Ligand-based virtual screening identifies a family of selective cannabinoid receptor 2 agonists.
The cannabinoid receptor 2 (CB2R) has been linked with the regulation of inflammation, and selective receptor activation has been proposed as a target for the treatment of a range of inflammatory diseases such as atherosclerosis and arthritis. In order to identify selective CB2R agonists with approp...
| Main Authors: | , , , , , , |
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| Format: | Journal article |
| Language: | English |
| Published: |
Elsevier
2015
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| _version_ | 1826293915401060352 |
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| author | Gianella-Borradori, M Christou, I Bataille, C Cross, R Wynne, G Greaves, D Russell, A |
| author_facet | Gianella-Borradori, M Christou, I Bataille, C Cross, R Wynne, G Greaves, D Russell, A |
| author_sort | Gianella-Borradori, M |
| collection | OXFORD |
| description | The cannabinoid receptor 2 (CB2R) has been linked with the regulation of inflammation, and selective receptor activation has been proposed as a target for the treatment of a range of inflammatory diseases such as atherosclerosis and arthritis. In order to identify selective CB2R agonists with appropriate physicochemical and ADME properties for future evaluation in vivo, we first performed a ligand-based virtual screen. Subsequent medicinal chemistry optimisation studies led to the identification of a new class of selective CB2R agonists. Several examples showed high levels of activity (EC50<200nM) and binding affinity (Ki<200nM) for the CB2R, and no detectable activity at the CB1R. The most promising example, DIAS2, also showed favourable in vitro metabolic stability and absorption properties along with a clean selectivity profile when evaluated against a panel of GPCRs and kinases. |
| first_indexed | 2024-03-07T03:37:32Z |
| format | Journal article |
| id | oxford-uuid:bccc129a-d42b-4913-bd2d-80311abd5aa6 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T03:37:32Z |
| publishDate | 2015 |
| publisher | Elsevier |
| record_format | dspace |
| spelling | oxford-uuid:bccc129a-d42b-4913-bd2d-80311abd5aa62022-03-27T05:27:04ZLigand-based virtual screening identifies a family of selective cannabinoid receptor 2 agonists.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:bccc129a-d42b-4913-bd2d-80311abd5aa6EnglishSymplectic Elements at OxfordElsevier2015Gianella-Borradori, MChristou, IBataille, CCross, RWynne, GGreaves, DRussell, AThe cannabinoid receptor 2 (CB2R) has been linked with the regulation of inflammation, and selective receptor activation has been proposed as a target for the treatment of a range of inflammatory diseases such as atherosclerosis and arthritis. In order to identify selective CB2R agonists with appropriate physicochemical and ADME properties for future evaluation in vivo, we first performed a ligand-based virtual screen. Subsequent medicinal chemistry optimisation studies led to the identification of a new class of selective CB2R agonists. Several examples showed high levels of activity (EC50<200nM) and binding affinity (Ki<200nM) for the CB2R, and no detectable activity at the CB1R. The most promising example, DIAS2, also showed favourable in vitro metabolic stability and absorption properties along with a clean selectivity profile when evaluated against a panel of GPCRs and kinases. |
| spellingShingle | Gianella-Borradori, M Christou, I Bataille, C Cross, R Wynne, G Greaves, D Russell, A Ligand-based virtual screening identifies a family of selective cannabinoid receptor 2 agonists. |
| title | Ligand-based virtual screening identifies a family of selective cannabinoid receptor 2 agonists. |
| title_full | Ligand-based virtual screening identifies a family of selective cannabinoid receptor 2 agonists. |
| title_fullStr | Ligand-based virtual screening identifies a family of selective cannabinoid receptor 2 agonists. |
| title_full_unstemmed | Ligand-based virtual screening identifies a family of selective cannabinoid receptor 2 agonists. |
| title_short | Ligand-based virtual screening identifies a family of selective cannabinoid receptor 2 agonists. |
| title_sort | ligand based virtual screening identifies a family of selective cannabinoid receptor 2 agonists |
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