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.

Integrin β1 is an essential factor in vasculogenic mimicry of human cancer cells

“…We carried out western blot using a slightly modified version of previously described methods. [23][24][25][26] Cells were seeded on Matrigel precoated dishes (20 μg/cm 2 Matrigel) as necessary and cultured at 37°C.…”

Copper‐Catalyzed Sulfimidation in Aqueous Media: a Fast, Chemoselective and Biomolecule‐Compatible Reaction

“…(4‐(Benzyloxy)phenyl)(methyl)sulfane was employed as a substrate to access ( N ‐arylsulfonyl)sulfimide‐based drug 16 . This compound has been studied in the context of cancer treatment and inhibits melanoma cell migration ( vide supra ) [26,27] . Both catalysts selectively provided the drug after clean conversion of the substrate with moderate to good yields (up to 48 %).…”

“…For example, (N-arylsulfonyl)sulfimide-based drugs (ArSO 2 N=SR'R'', with R' = alkyl and R'' = aryl) were reported to inhibit osteoclastogenesis and bind to proteins (e. g., pirin), causing inhibition of melanoma cell migration. [26,27] Hence, performing sulfimidation reactions in biological settings presents opportunities for the controlled and on demand synthesis of drugs. Motivated by this potential application, we set out to explore transition metalcatalyzed sulfimidation reactions in water for future in vivo application.…”

Methionine aminopeptidase‑2 is a pivotal regulator of vasculogenic mimicry

“…We performed western blot analysis as previously described ( 32 – 35 ). Cells were cultured in a 60-mm dish and lysed in lysis buffer [50 mM Tris-HCl, pH 7.5, 150 mM NaCl, 0.1% (w/v) sodium dodecyl sulfate, 1% (v/v) Triton X-100, 1% (w/v) sodium deoxycholate, and 1 mM phenylmethylsulfonyl fluoride] at 4°C with sonication.…”