Hotline:400-820-3792Inhibitors?ScreeningLibraries?Proteinswww.MedChemEUCT943Cat.No.:HY-112435CASNo.:1450666-80-4分?式:C??H??F?N?O分?量:427.42作?靶點:PI4K;Parasite作?通路:PI3K/Akt/mTOR;Anti-infection儲存?式:Powder-20°C3years4°C2yearsInsolvent-80°C6months-20°C1month溶解性數(shù)據(jù)體外實驗DMSO:250mg/mL(584.90mM;Needultrasonic)MassSolvent1mg5mg10mgConcentration制備儲備液1mM2.3396mL11.6981mL23.3962mL5mM0.4679mL2.3396mL4.6792mL10mM0.2340mL1.1698mL2.3396mL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備液；?旦配成溶液，請分裝保存，避免反復凍融造成的產(chǎn)品失效。儲備液的保存?式和期限：-80°C,6months;-20°C,1month。-80°C儲存時，請在6個?內(nèi)使?，-20°C儲存時，請在1個?內(nèi)使?。體內(nèi)實驗請根據(jù)您的實驗動物和給藥?式選擇適當?shù)娜芙?案。以下溶解?案都請先按照InVitro?式配制澄的儲備液，再依次添加助溶劑：(為保證實驗結(jié)果的可靠性，澄的儲備液可以根據(jù)儲存條件，適當保存；體內(nèi)實驗的?作液，建議您現(xiàn)?現(xiàn)配，當天使?；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%salineSolubility:≥2.08mg/mL(4.87mM);Clearsolution1/2MasterofBioactiveMolecules—您?邊的抑制劑?師www.MedChemE2.請依序添加每種溶劑：10%DMSO>>90%(20%SBE-β-CDinsaline)Solubility:≥2.08mg/mL(4.87mM);Clearsolution3.請依序添加每種溶劑：10%DMSO>>90%cornoilSolubility:≥2.08mg/mL(4.87mM);ClearsolutionBIOLOGICALACTIVITY?物活性UCT943新?代惡性瘧原?PlasmodiumfalciparumPI4K抑制劑。UCT943抑制P.vivaxPI4K(PvPI4K)酶，IC50為23nM[1]。IC50&TargetPvPI4KPlasmodium23nM(IC50)體外研究UCT943maintainshighinvitroselectivity(>200-fold)fortheparasitePvPI4KversusthehumanPI4Kβisozyme(IC50ofPI4Kβ,5.4μM),inhibitionofwhichislinkedtoimmunosuppressiveeffects[1].InvitrocytotoxicityofUCT943istestedagainstL6cells,chinesehamsterovarian(CHO),Vero,andHepG2cells,with50%cytotoxicconcentrations(CC50s)of12,17,113,and13μM,respectively[1].體內(nèi)研究UCT943showsexcellentinvivoefficacyinthePlasmodiumberghei(10mg/kgand3mg/kg;oraladministration;daily;4days)andP.falciparumNSG(NOD-scidIL-2Rγnull)mousemodels(0.01,0.1,0.3,1.1and10mg/kg;oraladministration;onceperday;4days).Whendosedat10mg/kgperos(p.o.),UCT943reducesparasitemiaby>99.9%inthemouseP.bergheiinfectionmodelandcuresallmice,with>30meansurvivaldays(MSD).At3mg/kgp.o.,nocompletecureisachieved,andMSDis10days,albeitparasitemiaisreducedby99%.Theresulting90%effectivedose(ED90)is1.0mg/heP.bergheiinfectionmodel.TheED90is0.25mg/kgintheP.falciparum-infectedNSGmousemodel[1].AnimalModel:MicewithP.bergheiandP.falciparumNOD-scidIL-2Rγnull(NSG)models[1]Dosage:10mg/kgand3mg/kgforP.bergheimodel;0.01,0.1,0.3,1.1and10mg/kgforP.falciparumNOD-scidIL-2Rγnull(NSG)modelAdministration:Oraladministration;daily;4daysforP.bergheimodelOraladministration;onceperday;4daysforP.falciparumNOD-scidIL-2Rγnull(NSG)modelResult:TheED90is1.0mg/kgintheP.bergheiinfectionmodel.TheED90is0.25mg/kgintheP.falciparum-infectedNSGmousemodel.REFERENCES[1].BrunschwigC,etal.UCT943,aNext-GenerationPlasmodiumfalciparumPI4KInhibitorPreclinicalCandidatefortheTreatmentofMalaria.AntimicrobAgentsChemother.2018Aug27;62(9).pii:e00012-18.McePdfHeight2/2MasterofBioactiveMolecules—您?邊的抑制劑?師www.MedChemECaution:Producthasnotbeenfullyv