Abstract
Prevalence of type 2 diabetes has increased dramatically in the last decades. Current medicines are not yet capable to efficiently prevent or reverse progression of the disease and its associated comorbidities. As a consequence, there is a great need for novel antidiabetic drugs. Treatments of type 2 diabetes that are based on enhanced and sustained action of insulinotropic incretin hormones such as GLP-1 have received much attention in the past years. Treatment strategies include administration of: 1) GLP-1 analogues that are resistant to degradation by the serine protease DPP-IV, and 2) small molecule DPP-IV inhibitors that are able to provide sustained action of endogenous GLP-1, again by preventing its degradation. This review summarizes recent research results for the second approach. It briefly touches upon the advantages that treatment of type 2 diabetes with DPP-IV inhibitors may offer over current medications. In the main section, several important structural classes of DPP-IV inhibitors are described and compared based on literature data. Specific attention is given to the analysis of several X-ray structures of enzyme-inhibitor co-crystals. Finally, as clinical data are steadily emerging for some of the most advanced development candidates, the last section of this review is providing a brief overview of some efficacy data from recent clinical studies with DPP-IV inhibitors.
Keywords: hypoglycemia, GLP-1, peptidomimetics, Cyanopyrrolidines, cyclization, monotherapy
Current Topics in Medicinal Chemistry
Title: Inhibitors of Dipeptidyl Peptidase IV - Recent Advances and Structural Views
Volume: 5 Issue: 16
Author(s): Daniel Hunziker, Michael Hennig and Jens-Uwe Peters
Affiliation:
Keywords: hypoglycemia, GLP-1, peptidomimetics, Cyanopyrrolidines, cyclization, monotherapy
Abstract: Prevalence of type 2 diabetes has increased dramatically in the last decades. Current medicines are not yet capable to efficiently prevent or reverse progression of the disease and its associated comorbidities. As a consequence, there is a great need for novel antidiabetic drugs. Treatments of type 2 diabetes that are based on enhanced and sustained action of insulinotropic incretin hormones such as GLP-1 have received much attention in the past years. Treatment strategies include administration of: 1) GLP-1 analogues that are resistant to degradation by the serine protease DPP-IV, and 2) small molecule DPP-IV inhibitors that are able to provide sustained action of endogenous GLP-1, again by preventing its degradation. This review summarizes recent research results for the second approach. It briefly touches upon the advantages that treatment of type 2 diabetes with DPP-IV inhibitors may offer over current medications. In the main section, several important structural classes of DPP-IV inhibitors are described and compared based on literature data. Specific attention is given to the analysis of several X-ray structures of enzyme-inhibitor co-crystals. Finally, as clinical data are steadily emerging for some of the most advanced development candidates, the last section of this review is providing a brief overview of some efficacy data from recent clinical studies with DPP-IV inhibitors.
Export Options
About this article
Cite this article as:
Hunziker Daniel, Hennig Michael and Peters Jens-Uwe, Inhibitors of Dipeptidyl Peptidase IV - Recent Advances and Structural Views, Current Topics in Medicinal Chemistry 2005; 5 (16) . https://dx.doi.org/10.2174/156802605775009685
DOI https://dx.doi.org/10.2174/156802605775009685 |
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
-
Advances in Structural Modifications and Biological Activities of Berberine: An Active Compound in Traditional Chinese Medicine
Mini-Reviews in Medicinal Chemistry Pharmacological Treatments for Obesity
Immunology, Endocrine & Metabolic Agents in Medicinal Chemistry (Discontinued) Current Therapeutic Concepts in Peripartum Cardiomyopathy
Current Pharmaceutical Design Is Atorvastatin Superior to Other Statins? Analysis of the Clinical Trials with Atorvastatin Having Cardiovascular Endpoints
Reviews on Recent Clinical Trials A Comprehensive Analysis of Unique and Recurrent Copy Number Variations in Alzheimer’s Disease and its Related Disorders
Current Alzheimer Research Medication-Induced Nephrotoxicity in Older Patients
Current Drug Metabolism Hypothalamic Glucose Sensing and Glycaemic Disease
Current Diabetes Reviews Oral Inflammation and Bacteremia: Implications for Chronic and Acute Systemic Diseases Involving Major Organs
Cardiovascular & Hematological Disorders-Drug Targets Defining the Mechanism of Action of 4-Phenylbutyrate to Develop a Small-Molecule-Based Therapy for Alzheimers Disease
Current Medicinal Chemistry Autoantibodies for Cardiac Channels and Sudden Cardiac Death and its Relationship to Autoimmune Disorders
Current Cardiology Reviews Effect of Vitamin D<sub>3</sub> on Lifespan in Caenorhabditis elegans
Current Aging Science Editorial [ Has the Time Come for a New Definition of Microalbuminuria? ]
Current Vascular Pharmacology New Approaches in Drug Delivery Systems: Application for Diabetes Treatment
Infectious Disorders - Drug Targets Cytoprotection by Natural and Synthetic Polyphenols in the Heart: Novel Mechanisms and Perspectives
Current Pharmaceutical Design Long-Chain-Fatty-Acid CoA Ligases: The Key to Fatty Acid Activation, Formation of Xenobiotic Acyl-CoA Thioesters and Lipophilic Xenobiotic Conjugates
Current Medicinal Chemistry - Immunology, Endocrine & Metabolic Agents The Vicious Circle of Leptin and Obesity
Current Nutrition & Food Science Magnetic Resonance Imaging Findings of Sixth Cranial Nerve Palsies in Patients Presenting with Diplopia
Current Medical Imaging Visfatin/PBEF and Atherosclerosis-Related Diseases
Current Vascular Pharmacology Processed Foods, Dysbiosis, Systemic Inflammation, and Poor Health
Current Nutrition & Food Science NAMPT in Regulated NAD Biosynthesis and its Pivotal Role in Human Metabolism
Current Medicinal Chemistry