Tyk2-IN-5-DataSheet-生命科学试剂-MedChemExpress

Hotline:400-820-3792Inhibitors•ScreeningLibraries•Proteinswww.MedChemETyk2-IN-5Cat.No.:HY-111745CASNo.:1797432-62-2分⼦式:C₂₁H₁₉FN₈O₂分⼦量:434.43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:43.33mg/mL(99.74mM;Needultrasonic)MassSolvent1mg5mg10mgConcentration制备储备液1mM2.3019mL11.5093mL23.0187mL5mM0.4604mL2.3019mL4.6037mL10mM0.2302mL1.1509mL2.3019mL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:≥2.17mg/mL(5.00mM);ClearsolutionBIOLOGICALACTIVITY⽣物活性Tyk2-IN-5(compound6)⼀种强效的、具有选择性和⼝服活性的酪氨酸激酶2(Tyk2)抑制剂，作⽤于JH2结构域。Tyk2-IN-5对Tyk2JH2的Ki值为0.086nM，对IFNα的IC50值为25nM。Tyk2-IN-5能⾼效地抑制药效学⼤⿏模型中IFNγ的产⽣，对⼤⿏关节炎模型具有完全的疗效。IC50&TargetTyk2JH2IFNα0.086nM(Ki)25nM(IC50)体外研究Tyk2-IN-5inhibitsJak1-3withIC50valuesof>2μManddisplaystheJak1-3dependentcellularactivitiesof>12.5μM(IC50values)[1].体内研究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—您⾝边的抑制剂⼤师www.MedChemE(%)86114REFERENCES[1].LiuC,etal.IdentificationofImidazo[1,2-b]pyridazineDerivativesasPotent,Selective,andOrallyActiveTyk2JH2Inhibitors.ACSMedChemLett.2019Feb21;10(3):383-388.McePdfHeightCaution:Producthasnotbeenfullyvalidatedformedicalappli