Abstract
Purpose :
In this study, we explored the anti-angiogenic function of EGT022 on VEGF-induced endothelial cells
Methods :
angiogenesis inhibition assay
Results :
EGT022 was able to significantly inhibited angiogenesis including proliferation, migration, tube formation, and permeability in HUVEC cells. We also showed that EGT022 binds directly to integrin αvβ3, dephosphorylates integrin β3, and inhibits phosphorylation of VEGFR2. In addition, EGT022 inhibits the phosphorylation of PLC-γ1 and the activation of NFAT, a downstream pathway of VEGF, in HUVEC cells. These results clearly demonstrate that EGT022 is an effective integrin β3 antagonist acting as an anti-angiogenic role on endothelial cells and has the potential to treat diseases directly related to VEGF-induced neovascularization.
Conclusions :
Therefore, intravitreal injection of EGT022 can block harmful VEGF signaling, like current injectable anti-VEGF therapies such as Aflibercept (96.6 kDa), Bevacizumab (149 kDa), Brolucizumab (26 kDa), and Ranibizumab (49 kDa) for the treatment of neovascular (wet) age-related macular degeneration (AMD). In particular, EGT022 has the lowest molecular weight of 12 kDa compared to current anti-VEGF drugs, which can promote diffusion in vitreous humor and reaching the retina, resulting in better efficacy.
This abstract was presented at the 2023 ARVO Annual Meeting, held in New Orleans, LA, April 23-27, 2023.