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 Research

Volumn 63, Issue 2, 2003, Pages 375-381

  Golas, Jennifer M ^a   Arndt, Kim ^a   Etienne, Carlo ^a   Lucas, Judy ^a   Nardin, Danielle ^a   Gibbons, James ^a   Frost, Philip ^a   Ye, Fei ^a   Boschelli, Diane H ^a   Boschelli, Frank ^a  

^a WYETH RESEARCH   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

4 ANILINO 3 QUINOLINECARBONITRILE; BCR ABL PROTEIN; BOSUTINIB; HEMATOPOIETIC CELL KINASE; IMATINIB; PROTEIN; PROTEIN KINASE LYN; PROTEIN TYROSINE KINASE INHIBITOR; QUINOLINE DERIVATIVE; STAT5 PROTEIN; UNCLASSIFIED DRUG;

ANIMAL EXPERIMENT; ANIMAL MODEL; APOPTOSIS; ARTICLE; CANCER CELL CULTURE; CELL PROLIFERATION; CELL SURVIVAL; CHRONIC MYELOID LEUKEMIA; CONTROLLED STUDY; DRUG STRUCTURE; ENZYME ACTIVITY; HUMAN; HUMAN CELL; MOUSE; NONHUMAN; NUDE MOUSE; PRIORITY JOURNAL; PROTEIN PHOSPHORYLATION;

ANILINE COMPOUNDS; ANIMALS; ANTINEOPLASTIC AGENTS; CELL DIVISION; CELL SURVIVAL; DNA-BINDING PROTEINS; ENZYME INHIBITORS; FEMALE; HUMANS; K562 CELLS; LEUKEMIA, MYELOID, CHRONIC; MICE; MILK PROTEINS; NITRILES; PHOSPHORYLATION; PROTEIN-TYROSINE KINASES; PROTO-ONCOGENE PROTEINS C-ABL; QUINOLINES; SRC-FAMILY KINASES; STAT5 TRANSCRIPTION FACTOR; TRANS-ACTIVATORS; XENOGRAFT MODEL ANTITUMOR ASSAYS;

EID: 0037439689     PISSN: 00085472     EISSN: None     Source Type: Journal    
DOI: None     Document Type: Article

References (64)

