MK8722-DataSheet-生命科学试剂-MedChemExpressVIP

Hotline:400-820-3792Inhibitors•ScreeningLibraries•Proteinswww.MedChemEMK8722Cat.No.:HY-111363CASNo.:1394371-71-1分⼦式:C₂₄H₂₀ClN₃O₄分⼦量:449.89作⽤靶点:AMPK作⽤通路:Epigenetics;PI3K/Akt/mTOR储存⽅式:Powder-20°C3years4°C2yearsInsolvent-80°C6months-20°C1month溶解性数据体外实验DMSO:31.25mg/mL(69.46mM;Needultrasonic)MassSolvent1mg5mg10mgConcentration制备储备液1mM2.2228mL11.1138mL22.2277mL5mM0.4446mL2.2228mL4.4455mL10mM0.2223mL1.1114mL2.2228mL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:2.08mg/mL(4.62mM);Clearsolution;Needultrasonic1/3MasterofBioactiveMolecules—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:≥2.08mg/mL(4.62mM);Clearsolution3.请依序添加每种溶剂：10%DMSO>>90%cornoilSolubility:≥2.08mg/mL(4.62mM);ClearsolutionBIOLOGICALACTIVITY⽣物活性MK8722⼀种有效的全⾝pan-AMPK激活剂。IC50&TargetAMPK体外研究MK8722(MK-8722)isapotent,direct,allostericactivatorofall12mammalianAMPKcomplexes.MK8722activatespAMPKcomplexeswithincreasedpotencyandmagnitudeversusAMP,withEC50valuesof~1to60nMandincreasedactivationbyfactorsof~4to24.AlthoughMK8722exhibitshigheraffinityforβ1-containing(~1to6nM)versusβ2-containing(~15to63nM)pAMPKcomplexes,itisthemostpotentactivatorofβ2complexesreportedtodate.pAMPKactivationbymaximalAMPplusMK8722issynergistic,demonstratingthattheagentsactatdistinctsites[1].体内研究ChronicantihyperglycemicefficacyofMK8722(MK-8722)isevaluatedindb/dbmice,aleptinreceptor-deficientT2DMmodel.Once-dailyadministrationofMK8722resultsindose-dependentloweringofambientbloodglucose.Ontreatmentday12,glucosereductionsafterMK8722treatment(30mpk/day)arecomparabletothoseobservedwiththePPARγagonistBRL49653(3mpk/day).UnlikeBRL49653,theglucose-loweringactionofMK8722manifestswithoutsignificanteffectsonbodyweight,whichisaconsistentfinding.Dose-dependentincreasesintissuepACCaremaintainedthroughoutthedosingperiod.Chronicefficacy,withouttachyphylaxis,isalsoobservedinadditionaldysmetabolicanddiabeticrodentmodels.Inallcases,efficacyisassociatedwithtroughMK8722plasmalevelscomparabletotheconcentrationsrequiredtoacutelystimulateskeletalmuscleglucoseuptake.ChronicMK8722dosinginmicealsoincreasesmuscleGlut4proteinlevels,possiblycontributingtoefficacy[1].PROTOCOLAnimalMice[1]Administration[1]HousingLeanC57BL/6miceat10-12weeksofageandC57BL/6eDIOmiceat16weeksofageareused.db/dbmiceat7weeksofageareused.Animalsaremaintainedona12hr/12hrlight-darkcyclewithfreeaccesstofoodandwaterwiththetemperaturemaintainedat22ºC.FourleanC57BL/6micearehousedinastandardcage.eDIOmiceareindividuallycaged.Eightdb/dbmicearehousedinalargerodentcage.C57BL/6miceanddb/dbmicearemaintainedonregularrodentchowdiet7012(5%dietaryfat;3.75kcal/g)for1-2weeksbeforereceivingcompoundtreatments.eDIOmicearemaintainedon60%kcal%fatdiet.OraldosingofMK8722instandardvehicle,orvehiclealone,isperformedusing10mL/kgbodyweight.TheeffectofMK8722onvariousmetabolicparametersisestablishedbycomparisontovehicletreatedanimals[1].MCEhasnotindependentlyconfirmedtheaccuracyofthesemethods.Theyareforreferenceonly.2/3MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemE户使⽤本产品发表的科研⽂献•MolCell.2021Feb4;81(3):629-637.e5.•Autophagy.2021Mar28;1-18.•BiochemPharmacol.2021Jan;183:114337.•SciRep.2021Jun11;11(1):12387.•STARProtoc.2021,100496.Seemorecustomervalidationsonwww.MedChemEREFERENCES[1].MyersRW,etal.Systemicpan-AMPKactivatorMK-8722improvesglucosehomeostasisbutinducescardiachypertrophy.Science.2017Aug4;357(6350):507-511