2. Academic Validation
  3. Inhibition of Glucose Transporters and Glutaminase Synergistically Impairs Tumor Cell Growth

Inhibition of Glucose Transporters and Glutaminase Synergistically Impairs Tumor Cell Growth

  • Cell Chem Biol. 2019 Sep 19;26(9):1214-1228.e25. doi: 10.1016/j.chembiol.2019.06.005.
Elena S Reckzeh 1,  George Karageorgis 2,  Melanie Schwalfenberg 2,  Javier Ceballos 2,  Jessica Nowacki 2,  Marcus C M Stroet 2,  Aylin Binici 2,  Lena Knauer 3,  Silke Brand 2,  Axel Choidas 4,  Carsten Strohmann 3,  Slava Ziegler 2,  Herbert Waldmann 5
Affiliations

Affiliations

  • 1 Max Planck Institute of Molecular Physiology, Department of Chemical Biology, Otto-Hahn-Strasse 11, 44227 Dortmund, Germany; Technical University Dortmund, Faculty of Chemistry and Chemical Biology, Otto-Hahn-Strasse 6, 44227 Dortmund, Germany.
  • 2 Max Planck Institute of Molecular Physiology, Department of Chemical Biology, Otto-Hahn-Strasse 11, 44227 Dortmund, Germany.
  • 3 Technical University Dortmund, Faculty of Chemistry and Chemical Biology, Otto-Hahn-Strasse 6, 44227 Dortmund, Germany.
  • 4 Lead Discovery Center GmbH, Otto-Hahn-Strasse 15, 44227 Dortmund, Germany.
  • 5 Max Planck Institute of Molecular Physiology, Department of Chemical Biology, Otto-Hahn-Strasse 11, 44227 Dortmund, Germany; Technical University Dortmund, Faculty of Chemistry and Chemical Biology, Otto-Hahn-Strasse 6, 44227 Dortmund, Germany. Electronic address: herbert.waldmann@mpi-dortmund.mpg.de.
PMID: 31303578 DOI: 10.1016/j.chembiol.2019.06.005
Abstract

Cancer cells sustain growth by altering their metabolism to accelerated aerobic glycolysis accompanied by increased glucose demand and employ glutamine as additional nutrient source. This metabolic adaptation induces upregulation of glucose transporters GLUT-1 and -3, and simultaneous targeting of both transporters and of glutamine metabolism may offer a promising approach to inhibit Cancer cell growth. We describe the discovery of the very potent glucose uptake inhibitor Glutor, which targets glucose transporters GLUT-1, -2, and -3, attenuates glycolytic flux and potently and selectively suppresses growth of a variety of Cancer cell lines. Co-treatment of colon Cancer cells with Glutor and Glutaminase Inhibitor CB-839 very potently and synergistically inhibits Cancer cell growth. Such a dual inhibition promises to be particularly effective because it targets the metabolic plasticity as well as metabolic rescue mechanisms in Cancer cells.

Keywords

GLUT-1; GLUT-3; Warburg effect; co-treatment; glutaminase; metabolic plasticity; small molecule.

Figures
Products
  • Cat. No.
    Product Name
    Description
    Target
    Research Area
  • HY-158302
    ≥99.0%, GLUT 1/2/3 Inhibitor