keyword
MENU ▼
Read by QxMD icon Read
search

cytochrome p450 3A4

keyword
https://www.readbyqxmd.com/read/28702667/microengineered-cultures-containing-human-hepatic-stellate-cells-and-hepatocytes-for-drug-development
#1
Matthew D Davidson, David A Kukla, Salman R Khetani
In non-alcoholic steatohepatitis (NASH), hepatic stellate cells (HSC) differentiate into myofibroblast-like cells that cause fibrosis, which predisposes patients to cirrhosis and hepatocellular carcinoma. Thus, modeling interactions between activated HSCs and hepatocytes in vitro can aid in the development of anti-NASH/fibrosis therapeutics and lead to a better understanding of disease progression. Species-specific differences in drug metabolism and disease pathways now necessitate the supplementation of animal studies with data acquired using human liver models; however, current models do not adequately model the negative effects of primary human activated HSCs on the phenotype of otherwise well-differentiated primary human hepatocytes (PHHs) as in vivo...
July 12, 2017: Integrative Biology: Quantitative Biosciences From Nano to Macro
https://www.readbyqxmd.com/read/28696416/cytochrome-p450-interactions-are-common-and-consequential-in-massachusetts-hospital-discharges
#2
T H McCoy, V M Castro, A Cagan, L Snapper, A Roberson, R H Perlis
Despite the recognition that drug-drug interactions contribute substantially to preventable health-care costs, the prevalence of such interactions related to the cytochrome P450 system in clinical practice remains poorly characterized. This study drew retrospective hospital discharge cohorts from a large health claims data set and a large health system data set. For every hospital discharge, frequency of co-occurrence of substrates and inducers or inhibitors at cytochrome P450 2D6, 2C19, 3A4 and 1A2 were determined...
July 11, 2017: Pharmacogenomics Journal
https://www.readbyqxmd.com/read/28685969/the-cytochrome-p450-3a4-has-three-major-conformations-new-clues-to-drug-recognition-by-this-promiscuous-enzyme
#3
Lydia Benkaidali, François André, Gautier Moroy, Bahoueddine Tangour, François Maurel, Michel Petitjean
We computed the channels of the 3A4 isoform of the cytochrome P450 3A4 (CYP) on the basis of 24 crystal structures extracted from the Protein Data Bank (PDB). We identified three major conformations (denoted C, O1 and O2) using an enhanced version of the CCCPP software that we developed for the present work, while only two conformations (C and O(2) ) are considered in the literature. We established the flowchart of definition of these three conformations in function of the structural and physicochemical parameters of the ligand...
July 7, 2017: Molecular Informatics
https://www.readbyqxmd.com/read/28685622/induction-of-human-cytochrome-p450-3a4-by-the-irreversible-myeloperoxidase-inactivator-pf-06282999-is-mediated-by-the-pregnane-x-receptor
#4
Jamie E Moscovitz, Zhiwu Lin, Nathaniel Johnson, Meihua Tu, Theunis Goosen, Yan Weng, Amit S Kalgutkar
1. 2-(6-(5-Chloro-2-methoxyphenyl)-4-oxo-2-thioxo-3,4-dihydropyrimidin-1(2H)-yl) acetamide (PF-06282999) is a member of the thiouracil class of irreversible inactivators of human myeloperoxidase enzyme and a candidate for the treatment of cardiovascular disease. PF-06282999 is an inducer of CYP3A4 mRNA and midazolam-1'-hydroxylase activity in human hepatocytes, which is consistent with PF-06282999-dose dependent decreases in mean maximal plasma concentrations (Cmax) and area under the plasma concentration time curve (AUC) of midazolam in humans following 14-day treatment with PF-06282999...
July 7, 2017: Xenobiotica; the Fate of Foreign Compounds in Biological Systems
https://www.readbyqxmd.com/read/28676933/association-of-nr1i2-cyp3a5-and-abcb1-genetic-polymorphisms-with-variability-of-temsirolimus-pharmacokinetics-and-toxicity-in-patients-with-metastatic-bladder-cancer
#5
Litaty C Mbatchi, Matthieu Gassiot, Philippe Pourquier, Alejando Goberna, Hakim Mahammedi, Loic Mourey, Florence Joly, Serge Lumbroso, Alexandre Evrard, Nadine Houede
PURPOSE: Temsirolimus is a mammalian target of rapamycin (mTOR) inhibitor that exhibits antitumor activity in renal cell carcinoma and mantle cell lymphoma. The metabolism of temsirolimus and its active metabolite sirolimus mainly depends on cytochrome P450 3A4/5 (CYP3A4/A5) and the ABCB1 transporter. Differently from sirolimus, no pharmacogenetic study on temsirolimus has been conducted. Therefore, the aim of this pilot study was to identify genetic determinants of the inter-individual variability in temsirolimus pharmacokinetics and toxicity...
