Abexinostat-CRA-024781-DataSheet-生命科学试剂-MedChemExpress

Hotline:400-820-3792Inhibitors•ScreeningLibraries•Proteinswww.MedChemEAbexinostatCat.No.:HY-10990CASNo.:783355-60-2Synonyms:CRA024781;PCI-24781分⼦式:C₂₁H₂₃N₃O₅分⼦量:397.42作⽤靶点:HDAC作⽤通路:CellCycle/DNADamage;Epigenetics储存⽅式:Powder-20°C3years4°C2years*该产品在溶液状态不稳定，建议您现⽤现配，即刻使⽤。溶解性数据体外实验DMSO:3.33mg/mL(8.38mM;Needultrasonic)MassSolvent1mg5mg10mgConcentration制备储备液1mM2.5162mL12.5811mL25.1623mL5mM0.5032mL2.5162mL5.0325mL10mM---------请根据产品在不同溶剂中的溶解度，选择合适的溶剂配制储备液；该产品在溶液状态不稳定，建议您现⽤现配，即刻使⽤.体内实验请根据您的实验动物和给药⽅式选择适当的溶解⽅案。以下溶解⽅案都请先按照InVitro⽅式配制澄的储备液，再依次添加助溶剂：(为保证实验结果的可靠性，澄的储备液可以根据储存条件，适当保存；体内实验的⼯作液，建议您现⽤现配，当天使⽤；以下溶剂前显⽰的百分⽐指该溶剂在您配制终溶液中的体积占⽐；如在配制过程中出现沉淀、析出现象，可以通过加热和/或超声的⽅式助溶)1.请依序添加每种溶剂：20%HP-β-CDinsalineSolubility:6mg/mL(15.10mM);Suspendedsolution;Needultrasonic1/3MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemEBIOLOGICALACTIVITY⽣物活性Abexinostat(CRA024781)⼀种新的泛HDAC抑制剂，主靶向HDAC1的Ki值为7nM。Abexinostat也抑制MBLAC2⽔解酶活性，EC50⼩于10nM。IC50&TargetHDAC1HDAC3/SMRTHDAC6HDAC27nM(Ki)8.2nM(Ki)17nM(Ki)19nM(Ki)HDAC10HDAC8MBLAC224nM(Ki)280nM(Ki)<10nM(EC50)体外研究Abexinostat(CRA024781)exhibitspotentantitumoractivityagainstavarietyoftumorcelllineswithGI50%rangingfrom0.15μMto3.09μM.Abexinostat(CRA024781)alsohasanantiproliferativeeffectonHUVECendothelialcellswithGI50%of0.43μM.Abexinostat(CRA024781)treatmentcausesdose-dependentaccumulationofbothacetylatedhistonesandacetylatedtubulininHCT116orDLD-1cells,inducesexpressionofp21,andleadstoPARPcleavageandaccumulationoftheγH2AX[1].InhibitionofHDACenzymesbyAbexinostat(CRA024781)leadstoasignificantreductioninthetranscriptionofgenesspecificallyassociatedwithHR,includingRAD51.ConsistentwithinhibitionofHR,Abexinostat(CRA024781)treatmentresultsinadecreasedabilitytoperformhomologydirectedrepairofI-SceI-inducedchromosomebreaksintransfectedCHOcells[2].Abexinostat(CRA024781)inducesSphasedepletion,G2cellcyclearrest,andapoptosisinsofttissuesarcoma(STS)cells.Abexinostat(CRA024781)inducesRad51transcriptionalrepressioninSTScellspotentiallymediatedviaenhancedE2F1bindingtotheRad51proximalpromoter[3].体内研究Abexinostat(CRA024781)parenterallyadministeredtomiceharboringHCT116orDLD-1colontumorxenograftsresultsinastatisticallysignificantreductionintumorgrowth.Inhibitionoftumorgrowthisaccompaniedbyanincreaseintheacetylationofα-tubulininperipheralbloodmononuclearcells,andanalterationintheexpressionofmanygenesinthetumors,includingseveralinvolvedinapoptosisandcellgrowth[1].PROTOCOLCellAssay[1]TentumorcelllinesandHUVECareculturedforatleasttwodoublingtimes,andgrowthismonitoredattheendofcompoundexposureusinganAlamarbluefluorometriccellproliferationassay.Thecompoundisassayedintriplicatewellsin96-wellplatesatnineconcentrationsusinghalf-logintervalsrangingfrom0.0015to10μmol/L.ThefinalDMSOconcentrationineachwellis0.15%.Theconcentrationrequiredtoinhibitcellgrowthby50%and95%confidenceintervalsareestimatedfromnonlinearregressionusingafour-parameterlogisticequation[1].MCEhasnotindependentlyconfirmedtheaccuracyofthesemethods.Theyareforreferenceonly.AnimalHCT116andDLD-1tumorcellsareimplanteds.c.infemaleBALB/cnu/numiceat3×106permouse.Administration[1]TreatmentwithAbexinostat(CRA024781)startedwhentheaveragetumorvolumeis-100mm[1].Micebearinghumancolontumorxenograftsaredosedi.v.withAbexinostat(CRA024781)usingvariousdosagesandschedulestoassesstheantitumoractivityofAbexinostat(CRA024781)[1].2/3MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemEMCEhasnotindependentlyconfirmedtheaccuracyofthesemethods.Theyareforreferenceonly.户使⽤本产品发表的科研⽂献•ProcNatlAcadSciUSA.2019Feb19;116(8):2961-2966.•Viruses.2020Jun3;12(6):609.•bioRxiv.2021Jan5.•MethodsMolBiol.2018;1711:351-398.Seemorecustomervalidationsonwww.MedChemEREFERENCES[1].LechnerS,etal.TargetdeconvolutionofHDACpharmacopoeiarevealsMBLAC2ascommonoff-target.NatChemBiol.2022Aug;18(8):812-820.[2].BuggyJJ,etal.CRA-024781:anovelsyntheticinhibitorofhistonedeacetylaseenzymeswithantitumoractivityinvitroandinvivo.MolCancerTher,2006,5(5),1309-1317.[3].AdimoolamS,etal.HDACinhibitorPCI-24781decreasesRAD51expressionandinhibitshomologousrecombination.ProcNatlAcadSciUSA,2007,104(49),19482-19487.[4].LopezG,etal.CombiningPCI-24781,anovelhistonedeacetylaseinhibitor,withchemotherapyforthetreatmentofsofttissuesarcoma.ClinCanc