Evidence map›Paper›PMID 33479319›Full record

ArticleScientific reports2021

The antimalarial efficacy and mechanism of resistance of the novel chemotype DDD01034957.

Celia Miguel-Blanco, James M Murithi, Ernest Diez Benavente, Fiona Angrisano, Katarzyna A Sala, Donelly A van Schalkwyk, Manu Vanaerschot, Frank Schwach, Matthew J Fuchter, Oliver Billker and 9 more

Abstract read
In one paragraph

Article in Scientific reports, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
–field-weighted citation impact
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

2 citing papers in PubMed.

  1. Review
  2. 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

19 authors.

Celia Miguel-BlancoGlobal Health, GlaxoSmithKline, Tres Cantos, 28760, Madrid, Spain.
James M MurithiDepartment of Microbiology and Immunology, Columbia University Irving Medical Center, New York, NY, 10032, USA.
Ernest Diez BenaventeDepartment of Infection Biology, Faculty of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London, WC1E 7HT, UK.
Fiona AngrisanoDivision of Microbiology and Parasitology, Department of Pathology, Cambridge University, Tennis Court Road, Cambridge, CB2 1QP, UK.
Katarzyna A SalaDepartment of Life Sciences, Imperial College London, South Kensington, London, SW7 2AZ, UK.
Donelly A van SchalkwykDepartment of Infection Biology, Faculty of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London, WC1E 7HT, UK.
Manu VanaerschotDepartment of Microbiology and Immunology, Columbia University Irving Medical Center, New York, NY, 10032, USA.
Frank SchwachParasites and Microbes Programme, Wellcome Trust Sanger Institute, Hinxton, CB10 1SA, UK.
Matthew J FuchterDepartment of Chemistry, Molecular Sciences Research Hub, Imperial College London, White City Campus, Wood Lane, London, W12 OBZ, UK.
Oliver BillkerParasites and Microbes Programme, Wellcome Trust Sanger Institute, Hinxton, CB10 1SA, UK.
Colin J SutherlandDepartment of Infection Biology, Faculty of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London, WC1E 7HT, UK.
Susana G CampinoDepartment of Infection Biology, Faculty of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London, WC1E 7HT, UK.
Taane G ClarkDepartment of Infection Biology, Faculty of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London, WC1E 7HT, UK.
Andrew M BlagboroughDivision of Microbiology and Parasitology, Department of Pathology, Cambridge University, Tennis Court Road, Cambridge, CB2 1QP, UK.
David A FidockDepartment of Microbiology and Immunology, Columbia University Irving Medical Center, New York, NY, 10032, USA.
Esperanza HerrerosGlobal Health, GlaxoSmithKline, Tres Cantos, 28760, Madrid, Spain.
Francisco Javier GamoGlobal Health, GlaxoSmithKline, Tres Cantos, 28760, Madrid, Spain.
Jake BaumDepartment of Life Sciences, Imperial College London, South Kensington, London, SW7 2AZ, UK.
Michael J DelvesDepartment of Infection Biology, Faculty of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London, WC1E 7HT, UK. michael.delves@lshtm.ac.uk.

Funding

Biotechnology and Biological Sciences Research Council BB/R013063/1Medical Research Council MR/M01360X/1Medical Research Council MR/N00227X/1Medical Research Council MR/N010469/1Medical Research Council MR/R020973/1Medical Research Council MR/R025576/1Medical Research Council MR/T016124/1Wellcome TrustWellcome Trust 100993/Z/13/ZWellcome Trust 206194/Z/17/Z
6 · The paper itself

Abstract

New antimalarial therapeutics are needed to ensure that malaria cases continue to be driven down, as both emerging parasite resistance to frontline chemotherapies and mosquito resistance to current insecticides threaten control programmes. Plasmodium, the apicomplexan parasite responsible for malaria, causes disease pathology through repeated cycles of invasion and replication within host erythrocytes (the asexual cycle). Antimalarial drugs primarily target this cycle, seeking to reduce parasite burden within the host as fast as possible and to supress recrudescence for as long as possible. Intense phenotypic drug screening efforts have identified a number of promising new antimalarial molecules. Particularly important is the identification of compounds with new modes of action within the parasite to combat existing drug resistance and suitable for formulation of efficacious combination therapies. Here we detail the antimalarial properties of DDD01034957-a novel antimalarial molecule which is fast-acting and potent against drug resistant strains in vitro, shows activity in vivo, and possesses a resistance mechanism linked to the membrane transporter PfABCI3. These data support further medicinal chemistry lead-optimization of DDD01034957 as a novel antimalarial chemical class and provide new insights to further reduce in vivo metabolic clearance.

Indexed as

AnimalsAntimalarialsDrug ResistanceErythrocytesHost-Parasite InteractionsHumansInhibitory Concentration 50MalariaMiceMolecular StructurePlasmodiumPlasmodium bergheiPlasmodium falciparumSpecies SpecificityAntimalarials

Identifiers

PMID33479319
PMCPMC7820608

What OpenQuestion holds

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Registered trials

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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.