Discovery of non-glycoside sodium-dependent glucose co-transporter 2 (SGLT2) inhibitors by ligand-based virtual screening

  • J Med Chem. 2010 Dec 23;53(24):8770-4. doi: 10.1021/jm101080v.
Jian-Sung Wu  1 ,  Yi-Hui Peng ,  Jiun-Ming Wu ,  Chieh-Jui Hsieh ,  Szu-Huei Wu ,  Mohane Selvaraj Coumar ,  Jen-Shin Song ,  Jinq-Chyi Lee ,  Chi-Hui Tsai ,  Chiung-Tong Chen ,  Yu-Wei Liu ,  Yu-Sheng Chao ,  Su-Ying Wu
Affiliations
  • 1. Institute of Biotechnology and Pharmaceutical Research, National Health Research Institutes, Zhunan Town, Miaoli County 350, Taiwan, Republic of China.
PMID: 21090651 DOI: 10.1021/jm101080v
Abstract

A ligand-based virtual screening strategy (a combination of pharmacophore model generation, shape-based scoring, and structure clustering analysis) was developed to discover novel SGLT2 inhibitors. The best pharmacophore model, generated from eight glycoside inhibitors, was utilized to virtually screen three chemical databases that led to the identification of three non-glycoside SGLT2 inhibitors. This is the first report of the generation of a pharmacophore model from Glycosides that has then been used to discover novel non-glycosides hits.