1,330 results match your criteria microsomal cyp


Impact of Curcumin on Microsomal Enzyme Activities: Drug Interaction and Chemopreventive Studies.

Curr Med Chem 2021 Mar 29. Epub 2021 Mar 29.

Applied Biomedical Research Center, Mashhad University of Medical Sciences, Mashhad. Iran.

Curcumin, a yellow pigment in Asian spice, is a natural polyphenol component of Curcuma longa rhizome. Curcuminoid components include curcumin, demethoxycurcumin (DMC), and bisdemethoxycurcumin (BDMC). Previous studies established curcumin as a safe agent based on preclinical and clinical evaluations and curcuminoids have been approved by the US Food and Drug Administration (FDA) as "Generally Recognized as Safe" (GRAS). Read More

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Discovery of N-amido-phenylsulfonamide derivatives as novel microsomal prostaglandin E synthase-1 (mPGES-1) inhibitors.

Bioorg Med Chem Lett 2021 Jun 26;41:127992. Epub 2021 Mar 26.

Research Institute for Basic Sciences and Department of Chemistry, College of Sciences, Kyung Hee University, Seoul 02447, Republic of Korea; KHU-KIST Department of Converging Science and Technology, Kyung Hee University, Seoul 02447, Republic of Korea. Electronic address:

Our previous research showed that N-carboxy-phenylsulfonyl hydrazide (scaffold A) could reduce LPS-stimulated PGE levels in RAW 264.7 macrophage cells by an inhibition of mPGES-1 enzyme. However, a number of scaffold A derivatives showed the drawbacks such as the formation of regioisomers and poor liver metabolic stability. Read More

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In vitro and in silico studies of interaction of synthetic 2,6,9-trisubstituted purine kinase inhibitors BPA-302, BP-21 and BP-117 with liver drug-metabolizing cytochromes P450

Physiol Res 2020 12;69(Suppl 4):S627-S636

Department of Pharmacology, Faculty of Medicine, Palacký University Olomouc, Czech Republic.

An evaluation of possible interactions with enzymes of drug metabolism (cytochromes P450, CYP) is an important part of studies on safety and, in general, on the properties of any drug or biologically active compound. The article is focused on the preliminary metabolic study of selected 2,6,9-trisubstituted purine kinase inhibitors with significant anticancer activities which we have developed. The compounds BP-21 and BP-117 represent strong CDK inhibitors and the compound BPA-302 was developed as selective FLT3-ITD kinase inhibitor. Read More

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December 2020

Murburn precepts for cytochrome P450 mediated drug/xenobiotic metabolism and homeostasis.

Curr Drug Metab 2021 Jan 17. Epub 2021 Jan 17.

Satyamjayatu: The Science & Ethics Foundation, Snehatheeram, Kulappully, Shoranur-2 (PO), Kerala. India.

Aims: We aim to demonstrate why deeming diffusible reactive oxygen species (DROS) as toxic wastes does not afford a comprehensive understanding of cytochrome P450 mediated microsomal xenobiotic metabolism (mXM).

Background: Current pharmacokinetic investigations consider reactive oxygen species formed in microsomal reactions as toxic waste products, whereas our works (Manoj et al., 2016) showed that DROS are the reaction mainstay in cytochrome P450 mediated metabolism and that they play significant roles in explaining several unexplained physiologies (Parashar et al. Read More

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January 2021

Elucidation of plasma protein binding, blood partitioning, permeability, CYP phenotyping and CYP inhibition studies of Withanone using validated UPLC method: An active constituent of neuroprotective herb Ashwagandha.

J Ethnopharmacol 2021 Apr 16;270:113819. Epub 2021 Jan 16.

Pharmaceutics & Pharmacokinetics Division, CSIR-Central Drug Research Institute, Lucknow, 226031, India; Academy of Scientific and Innovative Research (AcSIR), Ghaziabad, 201002, India. Electronic address:

Ethnopharmacological Relevance: Withanone (WN), an active constituent of Withania somnifera commonly called Ashwagandha has remarkable pharmacological responses along with neurological activities. However, for a better understanding of the pharmacokinetic and pharmacodynamic behavior of WN, a comprehensive in-vitro ADME (absorption, distribution, metabolism, and excretion) studies are necessary.

