Hotline:400-820-3792Inhibitors?ScreeningLibraries?Proteinswww.MedChemEGSK-923295Cat.No.:HY-10299CASNo.:1088965-37-0分?式:C??H??ClN?O?分?量:592.13作?靶點(diǎn):Kinesin;Apoptosis作?通路:CellCycle/DNADamage;Cytoskeleton;Apoptosis儲存?式:Powder-20°C3years4°C2yearsInsolvent-80°C6months-20°C1month溶解性數(shù)據(jù)體外實(shí)驗(yàn)DMSO:30mg/mL(50.66mM;Needultrasonic)MassSolvent1mg5mg10mgConcentration制備儲備液1mM1.6888mL8.4441mL16.8882mL5mM0.3378mL1.6888mL3.3776mL10mM0.1689mL0.8444mL1.6888mL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；?旦配成溶液，請分裝保存，避免反復(fù)凍融造成的產(chǎn)品失效。儲備液的保存?式和期限：-80°C,6months;-20°C,1month。-80°C儲存時，請在6個?內(nèi)使?，-20°C儲存時，請在1個?內(nèi)使?。體內(nèi)實(shí)驗(yàn)請根據(jù)您的實(shí)驗(yàn)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(shí)驗(yàn)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(shí)驗(yàn)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：10%DMSO>>40%PEG300>>5%Tween-80>>45%salineSolubility:≥3mg/mL(5.07mM);Clearsolution1/3MasterofBioactiveMolecules—您?邊的抑制劑?師www.MedChemE2.請依序添加每種溶劑：10%DMSO>>90%(20%SBE-β-CDinsaline)Solubility:3mg/mL(5.07mM);Suspendedsolution;Needultrasonic3.請依序添加每種溶劑：10%DMSO>>90%cornoilSolubility:≥3mg/mL(5.07mM);ClearsolutionBIOLOGICALACTIVITY?物活性GSK-923295?種特異性的變構(gòu)絲粒相關(guān)蛋?-E(CENP-E)驅(qū)動蛋?ATPase活性抑制劑，作?于?類和?類此酶，Ki分別為3.2±0.2nM和1.6±0.1nM。IC50&TargetCENP-E1.6nM(Ki,CanineCENP-E)體外研究GSK-923295(GSK923295)isafirst-in-class,specific,allostericinhibitorofCENP-Ekinesinmotorfunction.GSK923295isuncompetitivewithbothATPandMT,inhibitingCENP-EMT-stimulatedATPaseactivitywithaKiof3.2±0.2nMand1.6±0.1nMforhumanandcanine,respectively.GSK923295inhibitsreleaseofinorganicphosphateandstabilizedCENP-Emotordomaininteractionwithmicrotubules[1].GSK923295hasbroadgrowthinhibitoryactivityinapanelof237cancercelllinesandproducessignificanttumorgrowth-delayin8ofthe11mousexenografttumormodelswithIC50sof17.2nM,55.6nM,42nM,and51.9nMforSW48,RKO(BRAFmutant),SW620(KRASmutant),andHCT116(KRASmutant),respectively[2].GSK923295isapotentandselectivesmallmoleculeinhibitorofhumanCENPEwithaKiof3.2nM.GSK923295demonstratesbroadefficacyagainstapanelof19humanneuroblastomaderivedcelllineswithanaveragegrowthIC50of41nM[3].體內(nèi)研究XenograftsofmicetreatedwithGSK-923295(GSK923295)showssignificanttumorgrowthdelaycomparedtothecontrolarm(NB-EBc1p[3].PROTOCOLCellAssay[1]Cell-growthinhibitionassaysareperformedbyMDSin384-wellplates,andDNAcontentoffixedcellsstainedwithDAPIusinganIncell1000(GE)isanalyzed.DNAcontentisdetermined24hafterseeding(T0)andafterexposuretovaryingconcentrationsofGSK-923295(0.01nM,0.1nM,1nM,10nM,100nM,1μM,10μM,and100μM)foranadditional72h(T72).AllT72measurementsarenormalizedtoT0.CurvesareanalyzedusingtheXLfitcurve-fittingtooltodeterminetheconcentrationofGSK923295yielding50%growthinhibitionrelativetoT0andYmaxvalues(GI50)[1].MCEhasnotindependentlyconfirmedtheaccuracyofthesemethods.Theyareforreferenceonly.AnimalMice[3]Administration[3]CB17scidmiceareusedtopropagatesubcutaneouslyimplantedneuroblastomatumors.Tumordiametersaremeasuredusingcalipers.Tumorvolumesarecalculated.Oncetumorvolumeexceeds200mm3,micearerandomized(n=10perarm)toreceiveeitherGSK923295125mg/kgIPorvehicle(96%acidifiedwater,2%DMAC,2%CREM)foratotalof6dosesusinga3dayson,4daysoff,3daysonregimen.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(xiàn)?Science.2015May15;348(6236):799-803.?Science.2014Oct10;346(6206):244-7.?NatCellBiol.2015Sep;17(9):1134-44.?NatCellBiol.2014Dec;16(12):1249-56.?NatCellBiol.2012Feb5;14(3):295-303.Seemorecustomervalidationsonwww.MedChemEREFERENCES[1].WoodKW,etal.Antitumoractivityofanallostericinhibitorofcentromere-associatedprotein-E.ProcNatlAcadSciUSA.2010Mar30;107(13):5839-44.[2].MayesPA,etal.Mitogen-activatedproteinkinase(MEK/ERK)inhibitionsensitizescancercellstocentromere-associatedproteinE(CENP-E)inhibition.IntJCancer.2013Feb1;132(3):E149-57.[3].BalamuthNJ,etal.Serialtranscriptomeanalysisandcross-speciesintegrationidentifiescentromere-associatedproteinEasanovelneuroblastomatarget.CancerRes.2010Ap