| 王萍,王蕾,李春艳,等.基于FAK的药物筛选及海洋小分子CY308抗乳腺癌研究[J].中国海洋药物,2021,40(5):23-28. |
| 基于FAK的药物筛选及海洋小分子CY308抗乳腺癌研究 |
| Drugs screening on FAK and the anti-breast cancer effects of a marine derived inhibitor of CY308 |
| 投稿时间：2021-04-23 修订日期：2021-09-06 |
| DOI： |
| 中文关键词: 局部黏着斑激酶 FAK小分子抑制剂 虚拟筛选 癌症治疗 |
| English Keywords:Focal Adhesion Kinase FAK inhibitor Virtual screening Anti-cancer |
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| 中文摘要: |
| 目的 从已知化合物中挖掘出新型的对FAK具有较强作用的化合物，并进行了药理活性的体外初筛，以期得到效果更好、选择性更高的FAK抑制剂。方法 首先采用Autodock vina从SPECS数据库进行FAK小分子抑制剂的计算机虚拟筛选，再通过rdkit操作环境进行类药5原则筛选后，采用Ward方法对化合物进行分层聚类，然后选出6类得分最高的化合物进行FAK抑制活性检测和进一步的实验验证。 结果 计算机辅助药物虚拟筛选得到的6个代表化合物在MDA-MB-231-FAKWT细胞上均具有一定的FAK激酶抑制活性，其中以CY308的活性最优，IC50为6umol/L。并进一步利用SPR技术证实了活性化合物CY308与FAK有较强的结合，并采用分子对接对其结合位点进行了预测。 |
| English Summary: |
| Abstract: Objective To screen out a novel compound with strong inhibition to FAK with better effect and higher selectivity from known compounds databases，and evaluated the pharmacological activity by in vitro cellular assays. Methods Firstly, the computer virtual screening of FAK small molecule inhibitors was performed by Auto-dock vina from SPECS database, and then the five principles of drug screening were carried out through the RDKit operating environment, and furthermore, the screened compounds were clustered hierarchically by Ward method. Finally, six compounds with the highest scores were selected for FAK inhibitory activity detection and further experimental verification. Results Computer-assisted drug virtual screening showed that all the six compounds exhibited certain FAK kinase inhibitory activity in MDA-MB-231-FAKWT cells. Among them, CY308 showed the best activity with IC50 of 6 μmol/L. Further in, the strong binding between FAK and CY308 was confirmed by SPR, and the binding sites were also predicted by molecular docking. |
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