Research graph
References from The plasmepsin-piperaquine paradox persists in Plasmodium falciparum. Local targets link to admitted publications; unresolved targets remain external evidence.
Unresolved reference
External reference
Determinants of dihydroartemisinin-piperaquine treatment failure in Plasmodium falciparum malaria in Cambodia, Thailand, and Vietnam: a prospective clinical, pharmacological, and genetic study
2019 · External reference
Efficacy of dihydroartemisinin-piperaquine for treatment of uncomplicated Plasmodium falciparum and Plasmodium vivax in Cambodia, 2008 to 2010
10.1128/aac.00686-12 · 2013 · External reference
Evidence of Plasmodium falciparum malaria multidrug resistance to artemisinin and piperaquine in Western Cambodia: Dihydroartemisinin-piperaquine open-label multicenter clinical assessment
10.1128/aac.00835-15 · 2015 · External reference
Plasmodium falciparum dihydroartemisinin-piperaquine failures in Cambodia are associated with mutant K13 parasites presenting high survival rates in novel piperaquine in vitro assays: retrospective and prospective investigations
10.1186/s12916-015-0539-5 · 2015 · External reference
Dihydroartemisinin-piperaquine failure associated with a triple mutant including kelch13 C580Y in Cambodia: an observational cohort study
10.1016/s1473-3099(15)70049-6 · 2015 · External reference
Ex vivo piperaquine resistance developed rapidly in Plasmodium falciparum isolates in northern Cambodia compared to Thailand
10.1186/s12936-016-1569-y · 2016 · External reference
Unresolved reference
External reference
Spread of artemisinin resistance in Plasmodium falciparum malaria
10.1056/nejmoa1314981 · 2014 · External reference
A molecular marker of artemisinin-resistant Plasmodium falciparum malaria
10.1038/nature12876 · 2014 · External reference
Drug resistance. K13-propeller mutations confer artemisinin resistance in Plasmodium falciparum clinical isolates
10.1126/science.1260867 · 2015 · External reference
10.1093/molbev/msw228
10.1093/molbev/msw228 · External reference
Independent emergence of artemisinin resistance mutations among Plasmodium falciparum in Southeast Asia
10.1093/infdis/jiu491 · 2015 · External reference
Role of Plasmodium falciparum kelch 13 protein mutations in P. falciparum populations from northeastern Myanmar in mediating artemisinin resistance
10.1128/mbio.01134-19 · 2020 · External reference
A surrogate marker of piperaquine-resistant Plasmodium falciparum malaria: a phenotype-genotype association study
10.1016/s1473-3099(16)30415-7 · 2017 · External reference
Genetic markers associated with dihydroartemisinin-piperaquine failure in Plasmodium falciparum malaria in Cambodia: a genotype-phenotype association study
10.1016/s1473-3099(16)30409-1 · 2017 · External reference
Inactivation of Plasmepsins 2 and 3 sensitizes Plasmodium falciparum to the antimalarial drug piperaquine
10.1128/aac.02309-17 · 2018 · External reference
Overexpression of plasmepsin II and plasmepsin III does not directly cause reduction in Plasmodium falciparum sensitivity to artesunate, chloroquine and piperaquine
10.1016/j.ijpddr.2018.11.004 · 2019 · External reference
Association of a novel mutation in the Plasmodium falciparum chloroquine resistance transporter with decreased piperaquine sensitivity
10.1093/infdis/jix334 · 2017 · External reference
Emerging Southeast Asian PfCRT mutations confer Plasmodium falciparum resistance to the first-line antimalarial piperaquine
10.1038/s41467-018-05652-0 · 2018 · External reference
A variant PfCRT isoform can contribute to Plasmodium falciparum resistance to the first-line partner drug piperaquine
10.1128/mbio.00303-17 · 2017 · External reference
Piperaquine-resistant PfCRT mutations differentially impact drug transport, hemoglobin catabolism and parasite physiology in Plasmodium falciparum asexual blood stages
10.1371/journal.ppat.1010926 · 2022 · External reference
Mutant PfCRT can mediate piperaquine resistance in African Plasmodium falciparum with reduced fitness and increased susceptibility to other antimalarials
10.1093/infdis/jiac365 · 2022 · External reference
