ArticlePLoS neglected tropical diseases2014
Imatinib treatment causes substantial transcriptional changes in adult Schistosoma mansoni in vitro exhibiting pleiotropic effects.
Article in PLoS neglected tropical diseases, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 32 citations in OpenAlex.
- Evaluation of Imatinib and Its Combination With Albendazole AgainstJournal of parasitology research · 2026Article
- Assessment of reference genes at six different developmental stages of Schistosoma mansoni for quantitative RT-PCR.Scientific reports · 2021Article
- High-resolution AP-SMALDI MSI as a tool for drug imaging in Schistosoma mansoni.Analytical and bioanalytical chemistry · 2021Article
- Protein Kinases: Potential Drug Targets AgainstFrontiers in cellular and infection microbiology · 2021Review
- Drug-induced reactive oxygen species-mediated inhibitory effect on growth of Trypanosoma evansi in axenic culture system.Parasitology research · 2020Article
- Targeting Kinases inFrontiers in veterinary science · 2020Article
- Differential gene expression, including Sjfs800, in Schistosoma japonicum females at pre-pairing, initial pairing and oviposition.Parasites & vectors · 2019Article
- The ABL kinase inhibitor imatinib causes phenotypic changes and lethality in adult Schistosoma japonicum.Parasitology research · 2019Article
- Sorafenib and praziquantel synergistically attenuate Schistosoma japonicum-induced liver fibrosis in mice.Parasitology research · 2018Article
- Tyrosine kinase 4 is involved in the reproduction of the platyhelminth parasite Schistosoma japonicum.Parasites & vectors · 2017Article
- Defining the Schistosoma haematobium kinome enables the prediction of essential kinases as anti-schistosome drug targets.Scientific reports · 2015Article
- Targeting Filarial Abl-like Kinases: Orally Available, Food and Drug Administration-Approved Tyrosine Kinase Inhibitors Are Microfilaricidal and Macrofilaricidal.The Journal of infectious diseases · 2015Article
- Serum albumin and α-1 acid glycoprotein impede the killing of Schistosoma mansoni by the tyrosine kinase inhibitor Imatinib.International journal for parasitology. Drugs and drug resistance · 2014Article
- Receptor tyrosine kinases and schistosome reproduction: new targets for chemotherapy.Frontiers in genetics · 2014Review
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Authors and funding
9 authors at 6 institutions in 4 countries.
Funding
Abstract
backgroundSchistosome parasites cause schistosomiasis, one of the most important infectious diseases worldwide. For decades Praziquantel (PZQ) is the only drug widely used for controlling schistosomiasis. The absence of a vaccine and fear of PZQ resistance have motivated the search for alternatives. Studies on protein kinases (PKs) demonstrated their importance for diverse physiological processes in schistosomes. Among others two Abl tyrosine kinases, SmAbl1 and SmAbl2, were identified in Schistosoma mansoni and shown to be transcribed in the gonads and the gastrodermis. SmAbl1 activity was blocked by Imatinib, a known Abl-TK inhibitor used in human cancer therapy (Gleevec/Glivec). Imatinib exhibited dramatic effects on the morphology and physiology of adult schistosomes in vitro causing the death of the parasites. METHODOLOGY/PRINCIPAL
findingsHere we show modeling data supporting the targeting of SmAbl1/2 by Imatinib. A biochemical assay confirmed that SmAbl2 activity is also inhibited by Imatinib. Microarray analyses and qRT-PCR experiments were done to unravel transcriptional processes influenced by Imatinib in adult schistosomes in vitro demonstrating a wide influence on worm physiology. Surface-, muscle-, gut and gonad-associated processes were affected as evidenced by the differential transcription of e.g. the gynecophoral canal protein gene GCP, paramyosin, titin, hemoglobinase, and cathepsins. Furthermore, transcript levels of VAL-7 and egg formation-associated genes such as tyrosinase 1, p14, and fs800-like were affected as well as those of signaling genes including a ribosomal protein S6 kinase and a glutamate receptor. Finally, a comparative in silico analysis of the obtained microarray data sets and previous data analyzing the effect of a TGFβR1 inhibitor on transcription provided first evidence for an association of TGFβ and Abl kinase signaling. Among others GCP and egg formation-associated genes were identified as common targets. CONCLUSIONS/SIGNIFICANCE: The data affirm broad negative effects of Imatinib on worm physiology substantiating the role of PKs as interesting targets.
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