Vanderslice Peter, Woodside Darren G
Encysive Pharmaceuticals, Department of Drug Discovery, Biological Sciences, 7000 Fannin, 19th Floor, Houston, TX 77030, USA.
Expert Opin Investig Drugs. 2006 Oct;15(10):1235-55. doi: 10.1517/13543784.15.10.1235.
Integrins are a family of heterodimeric cell surface receptors that mediate adhesion events crucial to cellular migration, proliferation and activation. Although critical to a normal immune response, integrins can also facilitate the progression of many inflammatory and autoimmune disorders. As such, they have attracted the attention of the pharmaceutical industry. Several humanised monoclonal antibodies directed against integrin targets have proven to be successful in clinical trials and have been approved for use in humans. This has not only resulted in effective therapies for patients, but also has provided important proof-of-concept studies for the development of small-molecule antagonists. This review focuses on those integrin subclasses that are being evaluated for their potential role in pulmonary, dermatological, gastrointestinal or rheumatic diseases. These include the alpha4 and beta2 integrins, as well as an emerging group of targets from the collagen-binding family of integrins. Interfering with integrin signalling pathways represents a future area of interest. The rationale for pursuing these targets, as well as the drugs presently under development, are discussed.
整合素是一类异二聚体细胞表面受体家族，介导对细胞迁移、增殖和激活至关重要的黏附事件。尽管对正常免疫反应至关重要，但整合素也可促进许多炎症和自身免疫性疾病的进展。因此，它们引起了制药行业的关注。几种针对整合素靶点的人源化单克隆抗体已在临床试验中证明是成功的，并已被批准用于人类。这不仅为患者带来了有效的治疗方法，也为小分子拮抗剂的开发提供了重要的概念验证研究。本综述重点关注那些正在评估其在肺部、皮肤病学、胃肠道或风湿性疾病中潜在作用的整合素亚类。这些包括α4和β2整合素，以及整合素胶原结合家族中一组新兴的靶点。干扰整合素信号通路是未来一个感兴趣的领域。本文讨论了研究这些靶点的基本原理以及目前正在开发的药物。