Impact of piperaquine resistance in Plasmodium falciparum on malaria treatment effectiveness in The Guianas: a descriptive epidemiological study
10.1016/s1473-3099(23)00502-9 · 2024 · External reference
Evolution and expansion of multidrug-resistant malaria in southeast Asia: a genomic epidemiology study
10.1016/s1473-3099(19)30392-5 · 2019 · External reference
Dihydroartemisinin-piperaquine resistance in Plasmodium falciparum malaria in Cambodia: a multisite prospective cohort study
10.1016/s1473-3099(15)00487-9 · 2016 · External reference
Molecular epidemiology of resistance to antimalarial drugs in the Greater Mekong subregion: an observational study
10.1016/s1473-3099(20)30228-0 · 2020 · External reference
Evidence for the early emergence of piperaquine-resistant Plasmodium falciparum malaria and modeling strategies to mitigate resistance
2022 · External reference
Plasmepsin II-III copy number accounts for bimodal piperaquine resistance among Cambodian Plasmodium falciparum
10.1038/s41467-018-04104-z · 2018 · External reference
Four plasmepsins are active in the Plasmodium falciparum food vacuole, including a protease with an active-site histidine
10.1073/pnas.022630099 · 2002 · External reference
Order and specificity of the Plasmodium falciparum hemoglobin degradation pathway
10.1172/jci117140 · 1994 · External reference
Hemoglobin degradation in the human malaria pathogen Plasmodium falciparum: a catabolic pathway initiated by a specific aspartic protease
10.1084/jem.173.4.961 · 1991 · External reference
Biosynthesis and maturation of the malaria aspartic hemoglobinases plasmepsins I and II
10.1074/jbc.272.23.14961 · 1997 · External reference
The role of Plasmodium falciparum food vacuole plasmepsins
10.1074/jbc.m409740200 · 2005 · External reference
A comprehensive RNA handling and transcriptomics guide for high-throughput processing of Plasmodium blood-stage samples
10.1186/s12936-020-03436-w · 2020 · External reference
Role of Plasmodium falciparum digestive vacuole plasmepsins in the specificity and antimalarial mode of action of cysteine and aspartic protease inhibitors
10.1128/aac.00882-09 · 2009 · External reference
Plasmodium falciparum ensures its amino acid supply with multiple acquisition pathways and redundant proteolytic enzyme systems
10.1073/pnas.0601876103 · 2006 · External reference
Recent advances in understanding the mechanism of hemozoin (malaria pigment) formation
10.1016/j.jinorgbio.2007.12.004 · 2008 · External reference
Mechanisms of hematin crystallization and inhibition by the antimalarial drug chloroquine
10.1073/pnas.1501023112 · 2015 · External reference
Development of copy number assays for detection and surveillance of piperaquine resistance associated plasmepsin 2/3 copy number variation in Plasmodium falciparum
10.1186/s12936-020-03249-x · 2020 · External reference
Characterization of native and recombinant falcipain-2, a principal trophozoite cysteine protease and essential hemoglobinase of Plasmodium falciparum
10.1074/jbc.m004459200 · 2000 · External reference
Irreversible effect of cysteine protease inhibitors on the release of malaria parasites from infected erythrocytes
10.1111/j.1462-5822.2008.01242.x · 2009 · External reference
Structure and inhibition of plasmepsin II, a hemoglobin-degrading enzyme from Plasmodium falciparum
10.1073/pnas.93.19.10034 · 1996 · External reference
Optimization of a multi-well colorimetric assay to determine haem species in Plasmodium falciparum in the presence of anti-malarials
10.1186/s12936-015-0729-9 · 2015 · External reference
Insights into the role of heme in the mechanism of action of antimalarials
10.1021/cb300454t · 2013 · External reference
Metabolomic profiling of the malaria box reveals antimalarial target pathways
10.1128/aac.01224-16 · 2016 · External reference
Kinetic modelling of the response of Plasmodium falciparum to chloroquine and its experimental testing in vitro. Implications for mechanism of action of and resistance to the drug
10.1016/0006-2952(90)90302-2 · 1990 · External reference
Susceptibility of human malaria parasites to chloroquine is pH dependent
