Advances in the Development of Non-steroidal Mineralocorticoid-receptor Antagonists
| Autor: | Pérez-Gordillo, Felipe L., Pérez de Vega, M. Jesús, Gerona-Navarro, G., Rodríguez, Y., Alvarez de la Rosa, Diego, González-Muñiz, Rosario, Martín-Martínez, Mercedes |
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| Přispěvatelé: | Ministerio de Economía y Competitividad (España) |
| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
0303 health sciences
03 medical and health sciences Clinical trials 0302 clinical medicine Mineralocorticoid receptor InformationSystems_INFORMATIONSTORAGEANDRETRIEVAL MR antagonist 030204 cardiovascular system & hematology Structure-activity relationship GeneralLiterature_REFERENCE(e.g. dictionaries encyclopedias glossaries) 3. Good health 030304 developmental biology |
| Zdroj: | Aldosterone-Mineralocorticoid Receptor-Cell Biology to Translational Medicine Digital.CSIC. Repositorio Institucional del CSIC instname |
| Popis: | The mineralocorticoid receptor (MR) belongs to the nuclear receptor superfamily and regulates body fluid and electrolyte balance. In the last years, much effort has been put into the development of non-steroidal MR antagonists that overcome the side effects of the marketed steroid drugs, and can be used for the treatment of hypertension and heart failure, among others. Initially, MR was identified in epithelial cells, however it also plays important roles in non-epithelial tissues. In this sense, it is of interest to discover ligands that might induce different MR conformational changes, leading to specific coregulator interactions, which could confer tissue-specific effects. Different series of non-steroidal ligands with diverse central scaffolds has been described, which shows antihypertensive and cardiorenal protective effects. This review covers a description of different non-steroidal MR antagonist families, with special focus on compounds under clinical development. The analysis of the three-dimensional (3D) structures of non-steroidal MR antagonists in complex with the MR ligand-binding domain (LBD), recently reported, highlights the interactions crucial for binding. The structure-activity relationships of known ligands, together with the insights provided by the 3D structures of ligand - LBD MR complexes, could help in the development of non-steroidal MR antagonists with improved properties. This publication is based upon work from the EU COST Action ADMIRE BM1301 in Aldosterone and Mineralocorticoid Receptor (MR) Physiology and Pathophysiology (www.admirecosteu.com). Also supported by grants from Ministerio de Economia y Competitividad (MINECO, Spain; grant SAF2015-66275- C2-2-R and BFU2016-78374-R), CUNY (CCRG-1532), and the Hostos Office of Academic Affairs, US National Institute of Health (NIGMS) SC2GM111231 |
| Databáze: | OpenAIRE |
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