Selective protein kinase C inhibitors and their applications

Current Drug Targets - Cardiovascular and Haematological Disorders

Volumn 3, Issue 4, 2003, Pages 301-307

  Shen, Garry X ^a  

^a UNIVERSITY OF MANITOBA   (Canada)

Author keywords

Cancer therapy; Diabetic vascular complications; Gene therapy; Inhibitors for PKC isoforms; Protein kinase C (PKC)

Indexed keywords

2 (2 CHLORO 4 IODOANILINO) N CYCLOPROPYLMETHOXY 3,4 DIFLUOROBENZAMIDE; 2 [1 (3 AMIDINOTHIOPROPYL) 1H INDOL 3 YL] 3 (1 METHYL 1H INDOL 3 YL)MALEIMIDE; 2 [1 (3 DIMETHYLAMINOPROPYL) 3 INDOLYL] 3 (3 INDOLYL)MALEIMIDE; 2 [1 (3 DIMETHYLAMINOPROPYL) 5 METHOXY 1H INDOL 3 YL] 3 (1H INDOL 3 YL)MALEIMIDE; 7 HYDROXYSTAUROSPORINE; ADENOVIRUS VECTOR; ANTISENSE OLIGONUCLEOTIDE; CALPHOSTIN C; DOXORUBICIN; ENZYME INHIBITOR; FLUOROURACIL; ISIS 3251; ISIS 3521; LY 379196; MIDOSTAURIN; PHOSPHOLIPID; PROTEIN KINASE C; PROTEIN KINASE C ALPHA; PROTEIN KINASE C BETA; PROTEIN KINASE C DELTA; PROTEIN KINASE C EPSILON; PROTEIN KINASE C INHIBITOR; PROTEIN SERINE THREONINE KINASE; RIBOZYME; RO 317208; ROTTLERIN; RUBOXISTAURIN; SAFINGOL; SPHINGOSINE; STAUROSPORINE; STAUROSPORINE DERIVATIVE; UNCLASSIFIED DRUG; UNINDEXED DRUG; VIRUS VECTOR;

ALOPECIA; BLADDER CARCINOMA; CELL ACTIVITY; CHRONIC LYMPHATIC LEUKEMIA; CLINICAL TRIAL; COLORECTAL CANCER; DIABETES MELLITUS; DIABETIC ANGIOPATHY; DIABETIC NEPHROPATHY; DIABETIC RETINOPATHY; DIARRHEA; DISEASE COURSE; DISEASE MODEL; DRUG EFFICACY; DRUG SAFETY; DRUG SELECTIVITY; DRUG STRUCTURE; ECZEMA; ENZYME ACTIVATION; ENZYME ANALYSIS; ENZYME SPECIFICITY; FATIGUE; GASTROINTESTINAL DISEASE; GENE THERAPY; GROWTH RETARDATION; HUMAN; HYPERGLYCEMIA; HYPOTENSION; LETHARGY; LUNG DISEASE; LUNG NON SMALL CELL CANCER; MALIGNANT NEOPLASTIC DISEASE; MELANOMA; METABOLIC ACIDOSIS; METASTASIS INHIBITION; MUCOSA INFLAMMATION; NAUSEA AND VOMITING; NEUTROPENIA; NONHODGKIN LYMPHOMA; NONHUMAN; PROSTATE CANCER; PROTEIN FAMILY; REVIEW; RISK ASSESSMENT; SIGNAL TRANSDUCTION; SOLID TUMOR; TISSUE SPECIFICITY; VASCULAR ENDOTHELIUM; VASODILATATION;

ANIMALS; DIABETIC ANGIOPATHIES; ENZYME INHIBITORS; GENE THERAPY; HUMANS; ISOENZYMES; NEOPLASMS; PROTEIN KINASE C;

EID: 0346957401     PISSN: 15680061     EISSN: None     Source Type: Journal    
DOI: 10.2174/1568006033481375     Document Type: Review

References (82)

