Hotline:400-820-3792Inhibitors?ScreeningLibraries?Proteinswww.MedChemETyk2-IN-5Cat.No.:HY-111745CASNo.:1797432-62-2分?式:C??H??FN?O?分?量:434.43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:43.33mg/mL(99.74mM;Needultrasonic)MassSolvent1mg5mg10mgConcentration制備儲備液1mM2.3019mL11.5093mL23.0187mL5mM0.4604mL2.3019mL4.6037mL10mM0.2302mL1.1509mL2.3019mL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:≥2.17mg/mL(5.00mM);ClearsolutionBIOLOGICALACTIVITY?物活性Tyk2-IN-5(compound6)?種強效的、具有選擇性和?服活性的酪氨酸激酶2(Tyk2)抑制劑，作?于JH2結(jié)構(gòu)域。Tyk2-IN-5對Tyk2JH2的Ki值為0.086nM，對IFNα的IC50值為25nM。Tyk2-IN-5能?效地抑制藥效學(xué)??模型中IFNγ的產(chǎn)?，對??關(guān)節(jié)炎模型具有完全的療效。IC50&TargetTyk2JH2IFNα0.086nM(Ki)25nM(IC50)體外研究Tyk2-IN-5inhibitsJak1-3withIC50valuesof>2μManddisplaystheJak1-3dependentcellularactivitiesof>12.5μM(IC50values)[1].體內(nèi)研究Tyk2-IN-5(5,10mg/kg;p.o.;twicedailyfor20days)showshighlyefficaciousinaratadjuvantarthritismodel[1].Tyk2-IN-5(1,10mg/kg;p.o.;single)inhibitsIL-12/IL-18inducedIFNγproductioninadose-dependentmanner[1].Tyk2-IN-5(10mg/kg;p.o.;single)showsahighoralexposureandbioavailability(114%)inrat[1].AnimalModel:Lewismalerats(ratadjuvantarthritismodel)[1].Dosage:5,10mg/kgAdministration:Oraladministration;twicedailyfor20daysResult:Demonstratedfullefficacytopreventtherats′pawfromswelling.AnimalModel:Lewismalerats(IL-12/IL-18-induced)[1].Dosage:1,10mg/kgAdministration:Oraladministration;singleResult:InhibitedIL-12/IL-18inducedIFNγproductionby45%and77%atdosesof1and10mg/kg,respectively.AnimalModel:Lewismalerats,mouse[1].Dosage:10mg/kgAdministration:Oraladministration;singleResult:1.19PharmacokineticParametersofTyk2-IN-5inmouseandrat[1].PO(10mg/kg)mouseratCmax(μM)159.4AUC0-24(μM?h)1957CL(mL/min/kg)167.8F2/3MasterofBioactiveMolecules—您?邊的抑制劑?師www.MedChemE(%)86114REFERENCES[1].LiuC,etal.IdentificationofImidazo[1,2-b]pyridazineDerivativesasPotent,Selective,andOrallyActiveTyk2JH2Inhibitors.ACSMedChemLett.2019Feb21;10(3):383-388.McePdfHeightCaution:Producthasnotbeenfullyvalidatedformedicalappli