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Enzyme Inhibition

Enzyme inhibition studies evaluate a compound’s inhibitory effect on drug-metabolizing enzymes to predict the potential for drug-drug interactions that may increase toxicity or reduce therapeutic effect of concomitant medications. To learn more about this service, visit our Enzyme Inhibition contract service page.

 

Webinars

ADME 101: Model-Based Approaches to DDI Risk Prediction – Navigating the Transition from In Vitro Data to In Silico Modeling

This informative ADME 101 discusses In Vitro to In Vivo Extrapolation (IVIVE) and how a model-based approach following routine perpetrator potential studies (i.e. CYP inhibition, CYP induction, and transporter inhibition) assessing clinical potential may eliminate the need of conducting clinical studies. Listen in as Dr. Limaye outlines a step–wise approach for bringing robustness to the prediction, including...
Webinars

Suicide by Binding: Putting Time-Dependent Inhibition of CYP Enzymes into Perspective

Presenter: Brian Ogilvie, Ph.D., SEKISUI XenoTech Vice President of Scientific Consulting with special guest for Q&A, Lois Haupt, SEKISUI XenoTech Principal Scientist in Program Oversight Many...
Blog

Drug-Drug Interaction (DDI) Prediction Models Following In Vitro Studies in Preclinical Development

In preclinical development, a drug will be evaluated for potential to cause a drug-drug interaction (DDI) using in vitro experiments and then calculations that...

Webinars

In Vitro Inhibition Studies: Elements of Design and Important Considerations in Data Analysis

Presenter: Jennifer Horkman, Senior Scientist in Program Oversight at SEKISUI XenoTech When evaluating drug-drug interaction (DDI) risk of an investigational drug, a battery of studies is needed to investigate victim/perpetrator...
Blog

ADME and Drug-Drug Interactions for the Toxicologist

Highlights from the recent webinar presented by our newest expert consultant, Dr. Pallavi Limaye In her recent webinar (now available for...

Webinars

Comparison Between the Final US FDA, Japan PMDA, and EMA In Vitro DDI Guidance Documents: Are We Finally Harmonized?

Presenter: Brian Ogilvie, Ph.D., SEKISUI XenoTech Vice President of Scientific Consulting In January, the FDA published its final guidance for industry on in vitro drug-drug interaction (DDI) studies. Dr. Ogilvie...
Webinars

The Basics of In Vitro Xenobiotic Metabolism and Drug-Drug Interaction Investigations: Applicability to All Xenobiotics

Since SOT’s 59th Annual Meeting and ToxExpo has been canceled due to COVID-19 concerns, we are bringing the tradeshow to you! SOT is hosting this...
Blog

In Vitro Evaluation of Drug-Drug Interaction (DDI) Potential

In its most recent in vitro drug interaction guidance update, the US Food and Drug Administration (FDA) emphasized harmony with the...

Blog

Four ways to optimize preclinical in vitro data to mitigate risk of late-stage clinical failure

1. Collect high-quality data to make informed, confident go/no go decisions for moving your drug candidate forward If you need...

Blog

Timing of In Vitro Studies: Early, Thorough ADME for Your Compound’s Success

Beyond the need for evidence that a drug works, Food and Drug Administration (FDA) and other regulatory bodies around the...

Scientific Posters

The evaluation of induction and inhibition potency of various drugs on CYP3A4 and OATP1B1/1B3

Presented at the 34th JSSX Annual Meeting in Tsukuba, Japan Authors Ryota Takeuchi, Rena Kusano, Tomoko Sasai, Takami Sarashina, Ryo Fujino, Kenta Hashizume  Drug Development...
Blog

What In Vitro Metabolism and DDI Studies Do I Actually Need?

Though there is no ‘roadmap’ spelling out required studies to achieve regulatory approval for clinical entry, a drug candidate’s metabolism...

