Potent Inhibition of the Cytochrome P-450 3A-Mediated Human Liver Microsomal Metabolism of a Novel HIV Protease Inhibitor by...
1990) Enzyme induction in the cytochrome P-450 system. Pharmacol Ther 45:241-298. ... The reaction was started by adding the NADPH-generating system, and the incubation was conducted at 37°C for 20 min. The ratio ... cytochrome P-450. AUC. area under the curve. Cmax. maximal plasma concentration. ... 1996) Catalytic role of cytochrome P4502B6 in the N-demethylation of S-mephenytoin. Drug Metab Dispos 24:948-954. ...http://dmd.aspetjournals.org/content/27/8/902.long
Cimetidine: An inhibitor and an inducer of rat liver microsomal cytochrome p-450 - UQ eSpace
1. Cimetidine pretreatment of male Sprague-Dawley rats caused a significant increase in the specific content of total hepatic cytochrome P-450, supporting the hypothesis that this H2-receptor antagonist has monooxygenase induction effects. 2. Quantitative ultrastructural studies of liver of cimetidine-pretreated animals also supported this hypothesis in showing a significant proliferation of smooth endoplasmic reticulum. These ultrastructural changes were qualitatively similar to those produced by treatment of rats with phenobarbital, a well-characterized monooxygenase-inducing agent whose effects were studied for comparative purposes. 3. Competitive inhibition of metoprolol αhydroxylation by cimetidine in liver microsomes prepared from untreated animals (Ki = 18.8 μM) was also demonstrated. 4. These results allowed testing of the hypothesis (Burnet el al. 1986) that inhibition of a defined monooxygenase should lead to induction of the synthesis of the relevant cytochrome ...https://espace.library.uq.edu.au/view/UQ:401496
Multiple cytochrome P450 enzymes responsible for the oxidative metabolism of the substituted (S)-3-phenylpiperidine, (S,S)-3-[3...
(S,S)-3-[3-(Methylsulfonyl)phenyl]-1-propylpiperidine hydrochloride [(-)-OSU6162] is a weak dopamine D2 receptor modulator that possesses potential for the treatment of levodopa (L-DOPA)-induced dyskinesias in patients with Parkinson's disease. In this report, incubations with human liver microsomes revealed that (-)-OSU6162 is selectively metabolized via N-dealkylation to yield N-depropyl (-)-OSU6162. Kinetics evidence is presented that the N-depropylation of (-)-OSU6162 in human hepatic microsomes is mediated by multiple cytochrome p450 (p450) enzymes, in particular CYP2D6. This hypothesis is borne out by several lines of in vitro evidence; 1). incubations of (-)-OSU6162 (5 micro M) with hepatic microsomes from a panel of human donors showed that (-)-OSU6162 N-depropylase activity correlated well with CYP2D6-catalyzed dextromethorphan O-demethylase activity but not with other p450 enzyme-specific activities; 2). quinidine, a CYP2D6-specific inhibitor, ...https://www.semanticscholar.org/paper/Multiple-cytochrome-P450-enzymes-responsible-for-t-Wienkers-Wynalda/7533adc2508b6a5770442742a896dcf4a2b13aaf
DSpace at EWHA: 백서에서 Cholesterol과 인삼 투여가 Hepatic Cytochrome P-450, b (5) 및 2-AAF의 Hydroxylation에 미치는 영향
hepatic microsomal mixed function oxidase system의 중추인 cytochrome p-450은 주위환경, 약물, 식이 및 영양 상태에따라 활성이 변화하는것으로 알려져있다. 또한 이 효소계를 통하여 대사되는 2-acetylaminofluorene은 guinea pig를 제외한 모든 동물에서 간암을 일으키는 물질이라는것이 밝혀져서 연구의 대상이 되고있다. 최근 cholesterol은 성인병에 있어 그 원인 인자로서 중요성이 알려지고 있으며 cytochrome p-450과 b_(5)와의 연관성이 보고된바있다. 한편 인삼은 항암작용, 대사촉진, 간조직에서의 해독작용등 여러가지 기능이 보고되어 있다. 이에 저자는 cholesterol을 투여한 흰쥐에서 hepatic microsomal cytochrome p-450 및 b_(5)의 활성에대한 영향과 2-AAF의 ring-hydroxylation과 N-hydroxylation의 변화를 관찰하고, cholesterol과 인삼을 통시에 투여한 군과 비교관찰하여 다음과 같은 결론을 얻었다. 1) 정상 ...http://dspace.ewha.ac.kr/handle/2015.oak/206686
Expression of adrenal cytochromes P-450 in testosterone-induced hypertension. | Hypertension
