title: The Clinically Tested Gardos Channel Inhibitor Senicapoc Exhibits Antimalarial Activity.
abstract: Senicapoc, a Gardos channel inhibitor, prevented erythrocyte dehydration in clinical trials of patients with sickle cell disease. We tested the hypothesis that senicapoc-induced blockade of the Gardos channel inhibits Plasmodium growth. Senicapoc inhibited in vitro growth of human and primate plasmodia during the clinical blood stage. Senicapoc treatment suppressed P. yoelii parasitemia in vivo in C57BL/6 mice. The reassuring safety and biochemical profile of senicapoc encourage its use in antimalarial development.
authors.affiliation: Department of Immunology and Infectious Diseases, Harvard School of Public Health, Boston, Massachusetts, USA Division of Hematology/Oncology, Boston Children's Hospital, Boston, Massachusetts, USA Department of Pediatrics, Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: Venée N
authors.initials: VN
authors.lastname: Tubman
authors.affiliation: Department of Genetics and Complex Diseases, Harvard School of Public Health, Boston, Massachusetts, USA.
authors.forename: Pedro
authors.initials: P
authors.lastname: Mejia
authors.affiliation: Renal Division and Vascular Biology Research Center, Beth Israel Deaconess Medical Center, Boston, Massachusetts, USA.
authors.forename: Boris E
authors.initials: BE
authors.lastname: Shmukler
authors.affiliation: Department of Immunology and Infectious Diseases, Harvard School of Public Health, Boston, Massachusetts, USA.
authors.forename: Amy K
authors.initials: AK
authors.lastname: Bei
authors.affiliation: Renal Division and Vascular Biology Research Center, Beth Israel Deaconess Medical Center, Boston, Massachusetts, USA Department of Medicine, Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: Seth L
authors.initials: SL
authors.lastname: Alper
authors.affiliation: Department of Genetics and Complex Diseases, Harvard School of Public Health, Boston, Massachusetts, USA.
authors.forename: James R
authors.initials: JR
authors.lastname: Mitchell
authors.affiliation: Department of Laboratory Medicine, Boston Children's Hospital, Boston, Massachusetts, USA carlo.brugnara@childrens.harvard.edu mduraisi@hsph.harvard.edu.
authors.forename: Carlo
authors.initials: C
authors.lastname: Brugnara
authors.affiliation: Department of Immunology and Infectious Diseases, Harvard School of Public Health, Boston, Massachusetts, USA carlo.brugnara@childrens.harvard.edu mduraisi@hsph.harvard.edu.
authors.forename: Manoj T
authors.initials: MT
authors.lastname: Duraisingh
mesh_terms: D000081:Acetamides / Q000494:pharmacology*; D000818:Animals; D000962:Antimalarials / Q000494:pharmacology*; D001692:Biological Transport / Q000187:drug effects; D004912:Erythrocytes / Q000187:drug effects / Q000378:metabolism / Q000469:parasitology; D006790:Host-Parasite Interactions; D006801:Humans; D051660:Intermediate-Conductance Calcium-Activated Potassium Channels / Q000037:antagonists & inhibitors / Q000378:metabolism; D008253:Macaca mulatta; D051379:Mice; D008810:Mice, Inbred C57BL; D010963:Plasmodium falciparum / Q000187:drug effects* / Q000254:growth & development / Q000378:metabolism; D016790:Plasmodium knowlesi / Q000187:drug effects* / Q000254:growth & development / Q000378:metabolism; D010967:Plasmodium yoelii / Q000187:drug effects* / Q000254:growth & development / Q000378:metabolism; D014320:Triphenylmethyl Compounds / Q000494:pharmacology*; D053058:Trophozoites / Q000187:drug effects* / Q000254:growth & development / Q000378:metabolism; D014867:Water / Q000378:metabolism
chemical_list: D000081:Acetamides; D000962:Antimalarials; D051660:Intermediate-Conductance Calcium-Activated Potassium Channels; C496923:KCNN4 protein, human; C496925:Kcnn4 protein, mouse; D014320:Triphenylmethyl Compounds; D014867:Water; C472774:senicapoc