Displacement assay for the detection of stabilizers of inactive kinase conformations

Journal of Medicinal Chemistry

Volumn 53, Issue 1, 2010, Pages 357-367

  Klüter, Sabine ^a   Grütter, Christian ^a   Naqvi, Tabassum ^b   Rabiller, Matthias ^a   Simard, Jeffrey R ^a   Pawar, Vijaykumar ^a   Getlik, Matthäus ^a   Rauh, Daniel ^a  

^a CHEMICAL GENOMICS CENTRE OF THE MAX PLANCK SOCIETY   (Germany)

^b DiscoveRx Corporation   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ADENOSINE TRIPHOSPHATE; MITOGEN ACTIVATED PROTEIN KINASE 14; PROTEIN KINASE; PROTEIN KINASE INHIBITOR; PYRAZOLE DERIVATIVE;

ARTICLE; DRUG PROTEIN BINDING; ENZYME ACTIVITY; ENZYME BINDING; ENZYME CONFORMATION; ENZYME INACTIVATION; ENZYME INHIBITION; ENZYME STABILITY; X RAY CRYSTALLOGRAPHY;

CRYSTALLOGRAPHY, X-RAY; DRUG DESIGN; MITOGEN-ACTIVATED PROTEIN KINASE 9; MODELS, MOLECULAR; P38 MITOGEN-ACTIVATED PROTEIN KINASES; PROTEIN CONFORMATION; PROTEIN KINASE INHIBITORS; PYRAZOLES; STRUCTURE-ACTIVITY RELATIONSHIP; UREA;

EID: 74849131970     PISSN: 00222623     EISSN: None     Source Type: Journal    
DOI: 10.1021/jm901297e     Document Type: Article

References (44)

