Trabectedin-Ecteinascidin-743-DataSheet-生命科學試劑-MedChemExpress

Hotline:400-820-3792Inhibitors?ScreeningLibraries?Proteinswww.MedChemETrabectedinCat.No.:HY-50936CASNo.:114899-77-3Synonyms:Ecteinascidin743;ET-743分?式:C??H??N?O??S分?量:761.84作?靶點:ReactiveOxygenSpecies;Apoptosis作?通路:Immunology/Inflammation;MetabolicEnzyme/Protease;NF-κB;Apoptosis儲存?式:-20°C,protectfromlight,storedundernitrogen*該產(chǎn)品在溶液狀態(tài)不穩(wěn)定，建議您現(xiàn)?現(xiàn)配，即刻使?。溶解性數(shù)據(jù)體外實驗DMSO:33.33mg/mL(43.75mM;Needultrasonic)MassSolvent1mg5mg10mgConcentration制備儲備液1mM1.3126mL6.5631mL13.1261mL5mM0.2625mL1.3126mL2.6252mL10mM0.1313mL0.6563mL1.3126mL請根據(jù)產(chǎn)品在不同溶劑中的溶解度，選擇合適的溶劑配制儲備液；該產(chǎn)品在溶液狀態(tài)不穩(wěn)定，建議您現(xiàn)?現(xiàn)配，即刻使?.體內實驗請根據(jù)您的實驗動物和給藥?式選擇適當?shù)娜芙?案。以下溶解?案都請先按照InVitro?式配制澄的儲備液，再依次添加助溶劑：(為保證實驗結果的可靠性，澄的儲備液可以根據(jù)儲存條件，適當保存；體內實驗的?作液，建議您現(xiàn)?現(xiàn)配，當天使?；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.請依序添加每種溶劑：10%DMSO>>90%(20%SBE-β-CDinsaline)Solubility:≥2.5mg/mL(3.28mM);Clearsolution2.請依序添加每種溶劑：10%DMSO>>90%cornoil1/3MasterofBioactiveMolecules—您?邊的抑制劑?師www.MedChemESolubility:≥2.5mg/mL(3.28mM);Clearsolution3.請依序添加每種溶劑：5%DMSO>>40%PEG300>>5%Tween-80>>50%salineSolubility:≥2.5mg/mL(3.28mM);ClearsolutionBIOLOGICALACTIVITY?物活性Trabectedin(Ecteinascidin743;ET-743)?種四氫異喹啉?物堿，具有有效的抗腫瘤活性。Trabectedin與DNA的?溝結合，阻斷應激誘導的蛋?質的轉錄，誘導DNA?架裂解和癌細胞凋亡(apoptosis)，并增加MCF-7和MDA-MB-453細胞中ROS的?成。Trabectedin可?于軟組織?瘤和巢癌的研究。IC50&TargetIC50:0.1nM(MX-1cells),1.5nM(MCF7cells)and3.7nM(MCF7/DXRcells)[1]Reactiveoxygenspecies(ROS)[2]Apoptosis[2]體外研究Trabectedin(ET-743;10nM;24-72hours;MCF7cells)treatmentresultsincellaccumulationinlateStoG2phase[1].TrabectedininhibitscellgrowthofMX-1,MCF7andMCF7/DXRcellswithIC50valuesof0.1nM,1.5nMand3.7nM,respectively[1].Trabectedininducescytotoxicityandapoptosisinbothbreastcancercellsinatimeandconcentration-dependentmanner.Theexpressionlevelsofthedeathreceptorpathwaymolecules,TRAIL-R1/DR4,TRAIL-R2/DR5,FAS/TNFRSF6,TNFRI/TNFRSF1A,andFADDaresignificantlyincreasedby2.6-,3.1-,1.7-,11.2-and4.0-foldbyTrabectedintreatmentinMCF-7cells.InMDA-MB-453cells,themitochondrialpathwayrelatedpro-apoptoticproteinsBax,Bad,Cytochromec,Smac/DIABLO,andCleavedCaspase-3expressionsareinducedby4.2-,3.6-,4.8-,4.5-,and4.4-fold,andtheexpressionlevelsofanti-apoptoticproteinsBcl-2andBcl-XLarereducedby4.8-and5.2-foldinMDA-MB-453cells[2].InvitrotreatmentwithnoncytotoxicconcentrationsofTrabectedinselectivelyinhibitstheproductionofCCL2,CXCL8,IL-6,VEGF,andPTX3bymyxoidliposarcoma(MLS)primarytumorculturesand/orcelllines[3].CellCycleAnalysis[1]CellLine:MCF7cellsConcentration:10nMIncubationTime:24hours,48hours,72hoursResult:LedtopronouncedS-G2-Maccumulation.體內研究Trabectedin(ET-743;30-50μg/kg;intravenousinjection;everythreedays;femaleathymicnudemice)treatmentincreasestheantitumoreffectsinnudemicebearingMX-1mammarycarcinomaxenograftswithoutincreasingtoxicity[1].Axenograftmousemodelofhumanmyxoidliposarcoma(MLS)showsmarkedreductionofCCL2,CXCL8,CD68+infiltratingmacrophages,CD31+tumorvessels,andpartialdecreaseofPTX3afterTrabectedintreatment[3].2/3MasterofBioactiveMolecules—您?邊的抑制劑?師www.MedChemEAnimalModel:Femaleathymicnudemicebearingthenu/nugene(5-6weeksold,18-20g)injectedwithMX-1cells[1]Dosage:30μg/kg,40μg/kg,50μg/kgAdministration:Intravenousinjection;everythreedaysResult:IncreasedtheantitumoreffectsinnudemicebearingMX-1mammarycarcinomaxenograftswithoutincreasingtoxicity.REFERENCES[1].TakahashiN,etal.Sequence-dependentsynergisticcytotoxicityofecteinascidin-743andNSC125973inhumanbreastcancercelllinesinvitroandinvivo.CancerRes.2002Dec1;62(23):6909-15.[2].GermanoG,etal.Antitumorandanti-inflammatoryeffectsoftrabectedinonhumanmyxoidliposarcomacells.CancerRes.2010Mar15;70(6):2235-44.[3].AtmacaH,etal.AdiverseinductionofapoptosisbytrabectedininMCF-7(HER2-/ER+)andMDA-MB-453(HER2+/ER-)breastcancercells.ToxicolLett.2013Jun20;221(2):128-136.