Hotline:400-820-3792Inhibitors ? ScreeningLibraries ? Proteinswww.MedChemENMac1Cat.No.:HY-115507CASNo.:1332290-68-2分子式:C??H??O?分子量:380.48作用靶點(diǎn):AMPK;mTOR;ERK;OxidativePhosphorylation;ReactiveOxygenSpecies(ROS);Ras作用通路:Epigenetics;PI3K/Akt/mTOR;MAPK/ERKPathway;StemCell/Wnt;MetabolicEnzyme/Protease;Immunology/Inflammation;NF-κB;GPCR/GProtein儲(chǔ)存方式:PleasestoretheproductundertherecommendedconditionsintheCertificateofAnalysis.BIOLOGICALACTIVITY生物活性NMac1是一種具有口服活性的Nm23/NDPK激活劑。NMac1直接與Nm23-H1結(jié)合并激活重組Nm23-H1的NDPK活性，EC50為10.7uM。NMac1在MDA-MB-231細(xì)胞中誘導(dǎo)AMPK活化并抑制mTOR和ERK，誘導(dǎo)線粒體OXPHOS失調(diào)，抑制線粒體ROS進(jìn)而誘導(dǎo)線粒體功能障礙。NMac1抑制MDA-MB-231細(xì)胞中的復(fù)合物I活性，抑制Rac1活化后形態(tài)學(xué)和肌動(dòng)蛋白細(xì)胞骨架組織的變化。NMac1抑制腫瘤侵襲，遷移以及轉(zhuǎn)移。NMac1可用于轉(zhuǎn)移性腫瘤如乳腺癌的研究。NMac1可以從姜cassumunarRoxb中分離出。體外研究NMac1inhibitstheproliferationofcancercellsunderglucosestarvation(IC50sof7.197and2.849μM)inMDA-MB-231andMCF7cells[1].NMac1(0-20μM,0-20h)inducesAMPKactivationandinhibitsmTORandERKintheabsenceofglucoseinMDA-MB-231cells[1].NMac1(0-20μM,0-20h)inducesmitochondrialdysfunctionbyinhibitingATPproductionandreducingthemitochondrialmembranepotentialinMDA-MB-231cells[1].NMac1(0-10μM,0-100min)inducesATPdepletionbyreducingoxygenconsumptionrate,producingmitochondrialROSandinducingdysregulationofmitochondrialATPproductionsystemOXPHOSintheabsenceofglucoseinMDA-MB-231cells[1].NMac1(250-500μM,0-100min)inhibitscomplexIactivityinMDA-MB-231cells[1].NMac1(0-30μM,2-14days)inhibitstheproliferationofMDA-MB-231spheroidcellsinadose-dependentmanner[1].NMac1(0-25μM,16-24h)inhibitsRac1activationthroughNDPKactivationofNm23-H1,reducestheinvasionandmigrationinMDA-MB-231cells[2].1/3 MasterofBioactiveMolecules—您身邊的抑制劑大師www.MedChemEWesternBlotAnalysis[1]CellLine:MDA-MB-231cellsConcentration:0,5,10,12.5,20μMIncubationTime:0,2,4,8,12,16,20hResult:InducedAMPKactivationandinhibitedmTOR,ERK,andpS6K,rapidlyinducesAMPKactivationwithin2hoursunderglucosedepletion.Immunofluorescence[1]CellLine:MDA-MB-231cellsConcentration:12.5μMIncubationTime:6hResult:Deterioratedthemitochondrialintegrityofcellsintheabsenceofglucose,reducedTOM20levels.WesternBlotAnalysis[2]CellLine:MDA-MB-231cellsConcentration:0,5,10,25μMIncubationTime:16hResult:ReducedRac1activation.CellMigrationAssay[2]CellLine:MDA-MB-231cellsConcentration:0,5,10,25μMIncubationTime:24hResult:Reducedtheinvasionandmigrationinadosedependentmanner,withoutaffectingtheirproliferation.體內(nèi)研究NMac1(10mg/kg,p.o.,onceaday,21days)inhibitsbreastcancermetastasiswithoutaffectingprimarytumorsizeinbreastcancermetastasismousemodel[2].AnimalModel:Breastcancer(MDA-MB-231-Luc-D3H2LNcells,1?×?106)metastasisNOD/SCIDmicemodel[2]2/3 MasterofBioactiveMolecules—您身邊的抑制劑大師www.MedChemEDosage:10mg/kgAdministration:p.o.,onceaday,21daysResult:Significantlyinhibitedbreastcancermetastasiswithoutaffectingprimarytumorsize.REFERENCESKimB,etal.Nm23-H1activatorphenylbutenoiddimerexertscytotoxiceffectsonmetastaticbreastcancercellsbyinducingmitochondrialdysfunctiononlyunderglucosestarvation.SciRep.2021Dec7;11(1):23549.LeeJJ,etal.SmallmoleculeactivatorofNm23/NDPKasaninhibitorofmetastasis.SciRep.2018Jul19;8(1):10909.McePdfHeightCaution:Producthasnotbe