Abexinostat-CRA-024781-DataSheet-生命科學(xué)試劑-MedChemExpress

Hotline:400-820-3792Inhibitors?ScreeningLibraries?Proteinswww.MedChemEAbexinostatCat.No.:HY-10990CASNo.:783355-60-2Synonyms:CRA024781;PCI-24781分?式:C??H??N?O?分?量:397.42作?靶點:HDAC作?通路:CellCycle/DNADamage;Epigenetics儲存?式:Powder-20°C3years4°C2years*該產(chǎn)品在溶液狀態(tài)不穩(wěn)定，建議您現(xiàn)?現(xiàn)配，即刻使?。溶解性數(shù)據(jù)體外實驗DMSO:3.33mg/mL(8.38mM;Needultrasonic)MassSolvent1mg5mg10mgConcentration制備儲備液1mM2.5162mL12.5811mL25.1623mL5mM0.5032mL2.5162mL5.0325mL10mM---------請根據(jù)產(chǎn)品在不同溶劑中的溶解度，選擇合適的溶劑配制儲備液；該產(chǎn)品在溶液狀態(tài)不穩(wěn)定，建議您現(xiàn)?現(xiàn)配，即刻使?.體內(nèi)實驗請根據(jù)您的實驗動物和給藥?式選擇適當(dāng)?shù)娜芙?案。以下溶解?案都請先按照InVitro?式配制澄的儲備液，再依次添加助溶劑：(為保證實驗結(jié)果的可靠性，澄的儲備液可以根據(jù)儲存條件，適當(dāng)保存；體內(nèi)實驗的?作液，建議您現(xiàn)?現(xiàn)配，當(dāng)天使?；以下溶劑前顯?的百分?指該溶劑在您配制終溶液中的體積占?；如在配制過程中出現(xiàn)沉淀、析出現(xiàn)象，可以通過加熱和/或超聲的?式助溶)1.請依序添加每種溶劑：20%HP-β-CDinsalineSolubility:6mg/mL(15.10mM);Suspendedsolution;Needultrasonic1/3MasterofBioactiveMolecules—您?邊的抑制劑?師www.MedChemEBIOLOGICALACTIVITY?物活性Abexinostat(CRA024781)?種新的泛HDAC抑制劑，主靶向HDAC1的Ki值為7nM。Abexinostat也抑制MBLAC2?解酶活性，EC50?于10nM。IC50&TargetHDAC1HDAC3/SMRTHDAC6HDAC27nM(Ki)8.2nM(Ki)17nM(Ki)19nM(Ki)HDAC10HDAC8MBLAC224nM(Ki)280nM(Ki)<10nM(EC50)體外研究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].體內(nèi)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?邊的抑制劑?師www.MedChemEMCEhasnotindependentlyconfirmedtheaccuracyofthesemethods.Theyareforreferenceonly.戶使?本產(chǎn)品發(fā)表的科研?獻?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