Discovery of a σ

Aniline Compounds / chemistry Animals Drug Discovery Female Gene Expression Profiling Heterocyclic Compounds, 2-Ring / chemistry Humans Mice Molecular Structure Proteome / genetics Receptors, sigma / antagonists & inhibitors Small Molecule Libraries / chemistry Temperature Tumor Cells, Cultured Sigma-1 Receptor
antagonist cellular thermal shift assay lysosomotropism morphological profiling small molecule target identification thermal proteome profiling

Journal

Cell chemical biology
ISSN: 2451-9448
Titre abrégé: Cell Chem Biol
Pays: United States
ID NLM: 101676030

Informations de publication

Date de publication:
17 06 2021
Historique:
received: 23 09 2020
revised: 09 11 2020
accepted: 06 01 2021
pubmed: 11 2 2021
medline: 16 11 2021
entrez: 10 2 2021
Statut: ppublish

Résumé

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 (σ

Identifiants

DOI: 10.1016/j.chembiol.2021.01.009 PMID: 33567254
pubmed: 33567254
pii: S2451-9456(21)00009-X
doi: 10.1016/j.chembiol.2021.01.009
pii:
doi:

Substances chimiques

Aniline Compounds 0
Heterocyclic Compounds, 2-Ring 0
N,N-bis(2-(8-carbamoyl-4-oxo-3H,4H-imidazotetrazin-3-yl)ethyl)-4-methylaniline 0
Proteome 0
Receptors, sigma 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

848-854.e5

Informations de copyright

Copyright © 2021 Elsevier Ltd. All rights reserved.

Déclaration de conflit d'intérêts

Declaration of interests The authors declare no competing interest.

Auteurs

Julian Wilke (J)

Max Planck Institute of Molecular Physiology, Otto-Hahn-Str. 11, 44227 Dortmund, Germany; TU Dortmund University, Emil-Figge-Str. 72, 44221 Dortmund, Germany; RIKEN-Max Planck Joint Research Division for Systems Chemical Biology, RIKEN Center for Sustainable Resource Science, 2-1 Hirosawa, Wako, Saitama 351-0198, Japan.

Tatsuro Kawamura (T)

Max Planck Institute of Molecular Physiology, Otto-Hahn-Str. 11, 44227 Dortmund, Germany; RIKEN-Max Planck Joint Research Division for Systems Chemical Biology, RIKEN Center for Sustainable Resource Science, 2-1 Hirosawa, Wako, Saitama 351-0198, Japan.

Hao Xu (H)

Key Laboratory of Pesticides & Chemical Biology Ministry of Education, College of Chemistry, Central China Normal University, 152 Luoyu Road, Wuhan, Hubei, 430079, China.

Alexandra Brause (A)

Max Planck Institute of Molecular Physiology, Otto-Hahn-Str. 11, 44227 Dortmund, Germany.

Alexandra Friese (A)

Max Planck Institute of Molecular Physiology, Otto-Hahn-Str. 11, 44227 Dortmund, Germany.

Malte Metz (M)

Max Planck Institute of Molecular Physiology, Otto-Hahn-Str. 11, 44227 Dortmund, Germany.

Dirk Schepmann (D)

Institut für Pharmazeutische und Medizinische Chemie der Universität Münster, Corrensstraße 48, 48149 Münster, Germany.

Bernhard Wünsch (B)

Institut für Pharmazeutische und Medizinische Chemie der Universität Münster, Corrensstraße 48, 48149 Münster, Germany.

Antonia Artacho-Cordón (A)

Department of Pharmacology and Institute of Neuroscience, University of Granada, Avenida de la Investigación, 11, 18016 Granada, Spain.

Francisco R Nieto (FR)

Department of Pharmacology and Institute of Neuroscience, University of Granada, Avenida de la Investigación, 11, 18016 Granada, Spain.

Nobumoto Watanabe (N)

RIKEN-Max Planck Joint Research Division for Systems Chemical Biology, RIKEN Center for Sustainable Resource Science, 2-1 Hirosawa, Wako, Saitama 351-0198, Japan; Bio-Active Compounds Discovery Research Unit, RIKEN Center for Sustainable Resource Science, 2-1 Hirosawa, Wako, Saitama 351-0198, Japan.

Hiroyuki Osada (H)

RIKEN-Max Planck Joint Research Division for Systems Chemical Biology, RIKEN Center for Sustainable Resource Science, 2-1 Hirosawa, Wako, Saitama 351-0198, Japan; Chemical Biology Research Group, RIKEN Center for Sustainable Resource Science, 2-1 Hirosawa, Wako, Saitama 351-0198, Japan.

Slava Ziegler (S)

Max Planck Institute of Molecular Physiology, Otto-Hahn-Str. 11, 44227 Dortmund, Germany.

Herbert Waldmann (H)

Max Planck Institute of Molecular Physiology, Otto-Hahn-Str. 11, 44227 Dortmund, Germany; TU Dortmund University, Emil-Figge-Str. 72, 44221 Dortmund, Germany. Electronic address: herbert.waldmann@mpi-dortmund.mpg.de.

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Classifications MeSH

questionsmedicales.fr › Composés chimiques organiques › Amines › Dérivés de l'aniline › Discovery of a σ
questionsmedicales.fr › Eucaryotes › Animaux › Discovery of a σ
questionsmedicales.fr › Techniques d'investigation › Développement de médicament › Découverte de médicament › Discovery of a σ
questionsmedicales.fr › Techniques d'investigation › Techniques génétiques › Analyse de profil d'expression de gènes › Discovery of a σ
questionsmedicales.fr › Composés hétérocycliques › Composés hétérocycliques à cycles fusionnés › Composés hétérobicycliques › Discovery of a σ
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › Discovery of a σ
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Rodentia › Muridae › Murinae › Souris › Discovery of a σ
questionsmedicales.fr › Phénomènes chimiques › Structure moléculaire › Discovery of a σ
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéome › Discovery of a σ
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines membranaires › Récepteurs de surface cellulaire › Récepteurs peptidiques › Récepteur aux neuropeptides › Récepteurs aux opioïdes › Récepteur sigma › Discovery of a σ
questionsmedicales.fr › Actions chimiques et utilisations › Utilisations spécialisées de produits chimiques › Produits chimiques de laboratoire › Bibliothèques de petites molécules › Discovery of a σ
questionsmedicales.fr › Environnement et santé publique › Environnement › Concepts météorologiques › Atmosphère › Temps (météorologie) › Température › Discovery of a σ
questionsmedicales.fr › Cellules › Cellules cultivées › Cellules cancéreuses en culture › Discovery of a σ