Doranidazole-PR-350-生命科学试剂-MCE

Hotline:400-820-3792Inhibitors•ScreeningLibraries•Proteinswww.MedChemEDoranidazoleCat.No.:HY-105095CASNo.:149838-23-3Synonyms:PR350;RP343分⼦式:C₈H₁₃N₃O₆分⼦量:247.21作⽤靶点:BiochemicalAssayReagents作⽤通路:Others储存⽅式:PleasestoretheproductundertherecommendedconditionsintheCertificateofAnalysis.BIOLOGICALACTIVITY⽣物活性Doranidazole(PR350)⼀种放射增敏剂。Doranidazole可提⾼乏氧SCCVII细胞的放射敏感性。在肿瘤照射前静脉注射Doranidazole可显著增强放射诱导的SCCVII肿瘤⽣长延迟。Doranidazole对肿瘤的放射敏感性增强程度取决于肿瘤的氧合状态。Doranidazole可⽤于淋巴瘤和乏氧胰腺肿瘤的研究[1][2][3]。体外研究Doranidazole(1mM)significantlyenhancestheradiosensitivityofhypoxicSCCVIIcellsinvitro[1].Doranidazole(0.1-3.0mM)candose-dependentlyincreaseradiation-inducedmicronucleusformationinhypoxicSCCVIIcells[1].Doranidazole(1mM)enhancesradiation-inducedapoptosisinMouseL5178Ylymphomacellsunderhypoxicconditions[2].体内研究Doranidazole(50-200mg/kg,tailveininjection,once)significantlyenhancestheradiosensitivityofSCCVIItumorcellsinmice[1].Doranidazole(50-200mg/kg,tailveininjection,once)significantlyenhancesradiation-inducedgrowthdelayofSCCVIItumorsinmiceandreducestheradiationdoserequired[1].Doranidazole(200mg/kg,tailveininjection,once)canenhancetheradiosensitizationresponseofCFPAC-1tumorsinnudemice,buthasnoradiosensitizingeffectonMIAPaCa-2tumors[1].Doranidazole(50-200mg/kg,tailveininjection,once)exhibitsaradiosensitizingeffectthatcorrelateswithtumoroxygenationstatus;tumorswithhighhypoxia(suchasSCCVIIandCFPAC-1)respondbetter,whilewell-oxygenatedtumors(suchasMIAPaCa-2)shownosensitizingeffect[1].Doranidazole(100-250mg/kg,i.v.,once)showsaclearradiosensitizingeffectonallfourpancreaticcancercelllinesinxenograftnudemice,andtheeffectisdose-dependent[3].1/3MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemEAnimalModel:FemaleC3H/HeNmiceweresubcutaneouslyinoculatedwithSCCVIIcells(approximately2×106cells)intherighthindleg[1].Dosage:50mg/kg,100mg/kg,200mg/kgAdministration:Tailveininjection,onceResult:TheSERswere1.09-1.36at10minafter50-200mg/kginjection,indicatingcausedsignificantradiosensitizationoftumorswithin10minafterthedrugadministration.ThemaximumradiosensitizationoftumorwithaSERof1.47occurred20minafteradministrationat200mg/kg.Considerableradiosensitizationwasstillevident40-0minafterdrugadministration.AnimalModel:FemaleC3H/HeNmiceweresubcutaneouslyinoculatedwithSCCVIIcells(approximately2×106cells)intherighthindleg[1].Dosage:50mg/kg,100mg/kg,200mg/kgAdministration:Tailveininjection,onceResult:Anadministrationof200mg/kgaloneexertednoeffectonthegrowthofSCCVIItumors.100mg/kgwasslightlyslowerthanthatofthetumorsirradiatedaftersalineinjection.Theradiation-inducedgrowthdelaywasfurtherenhancedwith200mg/kg.Combining200mg/kgwithirradiationextendedthetumordoublingtimeto36days.Reducetherequiredradiationdose.AnimalModel:BALB/c-nu/nunudemiceweresubcutaneouslyinoculatedwithHumanpancreatictumorcells(CFPAC-1andMIAPaca-2)intherighthindleg(approximately5×106cellswereinoculatedfirst,andafterthetumorgrewto1cmindiameter,itwascutintosmallpiecesandtransplantedintonewmicetoensurethatthetumorswereofuniformsize)[1].Dosage:200mg/kgAdministration:Tailveininjection,onceResult:CombinedirradiationprolongedtheregenerationtimeofCFPAC-1tumorsto91days.Nosignificantdifferenceintumorgrowthdelaybetweenthecombinedirradiationgroupandtheirradiation-alonegroupinMIAPaCa-2tumors,whichmayberelatedtothebetteroxygenationstatusofthesetumors.AnimalModel:Fourhumanpancreaticcancercelllines(SUIT-2,PANC-1,MIAPaCa-2,andBxPC-3)intheirexponentialgrowthphaseweresubcutaneouslyinoculatedat106cellspercellinthebackof6-week-oldmaleBalb/cnudemice[3].Dosage:100mg/kg,250mg/kg2/3MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemEAdministration:I.v.,onceResult:Atadoseof100mg/kg,theSERwas1.15–1.3(SUIT-2:1.15,PANC-1:1.3,MIAPaCa-2:1.2,BxPC-3:1.25).Atadoseof250mg/kg,theSERincreasedto1.35–1.45(SUIT-2:1.35,PANC-1:1.45,MIAPaCa-2:1.4,BxPC-3:1.35).REFERENCES[1].YahiroT,etal.Effectsofhypoxiccellradiosensitizerdoranidazole(PR-350)ontheradioresponseofmurineandhumantumorcellsinvitroandinvivo.JRadiatRes.2005Sep;46(3):363-72.[2].MizuhoAoki,etal.EffectofaHypoxicCellSensitizerDoranidazoleontheRadiation-inducedApoptosisofMouseL5178YLymphomaCells,JournalofRadiationResearch,Volume43,Issue2,June2002,Pages161–166.[3].ShibamotoY,etal.Radiosensitivityofhumanpancreaticcancercellsinvitroandinvivo,andtheeffectofanewhypoxiccellsensitizer,doranidazole.R