10.1073/pnas.82.9.2784 · 1985 · External reference
Simulation of kinetic data on the influx and efflux of chloroquine by erythrocytes infected with Plasmodium falciparum. Evidence for a drug-importer in chloroquine-sensitive strains
10.1016/0006-2952(91)90407-v · 1991 · External reference
PfCRT and the trans-vacuolar proton electrochemical gradient: regulating the access of chloroquine to ferriprotoporphyrin IX
10.1111/j.1365-2958.2006.05368.x · 2006 · External reference
Hemoglobin degradation in the malaria parasite Plasmodium falciparum: an ordered process in a unique organelle
10.1073/pnas.87.8.2931 · 1990 · External reference
The pH of the digestive vacuole of Plasmodium falciparum is not associated with chloroquine resistance
10.1242/jcs.02795 · 2006 · External reference
Evaluation of pH during cytostomal endocytosis and vacuolar catabolism of haemoglobin in Plasmodium falciparum
10.1042/bj20070934 · 2007 · External reference
Quantitative pH measurements in Plasmodium falciparum-infected erythrocytes using pHluorin
10.1111/j.1462-5822.2006.00847.x · 2007 · External reference
A verapamil-sensitive chloroquine-associated H+ leak from the digestive vacuole in chloroquine-resistant malaria parasites
10.1242/jcs.016758 · 2008 · External reference
Uptake of [3H]chloroquine by drug-sensitive and -resistant strains of the human malaria parasite Plasmodium falciparum
10.1016/0006-2952(86)90668-4 · 1986 · External reference
Alkalinization of the food vacuole of malaria parasites by quinoline drugs and alkylamines is not correlated with their antimalarial activity
10.1016/0006-2952(89)90550-9 · 1989 · External reference
Acidification of the malaria parasite’s digestive vacuole by a H+-ATPase and a H+-pyrophosphatase
10.1074/jbc.m208648200 · 2003 · External reference
Genetic disruption of the Plasmodium falciparum digestive vacuole plasmepsins demonstrates their functional redundancy
10.1074/jbc.m409605200 · 2004 · External reference
Critical roles for the digestive vacuole plasmepsins of Plasmodium falciparum in vacuolar function
10.1111/j.1365-2958.2007.05768.x · 2007 · External reference
Plasmepsin 4, the food vacuole aspartic proteinase found in all Plasmodium spp. infecting man
10.1016/s0166-6851(03)00137-3 · 2003 · External reference
Cellular uptake of chloroquine is dependent on binding to ferriprotoporphyrin IX and is independent of NHE activity in Plasmodium falciparum
10.1083/jcb.145.2.363 · 1999 · External reference
Influence of LAR and VAR on para-aminopyridine antimalarials targetting haematin in chloroquine-resistance
2016 · External reference
Activity of piperaquine and other 4-aminoquinoline antiplasmodial drugs against chloroquine-sensitive and resistant blood-stages of Plasmodium falciparum. Role of beta-haematin inhibition and drug concentration in vacuolar water- and lipid-phases
10.1016/j.bcp.2007.03.011 · 2007 · External reference
Synthetic Hemozoin (β-Hematin) Crystals Nucleate at the Surface of Neutral Lipid Droplets that Control Their Sizes
10.1021/cg4009416 · 2013 · External reference
The neutral lipid composition present in the digestive vacuole of Plasmodium falciparum concentrates heme and mediates β-hematin formation with an unusually low activation energy
10.1021/bi101397u · 2010 · External reference
A Kelch13-defined endocytosis pathway mediates artemisinin resistance in malaria parasites
10.1126/science.aax4735 · 2020 · External reference
The parasitophorous vacuole nutrient channel is critical for drug access in malaria parasites and modulates the artemisinin resistance fitness cost
10.1016/j.chom.2021.11.002 · 2021 · External reference
A Plasmodium falciparum genetic cross reveals the contributions of pfcrt and plasmepsin II/III to piperaquine drug resistance
10.1128/mbio.00805-24 · 2024 · External reference
Origins of the current outbreak of multidrug-resistant malaria in southeast Asia: a retrospective genetic study
10.1016/s1473-3099(18)30068-9 · 2018 · External reference
The natural function of the malaria parasite’s chloroquine resistance transporter
10.1038/s41467-020-17781-6 · 2020 · External reference
