Insights into Ecto-5’-Nucleotidase as a New Target for Cancer Therapy: A Medicinal Chemistry Study

Author(s): Patricia Frasson Corbelini, Fabricio Figueiro, Gustavo Machado das Neves, Saulo Andrade, Daniel Fabio Kawano, Ana Maria Oliveira Battastini, Vera Lucia Eifler-Lima

Journal Name: Current Medicinal Chemistry

Volume 22 , Issue 15 , 2015

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Abstract:

Ecto-5’-nucleotidase (ecto-5’-NT, 5’-NT, eN, CD73) is a membrane ectoenzyme that is primarily responsible for the extracellular production of adenosine from AMP. Ecto-5'-NT is overexpressed in various types of cancer cells, leading to elevated concentrations of adenosine in the tumour microenvironment. Adenosine has also been found to be important in cancer pathogenesis, showing strong immunosuppressive effects over antitumour T cells and macrophages and promoting neovascularization and cell adherence. These actions support tumour growth and development. It has been suggested that the inhibition of ecto-5’-NT results in lower extracellular concentrations of adenosine within the tumour microenvironment, which would directly affect cancer cells and render malignant cells more susceptible to host defence systems. Such mechanisms are proposed to represent promising new targets for cancer therapy. The aim of this review is to explore the biochemical and structural features of ecto-5’-NT, including a brief analysis of its active site by molecular modelling, as a means of evaluating whether the inhibition of this enzyme does indeed represent a feasible strategy for treating cancer. Known inhibitors and possible prototypes that could be used to target ecto-5’-NT during cancer therapy are also discussed.

Keywords: Adenosine, cancer therapy, Ecto-5’-nucleotidase, enzyme inhibition, new target, purinergic signalling.

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Article Details

VOLUME: 22
ISSUE: 15
Year: 2015
Page: [1776 - 1792]
Pages: 17
DOI: 10.2174/0929867322666150408112615
Price: $65

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