F-16438s, novel binding inhibitors of CD44 and hyaluronic acid. I. Establishment of an assay method and biological activity.
In an attempt to obtain inhibitors of hyaluronic acid (HA) binding to its receptor, CD44, we established an efficient assay method to detect and quantify binding using fluorescein-labeled HA and HEK293 cells stably expressing CD44. As a result of the screening of culture broths of microorganisms, we found fungus strain Gloeoporus dichrous SANK 30502 produced inhibitory activity in this new assay. Five compounds, F-16438 A, B, E, F and G, were isolated from the fermentation broths, and their IC50 values were determined to be 10.3, 13.5, 27.3, 12.0 and 13.0 microM, respectively. F-16438 A, B, E, F and G are the first reported inhibitors of binding HA to CD44. F-16438 A, B, E and F have novel structures.
Harada
Hosami
H
Lead Discovery Research Laboratories, Sankyo Co., Ltd., 1-2-58 Hiromachi, Shinagawa-ku, Tokyo 140-8710, Japan.
Nakata
Tomoko
T
Hirota-Takahata
Yuki
Y
Tanaka
Isshin
I
Nakajima
Mutsuo
M
Takahashi
Masaaki
M
D002460:Cell Line; D004705:Endocytosis; D006801:Humans; D018960:Hyaluronan Receptors / Q000378:metabolism*; D006820:Hyaluronic Acid / Q000037:antagonists & inhibitors* / Q000378:metabolism; D008362:Mannosides / Q000494:pharmacology*; D020072:Polyporales / Q000378:metabolism*; D012459:Salicylates / Q000494:pharmacology*
D018960:Hyaluronan Receptors; D008362:Mannosides; D012459:Salicylates; D006820:Hyaluronic Acid