School of Chinese Medicine
11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) is a key metabolic enzyme that catalyzing the intracellular conversion of inactive glucocorticoids to physiologically active ones. Work over the past decade has demonstrated the aberrant overexpression of 11β-HSD1 contributed to the pathophysiological process of metabolic diseases like obesity, type 2 diabetes mellitus, and metabolic syndromes. The inhibition of 11β-HSD1 represented an attractive therapeutic strategy for the treatment of metabolic diseases. Therefore, great efforts have been devoted to developing 11β-HSD1 inhibitors based on the diverse molecular scaffolds. This review focused on the structural features of the most important 11β-HSD1 inhibitors and categorized them into natural products derivatives and synthetic compounds. We also briefly discussed the optimization process, binding modes, structure-activity relationships (SAR) and biological evaluations of each inhibitor. Moreover, the challenges and directions for 11β-HSD1 inhibitors were discussed, which might provide some useful clues to guide the future discovery of novel 11β-HSD1 inhibitors.
11β-HSD1, inhibitor sMetabolic syndrome, Obesity, Type 2 diabetes, Structure-activity relationships, Molecular modeling
Source Publication Title
European Journal of Medicinal Chemistry
Link to Publisher's Edition
Zhong, C., Wang, S., Lei, D., Xie, D., Liu, J., Ren, F., Lu, A., & Zhang, G. (2020). Progress in 11β-HSD1 inhibitors for the treatment of metabolic diseases: A comprehensive guide to their chemical structure diversity in drug development. European Journal of Medicinal Chemistry, 191. https://doi.org/10.1016/j.ejmech.2020.112134
Available for download on Sunday, May 01, 2022