A novel mechanism by which small molecule inhibitors induce the DFG flip in Aurora A

ACS Chemical Biology

Volumn 7, Issue 4, 2012, Pages 698-706

  Martin, Mathew P ^a   Zhu, Jin Yi ^a   Lawrence, Harshani R ^a   Pireddu, Roberta ^a   Luo, Yunting ^a   Alam, Riazul ^a   Ozcan, Sevil ^a   Sebti, Said M ^a   Lawrence, Nicholas J ^a   Schönbrunn, Ernst ^a  

^a H LEE MOFFITT CANCER CENTER AND RESEARCH INSTITUTE   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ASPARTIC ACID; AURORA A KINASE; BISANILINOPYRIMIDINE INHIBITOR; GLYCINE; HALOGEN; NITRILE; PHENYLALANINE; PROTEIN SERINE THREONINE KINASE INHIBITOR; UNCLASSIFIED DRUG;

AMINO TERMINAL SEQUENCE; ARTICLE; BINDING AFFINITY; CELL DIVISION; CRYSTAL STRUCTURE; DRUG BINDING; DRUG MECHANISM; DRUG POTENTIATION; ENZYME CONFORMATION; IC 50; PRIORITY JOURNAL; PROTEIN FUNCTION; PROTEIN MOTIF; PROTEIN STRUCTURE;

CELL DIVISION; DRUG DESIGN; HUMANS; OLIGOPEPTIDES; PROTEIN CONFORMATION; PROTEIN KINASE INHIBITORS; PROTEIN-SERINE-THREONINE KINASES;

EID: 84860127915     PISSN: 15548929     EISSN: 15548937     Source Type: Journal    
DOI: 10.1021/cb200508b     Document Type: Article

References (49)

