Tyrosine kinase ihibitors for the treatment of chronic myeloid leukemia

Anti-Cancer Agents in Medicinal Chemistry

Volumn 9, Issue 8, 2009, Pages 853-863

  Tolomeo, Manlio ^a,b   Dieli, Francesco ^a   Gebbia, Nicola ^a   Simoni, Daniele ^b  

^a UNIVERSITY OF PALERMO   (Italy)

^b UNIVERSITY OF FERRARA   (Italy)

Author keywords

Bcr Abl; Chronic myelogenous leukemia; Tyrosine kinase inhibitors

Indexed keywords

2 [2 METHOXY 5 (2,4,6 TRIMETHOXYSTYRYLSULFONYLMETHYL)ANILINO]PROPIONIC ACID; 4 (3 DIMETHYLAMINO 1 PYRROLIDINYLMETHYL) 3 TRIFLUOROMETHYL N [4 METHYL 3 [[4 (5 PYRIMIDINYL) 2 PYRIMIDINYL]AMINO]PHENYL]BENZAMIDE; 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; 7 [4 [2 (2 METHOXYETHYLAMINO)ETHOXY]PHENYL] 5 (4 METHOXYPHENYL) 7H PYRROLO[2,3 D]PYRIMIDIN 4 AMINE; [4 [2 CYCLOPENTYL 9 (3 HYDROXYPHENETHYL)PURIN 6 YLAMINO]PHENYL]DIMETHYLPHOSPHINE OXIDE; ABELSON KINASE; ADENOSINE TRIPHOSPHATE; ALPHA INTERFERON; AP 23848; BCR ABL PROTEIN; BOSUTINIB; BUSULFAN; CYTARABINE; DASATINIB; GNF 2; HYDROXYUREA; IMATINIB; MITOGEN ACTIVATED PROTEIN KINASE INHIBITOR; NILOTINIB; PHOSPHATIDYLINOSITOL 3 KINASE INHIBITOR; PROTEIN BCL 2 INHIBITOR; PROTEIN FARNESYLTRANSFERASE INHIBITOR; PROTEIN INHIBITOR; PROTEIN TYROSINE KINASE; PROTEIN TYROSINE KINASE INHIBITOR; PURINE DERIVATIVE; UNCLASSIFIED DRUG; UNINDEXED DRUG; ANTINEOPLASTIC AGENT; PROTEIN KINASE INHIBITOR;

ABDOMINAL PAIN; ALLOGENIC BONE MARROW TRANSPLANTATION; APOPTOSIS; BINDING SITE; BONE MARROW SUPPRESSION; CANCER CELL; CANCER RESISTANCE; CELL CYCLE; CELL GROWTH; CHRONIC MYELOID LEUKEMIA; CLINICAL TRIAL; CYTOPENIA; DIARRHEA; DRUG DESIGN; DRUG ERUPTION; DRUG MECHANISM; DRUG PROTEIN BINDING; DRUG STRUCTURE; DRUG TARGETING; EXTRACELLULAR MATRIX; GENE AMPLIFICATION; HEMATOLOGIC MALIGNANCY; HUMAN; IN VITRO STUDY; IN VIVO STUDY; LEUKEMIA; LEUKEMOGENESIS; LOW DRUG DOSE; NAUSEA; NEUTROPENIA; NONHUMAN; POINT MUTATION; REVIEW; SIDE EFFECT; THROMBOCYTOPENIA; VOMITING; DRUG ANTAGONISM; GENETICS; PATHOLOGY; PHYSIOLOGY;

ANTINEOPLASTIC AGENTS; APOPTOSIS; FUSION PROTEINS, BCR-ABL; HUMANS; LEUKEMIA, MYELOGENOUS, CHRONIC, BCR-ABL POSITIVE; PROTEIN KINASE INHIBITORS; PROTEIN-TYROSINE KINASES;

EID: 73449144420     PISSN: 18715206     EISSN: None     Source Type: Journal    
DOI: 10.2174/187152009789124637     Document Type: Review

References (84)

1. Vlahovic, G.; Crawford, J. Activation of tyrosine kinases in cancer. Oncologist, 2003, 8(6), 531-8.
2. Paul, M.K.; Mukhopadhyay, A.K. Tyrosine kinase - Role and significance in Cancer. Int. J. Med. Sci., 2004, 1(2), 101-115.
