Hotline:400-820-3792Inhibitors?ScreeningLibraries?Proteinswww.MedChemESKA-121Cat.No.:HY-107414CASNo.:1820708-73-3分?式:C??H??N?O分?量:198.22作?靶點(diǎn):PotassiumChannel作?通路:MembraneTransporter/IonChannel儲(chǔ)存?式:Powder-20°C3years4°C2yearsInsolvent-80°C6months-20°C1month溶解性數(shù)據(jù)體外實(shí)驗(yàn)DMSO:≥42.86mg/mL(216.22mM)*"≥"meanssoluble,butsaturationunknown.MassSolvent1mg5mg10mgConcentration制備儲(chǔ)備液1mM5.0449mL25.2245mL50.4490mL5mM1.0090mL5.0449mL10.0898mL10mM0.5045mL2.5224mL5.0449mL請(qǐng)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(chǔ)備液；?旦配成溶液，請(qǐng)分裝保存，避免反復(fù)凍融造成的產(chǎn)品失效。儲(chǔ)備液的保存?式和期限：-80°C,6months;-20°C,1month。-80°C儲(chǔ)存時(shí)，請(qǐng)?jiān)?個(gè)?內(nèi)使?，-20°C儲(chǔ)存時(shí)，請(qǐng)?jiān)?個(gè)?內(nèi)使?。BIOLOGICALACTIVITY?物活性SKA-121?種選擇性的KCa3.1激活劑。SKA-121作?于KCa3.1和KCa2.3，EC50分別為109nM和4.4μM。IC50&TargetEC50:109nM(KCa3.1),4.4μM(KCa2.3)[1]1/2MasterofBioactiveMolecules—您?邊的抑制劑?師www.MedChemE體外研究SKA-121,acompoundgeneratedthroughanisostericreplacementapproach.SKA-121isatypicalpositive-gatingmodulatorandshiftsthecalcium-concentrationresponsecurveofKCa3.1totheleft.SKA-121displays41-foldselectivityforKCa3.1(EC50109nM±14nM)overKCa2.3(EC504.4±1.6μM).SKA-121is200-to400-foldselectiveoverrepresentativeKV(KV1.3,KV2.1,KV3.1,andKV11.1),NaV(NaV1.2,NaV1.4,NaV1.5,andNaV1.7),aswellasCaV1.2channels[1].體內(nèi)研究Inbloodpressuretelemetryexperiments,SKA-121(100mg/kgi.p.)significantlylowersmeanarterialbloodpressureinnormotensiveandhypertensivewild-typebutnotinKCa3.1-/-mice.SKA-121canbeusedasanewKCa3.1selectivepharmacologicaltoolcompounddespiteitsrelativelyshorthalf-lifeinmice.Alowerdoseof30mg/kgofSKA-121doesnotproducesignificantalterationsinMAP.Thevehicle,peanutoil/DMSO(9:1v/v,forSKA-121),doesnotcausesignificantalterationsinMAPorHR.SKA-121hasashorthalf-life(~20minutes),andplasmadecayisextremelyrapid(21.3±2.4μMat5minutes;483±231nMat1hourand53±44nMat4hours).SinceSKA-121isrelativelywellsoluble(logP=1.79)andcanpotentiallybeaddedtodrinkingwaterinanimalexperiments,itorallyisalsoadministered,andfindthatithasanoralavailabilityofroughly25%[1].PROTOCOLKinaseAssay[1]TofullyevaluatetheselectivityofthenaphthooxazoleSKA-121,seven-pointconcentration-responsecurvesonKCa2.1,KCa2.2,KCa2.3andKCa3.1aredeterminedwith250nMfreeCa2+intheinternalsolution[1].MCEhasnotindependentlyconfirmedtheaccuracyofthesemethods.Theyareforreferenceonly.AnimalMice[1]Administration[1]Twelve-week-oldmaleC57Bl/6Jmiceareused.Fori.v.application,SKA-121isdissolvedat5mg/mLinamixtureof10%CremophorELand90%phosphate-bufferedsalineandtheninjectedat10?mg/kgintothetailvein(n=8micepercompound).Anothergroupofmice(n=8)receiveSKA-121orally.Atvarioustimepointsaftertheinjection,bloodiscollectedintoEDTAbloodsamplecollectiontubeseitherfromthesaphenousveinorbycardiacpunctureunderdeepisofluraneanesthesia.Afterthecardiacpuncture,micearesacrificedbycuttingtheheart,andthenthebrainisremoved.Individualmicearetypicallyusedforthreetimespoints(twobloodcollectionsfromthesaphenousveinplustheterminalbloodcollection).MCEhasnotindependentlyconfirmedtheaccuracyofthesemethods.Theyareforreferenceonly.戶使?本產(chǎn)品發(fā)表的科研?獻(xiàn)?IntJMolSci.2022Aug3;23(15):8603.Seemorecustomervalidationsonwww.MedChemEREFERENCES[1].ColemanN,etal.NewpositiveCa2+-activatedK+channelgatingmodulatorswithselectivityforKCa3.1.MolPharmacol.2014Sep;86(3):342-57.McePdfHeight2/2MasterofBioactiveMolecules—您?邊的抑制劑?師www.MedChemECaution:Prod