治疗炎症性肠道疾病的新兴靶点与药物

Emerging targets and drugs of inflammatory bowel disease

炎症性肠道疾病(inflammatory bowel disease,IBD)是一种慢性的、反复的肠道炎症疾病。临床上常用的治疗药物在长期应用后都存在疗效不佳、不良反应多等缺点。新型生物疗法如抗肿瘤坏死因子单抗在克服常用药不良反应的同时,也存在价格昂贵、不易储存和应用后耐药和复发等问题。近年来,针对IBD新的治疗药物不断出现,如抑制淋巴细胞迁移的调节剂(整合素抑制剂和鞘氨醇-1磷脂受体激动剂)已进入IBD的临床治疗。还有炎性细胞因子抑制剂[白细胞介素23抑制剂、Janus激酶(Janus kinases,JAKs)抑制剂、磷酸二酯酶抑制剂等]、靶向纤维化和肠道组织降解和重塑的抑制剂(基质金属蛋白酶抑制剂)等也正在进行IBD的临床试验评估。本文以药物作用机制为切入点,总结和梳理了当前IBD治疗的主流药物和一些新兴药物的进展,并介绍其作用靶点,以期为IBD药物的设计和研发提供新的思路。

Inflammatory bowel disease(IBD)is a chronic,repeated intestinal inflammatory disease.Clinically commonly used therapeutic drugs have some disadvantages,such as poor efficacy and many adverse reactions after long-term application.Although new biological therapies such as anti-tumor necrosis factor agents,overcome common adverse reactions,also have problems such as high price,difficult storage,drug resistance and recurrence after application.In recent years,many new therapeutic methods for inflammatory bowel disease have emerged,for example,modulators that inhibit lymphocyte migration(integrin inhibitors and sphingosine 1-phosphate receptor agonists)have been introduced into the clinical treatment of inflammatory bowel disease,inflammatory cytokine inhibitors(interleukin-23 inhibitors,Janus kinase inhibitors,phosphodiesterase inhibitors,etc.)and inhibitors targeting fibrosis and intestinal tissue degradation and remodeling(matrix metalloproteinase inhibitors)are also being evaluated in clinical trials of IBD.Based on the mechanisms of action,this paper intends to outline the current mainstream IBD therapies and some emerging drugs,and briefly introduce their targets to provide reference for IBD drug design and development.