The Generation, Detection, and Effects of Reactive Drug Metabolites

Third-generation antiepileptic drugs: mechanisms of action, pharmacokinetics and interactions

(2014) Jarogniew J. Łuszczki   Pharmacological Reports

Oxidant stress, mitochondria, and cell death mechanisms in drug-induced liver injury: Lessons learned from acetaminophen hepatotoxicity

(2012) Hartmut Jaeschke et al.   DRUG METABOLISM REVIEWS

Enhanced Screening of Glutathione-Trapped Reactive Metabolites by In-Source Collision-Induced Dissociation and Extraction of Product Ion Using UHPLC-High Resolution Mass Spectrometry

(2011) Xiaochun Zhu et al.   ANALYTICAL CHEMISTRY

Structural Alert/Reactive Metabolite Concept as Applied in Medicinal Chemistry to Mitigate the Risk of Idiosyncratic Drug Toxicity: A Perspective Based on the Critical Examination of Trends in the Top 200 Drugs Marketed in the United States

(2011) Antonia F. Stepan et al.   CHEMICAL RESEARCH IN TOXICOLOGY

Chemistry and Reactivity of Acyl Glucuronides

(2011) Andrew V. Stachulski   CURRENT DRUG METABOLISM

Managing the challenge of chemically reactive metabolites in drug development

(2011) B. Kevin Park et al.   NATURE REVIEWS DRUG DISCOVERY

Design and synthesis of conformationally constrained N,N-disubstituted 1,4-diazepanes as potent orexin receptor antagonists

(2010) Paul J. Coleman et al.   BIOORGANIC & MEDICINAL CHEMISTRY LETTERS

Acyl glucuronides: the good, the bad and the ugly

(2010) Sophie L. Regan et al.   BIOPHARMACEUTICS & DRUG DISPOSITION

Cytochrome P450-Mediated Epoxidation of 2-Aminothiazole-Based AKT Inhibitors: Identification of Novel GSH Adducts and Reduction of Metabolic Activation through Structural Changes Guided by in Silico and in Vitro Screening

(2010) Raju Subramanian et al.   CHEMICAL RESEARCH IN TOXICOLOGY

Crucial Role of Nrf3 in Smooth Muscle Cell Differentiation From Stem Cells

(2010) Anna Elena Pepe et al.   CIRCULATION RESEARCH

Reactivity of in vitro activated human T lymphocytes to p-phenylenediamine and related substances

(2010) Claudia Skazik et al.   CONTACT DERMATITIS

Plasma Stability-Dependent Circulation of Acyl Glucuronide Metabolites in Humans: How Circulating Metabolite Profiles of Muraglitazar and Peliglitazar Can Lead to Misleading Risk Assessment

(2010) D. Zhang et al.   DRUG METABOLISM AND DISPOSITION

Toxicological Evaluation of Acyl Glucuronides of Nonsteroidal Anti-Inflammatory Drugs Using Human Embryonic Kidney 293 Cells Stably Expressing Human UDP-Glucuronosyltransferase and Human Hepatocytes

(2010) T. Koga et al.   DRUG METABOLISM AND DISPOSITION

Predictability of Idiosyncratic Drug Toxicity Risk for Carboxylic Acid-Containing Drugs Based on the Chemical Stability of Acyl Glucuronide

(2010) R. Sawamura et al.   DRUG METABOLISM AND DISPOSITION

Long Isoforms of NRF1 Contribute to Arsenic-Induced Antioxidant Response in Human Keratinocytes

(2010) Rui Zhao et al.   ENVIRONMENTAL HEALTH PERSPECTIVES

Hepatic Clearance of Reactive Glucuronide Metabolites of Diclofenac in the Mouse Is Dependent on Multiple ATP-Binding Cassette Efflux Transporters

(2010) J. S. Lagas et al.   MOLECULAR PHARMACOLOGY

Xenobiotic, Bile Acid, and Cholesterol Transporters: Function and Regulation

(2010) C. D. Klaassen et al.   PHARMACOLOGICAL REVIEWS

Investigation of the Crossreactivity of Mycophenolic Acid Glucuronide Metabolites and of Mycophenolate Mofetil in the Cedia MPA Assay

(2010) Maria Shipkova et al.   THERAPEUTIC DRUG MONITORING

Induction of heat shock proteins for protection against oxidative stress

(2009) Bernadett Kalmar et al.   ADVANCED DRUG DELIVERY REVIEWS

The impact of cytokines on the expression of drug transporters, cytochrome P450 enzymes and chemokine receptors in human PBMC