Chronic treatment of rats with the naturally occurring androgen, testosterone, leads to hypertension and cardiovascular disease. This effect is believed to be mediated through the adrenal gland and in particular by action on the steroid 11 beta-hydroxylase enzyme system. To study the possible mechanism of this effect, the enzyme system was examined at several time periods up to the time that hypertension develops. Rats were treated with testosterone (10 mg/day) for 3, 7, 21, and 42 days. Levels of cytochrome P-450(11) beta enzyme and messenger RNA (mRNA) were determined as well as 11 beta-hydroxylase enzyme activity. A significant decrease in enzyme activity was observed after 3 days of treatment. This correlates with a profound decrease in the level of cytochrome P-450(11) beta enzyme as determined by Western blot analysis. A large decrease ...http://hyper.ahajournals.org/content/18/4/523
Cytochrome P-420: Tubular Aggregates from Hepatic Microsomes | Science
Aggregates were formed when clear supernatants from hepatic microsomes that had been treated with steapsin were desalted and concentrated. These aggregates contain large numbers of uniform tubular elements. These structures resemble microtubules seen in many cells but differ in their substructure. The aggregates were rich in cytochrome P-420. Unlike soluble cytochrome P-420, the cytochrome P-420 contained in the aggregates combines with drugs to give the characteristic difference spectra normally seen only with cytochrome P-450 contained in intact microsomes. ...http://science.sciencemag.org/content/165/3900/1371
Polyclonal antibody for human cytochrome P450 enzyme CYP2D6 - Quicktech
Rabbit anti-human cytochrome P450 enzyme CYP2D6 (polyclonal antibody). O-demethylation of xenobiotics, CYP2D6 is involved in the metabolism and elimination of approximately 25% of clinically used drugs in humans1. Primarily expressed in the liver and areas of the CNS. CYP2D1 and CYP2D4 have a similar function in rats2.. CODE NUMBER: RT01.. QUANTITY: 0.1 mL.. SPECIFICITY: Reacts with human cytochrome P450 enzyme CYP2D6 in hepatic microsomal fraction. No cross-reactivity with other cytochrome P450 enzymes.. IMMUNOGEN: Synthetic peptide.. SUGGESTED APPLICATIONS: Western blot, immunohistochemistry on frozen and formaldehyde treated sections. Optimal working dilutions must be determined by end user.. SPECIES REACTIVITY: Human.. FORMAT: Rabbit antiserum.. PRESENTATION: Liquid. No preservatives.. STORAGE/HANDLING: Maintain at -20°C in undiluted aliquots for up to 12 months. Avoid repeated freeze/thaw cycles.. For ...http://quicktech.imperialinnovations.co.uk/i/Antibodies/CYP2D6.html
PAb for rat Cytochrome P450 enzymes CYP1A1 & CYP1A2 - Quicktech
Rabbit anti-rat cytochrome P450 enzymes CYP1A1 and CYP1A2 (polyclonal antibody). Involved in metabolism of xenobiotics, drugs and polyunsaturated fatty acids. Implicated in metabolism of some polycyclic hydrocarbons to carcinogenic intermediates. CODE NUMBER: R1V.. QUANTITY: 0.1 mL.. SPECIFICITY: Reacts with rat cytochrome P450 enzymes CYP1A1 and CYP1A2 in hepatic microsomal fraction. No cross-reactivity with other cytochrome P450 enzymes.. IMMUNOGEN: Synthetic peptide.. SUGGESTED APPLICATIONS: Western blot: useful for the simultaneous detection of rat CYP1A1 (57 kDa) and CYP1A2 (54 kDa), which can be separated by SDS-polyacrylamide electrophoresis. Immunohistochemistry on frozen and formaldehyde treated sections. Optimal working dilutions must be determined by end user.. SPECIES REACTIVITY: Rat.. FORMAT: Rabbit antiserum.. PRESENTATION: Liquid. No preservatives.. STORAGE/HANDLING: Maintain at -20°C in ...http://quicktech.imperialinnovations.co.uk/i/Antibodies/R1V_ratCYP1A1CYP1A2.html
Influence of Sulforaphane Metabolites on Activities of Human Drug-Metabolizing Cytochrome P450 and Determination of...
