Please use this identifier to cite or link to this item:
https://doi.org/10.1016/j.bmc.2009.05.072
DC Field | Value | |
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dc.title | Synergism of virtual screening and medicinal chemistry: Identification and optimization of allosteric antagonists of metabotropic glutamate receptor 1 | |
dc.contributor.author | Noeske, T. | |
dc.contributor.author | Trifanova, D. | |
dc.contributor.author | Kauss, V. | |
dc.contributor.author | Renner, S. | |
dc.contributor.author | Parsons, C.G. | |
dc.contributor.author | Schneider, G. | |
dc.contributor.author | Weil, T. | |
dc.date.accessioned | 2014-10-16T08:42:39Z | |
dc.date.available | 2014-10-16T08:42:39Z | |
dc.date.issued | 2009-08-01 | |
dc.identifier.citation | Noeske, T., Trifanova, D., Kauss, V., Renner, S., Parsons, C.G., Schneider, G., Weil, T. (2009-08-01). Synergism of virtual screening and medicinal chemistry: Identification and optimization of allosteric antagonists of metabotropic glutamate receptor 1. Bioorganic and Medicinal Chemistry 17 (15) : 5708-5715. ScholarBank@NUS Repository. https://doi.org/10.1016/j.bmc.2009.05.072 | |
dc.identifier.issn | 09680896 | |
dc.identifier.uri | http://scholarbank.nus.edu.sg/handle/10635/94999 | |
dc.description.abstract | We report the identification of novel potent and selective metabotropic glutamate receptor 1 (mGluR1) antagonists by virtual screening and subsequent hit optimization. For ligand-based virtual screening, molecules were represented by a topological pharmacophore descriptor (CATS-2D) and clustered by a self-organizing map (SOM). The most promising compounds were tested in mGluR1 functional and binding assays. We identified a potent chemotype exhibiting selective antagonistic activity at mGluR1 (functional IC50 = 0.74 ± 0.29 μM). Hit optimization yielded lead structure 16 with an affinity of Ki = 0.024 ± 0.001 μM and greater than 1000-fold selectivity for mGluR1 versus mGluR5. Homology-based receptor modelling suggests a binding site compatible with previously reported mutation studies. Our study demonstrates the usefulness of ligand-based virtual screening for scaffold-hopping and rapid lead structure identification in early drug discovery projects. © 2009 Elsevier Ltd. All rights reserved. | |
dc.description.uri | http://libproxy1.nus.edu.sg/login?url=http://dx.doi.org/10.1016/j.bmc.2009.05.072 | |
dc.source | Scopus | |
dc.subject | Antagonist | |
dc.subject | Metabotropic | |
dc.subject | mGluR1 | |
dc.subject | Self-organizing map | |
dc.subject | Virtual screening | |
dc.type | Article | |
dc.contributor.department | CHEMISTRY | |
dc.description.doi | 10.1016/j.bmc.2009.05.072 | |
dc.description.sourcetitle | Bioorganic and Medicinal Chemistry | |
dc.description.volume | 17 | |
dc.description.issue | 15 | |
dc.description.page | 5708-5715 | |
dc.description.coden | BMECE | |
dc.identifier.isiut | 000268099700040 | |
Appears in Collections: | Staff Publications |
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