Adenosine Receptors as Novel Targets for the Treatment of Various Cancers

Author(s): Bapi Gorain, Hira Choudhury*, Gan Sook Yee, Subrat Kumar Bhattamisra*

Journal Name: Current Pharmaceutical Design

Volume 25 , Issue 26 , 2019

Become EABM
Become Reviewer

Abstract:

Adenosine is a ubiquitous signaling nucleoside molecule, released from different cells within the body to act on vasculature and immunoescape. The physiological action on the proliferation of tumour cell has been reported by the presence of high concentration of adenosine within the tumour microenvironment, which results in the progression of the tumour, even leading to metastases. The activity of adenosine exclusively depends upon the interaction with four subtypes of heterodimeric G-protein-coupled adenosine receptors (AR), A1, A2A, A2B, and A3-ARs on the cell surface. Research evidence supports that the activation of those receptors via specific agonist or antagonist can modulate the proliferation of tumour cells. The first category of AR, A1 is known to play an antitumour activity via tumour-associated microglial cells to prevent the development of glioblastomas. A2AAR are found in melanoma, lung, and breast cancer cells, where tumour proliferation is stimulated due to inhibition of the immune response via inhibition of natural killer cells cytotoxicity, T cell activity, and tumourspecific CD4+/CD8+ activity. Alternatively, A2BAR helps in the development of tumour upon activation via upregulation of angiogenin factor in the microvascular endothelial cells, inhibition of MAPK and ERK 1/2 phosphorylation activity. Lastly, A3AR is expressed in low levels in normal cells whereas the expression is upregulated in tumour cells, however, agonists to this receptor inhibit tumour proliferation through modulation of Wnt and NF-κB signaling pathways. Several researchers are in search for potential agents to modulate the overexpressed ARs to control cancer. Active components of A2AAR antagonists and A3AR agonists have already entered in Phase-I clinical research to prove their safety in human. This review focused on novel research targets towards the prevention of cancer progression through stimulation of the overexpressed ARs with the hope to protect lives and advance human health.

Keywords: Adenosine, adenosine receptors, receptor modulators, cancer, signalling pathways, tumour cell.

[1]
Zimmermann H. Extracellular metabolism of ATP and other nucleotides. Naunyn Schmiedebergs Arch Pharmacol 2000; 362(4-5): 299-309.
[http://dx.doi.org/10.1007/s002100000309] [PMID: 11111825]
[2]
Fredholm BB. Adenosine receptors as drug targets. Exp Cell Res 2010; 316(8): 1284-8.
[http://dx.doi.org/10.1016/j.yexcr.2010.02.004] [PMID: 20153317]
[3]
Newby AC. Adenosine and the concept of “retaliatory metabolites”. Trends Biochem Sci 1984; 9(2): 42-4.
[http://dx.doi.org/10.1016/0968-0004(84)90176-2]
[4]
Linden J. Adenosine in tissue protection and tissue regeneration. Mol Pharmacol 2005; 67(5): 1385-7.
[http://dx.doi.org/10.1124/mol.105.011783] [PMID: 15703375]
[5]
McGaraughty S, Cowart M, Jarvis MF, Berman RF. Anticonvulsant and antinociceptive actions of novel adenosine kinase inhibitors. Curr Top Med Chem 2005; 5(1): 43-58.
[http://dx.doi.org/10.2174/1568026053386845] [PMID: 15638777]
[6]
van Calker D, Müller M, Hamprecht B. Adenosine regulates via two different types of receptors, the accumulation of cyclic AMP in cultured brain cells. J Neurochem 1979; 33(5): 999-1005.
[http://dx.doi.org/10.1111/j.1471-4159.1979.tb05236.x] [PMID: 228008]
[7]
Seino S, Shibasaki T. PKA-dependent and PKA-independent pathways for cAMP-regulated exocytosis. Physiol Rev 2005; 85(4): 1303-42.
[http://dx.doi.org/10.1152/physrev.00001.2005] [PMID: 16183914]
[8]
Poulsen SA, Quinn RJ. Adenosine receptors: new opportunities for future drugs. Bioorg Med Chem 1998; 6(6): 619-41.
[http://dx.doi.org/10.1016/S0968-0896(98)00038-8] [PMID: 9681130]
[9]
Glukhova A, Thal DM, Nguyen AT, et al. Structure of the Adenosine A1 Receptor Reveals the Basis for Subtype Selectivity. Cell 2017; 168(5): 867-77.
[http://dx.doi.org/10.1016/j.cell.2017.01.042] [PMID: 28235198]
[10]
Offermanns S, Simon MI. G alpha 15 and G alpha 16 couple a wide variety of receptors to phospholipase C. J Biol Chem 1995; 270(25): 15175-80.
[http://dx.doi.org/10.1074/jbc.270.25.15175] [PMID: 7797501]
[11]
Fresco P, Diniz C, Gonçalves J. Facilitation of noradrenaline release by activation of adenosine A(2A) receptors triggers both phospholipase C and adenylate cyclase pathways in rat tail artery. Cardiovasc Res 2004; 63(4): 739-46.
[http://dx.doi.org/10.1016/j.cardiores.2004.05.015] [PMID: 15306230]
[12]
Linden J. Structure and function of A1 adenosine receptors. FASEB J 1991; 5(12): 2668-76.
[http://dx.doi.org/10.1096/fasebj.5.12.1916091] [PMID: 1916091]
[13]
Kazemi MH, Raoofi Mohseni S, Hojjat-Farsangi M, et al. Adenosine and adenosine receptors in the immunopathogenesis and treatment of cancer. J Cell Physiol 2018; 233(3): 2032-57.
[http://dx.doi.org/10.1002/jcp.25873] [PMID: 28233320]
[14]
Leone RD, Emens LA. Targeting adenosine for cancer immunotherapy. J Immunother Cancer 2018; 6(1): 57.
[http://dx.doi.org/10.1186/s40425-018-0360-8] [PMID: 29914571]
[15]
Fishman P, Bar-Yehuda S, Synowitz M, et al. Adenosine receptors and cancer. Handb Exp Pharmacol 2009; 193: 399-441.
[http://dx.doi.org/10.1007/978-3-540-89615-9_14]
[16]
Salmon JE, Cronstein BN. Fc gamma receptor-mediated functions in neutrophils are modulated by adenosine receptor occupancy. A1 receptors are stimulatory and A2 receptors are inhibitory. J Immunol 1990; 145(7): 2235-40.
[PMID: 2168919]
[17]
Merrill JT, Shen C, Schreibman D, et al. Adenosine A1 receptor promotion of multinucleated giant cell formation by human monocytes: a mechanism for methotrexate-induced nodulosis in rheumatoid arthritis. Arthritis Rheum 1997; 40(7): 1308-15.
[PMID: 9214432]
[18]
Lee HT, Gallos G, Nasr SH, Emala CW. A1 adenosine receptor activation inhibits inflammation, necrosis, and apoptosis after renal ischemia-reperfusion injury in mice. J Am Soc Nephrol 2004; 15(1): 102-11.
