A highly selective dual insulin receptor (IR)/insulin-like growth factor 1 receptor (IGF-1R) inhibitor derived from an extracellular signal-regulated kinase (ERK) inhibitor

Journal of Biological Chemistry

Volumn 288, Issue 39, 2013, Pages 28068-28077

  Anastassiadis, Theonie ^a,c   Duong Ly, Krisna C ^a   Deacon, Sean W ^b   Lafontant, Alec ^a   Ma, Haiching ^b   Devarajan, Karthik ^a   Dunbrack Jr , Roland L ^a   Wu, Jinhua ^a   Peterson, Jeffrey R ^a  

^a FOX CHASE CANCER CENTER   (United States)

^b REACTION BIOLOGY CORPORATION   (United States)

^c UNIVERSITY OF PENNSYLVANIA   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

BROAD SPECTRUM; EXTRACELLULAR SIGNAL-REGULATED KINASE; GROWTH FACTOR; INSULIN RECEPTORS; KINASE INHIBITORS; SELECTIVE INHIBITORS; SMALL MOLECULES; THERAPEUTIC AGENTS;

INSULIN;

ENZYME INHIBITION;

1 [4 [(5 CYCLOPROPYL 1H PYRAZOL 3 YL)AMINO]PYRROLO[2,1 F][1,2,4]TRIAZIN 2 YL] N (6 FLUORO 3 PYRIDINYL) 2 METHYL 2 PYRROLIDINECARBOXAMIDE; ADENOSINE TRIPHOSPHATE; FR 180204; INSULIN RECEPTOR; IRFIN 1; LINSITINIB; MITOGEN ACTIVATED PROTEIN KINASE INHIBITOR; SOMATOMEDIN C RECEPTOR; UNCLASSIFIED DRUG;

ARTICLE; CONTROLLED STUDY; DRUG BINDING; DRUG BINDING SITE; DRUG SCREENING; DRUG SELECTIVITY; DRUG STRUCTURE; ENZYME INHIBITION; PRIORITY JOURNAL; PROTEIN CONFORMATION;

ENZYME INHIBITORS; ERK; HIGH THROUGHPUT SCREENING (HTS); INSULIN RECEPTOR; INSULIN-LIKE GROWTH FACTOR 1 RECEPTOR; KINASE INHIBITOR; RECEPTOR TYROSINE KINASE; SMALL-MOLECULE INHIBITION; X-RAY CRYSTALLOGRAPHY;

ADENOSINE TRIPHOSPHATE; ANIMALS; CHO CELLS; CRICETULUS; CRYSTALLOGRAPHY, X-RAY; DOSE-RESPONSE RELATIONSHIP, DRUG; DRUG DESIGN; GENE EXPRESSION REGULATION; HUMANS; MAP KINASE SIGNALING SYSTEM; MUTATION; PHOSPHORYLATION; PROTEIN CONFORMATION; PROTEIN KINASE INHIBITORS; PYRAZOLES; PYRIDAZINES; RECEPTOR, IGF TYPE 1; RECEPTOR, INSULIN;

EID: 84884782820     PISSN: 00219258     EISSN: 1083351X     Source Type: Journal    
DOI: 10.1074/jbc.M113.505032     Document Type: Article

References (45)

