AICA-riboside (acadesine), an activator of AMP-activated protein kinase with potential for application in hematologic malignancies

Expert Opinion on Investigational Drugs

Volumn 19, Issue 4, 2010, Pages 571-578

  Van Den Neste, Eric ^a,b   Van Den Berghe, Georges ^a   Bontemps, Françoise ^a  

^a DE DUVE INSTITUTE   (Belgium)

^b CLINIQUES UNIVERSITAIRES SAINT LUC   (Belgium)

Author keywords

Acadesine; AICA riboside; AICAR; Apoptosis; Chronic lymphocytic leukemia; ZMP

Indexed keywords

5 AMINO 4 IMIDAZOLECARBOXAMIDE RIBOSIDE; ACETYL COENZYME A CARBOXYLASE; ADENOSINE KINASE; ADENYLATE KINASE; GLUCOSE TRANSPORTER 4; GUANOSINE TRIPHOSPHATE; HYDROXYMETHYLGLUTARYL COENZYME A REDUCTASE KINASE; INOSINE PHOSPHATE; PROTEIN P53; 5 AMINO 4 IMIDAZOLECARBOXAMIDE; RIBONUCLEOSIDE;

APOPTOSIS; CANCER GROWTH; CELL PROLIFERATION; CHRONIC LYMPHATIC LEUKEMIA; CLINICAL TRIAL; DIABETES MELLITUS; DRUG DOSE ESCALATION; DRUG METABOLISM; DRUG SAFETY; DRUG STRUCTURE; DRUG TOLERABILITY; ENZYME ACTIVATION; ENZYME INHIBITION; EXERCISE; HEART MUSCLE ISCHEMIA; HEART PROTECTION; HEMATOLOGIC MALIGNANCY; HUMAN; NON INSULIN DEPENDENT DIABETES MELLITUS; NONHUMAN; PROTEIN PHOSPHORYLATION; REVIEW; STRUCTURE ANALYSIS; ANALOGS AND DERIVATIVES; ANIMAL; CLINICAL TRIAL (TOPIC); DRUG EFFECTS; ENZYMOLOGY; HEMATOLOGIC NEOPLASMS; METABOLISM; PHYSIOLOGY; TRENDS;

AMINOIMIDAZOLE CARBOXAMIDE; AMP-ACTIVATED PROTEIN KINASES; ANIMALS; CLINICAL TRIALS AS TOPIC; ENZYME ACTIVATION; HEMATOLOGIC NEOPLASMS; HUMANS; RIBONUCLEOSIDES;

EID: 77952488995     PISSN: 13543784     EISSN: None     Source Type: Journal    
DOI: 10.1517/13543781003703694     Document Type: Review

References (66)

