作　　者： (黄溪）; (郑杰）;

机构地区： 桂林航天工业学院,广西桂林541004

出　　处： 《计算机与应用化学》 2017年第8期639-644,共6页

摘　　要： 采用Sybyl-X软件中Surflex-Dock分子对接模块,评价选择性激素类药物(他莫昔芬、托瑞米芬、雷洛昔芬、阿佐昔芬、苯卓昔芬、拉索昔芬)与雌激素受体(ER)、孕激素受体(PR)、甲状腺激素受体(TR)、糖皮质激素受体(GR)、雄性激素受体(AR)的结合模式。以打分函数Total-Score为标准,评价激素类药物与受体之间的亲和强弱关系,探讨药物与靶标的作用机制。结果表明:激素类受体拮抗药物在作用靶点(ER、PR)有良好的结合作用,同时也不同程度地通过极性、疏水、溶剂化等作用,结合其它激素类受体(TR,AR,GR),可能导致不良反应及毒副作用。在一定程度上解释了长期使用激素类拮抗药物可能产生毒副作用的机理,为激素类药物研究提供一定的理论依据。 Binding modes between breast cancer antagonistic drugs （tamoxifen, toremifene, raloxifene, arzoxifene, bazedoxifene, lasofoxifene） and hormone receptors （Estrogen Receptor, Progesterone Receptor, Thyroid Receptor, Glucocorticoid Receptor, Androgen Receptor）, were simulated through the Surflex-Dock module of Sybyl-X software. With the Total-Score as the standard, the strength of affinity between the antagonism of drug and receptor was evaluated, revealing the mechanism of drugs and targets. Result： Antagonistic drugs have a good combination in breast estrogen and progesterone receptors, which could also combine with other hormone receptors （TR, AR, GR） through the polarity, hydrophobic, solvation and other effects, inhibiting target activity and producing adverse reactions and toxic side effect. To some extent, molecular docking simulation can explain the toxicology of long-term use of these drugs and provide theoretical basis for modem studies on antagonistic drugs.

关 键 词： 分子对接 雌激素受体调节剂 毒副作用