1. Newton, A.C. Protein kinase C: structural and spatial regulation by phosphorylation, cofactors, and macromolecular interactions. Chem. Rev., 2001, 101, 2353-2364.
2. Inoue, M., Kishimoto, A., Takai, Y. and Nishizuka, Y. Studies on a cyclic nucleotide-independent protein kinase and its proenzyme in mammalian tissues. II. Proenzyme and its activation by calcium-dependent protease from rat brain. J. Biol. Chem., 1977, 232, 7610-7616.
3. Mochly-Rosen, D. and Kauvar, L.M. Modulating protein kinase C signal transduction. Adv. Pharmacol., 108, 44, 91-145.
4. Naor, Z., Benard, O. and Seger, R. Activation of MAPK cascades by G-protein-coupled receptors: the case of gonadotropin-releasing hormone receptor. Trends Endocrinol. Metab., 2000, 11,91-99.
5. Wooten, M.W., Seibenhener, M.L., Neidigh, K.B. and Vandenplas, M.L. Mapping of atypical protein kinase C within the nerve growth factor signaling cascade: relationship to differentiation and survival of PC12 cells. Mol. Cell Biol., 2000, 20, 4494-4504.
6. Kawamoto, S. and Hidaka, H. 1-(5-Isoquinolinesulfonyl)-2-methylpiperazine (H-7) is a selective inhibitor of protein kinase C in rabbit platelets. Biochem. Biophys. Res. Commun., 1984, 125, 258-264.
7. Shen, X.Y., Hamilton, T.A. and DiCorleto, P.E. Lipopolysaccharide-induced expression of the competence gene KC in vascular endothelial cells is mediated through protein kinase C. J. Cell Physiol. 1989, 140, 44-51.
8. Tamaoki, T., Nomoto, H., Takahashi, I., Kato, Y., Morimoto, M. and Tomita, F. Staurosporine, a potent inhibitor of phospholipid/Ca++dependent protein kinase. Biochem. Biophys. Res. Commun., 1986, 135, 397-402.
9. Casnellie, J.E. Protein kinase inhibitors: probes for the functions of protein phosphorylation. Adv. Pharmacol., 1991, 22, 167-205.
10. Buchholz, R.A., Dundore, R.L., Cumiskey W.R. Harris, A.L. and Silver, P.J. Protein kinase inhibitors and blood pressure control in spontaneously hypertensive rats. Hypertension, 1991, 17, 91-100.
11. Kobayashi, E., Nakano, H., Morimoto, M. and Tamaoki, T. Calphostin C (UCN-1028C), a novel microbial compound, is a highly potent and specific inhibitor of protein kinase C. Biochem. Biophys. Res. Commun., 1989, 159, 548-553.
12. Borek, C., Ong, A., Stevens, V.L., Wang, E. and Merrill, A.H. Jr. Long-chain (sphingoid) bases inhibit multistage carcinogenesis in mouse C3H/10T1/2 cells treated with radiation and phorbol 12-myristate 13-acetate. Proc. Natl. Acad. Sci. USA., 1991, 88, 1953-1957.
13. Kedderis, L.B., Bozigian, H.P., Kleeman, J.M., Hall, R.L., Palmer, T.E., Harrison, S.D., Jr. and Susick, R.L., Jr. Toxicity of the protein kinase C inhibitor safingol administered alone and in combination with chemotherapeutic agents. Fundam Appl. Toxicol., 1995, 25, 201-217.
14. Mizuno, K., Saido, T.C., Ohno, S., Tamaoki, T. and Suzuki, K. Staurosporine-related compounds, K252a and UCN-01, inhibit both cPKC and nPKC. FEBS Lett., 1993, 330, 114-116.
15. Meyer, T., Regenass, U., Fabbro, D., Alteri, E., Rosel, J., Muller, M., Caravatti, G. and Matter, A. Int. J. A derivative of staurosporine (CGP 41 251) shows selectivity for protein kinase C inhibition and in vitro anti-proliferative as well as in vivo anti-tumor activity. Cancer, 1989, 43, 851-856.
