GSK-923295-DataSheet-生命科学试剂-MedChemExpress

Hotline:400-820-3792Inhibitors•ScreeningLibraries•Proteinswww.MedChemEGSK-923295Cat.No.:HY-10299CASNo.:1088965-37-0分⼦式:C₃₂H₃₈ClN₅O₄分⼦量:592.13作⽤靶点:Kinesin;Apoptosis作⽤通路:CellCycle/DNADamage;Cytoskeleton;Apoptosis储存⽅式:Powder-20°C3years4°C2yearsInsolvent-80°C6months-20°C1month溶解性数据体外实验DMSO:30mg/mL(50.66mM;Needultrasonic)MassSolvent1mg5mg10mgConcentration制备储备液1mM1.6888mL8.4441mL16.8882mL5mM0.3378mL1.6888mL3.3776mL10mM0.1689mL0.8444mL1.6888mL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；⼀旦配成溶液，请分装保存，避免反复冻融造成的产品失效。储备液的保存⽅式和期限：-80°C,6months;-20°C,1month。-80°C储存时，请在6个⽉内使⽤，-20°C储存时，请在1个⽉内使⽤。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：10%DMSO>>40%PEG300>>5%Tween-80>>45%salineSolubility:≥3mg/mL(5.07mM);Clearsolution1/3MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemE2.请依序添加每种溶剂：10%DMSO>>90%(20%SBE-β-CDinsaline)Solubility:3mg/mL(5.07mM);Suspendedsolution;Needultrasonic3.请依序添加每种溶剂：10%DMSO>>90%cornoilSolubility:≥3mg/mL(5.07mM);ClearsolutionBIOLOGICALACTIVITY⽣物活性GSK-923295⼀种特异性的变构丝粒相关蛋⽩-E(CENP-E)驱动蛋⽩ATPase活性抑制剂，作⽤于⼈类和⽝类此酶，Ki分别为3.2±0.2nM和1.6±0.1nM。IC50&TargetCENP-E1.6nM(Ki,CanineCENP-E)体外研究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].体内研究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—您⾝边的抑制剂⼤师www.MedChemEMCEhasnotindependentlyconfirmedtheaccuracyofthesemethods.Theyareforreferenceonly.户使⽤本产品发表的科研⽂献•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