(R)-Roscovitine (CYC202, Seliciclib)

Inhibitors of Cyclin-Dependent Kinases as Anti-Tumor Agents

Volumn , Issue , 2006, Pages 187-225

  Meijer, Laurent ^a   Bettayeb, Karima ^a   Galons, Hervé ^b  

^a CNRS   (France)

^b UNIVERSITÉ PARIS DESCARTES   (France)

Author keywords

[No Author keywords available]

Indexed keywords

EID: 84872418434     PISSN: None     EISSN: None     Source Type: Book    
DOI: 10.1201/9781420005400     Document Type: Chapter

References (150)

1. Abal, M., Bras-Goncalves, R., Judde, J.G., Fsihi, H., De Cremoux, P., Louvard, D., Magdelenat, H., Robine, S., and Poupon, M.F. Enhanced sensitivity to irinotecan by Cdk1 inhibition in the p53-deficient HT29 human colon cancer cell line. Oncogene 23, 1737, 2004.
2. Akli, S. and Keyomarsi, K. Low-molecular-weight cyclin E: the missing link between biology and clinical outcome. Breast Cancer Res., 6, 188, 2004.
3. Aleem, E., Kiyokawa, H., and Kaldis, P. Cdc2-cyclin E complexes regulate the G1/S phase transition. Nat. Cell Biol., 7, 831, 2005.
4. Alessi, F., Quarta, S., Savio, M., Riva, F., Stivala, L.A., Scovassi, A.I., Meijer, L., and Prosperi, E. The cyclin-dependent kinase inhibitors olomoucine and roscovitine arrest human fibroblasts in G1 phase by inhibition of CDK2 kinase activity. Exp. Cell Res., 245, 8, 1998.
5. Alvi, A.J., Austen, B., Weston, V.J., Fegan, C., MacCallum, D., Gianella-Borradori, A., Lane, D.P., Hubank, M., Powell, J.E., Wei, W., Taylor, A.M., Moss, P.A., and Stankovic, T. A novel CDK inhibitor, CYC202 (R-roscovitine), overcomes the defect in p53- dependent apoptosis in B-CLL by down-regulation of genes involved in transcription regulation and survival. Blood, 105, 4484, 2005.
6. Arion, D., Meijer, L., Brizuela, L., and Beach, D. Cdc2 is a component of the M-phase specific histone H1 kinase: evidence for identity with MPF. Cell, 55, 371, 1988.
7. Atanasova, G., Jans, R., Zhelev, N., Mitev, V., and Poumay, Y. Effects of the cyclin-dependent kinase inhibitor CYC202 (R)-roscovitine) on the physiology of cultured human keratinocytes. Biochem. Pharmacol.,70, 824, 2005.
8. Azevedo, W.F., Leclerc, S., Meijer, L., Havlicek, L., Strnad, M., and Kim, S.H. Inhibition of cyclin-dependent kinases by purine analogues: crystal structure of human cdk2 complexed with roscovitine. Eur. J. Biochem., 243, 518, 1997.
9. Bach, S., Knockaert, M., Lozach, O., Reinhardt, J., Baratte, B., Schmitt, S., Coburn, S.P., Tang, L., Jiang. T., Liang, D.C., Galons, H., Dierick, J.F., Totzke, F., Schächtele, C., Lerman, A.S., Carnero, A., Wan, Y., Gray, N., and Meijer, L. Roscovitine targets: Protein kinases and pyridoxal kinase. J. Biol. Chem., 280, 31208, 2005.
10. Bach, S., Blondel, M., and Meijer, L. Evaluation of CDK inhibitors’ selectivity: from affinity chromatography to yeast genetics. In Monographs on Enzyme Inhibitors. Vol. 2. CDK Inhibitors and Their Potential as Anti-Tumor Agents, E. Yue and P.J. Smith, Eds. CRC Press, submitted, 2006.
11. Bain, J., McLauchlan, H., Elliott, M., and Cohen, P. The specificities of protein kinase inhibitors: an update. Biochem. J., 371, 199, 2003.
12. Barrie, S.E., Eno-Amooquaye, E., Hardcastle, A., Platt, G., Richards, J., Bedford, D., Workman, P., Aherne, W., Mittnacht, S., and Garrett, M.D. High-throughput screening for the identification of small-molecule inhibitors of retinoblastoma protein phosphorylation in cells. Anal. Biochem., 320, 66, 2003.
13. Becker, F., Murthi, K., Smith, C., Come, J., Costa-Roldan, N., Kaufmann, C., Hanke, U., Degenhart, C., Baumann, S., Wallner, W., Huber, A., Dedier, S., Dill, S., Kinsman, D., Hediger, M., Bockovich, N., Meier-Ewert, S., Kluge, A.F., and Kley, N. A three hybrid approach to scanning the proteome for targets of small molecule kinase inhibitors. Chem. Biol., 11, 211, 2004.
14. Benson, C., Kaye, S., Workman, P., Garrett, M., Walton, M., and de Bono, J. Clinical anticancer drug development: targeting the cyclin-dependent kinases. Br. J. Cancer, 92, 7, 2005.
15. Blaydes, J.P., Craig, A.L., Wallace, M., Ball, H.M., Traynor, N.J., Gibbs, N.K., and Hupp, T.R. Synergistic activation of p53-dependent transcription by two cooperating damage recognition pathways. Oncogene, 19, 3829, 2000.