1. Gruber HE, Hoffer ME, McAllister DR, et al. Increased adenosine concentration in blood from ischemic myocardium by AICA riboside. Effects on flow, granulocytes, and injury. Circulation 1989;80:1400-1411
2. Vincent MF, Marangos PJ, Gruber HE, Van den Berghe G. Inhibition by AICA riboside of gluconeogenesis in isolated rat hepatocytes. Diabetes 1991;40:1259-1266
3. Van den Berghe G, Gruber H. Method for lowering blood lipid levels. WO9303734; 1993
4. Hardie DG, Hawley SA, Scott JW. AMP-activated protein kinase-development of the energy sensor concept. J Physiol 2006;574:7-15
5. Sullivan JE, Brocklehurst KJ, Marley AE, et al. Inhibition of lipolysis and lipogenesis in isolated rat adipocytes with AICAR, a cell-permeable activator of AMP-activated protein kinase. FEBS Lett 1994;353:33-36
6. Bochner BR, Ames BN. ZTP (5-amino 4-imidazole carboxamide riboside 5'-triphosphate): a proposed alarmone for 10-formyl-tetrahydrofolate deficiency. Cell 1982;29:929-937
7. Carling D, Clarke PR, Zammit VA, Hardie DG. Purification and characterization of the AMP-activated protein kinase. Copurification of acetyl-CoA carboxylase kinase and 3-hydroxy-3-methylglutaryl-CoA reductase kinase activities. Eur J Biochem 1989;186:129-136
8. Henin N, Vincent MF, Gruber HE, Van den Berghe G. Inhibition of fatty acid and cholesterol synthesis by stimulation of AMP-activated protein kinase. FASEB J 1995;9:541-546
9. Corton JM, Gillespie JG, Hawley SA, Hardie DG. 5-aminoimidazole-4- carboxamide ribonucleoside. A specific method for activating AMP-activated protein kinase in intact cells? Eur J Biochem 1995;229:558-565
10. Hardie DG. AMP-activated protein kinase: the guardian of cardiac energy status. J Clin Invent 2004;117:465-468
11. Dixon R, Gourzis J, McDermott D, et al. AICA-riboside: safety, tolerance, and pharmacokinetics of a novel adenosine-regulating agent. J Clin Pharmacol 1991;31:342-347
12. Drew BG, Kingwell BA. Acadesine, an adenosine-regulating agent with the potential for widespread indications. Expert Opin Pharmacother 2008;9:2137-2144
13. Winder WW, Hardie DG. AMP-activated protein kinase, a metabolic master switch: possible roles in type 2 diabetes. Am J Physiol 1999;277:E1-10
14. Vincent MF, Erion MD, Gruber HE, Van den Berghe G. Hypoglycaemic effect of AICAriboside in mice. Diabetologia 1996;39:1148-1155
15. Bergeron R, Previs SF, Cline GW, et al. Effect of 5-aminoimidazole-4- carboxamide-1-beta-D-ribofuranoside infusion on in vivo glucose and lipid metabolism in lean and obese Zucker rats. Diabetes 2001;50:1076-1082
16. Schimmack G, Defronzo RA, Musi N. AMP-activated protein kinase: role in metabolism and therapeutic implications. Diabetes Obes Metab 2006;8:591-602
17. Consoli A, Nurjhan N, Capani F, Gerich J. Predominant role of gluconeogenesis in increased hepatic glucose production in NIDDM. Diabetes 1989;38:550-557 (Pubitemid 19125601)
18. Erion MD, van Poelje PD, Dang Q, et al. MB06322 (CS-917): a potent and selective inhibitor of fructose 1,6-bisphosphatase for controlling gluconeogenesis in type 2 diabetes. Proc Natl Acad Sci USA 2005;102:7970-7975
19. van Poelje PD, Potter SC, Chandramouli VC, et al. Inhibition of fructose 1,6-bisphosphatase reduces excessive endogenous glucose production and attenuates hyperglycemia in Zucker diabetic fatty rats. Diabetes 2006;55:1747-1754
20. Gumbiner B, Bullough D, Watling S, et al. Pronounced glucose (G) reduction in poorly controlled T2DM with MB07803, a novel fructose-1,6- bisphosphatase inhibitor (FBPaseI) with reduced potential for acid-base disturbance vs the 1st generation FBPaseI CS-917. Late breaking abstract nr 11-LB, presented at the 69th Meeting of the American Diabetes Association; 5-9 June 2009; New Orleans, LA
21. Merrill GF, Kurth EJ, Hardie DG, Winder WW. AICA riboside increases AMP-activated protein kinase, fatty acid oxidation, and glucose uptake in rat muscle. Am J Physiol 1997;273:E1107-12
22. Kurth-Kraczek EJ, Hirshman MF, Goodyear LJ, Winder WW. 5¢ AMP-activated protein kinase activation causes GLUT4 translocation in skeletal muscle. Diabetes 1999;48:1667-1671
23. Narkar VA, Downes M, Yu RT, et al. AMPK and PPARdelta agonists are exercise mimetics. Cell 2008;134:405-415
