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1、SendOrdersofReprintsatreprints@benthamscience.net1858CurrentMedicinalChemistry,2013,20,1858-1886HistoneDeacetylaseInhibitors:AnAttractiveStrategyforCancerTherapy*JiyangLi,GuangqiangLiandWenqingXuInstituteofRadiationMedicine,ChineseAcademyofMedicalScience
2、s&PekingUnionMedicalCollege,Tianjin,PeopleRepublicofChinaAbstract:HistonedeacetylasesareabletocatalyzethehydrolysisofN-acetyllysineresiduesofhistoneswhichpackagechromosomalDNA.Thereforetheyplayanimportantroleinmediatinggeneexpressionandcellproliferation.
3、HDACin-hibitorshavenotonlyshownpromiseasantiparasitic,antineurodegenerative,antirheumatologicagentsandimmunosup-pressant,butaspotentanticanceragentsbyinducingcellcyclearrest,differentiationandapoptosis.Thisreviewhighlightsrecentdevelopmentindesign,synthe
4、sisandbiologicalevaluationofHDACinhibitorsforcancertherapy.Keywords:Antitumordrugs,cancertherapy,cyclicpeptide,drugdiscovery,epigeneticregulation,histonedeacetylase,hdacisoforms,histonedeacetylaseinhibitors,hybridcompounds,multi-targetedinhibitor.INTRODU
5、CTIONNH+Nucleosome,whichisthebasicunitofchromatin,com-C3HATCNHOCHOCHprisesaDNAwrappedaroundacorehistoneoctamer,whichiscomposedofaH3–H4tetramerandtwoH2A-H2Bdim-NHHDACNHOmers[1].Thus,DNAiscompactedinasmallersizewhichisrequiredforbeingstoredineukaryoticnucl
6、eus.Butsome-times,thehighdegreeofcompactionwouldbeunnecessary.Forexample,whenDNAreplicationandgenetranscriptionchromatincompactedDNAunfoldedbegan,DNAmustbereleasedandbeloose.Accordingly,aquestionarised.Howwouldthesetwocontraryprocesseshappen?HATs(histone
7、acetyltransferases)andHDACs(his-tonedeacetylases)areonepairofanswers[2].genesilencetranscriptionalactivationInhistoneprotein,themodificationofterminal-aminotranscriptionalinhibitionreplicationactivatedgroupofspecificlysineresidueswasveryimportantfortran
8、-proliferationstimulatedgeneexpressionscriptionalprocesses[3].As(Fig.1)displayed,whenarrowturnedrightwhichmeantlysineresiduewasacetylatedbyFig.(1).TheProcessofHistoneAcetylationandDeacetylation.HATs,theinteractionbetweenhi