16. Seynaeve, C.M., Stetler-Stevenson, M., Sehers, S. Kaur, G., Sausville, E.A. and Worland, P.J. Cell cycle arrest and growth inhibition by the protein kinase antagonist UCN-01 in human breast carcinoma cells. Cancer Res., 1993, 53, 2081-2086.
17. Seynaeve, C.M., Kazanietz, M.G., Blumberg, P.M., Sausville, E.A. and Worland, P.J. Differential inhibition of protein kinase C isozymes by UCN-01, a staurosporine analogue. Mol. Pharmacol., 1994, 45, 1207-1214.
18. Dai, Y., Yu, C., Singh, V., Tang, L., Wang, Z., McInistry, R., Dent, P. and Grant, S. Pharmacological inhibitors of the mitogen-activated protein kinase (MAPK) kinase/MAPK cascade interact synergistically with UCN-01 to induce mitochondrial dysfunction and apoptosis in human leukemia cells. Cancer Res., 2001, 61, 5106-5115.
19. Marte, B.M., Meyer, T., Stabel, S., Standke, G.J., Jaken, S., Fabbro, D. and Hynes, N.E. Protein kinase C and mammary cell differentiation: involvement of protein kinase C alpha in the induction of beta-casein expression. Cell Growth Differ., 1994, 5, 239-247.
20. Fabbro, D., Ruetz, S., Bodis, S., Pruschy, M., Csermak, K., Man, A., Campochiaro, P., Wood, J., O'Reilly, T. and Meyer, T. PKC412 - a protein kinase inhibitor with a broad therapeutic potential. Anticancer Drug Des., 2000, 15, 17-28.
21. Martiny-Baron, G., Kazanietz, M.G., Mischak, H., Blumberg, P.M., Kochs, G., Hug, H., Marme, D. and Schachtele, C. Selective inhibition of protein kinase C isozymes by the indolocarbazole Go 6976. J. Biol. Chem., 1993, 268, 9194-9197.
22. Wilkinson, S.E., Parker, P.J. and Nixon, J.S. Isoenzyme specificity of bisindolylmaleimides, selective inhibitors of protein kinase C. Biochem. J., 1993, 294 ( Pt 2), 335-337.
23. Courage, C., Snowden, R. and Gescher, A. Differential effects of staurosporine analogues on cell cycle, growth and viability in A549 cells. Br. J. Cancer, 1996, 74, 1199-1205.
24. Teicher, B.A., Alvarez, E., Mendelsohn, L.G., Ara, G., Menon, K. and Ways, D.K. Enzymatic rationale and preclinical support for a potent protein kinase C beta inhibitor in cancer therapy. Adv. Enzyme Regul., 1999, 39, 313-327.
25. Jirousek, M.R., Gillig, J.R., Gonzalez, C.M., Heath, W.F. and McDonald, J.H. 3rd, Neel, D.A., Rito, C.J., Singh, U., Stramm, L.E., Melikian-Badalian, A., Baevsky, M., Ballas, L.M., Hall, S.E., Winneroski, L.L., Faul, M.M. (S)-13-[(dimethylamino)methyl]-10,11,14,15-tetrahydro-4,9:16, 21-dimetheno-1H, 13H-dibenzo[e,k]pyrrolo[3,4-h][1,4,13]oxadiazacyclohexadecene-1,3(2H)-d ione (LY333531) and related analogues: isozyme selective inhibitors of protein kinase C beta. J. Med. Chem., 1996, 39, 2664-2671.
26. Way, K.J., Chou, E. and King, G.L. Identification of PKC-isoform-specific biological actions using pharmacological approaches. Trends. Pharmacol. Sci., 2000, 21, 181-187.
27. Ren, S., Shatadal, S. and Shen, G.X. Protein kinase C-beta mediates lipoprotein-induced generation of PAI-1 from vascular endothelial cells. Am. J. Physiol., 2000, 278, E656-E662.
28. Ishii, H., Jirousek, M.R., Koya, D., Takagi, C., Xia, P., Clermont, A., Bursell, S.E., Kern, T.S., Ballas, L.M., Heath, W.F, Stramm, L.E., Feener, E.P. and King, G.L. Amelioration of vascular dysfunctions in diabetic rats by an oral PKC beta inhibitor. Science, 1996, 272, 728-731.
