MRT199665-DataSheet-生命科學(xué)試劑-MedChemExpress

Hotline:400-820-3792Inhibitors?ScreeningLibraries?Proteinswww.MedChemEMRT199665Cat.No.:HY-120877CASNo.:1456858-57-3分?式:C??H??N?O?分?量:469.58作?靶點(diǎn):Salt-inducibleKinase(SIK);AMPK;Apoptosis作?通路:Immunology/Inflammation;Epigenetics;PI3K/Akt/mTOR;Apoptosis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:125mg/mL(266.20mM;Needultrasonic)MassSolvent1mg5mg10mgConcentration制備儲(chǔ)備液1mM2.1296mL10.6478mL21.2956mL5mM0.4259mL2.1296mL4.2591mL10mM0.2130mL1.0648mL2.1296mL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:≥2.08mg/mL(4.43mM);Clearsolution2.請(qǐng)依序添加每種溶劑：10%DMSO>>90%(20%SBE-β-CDinsaline)Solubility:≥2.08mg/mL(4.43mM);Clearsolution3.請(qǐng)依序添加每種溶劑：10%DMSO>>90%cornoilSolubility:≥2.08mg/mL(4.43mM);ClearsolutionBIOLOGICALACTIVITY?物活性MRT199665?種有效的，ATP競(jìng)爭(zhēng)性的，選擇性MARK/SIK/AMPK抑制劑，對(duì)MARK1/MARK2/MARK3/MARK14，AMPKα1/AMPKα2和SIK1/SIK2/SIK3的IC50分別為2/2/3/2nM，10/10nM和110/12/43nM[1]。MRT199665作?于MEF2C激活的?急性髓性??病(AML)細(xì)胞，引起凋亡(apoptosis)[2]。MRT199665抑制SIK底物CRTC3磷酸化(在S370位點(diǎn))[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)體外研究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?邊的抑制劑?師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