TMC-2A, -2B and -2C, novel dipeptidyl peptidase IV inhibitors produced by Aspergillus oryzae A374. I. Taxonomy of producing strain, fermentation, and biochemical properties.
TMC-2A(1), -2B (2) and -2C (3), novel dipeptidyl peptidase IV (DPIV) inhibitors, were isolated from the fermentation broth of Aspergillus oryzae A374. TMC-2A, -2B and -2C inhibited rat kidney DPIV with IC50 value of 8.1 microM, 17 microM, and 20 microM, respectively, as well as human DPIV prepared from mononuclear cells and adenocarcinoma cells. TMC-2 compounds inhibited only DPIV among the proteases tested, indicating their high selectivity for DPIV. The kinetic analyses revealed that TMC-2A was an uncompetitive inhibitor. Taxonomy and fermentation of the producing strain are also described.
Nonaka
N
N
Lead Generation Research Laboratory, Tanabe Seiyaku Co., Ltd., Saitama, Japan.
Asai
Y
Y
Nishio
M
M
Takahashi
K
K
Okuda
T
T
Tanaka
S
S
Sugita
T
T
Ohnuki
T
T
Komatsubara
S
S
D000818:Animals; D001236:Aspergillus oryzae; D002478:Cells, Cultured; D004152:Dipeptidyl-Peptidases and Tripeptidyl-Peptidases / Q000037:antagonists & inhibitors*; D004791:Enzyme Inhibitors / Q000302:isolation & purification* / Q000494:pharmacology*; D005285:Fermentation; D006801:Humans; D007211:Indoles / Q000302:isolation & purification* / Q000494:pharmacology*; D007546:Isoquinolines / Q000302:isolation & purification* / Q000494:pharmacology*; D007668:Kidney / Q000187:drug effects / Q000201:enzymology; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley
D004791:Enzyme Inhibitors; D007211:Indoles; D007546:Isoquinolines; C108548:TMC 2A; C108549:TMC 2B; C108550:TMC 2C; D004152:Dipeptidyl-Peptidases and Tripeptidyl-Peptidases