藥物滲透性(透膜能力)對(duì)藥物生物利用度影響重大,在藥物研發(fā)過(guò)程中先導(dǎo)化合物的滲透性影響其成藥幾率。很多藥物由于滲透性不佳而遭撤市,因此在藥物研發(fā)早期對(duì)先導(dǎo)化合物進(jìn)行滲透性預(yù)測(cè),可以加速藥物研發(fā)進(jìn)程、節(jié)約研發(fā)經(jīng)費(fèi)。通過(guò)對(duì)現(xiàn)有預(yù)測(cè)藥物滲透性的理論方法(定量構(gòu)效關(guān)系、自由能差法、分子動(dòng)力學(xué)模擬等)和有關(guān)軟件(ADMET Predictor、GastroPlus、QikProp、Volsurf等)進(jìn)行介紹,并評(píng)價(jià)了其優(yōu)缺點(diǎn),以期根據(jù)需要選擇合適理論方法,提高預(yù)測(cè)的準(zhǔn)確性。

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 Many drugs were withdrawn from market due to poor permeability.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.

國(guó)家自然科學(xué)基金資助項(xiàng)目(21103125)