TAN-1120, a new anthracycline with potent angiostatic activity.
A potent angiogenesis-inhibitory compound TAN-1120 was found to be produced by a Streptomyces species isolated from a soil sample. The producing organism was characterized as a new subspecies of S. triangulatus and named S. triangulatus subsp. angiostaticus subsp. nov. due to its specific ability to produce the compound. This substance was isolated as a red powder by a combination of organic solvent extraction, silica gel column chromatography and preparative HPLC using an ODS column. Its structure was elucidated by chemical reactions and spectral analyses to be a new baumycin-group anthracycline. Reduction of TAN-1120 gave two compounds, a deoxy derivative and baumycin A1. TAN-1120 showed remarkably potent angiostatic activity in two conventional angiogenesis assay systems in vivo, while doxorubicin and daunomycin had far weaker activity. It strongly inhibited proliferation of vascular endothelial cells did not prevent capillary cord formation in vitro by the endothelial cells on extracellular matrix-coated plates. TAN-1120 is one of the most potent angiostatic agents reported.
Nozaki
Y
Y
Discovery Research Division, Takeda Chemical Industries, Ltd., Osaka, Japan.
Hida
T
T
Iinuma
S
S
Ishii
T
T
Sudo
K
K
Muroi
M
M
Kanamaru
T
T
D016475:3T3 Cells / Q000187:drug effects; D000818:Animals; D018943:Anthracyclines; D000903:Antibiotics, Antineoplastic / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology; D002417:Cattle; D002642:Chick Embryo; D004730:Endothelium, Vascular / Q000187:drug effects; D005285:Fermentation; D006801:Humans; D051379:Mice; D008826:Microbial Sensitivity Tests; D009389:Neovascularization, Pathologic / Q000517:prevention & control*; D011550:Pseudomonas aeruginosa / Q000187:drug effects; D051381:Rats; D013302:Streptomyces / Q000737:chemistry*; D014407:Tumor Cells, Cultured / Q000187:drug effects
D018943:Anthracyclines; D000903:Antibiotics, Antineoplastic; C081412:TAN 1120