Flying under the radar: The new wave of BCR-ABL inhibitors

Nature Reviews Drug Discovery

Volumn 6, Issue 10, 2007, Pages 834-848

  Quintás Cardama, Alfonso ^a   Kantarjian, Hagop ^a   Cortes, Jorge ^a  

^a UNIVERSITY OF TEXAS MD ANDERSON CANCER CENTER   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

3 [6 [[4 (TRIFLUOROMETHOXY)PHENYL]AMINO] 4 PYRIMIDINYL]BENZAMIDE; 4 AMINO 7 TERT BUTYL 5 (4 CHLOROPHENYL)PYRAZOLO[3,4 D]PYRIMIDINE; 4 AMINO 7 TERT BUTYL 5 (4 METHYLPHENYL)PYRAZOLO[3,4 D]PYRIMIDINE; 6 (2,6 DICHLOROPHENYL) 2 (4 FLUORO 3 METHYLANILINO) 8 METHYL 8H PYRIDO[2,3 D]PYRIMIDIN 7 ONE; 6 (2,6 DICHLOROPHENYL) 2 [3 (HYDROXYMETHYL)ANILINO] 8 METHYLPYRIDO[2,3 D]PYRIMIDIN 7(8H) ONE; 6 (2,6 DICHLOROPHENYL) 8 METHYL 2 (3 METHYLTHIOANILINO) 8H PYRIDO[2,3 D]PYRIMIDIN 7 ONE; [4 [2 CYCLOPENTYL 9 (3 HYDROXYPHENETHYL)PURIN 6 YLAMINO]PHENYL]DIMETHYLPHOSPHINE OXIDE; ANTILEUKEMIC AGENT; AP 23848; AURORA KINASE INHIBITOR; AZD 0530; BCR ABL PROTEIN KINASE INHIBITOR; BOSUTINIB; CGP 5148B; CGP 76030; CYCLOPROPANECARBOXYLIC ACID [4 [4 (4 METHYL 1 PIPERAZINYL) 6 (5 METHYL 2H PYRAZOL 3 YLAMINO) 2 PYRIMIDINYLTHIO]PHENYL]AMIDE; CYCLOSPORIN A; DASATINIB; DORAMAPIMOD; GNF 2; IMATINIB; INNO 406; NILOTINIB; NS 187; ON 012380; ON 01910; PROTEIN KINASE INHIBITOR; PURINE DERIVATIVE; PYRIDO[2,3 D]PYRIMIDINE DERIVATIVE; PYRIMIDINE DERIVATIVE; TG 101114; UNCLASSIFIED DRUG; UNINDEXED DRUG; XL 228;

ACUTE LYMPHOBLASTIC LEUKEMIA; ANTINEOPLASTIC ACTIVITY; BONE MARROW SUPPRESSION; CHRONIC MYELOID LEUKEMIA; CLINICAL TRIAL; CONGESTIVE HEART FAILURE; CONTINUOUS INFUSION; DIARRHEA; DRUG BLOOD LEVEL; DRUG DESIGN; DRUG DOSE COMPARISON; DRUG DOSE ESCALATION; DRUG EFFICACY; DRUG ERUPTION; DRUG HALF LIFE; DRUG HYPERSENSITIVITY; DRUG POTENTIATION; DRUG PROTEIN BINDING; DRUG SAFETY; DRUG STRUCTURE; DRUG TARGETING; DRUG TOLERABILITY; DRUG TREATMENT FAILURE; ENZYME INHIBITION; EVIDENCE BASED MEDICINE; GENE MUTATION; GENETIC POLYMORPHISM; HUMAN; LEUKEMOGENESIS; LUNG EDEMA; MINIMAL RESIDUAL DISEASE; MONOTHERAPY; NAUSEA; NONHUMAN; OUTCOME ASSESSMENT; PLEURA EFFUSION; PRIORITY JOURNAL; REVIEW; SINGLE DRUG DOSE; STRUCTURE ACTIVITY RELATION; UNSPECIFIED SIDE EFFECT; VOMITING;

ANIMALS; ANTINEOPLASTIC AGENTS; CLINICAL TRIALS; DRUG DESIGN; DRUG RESISTANCE, NEOPLASM; HUMANS; LEUKEMIA, MYELOID, CHRONIC; MODELS, MOLECULAR; POINT MUTATION; PROTEIN BINDING; PROTEIN KINASE INHIBITORS; PROTEIN-TYROSINE KINASES;

EID: 34848929062     PISSN: 14741776     EISSN: 14741784     Source Type: Journal    
DOI: 10.1038/nrd2324     Document Type: Review

References (130)

1. Shtivelman, E., Lifshitz, B., Gale, R. P. & Canaani, E. Fused transcript of ABL and BCR genes in chronic myelogenous leukaemia. Nature 315, 550-554 (1985).