3. Groffen, J.; Heistenkamp, N. Chronic myeloid leukemia; Goldman JM: London, 1987.
4. Bernards, A.; Rubin, C.M.; Westbrook, C.A.; Paskind, M.; Baltimore, D. The first intron in the human c-abl gene is at least 200 kilobases long and is a target for translocations in chronic myelogenous leukemia. Mol. Cell. Biol., 1987, 7(9), 3231-3236.
5. Grosveld, G.; Verwoerd, T.; van Agthoven, T.; de Klein, A.; Ramachandran, K.L.; Heisterkamp, N.; Stam, K.; Groffen, J. The chronic myelocytic cell line K562 contains a breakpoint in bcr and produces a chimeric bcr/c-abl transcript. Mol. Cell Biol. Mol. Cell. Biol., 1986, 6(2), 607-616.
6. Groffen, J.; Stephenson, J.R.; Heiserkamp, N.; de Klein, A.; Bertram, C.R.; Grosveld, G. Philadelphia chromosomal breakpoints are clustered within a limited region, bcr, on chromosome 22. Cell, 1984, 36(1), 93-99.
7. Heisterkamp, N.; Stam, K.; Groffen, J.; de Klein, A.; Grosveld, G. Structural organization of the bcr gene and its role in the Ph' translocation. Nature, 1985, 315(6022), 758-21.
8. Shtivelman, E.; Lifshitz, B.; Gale, R.P.; Canaani, E. Fused transcript of abl and bcr genes in chronic myelogenous leukaemia. Nature, 1985, 315(6020), 550-4.
9. Kurzrock, R.; Shtalrid, M.; Gutterman, J.U.; Koller, C.A.; Walters, R.; Trujillo, J.M.; Talpaz, M. Molecular analysis of chromosome 22 breakpoints in adult Philadelphia-positive acute lymphoblastic leukaemia. Br. J. Haematol., 1987, 67(1), 55-9.
10. Chan, L.C.; Karhi, K.K.; Rayter, S.I.; Heisterkamp, N.; Eridani, S.; Powles, R.; Lawler, S.D.; Groffen, J.; Faulkes, J.G.; Greaves, M.F. A novel abl protein expressed in Philadelphia chromosome positive acute lymphoblastic leukaemia. Nature, 1987, 325(6105), 635-7.
11. Brasher, B.B.; Roumiantsev, S.; Van Etten, R.A. Mutational analysis of the regulatory function of the c-Abl Src homology 3 domain. Oncogene, 2001, 20(53), 7744-52.
12. Brasher, B.B.; Van Etten, R.A. c-Abl has high intrinsic tyrosine kinase activity that is stimulated by mutation of the Src homology 3 domain and by autophosphorylation at two distinct regulatory tyrosines. J. Biol. Chem., 2000, 275(45), 35631-7.
13. Evans, C.A.; Owen-Lynch, P.J.; Whetton, A.D.; Dive, C. Activation of the Abelson tyrosine kinase activity is associated with suppression of apoptosis in hemopoietic cells. Cancer Res., 1993, 53(8), 1735-8.
14. Smith, K.M.; Yacobi, R.; Van Etten, R.A. Autoinhibition of Bcr-Abl through its SH3 domain. Mol. Cell., 2003, 12(1), 27-37.
15. Van Etten, R.A. Mechanisms of transformation by the BCR-ABL oncogene: new perspectives in the post-imatinib era. Leuk. Res., 2004, 28(Suppl 1), S21-8.
16. Konopka, J.B.; Watanabe, S.M.; Witte, O.N. An alteration of the human c-abl protein in K562 leukemia cells unmasks associated tyrosine kinase activity. Cell, 1984, 37(3), 1035-42.
17. Bedi, A.; Zehnbauer, B.A.; Barber, J.P.; Sharkis, S.J.; Jones, R.J. Inhibition of apoptosis by BCR-ABL in chronic myeloid leukemia. Blood, 1994, 83(8), 2038-44.
18. Sirard, C.; Laneuville, P.; Dick, J. Expression of bcr-abl abrogates factor-dependent growth of human hematopoietic M07E cells by an autocrine mechanism. Blood, 1994, 83(6), 1575-85.
