title: Insights into Ecto-5'-Nucleotidase as a New Target for Cancer Therapy: A Medicinal Chemistry Study.
abstract: Ecto-5'-nucleotidase (ecto-5'-NT, 5'-NT, eN, CD73) is a membrane ecto-enzyme that is primarily responsible for the extracellular production of adenosine from AMP. Ecto-5'-NT is over expressed in various types of cancer cells, leading to elevated concentrations of adenosine in the tumor microenvironment. Adenosine has also been found to be important in cancer pathogenesis, showing strong immunosuppressive effects over antitumor T cells and macrophages and promoting neovascularization and cell adherence. These actions support tumor growth and development. It has been suggested that the inhibition of ecto-5'-NT results in lower extracellular concentrations of adenosine within the tumor microenvironment, which would directly affect cancer cells and render malignant cells more susceptible to host defense 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 modeling, 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.
authors: Patricia Frasson
authors: PF
authors: Corbelini
authors: Fabrício
authors: F
authors: Figueiró
authors: Gustavo Machado
authors: GM
authors: das Neves
authors: Saulo
authors: S
authors: Andrade
authors: Daniel Fábio
authors: DF
authors: Kawano
authors: Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Rua Ramiro Barcelos 2600-anexo, CEP 90035-000, Porto Alegre/RS, Brazil. abattastini@gmail.com.
authors: Ana Maria
authors: AM
authors: Oliveira Battastini
authors: Laboratório de Síntese Orgânica Medicinal/LaSOM, Faculdade de Farmácia, Universidade Federal do Rio Grande do Sul, Av. Ipiranga 2752, CEP 90610-000, Porto Alegre/RS, Brazil. veraeifler@ufrgs.br.
authors: Vera Lucia
authors: VL
authors: Eifler-Lima