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How polypharmacologic is each chemogenomics library?


ABSTRACT: Aim:High-throughput phenotypic screens have emerged as a promising avenue for small-molecule drug discovery. The challenge faced in high-throughput phenotypic screens is target deconvolution once a small molecule hit is identified. Chemogenomics libraries have emerged as an important tool for meeting this challenge. Here, we investigate their target-specificity by deriving a 'polypharmacology index' for broad chemogenomics screening libraries. Methods:All known targets of all the compounds in each library were plotted as a histogram and fitted to a Boltzmann distribution, whose linearized slope is indicative of the overall polypharmacology of the library. Results & conclusion:Comparison of libraries clearly distinguished the most target-specific library, which might be assumed to be more useful for target deconvolution in a phenotypic screen.

SUBMITTER: Ni E 

PROVIDER: S-EPMC7052528 | biostudies-literature | 2020 Feb

REPOSITORIES: biostudies-literature

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How polypharmacologic is each chemogenomics library?

Ni Eric E   Kwon Eehjoe E   Young Lauren M LM   Felsovalyi Klara K   Fuller Jennifer J   Cardozo Timothy T  

Future drug discovery 20200205 1


<h4>Aim</h4>High-throughput phenotypic screens have emerged as a promising avenue for small-molecule drug discovery. The challenge faced in high-throughput phenotypic screens is target deconvolution once a small molecule hit is identified. Chemogenomics libraries have emerged as an important tool for meeting this challenge. Here, we investigate their target-specificity by deriving a 'polypharmacology index' for broad chemogenomics screening libraries.<h4>Methods</h4>All known targets of all the  ...[more]

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