Suppression of pathological ocular neovascularization by a small molecule, SU1498

Tao Shu-Ya; Zhang Qiu-Yang; Li Jing-Jing; Yao Jin; Yan Biao

doi:10.1016/j.biopha.2020.110248

Suppression of pathological ocular neovascularization by a small molecule, SU1498

Biomed Pharmacother. 2020 Aug:128:110248. doi: 10.1016/j.biopha.2020.110248. Epub 2020 May 23.

Authors

Tao Shu-Ya¹, Zhang Qiu-Yang¹, Li Jing-Jing², Yao Jin³, Yan Biao⁴

Affiliations

¹ The Affiliated Eye Hospital, Nanjing Medical University, Nanjing, China; The Fourth School of Clinical Medicine, Nanjing Medical University, Nanjing, China.
² The Fourth School of Clinical Medicine, Nanjing Medical University, Nanjing, China.
³ The Affiliated Eye Hospital, Nanjing Medical University, Nanjing, China; The Fourth School of Clinical Medicine, Nanjing Medical University, Nanjing, China. Electronic address: jinyao1972@126.com.
⁴ Eye Institute, Eye & ENT Hospital, Shanghai Medical College, Fudan University, Shanghai, China; Shanghai Key Laboratory of Visual Impairment and Restoration, Shanghai, China; National Health Commission (NHC) Key Laboratory of Myopia, Fudan University, Shanghai, China. Electronic address: biao.yan@fdeent.org.

PMID: 32454287
DOI: 10.1016/j.biopha.2020.110248

Abstract

Selective inhibition of vascular endothelial growth factor receptor (VEGFR), particularly VEGFR-2, is an efficient method for the treatment of ocular neovascularization. SU1498 is a specific inhibitor of VEGFR-2. In this study, we investigated the role of SU1498 in ocular neovascularization. Administration of SU1498 did not show any cytotoxicity and tissue toxicity at the tested concentrations. Administration of SU1498 reduced the size and thickness of choroidal neovascularization and decreased the mean length and mean number of corneal neovascular vessels induced by alkali burn. Pretreatment of SU1498 significantly reduced the proliferation, migration, and tube formation ability of HUVECs. SU1498 played the anti-angiogenic role through the regulation of p38-MAPK signaling. Taken together, inhibition of VEGFR-2 by SU1498 provides a novel therapeutic approach for ocular neovascularization.

Keywords: MAPK signaling; Ocular neovascularization; VEGFR-2 inhibitor.

MeSH terms

Angiogenesis Inhibitors / pharmacology*
Animals
Cell Movement / drug effects
Cell Proliferation / drug effects
Cells, Cultured
Choroid / blood supply*
Choroidal Neovascularization / metabolism
Choroidal Neovascularization / pathology
Choroidal Neovascularization / prevention & control*
Cinnamates / pharmacology*
Cornea / blood supply*
Corneal Neovascularization / metabolism
Corneal Neovascularization / pathology
Corneal Neovascularization / prevention & control*
Disease Models, Animal
Endothelial Cells / drug effects*
Endothelial Cells / metabolism
Endothelial Cells / pathology
Human Umbilical Vein Endothelial Cells / drug effects
Human Umbilical Vein Endothelial Cells / metabolism
Humans
Male
Mice, Inbred C57BL
Neovascularization, Physiologic / drug effects
Signal Transduction
Vascular Endothelial Growth Factor Receptor-2 / antagonists & inhibitors*
Vascular Endothelial Growth Factor Receptor-2 / metabolism

Substances

Angiogenesis Inhibitors
Cinnamates
SU 1498
KDR protein, human
Kdr protein, mouse
Vascular Endothelial Growth Factor Receptor-2