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抗整合素作为新型药物研发靶点:潜在的治疗和诊断意义。

Anti-integrin as novel drug-discovery targets: potential therapeutic and diagnostic implications.

作者信息

Mousa Shaker A

机构信息

Albany College of Pharmacy, 106 New Scotland Avenue, Albany, NY 12208-3492, USA.

出版信息

Curr Opin Chem Biol. 2002 Aug;6(4):534-41. doi: 10.1016/s1367-5931(02)00350-2.

Abstract

The role of integrin and extracellular matrix proteins in various pathological processes (including angiogenesis, thrombosis, apoptosis and cell migration and proliferation), leading to both acute and chronic disease states (e.g. ocular diseases, metastasis, unstable angina, myocardial infarction, stroke, osteoporosis, a wide range of inflammatory diseases, vascular remodeling and neurodegenerative disorders) has been recently documented. A key success in this field is evident from the potential role of the platelet GPIIb/IIIa (alphaIIbbeta3) integrin in the prevention, treatment and perhaps diagnosis of various thromboembolic disorders. Additionally, progress has been shown in the development of leukocyte alpha4beta1 antagonists for various inflammatory indications and alphav integrin antagonists for angiogenesis and vascular-related disorders. However, the exact modes of action of certain integrin antagonists are still not fully clear. Integrin antagonists in clinical or pre-clinical development are expected to be used as a stand-alone therapy or, better, as an adjunct to other pharmacotherapy, radiotherapy or interventional procedures.

摘要

整合素和细胞外基质蛋白在各种病理过程(包括血管生成、血栓形成、细胞凋亡以及细胞迁移和增殖)中所起的作用,这些病理过程会导致急性和慢性疾病状态(如眼部疾病、转移、不稳定型心绞痛、心肌梗死、中风、骨质疏松症、多种炎症性疾病、血管重塑和神经退行性疾病),最近已有文献记载。血小板糖蛋白IIb/IIIa(αIIbβ3)整合素在预防、治疗以及或许还可用于诊断各种血栓栓塞性疾病方面的潜在作用,明显体现了该领域的一项重大成果。此外,在开发用于各种炎症适应症的白细胞α4β1拮抗剂以及用于血管生成和血管相关疾病的αv整合素拮抗剂方面也已取得进展。然而,某些整合素拮抗剂的确切作用方式仍不完全清楚。处于临床或临床前开发阶段的整合素拮抗剂有望作为单一疗法使用,或者更好的是,作为其他药物治疗、放射治疗或介入程序的辅助药物使用。

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