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http://dx.doi.org/10.5483/BMBRep.2010.43.11.711

Chemical kinomics: a powerful strategy for target deconvolution  

Kim, Do-Hee (Life/Health Division, Korea Institute of Science and Technology)
Sim, Tae-Bo (Life/Health Division, Korea Institute of Science and Technology)
Publication Information
BMB Reports / v.43, no.11, 2010 , pp. 711-719 More about this Journal
Abstract
Kinomics is an emerging and promising approach for deciphering kinomes. Chemical kinomics is a discipline of chemical genomics that is also referred to as "chemogenomics", which is derived from chemistry and biology. Chemical kinomics has become a powerful approach to decipher complicated phosphorylation-based cellular signaling networks with the aid of small molecules that modulate kinase functions. Moreover, chemical kinomics has played a pivotal role in the field of kinase drug discovery as it enables identification of new molecular targets of small molecule kinase modulators and/or exploitation of novel functions of known kinases and has also provided novel chemical entities as hit/lead compounds. In this short review, contemporary chemical kinomics technologies such as activity-based protein profiling, T7 kinasetagged phages, kinobeads, three-hybrid systems, fluorescenttagged kinase binding assays, and chemical genomic profiling are discussed along with a novel allosteric Bcr-Abl kinase inhibitor (GNF-2/GNF-5) as a successful application of chemical kinomics approaches.
Keywords
Chemical kinomics; Kinase inhibitor; Protein kinase; Target identification;
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1 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.   DOI   ScienceOn
2 Cowan-Jacob, S. W., Guez, V., Fendrich, G., Griffin, J. D., Fabbro, D., Furet, P., Liebetanz, J., Mestan, J. and Manley, P. W. (2004) Imatinib (STI571) resistance in chronic myelogenous leukemia: molecular basis of the underlying mechanisms and potential strategies for treatment. Mini Rev. Med. Chem. 4, 285-299.   DOI   ScienceOn
3 Gygi, S. P., Rist, B., Gerber, S. A., Turecek, F., Gelb, M. H. and Aebersold, R. (1999) Quantitative analysis of complex protein mixtures using isotope-coded affinity tags. Nat. Biotechnol. 17, 994-999.   DOI   ScienceOn
4 Peters, E. C. and Gray, N. S. (2007) Chemical proteomics identifies unanticipated targets of clinical kinase inhibitors. ACS Chem. Biol. 2, 661-664.   DOI   ScienceOn
5 Abida, W. M., Carter, B. T., Althoff, E. A., Lin, H. and Cornish, V. W. (2002) Receptor-dependence of the transcription read-out in a small molecule three-hybrid system. Chembiochem 3, 887-895.   DOI   ScienceOn
6 Gallagher, S. S., Miller, L. W. and Cornish, V. W. (2007) An orthogonal dexamethasone-trimethoprim yeast threehybrid system. Anal. Biochem. 363, 160-162.   DOI   ScienceOn
7 Spencer, D. M., Wandless, T. J., Schreiber, S. L. and Crabtree, G. R. (1993) Controlling signal transduction with synthetic ligands. Science 262, 1019-1024.   DOI
8 Caligiuri, M., Molz, L., Liu, Q., Kaplan, F., Xu, J. P., Majeti, J. Z., Ramos-Kelsey, R., Murthi, K., Lievens, S., Tavernier, J. and Kley, N. (2006) MASPIT: three-hybrid trap for quantitative proteome fingerprinting of small moleculeprotein interactions in mammalian cells. Chem. Biol. 13, 711-722.   DOI   ScienceOn
9 Jester, B. W., Cox, K. J., Gaj, A., Shomin, C. D., Porter, J. R. and Ghosh, I. (2010) A coiled-coil enabled split-luciferase three-hybrid system: applied toward profiling inhibitors of protein kinases. J. Am. Chem. Soc. 132, 11727-11735.   DOI   ScienceOn
10 Smith, G. P. (1985) Filamentous fusion phage: novel expression vectors that display cloned antigens on the virion surface. Science 228, 1315-1317.   DOI
