Diprovocim-DataSheet-生命科学试剂-MCE

Hotline:400-820-3792Inhibitors•ScreeningLibraries•Proteinswww.MedChemEDiprovocimCat.No.:HY-123942CASNo.:2170867-89-5分⼦式:C₅₆H₅₆N₆O₆分⼦量:909.08作⽤靶点:Toll-likeReceptor(TLR);TNFReceptor;p38MAPK;NF-κB作⽤通路:Immunology/Inflammation;Apoptosis;MAPK/ERKPathway;NF-κB储存⽅式:Powder-20°C3years4°C2yearsInsolvent-80°C6months-20°C1month溶解性数据体外实验DMSO:33.33mg/mL(36.66mM;ultrasonicandwarmingandheatto60°C)H2O:<0.1mg/mL(ultrasonic)(insoluble)MassSolvent1mg5mg10mgConcentration制备储备液1mM1.1000mL5.5001mL11.0001mL5mM0.2200mL1.1000mL2.2000mL10mM0.1100mL0.5500mL1.1000mL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)1/3MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemE1.请依序添加每种溶剂：10%DMSO>>90%cornoilSolubility:2.5mg/mL(2.75mM);Suspendedsolution;NeedultrasonicBIOLOGICALACTIVITY⽣物活性Diprovocim⼀种有效的TLR1/TLR2激动剂。Diprovocim在⼈THP-1细胞中引发完全激动剂活性(EC50=110pM)。Diprovocim刺激⼩⿏巨噬细胞释放TNF-α(EC50=1.3nM)。Diprovocim激活下游MAPK和NF-κB信号通路。Diprovocim在⼩⿏中显⽰出很强的佐剂活性，尤其促进细胞免疫反应。IC50&TargetTLR1TLR2p38MAPKNF-κB体外研究Diprovocim(5nMinTHP-1and500nMinmouseperitonealmacrophage;15-120mins)inducesphosphorylationofIKKα,IKKβ,p38,JNK,andERK,aswellasdegradationofIκBαinTHP-1cellsandmouseperitonealmacrophages[2].Diprovocim(0.01-10000nM;4hours)inducesdose-dependentTNFproductionbyTHP-1cells(EC50=110pM)andhumanperipheralbloodmononuclearcells(PBMC)(EC50=875pM)andbymouseperitonealmacrophages(EC50=1.3nM)andbonemarrow-deriveddendriticcells(BMDC)(EC50=6.7nM).InadditiontoTNF,DiprovociminducedIL-6productionbymouseBMDC[2].WesternBlotAnalysis[2]CellLine:THP-1cellsandmouseperitonealmacrophagesConcentration:5nMinTHP-1and500nMinmouseperitonealmacrophagesIncubationTime:15,30,60,120minsResult:InducedphosphorylationofIKKα,IKKβ,p38,JNK,andERK,aswellasdegradationofIκBα.体内研究Diprovocim(10mg/kg)usesasanadjuvantandmixedwithovalbumin(OVA;100μg)byi.m.inducessimilarlevelsofserumOVA-specificIgGafter14days[2].Diprovocim(10mg/kg;i.m.)mixedwithovalbumin(OVA;100μg)beforeinoculationwithB16-OVAcellsimmunizessignificantlyslowstumorgrowthratebutfailedtoprolongsurvivalrelativetoOVAaloneafter7days[2].AnimalModel:WTorTlr2−/−C57BL/6Jmice[2]Dosage:10mg/kgAdministration:IMResult:InducedsimilarlevelsofserumOVA-specificIgG,whichwerehighlyelevatedcomparedwithlevelsinducedbyimmunizationwithOVAplusvehiclebyi.m.with100μgOVAmixedwiththisdrug.2/3MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemEREFERENCES[1].MatthewDMorin,etal.Diprovocims:ANewandExceptionallyPotentClassofToll-likeReceptorAgonists.JAmChemSoc.2018Oct31;140(43):14440-14454.[2].YingWang,etal.AdjuvanteffectofthenovelTLR1/TLR2agonistDiprovocimsynergizeswithanti-PD-L1toeliminatemelanomainmice.ProcNatlAcadSciUSA.2018Sep11;115(37):E8698-E8706.McePdfHeightCaution:Producthasnotbeenful