Anticancer-agent-81-DataSheet-生命科學(xué)試劑-MedChemExpress

Hotline:400-820-3792Inhibitors?ScreeningLibraries?Proteinswww.MedChemEAnticanceragent81Cat.No.:HY-151207分?式:C??H??N?O?分?量:762.89作?靶點(diǎn):Apoptosis;ADCCytotoxin作?通路:Apoptosis;Antibody-drugConjugate/ADCRelated儲(chǔ)存?式:PleasestoretheproductundertherecommendedconditionsintheCertificateofAnalysis.BIOLOGICALACTIVITY?物活性Anticanceragent81(Compound37b3)?種抗癌劑，能誘導(dǎo)腫瘤細(xì)胞周期阻滯和凋亡(apoptosis)。Anticanceragent81可作為有效載荷與Trastuzumab(HY-P9907)結(jié)合得到抗體偶聯(lián)藥物(ADC)T-PBA。T-PBA維持了Trastuzumab的靶向模式和內(nèi)化能?。體外研究Anticanceragent81(Compound37b3)(72h)showscytotoxicityagainstSKOV3,MDA-MB-231andNCI-N87cells[1].Anticanceragent81(0-5μM)inducesDNAinterstrandcross-linking[1].Anticanceragent81(0-3nM;24h)arrestsSKOV3cellcycleattheS-phase[1].Anticanceragent81(0-3nM;48h)inducesSKOV3cellapoptosis[1].Anticanceragent81(25nM;12h)actsonDNAinthenucleusafterenteringSKOV3cellsandMDA-MB-231cells[1].Anticanceragent81inducesDDRsignalingpathwaysviacross-linkingDNAandthenactivatesthecaspasecascadeandPARP,finallyleadingtocellcyclearrestandapoptosis[1].Anticanceragent81covalentlybindstotheDNAsequencesandactsonthemajorgrooveofDNA[1].CellCytotoxicityAssay[1]CellLine:SKOV3,MDA-MB-231andNCI-N87Concentration:IncubationTime:72hResult:ShowedcytotoxicitywithIC50sof0.17±0.07,0.90±0.11and0.94±0.14nMagainstSKOV3,MDA-MB-231andNCI-N87cells,respectively.1/3MasterofBioactiveMolecules—您?邊的抑制劑?師www.MedChemECellCycleAnalysis[1]CellLine:SKOV3Concentration:0.33,1and3nMIncubationTime:24hResult:InhibitedthecellcycleattheS-phase.ApoptosisAnalysis[1]CellLine:SKOV3Concentration:0.33,1and3nMIncubationTime:48hResult:Inducedcellapoptosisinaconcentration-dependentmanner.WesternBlotAnalysis[1]CellLine:SKOV3andNCI-N87Concentration:0.02,0.1,0.5,2.5and12.5nMIncubationTime:48hResult:Inducedthephosphorylationofhistone2AX(γ-H2AX)inadose-dependentmanner.InducedthecleavageofPARP(cPARP)andcaspase3(cCas3)inaconcentration-dependentmanner.體內(nèi)研究T-PBA(1-10mg/kg;i.v.;every3daysfor4times)couldsignificantlydelaytumorgrowthintwoHer2-positivexenograftmodelsinmicewithoutobvioustoxicityandsideeffects,andtheeffectisbetterthanTrastuzumab[1].AnimalModel:Femalebalb/cnudemice,SKOV3andNCI-N87tumormodel[1]Dosage:1,5and10mg/kgAdministration:Tailveininjectionondays0,3,6,and9Result:Inhibitedtumorgrowthinadose-dependentmanner(57.5%inhibitionat1mg/kg,70.0%inhibitionat5mg/kg,and91.5%inhibitionat10mg/kginSKOV3tumormodel;thetumorgrowthinhibitoryratewas50.2%for1mg/kg,88.0%for5mg/kg,and97.1%for10mg/kginNCI-N87tumormodel)withoutobvioussideeffects.REFERENCES2/3MasterofBioactiveMolecules—您?邊的抑制劑?師www.MedChemE[1].LaiW,etal.Design,Synthesis,andBioevaluationofaNovelHybridMolecularPyrrolobenzodiazepine-AnthracenecarboxyimideasaPayloadforAntibody-DrugConjugate.JMedChem.2022Aug18.McePdfHeightCaution:Producthasnotbeenfullyvalidate