[http://dx.doi.org/10.1097/01.ASN.0000102474.68613.AE] [PMID: 14694162]
[19]
Tsutsui S, Schnermann J, Noorbakhsh F, et al. A1 adenosine receptor upregulation and activation attenuates neuroinflammation and demyelination in a model of multiple sclerosis. J Neurosci 2004; 24(6): 1521-9.
[http://dx.doi.org/10.1523/JNEUROSCI.4271-03.2004] [PMID: 14960625]
[20]
Liao Y, Takashima S, Asano Y, et al. Activation of adenosine A1 receptor attenuates cardiac hypertrophy and prevents heart failure in murine left ventricular pressure-overload model. Circ Res 2003; 93(8): 759-66.
[http://dx.doi.org/10.1161/01.RES.0000094744.88220.62] [PMID: 12970111]
[21]
Sun C-X, Young HW, Molina JG, Volmer JB, Schnermann J, Blackburn MR. A protective role for the A1 adenosine receptor in adenosine-dependent pulmonary injury. J Clin Invest 2005; 115(1): 35-43.
[http://dx.doi.org/10.1172/JCI22656] [PMID: 15630442]
[22]
van Galen PJ, Stiles GL, Michaels G, Jacobson KA. Adenosine A1 and A2 receptors: structure-function relationships. Med Res Rev 1992; 12(5): 423-71.
[http://dx.doi.org/10.1002/med.2610120502] [PMID: 1513184]
[23]
Rosenberg D, Groussin L, Jullian E, Perlemoine K, Bertagna X, Bertherat J. Role of the PKA-regulated transcription factor CREB in development and tumorigenesis of endocrine tissues. Ann N Y Acad Sci 2002; 968: 65-74.
[http://dx.doi.org/10.1111/j.1749-6632.2002.tb04327.x] [PMID: 12119268]
[24]
Löffler I, Grün M, Böhmer FD, Rubio I. Role of cAMP in the promotion of colorectal cancer cell growth by prostaglandin E2. BMC Cancer 2008; 8: 380.
[http://dx.doi.org/10.1186/1471-2407-8-380] [PMID: 19099561]
[25]
Sakamoto KM, Frank DA. CREB in the pathophysiology of cancer: implications for targeting transcription factors for cancer therapy. Clin Cancer Res 2009; 15(8): 2583-7.
[http://dx.doi.org/10.1158/1078-0432.CCR-08-1137] [PMID: 19351775]
[26]
Boettcher M, Lawson A, Ladenburger V, et al. High throughput synthetic lethality screen reveals a tumorigenic role of adenylate cyclase in fumarate hydratase-deficient cancer cells. BMC Genomics 2014; 15: 158.
[http://dx.doi.org/10.1186/1471-2164-15-158] [PMID: 24568598]
[27]
Yu S-J, Yu J-K, Ge W-T, Hu H-G, Yuan Y, Zheng S. SPARCL1, Shp2, MSH2, E-cadherin, p53, ADCY-2 and MAPK are prognosis-related in colorectal cancer. World J Gastroenterol 2011; 17(15): 2028-36.
[http://dx.doi.org/10.3748/wjg.v17.i15.2028] [PMID: 21528083]
[28]
Hong S-H, Goh S-H, Lee S-J, et al. Upregulation of adenylate cyclase 3 (ADCY3) increases the tumorigenic potential of cells by activating the CREB pathway. Oncotarget 2013; 4(10): 1791-803.
[http://dx.doi.org/10.18632/oncotarget.1324] [PMID: 24113161]
[29]
Shaban M, Smith RA, Stone TW. Purine suppression of proliferation of Sertoli-like TM4 cells in culture. Cell Prolif 1995; 28(12): 673-82.
[http://dx.doi.org/10.1111/j.1365-2184.1995.tb00053.x] [PMID: 8634374]
[30]
Synowitz M, Glass R, Färber K, et al. A1 adenosine receptors in microglia control glioblastoma-host interaction. Cancer Res 2006; 66(17): 8550-7.
[http://dx.doi.org/10.1158/0008-5472.CAN-06-0365] [PMID: 16951167]
[31]
Gebicke-Haerter PJ, Christoffel F, Timmer J, Northoff H, Berger M, Van Calker D. Both adenosine A1- and A2-receptors are required to stimulate microglial proliferation. Neurochem Int 1996; 29(1): 37-42.
[http://dx.doi.org/10.1016/0197-0186(95)00137-9] [PMID: 8808787]
[32]
Saito M, Yaguchi T, Yasuda Y, Nakano T, Nishizaki T. Adenosine suppresses CW2 human colonic cancer growth by inducing apoptosis via A(1) adenosine receptors. Cancer Lett 2010; 290(2): 211-5.
[http://dx.doi.org/10.1016/j.canlet.2009.09.011] [PMID: 19822392]
[33]
Kaur T, Borse V, Sheth S, et al. Adenosine A1 receptor protects against cisplatin ototoxicity by suppressing the NOX3/STAT1 Inflammatory Pathway in the Cochlea. J Neurosci 2016; 36(14): 3962-77.
[34]
Blay J. Adenosine and tumor microenvironment. In: Schwab M. (eds) Encyclopedia of Cancer. Springer, Berlin, Heidelberg.
[35]
Ghiringhelli F, Bruchard M, Chalmin F, Rébé C. Production of adenosine by ectonucleotidases: a key factor in tumor immunoescape. J Biomed Biotechnol 2012; 2012473712
[http://dx.doi.org/10.1155/2012/473712] [PMID: 23133312]
[36]
Gessi S, Varani K, Merighi S, et al. Pharmacological and biochemical characterization of A3 adenosine receptors in Jurkat T cells. Br J Pharmacol 2001; 134(1): 116-26.
[http://dx.doi.org/10.1038/sj.bjp.0704254] [PMID: 11522603]
[37]
Khoo H-E, Ho C-L, Chhatwal VJS, Chan STF, Ngoi S-S, Moochhala SM. Differential expression of adenosine A1 receptors in colorectal cancer and related mucosa. Cancer Lett 1996; 106(1): 17-21.
[http://dx.doi.org/10.1016/0304-3835(96)04289-9] [PMID: 8827042]
[38]
Mirza A, Basso A, Black S, et al. RNA interference targeting of A1 receptor-overexpressing breast carcinoma cells leads to diminished rates of cell proliferation and induction of apoptosis. Cancer Biol Ther 2005; 4(12): 1355-60.
[http://dx.doi.org/10.4161/cbt.4.12.2196] [PMID: 16294023]
[39]
Zhou Y, Tong L, Chu X, et al. The adenosine A1 receptor antagonist DPCPX inhibits tumor progression via the ERK/JNK pathway in renal cell carcinoma. Cell Physiol Biochem 2017; 43(2): 733-42.