July 4, 2017: Cancer Chemotherapy and Pharmacology
https://www.readbyqxmd.com/read/28667459/clinical-pharmacokinetics-and-pharmacodynamics-of-panobinostat
#6
REVIEW
Mathilde Van Veggel, Elsbeth Westerman, Paul Hamberg
Histone deacetylase (HDAC) inhibitors cause an increase in acetylation that leads to an increase in DNA transcription and accumulation of different proteins, reducing cell proliferation and inducing cell death. Panobinostat is a first-in-line HDAC inhibitor approved for treating multiple myeloma in combination with bortezomib and dexamethasone. It is a pan-deacetylase inhibitor and therefore inhibits not only HDAC but also other deacetylases. The main mechanism of action of panobinostat is to inhibit HDAC, which causes cell cycle arrest and apoptosis, leading to it being an antineoplastic drug...
June 30, 2017: Clinical Pharmacokinetics
https://www.readbyqxmd.com/read/28664876/scaling-up-of-a-heparg-progenitor-cell-based-bioartificial-liver-optimization-for-clinical-application-and-transport
#7
Martien van Wenum, Philipp Treskes, Chung-Yin Tang, Esmee J Coppens, Koen Jansen, Erik J Hendriks, Sandrine Camus, Thomas M van Gulik, Robert A F M Chamuleau, Ruurdtje Hoekstra
A new generation of bioartificial livers, based on differentiated proliferative hepatocyte sources, has been developed. Several practicable and regulatory demands have to be addressed before these can be clinically evaluated. We identified three main hurdles: (1) expansion and preservation of the biocomponent, (2) development of scaled-up culture conditions and (3) transport of the device to the bedside. In this study we address these three issues for the HepaRG-progenitor cell line-loaded AMC-Bioartificial Liver...
June 30, 2017: Biofabrication
https://www.readbyqxmd.com/read/28648140/oxidation-of-1-chloropyrene-by-human-cyp1-family-and-cyp2a-subfamily-cytochrome-p450-enzymes-catalytic-roles-of-two-cyp1b1-and-five-cyp2a13-allelic-variants
#8
Tsutomu Shimada, Norie Murayama, Kensaku Kakimoto, Shigeo Takenaka, Young-Ran Lim, Sora Yeom, Donghak Kim, Hiroshi Yamazaki, F Peter Guengerich, Masayuki Komori
1. Chloropyrene, one of the major chlorinated polycyclic aromatic hydrocarbon contaminants, was incubated with human cytochrome P450 (P450 or CYP) enzymes including CYP1A1, 1A2, 1B1, 2A6, 2A13, 2B6, 2C9, 2D6, 2E1, 3A4, and 3A5. Catalytic differences in 1-chloropyrene oxidation by polymorphic two CYP1B1 and five CYP2A13 allelic variants were also examined. 2. CYP1A1 oxidized 1-chloropyrene at the 6- and 8-positions more actively than at the 3-position, while both CYP1B1.1 and 1B1.3 preferentially catalyzed 6-hydroxylation...
June 26, 2017: Xenobiotica; the Fate of Foreign Compounds in Biological Systems
https://www.readbyqxmd.com/read/28645477/the-overexpression-of-cpr-and-p450-3a4-in-pancreatic-cancer-cells-changes-the-metabolic-profile-and-increases-the-cytotoxicity-and-pro-apoptotic-activity-of-acridine-antitumor-agent-c-1748
#9
Barbara Borowa-Mazgaj, Anna Mróz, Ewa Augustin, Ewa Paluszkiewicz, Zofia Mazerska
Drug resistance is one of the major cause of pancreatic cancer treatment failure. Thus, it is still imperative to develop new active compounds and novel approach to improve drug efficacy. Here we present 9-amino-1-nitroacridine antitumor agent, C-1748, developed in our laboratory, as a candidate for pancreatic cancer treatment. We examined (i) the cellular response of pancreatic cancer cell lines: Panc-1, MiaPaCa-2, BxPC-3 and AsPC-1, differing in expression levels of commonly mutated genes for this cancer type, to C-1748 treatment and (ii) the role of P450 3A4 isoenzyme and cytochrome P450 reductase (CPR) in the modulation of this response...
June 20, 2017: Biochemical Pharmacology
https://www.readbyqxmd.com/read/28640225/herb-drug-interaction-between-the-traditional-hepatoprotective-formulation-and-sorafenib-on-hepatotoxicity-histopathology-and-pharmacokinetics-in-rats
#10
Chin-Tsung Ting, Yung-Yi Cheng, Tung-Hu Tsai
Sorafenib has been used as a standard therapy for advanced hepatocellular carcinoma (HCC). In Asia, patients with HCC are potentially treated with the combination of sorafenib and Chinese herbal medicines to improve the efficiency and reduce the side effects of sorafenib. However, limited information about the herb-drug interactions is available. We hypothesize that the Chinese herbal medicine may exert hepatoprotective effects on the sorafenib-treated group. The aim of this study is to investigate the pharmacokinetic mechanism of drug-drug interactions of sorafenib including interacting with hepatoprotective formulation, Long-Dan-Xie-Gan-Tang formulation (LDXGT) and with two cytochrome P450 3A4 (CYP3A4) inhibitors, grapefruit juice and ketoconazole...
