Identification of non-lipid LPA3 antagonists by virtual screening.
Bioorg Med Chem
; 16(11): 6207-17, 2008 Jun 01.
Article
en En
| MEDLINE
| ID: mdl-18467108
ABSTRACT
In the present study, we utilized virtual screening to identify LPA(3) antagonists. We have developed a three-point structure-based pharmacophore model based on known LPA(3) antagonists. This model was used to mine the NCI database. Docking, pharmacophore development, and database mining produced new, non-lipid leads. Experimental testing of seven computationally selected pharmacophore hits produced one potentiator and three antagonists, one of which displays both LPA(3) selectivity and nanomolar potency. Similarity searching in the ChemBridge database using the most promising lead as the search target produced four additional LPA(3) antagonists and a potent dual LPA(1&2) antagonist.
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Simulación por Computador
/
Lisofosfolípidos
/
Modelos Moleculares
/
Modelos Químicos
Tipo de estudio:
Diagnostic_studies
/
Prognostic_studies
/
Screening_studies
Límite:
Animals
Idioma:
En
Revista:
Bioorg Med Chem
Asunto de la revista:
BIOQUIMICA
/
QUIMICA
Año:
2008
Tipo del documento:
Article
País de afiliación:
Estados Unidos