SAR-20347-DataSheet-生命科學(xué)試劑-MedChemExpress

Hotline:400-820-3792Inhibitors?ScreeningLibraries?Proteinswww.MedChemESAR-20347Cat.No.:HY-100895CASNo.:1450881-55-6分?式:C??H??ClFN?O?分?量:444.84作?靶點:JAK作?通路:Epigenetics;JAK/STATSignaling;ProteinTyrosineKinase/RTK;StemCell/Wnt儲存?式:Powder-20°C3years4°C2yearsInsolvent-80°C6months-20°C1month溶解性數(shù)據(jù)體外實驗DMSO:100mg/mL(224.80mM;Needultrasonicandwarming)MassSolvent1mg5mg10mgConcentration制備儲備液1mM2.2480mL11.2400mL22.4800mL5mM0.4496mL2.2480mL4.4960mL10mM0.2248mL1.1240mL2.2480mL請根據(jù)產(chǎn)品在不同溶劑中的溶解度選擇合適的溶劑配制儲備液；?旦配成溶液，請分裝保存，避免反復(fù)凍融造成的產(chǎn)品失效。儲備液的保存?式和期限：-80°C,6months;-20°C,1month。-80°C儲存時，請在6個?內(nèi)使?，-20°C儲存時，請在1個?內(nèi)使?。體內(nèi)實驗請根據(jù)您的實驗動物和給藥?式選擇適當(dāng)?shù)娜芙?案。以下溶解?案都請先按照InVitro?式配制澄的儲備液，再依次添加助溶劑：(為保證實驗結(jié)果的可靠性，澄的儲備液可以根據(jù)儲存條件，適當(dāng)保存；體內(nèi)實驗的?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?；如在配制過程中出現(xiàn)沉淀、析出現(xiàn)象，可以通過加熱和/或超聲的?式助溶)1.請依序添加每種溶劑：10%DMSO>>40%PEG300>>5%Tween-80>>45%saline1/3MasterofBioactiveMolecules—您?邊的抑制劑?師www.MedChemESolubility:≥2.5mg/mL(5.62mM);Clearsolution2.請依序添加每種溶劑：10%DMSO>>90%(20%SBE-β-CDinsaline)Solubility:≥2.5mg/mL(5.62mM);ClearsolutionBIOLOGICALACTIVITY?物活性SAR-20347TYK2，JAK1，JAK2和JAK3的抑制劑，其IC50值分別為0.6,23,26和41nM。IC50&TargetJAK1JAK2JAK3Tyk223nM(IC50)26nM(IC50)41nM(IC50)0.6nM(IC50)體外研究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].體內(nèi)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?邊的抑制劑?師www.MedChemEphotographsaretaken[1].MCEhasnotindependentlyconfirmedtheaccuracyofthesemethods.Theyareforreferenceonly.戶使?本產(chǎn)品發(fā)表的科研?獻?CellRes.2019Mar;29(3):193-205.Seemorecustomervalidationsonwww.MedChemEREFERENCES[1].WorksMG,etal.InhibitionofTYK2andJAK1amelioratesimiquimod-inducedpsoriasis-likedermatitisbyinhibitingIL-22andtheIL-23/IL-17axis.JImmunol.2014Oct1;193(7):3278-8