Hotline:400-820-3792Inhibitors?ScreeningLibraries?Proteinswww.MedChemEApratoxinACat.No.:HY-P3989CASNo.:350791-64-9Synonyms:(-)-ApratoxinA分?式:C??H??N?O?S分?量:840.12作?靶點:HSP;Apoptosis;EndogenousMetabolite作?通路:CellCycle/DNADamage;MetabolicEnzyme/Protease;Apoptosis儲存?式:PleasestoretheproductundertherecommendedconditionsintheCertificateofAnalysis.BIOLOGICALACTIVITY?物活性ApratoxinA?種藍藻代謝物，通過誘導G1細胞周期停滯和凋亡級聯反應來介導抗增殖活性。ApratoxinA與Hsp70/Hsc70結合以促進Hsp90戶蛋?的降解。ApratoxinA可以特異性結合Sec61復合體。IC50&TargetHSP70HSP90體外研究ApratoxinA(5,50nM;24,48h)inducesG1cellcyclearrestandapoptosis.ApratoxinAdoesnotshowanygrowth-inhibitoryactivityinyeastcells[1].ApratoxinA(50nM;1-24h)inhibitsTyr705phosphorylationofSTAT3[1].CellCycleAnalysis[1]CellLine:U2OScellsConcentration:5,50nMIncubationTime:24,48hResult:Resultedinanaccumulationofcellsharboring2N(diploid)contentofchromo-somes,suggestingG1-phasecellcyclearrest.Showedacompleteblockincellcycleprogressionwith5nMfor48h.ApoptosisAnalysis[1]1/3MasterofBioactiveMolecules—您?邊的抑制劑?師www.MedChemECellLine:U2OScellsConcentration:50nMIncubationTime:0-48hResult:Asub-G1populationemerged50nM,suggestingcellularapoptosis.Had20-foldhighercaspase-3activityafter48h.WesternBlotAnalysis[1]CellLine:U2OScellsConcentration:50nMIncubationTime:1,4,12,24hResult:hadnoeffectonphosphorylationofSer727,butstronglyinhibitedconstitutivephosphorylationatTyr705ofSTAT3.體內研究ApratoxinA(0.5-1mg/kg;IV;every7days;for2totaldoses(BxPC-3T1study)or3doses(A549study))hasdose-dependentanticanceractivities[2].ApratoxinA(1mg/kg;IV)showsahighvolumeofdistribution(Vss=19.31L/kg)andmoderatehalf-life(11.57hours)[2].AnimalModel:6-weekoldfemaleNCrnu/numicewithBxPC-3T1orA549cells[1]Dosage:0.5,0.75,1mg/kgAdministration:IV;every7days;for2totaldoses(BxPC-3T1study)or3doses(A549study)Result:ForBxPC3T1model,both1mg/kgand0.75mg/kgwerefoundtoexceedtheMTDwithatreatedversusvehiclecontroleffectontumorsize(T/Cratio)of53%and41%,respectively.Itinducedseverebodyweightlossrightafterfirstdoseinboth1mg/kgand0.75mg/kg.IntheA549model,0.6mg/kg,0.5mg/kg,and0.4mg/kgshowedT/Cratiosof30%,24%,and41%,respectively.AnimalModel:Athymic(NCrnu/nu)micewithA549tumorcells[2]Dosage:1mg/kgAdministration:IVResult:Showedahighvolumeofdistribution(Vss=19.31L/kg)andmoderatehalf-life(11.57hours).2/3MasterofBioactiveMolecules—您?邊的抑制劑?師www.MedChemEREFERENCES[1].HendrikLuesch,etal.AfunctionalgenomicsapproachtothemodeofactionofapratoxinA.NatChemBiol.2006Mar;2(3):158-67.[2].Kuan-ChunHuang,etal.ApratoxinAShowsNovelPancreas-TargetingActivitythroughtheBindingofSec61.MolCancerTher.2016Jun;15(6):1208-16.[3].ShensiShen,etal.CyclodepsipeptidetoxinpromotesthedegradationofHsp90clientproteinsthroughchaperone-mediatedautophagy.JCellBiol.2009May18;185(4):629-39.McePdfHeightCaution:Producthasnotbeenfullyvalida