Synthesis, Experimental and Computational Evaluation of SERAAK1 as a 5-HT2A Receptor Ligand
Many drug discovery efforts have identified potentially promising molecules; however, a common limitation of these reports is the lack of further experimental confirmation of pharmacokinetic properties and behavioral effects of discovered compounds. In this study, we aim to address this limitation....
| Autores: | , , , , , , , , , , |
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| Tipo de recurso: | artículo |
| Fecha de publicación: | 2025 |
| País: | España |
| Institución: | Universidad de Santiago de Compostela (USC) |
| Repositorio: | Minerva. Repositorio Institucional de la Universidad de Santiago de Compostela |
| Idioma: | inglés |
| OAI Identifier: | oai:minerva.usc.gal:10347/41629 |
| Acceso en línea: | https://hdl.handle.net/10347/41629 |
| Access Level: | acceso abierto |
| Palabra clave: | 5-HT2A receptor ADMET Antidepressants Antipsychotics In vivo studies Molecular modeling 320808 Mecanismos de acción de los medicamentos 320909 Psicofarmacología 320990 Farmacología experimental |
| Sumario: | Many drug discovery efforts have identified potentially promising molecules; however, a common limitation of these reports is the lack of further experimental confirmation of pharmacokinetic properties and behavioral effects of discovered compounds. In this study, we aim to address this limitation. Therefore, we build on our previous virtual screening campaign by synthesizing, analyzing in silico, and evaluating experimentally the SERAAK1 compound, which was initially identified as a ligand for 5-HT1A, 5-HT2A, and D2 receptors. Through these investigations, we discovered that SERAAK1 binds to the orthosteric pocket of the 5-HT2A receptor in a similar mechanism to that known for marketed antipsychotic medications. Molecular dynamics simulations revealed that the SERAAK1 compound remains stable in the orthosteric binding pocket of the 5-HT2A receptor. The determination of the ADMET parameters indicated the directions for further optimization of the compounds. In vivo studies demonstrated the anxiolytic and antidepressant properties of the SERAAK1 compound. |
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