Hotline:400-820-3792Inhibitors?ScreeningLibraries?Proteinswww.MedChemELOC14Cat.No.:HY-100432CASNo.:877963-94-5分?式:C??H??N?O?S分?量:317.41作?靶點(diǎn):Others作?通路:Others儲(chǔ)存?式:4°C,protectfromlight*該產(chǎn)品在溶液狀態(tài)不穩(wěn)定，建議您現(xiàn)?現(xiàn)配，即刻使?。溶解性數(shù)據(jù)體外實(shí)驗(yàn)DMSO:50mg/mL(157.52mM;ultrasonicandwarmingandheatto60°C)MassSolvent1mg5mg10mgConcentration制備儲(chǔ)備液1mM3.1505mL15.7525mL31.5050mL5mM0.6301mL3.1505mL6.3010mL10mM0.3150mL1.5752mL3.1505mL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；該產(chǎn)品在溶液狀態(tài)不穩(wěn)定，建議您現(xiàn)?現(xiàn)配，即刻使?.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:≥2.08mg/mL(6.55mM);Clearsolution2.請(qǐng)依序添加每種溶劑：10%DMSO>>90%(20%SBE-β-CDinsaline)Solubility:≥2.08mg/mL(6.55mM);Clearsolution3.請(qǐng)依序添加每種溶劑：10%DMSO>>90%cornoil1/2MasterofBioactiveMolecules—您?邊的抑制劑?師www.MedChemESolubility:≥2.08mg/mL(6.55mM);ClearsolutionBIOLOGICALACTIVITY?物活性LOC14蛋?質(zhì)?硫鍵異構(gòu)酶(PDI)抑制劑(EC50=500nM;Kd=62nM)。LOC14在??肝微粒體和?漿中表現(xiàn)出?穩(wěn)定性，低內(nèi)在微粒體除率和低?漿蛋?結(jié)合。LOC14抑制PDIA3活性，降低肺上?細(xì)胞中HA的分?內(nèi)?硫鍵和隨后的寡聚化。IC50&TargetKd:62nM(PDI)[1]體外研究LOC14(0.01-100μM;24hours)exhibitsthecapacitytoinhibitrecombinant(r)PDIA3atanIC50ofapproximately5μM[3].CellViabilityAssay[3]CellLine:MTECcellsConcentration:0.01μM;0.1μM;0.5μM;1μM;5μM;10μM;100μMIncubationTime:24hoursResult:Inhibitedrecombinant(r)PDIA3activity.體內(nèi)研究LOC14(orallyadministeredbygavage;20mg/kg;oncedaily;12-28weeks)significantlyimprovesmotorfunction,attenuatedbrainatrophyandextendedsurvivalintheN171–82QHDmice[2].AnimalModel:MaleN171–82QHDmice[2]Dosage:20mg/kgAdministration:Orallyadministeredbygavage;20mg/kg;oncedaily;12-28weeksResult:ImprovedmotorfunctioninHDmice.REFERENCES[1].KaplanA,etal.Smallmolecule-inducedoxidationofproteindisulfideisomeraseisneuroprotective.ProcNatlAcadSciUSA.2015Apr28;112(17):E2245-52.[2].ChamberlainN,etal.LungepithelialproteindisulfideisomeraseA3(PDIA3)playsanimportantroleininfluenzainfection,inflammation,andairwaymechanics.RedoxBiol.2019Apr;22:101129.[3].ZhouX,etal.SmallmoleculemodulatorofproteindisulfideisomeraseattenuatesmutanthuntingtintoxicityandinhibitsendoplasmicreticulumstressinamousemodelofHuntington'sdisease.HumMolGenet.2018May1;27(9):1545-1555.McePdfHeitCaution:Producthasnotbeenfullyvalidatedformedicalapplications.gh