Hotline:400-820-3792Inhibitors ? ScreeningLibraries ? Proteinswww.MedChemEP-gpinhibitor30Cat.No.:HY-178349分子式: C??H??FN?O?分子量: 386.38作用靶點(diǎn): P-glycoprotein;Apoptosis;Autophagy作用通路: MembraneTransporter/IonChannel;Apoptosis;Autophagy儲(chǔ)存方式: PleasestoretheproductundertherecommendedconditionsintheCertificateofAnalysis.BIOLOGICALACTIVITY生物活性P-gpinhibitor30是一種強(qiáng)效的P-gp抑制劑，能逆轉(zhuǎn)乳腺癌的多藥耐藥性，使耐藥細(xì)胞對(duì)Doxorubicin(ADM)(HY-15142)敏感。P-gpinhibitor30與ADM聯(lián)合使用時(shí)，可促進(jìn)耐藥乳腺癌細(xì)胞細(xì)胞凋亡(apoptosis)，誘導(dǎo)自噬(autophagy)，抑制細(xì)胞增殖、遷移和侵襲。P-gpinhibitor30在體外和體內(nèi)均能抑制乳腺癌腫瘤生長(zhǎng)。P-gpinhibitor30可用于耐藥性乳腺癌的相關(guān)研究[1]。體外研究P-gpinhibitor30(compoundA38)(0.1μM)reversesADMresistanceinMDA-MB-231/ADMcells,potentlyreducingtheIC50ofADMfrom785.46μMto2.05μM[1].P-gpinhibitor30(0.125-4μM)significantlyinhibitsP-gpATPaseactivityatdifferentconcentrationsinaconcentration-dependentmanner[1].P-gpinhibitor30interactswithP-gptoinhibititsfunctionwithoutdownregulatingitsexpression,andstabilizestheprotein,therebyreducingitsdegradationinMCF7/ADMcellsuponincreasingtemperature[1].P-gpinhibitor30(6h)significantlyincreasesRh123intensityinMCF7/ADMcellsandincreasestheaccumulationofADMandinhibitstheeffluxofRh123inMDA-MB-231/ADMcells[1].P-gpinhibitor30(0.1-1μM,24h-15days)promotesapoptosis,inhibitscellproliferation,andsuppressesthemigrationandinvasionofbreastcancerdrug-resistantcells(MCF7/ADMandMDA-MB-231/ADMcells),whencombinedwithADM,demonstratingthatitsensitizesthesecellstoADM[1].P-gpinhibitor30(0.1μM)leadstotheaccumulationofautophagosomesandsignificantlyincreasestheexpressionofautophagy-relatedproteinsinMCF7/ADMandMDA-MB-231/ADMcellswhencombinedwithADM,therebyinducingcelldeath[1].P-gpinhibitor30(1-10days)significantlyreducesthetumorvolumeofbothMCF7/ADMandMDA-MB-231/ADMcellswhencombinedwithADMina3Dtumorspheroidmodel[1].WesternBlotAnalysis[1]1/3 MasterofBioactiveMolecules—您身邊的抑制劑大師www.MedChemECellLine:MCF7/ADMandMDA-MB-231/ADMcellsConcentration:0.1μMIncubationTime:24hResult:SignificantlyincreasestheexpressionlevelofLC3whencombinedwithADM.ApoptosisAnalysis[1]CellLine:MCF7/ADMandMDA-MB-231/ADMcellsConcentration:0.1,0.5and1μMIncubationTime:48hResult:SignificantlyincreasedADM-inducedapoptosisinadose-dependentmannercomparedtotheMCF7/ADMcontrolgroup.SignificantlyincreasedADM-inducedapoptosisonMDA-MB-231/ADMcells.CellProliferationAssay[1]CellLine:MCF7/ADMandMDA-MB-231/ADMcellsConcentration:0.1,0.5and1μMIncubationTime:15daysResult:SignificantlyinhibitedtheproliferationofMCF7/ADMcellsinadose-dependentmannercomparedtotheMCF7/ADMcontrolgroupwhencombinedwithADM.Resultedinonlyafewcellssurvivedataconcentrationof1μM.Markedlyinhibitedtheproliferationofdrug-resistantbreastcancercellswhencombinedwithADM.CellMigrationAssay[1]CellLine:MCF7/ADMandMDA-MB-231/ADMcellsConcentration:0.1μMIncubationTime:36hResult:Suppressedthemigrationabilityofbreastcancerdrug-resistantcellswhencombinedwithADM.CellInvasionAssay[1]CellLine:MCF7/ADMandMDA-MB-231/ADMcells2/3 MasterofBioactiveMolecules—您身邊的抑制劑大師www.MedChemEConcentration:0.1μMIncubationTime:24hResult:Suppressedtheinvasionabilityofbreastcancerdrug-resistantcellswhencombinedwithADM.體內(nèi)研究P-gpinhibitor30(2mg/kg,i.p.,every2daysfor14days)showsantitumoreffectswhencombinedwithADMinMCF-7/ADMmousemodel[1].AnimalModel:FemaleBALB/cnudemice(4-5weeksold)subcutaneouslyinjectedwithMCF-7/ADMcells[1]Dosage:2mg/kgAdministration:i.p.,every2daysfor14daysResult:SignificantlyreducedtumorsizewhencombinedwithADM(10mg/kg),withefficacycomparabletoTariquidar(HY-10550).Showedsignificantlylowertumorweightthanthatofothergroups.Showednosignificantlosscomparedtocontrol.Causednosignificanttissuecellnecrosis.REFERENCESXueWH,etal.DiscoveryofaheterocyclicaromaticamidebasedP-gpinhibitorascoadjutantregulatingautophagyagainstdrugresistanceinbreastcancer.EurJMedChem.2025Dec15;300:118151