Hotline:400-820-3792Inhibitors?ScreeningLibraries?Proteinswww.MedChemESPL-707Cat.No.:HY-111360CASNo.:2195361-33-0分?式:C??H??FN?O?分?量:505.54作?靶點(diǎn):γ-secretase作?通路:NeuronalSignaling;StemCell/Wnt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:100mg/mL(197.81mM;Needultrasonic)MassSolvent1mg5mg10mgConcentration制備儲(chǔ)備液1mM1.9781mL9.8904mL19.7808mL5mM0.3956mL1.9781mL3.9562mL10mM0.1978mL0.9890mL1.9781mL請(qǐng)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(qǐng)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(qǐng)?jiān)?個(gè)?內(nèi)使?，-20°C儲(chǔ)存時(shí)，請(qǐng)?jiān)?個(gè)?內(nèi)使?。體內(nèi)實(shí)驗(yàn)請(qǐng)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(qǐng)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(qǐng)依序添加每種溶劑：10%DMSO>>40%PEG300>>5%Tween-80>>45%salineSolubility:≥5mg/mL(9.89mM);Clearsolution1/2MasterofBioactiveMolecules—您?邊的抑制劑?師www.MedChemE2.請(qǐng)依序添加每種溶劑：10%DMSO>>90%cornoilSolubility:≥5mg/mL(9.89mM);ClearsolutionBIOLOGICALACTIVITY?物活性SPL-707?服有效的，選擇性的信號(hào)肽肽酶樣2a(SPPL2a)抑制劑，對(duì)hSPPL2a的IC50為77nM。SPL-707抑制γ-分泌酶(γ-secretase;IC50=6.1μM)和SPP(IC50=3.7μM)。SPL-707具有靶向B細(xì)胞和樹突狀細(xì)胞的??免疫疾病的研究潛?。IC50&TargetIC50:77nM(SPPL2a),6.1μM(γ-secretase)and3.7μM(SPP)[1]體外研究SPL-707(Compound40)inhibitsmouseSPPL2a(IC50=0.18μM),ratSPPL2a(IC50=0.056μM)andhumanSPPL2a(IC50=0.16μM),humanSPPL2b(IC50=0.43μM)byahighcontentimagingassay(HCA)[1].體內(nèi)研究SPL-707(Compound40;3-30mg/kg;orally;b.i.d.;for11days)leadstoareductioninBcellsandmyeloiddendriticcellswithoutaffectingγ-secretaseactivity[1].SPL-707(3mg/kgofpoand1mg/kgofiv)hasaCLof6mL/min?kg,andanAUCof8787h?nM[1].SPL-707(1,3mg/kg;b.i.d.;firstdoseat0h,seconddoseat8h)achievesfullinhibitionofCD74/p8processinginspleeninfemaleLewisrats[1].AnimalModel:Micewith5-12weeksofage[1]Dosage:3,10,and30mg/kgAdministration:Orally;b.i.d.(with8and16hdosingintervals);for11daysResult:LedtoareductioninBcellsandmyeloiddendriticcellswithoutaffectingγ-secretaseactivity.AnimalModel:FemaleSprague?Dawleyrat[1]Dosage:3mg/kgofpoand1mg/kgofiv(PharmacokineticAnalysis)Administration:POorIVResult:HadaCLof6mL/min?kg,andanAUCof8787h?nM.REFERENCES[1].VelcickyJ,etal.DiscoveryoftheFirstPotent,Selective,andOrallyBioavailableSignalPeptidePeptidase-Like2a(SPPL2a)InhibitorDisplayingPronouncedImmunomodulatoryEffectsInVivo.JMedChem.2018Feb8;61(3):865-880.McePdfHeightCaution:Producthasnotbeenfullyvalidatedformedicalapplicati