Nucleoside transporters: Biological insights and therapeutic applications

Future Medicinal Chemistry

Volumn 4, Issue 11, 2012, Pages 1461-1478

  Choi, Jung Suk ^a   Berdis, Anthony J ^a  

^a CASE WESTERN RESERVE UNIVERSITY SCHOOL OF MEDICINE   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

CAPECITABINE; CLADRIBINE; CLOFARABINE; CONCENTRATIVE NUCLEOSIDE TRANSPORTER; CONCENTRATIVE NUCLEOSIDE TRANSPORTER 1; CONCENTRATIVE NUCLEOSIDE TRANSPORTER 2; CONCENTRATIVE NUCLEOSIDE TRANSPORTER 3; CYTARABINE; DILAZEP; DIPYRIDAMOLE; DRAFLAZINE; EQUILIBRATIVE NUCLEOSIDE TRANSPORTER; EQUILIBRATIVE NUCLEOSIDE TRANSPORTER 1; EQUILIBRATIVE NUCLEOSIDE TRANSPORTER 2; EQUILIBRATIVE NUCLEOSIDE TRANSPORTER 3; EQUILIBRATIVE NUCLEOSIDE TRANSPORTER 4; FLOXURIDINE; FLUDARABINE; FLUOROURACIL; GEMCITABINE; LAMIVUDINE; NELARABINE; NITROBENZYLTHIOINOSINE; NUCLEOSIDE TRANSPORTER; PENTOSTATIN; SOLUFLAZINE; STAVUDINE; UNCLASSIFIED DRUG; UNINDEXED DRUG; ZALCITABINE; ZIDOVUDINE;

BIOLOGICAL FUNCTIONS; BLOOD BRAIN BARRIER; BRAIN INFARCTION; BREAST CANCER; CARDIOVASCULAR FUNCTION; CELL FUNCTION; COLON CANCER; GENE EXPRESSION; HEART INFARCTION; HEMATOLOGIC MALIGNANCY; HUMAN; HUMAN IMMUNODEFICIENCY VIRUS INFECTION; HYPOXIA; INFLAMMATION; NONHUMAN; PANCREAS CANCER; PATHOPHYSIOLOGY; PRIORITY JOURNAL; PROTEIN EXPRESSION; PROTEIN FUNCTION; REVIEW; SODIUM TRANSPORT; STRUCTURE ACTIVITY RELATION; THROMBUS; VIRUS INFECTION;

ANTINEOPLASTIC AGENTS; BLOOD-BRAIN BARRIER; CARDIOVASCULAR DISEASES; HUMANS; NEOPLASMS; NUCLEOBASE, NUCLEOSIDE, NUCLEOTIDE, AND NUCLEIC ACID TRANSPORT PROTEINS; NUCLEOSIDES; STRUCTURE-ACTIVITY RELATIONSHIP;

EID: 84864651626     PISSN: 17568919     EISSN: 17568927     Source Type: Journal    
DOI: 10.4155/fmc.12.79     Document Type: Review

References (97)

1. Baldwin SA, Mackey JR, Cass CE, Young JD. Nucleoside transporters: molecular biology and implications for therapeutic development. Mol. Med. Today 5, 216-224 (1999). (Pubitemid 29282300)
2. Molina-Arcas M, Trigueros-Motos L, Casado FJ, Pastor-Anglada M. Physiological and pharmacological roles of nucleoside transporter proteins. Nucleosides Nucleotides Nucleic Acids 27, 769-778 (2008). (Pubitemid 351948553)
3. Löffler M, Morote-Garcia JC, Eltzschig SA, Coe IR, Eltzsching HK. Physiological roles of vascular nucleoside transporters. Arterioscler. Thromb. Vasc. Biol. 27, 1004-1013 (2007). (Pubitemid 46641985)
4. Young JD, Yao SY, Sun L, Class CE, Baldwin SA. Human equilitractive nucleoside transporter (ENT) family of nucleoside and nucleobase transporter proteins. Xenobiotica 38, 995-1021 (2008).