Sigma-Aldrich offers abstracts and full-text articles by [Alena Vanduchova, Veronika Tomankova, Pavel Anzenbacher, Eva Anzenbacherova].https://www.sigmaaldrich.com/catalog/papers/27779894
Polyclonal antibody for rat cytochrome P450 enzyme CYP3A1 - Quicktech
Heme-thiolate monooxygenase, involved in metabolism of several steroids, fatty acids, and xenobiotics. CYP3A4 & 5 are the two most predominant proteins within the CYP3A subfamily in human adults, which are collectively involved with the biotransformation of 50% of oxidatively metabolised drugs1.. DESCRIPTION: Rabbit anti-rat cytochrome P450 enzyme CYP3A1 (polyclonal antibody).. CODE NUMBER: RK07.. QUANTITY: 0.1 mL.. SPECIFICITY: Reacts with rat cytochrome P450 enzyme CYP3A1 in hepatic microsomal fraction. No cross-reactivity with other cytochrome P450 enzymes including CYP3A2.. IMMUNOGEN: Synthetic peptide.. SUGGESTED APPLICATIONS: Western blot, immunohistochemistry on frozen and formaldehyde treated sections. Optimal working dilutions must be determined by end user.. SPECIES REACTIVITY: Rat.. FORMAT: Rabbit antiserum.. PRESENTATION: Liquid. No preservatives.. STORAGE/HANDLING: Maintain at -20°C in undiluted ...http://quicktech.imperialinnovations.co.uk/i/Antibodies/CYP3A1.html
Polyclonal antibody for rat Cytochrome P450 enzyme CYP1A1 - Quicktech
Rabbit anti-rat cytochrome P450 enzyme CYP1A1 (polyclonal antibody). Involved in metabolism of xenobiotics, drugs and polyunsaturated fatty acids. Implicated in metabolism of some polycyclic hydrocarbons to carcinogenic intermediates. CODE NUMBER: R2U.. QUANTITY: 0.1 mL.. SPECIFICITY: Reacts with rat cytochrome P450 enzyme CYP1A1 in hepatic microsomal fraction. No cross-reactivity with other cytochrome P450 enzymes including CYP1A2.. IMMUNOGEN: Synthetic peptide.. SUGGESTED APPLICATIONS: Western blot, immunohistochemistry on frozen and formaldehyde treated sections. Optimal working dilutions must be determined by end user.. SPECIES REACTIVITY: Rat.. FORMAT: Rabbit antiserum.. PRESENTATION: Liquid. No preservatives.. STORAGE/HANDLING: Maintain at -20°C in undiluted aliquots for up to 12 months. Avoid repeated freeze/thaw cycles.. For research use only; not for use in diagnostic procedures. Not for human or ...http://quicktech.imperialinnovations.co.uk/i/Antibodies/rabbit-anti-rat.html
Recombinant Human Cytochrome P450 2D6 protein (ab73434) Protocols
There are no specific protocols for Recombinant Human Cytochrome P450 2D6 protein (ab73434). Please download our general protocols booklethttp://www.abcam.com/recombinant-human-cytochrome-p450-2d6-protein-ab73434-protocols.html
Recombinant Human Cytochrome P450 3A4 protein (ab114327)
Buy our Recombinant Human Cytochrome P450 3A4 protein. Ab114327 is a full length protein produced in Wheat germ and has been validated in WB, ELISA, SDS-PAGE…http://www.abcam.com/recombinant-human-cytochrome-p450-3a4-protein-ab114327.html
Recombinant Human Cytochrome P450 4A11/22 protein (ab114572)
Buy our Recombinant Human Cytochrome P450 4A11/22 protein. Ab114572 is a full length protein produced in Wheat germ and has been validated in WB, ELISA…http://www.abcam.com/recombinant-human-cytochrome-p450-4a1122-protein-ab114572.html
Cytochrome P450 oxidoreductase participates in nitric oxide consumption by rat brain | Biochemical Journal