1. Sawyers, C. L. Chronic myeloid leukemia. N. Engl. J. Med., 340: 1330-1340, 1999.
2. Kalidas, M., Kantarjian, H., and Talpaz, M. Chronic myelogenous leukemia. JAMA. 286: 895-898, 2001.
3. Faderl, S., Talpaz, M., Estrov, Z., O'Brien, S., Kurzrock, R., and Kantarjian, H. M. The biology of chronic myeloid leukemia. N. Engl. J. Med., 341: 164-172, 1999.
4. Druker, B. J., Sawyers, C. L., Capdeville, R., Ford, J. M., Baccarani, M., and Goldman, J. M. Chronic myelogenous leukemia (Am. Soc. Hematol. Educ. Program Book). Hematology, 87-112, 2001.
5. Talpaz, M., Kantarjian, H., Kurzrock, R., Trujillo, J. M., and Gutterman, J. U. Interferon-α produces sustained cytogenetic responses in chronic myelogenous leukemia, Philadelphia chromosome-positive patients. Ann. Intern. Med., 114: 532-538, 1991.
6. Clift, R. A., and Anasetti, C. Allografting for chronic myeloid leukaemia. Bailliere's Clin. Haematol., 10: 319-336, 1997.
7. Anderson, S. M., and Mladenovic, J. The Bcr-Abl oncogene requires both kinase activity and Src-homology 2 domain to induce cytokine secretion. Blood, 87: 238-244, 1996.
8. Druker, B. J., Tamura, S., Buchdunger, E., Ohno, S., Segal, G. M., Fanning, S., Zimmermann, J., and Lydon, N. B. Effects of a selective inhibitor of the Abl tyrosine kinase on the growth of Bcr-Abl positive cells. Nat. Med., 2: 561-566, 1996.
9. Mauro, M. J., and Druker, B. J. STI571: targeting Bcr-Abl as therapy for CML. Oncologist, 6: 233-238, 2001.
10. le Coutre, P., Mologni, L., Cleris, L., Marchesi, E., Buchdunger, E., Giardini, R., Formelli, F., and Gambacorti-Passerini, C. In vivo eradication of human Bcr/Abl-positive leukemia cells with an Abl kinase inhibitor. J. Natl. Cancer Inst. (Bethesda), 91: 163-168, 1999.
11. Druker, B. J., Sawyers, C. L., Kantarjian, H., Resta, D. J., Reese, S. F., Ford, J. M., Capdeville, R., and Talpaz, M. 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. N. Engl. J. Med., 344: 1038-1042, 2001.
12. Druker, B. J., Talpaz, M., Resta, D. J., Peng, B., Buchdunger, E., Ford, J. M., Lydon, N. B., Kantarjian, H., Capdeville, R., Ohno-Jones, S., and Sawyers, C. L. 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.
13. Talpaz, M., Silver, R. T., Druker, B. J., Goldman, J. M., Gambacorti-Passerini, C., Guilhot, F., Schiffer, C. A., Fischer, T., Deininger, M. W., Lennard, A. L., Hochhaus, A., Ottmann, O. G., Gratwohl, A., Baccarani, M., Stone, R., Tura, S., Mahon, F. X., Fernandes-Reese, S., Gathmann, I., Capdeville, R., Kantarjian, H. M., and Sawyers, C. L. Imatinib induces durable hematologic and cytogenetic responses in patients with accelerated phase chronic myeloid leukemia: results of a Phase 2 study. Blood, 99: 1928-1937, 2002.
14. Kantarjian, H., Sawyers, C., Hochhaus, A., Guilhot, F., Schiffer, C., Gambacorti-Passerini, C., Niederwieser, D., Resta, D., Capdeville, R., Zoellner, U., Talpaz, M., and Druker, B. Hematologic and cytogenetic responses to imatinib mesylate in chronic myelogenous leukemia. N. Engl. J. Med., 346: 645-652, 2002.
15. O'Dwyer, M. E., Mauro, M. J., and Druker, B. J. Recent advancements in the treatment of chronic myelogenous leukemia. Annu. Rev. Med., 53: 369-381, 2002.
16. Kantarjian, H., Melo, J. V., Tura, S., Giralt, S., and Talpaz, M. Chronic myelogenous leukemia: disease biology and current and future therapeutic strategies (Am. Soc. Hematol. Educ. Program Book). Hematology, 90-109, 2000.
17. Sakai, N., Ogiso, Y., Fujita, H., Watari, H., Koike, T., and Kuzumaki, N. Induction of apoptosis by a dominant negative H-Ras mutant (116Y) in K562 cells. Exp. Cell Res., 215: 131-136, 1994.
