A novel approach to predicting P450 mediated drug metabolism. CYP2D6 catalyzed N-dealkylation reactions and qualitative metabolite predictions using a combined protein and pharmacophore model for CYP2D6.

No abstract is available for this paper.

• Publication year

  1999

• Venue

  Journal of Medicinal Chemistry

• Publication date

  1999-09-09

• Fields of study

  Medicine, Chemistry

• Identifiers
  DOI 10.1021/JM991058VPMID 10514276
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

• Variable contribution of CYP2D6 to the N-dealkylation of S-(-)-propranolol by human liver microsomes.

  2003cited by this paper
• Cytochromes P450 mediating the N-demethylation of amitriptyline.

  2003cited by this paper
• Novel approach to predicting P450-mediated drug metabolism: development of a combined protein and pharmacophore model for CYP2D6.

  1999cited by this paper
• Hydroxylation and demethylation of the tricyclic antidepressant nortriptyline by cDNA-expressed human cytochrome P-450 isozymes.

  1997cited by this paper
• Extension of a predictive substrate model for human cytochrome P4502D6.

  1997cited by this paper
• Modeling the active sites of cytochrome P450s and glutathione S-transferases, two of the most important biotransformation enzymes.

  1997cited by this paper
• Metabolism of MPTP by cytochrome P4502D6 and the demonstration of 2D6 mRNA in human foetal and adult brain by in situ hybridization.

  1997cited by this paper
• Identification of three cytochrome P450 isozymes involved in N-demethylation of citalopram enantiomers in human liver microsomes.

  1997cited by this paper
• Molecular modelling of cytochrome P4502D6 (CYP2D6) based on an alignment with CYP102: structural studies on specific CYP2D6 substrate metabolism.

  1997cited by this paper
• Oxidation of methamphetamine and methylenedioxymethamphetamine by CYP2D6.

  1997cited by this paper
• 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine as a substrate of cytochrome P450 2D6: allosteric effects of NADPH-cytochrome P450 reductase.

  1997cited by this paper
• Role of CYP2D6 in the N-hydroxylation of procainamide.

  1997cited by this paper
• A refined substrate model for human cytochrome P450 2D6.

  1997cited by this paper
• Metabolism of amitriptyline with CYP2D6 expressed in a human cell line.

  1997cited by this paper
• Metabolism of the tricyclic antidepressant amitriptyline by cDNA-expressed human cytochrome P450 enzymes.

  1997cited by this paper
• Metabolism of clozapine by cDNA-expressed human cytochrome P450 enzymes.

  1997cited by this paper
• A model for human cytochrome P450 2D6 based on homology modeling and NMR studies of substrate binding.

  1996cited by this paper
• P450 superfamily: update on new sequences, gene mapping, accession numbers and nomenclature.

  1996cited by this paper
• Nomenclature for human CYP2D6 alleles.

  1996cited by this paper
• Identification of human liver cytochrome P450 enzymes that metabolize the nonsedating antihistamine loratadine. Formation of descarboethoxyloratadine by CYP3A4 and CYP2D6.

  1996cited by this paper
• A three-dimensional protein model for human cytochrome P450 2D6 based on the crystal structures of P450 101, P450 102, and P450 108.

  1996cited by this paper
• Influence of amino acid residue 374 of cytochrome P-450 2D6 (CYP2D6) on the regio- and enantio-selective metabolism of metoprolol.

  1996cited by this paper
• Identification of human cytochrome P450 isoforms involved in the stereoselective metabolism of mianserin enantiomers.

  1996cited by this paper
• Cytochrome P450-mediated metabolism of the HIV-1 protease inhibitor ritonavir (ABT-538) in human liver microsomes.

  1996cited by this paper
• The disposition of fluoxetine but not sertraline is altered in poor metabolizers of debrisoquin

  1996cited by this paper
• Metabolism of methoxyphenamine and 2-methoxyamphetamine in P4502D6-transfected cells and cell preparations.

  1995cited by this paper
• Escherichia coli expression of site-directed mutants of cytochrome P450 2B1 from six substrate recognition sites: substrate specificity and inhibitor selectivity studies.