In this study we present evidence that brain cells consume NO by a membrane-localized process that involves NADPH oxidation by CYPOR, a microsomal protein that transfers electrons from NADPH to an acceptor, classically a haem-containing cytochrome P450 . Cytochrome P450 inhibitors decreased NO consumption by brain membranes, suggesting that reduction of these proteins by CYPOR underlies NO consumption.. Cytochrome P450s perform hydroxylation reactions which, in the brain, are involved in diverse functions including steroid hormone synthesis, cholesterol homoeostasis and vitamin, eicosanoid and xenobiotic metabolism [28,29]. Both CYPOR and several members of the cytochrome P450 family are expressed in brain, though at much lower levels than in the liver (1-10%; ). Interestingly, NO has been shown to bind and inhibit several cytochrome P450s [31,32], making them intriguing candidates for NO consumption by brain ...http://www.biochemj.org/content/419/2/411
Arachidonic acid-induced endothelial-dependent relaxations of canine coronary arteries: Contribution of a cytochrome P-450...
Arachidonic acid (AA, 10(-8)-5 X 10(-6) M) induced dose-dependent relaxations of canine coronary arterial rings precontracted with dinoprost that were significantly greater (P less than .001) if the endothelium was intact. Cyclooxygenase inhibition with indomethacin displaced the dose-response curve to AA to the right but did not prevent the relaxant effects of the fatty acid. SKF-525A, an inhibitor of cytochrome P-450-dependent enzymes, also attenuated the response to AA although the combination of SKF-525A and indomethacin prevented any relaxant effect. Induction of cytochrome P-450-dependent enzymes in the coronary artery with 3-methylcholanthrene and beta-naphthoflavone given in vivo (40 mg/kg/day for 3 days) or depletion of these enzymes with cobalt chloride (24 mg/kg/day for 2 days) resulted in an enhancement or diminution, respectively, of AA-induced endothelial-dependent relaxations. These results implicate a ...https://www.iris.unisa.it/handle/11386/3131697
Polyclonal antibody for rat cytochrome P450 enzyme CYP3A2 - Quicktech
Heme-thiolate monooxygenase, involved in metabolism of several steroids, fatty acids, and xenobiotics. CYP3A4 & 5 are the two most predominant proteins within the CYP3A subfamily in human adults, which are collectively involved with the biotransformation of 50% of oxidatively metabolised drugs1.. DESCRIPTION: Rabbit anti-rat cytochrome P450 enzyme CYP3A2 (polyclonal antibody).. CODE NUMBER: RK08.. QUANTITY: 0.1 mL.. SPECIFICITY: Binds specifically to cytochrome P450 CYP3A2 in rat hepatic microsomal fraction. No cross-reactivity with other cytochrome P450 enzymes including CYP3A1.. IMMUNOGEN: Synthetic peptide.. SUGGESTED APPLICATIONS: Western blot, immunohistochemistry on frozen and formaldehyde treated sections. Optimal working dilutions must be determined by end user.. SPECIES REACTIVITY: Rat.. FORMAT: Rabbit antiserum.. PRESENTATION: Liquid. No preservatives.. STORAGE/HANDLING: Maintain at -20°C in undiluted aliquots for ...http://quicktech.imperialinnovations.co.uk/i/Antibodies/P450CYP32A.html
Identification of Novel Cytochrome P450s in the Acari - Northumbria Research Link
Graham, Kirsty, Sparagano, Olivier, Pérez de Léon, Adalberto, Bell-Sakyi, Lesley, Guerrero, F. and Finn, Robert (2012) Identification of Novel Cytochrome P450s in the Acari. In: 19th International Symposium on Microsomes and Drug Oxidations and 12th European ISSX Meeting, 17-21 June, 2012, Noordwijk aan Zee, the Netherlands. Full text not available from this repository. (Request a copy ...http://nrl.northumbria.ac.uk/14511/
