Summary of Study ST001175

This data is available at the NIH Common Fund's National Metabolomics Data Repository (NMDR) website, the Metabolomics Workbench,, where it has been assigned Project ID PR000787. The data can be accessed directly via it's Project DOI: 10.21228/M8Z97B This work is supported by NIH grant, U2C- DK119886.


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Study IDST001175
Study TitleMulti-omics analysis demonstrates unique mode of action of a potent new antimalarial compound, JPC-3210, against Plasmodium falciparum
Study SummaryThe increasing incidence of antimalarial drug resistance to the first-line artemisinins, and their combination partner drugs, underpins an urgent need for new antimalarial drugs, ideally with a novel mechanism of action. The recently developed 2-aminomethylphenol, JPC-3210, (MMV 892646) is an erythrocytic schizonticide with potent in vitro antimalarial activity against multidrug-resistant Plasmodium falciparum, low cytotoxicity, potent in vivo efficacy against murine malaria, and favourable preclinical pharmacokinetics, including a lengthy plasma elimination half-life. This study demonstrates the application of a “multi-omics” workflow based on high resolution orbitrap mass spectrometry to investigate the impact of JPC-3210 on biochemical pathways within P. falciparum infected red blood cells. Metabolomics and peptidomics analysis revealed a perturbation in hemoglobin metabolism following JPC-3210 exposure. The metabolomics data demonstrated a depletion in short hemoglobin-derived peptides, while peptidomics analysis showed a depletion in longer hemoglobin-derived peptides. In order to further elucidate the mechanism responsible for inhibition of hemoglobin metabolism, we used in vitro β-hematin polymerisation assays and showed JPC-3210 to be an intermediate inhibitor of β-hematin polymerisation, about 10-fold less potent then the quinoline antimalarials. Furthermore, quantitative proteomics analysis showed that JPC-3210 treatment results in a distinct proteomic signature in comparison to other known antimalarials. Whilst JPC-3210 clustered closely with mefloquine in the metabolomics and proteomics analyses, a key differentiating signature for JPC-3210 was the significant enrichment of parasite proteins involved in regulation of translation. In conclusion, multi-omics studies using high resolution mass spectrometry revealed JPC-3210 to possess a unique mechanism of action involving inhibition of hemoglobin digestion, depletion of DNA replication and synthesis proteins, and elevation of regulators of protein translation. Importantly, this mechanism is distinct from currently-used antimalarials, suggesting that JPC-3210 warrants further investigation as a potentially useful new antimalarial agent.
Monash University
Last NameSiddiqui
First NameGhizal
Address381 Royal Parade, Parkville
Submit Date2019-04-25
Raw Data AvailableYes
Raw Data File Type(s)raw(Thermo)
Analysis Type DetailLC-MS
Release Date2019-05-15
Release Version1
Ghizal Siddiqui Ghizal Siddiqui application/zip

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Subject type: Other; Subject species: Plasmodium falciparum (Factor headings shown in green)

mb_sample_id local_sample_id Condition
SA081519P_Aqm_1Aqm treated
SA081520P_Aqm_3Aqm treated
SA081521P_Aqm_2Aqm treated
SA081522P_Aqm_4Aqm treated
SA081523P_Atov_2Atov treated
SA081524P_Atov_4Atov treated
SA081525P_Atov_1Atov treated
SA081526P_Atov_3Atov treated
SA081533P_CQ_4CQ treated
SA081534P_CQ_3CQ treated
SA081535P_CQ_2CQ treated
SA081536P_CQ_1CQ treated
SA081537P_DHA_4DHA treated
SA081538P_DHA_3DHA treated
SA081539P_DHA_2DHA treated
SA081540P_DHA_1DHA treated
SA081541P_DMSO_6DMSO treated
SA081542P_DMSO_8DMSO treated
SA081543P_DMSO_7DMSO treated
SA081544P_DMSO_2DMSO treated
SA081545P_DMSO_3DMSO treated
SA081546P_DMSO_4DMSO treated
SA081547P_DMSO_5DMSO treated
SA081548P_JPC_3JPC treated
SA081549P_JPC_2JPC treated
SA081550P_JPC_1JPC treated
SA081551P_LF_1LF treated
SA081552P_LF_2LF treated
SA081553P_LF_4LF treated
SA081554P_LF_3LF treated
SA081555P_MQ_2MQ treated
SA081556P_MQ_1MQ treated
SA081557P_MQ_3MQ treated
SA081558P_MQ_4MQ treated
SA081559P_PYN_3PYN treated
SA081560P_PYN_4PYN treated
SA081561P_PYN_1PYN treated
SA081562P_PYN_2PYN treated
SA081569P_TQ_1TQ treated
SA081570P_TQ_2TQ treated
SA081571P_TQ_3TQ treated
SA081572P_TQ_4TQ treated
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