• 文献检索
  • 文档翻译
  • 深度研究
  • 学术资讯
  • Suppr Zotero 插件Zotero 插件
  • 邀请有礼
  • 套餐&价格
  • 历史记录
应用&插件
Suppr Zotero 插件Zotero 插件浏览器插件Mac 客户端Windows 客户端微信小程序
定价
高级版会员购买积分包购买API积分包
服务
文献检索文档翻译深度研究API 文档MCP 服务
关于我们
关于 Suppr公司介绍联系我们用户协议隐私条款
关注我们

Suppr 超能文献

核心技术专利：CN118964589B侵权必究
粤ICP备2023148730 号-1Suppr @ 2026

文献检索

告别复杂PubMed语法，用中文像聊天一样搜索，搜遍4000万医学文献。AI智能推荐，让科研检索更轻松。

立即免费搜索

文件翻译

保留排版，准确专业，支持PDF/Word/PPT等文件格式，支持 12+语言互译。

免费翻译文档

深度研究

AI帮你快速写综述，25分钟生成高质量综述，智能提取关键信息，辅助科研写作。

立即免费体验

奥洛珠单抗的发现与特性：一种靶向白细胞介素-6并中和gp130信号传导的人源化抗体

Discovery and characterization of olokizumab: a humanized antibody targeting interleukin-6 and neutralizing gp130-signaling.

作者信息

Shaw Stevan, Bourne Tim, Meier Chris, Carrington Bruce, Gelinas Rich, Henry Alistair, Popplewell Andrew, Adams Ralph, Baker Terry, Rapecki Steve, Marshall Diane, Moore Adrian, Neale Helen, Lawson Alastair

机构信息

UCB Pharma; Berkshire, UK.

Institute for Systems Biology; Seattle, WA USA.

出版信息

MAbs. 2014 May-Jun;6(3):774-82. doi: 10.4161/mabs.28612. Epub 2014 Apr 2.

DOI:10.4161/mabs.28612
PMID:24670876
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC4011921/
Abstract

Interleukin-6 (IL-6) is a critical regulator of the immune system and has been widely implicated in autoimmune disease. Here, we describe the discovery and characterization of olokizumab, a humanized antibody to IL-6. Data from structural biology, cell biology and primate pharmacology demonstrate the therapeutic potential of targeting IL-6 at "Site 3", blocking the interaction with the signaling co-receptor gp130.

摘要

白细胞介素-6（IL-6）是免疫系统的关键调节因子，在自身免疫性疾病中具有广泛影响。在此，我们描述了olokizumab（一种抗IL-6的人源化抗体）的发现及特性。来自结构生物学、细胞生物学和灵长类动物药理学的数据证明了在“位点3”靶向IL-6、阻断其与信号共受体gp130相互作用的治疗潜力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4a55/4011921/3819a2d68d92/mabs-6-773-g5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4a55/4011921/a22ef6056236/mabs-6-773-g1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4a55/4011921/0e9fca8a1ca6/mabs-6-773-g2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4a55/4011921/db7119ac4ada/mabs-6-773-g3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4a55/4011921/368ffaa1b992/mabs-6-773-g4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4a55/4011921/3819a2d68d92/mabs-6-773-g5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4a55/4011921/a22ef6056236/mabs-6-773-g1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4a55/4011921/0e9fca8a1ca6/mabs-6-773-g2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4a55/4011921/db7119ac4ada/mabs-6-773-g3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4a55/4011921/368ffaa1b992/mabs-6-773-g4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4a55/4011921/3819a2d68d92/mabs-6-773-g5.jpg

