Abstract
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.
| Original language | English |
|---|---|
| Pages (from-to) | 1152-1162 |
| Number of pages | 11 |
| Journal | FEBS Letters |
| Volume | 590 |
| Issue number | 8 |
| DOIs | |
| Publication status | Published - 2016 Apr 1 |
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Keywords
- concentrative nucleoside transporter
- equilibrative nucleoside transporter
- osteoclast differentiation
- osteoporosis
ASJC Scopus subject areas
- Biochemistry
- Biophysics
- Cell Biology
- Genetics
- Molecular Biology
- Structural Biology
Cite this
Identification of a novel compound that inhibits osteoclastogenesis by suppressing nucleoside transporters. / Katsuyama, Shun; Sugino, Kumi; Sasazawa, Yukiko; Nakano, Yoshihiko; Aono, Harumi; Morishita, Keisuke; Kawatani, Makoto; Umezawa, Kazuo; Osada, Hiroyuki; Simizu, Siro.
In: FEBS Letters, Vol. 590, No. 8, 01.04.2016, p. 1152-1162.Research output: Contribution to journal › Article
}
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
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
UR - http://www.scopus.com/inward/record.url?scp=84962710963&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84962710963&partnerID=8YFLogxK
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 -