5. Gray JH, Owen RP, Giacomini KM. The concentrative nucleoside transporter family, SLC28. Pflugers Arch. Eur. J. Physiol. 447, 728-734 (2004). (Pubitemid 38241458)
6. Wang J, Schaner ME, Thomassen S, Su SF, Piquette-Miller M, Giacomini KM. Functional and molecular characteristics of Na+-dependent nucleoside transporters. Pharm. Res. 14, 1524-1532 (1997). (Pubitemid 28009202)
7. King AE, Ackley MA, Cass CE, Young JD, Baldwin SA. Nucleoside transporters: from scavengers to novel therapeutic targets. Trends Pharmacol. Sci. 27, 416-425 (2006). (Pubitemid 44051567)
8. Volonté C, D'Ambrosi N. Membrane compartments and purinergic signalling: the purinome, a complex interplay among ligands, degrading enzymes, receptors and transporters. FEBS J. 276, 318-329 (2009).
9. Spragg RG, Hinshaw DB, Hyslop PA, Schraufstätter IU, Cochrane CG. Alterations in adenosine triphosphate and energy charge in cultured endothelial and P388D1 cells after oxidant injury. J. Clin. Invest. 76, 1471-1476 (1985). (Pubitemid 16193696)
10. Thorn JA, Jarvis SM. Adenosine transporters. Gen. Pharmacol. 27, 613-620 (1996). (Pubitemid 26233329)
11. Griffith DA, Jarvis SM. Nucleoside and nucleobase transport systems of mammalian cells. Biochim. Biophys. Acta 1286, 153-181 (1996). (Pubitemid 26426520)
12. Podgorska M, Kocbuch K, Pawelczyk T. Recent advances in studies on biochemical and structural properties of equilibrative and concentrative nucleoside transporters. Acta Biochim. Pol. 52, 749-758 (2005). (Pubitemid 43155002)
13. Yang D, Zhang Y, Nguyen HG et al. The A2B adenosine receptor protects against inflammation and excessive vascular adhesion. J. Clin. Invest. 116, 1913-1923 (2006). (Pubitemid 44033315)
14. Hyde RJ, Cass CE, Young JD, Baldwin SA. The ENT family of eukaryote nucleoside and nucleobase transporters: recent advances in the investigation of structure-function relationships and the identification of novel isoforms. Mol. Membr. Biol. 18, 53-63 (2001). (Pubitemid 32521597)
15. Crawford CR, Patel DH, Naeve C, Belt JA. Cloning of the human equilibrative, nitrobenzylmercaptopurine riboside (NBMPR)-insensitive nucleoside transporter ei by functional expression in a transportdeficient cell line. J. Biol. Chem. 273, 5288-5293 (1998). (Pubitemid 28108694)
16. Kong W, Engel K, Wang J. Mammalian nucleoside transporters. Curr. Drug Metab. 5, 63-84 (2004). (Pubitemid 38279408)
17. Griffiths M, Beaumont N, Yao SY et al. Cloning of a human nucleoside transporter implicated in the cellular uptake of adenosine and chemotherapeutic drugs. Nat. Med. 3, 89-93 (1997). (Pubitemid 27019148)
18. Clarke ML, Damaraju VL, Zhang J et al. The role of human nucleoside transporters in cellular uptake of 4́-thio-beta-darabinofuranosylcytosine and beta-darabinosylcytosine. Mol. Pharmacol. 70, 303-310 (2006).
