Progress in 11β-HSD1 inhibitors for the treatment of metabolic diseases: A comprehensive guide to their chemical structure diversity in drug development.


Department of Materials Science and Engineering, Southern University of Science and Technology, Shenzhen, Guangdong, 518055, China. Electronic address: [Email]


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 inhibitors,Metabolic syndrome,Molecular modeling,Obesity,Structure-activity relationships,Type 2 diabetes,

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