UCN-01 Kyowa Hakko Kogyo Co

Current Opinion in Investigational Drugs

Volumn 2, Issue 2, 2001, Pages 287-297

  Grosios, K ^a  

^a UNIVERSITY OF LEEDS   (United Kingdom)

Author keywords

[No Author keywords available]

Indexed keywords

7 HYDROXYSTAUROSPORINE; ALPHA1 GLYCOPROTEIN; ANTIMITOTIC AGENT; ANTINEOPLASTIC ANTIMETABOLITE; CAMPTOTHECIN; CISPLATIN; CYCLIN DEPENDENT KINASE; FLUOROURACIL; KW 2401; PROTEIN KINASE C; PROTEIN KINASE C INHIBITOR; PROTEIN P53; STAUROSPORINE;

ANAPLASTIC CARCINOMA; ANTINEOPLASTIC ACTIVITY; APOPTOSIS; BREAST CARCINOMA; CHRONIC LYMPHATIC LEUKEMIA; CLINICAL TRIAL; CONTINUOUS INFUSION; DOSE RESPONSE; DRUG CONTRAINDICATION; DRUG HALF LIFE; DRUG MEGADOSE; DRUG METABOLISM; DRUG POTENTIATION; DRUG SYNTHESIS; ENZYME INHIBITION; GLIOMA; HEADACHE; HUMAN; HYPOTENSION; IN VITRO STUDY; LARGE CELL LYMPHOMA; LUNG CARCINOMA; LUNG TOXICITY; MELANOMA; MYALGIA; NAUSEA; NONHUMAN; PANCREAS CARCINOMA; REFRACTORY PERIOD; REVIEW; STRUCTURE ACTIVITY RELATION; TREATMENT OUTCOME; VOMITING;

ALKALOIDS; ANIMALS; ANTINEOPLASTIC AGENTS; APOPTOSIS; CLINICAL TRIALS, PHASE I; CLINICAL TRIALS, PHASE II; CLINICAL TRIALS, PHASE III; ENZYME INHIBITORS; HUMANS; PROTEIN KINASE C; STAUROSPORINE; STRUCTURE-ACTIVITY RELATIONSHIP;

EID: 0035110776     PISSN: 09678298     EISSN: None     Source Type: Journal    
DOI: None     Document Type: Review

References (164)

