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A Fluorescence-Based High-Throughput Assay for the Identification of Anticancer Reagents Targeting Fructose-1,6-Bisphosphate Aldolase

SLAS News (Dec. 21, 2017) — An original research report by Eun Jeong Cho et al. (University of Texas at Austin) in the January 2018 Issue of SLAS Discovery presents a newly designed biochemical assay that is rapid, sensitive, inexpensive, and high-throughput screening (HTS)-friendly to identify antagonist against aldolase A (ALDOA). 

The authors demonstrate how to transform and integrate a traditional aldolase assay to an HTS-friendly platform by taking advantage of a commercially available nicotinamide adenine dinucleotide (NADH) detection system with enhanced sensitivity, reduced reagent requirements and reduced compound interference. This adaptation and optimization of a readily available assay kit to an HTS protocol represents a cost- and labor-efficient solution, because de novo assay development can require several months to years. In addition, the universal characteristics of this newly created assay platform highlight its instant accommodation to the analysis of many NADH-dependent enzymes and to other high-throughput applications.

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Current research supports the notion that many cancer cells develop a highly active glucose metabolism in order to grow continuously. Some studies show that hypoxia-inducible factors (HIFs) 1 and 2 mediate a cancer cell’s response to hypoxia and upregulate the transcription of several glycolytic enzymes. Inhibiting key enzymes, such as ALDOA, in these pathways is considered a potential strategy to treat cancer cells, but potent agents blocking ALDOA activity at low nM range haven’t been discovered. In addition, HTS campaigns to identify small molecular probes haven’t been reported.

Free, limited-time access to A Fluorescence-Based High-Throughput Assay for the Identification of Anticancer Reagents Targeting Fructose-1,6-Bisphosphate Aldolase is available at SLAS Discovery Online (http://journals.sagepub.com/toc/jbxb/23/1). SLAS Discovery is one of two MEDLINE-indexed scientific journals published by SLAS. For more information about SLAS and its journals, visit www.slas.org/journals.

 

 

 

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