  1995cited by this paper
• Regioselective and stereoselective oxidation of metoprolol and bufuralol catalyzed by microsomes containing cDNA-expressed human P4502D6.

  1995cited by this paper
• Three-dimensional models of human and other mammalian microsomal P450s constructed from an alignment with P450102 (P450bm3).

  1995cited by this paper
• Computer prediction and experimental validation of cytochrome P4502D6-dependent oxidation of GBR 12909.

  1995cited by this paper
• Identification of human CYP isoforms involved in the metabolism of propranolol enantiomers--N-desisopropylation is mediated mainly by CYP1A2.

  1995cited by this paper
• Application of 3-Dimensional Homology Modeling of Cytochrome P450 2B1 for Interpretation of Site-Directed Mutagenesis Results.

  1994cited by this paper
• Crystal structure and refinement of cytochrome P450terp at 2.3 A resolution.

  1994cited by this paper
• Structural determinants of cytochrome P450 2B1 specificity: evidence for five substrate recognition sites.

  1994cited by this paper
• Application of 3-dimensional homology modeling of cytochrome P450 2B1 for interpretation of site-directed mutagenesis results.

  1994cited by this paper
• Involvement of CYP2D6, CYP3A4, and other cytochrome P-450 isozymes in N-dealkylation reactions.

  1994cited by this paper
• Atypical metabolism of deprenyl and its enantiomer, (S)-(+)-N,alpha-dimethyl-N-propynylphenethylamine, by cytochrome P450 2D6.

  1994cited by this paper
• Characterization of the enzyme responsible for the metabolism of sumatriptan in human liver.

  1994cited by this paper
• Modeling protein-substrate interactions in the heme domain of cytochrome P450(BM-3).

  1994cited by this paper
• Crystal structure of hemoprotein domain of P450BM-3, a prototype for microsomal P450's.

  1993cited by this paper
• Metabolism of imipramine in vitro by isozyme CYP2D6 expressed in a human cell line, and observations on metabolite stability.

  1993cited by this paper
• Development of a pharmacophore for inhibition of human liver cytochrome P-450 2D6: molecular modeling and inhibition studies.

  1993cited by this paper
• Site-directed mutagenesis of mouse steroid 7 alpha-hydroxylase (cytochrome P-450(7) alpha): role of residue-209 in determining steroid-cytochrome P-450 interaction.

  1993cited by this paper
• Analysis of imipramine and three metabolites produced by isozyme CYP2D6 expressed in a human cell line.

  1993cited by this paper
• Engineering mouse P450coh to a novel corticosterone 15 alpha-hydroxylase and modeling steroid-binding orientation in the substrate pocket.

  1993cited by this paper
• A preliminary 3D model for cytochrome P450 2D6 constructed by homology model building

  1993cited by this paper
• A predictive model for substrates of cytochrome P450-debrisoquine (2D6).

  1992cited by this paper
• A three-dimensional molecular template for substrates of human cytochrome P450 involved in debrisoquine 4-hydroxylation.

  1991cited by this paper
• Structural function of residue-209 in coumarin 7-hydroxylase (P450coh). Enzyme-kinetic studies and site-directed mutagenesis.

  1991cited by this paper
• The role of lipophilicity in the inhibition of polymorphic cytochrome P450IID6 oxidation by beta-blocking agents in vitro.

  1991cited by this paper
• Determination of betaxolol and its metabolites in blood and urine by high-performance liquid chromatography with fluorimetric detection.

  1990cited by this paper
• High-resolution crystal structure of cytochrome P450cam.

  1987cited by this paper
• The molecular mechanisms of two common polymorphisms of drug oxidation--evidence for functional changes in cytochrome P-450 isozymes catalysing bufuralol and mephenytoin oxidation.

  1986cited by this paper
• The 2.6-A crystal structure of Pseudomonas putida cytochrome P-450.

  1985cited by this paper
• Substrate specificity of human liver cytochrome P-450 debrisoquine 4-hydroxylase probed using immunochemical inhibition and chemical modeling.

