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.
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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 |
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