Hotline:400-820-3792Inhibitors ? ScreeningLibraries ? Proteinswww.MedChemEL-744832Cat.No.:HY-116428CASNo.:160141-09-3分子式:C??H??N?O?S?分子量:559.78作用靶點(diǎn):FarnesylTransferase;Ras;TGF-βReceptor;Apoptosis作用通路:MetabolicEnzyme/Protease;GPCR/GProtein;MAPK/ERKPathway;TGF-beta/Smad;Apoptosis儲(chǔ)存方式:PleasestoretheproductundertherecommendedconditionsintheCertificateofAnalysis.BIOLOGICALACTIVITY生物活性L-744832是一種法尼基轉(zhuǎn)移酶(FarnesylTransferase)抑制劑。L-744,832能有效抑制H-Ras和N-Ras的法尼基化，但對(duì)K-Ras的處理影響較小。L-744,832不僅通過(guò)抑制Ras法尼基化直接靶向致癌通路，更通過(guò)表觀遺傳重編程恢復(fù)TGF-β信號(hào)，從而增強(qiáng)放療敏感性。L-744832可誘導(dǎo)細(xì)胞周期阻滯并誘導(dǎo)細(xì)胞凋亡(apoptosis)。L-744832可用于胰腺癌等Ras驅(qū)動(dòng)型腫瘤的聯(lián)合治療研究。IC50&TargetH-RasNRASrG4體外研究L-744832(0.1-50μM,24-72h)showssignificantdifferencesinsensitivityinPanc-1,Capan-2,BxPC-3,AsPC-1andCFPAC-1cellswithIC50sof1.3,2.1,12.3,14.3and>50μM[1].L-744832(0.1-50μM,72h)arrestthesensitivecelllines(Panc-1,Capan-2,BxPC-3andAsPC-1)intheG2/MphaseofthecellcycleandthearrestoccursduringthemitoticentrystagedownstreamoftheG2/Mcheckpoint[1].L-744832(10μM,24-72h)inducesabovefivetypesofcellapoptosis,andthecombinationofradiotherapycansignificantlyincreasetheapoptosisrateofMIAPaCa-2cells,whilethiseffectisnotobservedinBxPC-3cells[1][2].L-744832(0.1-10μM)withionizingradiationresultsinenhancedcytotoxicityinhumanpancreaticcancercells[1].L-744832(5-10μM)effectivelyinhibitsthefarnesylationofH-RasandN-RasandMIAPaCa-2cellsaremoresensitivethanBxPC-3cells[2].L-744832(5-10μM,3-6h)restorestheexpressionofTGF-βtypeIIreceptor(RII)throughregulatingDNMT1,therebyre-establishingthetumor-suppressingfunctionofTGF-β[2].CellCycleAnalysis[2]1/3 MasterofBioactiveMolecules—您身邊的抑制劑大師www.MedChemECellLine:Panc-1,Capan-2,BxPC-3,AsPC-1andCFPAC-1cellsConcentration:0.1,0.5,1,10,25and50μMIncubationTime:72hResult:Dose-dependentincreasedinG2/MphaseaccumulationandtheproportionofG2/MphasecellsinPanc-1cellsincreasednearlythreefold.ApoptosisAnalysis[2]CellLine:Panc-1,Capan-2,BxPC-3,AsPC-1andCFPAC-1cellsConcentration:10μMIncubationTime:72hResult:Showedchromatincondensationandnuclearfragmentation.Increasedtheapoptoticindexineachgroup,andthisoccurredinbothwild-typep53(Capan-2)cellsandmutantp53(Panc-1)cells.WesternBlotAnalysis[2]CellLine:Panc-1,Capan-2,BxPC-3,AsPC-1andCFPAC-1cellsConcentration:10μMIncubationTime:72hResult:SignificantlyincreasedtheactivityofCyclinB1/Cdc2kinase.RT-PCR[1]CellLine:MIAPaCa-2cellsConcentration:10μMIncubationTime:3and6hResult:ActivatedtheRIIpromotertoincreaseitsmRNAlevels.ReducedthemRNAlevelsofDNMT1.WesternBlotAnalysis[1]CellLine:MIAPaCa-2cellsConcentration:10μMIncubationTime:3and6h2/3 MasterofBioactiveMolecules—您身邊的抑制劑大師www.MedChemEResult: ActivatedtheRIIpromotertoincreaseitsproteinlevels.ReducedtheproteinlevelsofDNMT1.REFERENCESSongSY,etal.K-Ras-independenteffectsofthefarnesyltransferaseinhibitorL-744,832oncyclinB1/Cdc2kinaseactivity,G2/Mcellcycleprogressionandapoptosisinhumanpancreaticductaladenocarcinomacells.Neoplasia.2000May-Jun;2(3):261-72.AlcockRA,etal.Farnesyltransferaseinhibitor(L-744,832)restoresTGF-betatypeIIreceptorexpressionandenhancesradiationsensitivityinK-rasmutantpancreaticcancercelllineMIAPaCa-2.Oncogene.2002Nov7;21(51):7883-90.McePdfHeightCaution:Producthasno