Identification and characterization of a novel integrin-linked kinase inhibitor

Journal of Medicinal Chemistry

Volumn 54, Issue 18, 2011, Pages 6364-6374

  Lee, Su Lin ^a   Hsu, En Chi ^a   Chou, Chih Chien ^a   Chuang, Hsiao Ching ^a   Bai, Li Yuan ^b   Kulp, Samuel K ^a   Chen, Ching Shih ^a  

^a OHIO STATE UNIVERSITY   (United States)

^b CHINA MEDICAL UNIVERSITY   (Taiwan)

Author keywords

[No Author keywords available]

Indexed keywords

ANTINEOPLASTIC AGENT; EPIDERMAL GROWTH FACTOR RECEPTOR; GLYCOGEN SYNTHASE KINASE 3BETA; INTEGRIN LINKED KINASE; MYOSIN LIGHT CHAIN; N METHYL 3 [1 (4 (PIPERAZIN 1 YL)PHENYL) 5 (4' (TRIFLUOROMETHYL) (1,1' BIPHENYL] 4 YL) 1H PYRAZOL 3 YL]PROPANAMIDE; PROPIONAMIDE DERIVATIVE; PROTEIN KINASE B; SERINE; UNCLASSIFIED DRUG; Y BOX BINDING PROTEIN 1;

ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; ANTINEOPLASTIC ACTIVITY; APOPTOSIS; ARTICLE; AUTOPHAGY; BREAST CANCER; CANCER CELL CULTURE; CONTROLLED STUDY; DEPHOSPHORYLATION; DRUG IDENTIFICATION; DRUG POTENCY; HUMAN; HUMAN CELL; HUMAN TISSUE; IC 50; IN VITRO STUDY; MALE; MOUSE; NONHUMAN; PROSTATE CANCER; PROTEIN EXPRESSION; RANDOMIZED CONTROLLED TRIAL;

ADMINISTRATION, ORAL; ANIMALS; ANTINEOPLASTIC AGENTS; APOPTOSIS; AUTOPHAGY; CELL LINE, TUMOR; DRUG SCREENING ASSAYS, ANTITUMOR; HUMANS; MICE; MICE, NUDE; NEOPLASM TRANSPLANTATION; PIPERAZINES; PROTEIN-SERINE-THREONINE KINASES; PYRAZOLES; RECEPTOR, EPIDERMAL GROWTH FACTOR; RECEPTOR, ERBB-2; STRUCTURE-ACTIVITY RELATIONSHIP; TRANSPLANTATION, HETEROLOGOUS; Y-BOX-BINDING PROTEIN 1;

EID: 80052789436     PISSN: 00222623     EISSN: 15204804     Source Type: Journal    
DOI: 10.1021/jm2007744     Document Type: Article

References (42)