[http://dx.doi.org/10.1159/000481557] [PMID: 28950257]
[40]
Dastjerdi MN, Rarani MZ, Valiani A, Mahmoudieh M. The effect of adenosine A1 receptor agonist and antagonist on p53 and caspase 3, 8, and 9 expression and apoptosis rate in MCF-7 breast cancer cell line. Res Pharm Sci 2016; 11(4): 303-10.
[http://dx.doi.org/10.4103/1735-5362.189301] [PMID: 27651810]
[41]
Woodhouse EC, Amanatullah DF, Schetz JA, Liotta LA, Stracke ML, Clair T. Adenosine receptor mediates motility in human melanoma cells. Biochem Biophys Res Commun 1998; 246(3): 888-94.
[http://dx.doi.org/10.1006/bbrc.1998.8714] [PMID: 9618307]
[42]
Clark AN, Youkey R, Liu X, et al. A1 adenosine receptor activation promotes angiogenesis and release of VEGF from monocytes. Circ Res 2007; 101(11): 1130-8.
[http://dx.doi.org/10.1161/CIRCRESAHA.107.150110] [PMID: 17901362]
[43]
Carmeliet P. VEGF as a key mediator of angiogenesis in cancer. Oncology 2005; 69(Suppl. 3): 4-10.
[http://dx.doi.org/10.1159/000088478] [PMID: 16301830]
[44]
Mosenden R, Taskén K. Cyclic AMP-mediated immune regulation--overview of mechanisms of action in T cells. Cell Signal 2011; 23(6): 1009-16.
[http://dx.doi.org/10.1016/j.cellsig.2010.11.018] [PMID: 21130867]
[45]
Allard D, Turcotte M, Stagg J. Targeting A2 adenosine receptors in cancer. Immunol Cell Biol 2017; 95(4): 333-9.
[http://dx.doi.org/10.1038/icb.2017.8] [PMID: 28174424]
[46]
Stagg J, Divisekera U, Duret H, et al. CD73-deficient mice have increased antitumor immunity and are resistant to experimental metastasis. Cancer Res 2011; 71(8): 2892-900.
[http://dx.doi.org/10.1158/0008-5472.CAN-10-4246] [PMID: 21292811]
[47]
Jimenez JL, Punzón C, Navarro J, Muñoz-Fernández MA, Fresno M. Phosphodiesterase 4 inhibitors prevent cytokine secretion by T lymphocytes by inhibiting nuclear factor-kappaB and nuclear factor of activated T cells activation. J Pharmacol Exp Ther 2001; 299(2): 753-9.
[PMID: 11602691]
[48]
Bos JL, Rehmann H, Wittinghofer A. GEFs and GAPs: critical elements in the control of small G proteins. Cell 2007; 129(5): 865-77.
[http://dx.doi.org/10.1016/j.cell.2007.05.018] [PMID: 17540168]
[49]
Cheng X, Ji Z, Tsalkova T, Mei F. Epac and PKA: a tale of two intracellular cAMP receptors. Acta Biochim Biophys Sin 2008; 40(7): 651-62.
[http://dx.doi.org/10.1111/j.1745-7270.2008.00438.x] [PMID: 18604457]
[50]
Chrzanowska-Wodnicka M, Kraus AE, Gale D, White GC II, Vansluys J. Defective angiogenesis, endothelial migration, proliferation, and MAPK signaling in Rap1b-deficient mice. Blood 2008; 111(5): 2647-56.
[http://dx.doi.org/10.1182/blood-2007-08-109710] [PMID: 17993608]
[51]
Boussiotis VA, Freeman GJ, Berezovskaya A, Barber DL, Nadler LM. Maintenance of human T cell anergy: blocking of IL-2 gene transcription by activated Rap1. Science 1997; 278(5335): 124-8.
[http://dx.doi.org/10.1126/science.278.5335.124] [PMID: 9311917]
[52]
Blackburn MR, Vance CO, Morschl E, Wilson CN. Adenosine Receptors and Inflammation. Handb Exp Pharmacol 2009; 215-69.
[53]
Wilson JM, Kurtz CC, Black SG, et al. The A2B adenosine receptor promotes Th17 differentiation via stimulation of dendritic cell IL-6. J Immunol 2011; 186(12): 6746-52.
[http://dx.doi.org/10.4049/jimmunol.1100117] [PMID: 21593380]
[54]
Ohta A, Gorelik E, Prasad SJ, et al. A2A adenosine receptor protects tumors from antitumor T cells. Proc Natl Acad Sci USA 2006; 103: 13132-7.
[http://dx.doi.org/10.1073/pnas.0605251103]
[55]
Németh ZH, Lutz CS, Csóka B, et al. Adenosine augments IL-10 production by macrophages through an A2B receptor-mediated posttranscriptional mechanism. J Immunol 2005; 175(12): 8260-70.
[http://dx.doi.org/10.4049/jimmunol.175.12.8260] [PMID: 16339566]
[56]
Haskó G, Kuhel DG, Chen J-F, et al. Adenosine inhibits IL-12 and TNF-[α] production via adenosine A2a receptor-dependent and independent mechanisms. FASEB J 2000; 14(13): 2065-74.
[http://dx.doi.org/10.1096/fj.99-0508com] [PMID: 11023991]
[57]
Peterfreund RA, MacCollin M, Gusella J, Fink JS. Characterization and expression of the human A2a adenosine receptor gene. J Neurochem 1996; 66(1): 362-8.
[http://dx.doi.org/10.1046/j.1471-4159.1996.66010362.x] [PMID: 8522976]
[58]
Wei CJ, Li W, Chen J-F. Normal and abnormal functions of adenosine receptors in the central nervous system revealed by genetic knockout studies. Biochim Biophys Acta 2011; 1808(5): 1358-79.
[http://dx.doi.org/10.1016/j.bbamem.2010.12.018] [PMID: 21185258]
[59]
Antonioli L, Blandizzi C, Pacher P, Haskó G. Immunity, inflammation and cancer: a leading role for adenosine. Nat Rev Cancer 2013; 13(12): 842-57.
[http://dx.doi.org/10.1038/nrc3613] [PMID: 24226193]
[60]
Borea PA, Gessi S, Merighi S, Vincenzi F, Varani K. Pathological overproduction: the bad side of adenosine Br J Pharmacol 2017; 174: 1945-1960. 3.
[http://dx.doi.org/10.1111/bph.13763]
[61]
Merighi S, Mirandola P, Varani K, et al. A glance at adenosine receptors: novel target for antitumor therapy. Pharmacol Ther 2003; 100(1): 31-48.
[http://dx.doi.org/10.1016/S0163-7258(03)00084-6] [PMID: 14550503]
[62]
Muller-Haegele S, Muller L, Whiteside TL. Immunoregulatory activity of adenosine and its role in human cancer progression. Expert Rev Clin Immunol 2014; 10(7): 897-914.
