Strategies for the selective regulation of kinases with allosteric modulators: Exploiting exclusive structural features

ACS Chemical Biology

Volumn 8, Issue 1, 2013, Pages 58-70

  Fang, Zhizhou ^a   Grütter, Christian ^a   Rauh, Daniel ^a  

^a TU DORTMUND UNIVERSITY   (Germany)

Author keywords

[No Author keywords available]

Indexed keywords

8 [4 (1 AMINOCYCLOBUTYL)PHENYL] 9 PHENYL 1,2,4 TRIAZOLO[3,4 F][1,6]NAPHTHYRIDIN 3(2H) ONE; ADENOSINE TRIPHOSPHATE; BI 78D3; CHECKPOINT KINASE 1; CYCLIN DEPENDENT KINASE 2; ENZYME INHIBITOR; ERLOTINIB; GNF 2; MSC 1609119A 1; PHOSPHOINOSITIDE DEPENDENT PROTEIN KINASE 1; PHOSPHOTRANSFERASE; PS 48; RAPAMYCIN; SC 66; STRESS ACTIVATED PROTEIN KINASE 1; UNCLASSIFIED DRUG;

ALLOSTERISM; ENZYME BINDING; ENZYME CONFORMATION; ENZYME STABILITY; ENZYME STRUCTURE; PRIORITY JOURNAL; REVIEW;

ALLOSTERIC REGULATION; BINDING, COMPETITIVE; DRUG DELIVERY SYSTEMS; HUMANS; MOLECULAR CONFORMATION; PROTEIN KINASE INHIBITORS; PROTEIN KINASES;

EID: 84872511666     PISSN: 15548929     EISSN: 15548937     Source Type: Journal    
DOI: 10.1021/cb300663j     Document Type: Review

References (124)

1. Dar, A. C. and Shokat, K. M. (2011) The evolution of protein kinase inhibitors from antagonists to agonists of cellular signaling Annu. Rev. Biochem. 80, 769-795
2. Sos, M. L., Fischer, S., Ullrich, R., Peifer, M., Heuckmann, J. M., Koker, M., Heynck, S., Stückrath, I., Weiss, J., Fischer, F., Michel, K., Goel, A., Regales, L., Politi, K. A., Perera, S., Getlik, M., Heukamp, L. C., Ansén, S., Zander, T., Beroukhim, R., Kashkar, H., Shokat, K. M., Sellers, W. R., Rauh, D., Orr, C., Hoeflich, K. P., Friedman, L., Wong, K.-K., Pao, W., and Thomas, R. K. (2009) Identifying genotype-dependent efficacy of single and combined PI3K- and MAPK-pathway inhibition in cancer Proc. Natl. Acad. Sci. 106, 18351-18356
3. Rabiller, M., Getlik, M., Klüter, S., Richters, A., Tückmantel, S., Simard, J. R., and Rauh, D. (2010) Proteus in the world of proteins: conformational changes in protein kinases Arch. Pharm. 343, 193-206
4. Knight, Z. A., Lin, H., and Shokat, K. M. (2010) Targeting the cancer kinome through polypharmacology Nat. Rev. Cancer 10, 130-137
5. Zheng, J., Knighton, D. R., Eyck, L. F. T., Karlsson, R., Xuong, N., Taylor, S. S., and Sowadski, J. M. (1993) Crystal structure of the catalytic subunit of cAMP-dependent protein kinase complexed with magnesium-ATP and peptide inhibitor Biochemistry 32, 2154-2161 (Pubitemid 23094874)
6. Palmieri, L. and Rastelli, G. αC helix displacement as a general approach for allosteric modulation of protein kinases. Drug Discovery Today 2012, in press.