1. In vitro and in vivo antitumour effect of UCN-01, selective protein kinase C (PKC) inhibitor against various human lung cancer cell lines
2. Cell cycle arrest by the protein kinase antagonists UCN-01 and UCN-02 in human breast carcinoma cells
3. Modulation of endothelial autacoid release by protein kinase C: Feedback inhibition or non-specific attenuation of receptor-dependent cell activation?
4. Staurosporine-related compounds, K252a and UCN-01, inhibit both cPKC and nPKC
5. Enhancement of antitumour activity of mitomycin C in vitro and in vivo by UCN-01, a selective inhibitor of protein kinase C
6. Cell cycle arrest and growth inhibition by the protein kinase antagonist UCN-01 in human breast carcinoma cells
7. Effect of a potent selective protein kinase C inhibitor on histamine release from rat mast cells
8. Antitumor activity of UCN-01, a selective inhibitor of protein kinase C, in murine and human tumor models
9. 2+ influx through dihydropyridine-sensitive channels linked to activation of protein kinase C in vascular smooth muscle cells
10. Activation of the respiratory burst and tyrosine phosphorylation of proteins in human neutrophils: No direct relationship and involvement of protein kinase C-dependent and independent signalling pathways
11. In vitro and in vivo anti-tumor effect of UCN-01, a selective protein kinase C inhibitor, against lung and pancreatic cancer cells
12. Selective inhibition of PKC isozymes by UCN-01, a staurosporine analog
13. Effect of a selective protein kinase C (PKC) inhibitor UCN-01 on cell cycle progression of A549 lung carcinoma cells
14. Effect of KW-2401 (UCN-01) on cell-cycle progression (The fourth report): Mechanism of the G1 arrest
15. UCN-01: A new potential therapeutic agent for chronic lymphocytic leukemia
16. G1 phase accumulation induced by UCN-01, a protein kinase inhibitor is associated with dephosphorylation of Rb and CDK2, and induction of CDK inhibitor p21 in p53 mutated cells
17. UCN-01, 7-hydroxyl-staurosporine, inhibits kinase activity of cyclin-dependent kinases and reduces the phosphorylation of the retinoblastoma susceptibility gene product in A549 human lung cancer cell line
18. UCN-01 abrogates radiation-induced G2 arrest at non-toxic plasma concentrations
19. Comparison of staurosporine and four analogues: Their effects on growth, rhodamine 123 retention and binding to P-glycoprotein in multidrug-resistant MCF-7/Adr cells
20. Differential inhibition of cytosolic and membrane-derived protein kinase C activity by staurosporine and other kinase inhibitors
21. Comparison of ability of protein kinase C inhibitors to arrest cell growth and to alter cellular protein kinase C localisation
22. Business news in brief: Kyowa Hakko to start phase I studies on anticancer agent
23. Modelling study of protein kinase inhibitors: Binding mode of staurosporine and origin of the selectivity of CGP 52411
24. Inhibition of protein kinase C (PKC) arrests cell growth, induces apoptosis, and alters the effect of basic fibroblast growth factor (bFGF) on bcl-2 expression in chronic lymphoid malignancies
25. Chemosensitization of cancer cells by the staurosporine derivative CGP 41251 in association with decreased P-glycoprotein phosphorylation
26. G1 phase accumulation induced by UCN-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
27. Differing effects of staurosporine and UCN-01 on RB protein phosphorylation and expression of lung cancer cell lines
28. UCN-01: A potent abrogator of G2 checkpoint function in cancer cells with disrupted p53
29. 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
30. Downregulation of protein kinase C suppresses induction of apoptosis in human prostatic carcinoma cells
31. Apoptosis in 7-hydroxystaurosporine-treated T lymphoblasts correlates with activation of cyclin-dependent kinases 1 and 2 [published erratum appears in Cell Growth Differ 1995 Oct;6(10):1339]
32. UCN-01, an anti-tumor drug, is a selective inhibitor of the conventional PKC subfamily
33. Disposition in mice of 7-hydroxystaurosporine, a protein kinase inhibitor with antitumor activity
34. Heterogeneity of signal transduction: Mechanisms in human basophils and human skin mast cells. II. Effects of 7-O-Methyl-UCN001, NPC 15437 and bryostatin 1 and 2, four protein kinase C modulatory agents, on mediator release
35. Enhancement of cisplatin-induced cytotoxicity by 7-hydroxystaurosporine (UCN-01), a new G2-checkpoint inhibitor
36. Surprising pharmacokinetics of UCN-01 in patients with refractory neoplasms may be due to high degree of protein binding
37. Molecular correlates of enhancement of paclitaxel-induced apoptosis by co-treatment with 7-hydroxystaurosporin (UCN-01)
38. 7-Hydroxystaurosporine (UCN-01), a selective inhibitor of protein kinase C, blocks malignant glioma growth by inducing apoptosis independent of p53 and in a time-dependent manner
39. Role for the Cdc2 kinase in abrogation of radiation-induced G2 arrest by UCN-01, a potent kinase inhibitor presently in clinical trials
