MK8722-DataSheet-生命科學(xué)試劑-MedChemExpress

Hotline:400-820-3792Inhibitors?ScreeningLibraries?Proteinswww.MedChemEMK8722Cat.No.:HY-111363CASNo.:1394371-71-1分?式:C??H??ClN?O?分?量:449.89作?靶點:AMPK作?通路:Epigenetics;PI3K/Akt/mTOR儲存?式:Powder-20°C3years4°C2yearsInsolvent-80°C6months-20°C1month溶解性數(shù)據(jù)體外實驗DMSO:31.25mg/mL(69.46mM;Needultrasonic)MassSolvent1mg5mg10mgConcentration制備儲備液1mM2.2228mL11.1138mL22.2277mL5mM0.4446mL2.2228mL4.4455mL10mM0.2223mL1.1114mL2.2228mL請根據(jù)產(chǎn)品在不同溶劑中的溶解度選擇合適的溶劑配制儲備液；?旦配成溶液，請分裝保存，避免反復(fù)凍融造成的產(chǎn)品失效。儲備液的保存?式和期限：-80°C,6months;-20°C,1month。-80°C儲存時，請在6個?內(nèi)使?，-20°C儲存時，請在1個?內(nèi)使?。體內(nèi)實驗請根據(jù)您的實驗動物和給藥?式選擇適當?shù)娜芙?案。以下溶解?案都請先按照InVitro?式配制澄的儲備液，再依次添加助溶劑：(為保證實驗結(jié)果的可靠性，澄的儲備液可以根據(jù)儲存條件，適當保存；體內(nèi)實驗的?作液，建議您現(xiàn)?現(xiàn)配，當天使?；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.請依序添加每種溶劑：10%DMSO>>40%PEG300>>5%Tween-80>>45%salineSolubility:2.08mg/mL(4.62mM);Clearsolution;Needultrasonic1/3MasterofBioactiveMolecules—您?邊的抑制劑?師www.MedChemE2.請依序添加每種溶劑：10%DMSO>>90%(20%SBE-β-CDinsaline)Solubility:≥2.08mg/mL(4.62mM);Clearsolution3.請依序添加每種溶劑：10%DMSO>>90%cornoilSolubility:≥2.08mg/mL(4.62mM);ClearsolutionBIOLOGICALACTIVITY?物活性MK8722?種有效的全?pan-AMPK激活劑。IC50&TargetAMPK體外研究MK8722(MK-8722)isapotent,direct,allostericactivatorofall12mammalianAMPKcomplexes.MK8722activatespAMPKcomplexeswithincreasedpotencyandmagnitudeversusAMP,withEC50valuesof~1to60nMandincreasedactivationbyfactorsof~4to24.AlthoughMK8722exhibitshigheraffinityforβ1-containing(~1to6nM)versusβ2-containing(~15to63nM)pAMPKcomplexes,itisthemostpotentactivatorofβ2complexesreportedtodate.pAMPKactivationbymaximalAMPplusMK8722issynergistic,demonstratingthattheagentsactatdistinctsites[1].體內(nèi)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?邊的抑制劑?師www.MedChemE戶使?本產(chǎn)品發(fā)表的科研?獻?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