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Development and Characterization of a Fluorescent Probe for GLS1 and the Application for High-Throughput Screening of Allosteric Inhibitors.

08:00 EDT 11th October 2019 | BioPortfolio

Summary of "Development and Characterization of a Fluorescent Probe for GLS1 and the Application for High-Throughput Screening of Allosteric Inhibitors."

Glutaminase (GLS1) is a cancer energy metabolism protein which plays a predominant role in cell growth and proliferation. Due to its major involvement in malignant tumor, small-molecule GLS1 inhibitors are urgently needed to assess its therapeutic potential and for probing their underlying biology function. Recent studies showed that targeting the allosteric binding site represented a promising strategy for identifying potent and selective GLS1 inhibitors. Herein, we present the synthesis of two fluorescent probes targeting the allosteric binding site of GLS1 and their usage as mechanistic tools in multiple applicable assay platform. The fluorescence polarization (FP)-based binding assay enables easy, fast and reliable screen of allosteric inhibitors from our in-house compound library obtained through click chemistry method. The obtained compound C147 (named as CPU-L1) has been proved to be more potent and with greater solubility than the control compound CB839, which could serve as promising leads for further optimization as novel GLS1 inhibitors.

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This article was published in the following journal.

Name: Journal of medicinal chemistry
ISSN: 1520-4804
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Medical and Biotech [MESH] Definitions

Fluorescent probe capable of being conjugated to tissue and proteins. It is used as a label in fluorescent antibody staining procedures as well as protein- and amino acid-binding techniques.

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A type of scanning probe microscopy in which a probe systematically rides across the surface of a sample being scanned in a raster pattern. The vertical position is recorded as a spring attached to the probe rises and falls in response to peaks and valleys on the surface. These deflections produce a topographic map of the sample.

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