认识胞外-5’-核苷酸酶作为癌症治疗的新靶点：一项药物化学研究

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 and Daniel Fabio Kawano, Ana Maria Oliveira Battastini and Vera Lucia Eifler-Lima

Affiliation:

关键词: 腺苷，癌症治疗，胞外-5’-核苷酸酶，酶抑制，新靶点，嘌呤信号。

摘要: 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:

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