Integrin-based therapeutics: biological basis, clinical use and new drugs
Integrin-based therapeutics: biological basis, clinical use and new drugs
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DOI：
10.1038/nrd.2015.10
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发表时间：
2016-03-01
影响因子：
120.1
通讯作者：
Shattil, Sanford
中科院分区：
文献类型：
--
作者：
Ley, Klaus;Rivera-Nieves, Jesus;Shattil, Sanford
整合素是参与粘附和信号传导的可激活分子。在 24 种已知的人类整合素中，有 3 种目前是单克隆抗体、肽或小分子的治疗靶标：针对血小板 α IIb β 3 整合素的药物用于预防经皮冠状动脉介入治疗后的血栓形成并发症，而针对淋巴细胞 α 4 β 1 和 α 4 β 7 整合素的化合物可用于治疗多发性硬化症和炎症性肠病。针对 β 7 整合素（α 4 β 7 和 α E β 7 整合素）及其配体的新抗体和小分子正在临床开发中，用于治疗炎症性肠病。基于整合素的疗法已在许多患者中显示出临床上显着的益处，引起医学界对进一步开发新型整合素抑制剂的持续兴趣。值得注意的是，几乎所有正在使用或处于后期临床试验中的整合素拮抗剂都靶向配体结合位点或配体本身。
Integrins are activatable molecules that are involved in adhesion and signalling. Of the 24 known human integrins, 3 are currently targeted therapeutically by monoclonal antibodies, peptides or small molecules: drugs targeting the platelet alpha IIb beta 3 integrin are used to prevent thrombotic complications after percutaneous coronary interventions, and compounds targeting the lymphocyte alpha 4 beta 1 and alpha 4 beta 7 integrins have indications in multiple sclerosis and inflammatory bowel disease. New antibodies and small molecules targeting beta 7 integrins (alpha 4 beta 7 and alpha E beta 7 integrins) and their ligands are in clinical development for the treatment of inflammatory bowel diseases. Integrin-based therapeutics have shown clinically significant benefits in many patients, leading to continued medical interest in the further development of novel integrin inhibitors. Of note, almost all integrin antagonists in use or in late-stage clinical trials target either the ligand-binding site or the ligand itself.