Establishment of a selective evaluation method for DPP4 inhibitors based on recombinant human DPP8 and DPP9 proteins
作者机构：State Key Laboratory of Bioactive Substances and Functions of Natural MedicinesDiabetes Research CenterInstitute of Materia MedicaChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100050China
出 版 物：《Acta Pharmaceutica Sinica B》 (药学学报（英文版）)
年 卷 期：2014年第4卷第2期
页 面：135-140页
核心收录：
学科分类：1007[医学-药学(可授医学、理学学位)] 081704[工学-应用化学] 07[理学] 08[工学] 0817[工学-化学工程与技术] 070303[理学-有机化学] 0703[理学-化学]
基 金：We greatly appreciate Prof.Haihong Huang and Dr.Bei Han for the chemical synthesis of UAMC00132 sitagliptin.This work was supported by a fund from National Mega-project for Innova-tive Drugs(2012ZX09301002-004,China)
主 题：DPP4 DPP8 DPP9 Inhibitor Selective evaluation method
摘 要：Dipeptidyl peptidase 4(DPP4)is recognised as an attractive anti-diabetic drug target,and several DPP4 inhibitors are already on the *** members of the same gene family,dipeptidyl peptidase 8(DPP8)and dipeptidyl peptidase 9(DPP9)share high sequence and structural homology as well as functional activity with ***,the inhibition of their activities was reported to cause severe ***,the development of DPP4 inhibitors that do not have DPP8 and DPP9 inhibitory activity is critical for safe anti-diabetic *** achieve this goal,we established a selective evaluation method for DPP4 inhibitors based on recombinant human DPP8 and DPP9 proteins expressed by Rosetta *** this method,we used purified recombinant 120 kDa DPP8 or DPP9 protein from the Rosetta expression *** optimum concentrations of the recombinant DPP8 and DPP9 proteins were 30 ng/mL and 20 ng/mL,respectively,and the corresponding concentrations of their substrates were both 0.2 mmol/*** method was highly reproducible and reliable for the evaluation of the DPP8 and DPP9 selectivity for DPP4 inhibitor candidates,which would provide valuable guidance in the development of safe DPP4 inhibitors.
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