Evidence map›Paper›PMID 38486232›Full record

ArticleParasites & vectors2024

A phenotypic screen of the Global Health Priority Box identifies an insecticide with anthelmintic activity.

Harrison T Shanley, Aya C Taki, Joseph J Byrne, Nghi Nguyen, Tim N C Wells, Abdul Jabbar, Brad E Sleebs, Robin B Gasser

Open access · goldAbstract read
In one paragraph

Article in Parasites & vectors, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing papers in PubMed
6.4field-weighted citation impact, top 3% of its field
1 · What the graph read from it

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.

2 · The registry

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.

3 · Its place in the literature

Who cites it

5 citing papers in PubMed, 10 citations in OpenAlex.

  1. Article
  2. Article
  3. Evaluation of Serum Supplementation on the Development ofInternational journal of molecular sciences · 2025
    Article
  4. Review
  5. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

8 authors at 3 institutions in 2 countries.

Harrison T ShanleyDepartment of Veterinary Biosciences, Melbourne Veterinary School, Faculty of Science, The University of Melbourne, Parkville, VIC, 3010, Australia.
Aya C TakiDepartment of Veterinary Biosciences, Melbourne Veterinary School, Faculty of Science, The University of Melbourne, Parkville, VIC, 3010, Australia.
Joseph J ByrneDepartment of Veterinary Biosciences, Melbourne Veterinary School, Faculty of Science, The University of Melbourne, Parkville, VIC, 3010, Australia.
Nghi NguyenWalter and Eliza Hall Institute of Medical Research, Parkville, VIC, 3052, Australia.
Tim N C WellsMedicines for Malaria Venture (MMV), 1215, Geneva, Switzerland.
Abdul JabbarDepartment of Veterinary Biosciences, Melbourne Veterinary School, Faculty of Science, The University of Melbourne, Parkville, VIC, 3010, Australia.
Brad E SleebsDepartment of Veterinary Biosciences, Melbourne Veterinary School, Faculty of Science, The University of Melbourne, Parkville, VIC, 3010, Australia. sleebs@wehi.edu.au.
Robin B GasserDepartment of Veterinary Biosciences, Melbourne Veterinary School, Faculty of Science, The University of Melbourne, Parkville, VIC, 3010, Australia. robinbg@unimelb.edu.au.
University of Melbourne · AUWalter and Eliza Hall Institute of Medical Research · AUMedicines for Malaria Venture · CH

Funding

Australian Research Council LP220200614
6 · The paper itself

Abstract

backgroundInfection with parasitic nematodes (helminths), particularly those of the order Strongylida (such as Haemonchus contortus), can cause significant and burdensome diseases in humans and animals. Widespread drug (anthelmintic) resistance in livestock parasites, the absence of vaccines against most of these nematodes, and a lack of new and effective chemical entities on the commercial market demands the discovery of new anthelmintics. In the present study, we searched the Global Health Priority Box (Medicines for Malaria Venture) for new candidates for anthelmintic development.

methodsWe employed a whole-organism, motility-based phenotypic screening assay to identify compounds from the Global Health Priority Box with activity against larvae of the model parasite H. contortus, and the free-living comparator nematode Caenorhabditis elegans. Hit compounds were further validated via dose-response assays, with lead candidates then assessed for nematocidal activity against H. contortus adult worms, and additionally, for cytotoxic and mitotoxic effects on human hepatoma (HepG2) cells.

resultsThe primary screen against H. contortus and C. elegans revealed or reidentified 16 hit compounds; further validation established MMV1794206, otherwise known as 'flufenerim', as a significant inhibitor of H. contortus larval motility (half-maximal inhibitory concentration [IC

conclusionsThe in vitro efficacy of MMV1794206 against the most pathogenic stages of H. contortus, as well as the free-living C. elegans, suggests the potential for development as a broad-spectrum anthelmintic compound; however, the high toxicity towards mammalian cells presents a significant hindrance. Further work should seek to establish the protein-drug interactions of MMV1794206 in a nematode model, to unravel the mechanism of action, in addition to an advanced structure-activity relationship investigation to optimise anthelmintic activity and eliminate mammalian cell toxicity.

Indexed as

AnthelminticsAnti-Infective AgentsCarcinoma, HepatocellularInsecticidesLiver NeoplasmsAdultAnimalsCaenorhabditis elegansFemaleHealth PrioritiesHumansMammalsAnthelminticsAnti-Infective AgentsInsecticidesAnthelminticsAntiparasiticsCaenorhabditis elegansDrug discoveryFlufenerimGlobal Health Priority BoxHaemonchus contortusNematodesPhenotypic screening

Identifiers

PMID38486232
PMCPMC10938758
OpenAlexW4392806725

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

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.