Adenosine A2B receptor

ADORA2B
Identifiers
Aliases	ADORA2B, ADORA2, adenosine A2b receptor
External IDs	OMIM: 600446; MGI: 99403; HomoloGene: 20167; GeneCards: ADORA2B; OMA:ADORA2B - orthologs
Gene location (Human)
Chr.	Chromosome 17 (human)
End	15,975,746 bp
Gene location (Mouse)
Chr.	Chromosome 11 (mouse)
End	62,157,279 bp
RNA expression pattern
	Top expressed in
	mucosa of transverse colon; ; bronchial epithelial cell; ; retinal pigment epithelium; ; mucosa of sigmoid colon; ; gonad; ; olfactory zone of nasal mucosa; ; mucosa of paranasal sinus; ; nasal epithelium; ; skin of thigh; ; testicle;
	Top expressed in
	gastrula; ; retinal pigment epithelium; ; yolk sac; ; corneal stroma; ; Epithelium of choroid plexus; ; decidua; ; otic placode; ; lumbar subsegment of spinal cord; ; embryo; ; primary oocyte;
	More reference expression data
	More reference expression data
Gene ontology
Molecular function	G protein-coupled adenosine receptor activity; G protein-coupled receptor activity; signal transducer activity;
Cellular component	integral component of membrane; membrane; plasma membrane; integral component of plasma membrane; intracellular anatomical structure; synapse; Schaffer collateral - CA1 synapse; glutamatergic synapse;
Biological process	cellular response to extracellular stimulus; positive regulation of chronic inflammatory response to non-antigenic stimulus; G protein-coupled receptor signaling pathway; G protein-coupled adenosine receptor signaling pathway; excretion; positive regulation of guanylate cyclase activity; adenylate cyclase-activating G protein-coupled receptor signaling pathway; positive regulation of mast cell degranulation; activation of adenylate cyclase activity; cellular defense response; JNK cascade; positive regulation of interleukin-6 production; relaxation of vascular associated smooth muscle; positive regulation of chemokine production; positive regulation of vascular endothelial growth factor production; signal transduction; positive regulation of cGMP-mediated signaling; regulation of synaptic vesicle exocytosis;
	Sources:Amigo / QuickGO
Orthologs
	136
	11541
	ENSG00000170425
	ENSMUSG00000018500
	P29275
	Q60614
	NM_000676
	NM_007413
	NP_000667
	NP_031439
	Wikidata
View/Edit Human	View/Edit Mouse

The adenosine A_2B receptor, also known as ADORA2B, is a G-protein coupled adenosine receptor, and also denotes the human adenosine A_2b receptor gene which encodes it.^[5]

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 A_2B ligands has lagged somewhat behind the development of ligands for the other three adenosine receptor subtypes, but a number of A_2B-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

BAY 60-6583
NECA (N-ethylcarboxamidoadenosine)
(S)-PHPNECA - high affinity and efficacy at A_2B, but poor selectivity over other adenosine receptor subtypes
LUF-5835
LUF-5845 - partial agonist

Antagonists and inverse agonists

Compound 38:^[23] antagonist, high affinity and good subtype selectivity
ISAM-R56A:^[22] non-xanthinic high affinity selective antagonist (K_i: 1.50 nM)
ISAM-140:^[24] non-xanthinic selective antagonist (K_i = 3.49 nM).
ISAM-R324A:^[25] Soluble and metabolically stable non-xanthinic selective antagonist (K_i = 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

^ ^a ^b ^c GRCh38: Ensembl release 89: ENSG00000170425 – Ensembl, May 2017
^ ^a ^b ^c GRCm38: Ensembl release 89: ENSMUSG00000018500 – Ensembl, May 2017
^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^ ^a ^b "Entrez Gene: ADORA2B adenosine A2b receptor".
^ 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.
^ 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.
^ 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.
^ 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.
^ 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.
^ 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.
^ 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.
^ 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.
^ 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.
^ 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.
^ 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.
^ 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.
^ 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.
^ 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.
^ 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.
^ 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.
^ ^a ^b Tay AH, Prieto-Díaz R, Neo S, Tong L, Chen X, Carannante V, et al. (May 2022). "A_2B 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.
^ 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.
^ 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.
^ 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 A_2B Adenosine Receptor Antagonists". Journal of Medicinal Chemistry. 66 (1): 890–912. doi:10.1021/acs.jmedchem.2c01768. PMC 9841532. PMID 36517209.
^ Jiang J, Seel CJ, Temirak A, Namasivayam V, Arridu A, Schabikowski J, et al. (April 2019). "A_2B Adenosine Receptor Antagonists with Picomolar Potency". Journal of Medicinal Chemistry. 62 (8): 4032–4055. doi:10.1021/acs.jmedchem.9b00071. PMID 30835463. S2CID 73472174.

External links

"Adenosine Receptors: A_2B". IUPHAR Database of Receptors and Ion Channels. International Union of Basic and Clinical Pharmacology. Archived from the original on 2016-03-03. Retrieved 2008-11-25.
Human ADORA2B genome location and ADORA2B gene details page in the UCSC Genome Browser.

[refGRCh38Ensembl-1] GRCh38: Ensembl release 89: ENSG00000170425 – Ensembl, May 2017

[refGRCm38Ensembl-2] 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.

[entrez-5] "Entrez Gene: ADORA2B adenosine A2b receptor".

[pmid12109910-6] 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.

[pmid12369946-7] 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.

[pmid14998332-8] 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.

[pmid16375751-9] 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.

[pmid17168717-10] 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.

[pmid16847822-11] 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.

[pmid16275090-12] 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.

[pmid16392813-13] 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.

[pmid18077171-14] 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.

[pmid18226909-15] 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.

[pmid12570760-16] 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.

[pmid17874974-17] 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.

[pmid18536750-18] 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.

[pmid18758473-19] 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.

[pmid19075778-20] 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.

[pmid19194991-21] 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.

[Tay_e004592-22] Tay AH, Prieto-Díaz R, Neo S, Tong L, Chen X, Carannante V, et al. (May 2022). "A_2B 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 A_2B 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). "A_2B Adenosine Receptor Antagonists with Picomolar Potency". Journal of Medicinal Chemistry. 62 (8): 4032–4055. doi:10.1021/acs.jmedchem.9b00071. PMID 30835463. S2CID 73472174.

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Adenosine A2B receptor

Mechanism

Gene

Ligands

Agonists

Antagonists and inverse agonists

References

Further reading

External links

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