Trial reportThe pharmacogenomics journal2011
In silico and in vitro pharmacogenetics: aldehyde oxidase rapidly metabolizes a p38 kinase inhibitor.
Trial report in The pharmacogenomics journal, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
28 citing papers in PubMed, 86 citations in OpenAlex.
- Twenty-first century mouse genetics is again at an inflection point.Lab animal · 2025Review
- Article
- Roles of selected non-P450 human oxidoreductase enzymes in protective and toxic effects of chemicals: review and compilation of reactions.Archives of toxicology · 2022Review
- An automated multi-modal graph-based pipeline for mouse genetic discovery.Bioinformatics (Oxford, England) · 2022Article
- Mouse Genetic Reference Populations: Cellular Platforms for Integrative Systems Genetics.Trends in genetics : TIG · 2021Review
- What Have We Learned (or Expect to) From Analysis of Murine Genetic Models Related to Substance Use Disorders?Frontiers in psychiatry · 2021Review
- The Effect of Population Structure on Murine Genome-Wide Association Studies.Frontiers in genetics · 2021Article
- Enzyme Kinetics, Pharmacokinetics, and Inhibition of Aldehyde Oxidase.Methods in molecular biology (Clifton, N.J.) · 2021Article
- Site-Directed Mutagenesis at the Molybdenum Pterin Cofactor Site of the Human Aldehyde Oxidase: Interrogating the Kinetic Differences Between Human and Cynomolgus Monkey.Drug metabolism and disposition: the biological fate of chemicals · 2020Article
- Understanding the Metabolism of Proteolysis Targeting Chimeras (PROTACs): The Next Step toward Pharmaceutical Applications.Journal of medicinal chemistry · 2020Article
- Predicting liver cytosol stability of small molecules.Journal of cheminformatics · 2020Article
- In Vitro Metabolism by Aldehyde Oxidase Leads to Poor Pharmacokinetic Profile in Rats for c-Met Inhibitor MET401.European journal of drug metabolism and pharmacokinetics · 2019Article
- Fast Methods for Prediction of Aldehyde Oxidase-Mediated Site-of-Metabolism.Computational and structural biotechnology journal · 2019Article
- Xenobiotica-metabolizing enzymes in the skin of rat, mouse, pig, guinea pig, man, and in human skin models.Archives of toxicology · 2018Review
- Selective Heteroaryl N-Oxidation of Amine-Containing Molecules.Organic letters · 2018Article
- A novel in vitro allometric scaling methodology for aldehyde oxidase substrates to enable selection of appropriate species for traditional allometry.Xenobiotica; the fate of foreign compounds in biological systems · 2018Article
- Identification of cryptolepine metabolites in rat and human hepatocytes and metabolism and pharmacokinetics of cryptolepine in Sprague Dawley rats.BMC pharmacology & toxicology · 2017Article
- Continuous Intestinal Absorption Model Based on the Convection-Diffusion Equation.Molecular pharmaceutics · 2017Article
- Pyrido[3,4-d]pyrimidin-4(3H)-one metabolism mediated by aldehyde oxidase is blocked by C2-substitution.Xenobiotica; the fate of foreign compounds in biological systems · 2017Article
- ecoAO: A Simple System for the Study of Human Aldehyde Oxidases Role in Drug Metabolism.ACS omega · 2017Article
Corrections and comments
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Authors and funding
9 authors at 1 institution in 1 country.
Funding
Abstract
The clinical development of a candidate p38 kinase inhibitor was terminated because of its unexpectedly rapid clearance in human subjects. Its short half-life and metabolic profile in human beings were vastly different from that in rats, dogs, and monkeys characterized during routine pre-clinical studies. Mice generated the predominant drug (4-hydroxylated) metabolite produced in human beings, which was not found in other species. The data from a murine in vitro drug biotransformation assay that used liver extracts from 14 inbred mouse strains were analyzed by haplotype-based computational genetic analysis. This led to the identification of aldehyde oxidase-1 (AOX1) as the enzyme responsible for the rapid metabolism of this drug. Specific enzyme inhibitors and expressed recombinant enzymes were used to confirm that AOX catalyzed the formation of the 4-hydroxylated drug metabolite in mouse and man. Genetic variation within Aox1 regulated the level of hepatic Aox1 mRNA, AOX1 protein, and enzyme activity among the inbred strains. Thus, computational murine pharmacogenetic analysis can facilitate the identification and characterization of drug metabolism pathways that are differentially utilized by humans and other species.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.