2. Ben-Neriah, Y., Daley, G. O., Mes-Masson, A. M., Witte. O. N. & Baltimore, D. The chronic myelogenous leukemia-specific p210 protein is the product of the BCR/ABL hybrid gene. Science 233, 212-214 (1986).
3. Ravandi, F. et al. Chronic myelogenous leukaemia with p185(BCR/ ABL) expression: Characteristics and clinical significance. Br. J. Haematol. 107, 581-586 (1999).
4. Daley, G. O., Van Etten, R. A. & Baltimore, D. Induction of chronic myelogenous leukemia in mice by the p210 Bcr/Abl gene of the Philadelphia chromosome. Science 247, 824-830 (1990).
5. Lugo, T. G., Pendergast, A. M., Muller, A. J. & Witte, O. N. Tyrosine kinase activity and transformation potency of BCR-ABL oncogene products. Science 247, 1079-1082 (1990).
6. Druker, B. J. et al. Effects of a selective inhibitor of the Abl tyrosine kinase on the growth of BCR-ABL positive cells. Nature Med. 2, 561-566 (1996).
7. Druker, B. J. et al. Efficacy and safety of a specific inhibitor of the BCR-ABL tyrosine kinase in chronic myeloid leukemia. N. Engl. J. Med. 344, 1031-1037 (2001).
8. Huse, M. & Kuriyan, J. The conformational plasticity of protein kinases. Cell 109, 275-282 (2002).
9. Schindler, T. et al. Structural mechinism for STI-571 inhibition of abelson tyrosine kinase. Science 289, 1938-1942 (2000).
10. Druker, B. J. et al. Five-year follow-up of patients receiving imatinib for chronic myeloid leukemia. N. Engl. J. Med. 355, 2408-2417 (2006).
11. Druker, B. J. et al. Activity of a specific inhibitor of the BCR-ABL tyrosine kinase in the blast crisis of chronic Tyeloid leukemia and acute lymphoblastic leukemia with the Philadelphia chromosome. N. Engl. J. Med. 344, 1038-1042 (2001).
12. Hochhaus, A. & La Rosee, P. Imatinib therapy in Chronic myelogenous leukemia: Strategies to avoid and overcome resistance. Leukemia 18, 1321-1331 (2004).
13. Shah, N. P. et al. Multiple BCR-ABL kinase domain mutations confer polyclonal resistance to the tyrosine kinase inhibitor imatinib (ST1571) in chronic phase and blast crisis chronic myeloid leukemia. Cancer Cell 2, 117-125 (2002).
14. Gorre, M. E. et al. Clinical resistance to STI-571 cancer therapy caused by BCR-ABL gene mutation or amplification. Science 293, 876-880 (2001).
15. Lowenberg, B. Minimal residual disease in chronic myeloid leukemia. N. Engl. J. Med. 349, 1399-1401 (2003).
16. Corbin, A. S., La Rosee, P., Stoffregen, E. P., Druker, B. J. & Deininger, M. W. Several BCR-ABL kinase domain mutants associated with imatinib mesylate resistance remain sensitive to imatinib. Blood 101, 4611-4614 (2003).
17. Gambacorti-Passerini, C. B, et al. Molecular mechanisms of resistance to imatinib in Philadelphia-chromosome-positive leukaemias. Lancet Oncol. 4, 75-85 (2003).
