XAV-939-DataSheet-生命科學(xué)試劑-MedChemExpressVIP

Hotline:400-820-3792Inhibitors?Agonists?ScreeningLibrarieswww.MedChemEXAV-939Cat.No.:HY-15147CASNo.:284028-89-3分?式:C??H??F?N?OS分?量:312.31作?靶點(diǎn):β-catenin;PARP作?通路:StemCell/Wnt;CellCycle/DNADamage;Epigenetics儲(chǔ)存?式:Powder-20°C3years4°C2yearsInsolvent-80°C6months-20°C1month溶解性數(shù)據(jù)體外實(shí)驗(yàn)DMSO:10.42mg/mL(33.36mM;Needultrasonic)掃描?維碼，H2O:<0.1mg/mL(insoluble)運(yùn)?溶解?案計(jì)算器獲得適合您實(shí)驗(yàn)體系的溶解?案MassSolvent1mg5mg10mgConcentration制備儲(chǔ)備液1mM3.2019mL16.0097mL32.0195mL5mM0.6404mL3.2019mL6.4039mL10mM0.3202mL1.6010mL3.2019mL請(qǐng)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(chǔ)備液，并請(qǐng)注意儲(chǔ)備液的保存?式和期限。體內(nèi)實(shí)驗(yàn)請(qǐng)根據(jù)您的實(shí)驗(yàn)動(dòng)物和給藥?式選擇適當(dāng)?shù)娜芙?案。以下溶解?案都請(qǐng)先按照InVitro?式配制澄的儲(chǔ)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(chǔ)備液可以根據(jù)儲(chǔ)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(qǐng)依序添加每種溶劑：10%DMSO40%PEG3005%Tween-8045%salineSolubility:2mg/mL(6.40mM);Suspendedsolution;Needultrasonic此?案可獲得2mg/mL(6.40mM)的均勻懸濁液，懸濁液可?于?服和腹腔注射。以1mL?作液為例，取100μL20.0mg/mL的澄DMSO儲(chǔ)備液加到400μLPEG300中，混合均勻；向上述體系中加?50μLTween-80，混合均勻；然后繼續(xù)加?450μL?理鹽?定容?1mL。1/4www.MedChemEwww.MedChemE2.請(qǐng)依序添加每種溶劑：10%DMSO90%(20%SBE-β-CDinsaline)Solubility:2mg/mL(6.40mM);Suspendedsolution;Needultrasonic此?案可獲得2mg/mL(6.40mM)的均勻懸濁液，懸濁液可?于?服和腹腔注射。以1mL?作液為例，取100μL20.0mg/mL的澄DMSO儲(chǔ)備液加到900μL20%的SBE-β-CD?理鹽??溶3.液中，混合均勻。請(qǐng)依序添加每種溶劑：10%DMSO90%cornoilSolubility:≥1.04mg/mL(3.33mM);Clearsolution此?案可獲得≥1.04mg/mL(3.33mM，飽和度未知)的澄溶液，此?案不適?于實(shí)驗(yàn)周期在半個(gè)?以上的實(shí)驗(yàn)。以1mL?作液為例，取100μL10.4mg/mL的澄DMSO儲(chǔ)備液加到900μL??油中，混合均勻。BIOLOGICALACTIVITY?物活性XAV-939有效的tankyrase抑制劑，靶向Wnt/β-catenin途徑。XAV-939通過tankyrase1和tankyrase2(IC50分別為5和2nM)來穩(wěn)定axin，從?刺激β-catenin降解。XAV939與TNKS1和TNKS2的催化(PARP)域緊密結(jié)合(Kd分別為99和93nM)。IC50&TargetTNKS2TNKS1ARTD2ARTD12nM(IC50)5nM(IC50)479nM(IC50)5500nM(IC50)體外研究XAV939alsobindstorecombinantPARP1,althoughwithasignificantlylowerbindingaffinity(Kd=1.2μM).XAV939(1μM)stronglyinhibisSTFactivityinSW480cells,Wnt3a-stimulatedSTFactivityinHEK293cells,butdoesnotaffectCRE,NF-κBorTGF-βluciferasereporters.XAV939regulatesaxinlevelsthroughtankyraseinhibitioninHEK293cell[1].XAV939(0.5μM,1.0μM)reducesDNA-PKcsproteinlevels50%oftherelativeDMSOcontrolinhumanlymphoblasts[2].XAV939inducesasecondwaveofpro-cardiomyocytegeneexpressionasshownbyincreasedMesp1andIsl1expression2to4daysafterWntinhibition,andbyincreasedNkx2.5expression4to6daysafterXAV939addition[3].XAV-939(10nM)hasasuppressiveeffectonelevatedMMP-13levelsinbothIL-1β-inducedSW1353cells[4].