Abstract
Virtual screening methods using structure-based, pharmacophore-based and descriptor based protocols may be used to identify ligands for the G-protein coupled receptor target family. A complementary approach is the synthesis and screening of compound libraries designed using privileged motifs and / or based on validated hit molecules. A virtual screening approach based on molecular docking performed with GOLD using a templated homology model and a consensus scoring procedure can identify vasopressin 1a receptor antagonists. In a separate project a library design and synthesis approach based around validated hit GPCR ligands led to the identification of potent oxytocin antagonists. Subsequent optimisation of the initial library compounds has provided compounds that are now being evaluated in the clinic for the treatment of preterm labour.
Keywords: gpcr, gold, oxytocin, pharmacophore, preterm labour, vasopressin, virtual screening
Combinatorial Chemistry & High Throughput Screening
Title: The Selection and Design of GPCR Ligands: From Concept to the Clinic
Volume: 7 Issue: 5
Author(s): Mark Ashton, Michael H. Charlton, Matthias K. Schwarz, Russell J. Thomas and Mark Whittaker
Affiliation:
Keywords: gpcr, gold, oxytocin, pharmacophore, preterm labour, vasopressin, virtual screening
Abstract: Virtual screening methods using structure-based, pharmacophore-based and descriptor based protocols may be used to identify ligands for the G-protein coupled receptor target family. A complementary approach is the synthesis and screening of compound libraries designed using privileged motifs and / or based on validated hit molecules. A virtual screening approach based on molecular docking performed with GOLD using a templated homology model and a consensus scoring procedure can identify vasopressin 1a receptor antagonists. In a separate project a library design and synthesis approach based around validated hit GPCR ligands led to the identification of potent oxytocin antagonists. Subsequent optimisation of the initial library compounds has provided compounds that are now being evaluated in the clinic for the treatment of preterm labour.
Export Options
About this article
Cite this article as:
Ashton Mark, Charlton H. Michael, Schwarz K. Matthias, Thomas J. Russell and Whittaker Mark, The Selection and Design of GPCR Ligands: From Concept to the Clinic, Combinatorial Chemistry & High Throughput Screening 2004; 7 (5) . https://dx.doi.org/10.2174/1386207043328607
DOI https://dx.doi.org/10.2174/1386207043328607 |
Print ISSN 1386-2073 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5402 |
- 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
-
Meet Our Editor:
Inflammation & Allergy - Drug Targets (Discontinued) Breaking the Skin Barrier: Achievements and Future Directions
Current Pharmaceutical Design Psoriatic Arthritis and its Novel Therapeutics
Current Rheumatology Reviews The Role of Obesity in Cardiomyopathy and Nephropathy
Current Pharmaceutical Design Modulation of GABAA Receptors in the Treatment of Epilepsy
Current Pharmaceutical Design Phosphocitrate, A Potential Therapeutic Agent for Calcium Crystal Deposition Diseases
Current Rheumatology Reviews Opiate Drug Use and the Pathophysiology of NeuroAIDS
Current HIV Research The Etiology of Hypertension in the Metabolic Syndrome Part Four: The Systemic Perspective – The Role of the Neuroendocrine and Immune Systems,and the Challenge of Integration
Current Vascular Pharmacology The NMDA Receptor NR2B Subunit: A Valid Therapeutic Target for Multiple CNS Pathologies
Current Medicinal Chemistry Editorial [Alcohol, the Lungs and Oxidative Stress]
Current Respiratory Medicine Reviews Stem Cells in Amyotrophic Lateral Sclerosis: Motor Neuron Protection or Replacement?
CNS & Neurological Disorders - Drug Targets Neuropeptides as Possible Targets in Sleep Disorders: Special Emphasis on Hypocretin-Deficient Narcolepsy
CNS & Neurological Disorders - Drug Targets Synthesis and Medicinal Applications of N-Aryl-C-nitroazoles
Mini-Reviews in Medicinal Chemistry Ureas: Applications in Drug Design
Current Medicinal Chemistry Endocannabinoid System: Emerging Role from Neurodevelopment to Neurodegeneration
Mini-Reviews in Medicinal Chemistry Increased CCL2 Expression and Macrophage/Monocyte Migration During Microbicide-Induced Vaginal Irritation
Current HIV Research An Updated Review on the Role of Single Nucleotide Polymorphisms in COVID-19 Disease Severity: A Global Aspect
Current Pharmaceutical Biotechnology The New Immunosuppression: Intervention at the Dendritic Cell-T-Cell Interface
Current Drug Targets - Immune, Endocrine & Metabolic Disorders Clinical Management of the Cardiovascular Failure in Sepsis
Current Vascular Pharmacology Computational and Experimental Advances in Drug Repositioning for Accelerated Therapeutic Stratification
Current Topics in Medicinal Chemistry