ArticleAntimicrobial agents and chemotherapy2008
Glycogen synthase kinase 3 is a potential drug target for African trypanosomiasis therapy.
Article in Antimicrobial agents and chemotherapy, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers.
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46 citing papers in PubMed, 92 citations in OpenAlex.
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- Translational control byRNA (New York, N.Y.) · 2023Article
- Development of a 2,4-Diaminothiazole Series for the Treatment of Human African Trypanosomiasis Highlights the Importance of Static-Cidal Screening of Analogues.Journal of medicinal chemistry · 2023Article
- Targeted protein degradation might present a novel therapeutic approach in the fight against African trypanosomiasis.European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences · 2023Article
- The critical role of mode of action studies in kinetoplastid drug discovery.Frontiers in drug discovery · 2023Article
- Repurposing the Kinase Inhibitor Mavelertinib for Giardiasis Therapy.Antimicrobial agents and chemotherapy · 2022Article
- Naphthoquinone as a New Chemical Scaffold for Leishmanicidal Inhibitors ofBiomedicines · 2022Article
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- Identification of Schistosoma japonicum GSK3β interacting partners by yeast two-hybrid screening and its role in parasite survival.Parasitology research · 2020Article
- Selectivity and Physicochemical Optimization of Repurposed Pyrazolo[1,5-Journal of medicinal chemistry · 2020Article
- A Radioactive-free Kinase Inhibitor Discovery Assay Against theBio-protocol · 2020Article
- Indirubin Analogues InhibitAntimicrobial agents and chemotherapy · 2019Article
- Molecular cloning and transcriptional and functional analysis of glycogen synthase kinase-3β in Haemaphysalis longicornis (Acari, Ixodidae).Parasite (Paris, France) · 2019Article
- Unveiling the Kinomes ofComputational and structural biotechnology journal · 2019Article
- Kinome chemoproteomics characterization of pyrrolo[3,4-c]pyrazoles as potent and selective inhibitors of glycogen synthase kinase 3.Molecular omics · 2018Article
- Identification of a RAC/AKT-like gene in Leishmania parasites as a putative therapeutic target in leishmaniasis.Parasites & vectors · 2017Article
- Glycogen Synthase Kinase 3β Promotes the Endocytosis of Transferrin in the African Trypanosome.ACS infectious diseases · 2016Article
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Authors and funding
12 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Development of a safe, effective, and inexpensive therapy for African trypanosomiasis is an urgent priority. In this study, we evaluated the validity of Trypanosoma brucei glycogen synthase kinase 3 (GSK-3) as a potential drug target. Interference with the RNA of either of two GSK-3 homologues in bloodstream-form T. brucei parasites led to growth arrest and altered parasite morphology, demonstrating their requirement for cell survival. Since the growth arrest after RNA interference appeared to be more profound for T. brucei GSK-3 "short" (Tb10.161.3140) than for T. brucei GSK-3 "long" (Tb927.7.2420), we focused on T. brucei GSK-3 short for further studies. T. brucei GSK-3 short with an N-terminal maltose-binding protein fusion was cloned, expressed, and purified in a functional form. The potency of a GSK-3-focused inhibitor library against the recombinant enzyme of T. brucei GSK-3 short, as well as bloodstream-form parasites, was evaluated with the aim of determining if compounds that inhibit enzyme activity could also block the parasites' growth and proliferation. Among the compounds active against the cell, there was an excellent correlation between activity inhibiting the T. brucei GSK-3 short enzyme and the inhibition of T. brucei growth. Thus, there is reasonable genetic and chemical validation of GSK-3 short as a drug target for T. brucei. Finally, selective inhibition may be required for therapy targeting the GSK-3 enzyme, and a molecular model of the T. brucei GSK-3 short enzyme suggests that compounds that selectively inhibit T. brucei GSK-3 short over the human GSK-3 enzymes can be found.
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