Aim Of The Study: A precise, accurate, and sensitive reverse-phase ultra-performance liquid chromatographic method of WN was developed and validated in rat plasma for the first time. Read More

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Differential effects on human cytochromes P450 by CRISPR/Cas9-induced genetic knockout of cytochrome P450 reductase and cytochrome b5 in HepaRG cells.

Sci Rep 2021 Jan 13;11(1):1000. Epub 2021 Jan 13.

Dr. Margarete Fischer-Bosch Institute of Clinical Pharmacology, Stuttgart, Germany.

HepaRG cells are increasingly accepted as model for human drug metabolism and other hepatic functions. We used lentiviral transduction of undifferentiated HepaRG cells to deliver Cas9 and two alternative sgRNAs targeted at NADPH:cytochrome P450 oxidoreductase (POR), the obligate electron donor for microsomal cytochromes P450 (CYP). Cas9-expressing HepaRG (vector control) cells were phenotypically similar to wild type HepaRG cells and could be differentiated into hepatocyte-like cells by DMSO. Read More

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January 2021

Predicting liver cytosol stability of small molecules.

J Cheminform 2020 Apr 7;12(1):21. Epub 2020 Apr 7.

National Center for Advancing Translational Sciences (NCATS), National Institutes of Health (NIH), 9800 Medical Center Drive, Rockville, MD, 20850, USA.

Over the last few decades, chemists have become skilled at designing compounds that avoid cytochrome P (CYP) 450 mediated metabolism. Typical screening assays are performed in liver microsomal fractions and it is possible to overlook the contribution of cytosolic enzymes until much later in the drug discovery process. Few data exist on cytosolic enzyme-mediated metabolism and no reliable tools are available to chemists to help design away from such liabilities. Read More

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An electron transfer competent structural ensemble of membrane-bound cytochrome P450 1A1 and cytochrome P450 oxidoreductase.

Commun Biol 2021 Jan 8;4(1):55. Epub 2021 Jan 8.

Molecular and Cellular Modeling Group, Heidelberg Institute for Theoretical Studies (HITS), Schloss-Wolfsbrunnenweg 35, 69118, Heidelberg, Germany.

Cytochrome P450 (CYP) heme monooxygenases require two electrons for their catalytic cycle. For mammalian microsomal CYPs, key enzymes for xenobiotic metabolism and steroidogenesis and important drug targets and biocatalysts, the electrons are transferred by NADPH-cytochrome P450 oxidoreductase (CPR). No structure of a mammalian CYP-CPR complex has been solved experimentally, hindering understanding of the determinants of electron transfer (ET), which is often rate-limiting for CYP reactions. Read More

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January 2021

Peripheral Selective Oxadiazolylphenyl Alanine Derivatives as Tryptophan Hydroxylase 1 Inhibitors for Obesity and Fatty Liver Disease.

J Med Chem 2021 01 8;64(2):1037-1053. Epub 2021 Jan 8.

Department of Chemistry, Gwangju Institute of Science and Technology, Gwangju 61005, Republic of Korea.

Tryptophan hydroxylase 1 (TPH1) has been recently suggested as a promising therapeutic target for treating obesity and fatty liver disease. A new series of 1,2,4-oxadiazolylphenyl alanine derivatives were identified as TPH1 inhibitors. Among them, compound was the most active in vitro, with an IC (half-maximal inhibitory concentration) value of 42 nM, showed good liver microsomal stability, and showed no significant inhibition of CYP and hERG. Read More

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January 2021

Abundance and Associated Variations of Cytochrome P450 Drug-Metabolizing Enzymes in the Liver of East Asian Adults: A Meta-Analysis.

Eur J Drug Metab Pharmacokinet 2021 Mar;46(2):225-233

Clinical Medical College, Yangzhou University, Yangzhou, China.

Background: Cytochrome P450 (CYP) enzymes are one of the main sources of variability in drug metabolic clearance. Information on their abundance levels is therefore crucial to optimize scaling factors for in vitro-in vivo extrapolation (IVIVE) to predict metabolic clearance.

