治疗2型糖尿病的新靶点药物研究进展  

Research progress on drugs with new targets in treatment of type 2 diabetes

作　　者：刘永贵[1] 解学星[1] 吴疆[1] 沈雪砚[1] 陈常青[1] 

机构地区：[1]天津药物研究院,天津300193

出　　处：《现代药物与临床》2015年第2期222-227,共6页Drugs & Clinic

摘　　要：糖尿病是一种代谢障碍性疾病,患病率逐年上升,已成为全球慢性非传染性疾病中最具流行性的疾病。糖尿病患者中以2型糖尿病患者为主,占比超过90%。现有糖尿病治疗药物主要包括磺脲类、双胍类、格列奈类、噻唑烷二酮类、α-葡萄糖苷酶抑制剂、胰高血糖素样肽-1(GLP-1)受体激动剂、二肽基肽酶IV(DPP-4)抑制剂和钠–葡萄糖协同转运蛋白2(SGLT2)抑制剂。它们在降糖控糖作用机制上各具特点和优势,但仍不能满足临床治疗的需求。随着研究人员的不断探索,一些治疗2型糖尿病的新靶点化合物已进入临床I、II期研究,并有多个化合物处于临床前研发中,有望成为2型糖尿病的治疗药物。介绍了葡萄糖激酶激动剂、胰高血糖素受体拮抗剂、G蛋白偶联受体119(GPR119)激动剂、腺苷酸活化蛋白激酶(AMPK)激动剂、游离脂肪酸受体1(FFAR1)激动剂、蛋白酪氨酸磷酸酶-1B(PTP-1B)抑制剂和11β-羟类固醇脱氢酶1(11β-HSD1)抑制剂的作用机制、研发进程和注意事项,希望为2型糖尿病治疗药物的研发提供参考。Diabetes is a kind of metabolic disorders. Its incidence is rising year by year, and has become one of the most popular non-communicable chronic diseases in the world. Above 90% of diabetic patients suffer type 2 diabetes. The current drugs for type 2 diabetes mainly include sulfonylureas, biguanides, glinides, thiazolidinediones, α-glucosidase inhibitor, glucagon-like peptide-1（GLP-1） receptor agonists, dipeptidyl peptidase IV（DPP-IV） inhibitors, and sodium-glucose co-transporter 2（SGLT2） inhibitors. Each has its characteristics and advantages on the hypoglycemic mechanism of controlling sugar, but can not meet the clinical demand. With the constant efforts of researchers, a lot of compounds with new targets for type 2 diabetes have been in phase I, or II clinical study, and a few are in pre-registration condition, which is expected to clinical application in treatment of type 2 diabetes mellitus as new drugs. In this paper, mechanisms of new targets, research process and notice of drugs for anti-type 2 diabetes, such as glucokinase agonists, glucagon receptor inhibitors, G-protein coupled receptor 119（GPR119） agonists, AMP-activated protein kinase（AMPK） agonists, free fatty acid receptor 1（FFAR1） agonists, protein tyrosine phosphatase-1B（PTP-1B） inhibitors, and 11β-hydroxysteroid dehy drogenase（11β-HSD） inhibitors are reviewed, which could provide a reference for R D of drugs for type 2 diabetes.

关 键 词：2型糖尿病 药物靶点 葡萄糖激酶激动剂 胰高血糖素受体拮抗剂 GPR119激动剂 AMPK激动剂 FFAR1激动剂 PTP-1B抑制剂 11β-HSD1抑制剂 

分 类 号：R977[医药卫生—药品]