SB216763ispotentandselectiveglycogensynthasekinase-3(GSK-3)inhibitor,withIC50valueof34.3nMforGSK-3αandGSK-3β,respectively.CustomerValidation•ToxicolApplPharmacol.2016Dec15;313:195-203.•HarvardMedicalSchoolLINCSLIBRARYDescriptionSB216763ispotentandselectiveglycogensynthasekinase-3(GSK-3)inhibitor,withIC50valueof34.3nMforGSK-3αandGSK-3β,respectively.IC50&TargetIC50:34.3nM(GSK-3α),34.3nM(GSK-3β)[5]InVitroSB-216763(10-20µM)inducesβ-cateninmediated-transcriptioninadose-dependentmannerinHEK293cells.SB-216763(10,15and20µM)canmaintainmESCswithapluripotent-likemorphologyinlong-termculture.SB-216763(10µM)canmaintainJ1mESCsinapluripotentstateformorethanamonth[2].SB-216763inhibitsGSK-3withIC50of34nM[3].SB-216763isequallyeffectiveatinhibitinghumanGSK-3αandGSK-3β[5].InVivoSB216763(20mg/kg,i.v.)significantlyimprovesthesurvivalofBLM-treatedmice.MicerandomizedtoreceiveBLMplusSB216763showsanoteworthyreduction,comparedwithBLM-treatedmice.SB216763(20mg/kg,i.v.)reducesthemagnitudeofBLM-inducedalveolitis[1].SB216763(0.2mg/kg,i.v.)witheither17β-E100orGeni100reversestheceilingeffectbecausetheseagentssignificantlyreduceinfarctsizewhentherabbits"heartsaresubmittedto30-minCAO[4].References[1].Gurrieri,etal.3-(2,4-dichlorophenyl)-4-(1-methyl-1H-indol-3-yl)-1H-pyrrole-2,5-dione(SB216763),aglycogensynthasekinase-3inhibitor,displaystherapeuticpropertiesinamousemodelofpulmonaryinflammationandfibrosis.J.Pharmacol.Exp.Ther.2010[2].KirbyLA,etal.Glycogensynthasekinase3(GSK3)inhibitor,SB-216763,promotespluripotencyinmouseembryonicstemcells.PLoSOne.2012;7(6):e39329.Epub2012Jun26.[3].WangM,etal.Thefirstsynthesisof[(11)C]SB-216763,anewpotentialPETagentforimagingofglycogensynthasekinase-3(GSK-3).BioorgMedChemLett.2011Jan1;21(1):245-9.Epub2010Nov11.[4].TheceilingeffectofpharmacologicalpostconditioningwiththephytoestrogengeNISTeinisreversedbytheGSK3betainhibitorSB216763[3-(2,4-dichlorophenyl)-4(1-methyl-1H-indol-3-yl)-1H-pyrrole-2,5-dione]throughmitochondrialATP-dependentpotassiumchannelopening.[5].CoghlanMP,etal.Selectivesmallmoleculeinhibitorsofglycogensynthasekinase-3modulateglycogenmetabolismandgenetranscription.ChemBiol.2000Oct;7(10):793-803.[6].WangW,etal.Inhibitionofglycogensynthasekinase3betaamelioratestriptolide-inducedacutecardiacinjurybydesensitizingmitochondrialpermeABIlitytransition.ToxicolApplPharmacol.2016Dec15;313:195-203.PreparingStockSolutionsConcentrationVolumeMass1mg5mg10mg1mM2.6938mL13.4691mL26.9382mL5mM0.5388mL2.6938mL5.3876mL10mM0.2694mL1.3469mL2.6938mLPleaserefertothesolubilityinformationtoselecttheappropriatesolvent.CellAssay[2]SB-216763isdissolvedin0.1%DMSO.MESCsmaintainedwithLIFor10µMSB-216763formorethanamonthareresUSPendedat40,000cells/mLinLIF-freemESCmedium.EBsarepreparedbyahangingdropprocedure.Briefly,20µLdropscontainingmESCsarePipettedontheinsideofa10-cmPetridishlid.ThelidsareplacedontoPetridishescontaining10mLofHBSSandtheEBsareallowedtoformandgrowfor4daysintheincubator.After4days,15-20EBsaretransferredtoawellcontainingLIF-freemESCmediumina24-wellplate.Themediumisexchangedeverytwodaysandautonomouslybeatingcellaggregatesareobservedandcounted.MCEhasnotindependentlyconfirmedtheaccuracyofthesemethods.Theyareforreferenceonly.AnimalAdministration[1]SB216763isdissolvedinvehicle(25%dimethylsulfoxide,25%polyethyleneglycol,and50%saline).Miceareallocatedtofourgroups(n=12/group)asfollows:1)intratrachealsaline+vehicle(25%dimethylsulfoxide,25%polyethyleneglycol,and50%saline),2)intratrachealsaline+SB216763(20mg/kg)dissolvedinvehicle,3)intratrachealBLM(3U/kg)+vehicle,and4)intratrachealBLM+SB216763(20mg/kg)invehicle.Anothersetofexperimentstoassesscytokineexpressionbyreversetranscription-PCRisconductedinthemice(n=12/group)toreceive1)intratrachealsaline+vehicle,2)intratrachealBLM,and3)intratrachealBLM+SB216763.Toinducepulmonaryfibrosis,BLMisintratracheallyadministeredinmice(n=15/group)onday0.BLMandsaline-treatedmiceareadministeredwithSB216763dissolvedinvehicleorvehiclealoneintravenouslyatday0andthenintraperitoneallytwiceaweekuntilday28.MicearesacrificedbyCO2 inhalationondays2,7,and28.IntheterminaldeoxynucleotidyltransferasedUTPnick-endlabeling(TUNEL)experiments,thecohortsofmiceareasfollows:saline-treated(n=6),BLM-treated(n=6),andBLM+SB216763-treated(n=6).MCEhasnotindependentlyconfirmedtheaccuracyofthesemethods.Theyareforreferenceonly.References[1].Gurrieri,etal.3-(2,4-dichlorophenyl)-4-(1-methyl-1H-indol-3-yl)-1H-pyrrole-2,5-dione(SB216763),aglycogensynthasekinase-3inhibitor,displaystherapeuticpropertiesinamousemodelofpulmonaryinflammationandfibrosis.J.Pharmacol.Exp.Ther.2010[2].KirbyLA,etal.Glycogensynthasekinase3(GSK3)inhibitor,SB-216763,promotespluripotencyinmouseembryonicstemcells.PLoSOne.2012;7(6):e39329.Epub2012Jun26.[3].WangM,etal.Thefirstsynthesisof[(11)C]SB-216763,anewpotentialPETagentforimagingofglycogensynthasekinase-3(GSK-3).BioorgMedChemLett.2011Jan1;21(1):245-9.Epub2010Nov11.[4].TheceilingeffectofpharmacologicalpostconditioningwiththephytoestrogengenisteinisreversedbytheGSK3betainhibitorSB216763[3-(2,4-dichlorophenyl)-4(1-methyl-1H-indol-3-yl)-1H-pyrrole-2,5-dione]throughmitochondrialATP-dependentpotassiumchannelopening.[5].CoghlanMP,etal.Selectivesmallmoleculeinhibitorsofglycogensynthasekinase-3modulateglycogenmetabolismandgenetranscription.ChemBiol.2000Oct;7(10):793-803.[6].WangW,etal.Inhibitionofglycogensynthasekinase3betaamelioratestriptolide-inducedacutecardiacinjurybydesensitizingmitochondrialpermeabilitytransition.ToxicolApplPharmacol.2016Dec15;313:195-203.MolecularWeight371.22FormulaC₁₉H₁₂Cl₂N₂O₂CASNo.280744-09-4StoragePowder-20°C3years 4°C2yearsInsolvent-80°C6months -20°C1monthShippingRoomtemperatureincontinentalUS;mayvaryelsewhereSolvent&Solubility10mMinDMSOSB216763isdissolvedinDMSOtomakestocksolutionsandthensuspendedinnormalsaline[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