Repurposing of Human Kinase Inhibitors in Neglected Protozoan Diseases. (11th July 2017)

• Record Type: Journal Article
• Authors: Dichiara, Maria; Marrazzo, Agostino; Prezzavento, Orazio; Collina, Simona; Rescifina, Antonio; Amata, Emanuele
• Is Part Of: ChemMedChem. Volume 12:Number 16(2017)
• Page Start: 1235
• Page End: 1253
• Publication Date: 2017-07-11
• Subjects: drug discovery -- kinase inhibitors -- neglected tropical diseases -- parasites -- repurposing; Pharmaceutical chemistry -- Periodicals; 615.19005
• DOI: 10.1002/cmdc.201700259
• Languages: English
• ISSNs: 1860-7179

Abstract

Abstract: Human African trypanosomiasis (HAT), Chagas disease, and leishmaniasis belong to a group of infectious diseases known as neglected tropical diseases and are induced by infection with protozoan parasites named trypanosomatids. Drugs in current use have several limitations, and therefore new candidate drugs are required. The majority of current therapeutic trypanosomatid targets are enzymes or cell‐surface receptors. Among these, eukaryotic protein kinases are a major group of protein targets whose modulation may be beneficial for the treatment of neglected tropical protozoan diseases. This review summarizes the finding of new hit compounds for neglected tropical protozoan diseases, by repurposing known human kinase inhibitors on trypanosomatids. Kinase inhibitors are grouped by human kinase family and discussed according to the screening (target‐based or phenotypic) reported for these compounds on trypanosomatids. This collection aims to provide insight into repurposed human kinase inhibitors and their importance in the development of new chemical entities with potential beneficial effects on the diseases caused by trypanosomatids. Abstract : Drugs redirected : Neglected tropical protozoan diseases are induced by parasites called trypanosomatids. Given the limitations of drugs in current use, the development of new candidates is needed. Eukaryotic protein kinases are a major group of protein targets whose modulation may be beneficial for the treatment of these diseases. This review focuses on recent efforts in finding new hit compounds by repurposing the major known human kinase inhibitors to fight trypanosomatids.