151. Development and application of a fluorescent glucose uptake assay for the high-throughput screening of non-glycoside SGLT2 inhibitors.
- Author
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Wu, Szu-Huei, Yao, Chun-Hsu, Hsieh, Chieh-Jui, Liu, Yu-Wei, Chao, Yu-Sheng, Song, Jen-Shin, and Lee, Jinq-Chyi
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GLYCOSIDES , *GLUCOSE transporters , *ENZYME inhibitors , *TYPE 2 diabetes treatment , *PHLORIZIN , *MEDICAL screening - Abstract
Sodium-dependent glucose co-transporter 2 (SGLT2) inhibitors are of current interest as a treatment for type 2 diabetes. Efforts have been made to discover phlorizin-related glycosides with good SGLT2 inhibitory activity. To increase structural diversity and better understand the role of non-glycoside SGLT2 inhibitors on glycemic control, we initiated a research program to identify non-glycoside hits from high-throughput screening. Here, we report the development of a novel, fluorogenic probe-based glucose uptake system based on a Cu(I)-catalyzed [3 + 2] cycloaddition. The safer processes and cheaper substances made the developed assay our first priority for large-scale primary screening as compared to the well-known [ 14 C]-labeled α-methyl- d -glucopyranoside ([ 14 C]-AMG) radioactive assay. This effort culminated in the identification of a benzimidazole, non-glycoside SGLT2 hit with an EC 50 value of 0.62 μM by high-throughput screening of 41,000 compounds. [ABSTRACT FROM AUTHOR]
- Published
- 2015
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