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Cancer pp 407-444 | Cite as

Bcr-Abl Kinase Inhibitors

Chapter
Part of the Topics in Medicinal Chemistry book series (TMC, volume 1)

Abstract

The hallmark of chronic myelogenous leukemia (CML) is the expression of Bcr-Abl, a constitutivelyactive form of the Abl tyrosine kinase. Imatinib, a 2-phenyl aminopyrimidine Bcr-Abl inhibitor developedby Novartis and marketed under the tradename of Gleevec (Glivec), is highly effective in treating CML patientswith early stage disease. However, patients with advanced disease often become resistant to imatinib. Thepredominant form of this resistance is the development of mutations in the Bcr-Abl protein. These pointmutations can be amino acid residues that make direct contact with imatinib or residues that do not allowBcr-Abl to adopt the inactive conformation. Since imatinib can only bind to the inactive conformation ofthe protein, both types of mutations prevent this inhibitor from binding. Several approaches have beentaken to identify additional Bcr-Abl inhibitors including: (1) more potent analogs of imatinib; (2) non-ATPcompetitive inhibitors of Bcr-Abl; and (3) dual inhibitors of both Bcr-Abl and members of the Src familyof kinases (SFKs) that bind to the active form of Bcr-Abl. The progress made on the development of thesenew agents, including compounds with activity against the highly resistant T315I mutation of Bcr-Abl, willbe discussed.

Bcr-Abl Abl CML Imatinib T315I 

Abbreviations

CML

chronic myelogenous leukemia

ALL

acute lymphoblastic leukemia

SFK

Src family kinase

GST

gastrointestinal stromal tumors

ASH

American Society of Hematology

AACR

American Association for Cancer Research

ASCO

American Society of Clinical Oncology

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Notes

Acknowledgments

I thank Frank Boschelli, Janis Upeslacis and Dennis Powell for their critical review of this manuscript.