18. Nagar, B. et al. Crystal structures of the kinase domain of c-Abl in complex with the small molecule inhibitors PD173955 and imatinib (STI-571). Cancer Res 62, 4236-4243 (2002).
19. Hantschel, O. et al. A myristoyl/phosphotyrosine switch regulates c-Abl. Cell 112, 845-857 (2003).
20. Azam, M., Latek, R. R. & Daley. G. O. Mechanisms of autoinhibition and STI-571/imatinib resistance revealed by mutagenesis of BCR-ABL. Cell 112, 831-843 (2003).
21. Skaggs, B. J. et al. Phosphorylation of the ATP-binding loop directs oncogenicity of drug-resistant BCR-ABL mutants. Proc. Natl Acad. Sci. USA 103, 19466-19471 (2006).
22. Donato, N. J. et al. BCR-ABL independence and LYN kinase overexpression in chronic myelogenous leukemia cells selected for resistance to ST1571. Blood 101, 690-698 (2003).
23. Guilhot, F, et al. Dasatinib induces significant hematologic and cytogenetic responses in patients with imatiniti-resistant or -intolerant chronic myeloid leukemia in accelerated phase. Blood 109, 4143-4150 (2007).
24. Kantarjian, H. et al. Nilotinib in imatinib-resistant CML and Philadelphia chromosome-positive ALL. N. Engl. J. Med. 354, 2542-2551 (2006).
25. Talpaz, M. et al. Dasatinib in imatinib-resistant Philadelphia chromosome-positive leukemias. N. Engl. J. Med. 354, 2531-2541 (2006).
26. Hochhaus, A. et al. Dasatinib induces notable hematologic and cytogenetic responses in chronic-phase chronic myeloid leukemia after failure of imatinib therapy. Blood 109, 2303-2309 (2007).
27. Caries, J. et al. Dasatinib induces complete hematologic and cytogenetic responses in patients with imatinib-resistant or -intolerant chronic myeloid leukemia in blast crisis. Blood 109, 3207-3213 (2006).
28. le Coutre, P, et al. A Phase II study of nilotinib, a novel tyrosine kinase inhibitor administered to imatinib-resistant and -intolerant patients with chronic myelogenous leukemia (CML) in chronic phase (CP). Blood 108, Abstract 165 (2006).
29. Kantarjiari, H. et al. A Phase II study of nilotinib a novel tyrosine kinase inhibitor administered to imatinib-resistant or intolerant patients with chronic myelogenous leukemia (CML) in accelerated phase (AP). Blood 108, Abstract 2169 (2006).
30. ALk). Blood 108, Abstract, 1862 (2006).
31. Lombardo, L. J. et al. Discovery of N-(2-chloro-6-methyl,
32. Weisberg, E. et al. Characterization of AMN 107, a selective inhibitor of native and reutant BCR-ABL Cancer Cell 7, 129-141 (2005).
33. Shah, N. P. et al. Overriding imatinib resistance with a novel ABL kinase inhibitor. Science 305, 399-401 (2004).
34. Gambacorti-Passerini, C., Gasser, M., Ahmed, S., Assouline, S. & Scapozza, L. Abl inhibitor BMS354825 binding mode in Abelson kinase revealed by molecular docking studies. Leukemia 19, 1267-1269 (2005).
35. Tokarski. J. S. et al. The structure of Dasatinib [BMS-354825) bound to activated ABL kinase domain elucidates its inhibitory activity against imatinib-resistant ABL mutants. Cancer Res 66, 5790-7 (2006).
36. Burgess, M. R., Skaggs, B. J., Shah, N. P., Lee, F. Y. & Sawyers, C. L. Comparative analysis of two clinically active BCR-ABL kinase inhibitors reveals the role of conformation-specific binding in resistance. Proc. Natl Acad. Sci. USA 102, 3395-3400 (2005).
