药物渗透性预测方法的研究进展

Research progress on prediction of drug permeability

药物渗透性(透膜能力)对药物生物利用度影响重大,在药物研发过程中先导化合物的渗透性影响其成药几率。很多药物由于渗透性不佳而遭撤市,因此在药物研发早期对先导化合物进行渗透性预测,可以加速药物研发进程、节约研发经费。通过对现有预测药物渗透性的理论方法(定量构效关系、自由能差法、分子动力学模拟等)和有关软件(ADMET Predictor、Gastro Plus、Qik Prop、Volsurf等)进行介绍,并评价了其优缺点,以期根据需要选择合适理论方法,提高预测的准确性。

Drug permeability （transmembrane ability） has significant effect on drug bioavailability and it affects the druggability of lead compound in drug development. Many drugs were withdrawn from market due to poor permeability. Therefore, performing permeability prediction for lead compounds in the early stage of drug development can accelerate the drug development progress and decrease R＆D fund. This review introduces both theoretical method （QSAR, free energy barrier, molecular dynamics, etc.） and software （ADMET Predictor, GastroPlus, QikProp, Volsurf, etc.） used to predict drug permeability, and evaluates the advantages and disadvantages of various methods, which may be helpful to select appropriate theoretical method and improve the accuracy of prediction.