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

Zhong Chuanxin, Wang Shengzheng, Dang Lei, Xie Duoli, Liu Jin, Ren Fuzeng, Aiping LYU, Ge Zhang*

*Corresponding author for this work

Research output: Contribution to journalReview articlepeer-review

4 Citations (Scopus)

Abstract

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.

Original languageEnglish
Article number112134
JournalEuropean Journal of Medicinal Chemistry
Volume191
DOIs
Publication statusPublished - 1 Apr 2020

Scopus Subject Areas

  • Pharmacology
  • Drug Discovery
  • Organic Chemistry

User-Defined Keywords

  • 11β-HSD1 inhibitors
  • Metabolic syndrome
  • Molecular modeling
  • Obesity
  • Structure-activity relationships
  • Type 2 diabetes

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