广告
P-糖蛋白
ATP结合盒运输机
流出
运输机
生物化学
计算生物学
ATP酶
化学
药物发现
结合位点
生物
血浆蛋白结合
药理学
药品
酶
基因
多重耐药
抗生素
作者
Shirin Mollazadeh,Amirhossein Sahebkar,Farzin Hadizadeh,Javad Behravan,Sepideh Arabzadeh
出处
期刊:Life Sciences
[Elsevier]
日期:2018-10-27
卷期号:214: 118-123
被引量:130
标识
DOI:10.1016/j.lfs.2018.10.048
摘要
P-glycoprotein (P-gp) is a member of ATP-binding cassette (ABC) superfamily which extrudes chemotherapeutic agents out of the cell. Suppression of this efflux activity has been the subject of numerous attempts to develop P-gp inhibitors. The aim of this review is to present up-to-date information on the structural and functional aspects of P-gp and its known inhibitors. The data presented also provide some information on drug discovery approaches for candidate P-gp inhibitors. Nucleotide-binding domains (NBDs) and drug-binding domains (DBDs) have been extensively studied to gain more information about P-gp inhibition and it looks that the ATPase activity of this pump has been the most attractive target for designing inhibitors. Hydrophobic and π-π (aromatic) interactions between P-gp binding domains and inhibitors are dominant intermolecular forces that have been reported in many studies using different methods. Many synthetic and natural products have been found to possess inhibitory or modulatory effects on drug transporter proteins. Log P value is an important factor in studying these inhibitors and has a crucial role on absorption, distribution, metabolism, and excretion (ADME) properties of candidate P-gp inhibitors.
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