37. Kerkela, R. et al. Cardiotoxicity of the cancer therapeutic agent imatinib mesylate. Nature Med. 12, 908-916 (2006).
38. Hatfield, A., Owen, S. & Pilot, P. R. In reply to 'Cardiotoxicity of the cancer therapeutic agent imatinib mesylate'. Nature Med. 13, 15-16 (2007).
39. Abram, C. L. & Courtneidge, S. A. Src family tyrosine kinases and growth factor signaling. Exp. Cell Res. 254, 1-13 (2000).
40. Straus. D. B. & Weiss, A. Genetic evidence for the involvement of the lck tyrosine kinase in signal transduction through the T cell antigen receptor. Cell 70, 585-593 (1992).
41. Stanglmaier, M., Warmuth, M., Kleinlein, I., Reis, S. & Hallek, M. The interaction of the BCR-ABL tyrosine kinase with the Src kinase Hck is mediated by multiple binding domains. Leukemia 17, 283-289 (2003).
42. Danhauser-Riedl, S., Warmuth, M., Druker, B. J., Emmerich, B. & Hallek, M. Activation of Src kinases p53/56lyn and p59hck by p210bcr/abl in myeloid cells. Cancer Res. 56. 3589-3596 (1996).
43. Hu, Y. et al. Requirement of Src kinases Lyn, Hck and Fgr for BCR-ABL1-induced B-lymphoblastic leukemia but not chronic myeloid leukemia. Nature Genet. 36, 453-461 (2004).
44. Warmuth, M. et al. The Src family kinase Hck interacts with BCR-ABL by a kinase-independent mechanism and phosphorylates the Grb2-binding site of Bcr. J. Biol. Chem. 272, 33260-33270 (1997).
45. Klejman, A. et al. The Src family kinase Hck couples BCR/ABL to STAT5 activation in myeloid leukemia cells, EMBO J. 21, 5766-5774 (2002).
46. Bhatia, R. et al. Persistence of malignant hematopoietic progenitors in chronic myelogenous leukemia patients in complete cytogenetic remission following imatinib mesylate treatment. Blood 101, 4701-4707 (2003).
47. Kerkhoff, E. & Rapp, U. R. Cell cycle targets of Ras/Raf signalling. Oncogene 17, 1457-1462 (1998).
48. Tetsuya N, T. K., Kazuhide M, et al. STAT5 as a molecular regulator of proliferation, differentiation and apoptosis in hematopoietic cells. EMBO J. 18, 4754-4765 (1999).
49. Dai, Y., Rahmani, M., Corey, S. J., Dent, P. & Grant, S. A Bcr/ Abl-independent, Lyn-dependent form of imatinib mesylate (ST1-571) resistance is associated with altered expression of Bcl-2. J. Biol. Chem. 279, 34227-34239 (2004).
50. Donato, N. J. et al. Imatinib mesylate resistance through BCR-ABL independence in chronic myelogenous leukemia. Cancer Res. 64 672-677 (2004).
51. Hofmann, W. K. et al. Relation between resistance of Philadelphia-chromosome-positive acute lymphoblastic leukaemia to the tyrosine kinase inhibitor ST1571 and gene-exppession profiles: A gene-expression study. Lancet 359, 481-486 (2002).
52. Levinson, N. M. et al. A Src-like inactive conformation in the abl tyrosine kinase domain. PLoS Biol. 4, e144 (2006).
53. Nagar, B. et al. Structural basis for the autoinhibition of c-Abl tyrosine kinase. Cell 112, 859-871 (2003).
54. Golas, J. M. et al. SKI-606, a 4-anilino-3-quinolinecarbonitrile dual inhibitor of Src and Abl kinases, is a potent antiproliferative agent against chronic myelogenous leukemia cells in culture and causes regression of K562 xenografts in nude mice. Cancer Res. 63, 375-381 (2003).
55. Puttini, M. et al. In vitro and in vivo activity of SKI-606, a novel Src-Abl inhibitor, against imatinib-resistant BCR-ABL + neoplastic cells. Cancer Res. 66, 11314-11322 (2006).
56. Konig, H. et al. The dual Src/Abl kinase inhibitor SKI-606 effectively inhibits BCR-ABL kinase activity and reduces proliferation of CML primitive progenitor cells. Blood 108, Abstract 1370 (2006).
