SIAIS056-生命科学试剂-MCE

Hotline:400-820-3792Inhibitors•ScreeningLibraries•Proteinswww.MedChemESIAIS056Cat.No.:HY-180969CASNo.:2378581-37-2分⼦式:C₃₅H₃₄ClN₉O₅S₂分⼦量:760.28作⽤靶点:PROTACs;Bcr-Abl作⽤通路:PROTAC;ProteinTyrosineKinase/RTK储存⽅式:PleasestoretheproductundertherecommendedconditionsintheCertificateofAnalysis.BIOLOGICALACTIVITY⽣物活性SIAIS056⼀种BCR-ABLPROTAC降解剂，其DC50值为0.18nM。SIAIS056在K562细胞时间依赖性地抑制BCR-ABL信号通路，伴随BCR-ABL及其下游分⼦STAT5和CRKL的磷酸化⽔平降低。SIAIS056能诱导降解多种临床相关的BCR-ABL耐药突变体，并对K562和32D-BCR-ABL细胞展现出抗增殖活性，并能在K562异种移植瘤模型中诱导显著的肿瘤消退。SIAIS056可⽤于⽩⾎病研究[1][2]。IC50&TargetBcr-Abl0.18μM(DC50)体外研究SIAIS056(2days)reducesanti-proliferativeactivityagainstK562and32D-BCR-ABLcells[1].SIAIS056(0-100μM,0-24h)time-dependentlyinhibitstheBCR-ABLsignalingpathway,accompaniedbydecreasedphosphorylationofBCR-ABLanditsdownstreammoleculesSTAT5andCRKLinK562cells[1].SIAIS056(0-300nM,16h)exertstheabilitytoovercomeresistancetoclinicaltyrosinekinaseinhibitorscausedby(orassociatedwith)themajorityofclinicallycommonBCR-ABLmutationsinmurinemyeloidcellline32D(includingBCR-ABL-WT,BCR-ABL-G250E,BCR-ABL-E255V,BCR-ABL-V299L,BCR-ABL-F317L,BCR-ABL-F317V,BCR-ABL-T315A)[1].WesternBlotAnalysis[1]CellLine:K562cellsConcentration:0,1,3,10,30and100nMIncubationTime:0,2,4,8,12,18and24h1/3MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemEResult:DramaticallydecreasedtheproteinlevelofBCR-ABLandc-ABLatdosedependentmanner(16h)andtimedependentmanner(30nM).InducedthedegradationofSrc,butnotPDGFRβ.DramaticallydecreasedBCR-ABLafter4htreatmentatthe30nM.Time-DependentlyinhibitedtheBCR-ABLsignalingaccompaniedwithdecreasedphosphorylationofBCRABLandthedownstreammoleculesSTAT5andCRKL.InduceddegradationofBCR-ABLandc-ABLat30nMfor8h,whichwassignificantlyblockedbyPomalidomide(HY-10984)(4μM,2h),Dasatinib(HY-10181)(100nM,2h),MG132(HY-13259)(2μM,2h),Pevonedistat(HY-70062)(3μM,2h).WesternBlotAnalysis[1]CellLine:K562cellsConcentration:0,10,100and300nMIncubationTime:16hResult:InduceddegradationofBCR-ABLmutationsinBCR-ABL-WT,BCR-ABL-G250E,BCR-ABL-E255V,BCR-ABL-V299L,BCR-ABL-F317L,BCR-ABL-F317VandBCR-ABL-T315A,butinBCR-ABL-T3151cells.体内研究SIAIS056(1-10mg/kg,i.p.,onceadayfor10days)induceseffectivedegradationofBCR-ABLproteinandsubstantialanti-leukemicactivityinamurinexenograftmousemodelofK562cells[1].AnimalModel:K562cells(2x106)induced-NOD/SCIDmouse[1]Dosage:1,3and10mg/kgAdministration:i.p.,onceadayfor10daysResult:Observedareductionintumorburdenat1mg/kg.Inducedcompletetumorregressionat10mg/kg,whichwasmaintainedevenafterdrugwithdrawal.Showedtumorgrowthinhibition(TGI)valuesof78.9%,93.8%,and98.8%forthe1,3,and10mg/kg.exhibitedsimilaranti-leukemicactivityat3mg/kgtothatofDasatinib(HY-10181)at5mg/kg(o.p.)(TGI:93.8%versus95.1%).Showedwelltolerateatthedoseof100mg/kg.Preservedtheweight.Showsedananti-CMLefficacyafter10days.ObservedtheBCR-ABLproteindegradationat4dayaswellassuppressionofBCR-ABLphosphorylation.2/3MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemEREFERENCES[1].ChenX,etal.Mightymini-PROTACs:anemergingclassofdegraders.EurJMedChem.2026Jan5;301:118202.[2].KangCH,etal.Inducedproteindegradationofanaplasticlymphomakinase(ALK)byproteolysistargetingchimera(PROTAC).BiochemBiophysResCommun.2018Oct28;505(2):542-547.McePdfHeightCaution:Producth