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Development of a chemogenomics library for phenotypic screening

Abstract : With the development of advanced technologies in cell-based phenotypic screening, phenotypic drug discovery (PDD) strategies have re-emerged as promising approaches in the identification and development of novel and safe drugs. However, phenotypic screening does not rely on knowledge of specific drug targets and needs to be combined with chemical biology approaches to identify therapeutic targets and mechanisms of actions induced by drugs and associated with an observable phenotype. In this study, we developed a system pharmacology network integrating drug-target-pathway-disease relationships as well as morphological profile from an existing high content imaging-based high-throughput phenotypic profiling assay known as Cell Painting. Furthermore, from this network, a chemogenomic library of 5000 small molecules that represent a large and diverse panel of drug targets involved in diverse biological effects and diseases has been developed. Such a platform and a chemogenomic library could assist in the target identification and mechanism deconvolution of some phenotypic assays. The usefulness of the platform is illustrated through examples.
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https://hal-cnrs.archives-ouvertes.fr/hal-03677229
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Submitted on : Tuesday, May 24, 2022 - 3:16:26 PM
Last modification on : Thursday, May 26, 2022 - 3:13:51 AM

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Bryan Dafniet, Natacha Cerisier, Batiste Boezio, Anaelle Clary, Pierre Ducrot, et al.. Development of a chemogenomics library for phenotypic screening. Journal of Cheminformatics, Chemistry Central Ltd. and BioMed Central, 2021, 13 (1), ⟨10.1186/s13321-021-00569-1⟩. ⟨hal-03677229⟩

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