Binding mode of the 4-anilinoquinazoline class of protein kinase inhibitor: X-ray crystallographic studies of 4-anilinoquinazolines bound to cyclin-dependent kinase 2 and p38 kinase

Journal of Medicinal Chemistry

Volumn 43, Issue 1, 2000, Pages 133-138

  Shewchuk, Lisa ^a   Hassell, Anne ^a   Wisely, Bruce ^a   Rocque, Warren ^a   Holmes, William ^a   Veal, James ^a   Kuyper, Lee F ^a  

^a GLAXOSMITHKLINE   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

4 ANILINOQUINAZOLINE; ADENOSINE TRIPHOSPHATE; PROTEIN KINASE INHIBITOR; QUINAZOLINE DERIVATIVE; UNCLASSIFIED DRUG;

ARTICLE; BINDING SITE; CHEMICAL STRUCTURE; CRYSTAL STRUCTURE; ENZYME INHIBITION; PROTEIN STRUCTURE; STEREOCHEMISTRY; X RAY CRYSTALLOGRAPHY;

ADENOSINE TRIPHOSPHATE; ANILINE COMPOUNDS; CDC2-CDC28 KINASES; CRYSTALLOGRAPHY, X-RAY; CYCLIN-DEPENDENT KINASE 2; CYCLIN-DEPENDENT KINASES; ENZYME INHIBITORS; MITOGEN-ACTIVATED PROTEIN KINASES; MODELS, MOLECULAR; P38 MITOGEN-ACTIVATED PROTEIN KINASES; PROTEIN BINDING; PROTEIN CONFORMATION; PROTEIN KINASE INHIBITORS; PROTEIN-SERINE-THREONINE KINASES; QUINAZOLINES;

EID: 0034642482     PISSN: 00222623     EISSN: None     Source Type: Journal    
DOI: 10.1021/jm990401t     Document Type: Article

References (50)

