Development of RET kinase inhibitors for targeted cancer therapy

Current Medicinal Chemistry

Volumn 18, Issue 2, 2011, Pages 162-175

  Mologni, L ^a  

^a UNIVERSITY OF MILANO BICOCCA   (Italy)

Author keywords

PTC; RET; Small molecule inhibitor; Target therapy; Thyroid cancer; Tyrosine kinase

Indexed keywords

4 (3 CHLOROANILINO) 6,7 DIMETHOXYQUINAZOLINE; 4 AMINO 7 TERT BUTYL 5 (4 CHLOROPHENYL)PYRAZOLO[3,4 D]PYRIMIDINE; 4 AMINO 7 TERT BUTYL 5 (4 METHYLPHENYL)PYRAZOLO[3,4 D]PYRIMIDINE; 6 (2,6 DICHLOROPHENYL) 8 METHYL 2 (3 METHYLTHIOANILINO) 8H PYRIDO[2,3 D]PYRIMIDIN 7 ONE; BMS 907351; CDP 13G; CEP 751; CPD 13G; CPD 2B; FOSTAMATINIB; GEFITINIB; GELDANAMYCIN; GENISTEIN; HERBIMYCIN A; IMATINIB; JNJ 38158471; K 252B; LESTAURTINIB; MOTESANIB; N TERT BUTYL 3 [5 METHYL 2 [4 (4 METHYL 1 PIPERAZINYL)PHENYLAMINO] 4 PYRIMIDINYLAMINO]BENZENESULFONAMIDE; NYP AST487; PROTEIN TYROSINE KINASE INHIBITOR; RAC1 PROTEIN; RAS PROTEIN; SEMAXANIB; SORAFENIB; STAUROSPORINE; SUNITINIB; TOZASERTIB; UNCLASSIFIED DRUG; VANDETANIB; XL 184;

ANTINEOPLASTIC ACTIVITY; ARTICLE; CANCER THERAPY; CATALYSIS; DRUG ACTIVITY; DRUG BINDING; DRUG EFFICACY; DRUG INHIBITION; DRUG MEGADOSE; DRUG STRUCTURE; GANGLIONEUROMA; HUMAN; IC 50; KIDNEY CARCINOMA; KIDNEY DEVELOPMENT; LIVER CELL CARCINOMA; MOLECULAR INTERACTION; NONHUMAN; PARATHYROID HYPERPLASIA; PHASE 1 CLINICAL TRIAL; PHASE 2 CLINICAL TRIAL; PHEOCHROMOCYTOMA; POINT MUTATION; PROTEIN PHOSPHORYLATION; SIGNAL TRANSDUCTION; SURVIVAL RATE; THYROID MEDULLARY CARCINOMA; TREATMENT RESPONSE;

ANTINEOPLASTIC AGENTS; HUMANS; INDOLES; NEOPLASMS; PROTEIN KINASE INHIBITORS; PROTO-ONCOGENE PROTEINS C-RET; PYRIMIDINES; QUINAZOLINES; STAUROSPORINE; UREA;

EID: 78751558425     PISSN: 09298673     EISSN: None     Source Type: Journal    
DOI: 10.2174/092986711794088308     Document Type: Article

References (99)

1. Sharma, S. V.; Settleman, J. Oncogene addiction: setting the stage for molecularly targeted cancer therapy. Genes Dev., 2007, 21, 3214-3231.
2. Hochhaus, A.; Druker, B.; Sawyers, C.; Guilhot, F.; Schiffer, C. A.; Cortes, J.; Niederwieser, D. W.; Gambacorti-Passerini, C.; Stone, R. M.; Goldman, J.; Fischer, T.; O'Brien, S. G.; Reiffers, J. J.; Mone, M.; Krahnke, T.; Talpaz, M.; Kantarjian, H. M. Favorable longterm follow-up results over 6 years for response, survival, and safety with imatinib mesylate therapy in chronic-phase chronic myeloid leukemia after failure of interferon-alpha treatment. Blood, 2008, 111, 1039-1043.
3. Kantarjian, H.; Sawyers, C.; Hochhaus, A.; Guilhot, F.; Schiffer, C.; Gambacorti-Passerini, C.; Niederwieser, D.; Resta, D.; Capdeville, R.; Zoellner, U.; Talpaz, M.; Druker, B.; Goldman, J.; O'Brien, S. G.; Russell, N.; Fischer, T.; Ottmann, O.; Cony-Makhoul, P.; Facon, T.; Stone, R.; Miller, C.; Tallman, M.; Brown, R.; Schuster, M.; Loughran, T.; Gratwohl, A.; Mandelli, F.; Saglio, G.; Lazzarino, M.; Russo, D.; Baccarani, M.; Morra, E. Hematologic and cytogenetic responses to imatinib mesylate in chronic myelogenous leukemia. N. Engl. J. Med., 2002, 346, 645-652.
4. Gunby, R. H.; Sala, E.; Tartari, C. J.; Puttini, M.; Gambacorti- Passerini, C.; Mologni, L. Oncogenic fusion tyrosine kinases as molecular targets for anti-cancer therapy. Anticancer Agents Med. Chem., 2007, 7, 594-611.