References

  1. 1.
    Goldman JM, Melo JV (2003) N Eng J Med 349:1451 CrossRefGoogle Scholar
  2. 2.
    Thijsen SFT, Schuurhuis GJ, Van Oostveen JW, Ossenkoppele GJ (1999) Leukemia 13:1646 CrossRefGoogle Scholar
  3. 3.
    Kalidas M, Kantarjian H, Talpaz M (2001) JAMA 286:895 CrossRefGoogle Scholar
  4. 4.
    Goldman JM, Druker BJ (2001) Blood 98:2039 CrossRefGoogle Scholar
  5. 5.
    Salesse S, Verfaillie CM (2002) Oncogene 21:8547 CrossRefGoogle Scholar
  6. 6.
    Faderl S, Talpaz M, Estrov Z, O'Brien S, Kurzrock R, Kantarjian HM (1999) N Engl J Med 341:164 CrossRefGoogle Scholar
  7. 7.
    Ribeiro R, Abromowitch M, Raimondi S, Murphy S, Behm F, Williams D (1987) Blood 70:948 Google Scholar
  8. 8.
    Bloomfield C, Goldman A, Alimena G, Berger R, Borgstrom G, Brandt L, Catovsky D, de la Chapelle A, Dewald G, Garson (1986) Blood 67:415 Google Scholar
  9. 9.
    Westbrook C, Hooberman A, Spino C, Dodge R, Larson R, Davey F, Wurster-Hill D, Sobol R, Schiffer C, Bloomfield C (1992) Blood 80:2983 Google Scholar
  10. 10.
    Faderl S, Jeha S, M. KH (2003) Cancer 98:1337 CrossRefGoogle Scholar
  11. 11.
    Buchdunger E, Zimmermann J, Mett H, Meyer T, Mueller M, Druker BJ, Lydon NB (1996) Cancer Res 56:100 Google Scholar
  12. 12.
    Zimmermann J, Buchdunger E, Mett H, Meyer T, Lydon NB (1997) Bioorg Med Chem Lett 7:187 CrossRefGoogle Scholar
  13. 13.
    Buchdunger E, Cioffi CL, Law N, Stover D, Ohno-Jones S, Druker BJ, Lydon NB (2000) J Pharmacol Exp Ther 295:139 Google Scholar
  14. 14.
    Boggon TJ, Eck MJ (2004) Oncogene 23:7918 CrossRefGoogle Scholar
  15. 15.
    Superti-Furga G, Courtneidge SA (1995) BioEssays 17:321 CrossRefGoogle Scholar
  16. 16.
    Druker BJ, Tamura S, Buchdunger E, Ohno S, Segal GM, Fanning S, Zimmermann J, Lydon NB (1996) Nat Med 2:561 CrossRefGoogle Scholar
  17. 17.
    Carroll M, Ohno-Jones S, Tamura S, Buchdunger E, Zimmermann J, Lydon NB, Gilliland DG, Druker BJ (1997) Blood 90:4947 Google Scholar
  18. 18.
    Gambacorti-Passerini C, Le Coutre P, Mologni L, Fanelli M, Bertazzoli C, Marchesi E, Di Nicola M, Biondi A, Corneo GM, Belotti D, Pogliani E, Lydon NB (1997) Blood Cells Mol Dis 23:380 CrossRefGoogle Scholar
  19. 19.
    Deininger MWN, Goldman JM, Lydon N, Melo JV (1997) Blood 90:3691 Google Scholar
  20. 20.
    Le Coutre P, Mologni L, Cleris L, Marchesi E, Buchdunger E, Giardini R, Formelli F, Gambacorti-Passerini C (1999) J Natl Cancer Inst 91:163 CrossRefGoogle Scholar
  21. 21.
    Druker BJ, Talpaz M, Resta DJ, Peng B, Buchdunger E, Ford JM, Lydon NB, Kantarjian H, Capdeville R, Ohno-Jones S, Sawyers CL (2001) N Engl J Med 344:1031 CrossRefGoogle Scholar
  22. 22.
    Druker BJ, Sawyers CL, Kantarjian H, Resta DJ, Reese SF, Ford JM, Capdeville R, Talpaz M (2001) N Engl J Med 344:1038 CrossRefGoogle Scholar
  23. 23.
    Lydon NB, Druker BJ (2004) Leukemia Res 28:S29 CrossRefGoogle Scholar
  24. 24.
    Cowan-Jacob SW, Guez V, Fendrich G, Griffin JD, Fabbro D, Furet P, Liebetanz J, Mestan J, Manley PW (2004) Mini-Reviews Med Chem 4:285 CrossRefGoogle Scholar
  25. 25.
    Crossman LC, O'Brien S (2004) Leukemia Res 28:S3 CrossRefGoogle Scholar
  26. 26.
    Deininger M, Buchdunger E, Druker BJ (2005) Blood 105:2640 CrossRefGoogle Scholar
  27. 27.
    Capdeville R, Buchdunger E, Zimmermann J, Matter A (2002) Nat Rev Drug Disc 1:493 CrossRefGoogle Scholar
  28. 28.
    Vasella D, Slater R (2003) Magic Cancer Bullet. Harper Business, New York Google Scholar
  29. 29.
    Tuveson DA, Willis NA, Jacks T, Griffin JD, Singer S, Fletcher CDM, Fletcher JA, Demetri GD (2001) Oncogene 20:5054 CrossRefGoogle Scholar
  30. 30.
    Demetri GD, von Mehren M, Blanke CD, Van den Abbeele AD, Eisenberg B, Roberts PJ, Heinrich MC, Tuveson DA, Singer S, Janicek M, Fletcher JA, Silverman SG, Silberman SL, Capdeville R, Kiese B, Peng B, Dimitrijevic S, Druker BJ, Corless C, Fletcher CD, Joensuu H (2002) N Engl J Med 347:472 CrossRefGoogle Scholar
  31. 31.
    Wiedmann MW, Caca K (2005) Curr Cancer Drug Targets 5:171 CrossRefGoogle Scholar
