Hotline:400-820-3792Inhibitors ? ScreeningLibraries ? Proteinswww.MedChemEWP-1034Cat.No.:HY-111275CASNo.:857064-42-7分子式:C??H??N?O?分子量:321.33作用靶點:JAK;STAT;Apoptosis;Caspase;PARP作用通路:Epigenetics;JAK/STATSignaling;ProteinTyrosineKinase/RTK;StemCell/Wnt;Apoptosis;CellCycle/DNADamage儲存方式:PleasestoretheproductundertherecommendedconditionsintheCertificateofAnalysis.BIOLOGICALACTIVITY生物活性 WP-1034是一種JAK-STAT抑制劑，在急性髓系白血病(AML)中具有促凋亡和抗白血病活性。WP-1034可阻斷Stat3和Stat5的激活。WP-1034可誘導(dǎo)細(xì)胞周期阻滯并觸發(fā)細(xì)胞凋亡(apoptosis)。WP-1034可用于AML研究[1]。體外研究WP-1034(1-6μM,7days)suppressesthecolony-forminggrowthofOCIM2andK562cellsinadose-dependentmanner,andinhibitsleukemiacolony-formingcellproliferationoffreshAMLcells[1].WP-1034(1-10μM,0-4h)inhibitsStat3andStat5phosphorylationinatime-anddose-dependentmannerinOCIM2cells,indicatingthatiteffectivelyinhibitsJak-StatsignalinginAMLcells[1].WP-1034(5μM,0-16h)inducesSub-G0phasecellcyclearrestinOCIM2cells[1].WP-1034(3-6μM)inducesapoptosisinOCIM2cellsinadose-dependentmannerwithcaspase3andPARPcleavage,andthiseffectisblockedbythecaspaseinhibitorAc-DEVD-CHO(HY-P1001)[1].CellProliferationAssay[1]CellLine:OCIM2,K562,AMLandmarrowcellsConcentration:1,2,2.5,3,4,5,6,7.5and10μMIncubationTime:7daysResult:Suppressedthecolony-forminggrowthofOCIM2cellsinadose-dependentmanneratconcentrationsrangingfrom1to5μM.1/3 MasterofBioactiveMolecules—您身邊的抑制劑大師www.MedChemEAlmostcompletelyabolishedcellproliferationatconcentrationsof≥4μM.InhibitedtheproliferationofK562cellsby>80%atconcentrationsof≥5μM.Aconcentrationofatleast10μMwasnecessarytoinhibitOCIM2cellproliferationby>80%.InhibitedtheproliferationofAMLcolony-formingblastsinadose-dependentmanneratconcentrationsrangingfrom1to6μM.SuppressedAMLcolony-formingblastproliferationatmorethan50%at5μM.AlmostcompletelyinhibitedAMLproliferationat6μM.Showedadose-dependentinhibitionofthegrowthofhealthymarrowbetween4to6μM.TheinhibitionofnormalmarrowcellswaslessthantheinhibitionofAMLblastcellsatthesameconcentrations.WesternBlotAnalysis[1]CellLine:OCIM2cellsConcentration:1,2.5,5,7.5and10μMIncubationTime:20and40min,1,2,3,and4hResult:Reducedphospho-Stat3andphospho-Stat5levelstoundetectablelevelsafterincubationtimesof≥1hour.Significantlydown-regulatedStat3andStat5phosphorylationatconcentrationsof1,2.5,5,7.5and10μMfor2hours.Showednoeffectonlevelsofphospho-Stat1.Induceddose-dependentcaspase3cleavage.Resultedinadose-dependentincreaseincleavedPARPproteinlevels.CellCycleAnalysis[1]CellLine:OCIM2cellsConcentration:5μMIncubationTime:0,2,4,6,and16hResult:InducedcellcyclearrestatSub-G0phaseat6hoursofincubation,witharound23%ofthecellsaccumulatingatsub-G0phaseat16hoursofincubation.ApoptosisAnalysis[1]CellLine:OCIM2cellsConcentration:4μM2/3 MasterofBioactiveMolecules—您身邊的抑制劑大師www.MedChemEIncubationTime:2hResult:InducedapoptoticcelldeathinOCIM2cells,andthiseffectwasblockedbythecaspaseinhibitorAc-DEVD-CHO.REFERENCES1.FaderlS,etal.WP-1034,anovelJAK-STATinhibitor,withproapoptoticandantileukemicactivityinacutemyeloidleukemia(AML).AnticancerRes.2005May-Jun;25(3B):1841-50.McePdfHeightCaution:Producthasnotb