Hotline:400-820-3792Inhibitors ? ScreeningLibraries ? Proteinswww.MedChemESV119Cat.No.:HY-177345CASNo.:913815-82-4分子式:C??H??N?O?分子量:403.56作用靶點(diǎn):SigmaReceptor;Apoptosis;Caspase作用通路:NeuronalSignaling;Apoptosis儲存方式:PleasestoretheproductundertherecommendedconditionsintheCertificateofAnalysis.BIOLOGICALACTIVITY生物活性SV119是一種選擇性σ-2受體(σ?receptor)配體(Ki≈5-10nM)。SV119通過激活caspase-3并促進(jìn)線粒體去極化，誘導(dǎo)多種人類癌細(xì)胞系凋亡(apoptosis)。SV119可以增強(qiáng)Paclitaxel(HY-B0015)等化療藥物的作用，增強(qiáng)對腫瘤細(xì)胞的細(xì)胞毒性。SV119在小鼠異種移植模型中單獨(dú)使用或聯(lián)合使用均可顯著抑制腫瘤生長。SV119可用于乳腺癌、前列腺癌和胰腺癌等癌癥的研究。IC50&TargetCaspase3Caspase-7體外研究SV119(0-10μM)inducescaspase-3/7dependentapoptosisagainstPanc1,CFPAC,ASPC,PancO2cells[1].SV119hasanEC50of23.3μMinMDA-MB-231cells(100%maximalcytotoxicity)and17.6μMinMCF-7cells(100%maximalcytotoxicity)forsigma-2receptor[2].SV119(30μM,24-48h)decreasesproteinlevelsoffull-lengthBid[2].SV119(0-10μM,24h)increasesapoptosisinASPC-1,CFPAC,Panc1,PancO2cellsincombinationwithGemcitabine(HY-17026)andPaclitaxel(HY-B0015)[4].SV119(10mM,1.5h)reducesthefluorescenceofcancerstemcell(CSC)inMDA-MB-435cells[5].SV119(SV119-PEG-AuNC/DOX,coverdensity(50%))significantlyreducestheformationandnumberofmammarycellsanddecreasesthestemnessofbreastCSCsincombinationwithphotothermalandchemotherapyinMDA-MB-435cells[5].ApoptosisAnalysis[4]CellLine:Panc02cells1/3 MasterofBioactiveMolecules—您身邊的抑制劑大師www.MedChemEConcentration:0,10μMIncubationTime:24hResult:InducedapoptosisincellsthatwerebothinG0aswellasinG1toG2/SphaseofthecellcycleincombinationwithGemcitabineandPaclitaxel,withmeanTUNEL-positivityrangedfrom16.1%to18.6%at10μM.IncreasedmeanTUNEL-positivityrangedfrom26.5%to70.5%ingemcitabinecombination(50nM)andfrom26.6%to53.8%inpaclitaxelcombination(50nM).InducedmoderateapoptosisinKi67negativecells(G0phase).體內(nèi)研究SV119(1mg/mouse,i.p.,once;everyotherday/daily,for7days)increasesapoptosisandslowstumorgrowthincombinationwithGemcitabineorPaclitaxelinpancreatictumorsC57BL/6micemodel[4].AnimalModel:Panc-02(106)pancreatictumorsC57BL/6mice(8-12weeksold)model[4]Dosage:1mg/mouseAdministration:i.p.,onceResult:Increasedapoptosisthatweretreatedwithconventionalchemotherapy(GemcitabineorPaclitaxel).AnimalModel:Panc-02(106)pancreatictumorsC57BL/6mice(8-12weeksold)model[4]Dosage:1mg/mouseandweeklygemcitabine(3mg/mouse,i.p.fortwoweeks)/dailypaclitaxel(0.3mg/mouse,i.p.for7days)Administration:i.p.everyotherday/daily,for7daysResult:Demonstratedanonsignificanttumorvolumeandsurvivaladvantage,significantlyslowedtumorgrowthincombinationwithGemcitabineandPaclitaxel.REFERENCESKashiwagiH,etal.Selectivesigma-2ligandspreferentiallybindtopancreaticadenocarcinomas:applicationsindiagnosticimagingandtherapy.MolCancer.2007Jul15;6:48.ZongyiLiu,etal.Sigma-2receptor-inducedcelldeath:anovelapproachtotriple-negativebreastcancertreatment.[abstract].In:Proceedingsofthe106thAnnualMeetingoftheAmericanAssociationforCancerResearch;2015Apr18-22;Philadelphia,PA.Philadelphia(PA):AACR;CancerRes2015;75(15Suppl):Abstractnr5428.HiroyukiKashiwagi,etal.Targeteddeliveryofproapoptotictherapeuticsinpancreascancer.CancerRes1May2008;68(9_Supplement):4084.KashiwagiH,etal.Sigma-2receptorligandspotentiateconventionalchemotherapiesandimprovesurvivalinmodelsofpancreaticadenocarcinoma.JTranslMed.2009Mar26;7:24.2/3 MasterofBioactiveMolecules—您身邊的抑制劑大師www.MedChemESunT,etal.UsingSV119-goldnanocageconjugatestoeradicatecancerstemcellsthroughacombinationofphotothermalandchemotherapies.AdvHealthcMater.2014Aug;3(8):1283-91.McePdfHeightCauti