Discovery of allosteric Bcr-Abl inhibitors from phenotypic screen to clinical candidate

Methods in Enzymology

Volumn 548, Issue C, 2014, Pages 173-188

  Gray, Nathanael S ^a   Fabbro, Doriano ^b  

^a DANA FARBER CANCER INSTITUTE   (United States)

^b Piqur Therapeutics AG   (Switzerland)

Author keywords

Allosteric inhibitor; BCR ABL; Kinase inhibitor; Myristate pocket binders; T315I gatekeeper mutation

Indexed keywords

ADENOSINE TRIPHOSPHATE; BCR ABL PROTEIN; GNF 5; LIGAND; PROTEIN INHIBITOR; UNCLASSIFIED DRUG; MYRISTIC ACID; NEW DRUG; PROTEIN KINASE INHIBITOR;

ALLOSTERISM; ARTICLE; BINDING SITE; CHRONIC MYELOID LEUKEMIA; CRYSTAL STRUCTURE; DRUG ACTIVITY; DRUG BINDING; DRUG DEVELOPMENT; HUMAN; NONHUMAN; PHENOTYPE; PRIORITY JOURNAL; STRUCTURE ACTIVITY RELATION; ANIMAL; ANTAGONISTS AND INHIBITORS; BINDING COMPETITION; CHEMICAL STRUCTURE; CHEMISTRY; CONFORMATION; DRUG SCREENING; ENZYME ACTIVE SITE; METABOLISM;

MURINAE; PYRONIA TITHONUS;

ADENOSINE TRIPHOSPHATE; ALLOSTERIC REGULATION; ANIMALS; BINDING SITES; BINDING, COMPETITIVE; CATALYTIC DOMAIN; DRUG DISCOVERY; DRUG EVALUATION, PRECLINICAL; DRUGS, INVESTIGATIONAL; FUSION PROTEINS, BCR-ABL; HUMANS; LIGANDS; MODELS, MOLECULAR; MOLECULAR CONFORMATION; MYRISTIC ACID; PROTEIN KINASE INHIBITORS;

EID: 84925433359     PISSN: 00766879     EISSN: 15577988     Source Type: Book Series    
DOI: 10.1016/B978-0-12-397918-6.00007-0     Document Type: Chapter

References (30)

