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Open AccessAbstract

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

1
Pharmaceutical Institute, Pharmaceutical Chemistry I, University of Bonn, D-53121 Bonn, Germany
2
Pharma Center Bonn, University of Bonn, D-53121 Bonn, Germany
Presented at the 2nd Molecules Medicinal Chemistry Symposium (MMCS): Facing Novel Challenges in Drug Discovery, Barcelona, Spain, 15–17 May 2019.
Presented at the 2nd Molecules Medicinal Chemistry Symposium (MMCS): Facing Novel Challenges in Drug Discovery, Barcelona, Spain, 15–17 May 2019.
Proceedings 2019, 22(1), 33; https://doi.org/10.3390/proceedings2019022033
Published: 7 August 2019
(This article belongs to the Proceedings of The Molecules Medicinal Chemistry Symposium)
PDF [134 KB, uploaded 7 August 2019]

Abstract

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 A2A and A2B receptor subtypes (A2AAR, A2BAR) on immune cells. In addition, activation of A2BARs by adenosine enhances cancer cell proliferation, metastasis, and angiogenesis. Blockade of A2A and A2B 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.
Keywords: adenosine; ATP; CD73; ectonucleotidases; immuno-oncology; inhibitors; NPP1; purine receptors adenosine; ATP; CD73; ectonucleotidases; immuno-oncology; inhibitors; NPP1; purine receptors
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).
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Müller, C.E. Tools and Drugs for Purine-Binding Targets—Important Players in Inflammation and Cancer. Proceedings 2019, 22, 33.

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