title: Discovery of non-glycoside sodium-dependent glucose co-transporter 2 (SGLT2) inhibitors by ligand-based virtual screening.
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.
authors.affiliation: Institute of Biotechnology and Pharmaceutical Research, National Health Research Institutes, Zhunan Town, Miaoli County 350, Taiwan, Republic of China.
authors.forename: Jian-Sung
authors.initials: JS
authors.lastname: Wu
authors.forename: Yi-Hui
authors.initials: YH
authors.lastname: Peng
authors.forename: Jiun-Ming
authors.initials: JM
authors.lastname: Wu
authors.forename: Chieh-Jui
authors.initials: CJ
authors.lastname: Hsieh
authors.forename: Szu-Huei
authors.initials: SH
authors.lastname: Wu
authors.forename: Mohane Selvaraj
authors.initials: MS
authors.lastname: Coumar
authors.forename: Jen-Shin
authors.initials: JS
authors.lastname: Song
authors.forename: Jinq-Chyi
authors.initials: JC
authors.lastname: Lee
authors.forename: Chi-Hui
authors.initials: CH
authors.lastname: Tsai
authors.forename: Chiung-Tong
authors.initials: CT
authors.lastname: Chen
authors.forename: Yu-Wei
authors.initials: YW
authors.lastname: Liu
authors.forename: Yu-Sheng
authors.initials: YS
authors.lastname: Chao
authors.forename: Su-Ying
authors.initials: SY
authors.lastname: Wu
mesh_terms: D000818:Animals; D001562:Benzimidazoles / Q000737:chemistry / Q000494:pharmacology; D016466:CHO Cells; D016000:Cluster Analysis; D003198:Computer Simulation; D006224:Cricetinae; D003412:Cricetulus; D016208:Databases, Factual; D015195:Drug Design; D006027:Glycosides / Q000737:chemistry; D008024:Ligands; D008958:Models, Molecular; D021281:Quantitative Structure-Activity Relationship; D051297:Sodium-Glucose Transporter 2 / Q000737:chemistry; D000077203:Sodium-Glucose Transporter 2 Inhibitors
chemical_list: D001562:Benzimidazoles; D006027:Glycosides; D008024:Ligands; D051297:Sodium-Glucose Transporter 2; D000077203:Sodium-Glucose Transporter 2 Inhibitors