RapamycinisaspecificmTORinhibitorwithIC50of0.1nM.CustomerValidation•Nature.2016Dec1;540(7631):119-123.•JClinInvest.2017Sep1;127(9):3339-3352.•NatCommun.2017Jun8;8:15617.•StemCellReports.2017Nov23.pii:S2213-6711(17)30483-6.•BiochemPharmacol.2016Dec15;122:42-61.•SciRep.2017Aug14;7(1):8119.•SciRep.2015Nov2;5:16024.•SciBull.2015Dec;60(24):2120-2128.•RespirRes.2017Jul11;18(1):136.•PLoSOne.2017Nov29;12(11):e0188748.•PLoSOne.2017Jun21;12(6):e0179772.•OncolLett.2017Oct;14(4):4715-4721.•ExpHematolOncol.2016Jul29;5:22.•AmJDigestDis.2015;2(2):95-99.•IntJPhysiolPathophysiolPharmacol.2015Mar20;7(1):54-60.•HarvardMedicalSchoolLINCSLIBRARYDescriptionRapamycinisaspecificmTORinhibitorwithIC50of0.1nM.IC50&TargetIC50:0.1nM(mTOR)[1]InVitroRapamycininhibitsendogenousmTORactivityinHEK293cellswithIC50of0.1nM,morepotentlythaniRapandAP21967withIC50of5nMand10nM,respectively[1].RapamycinexertsitsantitumoreffectonmalignantgliomacellsbyinducingautophagyandsuggestthatinmalignantgliomacellsadisruptionofthePI3K/AktsignalingpathwaycouldgreatlyenhancetheeffectivenessofmTORinhibitors.RapamycininhibitscellviABIlityinallthreecelllinesinadose-dependentmanner,buttheirsensitivitiesvaried.TheIC50levelsofT98G,U87-MG,andU373-MGcellsare2nM,1μM,and>25μM,respectively[3].InVivoTreatmentwithRapamycin(i.p,1.5mg/kg)almostcompletelypreventsthehypertrophicincreasesinplantarismuscleweightandfibresizeat7and14days[4].WTorLS/+micearetreateddailyRapamycin(2mg/kgbodyweighti.p.)for4weeks,followsbyanadditional4weeksofweeklyinjectionsofthesamedose.ThereissignificantreversaloftheabnormalfetalgeneexpressionprofileofheartsfromRapamycin-treatedLS/+mice[5].ClinicalTrialViewMoreCollapseReferences[1].EdwardsSR,etal.Therapamycin-bindingdomainoftheproteinkinasemammaliantargetofrapamycinisadestabilizingdomain.JBiolChem,2007,282(18),13395-13401.[2].LalicH,etal.Rapamycinenhancesdimethylsulfoxide-mediatedgrowtharrestinhumanmyelogenousleukemiacells.LeukLymphoma.2012Nov;53(11):2253-61.[3].TakeuchiH,etal.Synergisticaugmentationofrapamycin-inducedautophagyinmalignantgliomacellsbyphosphatidylinositol3-kinase/proteinkinaseBinhibitors.CancerRes,2005,65(8),3336-3346.[4].BodineSC,etal.Akt/mTORpathwayisacrucialregulatorofskeletalmusclehypertrophyandcanpreventmuscleatrophyinvivo.NatCellBiol,2001,3(11),1014-1019.[5].MarinTM,etal.RapamycinreverseshypertrophiccardiomyopathyinamousemodelofLEOPARDsyndrome-associatedPTPN11mutation.JClinInvest.2011Mar;121(3):1026-43.[6].HinoK,etal.Activin-AenhancesmTORsignalingtopromoteaberrantchondrogenesisinfibrodysplasiaossificansprogressiva.JClinInvest.2017Sep1;127(9):3339-3352.PreparingStockSolutionsConcentrationVolumeMass1mg5mg10mg1mM1.0939mL5.4694mL10.9389mL5mM0.2188mL1.0939mL2.1878mL10mM0.1094mL0.5469mL1.0939mLPleaserefertothesolubilityinformationtoselecttheappropriatesolvent.KinaseAssay[1]HEK293cellsareplatedat2-2.5×105cellsperwellofa12-wellplateandserum-starvedfor24hinDMEMonly.Cellsaremock-treatedortreatedwithRapamycin(0.05-50nM),iRap(0.5-500nM),orAP21967(0.5-500nM)for15minutesat37°C.Serumisaddedtoafinalconcentrationof20%for30minutesat37°C.CellsarelysedandcelllysatesareseparatedbySDS-PAGE.ResolvedproteinsaretransferredtoaPVDFmembraneandimmunoblottedwithaphosphospecificprimaryantibodyagainstThr389ofp70S6kinase.DataareanalyzedusingImageQuantandKaleidaGraph[1].MCEhasnotindependentlyconfirmedtheaccuracyofthesemethods.Theyareforreferenceonly.CellAssay[2]RapamycinisdissolvedinDMSOandstored,andthendilutedwithappropriatemediumbeforeuse[2].HL-60,NB4,U937,KG-1,andK562cellsarepassagedroutinelyinRPMI-1640supplementedwith10%heat-inactivatedFBS,2mML-glutamine,50U/mLpenicillinand50μg/mLstreptomycinina5%CO2humidifiedatmosphereat37°C.Fortheexperiments,exponentiallygrowingcellsareharvestedbycentrifugation,andresUSPendedinfreshmediumcontaining10%FBS.Thecellsareseededataninitialcelldensityof2×105/mLinBDFalconsix-wellplatesinthepresenceofvariousconcentrationsofDMSOor1μMATRA.Rapamycin(20nM)isadded20minpriortothedifferentiationagents.Atday2,0.3mLoffreshmediumisaddedtoeachwell.Theviablecellsaredeterminedbytrypanblueexclusionandquantifiedusingahemocytometer[2].MCEhasnotindependentlyconfirmedtheaccuracyofthesemethods.Theyareforreferenceonly.AnimalAdmiNISTration[4][5]Rapamycinisdissolvedin2%carboxymethylcellulose(Rat)[4].Rapamycinisdissolvedinethanolataconcentrationof20mg/mL,filtersterilized,resuspendedinvehicle(0.25%PEG,0.25%Tween-80)ataconcentrationof1mg/mL(Mice)[5].Rat[4]FemaleSprague-Dawleyrats(250-275g),theadultfemaleSDrats(225-250g)arerandomizedtotreatmentorvehiclegroupssothatthemeanstartingbodyweightsofeachgroupareequal.DrugtreatmentbeganonthedayofsurgeryoronthefirstdayofreloADIngafterthe14-daysuspension.Rapamycinisdeliveredoncedailybyintraperitonealinjectionatadoseof1.5mg/kg,dissolvedin2%carboxymethylcellulose.CsAisdeliveredoncedailybysubcutaneousinjectionatadoseof15mg/kg,dissolvedin10%methanolandoliveoil.FK506isdeliveredoncedailyviasubcutaneousinjectionatadoseof3mg/kg,dissolvedin10%ethanol,10%cremophorandsaline.Mice[5]Rapamycinisdissolvedinethanolataconcentrationof20mg/mL,filtersterilized,resuspendedinvehicle(0.25%PEG,0.25%Tween-80)ataconcentrationof1mg/mL,andinjectedi.p.(2mg/kgbodyweight),eitherdailyfor4weeksordailyfor4weeksfollowedbyweeklyinjectionsforanadditional4weeks.Injectionsbeganateither8weeks(priortoonsetofhypertrophy)or12weeks(afterestablishedhypertrophyisindicated)ofage,andmiceareassessedafter4weeksoftreatmentorafter8weeksoftreatment,asdetailedintheResultsandfigurelegends.Ascontrols,WTandLS/+micearetreatedwithvehiclealone.MCEhasnotindependentlyconfirmedtheaccuracyofthesemethods.Theyareforreferenceonly.References[1].EdwardsSR,etal.Therapamycin-bindingdomainoftheproteinkinasemammaliantargetofrapamycinisadestabilizingdomain.JBiolChem,2007,282(18),13395-13401.[2].LalicH,etal.Rapamycinenhancesdimethylsulfoxide-mediatedgrowtharrestinhumanmyelogenousleukemiacells.LeukLymphoma.2012Nov;53(11):2253-61.[3].TakeuchiH,etal.Synergisticaugmentationofrapamycin-inducedautophagyinmalignantgliomacellsbyphosphatidylinositol3-kinase/proteinkinaseBinhibitors.CancerRes,2005,65(8),3336-3346.[4].BodineSC,etal.Akt/mTORpathwayisacrucialregulatorofskeletalmusclehypertrophyandcanpreventmuscleatrophyinvivo.NatCellBiol,2001,3(11),1014-1019.[5].MarinTM,etal.RapamycinreverseshypertrophiccardiomyopathyinamousemodelofLEOPARDsyndrome-associatedPTPN11mutation.JClinInvest.2011Mar;121(3):1026-43.[6].HinoK,etal.Activin-AenhancesmTORsignalingtopromoteaberrantchondrogenesisinfibrodysplasiaossificansprogressiva.JClinInvest.2017Sep1;127(9):3339-3352.MolecularWeight914.17FormulaC₅₁H₇₉NO₁₃CASNo.53123-88-9StoragePowder-20°C3years 4°C2yearsInsolvent-80°C6months -20°C1monthShippingRoomtemperatureincontinentalUS;mayvaryelsewhereSolvent&SolubilityDMSO:≥28mg/mLRapamycinispreparedinvehicle(16%DMSOin0.5w/v%methylcellulose400)[6].*"

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