Receptors VEGF

VEGF receptor blockers Small receptor tyrosine kinase antagonists... 

Antibody targeting Use of mono-and bispecific antibodies to target components of angiogenic blood vessels (e.g., VEGF receptors, endoglin, L19 antigen) to deliver specific angio- and/or tumoricidal activity... 

Olsson AK, Dimberg A, Kreuger J et al (2006) VEGF receptor signaling in control of vascular function. Nat Rev Mol Cell Biol 7(5) 3 59-371... 

VEGF family - VEGF-A, B, C, D, E and PLGF VEGFR - VEGF receptor-1, 2, and 3 Formation and maintenance of vasculature... 

Shen J, Samul R, Silva RL et al (2006) Suppression of ocular neovascularization with siRNA targeting VEGF receptor 1. Gene Ther 13 (3) 225-234... 

All RTKs contain between one and three tyrosines in the kinase activation loop, which is composed of subdomains VII and VIII of the protein kinase catalytic core. Phosphorylation of these tyrosines has been shown to be critical for stimulation of catalytic activity and biological function for a number of RTKs, including insulin receptor, FGF receptor, VEGF receptor, PDGF receptor, Met (hepatocyte growth factor receptor), and TrkA (NGF receptor). A major exception is the EGF receptor, for which autophosphorylation of a conserved tyrosine in the activation loop does not seem to be involved in signaling. Substitution of tyrosine with phenylalanine has no effect on RTK activity or downstream signals. 

Similar chemistry was used to synthesize pyridyl(methyl)phthalazines, 193, inhibitors of the VEGF receptor tyrosine kinase. The active inhibitors 193 were formed by condensation of 192 with hydrazine, followed by POCI3 chlorination. <00JMC2310>. Furthermore, a simple substitution reaction with p-chloroaniline gave anilinophthalazine 194. 

Cross MJ, Dixelius J, Matsumoto T, et al. VEGF-receptor signal transduction. Trends Biochem Sci 2003 28 488-94. 

Katoh O, Tauchi H, Kawaishi K, et al. Expression of the vascular endothelial growth factor (VEGF) receptor gene, KDR, in hematopoietic cells and inhibitory effect of VEGF on apoptotic cell death caused by ionizing radiation. Cancer Res 1995 55(23) 5687-5692. 

Schlaeppi JM, Wood JM. Targeting vascular endothelial growth factor (VEGF) for anti-tumor therapy, by anti-VEGF neutralizing monoclonal antibodies or by VEGF receptor tyrosine kinase inhibitors. Cancer Metastasis Rev 1999 18 4734-81. 

Witte L, Hicklin DJ, Zhu Z, et al. Monoclonal antibodies targeting the VEGF receptor-2 (Flk-l/KDR) as an anti-angiogenic therapeutic strategy. Cancer Metastasis Rev 1998 17 155-161. 

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