11 Cravatt, B. F., Wright, A. T. and Kozarich, J. W. (2008) Activity-based protein profiling: from enzyme chemistry to proteomic chemistry. Annu. Rev. Biochem. 77, 383-414.   DOI   ScienceOn
12 Speers, A. E. and Cravatt, B. F. (2004) Chemical strategies for activity-based proteomics. Chembiochem 5, 41-47.   DOI   ScienceOn
13 Patricelli, M. P., Szardenings, A. K., Liyanage, M., Nomanbhoy, T. K., Wu, M., Weissig, H., Aban, A., Chun, D., Tanner, S. and Kozarich, J. W. (2007) Functional interrogation of the kinome using nucleotide acyl phosphates. Biochemistry 46, 350-358.   DOI   ScienceOn
14 Adam, G. C., Burbaum, J., Kozarich, J. W., Patricelli, M. P. and Cravatt, B. F. (2004) Mapping enzyme active sites in complex proteomes. J. Am. Chem. Soc. 126, 1363-1368.   DOI   ScienceOn
15 Liu, Y., Jiang, N., Wu, J., Dai, W. and Rosenblum, J. S. (2007) Polo-like kinases inhibited by wortmannin. Labeling site and downstream effects. J. Biol. Chem. 282, 2505-2511.   DOI   ScienceOn
16 Liu, Y., Shreder, K. R., Gai, W., Corral, S., Ferris, D. K. and Rosenblum, J. S. (2005) Wortmannin, a widely used phosphoinositide 3-kinase inhibitor, also potently inhibits mammalian polo-like kinase. Chem. Biol. 12, 99-107.   DOI   ScienceOn
17 Wymann, M. P., Bulgarelli-Leva, G., Zvelebil, M. J., Pirola, L., Vanhaesebroeck, B., Waterfield, M. D. and Panayotou, G. (1996) Wortmannin inactivates phosphoinositide 3-kinase by covalent modification of Lys-802, a residue involved in the phosphate transfer reaction. Mol. Cell. Biol. 16, 1722-1733.   DOI
18 Wong, S. and Witte, O. N. (2004) The BCR-ABL story: bench to bedside and back. Annu. Rev. Immunol. 22, 247-306.   DOI   ScienceOn
19 Gorre, M. E., Mohammed, M., Ellwood, K., Hsu, N., Paquette, R., Rao, P. N. and Sawyers, C. L. (2001) Clinical resistance to STI-571 cancer therapy caused by BCR-ABL gene mutation or amplification. Science 293, 876-880.   DOI   ScienceOn
20 von Bubnoff, N., Schneller, F., Peschel, C. and Duyster, J. (2002) BCR-ABL gene mutations in relation to clinical resistance of Philadelphia-chromosome-positive leukaemia to STI571: a prospective study. Lancet 359, 487-491.   DOI   ScienceOn
21 Adrian, F. J., Ding, Q., Sim, T., Velentza, A., Sloan, C., Liu, Y., Zhang, G., Hur, W., Ding, S., Manley, P., Mestan, J., Fabbro, D. and Gray, N. S. (2006) Allosteric inhibitors of Bcr-abl-dependent cell proliferation. Nat. Chem. Biol. 2, 95-102.   DOI   ScienceOn
22 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.   DOI   ScienceOn
23 Simard, J. R., Getlik, M., Grutter, C., Pawar, V., Wulfert, S., Rabiller, M. and Rauh, D. (2009) Development of a fluorescent-tagged kinase assay system for the detection and characterization of allosteric kinase inhibitors. J. Am. Chem. Soc. 131, 13286-13296.   DOI   ScienceOn
24 Son, M., Hayes, S. J. and Serwer, P. (1988) Concatemerization and packaging of bacteriophage T7 DNA in vitro: determination of the concatemers' length and appearance kinetics by use of rotating gel electrophoresis. Virology 162, 38-46.   DOI   ScienceOn
25 Okram, B., Nagle, A., Adrian, F. J., Lee, C., Ren, P., Wang, X., Sim, T., Xie, Y., Xia, G., Spraggon, G., Warmuth, M., Liu, Y. and Gray, N. S. (2006) A general strategy for creating "inactive-conformation" abl inhibitors. Chem. Biol. 13, 779-786.   DOI   ScienceOn
26 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. and Lockhart, D. J. (2005) A small molecule-kinase interaction map for clinical kinase inhibitors. Nat. Biotechnol. 23, 329-336.   DOI   ScienceOn
27 Dunn, J. J. and Studier, F. W. (1983) Complete nucleotide sequence of bacteriophage T7 DNA and the locations of T7 genetic elements. J. Mol. Biol. 166, 477-535.   DOI
28 Griffin, J. D. (2005) Interaction maps for kinase inhibitors. Nat. Biotechnol. 23, 308-309.   DOI   ScienceOn
