ArticleJournal of medicinal chemistry2017
Inhibition of Calcium Dependent Protein Kinase 1 (CDPK1) by Pyrazolopyrimidine Analogs Decreases Establishment and Reoccurrence of Central Nervous System Disease by Toxoplasma gondii.
Article in Journal of medicinal chemistry, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers, 1 of them a synthesis that pooled it.
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Who cites it
30 citing papers in PubMed, 1 synthesis or guideline pooled it, 69 citations in OpenAlex.
- Activities of anti-Toxoplasma drugs and compounds against tissue cysts in the last three decades (1987 to 2017), a systematic review.Parasitology research · 2018Pooled it
- Lead Optimization of TgCDPK1 Inhibitors for the Treatment of Toxoplasmosis.Journal of medicinal chemistry · 2026Article
- Potential Molecular Targets of the Broad-Range Antimicrobial Peptide Tyrothricin in the Apicomplexan ParasiteBiomedicines · 2026Article
- Structure-Based Drug Design of Novel Heterocyclic Scaffolds as TgCDPK1 Inhibitors.ChemMedChem · 2025Article
- Computational Structural Comparison of Toxoplasma gondii CDPK1 and Human BUB1 kinases: Implications for Selective Inhibitor Design.ACS omega · 2025Article
- Small molecule kinase inhibitor altiratinib inhibits brain cyst forming bradyzoites of Toxoplasma gondii.Journal of microbiology (Seoul, Korea) · 2025Article
- Construction of luciferase-expressing Neospora caninum and drug screening.Parasites & vectors · 2024Article
- Identification of Coumarin-Chalcone and Coumarin-Pyrazoline Derivatives as Novel Anti-Drug design, development and therapy · 2024Article
- LIMS-Kinase provides sensitive and generalizable label-freeCell reports. Physical science · 2023Article
- Global profiling of protein lysine malonylation in Toxoplasma gondii strains of different virulence and genetic backgrounds.PLoS neglected tropical diseases · 2022Article
- Bicyclic azetidines target acute and chronic stages of Toxoplasma gondii by inhibiting parasite phenylalanyl t-RNA synthetase.Nature communications · 2022Article
- Characterization of Calcium-Dependent Protein Kinase 2A, a Potential Drug Target Against Cryptosporidiosis.Frontiers in microbiology · 2022Article
- Toxoplasmosis: Current and Emerging Parasite Druggable Targets.Microorganisms · 2021Review
- 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
- Promising Drug Targets and Compounds with Anti-Microorganisms · 2021Review
- Toxoplasma gondii infection and its implications within the central nervous system.Nature reviews. Microbiology · 2021Review
- Protein kinases in Toxoplasma gondii.International journal for parasitology · 2021Review
- Orally Bioavailable Endochin-Like Quinolone Carbonate Ester Prodrug Reduces Toxoplasma gondii Brain Cysts.Antimicrobial agents and chemotherapy · 2020Article
- Discovery and Optimization of Triazine Nitrile Inhibitors ofACS chemical neuroscience · 2020Article
- Optimizing Pyrazolopyrimidine Inhibitors of Calcium Dependent Protein Kinase 1 for Treatment of Acute and Chronic Toxoplasmosis.Journal of medicinal chemistry · 2020Article
Corrections and comments
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Authors and funding
14 authors at 3 institutions in 2 countries.
Funding
Abstract
Calcium dependent protein kinase 1 (CDPK1) is an essential enzyme in the opportunistic pathogen Toxoplasma gondii. CDPK1 controls multiple processes that are critical to the intracellular replicative cycle of T. gondii including secretion of adhesins, motility, invasion, and egress. Remarkably, CDPK1 contains a small glycine gatekeeper residue in the ATP binding pocket making it sensitive to ATP-competitive inhibitors with bulky substituents that complement this expanded binding pocket. Here we explored structure-activity relationships of a series of pyrazolopyrimidine inhibitors of CDPK1 with the goal of increasing selectivity over host enzymes, improving antiparasite potency, and improving metabolic stability. The resulting lead compound 24 exhibited excellent enzyme inhibition and selectivity for CDPK1 and potently inhibited parasite growth in vitro. Compound 24 was also effective at treating acute toxoplasmosis in the mouse, reducing dissemination to the central nervous system, and decreasing reactivation of chronic infection in severely immunocompromised mice. These findings provide proof of concept for the development of small molecule inhibitors of CDPK1 for treatment of CNS toxoplasmosis.
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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.