Discovery of Motesanib

Kinase Inhibitor Drugs

Volumn , Issue , 2009, Pages 113-130

  Tasker, Andrew S ^a   Patel, Vinod F ^a  

^a AMGEN INC   (United States)

Author keywords

Discovery of motesanib; Lead optimization strategy; Motesanib and assessing activity along VEGF VEGFR signaling pathway

Indexed keywords

EID: 77955267962     PISSN: None     EISSN: None     Source Type: Book    
DOI: 10.1002/9780470524961.ch5     Document Type: Chapter

References (30)

1. Adamis, A.P., Shima, D.T., Yeo, K.T., et al. (1993). Synthesis and secretion of vascular permeability factor/vascular endothelial growth factor by human retinal pigment epithelial cells. Biochem Biophys Res Commun. 193 (2), 631-638.
2. Bold, G., Altmann, K.-H., Frei, J., et al. (2000). New anilinophthalazines as potent and orally well absorbed inhibitors of the VEGF receptor tyrosine kinases useful as antagonists of tumor-driven angiogenesis. J Med Chem. 43 (12), 2310-2323.
3. Carmeliet, P., and Jain, R.K. (2000). Angiogenesis in cancer and other diseases. Nature. 407, 249-257.
4. Cohen, M. H., Gootenberg, J., Keegan, P., et al. (2007). FDA drug approval summary:bevacizumab plus FOLFOX4 as second-line treatment of colorectal cancer. Oncologist. 12, 356-361.
5. Coxon, A., Bush, T., Saffran, D., et al. (2009). Broad antitumor activity in breast cancer xenografts by motesanib, a highly selective, oral inhibitor of VEGF, PDGF, and kit receptors. Clin Cancer Res. 15 (1), 110-118.
6. Detmar, M. (2000). The role of VEGF and thrombospondins in skin angiogenesis. J Dermatol Sci. 24, S78-S84.
7. Dominguez, C., Smith, L., Huang, Q., et al. (2007). Discovery of N-phenyl nicotinamides as potent inhibitors of Kdr. Bioorg Med Chem Lett. 17 (21), 6003-6008.
8. Drevs, J., Siegert, P., Medinger, M., et al. (2007). Phase I clinical study of AZD2171, an oral vascular endothelial growth factor signaling inhibitor, in patients with advanced solid tumors. J Clin Oncol. 25 (21), 3045-3054.
9. Dvorak, H. F. (2002). Vascular permeability factor/vascular endothelial growth factor:a critical cytokine in tumor angiogenesis and a potential target for diagnosis and therapy. J Clin Oncol. 20 (21), 4368-4380.
10. Faivre, S., Delgaldo, C., Vera, K., et al. (2006). Safety, pharmacokinetic, and antitumor activity of SU11248, a novel oral multitarget tyrosine kinase inhibitor, in patients with cancer. J Clin Oncol. 24 (1), 25-35.
11. Goodman, V. L., Rock, E. P., Dagher, R., et al. (2007). Approval summary: sunitinib for the treatment of imatinib refractory or intolerant gastrointestinal stromal tumors and advanced renal cell carcinoma. Clin Cancer Res. 13, 1367-1373.
12. Giatromanolaki, A., Sivridis, E., Athanassou, N., et al. (2001). The angiogenic pathway " vascular endothelial growth factor/flk-1(KDR)-receptor " in rheumatoid arthritis and osteoarthritis. J Pathol. 194 (1), 101-108.
13. Hurwitz, H., Fehrenbacher, L., Novotny, W., et al. (2004). Bevacizumab plus irinotecan, fluorouracil, and leucovorin for metastatic colorectal cancer. N Engl J Med. 350 (23), 2335-2342.
14. Hurwitz, H., Dowlati, A., Savage, S., et al. (2005). Safety, tolerability, and pharmacokinetics of oral administration of GW786034 in patients with solid tumors. J Clin Oncol. 23 (16S), 3012.
15. Larock, R. C., and Babu, S. (1987). Synthesis of nitrogen heterocycles via palladium-catalyzed intramolecular cyclization. Tetrahedron Lett. 28 (44), 5291-5294.
16. Li, B., Ogasawara, A. K., Yang, R., et al. (2002). KDR (VEGF receptor 2) is the major mediator for the hypotensive effect of VEGF. Hypertension. 39, 1095-1100.
17. Liu, P., Huang, L., Lu, Y., et al. (2007). Synthesis of heterocycles via ligand-free palladium catalyzed reductive Heck cyclization. Tetetrahedron Lett. 48 (13), 2307-2310.
18. McTigue, M. A., Wickersham, J. A., Pinko, C., et al. (1999). Crystal structure of the kinase domain of human vascular endothelial growth factor receptor 2: a key enzyme in angiogenesis. Structure. 7 (3), 319-330.
19. Mohammadi, M., Schlessinger, J., and Hubbard, S. R. (1996). Structure of the FGF receptor tyrosine kinase domain reveals a novel autoinhibitory mechanism. Cell. 86, 577-587.
20. Motzer, R. J., Michaelson, M. D., Redman, B. G., et al. (2006). Activity of SU11248, a multitargeted inhibitor of vascular endothelial growth factor receptor and platelet-derived growth factor receptor, in patients with metastatic renal cell carcinoma. J Clin Oncol. 24 (1), 16-24.
21. Polverino, A., Coxon, A., Starnes, C., et al. (2006). 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. 66 (17), 8715-8721.
22. Rosen, L. S., Kurzrock, R., Mulay, M., et al. (2007). Safety, pharmacokinetics, and efficacy of AMG 706, an oral multikinase inhibitor, in patients with advanced solid tumors. J Clin Oncol. 25 (17), 2369-2376.
23. Ryan, C., Stadler, W. M., Roth, B. J., et al. (2005). Safety and tolerability of AZD2171, a highly potent VEGFR inhibitor, in patients with advanced prostate adenocarcinoma . J Clin Oncol. 23 (204S), 3049.
24. Sandler, A., Gray, R., Perry, M. C., et al. (2006). Paclitaxel-carboplatin alone or with bevacizumab for non-small-cell lung cancer. N Engl J Med. 355, 2542-2550.
25. Schindler, T., Bornmann, W., Pellicena, P., et al. (2000). Structural mechanism for STI-571 inhibition of Abelson tyrosine kinase. Science. 289, 1938-1942.
26. Strumberg, D., Richly, H., Hilger, R. A., et al. (2005). Phase I clinical and pharmacokinetic study of the novel Raf kinase and vascular endothelial growth factor receptor inhibitor BAY 43-9006 in patients with advanced refractory solid tumors. J Clin Oncol. 23 (5), 965-972.
27. Thomas, A. L., Morgan, B., Horsfield, M. A., et al. (2005). Phase I study of the safety, tolerability, pharmacokinetics, and pharmacodynamics of PTK787/ZK 222584 administered twice daily in patients with advanced cancer. J Clin Oncol. 23 (18), 4162-4171.
28. Winn, M., De, B., Zydowsky, T. M., et al. (1993). 2-(Alkylamino)nicotinic acid and analogs. Potent angiotensin II antagonists. J Med Chem. 36 (18), 2676-2688.
29. Witte, L., Hicklin, D. J., Zhu, Z., et al. (1998). Monoclonal antibodies targeting the VEGF receptor-2 (Flk1/KDR) as an anti-angiogenic therapeutic strategy. Cancer Metastasis Rev. 17, 155-161.
30. Zhu, A. X. (2008). Development of sorafenib and other molecularly targeted agents in hepatocellular carcinoma. Cancer. 112, 250-259.