[http://dx.doi.org/10.1586/1744666X.2014.915739] [PMID: 24871693]
[63]
Gessi S, Bencivenni S, Battistello E, et al. Inhibition of A2A adenosine receptor signaling in cancer cells proliferation by the novel antagonist TP455. Front Pharmacol 2017; 8: 888.
[http://dx.doi.org/10.3389/fphar.2017.00888] [PMID: 29249971]
[64]
Young A, Ngiow SF, Barkauskas DS, et al. Co-inhibition of CD73 and A2AR adenosine signaling improves anti-tumor immune responses. Cancer Cell 2016; 30(3): 391-403.
[http://dx.doi.org/10.1016/j.ccell.2016.06.025] [PMID: 27622332]
[65]
Sitkovsky MV, Kjaergaard J, Lukashev D, Ohta A. Hypoxia-adenosinergic immunosuppression: tumor protection by T regulatory cells and cancerous tissue hypoxia. Clin Cancer Res 2008; 14(19): 5947-52.
[http://dx.doi.org/10.1158/1078-0432.CCR-08-0229] [PMID: 18829471]
[66]
Merighi S, Mirandola P, Milani D, et al. Adenosine receptors as mediators of both cell proliferation and cell death of cultured human melanoma cells. J Invest Dermatol 2002; 119(4): 923-33.
[http://dx.doi.org/10.1046/j.1523-1747.2002.00111.x] [PMID: 12406340]
[67]
Etique N, Grillier-Vuissoz I, Lecomte J, Flament S. Crosstalk between adenosine receptor (A2A isoform) and ERalpha mediates ethanol action in MCF-7 breast cancer cells. Oncol Rep 2009; 21(4): 977-81.
[PMID: 19287996]
[68]
Koszałka P, Gołuńska M, Urban A, et al. Specific activation of A3, A2A and A1 adenosine receptors in CD73-knockout mice affects B16F10 melanoma growth, neovascularization, angiogenesis and macrophage infiltration. PLoS One 2016; 11(3)e0151420
[http://dx.doi.org/10.1371/journal.pone.0151420] [PMID: 26964090]
[69]
Perez-Aso M, Mediero A, Low YC, Levine J, Cronstein BN. Adenosine A2A receptor plays an important role in radiation-induced dermal injury. FASEB J 2016; 30(1): 457-65.
[http://dx.doi.org/10.1096/fj.15-280388] [PMID: 26415936]
[70]
Beavis PA, Divisekera U, Paget C, et al. Blockade of A2A receptors potently suppresses the metastasis of CD73+ tumors. Proc Natl Acad Sci USA 2013; 110(36): 14711-6.
[http://dx.doi.org/10.1073/pnas.1308209110] [PMID: 23964122]
[71]
Waickman AT, Alme A, Senaldi L, Zarek PE, Horton M, Powell JD. Enhancement of tumor immunotherapy by deletion of the A2A adenosine receptor. Cancer Immunol Immunother 2012; 61(6): 917-26.
[http://dx.doi.org/10.1007/s00262-011-1155-7] [PMID: 22116345]
[72]
Sun Y, Huang P. Adenosine A2B receptor: From cell biology to human diseases. Front Chem 2016; 4: 37.
[http://dx.doi.org/10.3389/fchem.2016.00037] [PMID: 27606311]
[73]
Wei W, Du C, Lv J, et al. Blocking A2B adenosine receptor alleviates pathogenesis of experimental autoimmune encephalomyelitis via inhibition of IL-6 production and Th17 differentiation. J Immunol 2013; 190(1): 138-46.
[http://dx.doi.org/10.4049/jimmunol.1103721] [PMID: 23225885]
[74]
Schulte G, Fredholm BB. Signalling from adenosine receptors to mitogen-activated protein kinases. Cell Signal 2003; 15(9): 813-27.
[http://dx.doi.org/10.1016/S0898-6568(03)00058-5] [PMID: 12834807]
[75]
Ntantie E, Gonyo P, Lorimer EL, et al. An adenosine-mediated signaling pathway suppresses prenylation of the GTPase Rap1B and promotes cell scattering. Sci Signal 2013; 6(277): ra39-9.
[http://dx.doi.org/10.1126/scisignal.2003374] [PMID: 23716716]
[76]
Desmet CJ, Gallenne T, Prieur A, et al. Identification of a pharmacologically tractable Fra-1/ADORA2B axis promoting breast cancer metastasis. Proc Natl Acad Sci USA 2013; 110(13): 5139-44.
[http://dx.doi.org/10.1073/pnas.1222085110] [PMID: 23483055]
[77]
Adiseshaiah P, Lindner DJ, Kalvakolanu DV, Reddy SP. FRA-1 proto-oncogene induces lung epithelial cell invasion and anchorage-independent growth in vitro, but is insufficient to promote tumor growth in vivo. Cancer Res 2007; 67(13): 6204-11.
[http://dx.doi.org/10.1158/0008-5472.CAN-06-4687] [PMID: 17616677]
[78]
Fang M, Xia J, Wu X, et al. Adenosine signaling inhibits CIITA-mediated MHC class II transactivation in lung fibroblast cells. Eur J Immunol 2013; 43(8): 2162-73.
[http://dx.doi.org/10.1002/eji.201343461] [PMID: 23681904]
[79]
Xia J, Fang M, Wu X, et al. A2b adenosine signaling represses CIITA transcription via an epigenetic mechanism in vascular smooth muscle cells. Biochim Biophys Acta 2015; 1849(6): 665-76.
[http://dx.doi.org/10.1016/j.bbagrm.2015.03.001] [PMID: 25765819]
[80]
Shi B, Vinyals A, Alia P, et al. Differential expression of MHC class II molecules in highly metastatic breast cancer cells is mediated by the regulation of the CIITA transcription Implication of CIITA in tumor and metastasis development. Int J Biochem Cell Biol 2006; 38(4): 544-62.
[http://dx.doi.org/10.1016/j.biocel.2005.07.012] [PMID: 16343978]
[81]
Fernandez-Gallardo M, González-Ramírez R, Sandoval A, Felix R, Monjaraz E. Adenosine stimulate proliferation and migration in triple negative breast cancer cells. PLoS One 2016; 11(12)e0167445
[http://dx.doi.org/10.1371/journal.pone.0167445] [PMID: 27911956]
[82]
Iannone R, Miele L, Maiolino P, Pinto A, Morello S. Blockade of A2b adenosine receptor reduces tumor growth and immune suppression mediated by myeloid-derived suppressor cells in a mouse model of melanoma. Neoplasia 2013; 15(12): 1400-9.
[http://dx.doi.org/10.1593/neo.131748] [PMID: 24403862]
[83]
Cekic C, Sag D, Li Y, Theodorescu D, Strieter RM, Linden J. Adenosine A2B receptor blockade slows growth of bladder and breast tumors. J Immunol 2012; 188(1): 198-205.
[http://dx.doi.org/10.4049/jimmunol.1101845] [PMID: 22116822]
[84]
Atkinson MR, Townsend-Nicholson A, Nicholl JK, Sutherland GR, Schofield PR. Cloning, characterisation and chromosomal assignment of the human adenosine A3 receptor (ADORA3) gene. Neurosci Res 1997; 29(1): 73-9.
