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Showing 1 to 20 of 69 for “"CYP3A4"”.
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Ligand and Protein Dynamics of CYP3A4
Cytochrome P450 3A4 (CYP3A4) dominates drug metabolism in humans. Examples of promiscuity (binding and catalytic) and allosterism in CYP3A4 are ubiquitous but poorly understood. This work is dedicated to improving our understanding of the linkage between ligand binding and protein conformational …
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Estudos de modelagem molecular da piperina e CYP3A4 : a influência na biodisponibilidade de fármacos
… piperine. The complex formed with piperine and CYP3A4 was shown to be the most stable of all, with the binding energy of - 8.60 kcal/mol. This explain the related mechanism of interaction drug - herb, since the better anchoring of piperine in the active site of CYP3A4 can hinder the drug - …
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Structural Studies of Lipid-Bound Apolipoprotein A-I and Nanodisc-Embedded Cyp3A4 by SSNMR
Membrane proteins constitute more than half of all drug targets in the pharmaceutical industry today, which is not surprising given that a third of human genome codes for membrane proteins, and that they perform a large number and variety of cellular functions. However, membrane proteins to date …
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Prediction of CYP3A4 metabolic activity from whole genome RNA-seq data with feature selection machine learning methods
CYP3A4, one of the isozyme of the cytochromes P450 (CYPs), contributes significantly to drug clearance and drug-drug interactions. The goals of this project are to identify hepatically-expressed genes that are associated with CYP3A4 metabolic activity in human liver tissue and to predict CYP3A4 …
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Propoxyphene, Norpropoxyphene, and Proadifen (SKF-525A) Are Mechanism Based Inhibitors of CYP3A4, CYP3A5, and CYP3A in Human Liver Microsomes
… enzymes, and is an irreversible inhibitor of CYP3A4. The major metabolite of propoxyphene is norpropoxyphene, which has not been extensively studied for enzyme inhibition. Proadifen (SKF-525a) is not a marketed drug, but it is a known CYP inhibitor that is structurally similar to propoxyphene …
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THE IMPACT OF CYP3A4*22 AND CYP3A5*3 ON DEXAMETHASONE AND 6-HYDROXY-DEXAMETHASONE PHARMACOKINETICS IN PHASE 1/2 CANCER PATIENTS
CYP3A4 and CYP3A5 comprise the most abundantly expressed human CYP450 activity and participate in metabolism of an estimated 40% of all marketed drugs. However, their 10-100 fold inter-individual variability in activity may have a profound effect on outcomes from drug therapy. CYP3A4*22 and …
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Associations of genetic variants in ABCB1, ABCG2, CYP3A4, CYP3A5, and SLCO1B1 with statin-associated muscle symptom (SAMS) in South African populations
… to pharmacogenetic variability of ABCB1, ABCG2, CYP3A4, CYP3A5, and SLCO1B1, particularly in Asian and European populations. However, limited knowledge exists regarding the impact of pharmacogenetics on statin tolerance among South African patients. This study aimed to examine the relationships …
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Characterization of Monomeric Human Cytochrome P450 3A4 and Cytochrome P450 Reductase in Nanoscale Phospholipid Bilayer Discs
… that cause the conformational heterogeneity of CYP3A4 in other solubilization systems have complicated the complete biophysical characterization in comparison to similar soluble bacterial counterparts. The use of a discrete soluble nanoscale phospholipid bilayer system with an incorporated …
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Pharmacogenetics of resistant hypertension: evaluating the role of genetic variation in ABCB1, ADBR1, CES1, CYP3A4, CYP3A5, NEDD4L, NOS3, NR3C2 and SCNN1B among South African hypertensive patient
… in nine genes, namely, ABCB1, ADBR1, CES1, CYP3A4, CYP3A5, NEDD4L, NOS3, NR3C2 and SCNN1B, in the development of resistant hypertension in South African patients. Knowledge of pharmacogenetic variants that play a role in resistant hypertension may potentially improve treatment and management …
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Impact of CYP2C8 single nucleotide polymorphisms on in-vitro metabolism of imatinib to N-desmethyl imatinib
… to its main metabolite N-desmethyl imatinib by CYP3A4 and CYP2C8. In vitro human liver microsome (HLM) studies indicate imatinib autoinhibition of CYP3A4-mediated metabolism, suggesting a more significant role for CYP2C8 upon chronic dosing. CYP2C8 is polymorphic and functional effects of the …