19. Baldwin SA, Beal PR, Yao SY, King AE, Cass CE, Young JD. The equilibrative nucleoside transporter family, SLC29. Pflugers Arch. Eur. J. Physiol. 447, 735-743 (2004). (Pubitemid 38241459)
20. Osato DH, Huang CC, Kawamoto M et al. Functional characterization in yeast of genetic variants in the human equilibrative nucleoside transporter, ENT1. Pharmacogenetics 13, 297-301 (2003). (Pubitemid 36583998)
21. Kiss A, Farah K, Kim J, Garriock RJ, Drysdale TA, Hammond Jr. Molecular cloning and functional characterization of inhibitor-sensitive (mENT1) and inhibitorresistant (mENT2) equilibrative nucleoside transporters from mouse brain. Biochem. J. 352, 363-372 (2000). (Pubitemid 32011430)
22. Smith KM, Slugoski MD, Loewen SK et al. The broadly selective human Na+/nucleoside cotransporter (hCNT3) exhibits novel cation-coupled nucleoside transport characteristics. J. Biol. Chem. 280, 25436-25449 (2005). (Pubitemid 40962248)
23. Wang J, Giacomini KM. Molecular determinants of substrate selectivity in Na+-dependent nucleoside transporters. J. Biol. Chem. 272, 28845-28848 (1997). (Pubitemid 27498163)
24. Barnes K, Dobrzynski H, Foppolo S et al. Distribution and functional characterization of equilibrative nucleoside transporter-4, a novel cardiac adenosine transporter activated at acidic pH. Circ. Res. 99, 510-519 (2006). (Pubitemid 44337823)
25. Huang Q-Q, Yao SY, Ritzel MW, Paterson AR, Cass CE, Young JD. Cloning and functional expression of a complementary DNA encoding a mammalian nucleoside transport protein. J. Biol. Chem. 269, 17757-17760 (1994). (Pubitemid 24206156)
26. Ritzel MW, Yao SY, Huang MY, Elliott JF, Cass CE, Young JD. Molecular cloning and functional expression of cDNAs encoding a human Na+-nucleoside cotransporter (hCNT1). Am. J. Physiol. 272, C707-C714 (1997). (Pubitemid 27142601)
27. Che M, Ortiz DF, Arias IM. Primary structure and functional expression of a cDNA encoding the bile canicular, purinespecific Na+-nucleoside cotransporter. J. Biol. Chem. 270, 13596-13599 (1995).
28. Errasti-Murugarren E, Pastor-Anglada M, Casado FJ. Role of CNT3 in the transepithelial flux of nucleosides and nucleoside-derived drugs. J. Physiol. 582, 1249-1260 (2007). (Pubitemid 47104352)
29. Johnson ZL, Cheong CG, Lee SY. Crystal structure of a concentrative nucleoside transporter from Vibrio cholerae at 2.4 Å. Nature 483, 489-493 (2012). nn Describes the first crystal structure of a concentrative nucleoside transporter.
30. SenGupta DJ, Lum PY, Lai YA, Ballen AH, Schneider G, Unadkat JD. A single glycine mutation in the equilibrative nucleoside transporter gene, hENT1, alters nucleoside transport activity and sensitivity to nitrobenzylthioinosine. Biochemistry 41, 1512-1519 (2002). (Pubitemid 34112740)
31. Endres CJ, Sengupta DJ, Unadkat JD. Mutation of leucine-92 selectively reduces the apparent affinity of inosine, guanosine, NBMPR S6-(4-nitrobenzyl)- mercaptopurine riboside and dilazep for the human equilibrative nucleoside transporter, hENT1. Biochem. J. 380, 131-137 (2004). (Pubitemid 38725737)
32. Endres CJ, Unadkat JD, Residues Met89 and Ser160 in the human equilibrative nucleoside transporter 1 affect its affinity for adenosine, guanosine, S6-(4-nitrobenzyl)- mercaptopurine riboside and dipyridamole. Mol. Pharmacol. 67, 837-844 (2005). (Pubitemid 40365331)
33. Visser F, Sun L, Damaraju V et al. Residues 334 and 338 in transmembrane segment 8 of human equilibrative nucleoside transporter 1 are important determinants of inhibitor sensitivity, protein folding, and catalytic turnover. J. Biol. Chem. 282, 14148-14157 (2007). (Pubitemid 47100457)
34. Lai Y, Lee EW, Ton CC, Vijay S, Zhang H, Unadkat JD. Conserved residues F316 and G476 in the concentrative nucleoside transporter 1 (hCNT1) affect guanosine sensitivity and membrane expression, respectively. Am. J. Physiol. Cell Physiol. 288, C39-C45 (2005). (Pubitemid 39658425)
35. Gray JH, Mangravite LM, Owen RP et al. Functional and genetic diversity in the concentrative nucleoside transporter, CNT1, in human populations. Mol. Pharmacol. 65, 512-519 (2004). (Pubitemid 38264018)
36. Badagnani I, Chan W, Castro RA et al. Functional analysis of genetic variants in the human concentrative nucleoside transporter 3 (CNT3; SLC28A3). Pharmacogenomics J. 5, 157-165 (2005). (Pubitemid 40852217)
37. Park JS, Hughes SJ, Cunningham FK, Hammond Jr. Identification of cysteines involved in the effects of methanethiosulfonate reagents on human equilibrative nucleoside transporter 1. Mol. Pharmacol. 80, 735-746 (2011).