5. Takahashi, M.; Ritz, J.; Cooper, G. M. Activation of a novel human transforming gene, ret, by DNA rearrangement. Cell, 1985, 42, 581-588.
6. Ishiguro, Y.; Iwashita, T.; Murakami, H.; Asai, N.; Iida, K.; Goto, H.; Hayakawa, T.; Takahashi, M. The role of amino acids surrounding tyrosine 1062 in ret in specific binding of the shc phosphotyrosine-binding domain. Endocrinology, 1999, 140, 3992-3998.
7. Arighi, E.; Borrello, M. G.; Sariola, H. RET tyrosine kinase signaling in development and cancer. Cytokine Growth Factor Rev., 2005, 16, 441-467.
8. Coulpier, M.; Anders, J.; Ibanez, C. F. Coordinated activation of autophosphorylation sites in the RET receptor tyrosine kinase: importance of tyrosine 1062 for GDNF mediated neuronal differentiation and survival. J. Biol. Chem., 2002, 277, 1991-1999.
9. Airaksinen, M. S.; Titievsky, A.; Saarma, M. GDNF family neurotrophic factor signaling: four masters, one servant? Mol. Cell. Neurosci., 1999, 13, 313-325.
10. Gujral, T. S.; van Veelen, W.; Richardson, D. S.; Myers, S. M.; Meens, J. A.; Acton, D. S.; Dunach, M.; Elliott, B. E.; Hoppener, J. W.; Mulligan, L. M. A novel RET kinase-beta-catenin signaling pathway contributes to tumorigenesis in thyroid carcinoma. Cancer Res., 2008, 68, 1338-1346.
11. Ichihara, M.; Murakumo, Y.; Takahashi, M. RET and neuroendocrine tumors. Cancer Lett., 2004, 204, 197-211.
12. Schuchardt, A.; D'Agati, V.; Larsson-Blomberg, L.; Costantini, F.; Pachnis, V. Defects in the kidney and enteric nervous system of mice lacking the tyrosine kinase receptor Ret. Nature, 1994, 367, 380-383.
13. Manie, S.; Santoro, M.; Fusco, A.; Billaud, M. The RET receptor: function in development and dysfunction in congenital malformation. Trends Genet., 2001, 17, 580-589.
14. Hubbard, S. R.; Till, J. H. Protein tyrosine kinase structure and function. Annu Rev Biochem., 2000, 69, 373-398.
15. Engh, R. A.; Bossemeyer, D. Structural aspects of protein kinase control-role of conformational flexibility. Pharmacol. Ther., 2002, 93, 99-111.
16. Knowles, P. P.; Murray-Rust, J.; Kjaer, S.; Scott, R. P.; Hanrahan, S.; Santoro, M.; Ibanez, C. F.; McDonald, N. Q. Structure and chemical inhibition of the RET tyrosine kinase domain. J. Biol. Chem., 2006, 23, 23.
17. Iwashita, T.; Asai, N.; Murakami, H.; Matsuyama, M.; Takahashi, M. Identification of tyrosine residues that are essential for transforming activity of the ret proto-oncogene with MEN2A or MEN2B mutation. Oncogene, 1996, 12, 481-487.
18. Jhiang, S. M. The RET proto-oncogene in human cancers. Oncogene, 2000, 19, 5590-5597.
19. Gimm, O. Thyroid cancer. Cancer Lett., 2001, 163, 143-156.
20. Eng, C. RET proto-oncogene in the development of human cancer. J. Clin. Oncol., 1999, 17, 380-393.
21. Ito, S.; Iwashita, T.; Asai, N.; Murakami, H.; Iwata, Y.; Sobue, G.; Takahashi, M. Biological properties of Ret with cysteine mutations correlate with multiple endocrine neoplasia type 2A, familial medullary thyroid carcinoma, and Hirschsprung's disease phenotype. Cancer Res., 1997, 57, 2870-2872.
22. Plaza-Menacho, I.; Mologni, L.; Sala, E.; Gambacorti-Passerini, C.; Magee, A. I.; Links, T. P.; Hofstra, R. M.; Barford, D.; Isacke, C. M. Sorafenib functions to potently suppress RET tyrosine kinase activity by direct enzymatic inhibition and promoting RET lysosomal degradation independent of proteasomal targeting. J. Biol. Chem., 2007, 282, 29230-29240.
23. Gorre, M. E.; Mohammed, M.; Ellwood, K.; Hsu, N.; Paquette, R.; Rao, P. N.; Sawyers, C. L. Clinical resistance to STI-571 cancer therapy caused by BCR-ABL gene mutation or amplification. Science, 2001, 293, 876-880.
24. Yun, C. H.; Mengwasser, K. E.; Toms, A. V.; Woo, M. S.; Greulich, H.; Wong, K. K.; Meyerson, M.; Eck, M. J. The T790M mutation in EGFR kinase causes drug resistance by increasing the affinity for AT P. Proc. Natl. Acad. Sci. U S A, 2008, 105, 2070-2075.
