New compound sets identified from high throughput phenotypic screening against three kinetoplastid parasites: an open resource.
Sci Rep
; 5: 8771, 2015 Mar 05.
Article
em En
| MEDLINE
| ID: mdl-25740547
ABSTRACT
Using whole-cell phenotypic assays, the GlaxoSmithKline high-throughput screening (HTS) diversity set of 1.8 million compounds was screened against the three kinetoplastids most relevant to human disease, i.e. Leishmania donovani, Trypanosoma cruzi and Trypanosoma brucei. Secondary confirmatory and orthogonal intracellular anti-parasiticidal assays were conducted, and the potential for non-specific cytotoxicity determined. Hit compounds were chemically clustered and triaged for desirable physicochemical properties. The hypothetical biological target space covered by these diversity sets was investigated through bioinformatics methodologies. Consequently, three anti-kinetoplastid chemical boxes of ~200 compounds each were assembled. Functional analyses of these compounds suggest a wide array of potential modes of action against kinetoplastid kinases, proteases and cytochromes as well as potential host-pathogen targets. This is the first published parallel high throughput screening of a pharma compound collection against kinetoplastids. The compound sets are provided as an open resource for future lead discovery programs, and to address important research questions.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Kinetoplastida
/
Testes de Sensibilidade Parasitária
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Avaliação Pré-Clínica de Medicamentos
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Bibliotecas de Moléculas Pequenas
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Ensaios de Triagem em Larga Escala
Tipo de estudo:
Diagnostic_studies
/
Screening_studies
Limite:
Animals
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Humans
Idioma:
En
Revista:
Sci Rep
Ano de publicação:
2015
Tipo de documento:
Article
País de afiliação:
Espanha