KDM5B-IN-4-DataSheet-生命科学试剂-MCE

Hotline:400-820-3792Inhibitors • ScreeningLibraries • Proteinswww.MedChemEKDM5B-IN-4Cat.No.:HY-149091分子式: C₃₀H₃₀N₆O分子量: 490.6作用靶点: Others作用通路: Others储存方式: PleasestoretheproductundertherecommendedconditionsintheCertificateofAnalysis.BIOLOGICALACTIVITY生物活性KDM5B-IN-4(compound11ad)是一种新的赖氨酸去甲基化酶5B(KDM5B)抑制剂，对KDM5B的IC50为0.025μM。KDM5B-IN-4通过抑制PC-3细胞内KDM5B增加底物H3K4me1/2/3浓度。KDM5B-IN-4可将PC-3细胞阻滞在G2/M期。KDM5B-IN-4能下调PI3K/AKT通路蛋白。KDM5B-IN-4降低小鼠体内肿瘤体积且对脏器毒性较小[1]。IC50&TargetIC50:0.025μM(Lysinedemethylase5B,KDM5B)[1].体外研究KDM5B-IN-4(20μM,72h)hastargetedinhibitionofKDM5BandinductionofH3K4me1/2/3productioninPC-3cells[1].KDM5B-IN-4(0-20μM;72h)notonlytargetsKDM5Bincells,butalsoinducesH3K4me1/2/3accumulationinPC-3cells[1].KDM5B-IN-4(0-10μM,0-24h)inhibitedtheproliferationandmigrationofprostatecancercells,blockedthePC-3cycleintheG2/Mphase,andinducedapoptosisofPC-3cellstoacertainextent[1].WesternBlotAnalysis[1]CellLine:PC-3Concentration:0,2.5,5,10,20μMIncubationTime:72hResult:InducedtheconcentrationsofH3K4me1/2/3significantlydifferentfromthoseofthecontrol,andtheresultsobtainedweresimilartothoseobtainedusingtheCPI-455positivecontrol.1/3 MasterofBioactiveMolecules—您身边的抑制剂大师www.MedChemEHadnosignificanteffectonP110α,P85,andpAKTatlowconcentrationlevels(0-10μM),andP110α,P85,andpAKTweresignificantlydecreasedwhen11adwasathighconcentration(20μM).CellMigrationAssay[1]CellLine:PC-3Concentration:0,5,10μMIncubationTime:0,6,12,24hResult:Inhibitedcolonyformationinadosedependentmanner,especiallyathighdoses(10μM).CellCycleAnalysis[1]CellLine:PC-3Concentration:0,2.5,5,10μMIncubationTime:24hResult:BlockedthecellcycleatG2/Mphasein10μM.ApoptosisAnalysis[1]CellLine:PC-3Concentration:0,2.5,5,10μMIncubationTime:24hResult:InducedPC-3cellapoptosisinadose-dependentmanner(7.58%,26.14%,28.20%,45.66%).体内研究KDM5B-IN-4(50mg/kg,i.g.,50mg/kg/d,13days)treatmentat50mg/kgwasslightlybetterthantheefficacyofDOX[1].KDM5B-IN-4(50mg/kg,i.g.,50mg/kg/d,25days)didnotcausenoticeabledamagetothemice,confirmingthat11adhadnosignificanttoxicityorsideeffectsinvivo[1].PharmacokineticAnalysisinKDM5B-IN-4(compound11ad)XenograftModel[1]KDM5B-IN-4(compound11ad)药代动力学分析[1]ParameterT1/2(h)Tmax(h)Cmax(ng/mL)AUC0-t(h*ng/mL)MRT0-t(h)Vz(L/kg)Cl(L•h/kg)Fp.o.(25mg/kg)5.306.0411.673024.336.90//20.28%i.v.(5mg/kg)2.950.083551.6744437.6710.2919.510.49/AnimalModel:PC-3xenograftmodelinmaleSpraguee-Dawleyrats[1].2/3 MasterofBioactiveMolecules—您身边的抑制剂大师www.MedChemEDosage:25,50mg/kgAdministration:Intragastricadministrationtomice(i.g.)for25days,administeredoncedaily.Result:ComparedwithNaCltreatment,treatmentwith25mg/kgand50mg/kgsignificantlydecreasedtumorvolume.AnimalModel:PC-3xenograftmodelinmaleSpraguee-Dawleyrats[1].Dosage:2g/kgAdministration:Intragastricadministrationtomice(i.g.)for14days,administeredoncedaily.Result:Nosignificantlossofmajororgansinthehigh-doseandlow-dosegroups.REFERENCESCaoY,etal.Discoveryofanovel1H-pyrazole-[3,4-b]pyridine-basedlysinedemethylase5Binhibitorwithpotentialanti-prostatecanceractivitythatperturbsthephosphoinositide3-kinase/AKTpathway.EurJMedChem.2023May5;251:115250.McePdfHeightCaution:Producthasnot