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A Fluorescence-based Lymphocyte Assay Suitable for High-throughput Screening of Small Molecules
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Screening for antifibrotic compounds using high throughput system based on fluorescence polarization
Branko Stefanovic1, Lela Stefanovic2
1College of Medicine, Florida State University, 1115 W. Call St., Tallahassee, FL 32306, USA. branko.stefanovic@med.fsu.edu.
Biology
|May 17, 2014
Summary
Researchers developed a novel assay to find drugs targeting fibrosis. This assay identified a compound that inhibits type I collagen synthesis, offering a potential new treatment for fibroproliferative diseases.
Area of Science:
- Biochemistry
- Molecular Biology
- Drug Discovery
Background:
- Fibroproliferative diseases cause significant global mortality.
- These diseases involve excessive type I collagen synthesis.
- Current treatments for fibrosis are lacking.
Purpose of the Study:
- To identify novel therapeutic targets for fibrosis.
- To develop a high-throughput screening assay for antifibrotic compounds.
- To find chemical compounds that inhibit type I collagen synthesis.
Main Methods:
- Developed a fluorescence polarization-based high-throughput screening assay.
- Screened 50,000 chemical compounds for their ability to disrupt the LARP6-collagen 5'SL interaction.
- Investigated the mechanism of collagen type I synthesis inhibition.
Main Results:
- Identified a lead compound that inhibits type I collagen synthesis at nanomolar concentrations.
- The assay is adaptable for screening other protein-RNA interactions.
- The LARP6-collagen 5'SL interaction is a validated target for antifibrotic drug development.
Conclusions:
- The developed assay is effective for identifying inhibitors of protein-RNA interactions.
- A novel compound shows promise for treating fibroproliferative diseases.
- Targeting the LARP6-collagen 5'SL interaction is a viable strategy for antifibrotic drug development.
