P-glycoprotein(P-gp)is an important transmembrane ATP-binding cassette(ABC)drug efflux transporter expressed in various human tissues such as the intestines,liver,kidneys,and bloodbrain barrier.It limits the intracell...P-glycoprotein(P-gp)is an important transmembrane ATP-binding cassette(ABC)drug efflux transporter expressed in various human tissues such as the intestines,liver,kidneys,and bloodbrain barrier.It limits the intracellular concentration of xenobiotics by pumping them out of the cells,affecting drug pharmacokinetics and therapeutic effects.With its broad substrate specificity,it has the potential to remove a wide range of drugs from Chinese materia medica(CMM),including conventional medicines and active compounds.Increasing evidence has confirmed the superior therapeutic effectiveness of CMM in treating a wide range of diseases worldwide,as well as in conjunction with western drugs.As a result,herbal medicine-drug compounds have prompted widespread concern,with the majority of these interactions involving transporters such as P-gp.This review systematically summarizes the inhibition or induction of P-gp expression/function by active CMM compounds and the underlying regulatory mechanisms.It will aid in improving understanding of the synergistic or inhibiting effects associated with transporter P-gp as well as rational safety concerns for using CMM,particularly in combination with drugs.展开更多
目的:利用中药化学专业数据库与TCMSP分析平台,运用计算机辅助药物设计技术对转化生长因子-β1(TGF-β1)蛋白进行虚拟筛选,寻找潜在的中药小分子抑制剂。方法:通过Discovery Studio 2.5(DS)软件进行药效团模型的构建,应用Hypogen算法预...目的:利用中药化学专业数据库与TCMSP分析平台,运用计算机辅助药物设计技术对转化生长因子-β1(TGF-β1)蛋白进行虚拟筛选,寻找潜在的中药小分子抑制剂。方法:通过Discovery Studio 2.5(DS)软件进行药效团模型的构建,应用Hypogen算法预测出潜在活性位点,并分别使用Ramanchandran Plot和Profile-3D评估模型,利用优化的模型进行对实验中药小分子库进行虚拟筛选,最后对筛选出的中药进行ADMET性质预测和分子动力学模拟。结果:应用Hypogen算法成功预测出6个潜在活性位点且模型表现良好,成功从黄芪、丹参、三七中筛选出4种与TGF-β1结合良好的天然小分子化合物,并分析了其结合模式。结论:黄芪、丹参、三七的抑癌效果很可能是通过抑制TGF-β1的激活实现的。展开更多
基金the Macao Science and Technology Development Fund(No.0067/2019/A2 and No.0075/2019/AMJ)from the Macao Special Administrative Region。
文摘P-glycoprotein(P-gp)is an important transmembrane ATP-binding cassette(ABC)drug efflux transporter expressed in various human tissues such as the intestines,liver,kidneys,and bloodbrain barrier.It limits the intracellular concentration of xenobiotics by pumping them out of the cells,affecting drug pharmacokinetics and therapeutic effects.With its broad substrate specificity,it has the potential to remove a wide range of drugs from Chinese materia medica(CMM),including conventional medicines and active compounds.Increasing evidence has confirmed the superior therapeutic effectiveness of CMM in treating a wide range of diseases worldwide,as well as in conjunction with western drugs.As a result,herbal medicine-drug compounds have prompted widespread concern,with the majority of these interactions involving transporters such as P-gp.This review systematically summarizes the inhibition or induction of P-gp expression/function by active CMM compounds and the underlying regulatory mechanisms.It will aid in improving understanding of the synergistic or inhibiting effects associated with transporter P-gp as well as rational safety concerns for using CMM,particularly in combination with drugs.
文摘目的:利用中药化学专业数据库与TCMSP分析平台,运用计算机辅助药物设计技术对转化生长因子-β1(TGF-β1)蛋白进行虚拟筛选,寻找潜在的中药小分子抑制剂。方法:通过Discovery Studio 2.5(DS)软件进行药效团模型的构建,应用Hypogen算法预测出潜在活性位点,并分别使用Ramanchandran Plot和Profile-3D评估模型,利用优化的模型进行对实验中药小分子库进行虚拟筛选,最后对筛选出的中药进行ADMET性质预测和分子动力学模拟。结果:应用Hypogen算法成功预测出6个潜在活性位点且模型表现良好,成功从黄芪、丹参、三七中筛选出4种与TGF-β1结合良好的天然小分子化合物,并分析了其结合模式。结论:黄芪、丹参、三七的抑癌效果很可能是通过抑制TGF-β1的激活实现的。
