Discovery of Novel 11β-HSD1 Inhibitors by Pharmacophore-Based Virtual Screening

Bulletin of the Korean chemical society

Nam Doo Kim¹  Chang-Kyun Han¹  Soon Kil Ahn¹  Younho Lee¹ 

关键词: 11-HSD1;    Pharmacophore-based virtual screening;    Antidiabetic;    Glucocorticoid;    Molecular docking;   

DOI  :  

学科分类：化学（综合）

来源: Korean Chemical Society

【 摘 要 】

The 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) enzyme is involved in modulation of glucocorticoid activity within target tissues. This enzyme may contribute to obesity and/or metabolic disease through its action in adipose or liver tissue. Inhibition of 11β-HSD1 has major therapeutic potential for glucocorticoidassociated diseases, including obesity, diabetes (wound healing), and muscle atrophy. To develop such therapeutics, we performed a pharmacophore-based virtual screening (VS) for identification of novel 11β-HSD1 inhibitors and found that the VS hit compounds show potent inhibition of 11β-HSD1 enzyme activity. Further, we present a binding model for active compounds. The proposed pharmacophore may serve as a useful guideline for future design of new chemical entities as 11β-HSD1-targeted antidiabetic agents.

【 授权许可】

Unknown