Hotline:400-820-3792Inhibitors ? ScreeningLibraries ? Proteinswww.MedChemECDK8-IN-15Cat.No.:HY-162600CASNo.:2988020-03-5分子式:C??H??N?O?分子量:352.39作用靶點(diǎn):CDK作用通路:CellCycle/DNADamage儲(chǔ)存方式:PleasestoretheproductundertherecommendedconditionsintheCertificateofAnalysis.BIOLOGICALACTIVITY生物活性CDK8-IN-15(Compound46)是一種強(qiáng)有效的CDK8抑制劑，IC50值為57nM。它能增強(qiáng)CDK8的熱穩(wěn)定性并同時(shí)抑制NF-κB，也能選擇性抑制CDK家族和酪氨酸。此外，也能對(duì)體外TNF-α導(dǎo)致的牛皮癬起積極作用并增強(qiáng)Foxp3和IL-10的表達(dá)來減弱炎癥反應(yīng)，有望用于牛皮癬疾病的研究[1]。IC50&TargetCDK857nM(IC50)體外研究CDK8-IN-15exhibitsthehighestactivityagainstCDK8withanIC50valueof57.3nMandexertsapositiveeffectontheTNF-α-inducedpsoriasismodelofHaCatcellswithanIC50valueof4.6μM[1].CDK8-IN-15(5μM,4h)inhibitsCDK8enzymeactivityandenhancesthethermalstabilityofendogenousandexogenousCDK8inHEK293T-CDK8cells[1].CDK8-IN-15(0,1,2,4μM,75h)significantlyreducesthelevelsofCXCL1,CXCL2,IL-8inHEK293cells[1].CellViabilityAssay[1]CellLine:HaCatcellsConcentration:0,1μM,2μM,4μMIncubationTime:75hResult:Down-regulatedthelevelsofIL-8andIL-6inadose-dependentmannerwithvaluesof0,1μM,2μM,4μM.WesternBlotAnalysis[1]1/3 MasterofBioactiveMolecules—您身邊的抑制劑大師www.MedChemECellLine:HEK293T-CDK8cellsConcentration:5μMIncubationTime:4hResult:EnhancedthethermalstabilityofendogenousandexogenousCDK8.WesternBlotAnalysis[1]CellLine:HEK293cellsConcentration:1μMIncubationTime:0,1,2,4,8,12h.Result:HadagreatNF-κBtranscriptionalactivityinhibitoryeffectwithanIC50valueof1μM.體內(nèi)研究CDK8-IN-15(2MG/KG,ivand10MG/KG,p.o.)showshighpermeabilityandnoobviousinhibitionofthefivecytochromep450isoenzymes[1].CDK8-IN-15(1000MG/KG,i.g.)doesn’tcauseasignificanttissuedamage[1].CDK8-IN-15(5/10/20MG/KG,i.g.)mightenhanceIL-10productionandFoxp3expressionbytargetingCDK8,therebyalleviatingpsoriasis[1].AnimalModel:Rats[1]Dosage:2mg/kg,ivand10mg/kg,poAdministration:ivandpo,asingleadministrationResult:ShowedhighCaco-2permeabilityinratsAnimalModel:Imiquimod-inducedpsoriasismodelofmice[1]Dosage:5,10,20mg/kgAdministration:5%imiquimodcreamand5,10,20mg/kgdaily,p.o.Result:Alleviatedthesymptomsofimiquimod-inducedpsoriasisandincreasetheproductionsofTNF-αandIL-6inimiquimod-inducedpsoriasismodelofmiceAnimalModel:ICRmice[1].Dosage:1000mg/kgAdministration:i.g.,asingleadministrationResult:Didn’tcauseasignificanttissuedamageonICRmice2/3 MasterofBioactiveMolecules—您身邊的抑制劑大師www.MedChemEREFERENCESYanYY,etal.Thediscoveryofanovelpyrrolo[2,3-b]pyridineasaselectiveCDK8inhibitoroffersanewapproachagainstpsoriasis[J].2024May6;175,0753-3322.McePdfHeightCaution:Producthasnotbeenfullyvalidatedformedicalapp