目的 采用計算機輔助藥物設計的方法發(fā)現(xiàn)潛在的PTP1B抑制劑。方法 應用3D-QSAR藥效團模型中的Hypogen模塊構建藥效團模型，成本分析、測試集預測和Fisher檢驗3種方法來驗證該模型可用于預測化合物的生物活性的能力。運用該藥效團模型對ZINC數(shù)據(jù)庫進行虛擬篩選，得到Fit value值較高的先導化合物ZINC35671983。根據(jù)藥效團的特征對ZINC35671983進行結構改造得到相應化合物。將化合物用ADMET進行成藥預測。結果 ZINC35671983進行結構改造篩選獲得92個化合物，篩出對接得分高于ZINC3567198的8個化合物。結論 發(fā)現(xiàn)8個潛在的PTP1B抑制劑，這有助于發(fā)現(xiàn)新的PTP1B先導化合物。

Objective To identify Potential PTP1B inhibitors by computer-aided drug design. Methods The Hypogen module of 3D-QSAR pharmacophore model was used to construct the pharmacophore model, cost analysis, test set prediction and Fisher test to verify the ability of the model to predict the biological activity of the compound. The lead compound ZINC35671983 with high Fit value was obtained by virtual screening of ZINC database with the pharmacophore model. The corresponding compounds were obtained by structural modification of ZINC35671983 according to the characteristics of pharmacophore. The compounds were predicted by ADMET. Results ZINC35671983 obtained 92 compounds through structural modification screening, and screened out 8 compounds with higher docking scores than ZINC3567198. Conclusion A total of 8 potential PTP1B inhibitors were found which is helpful to find new PTP1B lead compounds.

R96

天津市醫(yī)學重點學科（?？疲┙ㄔO資助項目（TJYXZDXK-032A）