509 results match your criteria forms cyp

Interaction of silymarin components and their sulfate metabolites with human serum albumin and cytochrome P450 (2C9, 2C19, 2D6, and 3A4) enzymes.

Biomed Pharmacother 2021 Jun 9;138:111459. Epub 2021 Mar 9.

Department of Pharmacology, Faculty of Pharmacy, University of Pécs, Szigeti út 12, Pécs H-7624, Hungary; János Szentágothai Research Centre, University of Pécs, Ifjúság útja 20, Pécs H-7624, Hungary. Electronic address:

Silymarin is a mixture of flavonolignans isolated from the fruit of milk thistle (Silybum marianum (L.) Gaertner). Milk thistle extract is the active ingredient of several medications and dietary supplements to treat liver injury/diseases. 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

Back where it belongs: 11β-hydroxyandrostenedione compels the re-assessment of C11-oxy androgens in steroidogenesis.

Mol Cell Endocrinol 2021 04 2;525:111189. Epub 2021 Feb 2.

Department of Biochemistry, Stellenbosch University, Private Bag X1, Matieland, 7602, South Africa; Department of Chemistry and Polymer Science, Stellenbosch University, Private Bag X1, Matieland, 7602, South Africa. Electronic address:

Adrenal steroidogenesis has, for decades, been depicted as three biosynthesis pathways -the mineralocorticoid, glucocorticoid and androgen pathways with aldosterone, cortisol and androstenedione as the respective end products. 11β-hydroxyandrostenedione was not included as an adrenal steroid despite the adrenal output of this steroid being twice that of androstenedione. While it is the end of the line for aldosterone and cortisol, as it is in these forms that they exhibit their most potent receptor activities prior to inactivation and conjugation, 11β-hydroxyandrostenedione is another matter entirely. Read More

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Kinetics of cytochrome P450 3A4 inhibition by heterocyclic drugs defines a general sequential multi-step binding process.

J Biol Chem 2020 Dec 24:100223. Epub 2020 Dec 24.

Department of Biochemistry, Vanderbilt University School of Medicine, Nashville, Tennessee 37232-0146.

Cytochrome P450 (P450, CYP) 3A4 is the enzyme most involved in the metabolism of drugs and can also oxidize numerous steroids. This enzyme is also involved in one-half of pharmacokinetic drug-drug interactions, but details of the exact mechanisms of P450 3A4 inhibition are still unclear in many cases. Ketoconazole, clotrimazole, ritonavir, indinavir, and itraconazole are strong inhibitors; analysis of the kinetics of reversal of inhibition with the model substrate 7-benzoyl (OBz) quinoline showed lag phases in several cases, consistent with multiple structures of P450 3A4 inhibitor complexes. Read More

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December 2020

DNA Damage in AML-12 Hepatocytes and 3T3-L1 Adipocytes Treated with Clopidogrel.

Curr Drug Saf 2021 Jan 6. Epub 2021 Jan 6.

Marmara University, Faculty of Arts and Sciences, Division of Biology, Department of Molecular Biology, Istanbul. Turkey.

Background: Clopidogrel has been commonly prescribed as a selective P2Y12 receptor antagonist to reduce heart attack and stroke risk. Nearly 10 % of absorbed clopidogrel is metabolized by cytochrome P450 (CYP) enzymes in the liver to active forms and 90 % to inactive clopidogrel carboxylate by esterases.

Objective: Since different forms of clopidogrel have cytotoxic potential, our aim was to determinate the effect of clopidogrel (7. Read More

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January 2021

Cytochrome P450 content in primary tumors and liver metastases of patients with metastatic colorectal cancer.

Exp Oncol 2020 12;42(4):330-332

R.E. Kavetsky Institute of Experimental Pathology, Oncology and Radiobiology, NAS of Ukraine, Kyiv 03022, Ukraine.

Aim: To determine the content of low-spin form of cytochrome P450 in primary tumors and liver metastases of the patients with metastatic colorectal cancer (mCRC) and and assess its prognostic significance.

Materials And Methods: The levels of the oxidized and low-spin forms of cytochrome P450 in the tissues of patients with mCRC were studied by electron paramagnetic resonance. To detect CYP 1A2 and CYP 1B1 isoforms, Western blot analysis was used. Read More

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December 2020

Tobacco, cannabis, and liquorice: Hidden players altering albendazole metabolism in patients with hepatic alveolar echinococcosis.

J Hepatol 2021 Feb 11;74(2):471-473. Epub 2020 Dec 11.

