Preclinical and clinical development of cyclin-dependent kinase modulators

Journal of the National Cancer Institute

Volumn 92, Issue 5, 2000, Pages 376-387

  Senderowicz, Adrian M ^a,b   Sausville, Edward A ^a  

^a NATIONAL CANCER INSTITUTE   (United States)

^b NATIONAL INSTITUTES OF HEALTH   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

CYCLIN DEPENDENT KINASE INHIBITOR;

CANCER; CANCER CHEMOTHERAPY; CELL CYCLE; GROWTH REGULATION; HUMAN; PRIORITY JOURNAL; REVIEW; TRANSCRIPTION REGULATION;

EID: 0034162636     PISSN: 00278874     EISSN: None     Source Type: Journal    
DOI: 10.1093/jnci/92.5.376     Document Type: Review

References (132)

1. Sherr CJ. Cancer cell cycles. Science 1996;274:1672-7.
2. Hatakeyama M, Weinberg RA. The role of RB in cell cycle control. Prog Cell Cycle Res 1995;1:9-19.
3. Morgan DO, Fisher RP, Espinoza FH, Farrell A, Nourse J, Chamberlin H, et al. Control of eukaryotic cell cycle progression by phosphorylation of cyclin-dependent kinases. Cancer J Sci Am 1998;4 Suppl 1:577-83.
4. Morgan DO. Cyclin-dependent kinases: engines, clocks, and microprocessors. Annu Rev Cell Dev Biol 1997;13:261-91.
5. Rickert P, Seghezzi W, Shanahan F, Cho H, Lees E. Cyclin C/CDK8 is a novel CTD kinase associated with RNA polymerase II. Oncogene 1996; 12:2631-40.
6. Wei P, Garber ME, Fang SM, Fischer WH, Jones KA. A novel CDK9-associated C-type cyclin interacts directly with HIV-1 Tat and mediates its high-affinity, loop-specific binding to TAR RNA. Cell 1998;92: 451-62.
7. Grana X, De Luca A, Sang N, Fu Y, Claudio PP, Rosenblatt J, et al. PITALRE, a nuclear CDC2-related protein kinase that phosphorylates the retinoblastoma protein in vitro. Proc Natl Acad Sci USA 1994;91: 3834-8.
8. MacLachlan TK, Sang N, Giordano A. Cyclins, cyclin-dependent kinases and cdk inhibitors: implications in cell cycle control and cancer. Crit Rev Eukaryot Gene Expr 1995;5:127-56.
9. Edwards MC, Wong C, Elledge SJ. Human cyclin K, a novel RNA polymerase II-associated cyclin possessing both carboxy-terminal domain kinase and Cdk-activating kinase activity. Mol Cell Biol 1998;18:4291-300.
10. Peng J, Zhu Y, Milton JT, Price DH. Identification of multiple cyclin subunits of human P-TEFb. Genes Dev 1998;12:755-62.
11. Kaldis P, Russo AA, Chou HS, Pavletich NP, Solomon MJ. Human and yeast Cdk-activating kinases (CAKs) display distinct substrate specificities. Mol Biol Cell 1998;9:2545-60.
12. Tassan JP, Schultz SJ, Bartek J, Nigg EA. Cell cycle analysis of the activity, subcellular localization, and subunit composition of human CAK (CDK-activating kinase). J Cell Biol 1994;127:467-78.
13. Sherr CJ, Roberts JM. CDK inhibitors: positive and negative regulators of G1-phase progression. Genes Dev 1999;13:1501-12.
14. LaBaer J, Garrett MD, Stevenson LF, Slingerland JM, Sandhu C, Chou HS, et al. New functional activities for the p21 family of CDK inhibitors. Genes Dev 1997;11:847-62.
15. Cheng M, Olivier P, Diehl JA, Fero M, Roussel MF, Roberts JM, et al. The p21(Cip1) and p27(Kip1) CDK 'inhibitors' are essential activators of cyclin D-dependent kinases in murine fibroblasts. EMBO J 1999;18: 1571-83.
16. Bates S, Ryan KM, Phillips AC, Vousden KH. Cell cycle arrest and DNA endoreduplication following p21Waf1/Cip1 expression. Oncogene 1998; 17:1691-703.
