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Cardioprotective Melatonin: Translating from Proof-of-Concept Studies to Therapeutic Use
In this review we summarized the actual clinical data for a cardioprotective therapeutic role of melatonin, listed melatonin and its agonists in different stages of development, and evaluated the melatonin cardiovascular target tractability and prediction using machine learning on ChEMBL. To date, m...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6770816/ https://www.ncbi.nlm.nih.gov/pubmed/31491852 http://dx.doi.org/10.3390/ijms20184342 |
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author | Baltatu, Ovidiu Constantin Senar, Sergio Campos, Luciana Aparecida Cipolla-Neto, José |
author_facet | Baltatu, Ovidiu Constantin Senar, Sergio Campos, Luciana Aparecida Cipolla-Neto, José |
author_sort | Baltatu, Ovidiu Constantin |
collection | PubMed |
description | In this review we summarized the actual clinical data for a cardioprotective therapeutic role of melatonin, listed melatonin and its agonists in different stages of development, and evaluated the melatonin cardiovascular target tractability and prediction using machine learning on ChEMBL. To date, most clinical trials investigating a cardioprotective therapeutic role of melatonin are in phase 2a. Selective melatonin receptor agonists Tasimelteon, Ramelteon, and combined melatonergic-serotonin Agomelatine, and other agonists with registered structures in CHEMBL were not yet investigated as cardioprotective or cardiovascular drugs. As drug-able for these therapeutic targets, melatonin receptor agonists have the benefit over melatonin of well-characterized pharmacologic profiles and extensive safety data. Recent reports of the X-ray crystal structures of MT1 and MT2 receptors shall lead to the development of highly selective melatonin receptor agonists. Predictive models using machine learning could help to identify cardiovascular targets for melatonin. Selecting ChEMBL scores > 4.5 in cardiovascular assays, and melatonin scores > 4, we obtained 284 records from 162 cardiovascular assays carried out with 80 molecules with predicted or measured melatonin activity. Melatonin activities (agonistic or antagonistic) found in these experimental cardiovascular assays and models include arrhythmias, coronary and large vessel contractility, and hypertension. Preclinical proof-of-concept and early clinical studies (phase 2a) suggest a cardioprotective benefit from melatonin in various heart diseases. However, larger phase 3 randomized interventional studies are necessary to establish melatonin and its agonists’ actions as cardioprotective therapeutic agents. |
format | Online Article Text |
id | pubmed-6770816 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-67708162019-10-30 Cardioprotective Melatonin: Translating from Proof-of-Concept Studies to Therapeutic Use Baltatu, Ovidiu Constantin Senar, Sergio Campos, Luciana Aparecida Cipolla-Neto, José Int J Mol Sci Review In this review we summarized the actual clinical data for a cardioprotective therapeutic role of melatonin, listed melatonin and its agonists in different stages of development, and evaluated the melatonin cardiovascular target tractability and prediction using machine learning on ChEMBL. To date, most clinical trials investigating a cardioprotective therapeutic role of melatonin are in phase 2a. Selective melatonin receptor agonists Tasimelteon, Ramelteon, and combined melatonergic-serotonin Agomelatine, and other agonists with registered structures in CHEMBL were not yet investigated as cardioprotective or cardiovascular drugs. As drug-able for these therapeutic targets, melatonin receptor agonists have the benefit over melatonin of well-characterized pharmacologic profiles and extensive safety data. Recent reports of the X-ray crystal structures of MT1 and MT2 receptors shall lead to the development of highly selective melatonin receptor agonists. Predictive models using machine learning could help to identify cardiovascular targets for melatonin. Selecting ChEMBL scores > 4.5 in cardiovascular assays, and melatonin scores > 4, we obtained 284 records from 162 cardiovascular assays carried out with 80 molecules with predicted or measured melatonin activity. Melatonin activities (agonistic or antagonistic) found in these experimental cardiovascular assays and models include arrhythmias, coronary and large vessel contractility, and hypertension. Preclinical proof-of-concept and early clinical studies (phase 2a) suggest a cardioprotective benefit from melatonin in various heart diseases. However, larger phase 3 randomized interventional studies are necessary to establish melatonin and its agonists’ actions as cardioprotective therapeutic agents. MDPI 2019-09-05 /pmc/articles/PMC6770816/ /pubmed/31491852 http://dx.doi.org/10.3390/ijms20184342 Text en © 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Review Baltatu, Ovidiu Constantin Senar, Sergio Campos, Luciana Aparecida Cipolla-Neto, José Cardioprotective Melatonin: Translating from Proof-of-Concept Studies to Therapeutic Use |
title | Cardioprotective Melatonin: Translating from Proof-of-Concept Studies to Therapeutic Use |
title_full | Cardioprotective Melatonin: Translating from Proof-of-Concept Studies to Therapeutic Use |
title_fullStr | Cardioprotective Melatonin: Translating from Proof-of-Concept Studies to Therapeutic Use |
title_full_unstemmed | Cardioprotective Melatonin: Translating from Proof-of-Concept Studies to Therapeutic Use |
title_short | Cardioprotective Melatonin: Translating from Proof-of-Concept Studies to Therapeutic Use |
title_sort | cardioprotective melatonin: translating from proof-of-concept studies to therapeutic use |
topic | Review |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6770816/ https://www.ncbi.nlm.nih.gov/pubmed/31491852 http://dx.doi.org/10.3390/ijms20184342 |
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