F-12509A, a new sphingosine kinase inhibitor, produced by a discomycete.
In the course of our screening for inhibitors of sphingosine kinase, we found an active compound from a culture broth of a discomycete, Trichopezizella barbata SANK 25395. The structure of the compound, named F-12509A, was elucidated by a combination of spectroscopic analyses, to be a new sesquiterpene quinone consisting of a drimane moiety and a dihydroxybenzoquinone. Enzyme kinetic analyses showed that F-12509A inhibits sphingosine kinase activity in a competitive manner with respect to sphingosine, with a Ki value of 18 microM.
Kono
K
K
Pharmacology and Molecular Biology Research Laboratories, Researh Institute, Sankyo Co, Ltd, Shinagawa, Tokyo, Japan.
Tanaka
M
M
Ogita
T
T
Hosoya
T
T
Kohama
T
T
D000818:Animals; D001203:Ascomycota / Q000378:metabolism*; D016227:Benzoquinones / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D001921:Brain / Q000187:drug effects / Q000201:enzymology; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D007700:Kinetics; D008099:Liver / Q000187:drug effects / Q000201:enzymology; D008297:Male; D008861:Microsomes / Q000187:drug effects / Q000201:enzymology; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000037:antagonists & inhibitors*; D051381:Rats; D017208:Rats, Wistar; D013379:Substrate Specificity; D000099157:Sphingosine Kinase
D016227:Benzoquinones; D004791:Enzyme Inhibitors; D017853:Phosphotransferases (Alcohol Group Acceptor); D000099157:Sphingosine Kinase; C411675:F 12509A