title: Bumped kinase inhibitor 1294 treats established Toxoplasma gondii infection.
abstract: Toxoplasma gondii is a unicellular parasite that causes severe brain and eye disease. Current drugs for T. gondii are limited by toxicity. Bumped kinase inhibitors (BKIs) selectively inhibit calcium-dependent protein kinases of the apicomplexan pathogens T. gondii, cryptosporidia, and plasmodia. A lead anti-Toxoplasma BKI, 1294, has been developed to be metabolically stable and orally bioavailable. Herein, we demonstrate the oral efficacy of 1294 against toxoplasmosis in vivo.
authors.affiliation: VA Medical Center, Portland, Oregon, USA Division of Infectious Diseases, Oregon Health & Science University, Portland, Oregon, USA doggettj@ohsu.edu wvanvoorhis@medicine.washington.edu.
authors.forename: J Stone
authors.initials: JS
authors.lastname: Doggett
authors.affiliation: Division of Allergy and Infectious Diseases, University of Washington, Seattle, Washington, USA.
authors.forename: Kayode K
authors.initials: KK
authors.lastname: Ojo
authors.affiliation: Department of Biochemistry, University of Washington, Seattle, Washington, USA.
authors.forename: Erkang
authors.initials: E
authors.lastname: Fan
authors.affiliation: Department of Chemistry, University of Washington, Seattle, Washington, USA.
authors.forename: Dustin J
authors.initials: DJ
authors.lastname: Maly
authors.affiliation: Division of Allergy and Infectious Diseases, University of Washington, Seattle, Washington, USA doggettj@ohsu.edu wvanvoorhis@medicine.washington.edu.
authors.forename: Wesley C
authors.initials: WC
authors.lastname: Van Voorhis
mesh_terms: D000818:Animals; D000981:Antiprotozoal Agents / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D009281:Naphthalenes / Q000627:therapeutic use*; D010880:Piperidines / Q000627:therapeutic use*; D047428:Protein Kinase Inhibitors / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D011494:Protein Kinases / Q000187:drug effects*; D015800:Protozoan Proteins / Q000037:antagonists & inhibitors; D011720:Pyrazoles / Q000627:therapeutic use*; D014122:Toxoplasma / Q000187:drug effects*; D014123:Toxoplasmosis / Q000188:drug therapy*; D017871:Calcium-Calmodulin-Dependent Protein Kinases
chemical_list: D000981:Antiprotozoal Agents; D009281:Naphthalenes; D010880:Piperidines; D047428:Protein Kinase Inhibitors; D011494:Protein Kinases; D015800:Protozoan Proteins; D011720:Pyrazoles; D017871:Calcium-Calmodulin-Dependent Protein Kinases; C000615581:bumped kinase inhibitor 1294