16. Bloom, J. and Pagano, M. Deregulated degradation of the cdk inhibitor p27 and malignant transformation. Semin. Cancer Biol., 13, 41, 2003.
17. Borgne, A. and Golsteyn, R.M. The role of cyclin-dependent kinases in apoptosis. In Progress in Cell Cycle Research, L. Meijer, A. Jézéquel, and M. Roberge, Eds., Life in Progress Editions, Roscoff, France, 2003, p. 453.
18. Borgne, A., Versteege, I., Mahé, M., Studeny, A., Léonce, S., Rodriguez, M., Hickman, J.A., Meijer, L., and Golsteyn, R.M., 2006. Analysis of cyclin B1 in apoptosis and mitotic catastrophe induced by camptothecin treatment in HT29 cells. Oncogene, in press, 2006.
19. Boulanger, J., Vezina, A., Mongrain, S., Boudreau, F., Perreault, N., Auclair, B.A., Laine, J., Asselin, C., and Rivard, N. Cdk2-dependent phosphorylation of homeobox transcription factor CDX2 regulates its nuclear translocation and proteasome-mediated degradation in human intestinal epithelial cells. J. Biol. Chem., 280, 18095, 2005.
20. Byth, K.F., Geh, C., Forder, C.L., Oakes, S.E., and Thomas, A.P. The cellular phenotype of AZ703, a novel selective imidazo[1,2-a]pyridine cyclin-dependent kinase inhibitor. Mol. Cancer Ther., 5, 655, 2006.
21. Canduri, F., Uchoa, H.B., and de Azevedo, W.F. Molecular models of cyclin-dependent kinase 1 complexed with inhibitors. Biochem. Biophys. Res. Commun., 324, 661, 2004.
22. Cervenkova, K., Belejova, M., Chmela, Z., Rypka, M., Riegrova, D., Michnova, K., Michalikova, K., Surova, I., Brejcha, A., Hanus, J., Cerny, B., Fuksova, K., Havlícek, L., and Vesely, J. In vitro glycosidation potential towards olomoucine-type cyclin-dependent kinase inhibitors in rodent and primate microsomes. Physiol. Res., 52, 467, 2003.
23. Chang, T.S., Jeong, W., Choi, S.Y., Yu, S., Kang, S.W., and Rhee, S.G. Regulation of peroxiredoxin I activity by Cdc2-mediated phosphorylation. J. Biol. Chem., 277, 25370, 2002.
24. Chang, Y.T., Gray, N.G., Rosania, G.R., Sutherlin, D.P., Kwon, S., Norman, T.C., Sarohia, R., Leost, M., Meijer, L., and Schultz, P.G. Synthesis and application of functionally diverse 2,6,9-trisubstituted purine libraries as CDK inhibitors. Chem. Biol., 6, 361, 1999.
25. Chmela, Z., Rypka, M., Cervenkova, K., Lemr, K., Riegrova, D., and Vesely, J. Carboxylic acid is the main product of roscovitine biotransformation in mice in vivo: comparison with bohemine. Proceedings of the 13th International Conference on Cytochromes P450., Prague, June 29-July 3, 2003. D629C0041, 163, 2003.
26. Cohen, P. Protein kinases - the major drug targets of the twenty-first century? Nat. Rev. Drug Discovery, 1, 309, 2002.
27. Crescenzi, E., Palumbo, G., and Brady, H.J. Roscovitine modulates DNA repair and senescence: Implications for combination chemotherapy. Clin. Cancer Res., 11, 8158, 2005.
28. Cruz, J.C. and Tsai, L.H. A Jekyll and Hyde kinase: roles for Cdk5 in brain development and disease. Curr. Opin. Neurobiol., 14, 390, 2004.
29. David-Pfeuty T. Potent inhibitors of cyclin-dependent kinase 2 induce nuclear accumulation of wild-type p53 and nucleolar fragmentation in human untransformed and tumorderived cells. Oncogene, 18, 7409, 1999.
30. David-Pfeuty, T., Nouvian-Dooghe, Y., Sirri, V., Roussel, P., and Hernandez-Verdun, D. Common and reversible regulation of wild-type p53 function and of ribosomal biogenesis by protein kinases in human cells. Oncogene, 20, 5951, 2001.
31. Daub, H., Godl, K., Brehmer, D., Klebl, B. and Müller, G. Evaluation of kinase inhibitor selectivity by chemical proteomics. Assay Drug Dev. Technol. 2, 215-224, 2004.
32. De la Motte, S. and Gianella-Borradori, A. Pharmacokinetic model of R-roscovitine and its metabolite in healthy male subjects. Int. J. Clin. Pharmacol. Ther., 42, 232, 2004.
33. Di Giovanni, S., Movsesyan, V., Ahmed, F., Cernak, I., Schinelli, S., Stoica, B., and Faden, A.I. Cell cycle inhibition provides neuroprotection and reduces glial proliferation and scar formation after traumatic brain injury. Proc. Natl. Acad. Sci. U.S.A., 102, 8333, 2005.
34. Dobes, P., Otyepka, M., Strnad, M., and Hobza, P. Interaction energies for the purine inhibitor roscovitine with cyclin-dependent kinase 2: correlated Ab initio quantum-chemical, DFT and empirical calculations. Chemistry [Epub ahead of print], 2006.
