Medchemexpress/Actinomycin D(Synonyms: Dactinomycin; Actinomycin IV)/HY-17559/10mg

ActinomycinDinhibitsDNArepairwithIC₅₀of0.42μM.

IC50:0.42μM(DNArepair)^[1]

ActinomycinDisaninhibitorofDNAtranscriptionandreplication^[1].ActinomycinDmarkedlyreducesthevascularsmoothmusclecells(SMC)proliferationviatheinhibitionofBrdUincorporationat80nM.ThisisfurthersupportedbytheG1-phasearrestusingaflowcytometricanalysis.ActinomycinDisextremelypotentwithaninhibitoryconcentrationIC₅₀at0.4nM,whereasthelethaldoseLD50isat260microM.Theproteinexpressionlevelsofproliferatingcellnuclearantigen(PCNA),focaladhesionkinase(FAK),andRafareallsuppressedbyActinomycinD.Extracellularsignal-regulatedkinases(Erk)involvedincell-cyclearrestarefoundtoincreasebyActinomycinD^[2].

Thepluronicgelcontaining80nMand80μMActinomycinDisappliedtopicallytosurroundtheratcarotidadventitia,thethicknessofneointimaissubstantiallyreduced(45and55%,respectively)^[2].MiceintheActinomycinDandfludarABInegrouplivessignificantlylongerthanthecontrolgroupwithPvaluesof<0.001 and="" 0.007,="" respectively.="" interestingly,="" single="" treatment="" with="" actinomycin="" d="" is="" superior="" to="" fludarabine="" regarding="" overall="" survival="" (p="">^[3].

• [1].BarretJM,etal.EvaluationofDNArepairinhibitionbyantitumororantibioticdrugsusingachemiluminescencemicroplateassay.Carcinogenesis.1997Dec;18(12):2441-5.

  [2].WuCH,etal.ThemolecularmechanismofactinomycinDinpreventingneointimalformationinratcarotidarteriesafterballooninjury.JBiomedSci.2005;12(3):503-12.

  [3].MerkelO,etal.ActinomycinDinducesp53-independentcelldeathandprolongssurvivalinhigh-riskchroniclymphocyticleukemia.Leukemia.2012Dec;26(12):2508-16.

ActinomycinDisco-incubatedfor3hat30°Cwithareactionmixturecontaining:120mgofawhole-cellextractofHeLacells,70mMKCl,0.4mMeachofdGTP,dCTP,dATP,anddigoxygenylated-dUTPinreactionbuffercontaining40mMHepes-KOH(pH7.6),5mMMgCl₂,0.5mMDithiotreitol,2mMEGTA,10mMphosphocreatine,50mg/mLcreatinephosphate,and360mg/mLofbovineserumalbumin.Duringthisreaction,DNAdamageisrecognizedandtheexcisedpatchesarereplacedbyneosynthesizedDNAfragments.ThroughoutthisDNAsynthesis,digoxygenylated-dUMPsareincorporated.TheDNArepairreactionisstoppedbythreewashes^[1].MCEhasnotindependentlyconfirmedtheaccuracyofthesemethods.Theyareforreferenceonly.

ActinomycinDispreparedinphosphate-bufferedsaline(PBS)(Mice)^[3].

Mice^[3]
TheoriginalEμ-TCL1atransgenicmicehavebeenbackcrossedtoC57BL/6micefor>9generations.TheC57BL/6wild-typemiceareengraftedwithtumorcellsfromEμ-TCL-1transgenicmice.ThepercentageofCD5+/CD19+cellsintheperipheralbloodisroutinelycheckedinmicebytakingbloodfromthetailveinandanalyzingitviaflowcytometry.Whenthepercentageoftumorcellsintheperipheralbloodreached40-60%,treatmentisstarted.ActinomycinD(0.06 mg/kgby10days)isapplieddailyviai.p.injections.MCEhasnotindependentlyconfirmedtheaccuracyofthesemethods.Theyareforreferenceonly.

• [1].BarretJM,etal.EvaluationofDNArepairinhibitionbyantitumororantibioticdrugsusingachemiluminescencemicroplateassay.Carcinogenesis.1997Dec;18(12):2441-5.

  [2].WuCH,etal.ThemolecularmechanismofactinomycinDinpreventingneointimalformationinratcarotidarteriesafterballooninjury.JBiomedSci.2005;12(3):503-12.

  [3].MerkelO,etal.ActinomycinDinducesp53-independentcelldeathandprolongssurvivalinhigh-riskchroniclymphocyticleukemia.Leukemia.2012Dec;26(12):2508-16.

1255.42

C₆₂H₈₆N₁₂O₁₆

50-76-0

RoomtemperatureincontinentalUS;mayvaryelsewhere

DMSO:≥27mg/mL;DMSO:250mg/mL(Needultrasonic);Methanol:6.2mg/mL;Methanol:20mg/mL(Needultrasonic);H₂O:<12.5="">

*"<1 mg/ml"="" means="" slightly="" soluble="" or="" insoluble.="" "≥"="" means="" soluble,="" but="" saturation="">