ADH-6-TFA-DataSheet-生命科学试剂-MedChemExpress

Hotline:400-820-3792Inhibitors•ScreeningLibraries•Proteinswww.MedChemEADH-6TFACat.No.:HY-145785A分⼦式:C₃₁H₃₇F₃N₈O₁₁分⼦量:754.67作⽤靶点:MDM-2/p53;Apoptosis作⽤通路:Apoptosis储存⽅式:Powder-20°C3years4°C2yearsInsolvent-80°C6months-20°C1month溶解性数据体外实验DMSO:100mg/mL(132.51mM;Needultrasonic)MassSolvent1mg5mg10mgConcentration制备储备液1mM1.3251mL6.6254mL13.2508mL5mM0.2650mL1.3251mL2.6502mL10mM0.1325mL0.6625mL1.3251mL请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；⼀旦配成溶液，请分装保存，避免反复冻融造成的产品失效。储备液的保存⽅式和期限：-80°C,6months;-20°C,1month。-80°C储存时，请在6个⽉内使⽤，-20°C储存时，请在1个⽉内使⽤。BIOLOGICALACTIVITY⽣物活性ADH-6TFA⼀种三吡啶酰胺化合物。ADH-6TFA消除了突变p53DBD的聚集成核亚结构域的⾃组装。ADH-6TFA靶向并解离⼈类癌细胞中的突变p53聚集体，从⽽恢复p53的转录活性，导致细胞周期停滞和细胞凋亡(apoptosis)。ADH-6TFA具有研究癌症疾病的潜⼒。体外研究ADH-6(25μM,10h)TFAinhibitsaggregationofpR248W(indicatedbydotblotassay)[1].ADH-6(5μM,6h)TFAdissociatesintracellularmutantp53aggregatesinMIAPaCa-2cells[1].1/3MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemEADH-6(0-10μM,24or48h)TFAcausesselectivecytotoxicityincancercellsbearingmutantp53(MIAPaCa-2)[1].ADH-6(5μM,24h)TFAspecificallytargetsandreactivatesaggregation-pronemutantp53inMIAPaCa-2cells[1].CellViabilityAssay[1]CellLine:MIAPaCa-2(mutantR248Wp53),SK-BR-3(mutantR175Hp53)Concentration:0,2.5,5,7.5,10μMIncubationTime:24,48hResult:Causeddeathofcancercellsbearingmutant,butnotWT,p53.WesternBlotAnalysis[1]CellLine:MIAPaCa-2cellsConcentration:5μMIncubationTime:24hResult:Increasedexpressionofp53-inducibleMDM2andproapoptoticBax.体内研究ADH-6(intraperitonealinjection,15mg/kg,every2days,foratotalof12doses)TFAcausesregressionofmutantp53-bearingtumors[1].AnimalModel:MIAPaCa-2xenografts[1]Dosage:716.4ꢀµMin0.02%DMSOAdministration:Intraperitonealinjection,every2days,foratotalof12dosesResult:Reducedtumorgrowthrelativetothesaline-treatedcontrolgroup.Reducedmutantp53levelsandshrinkedxenograftsharboringaggregation-pronemutantp53.AnimalModel:MIAPaCa-2xenografts(pharmacokineticsassay)[1]Dosage:15mg/kgAdministration:Intraperitonealinjection,forasingledoseResult:Cmax:21ꢀµg/mL,T1/2:3.6hREFERENCES2/3MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemE[1].PalanikumarL,etal.Proteinmimeticamyloidinhibitorpotentlyabrogatescancer-associatedmutantp53aggregationandrestorestumorsuppressorfunction.NatCommun.2021;12(1):3962.McePdfHeightCaution:Producthasnotbeenfullyvalidatedformedicalapplications.Fo