Investigational A₃ adenosine receptor targeting agents

Abstract

Introduction : Adenosine is an endogenous nucleoside that accumulates in the extracellular space in response to metabolic stress and cell damage. Extracellular adenosine is a signaling molecule that signals by activating four GPCRs: the A₁, A_2A, A_2B and A₃ receptors. Since the discovery of A₃ adenosine receptors, accumulating evidence has identified these receptors as potential targets for therapeutic intervention.

Areas covered : A₃ adenosine receptors are expressed on the surface of most immune cell types, including neutrophils, macrophages, dendritic cells, lymphocytes and mast cells. A₃ adenosine receptor activation on immune cells governs a broad array of immune cell functions, which include cytokine production, degranulation, chemotaxis, cytotoxicity, apoptosis and proliferation. In accordance with their multitudinous immunoregulatory actions, targeting A₃ adenosine receptors has been shown to impact the course of a wide spectrum of immune-related diseases, such as asthma, rheumatoid arthritis, cancer, ischemia and inflammatory disorders.

Expert opinion : Given the existence of both preclinical and early clinical data supporting the utility of A₃ adenosine receptor ligands in treating immune-related diseases, further development of A₃ adenosine receptor ligands is anticipated.

Keywords::

• A₃ adenosine receptor
• asthma
• cancer
• IB-MECA
• rheumatoid arthritis

Notes

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