Evidence map›Paper›PMID 27147113›Full record

ArticleScientific reports2016

PfCRT and PfMDR1 modulate interactions of artemisinin derivatives and ion channel blockers.

Richard T Eastman, Pwint Khine, Ruili Huang, Craig J Thomas, Xin-Zhuan Su

Abstract read
In one paragraph

Article in Scientific reports, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.

0numbers the graph read from it
0cells of the map it votes in
11citing 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

11 citing papers in PubMed.

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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

5 authors.

Richard T EastmanLaboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA.
Pwint KhineLaboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA.
Ruili HuangDivision of Preclinical Development, National Center for Advancing Translational Sciences, National Institutes of Health, Bethesda, Maryland, USA.
Craig J ThomasDivision of Preclinical Development, National Center for Advancing Translational Sciences, National Institutes of Health, Bethesda, Maryland, USA.
Xin-Zhuan SuLaboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA.

Funding

Malaria Parasite Sexual Development, Drug Resistance, and EvolutionZIAAI000892 · NIAID · NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES · PI SU, XINZHUAN · 2009 to 2025
$23.3M
Development of novel antimalarial targets and combination therapies to address drug resistanceZIATR000245 · NCATS · NATIONAL CENTER FOR ADVANCING TRANSLATIONAL SCIENCES · PI THOMAS, CRAIG · 2016 to 2020
$1.3M
6 · The paper itself

Abstract

Treatment of the symptomatic asexual stage of Plasmodium falciparum relies almost exclusively on artemisinin (ART) combination therapies (ACTs) in endemic regions. ACTs combine ART or its derivative with a long-acting partner drug to maximize efficacy during the typical three-day regimen. Both laboratory and clinical studies have previously demonstrated that the common drug resistance determinants P. falciparum chloroquine resistance transporter (PfCRT) and multidrug resistance transporter (PfMDR1) can modulate the susceptibility to many current antimalarial drugs and chemical compounds. Here we investigated the parasite responses to dihydroartemisinin (DHA) and various Ca(2+) and Na(+) channel blockers and showed positively correlated responses between DHA and several channel blockers, suggesting potential shared transport pathways or mode of action. Additionally, we demonstrated that PfCRT and PfMDR1 could also significantly modulate the pharmacodynamic interactions of the compounds and that the interactions were influenced by the parasite genetic backgrounds. These results provide important information for better understanding of drug resistance and for assessing the overall impact of drug resistance markers on parasite response to ACTs.

Indexed as

AntimalarialsArtemisininsATP-Binding Cassette, Sub-Family C ProteinsCalcium Channel BlockersChloroquineDrug ResistanceDrug Therapy, CombinationGene Expression RegulationGenotypeLidocaineMembrane Transport ProteinsParasitic Sensitivity TestsPlasmodium falciparumProtozoan ProteinsSodium Channel BlockersAntimalarialsArtemisininsartenimolATP-Binding Cassette, Sub-Family C ProteinsCalcium Channel BlockersChloroquineLidocaineMdr1 protein, Plasmodium falciparumMembrane Transport ProteinsPfCRT protein, Plasmodium falciparumProtozoan ProteinsSodium Channel Blockers

Identifiers

PMID27147113
PMCPMC4857081

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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.