Adenozinski A2B receptor

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Adenotinski A2b receptor
Identifikatori
Simboli ADORA2B; ADORA2
Vanjski ID OMIM600446 MGI99403 HomoloGene20167 IUPHAR: A2B GeneCards: ADORA2B Gene
Pregled RNK izražavanja
PBB GE ADORA2B 205891 at tn.png
podaci
Ortolozi
Vrsta Čovek Miš
Entrez 136 11541
Ensembl ENSG00000170425 ENSMUSG00000018500
UniProt P29275 Q60614
RefSeq (mRNA) NM_000676 XM_906642
RefSeq (protein) NP_000667 XP_911735
Lokacija (UCSC) Chr 17:
15.79 - 15.82 Mb
Chr 11:
62.06 - 62.08 Mb
PubMed pretraga [1] [2]

Adenozinski A2B receptor (ADORA2B) je G-protein spregnuti adenozinski receptor. Ovaj protein je kodiran humanim ADORA2B genom.[1]

Mehanizam[uredi - уреди]

Ovaj integralni membranski protein stimuliše aktivnost adenilat ciklaze u prisustvu adenozina. On takođe interaguje sa netrinom-1, koji učestvuje u elongaciji aksona.

Gen[uredi - уреди]

Gen je lociran blizo regiona Smit-Magenisovog sindroma na hromozomu 17.[1]

Ligandi[uredi - уреди]

Istraživanja selektivnih A2B liganda su kasnila za razvojem liganda druga tri adenozinska receptora, međutim vremenom su brojna A2B-selektivna jedinjenja razvijena,[2][3][4][5][6][7][8][9][10][11] i istraživanja njihove potencijalne terapeutske primene su u toku.[12][13][14][15][16][17]

Agonisti

  • BAY 60-6583
  • NECA (N-etilkarboksamido adenozin)
  • (S)-PHPNECA - ina visok afinitet i efikasnost za A2B, alije nedovoljno selektivan u odnosu na druge adenozinske receptore
  • LUF-5835
  • LUF-5845 - parcijalni agonist

Antagonisti i inverzni agonisti

  • Jedinjenje 38:[18] antagonist, ima visok afinitet i znatnu selektivnost
  • ATL-801
  • CVT-6883
  • MRS-1706
  • MRS-1754
  • OSIP-339,391
  • PSB-603
  • PSB-0788
  • PSB-1115

Reference[uredi - уреди]

  1. 1.0 1.1 "Entrez Gene: ADORA2B adenosine A2b receptor". http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=136. 
  2. 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): 3271–9. doi:10.1021/jm0109762. PMID 12109910. 
  3. 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): 2285–98. PMID 12369946. 
  4. Baraldi PG, Tabrizi MA, Preti D, Bovero A, Romagnoli R, Fruttarolo F, Zaid NA, Moorman AR, Varani K, Gessi S, Merighi S, Borea PA (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): 1434–47. doi:10.1021/jm0309654. PMID 14998332. 
  5. 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): 1053–60. PMID 16375751. 
  6. Baraldi PG, Romagnoli R, Preti D, Fruttarolo F, Carrion MD, Tabrizi MA (2006). "Ligands for A2B adenosine receptor subtype". Current Medicinal Chemistry 13 (28): 3467–82. PMID 17168717. 
  7. Beukers MW, Meurs I, Ijzerman AP (September 2006). "Structure-affinity relationships of adenosine A2B receptor ligands". Medicinal Research Reviews 26 (5): 667–98. doi:10.1002/med.20069. PMID 16847822. 
  8. Elzein E, Kalla R, Li X, Perry T, Parkhill E, Palle V, Varkhedkar V, Gimbel A, Zeng D, Lustig D, Leung K, Zablocki J (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): 302–6. doi:10.1016/j.bmcl.2005.10.002. PMID 16275090. 
  9. Carotti A, Cadavid MI, Centeno NB, Esteve C, Loza MI, Martinez A, Nieto R, Raviña E, Sanz F, Segarra V, Sotelo E, Stefanachi A, Vidal B (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): 282–99. doi:10.1021/jm0506221. PMID 16392813. 
  10. Tabrizi MA, Baraldi PG, Preti D, Romagnoli R, Saponaro G, Baraldi S, Moorman AR, Zaid AN, Varani K, Borea PA (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): 2419–30. doi:10.1016/j.bmc.2007.11.058. PMID 18077171. 
  11. Stefanachi A, Brea JM, Cadavid MI, Centeno NB, Esteve C, Loza MI, Martinez A, Nieto R, Raviña E, Sanz F, Segarra V, Sotelo E, Vidal B, Carotti A (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): 2852–69. doi:10.1016/j.bmc.2008.01.002. PMID 18226909. 
  12. 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): 427–43. PMID 12570760. 
  13. Gao ZG, Jacobson KA (September 2007). "Emerging adenosine receptor agonists". Expert Opinion on Emerging Drugs 12 (3): 479–92. doi:10.1517/14728214.12.3.479. PMID 17874974. 
  14. Kolachala V, Ruble B, Vijay-Kumar M, Wang L, Mwangi S, Figler H, Figler R, Srinivasan S, Gewirtz A, Linden J, Merlin D, Sitaraman S (September 2008). "Blockade of adenosine A2B receptors ameliorates murine colitis". British Journal of Pharmacology 155 (1): 127–37. doi:10.1038/bjp.2008.227. PMC 2440087. PMID 18536750. 
  15. 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): 759–70. doi:10.1038/nrd2638. PMC 2568887. PMID 18758473. 
  16. Ham J, Rees DA (December 2008). "The adenosine a2b receptor: its role in inflammation". Endocrine, Metabolic & Immune Disorders Drug Targets 8 (4): 244–54. PMID 19075778. 
  17. 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): 752–9. doi:10.1002/jcp.21721. PMID 19194991. 
  18. Stefanachi A, Nicolotti O, Leonetti F, et al. (2008). "1,3-Dialkyl-8-(hetero)aryl-9-OH-9-deazaxanthines as potent A(2B) adenosine receptor antagonists: Design, synthesis, structure-affinity and structure-selectivity relationships". Bioorganic & medicinal chemistry 16: 9780. doi:10.1016/j.bmc.2008.09.067. PMID 18938084. 

Literatura[uredi - уреди]

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Spoljašnje veze[uredi - уреди]