19. Verfaille, C.M.; McCarthy, J.B.; McGlave, P.B. Mechanisms underlying abnormal trafficking of malignant progenitors in chronic myelogenous leukemia. Decreased adhesion to stroma and fibronectin but increased adhesion to the basement membrane components laminin and collagen type IV. J. Clin. Invest., 1992, 90(4), 1232-41.
20. Skorski, T.; Nieborowska-Skorska, M.; Wlodarski, P.; Wasik, M.; Trotta, R.; Kanakaraj, P.; Salomoni, P.; Antonyak, M.; Martinez, R.; Majewski, M.; Wong, A.; Perussia, B.; Calabretta, B. The SH3 domain contributes to BCR/ABL-dependent leukemogenesis in vivo: role in adhesion, invasion, and homing. Blood, 1998, 91(2), 406-18.
21. Henderson, Y.C.; Guo, X.Y.; Greenberger, J.; Deisseroth, A.B. Potential role of bcr-abl in the activation of JAK1 kinase. Clin. Cancer Res., 1997, 3(2), 145-9.
22. de Groot, R.P.; Raaijmakers, J.A.; Lammers, J.W.; Koenderman, L. STAT5-Dependent CyclinD1 and Bcl-xL expression in Bcr-Abltransformed cells. Mol. Cell. Biol. Res. Commun., 2000, 3(5), 299-305.
23. Shuai, K.; Halpern, J.; Hoeve, J.; Rao, X.; Sawyers, C.L. Constitutive activation of STAT5 by the BCR-ABL oncogene in chronic myelogenous leukemia. Oncogene, 1996, 13(2), 247-54.
24. Horita, M.; Andreu, E.J.; Benito, A.; Arbona, C.; Sanz, C.; Benet, I.; Prosper, F.; Fernandez-Luna, J.L. Blockade of the Bcr-Abl kinase activity induces apoptosis of chronic myelogenous leukemia cells by suppressing signal transducer and activator of transcription 5-dependent expression of Bcl-xL. J. Exp. Med., 2000, 191(6), 977-84.
25. Silva, M.; Benito, A.; Sanz, C.; Prosper, F.; Ekhterae, D.; Nuñez, G.; Fernandez-Luna, J.L. J. Erythropoietin can induce the expression of bcl-x(L) through Stat5 in erythropoietin-dependent progenitor cell lines. Biol. Chem., 1999, 274(32), 22165-9.
26. Pendergast, A.M.; Quilliam, L.A.; Cripe, L.D.; Bassing, C.H.; Dai, Z.; Li, N.; Batzer, A.; Rabun, K.M.; Der, C.J.; Schlessinger, J.; Gishizky, M. L. BCR-ABL-induced oncogenesis is mediated by direct interaction with the SH2 domain of the GRB-2 adaptor protein. Cell, 1993, 75(1), 175-85.
27. Franke, T.F.; Kaplan, D.R.; Cantley, L.C. PI3K: downstream AKTion blocks apoptosis. Cell, 1997, 88(4), 435-7.
28. Madrid, L.V.;Wang, C.-Y.; Guttridge, D.C.; Schottelius, A.; Baldwin, A.S.; Mayo, M. Akt suppresses apoptosis by stimulating the transactivation potential of the RelA/p65 subunit of NF-kappaB. Mol. Cell. Biol., 2000, 20(5), 1626-38.
29. Hoover, R.R.; Gerlach, M.J.; Koh, E.Y.; Daley, G.Q. Cooperative and redundant effects of STAT5 and Ras signaling in BCR/ABL transformed hematopoietic cells. Oncogene, 2001, 20(41), 5826-35.
30. Goetz, A.W.; van der Kuip, H.; Maya, R.; Oren, M.; Aulitzky, W.E. Requirement for Mdm2 in the survival effects of Bcr-Abl and interleukin 3 in hematopoietic cells. Cancer Res., 2001, 61(20), 7635-41.
31. Dou, Q.P.; McGuire, T.F.; Peng, Y.; An, B. Proteasome inhibition leads to significant reduction of Bcr-Abl expression and subsequent induction of apoptosis in K562 human chronic myelogenous leukemia cells. J. Pharmacol. Exp. Ther., 1999, 289(2), 781-90.
