Identification of novel liver X receptor activators by structure-based modeling.
J Chem Inf Model
; 52(5): 1391-400, 2012 May 25.
Article
em En
| MEDLINE
| ID: mdl-22489742
ABSTRACT
Liver X receptors (LXRs) are members of the nuclear receptor family. Activators of LXRs are of high pharmacological interest as LXRs regulate cholesterol, fatty acid, and carbohydrate metabolism as well as inflammatory processes. On the basis of different X-ray crystal structures, we established a virtual screening workflow for the identification of novel LXR modulators. A two-step screening concept to identify active compounds included 3D-pharmacophore filters and rescoring by shape alignment. Eighteen virtual hits were tested in vitro applying a reporter gene assay, where concentration-dependent activity was proven for four novel lead structures. The most active compound 10, a 1,4-naphthochinone, has an estimated EC50 of around 5 µM.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Simulação por Computador
/
Modelos Moleculares
/
Receptores Nucleares Órfãos
Tipo de estudo:
Diagnostic_studies
Idioma:
En
Ano de publicação:
2012
Tipo de documento:
Article