38. López-Navarro AT, Ortega MA, Peragón J, Bueno JD, Gil A, Sánchez-Pozo A. Deprivation of dietary nucleotides decreases protein synthesis in the liver and small intestine in rats. Gastroenterology 110, 1760-1769 (1996). (Pubitemid 26169213)
39. Chaudary N, Naydenova Z, Shuralyova I, Coe IR. Hypoxia regulates the adenosine transporter, mENT1, in the murine cardiomyocyte cell line, HL-1. Cardiovasc. Res. 61, 780-788 (2004). (Pubitemid 38249477)
40. Eltzschig HK, Abdulla P, Hoffman E et al. HIF-1-dependent repression of equilibrative nucleoside transporter (ENT) in hypoxia. J. Exp. Med. 202, 1493-1505 (2005). (Pubitemid 41746596)
41. Tattersall MH, Slowiaczek P, De Fazio A. Regional variation in human extracellular purine levels. J. Lab. Clin. Med. 102, 411-420 (1983). (Pubitemid 13009615)
42. Norman B, Sollevi A, Kaijser L, Jansson E. ATP breakdown products in human skeletal muscle during prolonged exercise to exhaustion. Clin. Physiol. 7, 503-510 (1987). (Pubitemid 18089626)
43. Olah ME, Stiles GL. The role of receptor structure in determining adenosine receptor activity. Pharmacol. Ther. 85, 55-75 (2000). (Pubitemid 30069477)
44. Pawelczyk T, Podgorska M, Sakowicz M. The effect of insulin on expression level of nucleoside transporters in diabetic rats. Mol. Pharmacol. 63, 81-88 (2003). (Pubitemid 36043811)
45. Sakowicz M, Szutowicz A, Pawelczyk T. Insulin and glucose induced changes in expression level of nucleoside transporters and adenosine transport in rat T lymphocytes. Biochem. Pharmacol. 68, 1309-1320 (2004). (Pubitemid 39179389)
46. Sakowicz M, Szutowicz A, Pawelczyk T. Differential effect of insulin and elevated glucose level on adenosine transport in rat B lymphocytes. Int. Immunol. 17, 145-154 (2005). (Pubitemid 40246579)
47. Fernández-Veledo S, Valdés R, Wallenius V, Casado FJ, Pastor-Anglada M. Up-regulation of the high-affinity pyrimidine-preferring nucleoside transporter concentrative nucleoside transporter 1 by tumor necrosis factor-alpha and interleukin-6 in liver parenchymal cells. J. Hepatol. 41, 538-544 (2004). (Pubitemid 39297787)
48. Mackey JR, Jennings LL, Clarke ML et al. Immunohistochemical variation of human equilibrative nucleoside transporter 1 protein in primary breast cancers. Clin. Cancer Res. 8, 110-116 (2002). (Pubitemid 34101465)
49. Mackey JR, Baldwin SA, Young JD, Cass CE. Nucleoside transport and its significance for anticancer drug resistance. Drug Resist. Updat. 5, 310-324 (1998).
50. Baxter GF. Role of adenosine in delayed preconditioning of myocardium. Cardiovasc. Res. 55, 483-494 (2002). (Pubitemid 34874943)
51. Tamura DY, Moore EE, Partrick DA, Johnson JC, Offner PJ, Silliman CC. Acute hypoxemia in humans enhances the neutrophil inflammatory response. Shock 17, 269-273 (2002).
52. Naydenova Z, Rose JB, Coe IR. Inosine and equilibrative nucleoside transporter 2 contribute to hypoxic preconditioning in the murine cardiomyocyte HL-1 cell line. Am. J. Physiol. Heart Circ. Physiol. 294, H2687-H2692 (2008).
