2. Academic Validation
  3. DCZ19931, a novel multi-targeting kinase inhibitor, inhibits ocular neovascularization

DCZ19931, a novel multi-targeting kinase inhibitor, inhibits ocular neovascularization

  • Sci Rep. 2022 Dec 13;12(1):21539. doi: 10.1038/s41598-022-25811-0.
Huiying Zhang # 1,  Bo Li # 2 3,  Jingjuan Ding # 1,  Rong Ye 1,  Zhijian Xu 2 3,  Qiuyang Zhang 1,  Siguo Feng 1,  Qin Jiang 4,  Weiliang Zhu 5 6,  Biao Yan 7 8 9
Affiliations

Affiliations

  • 1 The Affiliated Eye Hospital, Nanjing Medical University, Nanjing, China.
  • 2 State Key Laboratory of Drug Research, Shanghai, China.
  • 3 Drug Discovery and Design Center, Shanghai Institute of Materia Medica, Shanghai, China.
  • 4 The Affiliated Eye Hospital, Nanjing Medical University, Nanjing, China. jiangqin710@126.com.
  • 5 State Key Laboratory of Drug Research, Shanghai, China. wlzhu@simm.ac.cn.
  • 6 Drug Discovery and Design Center, Shanghai Institute of Materia Medica, Shanghai, China. wlzhu@simm.ac.cn.
  • 7 Eye & ENT Hospital, State Key Laboratory of Medical Neurobiology, Fudan University, Shanghai, China. biao.yan@fdeent.org.
  • 8 Shanghai Key Laboratory of Visual Impairment and Restoration, Shanghai, China. biao.yan@fdeent.org.
  • 9 National Health Commission (NHC) Key Laboratory of Myopia, Fudan University, Shanghai, China. biao.yan@fdeent.org.
  • # Contributed equally.
PMID: 36513701 DOI: 10.1038/s41598-022-25811-0
Abstract

Neovascularization is a prominent cause of irreversible blindness in a variety of ocular diseases. Current therapies for pathological neovascularization are concentrated on the suppression of vascular endothelial growth factors (VEGF). Despite the remarkable efficacy of anti-VEGF drugs, several problems still exist, including ocular complications and drug resistance. Thus, it is still required to design novel drugs for anti-angiogenic treatment. This study aimed to investigate the anti-angiogenic effects of a small molecule multi-target tyrosine kinase inhibitor, DCZ19931, on ocular neovascularization. The results showed that administration of DCZ19931 at the tested concentrations did not cause obvious cytotoxicity and tissue toxicity. DCZ19931 could reduce the size of choroidal neovascularization (CNV) lesions in laser-induced CNV model and suppress ocular neovascularization in oxygen-induced retinopathy (OIR) model. DCZ19931 could suppress VEGF-induced proliferation, migration, and tube formation ability of endothelial cells, exhibiting similar anti-angiogenic effects as Ranibizumab. DCZ19931 could reduce the levels of intercellular cell adhesion molecule-1 (ICAM-1) expression in vivo and in vitro. Network pharmacology prediction and western blots revealed that DCZ19931 exerted its anti-angiogenic effects through the inactivation of ERK1/2-MAPK signaling and p38-MAPK signaling. In conclusion, this study indicates that DCZ19931 is a promising drug for anti-angiogenic therapy for ocular diseases.

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