From a4ß2 Nicotinic Ligands to the Discovery of σ1 Receptor Ligands: Pharmacophore Analysis and Rational Design
Comparative analyses of the pharmacophoric elements required for σ1 and nicotinic ligands led to the identification of a potent and selective σ1 ligand (15). Compound 15 displayed high selectivity for the σ1 receptor (Ki, σ1 = 4.1 nM; Ki, σ2 = 1312 nM) with moderate binding affinity for the DAT (Ki...
| Main Authors: | , , , |
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| Format: | Journal Article |
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American Chemical Society
2012
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| Online Access: | http://hdl.handle.net/20.500.11937/17442 |
| _version_ | 1848749467610644480 |
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| author | Yu, L. Zhang, H. Gunosewoyo, Hendra Kozikowski, A. |
| author_facet | Yu, L. Zhang, H. Gunosewoyo, Hendra Kozikowski, A. |
| author_sort | Yu, L. |
| building | Curtin Institutional Repository |
| collection | Online Access |
| description | Comparative analyses of the pharmacophoric elements required for σ1 and nicotinic ligands led to the identification of a potent and selective σ1 ligand (15). Compound 15 displayed high selectivity for the σ1 receptor (Ki, σ1 = 4.1 nM; Ki, σ2 = 1312 nM) with moderate binding affinity for the DAT (Ki = 373 nM) and NET (Ki = 203 nM) in the PDSP broad screening panel of common CNS neurotransmitter transporters and receptors. The key finding in this present work is that a subtle structural modification could be used as a tool to switch a ligand’s selectivity between nAChRs and sigma receptors. |
| first_indexed | 2025-11-14T07:21:24Z |
| format | Journal Article |
| id | curtin-20.500.11937-17442 |
| institution | Curtin University Malaysia |
| institution_category | Local University |
| last_indexed | 2025-11-14T07:21:24Z |
| publishDate | 2012 |
| publisher | American Chemical Society |
| recordtype | eprints |
| repository_type | Digital Repository |
| spelling | curtin-20.500.11937-174422018-03-29T09:06:21Z From a4ß2 Nicotinic Ligands to the Discovery of σ1 Receptor Ligands: Pharmacophore Analysis and Rational Design Yu, L. Zhang, H. Gunosewoyo, Hendra Kozikowski, A. broad screening sigma-1 receptor alkoxyisoxazole Nicotinic acetylcholine receptor pharmacophore Comparative analyses of the pharmacophoric elements required for σ1 and nicotinic ligands led to the identification of a potent and selective σ1 ligand (15). Compound 15 displayed high selectivity for the σ1 receptor (Ki, σ1 = 4.1 nM; Ki, σ2 = 1312 nM) with moderate binding affinity for the DAT (Ki = 373 nM) and NET (Ki = 203 nM) in the PDSP broad screening panel of common CNS neurotransmitter transporters and receptors. The key finding in this present work is that a subtle structural modification could be used as a tool to switch a ligand’s selectivity between nAChRs and sigma receptors. 2012 Journal Article http://hdl.handle.net/20.500.11937/17442 10.1021/ml3002715 American Chemical Society restricted |
| spellingShingle | broad screening sigma-1 receptor alkoxyisoxazole Nicotinic acetylcholine receptor pharmacophore Yu, L. Zhang, H. Gunosewoyo, Hendra Kozikowski, A. From a4ß2 Nicotinic Ligands to the Discovery of σ1 Receptor Ligands: Pharmacophore Analysis and Rational Design |
| title | From a4ß2 Nicotinic Ligands to the Discovery of σ1 Receptor Ligands: Pharmacophore Analysis and Rational Design |
| title_full | From a4ß2 Nicotinic Ligands to the Discovery of σ1 Receptor Ligands: Pharmacophore Analysis and Rational Design |
| title_fullStr | From a4ß2 Nicotinic Ligands to the Discovery of σ1 Receptor Ligands: Pharmacophore Analysis and Rational Design |
| title_full_unstemmed | From a4ß2 Nicotinic Ligands to the Discovery of σ1 Receptor Ligands: Pharmacophore Analysis and Rational Design |
| title_short | From a4ß2 Nicotinic Ligands to the Discovery of σ1 Receptor Ligands: Pharmacophore Analysis and Rational Design |
| title_sort | from a4ß2 nicotinic ligands to the discovery of σ1 receptor ligands: pharmacophore analysis and rational design |
| topic | broad screening sigma-1 receptor alkoxyisoxazole Nicotinic acetylcholine receptor pharmacophore |
| url | http://hdl.handle.net/20.500.11937/17442 |