Pharmacology and toxicology of cytochrome P450 -- 60th anniversary /

Detalles Bibliográficos
Clasificación:Libro Electrónico
Otros Autores: Yamazaki, Hiroshi
Formato: eBook
Idioma:Inglés
Publicado: Cambridge, MA : Academic Press, 2022.
Colección:Advances in Pharmacology ; v. 95.
Temas:
Cytochrome P-450.
Cytochrome P-450
Acceso en línea:Texto completo
Tabla de Contenidos:
  • Intro
  • Pharmacology and Toxicology of Cytochrome P450
  • 60th Anniversary
  • Copyright
  • Contents
  • Contributors
  • Preface
  • Reference
  • In Memoriam-Tsuneo Omura
  • Chapter One: Roles of cytochrome P450 enzymes in pharmacology and toxicology: Past, present, and future
  • 1. Introduction
  • 2. Where is the P450 field today and what do we know?
  • 2.1. Roles of individual human P450s
  • 2.2. Abundance of P450s
  • 2.3. Regulation
  • 2.4. Catalytic mechanism
  • 2.5. Structures of P450s and binding of ligands
  • 3. P450s and drug metabolism
  • 3.1. P450s and pharmacokinetic issues
  • 3.1.1. Changing molecules to attenuate metabolism
  • 3.1.2. Variations in pharmacokinetics
  • 3.2. Drug-drug interactions
  • 3.2.1. Induction
  • 3.2.2. Inhibition
  • 3.2.2.1. Modes of inhibition
  • 3.2.2.2. Time-dependent inhibition
  • 3.2.2.3. Use of inhibitors to slow drug metabolism
  • 3.2.2.4. Clinical issues
  • 3.3. Toxicity issues
  • 3.3.1. Slow metabolism
  • 3.3.2. Bioactivation
  • 3.3.3. Human specific metabolites
  • 3.3.4. Human differences in regulation
  • 4. P450s as drug targets
  • 4.1. Current P450 inhibitors in use
  • 4.2. Future prospects for P450 inhibition
  • 4.3. Pest control
  • 4.4. Targeting accessory enzymes
  • 5. The future of P450 research
  • 5.1. Recent developments
  • 5.2. Questions regarding basic research
  • 5.3. Practical questions to be addressed
  • 6. Conclusion
  • Acknowledgments
  • Conflict of interest statement
  • References
  • Chapter Two: Pharmacogenetics of the cytochromes P450: Selected pharmacological and toxicological aspects
  • 1. Introduction
  • 2. Relevance of cytochrome P450 polymorphisms to warfarin dosing and bleeding risk
  • 2.1. Historic aspects of warfarin metabolism in relation to the cytochromes P450
  • 2.2. Warfarin dosing and relevance of P450 and other genotypes
  • 2.3. CYP2C9 genotype relevance more broadly.
  • 3. Idiosyncratic adverse drug reactions and cytochrome P450 polymorphisms
  • 3.1. Idiosyncratic liver injury and cytochrome P450 polymorphisms
  • 3.2. Idiosyncratic skin reactions and cytochrome P450 polymorphisms
  • 4. Cytochrome P450 polymorphisms and disease susceptibility
  • 4.1. Cancer
  • 4.2. Other diseases
  • 5. Conclusion
  • Conflict of interest
  • References
  • Chapter Three: Cytochrome P450 enzymes and metabolism of drugs and neurotoxins within the mammalian brain
  • 1. Introduction
  • 1.1. Xenobiotic metabolizing CYPs in the brain
  • 1.2. Studying CYPs in the brain
  • 2. CYP expression in the brain
  • 3. Factors influencing CYPs in the brain
  • 3.1. Endogenous factors
  • 3.1.1. Genetics
  • 3.1.2. Hormones
  • 3.2. Xenobiotics
  • 3.2.1. Transcriptional regulation and induction
  • 3.2.2. Post-transcriptional induction
  • 3.2.3. Inhibition
  • 4. Functional impact of brain CYP metabolism
  • 4.1. Drugs
  • 4.2. Neurotoxins
  • 5. Conclusion
  • Acknowledgments
  • Conflict of interest
  • References
  • Chapter Four: Mammalian cytochrome P450 biodiversity: Physiological importance, function, and protein and genomic structu ...