Laboratoire de Parasitologie-Mycologie, Centre Hospitalier Régional Universitaire de Besançon, Besançon, France; Centre National de Référence Echinococcoses, Centre Hospitalier Régional Universitaire de Besançon, Besançon, France; UMR 6249, Chronoenvironnement, Université de Franche-Comté, 25030 Besançon, France.

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February 2021

Our emerging understanding of the roles of long non-coding RNAs in normal liver function, disease, and malignancy.

JHEP Rep 2021 Feb 3;3(1):100177. Epub 2020 Sep 3.

Gastrointestinal Unit, Massachusetts General Hospital, Boston, MA 02114, USA.

Long non-coding RNAs (lncRNAs) are important biological mediators that regulate numerous cellular processes. New experimental evidence suggests that lncRNAs play essential roles in liver development, normal liver physiology, fibrosis, and malignancy, including hepatocellular carcinoma and cholangiocarcinoma. In this review, we summarise our current understanding of the function of lncRNAs in the liver in both health and disease, as well as discuss approaches that could be used to target these non-coding transcripts for therapeutic purposes. Read More

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February 2021

Effects of vanadium (sodium metavanadate) and aflatoxin-B1 on cytochrome p450 activities, DNA damage and DNA methylation in human liver cell lines.

Toxicol In Vitro 2021 Feb 23;70:105036. Epub 2020 Oct 23.

Mechanistic Studies Division. Environmental Health Science and Research Bureau. Health Canada. Sir Frederick G Banting Research Centre. 251 Sir Frederick Banting Driveway. AL:2203B. Ottawa, ON, K1A 0K9, Canada.

Vanadium is considered as "possibly carcinogenic to humans" (VO, IARC Group 2B), yet uncertainties persist related to the toxicity mechanisms of the multiple forms of vanadium. Exposure to vanadium often co-occurs with other metals or with organic compounds that can be transformed by cytochrome p450 (CYP) enzymes into DNA-reactive carcinogens. Therefore, effects of a soluble form of vanadium (sodium metavanadate, NaVO) and aflatoxin-B1 (AFB1) were tested separately and together, for induction of CYP activities, DNA damage (γH2AX and DNA alkaline unwinding assays), and DNA methylation changes (global genome and DNA repeats) in HepaRG or HepG2 liver cell lines. Read More

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February 2021

In vitro evaluation of antitrypanosomal activity and molecular docking of benzoylthioureas.

Parasitol Int 2021 Feb 5;80:102225. Epub 2020 Nov 5.

Departamento de Química, Centro de Ciências Exatas, Universidade Estadual de Londrina, Londrina, Paraná, Brazil.

A series of sixteen benzoylthioureas derivatives were initially evaluated in vitro against the epimastigote form of Trypanosoma cruzi. All of the tested compounds inhibited the growth of this form of the parasite, and due to the promising anti-epimastigote activity from three of these compounds, they were also assayed against the trypomastigote and amastigote forms. ADMET-Tox in silico predictions and molecular docking studies with two main enzymatic targets (cruzain and CYP-51) were performed for the three compounds with the highest activity. Read More

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February 2021

Nature-derived anticancer steroids outside cardica glycosides.

Fitoterapia 2020 Nov 16;147:104757. Epub 2020 Oct 16.

Department of Medical Imaging, Jinling Hospital, Medical School of Nanjing University, Nanjing, PR China. Electronic address:

Steriods which are ubiquitous in natural resources are important components of cell membranes and involved in several physiological functions. Steriods not only exerted the anticancer activity through inhibition of various enzymes and receptors in cancer cells, inclusive of aromatase, sulfatase, 5α-reductase, hydroxysteroid dehydrogenase and CYP 17, but also exhibited potential activity against various cancer forms including multidrug-resistant cancer with low cytotoxicity, and high bioavailability. Accordingly, steroids are useful scaffolds for the discovery of novel anticancer agents. Read More

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November 2020

Physiologically Based Pharmacokinetic Modeling Approach to Identify the Drug-Drug Interaction Mechanism of Nifedipine and a Proton Pump Inhibitor, Omeprazole.

Eur J Drug Metab Pharmacokinet 2021 Jan;46(1):41-51

Division of Quantitative Methods and Modeling, Office of Research and Standards, Office of Generic Drugs, Center for Drug Evaluation and Research, Food and Drug Administration, 10903 New Hampshire Avenue, Silver Spring, MD, 20993, USA.

Background And Objectives: Proton pump inhibitors (PPIs) can affect the intragastric release of other drugs from their dosage forms by elevating the gastric pH. They may also influence drug absorption and metabolism by interacting with P-glycoprotein or with the cytochrome P450 (CYP) enzyme system. Nifedipine is a Biopharmaceutics Classification System (BCS) class II drug with low solubility across physiologic pH and high permeability. Read More

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January 2021

Cannabidiol and Abnormal Liver Chemistries in Healthy Adults: Results of a Phase I Clinical Trial.