7. Jones, P. F., Jakubowicz, T., Pitossi, F. J., Maurer, F., and Hemmings, B. A. (1991) Molecular cloning and identification of a serine/threonine protein kinase of the second-messenger subfamily Proc. Natl. Acad. Sci. 88, 4171-4175 (Pubitemid 21914501)
8. Du, K. and Montminy, M. (1998) CREB is a regulatory target for the protein kinase Akt/PKB J. Biol. Chem. 273, 32377-32379 (Pubitemid 28557606)
9. van Weeren, P. C., de Bruyn, K. M. T., de Vries-Smits, A. M. M., van Lint, J., and Burgering, B. M. T. (1998) Essential role for protein kinase B (PKB) in insulin-induced glycogen synthase kinase 3 inactivation J. Biol. Chem. 273, 13150-13156
10. Cheng, J. Q., Lindsley, C. W., Cheng, G. Z., Yang, H., and Nicosia, S. V. (2005) The Akt/PKB pathway: molecular target for cancer drug discovery Oncogene 24, 7482-7492 (Pubitemid 41637988)
11. Eke, I., Koch, U., Hehlgans, S., Sandfort, V., Stanchi, F., Zips, D., Baumann, M., Shevchenko, A., Pilarsky, C., Haase, M., Baretton, G. B., Calleja, V., Larijani, B., Fässler, R., and Cordes, N. (2010) PINCH1 regulates Akt1 activation and enhances radioresistance by inhibiting PP1α J. Clin. Invest. 120, 2516-2527
12. Falasca, M. (2010) PI3K/Akt signalling pathway specific inhibitors: a novel strategy to sensitize cancer cells to anti-cancer drugs Curr. Pharm. Des. 16, 1410-1416
13. Wu, W.-I., Voegtli, W. C., Sturgis, H. L., Dizon, F. P., Vigers, G. P. A., and Brandhuber, B. J. (2010) Crystal structure of human AKT1 with an allosteric inhibitor reveals a new mode of kinase inhibition PLoS One 5, e12913
14. Okano, J.-I., Gaslightwala, I., Birnbaum, M. J., Rustgi, A. K., and Nakagawa, H. (2000) Akt/Protein kinase B isoforms are differentially regulated by epidermal growth factor stimulation J. Biol. Chem. 275, 30934-30942
15. Calleja, V., Laguerre, M., and Larijani, B. (2009) 3-D structure and dynamics of protein kinase B: new mechanism for the allosteric regulation of an AGC kinase J. Chem. Biol. 2, 11-25
16. Alessi, D. R., James, S. R., Downes, C. P., Holmes, A. B., Gaffney, P. R. J., Reese, C. B., and Cohen, P. (1997) Characterization of a 3-phosphoinositide-dependent protein kinase which phosphorylates and activates protein kinase Bα Curr. Biol. 7, 261-269 (Pubitemid 27176852)
17. Vincent, E. E., Elder, D. J. E., Thomas, E. C., Phillips, L., Morgan, C., Pawade, J., Sohail, M., May, M. T., Hetzel, M. R., and Tavaré, J. M. (2011) Akt phosphorylation on Thr308 but not on Ser473 correlates with Akt protein kinase activity in human non-small cell lung cancer Br. J. Cancer 104, 1755-1761
18. Yang, J., Cron, P., Thompson, V., Good, V. M., Hess, D., Hemmings, B. A., and Barford, D. (2002) Molecular mechanism for the regulation of protein kinase B/Akt by hydrophobic motif phosphorylation Mol. Cell 9, 1227-1240 (Pubitemid 34722302)
19. Sarbassov, D. D., Guertin, D. A., Ali, S. M., and Sabatini, D. M. (2005) Phosphorylation and regulation of Akt/PKB by the Rictor-mTOR complex Science 307, 1098-1101 (Pubitemid 40262113)
20. Carpten, J. D., Faber, A. L., Horn, C., Donoho, G. P., Briggs, S. L., Robbins, C. M., Hostetter, G., Boguslawski, S., Moses, T. Y., Savage, S., Uhlik, M., Lin, A., Du, J., Qian, Y.-W., Zeckner, D. J., Tucker-Kellogg, G., Touchman, J., Patel, K., Mousses, S., Bittner, M., Schevitz, R., Lai, M.-H. T., Blanchard, K. L., and Thomas, J. E. (2007) A transforming mutation in the pleckstrin homology domain of AKT1 in cancer Nature 448, 439-444 (Pubitemid 47123510)
21. Parikh, C., Janakiraman, V., Wu, W.-I., Foo, C. K., Kljavin, N. M., Chaudhuri, S., Stawiski, E., Lee, B., Lin, J., Li, H., Lorenzo, M. N., Yuan, W., Guillory, J., Jackson, M., Rondon, J., Franke, Y., Bowman, K. K., Sagolla, M., Stinson, J., Wu, T. D., Wu, J., Stokoe, D., Stern, H. M., Brandhuber, B. J., Lin, K., Skelton, N. J., and Seshagiri, S. (2012) Disruption of PH-kinase domain interactions leads to oncogenic activation of AKT in human cancers Proc. Natl. Acad. Sci. 109, 19368-19373
22. Yun, J. (2010) Allosteric AKT inhibitors as a targeted cancer therapy Cancer Biol. Ther. 9, 504-506
23. Lindsley, C. W., Zhao, Z., Leister, W. H., Robinson, R. G., Barnett, S. F., Defeo-Jones, D., Jones, R. E., Hartman, G. D., Huff, J. R., Huber, H. E., and Duggan, M. E. (2005) Allosteric Akt (PKB) inhibitors: discovery and SAR of isozyme selective inhibitors Bioorg. Med. Chem. Lett. 15, 761-764 (Pubitemid 40143162)
24. Ma, B. B. Y., Lui, V. W. Y., Hui, C. W. C., Lau, C. P. Y., Wong, C.-H., Hui, E. P., Ng, M. H., Tsao, S. W., Li, Y., and Chan, A. T. C. Preclinical evaluation of the AKT inhibitor MK-2206 in nasopharyngeal carcinoma cell lines. Invest. New Drugs 2012, in press.