32. Clarkson, B. and Strife, A. Linkage of proliferative and maturational abnormalities in chronic myelogenous leukemia and relevance to treatment. Leukemia, 1993, 7(11), 1683-721.
33. Kramer, A.; Loffler, H.; Bergmann, J.; Hochhaus, A.; Hehlmann, R. Proliferating status of peripheral blood progenitor cells from patients with BCR/ABL-positive chronic myelogenous leukemia. Leukemia, 2001,15(1), 62-8.
34. Ribeiro, R.C.; Abromowitch, M.; Raimondi, S.C.; Murphy, S.B.; Behm, F.; Williams, D.L. Clinical and biologic hallmarks of the Philadelphia chromosome in childhood acute lymphoblastic leukemia. Blood, 1987, 70(4), 948-53.
35. Wilson-Rawls, J.; Xie, S.; Liu, J.; Laneuville, P.; Arlinghaus, R.B. P210 Bcr-Abl interacts with the interleukin 3 receptor beta(c) subunit and constitutively induces its tyrosine phosphorylation. Cancer Res., 1996, 56(15), 3426-30.
36. Ghaffari, S.; Daley, G.Q.; Lodish, H.F. Growth factor independence and BCR/ABL transformation: promise and pitfalls of murine model systems and assays. Leukemia, 1999, 13(8), 1200-6.
37. Verfaillie, C.M.; Hurley, R.; Lundell, B.I.; Zhao, C.; Bhatia, R. Integrin-mediated regulation of hematopoiesis: do BCR/ABLinduced defects in integrin function underlie the abnormal circulation and proliferation of CML progenitors? Acta Haematol., 1997, 97(1-2), 40-52.
38. Gordon, M.Y.; Dowding, C.R.; Riley, G.P.; Goldman, J.M.; Greaves, M.F. Altered adhesive interactions with marrow stroma of haematopoietic progenitor cells in chronic myeloid leukaemia. Nature, 1987, 328(6128), 342-4.
39. Bazzoni, G.; Carlesso, N.; Griffin, J.D.; Hemler, M.E. Bcr/Abl expression stimulates integrin function in hematopoietic cell lines. J. Clin. Invest., 1996, 98(2), 521-8.
40. Salgia, R.; Li, J.L.; Ewaniuk, D.S.; Pear, W.; Pisick, E.; Burky, S.A.; Ernst, T.; Sattler, M.; Chen, L.B.; Griffin, J.D. BCR/ABL induces multiple abnormalities of cytoskeletal function. J. Clin. Invest., 1997, 100(1), 46-57.
41. Salgia, R.; Brunkhorst, B.; Pisick, E.; Li, J.L.; Lo, S.H.; Chen, L.B.; Griffin, J.D. Increased tyrosine phosphorylation of focal adhesion proteins in myeloid cell lines expressing p210BCR/ABL. Oncogene, 1995, 11(6), 1149-55.
42. van der Kuip, H.; Goetz, A.W.; Miething, C.; Duyster, J.; Aulitzky, W.E. Adhesion to fibronectin selectively protects Bcr-Abl+ cells from DNA damage-induced apoptosis. Blood, 2001, 98(5), 1532-41.
43. Bonifazi, F.; de Vivo, A.; Rosti, G.; Guilhot, F.; Guilhot, J.; Trabacchi, E.; Hehlmann, R.; Hochhaus, A.; Shepherd, P.C.; Steegmann, J.L.; Kluin-Nelemans, H.C.; Thaler, J.; Simonsson, B.; Louwagie, A.; Reiffers, J.; Mahon, F.X.; Montefusco, E.; Alimena, G.; Hasford, J.; Richards, S.; Saglio, G.; Testoni, N.; Martinelli, G.; Tura, S.; Baccarani, M.; Europena Study Group on Interferon in Chronic Myeloid Leukemia; Italian Cooperative Study Group on CML; France Intergroup of CML; German CML Study Group; UK Medical Research Council Working Party on CML; Spanish CML Study Group; Australian CML Study Group; Swedish CML Study Group. Chronic myeloid leukemia and interferon-alpha: a study of complete cytogenetic responders. Blood, 2001, 98(10), 3074-81.
