title: Seeking the Elusive Long-Acting Ozonide: Discovery of Artefenomel (OZ439).
abstract: The majority of frontline therapies for the treatment of malaria are combination drugs containing artemisinin (or its semisynthetic analogs), known as artemisinin combination therapies (ACTs). While generally efficacious, ACTs and the first generation fully synthetic ozonide, arterolane (OZ277, 1), suffer from rapid clearance requiring 3-day dosing regimens. Extensive structure-activity studies led to the discovery of a second-generation ozonide, artefenomel (OZ439, 2), which has overcome this limitation, maintaining the rapid onset of action and potent activity of the artemisinin derivatives while exhibiting greatly improved pharmacokinetics, low projected cost of goods, prophylactic activity, and the potential for a single dose cure.
authors.affiliation: Department of Pharmaceutical Sciences, University of Kentucky , Lexington, Kentucky 40508, United States.
authors.forename: Ho Shin
authors.initials: HS
authors.lastname: Kim
authors.affiliation: Department of Pharmaceutical Sciences, University of Kentucky , Lexington, Kentucky 40508, United States.
authors.forename: Jared T
authors.initials: JT
authors.lastname: Hammill
authors.affiliation: Department of Pharmaceutical Sciences, University of Kentucky , Lexington, Kentucky 40508, United States.
authors.forename: R Kiplin
authors.identifier: 0000-0002-9638-2060
authors.initials: RK
authors.lastname: Guy
mesh_terms: D000218:Adamantane / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D000818:Animals; D000962:Antimalarials / Q000737:chemistry* / Q000494:pharmacology* / Q000627:therapeutic use; D055808:Drug Discovery; D006801:Humans; D008288:Malaria / Q000188:drug therapy*; D010545:Peroxides / Q000737:chemistry* / Q000494:pharmacology* / Q000627:therapeutic use; D010961:Plasmodium / Q000187:drug effects*
chemical_list: D000962:Antimalarials; D010545:Peroxides; D000218:Adamantane; C558165:artefenomel