Clin Pharmacol Ther 2021 May 21;109(5):1224-1231. Epub 2020 Nov 21.

Greenwich Biosciences, 5750 Fleet St Ste 200, Carlsbad, CA, USA.

Liver safety concerns were raised in randomized controlled trials of cannabidiol (CBD) in patients with Lennox-Gastaut and Dravet syndromes, but the relevance of these concerns to healthy adults consuming CBD is unclear. The objective of this manuscript is to report on liver safety findings from healthy adults who received therapeutic daily doses of CBD for ~ 3.5 weeks and to investigate any correlation between transaminase elevations and baseline characteristics, pharmacogenetic, and pharmacokinetic data. Read More

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Triple Strategies to Improve Oral Bioavailability by Fabricating Coamorphous Forms of Ursolic Acid with Piperine: Enhancing Water-Solubility, Permeability, and Inhibiting Cytochrome P450 Isozymes.

Mol Pharm 2020 12 9;17(12):4443-4462. Epub 2020 Nov 9.

School of Pharmacy, China Pharmaceutical University, Nanjing 211198, PR China.

As a BCS IV drug, ursolic acid (UA) has low oral bioavailability mainly because of its poor aqueous solubility/dissolution, poor permeability, and metabolism by cytochrome P450 (CYP) isozymes, such as CYP3A4. Most UA preparations demonstrated a much higher dissolution than that of its crystalline form yet a low drug concentration in plasma due to their lower consideration or evaluation for the permeability and metabolism issues. In the current study, a supramolecular coamorphous system of UA with piperine (PIP) was prepared and characterized by powder X-ray diffraction, differential scanning calorimetry, and scanning electron microscopy. Read More

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December 2020

Inhibitory and inductive effects of 4- or 5-methyl-2-mercaptobenzimidazole, thyrotoxic and hepatotoxic rubber antioxidants, on several forms of cytochrome P450 in primary cultured rat and human hepatocytes.

Toxicol Rep 2020 12;7:979-985. Epub 2020 Aug 12.

Division of Pharmacology, National Institute of Health Sciences, 3-25-26, Tonomachi, Kawasaki, Kanagawa, 210-9501, Japan.

Effects of 4-methyl-2-mercaptobenzimidazole (4-MeMBI) and 5-methyl-2- mercaptobenzimidazole (5-MeMBI) on cytochrome P450 (CYP) activity were examined in primary cultured rat hepatocytes. Hepatocytes from male Wistar rats were cultured in the presence of 4-MeMBI or 5-MeMBI (0-400 μM), and the activity of CYPs 3A2/4 (48 and 96 h) and 1A1/2 (48 h) was determined by measuring the activity of testosterone 6β-hydroxylation and 7-ethoxyresorufin O-deethylation, respectively. As a result, 4-MeMBI and 5-MeMBI (≥12. Read More

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Structural insights into CYP107G1 from rapamycin-producing Streptomyces rapamycinicus.

Arch Biochem Biophys 2020 10 18;692:108544. Epub 2020 Aug 18.

Department of Biological Sciences, Konkuk University, Seoul, 05025, Republic of Korea. Electronic address:

Rapamycin is a clinically important macrolide agent with immunosuppressant and antiproliferative properties, produced by the actinobacterium, Streptomyces rapamycinicus. Two cytochrome P450 enzymes are involved in the biosynthesis of rapamycin. CYP107G1 and CYP122A2 catalyze the oxidation reactions of C27 and C9 of pre-rapamycin, respectively. Read More

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October 2020

An updated review of pharmacokinetic drug interactions and pharmacogenetics of statins.

Expert Opin Drug Metab Toxicol 2020 Sep 6;16(9):809-822. Epub 2020 Aug 6.

Department of Clinical Pharmacokinetics, Division of Clinical Pharmacy, Graduate School of Pharmaceutical Sciences, Kyushu University , Fukuoka, Japan.

Introduction: Hydroxymethylglutaryl-coenzyme A reductase inhibitors (statins) lower cholesterol synthesis in patients with hypercholesterolemia. Increased statin exposure is an important risk factor for skeletal muscle toxicity. Potent inhibitors of cytochrome P450 (CYP) 3A4 significantly increase plasma concentrations of the active forms of simvastatin, lovastatin, and atorvastatin. Read More

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September 2020

Altered expression of cytochrome P450 enzymes involved in metabolism of androgens and vitamin D in the prostate as a risk factor for prostate cancer.

