AES-350-DataSheet-生命科學(xué)試劑-MedChemExpress

Hotline:400-820-3792Inhibitors?ScreeningLibraries?Proteinswww.MedChemEAES-350Cat.No.:HY-138831CASNo.:847249-57-4分?式:C??H??N?O?分?量:312.36作?靶點(diǎn):HDAC;Apoptosis作?通路:CellCycle/DNADamage;Epigenetics;Apoptosis儲(chǔ)存?式:4°C,protectfromlight*Insolvent:-80°C,6months;-20°C,1month(protectfrom

light)溶解性數(shù)據(jù)體外實(shí)驗(yàn)DMSO:100mg/mL(320.14mM;Needultrasonic)MassSolvent1mg5mg10mgConcentration制備儲(chǔ)備液1mM3.2014mL16.0072mL32.0143mL5mM0.6403mL3.2014mL6.4029mL10mM0.3201mL1.6007mL3.2014mL請(qǐng)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(qǐng)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(protectfromlight)。-80°C儲(chǔ)存時(shí)，請(qǐng)?jiān)?個(gè)?內(nèi)使?，-20°C儲(chǔ)存時(shí)，請(qǐng)?jiān)?個(gè)?內(nèi)使?。體內(nèi)實(shí)驗(yàn)請(qǐng)根據(jù)您的實(shí)驗(yàn)動(dòng)物和給藥?式選擇適當(dāng)?shù)娜芙?案。以下溶解?案都請(qǐng)先按照InVitro?式配制澄的儲(chǔ)備液，再依次添加助溶劑：(為保證實(shí)驗(yàn)結(jié)果的可靠性，澄的儲(chǔ)備液可以根據(jù)儲(chǔ)存條件，適當(dāng)保存；體內(nèi)實(shí)驗(yàn)的?作液，建議您現(xiàn)?現(xiàn)配，當(dāng)天使?；以下溶劑前顯?的百分?指該溶劑在您配制終溶液中的體積占?；如在配制過程中出現(xiàn)沉淀、析出現(xiàn)象，可以通過加熱和/或超聲的?式助溶)1.請(qǐng)依序添加每種溶劑：10%DMSO>>40%PEG300>>5%Tween-80>>45%salineSolubility:≥2.5mg/mL(8.00mM);Clearsolution2.請(qǐng)依序添加每種溶劑：10%DMSO>>90%(20%SBE-β-CDinsaline)Solubility:≥2.5mg/mL(8.00mM);Clearsolution1/2MasterofBioactiveMolecules—您?邊的抑制劑?師www.MedChemE3.請(qǐng)依序添加每種溶劑：10%DMSO>>90%cornoilSolubility:≥2.5mg/mL(8.00mM);ClearsolutionBIOLOGICALACTIVITY?物活性AES-350?種有效的?服活性HDAC6抑制劑，IC50和Ki分別為0.0244μM和0.035μM。AES-350對(duì)HDAC-3、-8和-11的IC50值分別為0.187μM、0.245μM。AES-350通過抑制HDAC誘導(dǎo)AML細(xì)胞凋亡，可?于急性髓系??病(AML)研究。IC50&TargetHDAC6HDAC3HDAC1124.4nM(IC50)187nM(IC50)245nM(IC50)體外研究Incontrast,AES-350hassubmicromolaractivity(IC50=0.58±0.13μM)againstMV4-11cellsthantothatofvorinostat(IC50=0.31±0.061μM).AES-350ismoreligandefficientandexemplifiesalargetherapeuticindex(IC50>30μMinnoncancerousMRC-9cells).AES-350isalsoshowntobeeffectiveinAML-3(acutemyeloidleukemia)cells(IC50=0.73±0.12μM)[1].AES-350(0.25-4μM;18hours)inducesMV4-11cellsapoptosisinadose-dependentmanner.Thelateapoptosisratiosare8.74%,11.7%,16.08%,30.97%,and38.48%,respectivelyat0.25μM-4μM[1].AnELISAisperformedusingHeLacervicalcancercelllysates,andHeLacellshighlyexpressHDAC6andaresensitivetoAES-350.Correspondingly,ELISAassaysdepictedadose-dependentincreaseinHDAC6inhibition(IC50=0.58±0.13μM),WesternblotanalysisshowsthatAES-350(0.1-10μM)inducesadose-dependentincreaseinacetylatedα-tubulin(Ac-α-tubulin),asubstrateofHDAC[1].ApoptosisAnalysis[1]CellLine:MV4-11cellsConcentration:0.25μM;0.5μM;1.00μM;2.00μM;4.00μMIncubationTime:18hoursResult:Revealedacleardosedependentincreaseinthepercentageofcellsenteringlate-stageapoptosis,similartoSAHA.體內(nèi)研究AES-350(oralgavage;20mg/kg;singledose)exhibitsarelativegoodpharmacokinetic(PK)propertiesinCD-1mice.Thesingledoseoralbioavailability(F%)of51is19.8%.Incomparison,thereportedF%forSAHAinmiceissignificantlylower(8%)[1].REFERENCES[1].AndrewEShouksmith,etal.ClassI/IIb-SelectiveHDACInhibitorExhibitsOralBioavailabilityandTherapeuticEfficacyinAcuteMyeloidLeukemia.McePdfHeight2/2MasterofBioactiveMolecules—您?邊的抑制劑?師www.MedChemECaution:Producthasnotbeenfullyvalid