Hotline:400-820-3792Inhibitors?ScreeningLibraries?Proteinswww.MedChemETubulinpolymerization-IN-4Cat.No.:HY-144786分?式:C??H??ClN?O?分?量:400.86作?靶點:Microtubule/Tubulin;Apoptosis作?通路:CellCycle/DNADamage;Cytoskeleton;Apoptosis儲存?式:PleasestoretheproductundertherecommendedconditionsintheCertificateofAnalysis.BIOLOGICALACTIVITY?物活性Tubulinpolymerization-IN-4?種有效的微管蛋?聚合體(tubulinpolymerization)抑制劑，IC50為4.6μM。Tubulinpolymerization-IN-4對HeLa細胞可破壞微管蛋?聚合和?管系統，將細胞周期阻滯在G2/M期，誘導細胞凋亡(apoptosis)，抑制細胞的克隆發?和遷移[1]。IC50&TargetIC50:4.6μM(tubulin)[1]體外研究Tubulinpolymerization-IN-4(compound9j)(0-1μM;48hours)exhibitssub-micromolarinhibitoryactivitiesagainstHeLa,SiHaandMS751[1].Tubulinpolymerization-IN-4(3,6and12.5μM;0-20min)inhibitstubulinpolymerizationinaconcentration-dependentmannerwiththeinhibitionpercentagesof39%,54%,and77%at3,6and12.5μM[1].Tubulinpolymerization-IN-4(1-100μM;2hours)inhibitstheformationofEBI-β-tubulinadductinaconcentration-dependentmanner[1].Tubulinpolymerization-IN-4(0.2μM;1and2hours)disruptstheHUVEC-formedvasculartube[1].Tubulinpolymerization-IN-4(0.1-0.4μM;24hours)increasescelldistributiontotheG2/Mphaseinaconcentration-dependentmanner[1].Tubulinpolymerization-IN-4(0.1-0.4μM;24hours)inducesapoptosisofHeLacells[1].Tubulinpolymerization-IN-4(20,50,100nM;14days)reducesnewcolonyformationandsuppressesHeLacellgrowthfor14daysinadose-dependentmanner[1].Tubulinpolymerization-IN-4(0.1,0.2and0.4μM;24hours)effectivelyinhibitsthemigrationofHeLacellsinaconcentration-dependentmanner[1].Tubulinpolymerization-IN-4(0-200μM;24hours)exhibitsgoodrenalsafetyprofile,withIC50of188±16μMinHK-2cells[1].CellProliferationAssay1/3MasterofBioactiveMolecules—您?邊的抑制劑?師www.MedChemECellLine:HeLa,SiHaandMS751[1]Concentration:0-1μMIncubationTime:48hoursResult:Exhibitedsub-micromolarinhibitoryactivitiesagainstHeLa,SiHaandMS751withIC50sof0.09±0.02μM,0.15±0.01μM,0.11±0.03μM.CellCycleAnalysisCellLine:HeLacells[1]Concentration:0.1,0.2and0.4μMIncubationTime:24hoursResult:IncreasedcelldistributiontotheG2/Mphaseinaconcentration-dependentway,arresting24.7%,47.6%and71.7%ofthecellsinthisphaseat0.1,0.2and0.4μM,respectively.ApoptosisAnalysisCellLine:HeLacells[1]Concentration:0.1,0.2and0.4μMIncubationTime:24hoursResult:Induced35.9%,66.4%and84.4%ofcellpopulationundergoingapoptosisat0.1μM,0.2μM,0.4μM,respectively.CellCytotoxicityAssayCellLine:HK-2cells[1]Concentration:0-200μMIncubationTime:24hoursResult:Exhibitedgoodrenalsafetyprofile,withIC50of188±16μMinHK-2cells.體內研究Tubulinpolymerization-IN-4(100-1000mg/kg;IP,single)exhibitsextremelylowtoxicitywithLD50over1000mg/kg[1].Tubulinpolymerization-IN-4(30and60mg/kg;IP;dailyfor21days)inhibitsthetumorgrowth,withTGIof35%and58%atdosing30and60mg/kg[1].Tubulinpolymerization-IN-4(30mg/kg;IP;single)presentsthemodestpharmacokineticproperties[1].PharmacokineticParametersofTubulinpolymerization-IN-4inICRmice[1].2/3MasterofBioactiveMolecules—您?邊的抑制劑?師www.MedChemEIP(30mg/kg)T1/2(h)1.56±0.28Tmax(h)0.25Cmax(μg/L)6215±308AUC0-t(μg/L·h)5609±347AUC0-∞(μg/L·h)5940±347VZ/F(L/kg)11.35±1.29CLZ/F(L/h/kg)5.05±0.91MRT(h)1.77±0.43REFERENCES[1].HuoZ,LiuK,ZhangX,LiangY,SunX.Discoveryofpyrimidine-bridgedCA-4CBSIsforthetreatmentofcervicalcancerincombinationwithcisplatinwithsignificantlyreducednephrotoxicity.EurJMedChem.2022;235:114271.McePdfHeightCaution:Pro