Hotline:400-820-3792Inhibitors ? ScreeningLibraries ? Proteinswww.MedChemETyk2-IN-23Cat.No.:HY-178913CASNo.:2734918-75-1分子式:C??H??ClFN?O?分子量:495.98作用靶點(diǎn):JAK;STAT作用通路:Epigenetics;JAK/STATSignaling;ProteinTyrosineKinase/RTK;StemCell/Wnt儲(chǔ)存方式:PleasestoretheproductundertherecommendedconditionsintheCertificateofAnalysis.BIOLOGICALACTIVITY生物活性Tyk2-IN-23是一種強(qiáng)效的，具有口服活性的選擇性TYK2抑制劑(IC50=18nM)，對(duì)JAK1/2/3亞型的選擇性超過(guò)70倍。Tyk2-IN-23能有效抑制IFN-α和IL-10激活的TYK2依賴(lài)性信號(hào)通路中的p-STAT3。Tyk2-IN-23還能有效抑制H9細(xì)胞中IFN-α誘導(dǎo)的STAT1磷酸化。Tyk2-IN-23可用于斑禿和過(guò)敏性鼻炎的研究[1]。體外研究Tyk2-IN-23(Compound29i)(50nM-10μM,80min)potentlyinhibitsp-STAT3inTYK2-dependentsignalingactivatedbyIFN-α(IC50=230.6nM)andIL-10(IC50=501.6nM),butp-STAT3inductionbyIL-21,IL-23,orIL-27resultsinonlymarginalinhibition(IC50>2700nM)inhumanperipheralbloodmononuclearcells(hPBMC)[1].Tyk2-IN-23(0-10μM,1.5h)potentlyinhibitsIFN-α-inducedSTAT1phosphorylationinH9cells;incontrast,GM-CSF-inducedSTAT5phosphorylation(JAK2-dependent),IL-4-inducedSTAT6phosphorylation(JAK1/JAK3-mediated),andIL-6-inducedSTAT3phosphorylation(JAK1/JAK2/TYK2-cooperative)remainunaffectedevenat10000nM[1].Tyk2-IN-23(0.625-40μM,24h)showsnocytotoxicityatconcentrations≤10μMinRBL-2H3cells[1].Tyk2-IN-23(0-5μM,30min)concentration-dependentlyinhibitsthereleaseofβ-hexosaminidasefromCompound48/80trihydrochloride(HY-130592)(C48/80)-inducedRBL-2H3cells[1].CellViabilityAssay[1]CellLine:RBL-2H3cellsConcentration:0.625μM,1.25μM,2.5μM,5μM,10μM,20μM,40μMIncubationTime:24h1/3 MasterofBioactiveMolecules—您身邊的抑制劑大師www.MedChemEResult:Showednocytotoxicityatconcentrations≤10μMinRBL-2H3cells.WesternBlotAnalysis[1]CellLine:H9cells,THP-1cells,TF-1cellsConcentration:10nM,50nM,100nM,500nM,1000nM,5000nM,10000nMIncubationTime:Preincubatedfor1h,thenstimulatedbyIFN-α(1,000U/mL)for30minResult:SignificantlyinhibitedIFN-α-inducedSTAT1phosphorylationinH9cells.NosignificantinhibitoryeffectonIL-4-inducedSTAT6phosphorylationinTHP-1cells.NosignificantinhibitoryeffectonGM-CSF-inducedSTAT5andIL-6-inducedSTAT3phosphorylationinTF-1cells.體內(nèi)研究Tyk2-IN-23(Compound29i)(15-40mg/kg,intranasaldropsororalgavage,oncedaily,8-26days)effectivelyrelievesthesymptomsofAlopeciaareata(AR)andAllergicRhinitis(AA)inmicewithoutshowingsignificanttoxicity[1].AnimalModel:FemaleC57BL/6Jmice(6-8weeksold)underwentbasalsensitizationviaintraperitonealinjections(everyotherdayfor14days)of50μgOVAand2mgaluminumhydroxidedissolvedin200μLsaline(0.9%),fromdays14-20,dailynasalchallengeswereperformedwith2%OVAsolution(10μLpernostril)[1].Dosage:20mg/kg,40mg/kgAdministration:Intranasaldrops,oncedailyfor8daysResult:Dose-dependentlyreducedARsymptoms(frequencyofsneezingandnosescratching).ReducedOVA-specificIgE(OVA-sIgE)levels.Alleviatedinflammatorycellinfiltrationandepithelialproliferationinthenasalmucosa.Reducedmastcellinfiltrationanddegranulationrate.Reducedeosinophilinfiltration.Inhibitedgobletcellproliferation.AnimalModel:UsingfemaleC57BL/6Jmice(6-8weeksold),Alopeciaareata(AA)wasinducedbyhairremovalandcyclophosphamideinjection[1].Dosage:15mg/kg,30mg/kgAdministration:Oralgavage,oncedailyfor26daysResult:Promotedhairregenerationinadose-dependentmanner,withasignificantincreaseinhairlengthanddensityinthehigh-dosegroup(30mg/kg).Decreasedinpro-inflammatoryfactors(TNF-αandIL-23)andanincreaseintheanti-2/3 MasterofBioactiveMolecules—您身邊的抑制劑大師www.MedChemEinflammatoryfactorIL-10.REFERENCESTianY,etal.Identificationofanovelbenzyloxy-terminatedscaffoldasapotentandselectiveTYK2inhibitorforanti-inflammatorytherapy.EurJMedChem.2026Jan5;301:118211.McePdfHeightC