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210518s2021 nyu ob 001 0 eng |
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|a 2021023437
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|a 1536197289
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|a 9781536197280
|q (electronic bk.)
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|z 9781536194883
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|a (OCoLC)1252740035
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|a 616.99/4061
|2 23
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|a UAMI
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|a An introduction to p-glycoprotein /
|c M. Wahajuddin, PHD, FHEA, FRSB, FRSC, Principal Scientist, CSIR-Central Drug Research Institute, Lucknow (U.P.), India, Ravindra Varma Alluri, PHD, Associate Principal Scientist, Clinical Pharmacology and Safety Sciences, AstraZeneca R&D, Cambridge, UK, Rahul Dev Jayant, PHD, Assistant Professor, Texas Tech University Health Sciences Center, Texas, USA, editors.
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|a 2108
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|a New York :
|b Nova Science Publishers,
|c [2021]
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|a 1 online resource.
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|a text
|b txt
|2 rdacontent
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|a computer
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|2 rdamedia
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|a online resource
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|a Pharmacology - research, safety testing and regulation
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|a Includes bibliographical references and index.
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|a "P-glycoprotein (P-gp), encoded by the multidrug-resistance (MDR)-1 gene is one of the best studied efflux transporters that is linked to multidrug resistance in cancer chemotherapies. P-gp belongs to the ATP-binding cassette (ABC) transporter family of proteins that utilizes energy derived from hydrolysis of ATP to efflux endogenous and exogenous xenobiotics, metabolites and toxins from the intracellular space to the outside, thereby providing a general protective role. P-gp is expressed on the apical plasma membrane of all major drug eliminating organs such as the intestine (enterocytes), liver (bile canaliculi), kidney (proximal tubules), brain (endothelia of blood-brain barrier) and in certain tumor types. In the intestine and BBB, P-gp limits entry of drugs by actively pumping drugs back into the lumen or blood, respectively. In the liver and kidney, P-gp actively effluxes drugs, endogenous substances and metabolites into bile or urine, thereby removing them from the body. Upregulation of P-gp in tumor cells is noted in several cancers and is a hallmark for drug resistance. Additionally, P-gp is also shown to play a role in neurogenesis and maintaining homeostasis in the brain. Alteration of P-gp expression is observed in neurodegenerative diseases, highlighting its importance in maintaining normal brain health. Due to its central role in defining oral pharmacokinetics, systemic clearance, tissue exposure, organ health and chemoresistance, much of the research has been focused on modulating P-gp. Chemical inhibitors, formulation-based and epigenetic approaches are applied to modulate P-gp activity with a goal to improve oral pharmacokinetics, increase tumor and brain penetration, minimize organ toxicity and potentially treat neurodegenerative diseases. Although enormous research on P-gp has been published, a book chapter exclusively and comprehensively covering diverse aspects of P-gp, including the recent developments in the field, is required. With much enthusiasm from the publisher, we have collaborated to bring together wide-ranging topics on P-gp. This book contains 12 chapters covering the structure, function, regulation, distribution and expression of P-gp, its pharmacological importance in health and disease and role in pharmacokinetics and drug-drug interactions. Also included are computational approaches to identify selective inhibitors and tactics to modulate P-gp function using chemical inhibitors (synthesized or isolated from marine sources), formulation strategies or epigenetic approaches. The last chapter describes various methods to quantify P-gp expression levels and function in in vitro, in situ and in vivo settings. It is our sincere hope that this material will serve as an important desk reference for students, researchers and clinical scientists in academia, medical research and the pharmaceutical industry working in various fields such as pharmacology, pharmacy, toxicology, medicinal chemistry, pharmaceutical sciences, pharmacokinetics and computational biology"--
|c Provided by publisher.
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|a Description based on print version record and CIP data provided by publisher; resource not viewed.