1. Mora, A.; Komander, D.; van Aalten, D. M.; Alessi, D. R. PDK1, the master regulator of AGC kinase signal transduction Semin. Cell Dev. Biol. 2004, 15, 161-170 (Pubitemid 38251644)
2. Dong, L. Q.; Liu, F. PDK2: the missing piece in the receptor tyrosine kinase signaling pathway puzzle Am. J. Physiol. Endocrinol. Metab. 2005, 289, E187-196
3. Hresko, R. C.; Mueckler, M. mTOR.RICTOR is the Ser473 kinase for Akt/protein kinase B in 3T3-L1 adipocytes J. Biol. Chem. 2005, 280, 40406-40416 (Pubitemid 41780527)
4. Sarbassov, D. D.; Guertin, D. A.; Ali, S. M.; Sabatini, D. M. Phosphorylation and regulation of Akt/PKB by the rictor-mTOR complex Science 2005, 307, 1098-1101 (Pubitemid 40262113)
5. Delcommenne, M.; Tan, C.; Gray, V.; Rue, L.; Woodgett, J.; Dedhar, S. Phosphoinositide-3-OH kinase-dependent regulation of glycogen synthase kinase 3 and protein kinase B/AKT by the integrin-linked kinase Proc. Natl. Acad. Sci. U.S.A 1998, 95, 11211-11216 (Pubitemid 28450107)
6. Persad, S.; Attwell, S.; Gray, V.; Delcommenne, M.; Troussard, A.; Sanghera, J.; Dedhar, S. Inhibition of integrin-linked kinase (ILK) suppresses activation of protein kinase B/Akt and induces cell cycle arrest and apoptosis of PTEN-mutant prostate cancer cells Proc. Natl. Acad. Sci. U.S.A 2000, 97, 3207-3212 (Pubitemid 30183280)
7. Persad, S.; Attwell, S.; Gray, V.; Mawji, N.; Deng, J. T.; Leung, D.; Yan, J.; Sanghera, J.; Walsh, M. P.; Dedhar, S. Regulation of protein kinase B/Akt-serine 473 phosphorylation by integrin-linked kinase: critical roles for kinase activity and amino acids arginine 211 and serine 343 J. Biol. Chem. 2001, 276, 27462-27469
8. Hannigan, G. E.; Leung-Hagesteijn, C.; Fitz-Gibbon, L.; Coppolino, M. G.; Radeva, G.; Filmus, J.; Bell, J. C.; Dedhar, S. Regulation of cell adhesion and anchorage-dependent growth by a new beta 1-integrin-linked protein kinase Nature 1996, 379, 91-96 (Pubitemid 26008142)
9. Hannigan, G.; Troussard, A. A.; Dedhar, S. Integrin-linked kinase: a cancer therapeutic target unique among its ILK Nature Rev. Cancer 2005, 5, 51-63 (Pubitemid 40052325)
10. Legate, K. R.; Montanez, E.; Kudlacek, O.; Fassler, R. ILK, PINCH and parvin: the tIPP of integrin signalling Nature Rev. Mol. Cell Biol. 2006, 7, 20-31 (Pubitemid 43361569)
11. Fielding, A. B.; Dobreva, I.; McDonald, P. C.; Foster, L. J.; Dedhar, S. Integrin-linked kinase localizes to the centrosome and regulates mitotic spindle organization J. Cell Biol. 2008, 180, 681-689 (Pubitemid 351397766)
12. Wickstrom, S. A.; Lange, A.; Montanez, E.; Fassler, R. The ILK/PINCH/parvin complex: the kinase is dead, long live the pseudokinase! EMBO J. 2010, 29, 281-291
13. Troussard, A. A.; Mawji, N. M.; Ong, C.; Mui, A.; St-Arnaud, R.; Dedhar, S. Conditional knock-out of integrin-linked kinase demonstrates an essential role in protein kinase B/Akt activation J. Biol. Chem. 2003, 278, 22374-22378 (Pubitemid 36830287)
14. Deng, J. T.; Sutherland, C.; Brautigan, D. L.; Eto, M.; Walsh, M. P. Phosphorylation of the myosin phosphatase inhibitors, CPI-17 and PHI-1, by integrin-linked kinase Biochem. J. 2002, 367, 517-524 (Pubitemid 35216828)
15. Deng, J. T.; Van Lierop, J. E.; Sutherland, C.; Walsh, M. P. Ca2+-independent smooth muscle contraction. A novel function for integrin-linked kinase J. Biol. Chem. 2001, 276, 16365-16373
16. Graff, J. R.; Deddens, J. A.; Konicek, B. W.; Colligan, B. M.; Hurst, B. M.; Carter, H. W.; Carter, J. H. Integrin-linked kinase expression increases with prostate tumor grade Clin. Cancer Res. 2001, 7, 1987-1991 (Pubitemid 32994836)
