AZ1495-DataSheet-生命科学试剂-MedChemExpress

Hotline:400-820-3792Inhibitors•ScreeningLibraries•Proteinswww.MedChemEAZ1495Cat.No.:HY-111101CASNo.:2196204-23-4分⼦式:C₂₁H₃₁N₅O₂分⼦量:385.5作⽤靶点:IRAK作⽤通路:Immunology/Inflammation储存⽅式:Powder-20°C3years4°C2yearsInsolvent-80°C6months-20°C1month溶解性数据体外实验DMSO:10mg/mL(25.94mM;Needultrasonic)MassSolvent1mg5mg10mgConcentration制备储备液1mM2.5940mL12.9702mL25.9403mL5mM0.5188mL2.5940mL5.1881mL10mM0.2594mL1.2970mL2.5940mL请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；⼀旦配成溶液，请分装保存，避免反复冻融造成的产品失效。储备液的保存⽅式和期限：-80°C,6months;-20°C,1month。-80°C储存时，请在6个⽉内使⽤，-20°C储存时，请在1个⽉内使⽤。体内实验请根据您的实验动物和给药⽅式选择适当的溶解⽅案。以下溶解⽅案都请先按照InVitro⽅式配制澄的储备液，再依次添加助溶剂：(为保证实验结果的可靠性，澄的储备液可以根据储存条件，适当保存；体内实验的⼯作液，建议您现⽤现配，当天使⽤；以下溶剂前显⽰的百分⽐指该溶剂在您配制终溶液中的体积占⽐；如在配制过程中出现沉淀、析出现象，可以通过加热和/或超声的⽅式助溶)1.请依序添加每种溶剂：10%DMSO>>40%PEG300>>5%Tween-80>>45%salineSolubility:≥1mg/mL(2.59mM);Clearsolution1/4MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemE2.请依序添加每种溶剂：10%DMSO>>90%(20%SBE-β-CDinsaline)Solubility:≥1mg/mL(2.59mM);Clearsolution3.请依序添加每种溶剂：10%DMSO>>90%cornoilSolubility:≥1mg/mL(2.59mM);ClearsolutionBIOLOGICALACTIVITY⽣物活性AZ1495，⼀种弱碱，⼀种有效的⽩细胞介素-1受体相关激酶4(IRAK4)抑制剂，具有⼝服活性。AZ1495对IRAK4和IRAK1具有良好的理化和激酶选择性，其IC50值分别为0.005μM和0.023μM。AZ1495具有IRAK4抑制作⽤，Kd值为0.0007μM。AZ1495可⽤于弥漫⼤B细胞淋巴瘤(DLBCL)的研究。IC50&TargetIRAK4IRAK1CLK1CLK25nM(IC50)23nM(IC50)50nM(IC50)5nM(IC50)CLK4haspin8nM(IC50)4nM(IC50)体外研究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—您⾝边的抑制剂⼤师www.MedChemEIncubationTime:14hResult:InhibitedIκBαphosphorylationwithdose-dependentenceinOCI-LY10cells.Showedinductionofapoptosiscombinationwith10nMibrutinibbycleavageofcaspase3inOCI-LY10cells.体内研究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—您⾝边的抑制剂⼤师www.MedChe