Forskolinisapotentadenylatecyclaseactivator,withbinding(IC50=41nM)toandactivation(EC50=0.5μM)oftypeIadenylylcyclase.DescriptionForskolinisapotentadenylatecyclaseactivator,withbinding(IC50=41nM)toandactivation(EC50=0.5μM)oftypeIadenylylcyclase.IC50&TargetIC50:41nM(Adenylylcyclase)[1]EC50:0.5μM(Adenylylcyclase)[1]InVitroForskolin(Fsk)isanaturallyoccurringditerpeneisolatedfromColeusforskholii,directlyactivatesadenylylcyclase(AC)throughitscatalyticsubunittoincreaseintracellularlevelsofcyclicadenosinemonophosphate(cAMP)[1].Forskolin(Fsk)affectstheproliferationofthehumanT-celllinessuchasKit225andMT-2.ForskolintreatmentinhibitstheproliferationofbothKit225andMT-2cellsinadose-dependentmannerwithanIC50equalto~5μMFsk.Forskolintreatment(10-100μM)increasescAMPilevels~5-to20-foldabovebasallevels,whichreachemaximumlevelsbetween50-100μMForskolin[2].InVivoTheForskolin(Fsk)-treatedMrp4-/-miceshowsanincreasednumberofKi67-positiveandcleavedcaspase3-positiveECs,asignificantdecreaseintheamountofpericytecoverage,andareducednumberofemptysleeves.Inpupsexposedtohyperoxia(75%oxygen)fromP7toP12,theMrp4-/-miceshowsasignificantincreaseintheunvascularizedretinalarea[3].Theaveragebloodglucoseinthehealthyratgroupis102.12±1.94mg/dL,101.25±3.56forcontrolgroupand103±2.08inforskolingroup.Thedatashowsthatglucoselevelsattheendofthestudyarelowerinforskolingroup,withasignificantdifferenceaccordingtothestatisticaltestsapplied(p=0.03)[4].References[1].RobbinsJD,etal.Forskolincarbamates:bindingandactivationstudieswithtypeIadenylylcyclase.JMedChem.1996Jul5;39(14):2745-52.[2].RodriguezG,etal.Forskolin-inducIBLecAMPpathwaynegativelyregulatesT-cellproliferationbyuncouplingtheinterleukin-2receptorcomplex.JBiolChem.2013Mar8;288(10):7137-46.[3].MatsumiyaW,etal.ForskolinmodifiesretinalvasculardevelopmentinMrp4-knockoutmice.InvestOphthalmolVisSci.2012Dec7;53(13):8029-35.[4].Ríos-SilvaM,etal.EffectofchronicadmiNISTrationofforskolinonglycemiaandoxidativestressinratswithandwithoutexperimentaldiabetes.IntJMedSci.2014Mar11;11(5):448-52.PreparingStockSolutionsConcentrationVolumeMass1mg5mg10mg1mM2.4361mL12.1803mL24.3605mL5mM0.4872mL2.4361mL4.8721mL10mM0.2436mL1.2180mL2.4361mLPleaserefertothesolubilityinformationtoselecttheappropriatesolvent.KinaseAssay[2]ForJak3kinaseassays,Fsk-treatedMT-2cellsarelysed,clarified,andimmunoprecipitatedusingJak3antibody.Kinasereactionsarecarriedoutat30°Cfor20min.ForPKAkinaseassays,untreatedMT-2cellsarelysed,andJak3isimmunoprecipitatedandboundtoPASbeads.ImmunoprecipitatedJak3iswashedwithkinasebuffer(50mMHepes-NaOH(pH7.4),10mMMgCl2,0.5mMEGTA,0.5mMDTT,20μg/mLaprotinin,10μg/mLleupeptin,1μg/mLpepstatinA)andincubatedwith200μMATPandpurifiedproteinkinaseAcatalyticsubunit(PKAc)asindicatedinthefigurelegends.Kinasereactionsarecarriedoutat32°Cfor30minfollowedbyvigorouswashingofthebeadswithcoldkinasewashbuffer.For[γ-32P]ATPrADIolabeledkinaseassaysusingrecombinantJak3,Hek293cellsaretransfectedwithwildtype(WT)Jak3orkinase-deadJak3K855AusingLipofectamine2000accordingtothemanufacturer"sinstructions.CellsarelysedandimmunoprecipitatedwithJak3antibody.Jak3-boundPASbeadsarewashedthreetimesincoldlysisbufferfollowedbykinasebuffer.Kinasereactionsareinitiatedbyadding10μCi[γ-32P]ATP,10μMunlabeledATP,and1μgofpurifiedPKActoJak3-boundPASbeadreactionmixtures.Kinasereactionsareperformedat32°Cfor30min.Jak3-boundPASbeadsarewashedthreetimesinradioimmunoassaybuffer(10mMTris-HCl,pH7.4,75mMNaCl,20mMEDTA,10mMEGTA,20mMNa4P2O7,50mMNaF,20mM2-glycerolphosphate,1mMp-nitrophenylphosphate,0.1%TritonX-100)andonetimeinkinasewashbuffer.Thereactionsarestoppedbyadding2×SDS-PAGEsamplebufferfollowedbySDS-PAGE.CoomassiestainableJak3bandsareexcisedfromthePVDFmembraneandsubjectedtophosphoaminoacidanalysis[2].MCEhasnotindependentlyconfirmedtheaccuracyofthesemethods.Theyareforreferenceonly.CellAssay[2]Forskolin(Fsk)isdissolvedinDMSOandstored,andthendilutedwithappropriatemedia(DMSO1%)beforeuse[2].QuiescentKit225orMT-2cellsareseededinto96-wellplatesat5×104cellsperwell.Cellsarethenpretreatedfor1hwith1%DMSO(vehicle)orForskolinat1,5,10,25,50,and100μMconcentrations.ThecellsarestimulatedwithIL-2andculturedforanadditional20hat37°C.Controlcellsaretreatedwith1%DMSOfor20h.Duringthefinal4hofincubation,thecellsarepulsedwith[3H]thymidineataconcentrationof0.5μCi/200μL.Cellsareharvestedontofiberglassfiltersandanalyzedusingliquidscintillationcounting[2].MCEhasnotindependentlyconfirmedtheaccuracyofthesemethods.Theyareforreferenceonly.AnimalAdministration[3][4]ForskolinisdissolvedinDMSOandthendiluted(Mice)[3].Mice[3]C57BL/6Jmiceareused.Mrp4-knockoutmice,whichareestablishedandrepeatedlybackcrossedtotheC57BL/6Jmice.Forskolinisinjectedintraperitoneallyintoneonatalmiceatpostnataldays4(P4)and5(P5).MiceinjectedwithDMSOserveasthecontrols.ThetreatedmiceareeuthanizedatP6,andtheirretinasareisolatedforwhole-mountimmunohistochemistry(IHC).TheeffectofdifferentconcentrationsofForskolinonthesurvivalrateandretinalvasculatureisfirsttested,andtheoptimalconcentrationisdetermined,1.0μg/50μL(0.3mg/kg)atP4and1.5μg/50μL(0.5mg/kg)atP5,usedtocomparetheretinalvascularphenotypesbetweenWTmiceandMrp4-deficientmice.Rat[4]MaleWistarrats,aged10-14weeksold,withameanweightof300g±50g,aredividedintofourgroups;19areexperimentallyinducedtodevelopdiabetes,and8aremaintainedinahealthycondition.BothdiabeticandhealthyratsreceivenoForskolin(control),or6mg/kgperdayofForskolin,administeredorallyfor8weeks.BloodglucoselevelsaredeterminedineachgroupbeforeandafterForskolintreatment.Thediabeticratsaretestedtwoweeksafterconfirmingthepresenceofdiabetes(threeweeksaftertheinduction)andaftereightweeksofthedesignatedtreatment.MCEhasnotindependentlyconfirmedtheaccuracyofthesemethods.Theyareforreferenceonly.References[1].RobbinsJD,etal.Forskolincarbamates:bindingandactivationstudieswithtypeIadenylylcyclase.JMedChem.1996Jul5;39(14):2745-52.[2].RodriguezG,etal.Forskolin-induciblecAMPpathwaynegativelyregulatesT-cellproliferationbyuncouplingtheinterleukin-2receptorcomplex.JBiolChem.2013Mar8;288(10):7137-46.[3].MatsumiyaW,etal.ForskolinmodifiesretinalvasculardevelopmentinMrp4-knockoutmice.InvestOphthalmolVisSci.2012Dec7;53(13):8029-35.[4].Ríos-SilvaM,etal.Effectofchronicadministrationofforskolinonglycemiaandoxidativestressinratswithandwithoutexperimentaldiabetes.IntJMedSci.2014Mar11;11(5):448-52.MolecularWeight410.5FormulaC₂₂H₃₄O₇CASNo.66575-29-9StoragePowder-20°C3years 4°C2yearsInsolvent-80°C6months -20°C1monthShippingRoomtemperatureincontinentalUS;mayvaryelsewhereSolvent&SolubilityDMSO:≥32mg/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