| Identification | More | [Name]
Actinomycin D | [CAS]
50-76-0 | [Synonyms]
ACTINOMYCIN C
ACTINOMYCIN C1
ACTINOMYCIN C, STREPTOMYCES CHRYSOMALLUS
(-)-ACTINOMYCIN D
ACTINOMYCIN D
ACTINOMYCIN IV
CACTINOMYCIN
DACTINOMYCIN
1-ethanediyl)imino(2-(1-methylethyl)-carbonylimino(2-(1-hydroxyethyl)-1-oxo-
1-oxo-2,1-ethanediyl)-1,2-pyrrolidinediylcarbonyl(methylimino)(1-oxo-2,1-ethan
3h-phenoxazine-1,9-dicarboxamide,2-amino-n,n’-bis(hexadecahydro-2,5,9-trimethy
6-dimethyl-3-oxo-xatetra-azacyclohexadecin-10-yl)-
actd
actinomycin-(thre-val-pro-sar-meval)
actinomycin11cosmegen
actinomycin7
actinomycinaiv
actinomycindioicdacid,dilactone
actinomycini(sub1)
actinomycini1 | [EINECS(EC#)]
232-485-1 | [Molecular Formula]
C62 H86 N12 O16 | [MDL Number]
MFCD00070921 | [Molecular Weight]
1255.44 | [MOL File]
50-76-0.mol |
| Chemical Properties | Back Directory | [Appearance]
Actinomycin D is a combustible, bright red crystalline solid. | [Melting point ]
251-253 °C
| [Boiling point ]
848°C (rough estimate) | [density ]
1.0757 (rough estimate) | [refractive index ]
1.5700 (estimate) | [Fp ]
87℃ | [storage temp. ]
2-8°C
| [solubility ]
ethanol, DMSO: Stable in aqueous solutions at 2-8 °C.soluble
| [form ]
powder
| [color ]
red, powder
| [Stability:]
Stable, but light sensitive, especially in dilute solution. Incompatible with strong acids, strong bases, strong oxidizing agents. Combustible. | [optical activity]
[α]/D alpha: 28/D (Rotation: -315 degrees (c=0.25% in methanol)) | [Water Solubility ]
SOLUBLE | [Usage]
Antibiotic substance belonging to the actinomycin complex, produced by several Streptomyces spp. Antineoplastic | [Merck ]
13,2828 | [BRN ]
605235 | [CAS DataBase Reference]
50-76-0(CAS DataBase Reference) | [IARC]
3 (Vol. 10, Sup 7) 1987 | [EPA Substance Registry System]
50-76-0(EPA Substance) |
| Safety Data | Back Directory | [Hazard Codes ]
T+ | [Risk Statements ]
R28:Very Toxic if swallowed.
R61:May cause harm to the unborn child.
R40:Limited evidence of a carcinogenic effect.
R45:May cause cancer.
R26/27/28:Very Toxic by inhalation, in contact with skin and if swallowed . | [Safety Statements ]
S53:Avoid exposure-obtain special instruction before use .
S36/37/39:Wear suitable protective clothing, gloves and eye/face protection .
S45:In case of accident or if you feel unwell, seek medical advice immediately (show label where possible) .
S1:Keep locked up .
S36/37:Wear suitable protective clothing and gloves .
S28:After contact with skin, wash immediately with plenty of ... (to be specified by the manufacturer) .
