糖尿病相关VPAC、PAC受体及其药物研发的进展

Diabetes-Related VPAC, PAC Receptor and Its Progress in Drug Development

VPAC、PAC受体是近年发现的开发2型糖尿病药物的重要靶标,垂体腺苷酸环化酶激活多肽(PACAP)、血管活性肠肽(VIP)则是它们的天然配体,与受体结合激活后能促进葡萄糖依赖性胰岛素分泌,既能保护细胞又不引起胰高血糖素分泌和糖原分解,因此其配体相关化合物的开发研究成为开发2型糖尿病药物的重要方向。目前针对VPAC、PAC受体开发的配体类似物主要包括了肽类和非肽类小分子两大类,但它们仍然存在诸多不足,至今仅有一个药物进入到临床研究阶段。本综述系统总结了目前针对VPAC、PAC受体为靶标的肽类和非肽小分子药物的开发研究现状,可为将来此类药物的研发提供参考。

VPAC and PAC receptors are becoming important targets for the development of type 2 diabetes drugs in recently. Pituitary adenylate cyclase activating polypeptide(PACAP) and vasoactive intestinal peptide(VIP) are their natural ligands. When they have been activated by binding to the receptor, they promote glucose-dependent insulin secretion, which protects the sputum cells from glucagon secretion and glycogenolysis. Therefore, the development of new ligand or their analogs has been an important strategy for the development of drugs for type 2 diabetes. At present, the ligand analogs of VPAC and PAC receptors have been developed, they mainly include two major classes of peptides and non-peptide small molecules, but they still have many shortcomings. Until now,only one drug has been entered the clinic trail. The current status about research and development of peptide and non-peptide small molecule drugs targeting VPAC and PAC receptors have been summarized in this paper, and it will provide reference for the future development of new drugs.