25. Tamborini, E.; Bonadiman, L.; Greco, A.; Albertini, V.; Negri, T.; Gronchi, A.; Bertulli, R.; Colecchia, M.; Casali, P. G.; Pierotti, M. A.; Pilotti, S. A new mutation in the KIT AT P pocket causes acquired resistance to imatinib in a gastrointestinal stromal tumor patient. Gastroenterology, 2004, 127, 294-299.
26. Cranston, A. N.; Carniti, C.; Oakhill, K.; Radzio-Andzelm, E.; Stone, E. A.; McCallion, A. S.; Hodgson, S.; Clarke, S.; Mondellini, P.; Leyland, J.; Pierotti, M. A.; Whittaker, J.; Taylor, S. S.; Bongarzone, I.; Ponder, B. A. RET is constitutively activated by novel tandem mutations that alter the active site resulting in multiple endocrine neoplasia type 2B. Cancer Res., 2006, 66, 10179-10187.
27. Carlomagno, F.; Guida, T.; Anaganti, S.; Vecchio, G.; Fusco, A.; Ryan, A. J.; Billaud, M.; Santoro, M. Disease associated mutations at valine 804 in the RET receptor tyrosine kinase confer resistance to selective kinase inhibitors. Oncogene, 2004, 23, 6056-6063.
28. Bocciardi, R.; Mograbi, B.; Pasini, B.; Borrello, M. G.; Pierotti, M. A.; Bourget, I.; Fischer, S.; Romeo, G.; Rossi, B. The multiple endocrine neoplasia type 2B point mutation switches the specificity of the Ret tyrosine kinase towards cellular substrates that are susceptible to interact with Crk and Nck. Oncogene, 1997, 15, 2257-2265.
29. Gujral, T. S.; Singh, V. K.; Jia, Z.; Mulligan, L. M. Molecular mechanisms of RET receptor-mediated oncogenesis in multiple endocrine neoplasia 2B. Cancer Res., 2006, 66, 10741-10749.
30. Jhiang, S. M.; Sagartz, J. E.; Tong, Q.; Parker-Thornburg, J.; Capen, C. C.; Cho, J. Y.; Xing, S.; Ledent, C. Targeted expression of the ret/PTC1 oncogene induces papillary thyroid carcinomas. Endocrinology, 1996, 137, 375-378. (Pubitemid 26005013)
31. Michiels, F. M.; Chappuis, S.; Caillou, B.; Pasini, A.; Talbot, M.; Monier, R.; Lenoir, G. M.; Feunteun, J.; Billaud, M. Development of medullary thyroid carcinoma in transgenic mice expressing the RET protooncogene altered by a multiple endocrine neoplasia type 2A mutation. Proc. Natl. Acad. Sci. U S A, 1997, 94, 3330-3335.
32. Acton, D. S.; Velthuyzen, D.; Lips, C. J.; Hoppener, J. W. Multiple endocrine neoplasia type 2B mutation in human RET oncogene induces medullary thyroid carcinoma in transgenic mice. Oncogene, 2000, 19, 3121-3125.
33. Drosten, M.; Stiewe, T.; Putzer, B. M. Antitumor capacity of a dominant-negative RET proto-oncogene mutant in a medullary thyroid carcinoma model. Hum. Gene Ther., 2003, 14, 971-982.
34. De Martimprey, H.; Bertrand, J. R.; Fusco, A.; Santoro, M.; Couvreur, P.; Vauthier, C.; Malvy, C. siRNA nanoformulation against the ret/PTC1 junction oncogene is efficient in an in vivo model of papillary thyroid carcinoma. Nucleic Acids Res., 2008, 36, e2.
35. Wood, L. D.; Parsons, D. W.; Jones, S.; Lin, J.; Sjoblom, T.; Leary, R. J.; Shen, D.; Boca, S. M.; Barber, T.; Ptak, J.; Silliman, N.; Szabo, S.; Dezso, Z.; Ustyanksky, V.; Nikolskaya, T.; Nikolsky, Y.; Karchin, R.; Wilson, P. A.; Kaminker, J. S.; Zhang, Z.; Croshaw, R.; Willis, J.; Dawson, D.; Shipitsin, M.; Willson, J. K.; Sukumar, S.; Polyak, K.; Park, B. H.; Pethiyagoda, C. L.; Pant, P. V.; Ballinger, D. G.; Sparks, A. B.; Hartigan, J.; Smith, D. R.; Suh, E.; Papadopoulos, N.; Buckhaults, P.; Markowitz, S. D.; Parmigiani, G.; Kinzler, K. W.; Velculescu, V. E.; Vogelstein, B. The genomic landscapes of human breast and colorectal cancers. Science, 2007, 318, 1108-1113.
36. Futami, H.; Egawa, S.; Tsukada, T.; Maruyama, K.; Bandoh, S.; Noguchi, M.; Yamaguchi, K. A novel somatic point mutation of the RET Proto-oncogene in tumor tissues of small cell lung cancer patients. Jpn. J. Cancer Res., 1995, 86, 1127-1130.
