ArticleJournal of medicinal chemistry2013
Optimizing small molecule inhibitors of calcium-dependent protein kinase 1 to prevent infection by Toxoplasma gondii.
Article in Journal of medicinal chemistry, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers, 1 of them a synthesis that pooled it.
What it found
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
46 citing papers in PubMed, 1 synthesis or guideline pooled it.
- 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
- Structure-Based Drug Design of Novel Heterocyclic Scaffolds as TgCDPK1 Inhibitors.ChemMedChem · 2025Article
- TKL family kinases in human apicomplexan pathogens.Molecular and biochemical parasitology · 2024Review
- 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
- 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 Antiparasitic Activity ofMolecules (Basel, Switzerland) · 2022Article
- Bicyclic azetidines target acute and chronic stages of Toxoplasma gondii by inhibiting parasite phenylalanyl t-RNA synthetase.Nature communications · 2022Article
- Promising Drug Targets and Compounds with Anti-Microorganisms · 2021Review
- Protein kinases in Toxoplasma gondii.International journal for parasitology · 2021Review
- Dual-Stage Picolinic Acid-Derived Inhibitors ofACS medicinal chemistry letters · 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
- Identifying the Target of an Antiparasitic Compound inACS chemical biology · 2020Article
- Optimizing Pyrazolopyrimidine Inhibitors of Calcium Dependent Protein Kinase 1 for Treatment of Acute and Chronic Toxoplasmosis.Journal of medicinal chemistry · 2020Article
- Two old drugs, NVP-AEW541 and GSK-J4, repurposed against the Toxoplasma gondii RH strain.Parasites & vectors · 2020Article
- The effect of edelfosine on GRA1 and MIC3 expressions in acute toxoplasmosis.Parasitology research · 2020Article
- The Impact of BKI-1294 Therapy in Mice Infected With the Apicomplexan ParasiteFrontiers in veterinary science · 2020Article
- Discovery of Selective Toxoplasma gondii Dihydrofolate Reductase Inhibitors for the Treatment of Toxoplasmosis.Journal of medicinal chemistry · 2019Article
Corrections and comments
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Authors and funding
9 authors.
Funding
Abstract
Toxoplasma gondii is sensitive to bulky pyrazolo [3,4-d] pyrimidine (PP) inhibitors due to the presence of a Gly gatekeeper in the essential calcium dependent protein kinase 1 (CDPK1). Here we synthesized a number of new derivatives of 3-methyl-benzyl-PP (3-MB-PP, or 1). The potency of PP analogues in inhibiting CDPK1 enzyme activity in vitro (low nM IC(50) values) and blocking parasite growth in host cell monolayers in vivo (low μM EC(50) values) were highly correlated and occurred in a CDPK1-specific manner. Chemical modification of the PP scaffold to increase half-life in the presence of microsomes in vitro led to identification of compounds with enhanced stability while retaining activity. Several of these more potent compounds were able to prevent lethal infection with T. gondii in the mouse model. Collectively, the strategies outlined here provide a route for development of more effective compounds for treatment of toxoplasmosis and perhaps related parasitic diseases.
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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.