  32. 32.
    Gorre ME, Mohammed M, Ellwood K, Hsu N, Paquette R, Rao PN, Sawyers CL (2001) Science 293:876 CrossRefGoogle Scholar
  33. 33.
    Shah N, Sawyers CL (2003) Oncogene 22:7389 CrossRefGoogle Scholar
  34. 34.
    Corbin AS, La Rosee P, Stoffregen EP, Druker BJ, Deininger MW (2003) Blood 101:4611 CrossRefGoogle Scholar
  35. 35.
    von Bubnoff N, Peschel C, Duyster J (2003) Leukemia 17:829 CrossRefGoogle Scholar
  36. 36.
    Schindler T, Bornmann W, Pellicena P, Miller WT, Clarkson B, Kuriyan J (2000) Science 289:1938 CrossRefGoogle Scholar
  37. 37.
    Nagar B, Bornmann WG, Pellicena P, Schindler T, Veach DR, Miller WT, Clarkson B, Kuriyan J (2002) Cancer Res 62:4236 Google Scholar
  38. 38.
    Manley PW, Breitenstein W, Brueggen J, Cowan-Jacob SW, Furet P, Mestan J, Meyer T (2004) Bioorg Med Chem Lett 14:5793 CrossRefGoogle Scholar
  39. 39.
    Mestan J, Ellen W, Sandra C-J, Doriano F, Pascal F, Gabriele F, Gerard G, Dominique K, Markus G, James GD, Manley PW (2004) Annu Meeting Am Soc Hematol, Abstract 1978 Google Scholar
  40. 40.
    Weisberg E, Manley PW, Breitenstein W, Brueggen J, Cowan-Jacob SW, Ray A, Huntly B, Fabbro D, Fendrich G, Hall-Meyers E, Kung AL, Mestan J, Daley GQ, Callahan L, Catley L, Cavazza C, Mohammed A, Neuberg D, Wright RD, Gilliland DG, Griffin JD (2005) Cancer Cell 7:129 CrossRefGoogle Scholar
  41. 41.
    Manley P, Cowan-Jacob SW, Fendrich G, Mestan J (2005) Annu Meeting Am Soc Hematol, Abstract 3365 Google Scholar
  42. 42.
    Golemovic M, Verstovsek S, Giles F, Cortes J, Manshouri T, Manley PW, Mestan J, Dugan M, Alland L, Griffin JD, Arlinghaus RB, Sun T, Kantarjian H, Beran M (2005) Clin Cancer Res 11:4941 CrossRefGoogle Scholar
  43. 43.
    Martinelli G, Martelli AM, Grafone T, Mantovani I, Cappellini A, Tazzari PL, Ottaviani E, Soverini S, Amabile M, Renzulli M, Terragna C, Colarossi S, Iacobucci I, Poerio A, Baccarani M (2005) Annu Meeting Am Soc Hematol, Abstract 2004 Google Scholar
  44. 44.
    Martinelli G, Martelli AM, Grafone T, Rosti G, Mantovani I, Cappellini A, Tazzari PL, Ottaviani E, Renzulli M, Amabile M, Poerio A, Soverini S, Terragna C, Taccioli C, Bassi S, Baccarani M (2004) Annu Meeting Am Soc Hematol, Abstract 4687 Google Scholar
  45. 45.
    Ma G, Lu D, Wu Y, Liu J, Arlinghaus RB (1997) Oncogene 14:2367 CrossRefGoogle Scholar
  46. 46.
    Van Etten RA (2004) Leukemia Res 28:S21 CrossRefGoogle Scholar
  47. 47.
    Ottmann OG, Druker BJ, Sawyers CL, Goldman JM, Reiffers J, Silver RT, Tura S, Fischer T, Deininger MW, Schiffer CA, Baccarani M, Gratwohl A, Hochhaus A, Hoelzer D, Fernandes-Reese S, Gathmann I, Capdeville R, O'Brien SG (2002) Blood 100:1965 CrossRefGoogle Scholar
  48. 48.
    Verstovsek S, Golemovic M, Kantarjian H, Manshouri T, Estrov Z, Manley P, Sun T, Arlinghaus RB, Alland L, Dugan M, Cortes J, Giles F, Beran M (2005) Cancer 104:1230 CrossRefGoogle Scholar
  49. 49.
    Giles F, Kantarjian H, Wassmann B, Cortes J, O'Brien S, Tanaka C, Rae P, Mietlowski W, Romano A, Alland L, Dugan M, Albitar M, Ottmann O (2004) Annu Meeting Am Soc Hematol, Abstract 22 Google Scholar
  50. 50.
    Ottman O, Giles F, Wassman B, Hochhaus A, Rae P, Beran M, Albitar M, Dugan M, Kantarjian H (2005) Annu Meeting Am Soc Clin Oncol, Abstract 3015 Google Scholar
  51. 51.
    Kantarjian H, Ottman O, Cortes J, Wassman B, Hochhaus A, Alland L, Dugan M, Albitar M, Giles F (2005) Annu Meeting Am Soc Clin Oncol, Abstract 3014A Google Scholar
  52. 52.
    Giles F, Ottman O, Cortes J, Wassman B, Wunderle S, O'Brien S, Jones D, Hochhaus A, Verstovsek S, Rae P, Rose K, Alland L, Dugan M, Manley P, Beran M, Albitar M, Kantarjian H (2005) Annu Meeting Am Assoc Cancer Res, Abstract 3971 Google Scholar
  53. 53.
    Kantarjian H, M., Ottman O, Cortes J, Wassman M, Wunderle S, Bhalla K, Jones D, Hochhaus A, Rae P, Alland L, Dugan M, Albitar M, Giles F (2005) Annu Meeting Am Soc Hematol, Abstract 37 Google Scholar
  54. 54.