S22:Do not breathe dust . | [RIDADR ]
UN 3462 6.1/PG 2
| [WGK Germany ]
3
| [RTECS ]
AU1575000
| [F ]
8-10-21 | [HazardClass ]
6.1(a) | [PackingGroup ]
II | [HS Code ]
29419059 | [Hazardous Substances Data]
50-76-0(Hazardous Substances Data) | [Toxicity]
LD50 oral in rat: 7200ug/kg |
| Hazard Information | Back Directory | [General Description]
Bright red rhomboid prisms or red powder. | [Reactivity Profile]
ACTINOMYCIN D(50-76-0) can react with strong oxidizing agents, strong acids and strong bases. | [Air & Water Reactions]
Water soluble. | [Potential Exposure]
An antibiotic product from streptomyces, used as anticancer and veterinary drug | [Fire Hazard]
Flash point data for this chemical are not available. ACTINOMYCIN D is probably combustible. | [First aid]
Move victim to fresh air. Call 911 or emergency medical service. Give artificial respiration if victim is not breathing. Do not use mouth-to-mouth method if victim ingested or inhaled the substance; give artificial respiration with the aid of a pocket mask equipped with a one-way valve or other proper respiratory medical device. Administer oxygen if breathing is difficult. Remove and isolate contaminated clothing and shoes. In case of contact with substance, immediately flush skin or eyes with running water for at least 20 minutes. For minor skin contact, avoid spreading material on unaffected skin. Keep victim warm and quiet. Effects of exposure (inhalation, ingestion or skin contact) to substance may be delayed. Ensure that medical personnel are aware of the material(s) involved and take precautions to protect themselves. Medical observation is recommended for 24 to 48 hours after breathing overexposure, as pulmonary edema may be delayed. As first aid for pulmonary edema, a doctor or authorized paramedic may consider administering a drug or other inhalation therapy. | [Shipping]
UN2811 Toxic solids, organic, n.o.s., Hazard Class: 6.1; Labels: 6.1-Poisonous materials, Technical Name Required. | [Incompatibilities]
Incompatible with oxidizers (chlorates, nitrates, peroxides, permanganates, perchlorates, chlorine, bromine, fluorine, etc.); contact may cause fires or explosions. Keep away from alkaline materials, strong bases, strong acids, oxoacids, epoxides. | [Description]
Actinomycin D (50-76-0) is a cyclopeptide antibiotic and intercalating transcription inhibitor with anti-neoplastic activity. Potent inhibitor of RNA polymerase.1?Induces apoptosis in a variety of cancer cell lines2,3via the intrinsic pathway4.? Upregulates proapoptotic PUMA and downregulates Bcl-2 mRNA in peripheral blood lymphocytes.5 | [Chemical Properties]
Actinomycin D is a combustible, bright red crystalline solid. | [Chemical Properties]
red crystalline powder | [Originator]
Cosmegen,Merck Sharp and
Dohme,US,1965 | [Uses]
Actinomycin D is the most studied member of a family of unique bicyclic depsipeptides produced by several Streptomyces species. The depsipeptides are linked by a heterocyclic benzoxazone "anchor" that gives the metabolites a highly distinctive red/orange colour. Actinomycin D exhibits potent antibiotic and antitumour activity via DNA intercalation leading to the inhibition of nucleic acid synthesis. Tumour cell death has been demonstrated to occur by apoptosis. | [Uses]
An antineoplastic antibiotic that inhibits cell proliferation by forming a stable complex with DNA and blocking the movement of RNA polymerase which interferes with DNA-dependent RNA synthesis. Induces apoptosis. Potent antitumor agent. | [Uses]
Antibiotic substance belonging to the actinomycin complex, produced by several Streptomyces spp. Antineoplastic | [Uses]
antineoplastic, intercalating agent | [Definition]
ChEBI: Actinomycin D is an actinomycin. It has a role as a mutagen. | [Indications]
Dactinomycin (actinomycin D, Cosmegen) is one of a
family of chromopeptides produced by Streptomyces. It
is known to bind noncovalently to double-strand DNA
by partial intercalation, inhibiting DNA-directed RNA
synthesis. The drug is most toxic to proliferating cells,
but it is not specific for any one phase of the cell cycle.
Resistance to dactinomycin is caused by decreased ability
of tumor cells to take up and retain the drug, and it
is associated with cross-resistance to vinca alkaloids, the
anthracyclines, and certain other agents (multidrug resistance). | [Manufacturing Process]
An incubated culture of Actinomyces antibioticus was prepared using a
medium consisting of 1% tryptone-peptone, 0.5% starch, 0.2% K2HPO4, 0.2%
NaCl and 0.25% agar in distilled water, grown at a temperature of
approximately 25° to 35°C, the incubation being complete after 6 to 10 days.
50 liters of this incubated culture are extracted approximately six times with
ether, using 20 liters of ether for each extraction.
The final extract is faintly pale yellow in color, whereas the previous extracts
are orange. The combined ether extracts are concentrated to dryness and
about 3 grams of a reddish-brown residue is obtained. The residue is stirred
with approximately 400 cc of petroleum ether for two to three hours, the
solvent decanted and the residue treated again with approximately 400 cc of
petroleum ether. A pale yellow oil constituting crude actinomycin B is
recovered by evaporation from the petroleum ether.
The dark petroleum ether insoluble residue is dissolved in 1 liter of benzene
with gentle heating. Usually a small amount of black amorphous material
remains undissolved and is filtered off. The benzene solution is permitted to
drop through a chromatographic tower (60 x 5 cm) packed with aluminum
oxide (according to Brockman). The pigment is readily adsorbed. The column
is washed with about 1 liter of benzene during which operation very little
migration of the color bands occurs.