29. Bursell, S.E., Takagi, C., Clermont, A.C., Takagi, H., Mori, F., Ishii, H. and King, G.L. Specific retinal diacylglycerol and protein kinase C beta isoform modulation mimics abnormal retinal hemodynamics in diabetic rats. Invest. Ophthalmol. Vis. Sci., 1997, 38, 2711-2720.
30. Kowluru, R.A., Jirousek, M.R., Stramm, L., Farid, N., Engerman, R.L. and Kern, T.S. Abnormalities of retinal metabolism in diabetes or experimental galactosemia: V. Relationship between protein kinase C and ATPases. Diabetes, 1998, 47, 464-469.
31. Nonaka, A., Kiryu, J., Tsujikawa, A., Yamashiro, K., Miyamoto, K., Nishiwaki, H., Honda, Y. and Ogura, Y. Regulation of endothelial constitutive nitric oxide synthase gene expression in endothelial cells and in vivo : a specific vascular action of insulin Invest. Ophthalmol. Vis. Sci., 2000, 41, 2702-2706.
32. Xia, P., Aiello, L.P., Ishii, H., Jiang, Z.Y., Park, D.J., Robinson, G.S., Takagi, H., Newsome, W.P., Jirousek, M.R. and King, G.L. Regulation of endothelial constitutive nitric oxide synthase gene expression in endothelial cells and in vivo: a specific vascular action of insulin J. Clin. Invest., 1996, 98, 2018-2026.
33. Kuboki, K., Jiang, Z.Y., Takahara, N., Ha, S.W., Igarashi, M., Yamauchi, T., Feener, E.P., Herbert, T.P., Rhodes, C.J. and King, G.L. Regulation of endothelial constitutive nitric oxide synthase gene expression in endothelial cells and in vivo: a specific vascular action of insulin Circ., 2000, 101, 676-681.
34. Chen, S., Apostolova, M.D., Cherian, M.G. and Chakrabarti, S. Interaction of endothelin-1 with vasoactive factors in mediating glucose-induced increased permeability in endothelial cells. Lab. Invest., 2000, 80,1311-1321.
35. Koya, D., Jirousek, M.P., Lin, Y.W., Ishii, H., Kuboki, K. and King, G.L. Characterization of protein kinase C beta isoform activation on the gene expression of transforming growth factor-beta, extracellular matrix components, and prostanoids in the glomeruli of diabetic rats. J. Clin. Invest., 1997, 100, 115-126.
36. Yasuda, Y., Nakamura, J., Hamada, Y., Nakayama, M., Chaya, S., Naruse, K., Nakashima, E., Kato, K., Kamiya, H. and Hotta, N. Role of PKC and TGF-beta receptor in glucose-induced proliferation of smooth muscle cells. Biochem. Biophys. Res. Commun., 2001, 281, 71-77.
37. Cohen, M.P., Ziyadeh, F.N., Lautenslager, G.T., Cohen, J.A. and Shearman, C.W. Glycated albumin stimulation of PKC-beta activity is linked to increased collagen IV in mesangial cells. Am. J. Physiol., 1999, 276, F684-F690.
38. Ido, Y., Chang, K.C., Lejeune, W.S., Bjercke, R.J., Reiser, K.M., Williamson, J.R. and Tilton, R.G. Vascular dysfunction induced by AGE is mediated by VEGF via mechanisms involving reactive oxygen species, guanylate cyclase, and protein kinase C. Microcirculation, 2001, 8, 251-263.
39. Efendiev, R., Bertorello, A.M. and Pedemonte, C.H. PKC-beta and PKC-zeta mediate opposing effects on proximal tubule Na+,K+-ATPase activity. FEBS Lett., 1999, 456, 45-48.
40. Nakamura, J., Kato, K., Hamada, Y., Nakayama, M., Chaya, S., Nakashima, E., Naruse, K., Kasuya, Y., Mizubayashi, R., Miwa, K., Yasuda, Y., Kamiya, H., Ienaga, K., Sakakibara, F., Koh, N. and Hotta, N. A protein kinase C-beta-selective inhibitor ameliorates neural dysfunction in streptozotocin-induced diabetic rats. Diabetes, 1999, 48, 2090-2095.
