Corminboeuf Olivier, Leroy Xavier
Actelion Pharmaceuticals Ltd. , Gewerbestrasse 16, CH-4123 Allschwil, Switzerland.
J Med Chem. 2015 Jan 22;58(2):537-59. doi: 10.1021/jm501051x. Epub 2014 Nov 3.
The resolution of inflammation (RoI), once believed to be a passive process, has lately been shown to be an active and delicately orchestrated process. During the resolution phase of acute inflammation, novel mediators, including lipoxins and resolvins, which are members of the specialized pro-resolving mediators of inflammation, are produced. FPR2/ALXR, a receptor modulated by some of these lipids as well as by peptides (e.g., annexin A1), has been shown to be one of the receptors involved in the RoI. The aim of this perspective is to present the concept of the RoI from a medicinal chemistry point of view and to highlight the effort of the research community to discover and develop anti-inflammatory/pro-resolution small molecules to orchestrate inflammation by activation of FPR2/ALXR.
炎症消退(RoI)曾被认为是一个被动过程,最近研究表明它是一个活跃且精心编排的过程。在急性炎症的消退阶段,会产生包括脂氧素和消退素在内的新型介质,它们属于炎症的特异性促消退介质。FPR2/ALXR是一种受这些脂质以及肽类(如膜联蛋白A1)调节的受体,已被证明是参与炎症消退的受体之一。本文观点的目的是从药物化学角度阐述炎症消退的概念,并强调研究界为发现和开发抗炎/促消退小分子以通过激活FPR2/ALXR来调控炎症所做的努力。