37. Taniguchi, M.; Uehara, Y.; Matsuyama, M.; Takahashi, M. Inhibition of ret tyrosine kinase activity by herbimycin A. Biochem. Biophys. Res. Commun., 1993, 195, 208-214. (Pubitemid 23266518)
38. Cohen, M. S.; Hussain, H. B.; Moley, J. F. Inhibition of medullary thyroid carcinoma cell proliferation and RET phosphorylation by tyrosine kinase inhibitors. Surgery, 2002, 132, 960-966; discussion 966-967.
39. Ezzat, S.; Huang, P.; Dackiw, A.; Asa, S. L. Dual inhibition of RET and FGFR4 restrains medullary thyroid cancer cell growth. Clin. Cancer Res., 2005, 11, 1336-1341.
40. Puttini, M.; Redaelli, S.; Moretti, L.; Brussolo, S.; Gunby, R. H.; Mologni, L.; Marchesi, E.; Cleris, L.; Donella-Deana, A.; Drueckes, P.; Sala, E.; Lucchini, V.; Kubbutat, M.; Formelli, F.; Zambon, A.; Scapozza, L.; Gambacorti-Passerini, C. Characterization of compound 584, an Abl kinase inhibitor with lasting effects. Haematologica, 2008, 93, 653-661.
41. Skinner, M. A.; Safford, S. D.; Freemerman, A. J. RET tyrosine kinase and medullary thyroid cells are unaffected by clinical doses of STI571. Anticancer Res., 2003, 23, 3601-3606.
42. de Groot, J. W.; Zonnenberg, B. A.; van Ufford-Mannesse, P. Q.; de Vries, M. M.; Links, T. P.; Lips, C. J.; Voest, E. E. A phase II trial of imatinib therapy for metastatic medullary thyroid carcinoma. J. Clin. Endocrinol. Metab., 2007, 92, 3466-3469.
43. Frank-Raue, K.; Fabel, M.; Delorme, S.; Haberkorn, U.; Raue, F. Efficacy of imatinib mesylate in advanced medullary thyroid carcinoma. Eur. J. Endocrinol., 2007, 157, 215-220.
44. Pong, K.; Xu, R. Y.; Beck, K. D.; Zhang, T. J.; Louis, J. C. Inhibition of glial cell line-derived neurotrophic factor induced intracellular activity by K-252b on dopaminergic neurons. J. Neurochem., 1997, 69, 986-994.
45. Strock, C. J.; Park, J. I.; Rosen, M.; Dionne, C.; Ruggeri, B.; Jones-Bolin, S.; Denmeade, S. R.; Ball, D. W.; Nelkin, B. D. CEP-701 and CEP-751 inhibit constitutively activated RET tyrosine kinase activity and block medullary thyroid carcinoma cell growth. Cancer Res., 2003, 63, 5559-5563.
46. Carlomagno, F.; Vitagliano, D.; Guida, T.; Napolitano, M.; Vecchio, G.; Fusco, A.; Gazit, A.; Levitzki, A.; Santoro, M. The kinase inhibitor PP1 blocks tumorigenesis induced by RET oncogenes. Cancer Res., 2002, 62, 1077-1082.
47. Carlomagno, F.; Vitagliano, D.; Guida, T.; Basolo, F.; Castellone, M. D.; Melillo, R. M.; Fusco, A.; Santoro, M. Efficient inhibition of RET/papillary thyroid carcinoma oncogenic kinases by 4-amino-5-(4-chloro-phenyl)-7-(t-butyl) pyrazolo[3,4-d]pyrimidine (PP2). J. Clin. Endocrinol. Metab., 2003, 88, 1897-1902.
48. Schindler, T.; Sicheri, F.; Pico, A.; Gazit, A.; Levitzki, A.; Kuriyan, J. Crystal structure of Hck in complex with a Src familyselective tyrosine kinase inhibitor. Mol. Cell, 1999, 3, 639-648.
49. Liu, Y.; Bishop, A.; Witucki, L.; Kraybill, B.; Shimizu, E.; Tsien, J.; Ubersax, J.; Blethrow, J.; Morgan, D. O.; Shokat, K. M. Structural basis for selective inhibition of Src family kinases by PP1. Chem. Biol., 1999, 6, 671-678.
50. Carniti, C.; Perego, C.; Mondellini, P.; Pierotti, M. A.; Bongarzone, I. PP1 inhibitor induces degradation of RETMEN2A and RETMEN2B oncoproteins through proteosomal targeting. Cancer Res., 2003, 63, 2234-2243.
51. Morisi, R.; Celano, M.; Tosi, E.; Schenone, S.; Navarra, M.; Ferretti, E.; Costante, G.; Durante, C.; Botta, G.; D'Agostino, M.; Brullo, C.; Filetti, S.; Botta, M.; Russo, D. Growth inhibition of medullary thyroid carcinoma cells by pyrazolo-pyrimidine derivates. J. Endocrinol. Invest., 2007, 30, RC31-34.
