SAR-20347-DataSheet-生命科学试剂-MedChemExpress

Hotline:400-820-3792Inhibitors•ScreeningLibraries•Proteinswww.MedChemESAR-20347Cat.No.:HY-100895CASNo.:1450881-55-6分⼦式:C₂₁H₁₈ClFN₄O₄分⼦量:444.84作⽤靶点:JAK作⽤通路:Epigenetics;JAK/STATSignaling;ProteinTyrosineKinase/RTK;StemCell/Wnt储存⽅式:Powder-20°C3years4°C2yearsInsolvent-80°C6months-20°C1month溶解性数据体外实验DMSO:100mg/mL(224.80mM;Needultrasonicandwarming)MassSolvent1mg5mg10mgConcentration制备储备液1mM2.2480mL11.2400mL22.4800mL5mM0.4496mL2.2480mL4.4960mL10mM0.2248mL1.1240mL2.2480mL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:≥2.5mg/mL(5.62mM);Clearsolution2.请依序添加每种溶剂：10%DMSO>>90%(20%SBE-β-CDinsaline)Solubility:≥2.5mg/mL(5.62mM);ClearsolutionBIOLOGICALACTIVITY⽣物活性SAR-20347TYK2，JAK1，JAK2和JAK3的抑制剂，其IC50值分别为0.6,23,26和41nM。IC50&TargetJAK1JAK2JAK3Tyk223nM(IC50)26nM(IC50)41nM(IC50)0.6nM(IC50)体外研究WhenNK-92cellsarestimulatedwithIL-12,SAR-20347potentlyinhibitsIL-12-mediatedSTAT4phosphorylation,aTYK2-dependentevent,withanIC50of126nM.SAR-20347demonstratesaselectivityofTYK2>JAK1>JAK2>JAK3.CellswithoutIL-12intheculturemediahavenomeasureableIFN-γ,whilecellsincubatedwithIL-12andSAR-20347demonstratedose-dependentinhibitionofIFN-γproduction.SAR-20347dose-dependentlyinhibitstheproductionofsecretedembryonicalkalinephosphatase(SEAP)withgreatestinhibitionoccurringwith5μMofSAR-20347intheseexperiments[1].体内研究60mg/kgSAR-20347inhibitstheproductionofIFN-γintheserumby91%comparetovehicle-treatedanimals,demonstratingthatSAR-20347caninhibitTYK2signalinginvivo.SAR-20347treatmentsignificantlyreducesIL-17productionasmeasuredbyaveragesignalintensity,consistentwiththegeneexpressionanalysis[1].PROTOCOLKinaseAssay[1]KinasesarepreparedinBaseReactionBuffer(20mMHepespH7.5,10mMMgCl2,1mMEGTA,0.02%Brij35,0.02mg/mLBSA,0.1mMNa3VO4,2mMDTT,1%DMSO)andsubstrateisaddedwith1.5mMCaCl2,16μg/mLCalmodulin,and2mMMnCl2.VaryingconcentrationsofSAR-20347inDMSOareaddedtothekinasereactionalongwith10μM33P-ATP(activity0.01μCi/μLfinal)forIC50determination[1].MCEhasnotindependentlyconfirmedtheaccuracyofthesemethods.Theyareforreferenceonly.CellAssay[1]Cellsareplatedina96-wellv-bottomplateinstarvationmedium,incubatedwithSAR-20347(0.5%DMSO)for20minutesat37°C,5%CO2,andstimulatedwithindividualcytokines.P-STATlevelsaremeasuredinduplicateusingMSDplatesfollowingthemanufacturer'sinstructions(MSD).TheIC50isdeterminedbysubtractingbackground(nocytokine)andrelativetoDMSO/cytokinecontrol[1].MCEhasnotindependentlyconfirmedtheaccuracyofthesemethods.Theyareforreferenceonly.AnimalFemale7to9weekoldC57BL/6miceareused.Miceareadministeredvehicleor50mg/kgSAR-20347byAdministration[1]oralgavage30minutespriortoapplicationof62.5mg5%imiquimodcreamorcontrolcream.Anotherdoseofvehicleor50mg/kgSAR-20347isgiven5.5hoursfollowingthefirstdose.Thistreatmentisrepeatedfor5daysandonday3and4,animalsareinjectedwith100uLsalinetopreventdehydration.Eachday,themiceareassessedbythesameresearcherforredness.Onthe6thday,theanimalsareeuthanizedand2/3MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemEphotographsaretaken[1].MCEhasnotindependentlyconfirmedtheaccuracyofthesemethods.Theyareforreferenceonly.户使⽤本产品发表的科研⽂献•CellRes.2019Mar;29(3):193-205.Seemorecustomervalidationsonwww.MedChemEREFERENCES[1].WorksMG,etal.InhibitionofTYK2andJAK1amelioratesimiquimod-inducedpsoriasis-likedermatitisbyinhibitingIL-22andtheIL-23/IL-17axis.JImmunol.2014Oct1;193(7):3278-8