25. Hirai, H., Sootome, H., Nakatsuru, Y., Miyama, K., Taguchi, S., Tsujioka, K., Ueno, Y., Hatch, H., Majumder, P. K., Pan, B.-S., and Kotani, H. (2010) MK-2206, an allosteric Akt inhibitor, enhances antitumor efficacy by standard chemotherapeutic agents or molecular targeted drugs in vitro and in vivo Mol. Cancer Ther. 9, OF1-12
26. Barnett, S. F., Bilodeau, M. T., and Lindsley, C. W. (2005) The Akt/PKB family of protein kinases: a review of small molecule inhibitors and progress towards target validation Curr. Top. Med. Chem. 5, 109-125 (Pubitemid 40514509)
27. Hartnett, J. C., Barnett, S. F., Bilodeau, M. T., Defeo-Jones, D., Hartman, G. D., Huber, H. E., Jones, R. E., Kral, A. M., Robinson, R. G., and Wu, Z. (2008) Optimization of 2,3,5-trisubstituted pyridine derivatives as potent allosteric Akt1 and Akt2 inhibitors Bioorg. Med. Chem. Lett. 18, 2194-2197 (Pubitemid 351380851)
28. Siu, T., Li, Y., Nagasawa, J., Liang, J., Tehrani, L., Chua, P., Jones, R. E., Defeo-Jones, D., Barnett, S. F., and Robinson, R. G. (2008) The design and synthesis of potent and cell-active allosteric dual Akt 1 and 2 inhibitors devoid of hERG activity Bioorg. Med. Chem. Lett. 18, 4191-4194
29. Ahad, A. M., Zuohe, S., Du-Cuny, L., Moses, S. A., Zhou, L. L., Zhang, S., Powis, G., Meuillet, E. J., and Mash, E. A. (2011) Development of sulfonamide AKT PH domain inhibitors Bioorg. Med. Chem. 19, 2046-2054
30. Meuillet, E. J., Mahadevan, D., Vankayalapati, H., Berggren, M., Williams, R., Coon, A., Kozikowski, A. P., and Powis, G. (2003) Specific inhibition of the Akt1 pleckstrin homology domain by d -3-deoxy-phosphatidyl- myo-inositol analogues Mol. Cancer Ther. 2, 389-399
31. Kim, D., Sun, M., He, L., Zhou, Q.-H., Chen, J., Sun, X.-M., Bepler, G., Sebti, S. M., and Cheng, J. Q. (2010) A small molecule inhibits Akt through direct binding to Akt and preventing Akt membrane translocation J. Biol. Chem. 285, 8383-8394
32. Castillo, S. S., Brognard, J., Petukhov, P. A., Zhang, C., Tsurutani, J., Granville, C. A., Li, M., Jung, M., West, K. A., Gills, J. G., Kozikowski, A. P., and Dennis, P. A. (2004) Preferential inhibition of Akt and killing of Akt-dependent cancer cells by rationally designed phosphatidylinositol ether lipid analogues Cancer Res. 64, 2782-2792 (Pubitemid 38500616)
33. Kondapaka, S. B., Singh, S. S., Dasmahapatra, G. P., Sausville, E. A., and Roy, K. K. (2003) Perifosine, a novel alkylphospholipid, inhibits protein kinase B activation Mol. Cancer Ther. 2, 1093-1103
34. Kumar, C. C. and Madison, V. (2005) AKT crystal structure and AKT-specific inhibitors Oncogene 24, 7493-7501 (Pubitemid 41637989)
35. Jo, H., Lo, P.-K., Li, Y., Loison, F., Green, S., Wang, J., Silberstein, L. E., Ye, K., Chen, H., and Luo, H. R. (2011) Deactivation of Akt by a small molecule inhibitor targeting pleckstrin homology domain and facilitating Akt ubiquitination Proc. Natl. Acad. Sci. 108, 6486-6491
36. Yang, W.-L., Wu, C.-Y., Wu, J., and Lin, H.-K. (2010) Regulation of Akt signaling activation by ubiquitination Cell Cycle 9, 486-497
37. Yoshida, K., Komatsu, K., Wang, H.-G., and Kufe, D. (2002) c-Abl tyrosine kinase regulates the human Rad9 checkpoint protein in response to DNA damage Mol. Cell. Biol. 22, 3292-3300 (Pubitemid 34453971)
38. Radi, M., Crespan, E., Falchi, F., Bernardo, V., Zanoli, S., Manetti, F., Schenone, S., Maga, G., and Botta, M. (2010) Design and synthesis of thiadiazoles and thiazoles targeting the Bcr-Abl T315I mutant: from docking false positives to ATP-noncompetitive inhibitors ChemMedChem 5, 1226-1231
39. Faderl, S., Talpaz, M., Estrov, Z., and Kantarjian, H. M. (1999) Chronic myelogenous leukemia: biology and therapy Ann. Intern. Med. 131, 207-219 (Pubitemid 29365004)
40. Sawyers, C. L. (1999) Chronic myeloid leukemia N. Engl. J. Med. 340, 1330-1340 (Pubitemid 29196596)
