Hotline:400-820-3792Inhibitors ? ScreeningLibraries ? Proteinswww.MedChemETalaroconvolutinACat.No.:HY-N15742CASNo.:273199-42-1分子式:C??H??NO?分子量:487.67作用靶點(diǎn):Ferroptosis;ReactiveOxygenSpecies(ROS);p38MAPK作用通路:Apoptosis;Immunology/Inflammation;MetabolicEnzyme/Protease;NF-κB;MAPK/ERKPathway儲(chǔ)存方式:PleasestoretheproductundertherecommendedconditionsintheCertificateofAnalysis.BIOLOGICALACTIVITY生物活性TalaroconvolutinA是一種鐵死亡(ferroptosis)誘導(dǎo)劑。TalaroconvolutinA通過(guò)增加活性氧(ROS)水平而非GPX4途徑誘導(dǎo)鐵死亡。TalaroconvolutinA下調(diào)通道蛋白溶質(zhì)載體家族7成員11(SLC7A11)及上調(diào)花生四烯酸脂氧合酶3(ALOXE3)表達(dá)。TalaroconvolutinA抑制結(jié)直腸癌細(xì)胞HCT116和膀胱癌細(xì)胞SW480的生長(zhǎng)，IC50值分別為1.22μM和1.4μM。TalaroconvolutinA可用于結(jié)直腸癌和膀胱癌的研究。體外研究TalaroconvolutinA(0-40μM,24h)suppressesthegrowthofHCT116,SW480,andSW620cells,withtheIC50sof9.23,8.15,and5.82?μMin10%FBSmedium,respectively,withtheIC50sof1.22,1.40,and1.27?μMin1%FBSmedium,correspondingly[1].TalaroconvolutinA(0-40μM,48h)decreasesDNAsynthesisinHCT116cellsandSW480cells[1].TalaroconvolutinA(0-10μM,12days)suppressescellgrowthandinducescelldeathinSW480cells[1].TalaroconvolutinA(0-10μM,24h)killsCRCcellsbyincreasingROSlevels,butdoesnotinduceapoptosisorcellcyclearrestinSW480cells[1].TalaroconvolutinA(5μM,24h)inducesferroptosisandincreaseslipidperoxidationinSW480cells[1].TalaroconvolutinA(0-125μM,24h)inducesthedeathofcoloncancercellsbytheferroptosispathway[1].TalaroconvolutinA(5μM)enhancescellactivityinoverexpressedSLC7A11SW480cells,reducescellactivityinSLC7A11knocked-downSW480cells[1].TalaroconvolutinA(0-10μM)increasesALOXE3mRNAandproteinlevelsinSW480cells[1].TalaroconvolutinA(0-12μM,24h)inhibitstheproliferationofSW780andUM-UC-3cells,withIC50sof5.7and8.2μM,respectively,in10%FBSmedium,withtheIC50sof1.2and2.3μM,respectively,in1%FBSmedium[2].TalaroconvolutinA(0-12μM,24h)slowsDNAreplicationinSW780cells[2].TalaroconvolutinA(0-8μM,10days)inhibitstheclonogenicabilityofSW780cells[2].1/3 MasterofBioactiveMolecules—您身邊的抑制劑大師www.MedChemETalaroconvolutinA(0-7.5μM,24h)inhibitscellcycleinSW780cells[2].TalaroconvolutinA(0-15μM,24-48h)inducescelldeaththroughROS-inducedferroptosisinSW780cells,butdoesnotinducesignificantapoptosisinSW780cells[2].TalaroconvolutinAstillexhibitsanticanceractivityinSW780cellsandUM-UC-3cellsafterconjugationwithbiotin,indicatingthatbiotindoesnotdestroytheanticanceractivesite[2].TalaroconvolutinAinducesphosphoproteomicchangesbypullingdownMAPK1andMAPK14kinaseactivitiesinSW780cellsandUM-UC-3cells[2].TalaroconvolutinAinhibitsHelacells,BEL-7042cellsandα-glucosidaseactivity,withIC50sof14.9μM,26.7μM,and78.2μM,respectively[3].CellCycleAnalysis[1]CellLine:SW480cellsConcentration:0μM,5.0μM,10μMIncubationTime:24hResult:Didnotcausecellcyclearrest,butincreasedthesubG1peak.ApoptosisAnalysis[1]CellLine:SW480cellsConcentration:0μM,5.0μM,10μMIncubationTime:24hResult:Inducedcelldeathbutdidnotinduceearlyapoptosis.Ledtodrasticchangesinthemorphologyofthecellmembrane:themembranesurfacewasnolongersmoothandintact,buthadmultipleperforations.CellCycleAnalysis[2]CellLine:SW480cellsConcentration:0μM,2.5μM,5.0μM,7.5μMIncubationTime:24hResult:Inhibitedcellcycle,increasedp21/CIP,butdecreasedCCNA2andCCNB1attheproteinlevel.ApoptosisAnalysis[2]CellLine:SW480cellsConcentration:0μM,5μM,10μM,15μM2/3 MasterofBioactiveMolecules—您身邊的抑制劑大師www.MedChemEIncubationTime:48hResult:Didnotinducesignificantapoptosis.體內(nèi)研究TalaroconvolutinA(6mg/kg,i.p.,every2days,40days)suppressestumorgrowthinBalb/cnudemicebearingcancerHCT116cells[1].TalaroconvolutinA(6mg/kg,i.p.,every2days,24days)suppressesbladdertumorgrowthinvivoinaxenograftedmousemodel[2].AnimalModel:Balb/cnudemice(5-weekold).bearingcancerHCT116cells(5?×?106)[1]Dosage:6mg/kgAdministration:i.p.,every2days,40daysResult:Decreasedtumorgrowthspeed,didnotaffectbodyweight,routinebloodindex,histologicalmorphologyofliverandkidney.ReducedKi67andferroptosis-relatedmoleculeSLC7A11levelsbutincreasedthelevelofHMOX1.AnimalModel:SW780bladdercancercells(107cells)xenograftednudemice(female6-week-oldBALB/C-nudemice)model[2]Dosage:6mg/kgAdministration:i.p.,every2days,24daysResult:Reducedtumorgrowthrateandsize.DecreasedtheexpressionofthemarkerproteinKi67,repressedcellproliferationintransplantedtumors.HadnoserioustoxicityintheliverandkidneyREFERENCESXiaY,etal.Discoveryofanovelferroptosisinducer-talaroconvolutinA-killingcolorectalcancercellsinvitroandinvivo.CellDeathDis.2020Nov17;11(11):988.XiaY,etal.Proteomics,Transcriptomics,andPhosphoproteomicsRevealtheMechanismofTalaroconvolutin-ASuppressingBladderCancerviaBlockingCellCycleandTriggeringFerroptosis.MolCellProteomics.2023Dec;22(12):100672.WangP,etal.TwoNewSuccinimideDerivativesCladosporitinsAandBfromtheMangrove-derivedFungus