Regioselective oxidation of phospho‐NSAIDs by human cytochrome P450 and flavin monooxygenase isoforms: implications for their pharmacokinetic properties and safety

@article{Xie2012RegioselectiveOO,
  title={Regioselective oxidation of phospho‐NSAIDs by human cytochrome P450 and flavin monooxygenase isoforms: implications for their pharmacokinetic properties and safety},
  author={Gang Xie and Chi Chun Wong and Ka-Wing Cheng and Liqun Huang and Panayiotis Constantinides and Basil Rigas},
  journal={British Journal of Pharmacology},
  year={2012},
  volume={167}
}
  • G. Xie, C. Wong, B. Rigas
  • Published 1 September 2012
  • Biology, Medicine
  • British Journal of Pharmacology
Phospho‐ibuprofen (MDC‐917) and phospho‐sulindac (OXT‐328) are highly effective in cancer and arthritis treatment in preclinical models. Here, we investigated their metabolism by major human cytochrome P450s (CYPs) and flavin monooxygenases (FMOs). 
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24 Citations

The in vitro metabolism of phospho-sulindac amide, a novel potential anticancer agent.
Flavin monooxygenase metabolism: why medicinal chemists should matter.
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For the first time, a substrate-specificity and catalytic-activity model for FMO3, the most relevant isoform of the FMOs in humans, is reported and the application of this model to a series of compounds with unknown FMO metabolism is reported.
Roles of selected non-P450 human oxidoreductase enzymes in protective and toxic effects of chemicals: review and compilation of reactions
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An overview of the metabolic reactions of drugs, natural products, physiological compounds, and other (general) chemicals catalyzed by flavin monooxygenase, monoamine oxidase, NAD(P)H quinone oxidoreductase, and molybdenum hydroxylase enzymes, including roles as substrates, inducers, and inhibitors of the enzymes.
Comparative in vitro metabolism of phospho-tyrosol-indomethacin by mice, rats and humans.
An investigation into the contribution of flavin containing monooxygenases to the development and prevention of thiourea-induced pulmonary toxicity in the rat
TLDR
Evidence is contributed that FMO2 polymorphism may be relevant to humans and provides an animal model which can be used to study its implications and it was shown that pulmonary endothelial cells are the main target of acute NR678 oxidative injury and exhibit ultrastructural alterations, which are likely responsible for the perturbation of pulmonary vascular permeability.
Flavin-containing monooxygenase 3 (FMO3): genetic variants and their consequences for drug metabolism and disease
  • I. Phillips, E. Shephard
  • Biology, Chemistry
    Xenobiotica; the fate of foreign compounds in biological systems
  • 2019
TLDR
Genetic variants of human flavin-containing monooxygenase 3 (FMO3) have been associated with a number of disorders, but additional studies are needed to confirm or refute such associations.
Drug metabolism by flavin-containing monooxygenases of human and mouse
TLDR
Identification of roles for FMO1 and FMO5 in endogenous metabolism has implications for drug therapy and initiates an exciting area of research.
Recent Developments in Chimeric NSAIDs as Safer Anti‐Inflammatory Agents
TLDR
This review deals with approaches and strategies that have been employed in the last two decades and are being used currently in the design and development of safer NSAIDs.
Whole-cell dependent biosynthesis of N- and S-oxides using human flavin containing monooxygenases expressing budding yeast.
Relative Expression of Mouse Udp-Glucuronosyl Transferase 2b1 Gene in The Livers, Kidneys, And Hearts: The Influence of Nonsteroidal Anti-Inflammatory Drug Treatment.
TLDR
It was found that the mouse ugt2b1 gene was mainly expressed in the liver, as 14-day administration of different NSAIDs caused alterations in the expression of this gene, which may influence the metabolism of xenobiotic and endogenous compounds.
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