ArticleAntimicrobial agents and chemotherapy2015
In Vitro and In Vivo Effects of the Bumped Kinase Inhibitor 1294 in the Related Cyst-Forming Apicomplexans Toxoplasma gondii and Neospora caninum.
Article in Antimicrobial agents and chemotherapy, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 57 papers.
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Who cites it
57 citing papers in PubMed, 87 citations in OpenAlex.
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- Design, synthesis, and anti-Toxoplasma gondii evaluation of β-carboline derivatives.Parasites & vectors · 2025Article
- Pleiotropic Effects on Tachyzoite and Host Cell Proteomes in Knock-Out Clones of the Open Reading Frames 297720 and 319730 Constitutively Expressed inInternational journal of molecular sciences · 2025Article
- Versatile Imidazole Scaffold with Potent Activity against Multiple Apicomplexan Parasites.ACS infectious diseases · 2025Article
- Transient Adaptation ofInternational journal of molecular sciences · 2024Article
- Molecular Targets of the 5-Amido-Carboxamide Bumped Kinase Inhibitor BKI-1748 inInternational journal of molecular sciences · 2024Article
- An Early Treatment With BKI-1748 Exhibits Full Protection Against Abortion and Congenital Infection in Sheep Experimentally Infected With Toxoplasma gondii.The Journal of infectious diseases · 2024Article
- Single and combination treatment of Toxoplasma gondii infections with a bumped kinase inhibitor and artemisone in vitro and with artemiside in experimentally infected mice.Experimental parasitology · 2023Article
- Analysis of CDPK1 targets identifies a trafficking adaptor complex that regulates microneme exocytosis ineLife · 2023Article
- Analysis of CDPK1 targets identifies a trafficking adaptor complex that regulates microneme exocytosis inbioRxiv : the preprint server for biology · 2023Article
- Exploring the epidemiological role of the Eurasian lynx (International journal for parasitology. Parasites and wildlife · 2023Article
- Comparative Proteomic Analysis ofInternational journal of molecular sciences · 2023Article
- High prevalence rates ofInternational journal for parasitology. Parasites and wildlife · 2023Article
- In Vitro versus in Mice: Efficacy and Safety of Decoquinate and Quinoline-Pathogens (Basel, Switzerland) · 2023Article
- In vitro maturation of Toxoplasma gondii bradyzoites in human myotubes and their metabolomic characterization.Nature communications · 2022Article
- Common Molecular Targets of a Quinolone Based Bumped Kinase Inhibitor inInternational journal of molecular sciences · 2022Article
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Authors and funding
12 authors at 3 institutions in 3 countries.
Funding
Abstract
We report on the in vitro effects of the bumped kinase inhibitor 1294 (BKI-1294) in cultures of virulent Neospora caninum isolates Nc-Liverpool (Nc-Liv) and Nc-Spain7 and in two strains of Toxoplasma gondii (RH and ME49), all grown in human foreskin fibroblasts. In these parasites, BKI-1294 acted with 50% inhibitory concentrations (IC50s) ranging from 20 nM (T. gondii RH) to 360 nM (N. caninum Nc-Liv), and exposure of intracellular stages to 1294 led to the nondisjunction of newly formed tachyzoites, resulting in the formation of multinucleated complexes similar to complexes previously observed in BKI-1294-treated N. caninum beta-galactosidase-expressing parasites. However, such complexes were not seen in a transgenic T. gondii strain that expressed CDPK1 harboring a mutation (G to M) in the gatekeeper residue. In T. gondii ME49 and N. caninum Nc-Liv, exposure of cultures to BKI-1294 resulted in the elevated expression of mRNA coding for the bradyzoite marker BAG1. Unlike in bradyzoites, SAG1 expression was not repressed. Immunofluorescence also showed that these multinucleated complexes expressed SAG1 and BAG1 and the monoclonal antibody CC2, which binds to a yet unidentified bradyzoite antigen, also exhibited increased labeling. In a pregnant mouse model, BKI-1294 efficiently inhibited vertical transmission in BALB/c mice experimentally infected with one of the two virulent isolates Nc-Liv or Nc-Spain7, demonstrating proof of concept that this compound protected offspring from vertical transmission and disease. The observed deregulated antigen expression effect may enhance the immune response during BKI-1294 therapy and will be the subject of future studies.
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