57. +) chronic myelogenous leukemia (CML) or acute lymphocytic leukemia (ALL) relapsed, refractory or intolerant of imatinib. Blood 108, Abstract 168 (2006).
58. Quintas-Cardama, A. et al. Pleural effusion in patients (pts) with chronic myelogenous leukemia (CML) treated with dasatinib after imatinib failure. Blood 108, Abstract 2164 (2006).
59. Sawyers, C. L. et al. Imatinib induces hematologic and cylogenetic responses in patients with chronic myelogenous leukemia in myeloid blast crisis: Results of a Phase II study. Blood 99, 3530-3539 (2002).
60. Shah, N. et al. Dasatinib 50 mg or 70 mg BID compared to 100 mg or 140 mg OD in patients with CML in chronic phase (CP) who are resistant or intolerant to imatinib: One-year results of CA180034. J. Clin. Oncol. 25 (Suppl. 20), 7004 (2007).
61. Kimura, S., Niwa, T., Hirabayashi, K. & Maekawa, T. Development of NS-187, a potent and selective dual BCR-ABL/Lyn tyrosine kinase inhibitor. Cancer Chemother. Pharmocol. 58 (Suppl. 7), 55-61 (2006).
62. Kimura, S. et al. NS-187, a potent and selective dual BCR-ABL/Lyn tyrosine kinase inhibitor, is a novel agent for imatinib-resistant leukemia. Blood 106, 3948-3954(2005).
63. Naito, H. et al. In vivo antiproliferative effect of NS-187, a dual BCR-ABL/Lyn tyrosine kinase inhibitor, on leukemic cells harbouring Abl kinase domain mutations. Leuk. Res. 30, 1443-1446 (2006).
64. + leukemia cells in the central nervous system, and cyclosporine A augments its in vivo activity. Blood 109, 306-314 (2007).
65. Petzer, A.L. et al. Low concentrations of ST1571 in the cerebrospinal fluid: A case report. Br. J. Haematol. 117, 623-625 (2002).
66. Takayama, N., Sato, N., O'Brien, S. G., Ikeda, Y. & Okamoto, S. Imatinib mesylate has limited activity against the central nervous system involvement of Philadelphia chromosome-positive acute lymphoblastic leukaemia due to poor penetration into cerebrospinal fluid. Br. J. Haemotol. 119, 106-108 (2002).
67. Neville. K. et al. Plasma and cerebrospinal fluid pharmacokinetics of imatinib after administration to nonhuman primates. Clin. Cancer Res. 10, 2525-2529 (2004).
68. Pfeifer, H. et al. Risk and prognosis of central nervous system leukemia in patients with Philadelphia chromosome-positive acute leukemias treated with imatinib mesylate. Clin. Cancer Res. 9 4674-4681 (2003).
69. +) leukemias. Proc. Am. Soc. Cancer Res. Abstract 2637 (2007).
70. Hennequin, L. F. et al. N-(5-chloro- 1,3-benzodioxol-4-yl)-7-[2-(4-methylpiperazin-1-yl) ethoxyl-5- (tetrahydro-2H-pyran-4-yloxy)quinazolin-4-amine, a novel, highly selective, orally available, dual-specific c-Src/Abl kinase inhibitor. J. Med. Chem. 49, 6465-6488 (2006).
71. Hennequin, L. et al. The discovery of AZD0530: A novel, oral, highly selective and dual-specific inhibitor of the Src and Abl family kinases. Proc. Am. Assoc. Cancer Res. 46, 595 (2005).
72. Lockton, J. Phase I ascending single and multiple dose studies to assess the safety, tolerability and pharmacokinetics of AZD0530, a highly selective, dual specific Src/Abl inhibitor. J. Clin. Oncol. 23 (Suppl. 1), 3125 (2005).
73. Dalgamo, D. et al. Structural basis of Src tyrosine kinase inhibition with a new class of potent and selective trisubstituted purine-based compounds. Chem. Biol. Drug Des. 67, 46-57 (2006).
