Hotline:400-820-3792Inhibitors?ScreeningLibraries?Proteinswww.MedChemEADH-6TFACat.No.:HY-145785A分?式:C??H??F?N?O??分?量:754.67作?靶點(diǎn):MDM-2/p53;Apoptosis作?通路:Apoptosis儲(chǔ)存?式:Powder-20°C3years4°C2yearsInsolvent-80°C6months-20°C1month溶解性數(shù)據(jù)體外實(shí)驗(yàn)DMSO:100mg/mL(132.51mM;Needultrasonic)MassSolvent1mg5mg10mgConcentration制備儲(chǔ)備液1mM1.3251mL6.6254mL13.2508mL5mM0.2650mL1.3251mL2.6502mL10mM0.1325mL0.6625mL1.3251mL請根據(jù)產(chǎn)品在不同溶劑中的溶解度選擇合適的溶劑配制儲(chǔ)備液；?旦配成溶液，請分裝保存，避免反復(fù)凍融造成的產(chǎn)品失效。儲(chǔ)備液的保存?式和期限：-80°C,6months;-20°C,1month。-80°C儲(chǔ)存時(shí)，請?jiān)?個(gè)?內(nèi)使?，-20°C儲(chǔ)存時(shí)，請?jiān)?個(gè)?內(nèi)使?。BIOLOGICALACTIVITY?物活性ADH-6TFA?種三吡啶酰胺化合物。ADH-6TFA消除了突變p53DBD的聚集成核亞結(jié)構(gòu)域的?組裝。ADH-6TFA靶向并解離?類癌細(xì)胞中的突變p53聚集體，從?恢復(fù)p53的轉(zhuǎn)錄活性，導(dǎo)致細(xì)胞周期停滯和細(xì)胞凋亡(apoptosis)。ADH-6TFA具有研究癌癥疾病的潛?。體外研究ADH-6(25μM,10h)TFAinhibitsaggregationofpR248W(indicatedbydotblotassay)[1].ADH-6(5μM,6h)TFAdissociatesintracellularmutantp53aggregatesinMIAPaCa-2cells[1].1/3MasterofBioactiveMolecules—您?邊的抑制劑?師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.體內(nèi)研究ADH-6(intraperitonealinjection,15mg/kg,every2days,foratotalof12doses)TFAcausesregressionofmutantp53-bearingtumors[1].AnimalModel:MIAPaCa-2xenografts[1]Dosage:716.4?μMin0.02%DMSOAdministration:Intraperitonealinjection,every2days,foratotalof12dosesResult:Reducedtumorgrowthrelativetothesaline-treatedcontrolgroup.Reducedmutantp53levelsandshrinkedxenograftsharboringaggregation-pronemutantp53.AnimalModel:MIAPaCa-2xenografts(pharmacokineticsassay)[1]Dosage:15mg/kgAdministration:Intraperitonealinjection,forasingledoseResult:Cmax:21?μg/mL,T1/2:3.6hREFERENCES2/3MasterofBioactiveMolecules—您?邊的抑制劑?師www.MedChemE[1].PalanikumarL,etal.Proteinmimeticamyloidinhibitorpotentlyabrogatescancer-associatedmutantp53aggregationandrestorestumorsuppressorfunction.NatCommun.2021;12(1):3962.McePdfHeightCaution:Producthasnotbeenfullyvalidatedformedicalapplications.Fo