Evidence map›Paper›PMID 30602718›Full record

ArticleNature communications2019

Industrial scale high-throughput screening delivers multiple fast acting macrofilaricides.

Rachel H Clare, Catherine Bardelle, Paul Harper, W David Hong, Ulf Börjesson, Kelly L Johnston, Matthew Collier, Laura Myhill, Andrew Cassidy, Darren Plant and 21 more

Open access · goldAbstract readEvaluation Study
In one paragraph

Article in Nature communications, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
30citing papers in PubMed, 1 pooled it
10.8field-weighted citation impact, top 1% 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

30 citing papers in PubMed, 1 synthesis or guideline pooled it, 129 citations in OpenAlex.

  1. A Meta-Analysis ofG3 (Bethesda, Md.) · 2020
    Pooled it
  2. Article
  3. Article
  4. Article
  5. Autophagy is essential for anti-Frontiers in microbiology · 2026
    Article
  6. Article
  7. Article
  8. Dual RNA-seq in filarial nematodes andFrontiers in microbiology · 2024
    Article
  9. Combinations of the azaquinazoline anti-Frontiers in microbiology · 2024
    Article
  10. The cellular lives of Wolbachia.Nature reviews. Microbiology · 2023
    Review
  11. Article
  12. The Proteome and Lipidome of Extracellular Vesicles fromInternational journal of molecular sciences · 2023
    Article
  13. Article
  14. Article
  15. Article
  16. Review
  17. Thermal proteome profiling revealsFrontiers in pharmacology · 2022
    Article
  18. Current advances ofFrontiers in microbiology · 2022
    Review
  19. Review
  20. Development of Pyrazolopyrimidine Anti-ACS medicinal chemistry letters · 2021
    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

31 authors at 5 institutions in 3 countries.

