Ion channel drug discovery

384 Pages·2015·12.284 MB·English

by  Brian Cox, Martin Gosling

Ion Channel Drug Discovery
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RSC Drug Discovery Series
Editor-in-Chief:
Professor David Thurston, King’s College, London, UK
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7 Professor Ana Martinez, Medicinal Chemistry Institute-CSIC, Madrid, Spain
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39/ Advisor to the Board:
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0.1 Professor Robin Ganellin, University College London, UK
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g | d Titles in the Series:
or 1: Metabolism, Pharmacokinetics and Toxicity of Functional Groups
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s.rs 2: Emerging Drugs and Targets for Alzheimer’s Disease; Volume 1
ub 3: Emerging Drugs and Targets for Alzheimer’s Disease; Volume 2
p
p:// 4: Accounts in Drug Discovery
htt 5: New Frontiers in Chemical Biology
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4 o 6: Animal Models for Neurodegenerative Disease
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0 7: Neurodegeneration
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er 8: G Protein-Coupled Receptors
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3. em 9: Pharmaceutical Process Development
7:1ept 10: Extracellular and Intracellular Signaling
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on 12: New Horizons in Predictive Toxicology
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he 13: Drug Design Strategies: Quantitative Approaches
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16: Pharmaceutical Salts and Cocrystals
17: Polyamine Drug Discovery
18: Proteinases as Drug Targets
19: Kinase Drug Discovery
20: Drug Design Strategies: Computational Techniques and Applications
21: Designing Multi-Target Drugs
22: Nanostructured Biomaterials for Overcoming Biological Barriers
23: Physico-Chemical and Computational Approaches to Drug Discovery
24: Biomarkers for Traumatic Brain Injury
25: Drug Discovery from Natural Products
26: Anti-Inflammatory Drug Discovery
27: New Therapeutic Strategies for Type 2 Diabetes: Small Molecules
28: Drug Discovery for Psychiatric Disorders
29: Organic Chemistry of Drug Degradation
30: Computational Approaches to Nuclear Receptors
31: Traditional Chinese Medicine
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32: Successful Strategies for the Discovery of Antiviral Drugs
33: Comprehensive Biomarker Discovery and Validation for Clinical
Application
34: Emerging Drugs and Targets for Parkinson’s Disease
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00 35: Pain Therapeutics; Current and Future Treatment Paradigms
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F 36: Biotherapeutics: Recent Developments using Chemical and Molecular
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08 Biology
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73 37: Inhibitors of Molecular Chaperones as Therapeutic Agents
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84 38: Orphan Drugs and Rare Diseases
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78 39: Ion Channel Drug Discovery
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How to obtain future titles on publication:
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Ion Channel Drug Discovery
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9/ Horsham Research Centre, Horsham, UK
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Apartfromfairdealingforthepurposesofresearchfornon-commercialpurposesor
forprivatestudy,criticismorreview,aspermittedundertheCopyright,Designsand
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PublishedbyTheRoyalSocietyofChemistry,
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9/ This book is dedicated to the memory of our fathers, Raymond Cox
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org | This book is also dedicated to the exceptional talented individuals of Ciba,
sc. Ciba-Giegy and Novartis who worked at the Horsham site (1937–2014)
bs.r in their tireless pursuit of medicines to alleviate suffering.
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oi: Ionchannelsarelocatedwithintheplasmamembraneofnearlyallcellsand
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or numerous fundamental physiological functions including generating and
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s.r shaping action potentials, regulating cell volume and controlling epithelial
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u secretion to name but a few. Ion channel modulators have historically pro-
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p:// ventheirmajortherapeuticutilityinnumerousclinicalparadigmsincluding
n htt reductionofbloodpressure,analgesiaandlocalanaesthesia—howevertheir
4 o potential as targets for novel and efficacious therapeutics is yet to be fully
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er creasing number of diseases to genetic ion channel dysfunction (channelo-
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3. em pathies). This emphasizes not only the important physiological and
37:2Sept pathophysiological roles these proteins play but directs the drug discoverer
10:03 to not only new targets but a clear understanding of potentially how they
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interest and investment in ion channel modulation in both industrial and
academic settings. The coming years promise to be exciting times as these
new therapeutic opportunities are identified and realized.
Thisbookbuildsontheplatformcreatedbythehighlysuccessfulseriesof
Royal Society of Chemistry ‘Ion Channels as Therapeutic Targets’ meetings
in the last decade. These meetings, supported by both academic and
industrial scientists, have covered themes including advances in screening
technology, ion channel structure and modeling and up-to-date case
historiesofthediscoveryofmodulatorsofarangeofchannels,bothvoltage-
gated and non-voltage-gated channels.
Our goal was to provide a reference text of interest to a wide range of
readers by eliciting contributions from highly respected academic and
RSCDrugDiscoverySeriesNo.39
IonChannelDrugDiscovery
EditedbyBrianCoxandMartinGosling
rTheRoyalSocietyofChemistry2015
PublishedbytheRoyalSocietyofChemistry,www.rsc.org
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x Preface
industrial researchers covering a combination of recent advances in the
field,fromtechnologicalandmedicinalchemistryperspectives,aswellasan
introduction to the new ‘ion channel drug discoverer’. We thank the many
contributors to this book and hope you enjoy reading it as much as we did
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