Structural insights into FGFR kinase isoform selectivity: Diverse binding modes of AZD4547 and ponatinib in complex with FGFR1 and FGFR4

Structure

Volumn 22, Issue 12, 2014, Pages 1764-1774

  Tucker, Julie A ^a,b   Klein, Tobias ^a,c   Breed, Jason ^a   Breeze, Alexander L ^a,d   Overman, Ross ^a   Phillips, Chris ^a   Norman, Richard A ^a  

^a ASTRAZENECA   (United Kingdom)

^b NEWCASTLE UNIVERSITY   (United Kingdom)

^c BAYER PHARMA AG   (Germany)

^d UNIVERSITY OF LEEDS   (United Kingdom)

Author keywords

[No Author keywords available]

Indexed keywords

AZD 4547; BENZAMIDE DERIVATIVE; FIBROBLAST GROWTH FACTOR RECEPTOR 1; FIBROBLAST GROWTH FACTOR RECEPTOR 4; IMIDAZOLE DERIVATIVE; ISOPROTEIN; LIGAND; PIPERAZINE DERIVATIVE; PONATINIB; PROTEIN BINDING; PYRAZOLE DERIVATIVE; PYRIDAZINE DERIVATIVE;

CELL LINE; DRUG EFFECTS; ESCHERICHIA COLI; METABOLISM; PHOSPHORYLATION; SIGNAL TRANSDUCTION;

BENZAMIDES; CELL LINE; ESCHERICHIA COLI; IMIDAZOLES; LIGANDS; PHOSPHORYLATION; PIPERAZINES; PROTEIN BINDING; PROTEIN ISOFORMS; PYRAZOLES; PYRIDAZINES; RECEPTOR, FIBROBLAST GROWTH FACTOR, TYPE 1; RECEPTOR, FIBROBLAST GROWTH FACTOR, TYPE 4; SIGNAL TRANSDUCTION;

EID: 84914094459     PISSN: 09692126     EISSN: 18784186     Source Type: Journal    
DOI: 10.1016/j.str.2014.09.019     Document Type: Article

References (71)

