Adenosine A2B receptor

Last updated

ADORA2B
Identifiers
Aliases ADORA2B , ADORA2, adenosine A2b receptor
External IDs OMIM: 600446; MGI: 99403; HomoloGene: 20167; GeneCards: ADORA2B; OMA:ADORA2B - orthologs
Orthologs
SpeciesHumanMouse
Entrez
Ensembl
UniProt
RefSeq (mRNA)

NM_000676

NM_007413

RefSeq (protein)

NP_000667

NP_031439

Location (UCSC) Chr 17: 15.95 – 15.98 Mb Chr 11: 62.14 – 62.16 Mb
PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

The adenosine A2B receptor, also known as ADORA2B, is a G-protein coupled adenosine receptor, and also denotes the human adenosine A2b receptor gene which encodes it. [5]

Contents

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. [5]

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, [6] [7] [8] [9] [10] [11] [12] [13] [14] [15] and research into their potential therapeutic applications is ongoing. [16] [17] [18] [19] [20] [21] [22]

Agonists

Antagonists and inverse agonists


References

  1. 1 2 3 GRCh38: Ensembl release 89: ENSG00000170425 Ensembl, May 2017
  2. 1 2 3 GRCm38: Ensembl release 89: ENSMUSG00000018500 Ensembl, May 2017
  3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. 1 2 "Entrez Gene: ADORA2B adenosine A2b receptor".
  6. Volpini R, Costanzi S, Lambertucci C, Taffi S, Vittori S, Klotz KN, Cristalli G (July 2002). "N(6)-alkyl-2-alkynyl derivatives of adenosine as potent and selective agonists at the human adenosine A(3) receptor and a starting point for searching A(2B) ligands". Journal of Medicinal Chemistry. 45 (15): 3271–3279. doi:10.1021/jm0109762. PMID   12109910.
  7. Volpini R, Costanzi S, Lambertucci C, Vittori S, Cristalli G (2002). "Purine nucleosides bearing 1-alkynyl chains as adenosine receptor agonists". Current Pharmaceutical Design. 8 (26): 2285–2298. doi:10.2174/1381612023392856. PMID   12369946. Archived from the original on 2013-04-14.
  8. Baraldi PG, Tabrizi MA, Preti D, Bovero A, Romagnoli R, Fruttarolo F, et al. (March 2004). "Design, synthesis, and biological evaluation of new 8-heterocyclic xanthine derivatives as highly potent and selective human A2B adenosine receptor antagonists". Journal of Medicinal Chemistry. 47 (6): 1434–1447. doi:10.1021/jm0309654. PMID   14998332.
  9. Cacciari B, Pastorin G, Bolcato C, Spalluto G, Bacilieri M, Moro S (December 2005). "A2B adenosine receptor antagonists: recent developments". Mini Reviews in Medicinal Chemistry. 5 (12): 1053–1060. doi:10.2174/138955705774933374. PMID   16375751. Archived from the original on 2013-04-14.
  10. Baraldi PG, Romagnoli R, Preti D, Fruttarolo F, Carrion MD, Tabrizi MA (2006). "Ligands for A2B adenosine receptor subtype". Current Medicinal Chemistry. 13 (28): 3467–3482. doi:10.2174/092986706779010306. PMID   17168717. Archived from the original on 2013-04-14.
  11. Beukers MW, Meurs I, Ijzerman AP (September 2006). "Structure-affinity relationships of adenosine A2B receptor ligands". Medicinal Research Reviews. 26 (5): 667–698. doi:10.1002/med.20069. PMID   16847822. S2CID   24390495.
  12. Elzein E, Kalla R, Li X, Perry T, Parkhill E, Palle V, et al. (January 2006). "Novel 1,3-dipropyl-8-(1-heteroarylmethyl-1H-pyrazol-4-yl)-xanthine derivatives as high affinity and selective A2B adenosine receptor antagonists". Bioorganic & Medicinal Chemistry Letters. 16 (2): 302–306. doi:10.1016/j.bmcl.2005.10.002. PMID   16275090.
  13. Carotti A, Cadavid MI, Centeno NB, Esteve C, Loza MI, Martinez A, et al. (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. 49 (1): 282–299. doi:10.1021/jm0506221. PMID   16392813.
