title: F-16438s, novel binding inhibitors of CD44 and hyaluronic acid. I. Establishment of an assay method and biological activity.
abstract: 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.
authors.affiliation: Lead Discovery Research Laboratories, Sankyo Co., Ltd., 1-2-58 Hiromachi, Shinagawa-ku, Tokyo 140-8710, Japan.
authors.forename: Hosami
authors.initials: H
authors.lastname: Harada
authors.forename: Tomoko
authors.initials: T
authors.lastname: Nakata
authors.forename: Yuki
authors.initials: Y
authors.lastname: Hirota-Takahata
authors.forename: Isshin
authors.initials: I
authors.lastname: Tanaka
authors.forename: Mutsuo
authors.initials: M
authors.lastname: Nakajima
authors.forename: Masaaki
authors.initials: M
authors.lastname: Takahashi
mesh_terms: 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*
chemical_list: D018960:Hyaluronan Receptors; D008362:Mannosides; D012459:Salicylates; D006820:Hyaluronic Acid