Protein kinases as targets for anticancer agents: From inhibitors to useful drugs

Pharmacology and Therapeutics

Volumn 93, Issue 2-3, 2002, Pages 79-98

  Fabbro, Doriano ^a   Ruetz, Stephan ^a   Buchdunger, Elisabeth ^a   Cowan Jacob, Sandra W ^a   Fendrich, Gabriele ^a   Liebetanz, Janis ^a   Mestan, Jürgen ^a   O'Reilly, Terence ^a   Traxler, Peter ^a   Chaudhuri, Bhabatosh ^a   Fretz, Heinz ^a   Zimmermann, Jürg ^a   Meyer, Thomas ^a   Caravatti, Giorgio ^a   Furet, Pascal ^a   Manley, Paul W ^a  

^a NOVARTIS PHARMA AG   (Switzerland)

Author keywords

Cyclin dependent kinases; Epidermal growth factor kinase; PKI166; Protein kinase inhibitors; STI571

Indexed keywords

2,4 DIMETHYL 5 (2 OXO 1H INDOL 3 YLMETHYLENE) 3 PYRROLEPROPIONIC ACID; 6 (4 HYDROXYPHENYL) 4 (ALPHA METHYLBENZYLAMINO) 7H PYRROLO[2,3 D]PYRIMIDINE; 7 HYDROXYSTAUROSPORINE; ANTINEOPLASTIC AGENT; BCR ABL PROTEIN; BRYOSTATIN 1; CANERTINIB; CEP 2583; CGP 69846A; CGP 74372; CGP 79807; CGP 82996; EPIDERMAL GROWTH FACTOR RECEPTOR KINASE; ERLOTINIB; FLAVOPIRIDOL; GEFITINIB; GENE EXPRESSION MODULATOR 231; IMATINIB; INDISULAM; ISIS 3521; LAPATINIB; MIDOSTAURIN; PELITINIB; PLATELET DERIVED GROWTH FACTOR RECEPTOR; PROTEIN KINASE; PROTEIN KINASE INHIBITOR; PYRROLOPYRIMIDINE DERIVATIVE; ROSCOVITINE; SCIO 469; SEMAXANIB; UNCLASSIFIED DRUG; UNINDEXED DRUG; VANDETANIB; VASCULOTROPIN RECEPTOR; VATALANIB; PYRIMIDINE DERIVATIVE;

ANTINEOPLASTIC ACTIVITY; APOPTOSIS; CANCER; CANCER CHEMOTHERAPY; CELL DIFFERENTIATION; CELL GROWTH; CELL METABOLISM; CLINICAL TRIAL; CONFERENCE PAPER; GASTROINTESTINAL TUMOR; HUMAN; IN VITRO STUDY; IN VIVO STUDY; MOLECULAR WEIGHT; ONCOGENE; PRIORITY JOURNAL; SIGNAL TRANSDUCTION; ANIMAL; CELL CYCLE; DRUG EFFECT; METABOLISM; MOUSE; NEOPLASM; PHYSIOLOGY; REVIEW;

ANIMAL; ANTINEOPLASTIC AGENTS; CELL CYCLE; CLINICAL TRIALS; HUMAN; MICE; NEOPLASMS; PROTEIN KINASES; PYRIMIDINES; SIGNAL TRANSDUCTION; ANIMALS; HUMANS; PROTEIN KINASE INHIBITORS;

EID: 0035990893     PISSN: 01637258     EISSN: None     Source Type: Journal    
DOI: 10.1016/S0163-7258(02)00179-1     Document Type: Conference Paper

References (123)