  • 1. Introduction
  • 2. Results
  • 2.1. Early work implicating CYP2B in dietary specialization
  • 2.2. Functional assays implicating the role of P450s and of CYP2B in juniper ingestion by woodrats
  • 2.3. Enormous diversity of CYP2B isoforms in woodrats
  • 2.4. Background to biochemical and structural studies of woodrat CYP2B enzymes
  • 2.5. Studies of woodrat CYP2B enzymes and of monoterpene binding to human CYP2B6
  • 2.6. Role of enzyme induction in species differences
  • 3. Conclusion
  • 3.1. Summary of main results
  • 3.2. Reflections
  • 3.3. Future directions
  • Acknowledgments
  • Conflict of interest statement
  • References
  • Chapter Five: Atypical kinetics of cytochrome P450 enzymes in pharmacology and toxicology.
  • 1. Introduction
  • 2. Atypical Michaelis-Menten kinetics and proposed mechanisms
  • 2.1. Substrate inhibition kinetics in P450
  • 2.2. Drug inhibition of P450 in the presence of substrate inhibition
  • 3. Atypicalities in mechanism-based inactivation of cytochrome P450
  • 3.1. Complexities in the mechanism-based inactivation of CYP3A
  • 3.2. Probe substrate-dependent inactivation in CYP3A
  • 3.3. Isoform-dependent inactivation in CYP3A
  • 3.4. In vivo implications of atypicalities and complexities in mechanism-based inactivation
  • 4. Conclusion
  • Acknowledgments
  • Conflict of interest
  • References
  • Chapter Six: Biosynthesis using cytochrome P450 enzymes: Focus on synthesis of drug metabolites
  • 1. Introduction
  • 2. Utility of metabolite biosynthesis
  • 2.1. Discovery applications: Chemical diversity
  • 2.2. Early development: Meeting MIST requirements
  • 2.3. Late development
  • 3. Directed metabolite biosynthesis
  • 3.1. Metabolite isolation from incubation with expressed enzymes, microsomes, hepatocytes or in vivo
  • 3.2. Biosynthesis of metabolites using bioreactors
  • 3.3. Bioreactors with expressed mammalian CYPs
  • 3.4. Microbial bioreactors
  • 3.4.1. Examples of microbial-based bioreactors
  • 4. Conclusion
  • Conflict of interest statement
  • References
  • Chapter Seven: Use of engineered cytochromes P450 for accelerating drug discovery and development
  • 1. Introduction
  • 2. Lead candidate synthesis and late-stage functionalization of pharmaceutical compounds
  • 3. Production of drug metabolites
  • 4. Limitations of P450s as biocatalysts for the pharmaceutical industry
  • 5. Progress in changing properties of P450 systems
  • 6. Engineering of substrate specificity
  • 7. Engineering catalytic efficiency via the redox system
  • 8. Engineering the ability to use oxygen surrogates
  • 9. Progress in engineering thermostability.
  • 9.1. Thermostabilization of bacterial P450s
  • 9.2. Thermostabilization of eukaryotic P450 forms
  • 9.3. Engineering solvent tolerance
  • 10. Novel chemistry
  • 11. Conclusion
  • Acknowledgments
  • Author contributions
  • Conflict of interest statement
  • References
  • Chapter Eight: Assessing cytochrome P450 function using genetically engineered mouse models
  • 1. Introduction
  • 2. Available mouse models
  • 3. Assessing CYP function in the in vivo metabolism and toxicity of therapeutic drugs
  • 4. Assessing the function of CYPs in the in vivo metabolism, bioactivation, and toxicity of known or suspected chemical c ...