  1985cited by this paper

• Strategies for Assessing Acceptable Intakes for Novel N-Nitrosamines Derived from Active Pharmaceutical Ingredients.

  2022cites this paper
• Metabolic stability studies of lead compounds supported by separation techniques and chemometrics analysis.

  2020cites this paper
• Scaffold-hopping as a strategy to address metabolic liabilities of aromatic compounds.

  2020cites this paper
• Prediction of Aromatic Hydroxylation Sites for Human CYP1A2 Substrates Using Condensed Graph of Reactions

  2018cites this paper
• From Experiments to a Fast Easy-to-Use Computational Methodology to Predict Human Aldehyde Oxidase Selectivity and Metabolic Reactions.

  2018cites this paper
• Prediction of Aromatic Hydroxylation Sites for Human CYP1A2 Substrates Using Condensed Graph of Reactions

  2018cites this paper
• Linker Variation and Structure-Activity Relationship Analyses of Carboxylic Acid-based Small Molecule STAT3 Inhibitors.

  2018cites this paper
• Drug discovery: Standing on the shoulders of giants

  2017cites this paper
• Drug Metabolism in Preclinical Drug Development: A Survey of the Discovery Process, Toxicology, and Computational Tools.

  2017cites this paper
• Construction of Metabolism Prediction Models for CYP450 3A4, 2D6, and 2C9 Based on Microsomal Metabolic Reaction System

  2016cites this paper
• Contributions of Ionic Interactions and Protein Dynamics to Cytochrome P450 2D6 (CYP2D6) Substrate and Inhibitor Binding*

  2015cites this paper
• Further Optimization and Evaluation of Bioavailable, Mixed-Efficacy μ-Opioid Receptor (MOR) Agonists/δ-Opioid Receptor (DOR) Antagonists: Balancing MOR and DOR Affinities.

  2015cites this paper
• Identification and in silico prediction of metabolites of the model compound, tebufenozide by human CYP3A4 and CYP2C19.

  2015cites this paper
• Modeling of interactions between xenobiotics and cytochrome P450 (CYP) enzymes

  2015cites this paper
• Predicting the binding modes and sites of metabolism of xenobiotics.

  2015cites this paper
• Modeling of interactions between xenobiotics and cytochrome P 450 ( CYP ) enzymes

  2015cites this paper
• Chemokines: Chemokines and Their Receptors in Drug Discovery

  2015cites this paper
• Metabolism Site Prediction Based on Xenobiotic Structural Formulas and PASS Prediction Algorithm

  2014cites this paper
• Selective and Dual Targeting of CCR2 and CCR5 Receptors: A Current Overview

  2014cites this paper
• Antihypertensive Drugs Metabolism: An Update to Pharmacokinetic Profiles and Computational Approaches

  2014cites this paper
• Reactivity‐Based Approaches and Machine Learning Methods for Predicting the Sites of Cytochrome P450‐Mediated Metabolism

  2014cites this paper
• In silico prediction of cytochrome P450-mediated site of metabolism (SOM).

  2013cites this paper
• Computational approaches for preclinical ADMET optimization

  2013cites this paper
• Exposition and reactivity optimization to predict sites of metabolism in chemicals.

  2013cites this paper
• Pharmacophore modeling for ADME.

  2013cites this paper
• Application of Docking Methods: An Effective In Silico Tool for Drug Design

  2013cites this paper
• A REVIEW ON IN SILICO APPROACH IN PHARMACOLOGY *

  2013cites this paper
• 5. Soft Drugs

  2012cites this paper
• Substrate selectivity of drug-metabolizing cytochrome P450s predicted from crystal structures and in silico modeling

  2012cites this paper
• Characterization of Cupriavidus metallidurans CYP116B1 – A thiocarbamate herbicide oxygenating P450–phthalate dioxygenase reductase fusion protein

  2012cites this paper
• Pharmacophore, QSAR, and binding mode studies of substrates of human cytochrome P450 2D6 (CYP2D6) using molecular docking and virtual mutations and an application to chinese herbal medicine screening.

