BCR ABL KINASE INHIBITORS FOR CANCER THERAPY
Abstract
BCR-ABL tyrosine kinase inhibitors have started era of molecular targeted therapy and marked a greatest milestone in cancer drug discovery. Despite of impressive cytogenetic response rates achieved with several agents in patients with chronic myelogenous leukemia (CML) in chronic phase, those with advanced stage CML frequently obtain more modest responses that are in many instances of short duration. Several mechanisms of resistance to imatinib are also observed among patients that develop clinical resistance to imatinib. Some approaches are being pursued to overcome these mutations. Deregulated tyrosine kinase activity of the BCR-ABL fusion protein has been established as the causative molecular event in CML. BCR-ABL tyrosine kinase is an ideal target for pharmacological inhibition. Following the initial success of imatinib as frontline therapy for CML, several second generation therapeutic inhibitors have been developed with increased potency and the ability to inhibit the majority of imatinib resistant mutations. In addition, many other protein kinases implicated in signaling transduction downstream BCR-ABL play critical roles in the pathogenesis of CML, thus representing potential therapeutic targets revealed from several clinical studies. The objective of present article is on current developments of potential existing and new innovative BCR-ABL kinase inhibitors for tumor therapy and specificity of several new inhibitors.
Keywords:
BCR-ABL, Kinase Inhibitors, Cancer, Chronic Myelogenous Leukemia, ImatinibDOI
https://doi.org/10.25004/IJPSDR.2010.020201References
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23. Buchdunger E, Zimmermann J, Mett H. Inhibition of the Abl protein-tyrosine kinase in vitro and in vivo by a 2-phenylaminopyrimidine derivative. Cancer Res. 1996; 56:100-104.
24. Deininger MW, Vieira S, Mendiola R. BCRABL tyrosine kinase activity regulates the expression of multiple genes implicated in the pathogenesis of chronic myeloid leukemia. Cancer Res. 2000; 60:2049-2055.
25. Le Coutre P, Mologni L, Cleris L. In vivo eradication of human BCR/ABL-positive leukemia cells with an ABL kinase inhibitor. J Natl Cancer Inst. 1999; 91:163-168.
26. Zhang X, Ren R. Bcr-Abl efficiently induces a myeloproliferative disease and production of excess interleukin- 3 and granulocyte-macrophage colony-stimulating factor in mice: a novel model for chronic myelogenous leukemia. Blood. 1998; 92:3829-3840.
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28. Gorre ME, Ellwood-Yen K, Chiosis G, Rosen N, Sawyers CL. BCR-ABL point mutants isolated from patients with imatinib mesylate-resistant chronic myeloid leukemia remain sensitive to inhibitors of the BCR-ABL chaperone heat shock protein 90. Blood. 2002; 100: 3041–3044.
29. Gambacorti-Passerini CB, Gunby RH, Piazza R, Galietta A, Rostagno R, Scapozza L. Molecular mechanisms of resistance to imatinib in Philadelphia-chromosome-positive leukaemias. Lancet Oncol. 2003; 4: 75–85.
30. Hochhaus A, Kreil S, Corbin AS, La Rosee P, Muller MC, Lahaye T, Hanfstein B, Schoch C, Cross NC, Berger U, Gschaidmeier H, Druker BJ, Hehlmann R. Molecular and chromosomal mechanisms of resistance to imatinib (STI571) therapy. Leukemia. 2002; 16: 2190–2196.
31. Manley J, Mestan S, Cowan-Jacob M, Wartmann E, Weisberg D, Fabbro DG, Gillil JD. AMN107: inhibitory profile against wildtype and mutant forms of the Bcr-Abl tyrosine kinase. Proc. Am. Assoc. Cancer Res. 2005; 46: 1408 [Abst. 5985].
32. Golemovic S, Verstovsek F, Giles J, Cortes T, Manshouri PW, Manley J, Mestan M, Dugan L, Alland JD, Griffin RB, Arlinghaus T, Sun H, Kantarjian M. AMN107, a novel aminopyrimidine inhibitor of Bcr-Abl, has in vitro activity against imatinib-resistant chronic myeloid leukemia. Clin. Cancer Res. 2005; 11: 4941– 4947.
33. Yezhelyev MV, Koehl G, Guba M, Jauch KW, Ryan A, Barge A, Green T, Fennell M, Bruns CJ. Inhibition of Src tyrosine kinase as a treatment for human pancreatic cancer growing orthotopically in nude mice. Clin. Cancer Res. 2004; 10:8028– 8036.
34. Warmuth M, Simon N, Mitina O, Mathes R, Fabbro D, Manley PW, Buchdunger E, Forster K, Moarefi I, Hallek M. Dual-specific Src and Abl kinase inhibitors, PP1 and CGP76030, inhibit growth and survival of cells expressing STI571 resistant Bcr/Abl kinases. Blood. 2003; 101:664– 672.
35. Cowan-Jacob SW, Fendrich G, Manley PW, Jahnke W, Fabbro D, Liebetanz J, Meyer T. The crystal structure of a c-Src complex in an active conformation suggests possible steps in c-Src activation. Structure. 2005; 13:861-871.
36. Lee FY, Lombardo A, Camuso S, Castaneda K, Fager C, Flefleh I, Inigo K, Johnson D, Kan R, Luo K, McGlinchey S, Pang R, Peterson M, Wen R, Wild C, Fairchild T, Wong R, Borzilleri R, Kramer D. BMS- 354825 potently inhibits multiple selected oncogenic tyrosine kinases and possesses broad spectrum anti-tumor activities in vitro and in vivo. Proc. Am. Assoc. Cancer Res. 2005; 46:159 [Abst. 675].
37. 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, Wityak J, Borzilleri RM. Discovery of N-(2-chloro-6- methylphenyl)-2-(6-(4-(2-hydroxyethyl)-(piperazin-1-yl)-2-methylpyrimidin-4-amino)thiazole-5-carboxamide (BMS-354825), a dual Src/Abl kinase inhibitor with potent anti-tumor activity in preclinical assays. J. Med. Chem. 2004; 47: 6658-6661.
38. Boschelli DH, Wang YD, Johnson S, Wu B, Ye F, Sosa ACB, Golas JM, Boschelli F. 7-Alkoxy-4-phenylamino-3- uinolinecarbonitriles as dual inhibitors of Src and Abl kinases. J. Med. Chem. 2004; 47:1599-1601.
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01-04-2010
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“BCR ABL KINASE INHIBITORS FOR CANCER THERAPY”. International Journal of Pharmaceutical Sciences and Drug Research, vol. 2, no. 2, Apr. 2010, pp. 80-90, https://doi.org/10.25004/IJPSDR.2010.020201.
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Copyright (c) 2010 Dhara Patel, Maulik P. Suthar, Vipul Patel, Rajesh Singh
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How to Cite
“BCR ABL KINASE INHIBITORS FOR CANCER THERAPY”. International Journal of Pharmaceutical Sciences and Drug Research, vol. 2, no. 2, Apr. 2010, pp. 80-90, https://doi.org/10.25004/IJPSDR.2010.020201.
