Hotline:400-820-3792Inhibitors?ScreeningLibraries?Proteinswww.MedChemEWAY-262611Cat.No.:HY-11035CASNo.:1123231-07-1分?式:C??H??N?分?量:318.42作?靶點(diǎn):β-catenin作?通路:StemCell/Wnt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:≥42mg/mL(131.90mM)*"≥"meanssoluble,butsaturationunknown.MassSolvent1mg5mg10mgConcentration制備儲(chǔ)備液1mM3.1405mL15.7025mL31.4051mL5mM0.6281mL3.1405mL6.2810mL10mM0.3141mL1.5703mL3.1405mL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?。體內(nèi)實(shí)驗(yàn)請(qǐng)根據(jù)您的實(shí)驗(yàn)動(dòng)物和給藥?式選擇適當(dāng)?shù)娜芙?案。以下溶解?案都請(qǐng)先按照InVitro?式配制澄的儲(chǔ)備液，再依次添加助溶劑：(為保證實(shí)驗(yàn)結(jié)果的可靠性，澄的儲(chǔ)備液可以根據(jù)儲(chǔ)存條件，適當(dāng)保存；體內(nèi)實(shí)驗(yàn)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(guò)程中出現(xiàn)沉淀、析出現(xiàn)象，可以通過(guò)加熱和/或超聲的?式助溶)1.請(qǐng)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:≥1.67mg/mL(5.24mM);Clearsolution2.請(qǐng)依序添加每種溶劑：10%DMSO>>90%(20%SBE-β-CDinsaline)Solubility:≥1.67mg/mL(5.24mM);Clearsolution3.請(qǐng)依序添加每種溶劑：10%DMSO>>90%cornoilSolubility:≥1.67mg/mL(5.24mM);ClearsolutionBIOLOGICALACTIVITY?物活性WAY-262611Wnt/β-聯(lián)蛋?激動(dòng)劑，可增加?形成速率，在TCF-熒光素酶測(cè)定實(shí)驗(yàn)中的EC50值為0.63μM。WAY-262611也Dkk1的抑制劑。IC50&TargetEC50:0.63μM(β-Catenin)[1]體外研究WAY-262611hasthemostpotentactivityintheprimaryassay,lowkinaseinhibitionpotential,andhighsolubility[1].體內(nèi)研究WAY-262611hasexcellentpharmacokineticpropertiesandshowsadosedependentincreaseinthetrabecularboneformationrateinovariectomizedratsfollowingoraladministration.CalvariaefromwtmicetreatedwithWAY-262611showsstatisticallyincreasedBFR,whilesimilarlytreatedKOanimalsarenodifferentfromcontrol.ThisindicatesthatWAY-262611isactingviatheWntβ-cateninpathwayandmostlikelythroughinhibitionofDkk-1[1].PROTOCOLAnimalRats:WAY-262611isdissolvedinDMSOanddilutedwithsalineforiv(Rats).WAY-262611ispreparedinAdministration[1]0.5%methylcellulose/2%Tween-80forpoOVXrats14aretreatedorallywith5(po,vehicle=0.5%methylcellulose/2%Tween-80,qd,28days)atfourdoses.Trabecularboneformationrate(BFR)inthetibiaisestablishedinalldosegroupsattheendofthein-lifeportionofthestudy.Acleardoseresponseandactivityaslowas0.3mg/kg/dayareobserved[1].Mice:ToconfirmactivityviatheWntpathway,thecalvariaeofwildtype(wt)andDkk-1knockout(KO)micearetreatedwith5onceadayfor7days(DMSOsolution,scinjection).TheKOanimalsarenotexpectedtorespondbecauseoftheinherentinabilitytoinhibitamissingtargetprotein,whilewildtypeanimalswithfullyexpressedDkk-1areexpectedtoshowapharmacologicalresponse[1].MCEhasnotindependentlyconfirmedtheaccuracyofthesemethods.Theyareforreferenceonly.戶使?本產(chǎn)品發(fā)表的科研?獻(xiàn)?NatBiotechnol.2020Sep;38(9):1087-1096.?IntJBiochemCellBiol.2020Apr;121:105703.?JCellSci.2019May16;132(10):jcs228478.?Bone.2022Jun7;116456.?EvidBasedComplementAlternatMed.2019May30;2019:9692350.2/3MasterofBioactiveMolecules—您?邊的抑制劑?師www.MedChemESeemorecustomervalidationsonwww.MedChemEREFERENCES[1].PelletierJC,etal.(1-(4-(Naphthalen-2-yl)pyrimidin-2-yl)piperidin-4-yl)methanamine:awinglessbeta-cateninagonistthatincreasesboneformationrate.JMedChem.2009Nov26;52(22):6962-5.[2].LEnochson,etal.GDF5reducesMMP13expressioninhumanchondrocytesviaDKK1mediatedcanonicalWntsignalinginhibition.OsteoarthritisCartilage.2014Apr;22(4):566-77.McePdfHeightCaution:Product