41. Cotter, M.A., Jack, A.M. and Cameron, N.E. Effects of the protein kinase Cbeta inhibitor LY333531 on neural and vascular function in rats with streptozotocin-induced diabetes. Clin. Sci. (Lond.), 2002, 103, 311-321.
42. Nakamura, J., Kasuya, Y., Hamada, Y., Nakashima, E., Naruse, K., Yasuda, Y., Kato, K. and Hotta, N. Glucose-induced hyperproliferation of cultured rat aortic smooth muscle cells through polyol pathway hyperactivity. Diabetologia, 2001, 44, 480-487.
43. Ling, S., Little, P.J., Williams, M.R., Dai, A., Hashimura, K., Liu, J.P., Komesaroff, P.A. and Sudhir, K. High glucose abolishes the antiproliferative effect of 17beta-estradiol in human vascular smooth muscle cells. Am. J. Physiol. Endocrinol. Metab., 2002, 282, E746-E751.
44. Samokhin, G.P., Jirousek, M.R., Ways, D.K. and Henriksen, R.A. Effects of protein kinase C inhibitors on thromboxane production by thrombin-stimulated platelets. Eur. J. Pharmacol., 1999, 386, 297-303.
45. Lin, W.W. and Chen, B.C. Distinct PKC isoforms mediate the activation of cPLA2 and adenylyl cyclase by phorbol ester in RAW264.7 macrophages. Br. J. Pharmacol., 1998, 125, 1601-1609.
46. Lagaud, G.J., Masih-Khan E., Kai, S., van Breemen, C. and Dube, G.P. Influence of type II diabetes on arterial tone and endothelial function in murine mesenteric resistance arteries. J. Vasc. Res., 2001, 38, 578-589.
47. Kowluru, R.A. Diabetes-induced elevations in retinal oxidative stress, protein kinase C and nitric oxide are interrelated. Acta Diabetol., 2001, 38. 179-185.
48. Yoshiji, H., Kuriyama, S., Ways, D.K., Yoshii, J., Miyamoto, Y., Kawata, M., Ikenaka, Y., Tsujinoue, H., Nakatani, T., Shibuya, M. and Fukui, H. Protein kinase C lies on the signaling pathway for vascular endothelial growth factor-mediated tumor development and angiogenesis. Cancer Res., 1999, 59, 4413-4418.
49. Chen, B.C. and Lin, W.W. PKCbetaI mediates the inhibition of P2Y receptor-induced inositol phosphate formation in endothelial cells. Br. J. Pharmacol., 1999, 127, 1908-1914.
50. Wen, H.C. and Lin, W.W. Basal cPLA(2) phosphorylation is sufficient for Ca(2+)-induced full activation of cPLA(2) in A549 epithelial cells. J. Cell Biochem., 2000, 79, 601-609.
51. Gschwendt, M., Kielbassa, K., Kittstein, W. and, Marks, F. Tyrosine phosphorylation and stimulation of protein kinase C delta from porcine spleen by src in vitro. Dependence on the activated state of protein kinase C delta. FEBS Lett., 1994, 347, 85-89.
52. Pongracz, J., Webb, P., Wang, K., Deacon, E., Lunn, O.J. and Lord, J.M. Spontaneous neutrophil apoptosis involves caspase 3-mediated activation of protein kinase C-delta. J. Biol. Chem., 1999, 274, 37329-37334.
53. Kilpatrick, L.E., Lee, J.Y., Haines, K.M., Campbell, D.E., Sullivan, K.E. and Korchak, H.M. A role for PKC-delta and PI 3-kinase in TNF-alpha-mediated antiapoptotic signaling in the human neutrophil. Am. J. Physiol., 2002, 283, C48-C57.
54. Braiman, L., Alt, A., Kuroki, T., Ohba, M., Bak, A., Tennenbaum, T. and Sampson, S.R. Protein kinase Cdelta mediates insulin-induced glucose transport in primary cultures of rat skeletal muscle. Mol. Endocrinol., 1999, 13, 2002-2012.
55. Palmer, T.M. and Stiles, G.L. Stimulation of A(2A) adenosine receptor phosphorylation by protein kinase C activation: evidence for regulation by multiple protein kinase C isoforms. Biochemistry, 1999, 38, 14833-14842.