Evidence for regulation of hemoglobin metabolism and intracellular ionic flux by the Plasmodium falciparum chloroquine resistance transporter
10.1038/s41598-018-31715-9 · 2018 · External reference
The knock-down of the chloroquine resistance transporter PfCRT ss linked to oligopeptide handling in Plasmodium falciparum
10.1128/spectrum.01101-22 · 2022 · External reference
Chloroquine transport via the malaria parasite’s chloroquine resistance transporter
10.1126/science.1175667 · 2009 · External reference
Multiple drugs compete for transport via the Plasmodium falciparum chloroquine resistance transporter at distinct but interdependent sites
10.1074/jbc.m114.614206 · 2014 · External reference
Structure and drug resistance of the Plasmodium falciparum transporter PfCRT
10.1038/s41586-019-1795-x · 2019 · External reference
PfCRT mutations conferring piperaquine resistance in falciparum malaria shape the kinetics of quinoline drug binding and transport
10.1371/journal.ppat.1011436 · 2023 · External reference
Evaluation of the effect of gene duplication by genome editing on drug resistance in Plasmodium falciparum
10.3389/fcimb.2022.915656 · 2022 · External reference
Plasmodium falciparum resistance to piperaquine driven by PfCRT
10.1016/s1473-3099(19)30543-2 · 2019 · External reference
Mapping the genomic landscape of multidrug resistance in
2023 · External reference
Additional PfCRT mutations driven by selective pressure for improved fitness can result in the loss of piperaquine resistance and altered Plasmodium falciparum physiology
10.1128/mbio.01832-23 · 2024 · External reference
Plasmodium falciparum African PfCRT mutant isoforms conducive to piperaquine resistance are infrequent and impart a major fitness cost
2024 · External reference
Distribution and temporal dynamics of Plasmodium falciparum chloroquine resistance transporter mutations associated with piperaquine resistance in Northern Cambodia
10.1093/infdis/jiab055 · 2021 · External reference
Temporal and spatial dynamics of Plasmodium falciparum clonal lineages in Guyana
10.1371/journal.ppat.1012013 · 2024 · External reference
African isolates show a high proportion of multiple copies of the Plasmodium falciparum plasmepsin-2 gene, a piperaquine resistance marker
10.1186/s12936-019-2756-4 · 2019 · External reference
Protein complex directs hemoglobin-to-hemozoin formation in Plasmodium falciparum
10.1073/pnas.1218412110 · 2013 · External reference
Genome editing in the human malaria parasite Plasmodium falciparum using the CRISPR-Cas9 system
10.1038/nbt.2925 · 2014 · External reference
CRISPR-Cas9-modified pfmdr1 protects Plasmodium falciparum asexual blood stages and gametocytes against a class of piperazine-containing compounds but potentiates artemisinin-based combination therapy partner drugs
2016 · External reference
Transformation with human dihydrofolate reductase renders malaria parasites insensitive to WR99210 but does not affect the intrinsic activity of proguanil
10.1073/pnas.94.20.10931 · 1997 · External reference
Mefloquine resistance in Plasmodium falciparum and increased pfmdr1 gene copy number
10.1016/s0140-6736(04)16767-6 · 2004 · External reference
Genome wide gene amplifications and deletions in Plasmodium falciparum
10.1016/j.molbiopara.2007.05.005 · 2007 · External reference
Assessment and continued validation of the malaria SYBR green I-based fluorescence assay for use in malaria drug screening
10.1128/aac.01607-06 · 2007 · External reference
Metabolomics Workbench: An international repository for metabolomics data and metadata, metabolite standards, protocols, tutorials and training, and analysis tools
2016 · External reference
pH regulation in the intracellular malaria parasite, Plasmodium falciparum. H(+) extrusion via a V-type H(+)-ATPase
10.1074/jbc.274.47.33213 · 1999 · External reference
Acid extrusion from the intraerythrocytic malaria parasite is not via a Na(+)/H(+) exchanger
10.1016/j.molbiopara.2008.07.001 · 2008 · External reference
The membrane potential of the intraerythrocytic malaria parasite Plasmodium falciparum
10.1074/jbc.m311110200 · 2004 · External reference