1. Larsson, O., Girnita, A., and Girnita, L. (2005) Role of insulin-like growth factor 1 receptor signalling in cancer. Br J. Cancer 92, 2097-2101
2. Miller, B. S., and Yee, D. (2005) Type I insulin-like growth factor receptor as a therapeutic target in cancer. Cancer Res. 65, 10123-10127
3. Hartog, H., Wesseling, J., Boezen, H. M., and van der Graaf, W. T. (2007) The insulin-like growth factor 1 receptor in cancer: old focus, new future. Eur. J. Cancer 43, 1895-1904
4. Munshi, S., Hall, D. L., Kornienko, M., Darke, P. L., and Kuo, L. C. (2003) Structure of apo, unactivated insulin-like growth factor-1 receptor kinase at 1.5 A resolution. Acta Crystallogr. D Biol. Crystallogr 59, 1725-1730
5. Hubbard, S. R., Wei, L., Ellis, L., and Hendrickson, W. A. (1994) Crystal structure of the tyrosine kinase domain of the human insulin receptor. Nature 372, 746-754
6. Hubbard, S. R. (1997) Crystal structure of the activated insulin receptor tyrosine kinase in complex with peptide substrate and ATP analog.EMBO J. 16, 5572-5581
7. Jin, M., Wang, J., Buck, E., and Mulvihill, M. J. (2012) Small-molecule ATP-competitive dual IGF-1R and insulin receptor inhibitors: structural insights, chemical diversity and molecular evolution. Future Med. Chem. 4, 315-328
8. Vincent, E. E., Elder, D. J., Curwen, J., Kilgour, E., Hers, I., and Tavaré, J. M. (2013) Targeting non-small cell lung cancer cells by dual inhibition of the insulin receptor and the insulin-like growth factor-1 receptor. PLoS One 8, e66963
9. Fidler, M. J., Shersher, D. D., Borgia, J. A., and Bonomi, P. (2012) Targeting the insulin-like growth factor receptor pathway in lung cancer: problems and pitfalls. Ther. Adv. Med. Oncol 4, 51-60
10. Anastassiadis, T., Deacon, S. W., Devarajan, K., Ma, H., and Peterson, J. R. (2011) Comprehensive assay of kinase catalytic activity reveals features of kinase inhibitor selectivity. Nat. Biotechnol. 29, 1039-1045
11. Davis, M. I., Hunt, J. P., Herrgard, S., Ciceri, P., Wodicka, L. M., Pallares, G., Hocker, M., Treiber, D. K., and Zarrinkar, P. P. (2011) Comprehensive analysis of kinase inhibitor selectivity. Nat. Biotechnol. 29, 1046-1051
12. 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., Lélias, 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
13. Liu, Y., and Gray, N. S. (2006) Rational design of inhibitors that bind to inactive kinase conformations. Nat. Chem. Biol. 2, 358-364
14. R Development Core Team (2010) R: A language and environment for statistical computing. R Foundation for Statistical Computing Vienna, Austria
15. Yee, T. W. (2010) TheVGAMpackage for categorical data analysis. J. Stat. Softw. 32, 1-34
16. van der Loo, M. P. (2010) extremevalues: a package for outlier detection in univariate data. R package, version 2.2, Statistics Netherlands, The Hague, Netherlands
17. Favelyukis, S., Till, J. H., Hubbard, S. R., and Miller, W. T. (2001) Structure and autoregulation of the insulin-like growth factor 1 receptor kinase. Nat. Struct. Biol. 8, 1058-1063
18. Otwinowski, Z., Minor, W., and Charles W. Carter, Jr. (1997) Processing of X-ray diffraction data collected in oscillation mode in Methods in Enzymology, pp. 307-326, Academic Press, New York, NY
19. Vagin, A., and Teplyakov, A. (1997) MOLREP: an Automated Program for Molecular Replacement. J. Appl. Crystallogr. 30, 1022-1025
20. Wu, J., Tseng, Y. D., Xu, C. F., Neubert, T. A., White, M. F., and Hubbard, S. R. (2008) Structural and biochemical characterization of the KRLB region in insulin receptor substrate-2. Nat. Struct. Mol. Biol. 15, 251-258
21. Emsley, P., and Cowtan, K. (2004) Coot: model-building tools for molecular graphics. Acta Crystallogr. D Biol. Crystallogr. 60, 2126-2132