74. Wang, Y. et al. Bone-targeted 2,6,9-trisubstituted purines: Novel inhibitors of Src tyrosine kinase for the treatment of bone diseases. Bioorg. Med. Chem. Lett. 13, 3067-3070 (2003).
75. O'Hare, T. et al. Inhibition of wild-type and mutant BCR-ABL by AP23464, a potent ATP-based oncogenic protein kinase inhibitor: implications for CML. Blood 104, 2532-2539 (2004).
76. Azam, M. et al. Activity of dual SRC-ABL inhibitors highlights the role of BCR/ABL kinase dynamics in drug resistance. Proc. Natl Acad. Sci. USA 103, 9244-9249 (2006).
77. Corbin, A. S. et al. In vitro and in vivo activity of ATP-based kinase inhibitors AP23464 and AP23848 against activation-loop mutants of Kit. Blood 106, 227-234 (2005).
78. Hamby, J. M. et al. Structure-activity relationships for a novel series of pyrido[2,3-d]pyrimidine tyrosine kinase inhibitors. J. Med. Chem. 40, 2296-2303 (1997).
79. Huron, D. R. et al. A novel pyridopyrimidine inhibitor of abl kinase is a picomolar inhibitor of BCR-ABL-driven K562 cells and is effective against ST1571-resistant BCR-ABL mutants. Clin. Cancer Res. 9, 1267-1273 (2003).
80. Wolff, N. C. et al. PD166326, a novel tyrosine kinase inhibitor, has greater antileukemic activity than imatinib mesylate in a murine model of chronic myeloid leukemia. Blood 105, 3995-4003 (2005).
81. von Bubnoff, N., Barwisch, S., Speicher, M. R., Peschel, C. & Duyster, J. A cell-based screening strategy that predicts mutations in oncogenic tyrosine kinases: Implications for clinical resistance in targeted cancer treatment. Cell Cycle 4, 400-406 (2005).
82. Wisniewski, D. et al. Characterization of potent inhibitors of the BCR-ABL and the C-kit receptor tyrosine kinases. Cancer-Res. 62 4244-4255 (2002).
83. Dorsey, J. F., Jove, R., Kraker. A. J. & Wu, J. The pyrido[2,3-d]pyrimidine derivative PD 180970 inhibits p210BCR-Abl tyrosine kinase and induces apoptosis of K562 leukemic cells. Cancer Res. 60, 3127-3131 (2000).
84. La Rosee, P., Corbin, A. S., Stoffregen, E. P., Deininger, M. W. & Druker, B. J. Activity of the BCR-ABL kinase inhibitor PD 180970 against clinically relevant BCR-ABL isoforms that cause resistance to imatinib mesylate (Gleevec, ST1571). Cancer Res. 62, 7149-7153 (2002).
85. Lerma, E. I. et al. Novel compounds with antiproliferative activity against imatinib-resistant cell lines. Mol. Cancer Ther. 6, 655-666 (2007).
86. Hanke, J. H. et al. Discovery of a novel, potent, and Src family-selective tyrosine kinase inhibitor. Study of Lck- and FynT-dependent T cell activation. J. Biol. Chem. 271, 695-701 (1996).
87. Tatton, L., Morley, G. M., Chopra, R. & Khwaja, A. The Src-selective kinase inhibitor PP 1 also inhibits Kit and BCR-ABL tyrosine kinases. J. Biol. Chem. 278, 4847-4853 (2003).
88. Warmuth, M. et al. Dual-specific Src and Abl kinase inhibitors, PP1 and CGP76030, inhibit growth and survival of cells expressing imatinib mesylate-resistant BCR-ABL kinases. Blood 101, 664-672 (2003).
89. Adrian, F. J. et al. Allosteric inhibitors of BCR-ABL dependent cell proliferation. Nature Chem. Biol. 2, 95-102 (2006).
90. Gumireddy, K. et al. A non-ATP-competitive inhibitor of BCR-ABL overrides imatinib resistance. Proc. Natl Azad. Sci. USA 102 1992-1997 (2005).
