LOC14-DataSheet-生命科学试剂-MedChemExpress

Hotline:400-820-3792Inhibitors•ScreeningLibraries•Proteinswww.MedChemELOC14Cat.No.:HY-100432CASNo.:877963-94-5分⼦式:C₁₆H₁₉N₃O₂S分⼦量:317.41作⽤靶点:Others作⽤通路:Others储存⽅式:4°C,protectfromlight*该产品在溶液状态不稳定，建议您现⽤现配，即刻使⽤。溶解性数据体外实验DMSO:50mg/mL(157.52mM;ultrasonicandwarmingandheatto60°C)MassSolvent1mg5mg10mgConcentration制备储备液1mM3.1505mL15.7525mL31.5050mL5mM0.6301mL3.1505mL6.3010mL10mM0.3150mL1.5752mL3.1505mL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；该产品在溶液状态不稳定，建议您现⽤现配，即刻使⽤.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%salineSolubility:≥2.08mg/mL(6.55mM);Clearsolution2.请依序添加每种溶剂：10%DMSO>>90%(20%SBE-β-CDinsaline)Solubility:≥2.08mg/mL(6.55mM);Clearsolution3.请依序添加每种溶剂：10%DMSO>>90%cornoil1/2MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemESolubility:≥2.08mg/mL(6.55mM);ClearsolutionBIOLOGICALACTIVITY⽣物活性LOC14蛋⽩质⼆硫键异构酶(PDI)抑制剂(EC50=500nM;Kd=62nM)。LOC14在⼩⿏肝微粒体和⾎浆中表现出⾼稳定性，低内在微粒体除率和低⾎浆蛋⽩结合。LOC14抑制PDIA3活性，降低肺上⽪细胞中HA的分⼦内⼆硫键和随后的寡聚化。IC50&TargetKd:62nM(PDI)[1]体外研究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.体内研究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