18. Sawyers, C. L., McLaughlin, J., and Witte, O. N. Genetic requirement for Ras in the transformation of fibroblasts and hematopoietic cells by the Bcr-Abl oncogene. J. Exp. Med., 181: 307-313, 1995.
19. Kardinal, C., Konkol, B., Lin, H., Eulitz, M., Schmidt, E. K., Estrov, Z., Talpaz, M., Arlinghaus, R. B., and Feller, S. M. Chronic myelogenous leukemia blast cell proliferation is inhibited by peptides that disrupt Grb2-SoS complexes. Blood, 98: 1773-1781, 2001.
20. Peters, D. G., Hoover, R. R., Gerlach, M. J., Koh, E. Y., Zhang, H., Choe, K., Kirschmeier, P., Bishop, W. R., and Daley, G. Q. Activity of the farnesyl protein transferase inhibitor SCH66336 against Bcr/Abl-induced murine leukemia and primary cells from patients with chronic myeloid leukemia. Blood, 97: 1404-1412, 2001.
21. Reichert, A., Heisterkamp, N., Daley, G. Q., and Groffen, J. Treatment of Bcr/Abl-positive acute lymphoblastic leukemia in P190 transgenic mice with the farnesyl transferase inhibitor SCH66336. Blood, 97: 1399-1403, 2001.
22. Yu, C., Krystal, G., Varticovksi, L., McKinstry, R., Rahmani, M., Dent, P., and Grant, S. Pharmacologic mitogen-activated protein/extracellular 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., 62: 188-199, 2002.
23. Skorski, T., Nieborowska-Skorska, M., Szczylik, C., Kanakaraj, P., Perrotti, D., Zon, G., Gewirtz, A., Perussia, B., and Calabretta, B. C-Raf-1 serine/threonine kinase is required in Bcr/Abl-dependent and normal hematopoiesis. Cancer Res., 55: 2275-2278, 1995.
24. Neshat, M. S., Raitano, A. B., Wang, H. G., Reed, J. C., and Sawyers, C. L. The survival function of the Bcr-Abl oncogene is mediated by Bad-dependent and -independent pathways: roles for phosphatidylinositol 3-kinase and Raf. Mol. Cell. Biol., 20: 1179-1186, 2000.
25. Reuther, J. Y., Reuther, G. W., Cortez, D., Pendergast, A. M., and Baldwin, A. S., Jr. A requirement for NF-κB activation in Bcr-Abl-mediated transformation. Genes Dev., 12: 968-981, 1998.
26. Skorski, T., Kanakaraj, P., Nieborowska-Skorska, M., Ratajczak, M. Z., Wen, S. C., Zon, G., Gewirtz, A. M., Perussia, B., and Calabretta, B. Phosphatidylinositol-3 kinase activity is regulated by Bcr/Abl and is required for the growth of Philadelphia chromosome-positive cells. Blood, 86: 726-736, 1995.
27. Calabretta, B., and Skorski, T. Bcr/Abl regulation of PI-3 kinase activity. Leuk. Lymphoma, 23: 473-476, 1996.
28. de Groot, R. P., Raaijmakers, J. A., Lammers, J. W., Jove, R., and Koenderman, L. STAT5 activation by Bcr-Abl contributes to transformation of K562 leukemia cells. Blood, 94: 1108-1112, 1999.
29. Gesbert, F., and Griffin, J. D. Bcr/Abl activates transcription of the Bcl-X gene through STAT5. Blood, 96: 2269-2276, 2000.
30. Shuai, K., Halpern, J., ten Hoeve, J., Rao, X., and Sawyers, C. L. Constitutive activation of STAT5 by the Bcr-Abl oncogene in chronic myelogenous leukemia. Oncogene, 13: 247-254, 1996.
31. Sillaber, C., Gesbert, F., Frank, D. A., Sattler, M., and Griffin, J. D. STAT5 activation contributes to growth and viability in Bcr/Abl-transformed cells. Blood, 95: 2118-2125, 2000.
32. Sonoyama, J., Matsumura, I., Ezoe, S., Satoh, Y., Zhang, X., Kataoka, Y., Takai, E., Mizuki, M., Machii, T., Wakao, H., and Kanakura, Y. Functional cooperation among Ras, STAT5, and phosphatidylinositol 3-kinase is required for full oncogenic activities of Bcr/Abl in K562 cells. J. Biol. Chem., 277: 8076-8082, 2002.
33. Nichols, G. L., Raines, M. A., Vera, J. C., Lacomis, L., Tempst, P., and Golde, D. W. Identification of CrkL as the constitutively phosphorylated 39-kD tyrosine phosphoprotein in chronic myelogenous leukemia cells. Blood, 84: 2912-2918, 1994.
