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Medchemexpress/Actinomycin D(Synonyms: Dactinomycin; Actinomycin IV)/HY-17559/10mg
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Medchemexpress/Actinomycin D(Synonyms: Dactinomycin; Actinomycin IV)/HY-17559/10mg
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MedChemExp
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HY-17559-5mg
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ActinomycinDinhibitsDNArepairwithIC50of0.42μM.

CustomerValidation

  • •CancerLett.2017Aug18;407:45-56.
  • •CellDeathDis.2017Mar23;8(3):e2702.
  • •JExpClinCancerRes.2017Oct19;36(1):149.
  • •MolCarcinog.2017Mar;56(3):1082-1087.
Description

ActinomycinDinhibitsDNArepairwithIC50of0.42μM.

IC50&Target

IC50:0.42μM(DNArepair)[1]

InVitro

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

InVivo

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].

ClinicalTrial
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References

  • [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.

PreparingStockSolutions
ConcentrationVolumeMass1mg5mg10mg
1mM0.7965mL3.9827mL7.9655mL
5mM0.1593mL0.7965mL1.5931mL
10mM0.0797mL0.3983mL0.7965mL
Pleaserefertothesolubilityinformationtoselecttheappropriatesolvent.
KinaseAssay
[1]

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.

AnimalAdmiNISTration
[3]

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.

References

  • [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.

MolecularWeight

1255.42

Formula

C₆₂H₈₆N₁₂O₁₆

CASNo.

50-76-0

Storage
Powder-20°C3years
 4°C2years
Insolvent-80°C6months
 -20°C1month
Shipping

RoomtemperatureincontinentalUS;mayvaryelsewhere

Solvent&Solubility

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="">

Purity:99.89%

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