    La Rosee P, Holm-Eriksen S, Ernst T, Konig H, Erben P, Mueller M, Schenk Y, Emig M, Binckebanck A, Wunderle S, Alland L, Schuld P, Hehlmann R, Ottman OG, Hochhaus A (2005) Annu Meeting Am Soc Hematol, Abstract 497 Google Scholar
  55. 55.
    Von Bubnoff N, Veach DR, Van der Kuip H, Aulitzky WE, Saenger J, Seipel P, Bornmann WG, Peschel C, Clarkson B, Duyster J (2005) Blood 105:1652 CrossRefGoogle Scholar
  56. 56.
    von Bubnoff N, Saenger J, Manley PW, Mestan J, Peschel C, Duyster J (2005) Annu Meeting Am Soc Hematol, Abstract 1983 Google Scholar
  57. 57.
    Ray A, Cowan-Jacob S, Manley PW, Mestan J, Griffin JD (2005) Annu Meeting Am Soc Hematol, Abstract 494 Google Scholar
  58. 58.
    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 (2005) Blood 106:3948 CrossRefGoogle Scholar
  59. 59.
    Naito H, Kimura S, Nakaya Y, Naruoka H, Wakayama T, Kimura S, Ito S, Ashihara E, Maekawa T, Hirabayashi K (2005) Annu Meeting Am Soc Hematol, Abstract 1518 Google Scholar
  60. 60.
    Asaki T, Sugiyama Y, Hamamoto T, Higashioka M, Umehara M, Naito H, Niwa T (2006) Bioorg Med Chem Lett 16:1421 CrossRefGoogle Scholar
  61. 61.
    Gumireddy K, Baker SJ, Cosenza SC, John P, Kang AD, Robell KA, Reddy MVR, Reddy EP (2005) Proc Natl Acad Sci USA 102:1992 CrossRefGoogle Scholar
  62. 62.
    http://www.onconova.com , (Last visited on: Jan 05, 2006)
  63. 63.
    Gumireddy K, Reddy MVR, Cosenza SC, Nathan RB, Baker SJ, Papathi N, Jiang J, Holland J, Reddy EP (2005) Cancer Cell 7:275 CrossRefGoogle Scholar
  64. 64.
    Kaur G, Gazit A, Levitzki A, Stowe E, Cooney DA, Sausville EA (1994) Anti-Cancer Drug 5:213 CrossRefGoogle Scholar
  65. 65.
    Kaur G, Narayanan VL, Risbood PA, Hollingshead MG, Stinson SF, Varma RK, Sausville EA (2005) Bioorg Med Chem 13:1749 CrossRefGoogle Scholar
  66. 66.
    Svingen PA, Tefferi A, Kottke TJ, Kaur G, Narayanan VL, Sausville EA, Kaufmann SH (2000) Clin Cancer Res 6:237 Google Scholar
  67. 67.
    Mow BMF, Chandra J, Svingen PA, Hallgren CG, Weisberg E, Kottke TJ, Narayanan VL, Litzow MR, Griffin JD, Sausville EA, Tefferi A, Kaufmann SH (2002) Blood 99:664 CrossRefGoogle Scholar
  68. 68.
    Avramis IA, Laug WE, Sausville EA, Avramis VI (2003) Cancer Chemother Pharmacol 52:307 CrossRefGoogle Scholar
  69. 69.
    Deutsch E, Maggiorella L, Wen B, Bonnet ML, Khanfir K, Frascogna V, Turhan AG, Bourhis J (2004) Br J Cancer 91:1735 Google Scholar
  70. 70.
    Camirand A, Zakikhani M, Young F, Pollak M (2005) Breast Cancer Res 7:R465 CrossRefGoogle Scholar
  71. 71.
    Blum G, Gazit A, Levitzki A (2000) Biochemistry 39:15705 CrossRefGoogle Scholar
  72. 72.
    Camirand A, Pollak M (2004) Br J Cancer 90:1825 Google Scholar
  73. 73.
    Dorsey JF, Jove R, Kraker AJ, Wu J (2000) Cancer Res 60:3127 Google Scholar
  74. 74.
    Wisniewski D, Lambek CL, Liu C, Strife A, Veach DR, Nagar B, Young MA, Schindler T, Bornmann WG, Bertino JR, Kuriyan J, Clarkson B (2002) Cancer Res 62:4244 Google Scholar
  75. 75.
    Courtneidge SA (2002) Biochem Soc Trans 30:11 CrossRefGoogle Scholar
  76. 76.
    Ito H, Gardner-Thorpe J, Zinner MJ, Ashley SW, Whang EE (2003) Surgery 134:221 CrossRefGoogle Scholar
  77. 77.
    Wiener JR, Windham TC, Estrella VC, Parikh NU, Thall PF, Deavers MT, Bast RC, Mills GB, Gallick GE (2003) Gynecol Oncol 88:73 CrossRefGoogle Scholar
  78. 78.
    Myoui A, Nishimura R, Williams PJ, Hiraga T, Tamura D, Michigami T, Mundy GR, Yoneda T (2003) Cancer Res 63:5028 Google Scholar
  79. 79.
    Danhauser-Riedl S, Warmuth M, Druker BJ, Emmerich B, Hallek M (1996) Cancer Res 56:3589 Google Scholar
  80. 80.
    Warmuth M, Bergmann M, Priess A, Hauslmann K, Emmerich B, Hallek M (1997) J Biol Chem 272:33260 CrossRefGoogle Scholar
  81. 81.
    Roginskaya V, Zuo S, Caudell E, Nambudiri G, Kraker AJ, Corey SJ (1999) Leukemia 13:855 CrossRefGoogle Scholar
  82. 82.
    Lionberger JM, Wilson MB, Smithgall TE (2000) J Biol Chem 275:18581 CrossRefGoogle Scholar
  83. 83.
    Donato NJ, Wu JY, Stapley J, Gallick G, Lin H, Arlinghaus R, Talpaz M (2003) Blood 101:690 CrossRefGoogle Scholar
  84. 84.
