Citation: Peng-Fei Xiao, Rui Guo, Shao-Qiang Huang, Heng-Jun Cui, Sheng Ye, Zhiyuan Zhang. Discovery of dipeptidyl peptidase IV (DPP4) inhibitors based on a novel indole scaffold[J]. Chinese Chemical Letters, ;2014, 25(05): 673-676. doi: 10.1016/j.cclet.2014.03.047 shu

Discovery of dipeptidyl peptidase IV (DPP4) inhibitors based on a novel indole scaffold

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a Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing 100730, China;
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b National Institute of Biological Sciences (NIBS), Beijing 102206, China;
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c Life Sciences Institute, Zhejiang University, Hangzhou 310058, China

Corresponding author: Sheng Ye, Zhiyuan Zhang,
Received Date: 11 February 2014
Available Online: 17 March 2014
Fund Project: This work is supported by the National Natural Science Foundation of China (No. 21274154). (No. 21274154)

Dipeptidyl peptidase IV (DPP4) inhibitors are proven in the treatment of type 2 diabetes. We designed and synthesized a series of novel indole compounds that selectively inhibit the activity of DPP4 over dipeptidyl peptidase 9 (DPP9) (>200 fold). We further co-crystallized DPP4 with indole sulfonamide (compound 1) to confirm a proposed binding mode. Good metabolic stability of the indole compounds represents another positive attribute for further development.
- DPP4 inhibitor,
- Type 2 diabetes,
- De novo design,
- Indole scaffold,
- Crystal structure
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沈阳化工大学材料科学与工程学院沈阳 110142