(2009) NJ Liptrott et al.   BRITISH JOURNAL OF PHARMACOLOGY

Can In Vitro Metabolism-Dependent Covalent Binding Data Distinguish Hepatotoxic from Nonhepatotoxic Drugs? An Analysis Using Human Hepatocytes and Liver S-9 Fraction

(2009) Jonathon N. Bauman et al.   CHEMICAL RESEARCH IN TOXICOLOGY

In Vitro Screening of 50 Highly Prescribed Drugs for Thiol Adduct FormationComparison of Potential for Drug-Induced Toxicity and Extent of Adduct Formation

(2009) Jinping Gan et al.   CHEMICAL RESEARCH IN TOXICOLOGY

A Mechanistic Investigation into the Irreversible Protein Binding and Antigenicity ofp-Phenylenediamine

(2009) Claire Jenkinson et al.   CHEMICAL RESEARCH IN TOXICOLOGY

Multiple Adduction Reactions of Nitroso Sulfamethoxazole with Cysteinyl Residues of Peptides and Proteins: Implications for Hapten Formation

(2009) Hayley E. Callan et al.   CHEMICAL RESEARCH IN TOXICOLOGY

Structure−Activity Relationships for the Degradation Reaction of 1-β-O-Acyl Glucuronides. Part 2: Electronic and Steric Descriptors Predicting the Reactivity of 1-β-O-Acyl Glucuronides Derived from Benzoic Acids

(2009) Tadao Yoshioka et al.   CHEMICAL RESEARCH IN TOXICOLOGY

Structure−Activity Relationships for the Degradation Reaction of 1-β-O-Acyl Glucuronides. Part 3: Electronic and Steric Descriptors Predicting the Reactivity of Aralkyl Carboxylic Acid 1-β-O-Acyl Glucuronides

(2009) Akiko Baba et al.   CHEMICAL RESEARCH IN TOXICOLOGY

Effect of Mycophenolate Acyl-Glucuronide on Human Recombinant Type 2 Inosine Monophosphate Dehydrogenase

(2009) O. Gensburger et al.   CLINICAL CHEMISTRY

Glucuronidation and Covalent Protein Binding of Benoxaprofen and Flunoxaprofen in Sandwich-Cultured Rat and Human Hepatocytes

(2009) J. Q. Dong et al.   DRUG METABOLISM AND DISPOSITION

A Zone Classification System for Risk Assessment of Idiosyncratic Drug Toxicity Using Daily Dose and Covalent Binding

(2009) S. Nakayama et al.   DRUG METABOLISM AND DISPOSITION

Quantifying the Metabolic Activation of Nevirapine in Patients by Integrated Applications of NMR and Mass Spectrometries

(2009) A. Srivastava et al.   DRUG METABOLISM AND DISPOSITION

Quantitative Assessment of Reactive Metabolite Formation using 35S-labeled Glutathione

(2009) Hideo Takakusa et al.   Drug Metabolism and Pharmacokinetics

A Trapping Method for Semi-quantitative Assessment of Reactive Metabolite Formation Using [35S]Cysteine and [14C]Cyanide

(2009) Kazuko Inoue et al.   Drug Metabolism and Pharmacokinetics

Application of mechanism-based CYP inhibition for predicting drug–drug interactions

(2009) Zhi-Wei Zhou et al.   Expert Opinion on Drug Metabolism & Toxicology

Inhibiting the transcription factor HSF1 as an anticancer strategy

(2009) Luke Whitesell et al.   EXPERT OPINION ON THERAPEUTIC TARGETS

Oral medications with significant hepatic metabolism at higher risk for hepatic adverse events

(2009) Craig Lammert et al.   HEPATOLOGY

Acetaminophen dosing of humans results in blood transcriptome and metabolome changes consistent with impaired oxidative phosphorylation

(2009) Rick D. Fannin et al.   HEPATOLOGY

Characterization of p-Phenylenediamine–Albumin Binding Sites and T-Cell Responses to Hapten-Modified Protein

(2009) Claire Jenkinson et al.   JOURNAL OF INVESTIGATIVE DERMATOLOGY

"Danger" Conditions Increase Sulfamethoxazole-Protein Adduct Formation in Human Antigen-Presenting Cells

(2009) S. N. Lavergne et al.   JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS

A Study of the Specificity of Lymphocytes in Nevirapine-Induced Skin Rash

(2009) X. Chen et al.   JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS

InSitu Transient Spectroscopy for the Study of Glucuronidase Activity within Serum Albumin