    Klutchko SR, Hamby JM, Boschelli DH, Wu Z, Kraker AJ, Amar AM, Hartl BG, Shen C, Klohs WD, Steinkampf RW, Driscoll DL, Nelson JM, Elliott WL, Roberts BJ, Stoner CL, Vincent PW, Dykes DJ, Panek RL, Lu GH, Major TC, Dahring TK, Hallak H, Bradford LA, Showalter HDH, Doherty AM (1998) J Med Chem 41:3276 CrossRefGoogle Scholar
  85. 85.
    Kraker AJ, Hartl BG, Amar AM, Barvian MR, Showalter HDH, Moore CW (2000) Biochem Pharmacol 60:885 CrossRefGoogle Scholar
  86. 86.
    La Rosee P, Corbin AS, Stoffregen EP, Deininger MW, Druker BJ (2002) Cancer Res 62:7149 Google Scholar
  87. 87.
    Huron DR, Gorre ME, Kraker AJ, Sawyers CL, Rosen N, Moasser MM (2003) Clin Cancer Res 9:1267 Google Scholar
  88. 88.
    von Bubnoff N, Veach DR, Miller WT, Li W, Saenger J, Peschel C, Bornmann WG, Clarkson B, Duyster J (2003) Cancer Res 63:6395 Google Scholar
  89. 89.
    Veach DR, Lambek C, Liu C-Y, Duyster J, Beresten T, Li W, Wolff NC, Ilaria RL, Gelovani J, Miller WT, von Bubnoff N, Bornmann WG, Clarkson BD (2003) 226th Nat Meeting Am Chem Soc, Abstract MEDI-067 Google Scholar
  90. 90.
    Tipping AJ, Baluch S, Barnes DJ, Veach DR, Clarkson BM, Bornmann WG, Mahon FX, Goldman JM, Melo JV (2004) Leukemia 18:1352 CrossRefGoogle Scholar
  91. 91.
    Wolff NC, Veach DR, Tong WP, Bornmann WG, Clarkson B, Ilaria RL Jr (2005) Blood 105:3995 CrossRefGoogle Scholar
  92. 92.
    http://www.medicalnewstoday.com , (Last visited on: Jan 05, 2006)
  93. 93.
    Missbach M, Jeschke M, Feyen J, Muller K, Glatt M, Green J, Susa M (1999) Bone 24:437 CrossRefGoogle Scholar
  94. 94.
    Li B, Boast S, De los Santos K, Schieren I, Quiroz M, Teitelbaum SL, Tondravi MM, Goff SP (2000) Nat Genet 24:304 CrossRefGoogle Scholar
  95. 95.
    Missbach M, Altmann E, Widler L, Susa M, Buchdunger E, Mett H, Meyer T, Green J (2000) Bioorg Med Chem Lett 10:945 CrossRefGoogle Scholar
  96. 96.
    Widler L, Green J, Missbach M, Susa M, Altmann E (2001) Bioorg Med Chem Lett 11:849 CrossRefGoogle Scholar
  97. 97.
    Altmann E, Missbach M, Green J, Susa M, Wagenknecht HA, Widler L (2001) Bioorg Med Chem Lett 11:853 CrossRefGoogle Scholar
  98. 98.
    Altmann E, Widler L, Missbach M (2002) Mini-Reviews Med Chem 2:201 CrossRefGoogle Scholar
  99. 99.
    Warmuth M, Simon N, Mitina O, Mathes R, Fabbro D, Manley PW, Buchdunger E, Forster K, Moarefi I, Hallek M (2003) Blood 101:664 CrossRefGoogle Scholar
  100. 100.
    Hu Y, Liu Y, Pelletier S, Buchdunger E, Warmuth M, Fabbro D, Hallek M, Van Etten RA, Li S (2004) Nat Genet 36:453 CrossRefGoogle Scholar
  101. 101.
    Shakespeare WC, Metcalf CA III, Wang Y, Sundaramoorthi R, Keenan T, Weigele M, Bohacek RS, Dalgarno DC, Sawyer TK (2003) Curr Opin Drug Dis Dev 6:729 Google Scholar
  102. 102.
    Wang Y, Metcalf CA III, Shakespeare WC, Sundaramoorthi R, Keenan TP, Bohacek RS, Van Schravendijk MR, Violette SM, Narula SS, Dalgarno DC, Haraldson C, Keats J, Liou S, Mani U, Pradeepan S, Ram M, Adams S, Weigele M, Sawyer TK (2003) Bioorg Med Chem Lett 13:3067 CrossRefGoogle Scholar
  103. 103.
    Metcalf C III, Wang Y, Shakespeare W, Sundaramoorthi R, Keenan T, Dalgarno D, Bohacek R, Burns K, Roses J, van Schravendijk MR, Ram M, Keats J, Liou S, Adams S, Snodgrass J, Rivera V, Weigele M, Iuliucci J, Clackson T, Frame M, Brunton V, Sawyer T (2003) 226th Nat Meeting Am Chem Soc, Abstract COMP-079 Google Scholar
  104. 104.
    Dalgarno D, Bohacek R, Stehle T, Narula S, Metcalf C III, Shakespeare W, Sundaramoorthi R, Keenan T, Wang Y, Keats J, Ram M, Adams S, Van Schravandijk MR, Weigele M, Sawyer T (2003) AACR-NCI-EORTC Int Conf Mol Targets Cancer Ther, Abstract A5 Google Scholar
  105. 105.
    Dalgarno D, Stehle T, Narula S, Schelling P, Van Schravandijk MR, Adams S, Andrade L, Keats J, Ram M, Jin L, Grossman T, MacNeil I, Metcalf C III, Shakespeare W, Wang Y, Keenan T, Sundaramoorthi R, Bohacek R, Weigele M, Sawyer T (2006) Chem Biol Drug Des 67:46 CrossRefGoogle Scholar
  106. 106.