Current problems in the evaluation of chemical safety. - Surrey Research Insight Open Access
Current problems in the safety evaluation of chemicals, including species differences in chemical toxicity, the difficulty in predicting whether metabolism will result in detoxication or activation, the different metabolic roles of tissue cytochromes P-450, and the significance of oxygen radical formation, are reviewed. A number of specific chemical problems are discussed, including the safety evaluation of benzene, methylene dichloride, DDT, dieldrin, TCDD, the PCBs, and the hepatotoxic drugs: benoxaprofen and tienilic acid. Two novel methods for the prospective evaluation of chemical toxicity are described, namely (i) computer optimized parametric analysis for chemical toxicity (COMPACT) based on the computer graphic determination of chemical structure and its relationship to specific cytochromes P-450 and hence toxicity, and (ii) enzyme activation in chemical toxicity (ENACT) based on the induction of specific cytochromes P-450 by the ...http://epubs.surrey.ac.uk/823482/
www.MOLUNA.de Cytochrome P-450  - Major advances have been made in recent years in clarifying the molecular properties of the cytochrome P-450 system. These advances stem, in practical terms, from the generally recognized importance of cytochrome P-450 in the metabolism of drugs and in the bioactivation of xenobiotics to toxic products. The fascinating multiplicity andhttps://www.moluna.de/buch/4208648-cytochrome+p-450/
Predicting drug pharmacokinetics in humans from in vitro metabolism studies | Biochemical Society Transactions
The pharmaceutical industry is committed to market safer drugs with fewer side effects, predictable pharmacokinetic properties and quantifiable drug-drug interactions. There is an increasing need to develop robust, enhanced-throughput in vitro assays, which accurately extrapolate to humans. The major drug metabolizing human hepatic cytochrome P450s (CYPs; CYP1A2, 2C9, 2C19, 2D6 and 3A4) have been co-expressed functionally in Escherichia coli with human NADPH-cytochrome P450 reductase and validated as surrogates to their counterparts in human liver microsomes (HLM) with respect to their kinetic and inhibition properties. Using these recombinant enzymes, fully automated in vitro assays to assess CYP inhibition and determine the enzymology of drug oxidation have been developed and validated. IC50 values determined for a series of test compounds in HLM and recombinant CYPs were similar (r2 = 0.9, P , 0.001). There was a good correlation between the sum of ...http://www.biochemsoctrans.org/content/29/2/135
CYP2E1 | SelfDecode | Genome Analysis
hypothetical protein, flavoprotein-linked monooxygenase, microsomal monooxygenase, xenobiotic monooxygenase, 4-nitrophenol 2-hydroxylase, CPE1, Cyp2e, CYPIIE1, cytochrome P-450, cytochrome P450 2E1, cytochrome P450, 2e1, ethanol inducible, cytochrome P450-ALC, cytochrome P450 CYP2E1, cytochrome P450, family 2, subfamily e, polypeptide 1, cytochrome P-450-J, cytochrome P450-J, cytochrome P450RLM6, cytochrome P450 subfamily 2e1 (ethanol-inducible), cytochrome P450, subfamily 2E, polypeptide 1, cytochrome P450, subfamily IIE (ethanol-inducible), polypeptide 1, P450C2E, P450-J, P450RLM6, cyp2e1 ...https://www.selfdecode.com/gene/cyp2e1/
High-Throughput, 384-Well, LC-MS/MS CYP Inhibition Assay Using Automation, Cassette-Analysis Technique and Streamlined Data...