35. Du, J., Widlund, H.R., Horstmann, M.A., Ramaswamy, S., Ross, K., Huber, W.E., Nishimura, E.K., Golub, T.R., and Fisher, D.E. Critical role of CDK2 for melanoma growth linked to its melanocyte-specific transcriptional regulation by MITF. Cancer Cell, 6, 565, 2004.
36. Edamatsu, H., Gau, C.L., Nemoto, T., Guo, L., and Tamanoi, F. Cdk inhibitors, roscovitine and olomoucine, synergize with farnesyltransferase inhibitor (FTI) to induce efficient apoptosis of human cancer cell lines. Oncogene, 19, 3059, 2000.
37. Fabian, M.A., Biggs, W.H., Treiber, D.K., Atteridge, C.E., Azimioara, M.D., Benedetti, M.G., Carter, T.A., Ciceri, P., Edeen, P.T., Floyd, M., Ford, J.M., Galvin, M., Gerlach, J.L., Grotzfeld, R.M., Herrgard, S., Insko, D.E., Insko, M.A., Lai, A.G., Lelias, J.M., Mehta, S.A., Milanov, Z.V., Velasco, A.M., Wodicka, L.M., Patel, H.K., Zarrinkar, P.P., and Lockhart, D.J. A small molecule-kinase interaction map for clinical kinase inhibitors. Nat. Biotechnol., 23, 329, 2005.
38. Fischer, P.M. The design of drug candidate molecules as selective inhibitors of therapeutically relevant protein kinases. Curr. Med. Chem., 11, 1563, 2004.
39. Fischer, L., Endicott, J., and Meijer, L. Cyclin-dependent kinase inhibitors. In Cell Cycle Regulators as Therapeutic Targets, L. Meijer, A. Jézéquel and M. Roberge, Eds., Progr. Cell Cycle Res., Vol. 5, Life in Progress Editions, Station Biologique de Roscoff, France, 2003, p. 248.
40. Fischer, P.M. and Gianella-Borradori, A. Recent progress in the discovery and development of cyclin-dependent kinase inhibitors. Exp. Opin. Invest. Drugs, 14, 457, 2005.
41. Garriga, J. and Grana, X. Cellular control of gene expression by T-type cyclin/CDK9 complexes. Gene, 337, 15, 2004.
42. Gespach, C. Crosstalk between the cell cycle regulator Cdk2 and the Cdx2 tumor suppressor at the proliferation-differentiation interface. Oncogene, 24, 7953, 2005.
43. Gherardi, D., D’Agati, V., Chu, T.H.T., Barnett, A., Gianella-Borradori, A., Gelman, I.H., and Nelson, P.J. Reversal of collapsing glomerulopathy in mice with the cyclin-dependent kinase inhibitor CYC202. J. Am. Soc. Nephrol., 15, 1212, 2004.
44. Gil-Gomez, G., Berns, A., and Brady, H.J. A link between cell cycle and cell death: Bax and Bcl-2 modulate Cdk2 activation during thymocyte apoptosis. EMBO J., 17, 7209, 1998.
45. Goke, R., Barth, P., Schmidt, A., Samans, B., and Lankat-Buttgereit B. Programmed cell death protein 4 suppresses CDK1/cdc2 via induction of p21(Waf1/Cip1). Am. J. Physiol. Cell Physiol., 287, C1541, 2004.
46. Gray, N., Wodicka, L., Thunnissen, A.M., Norman, T., Kwon, S., Espinoza, F.H., Morgan, D.O., Barnes, G., Leclerc, S., Meijer, L., Kim, S.H., Lockhart, D.J., and Schultz, P.G. Exploiting chemical libraries, structure, and genomics in the search for new kinase inhibitors. Science, 281, 533, 1998.
47. Griffin, S.V., Krofft, R.D., Pippin, J.W., and Shankland S.J. Limitation of podocyte proliferation improves renal function in experimental crescentic glomerulonephritis. Kidney Int., 67, 977, 2005.
48. Gross, I., Lhermitte, B., Domon-Dell, C., Duluc, I., Martin, E., Gaiddon, C., Kedinger, M., and Freund, J.N. Phosphorylation of the homeotic tumor suppressor Cdx2 mediates its ubiquitin-dependent proteasome degradation. Oncogene, 24, 7955, 2005.
49. Guzi, T. Cyc-202 Cyclacel. Curr. Opin. Invest. Drugs, 5, 1311, 2004.
50. Haesslein, J.L. and Jullian, N. Recent advances in cyclin-dependent kinase inhibition. Purinebased derivatives as anti-cancer agents. Roles and perspectives for the future. Curr. Top. Med. Chem., 2, 1035, 2002.
51. Hahntow, I.N., Schneller, F., Oelsner, M., Weick, K., Ringshausen, I., Fend, F., Peschel, C., and Decker, T. Cyclin-dependent kinase inhibitor Roscovitine induces apoptosis in chronic lymphocytic leukemia cells. Leukemia, 18, 747, 2004.
52. Hakem, A., Sasaki, T., Kozieradzki, I., and Penninger, J.M. The cyclin-dependent kinase Cdk2 regulates thymocyte apoptosis. J. Exp. Med., 189, 957, 1999.