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|a Intro -- Contents -- Preface -- Acknowledgments -- Chapter 1 -- Introduction: Structure and Function -- Abstract -- Introduction -- Structure -- Topological Features of P-gp -- Functions of P-Glycoprotein -- Potential Mechanism of Action for Drug Disposition by P-Glycoprotein (P-gp) -- Molecular and Biological Functions of P-gp -- Role of P-gp in Various Pathologies -- Interactome Analysis of P-Gp and Associated Metabolic Pathways Using Protein Interaction Analysis and Pathway Enrichment Analysis -- Conclusion and Future Perspectives -- References -- Chapter 2
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|a Relative Distribution of P-glycoprotein (P-gp) and its Pharmacological Relevance -- Abstract -- Introduction -- Physiological Distribution of P-glycoprotein in Normal and Diseased Conditions -- Intestinal Epithelium -- Liver -- Kidneys -- Blood-Brain Barrier (BBB) -- Pharmacokinetics and Pharmacological Relevance -- Efflux Mechanisms and Effect of P-gp in Oral Bioavailability -- Efflux Mechanisms -- Effect on Oral Bioavailability -- Cerebral Disorders -- Alzheimer's Disease -- Epilepsy -- Tumors -- Ovarian Cancer -- Autoimmune Disorders -- Systemic Lupus Erythematosus (SLE)
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|a Rheumatoid Arthritis -- Role of P-gp in Development of Multidrug Resistance (MDR) -- Conclusion -- Declaration of Competing Interests -- Acknowledgments -- References -- Chapter 3 -- P-gp Pathophysiology: -- Post-Translational Modification -- and Affecting Signaling Cascades -- Abstract -- Introduction -- P-gp as a Lipid Flippase -- P-gp as a Vacuum Cleaner -- Effect of P-gp in Pathology -- Pathophysiology of Various Diseases Related to P-gp -- Signaling Transduction -- Pathway of P-gp Intracellular Trafficking -- Post-translational Moifications of Transporters -- Conclusion -- References
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|a Chapter 4 -- Mechanistic Comprehension towards the Role of P-Glycoprotein in Limiting the Pharmacokinetic and Pharmacological Efficacy of Drugs -- Abstract -- Introduction and Background -- Structure and Function of P-gp -- P-gp and Drug Pharmacokinetics/Bioavailability -- Effect of P-gp on Drug Absorption -- Effect of P-gp Upon Drug Distribution -- Effect of P-gp Upon Drug Metabolism -- Effect of P-gp Upon Drug Elimination -- Pathophysiology Behind P-gp and Drug Interaction -- Conclusion and Future Perspectives -- Acknowledgments -- Conflict of Interest -- References -- Chapter 5
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|a P-Glycoprotein, a Biological and Medicinal Chemistry/Radiochemistry Point of View -- Abstract -- Introduction -- A Biological Point of View: The P-Gp Interacting Mechanism -- Substrates, Inhibitors and Modulators: The Pivotal Role of P-Gp in the Therapy and Diagnosis of Pathological Conditions -- P-Glycoprotein Inducers and Activators -- A Medicinal Chemistry Point of View: Development of P-gp Interacting Compounds -- P-Gp Radiotracers -- P-gp Substrates -- P-gp Inhibitors -- Conclusion -- Conflict of Interest -- References -- Chapter 6 -- P-Glycoprotein: A New Insight in
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|a eBooks on EBSCOhost
|b EBSCO eBook Subscription Academic Collection - Worldwide
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|a Drug resistance in cancer cells.
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|a P-glycoprotein.
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|a Drug Resistance, Neoplasm
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|a Cellules cancéreuses
|x Résistance aux médicaments.
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|a P-glycoprotéine.
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|a Drug resistance in cancer cells
|2 fast
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|a P-glycoprotein
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|a Wahajuddin, M.,
|e editor.
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|a Varma Alluri, Ravindra,
|e editor.
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|a Dev Jayant, Rahul,
|e editor.
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|i Print version:
|t Introduction to p-glycoprotein
|d New York : Nova Science Publishers, [2021]
|z 9781536194883
|w (DLC) 2021023436
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