antimalarial iron chelator, fbs0701, shows asexual and gametocyte plasmodium falciparum activity and single oral dose cure in a murine malaria model抗疟铁螯合剂,fbs0701显示无性和配子母细胞活动和单剂量口服治疗恶性疟原虫疟疾在鼠模型.pdfVIP

Antimalarial Iron Chelator, FBS0701, Shows Asexual and Gametocyte Plasmodium falciparum Activity and Single Oral Dose Cure in a Murine Malaria Model 1 1 2 3 4 Patricia Ferrer , Abhai K. Tripathi , Martha A. Clark , Carla Cerami Hand , Hugh Young Rienhoff Jr. , David J. Sullivan, Jr.1* 1The Malaria Research Institute, W. Harry Feinstone Department of Molecular Microbiology and Immunology, The Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, United States of America, 2 Department of Microbiology and Immunology, University of North Carolina, Chapel Hill, North Carolina, United States of America, 3 Department of Epidemiology, School of Public Health, University of North Carolina Chapel Hill, North Carolina, United States of America, 4 FerroKin BioSciences, Inc., San Carlos, California, United States of America Abstract Iron chelators for the treatment of malaria have proven therapeutic activity in vitro and in vivo in both humans and mice, but their clinical use is limited by the unsuitable absorption and pharmacokinetic properties of the few available iron chelators. FBS0701, (S)3’’-(HO)-desazadesferrithiocin-polyether [DADFT-PE], is an oral iron chelator currently in Phase 2 human studies for the treatment of transfusional iron overload. The drug has very favorable absorption and pharmacokinetic properties allowing for once-daily use to deplete circulating free iron with human plasma concentrations in the high mM range. Here we show that FBS0701 has inhibition concentration 50% (IC50) of 6 mM for Plasmodium falciparum in contrast to the IC50 for deferiprone and deferoxamine at 15 and 30 mM respectively. In combination, FBS0701 interfere