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@ARTICLE{Koch:877590,
      author       = {Koch, Katharina and Hartmann, Rudolf and Tsiampali, Julia
                      and Uhlmann, Constanze and Nickel, Ann-Christin and He,
                      Xiaoling and Kamp, Marcel A. and Sabel, Michael and Barker,
                      Roger A. and Steiger, Hans-Jakob and Hänggi, Daniel and
                      Willbold, Dieter and Maciaczyk, Jaroslaw and Kahlert, Ulf
                      D.},
      title        = {{A} comparative pharmaco-metabolomic study of glutaminase
                      inhibitors in glioma stem-like cells confirms biological
                      effectiveness but reveals differences in target-specificity},
      journal      = {Cell death discovery},
      volume       = {6},
      number       = {1},
      issn         = {2058-7716},
      address      = {London},
      publisher    = {Nature Publishing Group816700},
      reportid     = {FZJ-2020-02312},
      pages        = {20},
      year         = {2020},
      abstract     = {Cancer cells upregulate anabolic processes to maintain high
                      rates of cellular turnover. Limiting the supply
                      ofmacromolecular precursors by targeting enzymes involved in
                      biosynthesis is a promising strategy in cancer
                      therapy.Several tumors excessively metabolize glutamine to
                      generate precursors for nonessential amino acids,
                      nucleotides,and lipids, in a process called glutaminolysis.
                      Here we show that pharmacological inhibition of glutaminase
                      (GLS)eradicates glioblastoma stem-like cells (GSCs), a small
                      cell subpopulation in glioblastoma (GBM) responsible for
                      therapyresistance and tumor recurrence. Treatment with small
                      molecule inhibitors compound 968 and CB839
                      effectivelydiminished cell growth and in vitro clonogenicity
                      of GSC neurosphere cultures. However, our
                      pharmaco-metabolicstudies revealed that only CB839 inhibited
                      GLS enzymatic activity thereby limiting the influx of
                      glutamine derivatesinto the TCA cycle. Nevertheless, the
                      effects of both inhibitors were highly GLS specific, since
                      treatment sensitivitymarkedly correlated with GLS protein
                      expression. Strikingly, we found GLS overexpressed in in
                      vitro GSC models ascompared with neural stem cells (NSC).
                      Moreover, our study demonstrates the usefulness of in vitro
                      pharmaco-metabolomics to score target specificity of
                      compounds thereby refining drug development and risk
                      assessment.},
      cin          = {IBI-7},
      ddc          = {610},
      cid          = {I:(DE-Juel1)IBI-7-20200312},
      pnm          = {552 - Engineering Cell Function (POF3-552)},
      pid          = {G:(DE-HGF)POF3-552},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:32337072},
      UT           = {WOS:000526352700001},
      doi          = {10.1038/s41420-020-0258-3},
      url          = {https://juser.fz-juelich.de/record/877590},
}