1,823 results match your criteria inhibited cyp

Drug-drug interaction potential and clinical pharmacokinetics of enerisant, a novel potent and selective histamine H receptor antagonist.

Xenobiotica 2021 Apr 28:1-10. Epub 2021 Apr 28.

Drug Metabolism and Pharmacokinetics, Drug Safety and Pharmacokinetics Laboratories, Research Headquarters, Taisho Pharmaceutical Co., Ltd., Saitama, Japan.

We evaluated the drug-drug interaction (DDI) potential of enerisant (TS-091), a histamine H receptor antagonist/inverse agonist, mediated by cytochrome P450 (CYP) and transporters, as well as the pharmacokinetics of enerisant in healthy male subjects.Enerisant did not inhibit CYP1A2, CYP2A6, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6, CYP2E1, or CYP3A4 and did not induce CYP1A2, CYP2B6, or CYP3A4. Enerisant inhibited organic cation transporter 2, multidrug and toxin extrusion protein (MATE) 1, and MATE2-K, but not P-glycoprotein (P-gp), breast cancer resistance protein, organic anion transporting polypeptide (OATP) 1B1, OATP1B3, organic anion transporter (OAT) 1, or OAT3. Read More

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The inhibition of CYP1A2, CYP2C9, and CYP2D6 by pterostilbene in human liver microsomes.

Pharmazie 2021 Apr;76(4):155-158

Department of Pharmaceutics, College of Pharmacy, King Saud University, Riyadh.

This study used human liver microsomes to assess pterostilbene's effect on the metabolic activity of cytochrome P450 (CYP) 1A2, CYP2C9, and CYP2D6. The metabolism of their substrates (phenacetin, tolbutamide, and dextromethorphan) was assayed by quantifying their relevant metabolites by HPLC. The IC value was used to express the strength of inhibition, and the value of a volume per dose index (VDI) was used to indicate the metabolic ability of the enzyme. Read More

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Cytochrome P450 Enzyme Inhibition and Herb-Drug Interaction Potential of Medicinal Plant Extracts Used for Management of Diabetes in Nigeria.

Eur J Drug Metab Pharmacokinet 2021 May;46(3):437-450

Department of Biomedical and Pharmaceutical Sciences, College of Pharmacy, University of Rhode Island, 7 Greenhouse Rd, Kingston, RI, 02881, USA.

Background And Objective: The use of herbal medicines is common in Africa, and patients often use a combination of herbs and drugs. Concurrent herbal and pharmaceuticals treatments can cause adverse effects through herb-drug interactions (HDI). This study evaluated the potential risk of HDI for five medicinal plants, Vernonia amygdalina, Ocimum gratissimum, Moringa oleifera, Azadirachta indica, and Picralima nitida, using in vitro assays. Read More

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inhibitory effects of glucosamine, chondroitin and diacerein on human hepatic CYP2D6.

Drug Metab Pers Ther 2021 Apr 8. Epub 2021 Apr 8.

School of Pharmacy, International Medical University, No. 126, Jalan Jalil Perkasa 19, Bukit Jalil, 57000Kuala Lumpur, Malaysia.

Objectives: Glucosamine, chondroitin and diacerein are natural compounds commonly used in treating osteoarthritis. Their concomitant intake may trigger drug-natural product interactions. Cytochrome P450 (CYP) has been implicated in such interactions. Read More

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Drug Metab Dispos 2021 Apr 2. Epub 2021 Apr 2.

Shanghai University of Traditional Chinese Medicine, China

Methylophiopogonanone A (MOA), an abundant homoisoflavonoid bearing a methylenedioxyphenyl (MDP) moiety, is one of the major consitituents in the Chinese herb This work aims to assess the inhibitory potentials of MOA against cytochrome P450 enzymes, as well as to decipher the molecular mechanisms for CYP inhibition by MOA. The results showed that MOA concentration-dependently inhibited CYPs1A, 2C8, 2C9, 2C19 and 3A in human liver microsomes (HLMs) in a reversible way, with IC values varying from 1.06 μM to 3. 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 Mar 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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Melatonin ameliorates cypermethrin-induced impairments by regulating oxidative stress, DNA damage and apoptosis in porcine Sertoli cells.

