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New screening method identifies inhibitors of cancer cell metabolism

Date:
November 18, 2019
Source:
University of California - Los Angeles Health Sciences
Summary:
A new screening system developed by scientists leverages redundancy in an important component of a cell - nucleotide metabolism - to help identify new drugs that specifically and potently block processes that are essential for cancer cell growth.
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A new screening system developed by scientists at the UCLA Jonsson Comprehensive Cancer Center leverages redundancy in an important component of a cell -- nucleotide metabolism -- to help identify new drugs that specifically and potently block processes that are essential for cancer cell growth.

There are many small molecule kinase inhibitors, such as Gleevec, that have been developed to target cancers and other diseases. However, scientists still don't fully understand the full effects of these drugs. Current screening methods do not capture the effects these inhibitors may have on other components of cells, such as biochemical metabolic networks. Using their understanding of metabolism, the team designed a new high-throughput screening system that allows for identification of selective inhibitors of metabolic pathways.

Working with the Molecular Screening Shared Resource at UCLA, the team performed a large scale analyses of 430 kinase inhibitors that have annotated targets within cellular signaling pathways and many of which are currently being used in the clinic. Unexpectedly, multiple inhibitors were found to block nucleotide metabolism and their targets were revealed using mechanistic studies.

This new metabolism-focused screening approach can be a powerful tool in getting new insight into how existing drugs impact metabolic networks and could potentially provide a new understanding into how these drugs are working in the clinic. In addition to characterization of existing compounds that are already being used for treating cancers and other diseases, this screening method could one day also be applied to identify new small molecule modulators of currently un-targeted metabolic pathways -- not only nucleotide metabolism -- which can help lead to new drug discoveries.


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Materials provided by University of California - Los Angeles Health Sciences. Note: Content may be edited for style and length.


Journal Reference:

  1. Evan R. Abt, Ethan W. Rosser, Matthew A. Durst, Vincent Lok, Soumya Poddar, Thuc M. Le, Arthur Cho, Woosuk Kim, Liu Wei, Janet Song, Joseph R. Capri, Shili Xu, Nanping Wu, Roger Slavik, Michael E. Jung, Robert Damoiseaux, Johannes Czernin, Timothy R. Donahue, Arnon Lavie, Caius G. Radu. Metabolic Modifier Screen Reveals Secondary Targets of Protein Kinase Inhibitors within Nucleotide Metabolism. Cell Chemical Biology, 2019; DOI: 10.1016/j.chembiol.2019.10.012

Cite This Page:

University of California - Los Angeles Health Sciences. "New screening method identifies inhibitors of cancer cell metabolism." ScienceDaily. ScienceDaily, 18 November 2019. <www.sciencedaily.com/releases/2019/11/191118190853.htm>.
University of California - Los Angeles Health Sciences. (2019, November 18). New screening method identifies inhibitors of cancer cell metabolism. ScienceDaily. Retrieved May 20, 2024 from www.sciencedaily.com/releases/2019/11/191118190853.htm
University of California - Los Angeles Health Sciences. "New screening method identifies inhibitors of cancer cell metabolism." ScienceDaily. www.sciencedaily.com/releases/2019/11/191118190853.htm (accessed May 20, 2024).

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