52. Wedge, S. R.; Ogilvie, D. J.; Dukes, M.; Kendrew, J.; Chester, R.; Jackson, J. A.; Boffey, S. J.; Valentine, P. J.; Curwen, J. O.; Musgrove, H. L.; Graham, G. A.; Hughes, G. D.; Thomas, A. P.; Stokes, E. S.; Curry, B.; Richmond, G. H.; Wadsworth, P. F.; Bigley, A. L.; Hennequin, L. F. ZD6474 inhibits vascular endothelial growth factor signaling, angiogenesis, and tumor growth following oral administration. Cancer Res., 2002, 62, 4645-4655.
53. Carlomagno, F.; Vitagliano, D.; Guida, T.; Ciardiello, F.; Tortora, G.; Vecchio, G.; Ryan, A. J.; Fontanini, G.; Fusco, A.; Santoro, M. ZD6474, an orally available inhibitor of KDR tyrosine kinase activity, efficiently blocks oncogenic RET kinases. Cancer Res., 2002, 62, 7284-7290.
54. Manning, G.; Whyte, D. B.; Martinez, R.; Hunter, T.; Sudarsanam, S. The protein kinase complement of the human genome. Science, 2002, 298, 1912-1934.
55. Gambacorti-Passerini, C. B.; Gunby, R. H.; Piazza, R.; Galietta, A.; Rostagno, R.; Scapozza, L. Molecular mechanisms of resistance to imatinib in Philadelphia-chromosome-positive leukaemias. Lancet Oncol., 2003, 4, 75-85.
56. Wells, S. A.; Jr.; Gosnell, J. E.; Gagel, R. F.; Moley, J.; Pfister, D.; Sosa, J. A.; Skinner, M.; Krebs, A.; Vasselli, J.; Schlumberger, M. Vandetanib for the treatment of patients with locally advanced or metastatic hereditary medullary thyroid cancer. J. Clin. Oncol., 2010, 28, 767-772.
57. Mologni, L.; Sala, E.; Riva, B.; Cesaro, L.; Cazzaniga, S.; Redaelli, S.; Marin, O.; Pasquato, N.; Donella-Deana, A.; Gambacorti-Passerini, C. Expression, purification, and inhibition of human RET tyrosine kinase. Protein Expr. Purif., 2005, 41, 177-185.
58. Tuccinardi, T.; Manetti, F.; Schenone, S.; Martinelli, A.; Botta, M. Construction and validation of a RET TK catalytic domain by homology modeling. J. Chem. Inf. Model., 2007, 47, 644-655.
59. Sun, L.; Tran, N.; Liang, C.; Tang, F.; Rice, A.; Schreck, R.; Waltz, K.; Shawver, L. K.; McMahon, G.; Tang, C. Design, synthesis, and evaluations of substituted 3-[(3 - or 4-carboxyethylpyrrol-2-yl) methylidenyl]indolin-2-ones as inhibitors of VEGF, FGF, and PDGF receptor tyrosine kinases. J. Med. Chem., 1999, 42, 5120-5130.
60. Sun, L.; Tran, N.; Tang, F.; App, H.; Hirth, P.; McMahon, G.; Tang, C. Synthesis and biological evaluations of 3-substituted indolin-2-ones: a novel class of tyrosine kinase inhibitors that exhibit selectivity toward particular receptor tyrosine kinases. J. Med. Chem., 1998, 41, 2588-2603.
61. Lanzi, C.; Cassinelli, G.; Pensa, T.; Cassinis, M.; Gambetta, R. A.; Borrello, M. G.; Menta, E.; Pierotti, M. A.; Zunino, F. Inhibition of transforming activity of the ret/ptc1 oncoprotein by a 2-indolinone derivative. Int. J. Cancer, 2000, 85, 384-390.
62. Cincinelli, R.; Cassinelli, G.; Dallavalle, S.; Lanzi, C.; Merlini, L.; Botta, M.; Tuccinardi, T.; Martinelli, A.; Penco, S.; Zunino, F. Synthesis, modeling, and RET protein kinase inhibitory activity of 3-and 4-substituted beta-carbolin-1-ones. J. Med. Chem., 2008, 51, 7777-7787.
63. Rizzi, E.; Cassinelli, G.; Dallavalle, S.; Lanzi, C.; Cincinelli, R.; Nannei, R.; Cuccuru, G.; Zunino, F. Synthesis and RET protein kinase inhibitory activity of 3-arylureidobenzylidene-indolin-2-ones. Bioorg. Med. Chem. Lett., 2007, 17, 3962-3968.
64. Lanzi, C.; Cassinelli, G.; Cuccuru, G.; Zaffaroni, N.; Supino, R.; Vignati, S.; Zanchi, C.; Yamamoto, M.; Zunino, F. Inactivation of Ret/Ptc1 oncoprotein and inhibition of papillary thyroid carcinoma cell proliferation by indolinone RPI-1. Cell. Mol. Life Sci., 2003, 60, 1449-1459.
65. Cuccuru, G.; Lanzi, C.; Cassinelli, G.; Pratesi, G.; Tortoreto, M.; Petrangolini, G.; Seregni, E.; Martinetti, A.; Laccabue, D.; Zanchi, C.; Zunino, F. Cellular effects and antitumor activity of RET inhibitor RPI-1 on MEN2A-associated medullary thyroid carcinoma. J. Natl. Cancer Inst., 2004, 96, 1006-1014.