53. Mubagwa K, Flameng W. Adenosine, adenosine receptors and myocardial protection: an updated overview. Cardiovasc. Res. 52, 25-39 (2001). (Pubitemid 32835236)
54. Eltzschig HK, Faigle M, Knapp S et al. Endothelial catabolism of extracellular adenosine during hypoxia: the role of surface adenosine deaminase and CD26. Blood 108, 1602-1610 (2006). (Pubitemid 44316128)
55. Eltzschig HK, Ibla JC, Furuta GT et al. Coordinated adenine nucleotide phosphohydrolysis and nucleoside signaling in posthypoxic endothelium: role of ectonucleotidases and adenosine A2B receptors. J. Exp. Med. 198, 783-796 (2003). (Pubitemid 37087777)
56. Eltzschig HK, Thompson LF, Karhausen J et al. Endogenous adenosine produced during hypoxia attenuates neutrophil accumulation: coordination by extracellular nucleotide metabolism. Blood 104, 3986-3992 (2004). (Pubitemid 39620148)
57. Thompson LF, Eltzschig HK, Ibla JC et al. Crucial role for ecto-5́-nucleotidase (CD73) in vascular leakage during hypoxia. J. Exp. Med. 200, 1395-1405 (2004). (Pubitemid 39657287)
58. Blackburn MR, Datta SK, Kellems RE. Adenosine deaminase-deficient mice generated using a two-stage genetic engineering strategy exhibit a combined immunodeficiency. J. Biol. Chem. 273, 5093-5100 (1998). (Pubitemid 28108669)
59. Blackburn MR, Kellems RE. Adenosine deaminase deficiency: metabolic basis of immune deficiency and pulmonary inflammation. Adv. Immunol. 86, 1-41 (2005). (Pubitemid 40215689)
60. Ohta A, Sitkovsky M. Role of G-proteincoupled adenosine receptors in downregulation of inflammation and protection from tissue damage. Nature 414, 916-920 (2001). (Pubitemid 34024743)
61. Eckle T, Krahn T, Grenz A et al. Cardioprotection by ecto-5́- nucleotidase (CD73) and A2B adenosine receptors. Circulation 115, 1581-1590 (2007). (Pubitemid 46648643)
62. Haas HL, Selbach O. Functions of neuronal adenosine receptors. Naunyn Schmiedebergs Arch. Pharmacol. 362, 375-381 (2000).
63. Pardridge WM, Yoshikawa T, Kang Y-S, Miller LP. Blood-brain barrier transport and brain metabolism of adenosine and adenosine analogs. J. Pharmacol. Exp. Ther. 268, 14-18 (1994). (Pubitemid 24039062)
64. Li JY, Boado RJ, Pardridge WM. Cloned blood-brain barrier adenosine transporter is identical to the rat concentrative Na+ nucleoside cotransporter CNT2. J. Cereb. Blood Flow Metab. 21, 929-936 (2001). (Pubitemid 32729828)
65. Anderson CM, Baldwin SA, Young JD, Cass CE, Parkinson FE. Distribution of mRNA encoding a nitrobenzylthioinosine-insensitive nucleoside transporter (ENT2) in rat brain. Brain Res. Mol. Brain Res. 70, 293-297 (1999). (Pubitemid 29317644)
66. Molina-Arcas M, Marcé S, Villamor N et al. Equilibrative nucleoside transporter-2 (hENT2) protein expression correlates with ex vivo sensitivity to fludarabine in chronic lymphocytic leukemia (CLL) cells. Leukemia 19, 64-68 (2005). (Pubitemid 40090078)
67. King KM, Damaraju VL, Vickers MF et al. A comparison of the transportability, and its role in cytotoxicity, of clofarabine, cladribine, and fludarabine by recombinant human nucleoside transporters produced in three model expression systems. Mol Pharmacol. 69, 346-353 (2006). (Pubitemid 43048921)
68. Elwi AN, Damaraju VL, Kuzma ML et al. Human concentrative nucleoside transporter 3 is a determinant of fludarabine transportability and cytotoxicity in human renal proximal tubule cell cultures. Cancer Chemother. Pharmacol. 63, 289-301 (2009).