17. Dulic V, Stein GH, Far DF, Reed SI. Nuclear accumulation of p21Cip1 at the onset of mitosis: a role at the G2/M-phase transition. Mol Cell Biol 1998;18:546-57.
18. rd, Chen X, Smeets M, Hengst L, Prives C, Reed SI. Effects of p21(Cip1/Waf1) at both the G1/S and the G2/M cell cycle transitions: pRb is a critical determinant in blocking DNA replication and in preventing endoreduplication [published erratum appears in Mol Cell Biol 1998;18:1763]. Mol Cell Biol 1998;18:629-43.
19. Zhang HS, Postigo AA, Dean DC. Active transcriptional repression by the Rb-E2F complex mediates G1 arrest triggered by p16INK4a. TGFbeta, and contact inhibition. Cell 1999;97:53-61.
20. Dyson N. The regulation of E2F by pRB-family proteins. Genes Dev 1998;12:2245-62.
21. DelSal G, Loda M, Pagano M. Cell cycle and cancer: critical events at the G1 restriction point. Crit Rev Oncog 1996;7:127-42.
22. Grana X, Reddy EP. Cell cycle control in mammalian cells: role of cyclins, cyclin dependent kinases (CDKs), growth suppressor genes and cyclin-dependent kinase inhibitors (CKIs). Oncogene 1995;11:211-9.
23. Pardee AB. Multiple molecular levels of cell cycle regulation. J Cell Biochem 1994;54:375-8.
24. Pines J. Cyclins and cyclin-dependent kinases: theme and variations. Adv Cancer Res 1995;66:181-212.
25. Sausville EA, Zaharevitz D, Gussio R, Meijer L, Louarn-Leost M, Kunick C, et al. Cyclin-dependent kinases: initial approaches to exploit a novel therapeutic target. Pharmacol Ther 1999;82:285-92.
26. Tsihlias J, Kapusta L, Slingerland J. The prognostic significance of altered cyclin-dependent kinase inhibitors in human cancer. Annu Rev Med 1999; 50:401-23.
27. Meijer L, Kim SH. Chemical inhibitors of cyclin-dependent kinases. Methods Enzymol 1997;283:113-28.
28. Zaharevitz DW, Gussio R, Leost M, Senderowicz AM, Lahusen T, Kunick C, et al. Discovery and initial characterization of the paullones, a novel class of small-molecule inhibitors of cyclin-dependent kinases. Cancer Res 1999;59:2566-9.
29. De Azevedo WF, Leclerc S, Meijer L, Havlicek L, Strnad M, Kim SH. Inhibition of cyclin-dependent kinases by purine analogues: crystal structure of human cdk2 complexed with roscovitine. Eur J Biochem 1997; 243:518-26.
30. Jin X, Nguyen D, Zhang WW, Kyritsis AP, Roth JA. Cell cycle arrest and inhibition of tumor cell proliferation by the p16INK4 gene mediated by an adenovirus vector. Cancer Res 1995;55:3250-3.
31. Chintala SK, Fueyo J, Gomez-Manzano C, Venkaiah B, Bjerkvig R, Yung WK, et al. Adenovirus-mediated p16/CDKN2 gene transfer suppresses glioma invasion in vitro. Oncogene 1997;15:2049-57.
32. Sandig V, Brand K, Herwig S, Lukas J, Bartek J, Strauss M. Adenovirally transferred p16INK4/CDKN2 and p53 genes cooperate to induce apoptotic tumor cell death. Nat Med 1997;3:313-9.
33. Craig C, Wersto R, Kim M, Ohri E, Li Z, Katayose D, et al. A recombinant adenovirus expressing p27Kip1 induces cell cycle arrest and loss of cyclin-Cdk activity in human breast cancer cells. Oncogene 1997;14: 2283-9.
34. Eastham JA, Hall SJ, Sehgal I, Wang J, Timme TL, Yang G, et al. In vivo gene therapy with p53 or p21 adenovirus for prostate cancer. Cancer Res 1995;55:5151-5.
35. Katayose Y, Kim M, Rakkar AN, Li Z, Cowan KH, Seth P. Promoting apoptosis: a novel activity associated with the cyclin-dependent kinase inhibitor p27. Cancer Res 1997;57:5441-5.
