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Streptozocin


ACCESSION NB: DB00428 (APRD00209)


TYPE: small molecule


GROUP: approved


DESCRIPTION:
An antibiotic that is produced by Stretomyces achromogenes. It is used as an antineoplastic agent and to induce diabetes in experimental animals. [PubChem]

VOLUME OF DISTRIBUTION: Not Available

CATEGORIES:
Antineoplastic Agents Antibiotics Antibiotics, Antineoplastic

ABSORPTION: Poor oral absorption (17-25%)

INDICATION:
For the treatment of malignant neoplasms of pancreas (metastatic islet cell carcinoma).

PHARMACODYNAMICS:
Streptozocin is an antitumour antibiotic consisting of a nitrosourea moiety interposed between a methyl group and a glucosamine. Streptozocin is indicated in the treatment of metastatic islet cell carcinoma of the pancreas. Streptozocin inhibits DNA synthesis in bacterial and mammalian cells. In bacterial cells, a specific interaction with cytosine moieties leads to degradation of DNA. The biochemical mechanism leading to mammalian cell death has not been definitely established; streptozocin inhibits cell proliferation at a considerably lower level than that needed to inhibit precursor incorporation into DNA or to inhibit several of the enzymes involved in DNA synthesis. Although streptozocin inhibits the progression of cells into mitosis, no specific phase of the cell cycle is particularly sensitive to its lethal effects.

MECHANISM OF ACTION:
Although its mechanism of action is not completely clear, streptozocin is known to inhibit DNA synthesis, interfere with biochemical reactions of NAD and NADH, and inhibit some enzymes involved in gluconeogenesis. Its activity appears to occur as a result of formation of methylcarbonium ions, which alkylate or bind with many intracellular molecular structures including nucleic acids. Its cytotoxic action is probably due to cross-linking of strands of DNA, resulting in inhibition of DNA synthesis.

PROTEIN BINDING:
Not Available

METABOLISM:
Primarily hepatic

TOXICITY:
Symptoms of overdose include nausea and vomiting, anorexia, myelosuppression; and nephrotoxicity.

AFECTED ORGANISMS:
Humans and other mammals