June 22, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/28637420/bioinformatics-insights-on-targets-receptors-of-amiodarone-in-human-and-acanthamoeba-castellanii
#11
Abdul Baig, Zohaib Rana, H R Ahmad
BACKGROUND: Amiodarone is prescribed for certain cardiac arrhythmias in medical practice. The drug targets and inhibits voltage dependent sodium (Na+v), calcium (Ca+2v), potassium (K+v) channels, and enzymes like cytochrome P450 and oxidosqualene cyclase. Past studies have shown that amiodarone exerts anti-amoebic effects against Trypanosoma cruzi and Acanthamoeba castellanii. OBJECTIVES: The presence of aforementioned targets and the type of cell death induced by amiodarone in these pathogenic eukaryotes like Acanthamoeba castellanii remain to be verified...
June 21, 2017: Infectious Disorders Drug Targets
https://www.readbyqxmd.com/read/28630772/severe-rhabdomyolysis-due-to-presumed-drug-interactions-between-atorvastatin-with-amlodipine-and-ticagrelor
#12
Iouri Banakh, Kavi Haji, Ross Kung, Sachin Gupta, Ravindranath Tiruvoipati
Atorvastatin and ticagrelor combination is a widely accepted therapy for secondary prevention of ischaemic heart disease. However, rhabdomyolysis is a well-known rare side effect of statins which should be considered when treatments are combined with cytochrome P450 3A4 enzyme inhibitors. We report a case of atorvastatin and ticagrelor associated severe rhabdomyolysis that progressed to multiorgan failure requiring renal replacement therapy, inotropes, intubation, and mechanical ventilation. Despite withdrawal of the precipitating cause and the supportive measures including renal replacement therapy, creatinine kinase increased due to ongoing rhabdomyolysis rapidly progressing to upper and lower limbs weakness...
2017: Case Reports in Critical Care
https://www.readbyqxmd.com/read/28618157/liver-microsomal-lipid-enhances-the-activity-and-redox-coupling-of-colocalized-cytochrome-p450-reductase-cytochrome-p450-3a4-in-nanodiscs
#13
Kang-Cheng Liu, John M X Hughes, Sam Hay, Nigel S Scrutton
The haem-containing mono-oxygenase cytochrome P450 3A4 (CYP3A4) and its redox partner NADPH-dependent cytochrome P450 oxidoreductase (CPR) are among the most important enzymes in human liver for metabolizing drugs and xenobiotic compounds. They are membrane-bound in the endoplasmic reticulum (ER). How ER colocalization and the complex ER phospholipid composition influence enzyme activity are not well understood. CPR and CYP3A4 were incorporated into phospholipid bilayer nanodiscs, both singly, and together in a 1 : 1 ratio, to investigate the significance of membrane insertion and the influence of varying membrane composition on steady-state reaction kinetics...
June 15, 2017: FEBS Journal
https://www.readbyqxmd.com/read/28616429/evaluation-of-the-interaction-of-intravenous-and-oral-voriconazole-with-oral-cyclosporine-in-iranian-hsct-patients
#14
Hamidreza Taghvaye Masoumi, Molouk Hadjibabaie, Mohammad Vaezi, Ardeshir Ghavamzadeh
OBJECTIVE: Voriconazole as a triazole antifungal agent is widely used for prophylaxis or treatment of fungal infections in allogeneic hematopoietic stem cell transplantation (HSCT). It can increase blood concentrations of other medications including cyclosporine A (CsA) which are substrates for cytochrome P450 3A4. The aim of this study was to evaluate comparatively the interaction between oral/intravenous (IV) voriconazole and oral CsA. METHODS: Twenty-nine recipients of allogeneic HSCT who had been already on a steady dose of CsA and were started on oral or IV voriconazole were evaluated in a prospective cohort study...
April 2017: Journal of Research in Pharmacy Practice
https://www.readbyqxmd.com/read/28614988/in-vitro-inhibitory-effects-of-dihydromyricetin-on-human-liver-cytochrome-p450-enzymes
#15
Lu Liu, Sen Sun, Hongbing Rui, Xiaohua Li
CONTEXT: Dihydromyricetin (DHM) is the most abundant and active flavonoid component isolated from Ampelopsis grossedentata (Hand-Mazz) W.T. Wang (Vitaceae) and it possesses numerous pharmacological activities. However, whether DHM affects the activity of human liver cytochrome P450 (CYP) enzymes remains unclear. MATERIALS AND METHODS: The inhibitory effects of DHM on eight human liver CYP isoforms (i.e., 1A2, 3A4, 2A6, 2E1, 2D6, 2C9, 2C19 and 2C8) were investigated in vitro using human liver microsomes (HLMs)...