  • 5. Conclusion
  • Acknowledgments
  • Conflict of interest statement
  • References
  • Chapter Nine: Expression and functional activity of cytochrome P450 enzymes in human hepatocytes with sustainable reprodu ...
  • 1. Introduction
  • 2. Preparation of hepatocytes (from chimeric mice)
  • 3. Expression and activity of human P450 enzymes
  • 4. P450 enzyme-dependent drug metabolism
  • 5. Human hepatocytes during 1- to 4-weeks of culture
  • 6. Conclusion
  • Acknowledgments
  • Conflict of interest
  • Author contributions
  • References
  • Chapter Ten: Cytochrome P450s in chimeric mice with humanized liver
  • 1. Introduction
  • 2. Characterization of humanized liver from chimeric mice
  • 2.1. Zonal expression of human P450 in the repopulated humanized liver
  • 2.2. Levels of gene expression of drug metabolizing enzymes and transporters
  • 2.3. Content of human P450 protein in liver microsomes
  • 2.4. Drug oxidation activity in liver microsomes
  • 3. In vivo drug metabolism by humanized liver mouse
  • 3.1. Tolbutamide
  • 3.2. Desloratadine
  • 3.3. Thalidomide
  • 3.4. Diclofenac
  • 4. Pharmacokinetic study using humanized liver mouse
  • 5. Drug interaction study using humanized liver mouse.
  • 6. Human P450-inactivated chimeric mouse model using mechanism-based inhibitor
  • 7. Conclusion
  • Conflict of interest
  • Acknowledgments
  • Author contributions
  • References
  • Chapter Eleven: Polymorphic cytochromes P450 in non-human primates
  • 1. Introduction
  • 2. Molecular characteristics of P450s
  • 2.1. CYP1A subfamily
  • 2.2. CYP1B subfamily
  • 2.3. CYP1D subfamily
  • 2.4. CYP2A subfamily
  • 2.5. CYP2B subfamily
  • 2.6. CYP2C subfamily
  • 2.7. CYP2D subfamily
  • 2.8. CYP2E subfamily
  • 2.9. CYP2F subfamily
  • 2.10. CYP2G subfamily
  • 2.11. CYP2J subfamily
  • 2.12. CYP3A subfamily
  • 2.13. CYP4A subfamily
  • 2.14. CYP4F subfamily
  • 3. Genetic polymorphisms
  • 3.1. Genetic variants identified
  • 3.2. Characterization of polymorphic P450s in vitro
  • 3.3. Drug elimination mediated by polymorphic P450s in vivo
  • 4. Conclusion
  • Acknowledgments
  • Conflicts of interest
  • References
  • Chapter Twelve: Cytochrome P450 enzymes in the pediatric population: Connecting knowledge on P450 expression with pediatr ...
  • 1. Introduction
  • 2. Developmental changes in cytochrome P450 enzyme expression
  • 2.1. CYP1A1
  • 2.2. CYP1A2
  • 2.3. CYP2A6
  • 2.4. CYP2B6
  • 2.5. CYP2C8
  • 2.6. CYP2C9
  • 2.7. CYP2C19
  • 2.8. CYP2D6
  • 2.9. CYP2E1
  • 2.10. CYP3A7, CYP3A5, and CYP3A4
  • 3. Utilization of P450 ontogeny for predicting pharmacokinetics of drugs in the pediatric population: Physiologically-bas ...
  • 4. Future challenges
  • 4.1. Performing more comprehensive basic science and clinical studies in children
  • 4.2. Disease effects on pediatric P450 expression
  • 4.3. Effects of pharmacogenetics and drug-drug interactions on pediatric P450 enzymes
  • 4.4. Pediatric PK prediction in an individual
  • 5. Conclusion
  • Acknowledgments
  • Conflict of interest
  • References
  • Chapter Thirteen: Cytochrome P450 polymorphism: From evolution to clinical use.

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