國家衛生研究院 NHRI:Item 3990099045/12996
English  |  正體中文  |  简体中文  |  全文筆數/總筆數 : 12189/12972 (94%)
造訪人次 : 966385      線上人數 : 827
RC Version 6.0 © Powered By DSPACE, MIT. Enhanced by NTU Library IR team.
搜尋範圍 查詢小技巧：
  • 您可在西文檢索詞彙前後加上"雙引號"，以獲取較精準的檢索結果
  • 若欲以作者姓名搜尋，建議至進階搜尋限定作者欄位，可獲得較完整資料
    •  進階搜尋
    主頁 ‧ 登入 ‧ 上傳 ‧ 說明 ‧ 關於NHRI ‧ 管理 到手機版


    請使用永久網址來引用或連結此文件: http://ir.nhri.org.tw/handle/3990099045/12996


    題名: Potent and orally active purine-based fetal hemoglobin inducers for treating Beta-thalassemia and sickle cell disease
    其他題名: Potent and orally active purine-based fetal hemoglobin inducers for treating β-thalassemia and sickle cell disease
    作者: Lai, ZS;Yeh, TK;Chou, YC;Hsu, T;Lu, CT;Kung, FC;Hsieh, MY;Lin, CH;Chen, CT;James Shen, CK;Jiaang, WT
    貢獻者: Institute of Biotechnology and Pharmaceutical Research
    摘要: Reactivation of fetal hemoglobin (HbF) expression by therapeutic agents has been suggested as an alternative treatment to modulate anemia and the related symptoms of severe β-thalassemia and sickle cell disease (SCD). Hydroxyurea (HU) is the first US FDA-approved HbF inducer for treating SCD. However, approximately 25% of the patients with SCD do not respond to HU. A previous study identified TN1 (1) as a small-molecule HbF inducer. However, this study found that the poor potency and oral bioavailability of compound 1 limits the development of this inducer for clinical use. To develop drug-like compounds, further structure-activity relationship studies on the purine-based structure of 1 were conducted. Herein, we report our discovery of a more potent inducer, compound 13a, that can efficiently induce γ-globin gene expression at non-cytotoxic concentrations. The molecular mechanism of 13a, for the regulation HbF expression, was also investigated. In addition, we demonstrated that oral administration of 13a can ameliorate anemia and the related symptoms in SCD mice. The results of this study suggest that 13a can be further developed as a novel agent for treating hemoglobinopathies, such as β-thalassemia and SCD.
    日期: 2021-01
    關聯: European Journal of Medicinal Chemistry. 2021 Jan;209:Article number 112938.
    Link to: http://dx.doi.org/10.1016/j.ejmech.2020.112938
    JIF/Ranking 2023: http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=0223-5234&DestApp=IC2JCR
    Cited Times(WOS): https://www.webofscience.com/wos/woscc/full-record/WOS:000600418500070
    Cited Times(Scopus): https://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=85093985022
    顯示於類別:[蔣維棠] 期刊論文
    [陳炯東] 期刊論文
    [葉燈光] 期刊論文

    文件中的檔案:

    檔案 描述 大小格式瀏覽次數
    SCP85093985022.pdf1811KbAdobe PDF321檢視/開啟


    在NHRI中所有的資料項目都受到原著作權保護.

    TAIR相關文章

    DSpace Software Copyright © 2002-2004  MIT &  Hewlett-Packard  /   Enhanced by   NTU Library IR team Copyright ©   - 回饋