1. F.H. Allen The Cambridge Structural Database: a quarter of a million crystal structures and rising Acta Crystallogr. B 58 2002 380 388
2. M. Azam, M.A. Seeliger, N.S. Gray, J. Kuriyan, and G.Q. Daley Activation of tyrosine kinases by mutation of the gatekeeper threonine Nat. Struct. Mol. Biol. 15 2008 1109 1118
3. J. Bange, D. Prechtl, Y. Cheburkin, K. Specht, N. Harbeck, M. Schmitt, T. Knyazeva, S. Müller, S. Gärtner, and I. Sures Cancer progression and tumor cell motility are associated with the FGFR4 Arg(388) allele Cancer Res. 62 2002 840 847
4. M.J. Birrer, M.E. Johnson, K. Hao, K.-K. Wong, D.-C. Park, A. Bell, W.R. Welch, R.S. Berkowitz, and S.C. Mok Whole genome oligonucleotide-based array comparative genomic hybridization analysis identified fibroblast growth factor 1 as a prognostic marker for advanced-stage serous ovarian adenocarcinomas J. Clin. Oncol. 25 2007 2281 2287
5. G. Bricogne, E. Blanc, M. Brandl, C. Flensburg, P. Keller, W. Paciorek, P. Roversi, A. Sharff, O.S. Smart, C. Vonrhein, and T.O. Womack BUSTER version 2.11.5 2011 Global Phasing Cambridge, UK
6. A.N. Brooks, E. Kilgour, and P.D. Smith Molecular pathways: fibroblast growth factor signaling: a new therapeutic opportunity in cancer Clin. Cancer Res. 18 2012 1855 1862
7. I.J. Bruno, J.C. Cole, M. Kessler, J. Luo, W.D.S. Motherwell, L.H. Purkis, B.R. Smith, R. Taylor, R.I. Cooper, S.E. Harris, and A.G. Orpen Retrieval of crystallographically-derived molecular geometry information J. Chem. Inf. Comput. Sci. 44 2004 2133 2144
8. S.A. Byron, H. Chen, A. Wortmann, D. Loch, M.G. Gartside, F. Dehkhoda, S.P. Blais, T.A. Neubert, M. Mohammadi, and P.M. Pollock The N550K/H mutations in FGFR2 confer differential resistance to PD173074, dovitinib, and ponatinib ATP-competitive inhibitors Neoplasia 15 2013 975 988
9. H. Chen, J. Ma, W. Li, A.V. Eliseenkova, C. Xu, T.A. Neubert, W.T. Miller, and M. Mohammadi A molecular brake in the kinase hinge region regulates the activity of receptor tyrosine kinases Mol. Cell 27 2007 717 730
10. G. Chen, X. Tian, Z. Liu, S. Zhou, B. Schmidt, D. Henne-Bruns, M. Bachem, and M. Kornmann Inhibition of endogenous SPARC enhances pancreatic cancer cell growth: modulation by FGFR1-III isoform expression Br. J. Cancer 102 2010 188 195
11. V.B. Chen, W.B. Arendall 3rd, J.J. Headd, D.A. Keedy, R.M. Immormino, G.J. Kapral, L.W. Murray, J.S. Richardson, and D.C. Richardson MolProbity: all-atom structure validation for macromolecular crystallography Acta Crystallogr. D Biol. Crystallogr. 66 2010 12 21
12. H. Chen, Z. Huang, K. Dutta, S. Blais, T.A. Neubert, X. Li, D. Cowburn, N.J. Traaseth, and M. Mohammadi Cracking the molecular origin of intrinsic tyrosine kinase activity through analysis of pathogenic gain-of-function mutations Cell Rep. 4 2013 376 384
13. H. Davies, C. Hunter, R. Smith, P. Stephens, C. Greenman, G. Bignell, J. Teague, A. Butler, S. Edkins, and C. Stevens Somatic mutations of the protein kinase gene family in human lung cancer Cancer Res. 65 2005 7591 7595
14. L.R. Desnoyers, R. Pai, R.E. Ferrando, K. Hötzel, T. Le, J. Ross, R. Carano, A. D'Souza, J. Qing, and I. Mohtashemi Targeting FGF19 inhibits tumor growth in colon cancer xenograft and FGF19 transgenic hepatocellular carcinoma models Oncogene 27 2008 85 97
15. L. Ding, G. Getz, D.A. Wheeler, E.R. Mardis, M.D. McLellan, K. Cibulskis, C. Sougnez, H. Greulich, D.M. Muzny, and M.B. Morgan Somatic mutations affect key pathways in lung adenocarcinoma Nature 455 2008 1069 1075
16. P. Emsley, B. Lohkamp, W.G. Scott, and K. Cowtan Features and development of Coot Acta Crystallogr. D Biol. Crystallogr. 66 2010 486 501
17. P. Evans Scaling and assessment of data quality Acta Crystallogr. D Biol. Crystallogr. 62 2006 72 82
