{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Murithi JM"],"funding":["National Institute of Allergy and Infectious Diseases","Medicines for Malaria Venture","Human Frontier Science Program","NIAID NIH HHS","NIEHS NIH HHS","U.S. Department of Defense","Bill and Melinda Gates Foundation","Wellcome Trust"],"pagination":["eabg6013"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC8530196"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["13(603)"],"pubmed_abstract":["The emergence and spread of <i>Plasmodium falciparum</i> resistance to first-line antimalarials creates an imperative to identify and develop potent preclinical candidates with distinct modes of action. Here, we report the identification of MMV688533, an acylguanidine that was developed following a whole-cell screen with compounds known to hit high-value targets in human cells. MMV688533 displays fast parasite clearance in vitro and is not cross-resistant with known antimalarials. In a <i>P. falciparum</i> NSG mouse model, MMV688533 displays a long-lasting pharmacokinetic profile and excellent safety. Selection studies reveal a low propensity for resistance, with modest loss of potency mediated by point mutations in PfACG1 and PfEHD. These proteins are implicated in intracellular trafficki"],"journal":["Science translational medicine"],"pubmed_title":["The antimalarial MMV688533 provides potential for single-dose cures with a high barrier to <i>Plasmodium falciparum</i> parasite resistance."],"pmcid":["PMC8530196"],"funding_grant_id":["AI109023","R01 AI124678","W81XWH-19-1-0086","R01 AI109023","OPP1201387","LT000976/2016-L","200909","R01 AI139179","T32 ES007020"],"pubmed_authors":["Desert P","Niles JC","Menegotto J","Augereau JM","Jimenez-Diaz MB","Gobeau N","Guillon JM","Nicolas MF","Doubovetzky M","Singh S","Cherkaoui-Rbati MH","Escudie F","Blasco B","Tumwebaze P","Price RN","Louit G","Yeo T","Klieber S","Courtemanche G","Leroy D","Mok S","Rouillier M","Merino R","Bebrevska L","Wirjanata G","Fraisse L","Bessila N","Angulo-Barturen I","Boulenc X","Vermat T","Gnadig NF","Pellet A","Tuffal G","Fidock DA","Uhlemann AC","Rubiano K","Bath J","Giraud E","Bozec T","Sanz LM","Bashyam S","Pascal C","Wittlin S","Marfurt J","Gamo FJ","Murithi JM","Cabanis MJ","Campbell S","Salle L","Noviyanti R","Joseph J","Cooper RA","Pasaje CFA","Rosenthal PJ","Baud D"],"additional_accession":[]},"is_claimable":false,"name":"The antimalarial MMV688533 provides potential for single-dose cures with a high barrier to <i>Plasmodium falciparum</i> parasite resistance.","description":"The emergence and spread of <i>Plasmodium falciparum</i> resistance to first-line antimalarials creates an imperative to identify and develop potent preclinical candidates with distinct modes of action. Here, we report the identification of MMV688533, an acylguanidine that was developed following a whole-cell screen with compounds known to hit high-value targets in human cells. MMV688533 displays fast parasite clearance in vitro and is not cross-resistant with known antimalarials. In a <i>P. falciparum</i> NSG mouse model, MMV688533 displays a long-lasting pharmacokinetic profile and excellent safety. Selection studies reveal a low propensity for resistance, with modest loss of potency mediated by point mutations in PfACG1 and PfEHD. These proteins are implicated in intracellular trafficki","dates":{"release":"2021-01-01T00:00:00Z","publication":"2021 Jul","modification":"2025-04-22T09:19:22.616Z","creation":"2025-04-05T22:59:01.783Z"},"accession":"S-EPMC8530196","cross_references":{"pubmed":["34290058"],"doi":["10.1126/scitranslmed.abg6013"]}}