相关实验视频

Updated: Jan 15, 2026

Mass Spectrometry and Luminogenic-based Approaches to Characterize Phase I Metabolic Competency of In Vitro Cell Cultures

Mass Spectrometry and Luminogenic-based Approaches to Characterize Phase I Metabolic Competency of In Vitro Cell Cultures

Published on: March 28, 2017

在Silico分子洞察到CYP3A介导的物种间的单酶解毒

Lorenzo Pedroni¹, Ronette Gehring², Jean-Lou C M Dorne³

¹Department of Food and Drug, University of Parma, Parma, Italy.

|October 10, 2025

概括

由于它们的CYP3A酶如何处理药物的差异,单素的毒性因物种而异. 这项研究使用了计算方法来解释这些变异的monensin排毒和毒性.

科学领域:

兽医药理学兽医药理学兽医药理学
计算毒理学计算毒理学
酶动力学酶动力学

背景情况:

素是一种离子体抗生素,具有显著的物种特异性毒性.
毒性差异与CYP3A媒介代谢的变化有关,特别是O-脱甲基化,这是一个关键的解毒途径.
马类 (equus caballus) 是最敏感的,猪类 (sus scrofa) 是部分耐受,而类 (gallus gallus) 是最耐受的.

研究的目的:

为了研究,猪和马的和CYP3A异型之间的分子相互作用.
通过使用in silico方法阐明单酶代谢和毒性的特定物种差异的基础.

主要方法:

利用了一个3D建模管道,结合了分子对接和动力学模拟.
应用机器学习用于对单酶-CYP3A相互作用的后处理分析.
检查了测试CYP3A异型的催化位点内的氨基酸残留的差异.

主要成果:

在CYP3A酶中鉴定了单酶结合亲和力和稳定性的跨物种和异型特异性差异.
发现了跨物种的催化位氨基酸残留的变化.
建立了观察到的单O脱甲基化效率和毒性差异的分子基础.

结论:

这项研究提供了对单酶解毒的物种间变异性的机制性见解.
包括3D建模和模拟在内的in silico方法是了解毒理学机制和风险评估的宝贵工具.
这些发现解释了马,猪和对单酶毒性的不同易感性.

关键词:

细胞染色体P450的使用.在的毒理学.分子建模分子建模单氨酸的使用方法 Monensin

更多相关视频

Unveiling Xenobiotic Transport and Effects in Isolated Mitochondria: Insights from Respirometric and Enzymatic Assays

Unveiling Xenobiotic Transport and Effects in Isolated Mitochondria: Insights from Respirometric and Enzymatic Assays

Published on: March 7, 2025

Investigation of Xenobiotics Metabolism In Salix alba Leaves via Mass Spectrometry Imaging

Investigation of Xenobiotics Metabolism In Salix alba Leaves via Mass Spectrometry Imaging

Published on: June 15, 2020

相关概念视频

Drug Metabolism: Phase II Reactions

Drug Metabolism: Phase II Reactions

Phase II reactions are essential for the detoxification and elimination of drugs from the body. These reactions involve the conjugation of parent drugs or their phase I metabolites with endogenous molecules, resulting in more hydrophilic drug conjugates. The primary conjugation reactions in this phase are sulfation and glucuronidation. Both sulfation and glucuronidation typically produce biologically inactive metabolites. However, in some cases involving prodrugs, active metabolites may be...

Physiological Pharmacokinetic Models: Incorporating Hepatic Transporter-Mediated Clearance

Physiological Pharmacokinetic Models: Incorporating Hepatic Transporter-Mediated Clearance

Drug transporters are critical in drug absorption, distribution, and excretion processes. They should be included in physiological-based pharmacokinetic (PBPK) models, which help predict human drug disposition. However, predicting this is challenging during drug development, especially when liver transport is involved. However, with a realistic representation of body transport processes, an accurate model may be possible.
A recent model describes pravastatin's hepatobiliary excretion,...

Pharmacokinetics: Drug–Drug Interactions

Pharmacokinetics: Drug–Drug Interactions

Drug interactions occur when the pharmacological effect of one drug is altered by another substance, either enhancing or diminishing its activity. The drug whose activity is altered is known as the object drug, and the substance causing the alteration is called the agent drug or the precipitant. The net effects of these interactions are mostly undesirable, leading to decreased effectiveness or increased adverse effects. In rare cases, interactions can be beneficial, such as the enhanced...