Laduviglusib-CHIR-99021-DataSheet-生命科學(xué)試劑-MedChemExpress

Hotline:400-820-3792Inhibitors?ScreeningLibraries?Proteinswww.MedChemELaduviglusibCat.No.:HY-10182CASNo.:252917-06-9Synonyms:CHIR-99021;CT99021分?式:C??H??Cl?N?分?量:465.34作?靶點(diǎn):GSK-3;Wnt;β-catenin;Autophagy作?通路:PI3K/Akt/mTOR;StemCell/Wnt;Autophagy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:16.67mg/mL(35.82mM;Needultrasonic)MassSolvent1mg5mg10mgConcentration制備儲(chǔ)備液1mM2.1490mL10.7448mL21.4897mL5mM0.4298mL2.1490mL4.2979mL10mM0.2149mL1.0745mL2.1490mL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(qǐng)依序添加每種溶劑：0.5%CMC-Na/salinewater1/3MasterofBioactiveMolecules—您?邊的抑制劑?師www.MedChemESolubility:5mg/mL(10.74mM);Suspensionsolution;Needultrasonic2.請(qǐng)依序添加每種溶劑：10%DMSO>>40%PEG300>>5%Tween-80>>45%salineSolubility:≥2.08mg/mL(4.47mM);Clearsolution3.請(qǐng)依序添加每種溶劑：10%DMSO>>90%(20%SBE-β-CDinsaline)Solubility:≥2.08mg/mL(4.47mM);Clearsolution4.請(qǐng)依序添加每種溶劑：10%DMSO>>90%cornoilSolubility:≥2.17mg/mL(4.66mM);Clearsolution5.請(qǐng)依序添加每種溶劑：20%SBE-β-CDadjustedtopH4-4.5with1NaceticSolubility:5mg/mL(10.74mM);Clearsolution;NeedultrasonicBIOLOGICALACTIVITY?物活性Laduviglusib(CHIR-99021)?種有效的，選擇性的，具有?服活性的GSK-3α/β抑制劑，IC50為10nM和6.7nM。Laduviglusib對(duì)GSK-3的選擇性?CDC2，ERK2和其他蛋?激酶?500倍以上。Laduviglusib還是?種有效的Wnt/β-catenin信號(hào)通路激活劑。CHIR-99021可增強(qiáng)??和?類胚胎?細(xì)胞的?我更新。Laduviglusib能誘導(dǎo)細(xì)胞?噬(autophagy)。IC50&TargetGSK-3βGSK-3αcdc26.7nM(IC50)10nM(IC50)8800nM(IC50)體外研究Laduviglusib(1-10μM,3days)reducestheviabilityoftheES-D3cellswithanIC50of4.9μM[2].Laduviglusib(5μM,48h)activatesthecanonicalWnt-pathwayinES-D3cellsandES-CCEcells[2].Laduviglusib(3μM,4days)inhibitsEScelldifferentiationintoneuralcells[3].Laduviglusib(1μM,2weeks)inhibitsadipogenesisbyblockinginductionofC/EBPαandPPARγin3T3-L1preadipocytes[4].Laduviglusib(2.5μM,24h)protectsLgr5+cellsagainstradiation-inducedapoptosis[5].CellViabilityAssay[2]CellLine:ES-D3cellsConcentration:1-10μMIncubationTime:3daysResult:ReducedtheviabilityoftheES-D3cellsby24.7%at2.5μM,56.3%at5μM,61.9%at7.5μMand69.2%at10μM體內(nèi)研究Laduviglusib(30mg/kg,p.o)rapidlylowersplasmaglucose[1].Laduviglusib(2mg/kg,i.p.)protectsmiceagainstradiation-inducedlethalGIinjury[5].AnimalModel:ZDFrats[1]Dosage:30mg/kg2/3MasterofBioactiveMolecules—您?邊的抑制劑?師www.MedChemEAdministration:OraladministrationResult:Loweredplasmaglucose,withamaximalreductionofnearly150mg/dl3-4hafteradministration.AnimalModel:WTC57BL/6mice[5]Dosage:2mg/kgAdministration:Intraperitonealinjection(i.p.)Result:BlockedcryptapoptosisandincreasedLgr5+cellsurvival.戶使?本產(chǎn)品發(fā)表的科研?獻(xiàn)?NatMed.2016May;22(5):547-56.?MilMedRes.2020Sep6;7(1):42.?CellStemCell.2022Sep1;29(9):1366-1381.e9.?CellStemCell.2022Jul7;29(7):1102-1118.e8.?MolCell.2022Jun3;S1097-2765(22)00480-4.Seemorecustomervalidationsonwww.MedChemEREFERENCES[1].RingDB,etal.Selectiveglycogensynthasekinase3inhibitorspotentiateactivationofglucosetransportandutilizationinvitroandinvivo.Diabetes.2003Mar;52(3):588-95.[2].BennettCN,etal.RegulationofWntsignalingduringadipogenesis.JBiolChem.2002Aug23;277(34):30998-1004.[3].NaujokO,etal.CytotoxicityandactivationoftheWnt/beta-cateninpathwayinmouseembryonicstemcellstreatedwithfourGSK3inhibitors.BMCResNotes.2014Apr29;7:273.[4].WangX,etal.Pharmacologicallyblockingp53-dependentapoptosisprotectsintestinalstemcellsandmicefromradiation.SciRep.2015Apr10;5:8566.[5].YeS,etal.Pleiotropyofglycogensynthasekinase-3inhibitionbyCHIR99021promotesself-renewalofembryonicstemcellsfromrefractorymousestrains.PLoSOne.2012;7(4):e35892.Mc