Discovery of FIXa inhibitors by combination of pharmacophore modeling, molecular docking, and 3D-QSAR modeling.
J Recept Signal Transduct Res
; 38(3): 213-224, 2018 Jun.
Article
em En
| MEDLINE
| ID: mdl-29724133
ABSTRACT
Human Coagulation Factor IXa (FIXa), specifically inhibited at the initiation stage of the blood coagulation cascade, is an excellent target for developing selective and safe anticoagulants. To explore this inhibitory mechanism, 86 FIXa inhibitors were selected to generate pharmacophore models and subsequently SAR models. Both best pharmacophore model and ROC curve were built through the Receptor-Ligand Pharmacophore Generation module. CoMFA model based on molecular docking and PLS factor analysis methods were developed. Model propagations values are q2 = 0.709, r2 = 0.949, and r2pred = 0.905. The satisfactory q2 value of 0.609, r2 value of 0.962, and r2pred value of 0.819 for CoMSIA indicated that the CoMFA and CoMSIA models are both available to predict the inhibitory activity on FIXa. On the basis of pharmacophore modeling, molecular docking, and 3D-QSAR modeling screening, six molecules are screened as potential FIXa inhibitors.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Trombose
/
Desenho de Fármacos
/
Fator IXa
/
Fibrinolíticos
Tipo de estudo:
Prognostic_studies
Limite:
Humans
Idioma:
En
Revista:
J Recept Signal Transduct Res
Assunto da revista:
BIOQUIMICA
/
FISIOLOGIA
Ano de publicação:
2018
Tipo de documento:
Article