DSM705-DataSheet-生命科学试剂-MedChemExpress

Hotline:400-820-3792Inhibitors•ScreeningLibraries•Proteinswww.MedChemEDSM705Cat.No.:HY-132171CASNo.:2653225-38-6分⼦式:C₁₉H₁₉F₃N₆O分⼦量:404.39作⽤靶点:DihydroorotateDehydrogenase;Parasite作⽤通路:MetabolicEnzyme/Protease;Anti-infection储存⽅式:PleasestoretheproductundertherecommendedconditionsintheCertificateofAnalysis.BIOLOGICALACTIVITY⽣物活性DSM705⼀种于吡咯的⼆氢乳酸脱氢酶(DHODH)抑制剂。DSM705对PlasmodiumDHODH和Plasmodium寄⽣⾍表现出纳尔级效⼒，对哺乳动物DHODH没有抑制作⽤。DSM705⼀种有效的抗疟化合物。IC50&TargetIC50:95nM(P.falciparumDHODH),52nM(P.vivaxDHODH)[1]体外研究DSM705showsinhibitoryactivityagainstP.falciparumDHODH(PfDHODH,IC50=95nM),P.vivaxDHODH(PvDHODH,IC50=52nM)andPf3D7cells(EC50=12nM),withnoinhibitionofthehumanenzyme[1].体内研究DSM705(3-200mg/kg;p.o.twiceadayfor6days)providesthemaximumrateofparasitekillingatthedoseof50mg/kgandfullysuppressesparasitemiabydays7-8[1].DSM705(2.6and24mg/kg;asinglep.o.)exhibitshighoralbioavailability(74%,70%),apparentt1/2(3.4,4.5h)andCmax(2.6,20μM)inSwissoutbredmice[1].DSM705(2.3mg/kg;asinglei.v.)exhibitsplasmaclearance(CL=2.8mL/min/kg)andVss(1.3L/kg)inmice[1].AnimalModel:SCIDmicewereinoculatedwithparasites[1]Dosage:3,10,20,50,100,200mg/kgAdministration:P.o.twiceadayfor6daysResult:Killedparasiteinadosedependentmannerandfullysuppressedparasitemiabydays7-1/2MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemE8.AnimalModel:SwissOutbredMice[1]Dosage:2.6and24mg/kgforp.o.;2.3mg/kgfori.v.(PharmacokineticAnalysis)Administration:Asinglep.o.andi.v.Result:P.o.:F=74/70%,t1/2=3.4/4.5h,Cmax=2.6/20μM.I.v.:CL=2.8mL/min/kg,Vss=1.3L/kg.REFERENCES[1].PalmerMJ,et,al.PotentAntimalarialswithDevelopmentPotentialIdentifiedbyStructure-GuidedComputationalOptimizationofaPyrrole-BasedDihydroorotateDehydrogenaseInhibitorSeries.JMedChem.2021May13;64(9):6085-6136.McePdfHeightCaution:Producthasnotbeenfullyvalidatedformedicalapplications.Forresearchuseonly.Tel:40