41. Gosser, Y. Q., Zheng, J., Overduin, M., Mayer, B. J., and Cowburn, D. (1995) The solution structure of Abl SH3, and its relationship to SH2 in the SH(32) construct Structure 3, 1075-1086
42. Pluk, H., Dorey, K., and Superti-Furga, G. (2002) Autoinhibition of c-Abl Cell 108, 247-259 (Pubitemid 34161144)
43. Nagar, B., Hantschel, O., Young, M. A., Scheffzek, K., Veach, D., Bornmann, W., Clarkson, B., Superti-Furga, G., and Kuriyan, J. (2003) Structural basis for the autoinhibition of c-Abl tyrosine kinase Cell 112, 859-871 (Pubitemid 36378887)
44. Hantschel, O., Nagar, B., Guettler, S., Kretzschmar, J., Dorey, K., Kuriyan, J., and Superti-Furga, G. (2003) A myristoyl/phosphotyrosine switch regulates c-Abl Cell 112, 845-857 (Pubitemid 36378886)
45. Bradley, W. D. and Koleske, A. J. (2009) Regulation of cell migration and morphogenesis by Abl-family kinases: emerging mechanisms and physiological contexts J. Cell Sci. 122, 3441-3454
46. Adrián, 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
47. Choi, Y., Seeliger, M. A., Panjarian, S. B., Kim, H., Deng, X., Sim, T., Couch, B., Koleske, A. J., Smithgall, T. E., and Gray, N. S. (2009) N -Myristoylated c-Abl tyrosine kinase localizes to the endoplasmic reticulum upon binding to an allosteric inhibitor J. Biol. Chem. 284, 29005-29014
48. Zhang, J., Adrián, 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
49. Iacob, R. E., Zhang, J., Gray, N. S., and Engen, J. R. (2011) Allosteric interactions between the myristate- and ATP-site of the Abl kinase PLoS One 6, e15929
50. Yang, J., Campobasso, N., Biju, M. P., Fisher, K., Pan, X.-Q., Cottom, J., Galbraith, S., Ho, T., Zhang, H., Hong, X., Ward, P., Hofmann, G., Siegfried, B., Zappacosta, F., Washio, Y., Cao, P., Qu, J., Bertrand, S., Wang, D.-Y., Head, M. S., Li, H., Moores, S., Lai, Z., Johanson, K., Burton, G., Erickson-Miller, C., Simpson, G., Tummino, P., Copeland, R. A., and Oliff, A. (2011) Discovery and characterization of a cell-permeable, small-molecule c-Abl kinase activator that binds to the myristoyl binding site Chem. Biol. 18, 177-186
51. Filippakopoulos, P., Kofler, M., Hantschel, O., Gish, G. D., Grebien, F., Salah, E., Neudecker, P., Kay, L. E., Turk, B. E., Superti-Furga, G., Pawson, T., and Knapp, S. (2008) Structural coupling of SH2-kinase domains links Fes and Abl substrate recognition and kinase activation Cell 134, 793-803
52. Grebien, F., Hantschel, O., Wojcik, J., Kaupe, I., Kovacic, B., Wyrzucki, A. M., Gish, G. D., Cerny-Reiterer, S., Koide, A., Beug, H., Pawson, T., Valent, P., Koide, S., and Superti-Furga, G. (2011) Targeting the SH2-kinase interface in Bcr-Abl inhibits leukemogenesis Cell 147, 306-319
53. Mora, A., Komander, D., van Aalten, D. M. F., and Alessi, D. R. (2004) PDK1, the master regulator of AGC kinase signal transduction Semin. Cell Dev. Biol. 15, 161-170 (Pubitemid 38251644)
54. Bayascas, J. R., Leslie, N. R., Parsons, R., Fleming, S., and Alessi, D. R. (2005) Hypomorphic mutation of PDK1 suppresses tumorigenesis in PTEN± mice Curr. Biol. 15, 1839-1846 (Pubitemid 41501519)
55. Alessi, D. R., Deak, M., Casamayor, A., Caudwell, F. B., Morrice, N., Norman, D. G., Gaffney, P., Reese, C. B., MacDougall, C. N., Harbison, D., Ashworth, A., and Bownes, M. (1997) 3-Phosphoinositide-dependent protein kinase-1 (PDK1): structural and functional homology with the Drosophila DSTPK61 kinase Curr. Biol. 7, 776-789 (Pubitemid 27441832)
56. Biondi, R. M., Cheung, P. C. F., Casamayor, A., Deak, M., Currie, R. A., and Alessi, D. R. (2000) Identification of a pocket in the PDK1 kinase domain that interacts with PIF and the C-terminal residues of PKA EMBO J. 19, 979-988 (Pubitemid 30119823)
57. Biondi, R. M., Kieloch, A., Currie, R. A., Deak, M., and Alessi, D. R. (2001) The PIF-binding pocket in PDK1 is essential for activation of S6K and SGK, but not PKB EMBO J. 20, 4380-4390 (Pubitemid 32772032)