69. García-Manteiga J, Molina-Arcas M, Casado FJ, Mazo A, Pastor-Anglada M. Nucleoside transporter profiles in human pancreatic cancer cells: role of hCNT1 in 2́,2́-difluorodeoxycytidine- induced cytotoxicity. Clin. Cancer Res. 9, 5000-5008 (2003). (Pubitemid 37323307)
70. Marcé S, Molina-Arcas M, Villamor N et al. Expression of human equilibrative nucleoside transporter 1 (hENT1) and its correlation with gemcitabine uptake and cytotoxicity in mantle cell lymphoma. Haematologica 91, 895-902 (2006). (Pubitemid 44023142)
71. Plunkett W, Huang P, Ghandi V. Metabolism and action of fludarabine phosphate. Semin. Oncol. 17, 3-17 (1990). (Pubitemid 20356424)
72. Ba Barrueco JR, Jacobsen DM, Chang CH, Brockman RW, Sirotnak FM. Proposed mechanism of therapeutic selectivity of 9-beta-d-arabinofuranosyl-2- fluoroadenine against murine leukemia based upon lower capacities for transport and phosphorylation in proliferative intestinal epithelium compared to tumor cells. Cancer Res. 47, 700-706 (1987). (Pubitemid 17027959)
73. Mackey JR, Mani RS, Selner M et al. Functional nucleoside transporters are required for gemcitabine influx and manifestations of toxicity in cancer cell lines. Cancer Res. 58, 4349-4357 (1998). (Pubitemid 28450036)
74. Ritzel MW, Ng AM, Yao SY et al. Molecular identification and characterization of novel human and mouse concentrative Na+- nucleoside cotransporter proteins (hCNT3 and mCNT3) broadly selective for purine and pyrimidine nucleosides (system cib). J. Biol. Chem. 276, 2914-2927 (2001).
75. Garcia-Manteiga J, Molina-Arcas M, Casado FJ, Mazo A, Pastor-Anglada M. Nucleoside transporter profiles in human pancreatic cancer cells: role of hCNT1 in 2́,2́-difluorodeoxycytidine-induced cytotoxicity. Clin. Cancer Res. 9, 5000-5008 (2003). (Pubitemid 37323307)
76. Bock AJ, Dong HP, Tropé CG, Staff AC, Risberg B, Davidson B. Nucleoside transporters are widely expressed in ovarian carcinoma effusions. Cancer Chemother. Pharmacol. 69, 467-475 (2012).
77. Hubeek I, Stam RW, Peters GJ et al. The human equilibrative nucleoside transporter 1 mediates in vitro cytarabine sensitivity in childhood acute myeloid leukaemia. Br. J. Cancer 93, 1388-1394 (2005). (Pubitemid 41752866)
78. Molina-Arcas M, Bellosillo B, Casado FJ et al. Fludarabine uptake mechanisms in B-cell chronic lymphocytic leukemia. Blood 101, 2328-2334 (2003). (Pubitemid 36304669)
79. Spratlin J, Sangha R, Glubrecht D et al. The absence of human equilibrative nucleoside transporter 1 is associated with reduced survival in patients with gemcitabine-treated pancreas adenocarcinoma. Clin. Cancer Res. 10, 6956-6961 (2004). (Pubitemid 39383046)
80. Giovannetti E, Del Tacca M, Mey V et al. Transcription analysis of human equilibrative nucleoside transporter-1 predicts survival in pancreas cancer patients treated with gemcitabine. Cancer Res. 66, 3928-3935 (2006).
81. Takagaki K, Katsuma S, Kaminishi Y et al. Gene-expression profiling reveals downregulation of equilibrative nucleoside transporter 1 (ENT1) in Ara-C-resistant CCRF-CEM-derived cells. J. Biochem. 136, 733-740 (2004). (Pubitemid 40364197)
82. Gusella M, Pasini F, Bolzonella C et al. Equilibrative nucleoside transporter 1 genotype, cytidine deaminase activity and age predict gemcitabine plasma clearance in patients with solid tumours. Br. J. Clin Pharmacol. 71, 437-444 (2011).
