title: Identification of a novel compound that inhibits osteoclastogenesis by suppressing nucleoside transporters.
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 [(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.
authors.affiliation: Department of Applied Chemistry, Faculty of Science and Technology, Keio University, Yokohama, Japan.
authors.forename: Shun
authors.initials: S
authors.lastname: Katsuyama
authors.affiliation: Chemical Biology Research Group, RIKEN CSRS, Wako, Saitama, Japan.
authors.forename: Kumi
authors.initials: K
authors.lastname: Sugino
authors.affiliation: Department of Applied Chemistry, Faculty of Science and Technology, Keio University, Yokohama, Japan.
authors.forename: Yukiko
authors.initials: Y
authors.lastname: Sasazawa
authors.affiliation: Department of Applied Chemistry, Faculty of Science and Technology, Keio University, Yokohama, Japan.
authors.forename: Yoshihiko
authors.initials: Y
authors.lastname: Nakano
authors.affiliation: Chemical Biology Research Group, RIKEN CSRS, Wako, Saitama, Japan.
authors.forename: Harumi
authors.initials: H
authors.lastname: Aono
authors.affiliation: Department of Applied Chemistry, Faculty of Science and Technology, Keio University, Yokohama, Japan.
authors.forename: Keisuke
authors.initials: K
authors.lastname: Morishita
authors.affiliation: Chemical Biology Research Group, RIKEN CSRS, Wako, Saitama, Japan.
authors.forename: Makoto
authors.initials: M
authors.lastname: Kawatani
authors.affiliation: Department of Molecular Target Medicine, Aichi Medical University School of Medicine, Nagakute, Aichi, Japan.
authors.forename: Kazuo
authors.initials: K
authors.lastname: Umezawa
authors.affiliation: Chemical Biology Research Group, RIKEN CSRS, Wako, Saitama, Japan.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Osada
authors.affiliation: Department of Applied Chemistry, Faculty of Science and Technology, Keio University, Yokohama, Japan.
authors.forename: Siro
authors.initials: S
authors.lastname: Simizu
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D051379:Mice; D008813:Mice, Inbred ICR; D033703:Nucleoside Transport Proteins / Q000378:metabolism*; D010010:Osteoclasts / Q000187:drug effects / Q000378:metabolism*; D010012:Osteogenesis / Q000187:drug effects* / Q000235:genetics; D053245:RANK Ligand / Q000494:pharmacology; D000067996:RAW 264.7 Cells; D015398:Signal Transduction / Q000187:drug effects; D054852:Small Molecule Libraries / Q000737:chemistry / Q000494:pharmacology*; D014316:Tritium / Q000378:metabolism
chemical_list: D033703:Nucleoside Transport Proteins; D053245:RANK Ligand; D054852:Small Molecule Libraries; D014316:Tritium
keywords: concentrative nucleoside transporter; equilibrative nucleoside transporter; osteoclast differentiation; osteoporosis