1. Protein kinases; Woodgett, J. R., Ed.; Oxford University Press: New York, 1994.
2. The protein kinase factsbook: Protein-serine kinases; Hardie, G., Hanks, S., Eds.; Academic Press Inc.: San Diego, CA, 1995.
3. The protein kinase factsbook: Protein-tyrosine kinases; Hardie, G., Hanks, S., Eds.; Academic Press Inc.: San Diego, CA, 1995.
4. Fry, D. W.; Kraker, A. J.; Connors, R. C.; Elliott, W. L.; Nelson, J. M.; Showalter, H. D.; Leopold, W. R. Strategies for the discovery of novel tyrosine kinase inhibitors with anticancer activity. Anticancer Drug Des. 1994, 9, 331-351.
5. Gray, N. S.; Wodicka, L.; Thunnissen, A.-M. W. H.; Norman, T. C.; Kwon, S.; Espinoza, F. H.; Morgan, D. O.; Barnes, G.; LeClerc, S.; Meijer, L.; Kim, S.-H.; Lockhart, D. J.; Schultz, P. G. Exploiting chemical libraries, structure, and genomics in the search for kinase inhibitors. Science 1998, 281, 533-538.
6. Groundwater, P. M.; Solomons, K. R. H.; Drewe, J. A.; Munawar, M. A. Protein kinase inhibitors. Prog. Med. Chem. 1996, 33, 233-329.
7. Lawrence, D. S.; Niu, J. Protein kinase inhibitors: The tyrosine-specific protein kinases. Pharmacol. Ther. 1998, 77, 81-114.
8. Lee, J. C.; Adams, J. L. Inhibitors of serine/threonine kinases. Curr. Opin. Biotechnol. 1995, 6, 657-661.
9. Patrick, D. R.; Heimbrook, D. C. Protein kinase inhibitors for the treatment of cancer. Drug Discov. Today 1996, 1, 325-330.
10. Adams, J. L.; Lee, D. Recent progress towards the identification of selective inhibitors of serine/threonine kinases. Curr. Opin. Drug Discuss. Dev. 1999, 2, 96-109.
11. Traxler, P. M. Protein tyrosine kinase inhibitors in cancer treatment. Expert Opin. Ther. Pat. 1997, 7, 571-588.
12. Myers, M. R.; He, W.; Hulme, C. Inhibitors of tyrosine kinases involved in inflammation and autoimmune disease. Curr. Pharm. Des. 1997, 3, 473-502.
13. Wei, L.; Hubbard, S. R.; Smith, R. F.; Ellis, L. Protein kinase superfamily - - comparisons of sequence data with three-dimensional structures. Curr. Opin. Struct. Biol. 1994,4, 450-455.
14. Hanks, S. K. Eucaryotic protein kinases. Curr. Opin. Struct. Biol. 1991, 1, 369-383.
15. Wakeling, A. E.; Barker, A. J.; Davies, D. H.; Brown, D. S.; Green, L. R.; Cartlidge, S. A.; Woodburn, J. R. Specific inhibition of epidermal growth factor receptor tyrosine kinase by 4-anilinoquinazolines. Breast Cancer Res. Treat. 1996, 38, 67-73.
16. Denny, W. A.; Rewcastle, G. W.; Bridges, A. J.; Fry, D. W.; Kraker, A. J. Structure-activity relationships for 4-anilinoquinazolines as potent inhibitors at the ATP binding site of the epidermal growth factor receptor in vitro. Clin. Exp. Pharm. Physiol. 1996, 23, 424-427.
17. 4-Anilinoquinazoline derivatives. Expert Opin. Ther. Pat. 1998, 8, 475-478.
18. Fry, D. W.; Kraker, A. J.; McMichael, A.; Ambrose, L. A.; Nelson, J. M.; Leopold, W. R.; Connors, R. W.; Bridges, A. J. A specific inhibitor of the epidermal growth factor receptor. Science 1994, 265, 1093-1095.
19. Palmer, B. D.; Trumpp-Kallmeyer, S.; Fry, D. W.; Nelson, J. M.; Showalter, H. D. H.; Denny, W. A. Tyrosine kinase inhibitors. 11. Soluble analogues of pyrrolo- and pyrazoloquinazolines as epidermal growth factor receptor inhibitors: Synthesis, biological evaluation, and modeling of the mode of binding. J. Med. Chem. 1997, 40, 1519-1529.
20. Traxler, P.; Green, J.; Mett, H.; Sequin, U.; Furet, P. Use of a pharmacophore model for the design of EGFR tyrosine kinase inhibitors: Isoflavones and 3-phenyl-4(1H)-quinolones. J. Med. Chem. 1999, 42, 1018-1026.
21. Traxler, P. M.; Furet, P.; Mett, H.; Buchdunger, E.; Meyer, T.; Lydon, N. 4-(Phenylamino)pyrrolopyrimidines: potent and selective, ATP site directed inhibitors of the EGF-receptor protein tyrosine kinase. J. Med. Chem. 1996, 39, 2285-2292.
22. Morgan, D. O. Cyclin-dependent kinases: Engines, clocks, and microprocessors. Annu. Rev. Cell Dev. Biol. 1997,13, 261-291.
23. New, L.; Han, J. The p38 MAP kinase pathway and its biological function. Trends Cardiovasc. Med. 1998, 8, 220-228.
24. Schulze-Gahmen, U.; De Bondt, H. L.; Kim, S.-H. High-resolution crystal structures of human cyclin-dependent kinase 2 with and without ATP: Bound waters and natural ligand as guides for inhibitor design. J. Med. Chem. 1996, 39, 4540-4546.
25. De Bondt, H. L.; Rosenblatt, J.; Jancarik, J.; Jones, H. D.; Morgan, D. O.; Kim, S.-H. Crystal structure of cyclin-dependent kinase 2. Nature 1993, 363, 595-602.
26. De Azevedo, W. F.; Leclerc, S.; Meijer, L.; Havlicek, L.; Strnad, M.; Kim, S.-H. Inhibition of cyclin-dependent kinases by purine analogues. Crystal structure of human cdk2 complexed with roscovitine. Eur. J. Biochem. 1997, 243, 518-526.
27. De Azevedo, W. F.; Mueller-Dieckmann, H.-J.; Schulze-Gahmen, U.; Worland, P. J.; Sausville, E.; Kim, S.-H. Structural basis for specificity and potency of a flavanoid inhibitor of human CDK2, a cell cycle kinase. Proc. Natl. Acad. Sci. U.S.A. 1996, 93.
