HG-9-91-01-SIK-inhibitor-1-DataSheet-生命科學(xué)試劑-MedChemExpress

Hotline:400-820-3792Inhibitors?ScreeningLibraries?Proteinswww.MedChemEHG-9-91-01Cat.No.:HY-15776CASNo.:1456858-58-4Synonyms:SIKinhibitor1分?式:C??H??N?O?分?量:567.68作?靶點(diǎn):Salt-inducibleKinase(SIK)作?通路:Immunology/Inflammation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:≥150mg/mL(264.23mM)*"≥"meanssoluble,butsaturationunknown.MassSolvent1mg5mg10mgConcentration制備儲(chǔ)備液1mM1.7616mL8.8078mL17.6156mL5mM0.3523mL1.7616mL3.5231mL10mM0.1762mL0.8808mL1.7616mL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)1/3MasterofBioactiveMolecules—您?邊的抑制劑?師www.MedChemE1.請(qǐng)依序添加每種溶劑：10%DMSO>>40%PEG300>>5%Tween-80>>45%salineSolubility:≥2.08mg/mL(3.66mM);Clearsolution2.請(qǐng)依序添加每種溶劑：10%DMSO>>90%(20%SBE-β-CDinsaline)Solubility:≥2.5mg/mL(4.40mM);Clearsolution3.請(qǐng)依序添加每種溶劑：10%DMSO>>90%cornoilSolubility:≥2.08mg/mL(3.66mM);ClearsolutionBIOLOGICALACTIVITY?物活性HG-9-91-01?種有效，選擇性的鹽誘導(dǎo)型激酶(SIK)抑制劑，作?于SIK1，SIK2和SIK3的IC50分別為0.92nM，6.6nM和9.6nM。IC50&TargetIC50:0.92/6.6/9.6nM(SIK1/2/3)[1]體外研究HG-9-91-01inhibitsanumberofproteintyrosinekinasesthatpossessathreonineresidueatthegatekeepersite,suchasSrcfamilymembers(Src,Lck,andYes),BTK,andtheFGFandEphrinreceptors[1].HG-9-91-01demonstratesastrongcorrelationbetweenthepotencyofSIK2inhibitionandenhancedIL-10production.Inagreementwiththesereports,pretreatingBMDCswithHG-9-91-01,arecentlydescribedinhibitorofSIK1-3,alongwithseveralotherkinases,resultsinconcentration-dependentpotentiationofzymosan-inducedIL-10productionwithanEC50~200nMandamaximumeffectsimilartothatobservedwithPGE2[2].HG-9-91-01hasmorethana100-foldgreaterpotencyagainstSIKsthanAMPK(IC50=4.5μM)inacell-freeassay.HG-9-91-01treatmentdosedependentlyincreasedmRNAexpressionofPck1andG6pcandthateffectissimilarincellstreatedwith4μMHG-9-91-01.Consistentwiththisobservation,thereisalsoadose-dependentincreaseinglucoseproductionfollowingHG-9-91-01treatment[3].PROTOCOLCellAssay[2]BonemarrowisharvestedfromfemursandtibiasofC57BL/6mice.Bone-marrow-deriveddendriticcells(BMDCs)aredifferentiatedDMEM.Culturesaredifferentiatedfor7dandroutinelyanalyzedfor>90%CD11c(allophycocyanin(APC)anti-CD11ccloneHL3)positivitybyflowcytometrybeforeuseinexperiments.Lentiviraltransductionofbonemarrowculturesisconductedbyadditionof293TculturesupernatantscontaininglentiviralparticlesencodingtheCREB-dependentluciferasereporterconstructorCRTC3targetingorcontrolshRNAs1dpostisolation.StableintegrationoflentiviralshRNAconstructsisselectedbyadditionofpuromycin(3μg/mL)onday4posttransduction.After2d,stablytransducedBMDCsarereleasedfromselectionandusedinsubsequentassays.Unlessotherwiseindicated,cellsaretreatedfor2dwithPGE2(5μM)orHG-9-91-01(0.5μM)oranequivalentconcentrationofDMSO(≤0.5%)andthenstimulatedfor18hwithLPS(100ng/mL),R848(10μg/mL),orZymosan(4μg/mL)[2].MCEhasnotindependentlyconfirmedtheaccuracyofthesemethods.Theyareforreferenceonly.戶使?本產(chǎn)品發(fā)表的科研?獻(xiàn)?NatureMetabolism.2021May;3(5):682-700.2/3MasterofBioactiveMolecules—您?邊的抑制劑?師www.MedChemE?CellRep.2017Jun13;19(11):2177-2184.?CellDeathDis.2022Feb25;13(2):188.?CellDeathDis.2020Jan13;11(1):25.?CellDeathDis.2019Oct31;10(11):826.Seemorecustomervalidationsonwww.MedChemEREFERENCES[1].ClarkK,etal.PhosphorylationofCRTC3bythesalt-induciblekinasescontrolstheinterconversionofclassicallyactivatedandregulatorymacrophages.ProcNatlAcadSciUSA.2012Oct16;109(42):16986-91.[2].SundbergTB,etal.Small-moleculescreeningidentifiesinhibitionofsalt-induciblekinasesasatherapeuticstrategytoenhanceimmunoregulatoryfunctionsofdendriticcells.ProcNatlAcadSciUSA.2014Aug26;111(34):12468-73.[3].PatelK,etal.TheLKB1-salt-induciblekinasepathwayfunctionsasakeygluconeogenicsuppressorintheliver.NatCommun.201