αβ-Tubulin-IN-1-DataSheet-生命科学试剂-MedChemExpress

Hotline:400-820-3792Inhibitors•ScreeningLibraries•Proteinswww.MedChemEαβ-Tubulin-IN-1Cat.No.:HY-144132CASNo.:2478584-74-4分⼦式:C₂₅H₁₉N₃O₃分⼦量:409.44作⽤靶点:Apoptosis;Microtubule/Tubulin作⽤通路:Apoptosis;CellCycle/DNADamage;Cytoskeleton储存⽅式:PleasestoretheproductundertherecommendedconditionsintheCertificateofAnalysis.BIOLOGICALACTIVITY⽣物活性αβ-Tubulin-IN-1⼀种有效且具有⼝服活性的αβ-Tubulin抑制剂。αβ-Tubulin-IN-1诱导细胞周期停滞在G2/M期和诱导细胞凋亡(apoptosis)。αβ-Tubulin-IN-1抑制肿瘤细胞迁移和转移。αβ-Tubulin-IN-1以剂量依赖性⽅式显⽰出显的抗肿瘤功效[1]。IC50&Targetαβ-Tubulin[1]体外研究αβ-Tubulin-IN-1(compound12b)(0,0.5,1,5,10,50µM;16h)promotesαβ-tubulindegradationinaconcentration-dependentmannerinHelaandK562(0-10µM)cells[1].αβ-Tubulin-IN-1exhibitspotentcytotoxicactivitytowardsensitivecellsandresistantcells[1].αβ-Tubulin-IN-1(0-300nM;48h)inducescellcyclearrestatG2/MandefficientapoptosisinA2780SandA2780Tcells[1].αβ-Tubulin-IN-1(0,1.25,2.5,5,10nM;24,48h)inhibitstumorcellmigrationandMetastasiswiththeinhibitionrateof76.21%and85.07%for24,48hinhumanumbilicalveinendothelialcells(HUVEC)[1].CellProliferationAssay[1]CellLine:Hela,A2780S,MCF-7,Raji,H460cellsConcentration:0-500nMIncubationTime:24hResult:Showedanti-proliferativeactivitywithIC50sof5,8,9,13,14nMforHela,A2780S,MCF-7,Raji,H460cells,respectively.1/3MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemEWesternBlotAnalysis[1]CellLine:HeLacellsConcentration:10µMIncubationTime:16hResult:Remarkablypromotedtubulindegradationbybindingtothecolchicinesite,andthedegradationprocessreliedontheubiquitin−proteasomepathway.CellViabilityAssay[1]CellLine:A2780S,A2780T,A549,A549T,MCF7,MCF7/ADRcellsConcentration:IncubationTime:24hResult:ExhibitedpotentcytotoxicactivitywithIC50sof16.4,13.1,60.1,63.8,11.3,13.5nMforA2780S,A2780T,A549,A549T,MCF7,MCF7/ADRcells,respectively.CellCycleAnalysis[1]CellLine:A2780S(PTX-sensitive),A2780T(PTX-resistant)cellsConcentration:0,3,10,30,100,300nMIncubationTime:48hResult:InducedcellcyclearrestatG2/MphasewiththethepercentagesofA2780SandA2780Tcellswere55.10%,72.18%at100nM,and79.54%,72.89%at300nM.ApoptosisAnalysis[1]CellLine:A2780S,A2780TcellsConcentration:0,3,10,30,100,300nMIncubationTime:48hResult:Inducedcellapoptosiswiththetotalnumbersoflateapoptoticcellswere3.7%,25.2%,30.6%at30,100,and300nM,and5.2%%lateapoptoticcellsincontrol.体内研究αβ-Tubulin-IN-1(5mg/kg;i.v.,p.o.)showsintravenousandoraladministrationapproachesareavailableinvivo[1].αβ-Tubulin-IN-1(10,20,40mg/kg;i.v.;3timesaweekfor2-4weeks)showssignificantantitumorefficacyinadosedependentmanner[1].PharmacokineticParametersofαβ-Tubulin-IN-1inrats[1].2/3MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemEroutei.v.p.o.dose(mg/kg)55T1/2(h)3.57±1.104.42±1.90CL(L/h/kg)1.52±0.395.06±1.70Vss(L/kg)8.08±4.1935.26±25.76AUC0-∞(µg/mL·h)3448.81±782.661058.74±285.62Cmax(µg/L)2601.47±444.20189.29±119.02F(%)30.70Rats,5mg/kgfori.v.,5mg/kgforp.o.[1].AnimalModel:Rats[1]Dosage:5mg/kgAdministration:I.v.orp.o.Result:Showedoralbioavailability(F=30.70%)withtheT1/2valuesforintravenousandoraladministrationapproachesare3.57hand4.42h,respectively.AnimalModel:5-6weeksfemaleBalb/Candathymicnudemice(A2780SandA2780TXenograft)Models[1]Dosage:10,20,40mg/kgfori.v.,40mg/kgforp.o.Administration:I.v.;3timesaweekfor2-4weeksResult:Showedsignificantantitumorefficacywithtumorgrowthinhibition(TGI)of66.06%,71.47%and92.41%at10,20and40mg/kginA2780Sxenograftnudemicemodel,and26.94%,37.2%,75.73%at10,20and40mg/kginPTX-resistantA2780Txenograftmodelfori.v.injection,didnotshowanacceptableantitumorefficacywith34.93%ofTGIatthe40mg/kgforp.o..REFERENCES[1].LiY,etal.Structure-BasedDesignandSynthesisofN-Substituted3-Amino-β-CarbolineDerivativesasPotentαβ-TubulinDegradationAgents.JMedChem.2022Feb10;65(3):2675-2693.Mc