24. Goransson O, McBride A, Hawley SA, et al. Mechanism of action of A-769662, a valuable tool for activation of AMP-activated protein kinase. J Biol Chem 2007;282:32549-32560
25. Richter EA, Kiens B, Wojtaszewski JF. Can exercise mimetics substitute for exercise? Cell Metab 2008;8:96-98
26. DeBerardinis RJ, Lum JJ, Hatzivassiliou G, Thompson CB. The biology of cancer: metabolic reprogramming fuels cell growth and proliferation. Cell Metab 2008;7:11-20
27. Weinberg F, Chandel NS. Mitochondrial metabolism and cancer. Ann NY Acad Sci 2009;1177:66-73
28. Xiang X, Saha AK, Wen R, et al. AMP-activated protein kinase activators can inhibit the growth of prostate cancer cells by multiple mechanisms. Biochem Biophys Res Commun 2004;321:161-167 (Pubitemid 39055618)
29. Swinnen JV, Beckers A, Brusselmans K, et al. Mimicry of a cellular low energy status blocks tumor cell anabolism and suppresses the malignant phenotype. Cancer Res 2005;65:2441-2448
30. Rattan R, Giri S, Singh AK, Singh I. 5-Aminoimidazole-4-carboxamide-1- beta-D-ribofuranoside inhibits cancer cell proliferation in vitro and in vivo via AMP-activated protein kinase. J Biol Chem 2005;280:39582-39593
31. Baumann P, Mandl-Weber S, Emmerich B, et al. Activation of adenosine monophosphate activated protein kinase inhibits growth of multiple myeloma cells. Exp Cell Res 2007;313:3592-3603 (Pubitemid 47404540)
32. Beckers A, Organe S, Timmermans L, et al. Methotrexate enhances the antianabolic and antiproliferative effects of 5-aminoimidazole-4-carboxamide riboside. Mol Cancer Ther 2006;5:2211-2217
33. Garcia-Gil M, Pesi R, Perna S, et al. 5 '-aminoimidazole-4-carboxamide riboside induces apoptosis in human neuroblastoma cells. Neuroscience 2003;117:811-820
34. Pesi R, Micheli V, Jacomelli G, et al. Cytosolic 5'-nucleotidase hyperactivity in erythrocytes of Lesch-Nyhan syndrome patients. Neuroreport 2000;11:1827-1831
35. Kefas BA, Heimberg H, Vaulont S, et al. AICA-riboside induces apoptosis of pancreatic beta cells through stimulation of AMP-activated protein kinase. Diabetologia 2003;46:250-254 (Pubitemid 36343889)
36. Meisse D, Van de Casteele M, Beauloye C, et al. Sustained activation of AMP-activated protein kinase induces c-Jun N-terminal kinase activation and apoptosis in liver cells. FEBS Lett 2002;526:38-42
37. Campas C, Lopez JM, Santidrian AF, et al. Acadesine activates AMPK and induces apoptosis in B-cell chronic lymphocytic leukemia cells but not in T lymphocytes. Blood 2003;101:3674-3680 (Pubitemid 36857958)
38. Campas C, Santidrian AF, Domingo A, Gil J. Acadesine induces apoptosis in B cells from mantle cell lymphoma and splenic marginal zone lymphoma. Leukemia 2005;19:292-294
39. Lopez JM, Santidrian AF, Campas C, Gil J. 5-Aminoimidazole-4-carboxamide riboside induces apoptosis in Jurkat cells, but the AMP-activated protein kinase is not involved. Biochem J 2003;370:1027-1032
40. Stefanelli C, Stanic I, Bonavita F, et al. Inhibition of glucocorticoid-induced apoptosis with 5-aminoimidazole-4-carboxamide ribonucleoside, a cell-permeable activator of AMP-activated protein kinase. Biochem Biophys Res Commun 1998;243:821-826
41. Culmsee C, Monnig J, Kemp BE, Mattson MP. AMP-activated protein kinase is highly expressed in neurons in the developing rat brain and promotes neuronal survival following glucose deprivation. J Mol Neurosci 2001;17:45-58
42. Ido Y, Carling D, Ruderman N. Hyperglycemia-induced apoptosis in human umbilical vein endothelial cells: inhibition by the AMP-activated protein kinase activation. Diabetes 2002;51:159-167
43. Blazquez C, Geelen MJ, Velasco G, Guzman M. The AMP-activated protein kinase prevents ceramide synthesis de novo and apoptosis in astrocytes. FEBS Lett 2001;489:149-153
44. Nishino Y, Miura T, Miki T, et al. Ischemic preconditioning activates AMPK in a PKC-dependent manner and induces GLUT4 up-regulation in the late phase of cardioprotection. Cardiovasc Res 2004;61:610-619
45. Russell RR III, Li J, Coven DL, et al. AMP-activated protein kinase mediates ischemic glucose uptake and prevents postischemic cardiac dysfunction, apoptosis, and injury. J Clin Invest 2004;114:495-503