1. Sandoval, D. A.; Obici, S.; Seeley, R. J. Targeting the CNS to treat type 2 diabetes. Nat. Rev. Drug Discovery 2009, 8, 386-398.
2. Cohen, P. Targeting protein kinases for the development of antiinflammatory drugs. Curr. Opin. Cell Biol. 2009, 21, 317-24.
3. Fabbro, D.; Ruetz, S.; Buchdunger, E.; Cowan-Jacob, S. W.; Fendrich, G.; Liebetanz, J.; Mestan, J.; O'Reilly, T.; Traxler, P.; Chaudhuri, B.; Fretz, H.; Zimmermann, J.; Meyer, T.; Caravatti, G.; Furet, P.; Manley, P. W. Protein kinases as targets for anticancer agents: from inhibitors to useful drugs. Pharmacol. Ther. 2002, 93, 79-98.
4. Gaestel, M.; Kotlyarov, A.; Kracht, M. Targeting innate immunity protein kinase signalling in inflammation. Nat. Rev. Drug Discovery 2009, 8, 480-499.
5. Zhang, J.; Yang, P. L.; Gray, N. S. Targeting cancer with small molecule kinase inhibitors. Nat. Rev. Cancer 2009, 9, 28-39.
6. Janne, P. A.; Gray, N.; Settleman, J. Factors underlying sensitivity of cancers to small-molecule kinase inhibitors. Nat. Rev. Drug Discovery 2009, 8, 709-723.
7. Bogoyevitch, M. A.; Fairlie, D. P. A new paradigm for protein kinase inhibition: blocking phosphorylation without directly targeting ATP binding. Drug Discovery Today 2007, 12, 622-633.
8. Vogtherr, M.; Saxena, K.; Hoelder, S.; Grimme, S.; Betz, M.; Schieborr, U.; Pescatore, B.; Robin, M.; Delarbre, L.; Langer, T.; Wendt, K. U.; Schwalbe, H. NMR characterization of kinase p38 dynamics in free and ligand-bound forms. Angew. Chem., Int. Ed. 2006, 45, 993-997.
9. Backes, A. C.; Zech, B.; Felber, B.; Klebl, B.; M̈uller, G. Smallmolecule inhibitors binding to protein kinase. Part II: the novel pharmacophore approach of type II and type III inhibition. Expert Opin. Drug Discovery 2008, 3, 1427-1449.
10. Liu, Y.; Gray, N. S. Rational design of inhibitors that bind to inactive kinase conformations. Nat. Chem. Biol. 2006, 2, 358-364.
11. Ma, H.; Deacon, S.; Horiuchi, K. The challenge of selecting protein kinase assays for lead discovery optimization. Expert Opin. Drug Discovery 2008, 3, 607-621.
12. Olive, D. M. Quantitative methods for the analysis of protein phosphorylation in drug development. Expert Rev. Proteomics 2004, 1, 327-341.
13. Getlik, M.; Gr̈utter, C.; Simard, J. R.; Kl̈uter, S.; Rabiller, M.; Rode, H. B.; Robubi, A.; Rauh, D. Hybrid compound design to overcome the gatekeeper T338M mutation in cSrc. J. Med. Chem. 2009, 3915-3926.
14. Naqvi, T.; Rouhani, R.; Singh, R. Improved Receptor Detection. WO 2003102154 (A2), 2003.
15. Zaman,G. J.; vanderLee,M.M.;Kok, J. J.;Nelissen,R.L.;Loomans, E. E. Enzyme fragment complementation binding assay for p38alpha mitogen-activated protein kinase to study the binding kinetics of enzyme inhibitors. Assay Drug Dev. Technol. 2006, 4, 411-420.
16. Naqvi, T.; Rouhani, R.; Singh, R. Short Enzyme Fragment Donor. WO 03093786 (A2), 2006.
17. Fabian, M. A.; Biggs, W. H., 3rd; Treiber, D. K.; Atteridge, C. E.; Azimioara, M. D.; Benedetti, M. G.; Carter, T. A.; Ciceri, P.; Edeen, P. T.; Floyd, M.; Ford, J. M.; Galvin, M.; Gerlach, J. L.; Grotzfeld, R. M.; Herrgard, S.; Insko, D. E.; Insko, M. A.; Lai, A. G.; Lelias, J. M.; Mehta, S. A.; Milanov, Z. V.; Velasco, A. M.; Wodicka, L. M.; Patel, H. K.; Zarrinkar, P. P.; Lockhart, D. J. A small molecule-kinase interaction map for clinical kinase inhibitors. Nat. Biotechnol. 2005, 23, 329-336.
18. Karaman,M.W.;Herrgard, S.;Treiber,D.K.;Gallant, P.;Atteridge, C. E.; Campbell, B. T.; Chan, K. W.; Ciceri, P.; Davis,M. I.; Edeen, P. T.; Faraoni, R.; Floyd, M.; Hunt, J. P.; Lockhart, D. J.;Milanov, Z. V.; Morrison, M. J.; Pallares, G.; Patel, H. K.; Pritchard, S.; Wodicka, L. M.; Zarrinkar, P. P. A quantitative analysis of kinase inhibitor selectivity. Nat. Biotechnol. 2008, 26, 127-132.
19. Pargellis, C.; Tong, L.; Churchill, L.; Cirillo, P. F.; Gilmore, T.; Graham, A. G.; Grob, P. M.; Hickey, E. R.; Moss, N.; Pav, S.; Regan, J. Inhibition of p38 MAP kinase by utilizing a novel allosteric binding site. Nat. Struct. Biol. 2002, 9, 268-272.
20. Cirillo, P. F.; Pargellis,C.;Regan, J. The non-diaryl heterocycle classes of p38MAPkinase inhibitors. Curr TopMedChem 2002, 2, 1021-1035.
21. Sullivan, J. E.; Holdgate, G. A.; Campbell, D.; Timms, D.; Gerhardt, S.; Breed, J.; Breeze, A. L.; Bermingham, A.; Pauptit, R. A.; Norman, R. A.; Embrey, K. J.; Read, J.; VanScyoc, W. S.; Ward, W. H. Prevention of MKK6-dependent activation by binding to p38alpha MAP kinase. Biochemistry 2005, 44, 16475-16490.
22. Regan, J.; Breitfelder, S.; Cirillo, P.; Gilmore, T.; Graham, A. G.; Hickey, E.;Klaus, B.; Madwed, J.; Moriak,M.; Moss,N.; Pargellis, C.; Pav, S.;Proto,A.; Swinamer,A.; Tong,L.;Torcellini, C. Pyrazole urea-based inhibitors of p38 MAP kinase: from lead compound to clinical candidate. J. Med. Chem. 2002, 45, 2994-3008.
