Biological activities of scyphostatin, a neutral sphingomyelinase inhibitor from a discomycete, Trichopeziza mollissima.
Scyphostatin is a specific inhibitor for mammalian neutral magnesium-dependent sphingomyelinase with a fifty percent inhibition concentration (IC50) value of 1.0 microM. When used to inhibit lysosomal acid sphingomyelinase, an approximately 50-fold greater concentration is required. In human peripheral monocytes, the compound inhibits bacterial lipopolysaccharide (LPS)-induced prostaglandin E2 production and LPS-induced interleukin-1beta production with IC50 values of 0.8 microM and 0.1 microM, respectively. In rat, p.o. administration of the compound has also been shown to inhibit carrageenin-induced paw edema. Thus, it is hoped that utility of scyphostatin as a pharmacological tool will contribute to our understanding of the role of ceramide in the cellular inflammation process.
Nara
F
F
Biological Research Laboratories, Sankyo Co., Ltd., Tokyo, Japan.
Tanaka
M
M
Masuda-Inoue
S
S
Yamasato
Y
Y
Doi-Yoshioka
H
H
Suzuki-Konagai
K
K
Kumakura
S
S
Ogita
T
T
D000577:Amides / Q000494:pharmacology* / Q000627:therapeutic use; D000818:Animals; D001203:Ascomycota / Q000378:metabolism*; D002351:Carrageenan; D002462:Cell Membrane / Q000201:enzymology; D015232:Dinoprostone / Q000096:biosynthesis; D004487:Edema / Q000139:chemically induced / Q000517:prevention & control; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005354:Fibrosarcoma / Q000201:enzymology; D006801:Humans; D007375:Interleukin-1 / Q000096:biosynthesis; D007938:Leukemia / Q000201:enzymology; D008070:Lipopolysaccharides / Q000494:pharmacology; D008247:Lysosomes / Q000201:enzymology; D008274:Magnesium / Q000494:pharmacology; D008297:Male; D051379:Mice; D009000:Monocytes / Q000187:drug effects / Q000378:metabolism; D011753:Pyrones / Q000494:pharmacology* / Q000627:therapeutic use; D051381:Rats; D017208:Rats, Wistar; D013108:Sphingomyelin Phosphodiesterase / Q000037:antagonists & inhibitors*; D014407:Tumor Cells, Cultured
D000577:Amides; D004791:Enzyme Inhibitors; D007375:Interleukin-1; D008070:Lipopolysaccharides; D011753:Pyrones; C121123:scyphostatin; D002351:Carrageenan; D013108:Sphingomyelin Phosphodiesterase; D008274:Magnesium; D015232:Dinoprostone