53. Havlícek, L., Hanus, J., Vesely, J., Leclerc, S., Meijer L., Shaw, G., and Strnad, M. Cytokininderived cyclin-dependent kinase inhibitors: Synthesis of cdc2 inhibitory activity of olomoucine and related compounds. J. Med. Chem., 40, 408, 1997.
54. Hunt, K.K. and Keyomarsi, K. Cyclin E as a prognostic and predictive marker in breast cancer. Semin. Cancer Biol., 15, 319, 2005.
55. Kim, E.H., Kim, S.U., Shin, D.Y., and Choi, K.S. Roscovitine sensitizes glioma cells to TRAILmediated apoptosis by downregulation of survivin and XIAP. Oncogene, 23, 446, 2004.
56. Knockaert, M., Gray, N., Damiens, E., Chang, Y.T., Grellier, P., Grant, K., Fergusson, D., Mottram, J., Soete, M., Dubremetz, J.F., LeRoch, K., Doerig, C., Schultz, P.G., and Meijer, L. Intracellular targets of cyclin-dependent kinase inhibitors: identification by affinity chromatography using immobilized inhibitors. Chem. Biol., 7, 411, 2000.
57. Knockaert, M., Greengard, P., and Meijer, L. Pharmacological inhibitors of cyclin-dependent kinases. Trends Pharmacol. Sci., 23, 417, 2002a.
58. Knockaert, M., Lenormand, P., Gray, N., Schultz, P., Pouyssegur, J., and Meijer, L. p42/p44MAPKS are intracellular targets of the CDK inhibitor purvalanol. Oncogene, 21, 6413, 2002b.
59. Knockaert, M. and Meijer, L. Identifying in vivo targets of cyclin-dependent kinase inhibitors by affinity chromatography. Biochem. Pharmacol., 64, 819, 2002.
60. Konishi, Y., Lehtinen, M., Donovan, N., and Bonni, A. Cdc2 phosphorylation of BAD links the cell cycle to the cell death machinery. Mol. Cell, 9, 1005, 2002.
61. Kotala, V., Uldrijan, S., Horky, M., Trbusek, M., Strnad, M., and Vojtesek, B. Potent induction of wild-type p53-dependent transcription in tumour cells by a synthetic inhibitor of cyclin-dependent kinases. Cell Mol Life Sci., 58, 1333, 2001.
62. Krude, T. Initiation of human DNA replication in vitro using nuclei from cells arrested at an initiation-competent state. J. Biol. Chem., 275, 13699, 2000.
63. Kwon, Y.G., Lee, S.Y., Choi, Y., Greengard, P., and Nairn, A.C. Cell cycle-dependent phosphorylation of mammalian protein phosphatase 1 by cdc2 kinase. Proc. Natl. Acad. Sci. U.S.A., 94, 2168, 1997.
64. Lacrima, K., Valentini, A., Lambertini, C., Taborelli, M., Rinaldi, A., Zucca, E., Catapano, C., Cavalli, F., Gianella-Borradori, A., Maccallum, D.E., and Bertoni, F. In vitro activity of cyclin-dependent kinase inhibitor CYC202 (Seliciclib, R-roscovitine) in mantle cell lymphomas. Ann. Oncol., 16, 1169, 2005.
65. Lam, L.T., Pickeral, O.K., Peng, A.C., Rosenwald, A., Hurt, E.M., Giltnane, J.M., Averett, L.M., Zhao H., Davis, R.E., Sathyamoorthy, M., Wahl, L.M., Harris, E.D., Mikovits, J.A., Monks, A.P., Hollingshead, M.G., Sausville, E.A., and Staudt, L.M. Genomicscale measurement of mRNA turnover and the mechanisms of action of the anticancer drug flavopiridol. Genome Biol., 2, RESEARCH0041, 2001.
66. Leach, C., Shenolikar, S., and Brautigan, D.L. Phosphorylation of phosphatase inhibitor-2 at centrosomes during mitosis. J. Biol. Chem., 278, 26015, 2003.
67. Legraverend, M. and Grierson, D.S. The purines: potent and versatile small molecule inhibitors and modulators of key biological targets. Bioorg. Med. Chem., 14, 3987, 2006.
68. Lipinski, C.A., Lombardo, F., Dominy, B.W., and Feeney, P.J. Experimental and computational approaches to estimate solubility and permeability in drug discovery and development settings. Adv. Drug Delivery Rev., 23, 3, 1997.
69. Ljungman, M. and Paulsen, M.T. The cyclin-dependent kinase inhibitor roscovitine inhibits RNA synthesis and triggers nuclear accumulation of p53 that is unmodified at Ser15 and Lys382. Mol. Pharmacol., 60, 785, 2001.
70. Lowe, M., Rabouille, C., Nakamura, N., Watson, R., Jackman, M., Jamsa, E., Rahman, D., Pappin, D.J., and Warren, G. Cdc2 kinase directly phosphorylates the cis-Golgi matrix protein GM130 and is required for Golgi fragmentation in mitosis. Cell, 94, 783, 1998.
71. Loyer, P., Trembley, J.H., Katona, R., Kidd, V.J., and Lahti, J.M. Role of CDK/cyclin complexes in transcription and RNA splicing. Cell Signal., 17, 1033, 2005.
72. Lu, W., Chen, L., Peng, Y., and Chen, J. Activation of p53 by roscovitine-mediated suppression of MDM2 expression. Oncogene, 20, 3206, 2001.
