ArticleJournal of medicinal chemistry2014
Optimization of an imidazopyridazine series of inhibitors of Plasmodium falciparum calcium-dependent protein kinase 1 (PfCDPK1).
Article in Journal of medicinal chemistry, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers, 1 of them a synthesis that pooled it.
What it found
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The trial behind it
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
25 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Plasmodial Kinase Inhibitors Targeting Malaria: Recent Developments.Molecules (Basel, Switzerland) · 2020Pooled it
- Imidazo[1,2‑ACS omega · 2026Review
- Development and experimental validation of a machine learning model for the prediction of new antimalarials.BMC chemistry · 2025Article
- Innovations in Antimalarial Drug Discovery: New Targets and Leads.Current drug targets · 2025Review
- Photoinduced Site-Selective Aryl C-H Borylation with Electron-Donor-Acceptor Complex Derived from BMolecules (Basel, Switzerland) · 2024Article
- Biological evaluation of novel side chain containing CQTrICh-analogs as antimalarials and their development asHeliyon · 2024Article
- Adapt or Die: Targeting Unique Transmission-Stage Biology for Malaria Elimination.Frontiers in cellular and infection microbiology · 2022Review
- CDPKs: The critical decoders of calcium signal at various stages of malaria parasite development.Computational and structural biotechnology journal · 2021Review
- An Update on Development of Small-Molecule Plasmodial Kinase Inhibitors.Molecules (Basel, Switzerland) · 2020Review
- Targeting the Malaria Parasite cGMP-Dependent Protein Kinase to Develop New Drugs.Frontiers in microbiology · 2020Review
- Malaria and tuberculosis as diseases of neglected populations: state of the art in chemotherapy and advances in the search for new drugs.Memorias do Instituto Oswaldo Cruz · 2020Review
- Antimalarial Drug Resistance and Novel Targets for Antimalarial Drug Discovery.Infection and drug resistance · 2020Review
- Potent bicyclic inhibitors of malarial cGMP-dependent protein kinase: approaches to combining improvements in cell potency, selectivity and structural novelty.Bioorganic & medicinal chemistry letters · 2019Article
- Sustainable Synthetic Approach for (Pyrazol-4-ylidene)pyridines By Metal Catalyst-Free Aerobic C(spACS omega · 2019Article
- Targeting malaria parasite invasion of red blood cells as an antimalarial strategy.FEMS microbiology reviews · 2019Review
- Potent inhibitors of malarial P. Falciparum protein kinase G: Improving the cell activity of a series of imidazopyridines.Bioorganic & medicinal chemistry letters · 2019Article
- l-Proline catalyzed one-pot synthesis of polysubstituted pyridine system incorporating benzothiazole moietyRSC advances · 2018Article
- Plasmodial Kinase Inhibitors: License to Cure?Journal of medicinal chemistry · 2018Article
- Synthesis and biological evaluation of imidazo[1,2-[Formula: see text]]pyridazines as inhibitors of TNF-[Formula: see text] production.Molecular diversity · 2018Article
- Screening the Medicines for Malaria Venture Pathogen Box across Multiple Pathogens Reclassifies Starting Points for Open-Source Drug Discovery.Antimicrobial agents and chemotherapy · 2017Article
Corrections and comments
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Authors and funding
11 authors.
Funding
Abstract
A structure-guided design approach using a homology model of Plasmodium falciparum calcium-dependent protein kinase 1 (PfCDPK1) was used to improve the potency of a series of imidazopyridazine inhibitors as potential antimalarial agents. This resulted in high affinity compounds with PfCDPK1 enzyme IC50 values less than 10 nM and in vitro P. falciparum antiparasite EC50 values down to 12 nM, although these compounds did not have suitable ADME properties to show in vivo efficacy in a mouse model. Structural modifications designed to address the ADME issues, in particular permeability, were initially accompanied by losses in antiparasite potency, but further optimization allowed a good balance in the compound profile to be achieved. Upon testing in vivo in a murine model of efficacy against malaria, high levels of compound exposure relative to their in vitro activities were achieved, and the modest efficacy that resulted raises questions about the level of effect that is achievable through the targeting of PfCDPK1.
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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.