66. Petrangolini, G.; Cuccuru, G.; Lanzi, C.; Tortoreto, M.; Belluco, S.; Pratesi, G.; Cassinelli, G.; Zunino, F. Apoptotic cell death induction and angiogenesis inhibition in large established medullary thyroid carcinoma xenografts by Ret inhibitor RPI-1. Biochem. Pharmacol., 2006, 72, 405-414.
67. Mologni, L.; Rostagno, R.; Brussolo, S.; Knowles, P. P.; Kjaer, S.; Murray-Rust, J.; Rosso, E.; Zambon, A.; Scapozza, L.; McDonald, N. Q.; Lucchini, V.; Gambacorti-Passerini, C. Synthesis, structureactivity relationship and crystallographic studies of 3-substituted indolin-2-one RET inhibitors. Bioorg. Med. Chem., 2010, 18, 1482-1496.
68. Mohammadi, M.; McMahon, G.; Sun, L.; Tang, C.; Hirth, P.; Yeh, B. K.; Hubbard, S. R.; Schlessinger, J. Structures of the tyrosine kinase domain of fibroblast growth factor receptor in complex with inhibitors. Science, 1997, 276, 955-960.
69. Fiedler, W.; Serve, H.; Dohner, H.; Schwittay, M.; Ottmann, O. G.; O'Farrell, A. M.; Bello, C. L.; Allred, R.; Manning, W. C.; Cherrington, J. M.; Louie, S. G.; Hong, W.; Brega, N. M.; Massimini, G.; Scigalla, P.; Berdel, W. E.; Hossfeld, D. K. A phase 1 study of SU11248 in the treatment of patients with refractory or resistant acute myeloid leukemia (AML) or not amenable to conventional therapy for the disease. Blood, 2005, 105, 986-993.
70. Fiedler, W.; Mesters, R.; Tinnefeld, H.; Loges, S.; Staib, P.; Duhrsen, U.; Flasshove, M.; Ottmann, O. G.; Jung, W.; Cavalli, F.; Kuse, R.; Thomalla, J.; Serve, H.; O'Farrell, A. M.; Jacobs, M.; Brega, N. M.; Scigalla, P.; Hossfeld, D. K.; Berdel, W. E. A phase 2 clinical study of SU5416 in patients with refractory acute myeloid leukemia. Blood, 2003, 102, 2763-2767.
71. Kim, D. W.; Jo, Y. S.; Jung, H. S.; Chung, H. K.; Song, J. H.; Park, K. C.; Park, S. H.; Hwang, J. H.; Rha, S. Y.; Kweon, G. R.; Lee, S. J.; Jo, K. W.; Shong, M. An orally administered multitarget tyrosine kinase inhibitor, SU11248, is a novel potent inhibitor of thyroid oncogenic RET/papillary thyroid cancer kinases. J. Clin. Endocrinol. Metab., 2006, 91, 4070-4076.
72. Mologni, L.; Sala, E.; Cazzaniga, S.; Rostagno, R.; Kuoni, T.; Puttini, M.; Bain, J.; Cleris, L.; Redaelli, S.; Riva, B.; Formelli, F.; Scapozza, L.; Gambacorti-Passerini, C. Inhibition of RET tyrosine kinase by SU5416. J. Mol. Endocrinol., 2006, 37, 199-212.
73. Carr, L.; Goulart, B.; Martins, R.; Keith, E.; Kell, E.; Wallace, S. Phase II trial of continuous dosing of sunitinib in advanced, FDG-PET avid, medullary thyroid carcinoma (MTC) and welldifferentiated thyroid cancer (WDTC). J. Clin. Oncol. (Meeting Abstracts), 2009, 27, 6056.
74. Cohen, E. E. W.; Needles, B. M.; Cullen, K. J.; Wong, S.; Wade, J.; Ivy, P. Phase 2 study of sunitinib in refractory thyroid cancer. J. Clin. Oncol. (Meeting Abstracts), 2008, 26, 6025.
75. Dawson, S. J.; Conus, N. M.; Toner, G. C.; Raleigh, J. M.; Hicks, R. J.; McArthur, G.; Rischin, D. Sustained clinical responses to tyrosine kinase inhibitor sunitinib in thyroid carcinoma. Anticancer Drugs, 2008, 19, 547-552.
76. Bugalho, M. J.; Domingues, R.; Borges, A. A case of advanced medullary thyroid carcinoma successfully treated with sunitinib. Oncologist, 2009, 14, 1083-1087.
77. Wilhelm, S. M.; Carter, C.; Tang, L.; Wilkie, D.; McNabola, A.; Rong, H.; Chen, C.; Zhang, X.; Vincent, P.; McHugh, M.; Cao, Y.; Shujath, J.; Gawlak, S.; Eveleigh, D.; Rowley, B.; Liu, L.; Adnane, L.; Lynch, M.; Auclair, D.; Taylor, I.; Gedrich, R.; Voznesensky, A.; Riedl, B.; Post, L. E.; Bollag, G.; Trail, P. A. B AY 43-9006 exhibits broad spectrum oral antitumor activity and targets the RAF/MEK/ERK pathway and receptor tyrosine kinases involved in tumor progression and angiogenesis. Cancer Res., 2004, 64, 7099-7109.