83. Nakano Y, Tanno S, Koizumi K et al. Gemcitabine chemoresistance and molecular markers associated with gemcitabine transport and metabolism in human pancreatic cancer cells. Br. J. Cancer 96, 457-463 (2007). (Pubitemid 46215217)
84. Visser F, Sun L, Damaraju V et al. Residues 334 and 338 in transmembrane segment 8 of human equilibrative nucleoside transporter 1 are important determinants of inhibitor sensitivity, protein folding, and catalytic turnover. J. Biol. Chem. 282, 14148-14157 (2007). (Pubitemid 47100457)
85. Markovic I, Segal M, Djuricic B, Redzic Z. Kinetics of nucleoside uptake by the basolateral side of the sheep choroid plexus epithelium perfused in situ. Exp Physiol. 93, 325-333 (2008). (Pubitemid 351257695)
86. Tromp RA, Spanjersberg RF, von Frijtag Drabbe Künzel JK, IJzerman AP. Inhibition of nucleoside transport proteins by C8-alkylamine-substituted purines. J. Med. Chem. 48, 321-329 (2005). (Pubitemid 40105271)
87. Gupte A, Buolamwini JK. Novel C2-purine position analogs of nitrobenzylmercaptopurine riboside as human equilibrative nucleoside transporter 1 inhibitors. Bioorg. Med. Chem. 15, 7726-7737 (2007). (Pubitemid 47575916)
88. Addo JK, Buolamwini JK. Design, synthesis, and evaluation of 5'-S-aminoethyl-N(6)- azidobenzyl-5́-thioadenosine biotin conjugate: a bifunctional photoaffinity probe for the es nucleoside transporter. Bioconjug. Chem. 15, 536-540 (2004). (Pubitemid 38657859)
89. Schaper W. Dipyridamole, an underestimated vascular protective drug. Cardiovasc. Drugs Ther. 19, 357-363 (2005). (Pubitemid 43029821)
90. Van Mouwerik TJ, Pangallo CA, Willson JK, Fischer PH. Augmentation of methotrexate cytotoxicity in human colon cancer cells achieved through inhibition of thymidine salvage by dipyridamole. Biochem. Pharmacol. 36, 809-814 (1987). (Pubitemid 17038023)
91. Marshman E, Newell DR, Calvert AH et al. Dipyridamole potentiates antipurine antifolate activity in the presence of hypoxanthine in tumor cells but not in normal tissues in vitro. Clin. Cancer Res. 4, 2895-2902 (1998). (Pubitemid 28523521)
92. Saravanan K, Barlow HC, Barton M et al. Nucleoside transport inhibitors: Structure-activity relationships for pyrimido5,4-dpyrimidine derivatives that potentiate pemetrexed cytotoxicity in the presence of α1-acid glycoprotein. J. Med. Chem. 54, 1847-1857 (2011).
93. Lin W, Buolamwini JK. Design, synthesis, and evaluation of 2-diethanolamino-4,8- diheptamethyleneimino-2-(N-aminoethyl-Nethanolamino)- 6-(N,N-diethanolamino) pyrimido5,4-dpyrimidine-fluorescein conjugate (8MDP-fluor), as a novel equilibrative nucleoside transporter probe. Bioconjug. Chem. 22, 1221-1227 (2011).
94. Sakumura T, Fujii Z, Umemoto S et al. Dilazep, a nucleoside transporter inhibitor, modulates cell cycle progression and DNA synthesis in rat mesangial cells in vitro. Cell Prolif. 33, 19-28 (2000). (Pubitemid 30162620)
95. Zhang J, Sun X, Smith KM et al. Studies of nucleoside transporters using novel autofluorescent nucleoside probes. Biochemistry 45, 1087-1098 (2006). (Pubitemid 43167176)
96. Paproski RJ, Young JD, Cass CE. Predicting gemcitabine transport and toxicity in human pancreatic cancer cell lines with the positron emission tomography tracer 3́-deoxy-3́- fluorothymidine. Biochem. Pharmacol. 79, 587-595 (2010).
97. Eng KT, Berdis AJ. A novel non-natural nucleoside that influences P-glycoprotein activity and mediates drug resistance. Biochemistry 49, 1640-1648 (2010).