Morphological Profiling Identifies a Common Mode of Action for Small Molecules with Different Targets.
antiproliferative
cell cycle
iron chelators
mode of action
phenotypic profiling
Journal
Chembiochem : a European journal of chemical biology
ISSN: 1439-7633
Titre abrégé: Chembiochem
Pays: Germany
ID NLM: 100937360
Informations de publication
Date de publication:
16 11 2020
16 11 2020
Historique:
received:
16
06
2020
revised:
02
07
2020
pubmed:
4
7
2020
medline:
7
7
2021
entrez:
4
7
2020
Statut:
ppublish
Résumé
Unbiased morphological profiling of bioactivity, for example, in the cell painting assay (CPA), enables the identification of a small molecule's mode of action based on its similarity to the bioactivity of reference compounds, irrespective of the biological target or chemical similarity. This is particularly important for small molecules with nonprotein targets as these are rather difficult to identify with widely employed target-identification methods. We employed morphological profiling using the CPA to identify compounds that are biosimilar to the iron chelator deferoxamine. Structurally different compounds with different annotated cellular targets provoked a shared physiological response, thereby defining a cluster based on their morphological fingerprints. This cluster is based on a shared mode of action and not on a shared target, that is, cell-cycle modulation in the S or G2 phase. Hierarchical clustering of morphological fingerprints revealed subclusters that are based on the mechanism of action and could be used to predict target-related bioactivity.
Identifiants
pubmed: 32618075
doi: 10.1002/cbic.202000381
pmc: PMC7754162
doi:
Substances chimiques
Iron Chelating Agents
0
Small Molecule Libraries
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
3197-3207Informations de copyright
© 2020 The Authors. Published by Wiley-VCH Verlag GmbH & Co. KGaA.
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