相似文献

1
Discovery and characterization of olokizumab: a humanized antibody targeting interleukin-6 and neutralizing gp130-signaling.奥洛珠单抗的发现与特性：一种靶向白细胞介素-6并中和gp130信号传导的人源化抗体
MAbs. 2014 May-Jun;6(3):774-82. doi: 10.4161/mabs.28612. Epub 2014 Apr 2.
2
Structural basis of clade-specific HIV-1 neutralization by humanized anti-V3 monoclonal antibody KD-247.人源化抗V3单克隆抗体KD-247对特定进化枝HIV-1中和作用的结构基础
FASEB J. 2015 Jan;29(1):70-80. doi: 10.1096/fj.14-252262. Epub 2014 Oct 28.
3
Probing binding mechanism of interleukin-6 and olokizumab: in silico design of potential lead antibodies for autoimmune and inflammatory diseases.探究白细胞介素-6与奥洛珠单抗的结合机制：针对自身免疫性和炎性疾病的潜在先导抗体的计算机辅助设计
J Recept Signal Transduct Res. 2016 Dec;36(6):601-616. doi: 10.3109/10799893.2016.1147584. Epub 2016 Mar 16.
4
Structural Determination of the Broadly Reactive Anti-IGHV1-69 Anti-idiotypic Antibody G6 and Its Idiotope.广泛反应性抗 IGHV1-69 抗独特型抗体 G6 及其独特型的结构测定。
Cell Rep. 2017 Dec 12;21(11):3243-3255. doi: 10.1016/j.celrep.2017.11.056.
5
One target-two different binding modes: structural insights into gevokizumab and canakinumab interactions to interleukin-1β.一个靶点两种不同结合模式：对 gevokizumab 和 canakinumab 与白细胞介素-1β相互作用的结构见解。
J Mol Biol. 2013 Jan 9;425(1):94-111. doi: 10.1016/j.jmb.2012.09.021. Epub 2012 Oct 3.
6
Synthetic mimetics of the gp130 binding site for viral interleukin-6 as inhibitors of the vIL-6-gp130 interaction.作为病毒白细胞介素-6与gp130相互作用抑制剂的病毒白细胞介素-6的gp130结合位点的合成模拟物。
Chem Biol Drug Des. 2008 May;71(5):494-500. doi: 10.1111/j.1747-0285.2008.00649.x. Epub 2008 Mar 25.
7
Conformational heterogeneity in antibody-protein antigen recognition: implications for high affinity protein complex formation.抗体-蛋白质抗原识别中的构象异质性：对高亲和力蛋白质复合物形成的影响。
J Biol Chem. 2014 Mar 7;289(10):7200-7210. doi: 10.1074/jbc.M113.492215. Epub 2014 Jan 16.
8
Identification and grafting of a unique peptide-binding site in the Fab framework of monoclonal antibodies.鉴定和嫁接单克隆抗体 Fab 框架中的独特肽结合位点。
Proc Natl Acad Sci U S A. 2013 Oct 22;110(43):17456-61. doi: 10.1073/pnas.1307309110. Epub 2013 Oct 7.
9
VEGF and the Fab fragment of a humanized neutralizing antibody: crystal structure of the complex at 2.4 A resolution and mutational analysis of the interface.血管内皮生长因子（VEGF）与人源化中和抗体的Fab片段：复合物的2.4埃分辨率晶体结构及界面的突变分析
Structure. 1998 Sep 15;6(9):1153-67. doi: 10.1016/s0969-2126(98)00116-6.
10
Therapeutic strategies for the clinical blockade of IL-6/gp130 signaling.阻断白细胞介素 6/糖蛋白 130 信号转导的治疗策略。
J Clin Invest. 2011 Sep;121(9):3375-83. doi: 10.1172/JCI57158. Epub 2011 Sep 1.

引用本文的文献

1
Deep Learning of Proteins with Local and Global Regions of Disorder.具有局部和全局无序区域的蛋白质的深度学习
ArXiv. 2025 Mar 29:arXiv:2502.11326v2.
2
Targeting inerleukin-6 for renoprotection.以白细胞介素-6为靶点实现肾脏保护。
Front Immunol. 2024 Dec 11;15:1502299. doi: 10.3389/fimmu.2024.1502299. eCollection 2024.
3
Advancing therapeutic frontiers: a pipeline of novel drugs for luminal and perianal Crohn's disease management.推进治疗前沿：用于治疗回肠和肛周克罗恩病的新型药物研发进程