體內(nèi)研究XAV-939(3mL,10nM)hasasuppressiveeffectonelevatedMMP-13levelsintheratOAmodel[4].XAV-939(1mg/mL,i.p.)amelioratesthepsoriasiformskindiseaseinducedbyIMQ.XAV-939resultsinasignificantdecreaseintheIMQ-inducedepidermalhyperplasia(indicatedbyacanthosis)anddermalinflammatoryinfiltratesinmice[5].PROTOCOLKinaseAssay[1]Toassesstheeffectofcompoundsonauto-PARsylationofTNKS,1μMGSTfusionproteincontainingtheSAMdomainandthePARPdomainofTNKS2(a.a.872-1166)ismixedwith5μMbiotin-NAD+and2μMXAV939orLDW643at30°Cfor2.5hours.SamplesareresolvedbySDSandprobedwithstreptavidinAlexaFluor680.ToassessPARsylationofaxin,recombinantfull-lengthTNKS2(expressed/purifiedasaN-terminalHis-taggedproteininbacteria)isincubatedwithGST-axin1(1-280)inthepresenceofbiotin-NAD+withorwithoutXAV939.TheproductsareresolvedandprobedwithStreptavidin-HRPandimagedusingaAlphaInnotechimager.ToassesstheeffectofXAV939,IWR-1-enod,IWR-1-exo,andABT-888onauto-2/4www.MedChemEwww.MedChemEPARsylationofTNKS2,His-taggedfull-lengthTNKS2isincubatedwith5μMbiotin-NAD+and3mMofindicatedcompounds.TheproductsareresolvedandprobedwithStreptavidin-HRP.LC/MS-basedhighthroughputauto-PARsylationassaysforPARP1,PARP2,TNKS1,andTNKS2aresetuptomonitortheformationofnicotinamide(aby-productofthePARsylationreaction)inthepresenceofsmallmoleculeinhibitors.MCEhasnotindependentlyconfirmedtheaccuracyofthesemethods.Theyareforreferenceonly.CellAssay[4]HumanSW1353chondrosarcomacellsareseededin96-wellplates(1×104cells/well)andaretreatedwithIcariin(0,5,10,20,40,80,or100μM).After24h,20μLMTT(5mg/mLinPBS)isaddedtoeachwellandplatesareincubatedat37°Cforanother4h.Supernatantsarethenremoved,and150μLDMSOisaddedtoeachwell.Afterplatesareshakenfor10min,opticaldensityvaluesmeasuredat570nmarerecordedusinganELISAreader.MCEhasnotindependentlyconfirmedtheaccuracyofthesemethods.Theyareforreferenceonly.AnimalC57BL/6Jmicearekeptunderspecificpathogen-freeconditions.XAV-939isinjectedi.p.,atadoseof1Administration[5]mg/mL,onceadayforsevenconsecutivedaysofIMQtreatment(injectionvolume100μL).Controlmiceareinjectedwith100μL10%DMSO/90%0.9%NaCl,thesolventforXAV-939.Toameliorateanysufferingofmiceobservedthroughouttheseexperimentalstudies,theyareeuthanizedbyCO2inhalation.MCEhasnotindependentlyconfirmedtheaccuracyofthesemethods.Theyareforreferenceonly.戶使?本產(chǎn)品發(fā)表的科研?獻(xiàn)?SciBull.64(2019)986-997.?ProcNatlAcadSciUSA.2021Jan12;118(2):e2009539118.?ProcNatlAcadSciUSA.2016Mar29;113(13):E1898-906.?JInvestDermatol.2019Jan;139(1):224-234.?BMCBiol.2020Oct27;18(1):151.Seemorecustomervalidationsonwww.MedChemEREFERENCES[1].HuangSM,etal.TankyraseinhibitionstabilizesaxinandantagonizesWntsignalling.Nature.2009Oct1;461(7264):614-620.[2].DregallaRC,etal.Regulatoryrolesoftankyrase1attelomeresandinDNArepair:suppressionofT-SCEandstabilizationofDNA-PKcs.Aging(AlbanyNY).2010Oct;2(10):691-708.[3].AoA,etal.DMH1,aNovelBMPSmallMoleculeInhibitor,IncreasesCardiomyocyteProgenitorsandPromotesCardiacDifferentiationinMouseEmbryonicStemCells.,PLoSOne.2012;7(7):e41627.[4].ZengL,etal.Chondroprotectiveeffectsandmulti-targetmechanismsofIcariininIL-1beta-inducedhumanSW1353chondrosarcomacellsandaratosteoarthritismodel.IntImmunopharmacol.2014Jan;18(1):175-81.[5].BaiJ,etal.EpigeneticdownregulationofSFRP4contributestoepidermalhyperplasiainpsoriasis.JImmunol.2015May1;194(9):4185-98.doi: