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
AlphaFold in Medicinal Chemistry: Opportunities and Challenges
AlphaFold, a groundbreaking AI tool for protein structure prediction, is revolutionizing drug discovery. Its near-atomic accuracy unlocks new avenues for designing targeted drugs and performing efficient virtual screening. However, AlphaFold's static predictions lack the dynamic nature of proteins, crucial for understanding drug action. This is especially true for multi-domain proteins, ...read more
Artificial intelligence for Natural Products Discovery and Development
Our approach involves using computational methods to predict the potential therapeutic benefits of natural products by considering factors such as drug structure, targets, and interactions. We also employ multitarget analysis to understand the role of drug targets in disease pathways. We advocate for the use of artificial intelligence in predicting ...read more
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
Chronic Kidney Disease
The scope of the special thematic issue includes but not limited to the mechanism of chronic kidney disease (CKD), the treatment of renal fibrosis and early diagnosis of CKD and so on. We also welcome manuscripts from other scientific research area with respect to internal medicine. Cell death has been ...read more
![](/images/wayfinder.jpg)
- 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
-
Autophagy : Moving Benchside Promises to Patient Bedsides
Current Cancer Drug Targets Role of CCK/Gastrin Receptors in Gastrointestinal/Metabolic Diseases and Results of Human Studies Using Gastrin/CCK Receptor Agonists/Antagonists in these Diseases
Current Topics in 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 Natural Anti-Cancer Agents: Implications in Gemcitabine-Resistant Pancreatic Cancer Treatment
Mini-Reviews in Medicinal Chemistry Inhibitory Effect on Replicative DNA Polymerases, Human Cancer Cell Proliferation, and In Vivo Anti-Tumor Activity by Glycolipids from Spinach
Current Medicinal Chemistry An Overview of Pharmacological and Clinical Aspects of <i>Spirulina</i>
Current Drug Discovery Technologies MicroRNA Regulation of Embryonic Stem Cell Pluripotency and Differentiation
Current Stem Cell Research & Therapy Repurposing of Metformin for Cancer Therapy: Updated Patent and Literature Review
Recent Patents on Anti-Cancer Drug Discovery The Chromogranin A-Derived Vasostatins: New Players in the Endocrine Heart
Current Medicinal Chemistry Zebrafish As a Genetic Model in Pre-Clinical Drug Testing and Screening
Current Medicinal Chemistry Technologies for Translational Imaging Using Generators in Oncology
Recent Patents on Anti-Cancer Drug Discovery Novel Molecular-Targeted Therapeutics for the Treatment of Cancer
Anti-Cancer Agents in Medicinal Chemistry Biological Modulation by Lectins and Their Ligands in Tumor Progression and Metastasis
Anti-Cancer Agents in Medicinal Chemistry Lipid Transmitter Signaling as a New Target for Treatment of Cocaine Addiction: New Roles for Acylethanolamides and Lysophosphatidic Acid
Current Pharmaceutical Design PARP Inhibitors: An Interesting Pathway also for Non-Small Cell Lung Cancer?
Current Pharmaceutical Design Plant Defensins and Defensin-Like Peptides - Biological Activities and Biotechnological Applications
Current Pharmaceutical Design Anticancer and Antibacterial Activity of Hyperforin and Its Derivatives
Anti-Cancer Agents in Medicinal Chemistry CFTR and MDR: ABC Transporters with Homologous Structure but Divergent Function
Current Genomics Nutraceuticals for Promoting Longevity
Current Nutraceuticals Biochemistry and Physiology of Anabolic Androgenic Steroids Doping
Mini-Reviews in Medicinal Chemistry