73. MacCallum, D.E., Melville, J., Frame, S., Watt, K., Anderson, S., Gianella-Borradori, A., Lane, D.P., and Green, S.R. Seliciclib (CYC202, R-Roscovitine) induces cell death in multiple myeloma cells by inhibition of RNA polymerase II-dependent transcription and down-regulation of Mcl-1. Cancer Res., 65, 5399, 2005.
74. Maggiorella, L., Deutsch, E., Frascogna, V., Chavaudra, N., Jeanson, L., Milliat, F., Eschwege, F., and Bourhis, J. Enhancement of radiation response by roscovitine in human breast carcinoma in vitro and in vivo. Cancer Res., 63, 2513, 2003.
75. Malumbres, M. and Barbacid, M. To cycle or not to cycle: a critical decision in cancer. Nat. Rev. Cancer, 1, 222, 2001.
76. Malumbres, M. and Barbacid, M. Mammalian cyclin-dependent kinases. Trends Biochem. Sci., 30, 630, 2005.
77. Mapelli, M., Massimiliano, L., Crovace, C., Seeliger, M., Tsai, L. H., Meijer, L., and Musacchio, A. Mechanism of CDK5/p25 binding by CDK inhibitors. J. Med. Chem., 48, 671, 2005.
78. Matsumoto, Y., Hayashi, K., and Nishida, E. Cyclin-dependent kinase 2 (Cdk2) is required for centrosome duplication in mammalian cells. Curr. Biol., 9, 429, 1999.
79. Maude, S.L. and Enders, G.H. Cdk inhibition in human cells compromises chk1 function and activates a DNA damage response. Cancer Res., 65, 780, 2005.
80. McClue, S.J., Blake, B., Clarke, R., Cowan, A., Cummings, L., Fischer, P.M., MacKenzie, M., Melville, J., Stewart, K., Wang, S., Zhelev, N., Zheleva, N., and Lane, D.P. In vitro and in vivo antitumor properties of the cyclin dependent kinase inhibitor CYC202 (R)-roscovitine). Int. J. Cancer., 102, 463, 2002.
81. Meijer, L. Le cycle cellulaire et sa régulation. Oncologie, 5, 1, 2003.
82. Meijer, L., Arion, D., Golsteyn, R., Pines, J., Brizuela, L., Hunt, T., and Beach, D. Cyclin is a component of the sea urchin egg M-phase specific histone H1 kinase. EMBO J., 8, 2275, 1989.
83. Meijer, L., Borgne, A., Mulner, O., Chong, J.P.J., Blow, J.J., Inagaki, N., Inagaki, M., Delcros, J.G., and Moulinoux, J.P. Biochemical and cellular effects of roscovitine, a potent and selective inhibitor of the cyclin-dependent kinases cdc2, cdk2 and cdk5. Eur. J. Biochem., 243, 527, 1997.
84. Meijer, L. and Pondaven, P. Cyclic activation of histone H1 kinase during the sea urchin egg mitotic divisions. Exp. Cell Res., 174, 116, 1988.
85. Meijer, L. and Raymond, E. Roscovitine and other purines as kinase inhibitors: from starfish oocytes to clinical trials. Acc. Chem. Res., 36, 417, 2003.
86. Mgbonyebi, O.P., Russo, J., Russo, I.H. Roscovitine induces cell death and morphological changes indicative of apoptosis in MDA-MB-231 breast cancer cells. Cancer Res., 59, 1903, 1999.
87. Mgbonyebi, O.P., Russo, J., Russo, I.H. Roscovitine inhibits the proliferative activity of immortal and neoplastic human breast epithelial cells. Anticancer Res., 18, 751, 1998.
88. Mihara, M., Shintani, S., Kiyota, A., Matsumura, T., and Wong, D.T. Cyclin-dependent kinase inhibitor (roscovitine) suppresses growth and induces apoptosis by regulating Bcl-x in head and neck squamous cell carcinoma cells. Int. J. Oncol., 21, 95, 2002.
89. Milovanceva-Popovska, M., Kunter, U., Ostendorf, T., Petermann, A., Rong, S., Eitner, F., Kerjaschki, D., Barnett, A., and Floege, J. R-roscovitine (CYC202) alleviates renal cell proliferation in nephritis without aggravating podocyte injury. Kidney Int., 67, 1362, 2005.
90. Mohapatra, S., Chu, B., Wei, S., Djeu, J., Epling-Burnette, P.K., Loughran, T., Jove, R., and Pledger, W.J. Roscovitine inhibits STAT5 activity and induces apoptosis in the human leukemia virus type 1-transformed cell line MT-2. Cancer Res., 63, 8523, 2003.
91. Mohapatra, S., Chu, B., Zhao, X., and Pledger, W.J. Accumulation of p53 and reductions in XIAP abundance promote the apoptosis of prostate cancer cells. Cancer Res., 65, 7717, 2005.
92. Erratum in Cancer Res., 65, 10635, 2005.
93. Neant, I., and Guerrier, P. 6-Dimethylaminopurine blocks starfish oocyte maturation by inhibiting a relevant protein kinase activity. Exp. Cell Res., 176, 68, 1988.
94. Nelson, P.J. and Shankland, S.J. Therapeutics in renal disease: the road ahead for antiproliferative targets. Nephron Exp. Nephrol., 103, e6, 2005.