Objective: This study aims to quantify the abundance data of hepatic drug-metabolizing CYP enzymes in East Asian subjects reported from various sources in the literature using meta-analysis. Read More

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The role of alcohol consumption on acetaminophen induced liver injury: Implications from a mathematical model.

J Theor Biol 2021 Jun 15;519:110559. Epub 2020 Dec 15.

PRECESIONheor, Los Angeles, CA, USA, Center for Collaborative Studies in Mathematical Biology, Illinois State University, Normal, IL, College of Health Solutions, Arizona State University, Tempe, AZ, USA.

Acetaminophen (APAP) overdose is one of the predominant causes of drug induced acute liver injury in the U.S and U.K. Read More

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Comparable Intestinal and Hepatic First-Pass Effect of YL-IPA08 on the Bioavailability and Effective Brain Exposure, a Rapid Anti-PTSD and Anti-Depression Compound.

Front Pharmacol 2020 27;11:588127. Epub 2020 Nov 27.

State Key Laboratory of Toxicology and Medical Countermeasures, Beijing Institute of Pharmacology and Toxicology, Beijing, China.

YL-IPA08, exerting rapid antidepressant-like and anxiolytic-like effects on behaviors by translocator protein (TSPO) mediation, is a novel compound that has been discovered and developed at our institute. Fit-for-purpose pharmacokinetic properties is urgently needed to be discovered as early as possible for a new compound. YL-IPA08 exhibited low bioavailability (∼6%) during the preliminary pharmacokinetics study in rats after oral administration. Read More

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November 2020

Identification of Enzymes Oxidizing the Tyrosine Kinase Inhibitor Cabozantinib: Cabozantinib Is Predominantly Oxidized by CYP3A4 and Its Oxidation Is Stimulated by cyt b Activity.

Biomedicines 2020 Nov 28;8(12). Epub 2020 Nov 28.

Department of Biochemistry, Faculty of Science, Charles University, Albertov 6, 12800 Prague 2, Czech Republic.

Herein, the in vitro metabolism of tyrosine kinase inhibitor cabozantinib, the drug used for the treatment of metastatic medullary thyroid cancer and advanced renal cell carcinoma, was studied using hepatic microsomal samples of different human donors, human recombinant cytochromes P450 (CYPs), flavin-containing mono-oxygenases (FMOs) and aldehyde oxidase. After incubation with human microsomes, three metabolites, namely cabozantinib -oxide, desmethyl cabozantinib and monohydroxy cabozantinib, were detected. Significant correlations were found between CYP3A4 activity and generation of all metabolites. Read More

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November 2020

Digital Microfluidics-Enabled Analysis of Individual Variation in Liver Cytochrome P450 Activity.

Anal Chem 2020 11 25;92(21):14693-14701. Epub 2020 Oct 25.

Faculty of Pharmacy, Drug Research Program, Division of Pharmaceutical Chemistry and Technology University of Helsinki, Viikinkaari 5 E 00014, Finland.

The superfamily of hepatic cytochrome P450 (CYP) enzymes is responsible for the intrinsic clearance of the majority of therapeutic drugs in humans. However, the kinetics of drug clearance via CYPs varies significantly among individuals due to both genetic and external factors, and the enzyme amount and function are also largely impacted by many liver diseases. In this study, we developed a new methodology, based on digital microfluidics (DMF), for rapid determination of individual alterations in CYP activity from human-derived liver samples in biopsy-scale. Read More

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November 2020

Development of a method to determine cytochrome P450 1A2, 2C9, 2D6 and 3A4 activity sheep hepatic microsomes.

J Pharmacol Toxicol Methods 2020 Nov - Dec;106:106934. Epub 2020 Oct 18.

UniSA: Clinical and Health Sciences, University of South Australia, Adelaide 5000, Australia. Electronic address:

Introduction: Ex vivo studies of human fetal hepatic drug metabolism are uncommon as it requires access to functional liver tissue and therefore raises practical and ethical concerns. Large animal models provide an alternative opportunity to study changes in cytochrome P450 (CYP) activity in the mother and fetus during pregnancy. We aimed to develop methods to determine the activity of CYP1A2, CYP2C9, CYP2D6 and CYP3A4 in sheep hepatic microsomes. Read More

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October 2020

Quasi-Irreversible Inhibition of CYP2D6 by Berberine.