56. Yedovitzky, M., Mochly-Rosen, D., Johnson, J.A., Gray, M.O., Ron, D., Abramovitch, E., Cerasi, E. and Nesher, R. Translocation inhibitors define specificity of protein kinase C isoenzymes in pancreatic beta-cells. J. Biol. Chem., 1997, 272, 1417-1420.
57. Wu, H.L., Albrightson, C. and Nambi, P, Selective inhibition of rat mesangial cell proliferation by a synthetic peptide derived from the sequence of the C2 region of PKCbeta. Peptides, 1999, 20, 675-678.
58. Farese, R.V., Standaert, M.L., Ishizuka, T., Yu, B., Hernandez, H., Waldron, C., Watson, J., Farese, J.P., Cooper, D.R. and Wickstrom, E. Antisense DNA downregulates protein kinase C isozymes (beta and alpha) and insulin-stimulated 2-deoxyglucose uptake in rat adipocytes. Antisense Res. Dev., 1991, 1, 35-42.
59. Liedtke, C.M. and Cole, T. Antisense oligodeoxynucleotide to PKC-delta blocks alpha 1-adrenergic activation of Na-K-2CI cotransport. Am. J. Physiol., 1997, 273, C1632-C1640.
60. Sullivan, S.M. Development of ribozymes for gene therapy. J. Invest. Dermatol., 1994, 103, 85S-89S.
61. Sioud, M. and Sorensen, D.R. A nuclease-resistant protein kinase C alpha ribozyme blocks glioma cell growth. Nat. Biotechnol., 1998, 16, 556-561.
62. Leirdal, M. and Sioud, M. Ribozyme inhibition of the protein kinase C alpha triggers apoptosis in glioma cells. Br. J. Cancer., 1999, 80, 1558-1564.
63. Myklebust, J.H., Smeland, E.B., Josefsen, D. and Sioud, M. Protein kinase C-alpha isoform is involved in erythropoietin-induced erythroid differentiation of CD34(+) progenitor cells from human bone marrow. Blood, 2000, 95, 510-518.
64. Rojnuckarin, P. and Kaushansky, K. Actin reorganization and proplatelet formation in murine megakaryocytes: the role of protein kinase calpha. Blood, 2001, 97, 154-161.
65. Su, Z.Z., Duigou, G.J. and Fisher, P.B. Low-level beta I protein kinase C expression in cloned rat embryo fibroblast cells enhances transformation induced by the adenovirus type 5 E1A gene. Mol. Carcinog., 1991, 4, 328-337.
66. Igarashi, M., Wakasaki, H., Takahara, N., Ishii, H., Jiang, Z.Y., Yamauchi, T., Kuboki, K., Meier, M., Rhodes, C.J. and King, G.L. Glucose or diabetes activates p38 mitogen-activated protein kinase via different pathways. J Clin Invest., 1999, 103, 185-195.
67. Park, J.Y., Takahara, N., Gabriele, A., Chou, E., Naruse, K., Suzuma, K., Yamauchi, T., Ha, S.W., Meier, M., Rhodes, C.J. and King. G.L. Induction of endothelin-1 expression by glucose: an effect of protein kinase C activation. Diabetes, 2000, 49, 1239-1248.
68. Kaneto, H., Suzuma, K., Sharma, A., Bonner-Weir, S., King, G.L. and Weir, G.C. Involvement of protein kinase C beta 2 in c-myc induction by high glucose in pancreatic beta-cells. J. Biol. Chem., 2002, 277, 3680-3685.
69. Etgen, G.J., Valasek, K.M., Broderick, C.L. and Miller, A.R. In vivo adenoviral delivery of recombinant human protein kinase C-zeta stimulates glucose transport activity in rat skeletal muscle. J. Biol. Chem., 1999, 274, 22139-22142.
70. Ohba, M., Ishino, K., Kashiwagi, M., Kawabe, S., Chida, K., Huh, N.H. and Kuroki, T. Induction of differentiation in normal human keratinocytes by adenovirus-mediated introduction of the eta and delta isoforms of protein kinase C. Mol. Cell Biol., 1998, 18, 5199-5207.