Title: High-Throughput, 384-Well, LC-MS/MS CYP Inhibition Assay Using Automation, Cassette-Analysis Technique and Streamlined Data Analysis. VOLUME: 5 ISSUE: 3. Author(s):Jason S. Halladay, Erlie Marie Delarosa, Daniel Tran, Leslie Wang, Susan Wong and S. Cyrus Khojasteh. Affiliation:Department of Drug Metabolism and Pharmacokinetics, Genentech, Inc., South San Francisco, California, 94080, United States. Keywords:Automation, Cytochrome P450, drug-drug interactions, high-throughput, human liver microsomes, inhibition, in vitro, new chemical entities (NCEs), mass spectrometry (MS), clinical trials. Abstract: Here we describe a high capacity and high-throughput, automated, 384-well CYP inhibition assay using wellknown HLM-based MS probes. We provide consistently robust IC50 values at the lead optimization stage of the drug discovery process. Our method uses the Agilent Technologies/Velocity11 BioCel 1200 system, timesaving techniques for sample analysis, and streamlined data ...http://www.eurekaselect.com/94648
Real time analysis of conformational control in electron transfer reactions of human cytochrome P450 reductase with cytochrome...
Protein domain dynamics and electron transfer chemistry are often associated, but real-time analysis of domain motion in enzyme-catalysed reactions and the elucidation of mechanistic schemes that relate these motions to the reaction chemistry are major challenges for biological catalysis research. Previously we suggested that reduction of human cytochrome P450 reductase with the reducing coenzyme NADPH is accompanied by major structural re-orientation of the FMN- and FAD-binding domains through an inferred dynamic cycle of 'open' and 'closed' conformations of the enzyme (PLoS Biol, 2011, e1001222). However, these studies were restricted to stopped-flow/FRET analysis of the reductive half-reaction, and were compromised by fluorescence quenching of the acceptor by the flavin cofactors. Here we have improved the design of the FRET system, by using dye pairs with near-IR fluorescence, and extended studies on human ...https://www.research.manchester.ac.uk/portal/en/publications/real-time-analysis-of-conformational-control-in-electron-transfer-reactions-of-human-cytochrome-p450-reductase-with-cytochrome-c
Identifying selective inhibitors of cytochrome P450 isoforms is a useful tool in defining the role of individual cytochrome P450s in the metabolism process. In this study, nine chemical inhibitors were selected based on literature data and were examined for their specificity toward cytochrome P450-mediated reactions in human liver microsomes. Furafylline was a potent, mechanism-based inhibitor for CYP1A2-mediated phenacetin O-deethylation. The probes sulfaphenazole (CYP2C9) and quinidine (CYP2D6) selectively inhibited tolbutamide methylhydroxylation and bufuralol 1'-hydroxylation, respectively. Additionally, the CYP2E1-catalyzed chlorzoxazone 6-hydroxylation was significantly inhibited by diethyldithiocarbamate. Of the CYP3A4 inhibitor probes used, troleandomycin proved to be the most specific for testosterone 6 beta-hydroxylation. ...http://dmd.aspetjournals.org/content/23/1/154
"Toll-like Receptor-4 Regulation of Hepatic Cyp3a11 Metabolism in a Mou" by Dalya Abdulla, Kerry B. Goralski et al.
Central nervous system (CNS) infection and inflammation severely reduce the capacity of cytochrome P-450 metabolism in the liver. We developed a mouse model to examine the effects of CNS inflammation on hepatic cytochrome P-450 metabolism. FVB, C57BL/6, and C3H/HeouJ mice were given Escherichia coli LPS (2.5 μg) by intracerebroventricular (ICV) injection. The CNS inflammatory response was confirmed by the elevation of TNF-α and/or IL-1β proteins in the brain. In all mouse strains, LPS produced a 60-70% loss in hepatic Cyp3a11 expression and activity compared with saline-injected controls. Adrenalectomy did not prevent the loss in Cyp3a11 expression or activity, thereby precluding the involvement of the hypothalamic-adrenal-pituitary axis. Endotoxin was detectable (1-10 ng/ml) in serum between 15 and 120 min after ICV dosing of 2.5 μg LPS. Peripheral administration of 2.5 μg LPS by intraperitoneal injection produced similar serum endotoxin levels and a ...https://source.sheridancollege.ca/fahcs_heal_publ/16/