    O'Hare T, Pollock R, Stoffregen EP, Keats JA, Abdullah OM, Moseson EM, Rivera VM, Tang H, Metcalf CA III, Bohacek RS, Wang Y, Sundaramoorthi R, Shakespeare WC, Dalgarno D, Clackson T, Sawyer TK, Deininger MW, Druker BJ (2004) Blood 104:2532 CrossRefGoogle Scholar
  107. 107.
    O'Hare T, Walters DK, Stoffregen EP, Sherbenou DW, Heinrich MC, Deininger MWN, Druker BJ (2005) Clin Cancer Res 11:6987 CrossRefGoogle Scholar
  108. 108.
    Corbin AS, Demehri S, Griswold IJ, Wang Y, Metcalf CA III, Sundaramoorthi R, Shakespeare WC, Snodgrass J, Wardwell S, Dalgarno D, Iuliucci J, Sawyer TK, Heinrich MC, Druker BJ, Deininger MWN (2005) Blood 106:227 CrossRefGoogle Scholar
  109. 109.
    Azam M, Nardi V, Shakespeare WC, Latek RR, Veach DR, Clarckson B, Bohacek R, Sawyer TK, Daley GQ (2005) Annu Meeting Am Soc Hematol, Abstract 1996 Google Scholar
  110. 110.
    http://www.ariad.com , (Last visited on: Jan 05, 2006)
  111. 111.
    Boschelli DH, Wang YD, Ye F, Wu B, Zhang N, Dutia M, Powell DW, Wissner A, Arndt K, Weber JM, Boschelli F (2001) J Med Chem 44:822 CrossRefGoogle Scholar
  112. 112.
    Boschelli DH, Ye F, Wang YD, Dutia M, Johnson SL, Wu B, Miller K, Powell DW, Yaczko D, Young M, Tischler M, Arndt K, Discafani C, Etienne C, Gibbons J, Grod J, Lucas J, Weber JM, Boschelli F (2001) J Med Chem 44:3965 CrossRefGoogle Scholar
  113. 113.
    Golas JM, Arndt K, Etienne C, Lucas J, Nardin D, Gibbons J, Frost P, Ye F, Boschelli DH, Boschelli F (2003) Cancer Res 63:375 Google Scholar
  114. 114.
    Donato NJ, Wu JY, Talpaz M, Dutia M, Ye F, Boschelli D, Boschelli F (2002) Annu Meeting Am Soc Hematol, Abstract 1434 Google Scholar
  115. 115.
    Grafone T, Mancini M, Ottaviani E, Renzulli M, Boschelli F, Ferraretti L, Santucci MA, Amabile M, Soverini S, Terragna C, Poerio A, Rosti G, Taccioli C, Baccarani M, Martinelli G (2004) Annu Meeting Am Soc Hematol, Abstract 1991 Google Scholar
  116. 116.
    Grafone T, Mancini M, Ottaviani E, Renzulli M, Boschelli F, Ferraretti L, Santucci MA, Soverini S, Amabile M, Terragna C, Poerio A, Rosti G, Taccioli C, Palmerini E, Baccarani M, Martinelli G (2005) Annu Meeting Am Assoc Cancer Res, Abstract 5984 Google Scholar
  117. 117.
    Boschelli DH, Boschelli F, Wu B, Ye F, Wang Y, Golas JM, Young T, Lucas J (2005) Haematologica Rep 1(8):28 Google Scholar
  118. 118.
    Renzulli M, Grafone T, Taccioli C, Terragna C, Boschelli F, Mancini M, Creo P, Ottaviani E, Colarossi S, Amabile M, Soverini S, Poerio A, Iacobucci I, Baccarani M, Martinelli G (2005) Annu Meeting Am Soc Hematol, Abstract 4870 Google Scholar
  119. 119.
    Boschelli DH, Wang YD, Johnson S, Wu B, Ye F, Barrios Sosa AC, Golas JM, Boschelli F (2004) J Med Chem 47:1599 CrossRefGoogle Scholar
  120. 120.
    Boschelli DH, Wu B, Barrios Sosa AC, Durutlic H, Ye F, Raifeld Y, Golas JM, Boschelli F (2004) J Med Chem 47:6666 CrossRefGoogle Scholar
  121. 121.
    Boschelli DH, Wu B, Barrios Sosa AC, Chen JJ, Golas JM, Boschelli F (2005) Bioorg Med Chem Lett 15:4681 CrossRefGoogle Scholar
  122. 122.
    Golas JM, Lucas J, Etienne C, Golas J, Discafani C, Sridharan L, Boghaert E, Arndt K, Ye F, Boschelli DH, Li F, Titsch C, Huselton C, Chaudhary I, Boschelli F (2005) Cancer Res 65:5358 CrossRefGoogle Scholar
  123. 123.
    http://www.cmlsupport.com/cml/newletters.html (2003) CML Update 2:1, (Last visited on: Jan 05, 2006)
  124. 124.
    MD Anderson (2003) Cancer Center Leukemia Insights Newsletter 8(2), http://www.mdanderson.org/publications/insights , (Last visited on: Jan 05, 2006)
  125. 125.
    Lee FY, Lombardo L, Borzilleri R, Camuso A, Castaneda S, Donato N, Fager K, Flefleh C, Gray h, Inigo I, Kan D, Luo R, Pang S, Wen M-L, Wild R, Wong TW, Talpaz M, Kramer R (2004) Annu Meeting Am Assoc Cancer Res, Abstract 3987 Google Scholar
  126. 126.
    Shah NP, Tran C, Lee FY, Sawyers CL (2004) Annu Meeting Am Assoc Cancer Res, Abstract 5624 Google Scholar
  127. 127.
    Wu JY, Donato NJ, Hong DS, Lee FY, Talpaz M (2004) Annu Meeting Am Assoc Cancer Res, Abstract 3850 Google Scholar
  128. 128.
