IWR-1-GMP-endo-IWR-1-GMP-生命科學(xué)試劑-MCE

Hotline:400-820-3792Inhibitors ? ScreeningLibraries ? Proteinswww.MedChemEIWR-1(GMP)Cat.No.:HY-12238GCASNo.:1127442-82-3Synonyms:endo-IWR1(GMP);IWR-1-endo(GMP)分子式:C??H??N?O?分子量:409.44作用靶點(diǎn):Organoid;Wnt作用通路:StemCell/Wnt儲(chǔ)存方式:PleasestoretheproductundertherecommendedconditionsintheCertificateofAnalysis.BIOLOGICALACTIVITY生物活性IWR-1(IWR-1-endo)(GMP)是GMP級(jí)別的IWR-1(HY-12238)。GMP級(jí)別的小分子可用做細(xì)胞療法中的輔助試劑。IWR-1(IWR-1-endo)是一種靶向Wnt/β-catenin的tankyrase抑制劑(IC50=180nM)。IWR-1參與經(jīng)典Wnt信號(hào)轉(zhuǎn)導(dǎo)的關(guān)鍵步驟，即β-catenin轉(zhuǎn)位至細(xì)胞核，隨后激活TCF/LEF并表達(dá)Wnt/β-catenin下游靶標(biāo)。IWR-1誘導(dǎo)Axin蛋白水平升高，同時(shí)伴隨β-catenin水平升高。IWR-1可用于抗腫瘤研究，以及骨肉瘤、結(jié)直腸癌和牛皮癬等疾病的研究[1][2][4]。體外研究IWR-1(GMP)iscytotoxicforosteosarcomacancerstem-likecells(CSCs)[1].IWR-1(GMP)suppressescellmigration,invasion,andmatrixmetalloproteinaseactivitiesofcolorectalcancercelllines[2].IWR-1(GMP)(2.5-10μM,48-96h)iseffectiveinreducingspheres’viabilityinaconcentration-andtime-dependentmannerinparentalandspheresfromMG-63andMNNG-HOScelllines[1].IWR-1(GMP)(10μM,96h)increasesthenumberofTUNEL-positivecells,reaching4.65-and15.83-folddifferencesrelativetocontrolat96handpromotedtheactivationofcaspases3/7reaching2.15-and1.27-foldinMG-63andMNNG-HOSspheres[1].IWR-1(GMP)(10μM,48h)inducesacellcyclearrestintheG2/MphaseinspheresderivedfromMG-63andMNNG-HOScelllinesandincreasesthepercentageofcellsintheSphaseslightly[1].IWR-1(GMP)(10μM,48h)inhibitssecondarysphere-formingefficacybyapproximately53%and55%ofthefirst-generation7-dayoldspheresinMG-6t4andMNNG-HOScells[1].IWR-1(GMP)(5-50μM,24-48h)decreasestheproliferationofHCT116cellsinadose-andtime-dependentmanner[2].IWR-1(GMP)(5-50μM,24-48h)inhibitsTNF-α-stimulatedmigrationinHCT116andHT29cells[2].1/4 MasterofBioactiveMolecules—您身邊的抑制劑大師www.MedChemECellViabilityAssay[1]CellLine:MG-63andMNNG-HOSspheresandparentcellsConcentration:2.5,5,7.5,10μMIncubationTime:48and96hResult:Reducedcellviabilitywhenconcentrationishigherthan5μM.Elicitedmorethan70%reductionofcellviabilityinspheresderivedfromthetwocelllinesat96hwith10μM.HadminimaleffectonparentalcellssincetheWnt/β-cateninsignalingisabsentinthesecells.IncreasedthesusceptibilityofspherestowardsDoxorubicin(HY-15142)whentreatedincombinationwithincreasingconcentrationsofDoxorubicin(0.01-100μM).WesternBlotAnalysis[1]CellLine:MG-63andMNNG-HOSspheresandparentcellsConcentration:10μMIncubationTime:96hResult:LedtoanupregulationofBakandadownregulationofBcl-2(keyproteinsinvolvedinmitochondrial-dependentapoptosis),whichcontributestoaBak/Bcl-2ratio>1thatpronethecellstoundergoapoptosis.RT-PCR[1]CellLine:MG-63andMNNG-HOSspheresandparentcellsConcentration:10μMIncubationTime:96hResult:LedtoanupregulationofBakandadownregulationofBcl-2(keyproteinsinvolvedinmitochondrial-dependentapoptosis),whichcontributestoaBak/Bcl-2ratio>1thatpronethecellstoundergoapoptosis.Resultsinahigherβ-cateninnuclear/cytoplasmicratioinspheres,indicatinganincreasedWnt/β-cateninpathwayactivationinosteosarcomaspheres.StabilizedAxin2proteinlevels.DiminishedtheproteinexpressionlevelsofCyclinD1inbothparentalcellsandspheres.WesternBlotAnalysis[2]CellLine:HCT116cellsConcentration:5,10,20,50μM2/4 