Multi-kinase-IN-8-生命科学试剂-MCE

Hotline:400-820-3792Inhibitors•ScreeningLibraries•Proteinswww.MedChemEMulti-kinase-IN-8Cat.No.:HY-179439分⼦式:C₂₅H₂₁N₇O₅S分⼦量:531.54作⽤靶点:COX;VEGFR;HIF/HIFProlyl-Hydroxylase;Caspase;Bcl-2Family;Apoptosis;MMP作⽤通路:Immunology/Inflammation;ProteinTyrosineKinase/RTK;MetabolicEnzyme/Protease;Apoptosis储存⽅式:PleasestoretheproductundertherecommendedconditionsintheCertificateofAnalysis.BIOLOGICALACTIVITY⽣物活性Multi-kinase-IN-8⼀种多激酶抑制剂。Multi-kinase-IN-8可抑制COX-1(IC50=12.6μM),COX-2(IC50=0.05μM)和VEGFR-2(IC50=0.12nM)。Multi-kinase-IN-8还能抑制肿瘤相关碳酸酐酶CAIX和CAXII(其Ki分别为31.5和386.9nM)，并通过上调Caspase-9和Bax下调Bcl-2来触发细胞周期阻滞和细胞凋亡(apoptosis)。Multi-kinase-IN-8可抑制PGE2，p-VEGFR-2，MMP-9及HIF-1α的表达，并对乳腺癌、肺癌和结直肠腺癌均表现出⽣长抑制活性[1]。IC50&TargetCOX-2COX-1VEGFR20.05μM(IC50)12.6μM(IC50)0.12nM(IC50)体外研究Multi-kinase-IN-8(Compound5j)inhibitstheproliferationofcancercelllines,withIC50of1.30μM(MB231cell),9.53μM(MCF-7cell),2.07μM(A549cell),and2.28μM(Caco-2cell),respectively[1].Multi-kinase-IN-8(2.07μM,72h)inhibitsVEGFR-2inCaco-2cells[1].Multi-kinase-IN-8(24hand48h)inducescellcyclearrestattheG1phaseinCaco-2cells[1].Multi-kinase-IN-8(24hand48h)inducescelldeathbytriggeringapoptosisinCaco-2cells[1].Multi-kinase-IN-8(24hand48h)downregulatesHIF-1αmRNAexpression,andreducesPGE2,totalVEGFR-2,p-VEGFR-2productioninMDA-MB231[1].Multi-kinase-IN-8hasselectivetargetingpotentialtowardsthetumor-associatedCAisoforms,particularlyhCAIX,duetoitsinteractionwiththecatalyticzincbindingsite[1].Multi-kinase-IN-8reducesexpressionlevelsoftheinitiatorcaspase-9andmitochondrialapoptoticmarkersBcl-2andBaxinCaco-2cells[1].CellMigrationAssay[1]1/3MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemECellLine:Caco-2cellsConcentration:2.07μMIncubationTime:72hResult:SuppressedCaco-2cellmigrationwith56.29%woundclosure.CellCycleAnalysis[1]CellLine:Caco-2cellsConcentration:IncubationTime:24hand48hResult:Increasedof%Caco-2cellsinG0/G1phasefrom62.07%inthecontrolto86.36%.Reducednearly3-foldin%Caco-2cellsinbothSphaseandG2/Mphase.ApoptosisAnalysis[1]CellLine:Caco-2cellsConcentration:IncubationTime:24hand48hResult:Increased42foldintotalapoptosis.IncreasedtheratioofannexinV-FITCpositiveearlyapoptoticcellsfrom0.54%to20.26%,whilstthepercentageoflateapoptoticcellsrosefrom0.22%to11%.Resultedinacombinedpercentageofearlyandlateapoptoticcellsthatsignificantlyexceededthepercentageofnecroticcells.(Earlyapoptoticcellsis20.26%,lateapoptoticcellsis11.32%,necroticcellsis3.61%).体内研究Multi-kinase-IN-8(Compound5j)(50mg/kg,s.c.,fiveconsecutivedays.)exhibitsantitumoractivityinanMDA-MB-231xenograftmodelestablishedinmaleBALB/cmice[1].AnimalModel:Cyclosporine(HY-100563A)-preconditioned(30mg/kg/day,for1week)maleBALB/cmiceandtheninjectedwithMDA-MB231cells(1×106permouse)[1].Dosage:50mg/kgAdministration:s.c.,daily,fiveconsecutivedays,dissolvedin100μLofDMSO(HY-Y0320C)/PBS(HY-K3005)(1:20,v/v).Result:Reducedtumorsize.Induced92.3%tumorregression.2/3MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemEHadnosignificantchangesinbodyweightwereobservedduringthetreatmentcourse,indicatingasatisfactorysafetyprofile.REFERENCES[1].El-AttarMAZ,et.al.Click-modifiableisatinhydrazonesasCOX-2,VEGFR-2,andcarbonicanhydraseinhibitors:Amulti-targetapproachtocancertherapy.EurJMedChem.2026Jan15;302(Pt1):118304.McePdfHeightCaution:Produ