Evidence map›Paper›PMID 20360736›Full record

ArticleNature2010

N-myristoyltransferase inhibitors as new leads to treat sleeping sickness.

Julie A Frearson, Stephen Brand, Stuart P McElroy, Laura A T Cleghorn, Ondrej Smid, Laste Stojanovski, Helen P Price, M Lucia S Guther, Leah S Torrie, David A Robinson and 16 more

Open access · greenAbstract read
In one paragraph

Article in Nature, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 172 papers.

0numbers the graph read from it
0cells of the map it votes in
172citing papers in PubMed
18.6field-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

172 citing papers in PubMed, 306 citations in OpenAlex.

  1. Article
  2. Research in pharmaceutical sciences · 2026
    Article
  3. Article
  4. ACS medicinal chemistry letters · 2026
    Article
  5. Review
  6. Molecules (Basel, Switzerland) · 2025
    Review
  7. Article
  8. Article
  9. Review
  10. Article
  11. Article
  12. Article
  13. Review
  14. Article
  15. Frontiers in pharmacology · 2025
    Article
  16. AdvancingFrontiers in molecular biosciences · 2025
    Article
  17. Article
  18. Ternary structure of Plasmodium vivaxN-myristoyltransferase with myristoyl-CoA and inhibitor IMP-0001173.Acta crystallographica. Section F, Structural biology communications · 2024
    Article
  19. Article
  20. Article

112 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

26 authors at 4 institutions in 2 countries.

Julie A FrearsonDrug Discovery Unit, Division of Biological Chemistry and Drug Discovery, University of Dundee, Dundee DD1 5EH, UK.
Stephen Brand
Stuart P McElroy
Laura A T Cleghorn
Ondrej Smid
Laste Stojanovski
Helen P Price
M Lucia S Guther
Leah S Torrie
David A Robinson
Irene Hallyburton
Chidochangu P Mpamhanga
James A Brannigan
Anthony J Wilkinson
Michael Hodgkinson
Raymond Hui
Wei Qiu
Olawale G Raimi
Daan M F van Aalten
Ruth Brenk
Ian H Gilbert
Kevin D Read
Alan H Fairlamb
Michael A J Ferguson
Deborah F Smith
Paul G Wyatt
Hull York Medical School · GBStructural Genomics Consortium · CAUniversity of Dundee · GBUniversity of York · GB

Funding

CIHR 1097737Medical Research Council G0900138Medical Research Council G0900138(90614)Wellcome Trust 077503Wellcome Trust 077705Wellcome Trust 085622Wellcome Trust 087590Wellcome Trust WT083481,
6 · The paper itself

Abstract

African sleeping sickness or human African trypanosomiasis, caused by Trypanosoma brucei spp., is responsible for approximately 30,000 deaths each year. Available treatments for this disease are poor, with unacceptable efficacy and safety profiles, particularly in the late stage of the disease when the parasite has infected the central nervous system. Here we report the validation of a molecular target and the discovery of associated lead compounds with the potential to address this lack of suitable treatments. Inhibition of this target-T. brucei N-myristoyltransferase-leads to rapid killing of trypanosomes both in vitro and in vivo and cures trypanosomiasis in mice. These high-affinity inhibitors bind into the peptide substrate pocket of the enzyme and inhibit protein N-myristoylation in trypanosomes. The compounds identified have promising pharmaceutical properties and represent an opportunity to develop oral drugs to treat this devastating disease. Our studies validate T. brucei N-myristoyltransferase as a promising therapeutic target for human African trypanosomiasis.

Indexed as

AcyltransferasesAminopyridinesAnimalsAntiparasitic AgentsBenzenesulfonamidesEnzyme AssaysEnzyme InhibitorsFemaleHumansMiceMolecular StructurePyrazolesRatsSulfonamidesTime FactorsTrypanosoma brucei bruceiAcyltransferasesAminopyridinesAntiparasitic AgentsBenzenesulfonamidesDDD 85646Enzyme Inhibitorsglycylpeptide N-tetradecanoyltransferasepyrazolePyrazolesSulfonamides

Identifiers

PMID20360736
PMCPMC2917743
OpenAlexW1971668778

What OpenQuestion holds

Textmetadata
LicenceTDM
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.