36. Wang X, Gorospe M, Huang Y, Holbrook NJ. p27Kip1 overexpression causes apoptotic death of mammalian cells. Oncogene 1997;15: 2991-7.
37. Lee SJ, Ha MJ, Lee J, Nguyen P, Choi YH, Pirnia F, et al. Inhibition of the 3-hydroxy-3-methylglutaryl-coenzyme A reductase pathway induces p53-independent transcriptional regulation of p21(WAF1/CIP1) in human prostate carcinoma cells. J Biol Chem 1998;273:10618-23.
38. Gray-Bablin J, Rao S, Keyomarsi K. Lovastatin induction of cyclin-dependent kinase inhibitors in human breast cells occurs in a cell cycle-independent fashion. Cancer Res 1997;57:604-9.
39. Hashemolhosseini S, Nagamine Y, Morley SJ, Desrivieres S, Mercep L, Ferrari S. Rapamycin inhibition of the G1 to S transition is mediated by effects on cyclin D1 mRNA and protein stability. J Biol Chem 1998;273: 14424-9.
40. Fahraeus R, Paramio JM, Ball KL, Lain S, Lane DP. Inhibition of pRb phosphorylation and cell-cycle progression by a 20-residue peptide derived from P16CDKN2/INK4A. Curr Biol 1996;6:84-91.
41. Ball KL, Lain S, Fahraeus R, Smythe C, Lane DP. Cell-cycle arrest and inhibition of Cdk4 activity by small peptides based on the carboxy-terminal domain of p21WAF1. Curr Biol 1997;7:71-80.
42. Bonfanti M, Taverna S, Salmona M, D'Incalci M, Broggini M. p21WAF1-derived peptides linked to an internalization peptide inhibit human cancer cell growth. Cancer Res 1997;57:1442-6.
43. Colas P, Cohen B, Jessen T, Grishina I, McCoy J, Brent R. Genetic selection of peptide aptamers that recognize and inhibit cyclin-dependent kinase 2. Nature 1996;380:548-50.
44. Chen YN, Sharma SK, Ramsey TM, Jiang L, Martin MS, Baker K, et al. Selective killing of transformed cells by cyclin/cyclin-dependent kinase 2 antagonists. Proc Natl Acad Sci U S A 1999;96:4325-9.
45. Kornmann M, Arber N, Korc M. Inhibition of basal and mitogen-stimulated pancreatic cancer cell growth by cyclin D1 antisense is associated with loss of tumorigenicity and potentiation of cytotoxicity to cisplatinum. J Clin Invest 1998;101:344-52.
46. Wang MB, Billings KR, Venkatesan N, Hall FL, Srivatsan ES. Inhibition of cell proliferation in head and neck squamous cell carcinoma cell lines with antisense cyclin D1. Otolaryngol Head Neck Surg 1998;119: 593-9.
47. Driscoll B, Wu L, Buckley S, Hall FL, Anderson KD, Warburton D. Cyclin D1 antisense RNA destabilizes pRb and retards lung cancer cell growth. Am J Physiol 1997;273:L941-9.
48. Watts CK, Sweeney KJ, Warlters A, Musgrove EA, Sutherland RL. Antiestrogen regulation of cell cycle progression and cyclin D1 gene expression in MCF-7 human breast cancer cells. Breast Cancer Res Treat 1994; 31:95-105.
49. Zhou Q, Stetler-Stevenson M, Steeg PS. Inhibition of cyclin D expression in human breast carcinoma cells by retinoids in vitro. Oncogene 1997;15: 107-15.
50. Adams J, Palombella VJ, Sausville EA, Johnson J, Destree A, Lazarus DD, et al. Proteasome inhibitors: a novel class of potent and effective antitumor agents. Cancer Res 1999;59:2615-22.
51. Wang Q, Fan S, Eastman A, Worland PJ, Sausville EA, O'Connor P. UCN-01: a potent abrogator of G2 checkpoint function in cancer cells with disrupted p53. J Natl Cancer Inst 1996;88:956-65.
