Journal ArticleDOI
Substrates of human hepatic cytochrome P450 3A4
TLDR
The major experimental system used to elucidate the role of CYP3A4 in the metabolic transformation of these substrates is the human liver microsome system, and cultured human hepatocytes and yeast/cultured cells genetically engineered to express CYP2A4 are also employed by the different investigators.About:
This article is published in Toxicology.The article was published on 1995-12-15. It has received 362 citations till now. The article focuses on the topics: Cytochrome P-450 CYP3A & Cytochrome P450.read more
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The nuclear pregnane X receptor: a key regulator of xenobiotic metabolism.
TL;DR: Although PXR evolved to protect the body, its activation by a variety of prescription drugs represents the molecular basis for an important class of harmful drug-drug interactions, so assays that detect PxR activity will be useful in developing safer prescription drugs.
Journal ArticleDOI
Summary of information on human cyp enzymes: human p450 metabolism data
TL;DR: This chapter is an update of the data on substrates, reactions, inducers, and inhibitors of human CYP enzymes published previously by Rendic and DiCarlo, now covering selection of the literature through 2001 in the reference section.
Journal ArticleDOI
Use of In Vitro and In Vivo Data to Estimate the Likelihood of Metabolic Pharmacokinetic Interactions
R J Bertz,G. R. Granneman +1 more
TL;DR: A database containing information about the clearance routes for over 300 drugs from multiple therapeutic classes, including analgesics, anti-infectives, psychotropics, anticonvulsants, cancer chemotherapeutics, gastrointestinal agents, cardiovascular agents and others, was constructed to assist in the semiquantitative prediction of the magnitude of potential interactions with drugs under development.
Journal ArticleDOI
The structure of human microsomal cytochrome P450 3A4 determined by X-ray crystallography to 2.05-A resolution.
Jason Yano,Michael R. Wester,Guillaume A. Schoch,Keith J. Griffin,C. David Stout,Eric F. Johnson +5 more
TL;DR: The structure of P450 3A4 should facilitate a better understanding of the substrate selectivity of the enzyme, and may diminish the efficiency of substrate oxidation, which may be improved by space restrictions imposed by the presence of a second substrate molecule.
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The orphan human pregnane X receptor mediates the transcriptional activation of CYP3A4 by rifampicin through a distal enhancer module.
TL;DR: The results provide evidence for the existence of a potent enhancer module, 8 kb distal to the transcription start point, which mediates the transcriptional induction of CYP3A4 by activators of hPXR and demonstrate cooperativity between elements within the distal enhancer region and cis-acting elements in the proximal promoter of CYp3A 4.
References
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Journal ArticleDOI
The human hepatic cytochromes P450 involved in drug metabolism.
TL;DR: The purpose of this review is to compare and contrast the human P 450s involved in drug metabolism with their related forms in the rat and other experimental species with respect to their relative levels of the various P450s and their metabolic capabilities.
Journal Article
Differential Activation of Cyclophosphamide and Ifosphamide by Cytochromes P-450 2B and 3A in Human Liver Microsomes
TL;DR: It is established that liver microsomal CYP2B and CYP3A preferentially catalyze cyclophosphamide and ifosphamide 4-hydroxylation, respectively, suggesting that liver P-450-inducing agents targeted at these enzymes might be used in cancer patients to enhance drug activation and therapeutic efficacy.
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Human liver microsomal steroid metabolism: Identification of the major microsomal steroid hormone 6β-hydroxylase cytochrome P-450 enzyme
TL;DR: Observations establish that P-450NF or a closely related enzyme is the major catalyst of steroid hormone 6 beta hydroxylation in human liver microsomes, and suggest that steroid 6beta hydroxyation may provide a useful, noninvasive monitor for the monooxygenase activity of this hepatic P- 450 form.
Journal Article
Cytochrome P-450 3A enzymes are responsible for biotransformation of FK506 and rapamycin in man and rat.
TL;DR: It is concluded that in human and rat liver FK506 and rapamycin are metabolized primarily by cytochrome P-450 3A4.
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Steroid hormone hydroxylase specificities of eleven cDNA-expressed human cytochrome P450s.
David J. Waxman,David P. Lapenson,Toshifumi Aoyama,Harry V. Gelboin,Frank J. Gonzalez,Ken Korzekwa +5 more
TL;DR: It is demonstrated that individual human cy tochrome P450 enzymes can hydroxylate endogenous steroid hormones with a high degree of stereospecificity and regioselectivity, and that some, but not all of the human cytochromes exhibit metabolite profiles similar to their rodent counterparts.