91. Lane H.A. & Nigg, E.A. Antibody microinjection reveals an essential role for human pole-like Kinase 1 (Plk 1) in the functional maturation of mitotic centrosomes. J. Cell Biol. 135, 1701-1713 (1996)
92. Gumireddy, K. et al. 0N01910, a non-ATP-competitive small molecule inhibitor of PIK1, is a potent anticancer agent. Cancer, Cell 7 275-286 (2005).
93. Carmena, M. & Earnshaw W.C. The cellular geography of aurora kinases. Nature Rev. Mol. Cell Biol. 4, 842-854 (2003).
94. Harrington, E. A. et al. VX-680; a potent And selective small-molecule inhibitor of the Aurora kinases. suppresses tumor growth in vivo. Nature Med. 10, 262-267 (2004).
95. Carter, T. A. et al. Inhibition of drug-resistant mutants of ABL, KIT, and EGF receptor kinases. Proc. Natl Acad. Sci. USA 102 11011-11016 (2005).
96. Hoover, R. & Harding, M. W. Synergistic activity of the Aurora kinase inhibitor MK-0457 (VX-680) with idarubicin, Ara-C, and inhibitors of BCR-ABL Blood 108, Abstract 1384 (2006).
97. Shah, N. et al. The most common dasatinib-resistant BCR-ABL kinase domain mutations in patients with chronic myeloid leukemia are sensitive to VX-680: Rationale for early combination kinase inhibitor therapy. Blood 108, Abstract 2175 (2006).
98. Cheetham, G. M., Charlton, P. A., Golec, J. M. & Pollard, J. R. Structural basis for potent inhibition of the Aurora kinases and a T3151 multi-drug resistant mutant form of ABL kinase by VX-680. Cancer Lett. 251, 323-329 (2007).
99. Young, M. A. et al. Structure of the kinase domain of an imatinib-resistant Abl mutant in complex with the Aurora kinase inhibitor VX-680. Cancer Res. 66, 1007-1014 (2006).
100. Giles, F. J. et al. MK-0457, a novel kinase inhibitor, is active in patients with chronic myeloid leukemia or acute lymphocytic leukemia with the T3151 BCR-ABL mutation. Blood 109, 500-502 (2007).
101. Giles, F. et al. MK-0457, a novel Aurora kinase and BCR-ABL inhibitor, is active against BCR-ABL T3151 mutant chronic myelogenous leukemia. Blood 108, Abstract 163 (2006).
102. Tauchi, T, et al. Activity of a novel Aurora kinase inhibitor, VE-465, against T3151 mutant form of BCR-ABL: In vitro and in vivo studies. Blood 108, Abstract 1358 (2006).
103. Modugno, M. et al. Targeted inhibition of the gatekeeper mutant T3151 of BCR-ABL by an Aurora kinase inhibitor. Proc. Am. Assoc. Cancer Res. Abstract 3253 (2007).
104. Regan, J. et al. Pyrazole urea-based inhibitors of p38 MAP kinase: from lead compound to clinical candidate. J. Med. Chem. 45, 2994-3008 (2002).
105. Kuma, Y. et al. BIRB796 inhibits all p38 MAPK isoforms in vitro and in vivo. J. Biol. Chem. 280, 19472-19479 (2005).
106. Fabian, M. A. et al. A small molecule-kinase interaction map for clinical kinase inhibitors. Nature Biotech. 23, 329-336 (2005).
107. O'Hare, T. & Druker, B. J. BIRB-796 is not an effective ABL(T3151) inhibitor. Nature Biotech. 23, 1209-1210 (2005).
108. Zhang, W. Inhibition of the drug-resistant T3151 mutant of BCR-ABL. Eur. J. Cancer Suppl. 4, 54 (2006).
109. Summy, J. M. et al. AP23846, a novel and highly potent Src family kinase inhibitor. reduces vascular endothelial growth factor and interleukin-B expression in human solid tumor cell lines and abrogates downstream angiogenic processes, Mol. Cancer Ther. 4, 1900-1911 (2005).
