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: 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: 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-RafV600E kinase.

背景：B-RafV600E激酶被确定为当前癌症治疗的重要靶标，并且II B型抑制剂在临床前研究中显示出良好的品质。因此，发现B-RafV600E激酶的新型II B抑制剂非常重要。

方法：为了发现B-RafV600E激酶的新型II B抑制剂，通过结合药效团建模，分子对接，3DQSAR模型和结合自由能（ΔGbind）计算研究，对ZINC数据库进行了虚拟筛选。通过使用MTT测定法测试了命中化合物对A375细胞系的抑制活性。

结果：筛选后获得了五种有前景的命中化合物，所有五种命中化合物均显示出对A375细胞系的良好抑制率。

结论：我们的工作中虚拟筛选的组合方法是有效的，可用于发现具有新骨架的新型抑制剂。此外，从筛选中获得的五种化合物对A375细胞系表现出良好的抑制率，可以认为这是开发出新的B-RafV600E激酶的II B抑制剂。