MK-3903-DataSheet-生命科学试剂-MedChemExpress

Hotline:400-820-3792Inhibitors•ScreeningLibraries•Proteinswww.MedChemEMK-3903Cat.No.:HY-107988CASNo.:1219737-12-8分⼦式:C₂₇H₁₉ClN₂O₃分⼦量:454.9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:≥100mg/mL(219.83mM)*"≥"meanssoluble,butsaturationunknown.MassSolvent1mg5mg10mgConcentration制备储备液1mM2.1983mL10.9914mL21.9829mL5mM0.4397mL2.1983mL4.3966mL10mM0.2198mL1.0991mL2.1983mL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%saline1/3MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemESolubility:≥2.5mg/mL(5.50mM);Clearsolution2.请依序添加每种溶剂：10%DMSO>>90%cornoilSolubility:≥2.5mg/mL(5.50mM);ClearsolutionBIOLOGICALACTIVITY⽣物活性MK-3903⼀种有效且有选择性的AMP激活的蛋⽩激酶(AMPK)激活剂，其EC50值为8nM。IC50&TargetAMPK8nM(EC50)体外研究MK-3903(compound42)isapotentandselectiveAMP-activatedproteinkinase(AMPK)activatorwithanEC50of8nM.MK-3903activates10ofthe12phosphorylatedAMPK(pAMPK)complexeswithEC50valuesintherangeof8to40nMandmaximalactivation>50%.MK-3903partiallyactivatespAMPK5(36%max)anditdoesnotactivatepAMPK6.MK-3903demonstrateslowpermeability(Papp=6×10-6cm/s)inLLC-PK1cells42andisasubstrateofhumanliveruptaketransportersOATP1B1andOATP1B3(organicaniontransporterproteins).ResultsshowthatMK-3903bindsmoderatelytotheprostanoidDP2(CRTH2)receptor(bindingIC50=1.8μM)butnotinthepresenceof10%humanserum(bindingIC50>86μM)[1].体内研究ThepharmacokineticsofMK-3903(compound42)inC57BL/6mice,SpraguetoDawleyrats,andbeagledogsarecharacterizedbymoderatesystemicplasmaclearance(5.0to13mL/min/kg),avolumeofdistributionatsteadystateof0.6to1.1L/kg,andaterminalhalflifeof~2h.AcuteoraladministrationofMK-3903(3,10,and30mg/kg)tohigh-fructosefeddb/+miceresultsinsignificantinhibitionofhepaticfattyacidsynthesis(FAS)forallthreedoses[1].PROTOCOLKinaseAssay[1]Theenzymaticreactionisperformed.Briefly,theAMPKcomplexofinterestisappropriatelydilutedinAMPKreactionbufferandincubatedatroomtemperaturefor30mintoyieldpAMPK.Then,MK-3903(compound42)andpAMPKarepre-incubatedbyaddingappropriatelydilutedMK-3903inDMSO(1.2μLtotal)tothereactionbuffercontainingpAMPK(15μLperwell),theplateisvortexedbrieflyandthenincubatedatroomtemperaturefor30min.Theplateissealedandincubatedatroomtemperaturefor60min,atwhichtimethereactionisstoppedbytheadditionofquenchbuffer.EC50sand%activationparametersarecalculatedfrom%productvs.activatorconcentrationplots[1].MCEhasnotindependentlyconfirmedtheaccuracyofthesemethods.Theyareforreferenceonly.AnimalDIOmiceat17weeksofageareusedinthisstudy.Miceareconditionedtodosingwithvehicle(5%TweenAdministration[1]80,0.25%methylcellulose,0.02%SDS)at5mL/kgBIDfor5days.Atthattime,micearebled,glucoseandinsulinmeasuredandtheanimalssortedintotreatmentgroupsbasedonglucose,insulinandbodyweight.EachgroupofanimalsreceivesadministrationofMK-3903(compound42)invehicleat3mg/kg,10mg/kg,30mg/kg,orvehiclealonefor12-dayBID.AnothergroupofmicereceivingMK-3903withvehicleat30mg/kgfor12-dayQDisincludedaswell.Foodintakeandbodyweightaremeasureddaily[1].2/3MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemEMCEhasnotindependentlyconfirmedtheaccuracyofthesemethods.Theyareforreferenceonly.户使⽤本产品发表的科研⽂献•DrugDesDevTher.2020Aug19;14:3385-3391.Seemorecustomervalidationsonwww.MedChemEREFERENCES[1].LanP,RomeroFA,etal.Hit-to-LeadOptimizationandDiscoveryof5-((5-([1,1'-Biphenyl]-4-yl)-6-chloro-1H-benzo[d]imidazol-2-yl)oxy)-2-methylbenzoicAcid(MK-3903):ANovelClassofBenzimidazole-BasedActivatorsofAMP-ActivatedProteinKinase.J