[http://dx.doi.org/10.1016/S0168-0102(97)00073-4] [PMID: 9293494]
[85]
Borea PA, Varani K, Vincenzi F, et al. The A3 adenosine receptor: history and perspectives. Pharmacol Rev 2015; 67(1): 74-102.
[http://dx.doi.org/10.1124/pr.113.008540] [PMID: 25387804]
[86]
Madi L, Ochaion A, Rath-Wolfson L, et al. The A3 adenosine receptor is highly expressed in tumor versus normal cells: potential target for tumor growth inhibition. Clin Cancer Res 2004; 10(13): 4472-9.
[http://dx.doi.org/10.1158/1078-0432.CCR-03-0651] [PMID: 15240539]
[87]
Feoktistov I, Ryzhov S, Goldstein AE, Biaggioni I. Mast cell-mediated stimulation of angiogenesis: cooperative interaction between A2B and A3 adenosine receptors. Circ Res 2003; 92(5): 485-92.
[http://dx.doi.org/10.1161/01.RES.0000061572.10929.2D] [PMID: 12600879]
[88]
Gessi S, Sacchetto V, Fogli E, et al. Modulation of metalloproteinase-9 in U87MG glioblastoma cells by A3 adenosine receptors. Biochem Pharmacol 2010; 79(10): 1483-95.
[http://dx.doi.org/10.1016/j.bcp.2010.01.009] [PMID: 20096265]
[89]
Merighi S, Benini A, Mirandola P, et al. Adenosine modulates vascular endothelial growth factor expression via hypoxia-inducible factor-1 in human glioblastoma cells. Biochem Pharmacol 2006; 72(1): 19-31.
[http://dx.doi.org/10.1016/j.bcp.2006.03.020] [PMID: 16682012]
[90]
Semenza GL. Targeting HIF-1 for cancer therapy. Nat Rev Cancer 2003; 3(10): 721-32.
[http://dx.doi.org/10.1038/nrc1187] [PMID: 13130303]
[91]
Merighi S, Benini A, Mirandola P, et al. Hypoxia inhibits paclitaxel-induced apoptosis through adenosine-mediated phosphorylation of bad in glioblastoma cells. Mol Pharmacol 2007; 72(1): 162-72.
[http://dx.doi.org/10.1124/mol.106.031849] [PMID: 17400763]
[92]
Madi L, Bar-Yehuda S, Barer F, Ardon E, Ochaion A, Fishman P. A3 adenosine receptor activation in melanoma cells: association between receptor fate and tumor growth inhibition. J Biol Chem 2003; 278(43): 42121-30.
[http://dx.doi.org/10.1074/jbc.M301243200] [PMID: 12865431]
[93]
Zhao Z, Makaritsis K, Francis CE, Gavras H, Ravid K. A role for the A3 adenosine receptor in determining tissue levels of cAMP and blood pressure: studies in knock-out mice. Biochim Biophys Acta 2000; 1500(3): 280-90.
[http://dx.doi.org/10.1016/S0925-4439(99)00111-8] [PMID: 10699369]
[94]
Jajoo S, Mukherjea D, Watabe K, Ramkumar V. Adenosine A(3) receptor suppresses prostate cancer metastasis by inhibiting NADPH oxidase activity. Neoplasia 2009; 11(11): 1132-45.
[http://dx.doi.org/10.1593/neo.09744] [PMID: 19881949]
[95]
Varani K, Maniero S, Vincenzi F, et al. 3 receptors are overexpressed in pleura from patients with mesothelioma and reduce cell growth via Akt/Nuclear factor-kB pathway 2011; 183(4): 522-30.
[96]
Cohen S, Stemmer SM, Zozulya G, et al. CF102 an A3 adenosine receptor agonist mediates anti-tumor and anti-inflammatory effects in the liver. J Cell Physiol 2011; 226(9): 2438-47.
[http://dx.doi.org/10.1002/jcp.22593] [PMID: 21660967]
[97]
Lee E-J, Min H-Y, Chung H-J, et al. A novel adenosine analog, thio-Cl-IB-MECA, induces G0/G1 cell cycle arrest and apoptosis in human promyelocytic leukemia HL-60 cells. Biochem Pharmacol 2005; 70(6): 918-24.
[http://dx.doi.org/10.1016/j.bcp.2005.06.017] [PMID: 16051194]
[98]
Fishman P, Bar-Yehuda S, Barer F, Madi L, Multani AS, Pathak S. The A3 adenosine receptor as a new target for cancer therapy and chemoprotection. Exp Cell Res 2001; 269(2): 230-6.
[http://dx.doi.org/10.1006/excr.2001.5327] [PMID: 11570815]
[99]
Fishman P, Bar-Yehuda S, Ohana G, et al. Adenosine acts as an inhibitor of lymphoma cell growth: a major role for the A3 adenosine receptor. Eur J Cancer 2000; 36(11): 1452-8.
[100]
Haskó G, Linden J, Cronstein B, Pacher P. Adenosine receptors: therapeutic aspects for inflammatory and immune diseases. Nat Rev Drug Discov 2008; 7(9): 759-70.
[http://dx.doi.org/10.1038/nrd2638] [PMID: 18758473]
[101]
Jacobson KA, Gao ZG. Adenosine receptors as therapeutic targets. Nat Rev Drug Discov 2006; 5(3): 247-64.
[http://dx.doi.org/10.1038/nrd1983] [PMID: 16518376]
[102]
Yu L, Huang Z, Mariani J, Wang Y, Moskowitz M, Chen J-F. Selective inactivation or reconstitution of adenosine A2A receptors in bone marrow cells reveals their significant contribution to the development of ischemic brain injury. Nat Med 2004; 10(10): 1081-7.
[http://dx.doi.org/10.1038/nm1103] [PMID: 15448683]
[103]
Cohen MV, Downey JM. Adenosine: trigger and mediator of cardioprotection. Basic Res Cardiol 2008; 103(3): 203-15.
[http://dx.doi.org/10.1007/s00395-007-0687-7] [PMID: 17999026]
[104]
Gottlieb SS, Brater DC, Thomas I, et al. BG9719 (CVT-124), an A1 adenosine receptor antagonist, protects against the decline in renal function observed with diuretic therapy. Circulation 2002; 105(11): 1348-53.
[http://dx.doi.org/10.1161/hc1102.105264] [PMID: 11901047]
[105]
Chen G-J, Harvey BK, Shen H, Chou J, Victor A, Wang Y. Activation of adenosine A3 receptors reduces ischemic brain injury in rodents. J Neurosci Res 2006; 84(8): 1848-55.
[http://dx.doi.org/10.1002/jnr.21071] [PMID: 17016854]
[106]
Guzman J, Yu JG, Suntres Z, et al. ADOA3R as a therapeutic target in experimental colitis: proof by validated high-density oligonucleotide microarray analysis. Inflamm Bowel Dis 2006; 12(8): 766-89.
