Hotline:400-820-3792Inhibitors?ScreeningLibraries?Proteinswww.MedChemEDSM265Cat.No.:HY-100184CASNo.:1282041-94-4分?式:C??H??F?N?S分?量:415.33作?靶點(diǎn):DihydroorotateDehydrogenase;Parasite作?通路:MetabolicEnzyme/Protease;Anti-infection儲(chǔ)存?式:Powder-20°C3years4°C2yearsInsolvent-80°C6months-20°C1month溶解性數(shù)據(jù)體外實(shí)驗(yàn)DMSO:50mg/mL(120.39mM;Needultrasonic)Ethanol:11.11mg/mL(26.75mM;Needultrasonic)MassSolvent1mg5mg10mgConcentration制備儲(chǔ)備液1mM2.4077mL12.0386mL24.0772mL5mM0.4815mL2.4077mL4.8154mL10mM0.2408mL1.2039mL2.4077mL請根據(jù)產(chǎn)品在不同溶劑中的溶解度選擇合適的溶劑配制儲(chǔ)備液；?旦配成溶液，請分裝保存，避免反復(fù)凍融造成的產(chǎn)品失效。儲(chǔ)備液的保存?式和期限：-80°C,6months;-20°C,1month。-80°C儲(chǔ)存時(shí)，請?jiān)?個(gè)?內(nèi)使?，-20°C儲(chǔ)存時(shí)，請?jiān)?個(gè)?內(nèi)使?。體內(nèi)實(shí)驗(yàn)請根據(jù)您的實(shí)驗(yàn)動(dòng)物和給藥?式選擇適當(dāng)?shù)娜芙?案。以下溶解?案都請先按照InVitro?式配制澄的儲(chǔ)備液，再依次添加助溶劑：(為保證實(shí)驗(yàn)結(jié)果的可靠性，澄的儲(chǔ)備液可以根據(jù)儲(chǔ)存條件，適當(dāng)保存；體內(nèi)實(shí)驗(yàn)的?作液，建議您現(xiàn)?現(xiàn)配，當(dāng)天使?；以下溶劑前顯?的百分?指該溶劑在您配制終溶液中的體積占?；如在配制過程中出現(xiàn)沉淀、析出現(xiàn)象，可以通過加熱和/或超聲的?式助溶)1.請依序添加每種溶劑：10%DMSO>>40%PEG300>>5%Tween-80>>45%saline1/2MasterofBioactiveMolecules—您?邊的抑制劑?師www.MedChemESolubility:≥2.75mg/mL(6.62mM);Clearsolution2.請依序添加每種溶劑：10%DMSO>>90%cornoilSolubility:≥2.75mg/mL(6.62mM);ClearsolutionBIOLOGICALACTIVITY?物活性DSM265?種長效的惡性瘧原??氫乳酸脫氫酶PfDHODH抑制劑，其IC50值為8.9nM。DSM265還可以抑制Pf3D7的?長，其EC50值為4.3nM。IC50&TargetIC50:8.9nM(PfDHODH)[1]EC50:4.3nM(P.falciparum3D7parasites)[1]體內(nèi)研究DSM265(0.5to75mg/kg;Oraladministration;twicedaily;for4days;NOD-scidIL-2Rγnull(NSG)mice)haspotentinvivoantimalarialactivitywith90%effectivedose(ED90)of3mg/kgperday(1.5mg/kgtwicedaily).Themaximumrateofparasitekillingoccurredatandaboveadoseof13mg/kgperday(6.4mg/kgtwicedaily).DSM265hasmoderateterminaleliminationhalf-life(t1/2)of2-4hoursformice(0.5to75mg/kg,oral)[2].AnimalModel:NOD-scidIL-2Rγnull(NSG)mice(23-36g)[2]Dosage:0.5to75mg/kgAdministration:Oraladministration;twicedaily;for4daysResult:Hadpotentantimalarialactivitywith90%effectivedose(ED90)of3mg/kgperday(1.5mg/kgtwicedaily).REFERENCES[1].KokkondaS,etal.Tetrahydro-2-naphthyland2-IndanylTriazolopyrimidinesTargetingPlasmodiumfalciparumDihydroorotateDehydrogenaseDisplayPotentandSelectiveAntimalarialActivity.JMedChem.2016Jun9;59(11):5416-31.[2].PhillipsMA,etal.Along-durationdihydroorotatedehydrogenaseinhibitor(DSM265)forpreventionandtreatmentofmalaria.SciTranslMed.2015Jul15;7(296):296ra111.McePdfHeightCaution:Producthasnotbeenfullyvalidatedformedicalapplications.For