role of RAC1 in resistance to targeted therapies in cancer.Small GTPases · 2024Review
87 more citing papers are in PubMed but not listed here.
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
Abstract
The Rho GTPase Rac regulates actin cytoskeleton reorganization to form cell surface extensions (lamellipodia) required for cell migration/invasion during cancer metastasis. Rac hyperactivation and overexpression are associated with aggressive cancers; thus, interference of the interaction of Rac with its direct upstream activators, guanine nucleotide exchange factors (GEFs), is a viable strategy for inhibiting Rac activity. We synthesized EHop-016, a novel inhibitor of Rac activity, based on the structure of the established Rac/Rac GEF inhibitor NSC23766. Herein, we demonstrate that EHop-016 inhibits Rac activity in the MDA-MB-435 metastatic cancer cells that overexpress Rac and exhibits high endogenous Rac activity. The IC(50) of 1.1 μM for Rac inhibition by EHop-016 is ∼100-fold lower than for NSC23766. EHop-016 is specific for Rac1 and Rac3 at concentrations of ≤5 μM. At higher concentrations, EHop-016 inhibits the close homolog Cdc42. In MDA-MB-435 cells that demonstrate high active levels of the Rac GEF Vav2, EHop-016 inhibits the association of Vav2 with a nucleotide-free Rac1(G15A), which has a high affinity for activated GEFs. EHop-016 also inhibits the Rac activity of MDA-MB-231 metastatic breast cancer cells and reduces Rac-directed lamellipodia formation in both cell lines. EHop-016 decreases Rac downstream effects of PAK1 (p21-activated kinase 1) activity and directed migration of metastatic cancer cells. Moreover, at effective concentrations (<5 μM), EHop-016 does not affect the viability of transformed mammary epithelial cells (MCF-10A) and reduces viability of MDA-MB-435 cells by only 20%. Therefore, EHop-016 holds promise as a targeted therapeutic agent for the treatment of metastatic cancers with high Rac activity.
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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.