Evidence map›Paper›PMID 37002199›Full record

ArticleNature communications2023

Nemacol is a small molecule inhibitor of C. elegans vesicular acetylcholine transporter with anthelmintic potential.

Sean Harrington, Jacob Pyche, Andrew R Burns, Tina Spalholz, Kaetlyn T Ryan, Rachel J Baker, Justin Ching, Lucien Rufener, Mark Lautens, Daniel Kulke and 5 more

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Nature communications, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed
1.1field-weighted citation impact, top 20% 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

4 citing papers in PubMed, 12 citations in OpenAlex.

  1. Review
  2. Advances in Anthelmintic Target Identification.International journal of molecular sciences · 2025
    Review
  3. Article
  4. 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

15 authors at 4 institutions in 4 countries.

Sean Harrington *Department of Pharmacology and Toxicology, University of Toronto, Toronto, ON, M5S 1A8, Canada.
Jacob Pyche *Department of Pharmacology and Toxicology, University of Toronto, Toronto, ON, M5S 1A8, Canada.
Andrew R BurnsThe Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, Toronto, ON, M5S 3E1, Canada.ORCID 0000-0002-8966-1280
Tina SpalholzDepartment of Neuroradiopharmaceuticals, Institute of Radiopharmaceutical Cancer Research, Helmholtz-Zentrum Dresden-Rossendorf, 04318, Leipzig, Germany.
Kaetlyn T RyanDepartment of Pathobiological Sciences, University of Wisconsin-Madison, Madison, WI, USA.ORCID 0000-0002-2051-7969
Rachel J BakerThe Department of Chemistry, University of Toronto, 80 St. George Street, Toronto, ON, M5S 3H6, Canada.ORCID 0000-0001-5514-8887
Justin ChingThe Department of Chemistry, University of Toronto, 80 St. George Street, Toronto, ON, M5S 3H6, Canada.ORCID 0000-0002-2511-216X
Lucien RufenerINVENesis Sàrl, Route de Neuchâtel 15A, 2072, St Blaise (NE), Switzerland.
Mark LautensThe Department of Chemistry, University of Toronto, 80 St. George Street, Toronto, ON, M5S 3H6, Canada.ORCID 0000-0002-0179-2914
Daniel KulkeResearch Parasiticides, Bayer Animal Health GmbH, Monheim, Germany.
Alexandre VernudachiINVENesis France Sàrl, 147 Avenue André Maginot, Tours, 37100, France.
Mostafa ZamanianDepartment of Pathobiological Sciences, University of Wisconsin-Madison, Madison, WI, USA.ORCID 0000-0001-9233-1760
Winnie Deuther-ConradDepartment of Neuroradiopharmaceuticals, Institute of Radiopharmaceutical Cancer Research, Helmholtz-Zentrum Dresden-Rossendorf, 04318, Leipzig, Germany.ORCID 0000-0003-3168-3062
Peter BrustDepartment of Neuroradiopharmaceuticals, Institute of Radiopharmaceutical Cancer Research, Helmholtz-Zentrum Dresden-Rossendorf, 04318, Leipzig, Germany.ORCID 0000-0001-5555-7058
Peter J RoyDepartment of Pharmacology and Toxicology, University of Toronto, Toronto, ON, M5S 1A8, Canada. peter.roy@utoronto.ca.ORCID 0000-0003-2959-2276
University of Toronto · CAHelmholtz-Zentrum Dresden-Rossendorf · DEUniversity of Wisconsin–Madison · USIowa State University · US

Funding

Molecular mechanisms controlling secretion in filarial nematode parasitesR01AI151171 · NIAID · UNIVERSITY OF WISCONSIN-MADISON · PI Mostafa Zamanian · 2020 to 2026
$2.4M
NIAID NIH HHS R01 AI151171
6 · The paper itself

Abstract

Nematode parasites of humans and livestock pose a significant burden to human health, economic development, and food security. Anthelmintic drug resistance is widespread among parasites of livestock and many nematode parasites of humans lack effective treatments. Here, we present a nitrophenyl-piperazine scaffold that induces motor defects rapidly in the model nematode Caenorhabditis elegans. We call this scaffold Nemacol and show that it inhibits the vesicular acetylcholine transporter (VAChT), a target recognized by commercial animal and crop health groups as a viable anthelmintic target. We demonstrate that it is possible to create Nemacol analogs that maintain potent in vivo activity whilst lowering their affinity to the mammalian VAChT 10-fold. We also show that Nemacol enhances the ability of the anthelmintic Ivermectin to paralyze C. elegans and the ruminant nematode parasite Haemonchus contortus. Hence, Nemacol represents a promising new anthelmintic scaffold that acts through a validated anthelmintic target.

Indexed as

AnthelminticsNematodaAnimalsCaenorhabditis elegansDrug ResistanceHumansIvermectinMammalsVesicular Acetylcholine Transport ProteinsAnthelminticsIvermectinVesicular Acetylcholine Transport Proteins

Identifiers

PMID37002199
PMCPMC10066365
OpenAlexW4362475371

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.