Virtual screening of B-Raf kinase inhibitors: A combination of pharmacophore modelling, molecular docking, 3D-QSAR model and binding free energy calculation studies.
Comput Biol Chem
; 70: 186-190, 2017 Oct.
Article
em En
| MEDLINE
| ID: mdl-28892749
ABSTRACT
B-Raf kinase has been identified as an important target in recent cancer treatment. In order to discover structurally diverse and novel B-Raf inhibitors (BRIs), a virtual screening of BRIs against ZINC database was performed by using a combination of pharmacophore modelling, molecular docking, 3D-QSAR model and binding free energy (ΔGbind) calculation studies in this work. After the virtual screening, six promising hit compounds were obtained, which were then tested for inhibitory activities of A375 cell lines. In the result, five hit compounds show good biological activities (IC50<50µM). The present method of virtual screening can be applied to find structurally diverse inhibitors, and the obtained five structurally diverse compounds are expected to develop novel BRIs.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Termodinâmica
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Algoritmos
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Ensaios de Seleção de Medicamentos Antitumorais
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Relação Quantitativa Estrutura-Atividade
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Proteínas Proto-Oncogênicas B-raf
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Inibidores de Proteínas Quinases
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Simulação de Acoplamento Molecular
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Antineoplásicos
Tipo de estudo:
Diagnostic_studies
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Screening_studies
Limite:
Humans
Idioma:
En
Revista:
Comput Biol Chem
Assunto da revista:
BIOLOGIA
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INFORMATICA MEDICA
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QUIMICA
Ano de publicação:
2017
Tipo de documento:
Article