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

Chuanxin，Zhong1,3; Shengzheng，Wang2; Lei，Dang1; Duoli，Xie1; Jin，Liu1,4; Fuzeng，Ren3; Aiping，Lu1; Ge，Zhang1

2020-04-01

10.1016/j.ejmech.2020.112134

EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY   影响因子和分区

0223-5234

1768-3254

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

SCI

英语

其他

Hong Kong Scholars Program[XJ201713]

Pharmacology & Pharmacy

Chemistry, Medicinal

WOS:000523562700015

ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER

CHEMISTRY

2-s2.0-85079628924

Scopus

1.Law Sau Fai Institute for Advancing Translational Medicine in Bone and Joint Diseases,School of Chinese Medicine,Hong Kong Baptist University,Hong Kong
2.Department of Medicinal Chemistry,School of Pharmacy,Fourth Military Medical University,Xi'an,710032,China
3.Department of Materials Science and Engineering,Southern University of Science and Technology,Shenzhen,518055,China
4.Institute for Research and Continuing Education (IRACE),Hong Kong Baptist University,Shenzhen,China

Chuanxin，Zhong,Shengzheng，Wang,Lei，Dang,et al. Progress in 11β-HSD1 inhibitors for the treatment of metabolic diseases: A comprehensive guide to their chemical structure diversity in drug development[J]. EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY,2020,191.

Chuanxin，Zhong.,Shengzheng，Wang.,Lei，Dang.,Duoli，Xie.,Jin，Liu.,...&Ge，Zhang.(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.

Chuanxin，Zhong,et al."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(2020).