78. Carlomagno, F.; Anaganti, S.; Guida, T.; Salvatore, G.; Troncone, G.; Wilhelm, S. M.; Santoro, M. BAY 43-9006 inhibition of oncogenic RET mutants. J. Natl. Cancer Inst., 2006, 98, 326-334.
79. Lierman, E.; Folens, C.; Stover, E. H.; Mentens, N.; Van Miegroet, H.; Scheers, W.; Boogaerts, M.; Vandenberghe, P.; Marynen, P.; Cools, J. Sorafenib is a potent inhibitor of FIP1L1-PDGFRalpha and the imatinib-resistant FIP1L1-PDGFRalpha T674I mutant. Blood, 2006, 108, 1374-1376.
80. Lam, E. T.; Ringel, M. D.; Kloos, R. T.; Prior, T. W.; Knopp, M. V.; Liang, J.; Sammet, S.; Hall, N. C.; Wakely, P. E.; Jr.; Vasko, V. V.; Saji, M.; Snyder, P. J.; Wei, L.; Arbogast, D.; Collamore, M.; Wright, J. J.; Moley, J. F.; Villalona-Calero, M. A.; Shah, M. H. Phase II clinical trial of sorafenib in metastatic medullary thyroid cancer. J. Clin. Oncol., 2010, 28, 2323-2330.
81. Kloos, R. T.; Ringel, M. D.; Knopp, M. V.; Hall, N. C.; King, M.; Stevens, R.; Liang, J.; Wakely, P. E.; Jr.; Vasko, V. V.; Saji, M.; Rittenberry, J.; Wei, L.; Arbogast, D.; Collamore, M.; Wright, J. J.; Grever, M.; Shah, M. H. Phase II trial of sorafenib in metastatic thyroid cancer. J. Clin. Oncol., 2009, 27, 1675-1684.
82. Hoftijzer, H.; Heemstra, K. A.; Morreau, H.; Stokkel, M. P.; Corssmit, E. P.; Gelderblom, H.; Weijers, K.; Pereira, A. M.; Huijberts, M.; Kapiteijn, E.; Romijn, J. A.; Smit, J. W. Beneficial effects of sorafenib on tumor progression, but not on radioiodine uptake, in patients with differentiated thyroid carcinoma. Eur. J. Endocrinol., 2009, 161, 923-931.
83. Gupta-Abramson, V.; Troxel, A. B.; Nellore, A.; Puttaswamy, K.; Redlinger, M.; Ransone, K.; Mandel, S. J.; Flaherty, K. T.; Loevner, L. A.; O'Dwyer, P. J.; Brose, M. S. Phase II trial of sorafenib in advanced thyroid cancer. J. Clin. Oncol., 2008, 26, 4714-4719.
84. Kober, F.; Hermann, M.; Handler, A.; Krotla, G. Effect of sorafenib in symptomatic metastatic medullary thyroid cancer. J. Clin. Oncol. (Meeting Abstracts), 2007, 25, 14065.
85. Akeno-Stuart, N.; Croyle, M.; Knauf, J. A.; Malaguarnera, R.; Vitagliano, D.; Santoro, M.; Stephan, C.; Grosios, K.; Wartmann, M.; Cozens, R.; Caravatti, G.; Fabbro, D.; Lane, H. A.; Fagin, J. A. The RET kinase inhibitor NVP-AST487 blocks growth and calcitonin gene expression through distinct mechanisms in medullary thyroid cancer cells. Cancer Res., 2007, 67, 6956-6964.
86. La Montagne, K. R.; Butler, J.; Borowski, V. B.; Fuentes-Pesquera, A. R.; Blevitt, J. M.; Huang, S.; Li, R.; Connolly, P. J.; Greenberger, L. M. A highly selective, orally bioavailable, vascular endothelial growth factor receptor-2 tyrosine kinase inhibitor has potent activity in vitro and in vivo. Angiogenesis, 2009, 12, 287-296.
87. Polverino, A.; Coxon, A.; Starnes, C.; Diaz, Z.; De Melfi, T.; Wang, L.; Bready, J.; Estrada, J.; Cattley, R.; Kaufman, S.; Chen, D.; Gan, Y.; Kumar, G.; Meyer, J.; Neervannan, S.; Alva, G.; Talvenheimo, J.; Montestruque, S.; Tasker, A.; Patel, V.; Radinsky, R.; Kendall, R. AMG 706, an oral, multikinase inhibitor that selectively targets vascular endothelial growth factor, platelet-derived growth factor, and kit receptors, potently inhibits angiogenesis and induces regression in tumor xenografts. Cancer Res., 2006, 66, 8715-8721.
