OlaparibisapotentPARPinhibitorwithIC50of5and1nMforPARP-1andPARP-2,respectively.CustomerValidation•CancerDiscov.2017Sep;7(9):984-998.•ClinCancerRes.2017Feb15;23(4):1001-1011.•Oncogene.2017Sep25.•IntJMolSci.2016Feb24;17(3):272.•IntJMolSci.2015Oct19;16(10):24820-38.•EurJPharmacol.2017Nov15;815:147-155.•CancerChemotherPharmacol.2017Oct;80(4):861-867.•HarvardMedicalSchoolLINCSLIBRARYDescriptionOlaparibisapotentPARPinhibitorwithIC50of5and1nMforPARP-1andPARP-2,respectively.IC50&TargetIC50:5/1nM(PARP-1/2)[1]InVitroOlaparib(AZD2281)isasingledigitnanomolarinhibitorofbothPARP-1andPARP-2thatshowsstandaloneactivityagainstBRCA1-deficientbreastcancercelllines.OlaparibisappliedtoSW620celllysates,andidentifiedtheIC50forPARP-1inhibitiontobearound6nMandthetotalablationofPARP-1activitytobeatconcentrationsof30−100nM[1].InVivoAnimalsbearingSW620xenograftedtumorsaretreatedwithOlaparib(10mg/kg,p.o.)incombinationwithTemozolomide(TMZ)(50mg/kg,p.o.)oncedailyfor5consecutivedays,afterwhichthetumorsarelefttogrowout[1].OlaparibincreasesvascularperfusioninCalu-6tumorsestablishedinaDWCmodel.AdmiNISTrationofolaparib(50mg/kg,p.o.)asasingleagent(toppanel)orincombinationwithrADIation(bottompanel)resultsinanincreaseinfluorescenceintensityintheCalu-6tumors[2].ClinicalTrialViewMoreCollapseReferences[1].MenearKA,etal.4-[3-(4-cyclopropanecarbonylpiperazine-1-carbonyl)-4-fluorobenzyl]-2H-phthalazin-1-one:anovelbioavailableinhibitorofpoly(ADP-ribose)polymerase-1.JMedChem.2008Oct23;51(20):6581-91[2].SenraJM,etal.InhibitionofPARP-1byolaparib(AZD2281)increasestheradiosensitivityofalungtumorxenograft.MolCancerTher.2011Oct;10(10):1949-58.[3].YasukawaM,etal.SynergeticEffectsofPARPInhibitorAZD2281andCisplatininOralSquamousCellCarcinomainVitroandinVivo.IntJMolSci.2016Feb24;17(3):272.[4].BianX,etal.PTENdeficiencysensitizesendometrioidendometrialcancertocompoundPARP-PI3KinhibitionbutnotPARPinhibitionasmonotherapy.Oncogene.2017Sep25.PreparingStockSolutionsConcentrationVolumeMass1mg5mg10mg1mM2.3017mL11.5085mL23.0171mL5mM0.4603mL2.3017mL4.6034mL10mM0.2302mL1.1509mL2.3017mLPleaserefertothesolubilityinformationtoselecttheappropriatesolvent.KinaseAssay[1]ThisassaydeterminedtheABIlityofOlaparibtoinhibitPARP-1enzymeactivity.PARP-2activityinhibitionismeasuredbyusingavariationofthePARP-1assayinwhichPARP-2protein(recombinant)isbounddownbyaPARP-2specificantibodyina96-wellwhite-walledplate.PARP-2activityismeasuredfollowing3H-NAD+DNAadditions.Afterwashing,scintillantisaddedtomeasure3H-incorporatedribosylations.Fortankyrase-1,anAlphaScreenassayisdevelopedinwhichHIS-taggedrecombinantTANK-1proteinisincubatedwithbiotinylatedNAD+ina384-wellProxiPlateassay.AlphabeadsareaddedtobindtheHISandbiotintagstocreateaproximitysignal,whereastheinhibitionofTANK-1activityisdirectlyproportionaltothelossofthissignal.Allexperimentsarerepeatedatleastthreetimes[1].MCEhasnotindependentlyconfirmedtheaccuracyofthesemethods.Theyareforreferenceonly.CellAssay[1]OlaparibisdissolvedinDMSOandstored,andthendilutedwithappropriatemediabeforeuse[1].ThePF50valueisthepotentiationfactor,whichiscalculatedastheratiooftheIC50ofthecontrolgrowthwithalkylatingagentmethylmethanesulfonate(MMS)dividedbytheIC50oftheMMScombinedwiththePARPinhibitor.HeLaBcellsareused,andOlaparibistestedatafixed200nMconcentrationforscreeningwithMMS.ForthetestingofOlaparibontheSW620colorectalcellline,theconcentrationsthatareusedare1,3,10,100and300nM.CellgrowthisassessedbytheuseofthesulforhodamineB(SRB)assay[1].MCEhasnotindependentlyconfirmedtheaccuracyofthesemethods.Theyareforreferenceonly.AnimalAdministration[2]OlaparibispreparedinPBS(containing10%DMSOand10%2-hydroxy-propyl-β-cyclodextrin)(Mice)[2].Mice[2]Micebearing220-250mm3tumorsarerandomizedinto4treatmentgroups(n=5):A;vehiclecontrol(10%DMSOinPBS/10%2-hydroxy-propyl-β-cyclodextrindailyfor5daysbyoralgavage),B;Olaparib(50mg/kgdailyfor5daysbyoralgavage),C;10Gyfractionatedradiotherapy(2Gydailyfor5days),D;Olapariband10Gy(5×2Gy)fractionatedradiotherapy(witholaparibgiven30minpriortoeachdaily2Gydoseofradiation).Tumorvolumemeasurementsaredetermineddailyuntiltheyreached1000mm3.Thenumberofdaysforeachindividualtumortoquadrupleinsizefromthestartofthetreatment(relativetumorvolume×4;RTV4)iscalculatedfortheindividualtumorsineachgroup.MCEhasnotindependentlyconfirmedtheaccuracyofthesemethods.Theyareforreferenceonly.References[1].MenearKA,etal.4-[3-(4-cyclopropanecarbonylpiperazine-1-carbonyl)-4-fluorobenzyl]-2H-phthalazin-1-one:anovelbioavailableinhibitorofpoly(ADP-ribose)polymerase-1.JMedChem.2008Oct23;51(20):6581-91[2].SenraJM,etal.InhibitionofPARP-1byolaparib(AZD2281)increasestheradiosensitivityofalungtumorxenograft.MolCancerTher.2011Oct;10(10):1949-58.[3].YasukawaM,etal.SynergeticEffectsofPARPInhibitorAZD2281andCisplatininOralSquamousCellCarcinomainVitroandinVivo.IntJMolSci.2016Feb24;17(3):272.[4].BianX,etal.PTENdeficiencysensitizesendometrioidendometrialcancertocompoundPARP-PI3KinhibitionbutnotPARPinhibitionasmonotherapy.Oncogene.2017Sep25.MolecularWeight434.46FormulaC₂₄H₂₃FN₄O₃CASNo.763113-22-0StoragePowder-20°C3years 4°C2yearsInsolvent-80°C6months -20°C1monthShippingRoomtemperatureincontinentalUS;mayvaryelsewhereSolvent&SolubilityDMSO:29mg/mLinvivo:OlaparibisdissolvedinDMSO(31.25mg/mL)andthendilutedwithPBS(DMSO:PBS=1:9).Olaparib(AZD2281)isdissolvedin200µLsterilizedwater)[3].Olaparibisdissolvedin10%hydroxypropyl-β-Cyclodextrinanddosedat50 mg/kgperday(i.p.)[4].*"

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