34. Rhodes, J., York, R. D., Tara, D., Tajinda, K., and Druker, B. J. CrkL functions as a nuclear adaptor and transcriptional activator in Bcr-Abl-expressing cells. Exp. Hematol., 28: 305-310, 2000.
35. Tari, A. M., Arlinghaus, R., and Lopez-Berestein, G. Inhibition of Grb2 and Crk1 proteins results in growth inhibition of Philadelphia chromosome positive leukemic cells. Biochem. Biophys. Res. Commun., 235: 383-388, 1997.
36. Raitano, A. B., Halpern, J. R., Hambuch, T. M., and Sawyers, C. L. The Bcr-Abl leukemia oncogene activates jun kinase and requires jun for transformation. Proc. Natl. Acad. Sci. USA, 92: 11746-11750, 1995.
37. Danhauser-Riedl, S., Warmuth, M., Druker, B. J., Emmerich, B., and Hallek, M. Activation of Src kinases p53/56Lyn and p59Hck by p210Bcr/Abl in myeloid cells. Cancer Res., 56: 3589-3596, 1996.
38. Ptasznik, A., Urbanowska, E., Chinta, S., Costa, M. A., Katz, B. A., Stanislaus, M. A., Demir, G., Linnekin, D., Pan, Z. K., and Gewirtz, A. M. Crosstalk between Bcr/Abl oncoprotein and CXCR4 signaling through a Src family kinase in human leukemia cells. J. Exp. Med., 196: 667-678, 2002.
39. Warmuth, M., Bergmann, M., Priess, A., Hauslmann, K., Emmerich, B., and Hallek, M. 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.
40. Lionberger, J. M., Wilson, M. B., and Smithgall, T. E. Transformation of myeloid leukemia cells to cytokine independence by Bcr-Abl is suppressed by kinase-defective Hck. J. Biol. Chem., 275: 18581-18585, 2000.
41. Sattler, M., Pride, Y. B., Quinnan, L. R., Verma, S., Malouf, N. A., Husson, H., Salgia, R., Lipkowitz, S., and Griffin, J. D. Differential expression and signaling of CBL and CBL-B in Bcr/Abl transformed cells. Oncogene, 21: 1423-1433, 2002.
42. Sattler, M., Mohi, M. G., Pride, Y. B., Quinnan, L. R., Malouf, N. A., Podar, K., Gesbert, F., Iwasaki, H., Li, S., Van Etten, R. A., Gu, H., Griffin, J. D., and Neel, B. G. Critical role for Gab2 in transformation by Bcr/Abl. Cancer Cell, 1: 479-492, 2002.
43. Gorre, M. E., Mohammed, M., Ellwood, K., Hsu, N., Paquette, R., Rao, P. N., and Sawyers, C. L. Clinical resistance to STI-571 cancer therapy caused by Bcr-Abl gene mutation or amplification. Science (Wash. DC), 293: 876-880, 2001.
44. von Bubnoff, N., Schneller, F., Peschel, C., and Duyster, J. Bcr-Abl gene mutations in relation to clinical resistance of Philadelphia-chromosome-positive leukaemia to STI571: a prospective study. Lancet, 359: 487-491, 2002.
45. Boschelli, D. H., Ye, F., Wang, Y. D., Dutia, M., Johnson, S. L., Wu, B., Miller, K., Powell, D. W., Yaczko, D., Young, M., Tischler, M., Arndt, K., Discafani, C., Etienne, C., Gibbons, J., Grod, J., Lucas, J., Weber, J. M., and Boschelli, F. Optimization of 4-phenylamino-3-quinolinecarbonitriles as potent inhibitors of Src kinase activity. J. Med. Chem., 44: 3965-3977, 2001.
46. Dorsey, J. F., Jove, R., Kraker, A. J., and Wu, J. The pyrido[2,3-D]pyrimidine derivative PD180970 inhibits p210Bcr-Abl tyrosine kinase and induces apoptosis of K562 leukemic cells. Cancer Res., 60: 3127-3131, 2000.
47. 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., and Clarkson, B. Characterization of potent inhibitors of the Bcr-Abl and the c-Kit receptor tyrosine kinases. Cancer Res., 62: 4244-4255, 2002.
48. Zimmermann, J., Buchdunger, E., Mett, H., Meyer, T., and Lydon, N. Potent and selective inhibitors of the Abl-kinase: phenylaminopyrimidine (PAP) derivatives. Bioorg. Med. Chem. Lett., 7: 187-192, 1997.
49. Deininger, M. W., Goldman, J. M., Lydon, N., and Melo, J. V. The tyrosine kinase inhibitor CGP57148B selectively inhibits the growth of Bcr-Abl-positive cells. Blood, 90: 3691-3698, 1997.
