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Dactinomycin


ACCESSION NB: DB00970 (APRD00124)


TYPE: small molecule


GROUP: approved


DESCRIPTION:
A compound composed of a two cyclic peptides attached to a phenoxazine that is derived from streptomyces parvullus. It binds to DNA and inhibits RNA synthesis (transcription), with chain elongation more sensitive than initiation, termination, or release. As a result of impaired mRNA production, protein synthesis also declines after dactinomycin therapy. (From AMA Drug Evaluations Annual, 1993, p2015)

VOLUME OF DISTRIBUTION: Not Available

CATEGORIES:
Antineoplastic Agents Anti-Bacterial Agents Nucleic Acid Synthesis Inhibitors Antibiotics Antibiotics, Antineoplastic Protein Synthesis Inhibitors

ABSORPTION: poorly absorbed from gastrointestinal tract

INDICATION:
For the treatment of Wilms' tumor, childhood rhabdomyosarcoma, Ewing's sarcoma and metastatic, nonseminomatous testicular cancer as part of a combination chemotherapy and/or multi-modality treatment regimen

PHARMACODYNAMICS:
Generally, the actinomycins exert an inhibitory effect on gram-positive and gram-negative bacteria and on some fungi. However, the toxic properties of the actinomycins (including dactinomycin) in relation to antibacterial activity are such as to preclude their use as antibiotics in the treatment of infectious diseases. Because the actinomycins are cytotoxic, they have an antineoplastic effect which has been demonstrated in experimental animals with various types of tumor implant. This cytotoxic action is the basis for their use in the treatment of certain types of cancer. Dactinomycin is believed to produce its cytotoxic effects by binding DNA and inhibiting RNA synthesis.

MECHANISM OF ACTION:
Good evidence exists that this drug bind strongly, but reversibly, to DNA, interfering with synthesis of RNA (prevention of RNA polymerase elongation) and, consequently, with protein synthesis.

PROTEIN BINDING:
5%

METABOLISM:
hepatic

TOXICITY:
hepatoxicity

AFECTED ORGANISMS:
Humans and other mammals