MD2-IN-1-DataSheet-生命科学试剂-MedChemExpressVIP

Hotline:400-820-3792Inhibitors•ScreeningLibraries•Proteinswww.MedChemEMD2-IN-1Cat.No.:HY-103483CASNo.:111797-22-9分⼦式:C₂₀H₂₂O₆分⼦量:358.39作⽤靶点:Toll-likeReceptor(TLR)作⽤通路:Immunology/Inflammation储存⽅式:Powder-20°C3years4°C2yearsInsolvent-80°C6months-20°C1month溶解性数据体外实验DMSO:50mg/mL(139.51mM;Needultrasonic)MassSolvent1mg5mg10mgConcentration制备储备液1mM2.7903mL13.9513mL27.9026mL5mM0.5581mL2.7903mL5.5805mL10mM0.2790mL1.3951mL2.7903mL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%salineSolubility:≥3.25mg/mL(9.07mM);Clearsolution1/3MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemE2.请依序添加每种溶剂：10%DMSO>>90%(20%SBE-β-CDinsaline)Solubility:3.25mg/mL(9.07mM);Suspendedsolution;Needultrasonic3.请依序添加每种溶剂：10%DMSO>>90%cornoilSolubility:≥3.25mg/mL(9.07mM);ClearsolutionBIOLOGICALACTIVITY⽣物活性MD2-IN-1髓样分化蛋⽩2(MD2)的抑制剂，对重组⼈MD2(rhMD2)的KD值为189μM。IC50&TargetKD:189μM(rhMD2)[1]体外研究Myeloiddifferentiationprotein2(MD2)isaco-receptorofTLR4.Amongthosederivatives,MD2-IN-1(compound20)showsthestrongestinhibitoryeffectonLPS-inducedexpressionofbothTNF-αandIL-6.Comparetothevehicle,LPSalonelargelyincreasestheamountofTLR4/MD2complex,whilepretreatmentwithMD2-IN-1inhibitstheincreaseofTLR4/MD2complextothevehiclelevel.SPRanalysisshowsthatMD2-IN-1exhibitsrecognizablebindingtorhMD2proteininadose-dependentmanner,withaKDvalueof189ꢀμM,whiletheKDvalueofxanthohumolbindingtoMD2is460ꢀμM.Pre-treatmentwithdifferentdosesofMD2-IN-1dose-dependentlyreducesFITC-LPSbindingtoMD2incellsurfacemembranes,witha65%inhibitionat10ꢀμMintermsofmeanfluorescenceintensity.PretreatmentwithMD2-IN-1alsodose-dependentlyblocksLPS-inducedMAPKphosphorylationintheMPMs[1].体内研究AdministrationofMD2-IN-1evidentlyreducestheLPS-inducedincreaseinproteinconcentrationsinBALF.Thelungwet/dryweightratioismarkedlyhigherintheLPS-treatedgroupthanthecontrolgroup,andMD2-IN-1treatmentreducesLPS-inducedpulmonaryedema.LPSalsocausesobservablelunghistopathologicchanges,includingareasofinflammatoryinfiltration,hemorrhage,interstitialedema,thickeningofthealveolarwall,andlungtissuedestruction.ThesehistopathologicalchangesareamelioratedintheMD2-IN-1treatmentgroup[1].PROTOCOLCellAssay[1]MouseRAW264.7macrophagesarestarvedfor3ꢀhbeforeexperimentation.CellsareincubatedwithorwithoutFITC-LPS(50ꢀμg/mL)inthepresenceorabsenceofMD2-IN-1(0.1,1and10ꢀμM)for30ꢀmin.Afterincubation,macrophagesarefixedwithparaformaldehydefor10ꢀminat4°CandwashedwithPBSbeforebeinganalyzedbyflowcytometry[1].MCEhasnotindependentlyconfirmedtheaccuracyofthesemethods.Theyareforreferenceonly.AnimalMaleSpragueDawley(SD)ratsarerandomlydividedintothreegroups,designated“control”(5rats,onlyAdministration[1]receivethevehicleof0.9%saline),“LPS”(7rats,receive5ꢀmg/kgLPSalone)and“MD2-IN-1(20)ꢀ+ꢀLPS”(6rats,receivebothMD2-IN-1and5ꢀmg/kgLPS).PriortoLPS-inducedAcutelunginjury(ALI),theMD2-IN-1+LPSgroupratsaretreatedintragastricallywithMD2-IN-1atadosageof20ꢀmg/kg/daycontinuouslyforoneweek.Underetheranesthesia,alltheratsareexposedtheirtracheaandchallengedwithintratrachealinstillationof50ꢀμLofLPS,whilethecontrolgroupchallengedwithintratrachealinstillationof50ꢀμLof0.9%2/3MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemEsaline.Ratsaretheneuthanizedwithketamineafter6ꢀhofLPSinduction[1].MCEhasnotindependentlyconfirmedtheaccuracyofthesemethods.Theyareforreferenceonly.REFERENCES[1].ZhangY,etal.DiscoveryofnewMD2inhibitorfromchalconederivativeswithanti-inflammatoryeffectsinLPS-inducedacutelunginjury.SciRep.2016Apr27;6:251