23. Simard, J. R.; Getlik, M.; Gr̈utter, C.; Pawar, V.; Wulfert, S.; Rabiller, M.; Rauh, D. Development of a fluorescent-tagged kinase assay system for the detection and characterization of allosteric kinase inhibitors. J. Am. Chem. Soc. 2009, 131, 13286-13296.
24. Simard, J. R.; Kl̈uter, S.; Gr̈utter, C.; Getlik, M.; Rabiller, M.; Rode, H. B.; Rauh, D. A new screening assay for allosteric inhibitors of cSrc. Nat. Chem. Biol. 2009, 5, 394-396.
25. 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.
26. Seeliger, M. A.; Nagar, B.; Frank, F.; Cao, X.; Henderson, M. N.; Kuriyan, J. c-Src binds to the cancer drug imatinib with an inactive Abl/c-Kit conformation and a distributed thermodynamic penalty. Structure 2007, 15, 299-311.
27. Zhang, J. H.; Chung, T. D.; Oldenburg, K. R. A simple statistical parameter for use in evaluation and validation of high throughput screening assays. J Biomol. Screening 1999, 4, 67-73.
28. Blencke, S.; Zech, B.; Engkvist, O.; Greff, Z.; Orfi, L.; Horvath, Z.; Keri, G.; Ullrich, A.; Daub, H. Characterization of a conserved structural determinant controlling protein kinase sensitivity to selective inhibitors. Chem. Biol. 2004, 11, 691-701.
29. Daub, H.; Specht, K.; Ullrich, A. Strategies to overcome resistance to targeted protein kinase inhibitors. Nat. Rev. Drug Discovery 2004, 3, 1001-1010.
30. Shaw, D.; Wang, S. M.; Villasenor, A. G.; Tsing, S.; Walter, D.; Browner, M. F.; Barnett, J.; Kuglstatter, A. The crystal structure of JNK2 reveals conformational flexibility in the MAP kinase insert and indicates its involvement in the regulation of catalytic activity. J. Mol. Biol. 2008, 383, 885-893.
31. Bukhtiyarova, M.; Northrop, K.; Chai, X.; Casper, D.; Karpusas, M.; Springman, E. Improved expression, purification, and crystallization of p38alpha MAP kinase. Protein Expression Purif. 2004, 37, 154-161.
32. Kabsch, W. Automatic processing of rotation diffraction data from crystals of initially unknown symmetry and cell constants. J. Appl. Crystallogr. 1993, 26, 795-800.
33. Read, R. J. Pushing the boundaries of molecular replacement with maximum likelihood. Acta Crystallogr., Sect. D: Biol. Crystallogr. 2001, 57, 1373-1382.
34. Michelotti, E. L.; Moffett, K. K.; Nguyen, D.; Kelly, M. J.; Shetty, R.; Chai, X.; Northrop, K.; Namboodiri, V.; Campbell, B.; Flynn, G. A.; Fujimoto, T.; Hollinger, F. P.; Bukhtiyarova, M.; Springman, E. B.; Karpusas, M. Two classes of p38alpha MAP kinase inhibitors having a common diphenylether core but exhibiting divergent binding modes. Bioorg. Med. Chem. Lett. 2005, 15, 5274-5279.
35. Emsley, P.; Cowtan, K. Coot: model-building tools for molecular graphics. Acta Crystallogr. D 2004, 60, 2126-2132.
36. Br̈unger, A. T.; Adams, P. D.; Clore, G. M.; DeLano, W. L.; Gros, P.; Grosse-Kunstleve, R. W.; Jiang, J. S.; Kuszewski, J.; Nilges, M.; Pannu, N. S.; Read, R. J.; Rice, L. M.; Simonson, T.; Warren, G. L. Crystallography & NMR system: a new software suite for macromolecular structure determination. Acta Crystallogr., Sect. D: Biol. Crystallogr. 1998, 54, 905-921.
37. Murshudov, G. N.; Vagin, A. A.; Dodson, E. J. Refinement of macromolecular structures by the maximum-likelihood method. Acta Crystallogr. D 1997, 53, 240-255.
38. Scḧuttelkopf, A. W.; van Aalten, D. M. PRODRG: a tool for highthroughput crystallography of protein-ligand complexes. Acta Crystallogr., Sect. D: Biol. Crystallogr. 2004, 60, 1355-1363.
39. Laskowski, R. A.; McArthur, M. W.; Moss, D. S.; Thornton, J. M. PROCHECK: a program to check the stereochemical quality of protein structures. J. Appl. Crystallogr. 1993, 26, 263-291.
40. DeLano, W. L. The PyMOL Molecular Graphics System. http:// www.pymol.org, 2002.
41. Dominguez, C.; Powers, D. A.; Tamayo, N. p38 MAP kinase inhibitors: many are made, but few are chosen. Curr. Opin. Drug Discovery Dev. 2005, 8, 421-430.
42. Lee, M. R.; Dominguez, C. MAP kinase p38 inhibitors: clinical results and an intimate look at their interactions with p38alpha protein. Curr. Med. Chem. 2005, 12, 2979-2994.
43. Hanke, J. H.; Gardner, J. P.; Dow, R. L.; Changelian, P. S.; Brissette, W. H.; Weringer, E. J.; Pollok, B. A.; Connelly, P. A. Discovery of a novel, potent, and Src family-selective tyrosine kinase inhibitor. Study of Lck- and FynT-dependent T cell activation. J. Biol. Chem. 1996, 271, 695-701.
44. Juers, D. H.; Jacobson, R. H.; Wigley, D.; Zhang, X. J.; Huber, R. E.; Tronrud, D. E.; Matthews, B. W. High resolution refinement of beta-galactosidase in a new crystal form reveals multiple metal-binding sites and provides a structural basis for alpha-complementation. Protein Sci. 2000, 9, 1685-1699.