MK-3903-DataSheet-生命科學(xué)試劑-MedChemExpress

Hotline:400-820-3792Inhibitors?ScreeningLibraries?Proteinswww.MedChemEMK-3903Cat.No.:HY-107988CASNo.:1219737-12-8分?式:C??H??ClN?O?分?量:454.9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:≥100mg/mL(219.83mM)*"≥"meanssoluble,butsaturationunknown.MassSolvent1mg5mg10mgConcentration制備儲備液1mM2.1983mL10.9914mL21.9829mL5mM0.4397mL2.1983mL4.3966mL10mM0.2198mL1.0991mL2.1983mL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(dāng)?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(dāng)保存；體內(nèi)實驗的?作液，建議您現(xiàn)?現(xiàn)配，當(dāng)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%saline1/3MasterofBioactiveMolecules—您?邊的抑制劑?師www.MedChemESolubility:≥2.5mg/mL(5.50mM);Clearsolution2.請依序添加每種溶劑：10%DMSO>>90%cornoilSolubility:≥2.5mg/mL(5.50mM);ClearsolutionBIOLOGICALACTIVITY?物活性MK-3903?種有效且有選擇性的AMP激活的蛋?激酶(AMPK)激活劑，其EC50值為8nM。IC50&TargetAMPK8nM(EC50)體外研究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].體內(nèi)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?邊的抑制劑?師www.MedChemEMCEhasnotindependentlyconfirmedtheaccuracyofthesemethods.Theyareforreferenceonly.戶使?本產(chǎn)品發(fā)表的科研?獻(xiàn)?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