Abstract
11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) catalyzes the interconversion of inactive cortisone to active cortisol in a NADPH dependent manner. Excess cortisol or 11β-HSD1 leads to insulin resistance and metabolic syndrome. Inhibition of 11β-HSD1 activity has been pursued vigorously by the pharmaceutical industry as a potential therapeutic strategy for the treatment of type 2 diabetes. As a result, a large number of chemical classes have been identified as potent and selective small molecule inhibitors for 11β-HSD1. Here we review the recent progress in the discovery and development of small molecule inhibitors of 11β-HSD1 by highlighting the medicinal chemistry, SAR, in vivo pharmacodynamic effects and efficacy of a few representative classes of inhibitors in models of diabetes. Furthermore, we also review the structural characteristics of each class of inhibitors by analyzing the inhibitor co-crystal structures of 11β- HSD1.
Keywords: 11β-HSD1, 11β-HSD2, metabolic syndrome, type 2 diabetes, sulfonamide, amide, triazole, insulin resistance, SAR, pharmacodynamic effects, efficacy, co-crystal structures, Glucocorticoids, anti-inflammatory hormones
Current Topics in Medicinal Chemistry
Title: Small Molecule 11β- Hydroxysteroid Dehydrogenase Type 1 Inhibitors
Volume: 11 Issue: 12
Author(s): Daqing Sun, Minghan Wang and Zhulun Wang
Affiliation:
Keywords: 11β-HSD1, 11β-HSD2, metabolic syndrome, type 2 diabetes, sulfonamide, amide, triazole, insulin resistance, SAR, pharmacodynamic effects, efficacy, co-crystal structures, Glucocorticoids, anti-inflammatory hormones
Abstract: 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) catalyzes the interconversion of inactive cortisone to active cortisol in a NADPH dependent manner. Excess cortisol or 11β-HSD1 leads to insulin resistance and metabolic syndrome. Inhibition of 11β-HSD1 activity has been pursued vigorously by the pharmaceutical industry as a potential therapeutic strategy for the treatment of type 2 diabetes. As a result, a large number of chemical classes have been identified as potent and selective small molecule inhibitors for 11β-HSD1. Here we review the recent progress in the discovery and development of small molecule inhibitors of 11β-HSD1 by highlighting the medicinal chemistry, SAR, in vivo pharmacodynamic effects and efficacy of a few representative classes of inhibitors in models of diabetes. Furthermore, we also review the structural characteristics of each class of inhibitors by analyzing the inhibitor co-crystal structures of 11β- HSD1.
Export Options
About this article
Cite this article as:
Sun Daqing, Wang Minghan and Wang Zhulun, Small Molecule 11β- Hydroxysteroid Dehydrogenase Type 1 Inhibitors, Current Topics in Medicinal Chemistry 2011; 11 (12) . https://dx.doi.org/10.2174/156802611795860988
DOI https://dx.doi.org/10.2174/156802611795860988 |
Print ISSN 1568-0266 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4294 |
Call for Papers in Thematic Issues
Chemistry Based on Natural Products for Therapeutic Purposes
The development of new pharmaceuticals for a wide range of medical conditions has long relied on the identification of promising natural products (NPs). There are over sixty percent of cancer, infectious illness, and CNS disease medications that include an NP pharmacophore, according to the Food and Drug Administration. Since NP ...read more
Current Trends in Drug Discovery Based on Artificial Intelligence and Computer-Aided Drug Design
Drug development discovery has faced several challenges over the years. In fact, the evolution of classical approaches to modern methods using computational methods, or Computer-Aided Drug Design (CADD), has shown promising and essential results in any drug discovery campaign. Among these methods, molecular docking is one of the most notable ...read more
Drug Discovery in the Age of Artificial Intelligence
In the age of artificial intelligence (AI), we have witnessed a significant boom in AI techniques for drug discovery. AI techniques are increasingly integrated and accelerating the drug discovery process. These developments have not only attracted the attention of academia and industry but also raised important questions regarding the selection ...read more
From Biodiversity to Chemical Diversity: Focus of Flavonoids
Flavonoids are the largest group of polyphenols, plant secondary metabolites arising from the essential aromatic amino acid phenylalanine (or more rarely from tyrosine) via the phenylpropanoid pathway. The flavan nucleus is the basic 15-carbon skeleton of flavonoids (C6-C3-C6), which consists of two phenyl rings (A and B) and a heterocyclic ...read more
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
- Announcements
Related Articles
-
Role of Estradiol and Progesterone in HIV Susceptibility and Disease Progression
Mini-Reviews in Medicinal Chemistry GH Supplementation Effects on Cardiovascular Risk in GH Deficient Adult Patients: A Systematic Review and Meta-analysis
Endocrine, Metabolic & Immune Disorders - Drug Targets Biomarkers of Chronic Kidney Disease - Mineral and Bone Disorder (CKD-MBD), A Review of Published Patents and Patent Applications
Recent Patents on Biomarkers Diabetic CVD – Focus on Vitamin D
Cardiovascular & Hematological Agents in Medicinal Chemistry The Gut Microbiome
Inflammation & Allergy - Drug Targets (Discontinued) Withdrawal Notice: Electrophoresis as a Tool for Early Cancer Diagnosis
Anti-Cancer Agents in Medicinal Chemistry Functional Null Mutations in the Gonosomal Homologue Gene TBL1Y are Associated with Non-Syndromic Coarctation of the Aorta
Current Molecular Medicine DNA Methyltransferase-1 Inhibitors as Epigenetic Therapy for Cancer
Current Cancer Drug Targets Do Not Say Ever Never More: The Ins and Outs of Antiangiogenic Therapies
Current Pharmaceutical Design Role of Class II Nuclear Receptors in Liver Carcinogenesis
Anti-Cancer Agents in Medicinal Chemistry Vitamin D and Cardiovascular Disease
Current Vascular Pharmacology Hyperglycaemia and Vitamin D: A Systematic Overview
Current Diabetes Reviews Targeting RAS Signaling Pathways in Juvenile Myelomonocytic Leukemia
Current Drug Targets Endometriosis Management: Workflow on Genomics and Proteomics and Future Biomolecular Pharmacotherapy
Current Medicinal Chemistry An Integrated and Disease-Oriented Growth Factor-Regulated Signal Transduction Network
Current Molecular Medicine Vitamin D and Vitamin D Receptor Activators in Treatment of Hypertension and Cardiovascular Disease
Cardiovascular & Hematological Disorders-Drug Targets Current Management of Neonatal Soft-tissue Sarcomas and Benign Tumors with Local Aggressiveness
Current Pediatric Reviews Genetics of Bladder Malignant Tumors in Childhood
Current Genomics Therapy Related Markers and Response Prediction Towards Multimodal Treatment of Carcinomas of the Upper Gastrointestinal Tract
Current Pharmacogenomics and Personalized Medicine Intestinal Immunomodulation. Role of Regulative Peptides and Promising Pharmacological Activities
Current Pharmaceutical Design