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Identification of a novel compound that inhibits osteoclastogenesis by suppressing nucleoside transporters
Author(s) -
Katsuyama Shun,
Sugino Kumi,
Sasazawa Yukiko,
Nakano Yoshihiko,
Aono Harumi,
Morishita Keisuke,
Kawatani Makoto,
Umezawa Kazuo,
Osada Hiroyuki,
Simizu Siro
Publication year - 2016
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1002/1873-3468.12146
Subject(s) - osteoclast , nucleoside , chemistry , nucleoside transporter , transporter , uridine , biochemistry , microbiology and biotechnology , biology , rna , in vitro , gene
We screened small‐molecule compounds that inhibit osteoclast differentiation to find new anti‐osteoporosis agents and found that a novel compound, SUKU‐1, suppressed osteoclastogenesis. We also synthesized 38 derivatives of SUKU‐1 and discovered that nine of them had inhibitory effects on osteoclastogenesis and that SUKU‐33 was the most potent inhibitor. Next, we investigated the mechanisms by which SUKU‐33 suppressed osteoclast differentiation. By measuring the uptake of [ 3 H]‐uridine in cells, we found that SUKU‐33 suppressed both equilibrative nucleoside transporters and concentrative nucleoside transporters. These results suggest that SUKU‐33 inhibits osteoclast differentiation by suppressing nucleoside transporters.