Discovering novel P38α inhibitors for the treatment of prostate cancer through virtual screening methods
Discovering novel P38α inhibitors for the treatment of prostate cancer through virtual screening methods
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通过虚拟筛选方法发现治疗前列腺癌的新型 P38α 抑制剂
DOI：
10.4155/fmc-2019-0223
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发表时间：
2019-12-01
影响因子：
4.2
通讯作者：
Huang, Hai
中科院分区：
文献类型：
--
作者：
Li, Kaiwen;Li, Zean;Huang, Hai
目的：P38 α在去势抵抗性前列腺癌的发展中起着至关重要的作用。发现新的P38 α抑制剂为开发新的抗癌药物提供了潜力。方法与结果：从Chemdiv和Enamine虚拟文库中筛选化合物，构建P38 α抑制剂样文库。通过虚拟筛选共发现58种新的P38 α抑制剂；其中化合物1、化合物5、化合物9的激酶IC50均低于10 μ m。在体外，这3种化合物均有抑制前列腺癌细胞存活的潜力，但只有化合物9能抑制前列腺癌细胞的增殖和迁移。结论：本研究发现的有效化合物通过靶向P38 α -丝裂原活化蛋白激酶信号通路发挥抗癌作用，值得进一步研究。
Aim: P38 alpha plays a crucial role in the development of castration-resistant prostate cancer. Discovering novel inhibitors of P38 alpha offers potential for the development of new anticancer drugs. Methods & results: Compounds from the Chemdiv and Enamine virtual libraries were filtered to construct the P38 alpha inhibitor-like library. A total of 58 new P38 alpha inhibitors were discovered via virtual screening; these included three compounds (compound 1, 5, 9) with kinase IC50 of below 10 mu M. In vitro, these three compounds have the potential to suppress the viabilities of prostate cancer cell lines, however, only compound 9 can inhibit the proliferation and migration of prostate cancer cells. Conclusion: The potent compounds discovered in this study demonstrate anticancer functions by targeting the P38 alpha mitogen-activated protein kinases signaling pathway and are worthy of further investigation.