In silico drug repurposing of FDA-approved drugs to predict new inhibitors for drug resistant T315I mutant and wild-type BCR-ABL1: A virtual screening and molecular dynamics study.
J Mol Graph Model
; 74: 234-240, 2017 06.
Article
en En
| MEDLINE
| ID: mdl-28458002
ABSTRACT
The BCR-ABL fusion gene is one of the major causes of 95% of Chronic Myeloid Leukemia (CML). While, BCR-ABL protein is currently being used as a major target to treat CML. Although, current FDA-approved drugs such as; Imatinib and Nilotinib have stupendously improved the patients 5-year's survival rates, the drug resistance has dramatically reduced their effects. So, more accurate and effective alternative treatments are crucially needed. To address this issue, we screened the FDA-approved drugs by virtual screening and binding free energy calculations to identify new inhibitors for the wild-type and T315I gatekeeper mutant ABL1. It was invigorating to identify that chlorohexidine, paromomycin and deferoxamine could inhibit the wild-type ABL1, while chlorohexidine and ritonavir could inhibit the T315I mutant ABL1. The applications of these newly identified drugs are not just an effortless hypothesis in drug discovery. These drugs can be evaluated in phase 2 clinical trials after a simple kinase selectivity assay.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Contexto en salud:
4_TD
/
6_ODS3_enfermedades_notrasmisibles
Problema de salud:
4_antimicrobial_resistance
/
6_leukemia
Asunto principal:
Proteínas de Fusión bcr-abl
/
Inhibidores de Proteínas Quinasas
/
Reposicionamiento de Medicamentos
/
Antineoplásicos
Tipo de estudio:
Diagnostic_studies
/
Prognostic_studies
/
Risk_factors_studies
/
Screening_studies
Límite:
Humans
Idioma:
En
Revista:
J Mol Graph Model
Asunto de la revista:
BIOLOGIA MOLECULAR
Año:
2017
Tipo del documento:
Article
País de afiliación:
Irán