22. Winn, M. D., Ballard, C. C., Cowtan, K. D., Dodson, E. J., Emsley, P., Evans, P. R., Keegan, R. M., Krissinel, E. B., Leslie, A. G., McCoy, A., McNicholas, S. J., Murshudov, G. N., Pannu, N. S., Potterton, E. A., Powell, H. R., Read, R. J., Vagin, A., and Wilson, K. S. (2011) Overview of the CCP4 suite and current developments. Acta Crystallogr. D Biol. Crystallogr. 67, 235-242
23. Murshudov, G. N., Vagin, A. A., and Dodson, E. J. (1997) Refinement of macromolecular structures by the maximum-likelihood method. Acta Crystallogr. D Biol. Crystallogr. 53, 240-255
24. Schneider, C. A., Rasband, W. S., and Eliceiri, K. W. (2012) NIH Image to ImageJ: 25 years of image analysis. Nat. Methods 9, 671-675
25. Ohori, M., Kinoshita, T., Okubo, M., Sato, K., Yamazaki, A., Arakawa, H., Nishimura, S., Inamura, N., Nakajima, H., Neya, M., Miyake, H., and Fujii, T. (2005) Identification of a selective ERK inhibitor and structural determination of the inhibitor-ERK2 complex. Biochem. Biophys. Res. Commun. 336, 357-363
26. Hari, S. B., Merritt, E. A., and Maly, D. J. (2013) Sequence determinants of a specific inactive protein kinase conformation. Chem. Biol. 20, 806-815
27. Deleted in proof
28. Buchanan, J. L., Newcomb, J. R., Carney, D. P., Chaffee, S. C., Chai, L., Cupples, R., Epstein, L. F., Gallant, P., Gu, Y., Harmange, J. C., Hodge, K., Houk, B. E., Huang, X., Jona, J., Joseph, S., Jun, H. T., Kumar, R., Li, C., Lu, J., Menges, T., Morrison, M. J., Novak, P. M., van der Plas, S., Radinsky, R., Rose, P. E., Sawant, S., Sun, J. R., Surapaneni, S., Turci, S. M., Xu, K., Yanez, E., Zhao, H., and Zhu, X. (2011) Discovery of 2,4-bis-arylamino-1,3- pyrimidines as insulin-like growth factor-1 receptor (IGF-1R) inhibitors. Bioorg. Med. Chem. Lett. 21, 2394-2399
29. Chamberlain, S. D., Redman, A. M., Wilson, J. W., Deanda, F., Shotwell, J. B., Gerding, R., Lei, H., Yang, B., Stevens, K. L., Hassell, A. M., Shewchuk, L. M., Leesnitzer, M. A., Smith, J. L., Sabbatini, P., Atkins, C., Groy, A., Rowand, J. L., Kumar, R., Mook, R. A., Jr., Moorthy, G., and Patnaik, S. (2009) Optimization of 4,6-bis-anilino-1H-pyrrolo[2,3-d]pyrimidine IGF-1R tyrosine kinase inhibitors towards JNK selectivity. Bioorg. Med. Chem. Lett. 19, 360-364
30. Heinrich, T., Gradler, U., Bottcher, H., Blaukat, A., and Shutes, A. (2010) Allosteric IGF-1R Inhibitors. ACS Medicinal Chemistry Letters 1, 199-203
31. Katayama, N., Orita, M., Yamaguchi, T., Hisamichi, H., Kuromitsu, S., Kurihara, H., Sakashita, H., Matsumoto, Y., Fujita, S., and Niimi, T. (2008) Identification of a key element for hydrogen-bonding patterns between protein kinases and their inhibitors. Proteins 73, 795-801
32. Lesuisse, D., Mauger, J., Nemecek, C., Maignan, S., Boiziau, J., Harlow, G., Hittinger, A., Ruf, S., Strobel, H., Nair, A., Ritter, K., Malleron, J. L., Dagallier, A., El-Ahmad, Y., Guilloteau, J. P., Guizani, H., Bouchard, H., and Venot, C. (2011) Discovery of the first non-ATP competitive IGF-1R kinase inhibitors: advantages in comparison with competitive inhibitors. Bioorg. Med. Chem. Lett. 21, 2224-2228
33. Mayer, S. C., Banker, A. L., Boschelli, F., Di, L., Johnson, M., Kenny, C. H., Krishnamurthy, G., Kutterer, K., Moy, F., Petusky, S., Ravi, M., Tkach, D., Tsou, H. R., and Xu, W. (2008) Lead identification to generate isoquinolinedione inhibitors of insulin-like growth factor receptor (IGF-1R) for potential use in cancer treatment. Bioorg. Med. Chem. Lett. 18, 3641-3645
