ArticlePloS one2014
Neospora caninum calcium-dependent protein kinase 1 is an effective drug target for neosporosis therapy.
Article in PloS one, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 50 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
50 citing papers in PubMed, 72 citations in OpenAlex.
- Chemical genetics reveals Leishmania KKT2 and CRK9 kinase activity is required for cell cycle progression.PLoS pathogens · 2026Article
- Review
- Computational Structural Comparison of Toxoplasma gondii CDPK1 and Human BUB1 kinases: Implications for Selective Inhibitor Design.ACS omega · 2025Article
- Review of neosporosis: Disease insights and control approaches.Open veterinary journal · 2025Review
- Proteome changes duringFrontiers in cellular and infection microbiology · 2025Article
- Molecular Targets of the 5-Amido-Carboxamide Bumped Kinase Inhibitor BKI-1748 inInternational journal of molecular sciences · 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
- Temporal transcriptomic changes in microRNAs involved in the host immune response and metabolism during Neospora caninum infection.Parasites & vectors · 2023Article
- Repurposing the Kinase Inhibitor Mavelertinib for Giardiasis Therapy.Antimicrobial agents and chemotherapy · 2022Article
- The interaction between free CaParasitology research · 2022Article
- Common Molecular Targets of a Quinolone Based Bumped Kinase Inhibitor inInternational journal of molecular sciences · 2022Article
- Vaccine-Linked Chemotherapy Approach: Additive Effects of Combining theFrontiers in veterinary science · 2022Article
- Endochin-like quinolones (ELQs) and bumped kinase inhibitors (BKIs): Synergistic and additive effects of combined treatments against Neospora caninum infection in vitro and in vivo.International journal for parasitology. Drugs and drug resistance · 2021Article
- Drug Target Validation of the Protein KinaseMicrobiology spectrum · 2021Article
- In vitro activity, safety and in vivo efficacy of the novel bumped kinase inhibitor BKI-1748 in non-pregnant and pregnant mice experimentally infected with Neospora caninum tachyzoites and Toxoplasma gondii oocysts.International journal for parasitology. Drugs and drug resistance · 2021Article
- Microneme Protein 6 Is Involved in Invasion and Egress byPathogens (Basel, Switzerland) · 2021Article
- One health therapeutics: Target-Based drug development for cryptosporidiosis and other apicomplexa diseases.Veterinary parasitology · 2021Review
- Reduced treatment frequencies with bumped kinase inhibitor 1369 are effective against porcine cystoisosporosis.International journal for parasitology. Drugs and drug resistance · 2020Article
- Comparative assessment of the effects of bumped kinase inhibitors on early zebrafish embryo development and pregnancy in mice.International journal of antimicrobial agents · 2020Article
- Taming the Boys for Global Good: Contraceptive Strategy to Stop Malaria Transmission.Molecules (Basel, Switzerland) · 2020Review
Corrections and comments
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Authors and funding
14 authors at 2 institutions in 2 countries.
Funding
Abstract
Despite the enormous economic importance of Neospora caninum related veterinary diseases, the number of effective therapeutic agents is relatively small. Development of new therapeutic strategies to combat the economic impact of neosporosis remains an important scientific endeavor. This study demonstrates molecular, structural and phenotypic evidence that N. caninum calcium-dependent protein kinase 1 (NcCDPK1) is a promising molecular target for neosporosis drug development. Recombinant NcCDPK1 was expressed, purified and screened against a select group of bumped kinase inhibitors (BKIs) previously shown to have low IC50s against Toxoplasma gondii CDPK1 and T. gondii tachyzoites. NcCDPK1 was inhibited by low concentrations of BKIs. The three-dimensional structure of NcCDPK1 in complex with BKIs was studied crystallographically. The BKI-NcCDPK1 structures demonstrated the structural basis for potency and selectivity. Calcium-dependent conformational changes in solution as characterized by small-angle X-ray scattering are consistent with previous structures in low Calcium-state but different in the Calcium-bound active state than predicted by X-ray crystallography. BKIs effectively inhibited N. caninum tachyzoite proliferation in vitro. Electron microscopic analysis of N. caninum cells revealed ultra-structural changes in the presence of BKI compound 1294. BKI compound 1294 interfered with an early step in Neospora tachyzoite host cell invasion and egress. Prolonged incubation in the presence of 1294 interfered produced observable interference with viability and replication. Oral dosing of BKI compound 1294 at 50 mg/kg for 5 days in established murine neosporosis resulted in a 10-fold reduced cerebral parasite burden compared to untreated control. Further experiments are needed to determine the PK, optimal dosage, and duration for effective treatment in cattle and dogs, but these data demonstrate proof-of-concept for BKIs, and 1294 specifically, for therapy of bovine and canine neosporosis.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.