Receptors vascular endothelial growth factor

Optimization of the large (MW = 512), lipophilic (clogP = 7.6), and very potent (Kj = 0.22 nM) Vascular Endothelial Growth Factor Receptor Tyrosine Kinase (VEGFR TK) inhibitor 8 (LLE = 2.1) to produce the development candidate axitinib (9) was recently reported [17]. 

L, Zinkewich-Peotti K, Jayson GC (2007) Phase I evaluation of CDP791, a PEGylated di-Fab conjugate that binds vascular endothelial growth factor receptor 2. Clin Cancer Res 13 7113-7118... 

B.K., Yu, S. and Hartman, G.D. (2004) Potent N-(l,3-thiazoyl-2-yl)pyridine-2-amine vascular endothelial growth factor receptor tyrosine kinase inhibitors with excellent pharmacokinetics and low affinity for the hERG ion channel. Journal of Medicinal Chemistry, 47, 6363-6372. 

Kinase domain receptor (vascular endothelial growth factor receptor 2)... 

Development of Angiogenesis Inhibitors to Vascular Endothelial Growth Factor Receptor 2 for Cancer Therapy... 

VEGFR Vascular endothelial growth factor receptor... 

STAT-3 Signal transducer and activator of transcription-3 VEGFR Vascular endothelial growth factor receptor... 

Epidermal growth factor receptor (EGFR) Fibroblast growth factor receptor (FGFR) Vascular endothelial growth factor receptor (VEGFR)... 

Geng L, Donnelly E, McMahon G, et al. Inhibition of vascular endothelial growth factor receptor signaling leads to reversal of tumor resistance to radiotherapy. Cancer Res 2001 61(6) 2413-2419. 

Fong TAT, Shawver LK, Sun L, et al. SU5416 is a potent and selective inhibitor of the vascular endothelial growth factor receptor (Flk-l/KDR) that inhibits tyrosine kinase catalysis, tumor vascularization, and growth of multiple tumor types. Cancer Res 1999 59 99-106. 

Lin P, Sankar S, Shan S, et al. Inhibition of tumor growth by targeting tumor endothelium using a soluble vascular endothelial growth factor receptor. Cell Growth Differ 1998 9(l) 49-58. 

Valter MM, Hugel A, Huang HJ, et al. Expression of the Ets-1 transcription factor in human astrocytomas is associated with Fms-like tyrosine kinase-1 (Flt-l)/vascular endothelial growth factor receptor-1 synthesis and neoangiogenesis. Cancer Res 1999 59(21) 5608-5614. 

Goldman C, Kendall RL, Cabrera G, et al. Paracrine expression of a native soluble vascular endothelial growth factor receptor inhibits tumor growth, metastasis, and mortality rate. Proc Natl Acad Sci 1998 95 8795-8800. 

Kozin SV, Boucher Y, Hicklin DJ, et al. Vascular endothelial growth factor receptor-2-blocking antibody potentiates radiation-induced long-term control of human tumor xenografts. Cancer Res 2001 61 39 14. 

Shaheen RM, Davis DW, Liu W, et al. Antiangiogenic therapy targeting the tyrosine kinase receptor for vascular endothelial growth factor receptor inhibits the growth of colon cancer liver metastasis and induces tumor and endothelial cell apoptosis. Cancer Res 1999 59(21) 5412-5416. 

Compound 57 has been identified as a vascular endothelial growth factor receptor-2 (VEGFR-2) kinase inhibitor of interest for the treatment of cancer <20030PD676>. 

Pavco, P.A., Bouhana, K.S., Gallegos, A.M., Agrawal, A., Blanchard, K.S., Grimm, S.L. et al. (2000) Anticancer and anti-metastatic activity of ribozymes targeting the messenger RNA of vascular endothelial growth factor receptors. Clin. Cancer Res., 6, 2094-2103. 

Paavonen, K., Puolakkainen, P., Jussila, L., Jahkola, T. and Alitalo, K. (2000) Vascular endothelial growth factor receptor-3 in lymphangiogenesis in wound healing. Am. J. Pathol, 156, 1499-1504. 

Piossek, C., Thierauch, K.-H., Schneider-Mergener, J., et al. (2003) Potent inhibition of angiogenesis by D, L-peptides derived from vascular endothelial growth factor receptor 2. Thromb Haemost. 90, 501-510. 

Strumberg D 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 23 965-972... 

Reardon DA et al (2009) Phase I pharmacokinetic study of the vascular endothelial growth factor receptor tyrosine kinase inhibitor vatalanib (PTK787) plus imatinib and hydroxyurea for malignant glioma. Cancer 115 2188-2198... 

Fox E et al (2010) A phase 1 trial and pharmacokinetic study of cediranib, an orally bioavail-able pan-vascular endothelial growth factor receptor inhibitor, in children and adolescents with refractory solid tumors. J Clin Oncol 28 5174-5181... 

Eskens FA et al (2006) The clinical toxicity profile of vascular endothelial growth factor (VEGF) and vascular endothelial growth factor receptor (VEGFR) targeting angiogenesis inhibitors a review. Eur J Cancer 42 3127-3139... 

Bussolati, B., Dunk, C., Mason, M., Kontos, C.D., and Ahmed, A. 2001. Vascular endothelial growth factor receptor-1 modulates vascular endothelial growth factor mediated angiogenesis via nitric oxide. Am. J. Pathol. 159 993-1008. 

Kroll, J., and Waltenberger, J. 1997. The vascular endothelial growth factor receptor KDR activates multiple signal transduction pathways in porcine aortic endothelial cells../. Biol. Chem. 272 32521-32527. 

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