CCR5 拮抗剂在类风湿关节炎中的未来前景如何？
What is the future of CCR5 antagonists in rheumatoid arthritis?
出版信息
Arthritis Res Ther. 2012 Mar 30;14(2):114. doi: 10.1186/ar3775.
Abstract
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
摘要
弗莱沙克及其同事报告了一项关于 C-C 趋化因子受体 5（CCR5）拮抗剂马拉维若治疗对甲氨蝶呤反应不足的类风湿关节炎（RA）患者的双盲安慰剂对照临床试验，结果显示其无效。另外两种 CCR5 拮抗剂，SCH351125 和 AZD5672，也未能显示临床疗效。此外，CCR5 阻断抗体不能抑制滑液诱导的单核细胞趋化。因此，CCR5 似乎不是 RA 治疗的理想靶点。鉴于 CCR5 的多种功能、趋化因子系统的冗余性以及试验中的患者选择，我们综述了趋化因子受体阻断在 RA 治疗中的最新认识。
相似文献
1
What is the future of CCR5 antagonists in rheumatoid arthritis?CCR5 拮抗剂在类风湿关节炎中的未来前景如何？
Arthritis Res Ther. 2012 Mar 30;14(2):114. doi: 10.1186/ar3775.
2
Maraviroc, a chemokine receptor-5 antagonist, fails to demonstrate efficacy in the treatment of patients with rheumatoid arthritis in a randomized, double-blind placebo-controlled trial.马拉维若，一种趋化因子受体-5 拮抗剂，在一项随机、双盲安慰剂对照试验中未能显示出治疗类风湿关节炎患者的疗效。
Arthritis Res Ther. 2012 Jan 17;14(1):R11. doi: 10.1186/ar3685.
3
Maraviroc, a chemokine CCR5 receptor antagonist for the treatment of HIV infection and AIDS.马拉维若，一种用于治疗HIV感染和艾滋病的趋化因子CCR5受体拮抗剂。
Curr Opin Investig Drugs. 2007 Aug;8(8):669-81.
4
Off-label use of maraviroc in clinical practice.马拉维若在临床实践中的超说明书用药。
Expert Rev Anti Infect Ther. 2016;14(1):5-8. doi: 10.1586/14787210.2016.1100535. Epub 2015 Oct 28.
5
CCR5 antagonism in HIV infection: current concepts and future opportunities.HIV 感染中的 CCR5 拮抗作用：当前概念和未来机遇。
Annu Rev Med. 2012;63:81-93. doi: 10.1146/annurev-med-052010-145454. Epub 2011 Oct 27.
6
Therapeutic use of CCR5 antagonists is supported by strong expression of CCR5 on CD8(+) T cells in progressive multifocal leukoencephalopathy-associated immune reconstitution inflammatory syndrome.在进行性多灶性白质脑病相关免疫重建炎症综合征中，CCR5在CD8(+) T细胞上的强烈表达支持了CCR5拮抗剂的治疗应用。
Acta Neuropathol. 2015 Mar;129(3):463-5. doi: 10.1007/s00401-015-1383-6. Epub 2015 Jan 15.
7
Blockade of CCR5 to protect the liver graft in HIV/HCV co-infected patients.阻断CCR5以保护HIV/HCV合并感染患者的肝移植。
J Hepatol. 2013 Sep;59(3):613-5. doi: 10.1016/j.jhep.2013.03.034. Epub 2013 Apr 9.
8
Author's reply.作者回复。
Drug Des Devel Ther. 2016;10:355-6.
9
Novel HIV treatment approved.新型艾滋病治疗方法获批。
Am J Health Syst Pharm. 2007 Sep 15;64(18):1886. doi: 10.2146/news070079.
10
Preclinical and clinical investigation of a CCR5 antagonist, AZD5672, in patients with rheumatoid arthritis receiving methotrexate.CCR5拮抗剂AZD5672在接受甲氨蝶呤治疗的类风湿关节炎患者中的临床前和临床研究。
Arthritis Rheum. 2010 Nov;62(11):3154-60. doi: 10.1002/art.27652.
引用本文的文献
1
RNA-seq and Network Analysis Reveal Unique Chemokine Activity Signatures in the Synovial Tissue of Patients With Rheumatoid Arthritis.RNA测序与网络分析揭示类风湿关节炎患者滑膜组织中独特的趋化因子活性特征
Front Med (Lausanne). 2022 May 4;9:799440. doi: 10.3389/fmed.2022.799440. eCollection 2022.
