AZ1495-DataSheet-生命科學(xué)試劑-MedChemExpress

Hotline:400-820-3792Inhibitors?ScreeningLibraries?Proteinswww.MedChemEAZ1495Cat.No.:HY-111101CASNo.:2196204-23-4分?式:C??H??N?O?分?量:385.5作?靶點:IRAK作?通路:Immunology/Inflammation儲存?式:Powder-20°C3years4°C2yearsInsolvent-80°C6months-20°C1month溶解性數(shù)據(jù)體外實驗DMSO:10mg/mL(25.94mM;Needultrasonic)MassSolvent1mg5mg10mgConcentration制備儲備液1mM2.5940mL12.9702mL25.9403mL5mM0.5188mL2.5940mL5.1881mL10mM0.2594mL1.2970mL2.5940mL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%salineSolubility:≥1mg/mL(2.59mM);Clearsolution1/4MasterofBioactiveMolecules—您?邊的抑制劑?師www.MedChemE2.請依序添加每種溶劑：10%DMSO>>90%(20%SBE-β-CDinsaline)Solubility:≥1mg/mL(2.59mM);Clearsolution3.請依序添加每種溶劑：10%DMSO>>90%cornoilSolubility:≥1mg/mL(2.59mM);ClearsolutionBIOLOGICALACTIVITY?物活性AZ1495，?種弱堿，?種有效的?細(xì)胞介素-1受體相關(guān)激酶4(IRAK4)抑制劑，具有?服活性。AZ1495對IRAK4和IRAK1具有良好的理化和激酶選擇性，其IC50值分別為0.005μM和0.023μM。AZ1495具有IRAK4抑制作?，Kd值為0.0007μM。AZ1495可?于彌漫?B細(xì)胞淋巴瘤(DLBCL)的研究。IC50&TargetIRAK4IRAK1CLK1CLK25nM(IC50)23nM(IC50)50nM(IC50)5nM(IC50)CLK4haspin8nM(IC50)4nM(IC50)體外研究AZ1495(compound28)(10μM,1h)haskinaseselectivityforIRAK4withIC50valuesof0.005μM(enzymeassay)and0.052μM(cellularassay),respectively[1].AZ1495(10μM,1h)haskinaseinhibitionforIRAK4withanIC50valueof0.005μMandKdvalueof0.0007μM[1].AZ1495(0.001-100μM,72h)inhibitsNF-κBactivationandgrowthofABC-DLBCLcelllinesinadosedependentmanner[1].AZ1495(0-3.3μM,14h)completelyinhibitsNF-κBsignalingandinducescelldeathatlowerconcentrationincombinationwithaBTKinhibitorinOCI-LY10cells[1].CellViabilityAssay[1]CellLine:OCI-LY10andSUDHL2cellsConcentration:0.001-100μMIncubationTime:72hResult:InhibitedgrowthofOCI-LY10cellsinadosedependentmanner,whereasSUDHL2,aGCB-celllinewasnotsensitiveandnoincreasedcellkillingtoIRAK4inhibitor.IncreasedthecelldeathinOCI-LY10cellsuponincreasingconcentrationsofcompound28andBTKibrutinib.WesternBlotAnalysis[1]CellLine:OCI-LY10cellsConcentration:0-3.3μM2/4MasterofBioactiveMolecules—您?邊的抑制劑?師www.MedChemEIncubationTime:14hResult:InhibitedIκBαphosphorylationwithdose-dependentenceinOCI-LY10cells.Showedinductionofapoptosiscombinationwith10nMibrutinibbycleavageofcaspase3inOCI-LY10cells.體內(nèi)研究AZ1495(compound28)(oral,daily,12.5mg/kg)ledstotumorregressioncombinationwithibrutinibinanABC-DLBCLmousemodel(OCI-LY10cells)[1].AZ1495(iv.,2mg/kgandoral,5mg/kg)ischaracterizedbyhighclearance(Cl)inrat(75mL/min/kg)andmoderatepredictionsbasedonhepatocytedata(Clint15μl/min/106cells,predictedclearance42mL/min/kg)withlowbioavailabilityconsistentwithahighfirstpasseffect[1].AZ1495(iv.,1mg/kg)haslowtheamountofactiverenalsecretionoccurringinthedog[1].AnimalModel:CB.17SCIDmice[1]Dosage:12.5mg/kgAdministration:oral,daily,12.5mg/kgResult:Hadmodestanti-tumoractivityassingleagentsbutacombinationofibrutinibledtotumorregressionandiswelltolerated.AnimalModel:rat[1]Dosage:2mg/kg,5mg/kgAdministration:iv.,2mg/kgandoral,5mg/kgResult:SpeciesDose(mg/kg)Cl(mL/min/kg)Vss(L/kg)POhalflife(h)IVhalflife(h)Fabs(%)F(%)Rat2，5752.12.00.810028Dog1293.0-3.3--AnimalModel:dog[1]Dosage:1mg/kgAdministration:iv.,1mg/kgResult:SpeciesDose(mg/kg)Cl(mL/min/kg)Vss(L/kg)POhalflife(h)IVhalflife(h)Fabs(%)F(%)Rat2，5752.12.00.810028Dog1293.0-3.3--REFERENCES[1].ScottJS,etal.DiscoveryandOptimizationofPyrrolopyrimidineInhibitorsofInterleukin-1ReceptorAssociatedKinase4(IRAK4)fortheTreatmentofMutantMYD88L265PDiffuseLargeB-CellLymphoma.JMedChem.2017Dec28;60(24):10071-10091.3/4MasterofBioactiveMolecules—您?邊的抑制劑?師www.MedChe