LY294002isabroad-spectruminhibitorofPI3K,withIC50of0.5/0.57/0.97μMforPI3Kα/δ/β,respectively,alsopotentlyinhibitsCK2withIC50of98nM.CustomerValidation•JExpMed.2016Dec12;213(13):2989-3005.•DevCell.2016Oct24;39(2):239-253.•CellMolLifeSci.2017Oct25.•CellPhysiolBiochem.2016;40:579-588.•EnvironPollut.2017Oct;229:964-975.•JMolMed(Berl).2017Nov3.•IntJBiolSci.2016Mar30;12(5):607-16.•JTraumaAcuteCareSurg.2017Oct;83(4):683-689.•ExpGerontol.2017Oct25;100:77-86.•IntJOncol.2016Jul;49(1):422-30.•BrainResBull.2017Aug24;134:236-245.•JCancer.2016Jun5;7(9):1114-24.•BiomedPharmacother.2017Jun15;93:130-145.•BiochemBiophysResCommun.2017Aug26;490(3):1059-1065.•BiomedicalResearch2017;28(8):3383-3386•BosnJBasicMedSci.2017May20;17(2):132-137.•LingnanModernClinicsinSurgery.Jun.2014,Vol.14No.3.DescriptionLY294002isabroad-spectruminhibitorofPI3K,withIC50of0.5/0.57/0.97μMforPI3Kα/δ/β,respectively,alsopotentlyinhibitsCK2withIC50of98nM.IC50&TargetIC50:0.5/0.57/0.97μM(PI3Kα/δ/β)[1]IC50:98nM(CK2)[2]InVitroLY294002(5μM)completelyinhibitsthephosphorylationofPKBInHepG2cells.LY294002(5μM)isalsoshowntoblockinsulin-inducedphosphorylationofPKBSer473inCHO-IRcells[1].LY294002isalsoapotentinhibitorofCK2(caseinkinase2)withIC50of98nM.LY294002isalsoabletoreducethekinaseactivityofbothisoformsoftheserine/threoninekinasesGSK3αandβ[2].WhentheCNE-2ZcelllineisculturedinmediumcontainingLY294002(0μM,10μM,25μM,50μM,and75μM)for24hand48h,cellproliferationisremarkablydecreasedinadose-dependentfashion[3].InVivoTreatmentwithLY294002(i.p.,50mg/kg,75mg/kg)significantlyreducesmeanNPCtumorburdenascomparedwiththecontrolgroup.Treatmentwith10mg/kgor25mg/kgLY294002islesseffectiveindecreasingtumorburden.MeanNPCtumorburdentreatedwithLY294002isremarkablydecreasedinadose-dependentmanner,whereasmeanbodyweightisnoobviousdifferencebetweencontrolandtreatedgroups(LY294002,10mg/kg,25mg/kg,50mg/kg,and75mg/kg)[3].References[1].ChaussadeC,etal.EvidenceforfunctionalredundancyofclassIAPI3Kisoformsininsulinsignalling.BiochemJ.2007Jun15;404(3):449-58.[2].GharbiSI,etal.ExploringthespecificityofthePI3KfamilyinhibitorLY294002.BiochemJ.2007May15;404(1):15-21.[3].JiangH,etal.Phosphatidylinositol3-kinaseinhibitor(LY294002)inducesapoptosisofhumannasopharyngealcarcinomainvitroandinvivo.JExpClinCancerRes.2010Apr22;29:34.[4].UedaK,etal.DifferentialeffectsofLY294002andwortmanninonneuronsandvascularendothelialcellsintheratretina.PharmacolRep.2013;65(4):854-62.PreparingStockSolutionsConcentrationVolumeMass1mg5mg10mg1mM3.2537mL16.2686mL32.5373mL5mM0.6507mL3.2537mL6.5075mL10mM0.3254mL1.6269mL3.2537mLPleaserefertothesolubilityinformationtoselecttheappropriatesolvent.KinaseAssay[2]PI3KinhibitionbyPI828andLY294002isdeterminedinarADIometricassayusingpurified,recombinantenzymes(classIAandclassIB)with1μMATP.Thekinasereactioniscarriedoutfor1hatroomtemperature(24°C)andisterminatedbyadditionofPBS.IC50valuesaresubsequentlydeterminedusingasigmoidaldose-responsecurvefit(variableslope).CK2andGSK3β(glycogensynthasekinase3β)inhibitionisestablishedbykinaseselectivityscreening.Inhibitor(10μM;PI828andLY294002)istestedagainsttheUpstatepanelofkinasesin10μMATP[2].MCEhasnotindependentlyconfirmedtheaccuracyofthesemethods.Theyareforreferenceonly.CellAssay[3]LY294002isdissolvedinDMSOandstored,andthendilutedwithappropriatemedia(DMSO0.5%)beforeuse[3].HumannasopharyngealcarcinomacelllineCNE-2Zisseededinto96-wellplatesat5000cells/well.Twenty-fourhoursaftercellsareseeded,themediumisremovedandreplacedinthepresenceofLY294002(0μM,10μM,25μM,50μM,and75μM)dissolvedinDMSOorDMSOonlyforanadditional24hand48h.ToavoidanynonspecifictoxiceffectsofDMSOoncellgrowth,DMSOconcentrationsaremaintainedat0.5%inallexperiments.MTTdye(5mg/mL)isaddedtoeachwell.ThereactionisstoppedbytheadditionofDMSO,andopticaldensityismeasuredat490nmonamultiwellplatereader.Backgroundabsorbanceofthemediumintheabsenceofcellsissubtracted.Allsamplesareassayedintriplicate,andthemeanforeachexperimentiscalculated.Resultsareexpressedasapercentageofcontrol,whichisconsideredtobe100%[3].MCEhasnotindependentlyconfirmedtheaccuracyofthesemethods.Theyareforreferenceonly.AnimalAdmiNISTration[3][4]LY294002isdissolvedinvehicle(DMSO).Mice[3]Athymicnudemiceareusedwhentheyare6-8weeks.Micearerandomlydividedintofreeseparatedintofivegroups(n=4mice).Micearehousedinthesameenvironmentwithcontrolledtemperature,humidity,anda12hlight/darkcycle.MiceareinoculatedsubcutaneouslywithCNE-2Zcells(1×106cells/mousein200μLofRPMI-1640)intotheflank.Thetumortakerateis100%.After1week,anintraperitonealinjectionisperformedtothexenograftmicewithdifferentdosageofLY294002(10mg/kg,25mg/kg,50mg/kg,and75mg/kgtwiceweekly(n=4mice),eachgroupfor4weeks.Treatedmicearemonitoredanysigns.Bodyweightandtumorssizearemeasuredtwiceaweek.Tumorsizeismeasuredusingcalipersandtumorvolumeiscalculated(volume=longaxis×shortaxis2).Attheendofthetreatment,allmiceareeuthanized.Onepartoftumortissueisfixedinformalinandembeddedinparaffin,andanotherpartisstoredat-70°C.Rat[4]MaleSprague-Dawleyratsweighing220-240gareanesthetizedbyintraperitoneallyinjectingpentobarbitalsodium(50mg/kg).Theanimalsaredividedinto3groups:NMDA+vehicle(DMSO)(n=46),NMDA+LY294002(50nmol)(n=25),andNMDA+Wortmannin(50nmol)(n=23).EitherLY294002orwortmanninmixedwith200nmolofNMDAinatotalvolumeof5μLisinjectedintothevitreouscavityofoneeye.ThesamevolumeofDMSOisinjectedintothevitreouscavityofthecontralateraleye,whichisusedasacontrol.Theinjectionsareperformedunderamicroscopeusinga32-gaugeneedle,whichisconnectedtoamicrosyringe.Theneedleisinsertedapproximately1mmbehindthecorneallimbus.Damagetoneuronsandbloodvesselsintheretinaisassessedat2and7daysaftertheinjection.TheeffectsoftheintravitrealtreatmentwitheitherLY294002orWortmanninaloneonretinalneuronsandbloodvesselsarealsoexamined.MCEhasnotindependentlyconfirmedtheaccuracyofthesemethods.Theyareforreferenceonly.References[1].ChaussadeC,etal.EvidenceforfunctionalredundancyofclassIAPI3Kisoformsininsulinsignalling.BiochemJ.2007Jun15;404(3):449-58.[2].GharbiSI,etal.ExploringthespecificityofthePI3KfamilyinhibitorLY294002.BiochemJ.2007May15;404(1):15-21.[3].JiangH,etal.Phosphatidylinositol3-kinaseinhibitor(LY294002)inducesapoptosisofhumannasopharyngealcarcinomainvitroandinvivo.JExpClinCancerRes.2010Apr22;29:34.[4].UedaK,etal.DifferentialeffectsofLY294002andwortmanninonneuronsandvascularendothelialcellsintheratretina.PharmacolRep.2013;65(4):854-62.MolecularWeight307.34FormulaC₁₉H₁₇NO₃CASNo.154447-36-6StoragePowder-20°C3years 4°C2yearsInsolvent-80°C6months -20°C1monthShippingRoomtemperatureincontinentalUS;mayvaryelsewhereSolvent&SolubilityDMSO:14.9mg/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