46. Jacobs RL, Lingrell S, Dyck JR, Vance DE. Inhibition of hepatic phosphatidylcholine synthesis by 5-aminoimidazole-4-carboxamide-1-beta-4- ribofuranoside is independent of AMP-activated protein kinase activation. J Biol Chem 2007;282:4516-4523
47. Meley D, Bauvy C, Houben-Weerts JH, et al. AMP-activated protein kinase and the regulation of autophagic proteolysis. J Biol Chem 2006;281:34870-34879
48. Guigas B, Taleux N, Foretz M, et al. AMP-activated protein kinase-independent inhibition of hepatic mitochondrial oxidative phosphorylation by AICA riboside. Biochem J 2007;404:499-507
49. Imamura K, Ogura T, Kishimoto A, et al. Cell cycle regulation via p53 phosphorylation by a 5'-AMP activated protein kinase activator, 5-aminoimidazole-4-carboxamide-1-beta-D-ribofuranoside, in a human hepatocellular carcinoma cell line. Biochem Biophys Res Commun 2001;287:562-567
50. Sengupta TK, Leclerc GM, Hsieh-Kinser TT, et al. Cytotoxic effect of 5-aminoimidazole-4-carboxamide-1-beta-4-ribofuranoside (AICAR) on childhood acute lymphoblastic leukemia (ALL) cells: implication for targeted therapy. Mol Cancer 2007;6:46
51. Coll-Mulet L, Iglesias-Serret D, Santidrian AF, et al. MDM2 antagonists activate p53 and synergize with genotoxic drugs in B-cell chronic lymphocytic leukemia cells. Blood 2006;107:4109-4114
52. Keating MJ, O'Brien S, Albitar M, et al. Early results of a chemoimmunotherapy regimen of fludarabine, cyclophosphamide, and rituximab as initial therapy for chronic lymphocytic leukemia. J Clin Oncol 2005;23:4079-4088
53. Wierda W, O'Brien S, Wen S, et al. Chemoimmunotherapy with fludarabine, cyclophosphamide, and rituximab for relapsed and refractory chronic lymphocytic leukemia. J Clin Oncol 2005;23:4070-4078 (Pubitemid 46211312)
54. Hallek M, Fingerle-Rowson G, Fink A-M, et al. Immunochemotherapy with fludarabine (F), cyclophosphamide (C), and rituximab (R) (FCR) versus fludarabine and cyclophosphamide (FC) improves response rates and progression-free survival (PFS) of previously untreated patients (pts) with advanced chronic lymphocytic leukemia (CLL). ASH Annual Meeting Abstracts. Blood 2008;112:325
55. Bosch F, Abrisqueta P, Villamor N, et al. Rituximab, fludarabine, cyclophosphamide, and mitoxantrone: a new, highly active chemoimmunotherapy regimen for chronic lymphocytic leukemia. J Clin Oncol 2009;27:4578-4584
56. Shanafelt TD, Kay NE. Comprehensive management of the CLL patient: a holistic approach. Hematology Am Soc Hematol Educ Program 2007;2007:324-331
57. Extermann M, Hurria A. Comprehensive geriatric assessment for older patients with cancer. J Clin Oncol 2007;25:1824-1831 (Pubitemid 46860271)
58. Morrison VA. Management of infectious complications in patients with chronic lymphocytic leukemia. Hematology Am Soc Hematol Educ Program 2007;2007:332-338
59. Tsimberidou AM, Keating MJ. Treatment of fludarabine-refractory chronic lymphocytic leukemia. Cancer 2009;115:2824-2836
60. O'Brien S. New agents in the treatment of CLL. Hematology Am Soc Hematol Educ Program 2008;2008:457-464
61. Zenz T, Benner A, Dohner H, Stilgenbauer S. Chronic lymphocytic leukemia and treatment resistance in cancer: the role of the p53 pathway. Cell Cycle 2008;7:3810-3814
62. Calissano C, Damle RN, Hayes G, et al. In vivo intra-and inter-clonal kinetic heterogeneity in B-cell chronic lymphocytic leukemia. Blood 2009;114:4832-4842
63. Dearden C. Disease-specific complications of chronic lymphocytic leukemia. Hematology Am Soc Hematol Educ Program 2008;2008:450-456
64. Maddocks KJ, Lin TS. Update in the management of chronic lymphocytic leukemia. J Hematol Oncol 2009;2:29
65. Zenz T, Habe S, Denzel T, et al. Detailed analysis of p53 pathway defects in fludarabine-refractory chronic lymphocytic leukemia (CLL): dissecting the contribution of 17p deletion, TP53 mutation, p53-p21 dysfunction, and miR34a in a prospective clinical trial. Blood 2009;114:2589-2597
66. Andersen NS, Pedersen LB, Laurell A, et al. Pre-emptive treatment with rituximab of molecular relapse after autologous stem cell transplantation in mantle cell lymphoma. J Clin Oncol 2009;27:4365-4370