[http://dx.doi.org/10.1097/00054725-200608000-00014] [PMID: 16917233]
[107]
Kolachala VL, Bajaj R, Chalasani M, Sitaraman SV. Purinergic receptors in gastrointestinal inflammation. Am J Physiol Gastrointest Liver Physiol 2008; 294(2): G401-10.
[http://dx.doi.org/10.1152/ajpgi.00454.2007] [PMID: 18063703]
[108]
Madi L, Cohen S, Ochayin A, Bar-Yehuda S, Barer F, Fishman P. Overexpression of A3 adenosine receptor in peripheral blood mononuclear cells in rheumatoid arthritis: involvement of nuclear factor-kappaB in mediating receptor level. J Rheumatol 2007; 34(1): 20-6.
[PMID: 17216675]
[109]
Schwarzschild MA, Agnati L, Fuxe K, Chen JF, Morelli M. Targeting adenosine A2A receptors in Parkinson’s disease. Trends Neurosci 2006; 29(11): 647-54.
[http://dx.doi.org/10.1016/j.tins.2006.09.004] [PMID: 17030429]
[110]
LeWitt PA, Guttman M, Tetrud JW, et al. Adenosine A2A receptor antagonist istradefylline (KW-6002) reduces “off” time in Parkinson’s disease: a double-blind, randomized, multicenter clinical trial (6002-US-005). Ann Neurol 2008; 63(3): 295-302.
[http://dx.doi.org/10.1002/ana.21315] [PMID: 18306243]
[111]
Khasim S, Pran Kishore D, Raghuprasad M, et al. 7-Amino-2-aryl/heteroaryl-5-oxo-5,8-dihydro[1,2,4]triazolo[1,5-a]pyridine-6-carbonitriles: Synthesis and Adenosine Receptor Binding Studies. Chem Biol Drug Des 2019; 94(2): 1568-73.
[http://dx.doi.org/10.1111/cbdd.13528]
[112]
Chandrasekaran B, Kishore Deb P, Rao Akkinepalli R. Structure-based Design and Pharmacological Study of Fluorinated Fused Quinazolines as Adenosine A 2B Receptor Antagonists. JSM Chem 2017; 5: 1041.
[113]
Balakumar C, Kishore DP, Rao KV, et al. Design, microwave-assisted synthesis and in silico docking studies of new 4H-pyrimido[2,1-b]benzothiazole-2-arylamino-3-cyano-4-ones as possible adenosine A2B receptor antagonists. Indian J Chem 2012; 51B: 1105-13.
[114]
Chandrasekaran B, Deb PK, Kachler S, Akkinepalli RR, Mailavaram R, Klotz K-N. Synthesis and adenosine receptors binding studies of new fluorinated analogues of pyrido[2,3-d]pyrimidines and quinazolines. Med Chem Res 2018; 27: 756-67.
[http://dx.doi.org/10.1007/s00044-017-2099-z]
[115]
Pran Kishore D, Balakumar C, Raghuram Rao A, Roy PP, Roy K. QSAR of adenosine receptor antagonists: Exploring physicochemical requirements for binding of pyrazolo[4,3-e]-1,2,4-triazolo[1,5-c]pyrimidine derivatives with human adenosine A(3) receptor subtype. Bioorg Med Chem Lett 2011; 21(2): 818-23.
[http://dx.doi.org/10.1016/j.bmcl.2010.11.094] [PMID: 21163647]
[116]
Deb PK, Mailavaram R, Chandrasekaran B, et al. Synthesis, adenosine receptor binding and molecular modelling studies of novel thieno[2,3-d]pyrimidine derivatives. Chem Biol Drug Des 2018; 91(4): 962-9.
[http://dx.doi.org/10.1111/cbdd.13155] [PMID: 29194979]
[117]
Hosseinzadeh H, Stone T. Adenosine in the central nervous system. Med J Islam Repub Iran 1996; 9: 361-8.
[118]
Hosseinzadeh H, Jaafari MR, Shamsara J. Selective inhibitory effect of adenosine A1 receptor agonists on the proliferation of human tumor cell lines. Iran Biomed J 2008; 12(4): 203-8.
[PMID: 19079533]
[119]
Dastjerdi MN, Valiani A, Mardani M, Ra MZ. Adenosine A1 receptor modifies P53 expression and apoptosis in breast cancer cell line Mcf-7. Bratisl Lek Listy 2016; 117(4): 242-6.
[http://dx.doi.org/10.4149/BLL_2016_046] [PMID: 27075390]
[120]
Lin Z, Yin P, Reierstad S, et al. Adenosine A1 receptor, a target and regulator of estrogen receptoralpha action, mediates the proliferative effects of estradiol in breast cancer. Oncogene 2010; 29(8): 1114-22.
[http://dx.doi.org/10.1038/onc.2009.409] [PMID: 19935720]
[121]
Glukhova A, Thal DM, Nguyen AT, et al. Structure of the Adenosine A1 Receptor Reveals the Basis for Subtype Selectivity. Cell 2017; 168(5): 867-77.
[http://dx.doi.org/10.1016/j.cell.2017.01.042] [PMID: 28235198]
[122]
Houthuys E, Brouwer M, Nyawouame F, et al. A novel adenosine A2A receptor antagonist optimized for high potency in adenosine-rich tumor microenvironment boosts antitumor immunity. Cancer Res 2017; 77: 1683-3.
[123]
Mediavilla-Varela M, Castro J, Chiappori A, et al. A novel antagonist of the immune checkpoint protein adenosine A2a receptor restores tumor-infiltrating lymphocyte activity in the context of the tumor microenvironment. Neoplasia 2017; 19(7): 530-6.
[http://dx.doi.org/10.1016/j.neo.2017.02.004] [PMID: 28582704]
[124]
Gessi S, Merighi S, Sacchetto V, Simioni C, Borea PA. Adenosine receptors and cancer. Biochim Biophys Acta 2011; 1808(5): 1400-12.
[http://dx.doi.org/10.1016/j.bbamem.2010.09.020] [PMID: 20888788]
[125]
Mediavilla-Varela M, Luddy K, Noyes D, et al. Antagonism of adenosine A2A receptor expressed by lung adenocarcinoma tumor cells and cancer associated fibroblasts inhibits their growth. Cancer Biol Ther 2013; 14(9): 860-8.
[http://dx.doi.org/10.4161/cbt.25643] [PMID: 23917542]
[126]
Preti D, Baraldi PG, Moorman AR, Borea PA, Varani K. History and perspectives of A2A adenosine receptor antagonists as potential therapeutic agents. Med Res Rev 2015; 35(4): 790-848.
[http://dx.doi.org/10.1002/med.21344] [PMID: 25821194]
[127]
Jazayeri A, Andrews SP, Marshall FH. Structurally enabled discovery of adenosine a2a receptor antagonists. Chem Rev 2017; 117(1): 21-37.