1. Recent progress towards the identification of selective inhibitors of serine/threonine protein kinases
2. Mice without telomerase: What can they teach us about human cancer?
3. Molecular targets for breast cancer therapy and prevention
4. Roots of clinical resistance to STI-571 cancer therapy
5. Oncogenic kinase signalling
6. How receptors talk to trimeric G proteins
7. Blockade of the epidermal growth factor receptor signaling by a novel tyrosine kinase inhibitor leads to apoptosis of endothelial cells and therapy of human pancreatic carcinoma
8. Abl protein-tyrosine kinase inhibitor STI571 inhibits in vitro signal transduction mediated by c-Kit and platelet-derived growth factor receptors
9. UICC study group on basic and clinical cancer research: Animal models for the natural history of cancer
10. Phosphotyrosyl-based motifs in the structure-based design of protein-tyrosine kinase-dependent signal transduction inhibitors
11. Pyrrolo[2, 3-d]pyrimidine and Pyrazolo[3,4-d]pyrimidine derivatives as selective inhibitors of the EGFR tyrosine kinase
12. Angiogenesis in cancer and other diseases
13. CGP 57148, a tyrosine kinase inhibitor, inhibits the growth of cells expressing BCR-ABL, TEL-ABL, and TEL-PDGFR fusion proteins
14. Cyclin D1/Cdk4 regulates retinoblastoma protein-mediated cell cycle arrest by site-specific phosphorylation
15. Chronic myelogenous leukemia: A review
16. Signal transduction drug discovery: Targets, mechanisms and structure-based design
17. Specificity and mechanism of action of some commonly used protein kinase inhibitors
18. Structural basis for specificity and potency of a flavonoid inhibitor of human CDK2, a cell cycle kinase
19. Inhibition of cyclin-dependent kinases by purine analogues: Crystal structure of human Cdk2 complexed with roscovitine
20. Crystal structure of cyclin-dependent kinase 2
21. The molecular biology of chronic myeloid leukemia
22. Pten and p27 cooperate in prostate cancer tumor suppression in the mouse
23. Effects of a selective inhibitor of the Abl tyrosine kinase on the growth of Bcr-Abl positive cells
24. Activity of a specific inhibitor of the BCR-ABL tyrosine kinase in the blast crisis of chronic myeloid leukemia and acute lymphoblastic leukemia with the Philadelphia chromosome
25. Efficacy and safety of a specific inhibitor of Bcr-Abl tyrosine kinase in chronic myeloid leukemia
26. The pathway to signal achievement
27. Structural aspects of protein kinase control - Role of conformational flexibility
28. Structure-activity studies supporting a postulated binding mode of STI571 to Abl kinase. Molecular targets and cancer therapeutics: Discovery, biology and clinical application
29. The biology of vascular endothelial growth factor
30. Relevance of tumor models for anticancer drug development
31. Modelling study of protein kinase inhibitors: Binding mode of staurosporine and origin of the selectivity of CGP 52411
32. Structure-based design of potent CDK1 inhibitors derived from Olomoucine
33. Cancer and genomics
34. Roots of clinical resistance to STI-571 cancer therapy
35. BCR/ABL regulates expression of the cyclin-dependent kinase inhibitor p27Kip1 through the phosphatidylinositol 3-kinase/AKT pathway
36. Molecular mechanisms of Bcr-Abl-induced oncogenesis
37. Clinical resistance to STI-571 cancer therapy caused by BCR-ABL gene mutation or amplification
38. Roots of clinical resistance to STI-571 cancer therapy
39. Cyclin-dependent protein kinases
40. Epidermal growth factor receptors: Critical mediators of multiple receptor pathways
41. The hallmarks of cancer
42. Rb function in cell-cycle regulation and apoptosis
43. 1
44. Cyclin dependent kinases
45. Cell cycle control and cancer
46. Inhibition of c-kit receptor tyrosine kinase activity by STI 571, a selective tyrosine kinase inhibitor
47. Gain-of-function mutations of c-kit in human gastrointestinal stromal tumors
48. Roots of clinical resistance to STI-571 cancer therapy
49. Indirubin, the active constituent of a Chinese antileukemia medicine, inhibits cyclin-dependent kinases
50. L
51. Crystal structure of the tyrosine kinase domain of the human insulin receptor
52. Signaling - 2000 and beyond
53. 2,6,9-Trisubstituted purines: Optimization towards highly potent and selective CDK1 inhibitors
54. Initial sequencing and analysis of the human genome
55. Signal transduction by the c-Jun N-terminal kinase (JNK) - From inflammation to development
56. Functions of the retinoblastoma protein
57. Characterization of novel inhibitors of cyclin-dependent kinases
58. Chronic myeloid leukemia
59. The consensus motif for phosphorylation by cyclin D1-Cdk4 is different from that for phosphorylation by cyclin A/E-Cdk2
60. The p16 status of tumor cell lines identifies small molecule inhibitors specific for cyclin-dependent kinase 4
61. Protein kinase inhibition by staurosporine revealed in details of the molecular interaction with Cdk2
