Z-VAD-FMKisacell-permeable,pan-caspaseinhibitor.CustomerValidation•CancerLett.2017Feb16;393:22-32.•CancerLett.2016Aug28;379(1):134-142.•AnalChem.2017Sep19;89(18):9788-9796.•EnvironSciTechnol.2017Dec5;51(23):13938-13948.•CellDeathDis.2017May25;8(5):e2810.•BrJPharmacol.2017Sep;174(17):2941-2961.•MolOncol.2017Aug;11(8):1035-1049.•Oncotarget.2017May9;8(19):31297-31304.•Oncotarget.2016Dec20;7(51):84810-84825.•SciRep.2017Nov23;7(1):16111.•SciRep.2017Oct19;7(1):13571.•SciRep.2017Jun7;7(1):2929.•SciRep.2016Dec1;6:38267.•ToxicolApplPharmacol.2016Feb1;292:56-64.•CancerMed.2017Feb;6(2):471-482.•JEthnopharmacol.2017Aug12;212:8-17.•BiomedPharmacother.2017Apr5;90:446-454.•OncolRep.2017Feb;37(2):1270-1276.•BiochemBiophysResCommun.2016Mar18;471(4):539-44.•ChineseJournalofCellBIOLOGy.2016,38(10):1232-1243.DescriptionZ-VAD-FMKisacell-permeable,pan-caspaseinhibitor.IC50&Targetpan-caspase[1]InVitroZ-VAD-FMKisabroad-spectrumcaspaseinhibitor,hasbeenshowntoinhibittheintracellularactivationofcaspase-likeproteases.TheinjectionofZ-VAD-FMKsuppressesthecaspase-3activityinlungtissues,andsignificantlydecreasesthenumberofterminaldUTPnick-endlabeling-positivecells[1].Z-VAD-FMKisadmiNISTeredintraperitoneallyat1hourbeforeand6hoursafterSAH.Expressionofcaspase-3andpositiveTUNELisexaminedasMarkersforapoptosis.Z-VAD-FMKsuppressesTUNELandcaspase-3staininginendothelialcells,decreasescaspase-3activation,reducesBBBpermeABIlity,relievesvasospasm,abolishesbrainedema,andimprovesneurologicaloutcome[2].Z-VAD-FMKisacell-permeablecaspaseinhibitor,efficientlyblockscelldeathinducedbySMNdeficiency[3].InVivoThesurvivalrateofmiceisprolongedsignificantlybytheinjectionofZ-VAD-FMK.AllmicesuccumbedtoLPSwithin30hours.Bycontrast,themicetreatedwithZ-VAD-FMKsurvivesignificantlylongerand27%ofthemicesurvivedmorethan7days[1].References[1].KawasakiM,etal.Protectionfromlethalapoptosisinlipopolysaccharide-inducedacutelunginjuryinmicebyacaspaseinhibitor.AmJPathol.2000Aug;157(2):597-603.[2].ParkS,etal.Neurovascularprotectionreducesearlybraininjuryaftersubarachnoidhemorrhage.Stroke.2004Oct;35(10):2412-7.[3].IlangovanR,etal.InhibitionofapoptosisbyZ-VAD-fmkinSMN-depletedS2cells.JBiolChem.2003Aug15;278(33):30993-9.PreparingStockSolutionsConcentrationVolumeMass1mg5mg10mg1mM2.1391mL10.6954mL21.3908mL5mM0.4278mL2.1391mL4.2782mL10mM0.2139mL1.0695mL2.1391mLPleaserefertothesolubilityinformationtoselecttheappropriatesolvent.CellAssay[3]Z-VAD-FMKisdissolvedinDMSOandstored,andthendilutedwithappropriatemediumbeforeuse[3].PCRproductscontainingcodingsequencesforthedSMN(forwardprimer:5′-TAATACGACTCACTATAGGGAAGACGTACGACGAGTCG-3′;andreverseprimer:5′-TAATACGACTCACTATAGGGGTGGTGCTGGCTTCTTTC-3′;productlength,601bps;boldanditalicslettersrepresentT7promotersequences)andcontrolDrosophilaPresenilin(dPsn)gene(forwardprimer:5′-TAATACGACTCACTATAGGGTGGCTGCTGTCAATCTC-3′;andreverseprimer:5′-TAATACGACTCACTATAGGGCGATAGCAACGCTTCTTG-3′;productlength:543bps)areobtainedandgel-purified.Double-strandedRNAs(dsRNA)aregeneratedbytranscriptionwithRibomaxT7TranscriptionkitanddigestedwithRnase-freeDNase.ThedsRNAproductsareethanolprecipitatedandannealedbyincubationat65°Cfor30minandthenslowlyallowedtocoolatroomtemperature.TheannealeddsRNAproductsareanalyzedona1%agaorsegeltoensurethemajorityofdsRNAexistedasasingleband.ThedsRNA(2μg)and/orplasmidDNAs(2μg)areintroducedintocellsbyusingCellfectin.Caspaseinhibitionisachievedbyusing50μMofZ-VAD-FMKintheculturemedium[3].MCEhasnotindependentlyconfirmedtheaccuracyofthesemethods.Theyareforreferenceonly.AnimalAdministration[1][2]Z-VAD-FMKisdissolvedat2mg/mLin1%DMSOinsterilesaline(Mice)[1].Z-VAD-FMKisdissolvedin1%DMSOandfurtherdilutedinphysiologicalbuffersolution(final[2].Mice[1]Miceusedinthisstudyare5-to6-week-old(20to22g)ICRmales.Miceareinjectedwith30mg/kgLPSfromE.coliSEROtypeO111:B4throughthetailvein.AsingleintravenousinjectionofZ-VAD.fmk(0.25mg)ismade15minutesbeforeLPSinjection,followedbythreeintravenousinjectionsofZ-VAD-FMK(0.1mgeach)perhour.Controlmiceareinjectedwiththesamevolumeof1%DMSOinsterilesaline.Rat[2]MaleSprague-Dawleyratsweighing300to350gareanesthetizedwithα-chloralose(40mg/kgIP)andurethane(400mg/kgIP).Animalsareintubated,andrespirationismaintainedwithasmallanimalrespirator.Rectaltemperatureismaintainedat37±0.5°Cwithaheatingpad.Theleftexternalcarotidarteryisisolatedanda4.0monofilamentnylonsutureisinsertedthroughtheinternalcarotidarterytoperforatethemiddlecerebralartery.SAHisconfirmedatautopsyineachrat.Sham-operatedratsunderwentthesameproceduresexceptthatthesutureiswithdrawnafterresistanceisfelt.Z-VAD-FMK(50μMper0.3mL)isinjectedintraperitoneallyat1hourbeforeand6hoursafterSAHinduction.Invehiclegroup,ratsunderwentSAHinductionandaretreatedwiththesamevolumeofvehicle(DMSOdilutedinphysiologicalbuffersolution).Notreatmentisappliedinsham-operatedanimals.MCEhasnotindependentlyconfirmedtheaccuracyofthesemethods.Theyareforreferenceonly.References[1].KawasakiM,etal.Protectionfromlethalapoptosisinlipopolysaccharide-inducedacutelunginjuryinmicebyacaspaseinhibitor.AmJPathol.2000Aug;157(2):597-603.[2].ParkS,etal.Neurovascularprotectionreducesearlybraininjuryaftersubarachnoidhemorrhage.Stroke.2004Oct;35(10):2412-7.[3].IlangovanR,etal.InhibitionofapoptosisbyZ-VAD-fmkinSMN-depletedS2cells.JBiolChem.2003Aug15;278(33):30993-9.MolecularWeight467.49FormulaC₂₂H₃₀FN₃O₇CASNo.187389-52-2StoragePowder-80°C2years -20°C1yearInsolvent-80°C6months -20°C1monthShippingRoomtemperatureincontinentalUS;mayvaryelsewhereSolvent&SolubilityDMSO:≥30mg/mL*"

托烷司琼临床评价药物相关作用适应症托烷司琼CAS号:89565-68-4英文名称:Tropisetron英文同义词:icf205-930;TROPICACID;TROPISETRON;SS-TROPISETRON;BETA-TROPISETRON;Tropisetron(ICS205930);TROPISHTRONHYDROCHLORIDE;Indole-3-carbonylchloride;3-Tropanylindole-3-carboxylate;lαH，5Αh-Tropan-3α-ylindole-3-carboxylate中文名称:托烷司琼中文同义词:托普西隆;托普西龙;曲匹西龙;托烷司琼;Β-托烷司琼;CS-348;Β-内托烷司琼;吲哚-3-甲酰氯;Β-托烷司琼(光学异构体);Β-托烷司琼,托烷司琼异构体CBNumber:CB3236404分子式:C17H20N2O2分子量:284.35MOLFile:89565-68-4.mol化学性质安全信息用途供应商112化学性质安全信息用途供应商112托烷司琼化学性质熔点:201-202°C沸点:448.5±35.0°C(Predicted)密度:1.26储存条件:2-8°C溶解度:H2O:soluble形态:solid酸度系数(pKa):15.38±0.30(Predicted)颜色:whiteCAS数据库:Chemicalbook89565-68-4(CASDataBaseReference)安全信息WGKGermany:3托烷司琼化学药品说明书托烷司琼|药物应用信息托烷司琼性质、用途与生产工艺临床评价Sorbe等报道本品对含顺铂(剂量50～89mg/m2)化疗方案引起的急性呕吐完全控制率为63%。58例恶性肿瘤化疗所致恶心、呕吐者，应用托烷司琼或昂丹司琼8mg分别在同一病人前后2个化疗周期的第1d给药前30min静脉注射，并用地塞米松10mg静脉滴注。结果两药控制急性及迟发性恶心、呕吐的疗效基本相似，均可达81%～100%。本品对强致吐化疗药物顺铂的止吐疗效突出。药物相关作用饮食可略为延长本品的吸收。本品与利福平、苯巴比妥等肝酶诱导药同时使用，可加快代谢，故快代谢型者需增加剂量，慢者则不必。西咪替丁等肝酶抑制药对本品血药浓度无明显影响。适应症托烷司琼临床用于预防和治疗癌症化疗引起的恶心和呕吐。化学性质结晶，熔点201-202℃(二氯甲烷-乙酸乙酯)。单盐酸托烷司琼(TropisetronMonohydroehloride)：C17H20N2O2?HCI。[105826-92-4]。熔点283-285℃(分解)。用途有高效性和选择性的5-HT3受体拮抗剂。用于化疗所致的呕吐。用途为5-羟色胺拮抗药生产方法托品醇(I)和酰氯(Ⅱ)反应，可得托烷司琼。托烷司琼上下游产品信息上游原料托品醇下游产品