Hotline:400-820-3792Inhibitors?Agonists?ScreeningLibrarieswww.MedChemEPhosphoramidemustard(cyclohexanamine)Cat.No.:HY-137316ACASNo.:1566-15-0分?式:C??H??Cl?N?O?P分?量:320.2作?靶點:DNAAlkylator/Crosslinker;DrugMetabolite作?通路:CellCycle/DNADamage;MetabolicEnzyme/Protease儲存?式:PleasestoretheproductundertherecommendedconditionsintheCOA.BIOLOGICALACTIVITY?物活性Phosphoramidemustardcyclohexanamine環(huán)磷酰胺(Cyclophosphamide,HY-17420)的主代謝物，具有抗腫瘤活性。Phosphoramidemustardcyclohexanamine能誘導(dǎo)巢顆粒細胞DNA加合物的形成，誘導(dǎo)DNA損傷，誘發(fā)巢DNA修復(fù)反應(yīng)[1][2]體外研究Phosphoramidemustardcyclohexanaminecausescytotoxicitythroughformingcross-linkedDNAadductswhichinhibitDNAstrandseparationduringreplication[1].PhosphoramidemustardcyclohexanaminedestroysrapidlydividingcellsbyformingNOR-G-OH,NOR-GandG-NOR-GadductswithDNA,potentiallyleadingtoDNAdamage[1].Phosphoramidemustardcyclohexanamine(3-6μM;48hours)reducescellviabilityinratspontaneouslyimmortalizedgranulosacells(SIGCs)[1].Phosphoramidemustardcyclohexanamine(3-6μM;24-48hours)inducesDNAadductformation[1].Phosphoramidemustardcyclohexanamine(3-6μM;24-48hours)inducesovarianDNAdamageinratovaries[1].PhosphoramidemustardcyclohexanamineincreasesDNAdamageresponses(DDR)gene(Atm,Parp1,Prkdc,Xrcc6,Brca1,Rad51)mRNAexpressionlevel[1].Phosphoramidemustardcyclohexanamine(3-6μM;24-48hours)increasedDDRproteins[1].CellViabilityAssay[1]CellLine:SIGCsConcentration:0.5μM,1μM,3μM,6μMIncubationTime:48hours1/3MasterofSmallMolecules—您?邊的抑制劑?師www.MedChemEResult:Reducedcellviabilityatconcentrationsof3μMandhigher.RT-PCR[1]CellLine:SIGCsConcentration:3μM,6μMIncubationTime:24hours,48hoursResult:IncreasedDDRgenemRNAexpressionlevels.WesternBlotAnalysis[1]CellLine:SIGCsConcentration:3μM,6μMIncubationTime:24hours,48hoursResult:GenerallyincreasedDDRproteins.體內(nèi)研究Phosphoramidemustardcyclohexanamine(2.1-20.7mg/kg;i.p.;daily;for5days)inhibitssubcutaneoustumorgrowthinrats[2].Phosphoramidemustardcyclohexanamine(86.0mg/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:86.0mg/kg(PharmacokineticAnalysis)Administration:IntravenousinjectionResult:Hadadisappearancehalf-lifeof15.1minutesinplasma.REFERENCES2/3MasterofSmallMolecules—您?邊的抑制劑?師www.MedChemE[1].ShanthiGanesan,etal.PhosphoramidemustardexposureinducesDNAadductformationandtheDNAdamagerepairresponseinratovariangranulosacells.ToxicolApplPharmacol.2015Feb1;282(3):252–258.[2].SGenka,etal.Brainandplasmapharmacokineticsandanticanceractivitiesofcyclophosphamideandphosphoramidemustardintherat.CancerChemotherPharmacol.1990;27(1):1-7.McePdfHeightCaution:Producthasnotbeenfullyval