XY221-生命科學試劑-MCE

Hotline:400-820-3792Inhibitors?ScreeningLibraries?Proteinswww.MedChemEXY221Cat.No.:HY-170380分?式:C??H??FN?O?分?量:559.63作?靶點:EpigeneticReaderDomain;Apoptosis;AMPK;c-Myc;PAK;Bcl-2Family作?通路:Epigenetics;Apoptosis;PI3K/Akt/mTOR;CellCycle/DNADamage;Cytoskeleton儲存?式:PleasestoretheproductundertherecommendedconditionsintheCertificateofAnalysis.BIOLOGICALACTIVITY?物活性XY221(Compound16o)選擇性抑制BRD4BD2，IC50為5.8nM。XY221展現(xiàn)出對泛pan-BD2和BRD4BD2域的?選擇性，分別?BRD4BD1?667倍，?BRD2/3/TBD2?9-32倍。XY221可誘導MV4-11細胞凋亡，并具有抗癌活性。IC50&TargetBRD4BD1BRD4BD2BRD3BD23869nM(IC50)5.8nM(IC50)70.98nM(Ki)體外研究XY221inhibitsBRD4BD2,BRD3BD2,BRD2BD2,BRDTBD2andBRD4BD1withIC50sof5.8,70.98,53.47,183,3869nM,respectively[1].XY221(72h)inhibitsMV4?11,LNCaP,HL-7702cellsproliferationwithIC50sof0.51,0.68,47.7μM,respectively[1].XY221(500-2000nM,72h)significantlyinducesantiproliferativeactivityandapoptosisinMV4?11cellline[1].XY221(1-10μM,2h)displayslongT1/2(>120min)inRLM(ratlivermicrosomes)andT1/2(>120min)inHLM(humanlivermicrosomes)[1].XY221(500-2000nM,72h)inhibitstargetgenesp21,ODC1,BRD4andthephosphorylationofAKTandAMPKinMV4?11cells[1]..XY221(2μM,72h)suppressesoncogeneMYCanditstargetgenep21andcell-cycle-relatedgeneBCL-2atmRNAlevelinMV4?11cells[1].WesternBlotAnalysis[1]CellLine:MV4?11cells1/2MasterofBioactiveMolecules—您?邊的抑制劑?師www.MedChemEConcentration:500,2000nMIncubationTime:24-72hResult:Inhibitedtargetgenesp21,ODC1,BRD4andthephosphorylationofAKTandAMPK.RealTimeqPCR[1]CellLine:MV4?11cellsConcentration:2μMIncubationTime:72hResult:Inhibitedtargetgenesp21,ODC1,BRD4andthephosphorylationofAKTandAMPK.SuppressedoncogeneMYCanditstargetgenep21andcell-cycle-relatedgeneBCL-2atmRNAlevel.體內(nèi)研究Intravenous(iv)andOral(po)PharmacokineticParametersforXY221inRatsrouteCmax(μg/L)Tmax(h)AUC(0-t)(μg/L·h)AUC(0-∞)(μg/L·h)T1/2(h)CI(L/h/kg)F(%)iv(5mg/kg)97900.03429142941.351.21po(25mg/kg)5673.67281128162.1313.1REFERENCES[1].TongJB,etal.DiscoveryofnovelBRD4-BD2inhibitorsviainsilicoapproaches:QSARtechniques,moleculardocking,andmoleculardynamicssimulations.MolDivers.2024Apr;28(2):671-692.McePdfHeightCaution:Producthasnotbeenfullyvalidatedformedicalapplications.Forresear