1. Dar, A. C. and Shokat, K. M. (2011) The evolution of protein kinase inhibitors from antagonists to agonists of cellular signaling Ann. Rev. Biochem. 80, 769-795
2. Carmena, M. and Earnshaw, W. C. (2003) The cellular geography of aurora kinases Nat. Rev. Mol. Cell. Biol. 4, 842-854 (Pubitemid 37411723)
3. Marumoto, T., Zhang, D., and Saya, H. (2005) Aurora-A-a guardian of poles Nat. Rev. Cancer 5, 42-50
4. Xu, X., Wang, X., Xiao, Z., Li, Y., and Wang, Y. (2011) Two TPX2-dependent switches control the activity of Aurora A PLoS One 6, e16757
5. Becker, M., Stolz, A., Ertych, N., and Bastians, H. (2010) Centromere localization of INCENP-Aurora B is sufficient to support spindle checkpoint function Cell Cycle 9, 1360-1372
6. Gritsko, T. M., Coppola, D., Paciga, J. E., Yang, L., Sun, M., Shelley, S. A., Fiorica, J. V., Nicosia, S. V., and Cheng, J. Q. (2003) Activation and overexpression of centrosome kinase BTAK/Aurora-A in human ovarian cancer Clin. Cancer Res. 9, 1420-1426 (Pubitemid 36418396)
7. Keen, N. and Taylor, S. (2004) Aurora-kinase inhibitors as anticancer agents Nat. Rev. Cancer 4, 927-936 (Pubitemid 39626216)
8. Harrington, E. A., Bebbington, D., Moore, J., Rasmussen, R. K., Ajose-Adeogun, A. O., Nakayama, T., Graham, J. A., Demur, C., Hercend, T., Diu-Hercend, A., Su, M., Golec, J. M., and Miller, K. M. (2004) VX-680, a potent and selective small-molecule inhibitor of the Aurora kinases, suppresses tumor growth in vivo Nat. Med. 10, 262-267 (Pubitemid 38667616)
9. Green, M. R., Woolery, J. E., and Mahadevan, D. (2011) Update on Aurora kinase targeted therapeutics in oncology Expert Opin. Drug Discovery 6, 291-307
10. Howard, S., Berdini, V., Boulstridge, J. A., Carr, M. G., Cross, D. M., Curry, J., Devine, L. A., Early, T. R., Fazal, L., Gill, A. L., Heathcote, M., Maman, S., Matthews, J. E., McMenamin, R. L., Navarro, E. F., O'Brien, M. A., O'Reilly, M., Rees, D. C., Reule, M., Tisi, D., Williams, G., Vinkovic, M., and Wyatt, P. G. (2009) Fragment-based discovery of the pyrazol-4-yl urea (AT9283), a multitargeted kinase inhibitor with potent aurora kinase activity J. Med. Chem. 52, 379-388
11. Gorgun, G., Calabrese, E., Hideshima, T., Ecsedy, J., Perrone, G., Mani, M., Ikeda, H., Bianchi, G., Hu, Y., Cirstea, D., Santo, L., Tai, Y.-T., Nahar, S., Zheng, M., Bandi, M., Carrasco, R. D., Raje, N., Munshi, N., Richardson, P., and Anderson, K. C. (2010) A novel Aurora-A kinase inhibitor MLN8237 induces cytotoxicity and cell-cycle arrest in multiple myeloma Blood 115, 5202-5213
12. Nagar, B., Bornmann, W. G., Pellicena, P., Schindler, T., Veach, D. R., Miller, W. T., Clarkson, B., and Kuriyan, J. (2002) Crystal structures of the kinase domain of c-Abl in complex with the small molecule inhibitors PD173955 and imatinib (STI-571) Cancer Res. 62, 4236-4243 (Pubitemid 34827278)
13. Seeliger, M. A., Ranjitkar, P., Kasap, C., Shan, Y., Shaw, D. E., Shah, N. P., Kuriyan, J., and Maly, D. J. (2009) Equally potent inhibition of c-Src and Abl by compounds that recognize inactive kinase conformations Cancer Res. 69, 2384-2392
14. Angell, R. M., Angell, T. D., Bamborough, P., Bamford, M. J., Chung, C. W., Cockerill, S. G., Flack, S. S., Jones, K. L., Laine, D. I., Longstaff, T., Ludbrook, S., Pearson, R., Smith, K. J., Smee, P. A., Somers, D. O., and Walker, A. L. (2008) Biphenyl amide p38 kinase inhibitors 4: DFG-in and DFG-out binding modes Bioorg. Med. Chem. Lett. 18, 4433-4437
15. Kuglstatter, A., Ghate, M., Tsing, S., Villasenor, A. G., Shaw, D., Barnett, J. W., and Browner, M. F. (2010) X-ray crystal structure of JNK2 complexed with the p38alpha inhibitor BIRB796: insights into the rational design of DFG-out binding MAP kinase inhibitors Bioorg. Med. Chem. Lett. 20, 5217-5220
