Abstract
Seven transmembrane G protein coupled receptors (7TM GPCRs) represent one of the largest gene familes in the human genome. Because of the size of the GPCR family, their proven history of being valuable targets for small molecule drug design, the fact that the absolute number of GPCRs that are targets for current medicines represents only a small fraction of the total encoded by the human genome, and that ligands for GPCRs do not have to enter the cell to exert their function, it is very likely that GPCRs will remain major targets for the pharmaceutical industry in the foreseeable future. Despite recent evidence indicating that GPCRs can provide information to cells, that does not require activation of G proteins ("signaling at zero G"), most of the GPCRs known to date function via interaction with and activation of heterotrimeric (αβγ) G proteins. Thus, assay systems translating ligand modulation of GPCRs into G protein-dependent intracellular responses are a key component of both basic research and the drug discovery process. This article will review the current knowledge and recent progress in understanding molecular aspects of specific receptor-G protein recognition. It will also highlight how the knowledge generated by such studies can be transformed into assay systems for GPCR drug discovery.
Keywords: GPCR, chimeric G protein, α subunit, βγ subunit, drug discovery, assay technology
Current Pharmaceutical Design
Title: G Proteins in Drug Screening: From Analysis of Receptor-G Protein Specificity to Manipulation of GPCR-Mediated Signalling Pathways
Volume: 12 Issue: 14
Author(s): Evi Kostenis
Affiliation:
Keywords: GPCR, chimeric G protein, α subunit, βγ subunit, drug discovery, assay technology
Abstract: Seven transmembrane G protein coupled receptors (7TM GPCRs) represent one of the largest gene familes in the human genome. Because of the size of the GPCR family, their proven history of being valuable targets for small molecule drug design, the fact that the absolute number of GPCRs that are targets for current medicines represents only a small fraction of the total encoded by the human genome, and that ligands for GPCRs do not have to enter the cell to exert their function, it is very likely that GPCRs will remain major targets for the pharmaceutical industry in the foreseeable future. Despite recent evidence indicating that GPCRs can provide information to cells, that does not require activation of G proteins ("signaling at zero G"), most of the GPCRs known to date function via interaction with and activation of heterotrimeric (αβγ) G proteins. Thus, assay systems translating ligand modulation of GPCRs into G protein-dependent intracellular responses are a key component of both basic research and the drug discovery process. This article will review the current knowledge and recent progress in understanding molecular aspects of specific receptor-G protein recognition. It will also highlight how the knowledge generated by such studies can be transformed into assay systems for GPCR drug discovery.
Export Options
About this article
Cite this article as:
Kostenis Evi, G Proteins in Drug Screening: From Analysis of Receptor-G Protein Specificity to Manipulation of GPCR-Mediated Signalling Pathways, Current Pharmaceutical Design 2006; 12 (14) . https://dx.doi.org/10.2174/138161206776873734
DOI https://dx.doi.org/10.2174/138161206776873734 |
Print ISSN 1381-6128 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4286 |
Call for Papers in Thematic Issues
"Tuberculosis Prevention, Diagnosis and Drug Discovery"
The Nobel Prize-winning discoveries of Mycobacterium tuberculosis and streptomycin have enabled an appropriate diagnosis and an effective treatment of tuberculosis (TB). Since then, many newer diagnosis methods and drugs have been saving millions of lives. Despite advances in the past, TB is still a leading cause of infectious disease mortality ...read more
Current Pharmaceutical challenges in the treatment and diagnosis of neurological dysfunctions
Neurological dysfunctions (MND, ALS, MS, PD, AD, HD, ALS, Autism, OCD etc..) present significant challenges in both diagnosis and treatment, often necessitating innovative approaches and therapeutic interventions. This thematic issue aims to explore the current pharmaceutical landscape surrounding neurological disorders, shedding light on the challenges faced by researchers, clinicians, and ...read more
Emerging and re-emerging diseases
Faced with a possible endemic situation of COVID-19, the world has experienced two important phenomena, the emergence of new infectious diseases and/or the resurgence of previously eradicated infectious diseases. Furthermore, the geographic distribution of such diseases has also undergone changes. This context, in turn, may have a strong relationship with ...read more
Melanoma and Non-Melanoma Skin Cancer Treatment: Standard of Care and Recent Advances
In this thematic issue, we aim to provide a standard of care of the diagnosis and treatment of melanoma and non-melanoma skin cancer. The editor will invite authors from different countries who will write review articles of melanoma and non-melanoma skin cancers. The Diagnosis, Staging, Surgical Treatment, Non-Surgical Treatment all ...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
-
Peptide Nucleic Acid Conjugates: Synthesis, Properties and Applications
Current Topics in Medicinal Chemistry Stereoselective Synthesis of Pyroglutamate Natural Product Analogs from α- Aminoacids and their Anti-Cancer Evaluation
Anti-Cancer Agents in Medicinal Chemistry Nitrogen-Containing Bisphosphonates and Cancer Immunotherapy
Current Pharmaceutical Design Target-oriented Mechanisms of Novel Herbal Therapeutics in the Chemotherapy of Gastrointestinal Cancer and Inflammation
Current Pharmaceutical Design Peptide-Based Anticancer Vaccines: Recent Advances and Future Perspectives
Current Medicinal Chemistry Nanoparticles: Properties and Applications in Cancer Immunotherapy
Current Pharmaceutical Design Synthesis of Benzophenonehydrazone Schiff Bases and their In Vitro Antiglycating Activities
Medicinal Chemistry Characterisation of Small Supernumerary Marker Chromosomes (sSMC) in Human
Current Genomics The Pentacyclic Triterpenoids in Herbal Medicines and Their Pharmacological Activities in Diabetes and Diabetic Complications
Current Medicinal Chemistry The Expression Patterns and Clinical Significance of microRNAs in Liver Diseases and Hepatocellular Carcinoma
Current Pharmaceutical Design Pathobiology and Therapeutic Implications of Tumor Acidosis
Current Medicinal Chemistry Pharmacology and Clinical Effect of Platonin, a Cyanine Photosensitizing Dye: Potential Molecular Targets
Current Pharmaceutical Biotechnology Natural Compounds in Anti-Leukaemic Therapy: A Review
Mini-Reviews in Medicinal Chemistry From Multiple PAR1 Receptor/Protein Interactions to their Multiple Therapeutic Implications
Current Topics in Medicinal Chemistry Epigenetic Regulation of Epithelial to Mesenchymal Transition
Current Cancer Drug Targets Formulation Optimization of Etoposide Loaded PLGA Nanoparticles by Double Factorial Design and their Evaluation
Current Drug Delivery Reactions of Hydrazones with Lead Tetraacetate in Organic Synthesis
Current Organic Chemistry DLEU1: A Functional Long Noncoding RNA in Tumorigenesis
Current Pharmaceutical Design Sulfur Containing Acridine Derivatives in Preclinical Studies with Cancer Cell Lines
Current Medicinal Chemistry NF-κB, a Potential Therapeutic Target for the Treatment of Multiple Sclerosis
CNS & Neurological Disorders - Drug Targets