Rachel H ClareCentre for Drugs and Diagnostics, Department of Parasitology, Liverpool School of Tropical Medicine, Pembroke Place, Liverpool, L3 5QA, UK.ORCID http://orcid.org/0000-0002-3945-0530
Catherine BardelleHit Discovery, Discovery Sciences, IMED Biotech Unit, AstraZeneca, Macclesfield, SK10 4TG, UK.
Paul HarperHit Discovery, Discovery Sciences, IMED Biotech Unit, AstraZeneca, Macclesfield, SK10 4TG, UK.
W David HongDepartment of Chemistry, University of Liverpool, Liverpool, L69 7ZD, UK.
Ulf BörjessonHit Discovery, Discovery Sciences, IMED Biotech Unit, AstraZeneca, Gothenburg, SE-431 83, Sweden.
Kelly L JohnstonCentre for Drugs and Diagnostics, Department of Parasitology, Liverpool School of Tropical Medicine, Pembroke Place, Liverpool, L3 5QA, UK.
Matthew CollierHit Discovery, Discovery Sciences, IMED Biotech Unit, AstraZeneca, Macclesfield, SK10 4TG, UK.
Laura MyhillCentre for Drugs and Diagnostics, Department of Parasitology, Liverpool School of Tropical Medicine, Pembroke Place, Liverpool, L3 5QA, UK.
Andrew CassidyCentre for Drugs and Diagnostics, Department of Parasitology, Liverpool School of Tropical Medicine, Pembroke Place, Liverpool, L3 5QA, UK.
Darren PlantHit Discovery, Discovery Sciences, IMED Biotech Unit, AstraZeneca, Macclesfield, SK10 4TG, UK.
Helen PlantHit Discovery, Discovery Sciences, IMED Biotech Unit, AstraZeneca, Macclesfield, SK10 4TG, UK.
Roger ClarkHit Discovery, Discovery Sciences, IMED Biotech Unit, AstraZeneca, Macclesfield, SK10 4TG, UK.
Darren A N CookCentre for Drugs and Diagnostics, Department of Parasitology, Liverpool School of Tropical Medicine, Pembroke Place, Liverpool, L3 5QA, UK.
Andrew StevenCentre for Drugs and Diagnostics, Department of Parasitology, Liverpool School of Tropical Medicine, Pembroke Place, Liverpool, L3 5QA, UK.
John ArcherCentre for Drugs and Diagnostics, Department of Parasitology, Liverpool School of Tropical Medicine, Pembroke Place, Liverpool, L3 5QA, UK.
Paul McGillanDepartment of Chemistry, University of Liverpool, Liverpool, L69 7ZD, UK.ORCID http://orcid.org/0000-0001-6361-1536
Sitthivut CharoensutthivarakulCentre for Drugs and Diagnostics, Department of Parasitology, Liverpool School of Tropical Medicine, Pembroke Place, Liverpool, L3 5QA, UK.ORCID http://orcid.org/0000-0002-4447-3438
Jaclyn BibbyDepartment of Chemistry, University of Liverpool, Liverpool, L69 7ZD, UK.
Raman SharmaCentre for Drugs and Diagnostics, Department of Parasitology, Liverpool School of Tropical Medicine, Pembroke Place, Liverpool, L3 5QA, UK.
Gemma L NixonDepartment of Chemistry, University of Liverpool, Liverpool, L69 7ZD, UK.
Barton E SlatkoGenome Biology Division, New England Biolabs, Inc, Ipswich, 01938, MA, USA.
Lindsey CantinGenome Biology Division, New England Biolabs, Inc, Ipswich, 01938, MA, USA.
Bo WuGenome Biology Division, New England Biolabs, Inc, Ipswich, 01938, MA, USA.
Joseph TurnerCentre for Drugs and Diagnostics, Department of Parasitology, Liverpool School of Tropical Medicine, Pembroke Place, Liverpool, L3 5QA, UK.ORCID http://orcid.org/0000-0002-2185-5476
Louise FordCentre for Drugs and Diagnostics, Department of Parasitology, Liverpool School of Tropical Medicine, Pembroke Place, Liverpool, L3 5QA, UK.ORCID http://orcid.org/0000-0001-7919-2866
Kirsty RichHit Discovery, Discovery Sciences, IMED Biotech Unit, AstraZeneca, Macclesfield, SK10 4TG, UK.
Mark WigglesworthHit Discovery, Discovery Sciences, IMED Biotech Unit, AstraZeneca, Macclesfield, SK10 4TG, UK.
Neil G BerryDepartment of Chemistry, University of Liverpool, Liverpool, L69 7ZD, UK.ORCID http://orcid.org/0000-0003-1928-0738
Paul M O'NeillDepartment of Chemistry, University of Liverpool, Liverpool, L69 7ZD, UK. P.M.Oneill01@liverpool.ac.uk.
Mark J TaylorCentre for Drugs and Diagnostics, Department of Parasitology, Liverpool School of Tropical Medicine, Pembroke Place, Liverpool, L3 5QA, UK.
Stephen A WardCentre for Drugs and Diagnostics, Department of Parasitology, Liverpool School of Tropical Medicine, Pembroke Place, Liverpool, L3 5QA, UK. Steve.Ward@lstmed.ac.uk.
Liverpool School of Tropical Medicine · GBAstraZeneca (United Kingdom) · GBUniversity of Liverpool · GBNew England Biolabs (United States) · USAstraZeneca (Sweden) · SE

Funding

Medical Research Council MC_PC_17167Medical Research Council MR/R025401/1
6 · The paper itself

Abstract

Nematodes causing lymphatic filariasis and onchocerciasis rely on their bacterial endosymbiont, Wolbachia, for survival and fecundity, making Wolbachia a promising therapeutic target. Here we perform a high-throughput screen of AstraZeneca's 1.3 million in-house compound library and identify 5 novel chemotypes with faster in vitro kill rates (<2 days) than existing anti-Wolbachia drugs that cure onchocerciasis and lymphatic filariasis. This industrial scale anthelmintic neglected tropical disease (NTD) screening campaign is the result of a partnership between the Anti-Wolbachia consortium (A∙WOL) and AstraZeneca. The campaign was informed throughout by rational prioritisation and triage of compounds using cheminformatics to balance chemical diversity and drug like properties reducing the chance of attrition from the outset. Ongoing development of these multiple chemotypes, all with superior time-kill kinetics than registered antibiotics with anti-Wolbachia activity, has the potential to improve upon the current therapeutic options and deliver improved, safer and more selective macrofilaricidal drugs.

Indexed as

Drug DiscoveryHigh-Throughput Screening AssaysAedesAnimalsCell LineFilaricidesWolbachiaFilaricides

Identifiers

PMID30602718
PMCPMC6315057
OpenAlexW2907834307

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.