ArticleInternational journal for parasitology. Drugs and drug resistance2014
Compound library screening identified Akt/PKB kinase pathway inhibitors as potential key molecules for the development of new chemotherapeutics against schistosomiasis.
Article in International journal for parasitology. Drugs and drug resistance, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed.
- An insulin-like signalling pathway model for Fasciola gigantica.BMC veterinary research · 2024Article
- Identifying potential drug targets in the kinomes of two monogenean species.Helminthologia · 2024Article
- Structural investigation of Trypanosoma cruzi Akt-like kinase as drug target against Chagas disease.Scientific reports · 2024Article
- A Broad Spectrum Antiparasitic Activity of Organotin (IV) Derivatives and Its Untargeted Proteomic Profiling UsingPathogens (Basel, Switzerland) · 2022Article
- The role of PI3'-lipid signalling in melanoma initiation, progression and maintenance.Experimental dermatology · 2022Review
- A survey of the kinome pharmacopeia reveals multiple scaffolds and targets for the development of novel anthelmintics.Scientific reports · 2021Article
- Article
- Cloning and functional complementation of ten Schistosoma mansoni phosphodiesterases expressed in the mammalian host stages.PLoS neglected tropical diseases · 2020Article
- Deep phosphoproteome analysis of Schistosoma mansoni leads development of a kinomic array that highlights sex-biased differences in adult worm protein phosphorylation.PLoS neglected tropical diseases · 2020Article
- UHPLC-MS-Based Metabolomics Analysis Reveals the Process of Schistosomiasis in Mice.Frontiers in microbiology · 2020Article
- Targeting Kinases inFrontiers in veterinary science · 2020Article
- Reference gene analysis and its use for kinase expression profiling in Fasciola hepatica.Scientific reports · 2019Article
- Design, Synthesis, and Characterization of Novel Small Molecules as Broad Range Antischistosomal Agents.ACS medicinal chemistry letters · 2018Article
- Glucose Uptake in the Human Pathogen Schistosoma mansoni Is Regulated Through Akt/Protein Kinase B Signaling.The Journal of infectious diseases · 2018Article
- Screening a repurposing library, the Medicines for Malaria Venture Stasis Box, against Schistosoma mansoni.Parasites & vectors · 2018Article
- The cholinomimetic morantel as an open channel blocker of the Ascaris suum ACR-16 nAChR.Invertebrate neuroscience : IN · 2016Article
- Compounds Derived from the Bhutanese Daisy, Ajania nubigena, Demonstrate Dual Anthelmintic Activity against Schistosoma mansoni and Trichuris muris.PLoS neglected tropical diseases · 2016Article
- Structure-Bioactivity Relationship for Benzimidazole Thiophene Inhibitors of Polo-Like Kinase 1 (PLK1), a Potential Drug Target in Schistosoma mansoni.PLoS neglected tropical diseases · 2016Article
- Defining the Schistosoma haematobium kinome enables the prediction of essential kinases as anti-schistosome drug targets.Scientific reports · 2015Article
- Venus Kinase Receptors at the Crossroads of Insulin Signaling: Their Role in Reproduction for Helminths and Insects.Frontiers in endocrinology · 2015Review
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6 authors.
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Abstract
Protein kinases (PKs) are one of the largest protein families in most eukaryotic organisms. These enzymes are involved in the control of cell proliferation, differentiation and metabolism and a large number of the anticancer drugs currently used are directed against PKs. The structure and function of PKs are well conserved throughout evolution. In schistosome parasites, PKs were shown to be involved in essential functions at every stage of the parasite life cycle, making these enzymes promising anti-parasite drug targets. In this study, we tested a panel of commercial inhibitors for various PKs and analyzed their effects on pairing and egg production by schistosomes as well as their toxicity towards schistosomula larvae. Results obtained confirmed the deleterious effect of PK targeting on Schistosoma mansoni physiology and the important function of different tyrosine and serine/threonine kinases in the biology and reproduction of this parasite. They also indicated for the first time that the Protein kinase B (also called Akt) which is a major downstream target of many receptor tyrosine kinases and a central player at the crossroads of signal transduction pathways activated in response to growth factors and insulin, can constitute a novel target for anti-schistosome chemotherapy. Structural and functional studies have shown that SmAkt is a conserved kinase and that its activity can be inhibited by commercially available Akt inhibitors. In treated adult worms, Akt/PKB kinase pathway inhibitors induced profound alterations in pairing and egg laying and they also greatly affected the viability of schistosomula larvae.
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