29 Becker, F., Murthi, K., Smith, C., Come, J., Costa-Roldan, N., Kaufmann, C., Hanke, U., Degenhart, C., Baumann, S., Wallner, W., Huber, A., Dedier, S., Dill, S., Kinsman, D., Hediger, M., Bockovich, N., Meier-Ewert, S., Kluge, A. F. and Kley, N. (2004) A three-hybrid approach to scanning the proteome for targets of small molecule kinase inhibitors. Chem. Biol. 11, 211-223.   DOI
30 Wolf-Yadlin, A., Sevecka, M. and MacBeath, G. (2009) Dissecting protein function and signaling using protein microarrays. Curr. Opin. Chem. Biol. 13, 398-405.   DOI   ScienceOn
31 Min, D. H. and Mrksich, M. (2004) Peptide arrays: towards routine implementation. Curr. Opin. Chem. Biol. 8, 554-558.   DOI   ScienceOn
32 Li, J., Rix, U., Fang, B., Bai, Y., Edwards, A., Colinge, J., Bennett, K. L., Gao, J., Song, L., Eschrich, S., Superti-Furga, G., Koomen, J. and Haura, E. B. (2010) A chemical and phosphoproteomic characterization of dasatinib action in lung cancer. Nat. Chem. Biol. 6, 291-299.   DOI   ScienceOn
33 Hunter, T. (1995) Protein kinases and phosphatases: the yin and yang of protein phosphorylation and signaling. Cell 80, 225-236.   DOI   ScienceOn
34 Ostman, A. and Bohmer, F. D. (2001) Regulation of receptor tyrosine kinase signaling by protein tyrosine phosphatases. Trends Cell Biol. 11, 258-266.   DOI   ScienceOn
35 Richardson, C. J., Gao, Q., Mitsopoulous, C., Zvelebil, M., Pearl, L. H. and Pearl, F. M. (2009) MoKCa databasemutations of kinases in cancer. Nucleic. Acids. Res. 37, D824-831.
36 Johnson, L. N., Noble, M. E. and Owen, D. J. (1996) Active and inactive protein kinases: structural basis for regulation. Cell 85, 149-158.   DOI   ScienceOn
37 Scapin, G. (2002) Structural biology in drug design: selective protein kinase inhibitors. Drug Discov. Today 7, 601-611.   DOI   ScienceOn
38 Grant, S. K. (2009) Therapeutic protein kinase inhibitors. Cell. Mol. Life Sci. 66, 1163-1177.   DOI
39 Bossemeyer, D. (1995) Protein kinases- structure and function. FEBS Lett. 369, 57-61.   DOI   ScienceOn
40 Johnson, L. N. and Lewis, R. J. (2001) Structural basis for control by phosphorylation. Chem. Rev. 101, 2209-2242.   DOI   ScienceOn
41 Fabbro, D. and Garcia-Echeverria, C. (2002) Targeting protein kinases in cancer therapy. Curr. Opin. Drug. Discov. Devel. 5, 701-712.
42 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. and Manley, P. W. (2002) Protein kinases as targets for anticancer agents: from inhibitors to useful drugs. Pharmacol. Ther. 93, 79-98.   DOI   ScienceOn
43 Croston, G. E. (2002) Functional cell-based uHTS in chemical genomic drug discovery. Trends Biotechnol. 20, 110-115.   DOI   ScienceOn
44 Graves, P. R. and Haystead, T. A. (2002) Molecular biologist's guide to proteomics. Microbiol. Mol. Biol. Rev. 66, 39-63   DOI
45 Zheng, X. S., Chan, T. F. and Zhou, H. H. (2004) Genetic and genomic approaches to identify and study the targets of bioactive small molecules. Chem. Biol. 11, 609-618.   DOI   ScienceOn
46 Kim, J. A. (2003) Targeted therapies for the treatment of cancer. Am. J. Surg. 186, 264-268.   DOI   ScienceOn
47 Manning, G., Whyte, D. B., Martinez, R., Hunter, T. and Sudarsanam, S. (2002) The protein kinase complement of the human genome. Science 298, 1912-1934.   DOI   ScienceOn
48 Zhang, J., Yang, P. L. and Gray, N. S. (2009) Targeting cancer with small molecule kinase inhibitors. Nat. Rev. Cancer 9, 28-39.   DOI   ScienceOn
49 Cohen, P. (2002) Protein kinases- the major drug targets of the twenty-first century? Nat. Rev. Drug Discov. 1, 309-315.   DOI   ScienceOn
50 Jeffery, D. A. and Bogyo, M. (2003) Chemical proteomics and its application to drug discovery. Curr. Opin. Biotechnol. 14, 87-95.   DOI   ScienceOn
51 Hunter, T. and Plowman, G. D. (1997) The protein kinases of budding yeast: six score and more. Trends Biochem. Sci. 22, 18-22.
