BIX-01294-trihydrochloride-DataSheet-生命科學試劑-MedChemExpress

Hotline:400-820-3792Inhibitors?ScreeningLibraries?Proteinswww.MedChemEBIX-01294trihydrochlorideCat.No.:HY-108239CASNo.:1392399-03-9分?式:C??H??Cl?N?O?分?量:600.02作?靶點:HistoneMethyltransferase;Autophagy作?通路:Epigenetics;Autophagy儲存?式:PleasestoretheproductundertherecommendedconditionsintheCertificateofAnalysis.BIOLOGICALACTIVITY?物活性BIX-01294trihydrochloride?種可逆且?度選擇性的G9a和GLP組蛋?甲轉移酶抑制劑，IC50分別為1.9μM和0.7μM。BIX-01294trihydrochloride通過與底物賴氨酸殘N端的氨酸競爭結合來抑制G9a/GLP。BIX-01294trihydrochloride?種(1H-1,4-diazepin-1-yl)-quinazolin-4-yl胺衍?物，可誘導壞死性凋亡(necroptosis)和?噬。BIX-01294trihydrochloride在復發(fā)性腫瘤細胞中具有抗腫瘤活性。IC50&TargetIC50:2.7μM(G9ainDELFIAassay)[2]IC50:1.9μMforG9aand0.7μMforGLP[5]體外研究BIX-01294(2μM;48h)trihydrochlorideselectivelyinhibitsrecurrenttumorcellgrowth[1].BIX-01294(1μM)trihydrochlorideleadstoamarkedincreaseinphosphorylationofS345ofMLKL[1].BIX-01294(1μM)trihydrochloridesignificantlyupregulatesthecanonicalp53targetsCdkn1a(p21)andGadd45ainrecurrenttumorcelllines[1].BIX-01294(1μM;6days)trihydrochloridecausesthereductioninH3K9me2levelsinprimaryandrecurrenttumorcells[1].BIX-01294trihydrochlorideleadstonecroptoticcelldeathinrecurrenttumorcells.Necrostatin-1(30μM)partiallyreversescelldeathinducedbyBIX-01294(750nM;24h)trihydrochloride[1].BIX-01294(4.1μM;for2days)trihydrochloridecausesarounda20%reduction,concomitantwithacomparableincreaseintheunmodifiedH3K9fragmentinH3K9me2inmouseEScells.BIX-01294trihydrochloridecausespronouncedreductioninH3K9me2andasmalldecreaseforH3K9me3andH3K9me1inwild-typeEScells[2].BIX-01294trihydrochloridehasnoinhibitionoftheotherhistonemethyltransferasesevenatconcentrationsof45μM.BIX-01294trihydrochloridedoesnotaffectSUV39H1(H320R)andPRMT1withinthetestedconcentrationrange(upto10μM)[2].1/3MasterofBioactiveMolecules—您?邊的抑制劑?師www.MedChemEBIX-01294trihydrochlorideinhibitsG9ainanuncompetitivemannerwithS-adenosyl-methionine(SAM)[2].BIX-01294(1μg/mL)causesreductionintheBrdUincorporationoffetalPASMCs.BIX-01294treatmentdecreasesthePASMCsmigrationinducedbyPDGF[3].CellViabilityAssay[1]CellLine:PrimaryorrecurrenttumorcellsConcentration:2μMIncubationTime:48hResult:Selectivelyinhibitedrecurrenttumorcellgrowth.體內(nèi)研究BIX-01294trihydrochloride(10mg/kg;IP;threetimesaweekfor2weeks)significantlyreducestumorgrowthandtumorburdeninrecurrenttumorcells.Primarytumorgrowthisnotinhibited[1].AnimalModel:FemaleMMTV-rtTA;TetO-Her2/neu(MTB;TAN)andTetO-Her2/neu(TAN)micewithrecurrentorprimarytumorcells[1]Dosage:10mg/kgAdministration:IP;threetimesaweekfor2weeksResult:Significantlyreducedtumorgrowthandtumorburdeninrecurrenttumorcells.Primarytumorgrowthwasnotinhibited.Slowedthegrowthoforthotopicrecurrenttumorsinathymicnuderecipients.戶使?本產(chǎn)品發(fā)表的科研?獻?JExpClinCancerRes.2018Aug17;37(1):196.?CellRep.2021,108959.?CellSyst.2018Apr25;6(4):424-443.e7.?CellDeathDis.2019Apr15;10(5):331.?CellDeathDis.2017Apr6;8(4):e2726.Seemorecustomervalidationsonwww.MedChemEREFERENCES[1].NathanielWMabe,etal.G9aPromotesBreastCancerRecurrencethroughRepressionofaPro-inflammatoryProgram.CellRep.2020Nov3;33(5):108341.[2].StefanKubicek,etal.ReversalofH3K9me2byasmall-moleculeinhibitorfortheG9ahistonemethyltransferase.MolCell.2007Feb9;25(3):473-81.[3].YangQ,etal.BIX-01294treatmentblockscellproliferation,migrationandcontractilityinovinefoetalpulmonaryarterialsmoothmuscle2/3MasterofBioactiveMolecules—您?邊的抑制劑?師www.MedChemEcells.CellProlif.2012Aug;45(4):335-44.[4].IwonaAnnaCiechomska,etal.BIX01294,aninhibitorofhistonemethyltransferase,inducesautophagy-dependentdifferentiationofgliomastem-likecells.SciRep[5].YanqiChang,etal.StructuralbasisforG9a-likeproteinlysinemethyltransferaseinhibitionbyBIX-01294.NatStructMolBiol.2009Mar;16(3):312-7.Mce