28. Lawrie, A. M.; Noble, M. E. M.; Tunnah, P.; Brown, N. R.; Johnson, L. N.; Endicott, J. A. Protein kinase inhibition by staurosporine revealed in details of the molecular interaction with CDK2. Nat. Struct. Biol. 1997, 4, 796-801.
29. Wilson, K. P.; McCaffrey, P. G.; Hsiao, K.; Pazhanisamy, S.; Galullo, V.; Bemis, G. W.; Fitzgibbon, M. J.; Caron, P. R.; Murcko, M. A.; Su, M. S. S. The structural basis for the specificity of pyridinylimidazole inhibitors of p38 MAP kinase. Chem. Biol. 1997, 4, 423-431.
30. Wilson, K. P.; Fitzgibbon, M. J.; Caron, P. R.; Griffith, J. P.; Chen, W.; McCaffrey, P. G.; Chambers, S. P.; Su, M. S.-S. Crystal structure of p38 mitogen-activated protein kinase. J. Biol. Chem. 1996, 277, 27696-27700.
31. Wang, Z.; Harkins, P. C.; Ulevitch, R. J.; Han, J.; Cobb, M. H.; Goldsmith, E. J. The structure of mitogen-activated protein kinase p38 at 2.1-A resolution. Proc. Natl. Acad. Sci. U.S.A. 1997, 94, 2327-2332.
32. Tong, L.; Pav, S.; White, D. M.; Rogers, S.; Crane, K. M.; Cywin, C. L.; Brown, M. L.; Pargellis, C. A. A highly specific inhibitor of human p38 MAP kinase binds in the ATP pocket. Nat. Struct. Biol. 1997, 4, 311-316.
33. Russo, A. A.; Jeffrey, P. D.; Pavletich, N. Structural basis of cyclin-dependent kinase activation by phosphorylation. Nat. Struct. Biol. 1996, 3, 696-700.
34. Jeffrey, P. D.; Russo, A. A.; Polyak, K.; Gibbs, E.; Hurwitz, J.; Massague, J.; Pavletich, N. Mechanism of CDK activation revealed by the structure of a cyclin A-CDK2 complex. Nature 1995, 376, 313-320.
35. Myers, M. R.; Setzer, N. N.; Spada, A. P.; Persons, P. E.; Ly, C. Q.; Maguire, M. P.; Zulli, A. L.; Cheney, D. L.; Zilberstein, A.; Johnson, S. E.; Franks, C. F.; Mitchell, K. J. The synthesis and SAR of new 4-(N-alkyl-N-phenyl)amino-6,7-dimethoxyquinazolines and 4-(N-alkyl-N-phenyl)aminopyrazolo[3,4-d]pyrimidines, inhibitors of CSF-1R tyrosine kinase activity. Bioorg. Med. Chem. Lett. 1997, 7, 421-424.
36. Anderson, G. M.; Kollman, P. A.; Domelsmith, L. N.; Houk, K. N. Methoxy group nonplanarity in o-dimethoxybenzenes. Simple predictive models for conformations and rotational barriers in alkoxyaromatics. J. Am. Chem. Soc. 1979, 101, 2344-2352.
37. Thomas, K. A.; Smith, G. M.; Thomas, T. B.; Feldman, R. J. Electronic distributions within protein phenylalanine aromatic rings are reflected by three-dimensional oxygen atom environments. Proc. Natl. Acad. Sci. U.S.A. 1982, 79, 4843-4847.
38. Lamb, M. L.; Jorgensen, W. L. Investigations of neurotrophic inhibitors of FK506 binding protein via Monte Carlo simulations. J. Med. Chem. 1998, 41, 3928-3939.
39. Schulze-Gahmen, U.; Brandsen, J.; Jones, H. D.; Morgan, D. O.; Meijer, L.; Vesely, J.; Kim, S.-H. Crystal structures of cyclin-dependent protein kinase 2 in complex with ATP and two inhibitors, olomoucine and isopentenyladenine. Proteins 1995, 22, 378-391.
40. Burley, S. K.; Petsko, G. A. Weakly polar interactions in proteins. Adv. Protein Chem. 1988, 39, 125-189.
41. Wang, Z.; Canagarajah, B. J.; Boehm, J. C.; Kassisa, S.; Cobb, M. H.; Young, P. R.; Abdel-Meguid, S.; Adams, J. L.; Goldsmith, E. J. Structural basis of inhibitor selectivity in MAP kinases. Structure 1998, 6, 1117-1128.
42. Frantz, B.; Klatt, T.; Pang, M.; Parsons, J.; Rolando, A.; Williams, H.; Tocci, M. J.; O'Keefe, S. J.; O'Neill, E. A. The activation state of p38 mitogen-activated protein kinase determines the efficiency of ATP competition for pyridinylimidazole inhibitor binding. Biochemistry 1998, 37, 13846-13853.
43. Narla, R. K.; Liu, X.-P.; Myers, D. E.; Uckun, F. 4-(3′-Bromo-4′-hydroxyphenyl)-amino-6,7-dimethoxyquinazoline: a novel quinazoline derivative with potent cytotoxic activity against human glioblastoma cells. Clin. Cancer Res. 1944, 4, 1405-1414.
44. Bridges, A. J.; Zhou, H.; Cody, D. R.; Rewcastle, G. W.; McMichael, A.; Showalter, H. D.; Fry, D. W.; Kraker, A. J.; Denny, W. A. Tyrosine kinase inhibitors: 8. An unusually steep structure-activity relationship for analogues of 4-(3-bromoanilino)-6,7-dimethoxyquinazoline (PD 153035), a potent inhibitor of the epidermal growth factor receptor. J. Med. Chem. 1996, 39, 267-276.
45. Bourne, Y.; Watson, M. H.; Hickey, M. J.; Holmes, W.; Rocque, W.; Reed, S. I. Crystal structure and mutational analysis of the human CDK2 kinase complex with cell cycle-regulatory protein CksHs1. Cell 1996, 84, 863-874.
46. Otwinowski, Z. In Oscillation data reduction program; Sawyer, L., Isaaca, N., Burley, S., Eds.; CCP4 Study Weekend; SERC Daresbury Laboratory: Daresbury, U.K., 1993; pp 56-62.
47. QUANTA User Guide; Molecular Simulations: San Diego, CA, 1996.
48. Brunger, A. T. XPLOR Version 3.1 Manual; Yale University Press: New Haven, CT, 1992.
49. Brunger, A. T. The free R value: a novel statistical quantity for assessing the accuracy of crystal structures. Nature 1992, 355, 472-474.
50. Pannu, N. S.; Read, R. J. Improved structure refinement through maximum likelihood. Acta Crystallogr. 1996, A52, 659-668.