ActinomycinDinhibitsDNArepairwithIC50of0.42μM.CustomerValidation•CancerLett.2017Aug18;407:45-56.•CellDeathDis.2017Mar23;8(3):e2702.•JExpClinCancerRes.2017Oct19;36(1):149.•MolCarcinog.2017Mar;56(3):1082-1087.DescriptionActinomycinDinhibitsDNArepairwithIC50of0.42μM.IC50&TargetIC50:0.42μM(DNArepair)[1]InVitroActinomycinDisaninhibitorofDNAtranscriptionandreplication[1].ActinomycinDmarkedlyreducesthevascularsmoothmusclecells(SMC)proliferationviatheinhibitionofBrdUincorporationat80nM.ThisisfurthersupportedbytheG1-phasearrestusingaflowcytometricanalysis.ActinomycinDisextremelypotentwithaninhibitoryconcentrationIC50at0.4nM,whereasthelethaldoseLD50isat260microM.Theproteinexpressionlevelsofproliferatingcellnuclearantigen(PCNA),focaladhesionkinase(FAK),andRafareallsuppressedbyActinomycinD.Extracellularsignal-regulatedkinases(Erk)involvedincell-cyclearrestarefoundtoincreasebyActinomycinD[2].InVivoThepluronicgelcontaining80nMand80μMActinomycinDisappliedtopicallytosurroundtheratcarotidadventitia,thethicknessofneointimaissubstantiallyreduced(45and55%,respectively)[2].MiceintheActinomycinDandfludarABInegrouplivessignificantlylongerthanthecontrolgroupwithPvaluesof[3].ClinicalTrialViewMoreCollapseReferences[1].BarretJM,etal.EvaluationofDNArepairinhibitionbyantitumororantibioticdrugsusingachemiluminescencemicroplateassay.Carcinogenesis.1997Dec;18(12):2441-5.[2].WuCH,etal.ThemolecularmechanismofactinomycinDinpreventingneointimalformationinratcarotidarteriesafterballooninjury.JBiomedSci.2005;12(3):503-12.[3].MerkelO,etal.ActinomycinDinducesp53-independentcelldeathandprolongssurvivalinhigh-riskchroniclymphocyticleukemia.Leukemia.2012Dec;26(12):2508-16.PreparingStockSolutionsConcentrationVolumeMass1mg5mg10mg1mM0.7965mL3.9827mL7.9655mL5mM0.1593mL0.7965mL1.5931mL10mM0.0797mL0.3983mL0.7965mLPleaserefertothesolubilityinformationtoselecttheappropriatesolvent.KinaseAssay[1]ActinomycinDisco-incubatedfor3hat30°Cwithareactionmixturecontaining:120mgofawhole-cellextractofHeLacells,70mMKCl,0.4mMeachofdGTP,dCTP,dATP,anddigoxygenylated-dUTPinreactionbuffercontaining40mMHepes-KOH(pH7.6),5mMMgCl2,0.5mMDithiotreitol,2mMEGTA,10mMphosphocreatine,50mg/mLcreatinephosphate,and360mg/mLofbovineserumalbumin.Duringthisreaction,DNAdamageisrecognizedandtheexcisedpatchesarereplacedbyneosynthesizedDNAfragments.ThroughoutthisDNAsynthesis,digoxygenylated-dUMPsareincorporated.TheDNArepairreactionisstoppedbythreewashes[1].MCEhasnotindependentlyconfirmedtheaccuracyofthesemethods.Theyareforreferenceonly.AnimalAdmiNISTration[3]ActinomycinDispreparedinphosphate-bufferedsaline(PBS)(Mice)[3].Mice[3]TheoriginalEμ-TCL1atransgenicmicehavebeenbackcrossedtoC57BL/6micefor>9generations.TheC57BL/6wild-typemiceareengraftedwithtumorcellsfromEμ-TCL-1transgenicmice.ThepercentageofCD5+/CD19+cellsintheperipheralbloodisroutinelycheckedinmicebytakingbloodfromthetailveinandanalyzingitviaflowcytometry.Whenthepercentageoftumorcellsintheperipheralbloodreached40-60%,treatmentisstarted.ActinomycinD(0.06 mg/kgby10days)isapplieddailyviai.p.injections.MCEhasnotindependentlyconfirmedtheaccuracyofthesemethods.Theyareforreferenceonly.References[1].BarretJM,etal.EvaluationofDNArepairinhibitionbyantitumororantibioticdrugsusingachemiluminescencemicroplateassay.Carcinogenesis.1997Dec;18(12):2441-5.[2].WuCH,etal.ThemolecularmechanismofactinomycinDinpreventingneointimalformationinratcarotidarteriesafterballooninjury.JBiomedSci.2005;12(3):503-12.[3].MerkelO,etal.ActinomycinDinducesp53-independentcelldeathandprolongssurvivalinhigh-riskchroniclymphocyticleukemia.Leukemia.2012Dec;26(12):2508-16.MolecularWeight1255.42FormulaC₆₂H₈₆N₁₂O₁₆CASNo.50-76-0StoragePowder-20°C3years 4°C2yearsInsolvent-80°C6months -20°C1monthShippingRoomtemperatureincontinentalUS;mayvaryelsewhereSolvent&SolubilityDMSO:≥27mg/mL;DMSO:250mg/mL(Needultrasonic);Methanol:6.2mg/mL;Methanol:20mg/mL(Needultrasonic);H2O:*"

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