110. Zhu, H. Enzymatic and cellular inhibition of BCR/ABL T3151 by a novel src/ABL inhibitor. Proc. Am. Assoc. Cancer Res. 47, Abstract 3771 (2006).
111. Zhu, H. Addressing BCR/ABL resistance: Evolving dasatinib to a novel inhibitor of the T3151 BCR/Abl mutation. Proc. Am. Assoc. Cancer Res. Abstract 3254 (2007).
112. Chen, R., Gandhi, V. & Plunkett, W. A sequential blockade strategy for the design of combination therapies to overcome oncogene addiction in chronic myelogenous leukemia. Cancer Res. 66, 10959-10966 (2006).
113. T3151 transcript disappearance in an imatinib-resistant CML patient treated with homoharringtonine: A new therapeutic challenge? Leukemia 31 May 2007 (doi:10.1038/ sj.leu.2404772).
114. Buchdunger, E. et al. Inhibition of the Abl protein-tyrosine kinase in vitro and in vivo by a 2-phenylaminopyrimidine derivative. Cancer Res. 56, 100-104 (1996).
115. Morris, S. W. et al. Fusion of a kinase gene, ALK, to a nucleolar protein gene, NPM, in non-Hodgkin's lymphoma. Science 263, 1281-1284 (1994).
116. Hofstra. R. M. et al. A mutation in the RET proto-oncogene associated with multiple endocrine neoplasia type 2B and sporadic medullary thyroid carcinoma. Nature 367, 375-376 (1994).
117. Hirota, S. et al. Gain-of-function mutations of c-KIT in human gastrointestinal stromal tumors. Science 279, 577-580 (1998).
118. Paez, J. G. et al. EGFR mutations in lung cancer: Correlation with clinical response to gefitinib therapy. Science 304, 1497-1500 (2004).
119. Lynch, T. J. et al. Activating mutations in the epidermal growth factor receptor underlying responsiveness of non-small-cell lung cancer to gefitinib. N. Engl. J. Med. 350, 2129-2139 (2004).
120. Tamborini, E. et al. A new mutation in the KIT ATP pocket causes acquired resistance to imatinib in a gastrointestinal stromal tumor patient. Gastroenterology 127, 294-299 (2004).
121. Kobayashi, S. et al. EGFR mutation and resistance of non-small-cell lung cancer to gefitinib. N. Engl. J. Med. 352 786-792 (2005).
122. Cools, J. et al. A tyrosine kinase created by fusion of the PDGFRA and FIP1L1 genes as a therapeutic target of imatinib in idiopathic hypereosinophilic syndrome. N. Engl. J. Med. 348, 1201-1214 (2003).
123. Robinson, D. R., Wu, Y. M. & Lin, S. F. The protein tyrosine kinase family of the human genome. Oncogene l9: 5548-5557 (2000).
124. Manning, G., Whyte. D. B., Martinez, R.; Hunter, T. & Sudarsanam, S. The protein kinase complement of the human genome. Science 298, 1912-1934 (2002).
125. Liu, Y. & Gray, N. S. Rational design of inhibitors that bind to inactive kinase conformations. Nature Chem. Biol. 2: 358-364 (2006).
126. Hubbard, S. R., Wei, L. Ellis, L. & Hendrickson, W. A. Crystal structure ofthe tyrosine kinase domain of the human insulin receptor. Nature 372, 746-754 (1994).
127. Blum. G., Gazit, A. & Levitzki, A. Substrate competitive inhibitors of IGF-1 receptor kinase. Biochemistry 39, 15705-15712 (2000).
128. Nigg, E. A. Mitotic kinases as regulators of cell division and its checkpoints. Nature Rev. Mol. Cell Biol. 2, 21-32 (2001).
129. Superti-Furga. G. & Courtneidge, S. A. Structure-function relationships in Src family and related protein tyrosine kinases. Bioessays 17, 321-330 (1995).
130. Cowan-Jacob, S. W. et al. Imatinib (ST1571) resistance in chronic myelogenous leukemia: Molecular basis of the underlying mechanisms and potential strategies for treatment. Mini Rev. Med. Chem. 4, 285-299 (2004).