40. Potentiation of camptothecin cytotoxicity in p52 mutant HT-29 cells by UCN-01, an abrogator of the S and G2 checkpoints
41. Synergistic interactions between UCN-01 and various anti-cancer agents in vitro: Relationship to p53 function
42. UCN-01 enhances CDDP cytotoxicity in ovarian cancer cells independent of p53 gene status and abrogation of G2 block
43. Dual potentiation of 1-(β-D-arabinofuranosyl)cytosine (ara-C) action by 7-hydroxystaurosporine (UCN-01) and L-threo-sphinganine (safingol; SPC-100270)
44. 7-Hydroxystaurosporine (UCN-01) causes redistribution of PCNA and abrogates cisplatin-induced S phase arrest
45. RB-dependent UCN-01-induced G1 growth arrest in NSCLC
46. UCN-01, a selective protein kinase C inhibitor, blocks glioma proliferation and induces apoptosis in vitro and inhibits glioma growth in vivo
47. UCN-01: A potent abrogator of G2 checkpoint function in cancer cells with disrupted p53
48. Differential activity of camptothecin and 7-hydroxystaurosporine (UCN-01) in human breast carcinoma cells: Relationship between apoptosis, DNA fragmentation, bcl-2, p53 and cytotoxicity
49. 7-Hydroxystaurosporine (UCN-01), a novel and potent inducer of apoptotic DNA fragmentation in human colon carcinoma and leukemia cells
50. Abrogation of cisplatin induced cell cycle arrest and enhancement of cisplatin induced cytotoxicity by 7-hydroxystaurosporine (UCN-01), a new G-2-checkpoint inhibitor
51. Activation of CDK1 and CDK2 by UCN-01, a selective PKC antagonist is associated with growth inhibition and induction of apoptosis in leukemic T-cells
52. The staurosporine analogs UCN-01 and CGP-41251 induce drug resistance in A549 lung carcinoma cells
53. 7-Hydroxystaurosporine (UCN-01), a selective inhibitor of protein kinase C, blocks malignant glioma growth by inducing apoptosis independent of p53 and in a time-dependent manner
54. Cellular relocalisation of protein kinase C-theta caused by staurosporine and some of its analogues
55. Protein kinase inhibitor-induced alterations of drug uptake, cell cycle and surface antigen expression in human multidrug-resistant (Pgp and MRP) promyelocytic leukemia HL-60 cells
56. 7-Hydroxystaurosporine (UCN-01) induces apoptosis in human colon carcinoma and leukemia cells independently of p53
57. 7-Hydroxystaurosporine (UCN-01) causes redistribution of proliferating cell nuclear antigen and abrogates cisplatin-induced S-phase arrest in Chinese hamster ovary cells
58. The antineoplastic agent bryostatin-1 induces proinflammatory cytokine production in human monocytes: Synergy with interleukin-2 and modulation of interleukin-2Rγ chain expression
59. Synergistic cytotoxicity between a protein kinase C inhibitor, UCN-01, and monoclonal antibody to the epidermal growth factor receptor on MDA-468 cells
60. UCN-01, a selective inhibitor of protein kinase C from streptomyces
61. UCN-01 and UCN-02, new selective inhibitors of protein kinase C. I. Screening, producing organism and fermentation
62. A new alkaloid AM-2282 of Streptomyces origin: Taxonomy, fermentation, isolation and preliminary characterization
63. UCN-01 and UCN-02, new selective inhibitors of protein kinase C. II. Purification, physiochemical properties, structural determination and biological activities
64. Potent and specific inhibitors of protein kinase C of microbial origin
65. New drugs in the R & D pipeline
66. Kyowa Hakko Kogyo Co Ltd - 1997 Semi-annual Report
67. Expression of Fas and Fas-ligand in activation-induced apoptotic lymphocytes treated with UCN-01
68. Induction of CDK2/p21(CIP1) and CDK4/p27(KIP1) complex formation in growth inhibition of p53(-) cells by UCN-01
69. Induction of E2F-1 in drug-induced apoptosis in the human HT29 colon carcinoma cell line
70. Enhancement of mitomycin C cytotoxicity by UCN-01 is mediated through S and/or G2 abrogation which might be dependent on mutated p53 protein function
71. Unpredicted clinical pharmacokinetics of UCN-01 caused by the specific binding to human α1-acid glycoprotein
72. Binding of UCN-01 to plasma proteins of humans, rats and dogs
73. Old and new therapies in chronic lymphocytic leukemia: Now is the time for a reassessment of therapeutic goals
74. The therapeutic potential of targeting the cell cycle
75. NCI-EORTC 10th Symposium (Part IV) Amsterdam, The Netherlands
76. UCN-01 suppresses thymidylate synthase gene expression and enhances 5- fluorouracil-induced apoptosis in a sequence-dependent manner
77. Protein kinase C inhibitor 7-OH-staurosporine (UCN-01) and CDK family kinase inhibitor flavopiridol down-regulate expression of survival genes and induce apoptosis in B-cell chronic lymphocytic leukemia (B-CLL)
78. UCN-01 suppresses thymidylate synthase and dihydrofolate reductase gene expression mediated by down-regulation of E2F-1 in human gastric cancer cells
79. Antineoplastic agents 1998 - Quinazoline derivatives
