BTK-IN-15-DataSheet-生命科学试剂-MedChemExpress

Hotline:400-820-3792Inhibitors•ScreeningLibraries•Proteinswww.MedChemEBTK-IN-15Cat.No.:HY-150752分⼦式:C₂₈H₂₄FN₅O₂分⼦量:481.52作⽤靶点:Btk;Pyroptosis作⽤通路:ProteinTyrosineKinase/RTK;Apoptosis;Immunology/Inflammation储存⽅式:PleasestoretheproductundertherecommendedconditionsintheCertificateofAnalysis.BIOLOGICALACTIVITY⽣物活性BTK-IN-15⼀种新型的布鲁顿酪氨酸激酶(BTK)抑制剂，具有良好⼝服活性。BTK-IN-15抑制BTK，IC50为0.7nM，并具有良好的激酶选择性和抗肿瘤活性，能诱导癌细胞凋亡(apoptosis)。IC50&TargetIC50:0.7nM(BTK)[1]体外研究BTKinhibitionisaneffectiveapproachagainstB-cellmalignancies[1].BTK-IN-15(compound42)demonstratesinhibitoryagainstTMD8withanIC50valueof2.6nM[1].BTK-IN-15(1μM;1h)displayssignificantselectivitytoBTKoverEGFRkinasewith0.05%and44%ofthecontrol,respectively[1].BTK-IN-15(0-1mM;72h)exertspotentanti-proliferativeactivityagainstahumanmantlecelllymphomacellline(REC-1)withanIC50valueof1.7nM[1].BTK-IN-15(0-1mM;2h)inhibitsBTKauto-phosphorylationwithanIC50valueof1.49nM[1].BTK-IN-15(0-100nM;48h)arrestscellcycleatG1phaseand(0-1mM;72h)inducesapoptosisinTMD8[1].BTK-IN-15showslowhERGchannelactivity(IC50=4.38μM),indicatinglowcardiotoxicity[1].WesternBlotAnalysis[1]CellLine:B-celllymphoma(DLBCL)TMD8cancercellsConcentration:0,0.15,0.46,1.37,4.12,12.35,37.04,111,333,1000nMIncubationTime:2hoursResult:InhibitedBTKauto-phosphorylationattheTyr223sitewithanIC50valueof1.49nM.1/3MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemECellCycleAnalysis[1]CellLine:B-celllymphoma(DLBCL)TMD8cancercellsConcentration:0,10,100nMIncubationTime:48hoursResult:ArrestedcellcycleprogressionatG1phaseinadose-dependentmanner,thepercentageofcellsintheG0/G1phaseincreasedfrom33.0to63.0%withadoserangeof1-100nM.ApoptosisAnalysis[1]CellLine:B-celllymphoma(DLBCL)TMD8cancercellsConcentration:0,10,100,1000nMIncubationTime:72hoursResult:InducedapoptosisofTMD8cellsinaweaklytriggeredconcentration-dependentmanner,withtheapoptosiscellvaluesof19%(10nM),25.2%(100nM),and31.4%(1000nM),respectively.体内研究BTK-IN-15(compound42)(12.5-50mg/kg;p.o.;twicedaily;21d)inhibitstumorgrowth(TGI=104%)atadosageof50mg/kginmice[1].BTK-IN-15(300,400,500mg/kg;p.o.;twicedaily;14d)hasbiologicalsafetyanddisplaysnoaffectagainstbodyweightinmicecomparedwithcontrol[1].BTK-IN-15(10mg/kg;p.o.)showsahighoralbioavailabilityof40.98%inmice[1].PharmacokineticsofBTK-IN-15inMice[1]RouteDose(mg/kg)Tmax(h)Cmax(ng/mL)AUC(0-t)(h•ng/mL)AUC(0-∞)(h•ng/mL)T1/2(h)Vz(L/kg)CL(L/h/kg)F(%)i.v.20.032245.391471.35718.330.672.792.8740.98p.o.100.391441.59718.331472.060.59AnimalModel:FemaleCB-17SCIDnudemicewithTMD8xenograftmodel[1]Dosage:12.5mg/kg,25mg/kg,and50mg/kgAdministration:Oralgavage;twicedaily;21daysResult:Inhibitedtumorgrowthatadosageof50mg/kgandreducedtumorvolumeafter21dayswithaTGIof104%.Reducedthecontentofwhitebloodcells,lymphocytesandmonocytes,whileshowednoeffectonredbloodcellandplatelets.AnimalModel:ICRmice(acclimationfor5days,18-20g)[1]2/3MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemEDosage:300,400,500mg/kgAdministration:Oralgavage;14daysResult:Demonstratednoaffectagainstbodyweightinmicecomparedwithcontrol.REFERENCES[1].MinjianYang,etal.Design,synthesis,andbiologicalevaluationofpyrrolopyrimidinederivativesasnovelBruton'styrosinekinase(BTK)inhibitors.EURJMED.2022Jul.114611.McePdfHeightCaution:Product