Actinomycin D

Names

[ CAS No. ]:
50-76-0

[ Name ]:
Actinomycin D

[Synonym ]:
dactinomycin
2-Amino-N,N'-bis[(6S,9R,10S,13R,18aS)-6,13-diisopropyl-2,5,9-trimethyl-1,4,7,11,14-pentaoxohexadecahydro-1H-pyrrolo[2,1-i][1,4,7,10,13]oxatetraazacyclohexadecin-10-yl]-4,6-dimethyl-3-oxo-3H-phenoxazine-1,9-dicarboxamide
noxazin-1,9-dicarboxamid
2-amino-4,6-diméthyl-3-oxo-N,N'-bis[(6S,9R,10S,13R,18aS)-2,5,9-triméthyl-6,13-bis(1-méthyléthyl)-1,4,7,11,14-pentaoxohexadécahydro-1H-pyrrolo[2,1-i][1,4,7,10,13]oxatétraazacyclohexadécin-10-yl]-3H-phé
Actinomycin AIV
2-Amino-4,6-dimethyl-3-oxo-N,N'-bis[(6S,9R,10S,13R,18aS)-2,5,9-trimethyl-6,13-bis(1-methylethyl)-1,4,7,11,14-pentaoxohexadecahydro-1H-pyrrolo[2,1-i][1,4,7,10,13]oxatetraazacyclohexadecin-10-yl]-3H-phe
3H-phenoxazine-1,9-dicarboxamide, 2-amino-N1,N9-bis[(6S,9R,10S,13R,18aS)-hexadecahydro-2,5,9-trimethyl-6,13-bis(1-methylethyl)-1,4,7,11,14-pentaoxo-1H-pyrrolo[2,1-i][1,4,7,10,13]oxatetraazacyclohexadecin-10-yl]-4,6-dimethyl-3-oxo-
Actinomycin X1
2-amino-4,6-dimethyl-3-oxo-N,N'-bis[(6S,9R,10S,13R,18aS)-2,5,9-trimethyl-6,13-bis(1-methylethyl)-1,4,7,11,14-pentaoxohexadecahydro-1H-pyrrolo[2,1-i][1,4,7,10,13]oxatetraazacyclohexadecin-10-yl]-3H-phenoxazine-1,9-dicarboxamide
EINECS 200-063-6
MFCD00070921
2-amino-4,6-dimethyl-3-oxo-N,N'-bis[(6S,9R,10S,13R,18aS)-2,5,9-trimethyl-1,4,7,11,14-pentaoxo-6,13-di(propan-2-yl)hexadecahydro-1H-pyrrolo[2,1-i][1,4,7,10,13]oxatetraazacyclohexadecin-10-yl]-3H-phenoxazine-1,9-dicarboxamide
MERACTINOMYCIN
Actinomycin I1
Acto-D
Actinomycin D
Chounghwamycin B
2-Amino-4,6-dimethyl-3-oxo-N,N'-bis[(6S,9R,10S,13R,18aS)-2,5,9-trimethyl-6,13-bis(1-methylethyl)-1,4,7,11,14-pentaoxohexadecahydro-1H-pyrrolo[2,1-i][1,4,7,10,13]oxatetraazacyclohexadecin-10-yl]-3H-phenoxazin-1,9-dicarboxamid
Dilactone actinomycin D acid
2-amino-4,6-diméthyl-3-oxo-N,N'-bis[(6S,9R,10S,13R,18aS)-2,5,9-triméthyl-6,13-bis(1-méthyléthyl)-1,4,7,11,14-pentaoxohexadécahydro-1H-pyrrolo[2,1-i][1,4,7,10,13]oxatétraazacyclohexadécin-10-yl]-3H-phénoxazine-1,9-dicarboxamide
3H-phenoxazine-1,9-dicarboxamide, 2-amino-N,N'-bis[(6S,9R,10S,13R,18aS)-hexadecahydro-2,5,9-trimethyl-6,13-bis(1-methylethyl)-1,4,7,11,14-pentaoxo-1H-pyrrolo[2,1-i][1,4,7,10,13]oxatetraazacyclohexadecin-10-yl]-4,6-dimethyl-3-oxo-
ACT
Oncostatin K
noxazine-1,9-dicarboxamide
3H-Phenoxazine-1,9-dicarboxamide, 2-amino-N,N-bis[(6S,9R,10S,13R,18aS)-hexadecahydro-2,5,9-trimethyl-6,13-bis(1-methylethyl)-1,4,7,11,14-pentaoxo-1H-pyrrolo[2,1-i][1,4,7,10,13]oxatetraazacyclohexadecin-10-yl]-4,6-dimethyl-3-oxo-
3H-Phenoxazine-1,9-dicarboxamide, 2-amino-N,N-bis[(6S,9R,10S,13R,18aS)-hexadecahydro-2,5,9-trimethyl-6,13-bis(1-methylethyl)-1,4,7,11,14-pentaoxo-1H-pyrrolo[2,1-i][1,4,7,10,13]oxatetraazacyclohe xadecin-10-yl]-4,6-dimethyl-3-oxo-

Biological Activity

[Description]:

Actinomycin D inhibits DNA repair with an IC50 of 0.42 μM.

