Open AccessSKLB1002, a potent inhibitor of VEGF receptor 2 signaling, inhibits endothelial angiogenic function in�vitro and ocular angiogenesis in�vivo
Author(s) -
Qiuyang Zhang,
Tao Shu-Ya,
Li-Yin Chang,
Jingjing Li,
XiuMiao Li,
Jin Yao,
Qin Jiang,
Biao Yan
Publication year - 2020
Publication title -
molecular medicine reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.727
H-Index - 56
eISSN - 1791-3004
pISSN - 1791-2997
DOI - 10.3892/mmr.2020.11056
Subject(s) - angiogenesis , corneal neovascularization , neovascularization , kinase insert domain receptor , vascular endothelial growth factor , pharmacology , biology , cancer research , in vivo , endothelial stem cell , cornea , vascular endothelial growth factor a , microbiology and biotechnology , in vitro , biochemistry , vegf receptors , neuroscience
Ocular angiogenesis is a major cause of severe vision loss, which can affect several parts of the eye, including the retina, choroid and cornea. Vascular endothelial growth factor receptor 2 (VEGFR2) inhibitors have demonstrated great potential for treating ocular angiogenesis and SKLB1002 is a potent inhibitor of VEGF receptor 2 signaling. The present study investigated the effects of SKLB1002 administration on ocular angiogenesis. SKLB1002 administration did not show obvious cytotoxicity and tissue toxicity at the tested concentrations. In an alkali‑burn corneal model, SKLB1002 administration significantly decreased the mean length and number of new corneal blood vessels. SKLB1002 administration significantly reduced endothelial cell proliferation, migration and tube formation in vitro. Mechanistically, SKLB1002 inhibited endothelial angiogenic functions by blocking the phosphorylation of ERK1/2, JNK and p38. Thus, selective inhibition of VEGFR‑2 through SKLB1002 administration is a promising therapy for ocular angiogenesis.