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Illuminating Dark Chemical Matter Using the Cell Painting Assay

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Τίτλος: Illuminating Dark Chemical Matter Using the Cell Painting Assay
Συγγραφείς: Pahl, Axel, Liu, Jie, PATIL, SOHAN, Rezaei Adariani, Soheila, Schölermann, Beate, Warmers, Jens, Bonowski, Jana, Koska, Sandra, Akbulut, Yasemin, Seitz, Carina, Sievers, Sonja, Ziegler, Slava, Waldmann, Herbert
Πηγή: http://lobid.org/resources/99370676049806441#!, 67(11):8862-8876.
Έτος έκδοσης: 2024
Συλλογή: Publisso (ZB MED-Publikationsportal Lebenswissenschaften)
Θεματικοί όροι: Small Molecule Libraries/chemistry [MeSH], Pyrimidines/pharmacology [MeSH], Pyrimidines/chemistry [MeSH], Cell Line, Tumor [MeSH], Article, DNA/chemistry [MeSH], Pyrimidines/chemical synthesis [MeSH], Humans [MeSH], Microtubules/drug effects [MeSH], Small Molecule Libraries/pharmacology [MeSH], Microtubules/metabolism [MeSH]
Περιγραφή: Screening for small-molecule modulators of disease-relevant targets and phenotypes is the first step on the way to new drugs. Large compound libraries have been synthesized by academia and, particularly, pharmaceutical companies to meet the need for novel chemical entities that are as diverse as possible. Screening of these compound libraries revealed a portion of small molecules that is inactive in more than 100 different assays and was therefore termed 'dark chemical matter' (DCM). Deorphanization of DCM promises to yield very selective compounds as they are expected to have less off-target effects. We employed morphological profiling using the Cell Painting assay to detect bioactive DCM. Within the DCM collection, we identified bioactive compounds and confirmed several modulators of microtubules, DNA synthesis, and pyrimidine biosynthesis. Profiling approaches are, therefore, powerful tools to probe compound collections for bioactivity in an unbiased manner and are particularly suitable for deorphanization of DCM.
Τύπος εγγράφου: article in journal/newspaper
Γλώσσα: English
Relation: https://repository.publisso.de/resource/frl:6485910; https://doi.org/10.1021/acs.jmedchem.4c00160; https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11181314/
DOI: 10.1021/acs.jmedchem.4c00160
Διαθεσιμότητα: https://repository.publisso.de/resource/frl:6485910
https://doi.org/10.1021/acs.jmedchem.4c00160
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11181314/
Rights: https://creativecommons.org/licenses/by/4.0/
Αριθμός Καταχώρησης: edsbas.AAA554DC
Βάση Δεδομένων: BASE
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PubType: Academic Journal
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  Data: Illuminating Dark Chemical Matter Using the Cell Painting Assay
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  Data: Screening for small-molecule modulators of disease-relevant targets and phenotypes is the first step on the way to new drugs. Large compound libraries have been synthesized by academia and, particularly, pharmaceutical companies to meet the need for novel chemical entities that are as diverse as possible. Screening of these compound libraries revealed a portion of small molecules that is inactive in more than 100 different assays and was therefore termed 'dark chemical matter' (DCM). Deorphanization of DCM promises to yield very selective compounds as they are expected to have less off-target effects. We employed morphological profiling using the Cell Painting assay to detect bioactive DCM. Within the DCM collection, we identified bioactive compounds and confirmed several modulators of microtubules, DNA synthesis, and pyrimidine biosynthesis. Profiling approaches are, therefore, powerful tools to probe compound collections for bioactivity in an unbiased manner and are particularly suitable for deorphanization of DCM.
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  Data: https://repository.publisso.de/resource/frl:6485910; https://doi.org/10.1021/acs.jmedchem.4c00160; https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11181314/
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  Data: 10.1021/acs.jmedchem.4c00160
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  Data: https://repository.publisso.de/resource/frl:6485910<br />https://doi.org/10.1021/acs.jmedchem.4c00160<br />https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11181314/
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