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Sökning: WFRF:(Dragoni Silvia)

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  • Persson Skare, Tor, et al. (författare)
  • Novel anti-VEGF therapeutics
  • Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
    • Excessive and chronic vascular leakage in pathologies such as eye diseases leads to edema, tissue ischemia and disease progression. To suppress vascular leakage by blocking vascular endothelial growth factor (VEGF) function is clinically beneficial. However, development of new, topically applied therapeutic options is important as intravitreal injections currently carried out to deliver anti-VEGF therapeutics is expensive and may have serious side effects. VEGF receptor-2 (VEGFR2) activates Src family kinases via binding the T cell specific adaptor (TSAd) to its phosphotyrosine residue Y951. These molecular interactions are required for gap formation at endothelial junctions and vascular leakage. Here, we describe the identification from a high throughput screen, of a small molecular weight inhibitor (LC1) which blocks the interaction between the phosphorylated VEGFR2 kinase domain and TSAd. LC1 binds to TSAd in surface plasmon resonance analysis. In intact cells, LC1 suppresses VEGFR2 kinase activity while if fails to inhibit kinase activity in an in vitro biochemical kinase screen of 35 kinases including VEGFR2. Superfusion of retinal explants blocks vascular leakage from retinal vessels. In conclusion, we have identified a compound which specifically blocks VEGFR2 function in endothelial cells.
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