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Related Experiment Video

Updated: Jun 11, 2026

High-throughput Screening for Chemical Modulators of Post-transcriptionally Regulated Genes

High-throughput Screening for Chemical Modulators of Post-transcriptionally Regulated Genes

Published on: March 3, 2015

Multi-pathway cellular analysis of compound selectivity.

Michael K Hancock¹, Connie S Lebakken, Jun Wang

¹Discovery Assays and Services, Invitrogen, Part of Life Technologies, Madison, WI 53719, USA.

Molecular Biosystems

|July 2, 2010

Summary

This summary is machine-generated.

Cellular pathway profiling reveals kinase inhibitor selectivity beyond traditional biochemical assays. This approach identifies novel therapeutic uses and potential safety concerns for drug repositioning.

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Area of Science:

Pharmacology
Molecular Biology
Drug Discovery

Background:

Kinase inhibitors are crucial therapeutics, but their selectivity is often assessed using biochemical assays.
Cellular assays provide a more accurate measure of biological selectivity for drug candidates.
Understanding compound-pathway interactions is key for identifying new therapeutic opportunities and potential liabilities.

Purpose of the Study:

To develop and demonstrate a multi-pathway profiling approach using cellular reporter gene assays.
To generate comprehensive cellular pathway selectivity profiles for known bioactive compounds.
To compare cellular selectivity with traditional biochemical profiling methods.

Main Methods:

Utilized CellSensor beta-lactamase transcriptional reporter gene assays to monitor endogenous signaling pathways.
Screened 32 known compounds across a panel of 12 key signaling pathways.
Generated compound-pathway selectivity maps based on cellular assay data.

Main Results:

Identified several kinase inhibitors exhibiting greater promiscuity in cellular assays than predicted biochemically.
Revealed sorafenib's activity on the JAK/STAT pathway, suggesting potential for treating specific leukemia/myeloproliferative disorders.
Demonstrated the ability of multi-pathway profiling to uncover both intended and unintended compound activities.

Conclusions:

Multi-pathway cellular profiling offers an efficient method for characterizing compound selectivity and activity.
This approach can reveal novel pathway engagements, facilitate drug repositioning, and identify potential safety issues.
Cellular selectivity profiling is essential for a comprehensive understanding of drug action and development.