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Fueled by the expertise of a team of international specialist authors, this first reference on the booming topic covers everything a drug researcher needs to know about targeting epigenetic mechanisms of disease. The first part of the book surveys current methodologies for finding and validating drug candidates that act via epigenetic mechanisms. The second part systematically surveys known and suspected drug targets within the epigenetic machinery, including the discovery and development of vorinostat, the first marketed epigenetic drug.
List of contents
PART I: General Aspects and MethodologiesNEW FRONTIERS IN EPIGENETIC MODIFICATIONSIntroductionDNA MethylationHistone Modifications and the Histone Code HypothesisOrigins of Specificity in Histone Binding Proteins/Modifying EnzymesHistone Modification Cross-TalkInhibitors of DNMTs and HDACsSTRUCTURAL BIOLOGY OF EPIGENETIC TARGETSIntroductionHistone AcetyltransferasesHistone DeacetylasesSirtuinsHistone Methylation EnzymesHistone DemethylasesDNA MethyltransferasesConcluding Remarks: The Challenge of Structural Studies of Epigenetic TargetsCOMPUTER- AND STRUCTURE-BASED LEAD IDENTIFICATION FOR EPIGENETIC TARGETSIntroductionComputer-Based Methods in Drug DiscoveryDNA MethyltransferasesHistone DeacetylasesHistone AcetyltransferasesHistone MethyltransferasesHistone DemethylasesHISTONE MODIFICATION ANALYSIS USING MASS SPECTROMETRYIntroductionHistone MoleculesCapillary ElectrophoresisReversed Phase ChromatographyMass SpectrometryIN VITRO ASSAYS FOR HISTONE-MODIFYING ENZYMESIntroductionScreening HierarchyGeneral Principles of Screening for Histone-Modifying EnzymesHistone DeacetylasesHistone AcetyltransferasesHistone MethyltransferasesHistone DemethylasesEPIGENETIC TARGETS IN DRUG DISCOVERY: CELL-BASED ASSAYS FOR HDAC INHIBITOR HIT VALIDATIONIntroductionIn Vitro Assays for HDAC InhibitorsCell-Based AssaysBiological Function-Based AssaysHDAC Isoform Functional AssaysAnticancer ActivityPerspectiveCHROMATIN IMMUNOPRECIPITATION CHIP: WET LAB MEETS IN SILICOBackground and OverviewThe Basic Principle of ChIPDifferent Variations of ChIPAnalysis of ChIP DataData Analysis ExamplesThe Future of ChIPPART II: Epigenetic Target Classes and Inhibitor DevelopmentDNA METHYLTRANSFERASE INHIBITORSIntroductionDNA MethylationDNA MethyltransferasesBiochemical Mechanism of DNA MethylationPhysiological Role of DNA MethylationDNA Methylation and DiseaseDNMT InhibitorsTherapeutic Applications of DNMT InhibitorsHISTONE DEACETYLASE INHIBITORSIntroductionMechanism and X-Ray Crystal StructureHistone Deacetylase InhibitorsNAD-DEPENDENT DEACETYLASES AS THERAPEUTIC TARGETSHistorical Perspective and Functions of Sir2 in YeastSirtuin Enzymatic Activity and its Modulation by Endogenous MoleculesSmall Molecule Inhibitors of SirtuinsSmall Molecule Activators of SirtuinsSIRT1 as a Therapeutic Target in Metabolic Syndrome and Type 2 DiabetesNeurological DiseasesINHIBITORS OF HISTONE ACETYLTRANSFERASES: DISCOVERY AND BIOMEDICAL PERSPECTIVESIntroductionHAT InhibitorsHISTONE METHYLTRANSFERASES AS NOVEL DRUG TARGETSIntroductionProtein MethylationHistone DemethylationHistone MethyltransferasesHistone Methyltransferase InhibitorsHISTONE DEMETHYLASESIntroductionChromatinHistone Methylation and DemethylationHistone DemethylasesLSD1/KDM1JmjC Domain-Containing Demethylases
About the author
Wolfgang Sippl is Professor of Pharmaceutical Chemistry at the Martin-Luther-University of Halle-Wittenberg (Germany). He is interested in 3D QSAR, molecular docking and molecular dynamics, and their applications in drug design and pharmacokinetics.
Summary
Fueled by the expertise of a team of international specialist authors, this first reference on the booming topic covers everything a drug researcher needs to know about targeting epigenetic mechanisms of disease.
The first part of the book surveys current methodologies for finding and validating drug candidates that act via epigenetic mechanisms. The second part systematically surveys known and suspected drug targets within the epigenetic machinery, including the discovery and development of vorinostat, the first marketed epigenetic drug.
Report
"The book provides an overview about the 'current methodologies for finding and validating drug candidates acting on epigenetic mechanisms. " ( RoSearch , December 2010)
"Provides a fresh overview within the epigenetic area. ... Effective in combining basic knowledge, methodologies, and drug discoveries in a field that is expanding daily. To the best of my knowledge, this is the first compendium that has these characteristics." ( ChemMedChem , 2010)
"Authoritative and comprehensive." ( ChemBioChem , October 2009)