    Shah NP, Tran C, Lee FY, Chen P, Norris D, Sawyers CL (2004) Science 305:399 CrossRefGoogle Scholar
  129. 129.
    Wityak J, Das J, Moquin RV, Shen Z, Lin J, Chen P, Doweyko AM, Pitt S, Pang S, Shen DR, Fang Q, de Fex HF, Schieven GL, Kanner SB, Barrish JC (2003) Bioorg Med Chem Lett 13:4007 CrossRefGoogle Scholar
  130. 130.
    Lombardo LJ, Lee FY, Chen P, Norris D, Barrish JC, Behnia K, Castaneda S, Cornelius LAM, Das J, Doweyko AM, Fairchild C, Hunt JT, Inigo I, Johnston K, Kamath A, Kan D, Klei H, Marathe P, Pang S, Peterson R, Pitt S, Schieven GL, Schmidt RJ, Tokarski J, Wen M-L, Wityak J, Borzilleri RM (2004) J Med Chem 47:6658 CrossRefGoogle Scholar
  131. 131.
    Tokarski JS, Newitt J, Lee FY, Lombardo L, Borzilleri R, Kish K, Xie D, Zhang Y, Cheng JD, Kiefer SE, Chang CYJ, Klei HE (2004) Annu Meeting Am Soc Hematol, Abstract 553 Google Scholar
  132. 132.
    Azam M, Latek RR, Daley GQ (2003) Cell 112:831 CrossRefGoogle Scholar
  133. 133.
    Burgess MR, Skaggs BJ, Shah NP, Lee FY, Sawyers CL (2005) Proc Natl Acad Sci USA 102:3395 CrossRefGoogle Scholar
  134. 134.
    Luo FR, Yang Z, Camuso A, Smykla R, Castenada S, Flefleh C, Fager K, Inigo I, Kan D, McGlinchey K, Wen M-L, Wild R, Borzilleri R, Lombardo L, Kramer R, Lee FY (2004) Annu Meeting Am Soc Hematol, Abstract 1987 Google Scholar
  135. 135.
    Lee FY, Wen M-L, Bhide R, Camuso A, Castaneda S, Fager K, Flefleh C, Inigo I, Kan D, Luo R, McGlinchey K, Smykla R, Wild R, Borzilleri R, Lombardo L (2005) Annu Meeting Am Soc Hematol, Abstract 1994 Google Scholar
  136. 136.
    Dai H, Marbach P, Lemaire M, Hayes M, Elmquist WF (2003) J Pharmacol Exp Ther 304:1085 CrossRefGoogle Scholar
  137. 137.
    Wild R, Castaneda S, Flefleh C, Fager K, Inigo I, Kan D, Smykla R, Camuso A, McGlinchey K, Wen M-L, Luo FR, Borzilleri R, Lombardo L, Kramer R, Lee FY (2004) Annu Meeting Am Soc Hematol, Abstract 1988 Google Scholar
  138. 138.
    Sawyers CL, Shah NP, Kantarjian HM, Donato N, Nicoll J, Bai SA, Huang F, Clark E, DeCillis AP, Talpaz M (2004) Annu Meeting Am Soc Hematol, Abstract 1 Google Scholar
  139. 139.
    Talpaz M, Kantarjian H, Shah NP, Donato N, Nicoll J, Bai SA, Huang F, Clark E, DeCillis AP, Sawyers C (2004) Annu Meeting Am Soc Hematol, Abstract 20 Google Scholar
  140. 140.
    Talpaz M, Kantarjian HM, Paquette R, Shah N, Cortes J, Nicoll J, Bai SA, Huang F, Decillis AP, Sawyers CL (2005) Annu Meeting Am Soc Clin Oncol, Abstract 6519 Google Scholar
  141. 141.
    Sawyers CL, Shah NP, Kantarjian HM, Cortes J, Paquette R, Nicoll J, Bai SA, Clark E, Decillis AP, Talpaz M (2005) Annu Meeting Am Soc Clin Oncol, Abstract 6520 Google Scholar
  142. 142.
    Sawyers CL, Kantarjian H, Shah N, Cortes J, Paquette R, Donato N, Nicoll J, Bleickardt E, Chen T-T, Talpaz M (2005) Annu Meeting Am Soc Hematol, Abstract 38 Google Scholar
  143. 143.
    Gao H, Talpaz M, Lee BN, Donato N, Cortes JE, Kantarjian HM, Reuben JM (2005) Annu Meeting Am Soc Clin Oncol, Abstract 6619 Google Scholar
  144. 144.
    Guilhot F, Apperley JF, Shah N, Kim DW, Grigg A, Cheng S, Iyer M, Cortes J (2005) Annu Meeting Am Soc Hematol, Abstract 39 Google Scholar
  145. 145.
    Talpaz M, Rousselot P, Kim DW, Guilhot F, Corm S, Bleickardt E, Zink R, Rosti G, Coutre S, Sawyers C (2005) Annu Meeting Am Soc Hematol, Abstract 40 Google Scholar
  146. 146.
    Hochhaus A, Baccarani M, Sawyers C, Nagler A, Facon T, Goldberg SL, Cervantes F, Larson RA, Voi M, Ezzeddine R, Kantarjian H (2005) Annu Meeting Am Soc Hematol, Abstract 41 Google Scholar
  147. 147.
    Ottman O, Martinelli G, Dombret H, Kantarjian H, Hochhaus A, Simonsson B, Aloe A, Apanovitch A, Shah N (2005) Annu Meeting Am Soc Hematol, Abstract 42 Google Scholar
  148. 148.
    Shah N, Nicoll J, Branford S, Hughes TP, Paquette RL, Talpaz M, Nicaise C, Huang F, Sawyers CL (2005) Annu Meeting Am Soc Hematol, Abstract 1093 Google Scholar
  149. 149.
    Jabbour E, Cortes J, Talpaz M, Jones D, O'Brien S, Nicaise C, Kantarjian H (2005) Annu Meeting Am Soc Hematol, Abstract 1091 Google Scholar
  150. 150.
