ArticleScientific reports2019
High-throughput screening of the Plasmodium falciparum cGMP-dependent protein kinase identified a thiazole scaffold which kills erythrocytic and sexual stage parasites.
Article in Scientific reports, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers, 1 of them a synthesis that pooled it.
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Who cites it
31 citing papers in PubMed, 1 synthesis or guideline pooled it, 55 citations in OpenAlex.
- High-throughput screening and meta-analysis for lead compounds in antimalarial drug discovery.Malaria journal · 2025Pooled it
- New thinking for the next generation of antimalarials.EMBO molecular medicine · 2026Review
- Accessing invasion-competent Plasmodium vivax merozoites reveals antibody-dependent NK cell activation.Research square · 2026Article
- Collateral hypersensitivity between ZY19489 and piperaquine neutralizes PfCRT-mediated drug efflux and Plasmodium falciparum resistance.Nature communications · 2026Article
- Article
- Structure, Mutation, Functional Domain Roles and Medical Implications of Glycerol Kinase.The protein journal · 2026Review
- Developments and challenges in hit progression within fragment-based drug discovery.Nature communications · 2026Review
- Article
- Activation loop phosphorylation and cGMP saturation of PKG regulate egress of malaria parasites.PLoS pathogens · 2024Article
- Review
- A Review on Synthetic Thiazole Derivatives as an Antimalarial Agent.Current drug discovery technologies · 2024Review
- Review
- Dephospho-Coenzyme A Kinase Is an Exploitable Drug Target against Plasmodium falciparum: Identification of Selective Inhibitors by High-Throughput Screening of a Large Chemical Compound Library.Antimicrobial agents and chemotherapy · 2022Article
- 1,3-Diarylpyrazolyl-acylsulfonamides Target HadAB/BC Complex inACS infectious diseases · 2022Article
- The anticancer human mTOR inhibitor sapanisertib potently inhibits multipleScience translational medicine · 2022Article
- Thiazole: A Versatile Standalone Moiety Contributing to the Development of Various Drugs and Biologically Active Agents.Molecules (Basel, Switzerland) · 2022Review
- Characterization of Competitive Inhibitors of Plasmodium falciparum cGMP-Dependent Protein Kinase.Chembiochem : a European journal of chemical biology · 2022Article
- Transporter-Mediated Solutes Uptake as Drug Target inFrontiers in pharmacology · 2022Review
- Discovery of Imidazole-Based Inhibitors ofACS medicinal chemistry letters · 2021Article
- The multi-target aspect of an MmpL3 inhibitor: The BM212 series of compounds bind EthR2, a transcriptional regulator of ethionamide activation.Cell surface (Amsterdam, Netherlands) · 2021Article
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 2 countries.
Funding
Abstract
Antimalarial drug resistance compels the quest for new compounds that target alternative pathways to current drugs. The Plasmodium cyclic GMP-dependent protein kinase (PKG) has essential functions in all of the major life cycle developmental stages. An imidazopyridine PKG inhibitor scaffold was previously shown to clear P. falciparum infection in a rodent model in vivo and blocked transmission to mosquitoes providing proof of concept for this target. To find new classes of PKG inhibitors to serve as alternative chemical starting points, we performed a high-throughput screen of the GSK Full Diversity Collection using recombinant P. falciparum PKG. We developed a robust enzymatic assay in a 1536-well plate format. Promising compounds were then tested for activity against P. falciparum asexual blood stage growth, selectivity and cytotoxicity. By using a scoring system we selected the 66 most promising PKG inhibitors (comprising nine clusters and seven singletons). Among these, thiazoles were the most potent scaffold with mid-nanomolar activity on P. falciparum blood stage and gamete development. Using Kinobeads profiling we identified additional P. falciparum protein kinases targeted by the thiazoles that mediate a faster speed of the kill than PKG-selective compounds. This scaffold represents a promising starting point to develop a new antimalarial.
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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.