Wikipedia

Adenosine A2B receptor

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]

ADORA2B
Identifiers
AliasesADORA2B, ADORA2, adenosine A2b receptor
External IDsOMIM: 600446; MGI: 99403; HomoloGene: 20167; GeneCards: ADORA2B; OMA:ADORA2B - orthologs
Orthologs
SpeciesHumanMouse
Entrez

136

11541

Ensembl

ENSG00000170425

ENSMUSG00000018500

UniProt

P29275

Q60614

RefSeq (mRNA)

NM_000676

NM_007413

RefSeq (protein)

NP_000667

NP_031439

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

Mechanism

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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

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The gene is located near the Smith-Magenis syndrome region on chromosome 17.[5]

Ligands

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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

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  • 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

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  • Compound 38:[23] antagonist, high affinity and good subtype selectivity
  • ISAM-R56A:[22] non-xanthinic high affinity selective antagonist (Ki: 1.50 nM)
  • ISAM-140:[24] non-xanthinic selective antagonist (Ki = 3.49 nM).
  • ISAM-R324A:[25] 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:[26] xanthinic antagonist with picomolar potency


References

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  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000170425 – Ensembl, May 2017
  2. ^ a b c 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. ^ a b "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.{{cite journal}}: CS1 maint: unfit URL (link)
  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.{{cite journal}}: CS1 maint: unfit URL (link)
  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.{{cite journal}}: CS1 maint: unfit URL (link)
  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.{{cite journal}}: CS1 maint: unfit URL (link)
  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. 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.{{cite journal}}: CS1 maint: unfit URL (link)
  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. ^ a b 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

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