TMC-69, a new antitumor antibiotic with Cdc25A inhibitory activity, produced by Chrysosporium sp. TC1068. Taxonomy, fermentation and biological activities.
A new antibiotic designated TMC-69 has been isolated from the fermentation broth of a fungal strain Chrysosporium sp. TC 1068. TMC-69 exhibited moderate in vitro cytotoxic activity. TMC-69-6H, a derivative of TMC-69 prepared by hydrogenation, possessed more potent in vitro cytotoxicity than TMC-69, and exhibited in vivo antitumor activity against murine P388 leukemia and B16 melanoma. TMC-69-6H was found to specifically inhibit Cdc25A and B phosphatases.
Hirano
N
N
Discovery Research Laboratory, Tanabe Seiyaku Co, Ltd, Saitama, Japan. hiranon@tanabe.co.jp
Kohno
J
J
Tsunoda
S
S
Nishio
M
M
Kishi
N
N
Okuda
T
T
Kawano
K
K
Komatsubara
S
S
Nakanishi
N
N
D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000494:pharmacology*; D001681:Biological Assay; D002455:Cell Division / Q000187:drug effects; D002912:Chrysosporium / Q000254:growth & development / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D006801:Humans; D006865:Hydrogenation; D020128:Inhibitory Concentration 50; D007941:Leukemia P388 / Q000188:drug therapy; D008546:Melanoma, Experimental / Q000188:drug therapy; D051379:Mice; D011714:Pyrans / Q000494:pharmacology*; D014407:Tumor Cells, Cultured; D020687:cdc25 Phosphatases / Q000037:antagonists & inhibitors* / Q000378:metabolism
D000903:Antibiotics, Antineoplastic; D004791:Enzyme Inhibitors; D011714:Pyrans; C433006:TMC-69; C433007:TMC-69-6H; C517004:CDC25A protein, human; C517005:Cdc25a protein, mouse; D020687:cdc25 Phosphatases