Discovery of a σ1 receptor antagonist by combination of unbiased cell painting and thermal proteome profiling.
Cell Chem Biol
; 28(6): 848-854.e5, 2021 06 17.
Article
em En
| MEDLINE
| ID: mdl-33567254
ABSTRACT
Phenotypic screening for bioactive small molecules is typically combined with affinity-based chemical proteomics to uncover the respective molecular targets. However, such assays and the explored bioactivity are biased toward the monitored phenotype, and target identification often requires chemical derivatization of the hit compound. In contrast, unbiased cellular profiling approaches record hundreds of parameters upon compound perturbation to map bioactivity in a broader biological context and may link a profile to the molecular target or mode of action. Herein we report the discovery of the diaminopyrimidine DP68 as a Sigma 1 (σ1) receptor antagonist by combining morphological profiling using the Cell Painting assay and thermal proteome profiling. Our results highlight that integration of complementary profiling approaches may enable both detection of bioactivity and target identification for small molecules.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Temas:
Geral
Base de dados:
MEDLINE
Assunto principal:
Temperatura
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Receptores sigma
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Proteoma
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Bibliotecas de Moléculas Pequenas
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Descoberta de Drogas
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Compostos Heterocíclicos com 2 Anéis
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Compostos de Anilina
Limite:
Animals
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Female
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Humans
Idioma:
En
Revista:
Cell Chem Biol
Ano de publicação:
2021
Tipo de documento:
Article