Abstract
G protein-coupled receptors (GPCRs) represent the family of proteins with the highest impact from social, therapeutic and economic point of view. Today, more than 50% of drug targets are based on GPCRs and the annual worldwide sales exceeds $50 billion. GPCRs are involved in all major disease areas such as cardiovascular, metabolic, neurodegenerative, psychiatric, cancer and infectious diseases. The classical drug discovery process has relied on screening compounds, which interact favorably with the GPCR of interest followed by further chemical engineering as a mean of improving efficacy and selectivity. In this review, methods for sophisticated chemical library screening procedures will be presented. Furthermore, development of cell-based assays for functional coupling of GPCRs to G proteins will be discussed. Finally, the possibility of applying structure-based drug design will be summarized. This includes the application of bioinformatics knowledge and molecular modeling approaches in drug development programs. The major efforts established through large networks of structural genomics on GPCRs, where recombinantly expressed GPCRs are subjected to purification and crystallization attempts with the intention of obtaining high-resolution structures, are presented as a promising future approach for tailor-made drug development.
Keywords: signal transduction, GPCR expression, drug screening, mammalian cell lines, neurotensin receptor (NTR)
Current Protein & Peptide Science
Title: Latest Development in Drug Discovery on G Protein-coupled Receptors
Volume: 7 Issue: 5
Keywords: signal transduction, GPCR expression, drug screening, mammalian cell lines, neurotensin receptor (NTR)
Abstract: G protein-coupled receptors (GPCRs) represent the family of proteins with the highest impact from social, therapeutic and economic point of view. Today, more than 50% of drug targets are based on GPCRs and the annual worldwide sales exceeds $50 billion. GPCRs are involved in all major disease areas such as cardiovascular, metabolic, neurodegenerative, psychiatric, cancer and infectious diseases. The classical drug discovery process has relied on screening compounds, which interact favorably with the GPCR of interest followed by further chemical engineering as a mean of improving efficacy and selectivity. In this review, methods for sophisticated chemical library screening procedures will be presented. Furthermore, development of cell-based assays for functional coupling of GPCRs to G proteins will be discussed. Finally, the possibility of applying structure-based drug design will be summarized. This includes the application of bioinformatics knowledge and molecular modeling approaches in drug development programs. The major efforts established through large networks of structural genomics on GPCRs, where recombinantly expressed GPCRs are subjected to purification and crystallization attempts with the intention of obtaining high-resolution structures, are presented as a promising future approach for tailor-made drug development.
Export Options
About this article
Cite this article as:
Latest Development in Drug Discovery on G Protein-coupled Receptors, Current Protein & Peptide Science 2006; 7 (5) . https://dx.doi.org/10.2174/138920306778559403
DOI https://dx.doi.org/10.2174/138920306778559403 |
Print ISSN 1389-2037 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5550 |
Call for Papers in Thematic Issues
Advancements in Proteomic and Peptidomic Approaches in Cancer Immunotherapy: Unveiling the Immune Microenvironment
The scope of this thematic issue centers on the integration of proteomic and peptidomic technologies into the field of cancer immunotherapy, with a particular emphasis on exploring the tumor immune microenvironment. This issue aims to gather contributions that illustrate the application of these advanced methodologies in unveiling the complex interplay ...read more
Artificial Intelligence for Protein Research
Protein research, essential for understanding biological processes and creating therapeutics, faces challenges due to the intricate nature of protein structures and functions. Traditional methods are limited in exploring the vast protein sequence space efficiently. Artificial intelligence (AI) and machine learning (ML) offer promising solutions by improving predictions and speeding up ...read more
Nutrition and Metabolism in Musculoskeletal Diseases
The musculoskeletal system consists mainly of cartilage, bone, muscles, tendons, connective tissue and ligaments. Balanced metabolism is of vital importance for the homeostasis of the musculoskeletal system. A series of musculoskeletal diseases (for example, sarcopenia, osteoporosis) are resulted from the dysregulated metabolism of the musculoskeletal system. Furthermore, metabolic diseases (such ...read more
Protein Folding, Aggregation and Liquid-Liquid Phase Separation
Protein folding, misfolding and aggregation remain one of the main problems of interdisciplinary science not only because many questions are still open, but also because they are important from the point of view of practical application. Protein aggregation and formation of fibrillar structures, for example, is a hallmark of a ...read more
Related Journals
- 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
Related Articles
-
Can Lipoprotein-associated Phospholipase A<sub>2</sub> be Used as a Predictor of Long-term Outcome in Patients with Acute Coronary Syndrome?
Current Cardiology Reviews Gene Therapy Approaches for Cardiovascular Diseases
Current Gene Therapy Targeting Trypanosoma cruzi Platelet-activating Factor Receptors: Scope for the Development of Novel Drugs to Treat Chagas Disease
Mini-Reviews in Medicinal Chemistry Novel Strategies for the Detection of Systolic and Diastolic Heart Failure
Current Cardiology Reviews Inflammation as a Therapeutic Target in Acute Ischemic Stroke Treatment
Current Topics in Medicinal Chemistry Treatment of Psoriasis: A Comprehensive Review of Entire Therapies
Current Drug Safety Does the Immune System Regulate Mood to Defend against Infection? Evidence from Studies of Immune Factors, Depression, and Antidepressants
Current Psychiatry Reviews A Comprehensive Study of Pharmacological Behaviors, Nano-Formulations, and Applications of Rosemary
The Natural Products Journal Nucleic Acid Aptamers Based on the G-Quadruplex Structure: Therapeutic and Diagnostic Potential
Current Medicinal Chemistry Oral Colonization by Nosocomial Pathogens During Hospitalization in Intensive Care Unit and Prevention Strategies
Recent Patents on Anti-Infective Drug Discovery Magnetic Field-Assisted Gene Delivery: Achievements and Therapeutic Potential
Current Gene Therapy Central Nervous System Circuitry and Peripheral Neural Sympathetic Activity Responsible for Essential Hypertension
Current Neurovascular Research EHT0202 in Alzheimers Disease: A 3-Month, Randomized, Placebo- Controlled, Double-Blind Study
Current Alzheimer Research Ursolic Acid and Oleanolic Acid: Pentacyclic Terpenoids with Promising Anti-Inflammatory Activities
Recent Patents on Inflammation & Allergy Drug Discovery Ozone: A Multifaceted Molecule with Unexpected Therapeutic Activity
Current Medicinal Chemistry Hypoxia Inducible Factor-1 as a Target for Neurodegenerative Diseases
Current Medicinal Chemistry New Developments in Molecular Diagnosis of Bacteremic Pneumococcal Pneumonia
Current Respiratory Medicine Reviews The Properties of Poly(3-hydroxybutyrate-co-3-hydroxyhexanoate) and its Applications in Tissue Engineering
Current Stem Cell Research & Therapy Practical Review of Mechanical Ventilation in Adults and Children in the Operating Room and Emergency Department
Reviews on Recent Clinical Trials Editorial (Thematic Issue: Nanopharmaceutics for Patient Care)
Current Nanomedicine