本文引用的文献

1
Sarilumab, a fully human monoclonal antibody against IL-6Rα in patients with rheumatoid arthritis and an inadequate response to methotrexate: efficacy and safety results from the randomised SARIL-RA-MOBILITY Part A trial.沙利鲁单抗，一种针对类风湿关节炎患者 IL-6Rα 的全人源单克隆抗体，对甲氨蝶呤应答不足：来自随机 SARIL-RA-MOBILITY Part A 试验的疗效和安全性结果。
Ann Rheum Dis. 2014 Sep;73(9):1626-34. doi: 10.1136/annrheumdis-2013-204405. Epub 2013 Dec 2.
2
A randomised, double-blind, parallel-group study of the safety and efficacy of subcutaneous tocilizumab versus intravenous tocilizumab in combination with traditional disease-modifying antirheumatic drugs in patients with moderate to severe rheumatoid arthritis (SUMMACTA study).托珠单抗皮下注射与静脉注射联合传统改善病情抗风湿药物治疗中重度类风湿关节炎的安全性和有效性的随机、双盲、平行分组研究（SUMMACTA 研究）。
Ann Rheum Dis. 2014 Jan;73(1):69-74. doi: 10.1136/annrheumdis-2013-203523. Epub 2013 Jul 31.
Therap Adv Gastroenterol. 2024 Dec 19;17:17562848241303651. doi: 10.1177/17562848241303651. eCollection 2024.
4
Monoclonal antibodies: From magic bullet to precision weapon.单克隆抗体：从“魔弹”到“精准武器”。
Mol Biomed. 2024 Oct 11;5(1):47. doi: 10.1186/s43556-024-00210-1.
5
CytoSIP: an annotated structural atlas for interactions involving cytokines or cytokine receptors.细胞 SIP：一个注释的结构图谱，用于涉及细胞因子或细胞因子受体的相互作用。
Commun Biol. 2024 May 24;7(1):630. doi: 10.1038/s42003-024-06289-0.
6
Novel and potential future therapeutic options in systemic autoimmune diseases.系统性自身免疫性疾病的新型和潜在未来治疗选择。
Front Immunol. 2024 Mar 15;15:1249500. doi: 10.3389/fimmu.2024.1249500. eCollection 2024.
7
The role of inflammation in autoimmune disease: a therapeutic target.炎症在自身免疫性疾病中的作用：一个治疗靶点。
Front Immunol. 2023 Oct 4;14:1267091. doi: 10.3389/fimmu.2023.1267091. eCollection 2023.
8
Characterization of HZ0412a, a novel potent humanized anti-IL-6 receptor antibody that blocks IL-6R binding to gp130.HZ0412a的特性研究，HZ0412a是一种新型强效人源化抗IL-6受体抗体，可阻断IL-6R与gp130的结合。
Antib Ther. 2023 May 11;6(2):119-126. doi: 10.1093/abt/tbad008. eCollection 2023 Apr.
9
New Targets and Strategies for Rheumatoid Arthritis: From Signal Transduction to Epigenetic Aspect.类风湿关节炎的新靶点和策略：从信号转导到表观遗传方面。
Biomolecules. 2023 Apr 28;13(5):766. doi: 10.3390/biom13050766.
10
The efficacy and safety of olokizumab for rheumatoid arthritis: a systematic review, pairwise, and network meta-analysis.奥洛昔单抗治疗类风湿关节炎的疗效和安全性：系统评价、成对和网络荟萃分析。
Clin Rheumatol. 2023 Jun;42(6):1503-1520. doi: 10.1007/s10067-023-06519-6. Epub 2023 Feb 16.
3
IL-6 trans-signaling via the soluble IL-6 receptor: importance for the pro-inflammatory activities of IL-6.白细胞介素 6 转导信号通过可溶性白细胞介素 6 受体：对白细胞介素 6 促炎活性的重要性。
Int J Biol Sci. 2012;8(9):1237-47. doi: 10.7150/ijbs.4989. Epub 2012 Oct 24.
4
A systematic comparison of free and bound antibodies reveals binding-related conformational changes.系统比较游离抗体和结合抗体揭示了与结合相关的构象变化。
J Immunol. 2012 Nov 15;189(10):4890-9. doi: 10.4049/jimmunol.1201493. Epub 2012 Oct 12.
5
Conservation of functional sites on interleukin-6 and implications for evolution of signaling complex assembly and therapeutic intervention.白细胞介素-6 功能位点的保守性及其对信号复合物组装进化和治疗干预的意义。
J Biol Chem. 2012 Nov 16;287(47):40043-50. doi: 10.1074/jbc.M112.405597. Epub 2012 Oct 1.
6
Evolving molecular targets in the treatment of nonmalignant gastrointestinal diseases.非恶性胃肠道疾病治疗中不断发展的分子靶点。
Clin Pharmacol Ther. 2012 Sep;92(3):306-20. doi: 10.1038/clpt.2012.77. Epub 2012 Jul 25.
7
Identifying bottlenecks in transient and stable production of recombinant monoclonal-antibody sequence variants in Chinese hamster ovary cells.鉴定中国仓鼠卵巢细胞中瞬时和稳定生产重组单克隆抗体序列变异体的瓶颈。
Biotechnol Prog. 2012 May-Jun;28(3):846-55. doi: 10.1002/btpr.1542. Epub 2012 May 21.
8
A phase II, double-blind, randomised, placebo-controlled study of BMS945429 (ALD518) in patients with rheumatoid arthritis with an inadequate response to methotrexate.一项评估 BMS945429（ALD518）在甲氨蝶呤治疗应答不足的类风湿关节炎患者中的 II 期、双盲、随机、安慰剂对照研究。
Ann Rheum Dis. 2012 Jul;71(7):1183-9. doi: 10.1136/annrheumdis-2011-200704. Epub 2012 Feb 10.
9
Tocilizumab for the treatment of rheumatoid arthritis and other systemic autoimmune diseases: current perspectives and future directions.托珠单抗治疗类风湿关节炎及其他全身性自身免疫性疾病：当前观点与未来方向
Int J Rheumatol. 2012;2012:946048. doi: 10.1155/2012/946048. Epub 2012 Jan 18.
10
Randomised phase II study of siltuximab (CNTO 328), an anti-IL-6 monoclonal antibody, in combination with mitoxantrone/prednisone versus mitoxantrone/prednisone alone in metastatic castration-resistant prostate cancer.随机 II 期研究表明，西妥昔单抗（CNTO 328），一种抗白细胞介素-6 的单克隆抗体，与米托蒽醌/泼尼松联合应用于转移性去势抵抗性前列腺癌，优于米托蒽醌/泼尼松单独应用。
Eur J Cancer. 2012 Jan;48(1):85-93. doi: 10.1016/j.ejca.2011.10.014. Epub 2011 Nov 28.