基于雌激素受体从传统中药库中筛选治疗乳腺癌的小分子拮抗剂

High-flux Virtual Screening Potential Antagonists from Traditional Chinese Medicine Based on Estrogen Receptor α

目的:运用计算机虚拟筛选技术从传统中药数据库(TCMSP)中寻找雌激素受体α(Estrogen receptorα,ER-α)的中药小分子拮抗剂。方法:以ER-α为靶点,运用分子对接技术进行首轮筛选,然后基于靶点与药物相互作用位点进行第二轮筛选,最后运用ADME/T预测进行第三轮筛选。结果:以原配体(他莫昔芬)为阳性对照,筛选出2个类药性良好的天然小分子化合物,它们与ER-α亲和力及相互作用基团均优于他莫昔芬(临床治疗乳腺癌的药物),并且确定了它们的中草药来源。结论:成功建立一整套高通量虚拟筛选ER-α拮抗剂的策略,该研究结果可促进从传统中药库中提取、设计以及实验合成新的治疗女性复发转移乳腺癌及用作乳腺癌手术后转移辅助治疗的药物。

Objective： Using the technology of computer virtual screening from Traditional Chinese Medicine Database Platform （ TCMSP ）fast search small molecule antagonists for estrogen receptorα （ ER-α）. Methods： ER-α as the target, the use of molecular docking technology for the first round of screening, and then based on the target point and drug interaction sites for the second round of screening, and finally use the ADME/T prediction for the third round of screening. Results ： The free binding energy of original ligand （ tamoxifen ）can he used as positive control, then not only obtained two compounds having a higher binding affinity than tamoxifen, hut also they have good drug-likeness. Their sources of traditonal Chinese medicine has been determined. Conclusion ： This study successfully established a high-throughput virtual screening strategy for ER-α antagonists, and it provides an important reference and a theoretical basis for the extraction of anti-mammary cancer compounds from Chinese herbal medicine and the design of medicine for treating breast cancer.