17. Ahmed, N.; Riley, C.; Oliva, K.; Stutt, E.; Rice, G. E.; Quinn, M. A. Integrin-linked kinase expression increases with ovarian tumour grade and is sustained by peritoneal tumour fluid J. Pathol. 2003, 201, 229-237 (Pubitemid 37258934)
18. Pontier, S. M.; Huck, L.; White, D. E.; Rayment, J.; Sanguin-Gendreau, V.; Hennessy, B.; Zuo, D.; St-Arnaud, R.; Mills, G. B.; Dedhar, S.; Marshall, C. J.; Muller, W. J. Integrin-linked kinase has a critical role in ErbB2 mammary tumor progression: implications for human breast cancer Oncogene 2010, 29, 3374-3385
19. Bravou, V.; Klironomos, G.; Papadaki, E.; Taraviras, S.; Varakis, J. ILK over-expression in human colon cancer progression correlates with activation of beta-catenin, down-regulation of E-cadherin and activation of the Akt-FKHR pathway J. Pathol. 2006, 208, 91-99 (Pubitemid 43025707)
20. Schaeffer, D. F.; Assi, K.; Chan, K.; Buczkowski, A. K.; Chung, S. W.; Scudamore, C. H.; Weiss, A.; Salh, B.; Owen, D. A. Tumor expression of integrin-linked kinase (ILK) correlates with the expression of the E-cadherin repressor snail: an immunohistochemical study in ductal pancreatic adenocarcinoma Virchows Arch. 2010, 456, 261-268
21. Ito, R.; Oue, N.; Zhu, X.; Yoshida, K.; Nakayama, H.; Yokozaki, H.; Yasui, W. Expression of integrin-linked kinase is closely correlated with invasion and metastasis of gastric carcinoma Virchows Arch. 2003, 442, 118-123 (Pubitemid 36337658)
22. Chan, J.; Ko, F. C.; Yeung, Y. S.; Ng, I. O.; Yam, J. W. Integrin-linked kinase overexpression and its oncogenic role in promoting tumorigenicity of hepatocellular carcinoma PLoS One 2011, 6, e16984
23. Zhu, J.; Song, X.; Lin, H. P.; Young, D. C.; Yan, S.; Marquez, V. E.; Chen, C. S. Using cyclooxygenase-2 inhibitors as molecular platforms to develop a new class of apoptosis-inducing agents J. Natl. Cancer Inst. 2002, 94, 1745-1757 (Pubitemid 36004351)
24. Zhu, J.; Huang, J. W.; Tseng, P. H.; Yang, Y. T.; Fowble, J.; Shiau, C. W.; Shaw, Y. J.; Kulp, S. K.; Chen, C. S. From the cyclooxygenase-2 inhibitor celecoxib to a novel class of 3-phosphoinositide-dependent protein kinase-1 inhibitors Cancer Res. 2004, 64, 4309-4318 (Pubitemid 38802438)
25. Garcia-Martinez, J. M.; Alessi, D. R. mTOR complex 2 (mTORC2) controls hydrophobic motif phosphorylation and activation of serum- and glucocorticoid-induced protein kinase 1 (SGK1) Biochem. J. 2008, 416, 375-385
26. Ikenoue, T.; Inoki, K.; Yang, Q.; Zhou, X.; Guan, K. L. Essential function of TORC2 in PKC and Akt turn motif phosphorylation, maturation and signalling EMBO J. 2008, 27, 1919-1931
27. Kalra, J.; Sutherland, B. W.; Stratford, A. L.; Dragowska, W.; Gelmon, K. A.; Dedhar, S.; Dunn, S. E.; Bally, M. B. Suppression of Her2/neu expression through ILK inhibition is regulated by a pathway involving TWIST and YB-1 Oncogene 2010, 29, 6343-6356
28. Stratford, A. L.; Habibi, G.; Astanehe, A.; Jiang, H.; Hu, K.; Park, E.; Shadeo, A.; Buys, T. P.; Lam, W.; Pugh, T.; Marra, M.; Nielsen, T. O.; Klinge, U.; Mertens, P. R.; Aparicio, S.; Dunn, S. E. Epidermal growth factor receptor (EGFR) is transcriptionally induced by the Y-box binding protein-1 (YB-1) and can be inhibited with Iressa in basal-like breast cancer, providing a potential target for therapy Breast Cancer Res. 2007, 9, R61
