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
-
Pharmacological Applications of Antioxidants: Lights and Shadows
Current Drug Targets Recent Developments of Amidine-like Compounds as Selective NOS Inhibitors
Current Enzyme Inhibition Total Phenolic Content and In vitro Antioxidant Activity of Endophytic Fungi Isolated from Calotropis procera L.
Current Bioactive Compounds Cutoff Values of D-Dimer and FDP in Plasma for the Diagnosis of Thrombosis
Vascular Disease Prevention (Discontinued) Development and Characterization of Spray Dried Microparticles for Pulmonary Delivery of Antifungal Drug
Current Drug Delivery Angiotensin-Converting Enzyme 2 Roles in the Pathogenesis of COVID-19
Current Hypertension Reviews Memory Impairment is Associated with Serum Methylarginines in Older Adults
Current Alzheimer Research Oleacein. Translation from Mediterranean Diet to Potential Antiatherosclerotic Drug
Current Pharmaceutical Design The Effect of Sex and Gender on Diabetic Complications
Current Diabetes Reviews Improved Methods of Extraction and In Vitro Evaluation of Antimicrobial Potential of Stem Bark of Terminalia arjuna
Current Biochemical Engineering (Discontinued) Vascular Inflammation and Atherosclerosis: The Role of Estrogen Receptors
Current Medicinal Chemistry Novel Drug Targets in Malaria Parasite with Potential to Yield Antimalarial Drugs with Long Useful Therapeutic Lives
Current Pharmaceutical Design Revolutionary Impact of Nanodrug Delivery on Neuroscience
Current Neuropharmacology Chemistry and Biology of Anti-Inflammatory Marine Natural Products:Molecules Interfering with Cyclooxygenase, NF-kB and Other Unidentified Targets
Current Medicinal Chemistry Using PK/PD to Optimize Antibiotic Dosing for Critically Ill Patients
Current Pharmaceutical Biotechnology Cardiac Complications Attributed to Hydroxychloroquine: A Systematic Review of the Literature Pre-COVID-19
Current Cardiology Reviews The Impact of Small Heat Shock Proteins (HspBs) in Alzheimer’s and Other Neurological Diseases
Current Pharmaceutical Design Linezolid - The First Oxazolidinone in the Treatment of Nosocomial MRSA Pneumonia
Recent Patents on Anti-Infective Drug Discovery The Changing Face of HIV/AIDS in Treated Patients
Current HIV Research Therapeutic Hypothermia in Brain Injuries and Related Diseases
Recent Patents on Inflammation & Allergy Drug Discovery