Conglobatin-DataSheet-生命科学试剂-MedChemExpress

Hotline:400-820-3792Inhibitors•Agonists•ScreeningLibrariesConglobatinCat.No.:HY-119906CASNo.:72263-05-9分⼦式:C₂₈H₃₈N₂O₆分⼦量:498.61作⽤靶点:HSP;Apoptosis作⽤通路:CellCycle/DNADamage;MetabolicEnzyme/Protease;Apoptosis储存⽅式:PleasestoretheproductundertherecommendedconditionsintheCertificateofAnalysis.BIOLOGICALACTIVITY⽣物活性Conglobatin(FW-04-806)⼀种从Streptomycesconglobatus培养物中分离得到的⼤环内酯双内酯。Conglobatin⼀种具有⼝服活性的Hsp90抑制剂，可以与Hsp90的N末端域结合，并破坏Hsp90-Cdc37复合物的形成。Conglobatin可诱导⼈乳腺癌细胞和⾷道鳞状细胞癌细胞凋亡，并在体内表现出抗肿瘤活性。IC50&TargetHSP90体外研究Conglobatin(6.25-100μM;48h)markedlyinhibitstheproliferationofSKBR3andMCF-7cells,withIC50sof12.11and39.44μM,respectively[2].ConglobatininhibitscellproliferationinEC109,KYSE70,KYSE450,KYSE150,KYSE180,andKYSE510cells,withIC50sof16.43,15.89,10.94,10.50,10.28,and9.31μM,respectively[3].Conglobatin(10-40μM;24h)displaysobviousarrestofSKBR3andMCF-7cellsintheG2/Mphase.Conglobatininducesapoptosisthroughcaspase-dependentpathwaysinSKBR3andMCF-7cells[2].Conglobatin(10-40μM;3-24h)reducesHsp90clientproteinlevelsandinducesproteasome-dependentdegradation[2].ConglobatinbindstotheN-terminalofHsp90,doesnotaffectATP-bindingcapabilityofHsp90,butinhibitsHsp90/Cdc37chaperone/co-chaperoneinteractions[2].CellProliferationAssay[2]CellLine:SKBR3andMCF-7cellsConcentration:6.25,12.5,25,50,100μMIncubationTime:48hours1/3Result:InhibitedtheproliferationofSKBR3andMCF-7cellsinadose-dependentmanner.CellCycleAnalysis[2]CellLine:SKBR3andMCF-7cellsConcentration:10,20,40μMIncubationTime:24hoursResult:IncreasedtheG2/McellpopulationanddecreasedthepopulationintheSandG0/G1phases.WesternBlotAnalysis[2]CellLine:SKBR3andMCF-7cellsConcentration:10,20,40μMIncubationTime:3,6,12,24hoursResult:DecreasedthelevelsoftheclientproteinsHER2,p-HER2,Raf-1,Akt,andp-Aktinadoseandtime-dependentmannerinSKBR3cells.ReducedthethelevelsoftheclientproteinsRaf-1,Akt,andp-Aktinadoseandtime-dependentmannerinMCF-7cells.体内研究Conglobatin(50-200mg/kg;i.g.q3dfor24d)inhibitsthetumorgrowthofSKBR3andMCF-7humanbreastcancerxenograftmodelsinadose-dependentmanner[2].Conglobatin(4-8mg/kg;i.p.dailyfor21days)inhibitstumorgrowthinEC109andKYSE510tumorxenograftmodelswithlowtoxicity[3]AnimalModel:BALB/c(nu/nu)athymicmicewithSKBR3andMCF-7tumorxenograft[2]Dosage:50,100,200mg/kgAdministration:Oralgavageevery3daysfor24daysResult:Showedinhibitionoftumorgrowthatarateof39.1%,52.7%,and67.5%intheSKBR3celllinegroupsand27.3%,39.8%,54.3%intheMCF-7celllinegroupsatthethreeincreasingdoses,respectively.Waswelltolerated.REFERENCES[1].WestleyJW,et,al.Conglobatin,anovelmacrolidedilactonefromStreptomycesconglobatusATCC31005.JAntibiot(Tokyo).1979Sep;32(9):874-7.2/3[2].HuangW,et,al.FW-04-806inhibitsproliferationandinducesapoptosisinhumanbreastcancercellsbybindingtoN-terminusofHsp90anddisruptingHsp90-Cdc37complexformation.MolCancer.2014Jun14;13:150.[3].LiLY,et,al.MacrolideanalogF806suppressesesophagealsquamouscellcarcinoma(ESCC)byblockingβ1integrinactivation.Oncotarget.2015Jun30;6(18):159