16. Solanki, S., Innocenti, P., Mas-Droux, C., Boxall, K., Barillari, C., van Montfort, R. L., Aherne, G. W., Bayliss, R., and Hoelder, S. (2011) Benzimidazole inhibitors induce a DFG-out conformation of never in mitosis gene A-related kinase 2 (Nek2) without binding to the back pocket and reveal a nonlinear structure-activity relationship J. Med. Chem. 54, 1626-1639
17. Choi, Y., Syeda, F., Walker, J. R., Finerty, P. J., Jr., Cuerrier, D., Wojciechowski, A., Liu, Q., Dhe-Paganon, S., and Gray, N. S. (2009) Discovery and structural analysis of Eph receptor tyrosine kinase inhibitors Bioorg. Med. Chem. Lett. 19, 4467-4470
18. Dietrich, J., Hulme, C., and Hurley, L. H. (2010) The design, synthesis, and evaluation of 8 hybrid DFG-out allosteric kinase inhibitors: a structural analysis of the binding interactions of Gleevec, Nexavar, and BIRB-796 Bioorg. Med. Chem. 18, 5738-5748
19. Filomia, F., De Rienzo, F., and Menziani, M. C. (2010) Insights into MAPK p38alpha DFG flip mechanism by accelerated molecular dynamics Bioorg. Med. Chem. 18, 6805-6812
20. Muller, K., Faeh, C., and Diederich, F. (2007) Fluorine in pharmaceuticals: looking beyond intuition Science 317, 1881-1886 (Pubitemid 47509426)
21. Lu, Y., Shi, T., Wang, Y., Yang, H., Yan, X., Luo, X., Jiang, H., and Zhu, W. (2009) Halogen bonding-a novel interaction for rational drug design? J. Med. Chem. 52, 2854-2862
22. Lu, Y., Wang, Y., Xu, Z., Yan, X., Luo, X., Jiang, H., and Zhu, W. (2009) C-X...H contacts in biomolecular systems: how they contribute to protein-ligand binding affinity J. Phys. Chem. B 113, 12615-12621
23. Parisini, E., Metrangolo, P., Pilati, T., Resnati, G., and Terraneo, G. (2011) Halogen bonding in halocarbon-protein complexes: a structural survey Chem. Soc. Rev. 40, 2267-2278
24. Metrangolo, P., Resnati, G., and Arman, H. D. (2008) Halogen Bonding: Fundamentals and Applications, Springer, New York.
25. Auffinger, P., Hays, F. A., Westhof, E., and Ho, P. S. (2004) Halogen bonds in biological molecules Proc. Natl. Acad. Sci. U.S.A. 101, 16789-16794 (Pubitemid 39601317)
26. Politzer, P., Lane, P., Concha, M. C., Ma, Y., and Murray, J. S. (2007) An overview of halogen bonding J. Mol. Model. 13, 305-311 (Pubitemid 46189160)
27. Murray, J. S., Lane, P., and Politzer, P. (2009) Expansion of the sigma-hole concept J. Mol. Model. 15, 723-729
28. Metrangolo, P. and Resnati, G. (2001) Halogen bonding: a paradigm in supramolecular chemistry Chemistry 7, 2511-2519 (Pubitemid 32594762)
29. Metrangolo, P., Meyer, F., Pilati, T., Resnati, G., and Terraneo, G. (2008) Halogen bonding in supramolecular chemistry Angew. Chem., Int. Ed. 47, 6114-6127
30. Politzer, P., Murray, J. S., and Clark, T. (2010) Halogen bonding: an electrostatically-driven highly directional noncovalent interaction Phys. Chem. Chem. Phys. 12, 7748-7757
31. Atkins, P. W. (1978) Physical Chemistry, Vol. 1, 1st ed., Oxford University Press, Oxford.
32. Neves-Petersen, M. T. and Petersen, S. B. (2003) Protein electrostatics: a review of the equations and methods used to model electrostatic equations in biomolecules - applications in biotechnology Biotechnol. Annu. Rev. 9, 315-395 (Pubitemid 41081513)
33. Stork, M. and Tavan, P. (2007) Electrostatics of proteins in dielectric solvent continua. II. First applications in molecular dynamics simulations J. Chem. Phys. 126, 165106
34. Nakamura, H. (1996) Roles of electrostatic interaction in proteins Q. Rev. Biophys. 29, 1-90 (Pubitemid 26190831)
35. Gunner, M. R., Saleh, M. A., Cross, E., ud-Doula, A., and Wise, M. (2000) Backbone dipoles generate positive potentials in all proteins: origins and implications of the effect Biophys. J. 78, 1126-1144 (Pubitemid 30141542)
