Targeting ecto-5′-nucleotidase: A comprehensive review into small molecule inhibitors and expression modulators

• Published in: European journal of medicinal chemistry 2023-02, Vol.247, p.115052-115052, Article 115052
• Main Authors: das Neves, Gustavo Machado, Kagami, Luciano Porto, Battastini, Ana Maria Oliveira, Figueiró, Fabrício, Eifler-Lima, Vera Lucia
• Format: Article
• Language: English
• Subjects: 5'-Nucleotidase; Adenosine - metabolism; Adenosine - pharmacology; Adenosine Monophosphate; Antineoplastic Agents - pharmacology; cd73; Cell Line; Ecto-5′-nucleotidase; Expression modulation; Medicinal chemistry; Purinergic signaling; Small molecule inhibitors
• ISSN: 0223-5234; 1768-3254
• DOI: 10.1016/j.ejmech.2022.115052

The purinergic signaling has drawn attention from academia and more recently from pharmaceutical industries as a potential therapeutic route for cancer treatment, since ATP may act as chemotactic agent and possess in vitro antineoplastic activity. On the other way, adenosine, produced in extracellular medium by ecto-5′-NT, acts as immunosuppressor and is related to neoangiogenesis, vasculogenesis and evasion to the immune system. Consequently, inhibitors of ecto-5′-NT may prevent tumor progression, reducing adenosine concentrations, preventing escape from the host's immune system and slowing cancer's growth. This review aims to highlight important biochemical and structural features of ecto-5′NT, highlight its expression profile in normal and cancer cell lines detailing compounds which may act as expression regulators and to review the several classes of ecto-5′NT inhibitors developed in the past 12 years, in order to build a general structure-activity relationship model to guide further compound design. [Display omitted] •The purinergic signaling is a potential therapeutic route for cancer treatment.•The CD73 overexpression is related to tumor cell survival.•Therefore CD73 inhibitors may prevent tumor progression.•This review comprises several classes of CD73 inhibitors developed over 12 years.•ADME properties and chemical space analysis were conducted for the CD73 inhibitors.