Identification of a novel compound that inhibits osteoclastogenesis by suppressing nucleoside transporters

Shun Katsuyama; Kumi Sugino; Yukiko Sasazawa; Yoshihiko Nakano; Harumi Aono; Keisuke Morishita; Makoto Kawatani; Kazuo Umezawa; Hiroyuki Osada; Siro Simizu

doi:10.1002/1873-3468.12146

Identification of a novel compound that inhibits osteoclastogenesis by suppressing nucleoside transporters

Shun Katsuyama, Kumi Sugino, Yukiko Sasazawa, Yoshihiko Nakano, Harumi Aono, Keisuke Morishita, Makoto Kawatani, Kazuo Umezawa, Hiroyuki Osada, Siro Simizu

Department of Applied Chemistry

Research output: Contribution to journal › Article › peer-review

7 Citations (Scopus)

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	https://doi.org/10.1002/1873-3468.12146
Publication status	Published - 2016 Apr 1

Keywords

concentrative nucleoside transporter
equilibrative nucleoside transporter
osteoclast differentiation
osteoporosis

ASJC Scopus subject areas

Biophysics
Structural Biology
Biochemistry
Molecular Biology
Genetics
Cell Biology

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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 › peer-review

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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.",

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author = "Shun Katsuyama and Kumi Sugino and Yukiko Sasazawa and Yoshihiko Nakano and Harumi Aono and Keisuke Morishita and Makoto Kawatani and Kazuo Umezawa and Hiroyuki Osada and Siro Simizu",

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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

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