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Methods Mol Biol. 2018;1713:93-108. doi: 10.1007/978-1-4939-7507-5_8.

Design, Synthesis, and Evaluation of GLUT Inhibitors.

Author information

1
Department of Pharmacy, University of Pisa, Via Bonanno 33, 56126, Pisa, Italy.
2
Department of Pharmacy, University of Pisa, Via Bonanno 33, 56126, Pisa, Italy. filippo.minutolo@unipi.it.

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:

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

PMID:
29218520
DOI:
10.1007/978-1-4939-7507-5_8
[Indexed for MEDLINE]

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