44. Mahon, F.X.; Delbrel, X.; Cony-Makhoul, P.; Faberes, C.; Boiron, J. M.; Barthe, C.; Bilhou-Nabera, C.; Pigneux, A.; Marit, G.; Reiffers J. Follow-up of complete cytogenetic remission in patients with chronic myeloid leukemia after cessation of interferon alfa. J. Clin. Oncol., 2002, 20(1), 214-20.
45. Druker, B.J.; Tamura, S.; Buchdunger, E.; Ohno, S.; Segal, G.M.; Fanning, S.; Zimmermann, J.; Lydon, N.B. Effects of a selective inhibitor of the Abl tyrosine kinase on the growth of Bcr-Abl positive cells. Nat. Med., 1996, 2(5), 561-6.
46. Deininger, M.W.; Goldman, J.M.; Lydon, N.; Melo, J.V. The tyrosine kinase inhibitor CGP57148B selectively inhibits the growth of BCR-ABL-positive cells. Blood, 1997, 90(9), 3691-8.
47. Buchdunger, E.; Cioffi, C.L.; Law, N.; Stover, D.; Ohno-Jones, S.; Druker, B.J.; Lydon, N.B. Abl protein-tyrosine kinase inhibitor STI571 inhibits in vitro signal transduction mediated by c-kit and platelet-derived growth factor receptors. J. Pharmacol. Exp. Ther., 2000, 295(1), 139-45.
48. Ottmann, O.G.; Druker, B.J.; Sawyers, C.L.; Goldman, J.M.; Reiffers, J.; Silver, R.T.; Tura, S.; Fischer, T.; Deininger, M.W.; Schiffer, C.A.; Baccarani, M.; Gratwohl, A.; Hochhaus, A.; Hoelzer, D.; Fernandes-Reese, S.; Gathmann, I.; Capdeville, R.; O'Brien, S.G. A phase 2 study of imatinib in patients with relapsed or refractory Philadelphia chromosome-positive acute lymphoid leukemias. Blood, 2002, 100(6), 1965-71.
49. Shah, N.P.; Nicoll, J.M.; Nagar, B.; Gorre, M.E.; Paquette, R.L.; Kuriyan, J.; Sawyers, C.L. Multiple BCR-ABL kinase domain mutations confer polyclonal resistance to the tyrosine kinase inhibitor imatinib (STI571) in chronic phase and blast crisis chronic myeloid leukemia. Cancer Cell, 2002, 2(2), 117-25.
50. Branford, S.; Rudzki, Z.; Walsh, S.; Grigg, A.; Arthur, C.; Taylor, K.; Herrmann, R.; Lynch, K.P.; Hughes, T.P. High frequency of point mutations clustered within the adenosine triphosphatebinding region of BCR/ABL in patients with chronic myeloid leukemia or Ph-positive acute lymphoblastic leukemia who develop imatinib (STI571) resistance. Blood, 2002, 99(9), 3472-5.
51. Gorre, M.E.; Mohammed, M.; Ellwood, K.; Hsu, N.; Paquette, R.; Rao, P.N.; Sawyers, C.L. Clinical resistance to STI-571 cancer therapy caused by BCR-ABL gene mutation or amplification. Science, 2001, 293(5531), 876-80.
52. Mahon, F.X.; Belloc, F.; Lagarde, V.; Chollet, C.; Moreau-Gaudry, F.; Reiffers, J.; Goldman, J.M.; Melo J.V. MDR1 gene overexpression confers resistance to imatinib mesylate in leukemia cell line models. Blood, 2003, 101(6), 2368-73.
53. Burger, H.; van Tol, H.; Boersma, A.W.M.; Brok, M.; Wiemer, E.A.C.; Stoter, G.; Nooter K. Imatinib mesylate (STI571) is a substrate for the breast cancer resistance protein (BCRP)/ABCG2 drug pump. Blood, 2004, 104(9), 2940-2.
54. Gambacorti-Passerini, C.; Barni, R.; le Coutre, P.; Zucchetti, M.; Cabrita, G.; Cleris, L.; Rossi, F.; Gianazza, E.; Brueggen, J.; Cozens, R.; Pioltelli, P.; Pogliani, E.; Corneo, G.; Formelli, F.; D'Incalci M. Role of alpha1 acid glycoprotein in the in vivo resistance of human BCR-ABL(+) leukemic cells to the abl inhibitor STI571. J. Natl. Cancer Inst., 2000, 92(20), 1641-50.