58. Balendran, A., Casamayor, A., Deak, M., Paterson, A., Gaffney, P., Currie, R., Downes, C. P., and Alessi, D. R. (1999) PDK1 acquires PDK2 activity in the presence of a synthetic peptide derived from the carboxyl terminus of PRK2 Curr. Biol. 9, 393-404 (Pubitemid 29205782)
59. Stroba, A., Schaeffer, F., Hindie, V., Lopez-Garcia, L., Adrian, I., Frhner, W., Hartmann, R. W., Biondi, R. M., and Engel, M. (2009) 3,5-Diphenylpent-2-enoic acids as allosteric activators of the protein kinase PDK1: structure-activity relationships and thermodynamic characterization of binding as paradigms for PIF-binding pocket-targeting compounds J. Med. Chem. 52, 4683-4693
60. Engel, M., Hindie, V., Lopez-Garcia, L. A., Stroba, A., Schaeffer, F., Adrian, I., Imig, J., Idrissova, L., Nastainczyk, W., Zeuzem, S., Alzari, P. M., Hartmann, R. W., Piiper, A., and Biondi, R. M. (2006) Allosteric activation of the protein kinase PDK1 with low molecular weight compounds EMBO J. 25, 5469-5480 (Pubitemid 44847188)
61. Wei, L., Gao, X., Warne, R., Hao, X., Bussiere, D., Gu, X.-J., Uno, T., and Liu, Y. (2010) Design and synthesis of benzoazepin-2-one analogs as allosteric binders targeting the PIF pocket of PDK1 Bioorg. Med. Chem. Lett. 20, 3897-3902
62. Hindie, V., Stroba, A., Zhang, H., Lopez-Garcia, L. A., Idrissova, L., Zeuzem, S., Hirschberg, D., Schaeffer, F., Jørgensen, T. J. D., Engel, M., Alzari, P. M., and Biondi, R. M. (2009) Structure and allosteric effects of low-molecular-weight activators on the protein kinase PDK1 Nat. Chem. Biol. 5, 758-764
63. Liu, Y. (2009) Chemical biology: caught in the activation Nature 461, 484-485
64. Williams, G. (2010) Elastic network model of allosteric regulation in protein kinase PDK1 BMC Struct. Biol. 10, 11
65. Bobkova, E. V., Weber, M. J., Xu, Z., Zhang, Y.-L., Jung, J., Blume-Jensen, P., Northrup, A., Kunapuli, P., Andersen, J. N., and Kariv, I. (2010) Discovery of PDK1 kinase inhibitors with a novel mechanism of action by ultra-high throughput screening J. Biol. Chem. 285, 18838-18846
66. Ip, Y. T. and Davis, R. J. (1998) Signal transduction by the c-Jun N -terminal kinase (JNK): from inflammation to development Curr. Opin. Cell Biol. 10, 205-219 (Pubitemid 28174763)
67. Adcock, I. M. and Caramori, G. (2001) Cross-talk between pro-inflammatory transcription factors and glucocorticoids Immunol. Cell Biol. 79, 376-384 (Pubitemid 32744283)
68. Vlahopoulos, S. and Zoumpourlis, V. C. (2004) JNK: a key modulator of intracellular signaling Biochemistry 69, 844-854
69. Bode, A. M. and Dong, Z. (2007) The functional contrariety of JNK Mol. Carcinog. 46, 591-598 (Pubitemid 47255173)
70. Mehan, S., Meena, H., Sharma, D., and Sankhla, R. (2011) JNK: a stress-activated protein kinase therapeutic strategies and involvement in Alzheimer's and various neurodegenerative abnormalities J. Mol. Neurosci. 43, 376-390
71. Davis, R. J. (2000) Signal transduction by the JNK group of MAP kinases Cell 103, 239-252
72. Whitmarsh, A. J., Cavanagh, J., Tournier, C., Yasuda, J., and Davis, R. J. (1998) A mammalian scaffold complex that selectively mediates MAP kinase activation Science 281, 1671-1674 (Pubitemid 28435582)
73. Dickens, M., Rogers, J. S., Cavanagh, J., Raitano, A., Xia, Z., Halpern, J. R., Greenberg, M. E., Sawyers, C. L., and Davis, R. J. (1997) A cytoplasmic inhibitor of the JNK signal transduction pathway Science 277, 693-696 (Pubitemid 27373916)
74. Heo, Y.-S., Kim, S.-K., Seo, C. I., Kim, Y. K., Sung, B.-J., Lee, H. S., Lee, J. I., Park, S.-Y., Kim, J. H., Hwang, K. Y., Hyun, Y.-L., Jeon, Y. H., Ro, S., Cho, J. M., Lee, T. G., and Yang, C.-H. (2004) Structural basis for the selective inhibition of JNK1 by the scaffolding protein JIP1 and SP600125 EMBO J. 23, 2185-2195 (Pubitemid 38833228)