18. D.M. French, B.C. Lin, M. Wang, C. Adams, T. Shek, K. Hötzel, B. Bolon, R. Ferrando, C. Blackmore, and K. Schroeder Targeting FGFR4 inhibits hepatocellular carcinoma in preclinical mouse models PLoS ONE 7 2012 e36713
19. P.R. Gavine, L. Mooney, E. Kilgour, A.P. Thomas, K. Al-Kadhimi, S. Beck, C. Rooney, T. Coleman, D. Baker, and M.J. Mellor AZD4547: an orally bioavailable, potent, and selective inhibitor of the fibroblast growth factor receptor tyrosine kinase family Cancer Res. 72 2012 2045 2056
20. R. Goetz, and M. Mohammadi Exploring mechanisms of FGF signalling through the lens of structural biology Nat. Rev. Mol. Cell Biol. 14 2013 166 180
21. J.M. Gozgit, M.J. Wong, L. Moran, S. Wardwell, Q.K. Mohemmad, N.I. Narasimhan, W.C. Shakespeare, F. Wang, T. Clackson, and V.M. Rivera Ponatinib (AP24534), a multitargeted pan-FGFR inhibitor with activity in multiple FGFR-amplified or mutated cancer models Mol. Cancer Ther. 11 2012 690 699
22. C. Greenman, P. Stephens, R. Smith, G.L. Dalgliesh, C. Hunter, G. Bignell, H. Davies, J. Teague, A. Butler, and C. Stevens Patterns of somatic mutation in human cancer genomes Nature 446 2007 153 158
23. H. Greulich, and P.M. Pollock Targeting mutant fibroblast growth factor receptors in cancer Trends Mol. Med. 17 2011 283 292
24. K.C. Hart, S.C. Robertson, M.Y. Kanemitsu, A.N. Meyer, J.A. Tynan, and D.J. Donoghue Transformation and Stat activation by derivatives of FGFR1, FGFR3, and FGFR4 Oncogene 19 2000 3309 3320
25. H.K. Ho, S. Pok, S. Streit, J.E. Ruhe, S. Hart, K.S. Lim, H.L. Loo, M.O. Aung, S.G. Lim, and A. Ullrich Fibroblast growth factor receptor 4 regulates proliferation, anti-apoptosis and alpha-fetoprotein secretion during hepatocellular carcinoma progression and represents a potential target for therapeutic intervention J. Hepatol. 50 2009 118 127
26. H.K. Ho, A.H.L. Yeo, T.S. Kang, and B.T. Chua Current strategies for inhibiting FGFR activities in clinical applications: opportunities, challenges and toxicological considerations Drug Discov. Today 19 2014 51 62
27. G.A. Holdgate Thermodynamics of binding interactions in the rational drug design process Exp. Opin. Drug Discov. 2 2007 1103 1114
28. Z. Huang, H. Chen, S. Blais, T.A. Neubert, X. Li, and M. Mohammadi Structural mimicry of a-loop tyrosine phosphorylation by a pathogenic FGF receptor 3 mutation Structure 21 2013 1889 1896
29. M.-F. Incardona, G.P. Bourenkov, K. Levik, R.A. Pieritz, A.N. Popov, and O. Svensson EDNA: a framework for plugin-based applications applied to X-ray experiment online data analysis J. Synchrotron Radiat. 16 2009 872 879
30. J.-H. Jang, K.-H. Shin, and J.-G. Park Mutations in fibroblast growth factor receptor 2 and fibroblast growth factor receptor 3 genes associated with human gastric and colorectal cancers Cancer Res. 61 2001 3541 3543
31. W. Kabsch XDS Acta Crystallogr. D Biol. Crystallogr. 66 2010 125 132
32. T. Klein, J. Tucker, G.A. Holdgate, R.A. Norman, and A.L. Breeze FGFR1 kinase inhibitors: close regioisomers adopt divergent binding modes and display distinct biophysical signatures ACS Med. Chem. Lett. 5 2014 166 171
33. A.P. Kornev, N.M. Haste, S.S. Taylor, and L.F. Eyck Surface comparison of active and inactive protein kinases identifies a conserved activation mechanism Proc. Natl. Acad. Sci. USA 103 2006 17783 17788
34. E. Krissinel, and K. Henrick Secondary-structure matching (SSM), a new tool for fast protein structure alignment in three dimensions Acta Crystallogr. D Biol. Crystallogr. 60 2004 2256 2268
35. H. Kurosu, M. Choi, Y. Ogawa, A.S. Dickson, R. Goetz, A.V. Eliseenkova, M. Mohammadi, K.P. Rosenblatt, S.A. Kliewer, and M. Kuro-o Tissue-specific expression of betaKlotho and fibroblast growth factor (FGF) receptor isoforms determines metabolic activity of FGF19 and FGF21 J. Biol. Chem. 282 2007 26687 26695
36. R.A. Laskowski, M.W. MacArthur, D.S. Moss, and J.M. Thornton PROCHECK: a program to check the stereochemical quality of protein structures J. Appl. Cryst. 26 1993 283 291