Pharmaceutics 2020 Sep 24;12(10). Epub 2020 Sep 24.

College of Pharmacy, Chungnam National University, Daejeon 34134, Korea.

In our previous study, Hwang-Ryun-Hae-Dok-Tang, which contains berberine (BBR) as a main active ingredient, inhibited cytochrome P450 (CYP) 2D6 in a quasi-irreversible manner. However, no information is available on the detailed mechanism of BBR-induced CYP2D6 inhibition. Thus, the present study aimed to characterize the inhibition mode and kinetics of BBR and its analogues against CYP2D6 using pooled human liver microsomes (HLM). Read More

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September 2020

Interspecies differences in cytochrome P450-mediated metabolism of neonicotinoids among cats, dogs, rats, and humans.

Comp Biochem Physiol C Toxicol Pharmacol 2021 Jan 3;239:108898. Epub 2020 Oct 3.

Faculty of Veterinary Medicine, Hokkaido University, Kita 18, Nishi 9, Kita-ku, Sapporo, Hokkaido 060-0818, Japan. Electronic address:

Neonicotinoid insecticides are used for agricultural and non-agricultural purposes worldwide. Pets are directly exposed to neonicotinoids in veterinary products and through environmental contamination. Cytochrome P450 (CYP) is among the most significant xenobiotic metabolizing enzymes that oxidizes several chemicals, including neonicotinoids. Read More

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January 2021

Contribution of Pulmonary CYP-mediated Bioactivation of Naphthalene to Airway Epithelial Injury in the Lung.

Toxicol Sci 2020 10;177(2):334-346

Department of Pharmacology and Toxicology, College of Pharmacy, University of Arizona, Tucson, Arizona 85721.

Previous studies have established that cytochrome P450 enzymes (CYPs) in both liver and lung are capable of bioactivating naphthalene (NA), an omnipresent air pollutant and possible human carcinogen, in vitro and in vivo. The aim of this study was to examine the specific contribution of pulmonary CYPs in airway epithelial cells to NA-induced airway toxicity. We used a lung-Cpr-null mouse model, which undergoes doxycycline-induced, Cre-mediated deletion of the Cpr (a redox partner of all microsomal CYPs) gene specifically in airway epithelial cells. Read More

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October 2020

Modulation of CYP2C9 activity and hydrogen peroxide production by cytochrome b.

Sci Rep 2020 09 23;10(1):15571. Epub 2020 Sep 23.

University Institute of Molecular Pathology Biomarkers, University of Extremadura, 06006, Badajoz, Spain.

Cytochromes P450 (CYP) play a major role in drug detoxification, and cytochrome b (cyt b5) stimulates the catalytic cycle of mono-oxygenation and detoxification reactions. Collateral reactions of this catalytic cycle can lead to a significant production of toxic reactive oxygen species (ROS). One of the most abundant CYP isoforms in the human liver is CYP2C9, which catalyzes the metabolic degradation of several drugs including nonsteroidal anti-inflammatory drugs. Read More

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September 2020

Evaluation of the pharmacokinetic drug-drug interaction potential of iohexol, a renal filtration marker.

Cancer Chemother Pharmacol 2020 10 18;86(4):535-545. Epub 2020 Sep 18.

Department of Pharmaceutical Sciences, School of Pharmacy, University of Pittsburgh, Pittsburgh, PA, USA.

Purpose: Carboplatin dose is calculated based on kidney function, commonly estimated with imperfect creatinine-based formulae. Iohexol is used to measure glomerular filtration rate (GFR) and allows calculation of a more appropriate carboplatin dose. To address potential concerns that iohexol administered during a course of chemotherapy impacts that therapy, we performed in vitro and in vivo pharmacokinetic drug-drug interaction evaluations of iohexol. Read More

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October 2020

Interaction Modes of Microsomal Cytochrome P450s with Its Reductase and the Role of Substrate Binding.

Int J Mol Sci 2020 Sep 11;21(18). Epub 2020 Sep 11.