75. Yan, C., Kaoud, T., Lee, S., Dalby, K. N., and Ren, P. (2011) Understanding the specificity of a docking interaction between JNK1 and the scaffolding protein JIP1 J. Phys. Chem. 115, 1491-1502
76. Stebbins, J. L., De, S. K., Machleidt, T., Becattini, B., Vazquez, J., Kuntzen, C., Chen, L.-H., Cellitti, J. F., Riel-Mehan, M., Emdadi, A., Solinas, G., Karin, M., and Pellecchia, M. (2008) Identification of a new JNK inhibitor targeting the JNK-JIP interaction site Proc. Natl. Acad. Sci. 105, 16809-16813
77. De, S. K., Chen, V., Stebbins, J. L., Chen, L.-H., Cellitti, J. F., Machleidt, T., Barile, E., Riel-Mehan, M., Dahl, R., Yang, L., Emdadi, A., Murphy, R., and Pellecchia, M. (2010) Synthesis and optimization of thiadiazole derivatives as a novel class of substrate competitive c-Jun N-terminal kinase inhibitors Bioorg. Med. Chem. 18, 590-596
78. Chen, T., Kablaoui, N., Little, J., Timofeevski, S., Tschantz, W. R., Chen, P., Feng, J., Charlton, M., Stanton, R., and Bauer, P. (2009) Identification of small-molecule inhibitors of the JIP-JNK interaction Biochem. J. 420, 283-294
79. Bartek, J. and Lukas, J. (2003) Chk1 and Chk2 kinases in checkpoint control and cancer Cancer Cell 3, 421-429 (Pubitemid 38340288)
80. Bucher, N. and Britten, C. D. (2008) G2 checkpoint abrogation and checkpoint kinase-1 targeting in the treatment of cancer Br. J. Cancer 98, 523-528 (Pubitemid 351214533)
81. Garrett, M. D. and Collins, I. (2011) Anticancer therapy with checkpoint inhibitors: what, where and when? Trends Pharmacol. Sci. 32, 308-316
82. Converso, A., Hartingh, T., Garbaccio, R. M., Tasber, E., Rickert, K., Fraley, M. E., Yan, Y., Kreatsoulas, C., Stirdivant, S., Drakas, B., Walsh, E. S., Hamilton, K., Buser, C. A., Mao, X., Abrams, M. T., Beck, S. C., Tao, W., Lobell, R., Sepp-Lorenzino, L., Zugay-Murphy, J., Sardana, V., Munshi, S. K., Jezequel-Sur, S. M., Zuck, P. D., and Hartman, G. D. (2009) Development of thioquinazolinones, allosteric Chk1 kinase inhibitors Bioorg. Med. Chem. Lett. 19, 1240-1244
83. Vanderpool, D., Johnson, T. O., Ping, C., Bergqvist, S., Alton, G., Phonephaly, S., Rui, E., Luo, C., Deng, Y.-L., Grant, S., Quenzer, T., Margosiak, S., Register, J., Brown, E., and Ermolieff, J. (2009) Characterization of the CHK1 allosteric inhibitor binding site Biochemistry 48, 9823-9830
84. Owen, D. J., Noble, M. E. M., Garman, E. F., Papageorigiou, A. C., and Johnson, L. N. (1995) Two structures of the catalytic domain of phosphorylase kinase: an active protein kinase complexed with substrate analogue and product Structure 3, 467
85. Bähr, C. and Groner, B. (2004) The insulin like growth factor-1 receptor (IGF-1R) as a drug target: novel approaches to cancer therapy Growth Horm. IGF Res. 14, 287-295 (Pubitemid 38878054)
86. Kato, H., Faria, T. N., Stannard, B., Roberts, C. T., Jr., and LeRoith, D. (1993) Role of tyrosine kinase activity in signal transduction by the insulin-like growth factor-I (IGF-I) receptor. Characterization of kinase-deficient IGF-I receptors and the action of an IGF-I-mimetic antibody (alpha IR-3) J. Biol. Chem. 268, 2655-2661 (Pubitemid 23057892)
87. Delafontaine, P., Song, Y.-H., and Li, Y. (2004) Expression, regulation, and function of IGF-1, IGF-1R, and IGF-1 binding proteins in blood vessels Arterioscler., Thromb., Vasc. Biol. 24, 435-444 (Pubitemid 38326135)
88. Hellawell, G. O., Turner, G. D. H., Davies, D. R., Poulsom, R., Brewster, S. F., and Macaulay, V. M. (2002) Expression of the type 1 insulin-like growth factor receptor is up-regulated in primary prostate cancer and commonly persists in metastatic disease Cancer Res. 62, 2942-2950 (Pubitemid 34525783)
89. Wang, Y. and Sun, Y. (2002) Insulin-like growth factor receptor-1 as an anti-cancer target: blocking transformation and inducing apoptosis Curr. Cancer Drug Targets 2, 191-207