55. Weisberg, E.; Manley, P.W.; Breitenstein, W.; Brüggen, J.; Cowan-Jacob, S.W.; Ray, A.; Huntly, B.; Fabbro, D.; Fendrich, G.; Hall-Meyers, E.; Kung, A.L.; Mestan, J.; Daley, G.Q.; Callahan, L.; Catley, L.; Cavazza, C.; Azam, M.; Neuberg, D.; Wright, R.D.; Gilliland, D.G.; Griffin, J.D. Characterization of AMN107, a selective inhibitor of native and mutant Bcr-Abl. Cancer Cell, 2005, 7(2), 129-41.
56. Weisberg, E.; Manely, P.; Mestan, J.; Cowan-Jacob, S.; Ray, A.; Griffin, J.D. AMN107 (nilotinib): a novel and selective inhibitor of BCR-ABL. Br. J. Cancer, 2006, 94(12), 1765-9.
57. Tokarski, J.S.; Newitt, J.; Lee, F.Y.; Lombardo, L.; Borzilleri, R.; Kish, K.; Xie, D.; Zhang, Y.; Cheng, J.D.; Kiefer, S.E.; Ying, C.; Chang, J.; Klei, H.E. The crystal structure of Abl kinase with BMS-354825, a dual SRC/ABL kinase inhibitor. Blood, 2004, 104, 160a; Abstr. 553.
58. Hochhaus, A.; Kantarjian, H.M.; Baccarani, M.; Lipton, J.H.; Apperley, J.F.; Druker, B.J.; Facon, T.; Goldberg, S.L.; Cervantes, F.; Niederwieser, D.; Silver, R.T.; Stone, R.M.; Hughes, T.P.; Muller, M.C.; Ezzeddine, R.; Countouriotis, A.M.; Shah, N.P. Dasatinib induces notable hematologic and cytogenetic responses in chronic-phase chronic myeloid leukemia after failure of imatinib therapy. Blood, 2007, 109(6), 2303-9.
59. Puttini, M.; Coluccia, A.M.; Boschelli, F.; Cleris, L.; Marchesi, E.; Donella-Deana, A.; Ahmed, S.; Redaelli, S.; Piazza, R.; Magistroni, V.; Andreoni, F.; Scapozza, L.; Formelli, F.; Gambacorti-Passerini, C. In vitro and in vivo activity of SKI-606, a novel Src-Abl inhibitor, against imatinib-resistant Bcr-Abl+ neoplastic cells. Cancer Res., 2006, 66(23), 11314-22.
60. Gambacorti-Passerini, C.; Blummedorf, T.; Kantarjian, H. Proceedings from the American Society of Clinical Onlcology Conference, Chicago/IL. 2007, Abstract # 7006.
61. Kimura, S.; Naito, H.; Segawa, H.; Kuroda, J.; Yuasa, T.; Sato, K.; Yokota, A.; Kamitsuji, Y.; Kawata, E.; Ashihara, E.; Nakaya, Y.; Naruoka, H.; Wakayama, T.; Nasu, K.; Asaki, T.; Niwa, T.; Hirabayashi, K.; Maekawa, T. NS-187, a potent and selective dual Bcr-Abl/Lyn tyrosine kinase inhibitor, is a novel agent for imatinibresistant leukemia. Blood, 2005, 106(12), 3948-51.
62. Naito, H.; Kimura, S.; Nakaya, Y.; Naruoka, H.; Kimura, S.; Ito, S.; Wakayama, T.; Maekawa, T.; Hirabayashi, K. 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., 2006, 30(11),1443-6.
63. O'Hare, T.; Pollock, R.; Stoffregen, E.P.; Keats, J.A.; Abdullah, O.M.; Moseson, E.M.; Rivera, V.M.; Tang, H.; Metcalf, C.A.; Bohacek, R.S.; Wang, Y.; Sundaramoorthi, R.; Shakespeare, W.C.; Dalgarno, D.; Clackson, T.; Sawyer, T.K.; Deininger, M.W.; Druker, B.J. Inhibition of wild-type and mutant Bcr-Abl by AP23464, a potent ATP-based oncogenic protein kinase inhibitor: implications for CML. Blood, 2004, 104(8), 2532-9.
