Advances in Small-Molecule GPR40 Agonists for Treatment of Type 2 Diabetes Mellitus

doi:10.6023/cjoc201511011

Chin. J. Org. Chem. ›› 2016, Vol. 36 ›› Issue (4): 736-743.DOI: 10.6023/cjoc201511011 Previous Articles Next Articles

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小分子GPR40激动剂作为抗II型糖尿病候选药物的研究进展

李鹤, 龙亚秋

中国科学院上海药物研究所受体结构和功能重点实验室上海 201203

收稿日期:2015-11-05 修回日期:2015-11-25 发布日期:2015-12-07
通讯作者: 龙亚秋 E-mail:yqlong@simm.ac.cn
基金资助:
国家自然科学基金(Nos.81325020,81361120410,81321092,81123004)资助项目.

Advances in Small-Molecule GPR40 Agonists for Treatment of Type 2 Diabetes Mellitus

Li He, Long Yaqiu

Chinese Academy of Sciences Key Laboratory of Receptor Research, Shanghai Institute of Materia. Medica, Chinese Academy of Sciences, Shanghai 201203

Received:2015-11-05 Revised:2015-11-25 Published:2015-12-07
Supported by:
Project supported by the National Natural Science Foundation of China (Nos. 81325020, 81361120410, 8132109, 81123004).

Currently, the majority of the chemotherapy for type 2 diabetes mellitus (T2DM) functions through glycemic control by administration of oral or injectable hypoglycemic drugs. Though a range of anti-diabetic drugs with different modes of action have been launched, there still remains a significant need for development of effective and highly safe anti-diabetic agents for the increasing diabetic population. GPR40 belongs to the GPCR family and the activation of GPR40 can amplify glucose-stimulated insulin secretion (GSIS). Due to the advantage of minimizing the hypoglycemia risk, GPR40 has drawn more and more attention and emerged as a promising new target for T2DM treatment. Therefore, the recent progress on the structural optimization and further development of small molecule GPR40 agonists as novel treatment for T2DM is reviewed, focused on those under clinical trials or at preclinical stage. A variety of small molecule GPR40 agonists were summarized from the literature and patents based on the pharmacophore model, including the critical phenylpropanoic acid core, the hydrophobic terminus and the linker. The structural features and advantage of different sources of GPR40 agonists were analyzed and highlighted.

Key words: type II diabetes mellitus, GPR40, agonists, glucose-stimulated insulin secretion, phenylpropanoic acid

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Li He, Long Yaqiu. Advances in Small-Molecule GPR40 Agonists for Treatment of Type 2 Diabetes Mellitus[J]. Chin. J. Org. Chem., 2016, 36(4): 736-743.

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小分子GPR40激动剂作为抗II型糖尿病候选药物的研究进展

Advances in Small-Molecule GPR40 Agonists for Treatment of Type 2 Diabetes Mellitus

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