  2012cites this paper
• Ligand-Based Site of Metabolism Prediction for Cytochrome P450 2D6.

  2012cites this paper
• Substrate selectivity of drug-metabolizing cytochrome P450s predicted from crystal structures and in silico modeling

  2012cites this paper
• Molecular similarity measures.

  2011cites this paper
• In silico modeling of p450 substrates, inhibitors, activators, and inducers.

  2011cites this paper
• Molecular simulations on proteins of biomedical interest : A. Ligand-protein hydration B. Cytochrome P450 2D6 and 2C9 C. Myelin associated glycoprotein (MAG)

  2011cites this paper
• Selecting Relevant Descriptors for Classification by Bayesian Estimates: A Comparison with Decision Trees and Support Vector Machines Approaches for Disparate Data Sets

  2011cites this paper
• RS-Predictor: A New Tool for Predicting Sites of Cytochrome P450-Mediated Metabolism Applied to CYP 3A4

  2011cites this paper
• Comparison of metabolic soft spot predictions of CYP3A4, CYP2C9 and CYP2D6 substrates using MetaSite and StarDrop.

  2011cites this paper
• Computational modeling of P450s for toxicity prediction

  2011cites this paper
• In silico prediction of cytochrome P450-mediated drug metabolism.

  2011cites this paper
• In silico site of metabolism prediction of cytochrome P450-mediated biotransformations

  2011influential citation
• The challenges of in silico contributions to drug metabolism in lead optimization

  2010cites this paper
• Using a homology model of cytochrome P450 2D6 to predict substrate site of metabolism

  2010cites this paper
• Novel Application of 2D and 3D-Similarity Searches To Identify Substrates among Cytochrome P450 2C9, 2D6, and 3A4

  2010cites this paper
• Structure‐based Drug Metabolism Predictions for Drug Design

  2010cites this paper
• Probing Small‐Molecule Binding to Cytochrome P450 2D6 and 2C9: An In Silico Protocol for Generating Toxicity Alerts

  2010cites this paper
• Cytochrome P450 Enzymes

  2010cites this paper
• Virtual screening for cytochromes p450: successes of machine learning filters.

  2009cites this paper
• Modeling Kinetics of Subcellular Disposition of Chemicals

  2009cites this paper
• In silico prediction of drug properties.

  2009cites this paper
• Integrating Crystallography into Early Metabolism Studies

  2009cites this paper
• Understanding CYP2D6 interactions.

  2009cites this paper
• QSAR models for P450 (2D6) substrate activity

  2009influential citation
• New insights into the structural characteristics and functional relevance of the human cytochrome P450 2D6 enzyme

  2009influential citation
• Medicinal chemistry strategies to reduce CYP2D6 inhibitory activity of lead candidates.

  2009cites this paper
• Substrate specificity, inhibitors and regulation of human cytochrome P450 2D6 and implications in drug development.

  2009cites this paper
• CYP2D6-Mediated Metabolism of a Novel Acyl Coenzyme A:Cholesterol Acyltransferase Inhibitor, Pactimibe, and Its Unique Plasma Metabolite, R-125528

  2008cites this paper
• 1 DRUG METABOLISM : SIGNIFICANCE AND CHALLENGES

  2008influential citation
• Modellierung von Cytochrom P450-Monooxygenasen

  2008cites this paper
• Structure-based Computational Approaches to Drug Metabolism

  2008cites this paper
• Recent advances in the in silico modelling of UDP glucuronosyltransferase substrates.

  2008cites this paper
• Novel Binding Mode of the Acidic CYP2D6 Substrates Pactimibe and Its Metabolite R-125528

  2008cites this paper
• Chapter 11 – Metabolic Stability

  2008cites this paper
• The Molecular Basis of CYP2D6-Mediated N-Dealkylation: Balance between Metabolic Clearance Routes and Enzyme Inhibition

  2008cites this paper
• Insights into drug metabolism by cytochromes P450 from modelling studies of CYP2D6‐drug interactions

  2008cites this paper
• New Combined Model for the Prediction of Regioselectivity in Cytochrome P450/3A4 Mediated Metabolism

  2008cites this paper
• Regioselectivity Prediction of CYP1A2-Mediated Phase I Metabolism

  2008cites this paper
• Designing rapid onset selective serotonin re-uptake inhibitors. Part 3: Site-directed metabolism as a strategy to avoid active circulating metabolites: structure-activity relationships of (thioalkyl)phenoxy benzylamines.

