A3 Adenosine Receptor Antibodies

The A3 adenosine receptor (A3AR, ADORA3) is a class A GPCR activated by the endogenous purine nucleoside adenosine. It predominantly couples to Gi/o proteins, leading to inhibition of adenylyl cyclase and modulation of MAPK, PI3K/Akt and ion-channel signaling, although coupling to other G proteins can occur depending on the cellular context. A3AR is expressed in many tissues, with particularly high levels in immune cells, including mast cells, eosinophils, neutrophils and macrophages, as well as in the heart, brain, liver and gastrointestinal tract. Activation of A3AR generally suppresses inflammatory signaling and can modulate immune-cell migration, cytokine production, mast-cell degranulation and tissue responses to cellular stress. The receptor has therefore attracted considerable interest as a therapeutic target for inflammatory diseases, including rheumatoid arthritis, inflammatory bowel disease, psoriasis and asthma, as well as for certain cardiovascular and neurodegenerative disorders. Several highly selective A3AR agonists have been developed, including IB-MECA (piclidenoson), CF101, and Cl-IB-MECA, while selective antagonists such as MRS1220 and LJ1251 are widely used as experimental pharmacological tools. Piclidenoson has progressed through multiple clinical trials, particularly for rheumatoid arthritis and other inflammatory indications, but it has not achieved broad regulatory approval as of 2026. A3AR antagonists and partial agonists have also been investigated for potential applications in cancer and CNS disorders, but none has become an established medicine. Overall, A3AR is a well-characterized adenosine receptor with substantial pharmacological validation and remains an attractive target for developing anti-inflammatory and immunomodulatory therapies. For more information on A3 receptor pharmacology please refer to the IUPHAR database. For further reading refer to:

Fredholm BB, Abbracchio MP, Burnstock G, Daly JW, Harden TK, Jacobson KA, Leff P, Williams M. Nomenclature and classification of purinoceptors. Pharmacol Rev. 1994 Jun;46(2):143-56. PMID: 7938164; PMCID: PMC4976594.

Fredholm BB, Frenguelli BG, Hills R, IJzerman AP, Jacobson KA, Klotz KN, Linden J, Müller CE, Schwabe U, Stiles GL. Adenosine receptors in GtoPdb v.2021.2. IUPHAR/BPS Guide to Pharmacology CITE. 2021; 2021(2).