In vitro study of 6-mercaptopurine oxidation catalysed by aldehyde oxidase and xanthine oxidase.

@article{Rashidi2007InVS,
  title={In vitro study of 6-mercaptopurine oxidation catalysed by aldehyde oxidase and xanthine oxidase.},
  author={Mohammad Reza Rashidi and Christine Beedham and John S Smith and Soodabeh Davaran},
  journal={Drug metabolism and pharmacokinetics},
  year={2007},
  volume={22 4},
  pages={
          299-306
        }
}
In spite of over 40 years of clinical use of 6-mercaptopurine, many aspects of complex pharmacology and metabolism of this drug remain unclear. It is thought that 6-mercaptopurine is oxidized to 6-thiouric acid through 6-thioxanthine or 8-oxo-6-mercaptopurine by one of two molybdenum hydroxylases, xanthine oxidase (XO), however, the role of other molybdenum hydroxylase, aldehyde oxidase (AO), in the oxidation of 6-mercaptopurine and possible interactions of AO substrates and inhibitors has not… 
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In Vitro Oxidative Metabolism of 6-Mercaptopurine in Human Liver: Insights into the Role of the Molybdoflavoenzymes Aldehyde Oxidase, Xanthine Oxidase, and Xanthine Dehydrogenase
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Investigation of the in vitro metabolism of 6MP to 6-thiouric acid (6TUA) in pooled human liver cytosol found evidence that three enzymes, AO, XO, and XDH, contribute to the production of 6TX intermediate, whereas only XO andXDH are involved in the conversion of 6 TX to 6TUA in pooled HLC.
Effects of Phenothiazines on Aldehyde Oxidase Activity Towards Aldehydes and N-Heterocycles: an In Vitro and In Silico Study
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The five studied phenothiazine drugs showed dual inhibitory effects on AOX activity towards aldehydes and N-heterocycles as two major classes of enzyme substrates.
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Combination of spectroscopic techniques and chemometric methods (PLS and PCR) has provided a simple but powerful method for simultaneous analysis of multicomponent mixtures.
Enzyme Kinetics, Pharmacokinetics, and Inhibition of Aldehyde Oxidase.
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Aldehyde oxidase (AO) appears to be amenable to computational predictions of both regioselectivity and rates of reaction, which holds promise for virtual screening.
Enzyme kinetics, inhibition, and regioselectivity of aldehyde oxidase.
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AO appears to be amenable to computational predictions of both regioselectivity and rates of reaction, which holds promise for virtual screening and the inhibition kinetics are complex, and multiple probe substrates should be used when assessing the potential for DDIs.
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There is evidence for an increasing relevance of AOX1 in the metabolism and clearance of new drugs, as measures aiming at controlling CYP450-dependent metabolism of prospective therapeutic agents are becoming routine.
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TLDR
An HPLC-MS/MS assay was developed to determine whether AP and its primary metabolite, oxypurinol, are retained within the cytosol for livers that were treated with AP during liver harvest and whether this could pose a problem for measuring in vitro XO activity.
Role of Aldehyde Oxidase and Xanthine Oxidase in the Metabolism of Purine-Related Drugs
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There is need for reliable methods to screen for, predict, and validate AOX-dependent metabolism of new drug candidates, as the current strategies of organic synthesis designed to avoid cytochrome P450 (CYP450)-dependent metabolism tend to enrich for new chemical structures efficiently oxidized by these enzymes.
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