plus-SJ733-SJ000557733-DataSheet-生命科学试剂-MedChemExpress

Hotline:400-820-3792Inhibitors•ScreeningLibraries•Proteinswww.MedChemE(+)-SJ733Cat.No.:HY-19556CASNo.:1424799-20-1Synonyms:SJ000557733分⼦式:C₂₄H₁₆F₄N₄O₂分⼦量:468.4作⽤靶点:Na+/K+ATPase;Parasite作⽤通路:MembraneTransporter/IonChannel;Anti-infection储存⽅式:Powder-20°C3years4°C2yearsInsolvent-80°C6months-20°C1month溶解性数据体外实验DMSO:50mg/mL(106.75mM;Needultrasonic)MassSolvent1mg5mg10mgConcentration制备储备液1mM2.1349mL10.6746mL21.3493mL5mM0.4270mL2.1349mL4.2699mL10mM0.2135mL1.0675mL2.1349mL请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；⼀旦配成溶液，请分装保存，避免反复冻融造成的产品失效。储备液的保存⽅式和期限：-80°C,6months;-20°C,1month。-80°C储存时，请在6个⽉内使⽤，-20°C储存时，请在1个⽉内使⽤。体内实验请根据您的实验动物和给药⽅式选择适当的溶解⽅案。以下溶解⽅案都请先按照InVitro⽅式配制澄的储备液，再依次添加助溶剂：(为保证实验结果的可靠性，澄的储备液可以根据储存条件，适当保存；体内实验的⼯作液，建议您现⽤现配，当天使⽤；以下溶剂前显⽰的百分⽐指该溶剂在您配制终溶液中的体积占⽐；如在配制过程中出现沉淀、析出现象，可以通过加热和/或超声的⽅式助溶)1.请依序添加每种溶剂：10%DMSO>>40%PEG300>>5%Tween-80>>45%saline1/3MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemESolubility:≥2.5mg/mL(5.34mM);Clearsolution2.请依序添加每种溶剂：10%DMSO>>90%(20%SBE-β-CDinsaline)Solubility:≥2.5mg/mL(5.34mM);Clearsolution3.请依序添加每种溶剂：10%DMSO>>90%cornoilSolubility:≥2.5mg/mL(5.34mM);ClearsolutionBIOLOGICALACTIVITY⽣物活性(+)-SJ733⼀种抗疟疾剂，也⼀个Na+-ATPasePfATP4抑制剂。IC50&TargetParasite,Na+-ATPasePfATP4[1]体外研究(+)-SJ733bindstoasinglereceptorsiteinP.falciparum-infectederythrocyteswithequivalentaffinitytoitsgrowth-inhibitorypotency(kd=50nM).(+)-SJ733hasnotexhibitedeithersignificantsafetyliabilitiesatanydoseinextensiveprofilinginvitroorsignificantsafetyortolerabilityliabilitiesineithersingle-orrepeat-dosestudiesatanydosetestedinanypreclinicalspecies(noobservedadverseeffectlevelandmaximumtolerateddose>240mg/kgfrom7-drepeatdosingstudyinrat).Therefore,(+)-SJ733isexpectedtohaveasafetymarginofatleast43-fold[1].体内研究TreatmentofP.falciparum-infectedNOD-scidIL2Rγnullmicewith(+)-SJ733causesrapidclearanceofparasites,whichare80%depletedwithinthefirst24handundetectableby48h.(+)-SJ733ishighlypotent

andefficaciousagainstP.falciparum3D70087/N9invivowhenadministeredasfoursequentialdailyoral

dosesintheNOD-scidIL2Rγnullmousemodel,witha90%effectivedose,(ED901.9mg/kg)andexposure[areaunderthecurveatED90(AUCED90),1.5μM⋅h]superiortoartesunate(11.1mg/kg;AUCED90not

determined),chloroquine(4.3mg/kg;AUCED903.1μM⋅h),andpyrimethamine(0.9mg/kg;AUCED905.μM⋅h)inthe

samemodel.WhentreatedwiththeED90dose,(+)-SJ733concentrationsinbloodremainabovetheaverageinvitro

EC90for6to10haftereachdose[1].PROTOCOLCellAssay[1]10mLofasynchronousculturesuspensions(2%hematocrit),atdifferentparasitedensities(104,105,106,107,and108parasites),areaddedtoeachwellofa6-wellplate.(+)-SJ733isaddedtoeachwelltomakeafinalcompoundconcentrationof1.8μM,correspondingto30×EC50ofthecompound.Threewellsareusedforeachparasitedensity.Platesareincubatedat37°Cunderanatmosphereof90%N2,5%O2,5%CO2for90daysunderconstantdrugpressure.Themediaofeachwellisreplaced3timesaweekwithfreshlymademediacontainingacompoundconcentrationof30×EC50.Inaddition,eachwellissplit(1:2)onceaweek.Parasiteoutgrowthismonitored3timesaweekbytransferringquadruplicate40μLaliquotsfromeachwellintoa384-wellassayplateanddeterminingparasitemiabyapreviouslydescribedmethod[1].MCEhasnotindependentlyconfirmedtheaccuracyofthesemethods.Theyareforreferenceonly.AnimalThepharmacokineticsof(+)-SJ733arestudiedinovernight-fastedmaleSpragueDawleyratsweighing267Administration[1]to291gpredose.Ratshaveaccesstowateradlibitumthroughoutthepre-andpost-dosesamplingperiod,2/3MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemEandaccesstofoodisreinstated4hpost-dose.(+)-SJ733isadministeredintravenouslyasa10minconstantrateinfusion(1.0mLperrat,n=3rats)andorallybygavage(10mL/kg,n=3rats).TheIVformulationconsistsofpH7.4isotonicphosphatebufferedsalinecontaining1%(w/v)hydroxypropyl-β-cyclodextrin,10%(v/v)ethanol,10%(v/v)propyleneglycoland40%(v/v)PEG400whereastheoralformulationisanaqueoussuspensionin0.5%(w/v)hydroxypropylmethylcellulose,0.5%(v/v)benzylalcoholand0.4%(v/v)Tween80.Aliquotsoftheformulationsareretainedforanalysisoftheactualdoseadministered.Samplesofarterialbloodandtotalurinearecollectedatvarioustimepointsupto24hpost-dose[1].MCEhasnotindependentlyconfirmedtheaccuracyofthesemethods.Theyareforreferenceonly.REFERENCES[1].Jimenez-DiazMB,etal.(+)-SJ733,aclinicalcandidateformalariathatactsthroughATP4toinducerapidhost-mediatedclearanceofPlasmodium.ProcNatlAcadS