[Antitumor agents targeting mammalian topoisomerases].
Topoisomerase II is now viewed as an important cellular target of antitumor drugs including both DNA intercalators (m-AMSA, ellipticine and Adriamycin) and the nonintercalator epipodophyllotoxin derivatives (VP-16 and VM-26). Topoisomerase I is also shown to be the cellular target of camptotecin. These drugs targeting topoisomerase have been used to establish a relationship between drug-induced cleavable complex formation and cytotoxicity. Mechanistically oriented screening based on the identification of these chemotherapeutic targets have identified a number of antitumor agents that induce topoisomerases mediated DNA cleavage. The new antitumor drugs targeting topoisomerases are reviewed.
Nakano
H
H
Tokyo Research Laboratories, Kyowa Hakko Co. Ltd., Japan.
D000677:Amsacrine / Q000494:pharmacology; D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000494:pharmacology*; D004250:DNA Topoisomerases, Type II / Q000235:genetics; D004224:Diterpenes / Q000494:pharmacology; D004317:Doxorubicin / Q000494:pharmacology; D005047:Etoposide / Q000494:pharmacology; D007941:Leukemia P388 / Q000188:drug therapy; D051379:Mice
D000903:Antibiotics, Antineoplastic; D004224:Diterpenes; D000677:Amsacrine; C047785:terpentecin; D005047:Etoposide; D004317:Doxorubicin; C039027:clerocidin; D004250:DNA Topoisomerases, Type II