52. Roberge M, Berlinck RG, Xu L, Anderson HJ, Lim LY, Curman D, et al. High-throughput assay for G2 checkpoint inhibitors and identification of the structurally novel compound isogranulatimide. Cancer Res 1998;58: 5701-6.
53. Carlson BA, Dubay MM, Sausville EA, Brizuela L, Worland PJ. Flavo-piridol induces G1 arrest with inhibition of cyclin-dependent kinase (CDK) 2 and CDK4 in human breast carcinoma cells. Cancer Res 1996; 56:2973-8.
54. Losiewicz MD, Carlson BA, Kaur G, Sausville EA, Worland PJ. Potent inhibition of CDC2 kinase activity by the flavonoid L86-8275. Biochem Biophys Res Commun 1994;201:589-95.
55. Singh SS, Sausville EA, Senderowicz AM. Cyclin D1 and Cdk6 are the targets for flavopiridol-mediated G1 block in MCF10A breast epithelial cell line [abstract]. Proc Am Assoc Cancer Res 1999;40:28.
56. Meijer L, Pondaven P. Cyclic activation of histone H1 kinase during sea urchin egg mitotic divisions. Exp Cell Res 1988;174:116-29.
57. Rialet V, 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 1991;11:1581-90.
58. Schulze-Gahmen U, Brandsen J, Jones HD, Morgan DO, Meijer L, Vesely J, et al. Multiple modes of ligand recognition: crystal structures of cyclin-dependent protein kinase 2 in complex with ATP and two inhibitors, olomoucine and isopentenyladenine. Proteins 1995;22:378-91.
59. Brooks EE, Gray NS, Joly A, Kerwar SS, Lum R, Mackman RL, et al. CVT-313, a specific and potent inhibitor of CDK2 that prevents neointimal proliferation. J Biol Chem 1997;272:29207-11.
60. Gray NS, Wodicka L, Thunnissen AM, Norman TC, Kwon S, Espinoza FH, et al. Exploiting chemical libraries, structure, and genomics in the search for kinase inhibitors. Science 1998;281:533-8.
61. Paull KD, Shoemaker RH, Hodes L, Monks A, Scudiero DA, Rubinstein L, et al. Display and analysis of patterns of differential activity of drugs against human tumor cell lines: development of mean graph and COMPARE algorithm. J Natl Cancer Inst 1989;81:1088-92.
62. van den Heuvel S, Harlow E. Distinct roles for cyclin-dependent kinases in cell cycle control. Science 1993;262:2050-4.
63. Buquet-Fagot C, Lallemand F, Montagne MN, Mester J. Effects of olomucine, a selective inhibitor of cyclin-dependent kinases, on cell cycle progression in human cancer cell lines. Anticancer Drugs 1997;8: 623-31.
64. Meijer L, Borgne A, Mulner O, Chong JP, Blow JJ, Inagaki N, et al. Biochemical and cellular effects of roscovitine, a potent and selective inhibitor of the cyclin-dependent kinases cdc2, cdk2 and cdk5. Eur J Biochem 1997;243:527-36.
65. Parker BW, Kaur G, Nieves-Neira W, Taimi M, Kolhagen G, Shimizu T, et al. Early induction of apoptosis in hematopoietic cell lines after exposure to flavopiridol. Blood 1998;91:458-65.
66. Park DS, Farinelli SE, Greene LA. Inhibitors of cyclin-dependent kinases promote survival of post-mitotic neuronally differentiated PC12 cells and sympathetic neurons. J Biol Chem 1996;271:8161-9.
67. Park DS, Morris EJ, Greene LA, Geller HM. GI/S cell cycle blockers and inhibitors of cyclin-dependent kinases suppress camptothecin-induced neuronal apoptosis. J Neurosci 1997;17:1256-70.
68. Meikrantz W, Schlegel R. Suppression of apoptosis by dominant negative mutants of cyclin-dependent protein kinases. J Biol Chem 1996;271: 10205-9.
69. Gervais JL, Seth P, Zhang H. Cleavage of CDK inhibitor p21(Cip1/Waf1) by caspases is an early event during DNA damage-induced apoptosis. J Biol Chem 1998;273:19207-12.
