MRT199665-DataSheet-生命科学试剂-MedChemExpress

Hotline:400-820-3792Inhibitors•ScreeningLibraries•Proteinswww.MedChemEMRT199665Cat.No.:HY-120877CASNo.:1456858-57-3分⼦式:C₂₈H₃₁N₅O₂分⼦量:469.58作⽤靶点:Salt-inducibleKinase(SIK);AMPK;Apoptosis作⽤通路:Immunology/Inflammation;Epigenetics;PI3K/Akt/mTOR;Apoptosis储存⽅式:Powder-20°C3years4°C2yearsInsolvent-80°C6months-20°C1month溶解性数据体外实验DMSO:125mg/mL(266.20mM;Needultrasonic)MassSolvent1mg5mg10mgConcentration制备储备液1mM2.1296mL10.6478mL21.2956mL5mM0.4259mL2.1296mL4.2591mL10mM0.2130mL1.0648mL2.1296mL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%saline1/3MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemESolubility:≥2.08mg/mL(4.43mM);Clearsolution2.请依序添加每种溶剂：10%DMSO>>90%(20%SBE-β-CDinsaline)Solubility:≥2.08mg/mL(4.43mM);Clearsolution3.请依序添加每种溶剂：10%DMSO>>90%cornoilSolubility:≥2.08mg/mL(4.43mM);ClearsolutionBIOLOGICALACTIVITY⽣物活性MRT199665⼀种有效的，ATP竞争性的，选择性MARK/SIK/AMPK抑制剂，对MARK1/MARK2/MARK3/MARK14，AMPKα1/AMPKα2和SIK1/SIK2/SIK3的IC50分别为2/2/3/2nM，10/10nM和110/12/43nM[1]。MRT199665作⽤于MEF2C激活的⼈急性髓性⽩⾎病(AML)细胞，引起凋亡(apoptosis)[2]。MRT199665抑制SIK底物CRTC3磷酸化(在S370位点)[3]。IC50&TargetMARK1MARK2MARK3MARK42nM(IC50)2nM(IC50)3nM(IC50)2nM(IC50)SIK1SIK2SIK3NUAK1110nM(IC50)12nM(IC50)43nM(IC50)3nM(IC50)NUAK2AMPKα1AMPKα2MELK120nM(IC50)10nM(IC50)10nM(IC50)29nM(IC50)TBK1IKKεBRSK25400nM(IC50)7700nM(IC50)10000nM(IC50)体外研究MRT199665(1μM;pre-treatedfor1h)increasesLPS(100ng/mL;stimulatedforupto24h)-stimulatedIL-10mRNAandNurr77mRNAproduction,andIL-10secretion[1].MRT199665(1nM-100μM;48hours)reducesleukemiagrowth[2].MRT199665treatmentcanblockMEF2CS222phosphorylationinacutemyeloidleukemias(AML)cells.MRT199665(10nM-1000nM;12hours)leadstoadose-dependentreductionintotalandpS222MEF2C.MRT199665alsocausesadecreaseoftotalMEF2Cprotein[2].WesternBlotAnalysis[2]CellLine:OCI-AML2andMOLM-13cellsConcentration:10,100,500,and1000nMIncubationTime:12hoursResult:Ledtoadose-dependentreductionintotalandpS222MEF2C,causingmorethan40%reductioninMEF2Cphosphorylationat10nMascomparedtountreatedcells.CellProliferationAssay[2]2/3MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemECellLine:HumanAMLcelllinesOCI-AML2,MV4-11,MOLM-13andKasumi-1withendogenousMEF2Cphosphorylation;humanAMLcelllinesNB-4,HEL,HL-60andU937lackingMEF2CConcentration:1nM,10nM,100nM,1μM,10μM,100μMIncubationTime:48hoursResult:HumanAMLcelllineswithendogenousMEF2Cphosphorylation(OCI-AML2,MV4–11,MOLM-13andKasumi-1)weremoresensitiveascomparedtocelllineslackingMEF2C(NB-4,HEL,HL-60andU937),withmeanIC50of26±13versus990±29nM,respectively.REFERENCES[1].ClarkK,etal.PhosphorylationofCRTC3bythesalt-induciblekinasescontrolstheinterconversionofclassicallyactivatedandregulatorymacrophages.ProcNatlAcadSciUSA.2012Oct16;109(42):16986-91.[2].BrownFC,etal.MEF2CPhosphorylationIsRequiredforChemotherapyResistanceinAcuteMyeloidLeukemia.CancerDiscov.2018Apr;8(4):478-497.[3].HutchinsonLD,etal.Salt-induciblekinases(SIKs)regulateTGFβ-mediatedtranscriptionalandapoptoticresponses.CellDeathDis.2020Jan22;11(1):49.McePdfHeightCaution:Produ