scholarly journals Estimation of the binding modes with important human cytochrome P450 enzymes, drug interaction potential, pharmacokinetics, and hepatotoxicity of ginger components using molecular docking, computational, and pharmacokinetic modeling studies

2015 ◽  
pp. 841 ◽  
Author(s):  
Shu-Feng Zhou ◽  
Jiaxuan Qiu ◽  
Zhi-Wei Zhou ◽  
Zhixue He ◽  
Xueji Zhang ◽  
...  
Keyword(s):  
Cytochrome P450 ◽  
Molecular Docking ◽  
Drug Interaction ◽  
Interaction Potential ◽  
Pharmacokinetic Modeling ◽  
Binding Modes ◽  
Cytochrome P450 Enzymes ◽  
Modeling Studies ◽  
Human Cytochrome

In vitro inhibitory mechanisms and molecular docking of 1′-S-1′-acetoxychavicol acetate on human cytochrome P450 enzymes

Phytomedicine ◽  
2017 ◽  
Vol 31 ◽  
pp. 1-9 ◽  
Author(s):  
A.K.M. Mahmudul Haque ◽  
Kok Hoong Leong ◽  
Yoke Lin Lo ◽  
Khalijah Awang ◽  
Noor Hasima Nagoor
Keyword(s):  
Cytochrome P450 ◽  
Molecular Docking ◽  
Cytochrome P450 Enzymes ◽  
Inhibitory Mechanisms ◽  
Human Cytochrome

scholarly journals Human cytochrome P450 enzymes bind drugs and other substrates mainly through conformational-selection modes

2019 ◽  
Vol 294 (28) ◽  
pp. 10928-10941 ◽  
Author(s):  
F. Peter Guengerich ◽  
Clayton J. Wilkey ◽  
Thanh T. N. Phan
Keyword(s):  
Cytochrome P450 ◽  
Model Simulation ◽  
Selection Model ◽  
Binding Modes ◽  
Cytochrome P450 Enzymes ◽  
Induced Fit ◽  
Conformational Selection ◽  
Human Cytochrome ◽  
Dominant Feature ◽  
Fat Soluble Vitamins

Cytochrome P450 (P450) enzymes are major catalysts involved in the oxidations of most drugs, steroids, carcinogens, fat-soluble vitamins, and natural products. The binding of substrates to some of the 57 human P450s and other mammalian P450s is more complex than a two-state system and has been proposed to involve mechanisms such as multiple ligand occupancy, induced-fit, and conformational-selection. Here, we used kinetic analysis of binding with multiple concentrations of substrates and computational modeling of these data to discern possible binding modes of several human P450s. We observed that P450 2D6 binds its ligand rolapitant in a mechanism involving conformational-selection. P450 4A11 bound the substrate lauric acid via conformational-selection, as did P450 2C8 with palmitic acid. Binding of the steroid progesterone to P450 21A2 was also best described by a conformational-selection model. Hexyl isonicotinate binding to P450 2E1 could be described by either a conformational-selection or an induced-fit model. Simulation of the binding of the ligands midazolam, bromocriptine, testosterone, and ketoconazole to P450 3A4 was consistent with an induced-fit or a conformational-selection model, but the concentration dependence of binding rates for varying both P450 3A4 and midazolam concentrations revealed discordance in the parameters, indicative of conformational-selection. Binding of the P450s 2C8, 2D6, 3A4, 4A11, and 21A2 was best described by conformational-selection, and P450 2E1 appeared to fit either mode. These findings highlight the complexity of human P450-substrate interactions and that conformational-selection is a dominant feature of many of these interactions.

scholarly journals Drug Interaction Potential of Osilodrostat (LCI699) Based on Its Effect on the Pharmacokinetics of Probe Drugs of Cytochrome P450 Enzymes in Healthy Adults

2017 ◽  
Vol 37 (5) ◽  
pp. 465-472 ◽  
Author(s):  
Sara Armani ◽  
Lillian Ting ◽  
Nicholas Sauter ◽  
Christelle Darstein ◽  
Anadya Prakash Tripathi ◽  
...  
Keyword(s):  
Cytochrome P450 ◽  
Drug Interaction ◽  
Interaction Potential ◽  
Healthy Adults ◽  
Cytochrome P450 Enzymes
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