70. Levkau B, Koyama H, Raines EW, Clurman BE, Herren B, Orth K, et al. Cleavage of p21Cip1/Waf1 and p27Kip1 mediates apoptosis in endothelial cells through activation of Cdk2: role of a caspase cascade. Mol Cell 1998;1:553-63.
71. Zhou BB, Li H, Yuan J, Kirschner MW. Caspase-dependent activation of cyclin-dependent kinases during Fas-induced apoptosis in Jurkat cells. Proc Natl Acad Sci U S A 1998:95:6785-90.
72. rd, Senderowicz AM, Szabo E. Induction of differentiation accompanies inhibition of cdk2 in a non-small cell lung cancer cell line. Int J Oncol 1999;15:161-6.
73. Rosania GR, Merlie J Jr, Gray N, Chang YT, Schultz PG, Heald R. A cyclin-dependent kinase inhibitor inducing cancer cell differentiation: biochemical identification using Xenopus egg extracts. Proc Natl Acad Sci USA 1999;96:4797-802.
74. Liu M, Subramanyam YV, Baskaran N. Preparation and analysis of cDNA from a small number of hematopoietic cells. Methods Enzymol 1999;303:45-55.
75. Sedlacek HH, Czech J, Naik R, Kaur G, Worland P, Losiewicz M, et al. Flavopiridol (L86-8275, NSC-649890), a new kinase inhibitor for tumor therapy. Int J Oncol 1996;9:1143-68.
76. Kaur G, Stetler-Stevenson M, Sebers S, Worland P, Sedlacek H, Myers C, et al. Growth inhibition with reversible cell cycle arrest of carcinoma cells by flavone L86-8275. J Natl Cancer Inst 1992;84:1736-40.
77. Carlson B, Pearlstein R, Naik R, Sedlacek H, Sausville E, Worland P. Inhibition of CDK2, CDK4 and CDK7 by flavopiridol and structural analogs [abstract]. Proc Am Assoc Cancer Res 1996;37:424.
78. Worland PJ, Kaur G, Stetler-Stevenson M, Sebers S, Sartor O, Sausville EA. Alteration of the phosphorylation state of p34cdc2 kinase by the flavone L86-8275 in breast carcinoma cells. Correlation with decreased H1l kinase activity. Biochem Pharmacol 1993;46:1831-40.
79. De Azevedo WF Jr, Mueller-Dieckmann HJ, Schulze-Gahmen U, Worland PJ, Sausville E, Kim SH. Structural basis for specificity and potency of a flavonoid inhibitor of human CDK2, a cell cycle kinase. Proc Natl Acad Sei U S A 1996;93:2735-40.
80. Michalides R, van Veelen N, Hart A, Loftus B, Wientjens E, Balm A. Overexpression of cyclin D1 correlates with recurrence in a group of forty-seven operable squamous cell carcinomas of the head and neck. Cancer Res 1995;55:975-8.
81. Gansauge S, Gansauge F, Ramadani M, Stobbe H, Rau B, Harada N, et al. Overexpression of cyclin D1 in human pancreatic carcinoma is associated with poor prognosis. Cancer Res 1997;57:1634-7.
82. Fredersdorf S, Burns J, Milne AM, Packham G, Fallis L, Gillett CE, et al. High level expression of p27(kip1) and cyclin D1 in some human breast cancer cells: inverse correlation between the expression of p27(kip1) and degree of malignancy in human breast and colorectal cancers. Proc Natl Acad Sci USA 1997;94:6380-5.
83. Carlson B, Lahusen T, Singh S, Loaiza-Perez A, Worland PJ, Pestell R, et al. Downregulation of cyclin D1 by transcriptional repression in MCF-7 human breast carcinoma cells induced by flavopiridol. Cancer Res 1999; 59:4634-11.
84. Arguello F, Alexander M, Sterry JA, Tudor G, Smith EM, Kalavar NT, et al. Flavopiridol induces apoptosis of normal lymphoid cells, causes immunosuppression, and has potent antitumor activity in vivo against human leukemia and lymphoma xenografts. Blood 1998;91:2482-90.
85. Byrd JC, Shinn C, Waselenko JK, Fuchs EJ, Lehman TA, Nguyen PL, et al. Flavopiridol induces apoptosis in chronic lymphocytic leukemia cells via activation of caspase-3 without evidence of bcl-2 modulation or dependence on functional p53. Blood 1998;92:3804-16.
