SP600125isabroad-spectrumJNKinhibitorforJNK1,JNK2andJNK3withIC50of40nM,40nMand90nM,respectively.CustomerValidation•Biomaterials.2017Mar22;130:14-27.•CellDeathDiffer.2017Mar;24(3):492-499.•Elife.2016Apr11;5.pii:e14087.•JAutoimmun.2017Nov20.pii:S0896-8411(17)30612-1.•FrontImmunol.2017Oct10;8:1278.•CancerLett.2017Feb16;393:22-32.•CellMolLifeSci.2017Oct25.•JMolCellCardiol.2015Dec;89(PtB):268-79.•FreeRADIcBiolMed.2017Jul9;112:49-59.•Oncotarget.2016Dec20;7(51):85079-85096.•OxidMedCellLongev.2017;2017:7426458.•OxidMedCellLongev.2017;2017:6175841.•CellSignal.2016Feb;28(2):81-93.•MolImmunol.2017May4;87:161-170.•ChemBiolInteract.2017Nov1;277:62-73.•IntJMolMed.2017Jul;40(1):164-174.•IntJMolMed.2017Jan;39(1):71-80.•UniversitätWürzburg.2016-4-27.•HarvardMedicalSchoolLINCSLIBRARY•ThirdMilitaryMedicalUniversityDescriptionSP600125isabroad-spectrumJNKinhibitorforJNK1,JNK2andJNK3withIC50of40nM,40nMand90nM,respectively.IC50&TargetIC50:40/40/90nM(JNK1/2/3)[1]InVitroSP600125isanATP-competitiveinhibitorofJNK2withaKivalueof0.19±0.06μM.SP600125inhibitsthephosphorylationofc-JunwithIC50of5μMto10μMinJurkatTcells.InCD4+cells,suchasTh0cellsisolatedfromeitherhumancordorperipheralblood,SP600125blockscellactivationanddifferentiationandinhibitstheexpressionofinflammatorygenesCOX-2,IL-2,IL-10,IFN-γ,andTNF-α,withIC50of5μMto12μM[1].InamousebetacellsMIN6,SP600125(20μM)inducesthephosphorylationofp38MAPKanditsdownstreamCREB-dependentpromoteractivation[2].InHCT116cells,SP600125(20μM)blockstheG2phasetomitosistransitionandinducesendoreplication.ThisABIlityofSP600125isindependentofJNKinhibition,butduetoitsinhibitionofCDK1-cyclinBactivationupstreamofAuroraAandPolo-likekinase1[3].InVivoAdmiNISTrationofSP600125at15or30mg/kgi.v.significantlyinhibitsTNF-αserumlevels,whereasoraladministrationdose-dependentlyblocksTNF-αexpressionwithsignificantinhibitionobservedat30mg/kgperos[1].SP600125attenuatesLPS-inducedALIinratsinvivo.TheexpressionlevelsofTNF-αandIL-6intheBALFinratsintheSP600125grouparesignificantlydecreased[4].References[1].BennettBL,etal.SP600125,ananthrapyrazoloneinhibitorofJunN-terminalkinase.ProcNatlAcadSciUSA,2001,98(24),13681-13686.[2].VaishnavD,etal.SP600125,aninhibitorofc-junN-terminalkinase,activatesCREBbyap38MAPK-mediatedpathway.BiochemBiophysResCommun,2003,307(4),855-860.[3].KimJA,etal.SP600125suppressesCdk1andinducesendoreplicationdirectlyfromG2phase,independentofJNKinhibition.Oncogene,2010,29(11),1702-1716.