29. Eke, I.; Leonhardt, F.; Storch, K.; Hehlgans, S.; Cordes, N. The small molecule inhibitor QLT0267 radiosensitizes squamous cell carcinoma cells of the head and neck PLoS One 2009, 4, e6434
30. Cary, L. A.; Guan, J. L. Focal adhesion kinase in integrin-mediated signaling Front. Biosci. 1999, 4, D102-113
31. Huang, Y.; Li, J.; Zhang, Y.; Wu, C. The roles of integrin-linked kinase in the regulation of myogenic differentiation J. Cell Biol. 2000, 150, 861-872
32. Su, J. L.; Chiou, J.; Tang, C. H.; Zhao, M.; Tsai, C. H.; Chen, P. S.; Chang, Y. W.; Chien, M. H.; Peng, C. Y.; Hsiao, M.; Kuo, M. L.; Yen, M. L. CYR61 regulates BMP-2-dependent osteoblast differentiation through the {alpha}v{beta}3 integrin/integrin-linked kinase/ERK pathway J. Biol. Chem. 2010, 285, 31325-31336
33. White, D. E.; Cardiff, R. D.; Dedhar, S.; Muller, W. J. Mammary epithelial-specific expression of the integrin-linked kinase (ILK) results in the induction of mammary gland hyperplasias and tumors in transgenic mice Oncogene 2001, 20, 7064-7072 (Pubitemid 33052198)
34. Tabe, Y.; Jin, L.; Tsutsumi-Ishii, Y.; Xu, Y.; McQueen, T.; Priebe, W.; Mills, G. B.; Ohsaka, A.; Nagaoka, I.; Andreeff, M.; Konopleva, M. Activation of integrin-linked kinase is a critical prosurvival pathway induced in leukemic cells by bone marrow-derived stromal cells Cancer Res. 2007, 67, 684-694 (Pubitemid 46192208)
35. Esfandiarei, M.; Yazdi, S. A.; Gray, V.; Dedhar, S.; van Breemen, C. Integrin-linked kinase functions as a downstream signal of platelet-derived growth factor to regulate actin polymerization and vascular smooth muscle cell migration BMC Cell Biol. 2010, 11, 16
36. Ishii, T.; Satoh, E.; Nishimura, M. Integrin-linked kinase controls neurite outgrowth in N1E-115 neuroblastoma cells J. Biol. Chem. 2001, 276, 42994-43003
37. Leung-Hagesteijn, C.; Hu, M. C.; Mahendra, A. S.; Hartwig, S.; Klamut, H. J.; Rosenblum, N. D.; Hannigan, G. E. Integrin-linked kinase mediates bone morphogenetic protein 7-dependent renal epithelial cell morphogenesis Mol. Cell. Biol. 2005, 25, 3648-3657 (Pubitemid 40559571)
38. Sawai, H.; Okada, Y.; Funahashi, H.; Matsuo, Y.; Takahashi, H.; Takeyama, H.; Manabe, T. Integrin-linked kinase activity is associated with interleukin-1 alpha-induced progressive behavior of pancreatic cancer and poor patient survival Oncogene 2006, 25, 3237-3246 (Pubitemid 43846308)
39. Codogno, P.; Meijer, A. J. Autophagy and signaling: their role in cell survival and cell death Cell Death Differ. 2005, 12 (Suppl 2) 1509-1518 (Pubitemid 41553987)
40. Troussard, A. A.; McDonald, P. C.; Wederell, E. D.; Mawji, N. M.; Filipenko, N. R.; Gelmon, K. A.; Kucab, J. E.; Dunn, S. E.; Emerman, J. T.; Bally, M. B.; Dedhar, S. Preferential dependence of breast cancer cells versus normal cells on integrin-linked kinase for protein kinase B/Akt activation and cell survival Cancer Res. 2006, 66, 393-403 (Pubitemid 43166047)
41. Kalra, J.; Warburton, C.; Fang, K.; Edwards, L.; Daynard, T.; Waterhouse, D.; Dragowska, W.; Sutherland, B. W.; Dedhar, S.; Gelmon, K.; Bally, M. QLT0267, a small molecule inhibitor targeting integrin-linked kinase (ILK), and docetaxel can combine to produce synergistic interactions linked to enhanced cytotoxicity, reductions in P-AKT levels, altered F-actin architecture and improved treatment outcomes in an orthotopic breast cancer model Breast Cancer Res. 2009, 11, R25
42. Matsumoto, K.; Bay, B. H. Significance of the Y-box proteins in human cancers J. Mol. Genet. Med. 2005, 1, 11-17