2
Polyphenols Targeting MAPK Mediated Oxidative Stress and Inflammation in Rheumatoid Arthritis.多酚通过 MAPK 靶向治疗类风湿性关节炎中的氧化应激和炎症。
Molecules. 2021 Oct 30;26(21):6570. doi: 10.3390/molecules26216570.
3
C-C chemokine receptor type 5 links COVID-19, rheumatoid arthritis, and Hydroxychloroquine: in silico analysis.C-C趋化因子受体5型与2019冠状病毒病、类风湿性关节炎及羟氯喹的关联：计算机模拟分析
Transl Med Commun. 2020;5(1):14. doi: 10.1186/s41231-020-00066-x. Epub 2020 Sep 9.
4
Role of Chemokines and Chemokine Receptors in Rheumatoid Arthritis.趋化因子及趋化因子受体在类风湿性关节炎中的作用
Immunotargets Ther. 2020 Mar 9;9:43-56. doi: 10.2147/ITT.S243636. eCollection 2020.
5
The potential risks of C-C chemokine receptor 5-edited babies in bone development.C-C趋化因子受体5基因编辑婴儿在骨骼发育方面的潜在风险。
Bone Res. 2019 Jan 29;7:4. doi: 10.1038/s41413-019-0044-0. eCollection 2019.
6
The HIV co-receptor CCR5 regulates osteoclast function.HIV 共受体 CCR5 调节破骨细胞功能。
Nat Commun. 2017 Dec 20;8(1):2226. doi: 10.1038/s41467-017-02368-5.
7
The multiple chemokine-binding bovine herpesvirus 1 glycoprotein G (BHV1gG) inhibits polymorphonuclear cell but not monocyte migration into inflammatory sites.多重趋化因子结合型牛疱疹病毒1糖蛋白G（BHV1gG）可抑制多形核细胞向炎症部位的迁移，但不影响单核细胞的迁移。
Mol Med. 2013;19(1):276-85. doi: 10.2119/molmed.2013.00339.
本文引用的文献
1
Maraviroc, a chemokine receptor-5 antagonist, fails to demonstrate efficacy in the treatment of patients with rheumatoid arthritis in a randomized, double-blind placebo-controlled trial.马拉维若，一种趋化因子受体-5 拮抗剂，在一项随机、双盲安慰剂对照试验中未能显示出治疗类风湿关节炎患者的疗效。
Arthritis Res Ther. 2012 Jan 17;14(1):R11. doi: 10.1186/ar3685.
2
3
Why CCR2 and CCR5 blockade failed and why CCR1 blockade might still be effective in the treatment of rheumatoid arthritis.CCR2 和 CCR5 阻断为何失败，以及 CCR1 阻断在类风湿关节炎治疗中为何可能仍然有效。
PLoS One. 2011;6(7):e21772. doi: 10.1371/journal.pone.0021772. Epub 2011 Jul 1.
4
Overcoming hurdles in developing successful drugs targeting chemokine receptors.克服开发针对趋化因子受体的成功药物的障碍。
Nat Rev Immunol. 2011 May;11(5):355-63. doi: 10.1038/nri2972. Epub 2011 Apr 15.
5
Baseline tumour necrosis factor alpha levels predict the necessity for dose escalation of infliximab therapy in patients with rheumatoid arthritis.基线肿瘤坏死因子 α 水平可预测类风湿关节炎患者接受英夫利昔单抗治疗时需要增加剂量。
Ann Rheum Dis. 2011 Jul;70(7):1208-15. doi: 10.1136/ard.2011.153023. Epub 2011 Apr 8.
6
CC chemokine receptor 5 (CCR5) desensitization: cycling receptors accumulate in the trans-Golgi network.CC 趋化因子受体 5（CCR5）脱敏：循环受体在反式高尔基网络中积累。
J Biol Chem. 2010 Dec 31;285(53):41772-80. doi: 10.1074/jbc.M110.153460. Epub 2010 Nov 1.
7
CCR5 blockade in rheumatoid arthritis: a randomised, double-blind, placebo-controlled clinical trial.CCR5 阻断在类风湿关节炎中的作用：一项随机、双盲、安慰剂对照临床试验。
Ann Rheum Dis. 2010 Nov;69(11):2013-6. doi: 10.1136/ard.2010.131235. Epub 2010 Aug 6.
8
Preclinical and clinical investigation of a CCR5 antagonist, AZD5672, in patients with rheumatoid arthritis receiving methotrexate.CCR5拮抗剂AZD5672在接受甲氨蝶呤治疗的类风湿关节炎患者中的临床前和临床研究。
Arthritis Rheum. 2010 Nov;62(11):3154-60. doi: 10.1002/art.27652.
Zotero 插件