64. Azam, M.; Nardi, V.; Shakespeare, W.C.; Metcalf, C.A.; Bohacek, R.S.; Wang, Y.; Sundaramoorthi, R.; Sliz, P.; Veach, D.R.; Bornmann, W.G.; Clarkson, B.; Dalgarno, D.C.; Sawyer, T.K.; Daley, G.Q. Activity of dual SRC-ABL inhibitors highlights the role of BCR/ABL kinase dynamics in drug resistance. Proc. Natl. Acad. Sci. USA, 2006, 103(24), 9244-9.
65. Dalgarno, D.; Stehle, T.; Narula, S.; Schelling, P.; van Schravendijk, M.R.; Adams, S.; Andrade, L.; Keats, J.; Ram, M.; Jin, L.; Grossman, T.; MacNeil, I.; Metcalf, C.; Shakespeare, W.; Wang, Y.; Keenan, T.; Sundaramoorthi, R.; Bohacek, R.; Weigele, M.; Sawyer, T. Structural basis of Src tyrosine kinase inhibition with a new class of potent and selective trisubstituted purine-based compounds. Chem. Biol. Drug Des., 2006, 67(1), 46-57.
66. Warmuth, M.; Simon, N.; Mitina, O.; Mathes, R.; Fabbro, D.; Manley, P.W.; Buchdunger, E.; Forster, K; Moarefi, I.; Hallek M. Dualspecific Src and Abl kinase inhibitors, PP1 and CGP76030, inhibit growth and survival of cells expressing imatinib mesylate-resistant Bcr-Abl kinases. Blood, 2003, 101(2), 664-72.
67. Wolff, N.C.; Veach, D.R.; Tong, W.P.; Bornmann, W.G.; Clarkson, B.; Ilaria, R.L. PD166326, a novel tyrosine kinase inhibitor, has greater antileukemic activity than imatinib mesylate in a murine model of chronic myeloid leukemia. Blood, 2005, 105(10), 3995-4003.
68. Wisniewski, D.; Lambek, C.L.; Liu, C.; Strife, A.; Veach, D.R.; Nagar, B.; Young, M.A.; Schindler, T.; Bornmann, W.G.; Bertino, J.R.; Kuriyan, J.; Clarkson, B. Characterization of potent inhibitors of the Bcr-Abl and the c-kit receptor tyrosine kinases. Cancer Res., 2002, 62(15), 4244-55.
69. Dorsey, J.F.; Jove, R.; Kraker, A.J.; Wu, J. The pyrido[2,3-d]pyrimidine derivative PD180970 inhibits p210Bcr-Abl tyrosine kinase and induces apoptosis of K562 leukemic cells. Cancer Res., 2000, 60(12), 3127-31.
70. Gumireddy, K.; Baker, S.J.; Cosenza, S.C.; John, P.; Kang, A.D.; Robell, K.A.; Reddy M.V.R.; Reddy, E.P. A non-ATP-competitive inhibitor of BCR-ABL overrides imatinib resistance. Proc. Natl. Acad. Sci. USA, 2005, 102(6), 1992-7.
71. Adrián, F.J.; Ding, Q.; Sim, T.; Velentza, A.; Sloan, C.; Liu, Y.; Zhang, G.; Hur, W.; Ding, S.; Manley, P.; Mestan, J.; Fabbro, D.; Gray, N.S. Allosteric inhibitors of Bcr-abl-dependent cell proliferation. Nat. Chem. Biol., 2006, 2(2), 95-102.
72. Prendergast, G.C.; Rane, N. Farnesyltransferase inhibitors: mechanism and applications. Expert Opin. Invest. Drugs, 2001, 10(12), 2105-16.
73. Cortes, J.; Albitar, M.; Thomas, D.; Giles, F.; Kurzrock, R.; Thibault, A.; Rackoff, W.; Koller, C.; O'Brien, S.; Garcia-Manero, G.; Talpaz, M.; Kantarjian, H. Efficacy of the farnesyl transferase inhibitor R115777 in chronic myeloid leukemia and other hematologic malignancies. Blood, 2003, 101(5), 1692-7.
