iMQT-020-生命科学试剂-MCE

Hotline:400-820-3792Inhibitors•ScreeningLibraries•Proteinswww.MedChemEiMQT_020Cat.No.:HY-179557CASNo.:2463893-46-9分⼦式:C₁₄H₈ClFN₂O₃分⼦量:306.68作⽤靶点:GlutathionePeroxidase;ReactiveOxygenSpecies(ROS);Apoptosis;Ferroptosis;PD-1/PD-L1作⽤通路:Apoptosis;MetabolicEnzyme/Protease;Immunology/Inflammation;NF-κB储存⽅式:PleasestoretheproductundertherecommendedconditionsintheCertificateofAnalysis.BIOLOGICALACTIVITY⽣物活性iMQT_020⼀种选择性变构SLC1A5_var抑制剂。iMQT_020可破坏SLC1A5_var的三聚体组装，导致癌细胞代谢危机并选择性抑制其⽣长。iMQT_020可降低⾕氨酰胺的补充代谢和氧化磷酸化，从⽽⼴泛扰乱癌细胞的代谢。iMQT_020可降低GSH⽔平并增加细胞内ROS和线粒体ROS的⽔平。iMQT_020可诱导细胞凋亡(apoptosis)和铁死亡(ferroptosis)。iMQT_020可通过表观遗传机制上调PD-L1的表达。iMQT_020可⽤于胰腺癌，肺癌和结肠癌的研究[1]。体外研究iMQT_020showsthestrongestinhibitoryeffectonmitochondrialglutamineuptake(IC50=6.156μM)ataconcentrationof10μM[1].iMQT_020(0-100μM)directlybindstoSLC1A5_varWTprotein(Kd=4.473μM),butdoesnotbindtoFIL/AAAmutants[1].iMQT_020(4μM)significantlyreducestheCDsignaloftheSLC1A5_varWTprotein,indicatingastructuralchange[1].iMQT_020(10μM)reducesglutamine-derivedTCAcyclemetabolites(suchasglutamate,αKG,succinicacid,etc.)anddownstreamproducts(suchasglutathione,proline)inMIAPaCa-2cells[1].iMQT_020(10μM,24h)reducesGSHlevelsinMIAPaCa-2cellsandincreasescellularROSandmitochondrialROS[1].iMQT_020(10μM,24h)reducesOCRandECARinSLC1A5_varWT-overexpressingMIAPaCa-2cells,butdidnotaffectFIL/AAAmutants[1].iMQT_020(10μM,24h)altersmitochondrialmorphologyinMIAPaCa-2cells(reducingfragmentation)anddecreasesmitochondrialmembranepotential(reducedTMREstaining)[1].iMQT_020(48h)selectivelyinhibitstheviabilityofcancercells(IC505-40μM)withoutaffectingnormalcells1/3MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemE[1].iMQT_020(10μM,24h)upregulatesPD-L1mRNAandproteinexpressioninhumanPDACcelllines(suchasSU.86.86,SW1990)andmousecarcinomacelllines(KPC,LLC,MC-38)[1].体内研究iMQT_020(75mg/kg,i.p.,oncedailyfor35days)inhibitstumorgrowthinmicexenograftedwithMIAPaCa-2cellsbyinducingapoptosisandferroptosis[1].iMQT_020(75mg/kg,i.p.,oncedailyfor35days)inhibitstumorgrowthinamouseorthotopictransplantationmodelofMIAPaCa-2cells[1].iMQT_020(75mg/kg,i.p.,oncedailyfor35days)inhibitsthegrowthofxenograftedtumorsofNCI-H1299humanlungcancercellsandCOLO205humancoloncancercellsinmice[1].iMQT_020(25mg/kg,i.p.,oncedailyfor21days),whenusedincombinationwithananti-PD-L1antibody(aPD-L1),synergisticallyinhibitsthegrowthofallogeneictumorsformedfromKPC,LLC,orMC-38cellsinmice[1].AnimalModel:Subcutaneousinjectionof5.0×106MIAPaCa-2humanpancreaticcancercellsintonudemicewasperformedtoestablishatumorxenograftmodel[1].Dosage:75mg/kgAdministration:I.p.,oncedailyfor35daysResult:Tumorvolumeandweightweresignificantlyreduced.Thenumberofcleavedcaspase-3(apoptosismarker)and4-HNE(lipidperoxidationmarker)positivecellsincreased,whilethenumberofCyclinD1andKi-67(proliferationmarker)positivecellsdecreased.AnimalModel:AthymicNCr-nu/nunudemicewereinjectedorallyintothepancreaswith5.0×105luciferase-labeledMIAPaCa-2cellstoformaninsitutumormodelthatsimulatesthepancreaticcancermicroenvironment[1].Dosage:75mg/kgAdministration:I.p.,oncedailyfor35daysResult:Tumorgrowthisinhibited,andtumorweightisreduced.AnimalModel:AthymicNCr-nu/nunudemiceweresubcutaneouslyinjectedwithNCI-H1299humanlungcancercellsorCOLO205humancoloncancercellstoformaxenograftmodel[1].Dosage:75mg/kgAdministration:I.p.,oncedailyfor35daysResult:Thetumorvolumeandweightweresignificantlyreduced,andimmunohistochemistryshowedincreasedapoptosisandferroptosismarkers.2/3MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemEAnimalModel:C57BL/6NmiceweresubcutaneouslyinjectedwithKPC(mousepancreaticcancercells),LLC(Lewislungcancercells),orMC-38(mousecoloncancercells)toestablishanallogeneictransplantationmodel[1].Dosage:25mg/kgAdministration:I.p.,oncedailyfor21daysResult:CombinedwithaPD-L1,itsignificantlyreducedtumorvolumeandweight.PD-L1expressionwasincreasedintumortissue,alongwithincreasedCD8+Tcellinfiltration,elevatedIFN-γandGranzymeBpositivecells,whilePD-1+Tcells,Tregcells,MDSCs,andTAMsweredecreased.Ki-67(proliferation)wasdecreased,andcleavedcaspase-3(apoptosis)wasincreased.REFERENCES[1].SungY,etal.Targetingcancerglutaminedependencywithafirst-in-classinhibitorofthemitochondrialglutaminetransporterSLC1A5_var.Nat