Adenosine A2B receptor

Mechanism

This integral membrane protein stimulates adenylate cyclase activity in the presence of adenosine. This protein also interacts with netrin-1, which is involved in axon elongation.

Gene

The gene is located near the Smith-Magenis syndrome region on chromosome 17.

Ligands

Research into selective A2B ligands has lagged somewhat behind the development of ligands for the other three adenosine receptor subtypes, but a number of A2B-selective compounds have now been developed, and research into their potential therapeutic applications is ongoing.

Agonists

• BAY 60-6583
• NECA (N-ethylcarboxamidoadenosine)
• (S)-PHPNECA - high affinity and efficacy at A2B, but poor selectivity over other adenosine receptor subtypes
• LUF-5835
• LUF-5845 - partial agonist

Antagonists and inverse agonists

• Compound 38: antagonist, high affinity and good subtype selectivity
• ISAM-R56A: non-xanthinic high affinity selective antagonist (Ki: 1.50 nM)
• ISAM-140: non-xanthinic selective antagonist (Ki = 3.49 nM).
• ISAM-R324A: Soluble and metabolically stable non-xanthinic selective antagonist (Ki = 6.10 nM).
• ATL-801
• CVT-6883
• MRS-1706
• MRS-1754
• OSIP-339,391
• PSB-603: xanthinic antagonist
• PSB-0788: xanthinic antagonist
• PSB-1115: xanthinic antagonist
• PSB-1901: xanthinic antagonist with picomolar potency

References

References

1. "Entrez Gene: ADORA2B adenosine A2b receptor".
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9. (January 2006). "Design, synthesis, and structure-activity relationships of 1-,3-,8-, and 9-substituted-9-deazaxanthines at the human A2B adenosine receptor". Journal of Medicinal Chemistry.
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17. (June 2009). "5'-N-ethylcarboxamide induces IL-6 expression via MAPKs and NF-kappaB activation through Akt, Ca(2+)/PKC, cAMP signaling pathways in mouse embryonic stem cells". Journal of Cellular Physiology.
18. (May 2022). "A_2B adenosine receptor antagonists rescue lymphocyte activity in adenosine-producing patient-derived cancer models". Journal for Immunotherapy of Cancer.
19. (November 2008). "1,3-Dialkyl-8-(hetero)aryl-9-OH-9-deazaxanthines as potent A2B adenosine receptor antagonists: design, synthesis, structure-affinity and structure-selectivity relationships". Bioorganic & Medicinal Chemistry.
20. (March 2016). "Discovery of Potent and Highly Selective A2B Adenosine Receptor Antagonist Chemotypes". Journal of Medicinal Chemistry.
21. (December 2022). "Exploring the Effect of Halogenation in a Series of Potent and Selective A_2B Adenosine Receptor Antagonists". Journal of Medicinal Chemistry.
22. (April 2019). "A_2B Adenosine Receptor Antagonists with Picomolar Potency". Journal of Medicinal Chemistry.