Theriogenology 2021 Jun 19;167:67-76. Epub 2021 Mar 19.

Department of Animals Sciences, College of Animal Sciences, Jilin University, Changchun, China. Electronic address:

Cypermethrin (CYP) is a widely used insecticide that may be harmful to nontarget species. However, the toxicity of CYP to porcine Sertoli cells (SCs) and its associated mechanism is not known. We investigated the toxicity of CYP and showed that CYP induced cytotoxicity in porcine SCs in a dose-dependent manner. Read More

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Dibenzyl trisulfide binds to and competitively inhibits the cytochrome P450 1A1 active site without impacting the expression of the aryl hydrocarbon receptor.

Toxicol Appl Pharmacol 2021 05 24;419:115502. Epub 2021 Mar 24.

Natural Products Institute, University of the West Indies, Mona, Kingston 7, Jamaica. Electronic address:

The toxicological manifestation of many pollutants relies upon their binding to the aryl hydrocarbon receptor (AHR), and it follows a cascade of reactions culminating in an elevated expression of cytochrome P450 (CYP) 1 enzymes. CYP1A1 and CYP1B1 are associated with enhanced carcinogenesis when chronically exposed to certain polyaromatic hydrocarbons, and their inhibition may lead to chemoprevention. We evaluated dibenzyl trisulfide (DTS), expressed in the ethnomedical plant, Petiveria alliacea, for such potential chemoprevention. Read More

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In vitro cytochrome P450- and transporter-mediated drug interaction potential of 6β-hydroxy-21-desacetyl deflazacort-A major human metabolite of deflazacort.

Pharmacol Res Perspect 2021 Apr;9(2):e00748

PTC Therapeutics Inc., South Plainfield, NJ, USA.

6β-Hydroxy-21-desacetyl deflazacort (6β-OH-21-desDFZ) is a major circulating but not biologically active metabolite of deflazacort (DFZ). In vitro studies were performed to evaluate cytochrome P450 (CYP)- and transporter-mediated drug interaction potentials of 6β-OH-21-desDFZ. Up to 50 µM, the highest soluble concentration in the test system, 6β-OH-21-desDFZ weakly inhibited (IC  > 50 µM) the enzyme activity of CYPs 1A2, 2B6, 2C8, 2C9, and 2D6, while moderately inhibiting CYP2C19 and CYP3A4 with IC values of approximately 50 and 35 μM, respectively. Read More

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Inhibition and Induction by Poziotinib of Different Rat Cytochrome P450 Enzymes and in an Cocktail Method.

Front Pharmacol 2020 5;11:593518. Epub 2021 Jan 5.

The Laboratory of Clinical Pharmacy, The Sixth Affiliated Hospital of Wenzhou Medical University, The People's Hospital of Lishui, Lishui, China.

Poziotinib is an orally active, irreversible, pan-HER tyrosine kinase inhibitor used to treat non-small cell lung cancer, breast cancer, and gastric cancer. Poziotinib is currently under clinical investigation, and understanding its drug-drug interactions is extremely important for its future development and clinical application. The cocktail method is most suitable for evaluating the activity of cytochrome P450 enzymes (CYPs). Read More

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January 2021

Ring closure strategy leads to potent RIPK3 inhibitors.

Eur J Med Chem 2021 May 9;217:113327. Epub 2021 Mar 9.

Jiangsu Key Laboratory of Neuropsychiatric Diseases and College of Pharmaceutical Sciences, Soochow University, Suzhou, Jiangsu, 215123, PR China. Electronic address:

Necroptosis is a form of regulated necrotic cell death that is independent of caspases. Receptor-interacting protein kinase 3 (RIPK3) has been identified as a key regulator for necroptosis, and has been proposed as a potential therapeutic target for the treatment of diseases associated with necroptosis. In this report, we describe the design, synthesis, and evaluation of a series of novel RIPK3 inhibitors. Read More

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Metabolism and interactions of Ivermectin with human cytochrome P450 enzymes and drug transporters, possible adverse and toxic effects.

Arch Toxicol 2021 Mar 15. Epub 2021 Mar 15.

Independent scientist, Haulikova 6, Zagreb, 10000, Croatia.

