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Teniposide


ACCESSION NB: DB00444 (APRD00649)


TYPE: small molecule


GROUP: approved


DESCRIPTION:
A semisynthetic derivative of podophyllotoxin that exhibits antitumor activity. Teniposide inhibits DNA synthesis by forming a complex with topoisomerase II and DNA. This complex induces breaks in double stranded DNA and prevents repair by topoisomerase II binding. Accumulated breaks in DNA prevent cells from entering into the mitotic phase of the cell cycle, and lead to cell death. Teniposide acts primarily in the G2 and S phases of the cycle. [PubChem]

VOLUME OF DISTRIBUTION: Not Available

CATEGORIES:
Antineoplastic Agents Enzyme Inhibitors Nucleic Acid Synthesis Inhibitors

INDICATION:
Teniposide is used for the treatment of refractory acute lymphoblastic leukaemia

PHARMACODYNAMICS:
Teniposide is a phase-specific cytotoxic drug, acting in the late S or early G 2 phase of the cell cycle, thus preventing cells from entering mitosis. Teniposide causes dose-dependent single- and double-stranded breaks in DNA and DNA: protein cross-links.

MECHANISM OF ACTION:
The mechanism of action appears to be related to the inhibition of type II topoisomerase activity since teniposide does not intercalate into DNA or bind strongly to DNA. Teniposide binds to and inhibits DNA topoisomerase II. The cytotoxic effects of teniposide are related to the relative number of double-stranded DNA breaks produced in cells, which are a reflection of the stabilization of a topoisomerase II-DNA intermediate.

AFECTED ORGANISMS:
Humans and other mammals