title: 1NM-PP1 treatment of mice infected with Toxoplasma gondii.
abstract: Bumped kinase inhibitors (BKIs) target analog-sensitive kinases, which the genomes of mammals rarely encode. Previously, we demonstrated that a BKI effectively suppressed the in vitro replication of Toxoplasma gondii, the causative pathogen of toxoplasmosis, by targeting T. gondii calcium-dependent protein kinase 1 (TgCDPK1) (Eukaryotic Cell, 9: 667-670). Here, we examined whether the BKI 1NM-PP1 reduced parasite replication in vivo. A high dose of 1NM-PP1, by intraperitoneal injection, just before the parasite inoculation effectively reduced the parasite load in the brains, livers, and lungs of T. gondii-infected mice, however, a low dose of 1NM-PP1 with oral administration didn't change the survival rates of infected mice.
authors.affiliation: Department of Veterinary Microbiology, Graduate School of Agricultural and Life Sciences, The University of Tokyo, Tokyo, Japan.
authors.forename: Tatsuki
authors.initials: T
authors.lastname: Sugi
authors.forename: Kentaro
authors.initials: K
authors.lastname: Kato
authors.forename: Kyousuke
authors.initials: K
authors.lastname: Kobayashi
authors.forename: Hitomi
authors.initials: H
authors.lastname: Kurokawa
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Takemae
authors.forename: Haiyan
authors.initials: H
authors.lastname: Gong
authors.forename: Frances C
authors.initials: FC
authors.lastname: Recuenco
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Iwanaga
authors.forename: Taisuke
authors.initials: T
authors.lastname: Horimoto
authors.forename: Hiroomi
authors.initials: H
authors.lastname: Akashi
mesh_terms: D000284:Administration, Oral; D000818:Animals; D000981:Antiprotozoal Agents / Q000627:therapeutic use*; D001921:Brain / Q000469:parasitology; D004305:Dose-Response Relationship, Drug; D005260:Female; D007274:Injections, Intraperitoneal; D008099:Liver / Q000469:parasitology; D008168:Lung / Q000469:parasitology; D051379:Mice; D008813:Mice, Inbred ICR; D059208:Parasite Load; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use*; D011720:Pyrazoles / Q000627:therapeutic use*; D011743:Pyrimidines / Q000627:therapeutic use*; D015996:Survival Rate; D014123:Toxoplasmosis / Q000188:drug therapy* / Q000401:mortality / Q000469:parasitology
chemical_list: C479693:1-tert-butyl-3-naphthalen-1-ylmethyl-1H-pyrazolo(3,4-d)pyrimidin-4-ylemine; D000981:Antiprotozoal Agents; D047428:Protein Kinase Inhibitors; D011720:Pyrazoles; D011743:Pyrimidines