37. B.C. Lin, M. Wang, C. Blackmore, and L.R. Desnoyers Liver-specific activities of FGF19 require Klotho beta J. Biol. Chem. 282 2007 27277 27284
38. Y. Liu, and N.S. Gray Rational design of inhibitors that bind to inactive kinase conformations Nat. Chem. Biol. 2 2006 358 364
39. Y. Liu, K. Shah, F. Yang, L. Witucki, and K.M. Shokat A molecular gate which controls unnatural ATP analogue recognition by the tyrosine kinase v-Src Bioorg. Med. Chem. 6 1998 1219 1226
40. S. McNicholas, E. Potterton, K.S. Wilson, and M.E.M. Noble Presenting your structures: the CCP4mg molecular-graphics software Acta Crystallogr. D Biol. Crystallogr. 67 2011 386 394
41. H.R. Mellor Targeted inhibition of the FGF19-FGFR4 pathway in hepatocellular carcinoma; translational safety considerations Liver Int. 34 2014 e1 e9
42. D.S. Millan, M.E. Bunnage, J.L. Burrows, K.J. Butcher, P.G. Dodd, T.J. Evans, D.A. Fairman, S.J. Hughes, I.C. Kilty, and A. Lemaitre Design and synthesis of inhaled p38 inhibitors for the treatment of chronic obstructive pulmonary disease J. Med. Chem. 54 2011 7797 7814
43. M. Mohammadi, J. Schlessinger, and S.R. Hubbard Structure of the FGF receptor tyrosine kinase domain reveals a novel autoinhibitory mechanism Cell 86 1996 577 587
44. G.N. Murshudov, P. Skubák, A.A. Lebedev, N.S. Pannu, R.A. Steiner, R.A. Nicholls, M.D. Winn, F. Long, and A.A. Vagin REFMAC5 for the refinement of macromolecular crystal structures Acta Crystallogr. D Biol. Crystallogr. 67 2011 355 367
45. F.H. Niesen, H. Berglund, and M. Vedadi The use of differential scanning fluorimetry to detect ligand interactions that promote protein stability Nat. Protoc. 2 2007 2212 2221
46. R.A. Norman, A.-K. Schott, D.M. Andrews, J. Breed, K.M. Foote, A.P. Garner, D. Ogg, J.P. Orme, J.H. Pink, and K. Roberts Protein-ligand crystal structures can guide the design of selective inhibitors of the FGFR tyrosine kinase J. Med. Chem. 55 2012 5003 5012
47. R.A. Norman, D. Toader, and A.D. Ferguson Structural approaches to obtain kinase selectivity Trends Pharmacol. Sci. 33 2012 273 278
48. T. O'Hare, C.A. Eide, and M.W. Deininger Bcr-Abl kinase domain mutations, drug resistance, and the road to a cure for chronic myeloid leukemia Blood 110 2007 2242 2249
49. T. O'Hare, W.C. Shakespeare, X. Zhu, C.A. Eide, V.M. Rivera, F. Wang, L.T. Adrian, T. Zhou, W.-S. Huang, and Q. Xu AP24534, a pan-BCR-ABL inhibitor for chronic myeloid leukemia, potently inhibits the T315I mutant and overcomes mutation-based resistance Cancer Cell 16 2009 401 412
50. R. Pai, D. French, N. Ma, K. Hotzel, E. Plise, L. Salphati, K.D.R. Setchell, J. Ware, V. Lauriault, and L. Schutt Antibody-mediated inhibition of fibroblast growth factor 19 results in increased bile acids synthesis and ileal malabsorption of bile acids in cynomolgus monkeys Toxicol. Sci. 126 2012 446 456
51. J.W. Pflugrath The finer things in X-ray diffraction data collection Acta Crystallogr. D Biol. Crystallogr. 55 1999 1718 1725
52. A. Roidl, P. Foo, W. Wong, C. Mann, S. Bechtold, H.J. Berger, S. Streit, J.E. Ruhe, S. Hart, A. Ullrich, and H.K. Ho The FGFR4 Y367C mutant is a dominant oncogene in MDA-MB453 breast cancer cells Oncogene 29 2010 1543 1552
53. J.E. Ruhe, S. Streit, S. Hart, C.-H. Wong, K. Specht, P. Knyazev, T. Knyazeva, L.S. Tay, H.L. Loo, and P. Foo Genetic alterations in the tyrosine kinase transcriptome of human cancer cell lines Cancer Res. 67 2007 11368 11376
54. J. Sadowski, J. Gasteiger, and G. Klebe Comparison of automatic three-dimensional model builders using 639 X-ray structures J. Chem. Inf. Comput. Sci. 34 1994 1000 1008
55. S. Schreiber, B. Feagan, G. D'Haens, J.F. Colombel, K. Geboes, M. Yurcov, V. Isakov, O. Golovenko, C.N. Bernstein, D. Ludwig BIRB 796 Study Group Oral p38 mitogen-activated protein kinase inhibition with BIRB 796 for active Crohn's disease: a randomized, double-blind, placebo-controlled trial Clin. Gastroenterol. Hepatol. 4 2006 325 334
