Application of automated machine learning in the identification of multi-target-directed ligands blocking PDE4B, PDE8A, and TRPA1 with potential use in the treatment of asthma and COPD.
AutoML
COPD
MTDL
QSAR model
asthma
Journal
Molecular informatics
ISSN: 1868-1751
Titre abrégé: Mol Inform
Pays: Germany
ID NLM: 101529315
Informations de publication
Date de publication:
07 2023
07 2023
Historique:
revised:
25
04
2023
received:
30
08
2022
accepted:
16
05
2023
medline:
13
7
2023
pubmed:
17
5
2023
entrez:
16
5
2023
Statut:
ppublish
Résumé
Asthma and COPD are characterized by complex pathophysiology associated with chronic inflammation, bronchoconstriction, and bronchial hyperresponsiveness resulting in airway remodeling. A possible comprehensive solution that could fully counteract the pathological processes of both diseases are rationally designed multi-target-directed ligands (MTDLs), combining PDE4B and PDE8A inhibition with TRPA1 blockade. The aim of the study was to develop AutoML models to search for novel MTDL chemotypes blocking PDE4B, PDE8A, and TRPA1. Regression models were developed for each of the biological targets using "mljar-supervised". On their basis, virtual screenings of commercially available compounds derived from the ZINC15 database were performed. A common group of compounds placed within the top results was selected as potential novel chemotypes of multifunctional ligands. This study represents the first attempt to discover the potential MTDLs inhibiting three biological targets. The obtained results prove the usefulness of AutoML methodology in the identification of hits from the big compound databases.
Identifiants
pubmed: 37193653
doi: 10.1002/minf.202200214
doi:
Substances chimiques
Ligands
0
TRPA1 protein, human
0
TRPA1 Cation Channel
0
PDE4B protein, human
EC 3.1.4.17
Cyclic Nucleotide Phosphodiesterases, Type 4
EC 3.1.4.17
PDE8A protein, human
EC 3.1.4.17
3',5'-Cyclic-AMP Phosphodiesterases
EC 3.1.4.17
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e2200214Informations de copyright
© 2023 Wiley-VCH GmbH.
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