2. Academic Validation
  3. CM082, a novel VEGF receptor tyrosine kinase inhibitor, can inhibit angiogenesis in vitro and in vivo

CM082, a novel VEGF receptor tyrosine kinase inhibitor, can inhibit angiogenesis in vitro and in vivo

  • Microvasc Res. 2021 Jul;136:104146. doi: 10.1016/j.mvr.2021.104146.
Handong Dan 1,  Xinlan Lei 2,  Xin Huang 2,  Ning Ma 2,  Yiqiao Xing 2,  Yin Shen 3
Affiliations

Affiliations

  • 1 Henan Eye Institute, Henan Eye Hospital, Henan Key Laboratory of Ophthalmology and Visual Science, Henan Provincial People's Hospital, People's Hospital of Zhengzhou University, People's Hospital of Henan University, No. 7 Weiwu Road, Zhengzhou 450000, Henan, China.
  • 2 Eye Center, Renmin Hospital of Wuhan University, No. 99 ZhangZhiDong Road, Wuhan 430060, Hubei, China.
  • 3 Eye Center, Renmin Hospital of Wuhan University, No. 99 ZhangZhiDong Road, Wuhan 430060, Hubei, China. Electronic address: yinshen@whu.edu.cn.
PMID: 33610563 DOI: 10.1016/j.mvr.2021.104146
Abstract

The goal of this study was to evaluate the effects of CM082, a novel vascular endothelial growth factor (VEGF) receptor-2 tyrosine kinase inhibitor, on human umbilical vein endothelial cells (HUVECs), and oxygen-induced retinopathy (OIR) mice. HUVECs were stimulated with rHuVEGF165 and then treated with CM082 to assess the antiangiogenic effects of CM082; subsequently, proliferation, wound-healing migration, Transwell invasion, tube formation assays, and Western blotting were performed in vitro. Retinal neovascularization tufts, avascular area, and TUNEL assays were estimated for OIR mice after intraperitoneal injection with CM082. CM082 significantly inhibited proliferation, migration, invasion, and tube formation induced by stimulation of HUVECs with rHuVEGF165; this inhibitory effect was mediated by blocking VEGFR2/KDR/Flk-1 activation. CM082 significantly inhibited retinal neovascularization and avascular area and did not increase Apoptosis in the retina of OIR mice. The findings demonstrated that CM082 exhibits highly antiangiogenic effects in HUVECs and OIR mice. Thus, it may serve as an alternative treatment for neovascular eye disease in the future.

Keywords

CM082; Human umbilical vein endothelial cells (HUVEC); Oxygen-induced retinopathy (OIR); Vascular endothelial growth factor (VEGF).

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