Center for Toxicogenomics and Human Health (ToxOmics), Genetics, Oncology and Human Toxicology, NOVA Medical School/Faculty of Medical Sciences, Universidade NOVA de Lisboa, 1169-056 Lisbon, Portugal.

The activity of microsomal cytochromes P450 (CYP) is strictly dependent on the supply of electrons provided by NADPH cytochrome P450 oxidoreductase (CPR). The variant nature of the isoform-specific proximal interface of microsomal CYPs implies that the interacting interface between the two proteins is degenerated. Recently, we demonstrated that specific CPR mutations in the FMN-domain (FD) may induce a gain in activity for a specific CYP isoform. Read More

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September 2020

Gender differences in plasma pharmacokinetics and hepatic metabolism of geissoschizine methyl ether from Uncaria hook in rats.

J Ethnopharmacol 2021 Jan 6;264:113354. Epub 2020 Sep 6.

Tsumura Kampo Research Laboratories, Tsumura & Co., 3586 Yoshiwara, Ami-machi, Inashiki-gun, Ibaraki, 300-1192, Japan. Electronic address:

Ethnopharmacological Relevance: Geissoschizine methyl ether (GM), an indole alkaloid from Uncaria hook, is an active ingredient in the traditional Japanese Kampo medicine yokukansan, which is used to treat neurosis, insomnia, irritability, and night crying in children.

Aim Of The Study: Recent our pharmacokinetic studies suggested that there may be gender differences in the plasma concentrations of GM in rats, but not in humans. However, the details of this difference remain unverified. Read More

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January 2021

Can A Recently Developed Pig Model Be Used for In Vivo Metabolism Studies of 7-Azaindole Derived Synthetic Cannabinoids? A Study Using 5F-MDMB-P7AICA.

J Anal Toxicol 2020 Sep 4. Epub 2020 Sep 4.

Department of Experimental and Clinical Toxicology, Institute of Experimental and Clinical Pharmacology and Toxicology, Center for Molecular Signaling (PZMS), Saarland University, 66421 Homburg, Germany.

New psychoactive substances (NPS), especially synthetic cannabinoids (SC) remain a public health concern. Due to ethical reasons, systematic controlled human studies to elucidate their toxicodynamics and/or toxicokinetics are usually not possible. However, such knowledge is necessary, for example, for determination of screening targets and interpretation of clinical and forensic toxicological data. Read More

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September 2020

Benoxacor is enantioselectively metabolized by rat liver subcellular fractions.

Chem Biol Interact 2020 Oct 28;330:109247. Epub 2020 Aug 28.

Department of Occupational and Environmental Health, The University of Iowa, Iowa City, IA, 52242, United States; Interdisciplinary Graduate Program in Human Toxicology, The University of Iowa, Iowa City, IA, 52242, United States; IIHR Hydroscience and Engineering, The University of Iowa, Iowa City, IA, 52242, United States. Electronic address:

This study investigated the enantioselective metabolism of benoxacor, an ingredient of herbicide formulations, in microsomes or cytosol prepared from female or male rat livers. Benoxacor was incubated for ≤30 min with microsomes or cytosol, and its enantioselective depletion was measured using gas chromatographic methods. Benoxacor was depleted in incubations with active microsomes in the presence and absence of NADPH, suggesting its metabolism by hepatic cytochrome P450 enzymes (CYPs) and microsomal carboxylesterases (CESs). Read More

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October 2020

Investigation of Clozapine and Olanzapine Reactive Metabolite Formation and Protein Binding by Liquid Chromatography-Tandem Mass Spectrometry.

Chem Res Toxicol 2020 09 17;33(9):2420-2431. Epub 2020 Aug 17.

Chemistry Department, Université du Québec à Montréal, Montréal, Québec H2X 2J6, Canada.

Drug-induced toxicity has, in many cases, been linked to oxidative metabolism resulting in the formation of reactive metabolites and subsequent covalent binding to biomolecules. Two structurally related antipsychotic drugs, clozapine (CLZ) and olanzapine (OLZ), are known to form similar nitrenium ion reactive metabolites. CLZ-derived reactive metabolites have been linked to agranulocytosis and hepatotoxicity. Read More

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September 2020

Kinetics of metabolism of deltamethrin and - and -permethrin . Studies using rat and human liver microsomes, isolated rat hepatocytes and rat liver cytosol.