80. Chronic lymphocytic leukemia
81. Platinum and Other Metal Coordination Compounds in Cancer Chemotherapy Eighth International Symposium, Keble College, Oxford, UK
82. Analogs of staurosporine: Potential anticancer drugs?
83. Kyowa Hakko Kogyo's R&D pipeline
84. Enhancement of fludarabine and gemcitabine toxicity by UCN-01 in a variety of human tumor cell lines
85. UCN-01 enhances roscovitine-induced apoptosis in deoxyadenosine-resistant mouse leukemia L-1210 cells
86. UCN-01 dose-dependent protective effect of normal tissues in mice
87. American Association for Cancer Research - 90th Annual Meeting (Part XII), Philadelphia, PA, USA
88. The checkpoint kinase Chk1 is a target of the anticancer agent UCN-01
89. Differences between human wild-type and UCN-01-resistant A549 lung carcinoma cells in susceptibility towards apoptosis induction and changes in G1 checkpoint function by UCN-01
90. Induction of apoptosis without cell cycle progression by UCN-01 abrogates gemcitabine induced S phase arrest in human myeloid ML-1 cells
91. Abrogation of irinotecan-mediated S and G2 arrest by 7-hydroxystaurosporine (UC-01) and the impact of p53 status
92. Regulation of 2′-C-cyano-2′-deoxy-1-β-D-arabinopento-furanosylcytosine (CNDAC) induced G2 arrest and apoptosis by UCN-01
93. Plasma pharmacokinetics and tissue distribution of UCN-01 in rats: Role of α1-acid glycoprotein binding
94. Effects of human α1-acid glycoprotein on uptake of UCN-01 by human pancreas cancer cell line
95. Altered pharmacokinetics and cardiohemodynamics of UCN-01 by human α1-acid glycoprotein in rats
96. UCN-01 enhances 5-fluorouracil-induced apoptosis through capase activation and ubiquitin-proteasome-dependent degradation of E2F-1
97. 7-Hydroxystaurosporine (UCN-01) inhibits nucleotide excision repair (NER): Attenuation of ERCC1-XPA interaction
98. Antitumor activity of UCN-01
99. Therapy of chronic lymphocytic leukemia: It is time to move on to the next important question
100. American Society of Clinical Oncology - 35th Annual Meeting (Part III), Atlanta, GA, USA
101. Phase I study of UCN-01 by 3-hour infusion
102. Phase I trial of infusional UCN-01, a novel protein kinase inhibitor, in patients with refractory neoplasms
103. 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
104. Developing new anti-cancer drugs: Novel targets and methodological problems
105. Characterisation of novel human lung carcinoma cell lines selected for resistance to anti-neoplastic analogues of staurosporine
106. Kinetic studies of protein kinase C inhibitor 7OH-staurosporine (UCN-01) and cdk family kinase inhibitor flavopiridol: Correlations between expression of survival genes and induction of apoptosis in B-cell chronic lymphocytic leukemia (B-CLL)
107. UCN-01 chemosensitizes human B-chronic lyphocytic leukemia (B-CLL) cells to the effects of fludarabine
108. Molecular cloning and expression of a cDNA encoding a novel isoenzyme of protein kinase C (nPKC). A new member of the nPKC family expressed in skeletal muscle, megakaryoblastic cells, and platelets [published erratum appears in J Biol Chem 1994 Dec 9;269(49):31322]
109. Binding of UCN-01 to plasma proteins of humans, rats and dogs
110. Unpredicted clinical pharmacokinetics of UCN-01 caused by the specific binding to human α-acid glycoprotein
111. Signal perception and transduction: The role of protein kinases
112. The structure-based design of ATP-site directed protein kinase inhibitors
113. The CHK1 protein kinase and the CDC25C regulatory pathway are targets of the anticancer agent UCN-01
114. The radiosensitizing agent UCN-01 inhibits the G2 checkpoint kinase HCHK1
115. CDS1/CHK2 cell cycle checkpoint protein kinase from human colon carcinoma HT29 cells - Regulation by autophosphorylation and DNA-dependent protein kinase and inhibition by cell cycle regulatory drugs
116. The kinase inhibitor UCN-01 potentiates fludarabine-mediated mitochondrial damage and apoptosis in a sequence dependent manner in human monocyte leukemia cells (U937)
117. Differential gene expression in human UCN-01-resistant small cell lung cancer cells
118. UCN-01 (7-hydroxystaurosporine) abrogates cisplatin-induced S and G2 arrest and enhances antitumor activity in vivo
119. Antitumor activity of UCN-01 on human tumor xenografts in nude mice
120. Action of UCN-01 on the mechanisms that regulate CDK2 function in F-ara-A arrested S-phase cells
121. The kinase inhibitor UCN-01 promotes 1-[β-D-arabinofuranosyl]cytosine-mediated mitochondrial dysfunction and apoptosis in human leukemia cells (U937) overexpressing Bcl-2 or its phosphorylation loop-deletant counterpart
122. A phase I and pharmacologic study of UCN-01, a protein kinase C inhibitor
123. UCN-01 suppresses E2F-1 mediated by ubiquitin-proteasome-dependent degradation
124. FTC grants final clearance for Pfizer/Warner-Lambert merger, transaction completed today
125. Meeting report on 8th International Symposium on Platinum and Other Metal Coordination Compounds in Cancer Chemotherapy