Scientific Posters

An assessment of in vitro inhibition of CYPs, UGTs and transporters by phosphodiester- or phosphorothioate-linked oligonucleotides

Presented at the 2019 Marbach Castle Drug-Drug Interaction Workshop in Germany by Dr. Brian W. Ogilvie. Authors The poster presented information based on the publication:...
Scientific Posters

Inhibitory effect of typical CYP inhibitors under long term incubation in human liver microsomes

Presented at the 33rd JSSX Annual Meeting / 2018 MDO Meeting in Japan Authors Sho Nishinoaki, Ryo Fujino, Kenta Hashizume, Tsutomu Negama Drug Development Solutions...
Publications

An assessment of the in vitro inhibition of cytochrome P450 enzymes (CYP), UDP-glucuronsyltransferases (UGT) and transporters by phosphodiester- or phosphorothioate-linked oligonucleotides

Faraz Kazmi, Phyllis Yerino, Chase McCoy, Andrew Parkinson, David B Buckley and Brian W Ogilvie Oligonucleotides represent an expanding class of pharmacotherapeutics in development for...
Publications

DDI Guidance Recommendations on Down-Regulation, CYP2C Induction and CYP2B6 Control

Considerations from the IQ Induction Working Group in Response to Drug-Drug Interaction Guidances from Regulatory Agencies: Focus on Down-regulation, CYP2C Induction and CYP2B6 Positive Control...
Blog

UGT Activities, Concomitant Drugs, and DDI

If you have concerns about how your compound may affect UDP-glucuronosyltransferase (UGT) induction and/or inhibition when combined with other therapeutic...

Blog

SEKISUI XenoTech Featured on Labiotech.EU

Understand which transporters are involved in a drug’s absorption, distribution & excretion Originally posted on Labiotech.EU How can you build the...

Scientific Posters

In Vitro Evaluation of Ketoconazole and its Alternatives as Non-CYP Inhibitors

The In Vitro Evaluation of Ketoconazole and its Alternative Clinical CYP3A4/5 Inhibitors (Ritonavir, Clarithromycin and Itraconazole) as Inhibitors of Non-CYP Enzymes ABSTRACT Ketoconazole is a...
Blog

XenoTech Scientists Publish Paper, Present Research Evaluating Ketoconazole and its Alternative Clinical CYP3A4-5 Inhibitors as Inhibitors of Drug Transporters

SEKISUI XenoTech scientists published a paper in Drug Metabolism and Disposition evaluating Ketoconazole and its alternative clinical CYP3A4-5 inhibitors as inhibitors of drug...

Publications

Global marine pollutants inhibit P-glycoprotein: Environmental levels, inhibitory effects, and cocrystal structure

The world’s oceans are a global reservoir of persistent organic pollutants to whichHumans and other animals are exposed. Although it is well known that these...
Webinars

Evaluation of Ketoconazole and its Alternative Clinical CYP3A4/5 Inhibitors as Inhibitors of Drug Transporters

Presented by: Lydia Vermeer, Ph.D., Senior Scientist, Drug Transport Ketoconazole is an orally available, synthetic, broad spectrum, antifungal agent. Approved in 1982 by the FDA...
Scientific Posters

Evaluation of Chemical Inhibitors for UDP-glucuronosyltransferase UGT Reaction Phenotyping Assays

Evaluation of Chemical Inhibitors for UDP-glucuronosyltransferase (UGT) Reaction Phenotyping Assays in Human Liver Microsomes In the development of a new chemical entity (NCE) reaction phenotyping studies...
Scientific Posters

UGT Inhibition Studies in the Presence or Absence of Alamethicin Evaluation of UGT1A1 and UGT2B7

UGT Inhibition Studies in the Presence or Absence of Alamethicin: Evaluation of UGT1A1 and UGT2B7 Inhibition in Human Liver Microsomes and Recombinant Enzymes The importance...
Publications

The reliability of estimating Ki values for direct, reversible inhibition of cytochrome P450 enzymes from corresponding IC50 values: A retrospective analysis of 343 experiments

Lois J. Haupt, Faraz Kazmi, Brian W. Ogilvie, David B. Buckley, Brian D. Smith, Sarah Leatherman, Brandy Paris, Oliver Parkinson, and Andrew Parkinson In the...
Publications