(2009) Carlos J. Bueno et al.   JOURNAL OF PHYSICAL CHEMISTRY B

Synthesis, transacylation kinetics and computational chemistry of a set of arylacetic acid 1β-O-acyl glucuronides

(2009) Neil G. Berry et al.   ORGANIC & BIOMOLECULAR CHEMISTRY

Rapid detection and characterization of reactive drug metabolitesin vitrousing several isotope-labeled trapping agents and ultra-performance liquid chromatography/time-of-flight mass spectrometry

(2009) Timo Rousu et al.   RAPID COMMUNICATIONS IN MASS SPECTROMETRY

Convenient syntheses of the in vivo carbohydrate metabolites of mycophenolic acid: reactivity of the acyl glucuronide

(2009) Amy E. Jones et al.   TETRAHEDRON LETTERS

Altered Disposition of Acetaminophen in Nrf2-null and Keap1-knockdown Mice

(2009) Scott A. Reisman et al.   TOXICOLOGICAL SCIENCES

NRF2 and KEAP1 mutations: permanent activation of an adaptive response in cancer

(2009) John D. Hayes et al.   TRENDS IN BIOCHEMICAL SCIENCES

Integrated HPLC-MS and1H-NMR spectroscopic studies on acyl migration reaction kinetics of model drug ester glucuronides

(2009) C. H. Johnson et al.   XENOBIOTICA

Quantitative assessment of the metabolic activation of alicyclic amines via aldehyde

(2009) Masahiro Miura et al.   JOURNAL OF PHARMACOLOGICAL AND TOXICOLOGICAL METHODS

Role of Biotransformation Studies in Minimizing Metabolism-Related Liabilities in Drug Discovery

(2008) Yue-Zhong Shu et al.   AAPS Journal

The Discovery of Taranabant, a Selective Cannabinoid‐1 Receptor Inverse Agonist for the Treatment of Obesity

(2008) William K. Hagmann   ARCHIV DER PHARMAZIE

The Nrf1 CNC/bZIP protein is a nuclear envelope-bound transcription factor that is activated by t-butyl hydroquinone but not by endoplasmic reticulum stressors

(2008) Yiguo Zhang et al.   BIOCHEMICAL JOURNAL

Sensitization to p-amino aromatic compounds: Study of the covalent binding of 2,5-dimethyl-p-benzoquinonediimine to a model peptide by electrospray ionization tandem mass spectrometry

(2008) Joan Eilstein et al.   BIOORGANIC & MEDICINAL CHEMISTRY

Trifluoromethylpyrimidine-based inhibitors of proline-rich tyrosine kinase 2 (PYK2): Structure–activity relationships and strategies for the elimination of reactive metabolite formation

(2008) Daniel P. Walker et al.   BIOORGANIC & MEDICINAL CHEMISTRY LETTERS

In VitroMetabolism and Covalent Binding of Enol-Carboxamide Derivatives and Anti-Inflammatory Agents Sudoxicam and Meloxicam: Insights into the Hepatotoxicity of Sudoxicam

(2008) R. Scott Obach et al.   CHEMICAL RESEARCH IN TOXICOLOGY

Can In Vitro Metabolism-Dependent Covalent Binding Data in Liver Microsomes Distinguish Hepatotoxic from Nonhepatotoxic Drugs? An Analysis of 18 Drugs with Consideration of Intrinsic Clearance and Daily Dose

(2008) R. Scott Obach et al.   CHEMICAL RESEARCH IN TOXICOLOGY

Peptide-Based In Vitro Assay for the Detection of Reactive Metabolites

(2008) Michael D. Mitchell et al.   CHEMICAL RESEARCH IN TOXICOLOGY

Application of Stable Isotope-Labeled Compounds in Metabolism and in Metabolism-Mediated Toxicity Studies

(2008) Abdul E. Mutlib   CHEMICAL RESEARCH IN TOXICOLOGY

Demonstration of the Metabolic Pathway Responsible for Nevirapine-Induced Skin Rash

(2008) Jie Chen et al.   CHEMICAL RESEARCH IN TOXICOLOGY

Covalent Modification at Cys151 Dissociates the Electrophile Sensor Keap1 from the Ubiquitin Ligase CUL3

(2008) Girish Rachakonda et al.   CHEMICAL RESEARCH IN TOXICOLOGY

Structure−Activity Relationships for Degradation Reaction of 1-β-O-Acyl Glucuronides: Kinetic Description and Prediction of Intrinsic Electrophilic Reactivity under Physiological Conditions

