Virtual Screening for Type ⅡB Inhibitors of B-RafV600E Kinase.

Background: B-Raf(V)(600E) 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-Raf(V)(600E) kinase. Methods: In order to discover novel II B inhibitors of B-Raf(V)(600E) kinase, virtual screening against ZINC database was performed by using a combination of pharmacophore modelling, molecular docking, 3D-QSAR model and binding free energy (Delta G(bind)) calculation studies. The inhibitory activities against A375 cell lines of the hit compounds were tested by using MTT assay. Results: Five promising hit compounds were obtained after screening, and all the five hit compounds showed good inhibitory rates against A375 cell lines. Conclusion: 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-Raf(V)(600E) kinase.