Further Characterization of the Metabolism of Desloratadine and its Cytochrome P450 and UDP-Glucuronosyltransferase (UGT) Inhibition Potential: Identification of Desloratadine as a Relatively Selective UGT2B10 Inhibitor

Presented by: Faraz Kazmi, Phyllis Yerino, Joanna E Barbara, and Andrew Parkinson Desloratadine (Clarinex), the major active metabolite of loratadine (Claritin), is a non-sedating antihistamine...
Scientific Posters

Evaluation of BSEP Inhibitors Using B-CLEAR® Human Hepatocytes to Predict Inhibition and Cholestasis

Evaluation of Clinically Relevant Inhibitors of BSEP Using B-CLEAR® Human Sandwich-Cultured Hepatocytes to Better Predict Inhibition and Cholestasis Drug-induced liver injury (DILI) is characterized as...
Scientific Posters

Comparison of Ki and IC50 Values for Prototypical Inhibitors

Comparison of Ki and IC50 Values for Prototypical Inhibitors of ABC Transporters P-gp and BCRP Ki values were determined for prototypical inhibitors of ABC transporters...
Scientific Posters

Comparison of Ki and IC50 Values for Prototypical Inhibitors of the Major Drug Uptake Transporters

Comparison of Ki and IC50 Values for Prototypical Inhibitors of the Major Drug Uptake Transporters We previously reported on the similarities and differences in Ki and IC50 values for various inhibitors...
Scientific Posters

In Vitro System-Dependent Inhibition

In Vitro System-Dependent Inhibition of Cytochrome P450 Enzymes (CYP), UDP-Glucuronosyltransferases (UGT) and Transporters by Oligonucleotides We previously examined the cytochrome P450 (CYP) inhibition potential of...
Publications

Anti-CD28 Monoclonal Antibody-stimulated Cytokines Released from Blood Suppress CYP1A2, CYP2B6 and CYP3A4 in Human Hepatocytes In Vitro

Maciej Czerwiński, Faraz Kazmi, Andrew Parkinson, and David B. Buckley Like most infections and certain inflammatory diseases, some therapeutic proteins cause a cytokine-mediated suppression of...
Publications

In vitro inhibition of human liver cytochrome P450 (CYP) and UDP-glucuronosyltransferase (UGT) enzymes by rose bengal: system-dependent effects on inhibitory potential

Faraz Kazmi, Lois J. Haupt, Jennifer R. Horkman, Brian D. Smith, David B. Buckley, Eric A. Wachter, and Jamie M. Singer 1. Rose bengal (4,5,6,7-tetrachloro-2′,4′,5′,7′-tetraiodofluorescein)...
Publications

2012 XenoTech Products & Services Catalog

The 2012 Products & Services Catalog was developed to provide an overview of our entire portfolio of capabilities, with a heavy emphasis on the services...
Scientific Posters

ISSX 2013 – HIV Protease Inhibitors

Substrate-Specific Inactivation of CYP3A by the HIV Protease Inhibitors Ritonavir, Saquinavir and Amprenavir HIV protease inhibitors (PIs), such as ritonavir, saquinavir, and amprenavir, produce profound...
Scientific Posters

ISSX 2013 – BCRP Transport Inhibition

System-dependent inhibition of BCRP transport by high- and low-permeable compounds in bi-directional MDCKII cells and membrane vesicles Breast cancer resistance protein (BCRP, ABCG2) is an...
Publications

Metabolism-Dependent Inhibition of CYP3A4 by Lapatinib: Evidence for Formation of a Metabolic Intermediate Complex with a Nitroso/Oxime Metabolite Formed via a Nitrone Intermediate

Barbara JE, Kazmi F, Parkinson A, Buckley DB Metabolism-dependent inhibition (MDI) of cytochrome P450 (P450) enzymes has the potential to cause clinically relevant drug-drug interactions....
Webinars

Exploring the Mechanism of CYP3A4 Inactivation by Lapatinib Through In Vitro Metabolite Char.