86. Konig A, Schwartz GK, Mohammad RM, Al-Katib A, Gabrilove JL. The novel cyclin-dependent kinase inhibitor flavopiridol downregulates Bcl-2 and induces growth arrest and apoptosis in chronic B-cell leukemia lines. Blood 1997;90:4307-12.
87. Patel V, Senderowicz AM, Pinto D Jr, Igishi T, Raffeld M, Quintanilla-Martinez L, et al. Flavopiridol, a novel cyclin-dependent kinase inhibitor, suppresses the growth of head and neck squamous cell carcinomas by inducing apoptosis. J Clin Invest 1998;102:1674-81.
88. Chien M, Astumian M, Liebowitz D, Rinker-Schaeffer C, Stadler W. In vitro evaluation of flavopiridol, a novel cell cycle inhibitor, in bladder cancer. Cancer Chemother Pharmacol 1999;44:81-7.
89. Schrump DS, Matthews W, Chen GA, Mixon A, Altorki NK. Flavopiridol mediates cell cycle arrest and apoptosis in esophageal cancer cells. Clin Cancer Res 1998;4:2885-90.
90. Bible KC, Kaufmann SH. Flavopiridol: a cytotoxic flavone that induces cell death in noncycling A549 human lung carcinoma cells. Cancer Res 1996;56:4856-61.
91. Brusselbach S, Nettelbeck DM, Sedlacek HH, Muller R. Cell cycle-independent induction of apoptosis by the anti-tumor drug flavopiridol in endothelial cells. Int J Cancer 1998;77:146-52.
92. Kerr JS, Wexler RS, Mousa SA, Robinson CS, Wexler EJ, Mohamed S, et al. Novel small molecule alpha v integrin antagonists: comparative anti-cancer efficacy with known angiogenesis inhibitors. Anticancer Res 1999;19:959-68.
93. Melillo G, Sausville EA, Cloud K, Lahusen T, Varresio L, Senderowicz A. Flavopiridol, a protein kinase inhibitor, down-regulates hypoxic induction of vascular endothelial growth factor expression in human monocytes. Cancer Res 1999;59:5433-7.
94. Schwartz G, Farsi K, Maslak P, Kelsen D, Spriggs D. Potentiation of apoptosis by flavopiridol in mitomycin-C-treated gastric and breast cancer cells. Clin Cancer Res 1997;3:1467-72.
95. Bible KC, Kaufmann SH. Cytotoxic synergy between flavopiridol (NSC 649890, L86-8275) and various antineoplastic agents: the importance of sequence of administration. Cancer Res 1997;57:3375-80.
96. Senderowicz AM, Headlee D, Stinson SF, Lush RM, Kalil N, Villalba L, et al. Phase I trial of continuous infusion flavopiridol, a novel cyclin-dependent kinase inhibitor, in patients with refractory neoplasms. J Clin Oncol 1998;16:2986-99.
97. Jager W, Zembsch B, Wolschann P, Pittenauer E, Senderowicz AM, Sausville E, et al. Metabolism of the anticancer drug flavopiridol, a new inhibitor of cyclin dependent kinases, in rat liver. Life Sci 1998;62:1861-73.
98. Lush R, Stinson S, Senderowicz A, Hill K, Feuer J, Headlee D, et al. Flavopiridol pharmacokinetics suggest entoerohepatic circulation. Clin Pharmacol Ther 1997;61:145.
99. Thomas J, Cleary J, Tutsch K, Arzoomanian R, Alberti D, Simon K, et al. Phase I clinical and pharmacokinetic trial of flavopiridol [abstract]. Proc Am Assoc Cancer Res 1997;38:222.
100. Schwartz G, Kaubisch A, Saltz L, Ilson D, O'Reilly E, Barazzuol J, et al. Phase I trial of sequential paclitaxel and the cyclin-dependent kinase inhibitor flavopiridol [abstract]. Proc ASCO 1999;18:160a.
101. Wright J, Blatner GL, Cheson BD. Clinical trials referral resource. Clinical trials of flavopiridol. Oncology (Huntingt) 1998;12:1018, 23-4.