126. Physiological modeling of altered pharmacokinetics of a novel anticancer drug, UCN-01 (7-hydroxystaurosporine), caused by slow dissociation of UCN-01 from human α1 acid glycoprotein
127. Identification of PKC-isoform-specific biological actions using pharmacological approaches
128. UCN-01 (7-hydroxystaurosporine) and other indolocarbazole compounds: A new generation of anti-cancer agents for the new century?
129. Decrease in susceptibility toward induction of apoptosis and alteration in G1 checkpoint function as determinants of resistance of human lung cancer cells against the anti-signaling drug UCN-01 (7-hydroxystaurosporine)
130. G1 checkpoint function including a cyclin-dependent kinase 2 regulatory pathway as potential determinant of 7-hydroxystaurosporine (UCN-01)-induced apoptosis and G1 phase accumulation
131. Altered pharmacokinetics of a novel anticancer drug, UCN-01, caused by specific high affinity binding to alpha 1 acid glycoprotein in humans
132. Apoptotic response to camptothecin and 7-hydroxystaurosporine (UCN-01) in the 8 human breast cancer cell lines of the NCI anticancer drug screen: Multifactorial relationships with topoisomerase I, protein kinase C, Bcl-2, p53, MDM-2 and caspase pathways
133. Activation-induced apoptosis of peripheral lymphocytes treated with 7-hydroxystaurosporine, UCN-01
134. UCN-01, a protein kinase C inhibitor, inhibits endothelial cell proliferation and angiogenic hypoxic response
135. Pharmacokinetics and pharmacodynamics of a novel protein kinase inhibitor, UCN-01
136. Protein kinase C inhibition by UCN-01 induces apoptosis in human glioma cells in a time-dependent fashion
137. UCN-01 abrogates G2 arrest through a Cdc2-dependent pathway that is associated with inactivation of the Wee1Hu kinase and activation of the Cdc25C phosphatase
138. Multimodality therapy: Radiation and continuous concomitant cis-platinum and PKC inhibition in a cervical carcinoma model
139. Development of a highly sensitive high-performance liquid chromatographic method for measuring an anticancer drug, UCN-01, in human plasma or urine
140. UCN-01, a protein kinase C inhibitor, inhibits endothelial cell proliferation and angiogenic hypoxic response
141. 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
142. The effect of UCN-01 (7-hydroxystaurosporine), a potent inhibitor of protein kinase C, on fractionated radiotherapy or daily chemotherapy of a murine fibrosarcoma
143. Unpredicted clinical pharmacology of UCN-01 caused by specific binding to human α1 acid glycoprotein
144. Modulation of apoptosis in rat thymocytes by analogs of staurosporine: Lack of direct association with inhibition of protein kinase C
145. Potentiation of the cytotoxicity of S-phase specific chemotherapeutic agents by UCN-01 (7-hydroxystaurosporine)
146. Enhancement of mitomycin C cytotoxicity by UCN-01 is mediated through S and/or G2 abrogation which might be dependent on mutated p53 protein function
147. Activation of PKCα downstream from caspases during apoptosis induced by 7-hydroxystaurosporine or the topoisomerase inhibitors, camptothecin and etoposide, in human myeloid leukemia HL60 cells
148. UCN-01: A promising new agent for B-cell chronic lymphocytic leukemia (B-CLL) that induces apoptosis independent of p53 status
149. 2 phase accumulation and enhances anti-tumor activity in xenograft models through putative inhibition of chk1 kinase
150. Preclinical and clinical development of CDK inhibitors
151. UCN-01 (7-hydroxystaurosporine) enhances 5-fluorouracil cytotoxicity through down-regulation of thymidylate synthetase messenger RNA
152. UCN-01 and camptothecin induce DNA double-strand breaks in p53 mutant tumor cells, but not in normal or p53 negative epithelial cells
153. Altered sensitivity of deoxyadenosine-resistant mouse leukemia L1210 cells to apoptosis induced by 7-hydroxystaurosporine
154. A high-performance liquid chromatography method using ultraviolet and fluorescence detection for the quantitation of UCN-01, 7-hydroxystaurosporine, from human plasma and saliva
155. Characterization of a binding site of UCN-01, a novel anticancer drug on α-acid glycoprotein
156. UCN-01 enhances the in vitro toxicity of clinical agents in human tumor cell lines
157. Structure-activity relationship of staurosporine analogs in regulating expression of endothelial nitric oxide synthase gene
158. Modulation of clinical drug resistance in a B cell lymphoma patient by the protein kinase inhibitor 7-hydroxystaurosporine: Presentation of a novel therapeutic paradigm
159. Inhibition of CDKs as a therapeutic modality
160. Rb interacts with histone deacetylase to repress transcription
161. The retinoblastoma protein pathway and restriction point
162. Potent selective inhibition of 7-O-methyl UCN-01 against protein kinase C
163. The protein kinase family: Conserved features and deduced phylogeny of the catalytic domains
164. UCN-01