62. In vivo eradication of human BCR/ABL-positive leukemia cells with an ABL kinase inhibitor
63. Induction of resistance to the Abelson inhibitor STI571 in human leukemic cells through gene amplification
64. Targeting signal transduction for disease therapy
65. Regulation of tyrosine kinase cascade by G-protein-coupled receptors
66. KIT extracellular and kinase domain mutations in gastrointestinal stromal tumors
67. Tumor suppressor genes
68. Selection and characterization of BCR-ABL positive cell lines with differential sensitivity to the tyrosine kinase inhibitor STI571: Diverse mechanisms of resistance
69. Cyclin-dependent kinase inhibitors: Novel anticancer agents
70. Structure and molecular design of tyrosine kinase inhibitors
71. Ras effectors
72. Tumor angiogenesis as a therapeutic target
73. Protein kinase inhibitors: Structural determinants for target specificity
74. A coiled-coil oligomerization domain of Bcr is essential for the transforming function of Bcr-Abl oncoproteins
75. Cyclin-dependent kinases inhibitors as potential anticancer, antineurodegenerative, antiviral and antiparasitic agents
76. Mutiple signaling converging on NF-kB
77. Mouse models for sporadic cancer
78. Lysophosphatidic acid: G-protein signalling and cellular responses
79. Mitotic kinases as regulators of cell division and its checkpoints
80. ARG tyrosine kinase activity is inhibited by STI571
81. In vivo antitumor activity of the EGFR inhibitor PKI166
82. Absence of p16INK4 protein is restricted to the subset of lung cancer lines that retains wildtype RB
83. Protein-protein interactions define specificity in signal transduction
84. Soft tissue leiomyosarcomas and malignant gastrointestinal stromal tumors: Differences in clinical outcome and expression of multidrug resistance proteins
85. In vivo imaging of light-emitting probes
86. Design of new inhibitors for CDC2 kinase based on a multiple pseudosubstrate structure
87. Inhibition of CDKs as a therapeutic modality
88. Structural mechanism for STI-571 inhibition of Abelson tyrosine kinase
89. Cell signaling by receptor tyrosine kinases
90. Multiple modes of ligand recognition: Crystal structures of cyclin-dependent protein kinase 2 in complex with ATP and two inhibitors, Olomoucine and isopentenyladenine
91. Small molecule modulators of cyclin-dependent kinases for cancer therapy
92. Preclinical and clinical development of cyclin-dependent kinase modulators
93. Protein-Protein Interactions: Lessons Learned
94. Cancer cell cycles
95. The Pezcoller lecture: Cancer cell cycles revisited
96. 1-phase progression
97. Novel Cdk inhibitors restore TGF-β Sensitivity in Cdk4 overexpressing epithelial cells
98. Inhibition of cyclin-dependent kinase 4 (Cdk4) by fascaplysin, a marine natural product
99. Selective in vivo and in vitro effects of a small molecule inhibitor of cyclin-dependent kinase 4
100. Cyclin-dependent kinase inhibitors for treating cancer
101. Tyrosine kinase inhibitors in cancer treatment
102. Strategies toward the design of novel and selective protein tyrosine kinase inhibitors
103. 4-(Phenylamino) pyrrolopyrimidines: Potent and selective, ATP site directed inhibitors of the EGF-receptor protein tyrosine kinase
104. Tyrosine kinase inhibitors: From rational design to clinical trials
105. STI571 inactivation of the gastrointestinal stromal tumor c-KIT oncoprotein: Biological and clinical implications
106. The ErbB-2/HER2 oncogenic receptor of adenocarcinomas: From orphanhood to multiple stromal ligands
107. Cycling, stressed-out and nervous: Cellular functions of c-Abl
108. Safety and efficacy of imatinib (STI571) in metastatic gastrointestinal stromal tumours: A phase I study
109. Induction of apoptosis in chronic myelogenous leukemia cells through nuclear entrapment of BCR-ABL tyrosine kinase
110. Epidermal growth factor receptor (EGF-R) and EGF-R mutations, function and possible role in clinical trials
111. Cell cycle check-point kinases: Checking in on the cell cycle
112. DNA damage: Chk1 and Cdc25, more than meets the eye
113. Regulation of cell death by the Abl tyrosine kinase
114. Molecular pathogenesis of chronic myeloid leukemia: Implications for new therapeutic strategies
115. Mechanism of resistance to the ABL tyrosine kinase inhibitor STI571 in BCR/ABL-transformed hematopoietic cell lines
116. Vasculogenesis, angiogenesis, and growth factors: Ephrins enter the fray at the border
117. Untangling the ErbB signalling network
118. (Phenylamino) pyrimidine (PAP) derivatives: A new class of potent and highly selective PDGF-receptor autophosphorylation inhibitors
119. Phenylamino-pyrimidine (PAP) derivatives: A new class of potent and selective inhibitors of protein kinase C (PRC)
120. Potent and selective inhibitors of the ABL-kinase: Phenylaminopyrimidine (PAP) derivatives
121. STI571 - A new treatment modality for CML?
122. Signaling pathways activated by oncogenic forms of Abl tyrosine kinase
123. Imaging metalloproteinase activity in vivo