Pharmacology and Toxicology of Cytochrome P450 - 60th Anniversary (Volume 95) (Advances in Pharmacology, Volume 95)

Copyright_2022_Advances-in-Pharmacology
	Copyright
Contributors_2022_Advances-in-Pharmacology
	Contributors
Preface_2022_Advances-in-Pharmacology
	Preface
		Reference
In-Memoriam-Tsuneo-Omura_2022_Advances-in-Pharmacology
	In Memoriam—Tsuneo Omura
Chapter-One---Roles-of-cytochrome-P450-enzymes-in-pharmac_2022_Advances-in-P
	Roles of cytochrome P450 enzymes in pharmacology and toxicology: Past, present, and future
		Introduction
		Where is the P450 field today and what do we know?
			Roles of individual human P450s
			Abundance of P450s
			Regulation
			Catalytic mechanism
			Structures of P450s and binding of ligands
		P450s and drug metabolism
			P450s and pharmacokinetic issues
				Changing molecules to attenuate metabolism
				Variations in pharmacokinetics
			Drug-drug interactions
				Induction
				Inhibition
					Modes of inhibition
					Time-dependent inhibition
					Use of inhibitors to slow drug metabolism
					Clinical issues
			Toxicity issues
				Slow metabolism
				Bioactivation
				Human specific metabolites
				Human differences in regulation
		P450s as drug targets
			Current P450 inhibitors in use
			Future prospects for P450 inhibition
			Pest control
			Targeting accessory enzymes
		The future of P450 research
			Recent developments
			Questions regarding basic research
			Practical questions to be addressed
		Conclusion
		Acknowledgments
		Conflict of interest statement
		References
Chapter-Two---Pharmacogenetics-of-the-cytochromes-P450--Se_2022_Advances-in-
	Pharmacogenetics of the cytochromes P450: Selected pharmacological and toxicological aspects
		Introduction
		Relevance of cytochrome P450 polymorphisms to warfarin dosing and bleeding risk
			Historic aspects of warfarin metabolism in relation to the cytochromes P450
			Warfarin dosing and relevance of P450 and other genotypes
			CYP2C9 genotype relevance more broadly
		Idiosyncratic adverse drug reactions and cytochrome P450 polymorphisms
			Idiosyncratic liver injury and cytochrome P450 polymorphisms
			Idiosyncratic skin reactions and cytochrome P450 polymorphisms
		Cytochrome P450 polymorphisms and disease susceptibility
			Cancer
			Other diseases
		Conclusion
		Conflict of interest
		References
Chapter-Three---Cytochrome-P450-enzymes-and-metabolism-of-_2022_Advances-in-
	Cytochrome P450 enzymes and metabolism of drugs and neurotoxins within the mammalian brain
		Introduction
			Xenobiotic metabolizing CYPs in the brain
			Studying CYPs in the brain
		CYP expression in the brain
		Factors influencing CYPs in the brain
			Endogenous factors
				Genetics
				Hormones
			Xenobiotics
				Transcriptional regulation and induction
				Post-transcriptional induction
				Inhibition
		Functional impact of brain CYP metabolism
			Drugs
			Neurotoxins
		Conclusion
		Acknowledgments
		Conflict of interest
		References
Chapter-Four---Mammalian-cytochrome-P450-biodiversity--Physiolo_2022_Advance
	Mammalian cytochrome P450 biodiversity: Physiological importance, function, and protein and genomic structu ...
		Introduction
		Results
			Early work implicating CYP2B in dietary specialization
			Functional assays implicating the role of P450s and of CYP2B in juniper ingestion by woodrats
			Enormous diversity of CYP2B isoforms in woodrats
			Background to biochemical and structural studies of woodrat CYP2B enzymes
			Studies of woodrat CYP2B enzymes and of monoterpene binding to human CYP2B6
			Role of enzyme induction in species differences
		Conclusion
			Summary of main results
			Reflections
			Future directions
		Acknowledgments
		Conflict of interest statement
		References
Chapter-Five---Atypical-kinetics-of-cytochrome-P450-enzy_2022_Advances-in-Ph
	Atypical kinetics of cytochrome P450 enzymes in pharmacology and toxicology
		Introduction
		Atypical Michaelis-Menten kinetics and proposed mechanisms
			Substrate inhibition kinetics in P450
			Drug inhibition of P450 in the presence of substrate inhibition
		Atypicalities in mechanism-based inactivation of cytochrome P450
			Complexities in the mechanism-based inactivation of CYP3A
			Probe substrate-dependent inactivation in CYP3A
			Isoform-dependent inactivation in CYP3A
			In vivo implications of atypicalities and complexities in mechanism-based inactivation
		Conclusion
		Acknowledgments
		Conflict of interest
		References
Chapter-Six---Biosynthesis-using-cytochrome-P450-enzymes-_2022_Advances-in-P
	Biosynthesis using cytochrome P450 enzymes: Focus on synthesis of drug metabolites
		Introduction
		Utility of metabolite biosynthesis
			Discovery applications: Chemical diversity
			Early development: Meeting MIST requirements
			Late development
		Directed metabolite biosynthesis
			Metabolite isolation from incubation with expressed enzymes, microsomes, hepatocytes or in vivo
			Biosynthesis of metabolites using bioreactors
			Bioreactors with expressed mammalian CYPs
			Microbial bioreactors
				Examples of microbial-based bioreactors
		Conclusion
		Conflict of interest statement
		References
Chapter-Seven---Use-of-engineered-cytochromes-P450-for-ac_2022_Advances-in-P
	Use of engineered cytochromes P450 for accelerating drug discovery and development
		Introduction
		Lead candidate synthesis and late-stage functionalization of pharmaceutical compounds
		Production of drug metabolites
		Limitations of P450s as biocatalysts for the pharmaceutical industry
		Progress in changing properties of P450 systems
		Engineering of substrate specificity
		Engineering catalytic efficiency via the redox system
		Engineering the ability to use oxygen surrogates
		Progress in engineering thermostability
			Thermostabilization of bacterial P450s
			Thermostabilization of eukaryotic P450 forms
			Engineering solvent tolerance
		Novel chemistry
		Conclusion
		Acknowledgments
		Author contributions
		Conflict of interest statement
		References
Chapter-Eight---Assessing-cytochrome-P450-function-using_2022_Advances-in-Ph
	Assessing cytochrome P450 function using genetically engineered mouse models
		Introduction
		Available mouse models
		Assessing CYP function in the in vivo metabolism and toxicity of therapeutic drugs
		Assessing the function of CYPs in the in vivo metabolism, bioactivation, and toxicity of known or suspected chemical c ...
