Department of Chemistry, School of Advanced Sciences, Vellore Institute of Technology, Vellore-632014, Tamil Nadu, India.
Department of Chemistry, Gupta College of Technological Sciences, Asansol-713301, West Bengal, India.
Mini Rev Med Chem. 2019;19(2):88-97. doi: 10.2174/1389557518666180423112154.
Diabetes mellitus is an emerging predator and affecting around 422 million adults worldwide. Higher levels of circulating insulin and increased pressure on the pancreas to produce insulin have been inferred as possible etiology for diabetes leading to a higher risk of pancreatic cancer. Out of several drug targets in hypoglycemic discovery, Dipeptidyl peptidase-IV (DPP-IV) has been considered an emerging target. It is a protease enzyme which inactivates incretin hormones i.e., Glucagonlike peptide 1 (GLP-1) and glucose-dependent insulin tropic polypeptide (GIP). Inhibition of DPP-4 results in the longer action of GLP-1 and GIP, therefore, DPP-4 inhibitors play an important role in maintaining glucose homeostasis. In comparison to early oral hypoglycemic, DPP-IV inhibitors are well tolerated and provide a better glycemic control over a longer period. These enzymes are expressed in a dimeric form on the surface of different cells such as prostate, liver and small intestinal epithelium cells. Disruption of the local signaling environment is an emerging factor in cancer development. Till date, not even a single DPP-IV inhibitor as anticancer has been developed. This review focuses on various features of the enzyme and their suitable inhibitors for target disease.
糖尿病是一种新兴的疾病，影响着全球约 4.22 亿成年人。循环胰岛素水平升高和胰腺产生胰岛素的压力增加被认为是导致糖尿病的可能病因，从而增加了患胰腺癌的风险。在低血糖发现的几个药物靶点中，二肽基肽酶-4 (DPP-4) 已被认为是一个新兴的靶点。它是一种蛋白酶，可使肠促胰岛素激素失活，即胰高血糖素样肽 1 (GLP-1) 和葡萄糖依赖性胰岛素释放肽 (GIP)。DPP-4 的抑制作用导致 GLP-1 和 GIP 的作用时间延长，因此，DPP-4 抑制剂在维持血糖稳态方面发挥着重要作用。与早期的口服降糖药相比，DPP-4 抑制剂具有更好的耐受性，并能在更长时间内更好地控制血糖。这些酶以二聚体形式表达在不同细胞的表面，如前列腺、肝脏和小肠上皮细胞。局部信号环境的破坏是癌症发展的一个新兴因素。迄今为止，尚未开发出任何一种作为抗癌药物的 DPP-4 抑制剂。本综述重点介绍了该酶的各种特性及其适合治疗疾病的抑制剂。