  14. Tabrizi MA, Baraldi PG, Preti D, Romagnoli R, Saponaro G, Baraldi S, et al. (March 2008). "1,3-Dipropyl-8-(1-phenylacetamide-1H-pyrazol-3-yl)-xanthine derivatives as highly potent and selective human A(2B) adenosine receptor antagonists". Bioorganic & Medicinal Chemistry. 16 (5): 2419–2430. doi:10.1016/j.bmc.2007.11.058. PMID   18077171.
  15. Stefanachi A, Brea JM, Cadavid MI, Centeno NB, Esteve C, Loza MI, et al. (March 2008). "1-, 3- and 8-substituted-9-deazaxanthines as potent and selective antagonists at the human A2B adenosine receptor". Bioorganic & Medicinal Chemistry. 16 (6): 2852–2869. doi:10.1016/j.bmc.2008.01.002. PMID   18226909.
  16. Volpini R, Costanzi S, Vittori S, Cristalli G, Klotz KN (2003). "Medicinal chemistry and pharmacology of A2B adenosine receptors". Current Topics in Medicinal Chemistry. 3 (4): 427–443. doi:10.2174/1568026033392264. PMID   12570760. Archived from the original on 2013-04-14.
  17. Gao ZG, Jacobson KA (September 2007). "Emerging adenosine receptor agonists". Expert Opinion on Emerging Drugs. 12 (3): 479–492. doi:10.1517/14728214.12.3.479. PMC   11790296 . PMID   17874974. S2CID   13777846.
  18. Kolachala V, Ruble B, Vijay-Kumar M, Wang L, Mwangi S, Figler H, et al. (September 2008). "Blockade of adenosine A2B receptors ameliorates murine colitis". British Journal of Pharmacology. 155 (1): 127–137. doi:10.1038/bjp.2008.227. PMC   2440087 . PMID   18536750.
  19. Haskó G, Linden J, Cronstein B, Pacher P (September 2008). "Adenosine receptors: therapeutic aspects for inflammatory and immune diseases". Nature Reviews. Drug Discovery. 7 (9): 759–770. doi:10.1038/nrd2638. PMC   2568887 . PMID   18758473.
  20. Ham J, Rees DA (December 2008). "The adenosine a2b receptor: its role in inflammation". Endocrine, Metabolic & Immune Disorders Drug Targets. 8 (4): 244–254. doi:10.2174/187153008786848303. PMID   19075778. Archived from the original on 2013-04-14.
  21. Kim MO, Kim MH, Lee SH, Suh HN, Lee YJ, Lee MY, Han HJ (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. 219 (3): 752–759. doi: 10.1002/jcp.21721 . PMID   19194991. S2CID   11066973.
  22. 1 2 Tay AH, Prieto-Díaz R, Neo S, Tong L, Chen X, Carannante V, et al. (May 2022). "A2B adenosine receptor antagonists rescue lymphocyte activity in adenosine-producing patient-derived cancer models". Journal for Immunotherapy of Cancer. 10 (5): e004592. doi:10.1136/jitc-2022-004592. PMC   9115112 . PMID   35580926.
  23. Stefanachi A, Nicolotti O, Leonetti F, Cellamare S, Campagna F, Loza MI, et al. (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. 16 (22): 9780–9789. doi:10.1016/j.bmc.2008.09.067. PMID   18938084.
  24. El Maatougui A, Azuaje J, González-Gómez M, Miguez G, Crespo A, Carbajales C, et al. (March 2016). "Discovery of Potent and Highly Selective A2B Adenosine Receptor Antagonist Chemotypes". Journal of Medicinal Chemistry. 59 (5): 1967–1983. doi:10.1021/acs.jmedchem.5b01586. PMID   26824742.
  25. Prieto-Díaz R, González-Gómez M, Fojo-Carballo H, Azuaje J, El Maatougui A, Majellaro M, et al. (December 2022). "Exploring the Effect of Halogenation in a Series of Potent and Selective A2B Adenosine Receptor Antagonists". Journal of Medicinal Chemistry. 66 (1): 890–912. doi:10.1021/acs.jmedchem.2c01768. PMC   9841532 . PMID   36517209.
  26. Jiang J, Seel CJ, Temirak A, Namasivayam V, Arridu A, Schabikowski J, et al. (April 2019). "A2B Adenosine Receptor Antagonists with Picomolar Potency". Journal of Medicinal Chemistry. 62 (8): 4032–4055. doi:10.1021/acs.jmedchem.9b00071. PMID   30835463. S2CID   73472174.

Further reading