The review presents metabolic properties of Ivermectin (IVM) as substrate and inhibitor of human P450 (P450, CYP) enzymes and drug transporters. IVM is metabolized, both in vivo and in vitro, by C-hydroxylation and O-demethylation reactions catalyzed by P450 3A4 as the major enzyme, with a contribution of P450 3A5 and 2C9. In samples from both in vitro and in vivo metabolism, a number of metabolites were detected and as major identified metabolites were 3″-O-demethylated, C4-methyl hydroxylated, C25 isobutyl-/isopropyl-hydroxylated, and products of oxidation reactions. Read More

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Stereoisomeric selectivity in the endocrine-disrupting potential of cypermethrin using in vitro, in vivo, and in silico assays.

J Hazard Mater 2021 Feb 20;414:125389. Epub 2021 Feb 20.

Key Laboratory of Microbial Technology for Industrial Pollution Control of Zhejiang Province, College of Environment, Zhejiang University of Technology, Hangzhou, Zhejiang 310032, PR China.

Despite the ubiquity of cypermethrin (CYP) stereoisomers in environment biota, the stereoisomeric selectivity of endocrine-disrupting potency of α-CYP, β-CYP, and θ-CYP has not been well studied. In this study, dual-luciferase reporter gene assays were adopted to analyze their potential endocrine-disrupting effects via four receptors (ERα, GRα, MR and RXR). The results showed that α-CYP was antagonistic to ERα, GRα, and MR with RIC of 9. Read More

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February 2021

Formalin-killed Propionibacterium acnes activates the aryl hydrocarbon receptor and modifies differentiation of SZ95 sebocytes in vitro.

Eur J Dermatol 2021 Feb;31(1):32-40

Department of Dermatology, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, PR China.

Background: Acne vulgaris is a common pilosebaceous disease associated with Propionibacterium acnes (P. acnes). Resolution of comedones may occur in association with shrunken sebaceous glands (SGs) containing de-differentiated cells, however the role of P. Read More

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February 2021

Effect of Pregnane X Receptor on Expression in Porcine Alveolar Macrophages during Infection.

Animals (Basel) 2021 Jan 30;11(2). Epub 2021 Jan 30.

Institute of Animal Science, Jiangsu Academy of Agricultural Sciences/Jiangsu Germplasm Resources Protection and Utilization Platform, Nanjing 210014, China.

(, ) is the causative agent of mycoplasma pneumonia of swine (MPS). infection causes inflammation in pigs and leads to considerable economic losses in the pig industry. Pregnane X receptor () is a pluripotent gene regulatory protein that plays an important role in regulating cytochrome P-450 (CYP) in pigs in the context of inflammatory responses, drug metabolism, homeostasis, etc. Read More

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January 2021

Can Organophosphates and Carbamates Cause Synergisms by Inhibiting Esterases Responsible for Biotransformation of Pyrethroids?

Environ Sci Technol 2021 02 20;55(3):1585-1593. Epub 2021 Jan 20.

Department of Plant and Environmental Sciences, University of Copenhagen, Thorvaldsensvej 40, 1871 Frederiksberg, Denmark.

Hydrolysis catalyzed by general esterases (GEs) is the most efficient route for hydrolyzation of pyrethroid insecticides. Organophosphate (OP) and carbamate (CB) insecticides are known to inhibit GEs in addition to acetylcholinesterase (AChE), which is their main target. We hypothesize that synergies can be induced by OPs and CBs when mixed with pyrethroids, due to their inhibition of GE-dependent detoxification of pyrethroids. Read More

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February 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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Vascular biotransformation of organic nitrates is independent of cytochrome P450 monooxygenases.

Br J Pharmacol 2021 Apr 18;178(7):1495-1506. Epub 2021 Feb 18.

Institute for Cardiovascular Physiology, Faculty of Medicine, Goethe University, Frankfurt am Main, Germany.

Background And Purpose: Organic nitrates such as nitroglycerin (NTG) or pentaerythritol tetranitrate (PETN) have been used for over a century in the treatment of angina or ischaemic heart disease. These compounds are prodrugs which release their nitrovasodilators upon enzymic bioactivation by aldehyde dehydrogenase (ALDH2) or cytochromes P450 (CYP). Whereas ALDH2 is known to directly activate organic nitrates in vessels, the contribution of vascular CYPs is unknown and was studied here. Read More

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Anthraquinones inhibit cytochromes P450 enzyme activity in silico and in vitro.

