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

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

Volume: 22 Issue: 15

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

Affiliation:

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

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.

Cite this article as:

Corbelini Frasson Patricia, Figueiro Fabricio, das Neves Machado Gustavo, Andrade Saulo, Kawano Fabio Daniel, Oliveira Battastini Maria Ana and Eifler-Lima Lucia Vera, Insights into Ecto-5’-Nucleotidase as a New Target for Cancer Therapy: A Medicinal Chemistry Study, Current Medicinal Chemistry 2015; 22 (15) . https://dx.doi.org/10.2174/0929867322666150408112615