52 Wales, T. E. and Engen, J. R. (2006) Hydrogen exchange mass spectrometry for the analysis of protein dynamics. Mass Spectrom. Rev. 25, 158-170.   DOI   ScienceOn
53 de Lorimier, R. M., Smith, J. J., Dwyer, M. A., Looger, L. L., Sali, K. M., Paavola, C. D., Rizk, S. S., Sadigov, S., Conrad, D. W., Loew, L. and Hellinga, H. W. (2002) Construction of a fluorescent biosensor family. Protein Sci. 11, 2655-2675.   DOI   ScienceOn
54 Torkamani, A., Kannan, N., Taylor, S. S. and Schork, N. J. (2008) Congenital disease SNPs target lineage specific structural elements in protein kinases. Proc. Natl. Acad. Sci. U.S.A. 105, 9011-9016.   DOI   ScienceOn
55 Simard, J. R., Kluter, S., Grutter, C., Getlik, M., Rabiller, M., Rode, H. B. and Rauh, D. (2009) A new screening assay for allosteric inhibitors of cSrc. Nat. Chem. Biol. 5, 394-396.   DOI   ScienceOn
56 Kung, C., Kenski, D. M., Dickerson, S. H., Howson, R. W., Kuyper, L. F., Madhani, H. D. and Shokat, K. M. (2005) Chemical genomic profiling to identify intracellular targets of a multiplex kinase inhibitor. Proc. Natl. Acad. Sci. U.S.A. 102, 3587-3592.   DOI   ScienceOn
57 Bishop, A. C., Ubersax, J. A., Petsch, D. T., Matheos, D. P., Gray, N. S., Blethrow, J., Shimizu, E., Tsien, J. Z., Schultz, P. G., Rose, M. D., Wood, J. L., Morgan, D. O. and Shokat, K. M. (2000) A chemical switch for inhibitor-sensitive alleles of any protein kinase. Nature 407, 395-401.   DOI   ScienceOn
58 Nagar, B., Hantschel, O., Seeliger, M., Davies, J. M., Weis, W. I., Superti-Furga, G. and Kuriyan, J. (2006) Organization of the SH3-SH2 unit in active and inactive forms of the c-Abl tyrosine kinase. Mol. Cell. 21, 787-798.   DOI   ScienceOn
59 Reimer, U., Reineke, U. and Schneider-Mergener, J. (2002) Peptide arrays: from macro to micro. Curr. Opin. Biotechnol. 13, 315-320.   DOI   ScienceOn
60 Bantscheff, M., Eberhard, D., Abraham, Y., Bastuck, S., Boesche, M., Hobson, S., Mathieson, T., Perrin, J., Raida, M., Rau, C., Reader, V., Sweetman, G., Bauer, A., Bouwmeester, T., Hopf, C., Kruse, U., Neubauer, G., Ramsden, N., Rick, J., Kuster, B. and Drewes, G. (2007) Quantitative chemical proteomics reveals mechanisms of action of clinical ABL kinase inhibitors. Nat. Biotechnol. 25, 1035-1044.   DOI   ScienceOn
61 Schutkowski, M., Reineke, U. and Reimer, U. (2005) Peptide arrays for kinase profiling. Chembiochem 6, 513-521.   DOI   ScienceOn
62 Hilhorst, R., Houkes, L., van den Berg, A. and Ruijtenbeek, R. (2009) Peptide microarrays for detailed, highthroughput substrate identification, kinetic characterization, and inhibition studies on protein kinase A. Anal. Biochem. 387, 150-161.   DOI   ScienceOn
63 Houseman, B. T., Huh, J. H., Kron, S. J. and Mrksich, M. (2002) Peptide chips for the quantitative evaluation of protein kinase activity. Nat. Biotechnol. 20, 270-274.   DOI   ScienceOn
64 Wang, Z. (2009) The peptide microarray-based assay for kinase functionality and inhibition study. Methods Mol. Biol. 570, 329-337.   DOI   ScienceOn
65 Li, T., Liu, D. and Wang, Z. (2009) Microarray-based Raman spectroscopic assay for kinase inhibition by gold nanoparticle probes. Biosens. Bioelectron. 24, 3335-3339.   DOI   ScienceOn
66 Wang, Z., Levy, R., Fernig, D. G. and Brust, M. (2006) Kinase-catalyzed modification of gold nanoparticles: a new approach to colorimetric kinase activity screening. J. Am. Chem. Soc. 128, 2214-2215.   DOI   ScienceOn
67 Rix, U., Hantschel, O., Durnberger, G., Remsing Rix, L. L., Planyavsky, M., Fernbach, N. V., Kaupe, I., Bennett, K. L., Valent, P., Colinge, J., Kocher, T. and Superti-Furga, G. (2007) Chemical proteomic profiles of the BCR-ABL inhibitors imatinib, nilotinib, and dasatinib reveal novel kinase and nonkinase targets. Blood 110, 4055-4063.   DOI   ScienceOn
68 Salemme, F. R. (2003) Chemical genomics as an emerging paradigm for postgenomic drug discovery. Pharmacogenomics 4, 257-267.   DOI   ScienceOn