S-R-WT-IDH1-Inhibitor-2-GSK321-DataSheet-生命科學(xué)試劑-MedChemExpress

Hotline:400-820-3792Inhibitors?ScreeningLibraries?Proteinswww.MedChemE(S,R)-WTIDH1Inhibitor2Cat.No.:HY-128888BCASNo.:1816272-18-0Synonyms:GSK321分?式:C??H??FN?O?分?量:501.55作?靶點(diǎn):IsocitrateDehydrogenase(IDH)作?通路:MetabolicEnzyme/Protease儲(chǔ)存?式:Powder-20°C3years4°C2yearsInsolvent-80°C6months-20°C1monthBIOLOGICALACTIVITY?物活性(S,R)-WTIDH1Inhibitor2(GSK321)?個(gè)有效的選擇性突變型IDH1抑制劑，抑制R132G、R132C、R132H和WTIDH1的IC50值分別為2.9、3.8、4.6和46nM，選擇性?IDH2?出100倍。(S,R)-WTIDH1Inhibitor2誘導(dǎo)細(xì)胞內(nèi)2-HG減少，髓細(xì)胞分化阻滯失效，在??病母細(xì)胞和更不成熟的?細(xì)胞?平誘導(dǎo)粒細(xì)胞分化。(S,R)-WTIDH1Inhibitor2可?于急性髓系??病(AML)及其他癌癥的研究。IC50&TargetIC50:2.9(R132G),3.8(R132C),4.6(R132H)and46nM(WTIDH1)[1]體外研究(S,R)-WTIDH1Inhibitor2(GSK321;0.1-10000nM;24h)inhibitsintracellular2-HGproductioninHT1080cellswithanEC50valueof85nM[1].(S,R)-WTIDH1Inhibitor2(0-5μM;48h;HT1080fibrosarcomacells)leadstoreductionofhistoneH3K9dimethylation(H3K9me2)[1].(S,R)-WTIDH1Inhibitor2(3μM;22d)decreasesintracellular2-HGinadose-dependentmanner(R132G,0.13-fold;R132C,0.15-fold;R132H,0.29-fold)[1].(S,R)-WTIDH1Inhibitor2(3μM;15d)affectsproliferationofprimaryIDH1mutantAMLcells[1].(S,R)-WTIDH1Inhibitor2(3μM;9d)inducesdifferentiationinprimaryIDH1mutantAMLblastsandimmaturestem-likecells[1].CellViabilityAssay[1]1/2MasterofBioactiveMolecules—您?邊的抑制劑?師www.MedChemECellLine:IDH1mutantAMLcellsConcentration:3μMIncubationTime:15daysResult:Increasedincellnumbers(2-foldto15-fold)inIDH1mutantAMLcells.CellCycleAnalysis[1]CellLine:IDH1mutantAMLcellsConcentration:3μMIncubationTime:15daysResult:Decreasedinquiescent(G0)-phasecellsandincreasedinG1-phaseinR132GIDH1.WesternBlotAnalysis[1]CellLine:HT1080fibrosarcomacellsConcentration:0,0.5and5μMIncubationTime:48hoursResult:InducedmarkedlydecreasedH3K9me2levels.體內(nèi)研究(S,R)-WTIDH1Inhibitor2(GSK321;150mg/kg;i.p.;daily,for15d;maleCD-1micewithIDH1mutantAMLxenograft)reducesleukemicblastsinvivo[1].AnimalModel:MaleCD-1micewithIDH1mutantAMLxenograft[1]Dosage:150mg/kgAdministration:Intraperitonealinjection;daily,for15daysResult:Decreasedin2HGinIDH1-mutantAMLcells.Decreasedinthepercentageofblastcells(SSClowCD45low/+)andarelativeincreaseinmaturelymphoidandgranulocytic/monocyticcells.REFERENCES[1].Okoye-OkaforUC,et,al.NewIDH1mutantinhibitorsfortreatmentofacutemyeloidleukemia.NatChemBiol.2015Nov;11(11):878-86.McePdfHeight2/2MasterofBioactiveMolecules—您?邊的抑制劑?師www.MedChemECaution:Producthasnotbeenfullyvalidatedformedicalapplicati