95. Noble, M.E., Endicott, J.A., and Johnson, L.N. Protein kinase inhibitors: insights into drug design from structure. Science, 303, 1800, 2004.
96. Nutley, B.P., Raynaud, F.I., Wilson, S.C., Fischer, P.M., Hayes, A., Goddard, P.M., McClue, S.J., Jarman, M., Lane, D.P., and Workman, P. Metabolism and pharmacokinetics of the cyclin-dependent kinase inhibitor R-roscovitine in the mouse. Mol. Cancer Ther., 4, 125, 2005.
97. O’Connor, D.S., Grossman, D., Plescia, J., Li, F., Zhang, H., Villa, A., Tognin, S., Marchisio, P.C., and Altieri, D.C. Regulation of apoptosis at cell division by p34cdc2 phosphorylation of survivin. Proc. Natl. Acad. Sci. U.S.A., 97, 13103, 2000.
98. O’Connor, D.S., Wall, N.R., Porter, A.C., and Altieri, D.C. A p34(cdc2) survival checkpoint in cancer. Cancer Cell., 2, 43, 2002.
99. Ortega, S., Prieto, I., Odajima, J., Martin, A., Dubus, P., Sotillo, R., Barbero, J.L., Malumbres, M., and Barbacid, M. Cyclin-dependent kinase 2 is essential for meiosis but not for mitotic cell division in mice. Nat. Genet., 35, 25, 2003.
100. Otyepka, M., Kriz, Z., and Koca, J. Dynamics and binding modes of free cdk2 and its two complexes with inhibitors studied by computer simulations. J. Biomol. Struct. Dyn., 2, 141, 2002.
101. Pareek, T.K., Keller, J., Kesavapany, S., Pant, H.C., Iadarola, M.J., Brady, R.O., and Kulkarni, A.B. Cyclin-dependent kinase 5 activity regulates pain signaling. Proc. Natl. Acad. Sci. U.S.A., 103, 791, 2006.
102. Park, S.S., Eom, Y.W., and Choi, K.S. Cdc2 and Cdk2 play critical roles in low dose doxorubicin-induced cell death through mitotic catastrophe but not in high dose doxorubicin-induced apoptosis. Biochem. Biophys. Res. Commun., 334, 1014, 2005.
103. Payton, M., Chung, G., Yakowec, P., Wong, A., Powers, D., Xiong, L., Zhang, N., Leal, J., Bush, T.L., Santora, V., Askew, B., Tasker, A., Radinsky, R., Kendall, R., and Coats, S. Discovery and evaluation of dual CDK1 and CDK2 inhibitors. Cancer Res., 66, 4299, 2006.
104. Price, P.M., Safirstein, R.L., and Megyesi, J. Protection of renal cells from cisplatin toxicity by cell cycle inhibitors. Am. J. Physiol. Renal Physiol., 286, F378, 2004.
105. Penuelas, S., Alemany, C., Noe, V., and Ciudad, C.J. The expression of retinoblastoma and Sp1 is increased by low concentrations of cyclin-dependent kinase inhibitors. Eur. J. Biochem., 24, 4809, 2003.
106. Pinhero, R., Liaw, P., and Yankulov, K. A uniform procedure for the purification of CDK7/CycH/MAT1, CDK8/CycC and CDK9/CycT1. Biol. Procedures Online, 6, 163, 2004.
107. Pippin, J.W., Qu, Q., Meijer, L., and Shankland, S.J. Direct in vivo inhibition of the nuclear cell cycle cascade in experimental mesangial proliferative glomerulonephritis with roscovitine, a novel CDK2 antagonist. J. Clin. Invest., 100, 2512, 1997.
108. Raje, N., Kumar, S., Hideshima, T., Roccaro, A., Ishitsuka, K., Yasui, H., Shiraishi, N., Chauhan, D., Munshi, N.C., Green, S.R., and Anderson, K.C. Seliciclib (CYC202 or R-roscovitine), a small-molecule cyclin-dependent kinase inhibitor, mediates activity via down-regulation of Mcl-1 in multiple myeloma. Blood, 106, 1042, 2005.
109. Rashidian, J., Iyirhiaro, G., Aleyasin, H., Rios, M., Vincent, I., Callaghan, S., Bland, R.J., Slack, R.S., During, M.J., and Park, D.S. Multiple cyclin-dependent kinases signals are critical mediators of ischemia/hypoxic neuronal death in vitro and in vivo. Proc. Natl. Acad. Sci. U.S.A., 102, 14080, 2005.
110. Raynaud, F.I., Fischer, P.M., Nutley, B.P., Goddard, P.M., Lane, D.P., and Workman, P. Cassette dosing pharmacokinetics of a library of 2,6,9-trisubstituted purine cyclindependent kinase 2 inhibitors prepared by parallel synthesis. Mol. Cancer Ther., 3, 353, 2004.
111. Raynaud, F.I., Whittaker, S.R., Fischer, P.M., McClue, S., Walton, M.I., Barrie, S.E., Garrett, M.D., Rogers, P., Clarke, S.J., Kelland, L.R., Valenti, M., Brunton, L., Eccles, S., Lane, D.P., and Workman, P. In vitro and in vivo pharmacokinetic-pharmacodynamic relationships for the trisubstituted aminopurine cyclin-dependent kinase inhibitors olomoucine, bohemine and CYC202. Clin. Cancer Res., 11, 4875, 2005.
