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December 2012 Volume 30 Issue 6

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RING-finger type E3 ubiquitin ligase inhibitors as novel candidates for the treatment of rheumatoid arthritis

  • Authors:
    • Naoko Yagishita
    • Satoko Aratani
    • Craig Leach
    • Tetsuya Amano
    • Yoshihisa Yamano
    • Ko Nakatani
    • Kusuki Nishioka
    • Toshihiro Nakajima
  • View Affiliations / Copyright

    Affiliations: Institute of Medical Science, St. Marianna University School of Medicine, Kawasaki, Kanagawa, Japan, Institute of Medical Science, Tokyo Medical University, Shinjuku, Tokyo, Japan, Progenra, Inc., Malvern, PA, USA, Bayside Misato Medical Center, Kochi, Japan
    Copyright: © Yagishita et al. This is an open access article distributed under the terms of Creative Commons Attribution License [CC BY_NC 3.0].
  • Pages: 1281-1286
    |
    Published online on: September 18, 2012
       https://doi.org/10.3892/ijmm.2012.1129
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Abstract

Rheumatoid arthritis (RA) significantly affects quality of life. We recently cloned synoviolin, a RING-type E3 ubiquitin ligase implicated in the endoplasmic reticulum-associated degradation (ERAD) pathway. Synoviolin is highly expressed in rheumatoid synovial cells and may be involved in the pathogenesis of RA. Inhibition of synoviolin activity is a potentially useful therapeutic approach for the treatment of RA. We conducted a high-throughput screen of small molecules to find inhibitors of synoviolin autoubiquitination activity. We identified two classes of small molecules, named LS-101 and LS-102, which inhibited synoviolin activity. LS-102 selectively inhibited synoviolin enzymatic activity, while LS-101 inhibited a broad array of RING-type E3 ligases. Moreover, these inhibitors suppressed the proliferation of rheumatoid synovial cells, and significantly reduced the severity of disease in a mouse model of RA. Our results suggest that inhibition of synoviolin is a potentially useful approach in the treatment of RA.
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Copy and paste a formatted citation
Spandidos Publications style
Yagishita N, Aratani S, Leach C, Amano T, Yamano Y, Nakatani K, Nishioka K and Nakajima T: RING-finger type E3 ubiquitin ligase inhibitors as novel candidates for the treatment of rheumatoid arthritis. Int J Mol Med 30: 1281-1286, 2012.
APA
Yagishita, N., Aratani, S., Leach, C., Amano, T., Yamano, Y., Nakatani, K. ... Nakajima, T. (2012). RING-finger type E3 ubiquitin ligase inhibitors as novel candidates for the treatment of rheumatoid arthritis. International Journal of Molecular Medicine, 30, 1281-1286. https://doi.org/10.3892/ijmm.2012.1129
MLA
Yagishita, N., Aratani, S., Leach, C., Amano, T., Yamano, Y., Nakatani, K., Nishioka, K., Nakajima, T."RING-finger type E3 ubiquitin ligase inhibitors as novel candidates for the treatment of rheumatoid arthritis". International Journal of Molecular Medicine 30.6 (2012): 1281-1286.
Chicago
Yagishita, N., Aratani, S., Leach, C., Amano, T., Yamano, Y., Nakatani, K., Nishioka, K., Nakajima, T."RING-finger type E3 ubiquitin ligase inhibitors as novel candidates for the treatment of rheumatoid arthritis". International Journal of Molecular Medicine 30, no. 6 (2012): 1281-1286. https://doi.org/10.3892/ijmm.2012.1129
Copy and paste a formatted citation
x
Spandidos Publications style
Yagishita N, Aratani S, Leach C, Amano T, Yamano Y, Nakatani K, Nishioka K and Nakajima T: RING-finger type E3 ubiquitin ligase inhibitors as novel candidates for the treatment of rheumatoid arthritis. Int J Mol Med 30: 1281-1286, 2012.
APA
Yagishita, N., Aratani, S., Leach, C., Amano, T., Yamano, Y., Nakatani, K. ... Nakajima, T. (2012). RING-finger type E3 ubiquitin ligase inhibitors as novel candidates for the treatment of rheumatoid arthritis. International Journal of Molecular Medicine, 30, 1281-1286. https://doi.org/10.3892/ijmm.2012.1129
MLA
Yagishita, N., Aratani, S., Leach, C., Amano, T., Yamano, Y., Nakatani, K., Nishioka, K., Nakajima, T."RING-finger type E3 ubiquitin ligase inhibitors as novel candidates for the treatment of rheumatoid arthritis". International Journal of Molecular Medicine 30.6 (2012): 1281-1286.
Chicago
Yagishita, N., Aratani, S., Leach, C., Amano, T., Yamano, Y., Nakatani, K., Nishioka, K., Nakajima, T."RING-finger type E3 ubiquitin ligase inhibitors as novel candidates for the treatment of rheumatoid arthritis". International Journal of Molecular Medicine 30, no. 6 (2012): 1281-1286. https://doi.org/10.3892/ijmm.2012.1129
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