102. Werner J, Kelsen D, Karpeh M, Inzeo D, Barazzuol J, Sugarman A, et al. The cyclin-dependent kinase inhibitor flavopiridol is an active and unexpectedly toxic agent in advanced gastric cancer [abstract]. Proc ASCO 1998;17:234a.
103. Shapiro G, Patterson A, Lynch C, Lucca J, Anderson I, Boral A, et al. A phase II trial of flavopiridol in patients with stage IV non-small cell lung cancer [abstract]. Proc ASCO 1999;18:522a.
104. Bennett S, Mani S, O'Reilly S, Wright J, Schilsky R, Vokes E, et al. Phase II trial of flavopiridol in metastatic colorectal cancer: preliminary results [abstract]. Proc ASCO 1999;18:277a.
105. Tamaoki T. Use and specificity of staurosporine, UCN-01, and calphostin C as protein kinase inhibitors. Methods Enzymol 1991;201:340-7.
106. Takahashi I, Kobayashi E, Asano K, Yoshida M, Nakano H. UCN-01, a selective inhibitor of protein kinase C from Streptomyces. J Antibiot (Tokyo) 1987;40:1782-4.
107. Takahashi I, Saitoh Y, Yoshida M, Sano H, Nakano H, Morimoto M, et al. UCN-01 and UCN-02, new selective inhibitors of protein kinase C. II. Purification, physico-chemical properties, structural determination and biological activities. J Antibiot (Tokyo) 1989;42:571-6.
108. Seynaeve CM, Kazanietz MG, Blumberg PM, Sausville EA, Worland PJ. Differential inhibition of protein kinase C isozymes by UCN-01, a staurosporine analogue. Mol Pharmacol 1994;45:1207-14.
109. Seynaeve CM, Stetler-Stevenson M, Sebers S, Kaur G, Sausville EA, Worland PJ. Cell cycle arrest and growth inhibition by the protein kinase antagonist UCN-01 in human breast carcinoma cells. Cancer Res 1993; 53:2081-6.
110. Wang Q, Worland PJ, Clark JL, Carlson BA, Sausville EA. Apoptosis in 7-hydroxystaurosporine-treated T lymphoblasts correlates with activation of cyclin-dependent kinases 1 and 2. Cell Growth Differ 1995;6:927-36.
111. Akinaga S, Gomi K, Morimoto M, Tamaoki T, Okabe M. Antitumor activity of UCN-01, a selective inhibitor of protein kinase C, in murine and human tumor models. Cancer Res 1991;51:4888-92.
112. Akinaga S, Nomura K, Gomi K, Okabe M. Effect of UCN-01, a selective inhibitor of protein kinase C, on the cell-cycle distribution of human epidermoid carcinoma, A431 cells. Cancer Chemother Pharmacol 1994; 33:273-80.
113. Akiyama T, Yoshida T, Tsujita T, Shimizu M, Mizukami T, Okabe M, et al. G1 phase accumulation induced by UCNI-01 is associated with dephosphorylation of Rb and CDK2 proteins as well as induction of CDK inhibitor p21/Cip1/WAF1/Sdi1 in p53-mutated human epidermoid carcinoma A431 cells. Cancer Res 1997;57:1495-501.
114. Yu L, Orlandi L, Wang P, Orr M, Senderowicz AM. Sausville EA, et al. UCN-01 abrogates G2 arrest through a cdc2-dependent pathway that is associated with inactivation of the WeelHu kinase and activation of the Cdc25C phosphatase. J Biol Chem 1998;273:33455-64.
115. Bunch RT, Eastman A. 7-Hydroxystaurosporine (UCN-01) causes redistribution of proliferating cell nuclear antigen and abrogates cisplatin-induced S-phase arrest in Chinese hamster ovary cells. Cell Growth Differ 1997;8:779-88.
116. Akinaga S, Nomura K, Gomi K, Okabe M. Enhancement of antitumor activity of mitomycin C in vitro and in vivo by UCN-01, a selective inhibitor of protein kinase C. Cancer Chemother Pharmacol 1993;32: 183-9.
117. Bunch RT, Eastman A. Enhancement of cisplatin-induced cytotoxicity by 7-hydroxystaurosporine (UCN-01), a new G2-checkpoint inhibitor. Clin Cancer Res 1996;2:791-7.