90. Gualberto, A. and Karp, D. D. (2009) Development of the monoclonal antibody figitumumab, targeting the insulin-like growth factor-1 receptor, for the treatment of patients with non-small-cell lung cancer Clin. Lung Cancer 10, 273-280
91. Weroha, S. J. and Haluska, P. (2008) IGF-1 receptor inhibitors in clinical trials: early lessons J. Mammary Gland Biol. Neoplasia 13, 471-483
92. Heinrich, T., Grädler, U., Böttcher, H., Blaukat, A., and Shutes, A. (2010) Allosteric IGF-1R inhibitors ACS Med. Chem. Lett. 1, 199-203
93. Heinrich, T., Böttcher, H., Gericke, R., Bartoszyk, G. D., Anzali, S., Seyfried, C. A., Greiner, H. E., and van Amsterdam, C. (2004) Synthesis and structure-activity relationship in a class of indolebutylpiperazines as dual 5-HT1A receptor agonists and serotonin reuptake inhibitors J. Med. Chem. 47, 4684-4692 (Pubitemid 39195559)
94. Halla, M. and Peters, G. (1996) Genetic alterations of cyclins, cyclin-dependent kinases, and Cdk inhibitors in human cancer Adv. Cancer Res. 68, 67-108 (Pubitemid 26099813)
95. van den Heuvel, S. and Harlow, E. (1993) Distinct roles for cyclin-dependent kinases in cell cycle control Science 262, 2050-2054 (Pubitemid 24041887)
96. Galderisi, U., Jori, F. P., and Giordano, A. (2003) Cell cycle regulation and neural differentiation Oncogene 22, 5208-5219 (Pubitemid 37059602)
97. Jeffrey, P. D., Russo, A. A., Polyak, K., Gibbs, E., Hurwitz, J., Massagué, J., and Pavletich, N. P. (2002) Mechanism of CDK activation revealed by the structure of a cyclinA-CDK2 complex Nature 376, 313-320
98. Russo, A. A., Jeffrey, P. D., Patten, A. K., Massagué, J., and Pavletich, N. P. (1996) Crystal structure of the p27Kip1 cyclin-dependent-kinase inhibitor bound to the cyclin A-Cdk2 complex Nature 382, 325-331 (Pubitemid 26260452)
99. McInnes, C., Andrews, M. J. I., Zheleva, D. I., Lane, D. P., and Fischer, P. M. (2003) Peptidomimetic design of CDK inhibitors targeting the recruitment site of the cyclin subunit Curr. Med. Chem. 3, 57-69 (Pubitemid 36131635)
100. Kontopidis, G., Andrews, M. J., McInnes, C., Plater, A., Innes, L., Renachowski, S., Cowan, A., and Fischer, P. M. (2009) Truncation and optimisation of peptide inhibitors of cyclin-dependent kinase 2-cyclin A through structure-guided design ChemMedChem 4, 1120-1128
101. Betzi, S., Alam, R., Martin, M. P., 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
102. Yang, Q. and Guan, K.-L. (2007) Expanding mTOR signaling Cell Res. 17, 666-681 (Pubitemid 47255937)
103. Schenone, S., Brullo, C., Musumeci, F., Radi, M., and Botta, M. (2011) ATP-competitive inhibitors of mTOR: an update Curr. Med. Chem. 18, 2995-3014
104. Choi, J., Chen, J., Schreiber, S. L., and Clardy, J. (1996) Structure of the FKBP12-rapamycin complex interacting with binding domain of human FRAP Science 273, 239-242 (Pubitemid 26285890)
105. Yonezawa, K., Tokunaga, C., Oshiro, N., and Yoshino, K.-I. (2004) Raptor, a binding partner of target of rapamycin Biochem. Biophys. Res. Commun. 313, 437-441 (Pubitemid 37543605)
106. Fasolo, A. and Sessa, C. (2008) mTOR inhibitors in the treatment of cancer Expert Opin. Invest. Drugs 17, 1717-1734
107. Motzer, R. J., Escudier, B., Oudard, S., Hutson, T. E., Porta, C., Bracarda, S., Grünwald, V., Thompson, J. A., Figlin, R. A., Hollaender, N., Urbanowitz, G., Berg, W. J., Kay, A., Lebwohl, D., Ravaud, A., and Group, R.-S. (2008) Efficacy of everolimus in advanced renal cell carcinoma: a double-blind, randomised, placebo-controlled phase III trial Lancet 372, 449-456
108. Klüter, S., Grütter, C., Naqvi, T., Rabiller, M., Simard, J. R., Pawar, V., Getlik, M., and Rauh, D. (2010) Displacement assay for the detection of stabilizers of inactive kinase conformations J. Med. Chem. 53, 357-367
109. Lebakken, C. S., Reichling, L. J., Ellefson, J. M., and Riddle, S. M. (2012) Detection of allosteric kinase inhibitors by displacement of active site probes J. Biomol. Screening 17, 813-821
