Beedham Christine
Honorary Senior Lecturer, Faculty of Life Sciences, School of Pharmacy and Medical Sciences, University of Bradford, Bradford, UK.
Xenobiotica. 2020 Jan;50(1):34-50. doi: 10.1080/00498254.2019.1626029. Epub 2019 Jun 19.
Despite expanding knowledge on the structure and reactivity of human aldehyde oxidase (hAOX1) many drugs enter human studies only to be removed from further clinical trials due to aldehyde oxidase (AOX)-catalysed metabolism.In addition to oxidation of numerous N-heterocycles and aldehydes, hAOX1 is also important in amide hydrolysis and reductive reactions.This article reviews the evidence for hAOX1 polymorphism and other genetic factors which affect hAOX1 expression and which may lead to attenuated drug metabolism.Difficulties in the selection of appropriate and models for predicting hAOX1 metabolism are considered in the context of its wide substrate specificity.
尽管人们对人类醛氧化酶（hAOX1）的结构和反应活性的了解不断增加，但许多药物进入人体研究后，却因醛氧化酶（AOX）催化的代谢作用而在进一步的临床试验中被淘汰。除了对众多氮杂环和醛类进行氧化外，hAOX1在酰胺水解和还原反应中也很重要。本文综述了hAOX1多态性以及其他影响hAOX1表达并可能导致药物代谢减弱的遗传因素的相关证据。鉴于hAOX1广泛的底物特异性，文中还讨论了选择合适的预测hAOX1代谢的方法和模型时所面临的困难。