  2008cites this paper
• Biotransformation of metoprolol by the fungus Cunninghamella blakesleeana

  2007cites this paper
• Reaction Site Mapping of Xenobiotic Biotransformations

  2007cites this paper
• AmineDB: Large scale docking of amines with CYP2D6 and scoring for druglike properties—towards defining the scope of the chemical defense against foreign amines in humans

  2007cites this paper
• State-of-the-art Tools for Computational Site of Metabolism Predictions: Comparative Analysis, Mechanistical Insights, and Future Applications

  2007cites this paper
• Generation of in-silico cytochrome P450 1A2, 2C9, 2C19, 2D6, and 3A4 inhibition QSAR models

  2007cites this paper
• Molecular modeling-guided site-directed mutagenesis of cytochrome P450 2D6.

  2007cites this paper
• Computational Approaches That Predict Metabolic Intermediate Complex Formation with CYP3A4 (+b5)

  2007cites this paper
• Methods for predicting human drug metabolism.

  2007cites this paper
• 2.01 – The Intersection of Strategy and Drug Research

  2007cites this paper
• Insights into drug metabolism from modelling studies of cytochrome P450-drug interactions.

  2006cites this paper
• Recursive partitioning for the prediction of cytochromes P450 2D6 and 1A2 inhibition: importance of the quality of the dataset.

  2006cites this paper
• Designing better drugs: predicting cytochrome P450 metabolism.

  2006cites this paper
• COMPARISON OF METHODS FOR THE PREDICTION OF THE METABOLIC SITES FOR CYP3A4-MEDIATED METABOLIC REACTIONS

  2006cites this paper
• Computational approaches for predicting CYP-related metabolism properties in the screening of new drugs.

  2006cites this paper
• Pharmacophore-based discovery of ligands for drug transporters.

  2006cites this paper
• Cytochrome P450-drug interactions: Computational binding mode and affinity predictions in CYP2D6

  2006cites this paper
• Computational models for predicting interactions with cytochrome p450 enzyme.

  2006cites this paper
• Functional interaction of nitrogenous organic bases with cytochrome P450: a critical assessment and update of substrate features and predicted key active-site elements steering the access, binding, and orientation of amines.

  2006cites this paper
• Utility of human/human-derived reagents in drug discovery and development: An industrial perspective.

  2006cites this paper
• Computational prediction of human drug metabolism

  2005cites this paper
• A 3D-QSAR model for CYP2D6 inhibition in the aryloxypropanolamine series.

  2005cites this paper
• Predicting Drug Metabolism – An Evaluation of the Expert System METEOR

  2005cites this paper
• Progress in cytochrome P450 active site modeling.

  2005cites this paper
• MetaSite: understanding metabolism in human cytochromes from the perspective of the chemist.

  2005cites this paper
• Cytochrome p450 in silico: an integrative modeling approach.

  2005cites this paper
• Crystal Structure of Human Cytochrome P450 2D6*

  2005cites this paper
• The role of phenylalanine 483 in cytochrome P450 2D6 is strongly substrate dependent.

  2005cites this paper
• Applications of Substructure-Based SAR in Toxicology

  2005cites this paper
• Polymorphic Cytochrome P450 2D6: Humanized Mouse Model and Endogenous Substrates

  2004influential citation
• Conformer- and alignment-independent model for predicting structurally diverse competitive CYP2C9 inhibitors.

  2004cites this paper
• Chemical Proteomic Tool for Ligand Mapping of CYP Antitargets: An NMR-Compatible 3D QSAR Descriptor in the Heme-Based Coordinate System

  2004cites this paper