[4].ZhengY,etal.JNKinhibitorSP600125protectsagainstlipopolysaccharide-inducedacutelunginjuryviaupregulationofclaudin-4.ExpTherMed.2014Jul;8(1):153-158.PreparingStockSolutionsConcentrationVolumeMass1mg5mg10mg1mM4.5407mL22.7035mL45.4071mL5mM0.9081mL4.5407mL9.0814mL10mM0.4541mL2.2704mL4.5407mLPleaserefertothesolubilityinformationtoselecttheappropriatesolvent.CellAssay[1]SP600125isdissolvedinDMSO(20mM)andstored,andthendilutedwithappropriatemedia(DMSO0.1%)beforuse[1].DeterminationofmRNAhalf-lifeisperformedessentially,exceptthatCD14+cellsarestimulatedwith(bacterial)lipopolysaccharide(LPS;50ng/mL)for2hbeforeadditionofactinomycinD(5μg/mL).SP600125(25μM)orvehicle(0.5%DMSOvol/vol)isaddedimmediatelyfollowingtheactinomycinD.Analysisisperformedbyusingreal-timereversetranscription(RT)-PCR.TotalRNAisextractedwithanRNeasyMinikit.TNFmRNAismeasuredbyrealtimeRT-PCR,usingaTNFTaqmanprobe.Alldataarenormalizedbyusingglyceraldehyde-3-phosphatedehydrogenase(GAPDH)expression.TheTNF-αforwardprimeris5′-CTGGCCCAGGCAGTCAGAT-3′andthereverseprimeris5′-TATCTCTCAGCTCCACGCCATT-3′.TheTaqmanprobesequenceis5′-FAM-CCTGTAGCCCATGTTGTAGCAAACCCTCA-TAMRA-3′[1].MCEhasnotindependentlyconfirmedtheaccuracyofthesemethods.Theyareforreferenceonly.AnimalAdministration[1][4]SP600125isdissolvedin30%PEG-400/20%polypropyleneglycol/15%CremophorEL/5%ethanol/30%saline(Mice)[1].Mice[1]FemaleCD-1mice(8-10weeksofage)aredosedi.v.orperoswithSP600125inPPCESvehicle(30%PEG-400/20%polypropyleneglycol/15%CremophorEL/5%ethanol/30%saline),finalvolumeof5mL/kg,15minbeforei.v.injectionwithLPSinsaline(0.5mg/kg).At90min,aterminalbleedisobtainedfromtheaBDominalvenacava,andtheserumisrecovered.SamplesareanalyzedformouseTNF-αbyusinganELISA.Rat[4]Atotalof40maleWistarratsarerandomlydividedintofourgroups(n=10):thecontrolgroup,LPSgroup,normalsalinegroup(NS)andtheSP600125group.Acutelunginjury(ALI)isinducedviaintratrachealinjectionofLPS.Briefly,theratsareanesthetizedwithpentobarbitalsodiumfollowedbyintratrachealinjectionof5mg/kgLPS.Theratsarethenplacedinaverticalpositionandrotatedfor1mintodistributetheLPSinthelungs.NormalsalineorSP600125isadministeredviaintraperitonealinjection(15mg/kg)10minaftertheLPSinjection.MCEhasnotindependentlyconfirmedtheaccuracyofthesemethods.Theyareforreferenceonly.References[1].BennettBL,etal.SP600125,ananthrapyrazoloneinhibitorofJunN-terminalkinase.ProcNatlAcadSciUSA,2001,98(24),13681-13686.[2].VaishnavD,etal.SP600125,aninhibitorofc-junN-terminalkinase,activatesCREBbyap38MAPK-mediatedpathway.BiochemBiophysResCommun,2003,307(4),855-860.[3].KimJA,etal.SP600125suppressesCdk1andinducesendoreplicationdirectlyfromG2phase,independentofJNKinhibition.Oncogene,2010,29(11),1702-1716.[4].ZhengY,etal.JNKinhibitorSP600125protectsagainstlipopolysaccharide-inducedacutelunginjuryviaupregulationofclaudin-4.ExpTherMed.2014Jul;8(1):153-158.MolecularWeight220.23FormulaC₁₄H₈N₂OCASNo.129-56-6StoragePowder-20°C3years 4°C2yearsInsolvent-80°C6months -20°C1monthShippingRoomtemperatureincontinentalUS;mayvaryelsewhereSolvent&SolubilityDMSO:≥45mg/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