Dactinomycin
Chromopeptide antibiotic that intercalates into DNA and inhibits RNA polymerase, used as a chemotherapeutic agent for pediatric and testicular cancers.
Chemical Identity
| Property | Value |
|---|---|
| Chemical Formula | C62H86N12O16 |
| Molecular Weight | 1255.42 Da |
| CAS Number | 50-76-0 |
| Peptide Class | Chromopeptide Antibiotic |
| Origin | Streptomyces parvulus |
Structure
Dactinomycin (actinomycin D) contains a planar phenoxazone chromophore (2-amino-4,6-dimethyl-3-oxo-phenoxazine-1,9-dicarboxylic acid) linked to two identical cyclic pentapeptide lactone rings (L-threonine, D-valine, L-proline, N-methylglycine, N-methyl-L-valine). The planar ring intercalates between adjacent GC base pairs.
Mechanism of Action
Dactinomycin intercalates into DNA at GC sequences, with the cyclic peptide portions lying in the minor groove. This blocks RNA polymerase movement and inhibits DNA-dependent RNA synthesis. It also inhibits topoisomerase II, preventing DNA unwinding. The drug is cell-cycle non-specific.
Clinical Applications
- Wilms tumor: Standard component of treatment regimens
- Rhabdomyosarcoma: VAC regimen component
- Ewing sarcoma: Multi-agent chemotherapy
- Gestational trophoblastic disease: Low-risk disease
- Testicular cancer: VAC regimen
Pharmacokinetics
- Half-life: 36 hours
- Distribution: Widely distributed, concentrates in nucleated cells
- Metabolism: Minimal hepatic metabolism
- Elimination: Biliary and renal
- Route: IV only (vesicant)
Safety and Side Effects
Myelosuppression (dose-limiting, nadir at 10-14 days), nausea/vomiting, mucositis, alopecia, and radiation recall dermatitis. Severe vesicant - extravasation causes tissue necrosis. Contraindicated in varicella or herpes zoster infections.
References
- Waksman, S.A., & Woodruff, H.B. (1940). Bacteriostatic and bactericidal substances produced by soil actinomyces. Proceedings of the Society for Experimental Biology and Medicine, 45, 609-614.
- Farber, S., et al. (1960). Clinical studies on actinomycin D. Cancer Research, 20, 939-949.
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