(2008) Akiko Baba et al.   CHEMICAL RESEARCH IN TOXICOLOGY

Recent advances in applications of liquid chromatography–tandem mass spectrometry to the analysis of reactive drug metabolites

(2008) Shuguang Ma et al.   CHEMICO-BIOLOGICAL INTERACTIONS

Covalent Binding and Tissue Distribution/Retention Assessment of Drugs Associated with Idiosyncratic Drug Toxicity

(2008) H. Takakusa et al.   DRUG METABOLISM AND DISPOSITION

Understanding the role of reactive metabolites in drug-induced hepatotoxicity: state of the science

(2008) Daniel J Antoine et al.   Expert Opinion on Drug Metabolism & Toxicology

Metabolic activation of carboxylic acids

(2008) Christian Skonberg et al.   Expert Opinion on Drug Metabolism & Toxicology

The hepatotoxic metabolite of acetaminophen directly activates the Keap1-Nrf2 cell defense system

(2008) Ian M. Copple et al.   HEPATOLOGY

Pathogenic role of natural killer T and natural killer cells in acetaminophen-induced liver injury in mice is dependent on the presence of dimethyl sulfoxide

(2008) Mary Jane Masson et al.   HEPATOLOGY

Nrf1 and Nrf2 Play Distinct Roles in Activation of Antioxidant Response Element-dependent Genes

(2008) Makiko Ohtsuji et al.   JOURNAL OF BIOLOGICAL CHEMISTRY

The Nrf3 Transcription Factor Is a Membrane-bound Glycoprotein Targeted to the Endoplasmic Reticulum through Its N-terminal Homology Box 1 Sequence

(2008) Yiguo Zhang et al.   JOURNAL OF BIOLOGICAL CHEMISTRY

Skin Sensitization to p-Phenylenediamine: The Diverging Roles of Oxidation and N-Acetylation for Dendritic Cell Activation and the Immune Response

(2008) Pierre Aeby et al.   JOURNAL OF INVESTIGATIVE DERMATOLOGY

Screening and characterization of reactive metabolites using glutathione ethyl ester in combination with Q-trap mass spectrometry

(2008) Bo Wen et al.   JOURNAL OF MASS SPECTROMETRY

The Many Roles for Fluorine in Medicinal Chemistry

(2008) William K. Hagmann   JOURNAL OF MEDICINAL CHEMISTRY

Reduced acetaminophen-induced liver injury in mice by genetic disruption of IL-1 receptor antagonist

(2008) Takuya Ishibe et al.   LABORATORY INVESTIGATION

Covalent Binding of the Nitroso Metabolite of Sulfamethoxazole Is Important in Induction of Drug-Specific T-Cell Responses in Vivo

(2008) L. Cheng et al.   MOLECULAR PHARMACOLOGY

Investigation of the immunogenicity of p-phenylenediamine and Bandrowski's base in the mouse

(2008) John Farrell et al.   TOXICOLOGY LETTERS

Effect of HIV-1-related protein expression on cardiac and skeletal muscles from transgenic rats

(2008) Jeffrey S Otis et al.   AIDS Research and Therapy

Metabolism and Toxicity of Drugs. Two Decades of Progress in Industrial Drug Metabolism

(2007) Thomas A. Baillie   CHEMICAL RESEARCH IN TOXICOLOGY

Mechanism-Based Inactivation of Human Cytochromes P450s: Experimental Characterization, Reactive Intermediates, and Clinical Implications

(2007) Paul F. Hollenberg et al.   CHEMICAL RESEARCH IN TOXICOLOGY

Activation of T-Cells from Allergic Patients and Volunteers by p-Phenylenediamine and Bandrowski's Base

(2007) Eve Marie Coulter et al.   JOURNAL OF INVESTIGATIVE DERMATOLOGY

Investigation of the effect of a panel of model hepatotoxins on the Nrf2-Keap1 defence response pathway in CD-1 mice

(2007) Laura E. Randle et al.   TOXICOLOGY

The Nrf2–Keap1 defence pathway: Role in protection against drug-induced toxicity

(2007) Ian M. Copple et al.   TOXICOLOGY

Induction of Mrp3 and Mrp4 transporters during acetaminophen hepatotoxicity is dependent on Nrf2

(2007) Lauren M. Aleksunes et al.   TOXICOLOGY AND APPLIED PHARMACOLOGY