Pharmacol Rep 2020 Oct 17;72(5):1161-1172. Epub 2020 Jul 17.

Department of Molecular Oncogenetics, Institute of Molecular Biology and Genetics of National Academy of Sciences of Ukraine, 150, Zabolotnogo Street, Kyiv, 03143, Ukraine.

Prostate cancer is the most common malignant disease among men. The signaling pathways, regulated by the androgen and vitamin D receptors, play a key role in prostate cancer. The intracellular level of androgens and vitamin D determines not only receptor functionality, but also the efficacy of cellular processes regulated by them (cell proliferation, apoptosis, differentiation etc. Read More

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October 2020

An androgen-independent mechanism underlying the androgenic effects of 3-methylcholanthrene, a potent aryl hydrocarbon receptor agonist.

Toxicol Res (Camb) 2020 Jun 14;9(3):271-282. Epub 2020 May 14.

Faculty of Pharmaceutical Sciences, Doshisha Women's College of Liberal Arts; Kodo, Kyotanabe 610-0395, Kyoto, Japan.

Aryl hydrocarbon receptor (AhR) and androgen receptor (AR) are ligand-activated transcription factors with profound cross-talk between their signal transduction pathways. Previous studies have shown that AhR agonists activate the transcription of AR-regulated genes in an androgen-independent manner; however, the underlying mechanism remains unclear. To decipher this mechanism, we evaluated the effects of 3-methylcholanthrene (3MC), a potent AhR agonist, on the transcription of AR-regulated genes in three AR-expressing cell lines. Read More

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Residues of anilinopyrimidine fungicides and suspected metabolites in wine samples.

J Chromatogr A 2020 Jul 28;1622:461104. Epub 2020 Apr 28.

Department of Analytical Chemistry, Nutrition and Food Sciences. Institute of Research on Chemical and Biological Analysis (IAQBUS). Universidade de Santiago de Compostela, Santiago de Compostela 15782, Spain. Electronic address:

The coexistence of the anilinopyrimidine fungicides pyrimethanil (PYR) and cyprodinil (CYP), and suspected metabolites in wine samples was investigated by liquid chromatography (LC) with tandem mass spectrometry (MS/MS), based on triple quadrupole (QqQ) and quadrupole time-of-flight (QTOF) MS instruments. For the first time, quantitative data obtained after solid-phase extraction (SPE) of wine samples have demonstrated the systematic presence of 4-hydroxyanilino derivatives of PYR and CYP in wines containing residues of parent fungicides, at concentrations from 0.2 to 58 ng mL. Read More

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Preference for -demethylation reactions in the oxidation of 2'-, 3'-, and 4'-methoxyflavones by human cytochrome P450 enzymes.

Xenobiotica 2020 Oct 30;50(10):1158-1169. Epub 2020 Apr 30.

Laboratory of Cellular and Molecular Biology, Veterinary Sciences, Osaka Prefecture University, Izumisano, Osaka, Japan.

2'-, 3'-, and 4'-Methoxyflavones (MeFs) were incubated with nine forms of recombinant human cytochrome P450 (P450 or CYP) enzymes in the presence of an NADPH-generating system and the products formed were analyzed with LC-MS/MS methods.CYP1B1.1 and 1B1. Read More

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October 2020

Toxicokinetics of α-zearalenol and its masked form in rats and the comparative biotransformation in liver microsomes from different livestock and humans.

J Hazard Mater 2020 Jul 7;393:121403. Epub 2019 Oct 7.

Institute of Apicultural Research, Chinese Academy of Agricultural Sciences, Key Laboratory of Bee Products for Quality and Safety Control, Bee Product Quality Supervision and Testing Center, Ministry of Agriculture, Beijing, 100093, People's Republic of China; College of Aminal Science and Technology, Anhui Agricultural University, Hefei, 230036, People's Republic of China. Electronic address:

Alpha-zearalenol (α-ZEL) and its masked form α-zearalenol-14 glucoside (α-ZEL-14G) have much higher oestrogenic activity than zearalenone. Owing to very limited toxicokinetic and metabolic data, no reference points could be established for risk assessment. To circumvent it, the toxicokinetic, metabolic profiles, and phenotyping of α-ZEL and α-ZEL-14G were comprehensively investigated in this study. Read More

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Comparison of steroid hormone hydroxylation mediated by cytochrome P450 3A subfamilies.

Arch Biochem Biophys 2020 03 27;682:108283. Epub 2020 Jan 27.

School of Pharmacy, Shujitsu University, 1-6-1 Nishigawara, Naka-ku, Okayama, 703-8516, Japan.

