title: The aminopeptidase inhibitor CHR-2863 is an orally bioavailable inhibitor of murine malaria.
abstract: Malaria remains a significant risk in many areas of the world, with resistance to the current antimalarial pharmacopeia an ever-increasing problem. The M1 alanine aminopeptidase (PfM1AAP) and M17 leucine aminopeptidase (PfM17LAP) are believed to play a role in the terminal stages of digestion of host hemoglobin and thereby generate a pool of free amino acids that are essential for parasite growth and development. Here, we show that an orally bioavailable aminopeptidase inhibitor, CHR-2863, is efficacious against murine malaria.
authors.affiliation: Malaria Biology Laboratory, Queensland Institute of Medical Research, Herston, Brisbane, Australia.
authors.forename: Tina S
authors.initials: TS
authors.lastname: Skinner-Adams
authors.forename: Christopher L
authors.initials: CL
authors.lastname: Peatey
authors.forename: Karen
authors.initials: K
authors.lastname: Anderson
authors.forename: Katharine R
authors.initials: KR
authors.lastname: Trenholme
authors.forename: David
authors.initials: D
authors.lastname: Krige
authors.forename: Christopher L
authors.initials: CL
authors.lastname: Brown
authors.forename: Colin
authors.initials: C
authors.lastname: Stack
authors.forename: Desire M M
authors.initials: DM
authors.lastname: Nsangou
authors.forename: Rency T
authors.initials: RT
authors.lastname: Mathews
authors.forename: Karine
authors.initials: K
authors.lastname: Thivierge
authors.forename: John P
authors.initials: JP
authors.lastname: Dalton
authors.forename: Donald L
authors.initials: DL
authors.lastname: Gardiner
mesh_terms: D000626:Aminopeptidases / Q000037:antagonists & inhibitors*; D000818:Animals; D000962:Antimalarials / Q000737:chemistry / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D005260:Female; D008288:Malaria / Q000469:parasitology; D051379:Mice; D008810:Mice, Inbred C57BL; D010963:Plasmodium falciparum / Q000187:drug effects / Q000472:pathogenicity
chemical_list: D000962:Antimalarials; D004791:Enzyme Inhibitors; D000626:Aminopeptidases