1. Drug Repurposing and De Novo Drug Discovery of Protein Kinase Inhibitors as New Drugs against Schistosomiasis.
- Author
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Pereira Moreira B, Weber MHW, Haeberlein S, Mokosch AS, Spengler B, Grevelding CG, and Falcone FH
- Subjects
- Animals, Helminth Proteins metabolism, Humans, Protein Serine-Threonine Kinases metabolism, Protein-Tyrosine Kinases metabolism, Anthelmintics therapeutic use, Drug Repositioning, Helminth Proteins antagonists & inhibitors, Protein Kinase Inhibitors therapeutic use, Protein Serine-Threonine Kinases antagonists & inhibitors, Protein-Tyrosine Kinases antagonists & inhibitors, Schistosoma enzymology, Schistosomiasis drug therapy, Schistosomiasis enzymology
- Abstract
Schistosomiasis is a neglected tropical disease affecting more than 200 million people worldwide. Chemotherapy relies on one single drug, praziquantel, which is safe but ineffective at killing larval stages of this parasite. Furthermore, concerns have been expressed about the rise in resistance against this drug. In the absence of an antischistosomal vaccine, it is, therefore, necessary to develop new drugs against the different species of schistosomes. Protein kinases are important molecules involved in key cellular processes such as signaling, growth, and differentiation. The kinome of schistosomes has been studied and the suitability of schistosomal protein kinases as targets demonstrated by RNA interference studies. Although protein kinase inhibitors are mostly used in cancer therapy, e.g., for the treatment of chronic myeloid leukemia or melanoma, they are now being increasingly explored for the treatment of non-oncological conditions, including schistosomiasis. Here, we discuss the various approaches including screening of natural and synthetic compounds, de novo drug development, and drug repurposing in the context of the search for protein kinase inhibitors against schistosomiasis. We discuss the status quo of the development of kinase inhibitors against schistosomal serine/threonine kinases such as polo-like kinases (PLKs) and mitogen-activated protein kinases (MAP kinases), as well as protein tyrosine kinases (PTKs). more...
- Published
- 2022
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