112. Rebhun, L.I., White, D., Sander, G., and Ivy, N. Cleavage inhibition in marine eggs by puromycin and 6-dimethylaminopurine. Exp. Cell Res., 77, 312, 1973.
113. Ribas, J., Boix, J., and Meijer, L. (R)-Roscovitine (CYC202, Seliciclib) sensitizes SH-SY5Y neuroblastoma cells to Nutlin-3 induced apoptosis. Exp. Cell Res., in press, 2006.
114. Rialet, V. and Meijer, L. A new screening test for antimitotic compounds using the universal M phase-specific protein kinase, p34cdc2/cyclin Bcdc13, affinity-immobilized on p13suc1- coated microtitration plates. Anticancer Res., 11, 1581, 1991.
115. Ribas, J. and Boix, J. Cell differentiation, caspase inhibition, and macromolecular synthesis blockage, but not BCL-2 or BCL-XL proteins, protect SH-SY5Y cells from apoptosis triggered by two CDK inhibitory drugs. Exp. Cell Res., 295, 9, 2004.
116. Rosato, R.R., Almenara, J.A., Maggio, S.C., Atadja, P., Craig, R., Vrana, J., Dent, P., and Grant, S. Potentiation of the lethality of the histone deacetylase inhibitor LAQ824 by the cyclin-dependent kinase inhibitor roscovitine in human leukemia cells. Mol. Cancer Ther., 4, 1772, 2005.
117. Rosemeyer, H. The chemodiversity of purine as a constituent of natural products. Chem. Div., 1, 361, 2004.
118. Sandal, T., Stapnes, C., Kleivdal, H., Hedin, L., and Doskeland, S.O. A novel, extraneuronal role for cyclin-dependent protein kinase 5 (CDK5): modulation of cAMP-induced apoptosis in rat leukemia cells. J. Biol. Chem., 277, 20783, 2002.
119. Schang, L.M. Effects of pharmacological cyclin-dependent kinase inhibitors on viral transcription and replication. Biochim. Biophys. Acta, 1697, 197, 2004.
120. Schang, L.M., Bantly, A., Knockaert, M., Shaheen, F., Meijer, L., Malim, M.H., Gray, N.S., and Schaffer, P.A. Pharmacological cyclin-dependent kinase inhibitors inhibit replication of wild-type and drug-resistant strains of herpes simplex virus and human immunodeficiency virus type 1 by targeting cellular, not viral, proteins. J. Virol., 76, 7874, 2002.
121. Shapiro, G.I. Cyclin-dependent kinase pathways as targets for cancer treatment. J. Clin. Oncol., 24, 1770, 2006.
122. Sirri, V., Hernandez-Verdun, D., and Roussel, P. Cyclin-dependent kinases govern formation and maintenance of the nucleolus. J. Cell Biol., 156, 969, 2002.
123. Smith, P.D., Crocker, S.J., Jackson-Lewis, V., Jordan-Sciutto, K.L., Hayley, S., Mount, M.P., O’Hare, M.J., Callaghan, S., Slack, R.S., Przedborski, S., Anisman, H., and Park, D.S. Cyclin-dependent kinase 5 is a mediator of dopaminergic neuron loss in a mouse model of Parkinson’s disease. Proc. Natl. Acad. Sci. U.S.A., 100, 13650, 2003.
124. Smith, P.D., O’Hare, M.J. and Park, D.S. CDKs: taking on a role as mediators of dopaminergic loss in Parkinson’s disease. Trends Mol. Med., 10, 445, 2004.
125. Somerville, L. and Cory, J.G. Enhanced roscovitine-induced apoptosis is mediated by a caspase-3-like activity in deoxyadenosine-resistant mouse leukemia L1210 cells. Anticancer Res., 20, 3347, 2000.
126. Tang, L., Li, M.H., Cao, P., Wang, F., Chang, W.R., Bach, S., Reinhardt, J., Koken, M., Galons, H., Wan, Y., Gray, N., Meijer, L., Jiang. T., and Liang, D.C. Crystal structure of pyridoxal kinase in complex with roscovitine and derivatives. J. Biol. Chem. 280, 31220, 2005.
127. Tirado, O.M., Mateo-Lozano, S., and Notario, V. Roscovitine is an effective inducer of apoptosis of Ewing’s sarcoma family tumor cells in vitro and in vivo. Cancer Res., 65, 9320, 2005.
128. Tsai, L.H., Lee, M.S., and Cruz, J. Cdk5, a therapeutic target for Alzheimer’s disease? Biochim. Biophys. Acta, 1697, 137, 2004.
129. Valsasina, B., Kalisz, H.M., and Isacchi, A. Kinase selectivity profiling by inhibitor affinity chromatography. Future Drugs, 1, 303, 2004.
130. Van Engeland, M., Kuijpers, H.J., Ramaekers, F.C., Reutelingsperger, C.P., and Schutte, B. Plasma membrane alterations and cytoskeletal changes in apoptosis. Exp. Cell Res., 235, 421, 1997.
131. Vermeulen, K., Van Bockstaele, D.R., and Berneman, Z.N. The cell cycle: a review of regulation, deregulation and therapeutic targets in cancer. Cell Prolif., 36, 131, 2003.