J Appl Toxicol 2021 Jan 12. Epub 2021 Jan 12.

Division of Toxicology, Office of Applied Research and Safety Assessment, Center for Food Safety and Applied Nutrition, U.S. Food and Drug Administration, Laurel, Maryland, USA.

Anthraquinones exhibit various pharmacological activities (e.g., antioxidant and laxative) and are commonly found in consumer products including foods, dietary supplements, drugs, and traditional medicines. 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

Identifying the Dominant Contribution of Human Cytochrome P450 2J2 to the Metabolism of Rivaroxaban, an Oral Anticoagulant.

Cardiovasc Drugs Ther 2021 Jan 7. Epub 2021 Jan 7.

Department of Clinical Pharmacology, College of Pharmacy, Dalian Medical University, 9 West Section, Lvshun South Road, Lvshunkou District, Dalian, 116044, China.

Purpose: Rivaroxaban, an oral anticoagulant, undergoes the metabolism mediated by human cytochrome P450 (CYP). The present study is to quantitatively analyze and compare the contributions of multiple CYPs in the metabolism of rivaroxaban to provide new information for medication safety.

Methods: The metabolic stability of rivaroxaban in the presence of human liver microsomes (HLMs) and recombinant CYPs was systematically evaluated to estimate the participation of various CYP isoforms. Read More

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January 2021

Investigation of CYP2B6, 3A4 and β-esterase interactions of Withania somnifera (L.) dunal in human liver microsomes and HepG2 cells.

J Ethnopharmacol 2021 Apr 1;270:113766. Epub 2021 Jan 1.

Division of Clinical Pharmacology, University of Stellenbosch, Cape Town, South Africa. Electronic address:

Ethnopharmacological Relevance: Withania somnifera (L.) Dunal (Solanaceae) is a traditional herb, used in African indigenous systems of medicine for the treatment of various diseases (including HIV/AIDS and tuberculosis). The relevance of clinically significant interactions of Withania with ARVs and anti-TB drugs needs to be investigated. Read More

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Nonlinear Disposition and Metabolic Interactions of Cannabidiol Through CYP3A Inhibition in Rats.

Cannabis Cannabinoid Res 2020 15;5(4):318-325. Epub 2020 Dec 15.

Division of Pharmacokinetics and Pharmacodynamics, Department of Pharmacology, Toxicology and Therapeutics, School of Pharmacy, Showa University, Tokyo, Japan.

Cannabidiol (CBD) is known to affect the pharmacokinetics of other drugs through metabolic inhibition of CYP2C19 and CYP3A4. However, there is a lack of evidence for such drug interactions. Therefore, we investigated the saturability of CBD metabolism and CBD-drug interactions through inhibition of CYP3A . Read More

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December 2020

Metamizole is a Moderate Cytochrome P450 Inducer Via the Constitutive Androstane Receptor and a Weak Inhibitor of CYP1A2.

Clin Pharmacol Ther 2020 Dec 17. Epub 2020 Dec 17.

Division of Clinical Pharmacology & Toxicology, University Hospital Basel, Basel, Switzerland.

Metamizole is an analgesic and antipyretic drug used intensively in certain countries. Previous studies have shown that metamizole induces cytochrome (CYP) 2B6 and possibly CYP3A4. So far, it is unknown whether metamizole induces additional CYPs and by which mechanism. Read More

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December 2020

Upadacitinib tartrate in rheumatoid arthritis.

Drugs Today (Barc) 2020 11;56(11):723-732

Department of Rheumatology and Clinical Immunology, University General Hospital of Larissa, Faculty of Medicine, School of Health Sciences, University of Thessaly, Larissa, Greece.

In rheumatoid arthritis (RA) there is an unmet therapeutic need, as a substantial proportion of patients does not achieve low disease activity or remission despite the use of conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) and/or biological DMARDs (bDMARDs). The Janus kinase (JAK) inhibitors are the most recently added drug category in the therapeutic armamentarium in RA. Upadacitinib tartrate (Rinvoq), a selective and reversible JAK1 inhibitor, inhibited interleukin (IL)-6 and IL-7 and ameliorated adjuvant-induced arthritis in preclinical studies. Read More

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November 2020

Modulation of CYP3A4 and CYP2C9 activity by Bulbine natalensis and its constituents: An assessment of HDI risk of B. natalensis containing supplements.

