Combined Analysis of Phenotypic and Target-Based Screening in Assay Networks.
J Biomol Screen
; 19(5): 782-90, 2014 Jun.
Article
em En
| MEDLINE
| ID: mdl-24563424
ABSTRACT
Small-molecule screens are an integral part of drug discovery. Public domain data in PubChem alone represent more than 158 million measurements, 1.2 million molecules, and 4300 assays. We conducted a global analysis of these data, building a network of assays and connecting the assays if they shared nonpromiscuous active molecules. This network spans both phenotypic and target-based screens, recapitulates known biology, and identifies new polypharmacology. Phenotypic screens are extremely important for drug discovery, contributing to the discovery of a large proportion of new drugs. Connections between phenotypic and biochemical, target-based screens can suggest strategies for repurposing both small-molecule and biologic drugs. For example, a screen for molecules that prevent cell death from a mutated version of superoxide-dismutase is linked with ALOX15. This connection suggests a therapeutic role for ALOX15 inhibitors in amyotrophic lateral sclerosis. An interactive version of the network is available online (http//swami.wustl.edu/flow/assay_network.html).
Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Bioensaio
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Descoberta de Drogas
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Ensaios de Triagem em Larga Escala
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Esclerose Lateral Amiotrófica
Idioma:
En
Ano de publicação:
2014
Tipo de documento:
Article