36. Falzon, C. T., Wang, F., and Pang, W. (2006) Orbital signatures of methyl in L-alanine J. Phys. Chem. B 110, 9713-9719 (Pubitemid 43952995)
37. Jones, L. H., Summerhill, N. W., Swain, N. A., and Mills, J. E. (2010) Aromatic chloride to nitrile transformation: medicinal and synthetic chemistry MedChemComm 1, 309-318
38. Fleming, F. F., Yao, L., Ravikumar, P. C., Funk, L., and Shook, B. C. (2010) Nitrile-containing pharmaceuticals: efficacious roles of the nitrile pharmacophore J. Med. Chem. 53, 7902-7917
39. Schneider, E. V., Bottcher, J., Blaesse, M., Neumann, L., Huber, R., and Maskos, K. (2011) The structure of CDK8/CycC implicates specificity in the CDK/cyclin family and reveals interaction with a deep pocket binder J. Mol. Biol. 412, 251-266
40. Schindler, T., Bornmann, W., Pellicena, P., Miller, W. T., Clarkson, B., and Kuriyan, J. (2000) Structural mechanism for STI-571 inhibition of abelson tyrosine kinase Science 289, 1938-1942
41. Pargellis, C., Tong, L., Churchill, L., Cirillo, P. F., Gilmore, T., Graham, A. G., Grob, P. M., Hickey, E. R., Moss, N., Pav, S., and Regan, J. (2002) Inhibition of p38 MAP kinase by utilizing a novel allosteric binding site Nat. Struct. Biol. 9, 268-272 (Pubitemid 34289898)
42. Zhang, J., Adrian, F. J., Jahnke, W., Cowan-Jacob, S. W., Li, A. G., Iacob, R. E., Sim, T., Powers, J., Dierks, C., Sun, F., Guo, G. R., Ding, Q., Okram, B., Choi, Y., Wojciechowski, A., Deng, X., Liu, G., Fendrich, G., Strauss, A., Vajpai, N., Grzesiek, S., Tuntland, T., Liu, Y., Bursulaya, B., Azam, M., Manley, P. W., Engen, J. R., Daley, G. Q., Warmuth, M., and Gray, N. S. (2010) Targeting Bcr-Abl by combining allosteric with ATP-binding-site inhibitors Nature 463, 501-506
43. Comess, K. M., Sun, C., Abad-Zapatero, C., Goedken, E. R., Gum, R. J., Borhani, D. W., Argiriadi, M., Groebe, D. R., Jia, Y., Clampit, J. E., Haasch, D. L., Smith, H. T., Wang, S., Song, D., Coen, M. L., Cloutier, T. E., Tang, H., Cheng, X., Quinn, C., Liu, B., Xin, Z., Liu, G., Fry, E. H., Stoll, V., Ng, T. I., Banach, D., Marcotte, D., Burns, D. J., Calderwood, D. J., and Hajduk, P. J. (2011) Discovery and characterization of non-ATP site inhibitors of the mitogen activated protein (MAP) kinases ACS Chem. Biol. 6, 234-244
44. Dong, Q., Dougan, D. R., Gong, X., Halkowycz, P., Jin, B., Kanouni, T., O'Connell, S. M., Scorah, N., Shi, L., Wallace, M. B., and Zhou, F. (2011) Discovery of TAK-733, a potent and selective MEK allosteric site inhibitor for the treatment of cancer Bioorg. Med. Chem. Lett. 21, 1315-1319
45. Betzi, S., Alam, R., Martin, M., Lubbers, D. J., Han, H., Jakkaraj, S. R., Georg, G. I., and Schonbrunn, E. (2011) Discovery of a potential allosteric ligand binding site in CDK2 ACS Chem. Biol. 6, 492-501
46. Kabsch, W. (1993) Automatic processing of rotation diffraction data from crystals of initially unknown symmetry and cell constants J. Appl. Crystallogr. 26, 795-800
47. (1994) The CCP4 suite: programs for protein crystallography, Acta Crystallogr. Sect. D: Biol. Crystallogr. 50, 760-763.
48. Adams, P. D., Afonine, P. V., Bunkoczi, G., Chen, V. B., Davis, I. W., Echols, N., Headd, J. J., Hung, L. W., Kapral, G. J., Grosse-Kunstleve, R. W., McCoy, A. J., Moriarty, N. W., Oeffner, R., Read, R. J., Richardson, D. C., Richardson, J. S., Terwilliger, T. C., and Zwart, P. H. (2010) PHENIX: a comprehensive Python-based system for macromolecular structure solution Acta Crystallogr., Sect. D: Biol. Crystallogr. 66, 213-221
49. Emsley, P. and Cowtan, K. (2004) Coot: model-building tools for molecular graphics Acta Crystallogr., Sect. D: Biol. Crystallogr. 60, 2126-2132 (Pubitemid 41742764)