TY - JOUR
T1 - Identification of a novel compound that inhibits osteoclastogenesis by suppressing nucleoside transporters
AU - Katsuyama, Shun
AU - Sugino, Kumi
AU - Sasazawa, Yukiko
AU - Nakano, Yoshihiko
AU - Aono, Harumi
AU - Morishita, Keisuke
AU - Kawatani, Makoto
AU - Umezawa, Kazuo
AU - Osada, Hiroyuki
AU - Simizu, Siro
N1 - Publisher Copyright:
© 2016 Federation of European Biochemical Societies.
Copyright:
Copyright 2017 Elsevier B.V., All rights reserved.
PY - 2016/4/1
Y1 - 2016/4/1
N2 - 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 [3H]-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.
AB - 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 [3H]-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.
KW - concentrative nucleoside transporter
KW - equilibrative nucleoside transporter
KW - osteoclast differentiation
KW - osteoporosis
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U2 - 10.1002/1873-3468.12146
DO - 10.1002/1873-3468.12146
M3 - Article
C2 - 27001232
AN - SCOPUS:84962710963
VL - 590
SP - 1152
EP - 1162
JO - FEBS Letters
JF - FEBS Letters
SN - 0014-5793
IS - 8
ER -