    Donato N, Wu J, Kong LY, Meng F, Lee F, Talpaz M (2005) Annu Meeting Am Soc Hematol, Abstract 1087 Google Scholar
  151. 151.
    Johnson FM, Saigal B, Talpaz M, Donato NJ (2005) Clin Cancer Res 11:6924 CrossRefGoogle Scholar
  152. 152.
    http://www.fda.gov/bbs/topics/NEWS/2006/NEW01400.html , (Last visited on: Jan 05, 2006)
  153. 153.
    Ple PA, Green TP, Hennequin LF, Curwen J, Fennell M, Allen J, Lambert-van der Brempt C, Costello G (2004) J Med Chem 47:871 CrossRefGoogle Scholar
  154. 154.
    Yezhelyev MV, Koehl G, Guba M, Brabletz T, Jauch KW, Ryan A, Barge A, Green T, Fennell M, Bruns CJ (2004) Clin Cancer Res 10:8028 CrossRefGoogle Scholar
  155. 155.
    Hennequin LF, Allen J, Costello GF, Fennell M, Green TP, Jacobs V, Morgentin R, Olivier A, Ple PA (2005) Annu Meeting Am Assoc Cancer Res, Abstract 2537 Google Scholar
  156. 156.
    Lockton JA, Smethurst D, Macpherson M, Tootell R, Marshall AL, Clack G, Gallagher NJ (2005) Annu Meeting Am Soc Clin Oncol, Abstract 3125 Google Scholar
  157. 157.
    Gallagher NJ, Lockton AJ, Macpherson M, Marshall A, Clack G (2005) Annu Meeting Am Assoc for Cancer Res, Abstract 3972 Google Scholar
  158. 158.
    O'Hare T, Walters DK, Stoffregen EP, Jia T, Manley PW, Mestan J, Cowan-Jacob SW, Lee FY, Heinrich MC, Deininger MWN, Druker BJ (2005) Cancer Res 65:4500 CrossRefGoogle Scholar
  159. 159.
    Deininger MWN, Bradeen H, Jia T, O'Hare T, Willis SG, Lee F, Druker BJ (2005) Annu Meeting Am Soc Hematol, Abstract 691 Google Scholar
  160. 160.
    Griffin JD, Weisberg EL (2005) Annu Meeting Am Soc Hematol, Abstract 694 Google Scholar
  161. 161.
    Fabian MA, Biggs WH, Treiber DK, Atteridge CE, Azimioara MD, Benedetti MG, Carter TA, Ciceri P, Edeen PT, Floyd M, Ford JM, Galvin M, Gerlach JL, Grotzfeld RM, Herrgard S, Insko DE, Insko MA, Lai AG, Lelias J-M, Mehta SA, Milanov ZV, Velasco AM, Wodicka LM, Patel HK, Zarrinkar PP, Lockhart DJ (2005) Nat Biotechnol 23:329 CrossRefGoogle Scholar
  162. 162.
    Carter TA, Wodicka LM, Shah NP, Velasco AM, Fabian MA, Treiber DK, Milanov ZV, Atteridge CE, Biggs WH III, Edeen PT, Floyd M, Ford JM, Grotzfeld RM, Herrgard S, Insko DE, Mehta SA, Patel HK, Pao W, Sawyers CL, Varmus H, Zarrinkar PP, Lockhart DJ (2005) Proc Natl Acad Sci USA 102:11011 CrossRefGoogle Scholar
  163. 163.
    O'Hare T, Druker BJ (2005) Nat Biotechnol 23:1209 CrossRefGoogle Scholar
  164. 164.
    http://www.vrtx.com , (Last visited on: Jan 05, 2006)
  165. 165.
    Burley SK (2005) Annu Meeting Am Soc Hematol, Abstract 698 Google Scholar
  166. 166.
    http://www.sgxpharma.com , (Last visited on: Jan 05, 2006)
  167. 167.
    http://www.newcmldrug.com , (Last visited on: Jan 05, 2006)
  168. 168.
    Cortes J, Garcia-Manero G, O'Brien S, Hernandez I, Rackoff W, Faderl S, Thomas D, Ferrajoli A, Talpaz M, Kantarjian H (2004) Annu Meeting Am Soc Hematol, Abstract 1011 Google Scholar
  169. 169.
    Cortes J, O'Brien S, Verstovsek S, Daley G, Koller C, Ferrajoli A, Pate O, Faderl S, Ravandi-Kashani F, Talpaz M, Zhu Y, Statkevich P, Sugrue M, Kantarjian H (2004) Annu Meeting Am Soc Hematol, Abstract 1009 Google Scholar
  170. 170.
    Kobayashi S, Boggon TJ, Dayaram T, Janne PA, Kocher O, Meyerson M, Johnson BE, Eck MJ, Tenen DG, Halmos B (2005) N Engl J Med 352:786 CrossRefGoogle Scholar
  171. 171.
    Pao W, Miller VA, Politi KA, Riely GJ, Somwar R, Zakowski MF, Kris MG, Varmus H (2005) PLoS Med 2:e73, http://www.plosmedicine.org , (Last visited on: Jan 05, 2006) CrossRefGoogle Scholar
  172. 172.
    Kwak EL, Sordella R, Bell DW, Godin-Heymann N, Okimoto RA, Brannigan BW, Harris PL, Driscoll DR, Fidias P, Lynch TJ, Rabindran SK, McGinnis JP, Wissner A, Sharma SV, Isselbacher KJ, Settleman J, Haber DA (2005) Proc Natl Acad Sci USA 102:7665 CrossRefGoogle Scholar

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© Springer-Verlag Berlin Heidelberg 2006

Authors and Affiliations

  1. 1.Chemical and Screening SciencesWyeth ResearchPearl RiverUSA

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