56. J.R. Simard, M. Getlik, C. Grütter, R. Schneider, S. Wulfert, and D. Rauh Fluorophore labeling of the glycine-rich loop as a method of identifying inhibitors that bind to active and inactive kinase conformations J. Am. Chem. Soc. 132 2010 4152 4160
57. M. Spinola, V. Leoni, C. Pignatiello, B. Conti, F. Ravagnani, U. Pastorino, and T.A. Dragani Functional FGFR4 Gly388Arg polymorphism predicts prognosis in lung adenocarcinoma patients J. Clin. Oncol. 23 2005 7307 7311
58. M. Spinola, V.P. Leoni, J. Tanuma, A. Pettinicchio, M. Frattini, S. Signoroni, R. Agresti, R. Giovanazzi, S. Pilotti, and L. Bertario FGFR4 Gly388Arg polymorphism and prognosis of breast and colorectal cancer Oncol. Rep. 14 2005 415 419
59. J.G. Taylor 6th, A.T. Cheuk, P.S. Tsang, J.-Y. Chung, Y.K. Song, K. Desai, Y. Yu, Q.-R. Chen, K. Shah, and V. Youngblood Identification of FGFR4-activating mutations in human rhabdomyosarcomas that promote metastasis in xenotransplanted models J. Clin. Invest. 119 2009 3395 3407
60. C. Thussbas, J. Nahrig, S. Streit, J. Bange, M. Kriner, R. Kates, K. Ulm, M. Kiechle, H. Hoefler, A. Ullrich, and N. Harbeck FGFR4 Arg388 allele is associated with resistance to adjuvant therapy in primary breast cancer J. Clin. Oncol. 24 2006 3747 3755
61. R.C. Turkington, D.B. Longley, W.L. Allen, L. Stevenson, K. McLaughlin, P.D. Dunne, J.K. Blayney, M. Salto-Tellez, S. Van Schaeybroeck, and P.G. Johnston Fibroblast growth factor receptor 4 (FGFR4): a targetable regulator of drug resistance in colorectal cancer Cell Death Dis. 5 2014 e1046
62. N. Turner, and R. Grose Fibroblast growth factor signalling: from development to cancer Nat. Rev. Cancer 10 2010 116 129
63. C. Vonrhein, C. Flensburg, P. Keller, A. Sharff, O. Smart, W. Paciorek, T. Womack, and G. Bricogne Data processing and analysis with the autoPROC toolbox Acta Crystallogr. D Biol. Crystallogr. 67 2011 293 302
64. M. Weinstein, X. Xu, K. Ohyama, and C.X. Deng FGFR-3 and FGFR-4 function cooperatively to direct alveogenesis in the murine lung Development 125 1998 3615 3623
65. M.D. Winn, C.C. Ballard, K.D. Cowtan, E.J. Dodson, P. Emsley, P.R. Evans, R.M. Keegan, E.B. Krissinel, A.G.W. Leslie, and A. McCoy Overview of the CCP4 suite and current developments Acta Crystallogr. D Biol. Crystallogr. 67 2011 235 242
66. G. Winter, C.M.C. Lobley, and S.M. Prince Decision making in xia2 Acta Crystallogr. D Biol. Crystallogr. 69 2013 1260 1273
67. X. Wu, H. Ge, B. Lemon, S. Vonderfecht, J. Weiszmann, R. Hecht, J. Gupte, T. Hager, Z. Wang, R. Lindberg, and Y. Li FGF19-induced hepatocyte proliferation is mediated through FGFR4 activation J. Biol. Chem. 285 2010 5165 5170
68. Y.W. Ye, Y. Zhou, L. Yuan, C.M. Wang, C.Y. Du, X.Y. Zhou, B.Q. Zheng, X. Cao, M.H. Sun, H. Fu, and Y.Q. Shi Fibroblast growth factor receptor 4 regulates proliferation and antiapoptosis during gastric cancer progression Cancer 117 2011 5304 5313
69. T.M. Zaid, T.-L. Yeung, M.S. Thompson, C.S. Leung, T. Harding, N.N. Co, R.S. Schmandt, S.Y. Kwan, C. Rodriguez-Aguay, and G. Lopez-Berestein Identification of FGFR4 as a potential therapeutic target for advanced-stage, high-grade serous ovarian cancer Clin. Cancer Res. 19 2013 809 820
70. W. Zhou, W. Hur, U. McDermott, A. Dutt, W. Xian, S.B. Ficarro, J. Zhang, S.V. Sharma, J. Brugge, and M. Meyerson A structure-guided approach to creating covalent FGFR inhibitors Chem. Biol. 17 2010 285 295
71. T. Zhou, L. Commodore, W.-S. Huang, Y. Wang, M. Thomas, J. Keats, Q. Xu, V.M. Rivera, W.C. Shakespeare, and T. Clackson Structural mechanism of the Pan-BCR-ABL inhibitor ponatinib (AP24534): lessons for overcoming kinase inhibitor resistance Chem. Biol. Drug Des. 77 2011 1 11