December 2017: Pharmaceutical Biology
https://www.readbyqxmd.com/read/28610444/midostaurin-for-the-treatment-of-acute-myeloid-leukemia
#16
Mrinal M Patnaik
Midostaurin is a multikinase tyrosine kinase inhibitor acting against targets known to be expressed in hematologic malignancies, especially acute myeloid leukemia. Midostaurin combined with chemotherapy followed by single-agent maintenance therapy elicited statistically significant and clinically meaningful improvement in overall survival versus placebo in patients with newly diagnosed FLT3-mutant acute myeloid leukemia. Although gastrointestinal events were more common with midostaurin, overall the drug was relatively well tolerated...
June 14, 2017: Future Oncology
https://www.readbyqxmd.com/read/28590129/high-level-production-and-properties-of-the-cysteine-depleted-cytochrome-p450-3a4
#17
Irina F Sevrioukova
Human drug-metabolizing cytochrome P450 3A4 (CYP3A4) is a dynamic enzyme with a large and highly malleable active site that can fit structurally diverse compounds. Despite extensive investigations, structure-function relationships and conformational dynamics in CYP3A4 are not fully understood. This study was undertaken to engineer a well-expressed and functionally active cysteine-depleted CYP3A4 that can be used in biochemical and biophysical studies. cDNA codon optimization and screening mutagenesis were utilized to boost the level of bacterial expression of CYP3A4 and identify the least harmful substitutions for all six non-heme-ligating cysteines...
June 7, 2017: Biochemistry
https://www.readbyqxmd.com/read/28558634/differential-regulation-of-cyp3a4-and-cyp3a5-and-its-implication-in-drug-discovery
#18
Ogheneochukome Lolodi, Yue-Ming Wang, William C Wright, Taosheng Chen
Cancer cells use several mechanisms to resist the cytotoxic effects of drugs, resulting in tumor progression and invasion. One such mechanism capitalizes on the body's natural defense against xenobiotics. Recent reports indicate that components of the xenobiotic response system are upregulated in some diseases, including many cancers. Such components include the pregnane X receptor and the cytochrome P450 3A4 and 3A5 enzymes. Intense research is ongoing to understand the functional ramifications of aberrant expression of these components in diseased states with the goal of designing novel drugs that can selectively target them...
May 30, 2017: Current Drug Metabolism
https://www.readbyqxmd.com/read/28546420/alterations-of-histone-modifications-contribute-to-pregnane-x-receptor-mediated-induction-of-cyp3a4-by-rifampicin
#19
Liang Yan, Yiting Wang, Jingyang Liu, Yali Nie, Xiaobo Zhong, Quancheng Kan, Lirong Zhang
Cytochrome P450 3A4 (CYP3A4) is one of the major drug-metabolizing enzymes in human and is responsible for the metabolism of 60% of the clinically used drugs. Many drugs are able to induce the expression of CYP3A4, which usually causes drug-drug interactions and adverse drug reactions. This study aims to explore the role of histone modifications in rifampicin-induced expression of CYP3A4 in LS174T cells. We found that the induction of CYP3A4 mRNA by rifampicin in LS174T cells was associated with increased levels of histone H3 lysine 4 trimethylation (H3K4me3) and H3 acetylation and a decreased level of histone H3 lysine 27 trimethylation (H3K27me3) in the CYP3A4 promoter...
May 25, 2017: Molecular Pharmacology
https://www.readbyqxmd.com/read/28539103/possible-oxcarbazepine-inductive-effects-on-aripiprazole-metabolism-a-case-report
#20
Ian R McGrane, Joshua G Loveland, Jose de Leon
Oxcarbazepine is a cytochrome P450 (CYP) 3A4 inducer, which is structurally similar to carbamazepine. Although lacking Food and Drug Administration approval, oxcarbazepine is sometimes prescribed to treat aggressive behavior in youth with autism spectrum disorder (ASD). These youths may also be taking second-generation antipsychotics, some of which are substrates of the CYP3A4 metabolic pathway. The combination of these medications may result in decreased serum antipsychotic concentrations, potentially reducing effectiveness...
January 1, 2017: Journal of Pharmacy Practice
keyword
keyword
46035
1
2
Fetch more papers »
Fetching more papers... Fetching...
Read by QxMD. Sign in or create an account to discover new knowledge that matter to you.
Remove bar
Read by QxMD icon Read
×

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"