College of Pharmacy, Dongguk University, Goyang 410-820, Korea.
Arch Pharm Res. 2012 Jan;35(1):3-7. doi: 10.1007/s12272-012-0121-z.
New classes of lipids such as lipoxins, resolvins, protectins and maresin are found to promote the resolution of inflammation. The resolving actions of these endogenous lipids are mediated by membrane receptors such as lipoxin A4 receptor/formyl peptide receptor 2 (ALX/FPR2) and cysteinyl leukotriene receptor 1 (CysLT1). Further, there exists G protein-coupled receptor 32 (GPR32), chemokine receptor-like (CMLKLR), LTB4 receptor 1 (BLT1) and unidentified high-affinity surface binding receptors in human polymorphonuclear leukocytes (PMN). In particular, RX-10001 (resolvin E1) and RX-10004 (synthetic analog of resolvin, phase II) are being studied clinically in many inflammatory diseases including dry eye, retinal disease, asthma, inflammatory bowel diseases, rheumatic arthritis and cardiovascular diseases by Resolvyx Pharmaceuticals. These novel lipid classes of inflammation resolving mediators might offers new opportunities for candidates of drugs modulating chronic inflammatory diseases. Here, the progress of resolvins as new drug candidates is introduced and research on the resolution phase of inflammation is emphasized.
新的脂类如脂氧素、消退素、保护素和maresin 被发现可以促进炎症的消退。这些内源性脂质的消退作用是通过膜受体介导的,如脂氧素 A4 受体/甲酰肽受体 2(ALX/FPR2)和半胱氨酰白三烯受体 1(CysLT1)。此外,在人类多形核白细胞(PMN)中还存在 G 蛋白偶联受体 32(GPR32)、趋化因子受体样(CMLKLR)、LTB4 受体 1(BLT1)和未识别的高亲和力表面结合受体。特别是,Resolvyx 制药公司正在研究 RX-10001(消退素 E1)和 RX-10004(消退素的合成类似物,二期)在包括干眼症、视网膜疾病、哮喘、炎症性肠病、风湿性关节炎和心血管疾病在内的许多炎症性疾病中的临床应用。这些新型的炎症消退介质的脂类可能为调节慢性炎症性疾病的药物候选物提供新的机会。本文介绍了作为新药候选物的消退素的研究进展,并强调了炎症消退阶段的研究。