Structure-based virtual screening approach to the discovery of novel PTPMT1 phosphatase inhibitors.
Bioorg Med Chem Lett
; 22(2): 1271-5, 2012 Jan 15.
Article
de En
| MEDLINE
| ID: mdl-22115589
ABSTRACT
Dual-specificity protein tyrosine phosphatase localized to mitochondrion 1 (PTPMT1) has recently proved to be a promising therapeutic target for the treatment of type II diabetes. Herein we report the first example for a successful application of the structure-based virtual screening to identify the novel inhibitors of human PTPMT1. These inhibitors were computationally screened for having desirable physicochemical properties as a drug candidate and reveal a high potency with IC(50) values ranging from 0.7 to 17.3µM. Therefore, they deserve consideration for further development by structure-activity relationship studies to optimize the antidiabetic activities. Structural features relevant to the stabilization of the newly identified inhibitors in the active site of PTPMT1 are addressed in detail.
Texte intégral:
1
Collection:
01-internacional
Base de données:
MEDLINE
Sujet principal:
Conception assistée par ordinateur
/
Antienzymes
/
Phosphohydrolase PTEN
/
Découverte de médicament
Type d'étude:
Diagnostic_studies
/
Screening_studies
Limites:
Humans
Langue:
En
Journal:
Bioorg Med Chem Lett
Sujet du journal:
BIOQUIMICA
/
QUIMICA
Année:
2012
Type de document:
Article