Hotline:400-820-3792Inhibitors ? ScreeningLibraries ? Proteinswww.MedChemETubulinpolymerization/P-gp-IN-1Cat.No.:HY-178466分子式:C??H??F?N?O?分子量:658.62作用靶點:Microtubule/Tubulin;P-glycoprotein;Apoptosis作用通路:CellCycle/DNADamage;Cytoskeleton;MembraneTransporter/IonChannel;Apoptosis儲存方式:PleasestoretheproductundertherecommendedconditionsintheCertificateofAnalysis.BIOLOGICALACTIVITY生物活性Tubulinpolymerization/P-gp-IN-1是一種Tubulinpolymerization/P-gp雙重抑制劑。Tubulinpolymerization/P-gp-IN-1可抑制微管蛋白聚合，并誘導(dǎo)G2/M期阻滯和細(xì)胞凋亡(apoptosis)。Tubulinpolymerization/P-gp-IN-1通過抑制P-gp的外排功能逆轉(zhuǎn)多藥耐藥性(MDR)。Tubulinpolymerization/P-gp-IN-1具有雙重功能：直接抗腫瘤活性和逆轉(zhuǎn)P-gp介導(dǎo)的Cisplatin(HY-17394)耐藥性。Tubulinpolymerization/P-gp-IN-1可穩(wěn)定結(jié)合微管蛋白的CBS結(jié)構(gòu)域(ΔG=?12.4kcal/mol)和P-gp的疏水性腔(ΔG=?10.8kcal/mol)。Tubulinpolymerization/P-gp-IN-1可用于耐藥性宮頸癌的研究[1]。體外研究Tubulinpolymerization/P-gp-IN-1(Compound6h)notonlyconfershighpotencyinsensitivecellssuchasHeLacells(IC50=6.69μM),CaSkicells(IC50=7.84μM),andSiHacells(IC50=16.68μM),butalsomaintainsnearlyequivalentefficacyagainstthedrug-resistantHeLa/DDPcellline(IC50=7.21μM),andshowsnosignificantcytotoxicityagainsthumannormalcervicalcells(IC50=51.95μM)[1].Tubulinpolymerization/P-gp-IN-1(4-16μM,24h)decreasesthelevelsofpolymerizedα-andβ-tubulin,whilethelevelsofdepolymerizedtubulinincrease,witheffectssimilartocolchicine(COL)butoppositetopaclitaxel(PTX),andcausesmicrotubulenetworkcontraction(especially8μMand16μM),andthecellmorphologychangedfromspindle-shapedtoround,withmicrotubulesremainingonlyintheperinuclearregioninHeLaandHeLa/DDPcells[1].Tubulinpolymerization/P-gp-IN-1(4-16μM,24h)notonlyinducesG2/Mcellcyclearrestbutalsoeffectivelytriggersapoptosisandsignificantlysuppressesinvitromigrationinaconcentration-dependentmannerinbothHeLaandHeLa/DDPcells[1].Tubulinpolymerization/P-gp-IN-1(0.25-1μM,48h)caneffectivelyreverseCisplatinresistanceinHeLa/DDPcells[1].Tubulinpolymerization/P-gp-IN-1(0.25-1μM,12h)notonlyconcentration-dependentlyinhibitsP-gp-mediatedeffluxbutalsomaintainsunchangedP-gpproteinlevelsat1μMinHeLa/DDPcells,andit1/3 MasterofBioactiveMolecules—您身邊的抑制劑大師www.MedChemEsignificantlystabilizesP-gpunderelevatedtemperaturesof61°C[1].WesternBlotAnalysis[1]CellLine:HeLacells,HeLa/DDPcellsConcentration:4μM,8μM,16μMIncubationTime:24hResult:Decreasedthelevelsofpolymerizedα-andβ-tubulin,whilethelevelsofdepolymerizedtubulinincreased,witheffectssimilartocolchicine(COL)butoppositetopaclitaxel(PTX).CellCycleAnalysis[1]CellLine:HeLacells,HeLa/DDPcellsConcentration:4μM,8μM,16μMIncubationTime:24hResult:IntheHeLacells,theproportionofG2/Mphasecellsincreasedfrom2.98%(control)to10.63%(4μM),19.05%(8μM)and30.75%(16μM).IntheHeLa/DDPcells,theproportionofG2/Mphasecellsincreasedfrom7.72%inthecontrolto13.41%(4μM),24.05%(8μM),and35.79%(16μM).ApoptosisAnalysis[1]CellLine:HeLacells,HeLa/DDPcellsConcentration:4μM,8μM,16μMIncubationTime:24hResult:ThepercentageofapoptoticHeLacellsincreaseddose-dependentlyfrom4.37%(control)to13.15%,40.60%,and92.80%,respectively.HeLa/DDPcellswiththeapoptoticpopulationincreasingfrom3.84%(control)to10.03%,24.76%,and67.40%with4,8,and16μM,respectively.CellMigrationAssay[1]CellLine:HeLacells,HeLa/DDPcellsConcentration:4μM,8μM,16μMIncubationTime:24hResult:IntheHeLacells,woundclosuredecreasedfrom46.59(control)to28.11%,20.43%,and3.35%withconcentrationsof4,8,and16μM.2/3 MasterofBioactiveMolecules—您身邊的抑制劑大師www.MedChemEIntheHeLa/DDPcells,woundclosureratesdecreasedfrom45.40%(control)to24.41%,7.47%,and1.94%withconcentrationsof4,8,and16μM.體內(nèi)研究Tubulinpolymerization/P-gp-IN-1(Compound6h)(0-400μM,96h)maintainsexcellentsafety(0%mortality;8.3%malformation)evenatconcentrationsupto400μMinzebrafishembryos[1].REFERENCESYanT,etal.Designandsynthesisofnovelquinoline-chalconederivativesasdualinhibitorsoftubulinpolymerizationandP-glycoproteintoovercomecisplatinresistanceincervicalcancer.BioorgChem.2025Oct;165