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Human Cytochrome P450 3A4 Over-Expressing IEC-18 and MDCK Cell Lines as an In-Vitro Model to Assess Gut Permeability and the Enzyme Metabolism
… of drug metabolism enzyme expression such as CYP3A4, which contributes to significant first-pass gut and liver metabolism for many drugs. Consequently, these cell lines are not sufficient to integrate metabolism when assessing drug absorption. Here, we tested MDCK and IEC-18 cells transiently …
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Structural Dynamics and Reaction Reversibility of Specific vs. Promiscuous Detoxification Enzymes
… detoxification enzymes cytochrome P450 3A4 (CYP3A4) and glutathione transferase A1-1 (GSTA1-1) with that of structurally related, substrate-specific counterparts CYP19A1 and GSTA4-4. Two aspects of enzyme behavior are considered: (I) structural dynamics in the absence and presence of ligands, …
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Selective Targeting of CYP3A5 Through Chemical and Genetic Approaches
… for drug response. Within this family are CYP3A4 and CYP3A5, which collectively metabolize greater than half of all currently prescribed drugs. These promiscuous enzymes can bind a broad and structurally diverse array of compounds, in turn leading to an increased risk of their modulation …
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Role of cytochrome P450 enzymes on alcohol/nicotine-mediated oxidative stress and cytotoxicity in monocytes/astrocytes: Implications for HIV-infected alcohol/tobacco users
… CYP2A6 and a major drug-metabolizing enzyme CYP3A4 are induced by alcohol, suggesting their role in unexpected alcohol-drug-tobacco interactions. Our central hypothesis is that CYP2A6, CYP2E1, and CYP3A4 play important role in alcohol, nicotine, and antiretroviral therapeutic (ART) drug …
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Global deconvolution of heterotropic cooperativity in cytochrome P450 3A4
Cytochrome P450 3A4 (CYP3A4) plays a central role in xenobiotic metabolism, and is of critical importance to both human health and the pharmaceutical industry. Its ability to interact with multiple molecules of the same substrate, or multiple substrates, leads to complex non-Michaelis kinetics, …
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Prodrug Approach to Improve Oral and Brain Absorption of HIV Protease Inhibitor, Lopinavir
… P-gp and MRP2 and extensive hepatic metabolism (CYP3A4 enzymes). Furthermore, brain LPV absorption is poor due to high efflux by P-gp and MRP2 at blood-brain barrier (BBB), plasma protein binding (99%) and extensive CYP3A4 metabolism. Hence, to improve oral and brain absorption of LPV …
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Electrochemical dynamics of cytochrome P450-3A4 isoenzyme biosensor for protease inhibitor antiretroviral drug
… heme thiolate, cytochrome P450 3A4 isoenzyme (CYP3A4), as biorecognition component. Secondly, each biosensor platform was evaluated by using an entirely different category of compound as model substrate, with the overall objective being the development of alternative analytical method for the …
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Vitamin D Levels Affect Survival in a BCR-ABL Acute Lymphoblastic Leukemia Mouse Model but Do Not Cause Vitamin-Drug Interactions
… if co-administered with drugs that are CYP3A4 substrates lead to marked drug-drug interactions. Because vitamin D is known to regulate intestinal CYP3A expression and gut CYP3A expression plays an important role in pre-systemic metabolism of CYP3A drugs, we determined the impact of …
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Vom Antioxidanz zum Genregulator : transkriptionelle Regulation von Phase I- und Phase II-Enzymen durch Vitamin E und antioxidative sekundäre Pflanzeninhaltsstoffe
… sowie des Promotors eines jeweiligen Zielgens (CYP3A4 bzw. GI-GPx) wurde in vitro mit Reportergenplasmiden untersucht. Es zeigte sich, dass sowohl Vitamin E-Formen als auch verschiedene sekundäre Pflanzeninhaltsstoffe PXR und/oder Nrf2 sowie die Promotoren der jeweiligen Zielgene CYP3A4 bzw. …
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Metabolic Factors Determining Outcome in Chemotherapy: Studies with Pazopanib
… this difference was attenuated in humanised CYP3A4/3A7 mouse liver microsomes when compared with human liver microsomes, suggesting that humanised mice represent a better model for human pazopanib metabolism in vitro.This species difference in metabolism was reflected in in vivo …
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