William Harvey Research Institute, Queen Mary University of London, London, UK.
Drug Discovery Biology, Actelion Pharmaceuticals Ltd, Allschwil, Switzerland.
Trends Pharmacol Sci. 2015 Nov;36(11):737-755. doi: 10.1016/j.tips.2015.07.007. Epub 2015 Nov 2.
Current medicines for the clinical management of inflammatory diseases act by inhibiting specific enzymes or antagonising specific receptors or blocking their ligands. In the past decade, a new paradigm in our understanding of the inflammatory process has emerged with the appreciation of genetic, molecular, and cellular mechanisms that are engaged to actively resolve inflammation. The 'resolution of acute inflammation' is enabled by counter-regulatory checkpoints to terminate the inflammatory reaction, promoting healing and repair. It may be possible to harness this knowledge for innovative approaches to the treatment of inflammatory pathologies. Here we discuss current translational attempts to develop agonists at proresolving targets as a strategy to rectify chronic inflammatory status. We reason this new approach will lead to the identification of better drugs that will establish a new branch of pharmacology, 'resolution pharmacology'.
目前用于炎症性疾病临床治疗的药物通过抑制特定的酶或拮抗特定的受体或阻断其配体来发挥作用。在过去的十年中,随着对参与积极解决炎症的遗传、分子和细胞机制的认识的深入,我们对炎症过程的理解出现了一个新的范例。“急性炎症的消退”是通过抑制炎症反应的负反馈调节点来实现的,从而促进愈合和修复。我们有可能利用这方面的知识,为治疗炎症性病变的创新方法提供支持。在这里,我们讨论了目前尝试开发促解决靶点激动剂的转化研究,以作为纠正慢性炎症状态的一种策略。我们认为这种新方法将有助于发现更好的药物,并为药理学开辟一个新的分支,即“解决药理学”。