[Related Catalog]:

Signaling Pathways >> Autophagy >> Autophagy

Signaling Pathways >> Cell Cycle/DNA Damage >> DNA/RNA Synthesis

Natural Products >> Others

Research Areas >> Cancer

[Target]

IC50: 0.42 μM (DNA repair)[1]

[In Vitro]

Actinomycin D is an inhibitor of DNA transcription and replication[1]. Actinomycin D markedly reduces the vascular smooth muscle cells (SMC) proliferation via the inhibition of BrdU incorporation at 80 nM. This is further supported by the G1-phase arrest using a flowcytometric analysis. Actinomycin D is extremely potent with an inhibitory concentration IC50 at 0.4 nM, whereas the lethal dose LD50 is at 260 microM. The protein expression levels of proliferating cell nuclear antigen (PCNA), focal adhesion kinase (FAK), and Raf are all suppressed by Actinomycin D. Extracellular signal-regulated kinases (Erk) involved in cell-cycle arrest are found to increase by Actinomycin D[2].

[In Vivo]

The pluronic gel containing 80 nM and 80μM Actinomycin D is applied topically to surround the rat carotid adventitia, the thickness of neointima is substantially reduced (45 and 55%, respectively)[2]. Mice in the Actinomycin D and fludarabine group lives significantly longer than the control group with P values of <0.001 and 0.007, respectively. Interestingly, single treatment with Actinomycin D is superior to fludarabine regarding overall survival (P=0.026)[3].

[Kinase Assay]

Actinomycin D is co-incubated for 3 h at 30°C with a reaction mixture containing: 120 mg of a whole-cell extract of HeLa cells, 70 mM KCl, 0.4 mM each of dGTP, dCTP, dATP, and digoxygenylated-dUTP in reaction buffer containing 40mM Hepes-KOH (pH 7.6), 5 mM MgCl2, 0.5 mM Dithiotreitol, 2 mM EGTA, 10 mM phosphocreatine, 50 mg/mL creatine phosphate, and 360 mg/mL of bovine serum albumin. During this reaction, DNA damage is recognized and the excised patches are replaced by neosynthesized DNA fragments. Throughout this DNA synthesis, digoxygenylated-dUMPs are incorporated. The DNA repair reaction is stopped by three washes[1].

[Animal admin]

Mice[3] The original Eμ-TCL1a transgenic mice have been backcrossed to C57BL/6 mice for >9 generations.The C57BL/6 wild-type mice are engrafted with tumor cells from Eμ-TCL-1 transgenic mice. The percentage of CD5+/CD19+ cells in the peripheral blood is routinely checked in mice by taking blood from the tail vein and analyzing it via flow cytometry. When the percentage of tumor cells in the peripheral blood reached 40-60%, treatment is started. Actinomycin D (0.06 mg/kg by 10 days) is applied daily via i.p. injections.

[References]

[1]. Barret JM, et al. Evaluation of DNA repair inhibition by antitumor or antibiotic drugs using a chemiluminescence microplateassay. Carcinogenesis. 1997 Dec;18(12):2441-5.

[2]. Wu CH, et al. The molecular mechanism of actinomycin D in preventing neointimal formation in rat carotid arteries after balloon injury. J Biomed Sci. 2005;12(3):503-12.

[3]. Merkel O, et al. Actinomycin D induces p53-independent cell death and prolongs survival in high-risk chronic lymphocytic leukemia. Leukemia. 2012 Dec;26(12):2508-16.

[Related Small Molecules]

Chemical & Physical Properties

[ Density]:
1.4±0.1 g/cm3

[ Boiling Point ]:
1386.0±65.0 °C at 760 mmHg

[ Melting Point ]:
251-253 °C

[ Molecular Formula ]:
C₆₂H₈₆N₁₂O₁₆

[ Molecular Weight ]:
1255.417

[ Flash Point ]:
792.1±34.3 °C

[ Exact Mass ]:
1254.628418

[ PSA ]:
359.98000

[ LogP ]:
-4.03

[ Vapour Pressure ]:
0.0±0.3 mmHg at 25°C

[ Index of Refraction ]:
1.656

[ Stability ]:
Stable, but light sensitive, especially in dilute solution. Incompatible with strong acids, strong bases, strong oxidizing agents. Combustible.

[ Water Solubility ]:
SOLUBLE

MSDS

Click to get detail MSDS

Safety Information

[ Symbol ]:

GHS06

[ Signal Word ]:
Danger

[ Hazard Statements ]:
H300

[ Precautionary Statements ]:
P264-P301 + P310

[ Personal Protective Equipment ]:
Eyeshields;Faceshields;full-face particle respirator type N100 (US);Gloves;respirator cartridge type N100 (US);type P1 (EN143) respirator filter;type P3 (EN 143) respirator cartridges

[ Hazard Codes ]:
T+:Verytoxic;

[ Risk Phrases ]:
R28;R40;R61

[ Safety Phrases ]:
S53-S36/37/39-S45-S1-S36/37-S28-S22

[ RIDADR ]:
UN 3462 6.1/PG 2

[ WGK Germany ]:
3

[ RTECS ]:
AU1575000

[ Packaging Group ]:
II

[ Hazard Class ]:
6.1(a)

[ HS Code ]:
29419000

Synthetic Route

Click to get detail synthetic route

Precursor & DownStream

Precursor

DownStream

Customs

[ HS Code ]: 29419000

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