118. Hsueh CT, Kelsen D, Schwartz GK. UCN-01 suppresses thymidylate synthase gene expression and enhances 5-fluorouracil-induced apoptosis in a sequence-dependent manner. Clin Cancer Res 1998;4:2201-6.
119. Husain A, Yan XJ, Rosales N, Aghajanian C, Schwartz GK, Spriggs DR. UCN-01 in ovary cancer cells: effective as a single agent and in combination with cis-diamminedichloroplatinum(II)independent of p53 status. Clin Cancer Res 1997;3:2089-97.
120. Pollack IF, Kawecki S, Lazo JS. Blocking of glioma proliferation in vitro and in vivo and potentiating the effects of BCNU and cisplatin: UCN-01, a selective protein kinase C inhibitor. J Neurosurg 1996;84:1024-32.
121. Shao RG, Cao CX, Shimizu T, O'Connor PM, Kohn KW, Pommier Y. Abrogation of an S-phase checkpoint and potentiation of camptothecin cytotoxicity by 7-hydroxystaurosporine (UCN-01) in human cancer cell lines, possibly influenced by p53 function. Cancer Res 1997;57:4029-35.
122. Tsuchida E, Urano M. The effect of UCN-01 (7-hydroxystaurosporine), a potent inhibitor of protein kinase C, on fractionated radiotherapy or daily chemotherapy of a murine fibrosarcoma. Int J Radiat Oncol Biol Phys 1997;39:1153-61.
123. Akiyama T, Shimizu M, Okabe M, Tamaoki T, Akinaga S. Differential effects of UCN-01, staurosporine and CGP 41 251 on cell cycle progression and CDC2/cyclin B1 regulation in A431 cells synchronized at M phase by nocodazole. Anticancer Drugs 1999;10:67-78.
124. Kawakami K, Futami H, Takahara J, Yamaguchi K. UCN-01, 7-hydroxylstaurosporine. inhibits kinase activity of cyclin-dependent kinases and reduces the phosphorylation of the retinoblastoma susceptibility gene product in A549 human lung cancer cell line. Biochem Biophys Res Commun 1996;219:778-83.
125. Shimizu E, Zhao MR, Nakanishi H, Yamamoto A, Yoshida S, Takada M, et al. Differing effects of staurosporine and UCN-01 on RB protein phosphorylation and expression of lung cancer cell lines. Oncology 1996;53: 494-504.
126. Courage C, Bradder SM, Jones T, Schultze-Mosgau MH, Gescher A. Characterisation of novel human lung carcinoma cell lines selected for resistance to anti-neoplastic analogues of staurosporine. Int J Cancer 1997;73:763-8.
127. Kurata N, Kuwabara T, Tanii H, Fuse E, Akiyama T, Akinaga S, et al. Pharmacokinetics and pharmacodynamics of a novel protein kinase inhibitors, UCN-01. Cancer Chemother Pharmacol 1999;44:12-8.
128. th National Cancer Institute-European Organization for Research on Treatment of Cancer Symposium Proceedings. Dordrecht (The Netherlands): Kluwer Academic Publishers; 1998. p. 111.
129. Sausville EA, Lush RD, Headlee D, Smith AC, Figg WD, Arbuck SG, et al. Clinical pharmacology of UCN-01: initial observations and comparison to preclinical models. Cancer Chemother Pharmacol 1998;42 Suppl:S54-9.
130. Fuse E, Tanii H, Kurata N, Kobayashi H, Shimada Y, Tamura T, et al. Unpredicted clinical pharmacology of UCN-01 caused by specific binding to human alphal-acid glycoprotein. Cancer Res 1998;58:3248-53.
131. Senderowicz AM, Headlee D, Lush R, Bauer K, Figg W, Murgo AS, et al. Phase I trial of infusional UCN-01, a novel protein kinase inhibitor, in patients with refractory neoplasms [abstract]. Proc ASCO 1999;18:159a.
132. Tamura T, Sasaki Y, Minami H, Fujii H, Ito K, Igarashi T, et al. Phase I study of UCN-01 by 3-hour infusion [abstract]. Proc ASCO 1999;18: 159a.