Abstract
An epidemic of metabolic diseases including type 2 diabetes and obesity is undermining the health of people living in industrialized societies. There is an urgent need to develop innovative therapeutics. The peroxisome proliferatoractivated receptor γ (PPARγ) is one of the ligand-activated transcription factors in the nuclear hormone receptor superfamily and a pivotal regulator of glucose and lipid homeostasis. The discovery of PPARγ as a target of multimodal insulin sensitizers, represented by thiazolidinediones (TZDs), has attracted remarkable scientific interest and had a great impact on the pharmaceutical industry. With the clinical success of the PPARγ agonists, pioglitazone (Actos) and rosiglitazone (Avandia), development of novel and potent insulin-sensitizing agents with diverse clinical profiles has been accelerated. Currently, a number of PPARγ agonists from different chemical classes and with varying pharmacological profiles are being developed. Despite quite a few obstacles to the development of PPAR-related drugs, PPARγ-targeted agents still hold promise. There are new concepts and encouraging evidence emerging that suggest this class can yield improved anti-diabetic agents. This review covers the discovery of TZDs, provides an overview of PPARγ including the significance of PPARγ as a drug target, describes the current status of a wide variety of novel PPARγ ligands including PPAR dual and pan agonists and selective PPARγ modulators (SPPARγMs), and highlights new approaches for identifying agents targeting PPARγ in the treatment of type 2 diabetes.
Keywords: Type 2 diabetes, peroxisome proliferator-activated receptor γ (PPARγ), insulin sensitizer, thiazolidinedione (TZD), PPARγ agonist, pioglitazone, rosiglitazone, selective PPARγ modulator (SPPARγM)
Current Topics in Medicinal Chemistry
Title: Peroxisome Proliferator-Activated Receptor γ Agonists as Insulin Sensitizers: From the Discovery to Recent Progress
Volume: 8 Issue: 17
Author(s): Nobuo Cho and Yu Momose
Affiliation:
Keywords: Type 2 diabetes, peroxisome proliferator-activated receptor γ (PPARγ), insulin sensitizer, thiazolidinedione (TZD), PPARγ agonist, pioglitazone, rosiglitazone, selective PPARγ modulator (SPPARγM)
Abstract: An epidemic of metabolic diseases including type 2 diabetes and obesity is undermining the health of people living in industrialized societies. There is an urgent need to develop innovative therapeutics. The peroxisome proliferatoractivated receptor γ (PPARγ) is one of the ligand-activated transcription factors in the nuclear hormone receptor superfamily and a pivotal regulator of glucose and lipid homeostasis. The discovery of PPARγ as a target of multimodal insulin sensitizers, represented by thiazolidinediones (TZDs), has attracted remarkable scientific interest and had a great impact on the pharmaceutical industry. With the clinical success of the PPARγ agonists, pioglitazone (Actos) and rosiglitazone (Avandia), development of novel and potent insulin-sensitizing agents with diverse clinical profiles has been accelerated. Currently, a number of PPARγ agonists from different chemical classes and with varying pharmacological profiles are being developed. Despite quite a few obstacles to the development of PPAR-related drugs, PPARγ-targeted agents still hold promise. There are new concepts and encouraging evidence emerging that suggest this class can yield improved anti-diabetic agents. This review covers the discovery of TZDs, provides an overview of PPARγ including the significance of PPARγ as a drug target, describes the current status of a wide variety of novel PPARγ ligands including PPAR dual and pan agonists and selective PPARγ modulators (SPPARγMs), and highlights new approaches for identifying agents targeting PPARγ in the treatment of type 2 diabetes.
Export Options
About this article
Cite this article as:
Cho Nobuo and Momose Yu, Peroxisome Proliferator-Activated Receptor γ Agonists as Insulin Sensitizers: From the Discovery to Recent Progress, Current Topics in Medicinal Chemistry 2008; 8 (17) . https://dx.doi.org/10.2174/156802608786413474
DOI https://dx.doi.org/10.2174/156802608786413474 |
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
-
Pathophysiology of Post-Operative Low Cardiac Output Syndrome
Current Vascular Pharmacology Myocardial Inflammation in Autoimmune Diseases: Investigation by Cardiovascular Magnetic Resonance and Endomyocardial Biopsy
Inflammation & Allergy - Drug Targets (Discontinued) Patent Ductus Arteriosus in Extreme Prematurity: Role of Echocar-diography and Other Imaging Techniques
Current Pediatric Reviews Novel Strategies for the Detection of Systolic and Diastolic Heart Failure
Current Cardiology Reviews A Murine Model of Vasculitis Induced by Fungal Polysaccharide
Cardiovascular & Hematological Agents in Medicinal Chemistry Current Pharmacologic Management of Pediatric Heart Failure in Congenital Heart Disease
Current Vascular Pharmacology Nursing Assessment, Education, and Care of Extremely Premature Neonates with Patent Ductus Arteriosus
Current Pediatric Reviews Long-Term Effects of Perinatal Glucocorticoid Treatment on the Heart
Current Pediatric Reviews The GH/IGF-1 Axis and Heart Failure
Current Cardiology Reviews Atypical Presentation Of Anti-Retroviral Therapy Induced Lactic Acidosis as Acute Right Ventricular Failure And Severe Pulmonary Hypertension
New Emirates Medical Journal From Dual Peroxisome Proliferator Activated Receptor Agonists to Selective Peroxisome Proliferator Activated Receptor Modulators
Recent Patents on Endocrine, Metabolic & Immune Drug Discovery Calcium Related Genes in Dogs as Potential Cardiac Biomarkers for the Detection of Chronic Mitral Valve Disease
Recent Patents on Biomarkers Amyloid Formation by Transthyretin: From Protein Stability to Protein Aggregation
Current Medicinal Chemistry - Immunology, Endocrine & Metabolic Agents The Fetal Cardiac Function
Current Cardiology Reviews Selective Peroxisome Proliferator-Activated Receptor-γ Modulation to Reduce Cardiovascular Risk in Patients with Insulin Resistance
Recent Patents on Cardiovascular Drug Discovery Perinatal Heart Programming: Long-term Consequences
Current Medicinal Chemistry Medical Complications in Anorexia and Bulimia Nervosa
Endocrine, Metabolic & Immune Disorders - Drug Targets The Failing Heart in Pediatric Dilated Cardiomyopathy Caused by Excessive Water Drinking: A Case Report and Brief Review
New Emirates Medical Journal Beta-Blockers are Associated with Decreased In-Hospital Mortality and Stroke in Acute Decompensated Heart Failure: Findings from a Retrospective Analysis of a 22-Year Registry in the Middle East (1991-2013)
Current Vascular Pharmacology Reduction of Autophagic Accumulation in Pompe Disease Mouse Model Following Gene Therapy
Current Gene Therapy