Scholarlink

Background <p>Fascioliasis is a zoonosis and neglected tropical disease with worldwide distribution and significant economic impact. The search for anthelmintic compounds against <i>Fasciola hepatica</i>, one of the parasitic liver flukes responsible for this disease, has become important due to widespread resistances against existing drugs. To facilitate drug discovery, a useful strategy is the identification of proteins that are vital for the parasite. Protein kinases (PKs) emerged as potential targets in several parasites, given their critical role in many biological processes. To date, knowledge of the PKs present in <i>F. hepatica</i> is fragmentary.</p> Results <p>We curated and classified the kinome of <i>F. hepatica</i> using a refined bioinformatics pipeline and found 245 PKs, which represented 2.14% of the parasite’s proteome. Classification of all PKs into their families and sub-families revealed the CMGC group as the largest PK group. A comparison of the kinomes of <i>F. hepatica</i> with medically important <i>Schistosoma</i> species and the human host revealed key similarities and differences. Based on orthology to human sequences, KEGG functional annotation predicted that 25% of 110 annotated PKs in <i>F. hepatica</i> are involved in cancer pathways. We prioritized a panel of related, small-molecule PK inhibitors to assess their efficacy against different <i>F. hepatica</i> life stages in vitro. Among these, vandetanib and ruboxistaurin showed lethal effects on immature flukes in vitro at 50&#xa0;µM concentration, and ruboxistaurin significantly reduced the motility of adult liver flukes.</p> Conclusion <p>These findings suggest that repurposing small-molecule PK inhibitors could be a good strategy for obtaining compounds to combat fascioliasis. The newly established <i>F. hepatica</i> kinome represents a resource for future target discovery.</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

Curation of the Fasciola hepatica kinome as a resource for drug target discovery

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2026年1月16日

查看全文
  • Sagar Ajmera,
  • Oliver Puckelwaldt,
  • Andreas J. Stroehlein,
  • Simone Haeberlein

摘要

Background

Fascioliasis is a zoonosis and neglected tropical disease with worldwide distribution and significant economic impact. The search for anthelmintic compounds against Fasciola hepatica, one of the parasitic liver flukes responsible for this disease, has become important due to widespread resistances against existing drugs. To facilitate drug discovery, a useful strategy is the identification of proteins that are vital for the parasite. Protein kinases (PKs) emerged as potential targets in several parasites, given their critical role in many biological processes. To date, knowledge of the PKs present in F. hepatica is fragmentary.

Results

We curated and classified the kinome of F. hepatica using a refined bioinformatics pipeline and found 245 PKs, which represented 2.14% of the parasite’s proteome. Classification of all PKs into their families and sub-families revealed the CMGC group as the largest PK group. A comparison of the kinomes of F. hepatica with medically important Schistosoma species and the human host revealed key similarities and differences. Based on orthology to human sequences, KEGG functional annotation predicted that 25% of 110 annotated PKs in F. hepatica are involved in cancer pathways. We prioritized a panel of related, small-molecule PK inhibitors to assess their efficacy against different F. hepatica life stages in vitro. Among these, vandetanib and ruboxistaurin showed lethal effects on immature flukes in vitro at 50 µM concentration, and ruboxistaurin significantly reduced the motility of adult liver flukes.

Conclusion

These findings suggest that repurposing small-molecule PK inhibitors could be a good strategy for obtaining compounds to combat fascioliasis. The newly established F. hepatica kinome represents a resource for future target discovery.