		Conclusion
		Acknowledgments
		Conflict of interest statement
		References
Chapter-Nine---Expression-and-functional-activity-of-cytochrom_2022_Advances
	Expression and functional activity of cytochrome P450 enzymes in human hepatocytes with sustainable reproducibility for in vitro phenotyping studies
		Introduction
		Preparation of hepatocytes (from chimeric mice)
		Expression and activity of human P450 enzymes
		P450 enzyme-dependent drug metabolism
		Human hepatocytes during 1- to 4-weeks of culture
		Conclusion
		Acknowledgments
		Conflict of interest
		Author contributions
		References
Chapter-Ten---Cytochrome-P450s-in-chimeric-mice-with_2022_Advances-in-Pharma
	Cytochrome P450s in chimeric mice with humanized liver
		Introduction
		Characterization of humanized liver from chimeric mice
			Zonal expression of human P450 in the repopulated humanized liver
			Levels of gene expression of drug metabolizing enzymes and transporters
			Content of human P450 protein in liver microsomes
			Drug oxidation activity in liver microsomes
		In vivo drug metabolism by humanized liver mouse
			Tolbutamide
			Desloratadine
			Thalidomide
			Diclofenac
		Pharmacokinetic study using humanized liver mouse
		Drug interaction study using humanized liver mouse
		Human P450-inactivated chimeric mouse model using mechanism-based inhibitor
		Conclusion
		Conflict of interest
		Acknowledgments
		Author contributions
		References
Chapter-Eleven---Polymorphic-cytochromes-P450-in-non_2022_Advances-in-Pharma
	Polymorphic cytochromes P450 in non-human primates
		Introduction
		Molecular characteristics of P450s
			CYP1A subfamily
			CYP1B subfamily
			CYP1D subfamily
			CYP2A subfamily
			CYP2B subfamily
			CYP2C subfamily
			CYP2D subfamily
			CYP2E subfamily
			CYP2F subfamily
			CYP2G subfamily
			CYP2J subfamily
			CYP3A subfamily
			CYP4A subfamily
			CYP4F subfamily
		Genetic polymorphisms
			Genetic variants identified
			Characterization of polymorphic P450s in vitro
			Drug elimination mediated by polymorphic P450s in vivo
		Conclusion
		Acknowledgments
		Conflicts of interest
		References
Chapter-Twelve---Cytochrome-P450-enzymes-in-the-pediatric-po_2022_Advances-i
	Cytochrome P450 enzymes in the pediatric population: Connecting knowledge on P450 expression with pediatric pharmacokinetics
		Introduction
		Developmental changes in cytochrome P450 enzyme expression
			CYP1A1
			CYP1A2
			CYP2A6
			CYP2B6
			CYP2C8
			CYP2C9
			CYP2C19
			CYP2D6
			CYP2E1
			CYP3A7, CYP3A5, and CYP3A4
		Utilization of P450 ontogeny for predicting pharmacokinetics of drugs in the pediatric population: Physiologically-bas ...
		Future challenges
			Performing more comprehensive basic science and clinical studies in children
			Disease effects on pediatric P450 expression
			Effects of pharmacogenetics and drug-drug interactions on pediatric P450 enzymes
			Pediatric PK prediction in an individual
		Conclusion
		Acknowledgments
		Conflict of interest
		References
Chapter-Thirteen---Cytochrome-P450-polymorphism--From-_2022_Advances-in-Phar
	Cytochrome P450 polymorphism: From evolution to clinical use
		Introduction
		Selection of CYP gene variants in relation to environmental and dietary factors
		Genetic selection in humans
		Genetic variants of CYP genes
		Examples of Functionality of CYP polymorphism
			CYP2A6 and smoking
			CYP2A6 and caffeine
		Missing heritability
			Variation in other loci
			NFIB
			Long read PCR for complete gene sequence
			Hidden haplotypes
			Rare variants
			Polymorphic gene synergy
		Pharmacogenomic labels
		Looking into the future
		Conclusion
		Acknowledgments
		Conflict of interests
		References
		Further reading