74. Miyoshi, T.; Nagai, T.; Ohmine, K.; Nakamura, M.; Kano, Y.; Muroi, K.; Komatsu, N.; Ozawa, K. Relative importance of apoptosis and cell cycle blockage in the synergistic effect of combined R115777 and imatinib treatment in BCR/ABL-positive cell lines. Bio. Chem. Pharmacol., 2005, 69(11), 1585-94.
75. Hoover, R.R.; Mahon, F.X.; Melo, J.V.; Daley, G.Q. Overcoming STI571 resistance with the farnesyl transferase inhibitor SCH66336. Blood, 2002, 100(3), 1068-71.
76. Dy, G.K.; Bruzek, L.M.; Croghan, G.A.; Mandrekar, S.; Erlichman, C.; Peethambaram, P.; Pitot, H.C.; Hanson, L.J.; Reid, J.M.; Furth, A.; Cheng, S.; Martell, R.E.; Kaufmann, S.H.; Adjei, A.A. A phase I trial of the novel farnesyl protein transferase inhibitor, BMS-214662, in combination with paclitaxel and carboplatin in patients with advanced cancer. Clin. Cancer Res., 2005, 11(5), 1877-83.
77. Puil, L.; Liu, J.; Gish, G.; Mbamalu, G.; Bowtell, D.; Pelicci, P.G.; Arlinghaus, R.; Pawson, T. Bcr-Abl oncoproteins bind directly to activators of the Ras signalling pathway. EMBO J., 1994, 13(4), 764-73.
78. James, J.A.; Smith, M.A.; Court, E.L.; Yip, C.; Ching, Y.; Willson, C.; Smith, J.G. An investigation of the effects of the MEK inhibitor U0126 on apoptosis in acute leukemia. Hematol. J., 2003, 4(6), 427-32.
79. Yu, C.; Krystal, G.; Varticovksi, L.; McKinstry, R.; Rahmani, M.; Dent, P.; Grant, S. Pharmacologic mitogen-activated protein/extra-cellular signal-regulated kinase kinase/mitogen-activated protein kinase inhibitors interact synergistically with STI571 to induce apoptosis in Bcr/Abl-expressing human leukemia cells. Cancer Res., 2002, 62(1), 188-99.
80. Klejman, A.; Rushen, L.; Morrione, A.; Slupianek, A.; Skorski, T. Phosphatidylinositol-3 kinase inhibitors enhance the anti-leukemia effect of STI571. Oncogene, 2002, 21(38), 5868-76.
81. Marley, S.B.; Lewis, J.L.; Schneider, H.; Rudd, C.E.; Gordon, M.Y. Phosphatidylinositol-3 kinase inhibitors reproduce the selective antiproliferative effects of imatinib on chronic myeloid leukaemia progenitor cells. Br. J. Haematol., 2004, 125(4), 500-11.
82. Tauchi, T.; Sumi, M.; Nakajima, A.; Sashida, G.; Shimamoto, T.; Ohyashiki, K. BCL-2 antisense oligonucleotide genasense is active against imatinib-resistant BCR-ABL-positive cells. Clin. Cancer Res., 2003, 9(11), 4267-73.
83. Tolomeo, M.; Grimaudo, S.; Di Cristina, A.; Pipitone, R.M.; Dusonchet, L.; Meli, M.; Crosta, L.; Gebbia, N.; Invidiata, F.P.; Titone, L.; Simoni, D. Galangin increases the cytotoxic activity of imatinib mesylate in imatinib-sensitive and imatinib-resistant Bcr-Abl expressing leukemia cells. Cancer Lett., 2008, 265(2), 289-97.
84. Kuroda, J.; Kimura, S.; Strasser, A.; Andreeff, M.; O'Reilly, L.A.; Ashihara, E.; Kamitsuji, Y.; Yokota, A.; Kawata, E.; Takeuchi, M.; Tanaka, R.; Tabe, Y.; Taniwaki, M.; Maekawa, T. Apoptosis-based dual molecular targeting by INNO-406, a second-generation Bcr-Abl inhibitor, and ABT-737, an inhibitor of antiapoptotic Bcl-2 proteins, against Bcr-Abl-positive leukemia. Cell Death Differ., 2007, 14(9), 1667-77.