National Institute of Chemistry, Ljubljana, Slovenia.
Curr Med Chem. 2010;17(22):2371-92. doi: 10.2174/092986710791698558.
The complex and widespread family of integrin receptors is involved in numerous physiological processes, such as tissue remodeling, angiogenesis, development of the immune response and homeostasis. In addition, their key role has been elucidated in important pathological disorders such as cancer, cardiovascular diseases, osteoporosis, autoimmune and inflammatory diseases and in the pathogenesis of infectious diseases, making them highly important targets for modern drug design campaigns. In this review we seek to present a concise overview of the small molecule antagonists of this diverse and highly complex receptor family. Integrin antagonists are classified according to the targeted integrin receptor and are discussed in four sections. First we present the fibrinogen alpha(IIb)beta3 and the vitronectin alpha (V)beta(3) receptor antagonists. The remaining selective integrin antagonists are examined in the third section. The final section is dedicated to molecules with dual or multiple integrin activity. In addition, the use of antibodies and peptidomimetic approaches to modulate the integrin receptors are discussed, as well providing the reader with an overall appreciation of the field.
整合素受体家族复杂且广泛,参与多种生理过程,如组织重塑、血管生成、免疫反应和内稳态的发展。此外,它们在癌症、心血管疾病、骨质疏松症、自身免疫和炎症性疾病等重要病理紊乱以及传染病的发病机制中的关键作用已经阐明,使它们成为现代药物设计活动的重要目标。在这篇综述中,我们试图对这个多样化且高度复杂的受体家族的小分子拮抗剂进行简洁概述。整合素拮抗剂根据靶向整合素受体进行分类,并分为四个部分进行讨论。首先,我们介绍纤维蛋白原α(IIb)β3 和 vitronectin α(V)β(3)受体拮抗剂。其余选择性整合素拮抗剂在第三部分进行检查。最后一部分专门讨论具有双重或多重整合素活性的分子。此外,还讨论了使用抗体和肽模拟物来调节整合素受体的方法,使读者对该领域有一个全面的了解。