Tools and Drugs for Purine-Binding Targets—Important Players in Inflammation and Cancer

Proceedings

Christa E. Müller¹ 

[1] Pharmaceutical Institute, Pharmaceutical Chemistry I, University of Bonn, D-53121 Bonn, Germany;

关键词: adenosine;    ATP;    CD73;    ectonucleotidases;    immuno-oncology;    inhibitors;    NPP1;    purine receptors;   

DOI  :  10.3390/proceedings2019022033

来源: DOAJ

【 摘 要 】

Despite decades of research, only few drugs have been approved that interact with purine receptors. Recently, new hypes and hopes have been created in the field, mainly due to the gold rush fever in immuno-oncology. Adenosine is one of the strongest immunosuppressant agents of the innate immune system. Cancer cells and tissues can release large amounts of ATP, which is immediately hydrolyzed by ectonucleotidases. These ecto-enzymes, including ectonucleotide pyrophosphatase/phosphodiesterase 1 (NPP1, CD203a), ectonucleoside diphospho­hydrolase 1 (NTPDase1, CD39), and ecto-5′-nucleotidase (CD73), are upregulated on many cancer cells, leading to the production of adenosine. The cloud of adenosine formed around cancer tissues contributes to immune escape by interacting with adenosine A_2A and A_2B receptor subtypes (A_2AAR, A_2BAR) on immune cells. In addition, activation of A_2BARs by adenosine enhances cancer cell proliferation, metastasis, and angiogenesis. Blockade of A_2A and A_2B adenosine receptors and/or inhibition of adenosine formation by blocking ectonucleotidases are being pursued as novel principles that activate the immune system to defeat cancer. Recent progress in the development of adenosine receptor antagonists and ectonucleotidase inhibitors will be presented and discussed.

【 授权许可】

Unknown