The column is then washed with benzene-acetone solution (15:85) whereby a
chromatogram develops. By continued washing, light yellow colored pigments
pass out of the column. When the main band (orange-red) reaches the lower
end of the column, a solution of 30:70 acetone-benzene is passed through the
column. The latter solvent elutes the pigment and when the eluate is very
pale in color, washing is discontinued.
The eluate is concentrated to dryness under reduced pressure, taken up in 25
cc of hot acetone, filtered, and diluted with ether. The pigment which
crystallizes as red-brick colored platelets is essentially pure but may be
recrystallized if desired from hot ethyl acetate. An analysis of the product
showed C = 59.01; H = 6.81; N = 13.38.
| [Brand name]
Cosmegen (Ovation). | [Therapeutic Function]
Cancer chemotherapy | [Biological Activity]
Anti-neoplastic antibiotic. Inhibits RNA polymerase and is a potent inducer of apoptosis. | [Mechanism of action]
Dactinomycin is cleared rapidly from plasma, does
not enter the brain, is not appreciably metabolized or
protein bound, and is gradually excreted in both bile
and urine.Virtually no drug is detected in CSF. | [Clinical Use]
Dactinomycin is used in curative combined treatment
of Wilms’ tumor, Ewing’s sarcoma, rhabdomyosarcoma,
and gestational choriocarcinoma. It is active in
testicular tumors, lymphomas, melanomas, and sarcomas,
although its use in most of these malignancies has
been supplanted by other agents. | [Side effects]
The major side effects of dactinomycin are severe
nausea, vomiting, and myelosuppression. Mucositis, diarrhea,
alopecia, and radiation recall reactions may occur.
The drug is immunosuppressive and carcinogenic. | [Veterinary Drugs and Treatments]
Dactinomycin has been used as adjunctive treatment of lymphoreticular
neoplasms,
bone and soft tissue sarcomas, and carcinomas
in small animals. It appears to have low efficacy against most carcinomas
and sarcomas. It is being investigated as a part of protocols
for rescue therapy for canine lymphomas. | [Drug interactions]
Potentially hazardous interactions with other drugs
Antipsychotics: increased risk of agranulocytosis
with clozapine - avoid.
Cytotoxics: increased risk of hepatotoxicity with
vincristine.
Vaccines: risk of generalised infections with live
vaccines - avoid. | [Metabolism]
Intravenous doses of dactinomycin are rapidly distributed
with high concentrations in bone marrow and nucleated
cells. It undergoes only minimal metabolism and is
slowly excreted in urine and bile. 15% is eliminated by
hepatic metabolism. Approximately 30% of the dose was
recovered in the urine and faeces in 1 week. | [storage]
+4°C | [Purification Methods]
It crystallises as bright red rhombic crystals from absolute EtOH or from MeOH/EtOH (1:3). It will also crystallise from EtOAc/cyclohexane (m 246-247o dec), CHCl3/pet ether ( m 245-246o dec), and EtOAc/MeOH/*C6H6 (m 241-243o dec). Its solubility in MeCN is 1mg/mL. [] D varies from -296o to -327o (c 0.2, MeOH). max (MeOH) 445, 240nm (log 4.43, 4.49), max (MeOH, 10N HCl, 1:1) 477nm (log 4.21) and max (MeOH, 0.1N NaOH) 458, 344, 285 (log 3.05, 4.28, 4.13). It is HIGHLY TOXIC, light sensitive and anti-neoplastic. [Bullock & Johnson, J Chem Soc 3280 1957, Beilstein 27 III/IV 9642.] | [References]
1) Wagner?et al.(2013)?RNA Polymerase II acts as an RNA-dependent RNA polymerase to extend and destabilize a non-coding RNA ; EMBO J.?32?781
2) J. Kleeff?et al.?(2000)?Actinomycin D induces apoptosis and inhibits growth of pancreatic cancer cells; Int. J. Cancer,?86?399
3) Kasim?et al.?(2013)?Live fluorescence and transmission-through-dye microscopic study of actinomycin D-induced apoptosis and apoptotic volume decrease?; Apoptosis,18?521
4) Liu?et al.?(2016)?Actinomycin D enhances killing of cancer cells by immunotoxin RG7787 through activation of the extrinsic pathway of apoptosis; Proc. Natl. Acad. Sci. USA,?113?10666
5) Kalousec?et al.?(2007)?Actinomycin D upregulates proapoptotic protein Puma and downregulates Bcl-2 mRNA in normal peripheral blood lymphocytes; Anticancer Drugs,?18?763
6) Matsuzaka?et al. (2016)?Characterization and functional analysis of extracellular vesicles and muscle-abundant miRNA in C2C12 myocytes and Mdx mice; PLoS One11(12)?e0167811 [Focus Biomolecules Citation] |
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