Nemorubicin-hydrochloride-Methoxymorpholinyl-doxorubicin-hydrochloride-生命科学试剂-MCE

Hotline:400-820-3792Inhibitors•ScreeningLibraries•Proteinswww.MedChemENemorubicinhydrochlorideCat.No.:HY-15794ACASNo.:108943-08-4Synonyms:Methoxymorpholinyldoxorubicinhydrochloride;FCE23762hydrochloride;PNU152243A分⼦式:C₃₂H₃₈ClNO₁₃分⼦量:680.1作⽤靶点:G-quadruplex作⽤通路:CellCycle/DNADamage储存⽅式:PleasestoretheproductundertherecommendedconditionsintheCertificateofAnalysis.BIOLOGICALACTIVITY⽣物活性Nemorubicinhydrochloride⼀种阿霉素衍⽣物，具有抗肿瘤活性。Nemorubicinhydrochloride不仅插⼊到双链DNA中，⽽且还产⽣了G-四联体(G-quadruplex)重的配体，使其结构稳定。体外研究Nemorubicinhydrochloridehasantitumoractivity,withIC70sof578±137nM,468±45nM,193±28nM,191±19nM,68±12nM,and131±9nMforHT-29,A2780,DU145,EM-2,JurkatandCEMcelllines,respectively[1].Nemorubicinactsthroughnucleotideexcisionrepair(NER)systemtoexertitsactivity.Nemorubicin(0-0.3μM)ismoreactiveintheL1210/DDPcellswithintactNERthanintheXPG-deficientL1210/0cells.CellsresistanttonemorubicinshowincreasedsensitivitytoUVdamage[3].Nemorubiciniscytotoxicto9L/3A4cells,withanIC50of0.2nM,120-foldlowerthanthatofP450-deficient9Lcells(IC50,23.9nM).NemorubicinalsopotentlyinhibitsAdeno-3A4infectedU251cellswithIC50of1.4nM.P450reductaseoverexpressionenhancescytotoxicityofNemorubicin[4].体内研究NemorubicinisconvertedtoPNU-159682byhumanlivercytochromeP450(CYP)3A4inrat,mouse,anddoglivermicrosomes[2].Nemorubicin(60µg/kg)inducessifnificanttumorgrowthdelayinscidmicebearing9L/3A4tumors,butshowsnoobviouseffectonthetumorgrowthdelayof9Ltumorsinmicebyi.v.orintratumoralinjection(i.t.).Nemorubicin(40µg/kg,i.p.)exhibitsnoantitumoractivityandnohosttoxicityinmicebearing9L/3A4tumors[4].PROTOCOL1/2MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemECellAssay[4]9LandCHOcellsareplatedintriplicatewellsofa96-wellplateat3000cellsperwell24hrpriortodrugtreatment.CellsaretreatedwithvariousconcentrationsofNemorubicinorIFAfor4d.Cellsarethenstainedwithcrystalviolet(A595)andrelativecellsurvivaliscalculated.IC50valuesaredeterminedfromasemi-logarithmicgraphofthedatapointsusingPrism4[4].MCEhasnotindependentlyconfirmedtheaccuracyofthesemethods.Theyareforreferenceonly.Animal9Land9L/3A4cellsaregrownassolidtumorsinmaleICR/FoxChaseSCIDmice.CellsculturedinDMEMAdministration[4]mediumto75%confluencearetrypsinizedandwashedinPBSandthenadjustedto2×107cells/mLofFBS-freeDMEM.Four-week-oldSCIDmice(18-20g)areimplantedwitheither9Lor9L/3A4tumorcellsbyinjectionof4×106cells/0.2mLofcellsuspension,s.c.oneachhindflank.Tumorsizes(lengthandwidth)aremeasuredtwiceaweekusingVerniercalipersbeginning7daftertumorimplantation.Whentheaveragetumorsizereach300to400mm3,NemorubicindissolvedinPBSisadministeredbytailveininjection(i.v.)orbydirectintratumoral(i.t.)injection(threeinjectionsspaced7dapart,eachat60µgNemorubicinperkgbodyweight).Intratumoralinjectionsareperformedusingasyringepumpseta1µL/switha30-gaugeneedle.Eachi.t.treatmentdoseisdividedintothreeinjectionspertumor,withtheinjectedvolumesetat50µLpertumorper25gmouse.Thus,fora30gmouse,atotalof120µLof15µg/mLofNemorubicinsolutionisadministered:20µLpersite×3sitespertumor×2tumors/mouse.Drug-freecontrolsareinjectedi.t.withthesamevolofPBS.Insomeexperiments,Nemorubicinisadministeredbyi.p.injectionat40or60µg/kgbodyweight.Tumorsizesandbodyweightsaremeasuredtwice/wkforthedurationofthestudy.Tumorvolumesarecalculatedusingtheformula:V=π/6(L×W)3/2.Percenttumorregressioniscalculatedas100×(V1-V2)/V1,whereV1isthetumorvolonthedayofdrugtreatmentandV2isthevolonthedaywhenthelargestthedecreaseintumorsizeisseenfollowingdrugtreatment.Tumordoublingtimeiscalculatedasthetimerequiredfortumorstodoubleinvolafterdrugtreatment[4].MCEhasnotindependentlyconfirmedtheaccuracyofthesemethods.Theyareforreferenceonly.户使⽤本产品发表的科研⽂献•Patent.US20240261422A1.Seemorecustomervalidationsonwww.MedChemEREFERENCES[1].QuintieriL,etal.FormationandantitumoractivityofPNU-159682,amajormetaboliteofnemorubicininhumanlivermicrosomes.ClinCancerRes.2005Feb15;11(4):1608-17.[2].QuintieriL,etal.InvitrohepaticconversionoftheanticanceragentnemorubicintoitsactivemetabolitePNU-159682inmice,ratsanddogs:acomparisonwithhumanlivermicrosomes.BiochemPharmacol.2008Sep15;76(6):784-95.[3].SabatinoMA,etal.Down-regulationofthenucleotideexcisionrepairgeneXPGasanewmechanismofdrugresistanceinhumanandmurinecancercells.MolCancer.2010Sep24;9:259.[4].LuH,etal.PotentiationofmethoxymorpholinyldoxorubicinantitumoractivitybyP4503A4genetransfer.CancerGeneTher.2009May;16(5):393-404.McePdfHeigh