What is the future of CCR5 antagonists in rheumatoid arthritis?

被引:8
|
作者
Takeuchi, Tsutomu [1 ]
Kameda, Hideto [1 ]
机构
[1] Keio Univ, Div Rheumatol, Dept Internal Med, Sch Med,Shinjyu Ku, Toky 1608582, Japan
关键词
DOUBLE-BLIND; CHEMOKINE; RECEPTORS; BLOCKADE; TRIAL;
D O I
10.1186/ar3775
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Fleishaker and colleagues reported on a double-blind placebo controlled clinical trial of a C-C chemokine-receptor type 5 (CCR5) antagonist, maraviroc, in rheumatoid arthritis (RA) patients with inadequate response to methotrexate, showing that it was ineffective. Two additional CCR5 antagonists, SCH351125 and AZD5672, also failed to demonstrate clinical efficacy. In addition, CCR5-blocking antibodies could not inhibit synovial fluid-induced monocyte chemotaxis. Thus, CCR5 appears not to be a desirable target in RA treatment. Given the multiple functions of CCR5, redundancies in the chemokine system, and patient selection in the trial, we overview the recent understanding for chemokine receptor blockade in the treatment of RA
引用
收藏
页数:2
相关论文
共 50 条
  • [41] The CCR5 32bp deletion protects against rheumatoid arthritis susceptibility.
    Pokorny, V
    McLean, L
    McQueen, F
    Merriman, T
    Yeoman, S
    ARTHRITIS AND RHEUMATISM, 2002, 46 (09): : S265 - S265
  • [42] Discovery of CCR5 antagonists containing the aminoguanidine group.
    Kesicki, EA
    Odingo, JO
    Oliver, AR
    Orme, MW
    Schweickart, VL
    Epp, A
    Gray, PW
    Fowler, KW
    ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY, 2001, 221 : U19 - U19
  • [43] Advances of CCR5 antagonists: From small molecules to macromolecules
    Qi, Baowen
    Fang, Qiang
    Liu, Shiyuan
    Hou, Wenli
    Li, Jian
    Huang, Yingchun
    Shi, Jianyou
    EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY, 2020, 208
  • [44] Regulation of chemokine receptor CCR5 on CD4 T cells and MIP1α production and CCR5 gene polymorphism in rheumatoid arthritis.
    Wang, CRR
    Liu, MF
    Chen, PC
    ARTHRITIS AND RHEUMATISM, 2001, 44 (09): : S109 - S109
  • [45] Association of the CCR5 gene with juvenile idiopathic arthritis
    Hinks, A.
    Martin, P.
    Flynn, E.
    Eyre, S.
    Packham, J.
    Barton, A.
    Worthington, J.
    Thomson, W.
    GENES AND IMMUNITY, 2010, 11 (07) : 584 - 589
  • [46] The discovery of tropane-derived CCR5 receptor antagonists
    Armour, DR
    de Groot, MJ
    Price, DA
    Stammen, BLC
    Wood, A
    Perros, M
    Burt, C
    CHEMICAL BIOLOGY & DRUG DESIGN, 2006, 67 (04) : 305 - 308
  • [47] Allosteric effects of antagonists on signalling by the chemokine receptor CCR5
    Haworth, Ben
    Lin, Hong
    Fidock, Mark
    Dorr, Pat
    Strange, Philip G.
    BIOCHEMICAL PHARMACOLOGY, 2007, 74 (06) : 891 - 897
  • [48] Association of the CCR5 gene with juvenile idiopathic arthritis
    A Hinks
    P Martin
    E Flynn
    S Eyre
    J Packham
    A Barton
    J Worthington
    W Thomson
    Genes & Immunity, 2010, 11 : 584 - 589
  • [49] CCR5 cell surface density and HIV-1 envelope sequences govern antiretroviral potency of CCR5 antagonists
    Miller, MD
    Lineberger, JE
    Dornadula, G
    Danzeisen, RC
    Blau, CR
    Danovich, RM
    Miller, MA
    Finke, PE
    Oates, BD
    Caldwell, CG
    Chen, P
    Meurer, LC
    Mills, SG
    Springer, MS
    Petropoulos, CJ
    Whitcomb, J
    Huang, W
    Fransen, S
    Simon, AJ
    Hazuda, DJ
    ANTIVIRAL THERAPY, 2003, 8 (03) : U66 - U67
  • [50] Primary genotypic resistance of HIV-1 to CCR5 antagonists in CCR5 antagonist treatment-naive patients
    Soulie, Cathia
    Malet, Isabelle
    Lambert-Niclot, Sidonie
    Tubiana, Roland
    Thevenin, Monique
    Simon, Anne
    Murphy, Robert
    Katlama, Christine
    Calvez, Vincent
    Marcelin, Anne-Genevieve
    AIDS, 2008, 22 (16) : 2212 - 2214