71. Suzuma, I., Suzuma, K., Ueki, K., Hata, Y., Feener, E.P., King, G.L. and Aiello, L.P. Stretch-induced retinal vascular endothelial growth factor expression is mediated by phosphatidylinositol 3-kinase and protein kinase C (PKC)-zeta but not by stretch-induced ERK1/2, Akt, Ras, or classical/novel PKC pathways. J. Biol. Chem., 2002, 277, 1047-1057.
72. Sausville, E.A., Arbuck, S.G., Messmann, R., Headlee, D., Bauer, K.S., Lush, R.M., Murgo, A., Figg, W.D., Lahusen, T., Jaken, S., Jing, X., Roberge, M., Fuse, E., Kuwabara, T. and Senderowicz, A.M. Phase 1 trial of 72-hour continuous infusion UCN-01 in patients with refractory neoplasms. J. Clin. Oncol., 2001,19, 2319-2333.
73. Thavasu, P., Propper, D., McDonald, A., Dobbs, N., Ganesan, T., Talbot, D., Braybrook, J., Caponigro, F., Hutchison, C., Twelves, C., Man, A., Fabbro, D., Harris, A. and Balkwill, F. The protein kinasc C inhibitor CGP41251 suppresses cytokine release and extracellular signal-regulated kinase 2 expression in cancer patients. Cancer Res., 1999, 59, 3980-3984.
74. Virchis, A., Ganeshaguru, K., Hart, S., Jones, D., Fletcher, L., Wright, F., Wickremasinghe, R., Man, A., Csermak, K., Meyer, T., Fabbro, D., Champain, K., Yap, A., Prentice, H.G. and Mehta, A. A novel treatment approach for low grade lymphoproliferative disorders using PKC412 (CGP41251), an inhibitor of protein kinase C. Hematol. J., 2002, 3, 131-136.
75. Li, K., Zhang, J., Sirois, P. and Hu, Y. Technology evaluation: ISIS-3521.Curr. Opin. Mol. Ther., 1999, 1, 393-398.
76. Mani, S., Rodin, C.M., Kunkel, K., Holmlund, J.T., Geary, R.S., Kindler, H.L., Dorr, F.A. and Ratain, M.J. Phase I clinical and pharmacokinetic study of protein kinase C-alpha antisense oligonucleotide ISIS 3521 administered in combination with 5-fluorouracil and leucovorin in patients with advanced cancer. Clin. Cancer Res., 2002, 8, 1042-1048.
77. Tolcher, A.W., Reyno, L., Venner, P.M., Ernst, S.D., Moore, M., Geary, R.S., Chi, K., Hall, S., Walsh, W., Dorr, A. and Eisenhauer, E. A Randomized Phase II and Pharmacokinetic Study of the Antisense Oligonucleotides ISIS 3521 and ISIS 5132 in Patients with Hormone-refractory Prostate Cancer. Clin. Cancer Res., 2002, 8, 2530-2535.
78. Cripps, M.C., Figueredo, A.T., Oza, A.M., Taylor, M.J., Fields, A.L., Holmlund, J.T., McIntosh, L.W., Geary, R.S. and Eisenhauer, E.A. Phase II Randomized Study of ISIS 3521 and ISIS 5132 in Patients with Locally Advanced or Metastatic Colorectal Cancer: A National Cancer Institute of Canada Clinical Trials Group Study. Clin Cancer Res. 2002, 8, 2188-2192.
79. Schwartz, G.K., Ward, D., Saltz, L., Casper, E.S., Spiess, T., Mullen, E., Woodworth, J., Venuti, R., Zervos, P., Storniolo, A.M. and Kelsen, D.P. A pilot clinical/pharmacological study of the protein kinase C-specific inhibitor safingol alone and in combination with doxorubicin. Clin. Cancer Res., 1997, 3, 537-543.
80. Beckman, J.A., Goldfine, A.B., Gordon, M.B., Garrett, L.A. and Creager, M.A. Inhibition of protein kinase Cbeta prevents impaired endothelium-dependent vasodilation caused by hyperglycemia in humans. Circ. Res., 2002, 90, 107-111.
81. Meier, M. and King, G.L. Protein kinase C activation and its pharmacological inhibition in vascular disease. Vasc. Med., 2000, 5, 173-185.
82. Frank, R.N. Potential new medical therapies for diabetic retinopathy: protein kinase C inhibitors. Am. J. Ophthalmol., 2002, 133, 693-698.