Phosphoramide-mustard-DataSheet-生命科学试剂-MedChemExpress

Hotline:400-820-3792Inhibitors•Agonists•ScreeningLibrarieswww.MedChemEPhosphoramidemustardCat.No.:HY-137316CASNo.:10159-53-2分⼦式:C₄H₁₁Cl₂N₂O₂P分⼦量:221.02作⽤靶点:DNAAlkylator/Crosslinker;DrugMetabolite作⽤通路:CellCycle/DNADamage;MetabolicEnzyme/Protease储存⽅式:PleasestoretheproductundertherecommendedconditionsintheCOA.BIOLOGICALACTIVITY⽣物活性Phosphoramidemustard环磷酰胺(Cyclophosphamide,HY-17420)的主代谢物，具有抗肿瘤活性。Phosphoramidemustard能诱导巢颗粒细胞DNA加合物的形成，诱导DNA损伤，诱发巢DNA修复反应[1][2]。IC50&TargetDNAAlkylator[1]体外研究Phosphoramidemustardcausescytotoxicitythroughformingcross-linkedDNAadductswhichinhibitDNAstrandseparationduringreplication[1].PhosphoramidemustarddestroysrapidlydividingcellsbyformingNOR-G-OH,NOR-GandG-NOR-GadductswithDNA,potentiallyleadingtoDNAdamage[1].Phosphoramidemustard(3-6μM;48hours)reducescellviabilityinratspontaneouslyimmortalizedgranulosacells(SIGCs)[1].Phosphoramidemustard(3-6μM;24-48hours)inducesDNAadductformation[1].Phosphoramidemustard(3-6μM;24-48hours)inducesovarianDNAdamageinratovaries[1].PhosphoramidemustardincreasesDNAdamageresponses(DDR)gene(Atm,Parp1,Prkdc,Xrcc6,Brca1,Rad51)mRNAexpressionlevel[1].Phosphoramidemustard(3-6μM;24-48hours)increasedDDRproteins[1].CellViabilityAssay[1]CellLine:SIGCsConcentration:0.5μM,1μM,3μM,6μM1/3MasterofSmallMolecules—您⾝边的抑制剂⼤师www.MedChemEIncubationTime:48hoursResult:Reducedcellviabilityatconcentrationsof3μMandhigher.RT-PCR[1]CellLine:SIGCsConcentration:3μM,6μMIncubationTime:24hours,48hoursResult:IncreasedDDRgenemRNAexpressionlevels.WesternBlotAnalysis[1]CellLine:SIGCsConcentration:3μM,6μMIncubationTime:24hours,48hoursResult:GenerallyincreasedDDRproteins.体内研究Phosphoramidemustard(2.1-20.7mg/kg;i.p.;daily;for5days)inhibitssubcutaneoustumorgrowthinrats[2].Phosphoramidemustard(59.4mg/kg;i.v.)hasaplasmadisappearancehalf-lifeof15.1minutes[2].AnimalModel:Rat,subcutaneouslyimplantedWalker256carcinosarcomatumor[2]Dosage:2.1mg/kg,4.8mg/kg,10.4mg/kg,20.7mg/kgAdministration:Intraperitonealinjection,oncedaily,for5consecutivedaysResult:Requiredtoproduce50%inhibitionofsubcutaneoustumorgrowthwithdoseof12mg/kg.AnimalModel:Rats[2]Dosage:59.4mg/kg(PharmacokineticAnalysis)Administration:IntravenousinjectionResult:Hasadisappearancehalf-lifeof15.1minutesinplasma.REFERENCES2/3MasterofSmallMolecules—您⾝边的抑制剂⼤师www.MedChemE[1].ShanthiGanesan,etal.PhosphoramidemustardexposureinducesDNAadductformationandtheDNAdamagerepairresponseinratovariangranulosacells.ToxicolApplPharmacol.2015Feb1;282(3):252–258.[2].SGenka,etal.Brainandplasmapharmacokineticsandanticanceractivitiesofcyclophosphamideandphosphoramidemustardintherat.CancerChemotherPharmacol.1990;27(1):1-7.McePdfHeightCaution:Producthasnotbeenfullyvalidatedf