Hydroxylation activity at the 6β-position of steroid hormones (testosterone, progesterone, and cortisol) by human cytochromes P450 (CYP) 3A4, polymorphic CYP3A5, and fetal CYP3A7 were compared to understand the catalytic properties of the major forms of human CYP3A subfamily. Testosterone, progesterone, and cortisol 6β-hydroxylation activities of recombinant CYP3A4, CYP3A5, and CYP3A7 were determined by liquid chromatography. Michaelis constants (K) for CYP3A7-mediated 6β-hydroxylation of testosterone, progesterone, and cortisol were similar to those of CYP3A4 and CYP3A5. Read More

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Circulating Extracellular Vesicles Containing Xenobiotic Metabolizing CYP Enzymes and Their Potential Roles in Extrahepatic Cells Via Cell-Cell Interactions.

Int J Mol Sci 2019 Dec 7;20(24). Epub 2019 Dec 7.

Department of Pharmaceutical sciences, University of Tennessee Health Science Center, 881 Madison Avenue, Memphis, TN 38163, USA.

The cytochrome P450 (CYP) family of enzymes is known to metabolize the majority of xenobiotics. Hepatocytes, powerhouses of CYP enzymes, are where most drugs are metabolized into non-toxic metabolites. Additional tissues/cells such as gut, kidneys, lungs, blood, and brain cells express selective CYP enzymes. Read More

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December 2019

Metabolite Profiling and Reaction Phenotyping for the Assessment of the Bioactivation of Bromfenac †.

Chem Res Toxicol 2020 01 23;33(1):249-257. Epub 2019 Dec 23.

MyoKardia, Inc. , 333 Allerton Avenue , South San Francisco , California 94080 , United States.

Bromfenac is a nonsteroidal anti-inflammatory drug that was approved and subsequently withdrawn from the market because of reported cases of acute hepatotoxicity. Recently, studies have revealed that bromfenac requires UDPGA and alamethicin supplemented human liver microsomes (HLM) to form a major metabolite, bromfenac indolinone (BI). Bromfenac and BI form thioether adducts through a bioactivation pathway in HLM and hepatocytes. Read More

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January 2020

Auriculatone Sulfate Effectively Protects Mice Against Acetaminophen-Induced Liver Injury.

Molecules 2019 Oct 9;24(20). Epub 2019 Oct 9.

State Key Laboratory of Functions and Applications of Medicinal Plants & School of Pharmacy, Guizhou Medical University, Guizhou 550025, China.

Acetaminophen (APAP) overdose is very common worldwide and has been widely recognized as the leading cause of drug-induced liver injury in the Western world. In our previous investigation, auriculatone, a natural product firstly obtained from , has demonstrated a potent protective effect against APAP-induced hepatotoxicity in HL-7702 cells. However, the poor water solubility and low bioavailability restrict its application. Read More

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October 2019

Assessing Drug Interaction and Pharmacokinetics of Loxoprofen in Mice Treated with CYP3A Modulators.

Pharmaceutics 2019 Sep 16;11(9). Epub 2019 Sep 16.

BK21 Plus KNU Multi-Omics based Creative Drug Research Team, College of Pharmacy, Research Institute of Pharmaceutical Sciences, Kyungpook National University, Daegu 41566, Korea.

Loxoprofen (LOX) is a non-selective cyclooxygenase inhibitor that is widely used for the treatment of pain and inflammation caused by chronic and transitory conditions. Its alcoholic metabolites are formed by carbonyl reductase (CR) and they consist of trans-LOX, which is active, and cis-LOX, which is inactive. In addition, LOX can also be converted into an inactive hydroxylated metabolite (OH-LOXs) by cytochrome P450 (CYP). Read More

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September 2019

Comparison of Steroid Hormone Hydroxylations by and Docking to Human Cytochromes P450 3A4 and 3A5.

J Pharm Pharm Sci 2019 ;22(1):332-339

School of Pharmacy, Shujitsu University, 1-6-1 Nishigawara, Naka-ku, Okayama 703-8516, Japan.

Purpose: Hydroxylation activity at the 6β-position of steroid hormones (testosterone, progesterone, and cortisol) by human cytochromes P450 (P450 or CYP) 3A4 and CYP3A5 and their molecular docking energy values were compared to understand the catalytic properties of the major forms of human CYP3A, namely, CYP3A4 and CYP3A5.

Methods: Testosterone, progesterone, and cortisol 6β-hydroxylation activities of recombinant CYP3A4 and CYP3A5 were determined by liquid chromatography. Docking simulations of these substrates to the heme moiety of reported crystal structures of CYP3A4 (Protein Data Bank code ITQN) and CYP3A5 (6MJM) were conducted. Read More

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