Abstract
Peroxisome proliferator-activated receptor gamma (PPARγ) is a ligand-dependent transcription factor that plays an important role in regulating glucose metabolism. Agonists of PPARγ, such as thiazolidinediones, have anti-hyperglycemic activity, and are therefore used to treat type 2 diabetes. However, the functional activity of PPARγ is manifested by heterodimers of PPARγ with retinoid X receptors (RXRs). Since RXR/PPARγ heterodimers can be activated not only by PPARγ agonists, but also by RXR agonists, RXR agonists are also attractive candidates for treatment of type 2 diabetes. However, RXR full agonists have side effects, such as triglyceride elevation and hypothyroidism. Therefore, RXR partial agonists have been developed as new anti-type 2 diabetes agent candidates with reduced side effects. In addition, RXR antagonists also show therapeutic potency in type 2 diabetes patients. Here, we review RXR full agonists, RXR antagonists, and RXR modulators (partial agonists) with reported anti-diabetic effects, and we discuss their potential suitability as anti-diabetic agents.
Keywords: Retinoid X receptors, Agonists, Antagonists, Partial-agonists, Diabetes, Glucose-lowering effects.
Current Topics in Medicinal Chemistry
Title:Retinoid X Receptor Ligands with Anti-Type 2 Diabetic Activity
Volume: 17 Issue: 6
Author(s): Ken-ichi Morishita and Hiroki Kakuta
Affiliation:
Keywords: Retinoid X receptors, Agonists, Antagonists, Partial-agonists, Diabetes, Glucose-lowering effects.
Abstract: Peroxisome proliferator-activated receptor gamma (PPARγ) is a ligand-dependent transcription factor that plays an important role in regulating glucose metabolism. Agonists of PPARγ, such as thiazolidinediones, have anti-hyperglycemic activity, and are therefore used to treat type 2 diabetes. However, the functional activity of PPARγ is manifested by heterodimers of PPARγ with retinoid X receptors (RXRs). Since RXR/PPARγ heterodimers can be activated not only by PPARγ agonists, but also by RXR agonists, RXR agonists are also attractive candidates for treatment of type 2 diabetes. However, RXR full agonists have side effects, such as triglyceride elevation and hypothyroidism. Therefore, RXR partial agonists have been developed as new anti-type 2 diabetes agent candidates with reduced side effects. In addition, RXR antagonists also show therapeutic potency in type 2 diabetes patients. Here, we review RXR full agonists, RXR antagonists, and RXR modulators (partial agonists) with reported anti-diabetic effects, and we discuss their potential suitability as anti-diabetic agents.
Export Options
About this article
Cite this article as:
Morishita Ken-ichi and Kakuta Hiroki, Retinoid X Receptor Ligands with Anti-Type 2 Diabetic Activity, Current Topics in Medicinal Chemistry 2017; 17 (6) . https://dx.doi.org/10.2174/1568026616666160617085545
DOI https://dx.doi.org/10.2174/1568026616666160617085545 |
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
-
Use of Anticancer Platinum Compounds in Combination Therapies and Challenges in Drug Delivery
Current Medicinal Chemistry The Possible Potency of Ocimum basilicum New Constituent on Glucosestimulated Insulin Secretion In Vitro and β-cell Function In Vivo
Letters in Drug Design & Discovery The Neurotrophic and Antiangiogenic Functions of PEDF: A Reflection of its Variable Phosphorylation States
Current Genomics Long Non-Coding RNA GAS5 in Age-Related Diseases
Current Medicinal Chemistry Topical Chemoprevention of Skin Cancers with Phytochemicals
Current Cancer Therapy Reviews FoxO Transcription Factors and Regenerative Pathways in Diabetes Mellitus
Current Neurovascular Research Peptide-Drug Conjugate: A Novel Drug Design Approach
Current Medicinal Chemistry Drug Transporters and Multiple Drug Resistance in the Most Common Pediatric Solid Tumors
Current Drug Metabolism miRNAs in Cancer Prevention and Treatment and as Molecular Targets for Natural Product Anticancer Agents
Current Cancer Drug Targets (Neuro)Transmitter Systems in Circulating Immune Cells: A Target of Immunopharmacological Interventions?
Current Medicinal Chemistry Molecular Signatures of Biomarkers in Cancer Development, Diagn osis, and its Prognostic Accuracy
Current Biomarkers (Discontinued) Micro-RNA and the Features of Metabolic Syndrome: A Narrative Review
Mini-Reviews in Medicinal Chemistry Recent Trends in Targeted Anticancer Prodrug and Conjugate Design
Current Medicinal Chemistry Anti-Cancer Effects of Asiatic Acid, a Triterpene from Centilla asiatica L: A Review
Anti-Cancer Agents in Medicinal Chemistry Review: The Role of MOP and DOP Receptors in Treatment of Diarrheapredominant Irritable Bowel Syndrome
Mini-Reviews in Medicinal Chemistry In vivo and in silico Investigation of Antidiabetic Activity of Fruit of Withania coagulans Dunal
Current Hypertension Reviews Establishing Genomic/Transcriptomic Links Between Alzheimer’s Disease and Type 2 Diabetes Mellitus by Meta-Analysis Approach
CNS & Neurological Disorders - Drug Targets Multiple Roles of the Extracellular Matrix in Inflammation
Current Pharmaceutical Design A Review of IGF1 Signaling and IGF1-related Long Noncoding RNAs in Chemoresistance of Cancer
Current Cancer Drug Targets A Structural Insight into Hydroxamic Acid Based Histone Deacetylase Inhibitors for the Presence of Anticancer Activity
Current Medicinal Chemistry