Sugi Tatsuki, Kato Kentaro, Kobayashi Kyousuke, Kurokawa Hitomi, Takemae Hitoshi, Gong Haiyan, Recuenco Frances C, Iwanaga Tatsuya, Horimoto Taisuke, Akashi Hiroomi
Department of Veterinary Microbiology, Graduate School of Agricultural and Life Sciences, The University of Tokyo, Tokyo, Japan.
J Vet Med Sci. 2011 Oct;73(10):1377-9. doi: 10.1292/jvms.11-0085. Epub 2011 Jun 16.
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.
撞击激酶抑制剂（BKIs）作用于对类似物敏感的激酶，而哺乳动物基因组很少编码这类激酶。此前，我们证明了一种BKI通过作用于弓形虫钙依赖性蛋白激酶1（TgCDPK1）有效地抑制了弓形虫（弓形虫病的致病病原体）的体外复制（《真核细胞》，9：667 - 670）。在此，我们研究了BKI 1NM - PP1是否能在体内减少寄生虫的复制。在接种寄生虫之前通过腹腔注射高剂量的1NM - PP1可有效降低弓形虫感染小鼠脑、肝和肺中的寄生虫负荷，然而，口服低剂量的1NM - PP1并未改变感染小鼠的存活率。
