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Design, Synthesis, and Evaluation of GLUT Inhibitors

  • Carlotta Granchi
  • Tiziano Tuccinardi
  • Filippo MinutoloEmail author
Protocol
Part of the Methods in Molecular Biology book series (MIMB, volume 1713)

Abstract

The Warburg effect describes how most cancer cells exhibit higher-than-normal glucose consumption, not only under hypoxic conditions, but also when normal oxygen levels are present. Although glucose transporter 1 (GLUT1) has been found to play a key role in the cellular uptake of glucose, especially in cancer cells, where it is generally overexpressed, it has not been given consideration as a suitable target for the development of anticancer drugs. In this chapter, an example of molecular design and realization of novel GLUT1 inhibitors, including in silico modeling, chemical synthesis, and biological characterization, is provided. This process started with the identification of a focused series of oxime derivatives, originally designed as estrogen receptor (ER) ligands, which were structurally optimized in order to direct their activity towards GLUT1 and to minimize their binding to the ERs, leading to the production of efficient and selective inhibitors of glucose uptake in cancer cells.

Keywords

Glucose transporters Warburg effect Inhibitors Cancer Molecular design Oximes 2-NBDG 

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Copyright information

© Springer Science+Business Media LLC 2018

Authors and Affiliations

  • Carlotta Granchi
    • 1
  • Tiziano Tuccinardi
    • 1
  • Filippo Minutolo
    • 1
    Email author
  1. 1.Department of PharmacyUniversity of PisaPisaItaly

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