132. Vesely, J., Havlicek, L., Strnad, M., Blow, J. J., Donella-Deana, A., Pinna, L., Letham, D. S., Kato, J. Y., Détivaud, L., Leclerc, S., and Meijer, L. Inhibition of cyclin-dependent kinases by purine derivatives. Eur. J. Biochem., 224, 771, 1994.
133. Vita, M., Abdel-Rehim, M., Nilsson, C., Hassan, Z., Skansen, P., Wan, H., Meurling, L., and Hassan, M. Stability, pKa and plasma protein binding of roscovitine J. Chromatogr. B, 821, 75, 2005a.
134. Vita, M., Abdel-Rehim, M., Olofsson, S., Hassan, Z, Meurling, L., Siden, A., Siden, M., Pettersson T., and Hassan, M. Tissue distribution, pharmacokinetics and identification of roscovitine metabolites in rat. Eur. J. Pharm. Sci., 25, 91, 2005b.
135. Vita, M., Meurling, L., Pettersson, T., Cruz-Siden, M., Siden, A., and Hassan, M. Analysis of roscovitine using novel high performance liquid chromatography and UV-detection method: pharmacokinetics of roscovitine in rat. J. Pharm. Biomed. Anal., 34, 425, 2004.
136. Vita, M., Skansen, P., Hassan, M., and Abdel-Rehim, M. Development and validation of a liquid chromatography and tandem mass spectrometry method for determination of roscovitine in plasma and urine samples utilizing on-line sample preparation. J. Chromatogr. B, 817, 303, 2005c.
137. Vlach, J., Hennecke, S., and Amati, B. Phosphorylation-dependent degradation of the cyclindependent kinase inhibitor p27. EMBO J., 16, 5334, 1997.
138. Wall, N.R., O’Connor, D.S., Plescia, J., Pommier, Y., and Altieri, D.C. Suppression of survivin phosphorylation on Thr34 by flavopiridol enhances tumor cell apoptosis. Cancer Res., 63, 230, 2003.
139. Wang, D., de La Fuente, C., Deng, L., Wang, L., Zilberman, I., Eadie, C., Healey, M., Stein, D., Denny, T., Harrison, L.E., Meijer, L., and Kashanchi, F. Inhibition of human immunodeficiency virus type 1 transcription by chemical cyclin-dependent kinase inhibitors. J. Virol., 75, 7266, 2001a.
140. Wang, J., Liu, S.H., Fu, Y.P., Wang, J.H., and Lu, Y.M. Cdk5 activation induces hippocampal CA1 cell death by directly phosphorylating NMDA receptors. Nat. Neurosci., 6, 1039, 2003.
141. Wang, S., McClue, S.J., Ferguson, J.R., Hull, J.D., Stokes, S., Parsons, S., Westwood, R., and Fischer, P.M. Synthesis and configuration of the cyclin-dependant kinase inhibitor roscovitine and its enantiomer. Tetrahedron: Asymmetry, 12, 2891, 2001b.
142. Weinmann, H. and Metternich, R. Drug discovery process for kinase inhibitors. ChemBio-Chemistry, 6, 455, 2005.
143. Wesierska-Gadek, J., Gueorguieva, M., and Horky, M. Dual action of cyclin-dependent kinase inhibitors: induction of cell cycle arrest and apoptosis: a comparison of the effects exerted by roscovitine and cisplatin. Pol. J. Pharmacol., 55, 895, 2003.
144. Wesierska-Gadek, J., Gueorguieva, M., and Horky, M. Roscovitine-induced up-regulation of p53AIP1 protein precedes the onset of apoptosis in human MCF-7 breast cancer cells. Mol. Cancer Ther., 4, 113, 2005.
145. Erratum in Mol. Cancer Ther., 4, 503, 2005.
146. Whittaker, S.R., Walton, M.I., Garrett, M.D., and Workman, P. The cyclin-dependent kinase inhibitor CYC202 (R-roscovitine) inhibits retinoblastoma protein phosphorylation, causes loss of Cyclin D1, and activates the mitogen-activated protein kinase pathway. Cancer Res., 64, 262, 2004.
147. Wojciechowski, J., Horky, M., Gueorguieva, M., and Wesierska-Gadek, J. Rapid onset of nucleolar disintegration preceding cell cycle arrest in roscovitine-induced apoptosis of human MCF-7 breast cancer cells. Int. J. Cancer, 106, 486, 2003.
148. Yu, C., Rahmani, M., Dai, Y., Conrad, D., Krystal, G., Dent, P., and Grant, S. The lethal effects of pharmacological cyclin-dependent kinase inhibitors in human leukemia cells proceed through a phosphatidylinositol 3-kinase/Akt-dependent process. Cancer Res., 63, 1822, 2003.
149. Zhang, M., Li, J., Chakrabarty, P., Bu, B., and Vincent, I. Cyclin-dependent kinase inhibitors attenuate protein hyperphosphorylation, cytoskeletal lesion formation, and motor defects in Niemann-Pick Type C mice. Am. J. Pathol., 165, 843, 2004a.
150. Zhang, G.J., Safran, M., Wei, W., Sorensen, E., Lassota, P., Zhelev, N., and Neuberg, D.S., Shapiro, G., and Kaelin, W.G. Jr. Bioluminescent imaging of Cdk2 inhibition in vivo. Nat. Med., 10, 643, 2004b.