MasterofBioactiveMolecules—您身邊的抑制劑大師www.MedChemEIncubationTime:0,4,8,24,48hResult:IncreasedthelevelsoftheepithelialmarkerE-cadherinwhilstdecreasedthemesenchymalmarkersN-cadherin,Vimentin,andSnaildose-andtime-dependently.InhibitedtheEMTprocessinHCT116cellseffectively.Decreasedβ-cateninexpressionandinhibitedtheEMT-likeexpressionalchangeswherebydecreasingN-cadherinandSnailandincreasingE-cadherinexpressions,eveninthepresenceofTNF-α(HY-P1860)(10ng/mLfor24h)-inducedEMTstimulation.DecreasedthephosphorylationofAktinaconcentration-andtime-dependentmanner.Decreasedthesurvivingexpressioninaconcentration-andtime-dependentmanner,therebypromotingtumorproliferationdirectlyorindirectlythroughregulatingcancercellhomeostasis.ReducedMMPactivitiesonlywhensurvivingwassuppressed.體內(nèi)研究IWR-1(5mg/kg,intratumorally,each2dfor12d)inducesamarkedinhibitionoftumorgrowthinosteosarcomamousemodel[1].IWR-1(GMP)(10mg/kg,s.c.,ondays1,3,5)amelioratesIL-36γ(2μg/mouseondays1,3,5)-mediatedexacerbationofpsoriaticskinlesionsinanImiquimod(IMQ)(HY-B0180)-inducedpsoriasis-likemicemodel[3].AnimalModel:Immunocompromisednudemice(6-weekoldfemaleSwissnude)wereinjectedsub-cutaneouslythepGL4-transfectedMNNG-HOScells(2×106cells/100mLPBS)[1]Dosage:5mg/kgAdministration:Intratumorally,each2dfor12dResult:Resultedinslowertumorgrowthrateandreductionintumorsizeby73%and71%incomparisontocontrolandtoDoxorubicin-treated(8mg/kg,i.p.,each4dfor12d)groups.EnhancedthetherapeuticefficacyofDoxorubicinshownbyagreaterreductionoftumorburdenattheendofthetreatmentinoppositetoDoxorubicinalone.AnimalModel:Balb/cmice(aged6-8weeks)withshavenbackandtreatedwithadailytopicaldoseofIMQcream[3]Dosage:10mg/kgAdministration:Subcutaneousinjection(s.c.)ondays1,3,5Result:Increasedepidermalthickeningwithkeratinocytethickness.SignificantlydiminishedtheeffectofIMQonhyperplasiaintheIMQ+IWR-1group.AmelioratedthepathologicalchangesinIL-36γ-inducedpsoriasiformskinlesion.3/4 MasterofBioactiveMolecules—您身邊的抑制劑大師www.MedChemEReversedIL-36γ-mediatedupregulationofinflammatoryfactors(IL-17AandIFN-γ)inpsoriaticlesions.ReversedIL-36γ-mediatedupregulationofβ-cateninandDKK1expression.客戶使用本產(chǎn)品發(fā)表的科研文獻(xiàn)CellStemCell.2025Jan7:S1934-5909(24)00450-8.AdvFunctMater.2023Dec22.NanoToday.21September2022.NatCommun.2024May23;15(1):4393.SciTotalEnviron.2022Feb25;809:152102.Seemorecustomervalidationsonwww.MedChemEREFERENCESSaraR.Martins-Neves,etal.,IWR-1,atankyraseinhibitor,attenuatesWnt/β-cateninsignalingincancerstem-likecellsandinhibitsinvivothegrowthofasubcutaneoushumanosteosarcomaxenograft,CancerLetters,Volume414,2018,Pages1-15,ISSN0304-3835.LeeSC,etal.,