[http://dx.doi.org/10.1021/acs.chemrev.6b00119] [PMID: 27333206]
[128]
Leone RD, Sun I-M, Oh M-H, et al. Inhibition of the adenosine A2a receptor modulates expression of T cell coinhibitory receptors and improves effector function for enhanced checkpoint blockade and ACT in murine cancer models. Cancer Immunol Immunother 2018; 67(8): 1271-84.
[http://dx.doi.org/10.1007/s00262-018-2186-0] [PMID: 29923026]
[129]
Willingham S, Ho P, Leone R, et al. Adenosine A2A receptor antagonist, CPI-444, blocks adenosine-mediated T cell suppression and exhibits anti-tumor activity alone and in combination with anti-PD-1 and anti-PD-L1. Ann Oncol 2016; 27(Suppl. 6): 1068P.
[http://dx.doi.org/10.1093/annonc/mdw378.22]
[130]
Patnaik A, Powderly J, Luke J, Miller R, Laport G. Phase 1/1b multicenter trial of the adenosine A2a receptor antagonist (A2aR) CPI-444 as single agent and in combination with atezolizumab (ATZ) in patients(Pts) with advanced cancers. Ann Oncol 2016; 27(6): 359-78.
[http://dx.doi.org/10.1093/annonc/mdw378.58]
[131]
Phase 1/1b Study to Evaluate the Safety and Tolerability of CPI- 444 Alone and in Combination With Atezolizumab in Advanced Cancers. ClinicalTrials.gov. [cited 30 Nov 2018]. Available from: https://clinicaltrials.gov/ct2/show/record/NCT02655822
[132]
Ohta A, Sitkovsky M. Caveats and cautions for the therapeutic targeting of the anti-inflammatory A2 adenosine receptors. Nat Rev Drug Discov 2006; 5: 800.
[http://dx.doi.org/10.1038/nrd1983-c1]
[133]
Hatfield SM, Sitkovsky M. A2A adenosine receptor antagonists to weaken the hypoxia-HIF-1α driven immunosuppression and improve immunotherapies of cancer. Curr Opin Pharmacol 2016; 29: 90-6.
[http://dx.doi.org/10.1016/j.coph.2016.06.009] [PMID: 27429212]
[134]
Panjehpour M, Castro M, Klotz K-N. Human breast cancer cell line MDA-MB-231 expresses endogenous A2B adenosine receptors mediating a Ca2+ signal. Br J Pharmacol 2005; 145(2): 211-8.
[http://dx.doi.org/10.1038/sj.bjp.0706180] [PMID: 15753948]
[135]
Koussémou M, Lorenz K, Klotz K-N. Human breast cancer cell line MDA-MB-231 expresses endogenous A 2B adenosine receptors mediating a Ca2+ signal. Br J Pharmacol 2018; 145: 211-8.
[136]
Mittal D, Sinha D, Barkauskas D, et al. Adenosine 2B Receptor Expression on Cancer Cells Promotes Metastasis. Cancer Res 2016; 76(15): 4372-82.
[http://dx.doi.org/10.1158/0008-5472.CAN-16-0544] [PMID: 27221704]
[137]
Mølck C, Ryall J, Failla LM, et al. The A2b adenosine receptor antagonist PSB-603 promotes oxidative phosphorylation and ROS production in colorectal cancer cells via adenosine receptor-independent mechanism. Cancer Lett 2016; 383(1): 135-43.
[http://dx.doi.org/10.1016/j.canlet.2016.09.018] [PMID: 27693637]
[138]
Galezowski M, Wegrzyn P, Bobowska A, et al. Characterization of novel dual A2A/A2B adenosine receptor antagonists for cancer immunotherapy. Cancer Res 2018; 78: 3770-0.
[139]
Gessi S, Merighi S, Borea PA, Cohen S, Fishman P. Adenosine Receptors and Current Opportunities to Treat Cancer. Adenosine Rec 2018; 34: 543-55.
[http://dx.doi.org/10.1007/978-3-319-90808-3_23]
[140]
Varani K, Maniero S, Vincenzi F, et al. A3 receptors are overexpressed in pleura from patients with mesothelioma and reduce cell growth via Akt/nuclear factor-κB pathway. Am J Respir Crit Care Med 2011; 183(4): 522-30.
[http://dx.doi.org/10.1164/rccm.201006-0980OC] [PMID: 20870754]
[141]
Varani K, Vincenzi F, Targa M, et al. The stimulation of A(3) adenosine receptors reduces bone-residing breast cancer in a rat preclinical model. Eur J Cancer 2013; 49(2): 482-91.
[http://dx.doi.org/10.1016/j.ejca.2012.06.005] [PMID: 22770890]
[142]
Gessi S, Fogli E, Sacchetto V, et al. Adenosine modulates HIF-1α, VEGF, IL-8, and foam cell formation in a human model of hypoxic foam cells. Arterioscler Thromb Vasc Biol 2010; 30(1): 90-7.
[http://dx.doi.org/10.1161/ATVBAHA.109.194902] [PMID: 19834107]
[143]
Fishman P, Bar-Yehuda S, Ohana G, et al. Adenosine acts as an inhibitor of lymphoma cell growth: a major role for the A3 adenosine receptor. Eur J Cancer 2000; 36(11): 1452-8.
[http://dx.doi.org/10.1016/S0959-8049(00)00130-1] [PMID: 10899660]
[144]
Vincenzi F, Targa M, Corciulo C, et al. The anti-tumor effect of a3 adenosine receptors is potentiated by pulsed electromagnetic fields in cultured neural cancer cells. PLoS One 2012; 7e39317
[http://dx.doi.org/10.1371/journal.pone.0039317]
[145]
Ohana G, Bar-Yehuda S, Barer F, Fishman P. Differential effect of adenosine on tumor and normal cell growth: focus on the A3 adenosine receptor. J Cell Physiol 2001; 186(1): 19-23.
[http://dx.doi.org/10.1002/1097-4652(200101)186:1<19:AID-JCP1011>3.0.CO;2-3] [PMID: 11147810]
[146]
Hofer M, Pospísil M, Vacek A, et al. Effects of adenosine A(3) receptor agonist on bone marrow granulocytic system in 5-fluorouracil-treated mice. Eur J Pharmacol 2006; 538(1-3): 163-7.
[http://dx.doi.org/10.1016/j.ejphar.2006.03.042] [PMID: 16643889]
[147]
Merimsky O, Bar-Yehuda S, Madi L, Fishman P. Modulation of the A3 adenosine receptor by low agonist concentration induces antitumor and myelostimulatory effects. Drug Dev Res 2003; 58: 386-9.
[http://dx.doi.org/10.1002/ddr.10182]
[148]
Bar-Yehuda S, Madi L, Barak D, et al. Agonists to the A3 adenosine receptor induce G-CSF production via NF-kappaB activation: a new class of myeloprotective agents. Exp Hematol 2002; 30(12): 1390-8.
