Academic Journal
Transient receptor potential channel activation targets multiple stages of the schistosome parasite.
| Τίτλος: | Transient receptor potential channel activation targets multiple stages of the schistosome parasite. |
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| Συγγραφείς: | Kulkarni S; EMD Serono Research and Development Institute Inc. (a Business of Merck KGaA., Darmstadt, Germany), Billerica, MA, USA., Park SK; Department of Cell Biology, Neurobiology and Anatomy, Medical College of Wisconsin, Milwaukee, WI, USA., Hamway Y; Institute for Medical Microbiology, Immunology and Hygiene, Technical University of Munich, Munich, Germany.; Center for Global Health, TUM School of Medicine, Technical University of Munich, Munich, Germany.; German Center for Infection and Research (DZIF), Partner site Munich, Munich, Germany., Friedrich L; Computational Chemistry and Biology, Global Research and Development, Discovery Technologies, the Healthcare Business of Merck KGaA, Darmstadt, Germany., Kaiser J; Computational Chemistry and Biology, Global Research and Development, Discovery Technologies, the Healthcare Business of Merck KGaA, Darmstadt, Germany., Chulkov EG; Department of Cell Biology, Neurobiology and Anatomy, Medical College of Wisconsin, Milwaukee, WI, USA., Rohr CM; Department of Cell Biology, Neurobiology and Anatomy, Medical College of Wisconsin, Milwaukee, WI, USA., Häberli C; Universität Basel, Basel, Switzerland.; Swiss Tropical and Public Health Institute, Allschwil, Switzerland., Horn M; Institute of Organic Chemistry and Biochemistry, Czech Academy of Sciences, Prague, Czechia., Bäurle THH; Site Management-Analytics, Merck Healthcare KGaA, Darmstadt, Germany., Pellegatti M; External consultant, Verona, Italy., Grosser G; Chemical and Preclinical Safety, Merck Healthcare KGaA, Darmstadt, Germany., Becker A; Site Management-Analytics, Merck Healthcare KGaA, Darmstadt, Germany., Afshar R; Global Health R&D of the Healthcare Business of Merck KGaA, Darmstadt, Germany, Ares Trading S.A. (an affiliate of Merck KGaA, Darmstadt, Germany), Eysins, Switzerland., Becker A; Translational Medicine, Quantitative Pharmacology, the Healthcare Business of Merck KGaA, Darmstadt, Germany., Mell NA; Global Healthcare Operations, Global CMC Development, Merck Healthcare KGaA, Darmstadt, Germany., Lignet F; Drug Discovery Technologies, the Healthcare Business of Merck KGaA, Darmstadt, Germany., Hewitt P; Chemical and Preclinical Safety, Merck Healthcare KGaA, Darmstadt, Germany., Hansen A; Chemical and Preclinical Safety, Merck Healthcare KGaA, Darmstadt, Germany., Brenneis C; Chemical and Preclinical Safety, Merck Healthcare KGaA, Darmstadt, Germany., Dvorak J; Institute of Organic Chemistry and Biochemistry, Czech Academy of Sciences, Prague, Czechia.; Department of Ecology, Center of Infectious Animal Diseases, Faculty of Environmental Sciences, Czech University of Life Sciences, Prague, Czechia., da Costa CP; Institute for Medical Microbiology, Immunology and Hygiene, Technical University of Munich, Munich, Germany.; Center for Global Health, TUM School of Medicine, Technical University of Munich, Munich, Germany.; German Center for Infection and Research (DZIF), Partner site Munich, Munich, Germany., Keiser J; Universität Basel, Basel, Switzerland.; Swiss Tropical and Public Health Institute, Allschwil, Switzerland., Marchant JS; Department of Cell Biology, Neurobiology and Anatomy, Medical College of Wisconsin, Milwaukee, WI, USA., Spangenberg T; Global Health R&D of the Healthcare Business of Merck KGaA, Darmstadt, Germany, Ares Trading S.A. (an affiliate of Merck KGaA, Darmstadt, Germany), Eysins, Switzerland. |
| Πηγή: | Science translational medicine [Sci Transl Med] 2026 Oct 07; Vol. 18 (870), pp. eaed8353. Date of Electronic Publication: 2026 Oct 07. |
| Τύπος έκδοσης: | Journal Article |
| Γλώσσα: | English |
| Στοιχεία περιοδικού: | Publisher: American Association for the Advancement of Science Country of Publication: United States NLM ID: 101505086 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1946-6242 (Electronic) Linking ISSN: 19466234 NLM ISO Abbreviation: Sci Transl Med Subsets: MEDLINE |
| Imprint Name(s): | Original Publication: Washington, DC : American Association for the Advancement of Science |
| Ιατρικοί όροι (MeSH): | Transient Receptor Potential Channels*/metabolism , Life Cycle Stages*/drug effects , Schistosoma mansoni*/drug effects , Schistosoma mansoni*/growth & development , Schistosoma mansoni*/metabolism , Schistosoma*/drug effects, Praziquantel/pharmacology ; Praziquantel/therapeutic use ; Prodrugs/pharmacology ; Prodrugs/chemistry ; Animals ; Mice ; Humans |
| Περίληψη: | Schistosomiasis, a neglected tropical disease caused by infection with parasitic blood flukes of the genus Schistosoma, affects more than 250 million people worldwide. Currently, patients rely on a single medicine, praziquantel (PZQ), discovered half a century ago. To combat drug resistance and reach elimination of the schistosome parasite, alternative drugs to PZQ are required that treat and prevent disease. Here, we describe a drug candidate, M5493, with potent activity against multiple parasite life cycle stages. The target is a parasite transient receptor potential ion channel, distinct from the target of PZQ. To circumvent its limited bioavailability, the active agent was converted to prodrug M5493, which displayed robust activity against the schistosome parasite at doses as low as 5 milligrams per kilogram in mice infected with Schistosoma mansoni. Unlike the benzodiazepine meclonazepam, which displays clinical antihelminthic activity through the same target, M5493 showed no sedating side effects given that it did not engage GABA |
| Substance Nomenclature: | 0 (Transient Receptor Potential Channels) 6490C9U457 (Praziquantel) 0 (Prodrugs) |
| Entry Date(s): | Date Created: 20261007 Date Completed: 20261007 Latest Revision: 20261007 |
| Update Code: | 20261008 |
| DOI: | 10.1126/scitranslmed.aed8353 |
| PMID: | 42842722 |
| Βάση Δεδομένων: | MEDLINE |
| ISSN: | 1946-6242 |
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| DOI: | 10.1126/scitranslmed.aed8353 |