Xenobiotica 2021 Jan 26;51(1):40-50. Epub 2020 Aug 26.

Faculty of Health and Medical Sciences, University of Surrey, Surrey, UK.

The kinetics of metabolism of deltamethrin (DLM) and - and -permethrin (CPM and TPM) was studied in male Sprague-Dawley rat and human liver microsomes. DLM metabolism kinetics was also studied in isolated rat hepatocytes, liver microsomes and cytosol. Apparent intrinsic clearance (CL) values for the metabolism of DLM, CPM and TPM by cytochrome P450 (CYP) and carboxylesterase (CES) enzymes in rat and human liver microsomes decreased with increasing microsomal protein concentration. Read More

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January 2021

Rapid and convenient biotransformation procedure for human drug metabolizing enzymes using permeabilized fission yeast cells.

Anal Biochem 2020 10 19;607:113704. Epub 2020 Jul 19.

School of Pharmaceutical Science and Technology, Health Sciences Platform, Tianjin University, Tianjin, 300072, China. Electronic address:

The development of convenient assays for the in vitro study of drug metabolizing enzymes (DMEs) such as cytochromes P450 (CYPs) and UDP-glucuronosyltransferases (UGTs) greatly facilitates metabolism studies of candidate drug compounds and other xenobiotics. We have developed and optimized an experimental approach that combines the advantages of recombinant expression in yeast with a microsomal-like biotransformation and thus allows for rapid and convenient enzymatic assays. Recombinant strains of the fission yeast Schizosaccharomyces pombe have previously been demonstrated to functionally express human CYPs and UGTs. Read More

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October 2020

Metabolism of bifenthrin, β-cyfluthrin, λ-cyhalothrin, cyphenothrin and esfenvalerate by rat and human cytochrome P450 and carboxylesterase enzymes.

Xenobiotica 2020 Dec 22;50(12):1434-1442. Epub 2020 Jul 22.

Faculty of Health and Medical Sciences, University of Surrey, Surrey, UK.

The metabolism of bifenthrin (BIF), β-cyfluthrin (CYFL), λ-cyhalothrin (CYHA), cyphenothrin (CYPH) and esfenvalerate (ESF) was studied in liver microsomes, liver cytosol and plasma from male Sprague-Dawley rats aged 90, 21 and 15 days and from adult humans. Pyrethroid metabolism was also studied with some human expressed cytochrome P450 (CYP) and carboxylesterase (CES) enzymes. All five pyrethroids were metabolised by adult (90 day old) rat hepatic microsomal CYP and CES enzymes and by cytosolic CES enzymes. Read More

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December 2020

Absorption, Distribution, Metabolism, and Excretion of Capmatinib (INC280) in Healthy Male Volunteers and In Vitro Aldehyde Oxidase Phenotyping of the Major Metabolite.

Drug Metab Dispos 2020 10 14;48(10):873-885. Epub 2020 Jul 14.

PK-Sciences, Novartis Pharma AG, Basel, Switzerland (U.G., Y.J., G.R., U.P., H.B., A.M., G.C., S.Z.); Preclinical Safety, Novartis Pharma AG, Basel, Switzerland (R.H.); Novartis Global Discovery Chemistry, Novartis Pharma AG, Basel, Switzerland (K.S., A.M.); and PRA Health Sciences, The Netherlands (J.J.v.L.).

Capmatinib (INC280), a highly selective and potent inhibitor of the MET receptor tyrosine kinase, has demonstrated clinically meaningful efficacy and a manageable safety profile in patients with advanced non-small-cell lung cancer harboring exon 14-skipping mutations. We investigated the absorption, distribution, metabolism, and excretion of capmatinib in six healthy male volunteers after a single peroral dose of 600 mg C-labeled capmatinib. The mass balance, blood and plasma radioactivity, and plasma capmatinib concentrations were determined along with metabolite profiles in plasma, urine, and feces. Read More

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October 2020