Actinomycin D
[CAS# 50-76-0]

Identification

• Classification: API >> Antineoplastic agents >> Antibiotic antineoplastic agents
• Name: Actinomycin D
• Synonyms: Dactinomycin; 2-Amino-N,N'-bis[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
• Molecular Formula: C₆₂H₈₆N₁₂O₁₆
• Molecular Weight: 1255.43
• CAS Registry Number: 50-76-0
• EC Number: 200-063-6
• SMILES: C[C@@H]1[C@@H](C(=O)N[C@@H](C(=O)N2CCC[C@H]2C(=O)N(CC(=O)N([C@H](C(=O)O1)C(C)C)C)C)C(C)C)NC(=O)C3=C4C(=C(C=C3)C)OC5=C(C(=O)C(=C(C5=N4)C(=O)N[C@H]6[C@H](OC(=O)[C@@H](N(C(=O)CN(C(=O)[C@@H]7CCCN7C(=O)[C@H](NC6=O)C(C)C)C)C)C(C)C)C)N)C

Properties

• Solubility: 10 mM (DMSO) (Expl.)
• Density: 1.4±0.1 g/cm³, Calc.^*
• Melting point: 241-243 °C
• Index of Refraction: 1.656, Calc.^*
• Boiling Point: 1386.0±65.0 °C (760 mmHg), Calc.^*
• Flash Point: 792.1±34.3 °C, Calc.^*

^* Calculated using Advanced Chemistry Development (ACD/Labs) Software.

Safety Data

• Hazard Symbols: GHS06;GHS08 Dander
• Risk Statements: H300-H350-H360
• Safety Statements: P203-P264-P270-P280-P301+P316-P318-P321-P330-P405-P501

Hazard Classification

Hazard	Class	Category Code	Hazard Statement
Acute toxicity	Acute Tox.	1	H300
Carcinogenicity	Carc.	1A	H350
Reproductive toxicity	Repr.	1A	H360
Acute toxicity	Acute Tox.	2	H300
Carcinogenicity	Carc.	1B	H350
Respiratory sensitization	Resp. Sens.	1	H334
Skin sensitization	Skin Sens.	1	H317
Reproductive toxicity	Repr.	2	H361

Discovery and Applications

Actinomycin D is a potent antibiotic and anticancer agent that was first discovered in the 1950s. It was isolated from the bacterium *Streptomyces parvullus*, a soil microorganism, by researchers at Merck & Co. in 1956. The compound belongs to a class of drugs known as actinomycins, which are characterized by their ability to inhibit DNA transcription by binding to the DNA template. This discovery was a significant milestone in the development of chemotherapeutic agents and provided new opportunities for the treatment of various cancers and other diseases.

The chemical structure of actinomycin D consists of a chromophore, which is a light-absorbing group, and a polypeptide chain that enables the compound to interact with DNA. The chromophore is responsible for its potent biological activity, while the polypeptide chain aids in its attachment to the DNA molecule. Actinomycin D works by intercalating between the base pairs of DNA, thereby preventing the proper functioning of RNA polymerase. This inhibition of RNA synthesis prevents the transcription of essential genes, leading to the suppression of protein production and ultimately, cell death. This mechanism of action makes actinomycin D a powerful agent against rapidly proliferating cells, such as cancer cells.

The primary application of actinomycin D is in the treatment of cancer, particularly in pediatric oncology. It has been used in the treatment of a variety of cancers, including Wilms' tumor, a type of kidney cancer that primarily affects children, and rhabdomyosarcoma, a cancer of the soft tissue. The drug is typically administered intravenously and is often used in combination with other chemotherapy agents to enhance its effectiveness. Actinomycin D has been shown to be highly effective in treating these cancers, particularly when used in early-stage or localized cases. Its ability to inhibit cell division and growth has made it a valuable tool in chemotherapy regimens.

Actinomycin D is also used in the treatment of certain rare cancers, such as Kaposi's sarcoma, which is commonly associated with HIV/AIDS, and trophoblastic tumors, which originate from placental tissue. Its ability to target rapidly dividing cells makes it a suitable treatment for cancers that are characterized by aggressive cell proliferation. In addition to its use in oncology, actinomycin D has been studied for its potential in the treatment of certain infectious diseases, although its primary use remains in cancer therapy.

While actinomycin D has proven to be an effective anticancer agent, it is associated with several side effects due to its toxicity. Common side effects include nausea, vomiting, suppression of bone marrow activity (leading to reduced blood cell counts), and potential damage to organs such as the liver and kidneys. These side effects can limit the drug’s use, particularly in patients with pre-existing organ dysfunction. However, the drug is often used in a carefully controlled setting, where the benefits of its potent anticancer activity outweigh the risks associated with its toxicity.

Researchers have also investigated the use of actinomycin D in combination with other therapeutic agents to improve its efficacy and reduce its side effects. For example, its combination with other chemotherapy drugs, such as vincristine and cyclophosphamide, has been shown to improve the overall outcomes of cancer treatments. The combination approach aims to target cancer cells through multiple mechanisms, potentially reducing the chances of resistance to the treatment.

Despite its usefulness, actinomycin D is not without limitations. One of the key challenges in its use is the development of resistance in cancer cells. Over time, cancer cells may evolve mechanisms to evade the effects of the drug, making it less effective. Researchers continue to explore ways to overcome this resistance, including the development of new formulations of actinomycin D or the discovery of additional compounds that can act synergistically with it.

In conclusion, actinomycin D is a critical drug in the field of chemotherapy, with a significant impact on the treatment of various cancers, particularly pediatric malignancies. Its discovery marked an important advancement in cancer therapy, and its ability to target DNA transcription has made it a valuable tool in the fight against cancer. However, its toxicity and the potential for resistance continue to present challenges, underscoring the need for ongoing research and the development of complementary therapeutic strategies.

References

1979. Acid ribonuclease activation in the chick oviduck by tissue damage, actinomycin D and progesterone. Journal of Steroid Biochemistry, 11(1).
DOI: 10.1016/0022-4731(79)90515-6

1979. Effect of liposome-entrapped methotrexate on ehrlich ascites tumor cells and uptake in primary liver cell tumor. Journal of Cancer Research and Clinical Oncology, 94(2).
DOI: 10.1007/bf00405346

1979. Studies on the efficiency of translation and on the stability of actin messenger ribonucleic acid in mouse sarcoma ascites cells. Biochemistry, 18(13).
DOI: 10.1021/bi00581a037