1. F.J. Adrian, Q. Ding, T. Sim, A. Velentza, C. Sloan, and Y. Liu Allosteric inhibitors of Bcr-abl-dependent cell proliferation Nature Chemical Biology 2 2006 95 102
2. A.S. Advani, and A.M. Pendergast Bcr-Abl variants: Biological and clinical aspects Leukemia Research 26 2002 713 720
3. E. Buchdunger, A. Matter, and B.J. Druker Bcr-Abl inhibition as a modality of CML therapeutics Biochimica et Biophysica Acta 1551 2001 M11 M18
4. J.E. Cortes, H.M. Kantarjian, T.H. Brummendorf, D.W. Kim, A.G. Turkina, and Z.X. Shen Safety and efficacy of bosutinib (SKI-606) in chronic phase Philadelphia chromosome-positive chronic myeloid leukemia patients with resistance or intolerance to imatinib Blood 118 2011 4567 4576
5. J.E. Cortes, D.W. Kim, H.M. Kantarjian, T.H. Brummendorf, I. Dyagil, and L. Griskevicius Bosutinib versus imatinib in newly diagnosed chronic-phase chronic myeloid leukemia: Results from the BELA trial Journal of Clinical Oncology 30 2012 3486 3492
6. X. Deng, B. Okram, Q. Ding, J. Zhang, Y. Choi, and F.J. Adrian Expanding the diversity of allosteric bcr-abl inhibitors Journal of Medicinal Chemistry 53 2010 6934 6946
7. S. Ding, N.S. Gray, X. Wu, Q. Ding, and P.G. Schultz A combinatorial scaffold approach toward kinase-directed heterocycle libraries Journal of the American Chemical Society 124 2002 1594 1596
8. Dodd, S. K., Furet, P., Grotzfeld, R. M., Jones, D. B., Manley, P., Marzinzik, A., et al. (2013). Benzamide derivatives for inhibiting the activity of ABL1, ABL2 and BCR-ABL1. WO 2013/171639 A1.
9. D. Fabbro, P.W. Manley, W. Jahnke, J. Liebetanz, A. Szyttenholm, and G. Fendrich Inhibitors of the Abl kinase directed at either the ATP- or myristate-binding site Biochimica et Biophysica Acta 1804 2010 454 462
10. P. Filippakopoulos, S. Muller, and S. Knapp SH2 domains: Modulators of nonreceptor tyrosine kinase activity Current Opinion in Structural Biology 19 2009 643 649
11. Furet, P., Grotzfeld, R. M., Jones, D. B., Manley, P., Marzinzik, A., Moussaoui, S., et al. (2013). Compounds and compositions for inhibiting the activity of ABL1, ABL2 and BCR-ABL1. WO 2013/171641 A1.
12. J.M. Golas, K. Arndt, C. Etienne, J. Lucas, D. Nardin, and J. Gibbons 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 63 2003 375 381
13. F. Grebien, O. Hantschel, J. Wojcik, I. Kaupe, B. Kovacic, and A.M. Wyrzucki Targeting the SH2-kinase interface in Bcr-Abl inhibits leukemogenesis Cell 147 2011 306 319
14. W.S. Huang, C.A. Metcalf, R. Sundaramoorthi, Y. Wang, D. Zou, and R.M. Thomas Discovery of 3-[2-(imidazo[1,2-b]pyridazin-3-yl)ethynyl]-4-methyl-N-{4-[(4-methylpiperazin-1-y l)methyl]-3-(trifluoromethyl)phenyl}benzamide (AP24534), a potent, orally active pan-inhibitor of breakpoint cluster region-abelson (BCR-ABL) kinase including the T315I gatekeeper mutant Journal of Medicinal Chemistry 53 2010 4701 4719
15. R.E. Iacob, T. Pene-Dumitrescu, J. Zhang, N.S. Gray, T.E. Smithgall, and J.R. Engen Conformational disturbance in Abl kinase upon mutation and deregulation Proceedings of the National Academy of Sciences of the United States of America 106 2009 1386 1391
16. R.E. Iacob, J. Zhang, N.S. Gray, and J.R. Engen Allosteric interactions between the myristate- and ATP-site of the Abl kinase PLoS One 6 2011 e15929
17. W. Jahnke, R.M. Grotzfeld, X. Pelle, A. Strauss, G. Fendrich, and S.W. Cowan-Jacob Binding or bending: Distinction of allosteric Abl kinase agonists from antagonists by an NMR-based conformational assay Journal of the American Chemical Society 132 2010 7043 7048
18. L.J. Lombardo, F.Y. Lee, P. Chen, D. Norris, J.C. Barrish, and K. Behnia Discovery of N-(2-chloro-6-methyl-phenyl)-2-(6-(4-(2-hydroxyethyl)-piperazin-1-yl)-2-methylpyrimidin-4-ylamino)thiazole-5-carboxamide (BMS-354825), a dual Src/Abl kinase inhibitor with potent antitumor activity in preclinical assays Journal of Medicinal Chemistry 47 2004 6658 6661
19. K. Mayer, G.H. Gielen, W. Willinek, M.C. Muller, and D. Wolf Fatal progressive cerebral ischemia in CML under third-line treatment with ponatinib Leukemia 28 2014 976 977
20. J.V. Melo The molecular biology of chronic myeloid leukaemia Leukemia 10 1996 751 756
21. B. Nagar, W.G. Bornmann, P. Pellicena, T. Schindler, D.R. Veach, and W.T. Miller Crystal structures of the kinase domain of c-Abl in complex with the small molecule inhibitors PD173955 and imatinib (STI-571) Cancer Research 62 2002 4236 4243
22. B. Nagar, O. Hantschel, M.A. Young, K. Scheffzek, D. Veach, and W. Bornmann Structural basis for the autoinhibition of c-Abl tyrosine kinase Cell 112 2003 859 871
23. T. O'Hare, D.K. Walters, E.P. Stoffregen, T. Jia, P.W. Manley, and J. Mestan In vitro activity of Bcr-Abl inhibitors AMN107 and BMS-354825 against clinically relevant imatinib-resistant Abl kinase domain mutants Cancer Research 65 2005 4500 4505
24. S. Pakakasama, S. Kajanachumpol, S. Kanjanapongkul, N. Sirachainan, A. Meekaewkunchorn, and V. Ningsanond Simple multiplex RT-PCR for identifying common fusion transcripts in childhood acute leukemia International Journal of Laboratory Hematology 30 2008 286 291
25. M. Puttini, A.M. Coluccia, F. Boschelli, L. Cleris, E. Marchesi, and A. Donella-Deana In vitro and in vivo activity of SKI-606, a novel Src-Abl inhibitor, against imatinib-resistant Bcr-Abl\+ neoplastic cells Cancer Research 66 23 2006 11314 11322 17114238 Epub 2006 Nov 17
26. L. Skora, J. Mestan, D. Fabbro, W. Jahnke, and S. Grzesiek NMR reveals the allosteric opening and closing of Abelson tyrosine kinase by ATP-site and myristoyl pocket inhibitors Proceedings of the National Academy of Sciences of the United States of America 110 2013 E4437 E4445
27. M. Warmuth, S. Kim, X.J. Gu, G. Xia, and F. Adrian Ba/F3 cells and their use in kinase drug discovery Current Opinion in Oncology 19 2007 55 60
28. E. Weisberg, P.W. Manley, W. Breitenstein, J. Bruggen, S.W. Cowan-Jacob, and A. Ray Characterization of AMN107, a selective inhibitor of native and mutant Bcr-Abl Cancer Cell 7 2005 129 141
29. J. Yang, N. Campobasso, M.P. Biju, K. Fisher, X.Q. Pan, and J. Cottom Discovery and characterization of a cell-permeable, small-molecule c-Abl kinase activator that binds to the myristoyl binding site Chemical Biology 18 2011 177 186
30. J. Zhang, F.J. Adrian, W. Jahnke, S.W. Cowan-Jacob, A.G. Li, and R.E. Iacob Targeting Bcr-Abl by combining allosteric with ATP-binding-site inhibitors Nature 463 2010 501 506