ArticleNature medicine2012
A high-throughput drug screen for Entamoeba histolytica identifies a new lead and target.
Article in Nature medicine, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 165 papers.
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Who cites it
165 citing papers in PubMed, 304 citations in OpenAlex.
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- Repurposing Auranofin for Oncology and Beyond: A Brief Overview of Clinical Trials as Mono- and Combination Therapy.Pharmaceuticals (Basel, Switzerland) · 2025Review
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- Ligand supplementation restores the cancer therapy efficacy of the antirheumatic drug auranofin from serum inactivation.Nature communications · 2025Article
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- Beyond gold: the chemoenhancing mechanism and therapeutic potential of auranofin in melanoma.Cancer biology & medicine · 2025Article
- Functional utility of gold complexes with phosphorus donor ligands in biological systems.Coordination chemistry reviews · 2025Article
- The "Doorstop Pocket" In Thioredoxin Reductases─An Unexpected Druggable Regulator of the Catalytic Machinery.Journal of medicinal chemistry · 2024Review
- Identification and characterization of archaeal-type FAD synthase as a novel tractable drug target from the parasitic protozoamSphere · 2024Article
- Introducing the NUATEI Consortium: A Mexican Research Program for the Identification of Natural and Synthetic Antimicrobial Compounds for Prevalent Infectious Diseases.Pharmaceuticals (Basel, Switzerland) · 2024Article
- Gold(I) ion and the phosphine ligand are necessary for the anti-Microbiology spectrum · 2024Article
- Antigiardial and antiamebic activities of fexinidazole and its metabolites: new drug leads for giardiasis and amebiasis.Antimicrobial agents and chemotherapy · 2024Article
- Miconazole-like Scaffold is a Promising Lead forJournal of medicinal chemistry · 2023Article
- Riluzole, a Derivative of Benzothiazole as a Potential Anti-Amoebic Agent againstPharmaceuticals (Basel, Switzerland) · 2023Article
- Structure ofInternational journal of molecular sciences · 2023Article
- Review
105 more citing papers are in PubMed but not listed here.
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Authors and funding
16 authors at 5 institutions in 2 countries.
Funding
Abstract
Entamoeba histolytica, a protozoan intestinal parasite, is the causative agent of human amebiasis. Amebiasis is the fourth leading cause of death and the third leading cause of morbidity due to protozoan infections worldwide(1), resulting in ~70,000 deaths annually. E. histolytica has been listed by the National Institutes of Health as a category B priority biodefense pathogen in the United States. Treatment relies on metronidazole(2), which has adverse effects(3), and potential resistance of E. histolytica to the drug is an increasing concern(4,5). To facilitate drug screening for this anaerobic protozoan, we developed and validated an automated, high-throughput screen (HTS). This screen identified auranofin, a US Food and Drug Administration (FDA)-approved drug used therapeutically for rheumatoid arthritis, as active against E. histolytica in culture. Auranofin was ten times more potent against E. histolytica than metronidazole. Transcriptional profiling and thioredoxin reductase assays suggested that auranofin targets the E. histolytica thioredoxin reductase, preventing the reduction of thioredoxin and enhancing sensitivity of trophozoites to reactive oxygen-mediated killing. In a mouse model of amebic colitis and a hamster model of amebic liver abscess, oral auranofin markedly decreased the number of parasites, the detrimental host inflammatory response and hepatic damage. This new use of auranofin represents a promising therapy for amebiasis, and the drug has been granted orphan-drug status from the FDA.
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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.