ArticleJournal of medicinal chemistry2012
Multiple determinants for selective inhibition of apicomplexan calcium-dependent protein kinase CDPK1.
Article in Journal of medicinal chemistry, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 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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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
44 citing papers in PubMed, 70 citations in OpenAlex.
- 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
- Bioactive Cyclopeptide Alkaloids and Ceanothane Triterpenoids fromMolecules (Basel, Switzerland) · 2025Article
- Anti-Cryptosporidium efficacy of BKI-1708, an inhibitor of Cryptosporidium calcium-dependent protein kinase 1.PLoS neglected tropical diseases · 2025Article
- Computational Structural Comparison of Toxoplasma gondii CDPK1 and Human BUB1 kinases: Implications for Selective Inhibitor Design.ACS omega · 2025Article
- Computational screening of FDA-approved drugs to identify potential TgDHFR, TgPRS, and TgCDPK1 proteins inhibitors against Toxoplasma gondii.Scientific reports · 2023Article
- Protein kinases in Toxoplasma gondii.International journal for parasitology · 2021Review
- CDPKs: The critical decoders of calcium signal at various stages of malaria parasite development.Computational and structural biotechnology journal · 2021Review
- Comparative assessment of the effects of bumped kinase inhibitors on early zebrafish embryo development and pregnancy in mice.International journal of antimicrobial agents · 2020Article
- Three-Dimensional Interactions Analysis of the Anticancer Target c-Src Kinase with Its Inhibitors.Cancers · 2020Review
- Taming the Boys for Global Good: Contraceptive Strategy to Stop Malaria Transmission.Molecules (Basel, Switzerland) · 2020Review
- Optimizing Pyrazolopyrimidine Inhibitors of Calcium Dependent Protein Kinase 1 for Treatment of Acute and Chronic Toxoplasmosis.Journal of medicinal chemistry · 2020Article
- Bumped Kinase Inhibitors as therapy for apicomplexan parasitic diseases: lessons learned.International journal for parasitology · 2020Review
- The Impact of BKI-1294 Therapy in Mice Infected With the Apicomplexan ParasiteFrontiers in veterinary science · 2020Article
- Loss in efficacy measures of tolfenamic acid in a tau knock-out model: Relevance to Alzheimer's disease.Experimental biology and medicine (Maywood, N.J.) · 2019Article
- Bumped kinase inhibitor 1369 is effective against Cystoisospora suis in vivo and in vitro.International journal for parasitology. Drugs and drug resistance · 2019Article
- Protein targets of thiazolidinone derivatives in Toxoplasma gondii and insights into their binding to ROP18.BMC genomics · 2018Article
- In vitro growth inhibition of Theileria equi by bumped kinase inhibitors.Veterinary parasitology · 2018Article
- Inhibition of Calcium Dependent Protein Kinase 1 (CDPK1) by Pyrazolopyrimidine Analogs Decreases Establishment and Reoccurrence of Central Nervous System Disease by Toxoplasma gondii.Journal of medicinal chemistry · 2017Article
- Extended-spectrum antiprotozoal bumped kinase inhibitors: A review.Experimental parasitology · 2017Review
Corrections and comments
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Authors and funding
19 authors at 1 institution in 1 country.
Funding
Abstract
Diseases caused by the apicomplexan protozoans Toxoplasma gondii and Cryptosporidium parvum are a major health concern. The life cycle of these parasites is regulated by a family of calcium-dependent protein kinases (CDPKs) that have no direct homologues in the human host. Fortuitously, CDPK1 from both parasites contains a rare glycine gatekeeper residue adjacent to the ATP-binding pocket. This has allowed creation of a series of C3-substituted pyrazolopyrimidine compounds that are potent inhibitors selective for CDPK1 over a panel of human kinases. Here we demonstrate that selectivity is further enhanced by modification of the scaffold at the C1 position. The explanation for this unexpected result is provided by crystal structures of the inhibitors bound to CDPK1 and the human kinase c-SRC. Furthermore, the insight gained from these studies was applied to transform an alternative ATP-competitive scaffold lacking potency and selectivity for CDPK1 into a low nanomolar inhibitor of this enzyme with no activity against SRC.
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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.