50. Buchdunger, E., Zimmermann, J., Mett, H., Meyer, T., Muller, M., Druker, B. J., and Lydon, N. B. Inhibition of the Abl protein-tyrosine kinase in vitro and in vivo by a 2-phenylaminopyrimidine derivative. Cancer Res., 56: 100-104, 1996.
51. Donato, N. J., Wu, J. Y., Zhang, L., Kantarjian, H., and Talpaz, M. Down-regulation of interleukin-3/granulocyte-macrophage colony-stimulating factor receptor β-chain in Bcr-Abl(+) human leukemic cells: association with loss of cytokine-mediated STAT5 activation and protection from apoptosis after Bcr-Abl inhibition. Blood, 97: 2846-2853, 2001.
52. Clark, S. S., McLaughlin, J., Timmons, M., Pendergast, A. M., Ben-Neriah, Y., Dow, L. W., Crist, W., Rovera, G., Smith, S. D., and Witte, O. N. Expression of a distinctive Bcr-Abl oncogene in Ph1-positive acute lymphocytic leukemia (ALL). Science (Wash. DC), 239: 775-777, 1988.
53. Carroll, M., Ohno-Jones, S., Tamura, S., Buchdunger, E., Zimmermann, J., Lydon, N. B., Gilliland, D. G., and Druker, B. J. CGP 57148, a tyrosine kinase inhibitor, inhibits the growth of cells expressing BCR-ABL, TEL-ABL, and TEL-PDGFR fusion proteins. Blood, 90: 4947-4952, 1997.
54. Spiekermann, K., Pau, M., Schwab, R., Schmieja, K., Franzrahe, S., and Hiddemann, W. Constitutive activation of STAT3 and STAT5 is induced by leukemic fusion proteins with protein tyrosine kinase activity and is sufficient for transformation of hematopoietic precursor cells. Exp. Hematol., 30: 262-271, 2002.
55. Liu, R. Y., Fan, C., Garcia, R., Jove, R., and Zuckerman, K. S. Constitutive activation of the JAK2/STAT5 signal transduction pathway correlates with growth factor independence of megakaryocytic leukemic cell lines. Blood, 93: 2369-2379, 1999.
56. Frank, D. A., and Varticovski, L. Bcr/Abl leads to the constitutive activation of STAT proteins and shares an epitope with tyrosine phosphorylated STATs. Leukemia (Baltimore), 10: 1724-1730, 1996.
57. Chai, S. K., Nichols, G. L., and Rothman, P. Constitutive activation of JAKs and STATs in Bcr-Abl-expressing cell lines and peripheral blood cells derived from leukemic patients. J. Immunol., 159: 4720-4728, 1997.
58. Carlesso, N., Frank, D. A., and Griffin, J. D. Tyrosyl phosphorylation and DNA binding activity of signal transducers and activators of transcription (STAT) proteins in hematopoietic cell lines transformed by Bcr/Abl. J. Exp. Med., 183: 811-820, 1996.
59. Klejman, A., Schreiner, S. J., Nieborowska-Skorska, M., Slupianek, A., Wilson, M., Smithgall, T. E., and Skorski, T. The Src family kinase Hck couples Bcr/Abl to STAT5 activation in myeloid leukemia cells. EMBO J., 21: 5766-5774, 2002.
60. Okutani, Y., Kitanaka, A., Tanaka, T., Kamano, H., Ohnishi, H., Kubota, Y., Ishida, T., and Takahara, J. Src directly tyrosine-phosphorylates STAT5 on its activation site and is involved in erythropoietin-induced signaling pathway. Oncogene, 20: 6643-6650, 2001.
61. Chin, H., Arai, A., Wakao, H., Kamiyama, R., Miyasaka, N., and Miura, O. Lyn physically associates with the erythropoietin receptor and may play a role in activation of the STAT5 pathway. Blood, 91: 3734-3745, 1998.
62. Million, R. P., and Van Etten, R. A. The Grb2 binding site is required for the induction of chronic myeloid leukemia-like disease in mice by the Bcr/Abl tyrosine kinase. Blood, 96: 664-670, 2000.
63. Goga, A., McLaughlin, J., Afar, D. E., Saffran, D. C., and Witte, O. N. Alternative signals to Ras for hematopoietic transformation by the Bcr-Abl oncogene. Cell, 82: 981-988, 1995.
64. Cortez, D., Kadlec, L., and Pendergast, A. M. Structural and signaling requirements for Bcr-Abl-mediated transformation and inhibition of apoptosis. Mol. Cell. Biol., 15: 5531-5541, 1995.