Characterization of B-5354c, a new sphingosine kinase inhibitor, produced by a marine bacterium.
B-5354c is a new inhibitor of sphingosine kinase from a novel marine bacterium, SANK 71896. Kinetic study revealed that B-5354c inhibits sphingosine kinase with a Ki value of 12/microM. The inhibition is noncompetitive with respect to sphingosine. The compound also inhibits sphingosine-1-phosphate formation in human platelets. Experiments using synthetic derivatives of B-5354c indicate that all the three functional groups, i.e., the long unsaturated aliphatic chain, 4-amino and 3-hydroxyl groups are necessary to inhibit sphingosine kinase.
Kono
K
K
Pharmacology and Molecular Biology Research Laboratories, Research Institute, Sankyo Co., Ltd., Shinagawa, Tokyo, Japan.
Tanaka
M
M
Ogita
T
T
Kohama
T
T
D010129:4-Aminobenzoic Acid / Q000737:chemistry / Q000494:pharmacology; D000818:Animals; D001792:Blood Platelets / Q000187:drug effects / Q000201:enzymology; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D006090:Gram-Negative Bacteria / Q000378:metabolism; D006801:Humans; D020128:Inhibitory Concentration 50; D007700:Kinetics; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000037:antagonists & inhibitors*; D051381:Rats; D013329:Structure-Activity Relationship; D013379:Substrate Specificity; D062366:para-Aminobenzoates; D000099157:Sphingosine Kinase
D010129:4-Aminobenzoic Acid; D004791:Enzyme Inhibitors; D017853:Phosphotransferases (Alcohol Group Acceptor); D062366:para-Aminobenzoates; D000099157:Sphingosine Kinase; C416812:B 5354c