88. Sherman, S. I.; Wirth, L. J.; Droz, J. P.; Hofmann, M.; Bastholt, L.; Martins, R. G.; Licitra, L.; Eschenberg, M. J.; Sun, Y. N.; Juan, T.; Stepan, D. E.; Schlumberger, M. J. Motesanib diphosphate in progressive differentiated thyroid cancer. N. Engl. J. Med., 2008, 359, 31-42.
89. Schlumberger, M. J.; Elisei, R.; Bastholt, L.; Wirth, L. J.; Martins, R. G.; Locati, L. D.; Jarzab, B.; Pacini, F.; Daumerie, C.; Droz, J.-P.; Eschenberg, M. J.; Sun, Y.-N.; Juan, T.; Stepan, D. E.; Sherman, S. Phase II study of safety and efficacy of motesanib in patients with progressive or symptomatic, advanced or metastatic medullary thyroid cancer. J. Clin. Oncol., 2009, 23, 3794-3801.
90. Pardanani, A.; Hood, J.; Lasho, T.; Levine, R. L.; Martin, M. B.; Noronha, G.; Finke, C.; Mak, C. C.; Mesa, R.; Zhu, H.; Soll, R.; Gilliland, D. G.; Tefferi, A. TG101209, a small molecule JAK2-selective kinase inhibitor potently inhibits myeloproliferative disorder-associated JAK2V617F and MPLW515L/K mutations. Leukemia, 2007, 21, 1658-1668.
91. Clemens, G. R.; Schroeder, R. E.; Magness, S. H.; Weaver, E. V.; Lech, J. W.; Taylor, V. C.; Masuda, E. S.; Baluom, M.; Grossbard, E. B. Developmental toxicity associated with receptor tyrosine kinase Ret inhibition in reproductive toxicity testing. Birth Defects Res. A Clin. Mol. Teratol., 2009, 85, 130-136.
92. Zhang, Y.; Guessous, F.; Kofman, A.; Schiff, D.; Abounader, R. XL-184, a MET, VEGFR-2 and RET kinase inhibitor for the treatment of thyroid cancer, glioblastoma multiforme and NSCLC. IDrugs, 2010, 13, 112-121.
93. Kurzrock, R.; Sherman, S.; Hong, D.; Ng, C.; Frye, J.; Janisch, L.; Ratain, M. J.; Salgia, R. A Phase 1 Study of XL184, a MET, VEGFR2, and RET Kinase Inhibitor, Administered Orally to Patients (pts) with Advanced Malignancies, Including a Subgroup of Pts with Medullary Thyroid Cancer (MTC). AACR-NCI-EORTC International Conference, 2008.
94. Harrington, E. A.; Bebbington, D.; Moore, J.; Rasmussen, R. K.; Ajose-Adeogun, A. O.; Nakayama, T.; Graham, J. A.; Demur, C.; Hercend, T.; Diu-Hercend, A.; Su, M.; Golec, J. M.; Miller, K. M. VX-680, a potent and selective small-molecule inhibitor of the Aurora kinases, suppresses tumor growth in vivo. Nat. Med., 2004, 10, 262-267.
95. Carter, T. A.; Wodicka, L. M.; Shah, N. P.; Velasco, A. M.; Fabian, M. A.; Treiber, D. K.; Milanov, Z. V.; Atteridge, C. E.; Biggs, W. H.; 3rd, Edeen, P. T.; Floyd, M.; Ford, J. M.; Grotzfeld, R. M.; Herrgard, S.; Insko, D. E.; Mehta, S. A.; Patel, H. K.; Pao, W.; Sawyers, C. L.; Varmus, H.; Zarrinkar, P. P.; Lockhart, D. J. Inhibition of drug-resistant mutants of ABL, KIT, and EGF receptor kinases. Proc. Natl. Acad. Sci. U S A, 2005, 102, 11011-11016.
96. 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.
97. Arlot-Bonnemains, Y.; Baldini, E.; Martin, B.; Delcros, J. G.; Toller, M.; Curcio, F.; Ambesi-Impiombato, F. S.; D'Armiento, M.; Ulisse, S. Effects of the Aurora kinase inhibitor VX-680 on anaplastic thyroid cancer-derived cell lines. Endocr. Relat. Cancer, 2008, 15, 559-568.
98. Brandt, W.; Mologni, L.; Preu, L.; Lemcke, T.; Gambacorti-Passerini, C.; Kunick, C. Inhibitors of the RET tyrosine kinase based on a 2-(alkylsulfanyl)-4- (3-thienyl) nicotinonitrile scaffold. Eur. J. Med. Chem., 2010, 45, 2919-2927.
99. Rosen, L. S.; Kurzrock, R.; Mulay, M.; Van Vugt, A.; Purdom, M.; Ng, C.; Silverman, J.; Koutsoukos, A.; Sun, Y. N.; Bass, M. B.; Xu, R. Y.; Polverino, A.; Wiezorek, J. S.; Chang, D. D.; Benjamin, R.; Herbst, R. S. Safety, pharmacokinetics, and efficacy of AMG 706, an oral multikinase inhibitor, in patients with advanced solid tumors. J. Clin. Oncol., 2007, 25, 2369-2376.