110. Jahnke, W., Blommers, M. J. J., Fernández, C., Zwingelstein, C., and Amstut, R. (2005) Strategies for the NMR-based identification and optimization of allosteric protein kinase inhibitors ChemBioChem 6, 1607-1610 (Pubitemid 41296967)
111. Jahnke, W., Grotzfeld, R. M., Pellé, X., Strauss, A., Fendrich, G., Cowan-Jacob, S. W., Cotesta, S., Fabbro, D., Furet, P., Mestan, J., and Marzinzik, A. L. (2010) Binding or bending: distinction of allosteric Abl kinase agonists from antagonists by an NMR-based conformational assay J. Am. Chem. Soc. 132, 7043-7048
112. Simard, J. R., Getlik, M., Grütter, C., Schneider, R., Wulfert, S., and Rauh, D. (2010) 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, 4152-4160
113. Simard, J. R., Klüter, S., Grütter, 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
114. Getlik, M., Simard, J. R., Termathe, M., Grütter, C., Rabiller, M., Otterlo, W. A. L. V., and Rauh, D. (2012) Fluorophore labeled kinase detects ligands that bind within the MAPK insert of p38α kinase PLoS One 7, e39713
115. Schneider, R., Becker, C., Simard, J. R., Getlik, M., Bohlke, N., Janning, P., and Rauh, D. (2012) Direct binding assay for the detection of type IV allosteric inhibitors of Abl J. Am. Chem. Soc. 134, 9138-9141
116. Rauch, J., Volinsky, N., Romano, D., and Kolch, W. (2011) The secret life of kinases: functions beyond catalysis Cell Commun. Signaling 9, 23
117. Palomo, V., Soteras, I., Perez, D. I., Pérez, C., Gil, C., Campillo, N. E., and Martinez, A. (2011) Exploring the binding sites of glycogen synthase kinase 3. Identification and characterization of allosteric modulation cavities J. Med. Chem. 54, 8461-8470
118. Warmus, J. S., Flamme, C., Zhang, L. Y., Barrett, S., Bridges, A., Chen, H., Gowan, R., Kaufman, M., Sebolt-Leopold, J., Leopold, W., Merriman, R., Ohren, J., Pavlovsky, A., Przybranowski, S., Tecle, H., Valik, H., Whitehead, C., and Zhang, E. (2008) 2-Alkylamino- and alkoxy-substituted 2-amino-1,3,4-oxadiazoles: O -alkyl benzohydroxamate esters replacements retain the desired inhibition and selectivity against MEK (MAP ERK kinase) Bioorg. Med. Chem. Lett. 18, 6171-6174
119. Fröhner, W., Lopez-Garcia, L. A., Neimanis, S., Weber, N., Navratil, J., Maurer, F., Stroba, A., Zhang, H., Biondi, R. M., and Engel, M. (2011) 4-Benzimidazolyl-3-phenylbutanoic acids as novel PIF-pocket-targeting allosteric inhibitors of protein kinase PKCζ J. Med. Chem. 54, 6714-6723
120. Choi, J., He, N., Sung, M.-K., Yang, Y., and Yoon, S. (2011) Sanguinarine is an allosteric activator of AMP-activated protein kinase Biochem. Biophys. Res. Commun. 413, 259-263
121. Deacon, S. W., Beeser, A., Fukui, J. A., Rennefahrt, U. E. E., Myers, C., Chernoff, J., and Peterson, J. R. (2008) An isoform-selective, small-molecule inhibitor targets the autoregulatory mechanism of p21-activated kinase Chem. Biol. 15, 322-331 (Pubitemid 351508427)
122. Pang, T., Zhang, Z.-S., Gu, M., Qiu, B.-Y., Yu, L.-F., Cao, P.-R., Shao, W., Su, M.-B., Li, J.-Y., Nan, F.-J., and Li, J. (2008) Small molecule antagonizes autoinhibition and activates AMP-activated protein kinase in cells J. Biol. Chem. 283, 16051-16060
123. Cool, B., Zinker, B., Chiou, W., Kifle, L., Cao, N., Perham, M., Dickinson, R., Adler, A., Gagne, G., Iyengar, R., Zhao, G., Marsh, K., Kym, P., Jung, P., Camp, H. S., and Frevert, E. (2006) Identification and characterization of a small molecule AMPK activator that treats key components of type 2 diabetes and the metabolic syndrome Cell Metab. 3, 403-416 (Pubitemid 43811782)
124. Dorn, G. W., Souroujon, M. C., Liron, T., Chen, C.-H., Gray, M. O., Zhou, H. Z., Csukai, M., Wu, G., Lorenz, J. N., and Mochly-Rosen, D. (1999) Sustained in vivo cardiac protection by a rationally designed peptide that causes ε protein kinase C translocation Proc. Natl. Acad. Sci. 96, 12798-12803 (Pubitemid 29513582)