ArticleAntimicrobial agents and chemotherapy2022
Ponatinib, Lestaurtinib, and mTOR/PI3K Inhibitors Are Promising Repurposing Candidates against Entamoeba histolytica.
Article in Antimicrobial agents and chemotherapy, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.
What it found
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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.
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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.
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Who cites it
6 citing papers in PubMed, 16 citations in OpenAlex.
- PI3K/AKT signaling in parasites and parasite diseases: Role and therapeutic potential.Virulence · 2025Review
- Repurposing of a library for high-content screening of inhibitors against Echinococcus granulosus.Parasites & vectors · 2024Article
- Pathogenicity and virulence ofVirulence · 2023Review
- Essential Oils and Terpenic Compounds as Potential Hits for Drugs against Amitochondriate Protists.Tropical medicine and infectious disease · 2023Review
- Alcohol Abuse Drug Disulfiram Is Effective against Cyst Stages of Entamoeba histolytica Parasite.Antimicrobial agents and chemotherapy · 2022Article
- Repurposing the Kinase Inhibitor Mavelertinib for Giardiasis Therapy.Antimicrobial agents and chemotherapy · 2022Article
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
Dysentery caused by Entamoeba histolytica affects millions of people annually. Current treatment regimens are based on metronidazole to treat invasive parasites combined with paromomycin for luminal parasites. Issues with treatment include significant side effects, inability to easily treat breastfeeding and pregnant women, the use of two sequential agents, and concern that all therapy is based on nitroimidazole agents, with no alternatives if clinical resistance emerges. Thus, the need for new drugs against amebiasis is urgent. To identify new therapeutic candidates, we screened 11,948 compounds assembled for the ReFRAME (Repurposing, Focused Rescue, and Accelerated Medchem) library against E. histolytica trophozoites. We identified 159 hits in the primary screen at 10 μM, and 46 compounds were confirmed in secondary assays. Overall, 26 were selected as priority molecules for further investigation, including 6 FDA approved, 5 orphan designations, and 15 that are currently in clinical trials (3 phase III, 7 phase II, and 5 phase I). We found that all 26 compounds are active against metronidazole-resistant E. histolytica, and 24 are able to block parasite recrudescence after drug removal. Additionally, 14 are able to inhibit encystation and 2 (lestaurtinib and LY-2874455) are active against mature cysts. Two classes of compounds are most interesting for further investigations: (i) the Bcr-Abl tyrosine kinase (TK) inhibitors, with ponatinib (50% effective concentration [EC
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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 Socratic graph.