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Towards Decoding Hepatotoxicity of Approved Drugs through Navigation of Multiverse and Consensus Chemical Spaces

Drug-induced liver injury (DILI) is the principal reason for failure in developing drug candidates. It is the most common reason to withdraw from the market after a drug has been approved for clinical use. In this context, data from animal models, liver function tests, and chemical properties could...

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Autores principales: López-López, Edgar, Medina-Franco, José L.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9855470/
https://www.ncbi.nlm.nih.gov/pubmed/36671561
http://dx.doi.org/10.3390/biom13010176
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author López-López, Edgar
Medina-Franco, José L.
author_facet López-López, Edgar
Medina-Franco, José L.
author_sort López-López, Edgar
collection PubMed
description Drug-induced liver injury (DILI) is the principal reason for failure in developing drug candidates. It is the most common reason to withdraw from the market after a drug has been approved for clinical use. In this context, data from animal models, liver function tests, and chemical properties could complement each other to understand DILI events better and prevent them. Since the chemical space concept improves decision-making drug design related to the prediction of structure–property relationships, side effects, and polypharmacology drug activity (uniquely mentioning the most recent advances), it is an attractive approach to combining different phenomena influencing DILI events (e.g., individual “chemical spaces”) and exploring all events simultaneously in an integrated analysis of the DILI-relevant chemical space. However, currently, no systematic methods allow the fusion of a collection of different chemical spaces to collect different types of data on a unique chemical space representation, namely “consensus chemical space.” This study is the first report that implements data fusion to consider different criteria simultaneously to facilitate the analysis of DILI-related events. In particular, the study highlights the importance of analyzing together in vitro and chemical data (e.g., topology, bond order, atom types, presence of rings, ring sizes, and aromaticity of compounds encoded on RDKit fingerprints). These properties could be aimed at improving the understanding of DILI events.
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spelling pubmed-98554702023-01-21 Towards Decoding Hepatotoxicity of Approved Drugs through Navigation of Multiverse and Consensus Chemical Spaces López-López, Edgar Medina-Franco, José L. Biomolecules Article Drug-induced liver injury (DILI) is the principal reason for failure in developing drug candidates. It is the most common reason to withdraw from the market after a drug has been approved for clinical use. In this context, data from animal models, liver function tests, and chemical properties could complement each other to understand DILI events better and prevent them. Since the chemical space concept improves decision-making drug design related to the prediction of structure–property relationships, side effects, and polypharmacology drug activity (uniquely mentioning the most recent advances), it is an attractive approach to combining different phenomena influencing DILI events (e.g., individual “chemical spaces”) and exploring all events simultaneously in an integrated analysis of the DILI-relevant chemical space. However, currently, no systematic methods allow the fusion of a collection of different chemical spaces to collect different types of data on a unique chemical space representation, namely “consensus chemical space.” This study is the first report that implements data fusion to consider different criteria simultaneously to facilitate the analysis of DILI-related events. In particular, the study highlights the importance of analyzing together in vitro and chemical data (e.g., topology, bond order, atom types, presence of rings, ring sizes, and aromaticity of compounds encoded on RDKit fingerprints). These properties could be aimed at improving the understanding of DILI events. MDPI 2023-01-14 /pmc/articles/PMC9855470/ /pubmed/36671561 http://dx.doi.org/10.3390/biom13010176 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/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 (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
López-López, Edgar
Medina-Franco, José L.
Towards Decoding Hepatotoxicity of Approved Drugs through Navigation of Multiverse and Consensus Chemical Spaces
title Towards Decoding Hepatotoxicity of Approved Drugs through Navigation of Multiverse and Consensus Chemical Spaces
title_full Towards Decoding Hepatotoxicity of Approved Drugs through Navigation of Multiverse and Consensus Chemical Spaces
title_fullStr Towards Decoding Hepatotoxicity of Approved Drugs through Navigation of Multiverse and Consensus Chemical Spaces
title_full_unstemmed Towards Decoding Hepatotoxicity of Approved Drugs through Navigation of Multiverse and Consensus Chemical Spaces
title_short Towards Decoding Hepatotoxicity of Approved Drugs through Navigation of Multiverse and Consensus Chemical Spaces
title_sort towards decoding hepatotoxicity of approved drugs through navigation of multiverse and consensus chemical spaces
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9855470/
https://www.ncbi.nlm.nih.gov/pubmed/36671561
http://dx.doi.org/10.3390/biom13010176
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