[http://dx.doi.org/10.1016/S0301-472X(02)00962-1] [PMID: 12482500]
[149]
Ohana G, Bar-Yehuda S, Arich A, et al. Inhibition of primary colon carcinoma growth and liver metastasis by the A3 adenosine receptor agonist CF101. Br J Cancer 2003; 89(8): 1552-8.
[http://dx.doi.org/10.1038/sj.bjc.6601315] [PMID: 14562031]
[150]
Harish A, Hohana G, Fishman P, Arnon O, Bar-Yehuda S. A3 adenosine receptor agonist potentiates natural killer cell activity. Int J Oncol 2003; 23(4): 1245-9.
[http://dx.doi.org/10.3892/ijo.23.4.1245] [PMID: 12964011]
[151]
Montinaro A, Forte G, Sorrentino R, et al. Adoptive immunotherapy with Cl-IB-MECA-treated CD8+ T cells reduces melanoma growth in mice. PLoS One 2012; 7(9)e45401
[http://dx.doi.org/10.1371/journal.pone.0045401] [PMID: 23028986]
[152]
Jacobson KA, Merighi S, Varani K, et al. A3 adenosine receptors as modulators of inflammation: from medicinal chemistry to therapy. Med Res Rev 2018; 38(4): 1031-72.
[http://dx.doi.org/10.1002/med.21456] [PMID: 28682469]
[153]
van Troostenburg AR, Clark EV, Carey WDH, et al. Tolerability, pharmacokinetics and concentration-dependent hemodynamic effects of oral CF101, an A3 adenosine receptor agonist, in healthy young men. Int J Clin Pharmacol Ther 2004; 42(10): 534-42.
[http://dx.doi.org/10.5414/CPP42534] [PMID: 15516022]
[154]
Bar-Yehuda S, Madi L, Silberman D, Gery S, Shkapenuk M, Fishman P. CF101, an agonist to the A3 adenosine receptor, enhances the chemotherapeutic effect of 5-fluorouracil in a colon carcinoma murine model. Neoplasia 2005; 7(1): 85-90.
[http://dx.doi.org/10.1593/neo.04364] [PMID: 15720820]
[155]
Bar-Yehuda S, Stemmer SM, Madi L, et al. The A3 adenosine receptor agonist CF102 induces apoptosis of hepatocellular carcinoma via de-regulation of the Wnt and NF-kappaB signal transduction pathways. Int J Oncol 2008; 33(2): 287-95.
[PMID: 18636149]
[156]
Stemmer SM, Benjaminov O, Medalia G, et al. CF102 for the treatment of hepatocellular carcinoma: a phase I/II, open-label, dose-escalation study. Oncologist 2013; 18(1): 25-6.
[http://dx.doi.org/10.1634/theoncologist.2012-0211] [PMID: 23299770]
[157]
Phase 2, Randomized, Double-Blind, Placebo-Controlled of the Efficacy and Safety of CF102 in Hepatocellular Carcinoma (HCC). ClinicalTrials.gov. [cited 30 Nov 2018]. Available from: https://clinicaltrials.gov/ct2/show/NCT02128958
[158]
Zhao Z, Yaar R, Ladd D, Cataldo LM, Ravid K. Overexpression of A3 adenosine receptors in smooth, cardiac, and skeletal muscle is lethal to embryos. Microvasc Res 2002; 63(1): 61-9.
[http://dx.doi.org/10.1006/mvre.2001.2366] [PMID: 11749073]
[159]
Kim SG, Ravi G, Hoffmann C, et al. p53-Independent induction of Fas and apoptosis in leukemic cells by an adenosine derivative, Cl-IB-MECA. Biochem Pharmacol 2002; 63(5): 871-80.
[http://dx.doi.org/10.1016/S0006-2952(02)00839-0] [PMID: 11911839]
[160]
Gao Z, Li BS, Day YJ, Linden J. A3 adenosine receptor activation triggers phosphorylation of protein kinase B and protects rat basophilic leukemia 2H3 mast cells from apoptosis. Mol Pharmacol 2001; 59(1): 76-82.
[http://dx.doi.org/10.1124/mol.59.1.76] [PMID: 11125027]
[161]
Lu J, Pierron A, Ravid K. An adenosine analogue, IB-MECA, down-regulates estrogen receptor α and suppresses human breast cancer cell proliferation. Cancer Res 2003; 63(19): 6413-23.
[PMID: 14559831]
[162]
Kim SJ, Min HY, Chung HJ, et al. Inhibition of cell proliferation through cell cycle arrest and apoptosis by thio-Cl-IB-MECA, a novel A3 adenosine receptor agonist, in human lung cancer cells. Cancer Lett 2008; 264(2): 309-15.
[http://dx.doi.org/10.1016/j.canlet.2008.01.037] [PMID: 18321638]
[163]
Deb PK. Recent updates in the computer aided drug design strategies for the discovery of agonists and antagonists of adenosine receptors. Curr Pharm Des 2019; 25(7): 747-9.
[http://dx.doi.org/10.2174/1381612825999190515120510] [PMID: 31232230]
[164]
Samanta PN, Kar S, Leszczynski J. Recent advances of in-silico modeling of potent antagonists for the adenosine receptors. Curr Pharm Des 2019; 25(7): 750-73.
[http://dx.doi.org/10.2174/1381612825666190304123545] [PMID: 30836910]
[165]
Al-Shar’i NA, Al-Balas QA. Molecular dynamics simulations of adenosine receptors: advances, applications and trends. Curr Pharm Des 2019; 25(7): 783-816.
[http://dx.doi.org/10.2174/1381612825666190304123414] [PMID: 30834825]
[166]
Mahmod Al-Qattan MN, Mordi MN. Molecular basis of modulating adenosine receptors activities. Curr Pharm Des 2019; 25(7): 817-31.
[http://dx.doi.org/10.2174/1381612825666190304122624] [PMID: 30834826]
[167]
Agrawal N, Chandrasekaran B, Al-Aboudi A. Recent advances in the in-silico structure-based and ligand-based approaches for the design and discovery of agonists and antagonists of A2A adenosine receptor. Curr Pharm Des 2019; 25(7): 774-82.
[http://dx.doi.org/10.2174/1381612825666190306162006] [PMID: 30848185]
[168]
Deb PK, Chandrasekaran B, Mailavaram R, Tekade RK, Jaber AMY. Molecular modeling approaches for the discovery of adenosine A2B receptor antagonists: current status and future perspectives. Drug Discov Today 2019.S1359-6446(19)30045-5.
[http://dx.doi.org/10.1016/j.drudis.2019.05.011] [PMID: 31103731]


Rights & PermissionsPrintExport Cite as

Article Details

VOLUME: 25
ISSUE: 26
Year: 2019
Page: [2828 - 2841]
Pages: 14
DOI: 10.2174/1381612825666190716102037
Price: $65

Article Metrics

PDF: 41
HTML: 3