34. Miller, L. M., Mayer, S. C., Berger, D. M., Boschelli, D. H., Boschelli, F., Di, L., Du, X., Dutia, M., Floyd, M. B., Johnson, M., Kenny, C. H., Krishnamurthy, G., Moy, F., Petusky, S., Tkach, D., Torres, N., Wu, B., and Xu, W. (2009) Lead identification to generate 3-cyanoquinoline inhibitors of insulin-like growth factor receptor (IGF-1R) for potential use in cancer treatment. Bioorg. Med. Chem. Lett. 19, 62-66
35. Nemecek, C., Metz, W. A., Wentzler, S., Ding, F. X., Venot, C., Souaille, C., Dagallier, A., Maignan, S., Guilloteau, J. P., Bernard, F., Henry, A., Grapinet, S., and Lesuisse, D. (2010) Design of potent IGF1-R inhibitors related to bis-azaindoles. Chem. Biol. Drug. Des. 76, 100-106
36. Parang, K., Till, J. H., Ablooglu, A. J., Kohanski, R. A., Hubbard, S. R., and Cole, P. A. (2001) Mechanism-based design of a protein kinase inhibitor. Nat. Struct. Biol. 8, 37-41
37. Patnaik, S., Stevens, K. L., Gerding, R., Deanda, F., Shotwell, J. B., Tang, J., Hamajima, T., Nakamura, H., Leesnitzer, M. A., Hassell, A. M., Shewchuck, L. M., Kumar, R., Lei, H., and Chamberlain, S. D. (2009) Discovery of 3,5-disubstituted-1H-pyrrolo[2,3-b]pyridines as potent inhibitors of the insulin-like growth factor-1 receptor (IGF-1R) tyrosine kinase. Bioorg. Med. Chem. Lett. 19, 3136-3140
38. Sampognaro, A. J., Wittman, M. D., Carboni, J. M., Chang, C., Greer, A. F., Hurlburt, W. W., Sack, J. S., and Vyas, D. M. (2010) Proline isosteres in a series of 2,4-disubstituted pyrrolo[1,2-f][1,2,4]triazine inhibitors of IGF-1R kinase and IR kinase. Bioorg Med. Chem. Lett. 20, 5027-5030
39. Velaparthi, U., Wittman, M., Liu, P., Stoffan, K., Zimmermann, K., Sang, X., Carboni, J., Li, A., Attar, R., Gottardis, M., Greer, A., Chang, C. Y., Jacobsen, B. L., Sack, J. S., Sun, Y., Langley, D. R., Balasubramanian, B., and Vyas, D. (2007) Discovery and initial SAR of 3-(1H-benzo[d]imidazol-2-yl) pyridin-2(1H)-ones as inhibitors of insulin-like growth factor 1-receptor (IGF-1R). Bioorg. Med. Chem. Lett. 17, 2317-2321
40. Wittman, M. D., Carboni, J. M., Yang, Z., Lee, F. Y., Antman, M., Attar, R., Balimane, P., Chang, C., Chen, C., Discenza, L., Frennesson, D., Gottardis, M. M., Greer, A., Hurlburt, W., Johnson, W., Langley, D. R., Li, A., Li, J., Liu, P., Mastalerz, H., Mathur, A., Menard, K., Patel, K., Sack, J., Sang, X., Saulnier, M., Smith, D., Stefanski, K., Trainor, G., Velaparthi, U., Zhang, G., Zimmermann, K., and Vyas, D. M. (2009) Discovery of a 2,4-disubstituted pyrrolo[1,2-f][1,2,4]triazine inhibitor (BMS-754807) of insulin-like growth factor receptor (IGF-1R) kinase in clinical development. J. Med. Chem. 52, 7360-7363
41. Wu, J., Li, W., Craddock, B. P., Foreman, K. W., Mulvihill, M. J., Ji, Q. S., Miller, W. T., and Hubbard, S. R. (2008) Small-molecule inhibition and activation-loop trans-phosphorylation of the IGF1 receptor. EMBO J. 27, 1985-1994
42. Carboni, J. M., Wittman, M., Yang, Z., Lee, F., Greer, A., Hurlburt, W., Hillerman, S., Cao, C., Cantor, G. H., Dell-John, J., Chen, C., Discenza, L., Menard, K., Li, A., Trainor, G., Vyas, D., Kramer, R., Attar, R. M., and Gottardis, M. M. (2009) BMS-754807, a small molecule inhibitor of insulin-like growth factor-1R/IR. Mol. Cancer Ther. 8, 3341-3349
43. Mulvihill, M. J., Cooke, A., Rosenfeld-Franklin, M., Buck, E., Foreman, K., Landfair, D., O'Connor, M., Pirritt, C., Sun, Y., Yao, Y., Arnold, L. D., Gibson, N. W., and Ji, Q. S. (2009) Discovery of OSI-906: a selective and orally efficacious dual inhibitor of the IGF-1 receptor and insulin receptor. Future Med. Chem. 1, 1153-1171
44. Knight, Z. A., and Shokat, K. M. (2005) Features of selective kinase inhibitors. Chem. Biol. 12, 621-637
45. Goldstein, D. M., Gray, N. S., and Zarrinkar, P. P. (2008) High-throughput kinase profiling as a platform for drug discovery. Nat. Rev. Drug. Discov. 7, 391-397