Title |
Development and Implementation of an HTS-Compatible Assay for the Discovery of Selective Small-Molecule Ligands for Pre-microRNAs
|
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Published in |
SLAS DISCOVERY: Advancing the Science of Drug Discovery, July 2017
|
DOI | 10.1177/2472555217717944 |
Pubmed ID | |
Authors |
Daniel A. Lorenz, Steve Vander Roest, Martha J. Larsen, Amanda L. Garner |
Abstract |
microRNAs (miRNAs) are small gene regulatory RNAs, and their expression has been found to be dysregulated in a number of human diseases. To facilitate the discovery of small molecules capable of selectively modulating the activity of a specific miRNA, we have utilized new high-throughput screening technology targeting Dicer-mediated pre-miRNA maturation. Pilot screening of ~50,000 small molecules and ~33,000 natural product extract libraries against pre-miR-21 processing indicated the potential of our assay for this goal, yielding a campaign Z' factor of 0.52 and an average plate signal-to-background (S/B) ratio of 13. Using two-dimensional screening against a second pre-miRNA, pre-let-7d, we evaluated the selectivity of confirmed hits. The results presented demonstrate how high-throughput screening can be used to identify selective small molecules for a target RNA. |
X Demographics
Geographical breakdown
Country | Count | As % |
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United States | 2 | 67% |
Unknown | 1 | 33% |
Demographic breakdown
Type | Count | As % |
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Members of the public | 3 | 100% |
Mendeley readers
Geographical breakdown
Country | Count | As % |
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Unknown | 28 | 100% |
Demographic breakdown
Readers by professional status | Count | As % |
---|---|---|
Researcher | 10 | 36% |
Student > Ph. D. Student | 4 | 14% |
Student > Bachelor | 3 | 11% |
Professor | 2 | 7% |
Student > Doctoral Student | 1 | 4% |
Other | 1 | 4% |
Unknown | 7 | 25% |
Readers by discipline | Count | As % |
---|---|---|
Chemistry | 8 | 29% |
Biochemistry, Genetics and Molecular Biology | 7 | 25% |
Pharmacology, Toxicology and Pharmaceutical Science | 2 | 7% |
Agricultural and Biological Sciences | 2 | 7% |
Nursing and Health Professions | 1 | 4% |
Other | 2 | 7% |
Unknown | 6 | 21% |