Molecular and Cellular Therapeutics, Royal College of Surgeons in Ireland, 123 St Stephens Green, Dublin 2, Ireland.
Nat Rev Drug Discov. 2010 Oct;9(10):804-20. doi: 10.1038/nrd3266.
The integrins are a large family of cell adhesion molecules that are essential for the regulation of cell growth and function. The identification of key roles for integrins in a diverse range of diseases, including cancer, infection, thrombosis and autoimmune disorders, has revealed their substantial potential as therapeutic targets. However, so far, pharmacological inhibitors for only three integrins have received marketing approval. This article discusses the structure and function of integrins, their roles in disease and the chequered history of the approved integrin antagonists. Recent advances in the understanding of integrin function, ligand interaction and signalling pathways suggest novel strategies for inhibiting integrin function that could help harness their full potential as therapeutic targets.
整合素是一大类细胞黏附分子,对于细胞生长和功能的调节至关重要。整合素在多种疾病(包括癌症、感染、血栓形成和自身免疫性疾病)中的关键作用已被确定,这揭示了它们作为治疗靶点的巨大潜力。然而,到目前为止,只有三种整合素的药理学抑制剂获得了上市批准。本文讨论了整合素的结构和功能、它们在疾病中的作用以及已批准的整合素拮抗剂的曲折历史。对整合素功能、配体相互作用和信号通路的理解的最新进展表明,抑制整合素功能的新策略可能有助于充分发挥其作为治疗靶点的潜力。