Phytomedicine 2021 Jan 19;81:153416. Epub 2020 Nov 19.

National Center for Natural Products Research, School of Pharmacy, The University of Mississippi, University, Mississippi 38677, United States; Department of BioMolecular Sciences, School of Pharmacy, The University of Mississippi, University, Mississippi 38677, United States. Electronic address:

Background: Bulbine natalensis is an African-folk medicinal plant used as a dietary supplement for enhancing sexual function and muscle strength in males by presumably boosting testosterone levels, but no scientific information is available about the possible herb-drug interaction (HDI) risk when bulbine-containing supplements are concomitantly taken with prescription drugs.

Purpose: This study was aimed to investigate the HDI potential of B. natalensis in terms of the pregnane X receptor (PXR)-mediated induction of major drug-metabolizing cytochrome P450 enzyme isoforms (i. Read More

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January 2021

Metabolism and Interactions of Chloroquine and Hydroxychloroquine with Human Cytochrome P450 Enzymes and Drug Transporters.

Curr Drug Metab 2020 ;21(14):1127-1135

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

Background: In clinical practice, chloroquine and hydroxychloroquine are often co-administered with other drugs in the treatment of malaria, chronic inflammatory diseases, and COVID-19. Therefore, their metabolic properties and the effects on the activity of cytochrome P450 (P450, CYP) enzymes and drug transporters should be considered when developing the most efficient treatments for patients.

Methods: Scientific literature on the interactions of chloroquine and hydroxychloroquine with human P450 enzymes and drug transporters, was searched using PUBMED. Read More

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January 2021

Intoxication of mammalian cells with binary clostridial enterotoxins is inhibited by the combination of pharmacological chaperone inhibitors.

Naunyn Schmiedebergs Arch Pharmacol 2020 Dec 7. Epub 2020 Dec 7.

Institute of Pharmacology and Toxicology, Ulm University Medical Center, 89081, Ulm, Germany.

Binary enterotoxins Clostridioides difficile CDT toxin, Clostridium botulinum C2 toxin, and Clostridium perfringens iota toxin consist of two separate protein components. The B-components facilitate receptor-mediated uptake into mammalian cells and form pores into endosomal membranes through which the enzymatic active A-components translocate into the cytosol. Here, the A-components ADP-ribosylate G-actin which leads to F-actin depolymerization followed by rounding of cells which causes clinical symptoms. Read More

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December 2020

Screening of Human CYP1A2 and CYP3A4 Inhibitors from Seaweed In Silico and In Vitro.

Mar Drugs 2020 Nov 29;18(12). Epub 2020 Nov 29.

School of Biological Sciences and Technology, Chonnam National University, Gwangju 61186, Korea.

Phenolic compounds and carotenoids are potential inhibitors of cytochrome P450s. Sixteen known compounds, phenolic compounds and carotenoids from seaweed were examined for potential inhibitory capacity against CYP1A2 and CYP3A4 in silico and in vitro. Morin, quercetin, and fucoxanthin inhibited the enzyme activity of CYP1A2 and CYP3A4 in a dose-dependent manner. Read More

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November 2020

The responses of the growth, cytochrome P450 isoenzymes activities and the metabolomics in earthworms to sublethal doses of dichlorvos in soil.

Ecotoxicol Environ Saf 2021 Jan 30;207:111547. Epub 2020 Oct 30.

Institute of Agricultural Quality Standard and Testing Technology, Chongqing Academy of Agricultural Sciences, Chongqing 401329, People's Republic of China.

In this paper, earthworms (Eisenia fetida) were exposed to sublethal doses of dichlorvos (spiked concentration of 0.1, 1.0, 10 mg/kg) in soil for 14 days, the metabolomics and activities of cytochrome P450 (CYP) isoenzymes (CYP1A2, CYP2C9 and CYP3A4) of earthworms were analyzed aiming to identify sensitive biomarkers and reveal possible mode of toxic action. Read More

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January 2021