Virtual Screening for Type II B Inhibitors of B-Raf
3DQSAR
B-RafV600E kinase
binding free energy calculation
molecular docking
pharmacophore modelling
type II B inhibitors
virtual screening.
Journal
Current computer-aided drug design
ISSN: 1875-6697
Titre abrégé: Curr Comput Aided Drug Des
Pays: United Arab Emirates
ID NLM: 101265750
Informations de publication
Date de publication:
2020
2020
Historique:
received:
08
08
2018
revised:
21
11
2018
accepted:
12
01
2019
pubmed:
2
2
2019
medline:
7
4
2021
entrez:
2
2
2019
Statut:
ppublish
Résumé
B-RafV600E kinase was identified as an important target in current cancer treatment, and the type II B inhibitors show good qualities in preclinical studies. Therefore, it is very important to discover novel II B inhibitors of B-RafV600E kinase. In order to discover novel II B inhibitors of B-RafV600E kinase, virtual screening against ZINC database was performed by using a combination of pharmacophore modelling, molecular docking, 3DQSAR model and binding free energy (ΔGbind) calculation studies. The inhibitory activities against A375 cell lines of the hit compounds were tested by using MTT assay. Five promising hit compounds were obtained after screening, and all the five hit compounds showed good inhibitory rates against A375 cell lines. The combined approach of the virtual screening in our work is effective, which can be used to discover novel inhibitors with a new skeleton. In addition, the five compounds obtained from the screening showed good inhibitory rates against A375 cell lines, which can be considered to develop new II B inhibitors of B-RafV600E kinase.
Sections du résumé
BACKGROUND
BACKGROUND
B-RafV600E kinase was identified as an important target in current cancer treatment, and the type II B inhibitors show good qualities in preclinical studies. Therefore, it is very important to discover novel II B inhibitors of B-RafV600E kinase.
METHODS
METHODS
In order to discover novel II B inhibitors of B-RafV600E kinase, virtual screening against ZINC database was performed by using a combination of pharmacophore modelling, molecular docking, 3DQSAR model and binding free energy (ΔGbind) calculation studies. The inhibitory activities against A375 cell lines of the hit compounds were tested by using MTT assay.
RESULTS
RESULTS
Five promising hit compounds were obtained after screening, and all the five hit compounds showed good inhibitory rates against A375 cell lines.
CONCLUSION
CONCLUSIONS
The combined approach of the virtual screening in our work is effective, which can be used to discover novel inhibitors with a new skeleton. In addition, the five compounds obtained from the screening showed good inhibitory rates against A375 cell lines, which can be considered to develop new II B inhibitors of B-RafV600E kinase.
Identifiants
pubmed: 30706826
pii: CAD-EPUB-96232
doi: 10.2174/1573409915666190130162821
doi:
Substances chimiques
Protein Kinase Inhibitors
0
Proto-Oncogene Proteins B-raf
EC 2.7.11.1
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
222-230Informations de copyright
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