特发性肺纤维化治疗靶点及药物研究进展  

Advances of targets and therapeutic drugs for idiopathic pulmonary fibrosis

作　　者：耿艳艳[1,2] 周植星[2] 胡倩倩[1,2] 于冰[2] 徐为人[2] 汤立达[2] 

机构地区：[1]天津医科大学,天津300070 [2]天津药物研究院天津市新药设计与发现重点实验室,天津300193

出　　处：《中国新药杂志》2015年第1期46-51,共6页Chinese Journal of New Drugs

基　　金：天津市应用基础与前沿技术研究计划(13JCZDJC28500)

摘　　要：近年来,对特发性肺纤维化(IPF)发病机制和治疗靶点的研究成为热点。一些细胞因子与IPF关系密切,其中转化生长因子-β(TGF-β)引导成纤维细胞和巨噬细胞至损伤处,直接诱发成纤维细胞转化为肌成纤维细胞并促进胶原合成;血小板源生长因子(PDGF)和碱性纤维母细胞生长因子(b FGF)与成纤维细胞增殖有关。此外,相关蛋白如赖氨酰氧化酶相关蛋白2(LOXL2)、ανβ6整合蛋白和溶血磷脂酸1受体(LPA1)等均为新的IPF治疗靶点。目前针对IPF治疗靶点的药物相继进入临床试验,吡非尼酮(Pirfenidone)为转化生长因子-β(TGF-β)抑制剂;尼达尼布(Nintedanib)为三重酪氨酸激酶抑制剂,作用于PDGF、VEGF和FGF受体;Simtuzumab是一种人源化单克隆抗体,作用于赖氨酰氧化酶相关蛋白2(LOXL2),阻断胶原交联,正处于IPFⅡ期临床试验。STX-100是一种人源化ανβ6特异性单克隆抗体,与ανβ6整合蛋白结合,阻止后者激活TGF-β。In recent years, the study of idiopathic pulmonary fibrosis （IPF） pathogenesis and therapeutic targets has become the hotspot of the international research. There is a close relationship between some cell factors and IPF. TGF-β recruits fibroblasts and macrophages to the site of injury, directly induces the differentiation of fibroblasts into myofibroblasts and promotes collagen synthesis. PDGF and bFGF potently promote fibroblast proliferation. Besides that, LOXL2, αvβ6 integrin and LPA1 are new targets of IPF. This review highlights the recent research as well as novel therapeutics being explored in clinical trials for the treatment of this devastating disease. Pirfenidone is an anti-inflammatory, anti-oxidant and antifibrotic agent that inhibits transforming growth factor-β in vitro, changes collagen synthesis and accumulation, and inhibits cell proliferation and extracellular matrix expression. Targeting multiple effector molecules is the strategy behind nintedanib, mainly blocking the receptors for PDGF, FGF and VEGF. Simtuzumab, a humanized monoclonal antibody, targets the enzyme lysyl oxidase-like-2 （LOXL2） , which catalyzes the crosslinking of collagen. STX-100, the humanized Mab, only inhibits αvβ6-mediated TGF-β activation.

关 键 词：特发性肺纤维化 靶点 治疗药物 

分 类 号：R974[医药卫生—药品]