Presented by: Joanna Barbara, Ph.D. Metabolism-dependent inhibition of cytochrome P450 enzymes has the potential to cause clinically-relevant drug-drug interactions. Alkylamine drugs are known for their propensity...
Scientific Posters

AAPS Transporter 2013 – Inhibitors of Uptake Transporters

Comparison of Ki and IC50 Values for Prototypical Inhibitors of Uptake Transporters Ki values were determined for prototypical inhibitors of uptake transporters with an experimental design incorporating...
Publications

Use of enzyme inhibitors to evaluate the conversion pathways of ester and amide prodrugs: A case study example with the prodrug ceftobiprole medocaril

Gary Eichenbaum, Jennifer Skibbe, Andrew Parkinson, Mark D. Johnson, Dawn Baumgardner, Brian Ogilvie, Etsuko Usuki, Fred Tonelli, Jeff Holsapple and Anne Schmitt-Hoffmann An approach was...
Scientific Posters

Esomeprazole, omeprazole sulfone, 5-O-desmethyl omeprazole and 5-hydroxylansoprazole are in vitro metabolism-dependent inhibitors of CYP2C19

Esomeprazole, omeprazole sulfone, 5-O-desmethyl omeprazole and 5-hydroxylansoprazole are in vitro metabolism-dependent inhibitors of CYP2C19 The intensively researched interaction between clopidogrel and proton pump inhibitors (PPIs) and the...
Scientific Posters

Can Ki values for direct inhibition of CYP enzymes be reliably estimated from IC50 values?

Regulatory agencies recommend that the potential for a drug candidate to cause clinically relevant, direct inhibition of cytochrome P450 (CYP) enzymes be estimated based on the ratio...
Scientific Posters

Evaluation of dilution, dialysis and ultracentrifugation methods to assess the reversibility of metabolism-dependent inhibitors (MDIs) of cytochrome P450 (CYP) enzymes

Evaluation of dilution, dialysis and ultracentrifugation methods to assess the reversibility of metabolism-dependent inhibitors (MDIs) of cytochrome P450 (CYP) enzymes Metabolism-dependent inhibition (MDI) of P450...
Publications

The Proton Pump Inhibitor, Omeprazole, but Not Lansoprazole or Pantoprazole, Is a Metabolism-Dependent Inhibitor of CYP2C19: Implications for Coadministration with Clopidogrel

Ogilvie BW, Yerino P, Kazmi F, Buckley DB, Rostami-Hodjegan A, Paris BL, Toren P, Parkinson A As a direct-acting inhibitor of CYP2C19 in vitro, lansoprazole...
Scientific Posters

In vitro inhibition and induction of human liver cytochrome P450 enzymes by NTBC and its metabolism in human liver microsomes

In vitro inhibition and induction ofHuman liver cytochrome P450 enzymes by NTBC and its metabolism in human liver microsomes 2-(2-Nitro-4-trifluoromethylbenzoyl)-1, 3-cyclohexanedione (NTBC, also known as...
Scientific Posters

Identification of a novel carbamoyl glucuronide as a metabolism-dependent inhibitior of CYP2C8

Glucuronidation is a major route of drug biotransformation and detoxification, whereby a drug is conjugated with glucuronic acid in a reaction catalyzed by UDP glucuronosyltransferases...
Scientific Posters

Pitfalls in the Design of Metabolism-Dependent CYP Inhibition (MDI) Experiments With a Dilution Step: Inhibitor Depletion by Metabolism and/or Microsomal Binding Leads to Underestimation of the Shifted IC50 Value

We previously demonstrated that, when a dilution step is used to assess MDI potential (i.e., IC50 shift experiments), IC50 values for direct-inhibition and MDI should...
Publications

Chapter 7: In Vitro Approaches for Studying the Inhibition of Drug-Metabolizing Enzymes and Identify

Thank you for your interest in SEKISUI XenoTech’s last edition of… Chapter 7: In Vitro Approaches for Studying the Inhibition of Drug-Metabolizing Enzymes and Identifying...

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