趋化因子受体CXCR4非肽类抑制剂药效团的设计

趋化因子受体CXCR4是HIV进入宿主细胞的辅助受体之一.为了研究其抗HIV抑制剂的构效关系,6个结构多样性和拥有高活性的抑制剂被作为训练集来构建药效团模型,然后对由活性抑制剂和非活性抑制剂构成的测试集进行筛选,通过应用受试者工作特征(receiver operator characteristic,ROC)曲线和计算富集因子(enrichment factor,EF)的方法评估每个模型的预测能力与合理性.最终得到一个具有较高的ROC曲线下面积(area under curve,AUC)与富集因子的药效团模型,可用于指导新颖CXCR4抑制剂的设计及相关抗艾滋病药物的研发.

Pharmacophoric Design for Non-peptide Inhibitors of Chemokine Acceptor CXCR4

CXCR4 is one of several chemokine receptors that HIV can use to infect host cells. To study the structure-activity relationship between chemokine receptor CXCR4 and its inhibitors,six inhibitors with structural diversity and high-activity were used to develop pharmacophore models,and then a molecular library consisting of active and decoy ligands was ap-plied to evaluate the predicting capability and rationality of every model by receiver operator characteristic（ROC）curve and enrichment factor（EF）value. The result should that a pharmacophore model with higher area under ROC curve and EF value was obtained,which can be used to guide the design of novel CXCR4 inhibitors and the development of the related anti-HIV drugs.