188宝金博页面版

  • 图案背景
  • 纯色背景
视图
标记
批注
批注本地保存成功，开通会员云端永久保存 去开通
sa3300049

上传于：2015-12-08

粉丝量：8

该文档贡献者很忙，什么也没留下。


  • 相关
  • 目录
  • 笔记
  • 书签

188宝金博页面版:更多相关文档

  • 高中学生自我规划能力培养研究 - 高中课程网

    星级： 2 页

  • Efficient synthesis of (2R,3S)- and (2S,3S)-2-amino-1,3,4-butanetriols through stereodivergent hydroxymethylation of d-glycerald

    星级： 4 页

  • An efficient synthesis of N-protected threo (2R,3S)-3-amino-1,2-epoxy phenylbutane

    星级： 4 页

  • An expeditious synthesis of (2R,3S)-3-tert-butoxycarbonylamino-1-isobutylamino-4-phenyl-2-butanol, a key building block of HIV p

    星级： 2 页

  • n-(2-amino-phenyl-sulfonyl)-n-(2-nitro-phenyl-sulfonyl)methylamine are

    星级： 10 页

  • Separation of 4-N,N-dimethylaminoazobenzene-4′-sulfonyl amino acids on polyamide sheets

    星级： 3 页

  • (2R,3S,4R)-3,4-Isopropyl-idenedi-oxy-2-(phenyl-sulfonyl-meth-yl)pyrrolidin-1-ol

    星级： 17 页

  • Study on fluorination-toxicity relationships. Syntheses of 1-N-[(2R,3R)- and (2R,3S)-4-amino-3-fluoro-2-hydroxybutanoyl] derivat

    星级： 20 页

  • N-[(3-Phenyl-sulfanyl-1-phenyl-sulfonyl-1H-indol-2-yl)meth-yl]propionamide

    星级： 11 页

暂无目录

点击鼠标右键菜单,创建目录

    暂无笔记

    选择文本，点击鼠标右键菜单，添加笔记

    暂无书签

    在左侧文档中，点击鼠标右键，添加书签

    188宝金博页面版: Characterization of (2R, 3S)-2-({[4-(2-butynyloxy)phenyl]sulfonyl}amino)-N,3-dihydroxybutanamide, a potent and selective inhibit

    下载积分： 3000

    内容提示： Characterization of (2R, 3S)-2-({[4-(2-butynyloxy)phenyl]sulfonyl}amino)-N,3-dihydroxybutanamide, a potent andselective inhibitor of TNF-a converting enzymeYuhua Zhang a, * , Martin Hegen a , Jun Xu b , James C. Keith Jr. a , Guixian Jin b ,Xuemei Du b , Terri Cummons b , Barbara J. Sheppard a , LinHong Sun a , Yi Zhu a ,Vikram R. Rao a , Qin Wang a , Weixin Xu a , Rebecca Cowling b ,Cheryl L. Nickerson-Nutter a , Jay Gibbons b , Jerry Skotnicki b ,Lih-Ling Lin a , Jeremy Levin ba Department of Inflammatio...

    文档格式：PDF | 页数：13 | 浏览次数：18 | 上传日期：2015-12-08 10:46:43 | 文档星级：
    Characterization of (2R, 3S)-2-({[4-(2-butynyloxy)phenyl]sulfonyl}amino)-N,3-dihydroxybutanamide, a potent andselective inhibitor of TNF-a converting enzymeYuhua Zhang a, * , Martin Hegen a , Jun Xu b , James C. Keith Jr. a , Guixian Jin b ,Xuemei Du b , Terri Cummons b , Barbara J. Sheppard a , LinHong Sun a , Yi Zhu a ,Vikram R. Rao a , Qin Wang a , Weixin Xu a , Rebecca Cowling b ,Cheryl L. Nickerson-Nutter a , Jay Gibbons b , Jerry Skotnicki b ,Lih-Ling Lin a , Jeremy Levin ba Department of Inflammation, Wyeth Research, 200 Cambridge Park Drive, Cambridge, MA 02140, USAb Wyeth Research, Pearl River, NY 10965, USAReceived 2 June 2004; received in revised form 13 August 2004; accepted 13 August 2004AbstractTNF-a converting enzyme (TACE) is a validated therapeutic target for the development of oral tumor necrosis factor-a(TNF-a) inhibitors. Here we report the pre-clinical results and characterization of a selective and potent TACE inhibitor, (2R,3S)-2-({[4-(2-butynyloxy)phenyl]sulfonyl}amino)-N,3-dihydroxybutanamide (TMI-2), in various in vitro and in vivo assays.TMI-2 is a potent TACE inhibitor in an enzymatic FRET assay (IC50=2 nM). It is more than 250-fold selective over MMP-1, -7, -9, -14, and ADAM-10 in vitro. In cell-based assays and human whole blood, TMI-2 inhibits lipopolysaccharide (LPS)-induced TNF secretion with IC50sb1 uM. Importantly, TMI-2 inhibits the spontaneous release of TNF-a in human synoviumtissue explants of rheumatoid arthritis patients with an IC50 of 0.8 AM. In vivo, TMI-2 potently inhibits LPS-induced TNF-aproduction in mice (ED50=3 mg/kg). In the adjuvant-induced arthritis (AIA) model in rats, treatment with TMI-2 at 30 mg/kgand 100 mg/kg p.o. b.i.d. was highly effective in reducing joint arthritis scores. In a semi-therapeutic collagen-induced arthritis(CIA) model in mice, TMI-2 is highly effective in reducing disease severity scores after oral treatment at 100 mg/kg twice perday. In summary, TMI-2 is a potent and selective TACE inhibitor that inhibits TNF-a production and reduces the arthritis scoresin pre-clinical models. TMI-2 represents a novel class of TACE inhibitors that may be effective and beneficial in the treatmentof rheumatoid arthritis as well as other TNF-mediated inflammatory autoimmune diseases.D 2004 Elsevier B.V. All rights reserved.Keywords: TNF; Selective TACE inhibitor; TMI-2; Rheumatoid arthritis1567-5769/$ - see front matter D 2004 Elsevier B.V. All rights reserved.doi:10.1016/j.intimp.2004.08.003* Corresponding author. Tel.: +1 617 665 5421; fax: +1 617 665 5499.E-mail address: yzhang@wyeth.com (Y. Zhang).International Immunopharmacology 4 (2004) 1845–1857www.elsevier.com/locate/intimp

    阅读了该文档的用户还阅读了这些文档

    188宝金博页面版:关于我们

    188宝金博页面版:帮助中心

    188宝金博页面版:关注我们

    • 新浪微博

    关注188宝金博页面版公众号

    188宝金博页面版
    阅读
    APP
    阅读
    返回
    顶部
    188宝金博页面版官网登录在线平台入口（2026已更新）—江苏协昌电子科技股份有限公司