Abstract
Cytochrome P450 (CYP) induction in rodents and humans is considered a liability for new chemical entities (NCEs) in drug discovery. In particular, CYP1A1 and CYP2B1/2 have been associated with the induction of liver tumors in oncogenicity studies during safety evaluation studies of potential drugs. In our laboratory, real time PCR (Taqman®) has been used to quantify the induction of rat hepatic CYP1A1 and CYP2B1/2 in precision – cut rat liver slices. A novel technology that does not require m-RNA isolation or RT-PCR, (developed by NanoString Technologies®) has been investigated to quantify CYP1A1 and CYP2B1/2 induction in rat liver slices. Seventeen commercially available compounds were evaluated using both Taqman® and NanoString® technologies. Precision-cut rat liver slices were incubated with individual compounds for 24 hr at 37°C in a humidified CO2 incubator and CYP1A1 and CYP2B1/2 m-RNA molecules were quantified. The results from the NanoString® technology were similar to those of the Taqman® with a high degree of correlation for both CYP isoforms (r2 > 0.85). Therefore, NanoString provides an additional new technology to evaluate the induction of CYP1A1 and 2B1/2, as well as potentially other enzymes or transporters in rat liver slices.
Keywords: NanoString®, Automation, HTP or High Throughput, Liver Slices, Real Time PCR, Cytochrome P450, Induction, CYP1A1, CYP2B1/2
Drug Metabolism Letters
Title: Evaluation of CYP1A1 and CYP2B1/2 m-RNA Induction in Rat Liver Slices Using the NanoString® Technology: A Novel Tool for Drug Discovery Lead Optimization
Volume: 3 Issue: 3
Author(s): Jairam R. Palamanda, Pramila Kumari, Nicholas Murgolo, Larry Benbow, Xinjie Lin and Amin A. Nomeir
Affiliation:
Keywords: NanoString®, Automation, HTP or High Throughput, Liver Slices, Real Time PCR, Cytochrome P450, Induction, CYP1A1, CYP2B1/2
Abstract: Cytochrome P450 (CYP) induction in rodents and humans is considered a liability for new chemical entities (NCEs) in drug discovery. In particular, CYP1A1 and CYP2B1/2 have been associated with the induction of liver tumors in oncogenicity studies during safety evaluation studies of potential drugs. In our laboratory, real time PCR (Taqman®) has been used to quantify the induction of rat hepatic CYP1A1 and CYP2B1/2 in precision – cut rat liver slices. A novel technology that does not require m-RNA isolation or RT-PCR, (developed by NanoString Technologies®) has been investigated to quantify CYP1A1 and CYP2B1/2 induction in rat liver slices. Seventeen commercially available compounds were evaluated using both Taqman® and NanoString® technologies. Precision-cut rat liver slices were incubated with individual compounds for 24 hr at 37°C in a humidified CO2 incubator and CYP1A1 and CYP2B1/2 m-RNA molecules were quantified. The results from the NanoString® technology were similar to those of the Taqman® with a high degree of correlation for both CYP isoforms (r2 > 0.85). Therefore, NanoString provides an additional new technology to evaluate the induction of CYP1A1 and 2B1/2, as well as potentially other enzymes or transporters in rat liver slices.
Export Options
About this article
Cite this article as:
Palamanda R. Jairam, Kumari Pramila, Murgolo Nicholas, Benbow Larry, Lin Xinjie and Nomeir A. Amin, Evaluation of CYP1A1 and CYP2B1/2 m-RNA Induction in Rat Liver Slices Using the NanoString® Technology: A Novel Tool for Drug Discovery Lead Optimization, Drug Metabolism Letters 2009; 3 (3) . https://dx.doi.org/10.2174/187231209789352094
DOI https://dx.doi.org/10.2174/187231209789352094 |
Print ISSN 1872-3128 |
Publisher Name Bentham Science Publisher |
Online ISSN 1874-0758 |
Related Articles
-
Anticancer Activity of Ocimum basilicum and the Effect of Ursolic Acid on the Cytoskeleton of MCF-7 Human Breast Cancer Cells
Letters in Drug Design & Discovery Lipidomics as Tools for Finding Biomarkers of Intestinal Pathology: From Irritable Bowel Syndrome to Colorectal Cancer
Current Drug Targets Fibroblast Growth Factor Receptor Signaling in Cancer Biology and Treatment
Current Signal Transduction Therapy Chondromodulin-I and Tenomodulin: The Negative Control of Angiogenesis in Connective Tissue
Current Pharmaceutical Design Conference Report: The Myriad Pathways of Neurodegeneration Discussed at NEUROCON 2015
Current Aging Science Development of Yeast Molecular Display Systems Focused on Therapeutic Proteins, Enzymes, and Foods: Functional Analysis of Proteins and its Application to Bioconversion
Recent Patents on Biotechnology Future Prospects for Targeted Alpha Therapy
Current Radiopharmaceuticals Targeting the PI3K/Akt/mTOR Axis by Apigenin for Cancer Prevention
Anti-Cancer Agents in Medicinal Chemistry Thymoquinone Inhibits Proliferation and Migration of MDA-MB-231 Triple Negative Breast Cancer Cells by Suppressing Autophagy, Beclin-1 and LC3
Anti-Cancer Agents in Medicinal Chemistry Curcumin Activates Erythrocyte Membrane Acetylcholinesterase
Letters in Drug Design & Discovery A Review on the Development in the Field of NIDDM based Thiazolidinedione PPARγ Agonists
Mini-Reviews in Medicinal Chemistry Advanced Platelet-Rich Fibrin Extract Treatment Promotes the Proliferation and Differentiation of Human Adipose-Derived Mesenchymal Stem Cells through Activation of Tryptophan Metabolism
Current Stem Cell Research & Therapy Nucleic Acid Carrier Systems Based on Polyethylenimine Conjugates for the Treatment of Metastatic Tumors
Current Medicinal Chemistry Editorial on the Occasion of the 20th Anniversary of Endocrine Metabolic Immune Disorders-Drug Targets Journal with a Kaleidoscopic Vision of Selected Publications
Endocrine, Metabolic & Immune Disorders - Drug Targets Small Molecule Toxins Targeting Tumor Receptors
Current Pharmaceutical Design Serial Analysis of Gene Expression (SAGE): 13 Years of Application in Research
Current Pharmaceutical Biotechnology Clinical Management of Diabetes Mellitus in the Older Adult Patient
Current Diabetes Reviews Molecular Targeted Approaches for Treatment of Pancreatic Cancer
Current Pharmaceutical Design Liposomal Drug Delivery: Recent Patents and Emerging Opportunities
Recent Patents on Drug Delivery & Formulation Expression Profiling of Estrogen Responsive Genes Using Genomic and Proteomic Techniques for the Evaluation of Endocrine Disruptors
Current Pharmacogenomics