HDAC-Top-IN-1-DataSheet-生命科學(xué)試劑-MedChemExpress

Hotline:400-820-3792Inhibitors?ScreeningLibraries?Proteinswww.MedChemEHDAC/Top-IN-1Cat.No.:HY-144654CASNo.:2411379-14-9分?式:C??H??FN?O?分?量:512.53作?靶點(diǎn):HDAC;Topoisomerase作?通路:CellCycle/DNADamage;Epigenetics儲(chǔ)存?式:PleasestoretheproductundertherecommendedconditionsintheCertificateofAnalysis.BIOLOGICALACTIVITY?物活性HDAC/Top-IN-1?種具有?服活性的、?譜的HDAC/Top雙重抑制劑，對(duì)HDAC1、HDAC2、HDAC3、HDAC6和HDAC8的IC50分別為0.036μM、0.14μM、0.059μM、0.089μM和9.8μM。HDAC/Top-IN-1能有效誘導(dǎo)HEL細(xì)胞凋亡(apoptosis)，能將細(xì)胞阻滯在S期[1]。IC50&TargetHDAC1HDAC2HDAC3HDAC634nM(IC50)140nM(IC50)59nM(IC50)89nM(IC50)HDAC89.8μM(IC50)體外研究HDAC/Top-IN-1(compound16j)(0-2μM;48hours)exhibitsremarkableinhibitoryactivitiesagainstthetestedcelllines[1].HDAC/Top-IN-1(20and100nM;24hours)dramaticallyincreasesacetyl-H3andacetyl-H4levelsinHELcells[1].HDAC/Top-IN-1(0.1and0.5μM;48hours)effectivelyinducesHELcellapoptosisinadose-dependentmanner[1].HDAC/Top-IN-1(0.02-0.5μM;48hours)arrestsHELcellsattheSphase[1].CellProliferationAssayCellLine:MCF-7,A549,HCT116,HepG-2,K562andHEL[1]Concentration:0-2μM1/3MasterofBioactiveMolecules—您?邊的抑制劑?師www.MedChemEIncubationTime:48hoursResult:Exhibitedremarkableinhibitoryactivitiesagainstthetestedcelllines,andIC50sof0.68,0.21,0.26,0.35and0.029μMinMCF-7,A549,HCT116,HepG-2,K562andHEL,respectively.WesternBlotAnalysisCellLine:HEL[1]Concentration:20and100nMIncubationTime:24hoursResult:Dramaticallyincreasedinacetyl-H3andacetyl-H4levels.ApoptosisAnalysisCellLine:HEL[1]Concentration:0.1and0.5μMIncubationTime:48hoursResult:Ledto56.02%and76.45%apoptoticcelldeathatconcentrationof0.1and0.5μM,respectivelyCellCycleAnalysisCellLine:HEL[1]Concentration:0.02,0.1and0.5μMIncubationTime:48hoursResult:TheratiosintheSphasewerechangeddramatically9.8%,15.4%,and25.8%at0.02,0.1and0.5μM,respectively.體內(nèi)研究HDAC/Top-IN-1exhibitsgoodmetabolicpropertieswithahalf-life(T1/2)of31.49min,andtheclearanceis173.32mL/min/mg[1].HDAC/Top-IN-1(5and10mg/kg;PO;daily,for14days)exhibitspotentoralantitumoractivity[1].AnimalModel:FemaleBALB/Cnudemice(5-6weeks,18-20g;injectedwithhumanK562cells)[1]Dosage:5and10mg/kgAdministration:PO;daily,for14days2/3MasterofBioactiveMolecules—您?邊的抑制劑?師www.MedChemEResult:Exhibitedpotentoralantitumoractivityat5mg/kgwithaTGIvalueof41.4%andaT/Cvalueof54.3%,andachievedbettertumorgrowthinhibitionwithaTGIof68.5%andaT/Cof25.5%.REFERENCES[1].WuS,HuangY,WangT,etal.Evodiamine-InspiredTopoisomerase-HistoneDeacetylaseDualInhibitors:NovelOrallyActiveAntitumorAgentsforLeukemiaTherapy.JMedChem.2022;65(6):4818-4831.McePdfHeightCaution:Producthasnotbeenfullyvalidatedformedical