title: Rapid screening the potential mechanism-based inhibitors of CYP3A4 from Tripterygium wilfordi based on computer approaches combined with in vitro bioassay.
abstract: CYP3A4 is the main human metabolizing enzyme, and many clinically relevant drug/herb-drug interactions (DDIs/HDIs) involving CYP3A4 are due to mechanism-based inhibition. In this study, pharmacophore model together with molecular docking (MD) are used to rapidly screen the potential CYP3A4 mechanism-based inhibitors from Tripterygium wilfordii, and in vitro experiments are conducted to validate the computational data. The results showed that the rate of computational prediction could be improved based on a combination of pharmacophore model and MD, and a combination of computational approaches might be a useful tool to identify potential mechanism-based inhibitor of CYP3A4 from herbal medicines.
authors.affiliation: Tianjin University of Traditional Chinese Medicine, Nankai District, Tianjin 300193, PR China.
authors.forename: Lili
authors.initials: L
authors.lastname: Wang
authors.affiliation: Tianjin University of Traditional Chinese Medicine, Nankai District, Tianjin 300193, PR China.
authors.forename: Yue
authors.initials: Y
authors.lastname: Hai
authors.affiliation: Tianjin University of Traditional Chinese Medicine, Nankai District, Tianjin 300193, PR China.
authors.forename: Lijun
authors.initials: L
authors.lastname: An
authors.affiliation: Tianjin University of Traditional Chinese Medicine, Nankai District, Tianjin 300193, PR China.
authors.forename: Junxiu
authors.initials: J
authors.lastname: Chen
authors.affiliation: Tianjin University of Traditional Chinese Medicine, Nankai District, Tianjin 300193, PR China.
authors.forename: Rongjia
authors.initials: R
authors.lastname: Liang
authors.affiliation: Tianjin University of Traditional Chinese Medicine, Nankai District, Tianjin 300193, PR China; State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, PR China. Electronic address: hexintn@163.com.
authors.forename: Xin
authors.initials: X
authors.lastname: He
mesh_terms: D000470:Alkaloids / Q000737:chemistry / Q000378:metabolism; D019540:Area Under Curve; D001665:Binding Sites; D002851:Chromatography, High Pressure Liquid; D051544:Cytochrome P-450 CYP3A / Q000737:chemistry / Q000378:metabolism*; D065692:Cytochrome P-450 CYP3A Inhibitors / Q000737:chemistry / Q000378:metabolism*; D005978:Glutathione / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D062105:Molecular Docking Simulation; D017434:Protein Structure, Tertiary; D012372:ROC Curve; D053719:Tandem Mass Spectrometry; D029757:Tripterygium / Q000201:enzymology*
chemical_list: D000470:Alkaloids; D065692:Cytochrome P-450 CYP3A Inhibitors; D051544:Cytochrome P-450 CYP3A; D005978:Glutathione
keywords: CYP3A4; In vitro experiment; Mechanism-based inhibitors; Molecular docking; Pharmacophore model; Tripterygium wilfordii