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

文献类型：期刊论文

作者Zhang, Huiying2; Li, Bo1,3; Ding, Jingjuan2; Ye, Rong2; Xu, Zhijian1,3; Zhang, Qiuyang2; Feng, Siguo2; Jiang, Qin2; Zhu, Weiliang1,3; Yan, Biao4,5,6
刊名SCIENTIFIC REPORTS
出版日期2022-12-13
卷号12期号:1页码:15
ISSN号2045-2322
DOI10.1038/s41598-022-25811-0
通讯作者Jiang, Qin(jiangqin710@126.com) ; Zhu, Weiliang(wlzhu@simm.ac.cn) ; Yan, Biao(biao.yan@fdeent.org)
英文摘要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.
WOS关键词DIABETIC-RETINOPATHY ; ANGIOGENESIS ; CELLS ; RANIBIZUMAB ; EXPRESSION ; ADHESION ; THERAPY ; ICAM-1 ; MAPK
资助项目National Natural Science Foundation of China[82070983] ; National Natural Science Foundation of China[22077131] ; National Natural Science Foundation of China[81872797] ; National Natural Science Foundation of China[81970909]
WOS研究方向Science & Technology - Other Topics
语种英语
出版者NATURE PORTFOLIO
WOS记录号WOS:001014759800077
源URL[http://119.78.100.183/handle/2S10ELR8/306436]  
专题新药研究国家重点实验室
通讯作者Jiang, Qin; Zhu, Weiliang; Yan, Biao
作者单位1.State Key Lab Drug Res, Shanghai, Peoples R China
2.Nanjing Med Univ, Affiliated Eye Hosp, Nanjing, Peoples R China
3.Shanghai Inst Mat Med, Drug Discovery & Design Ctr, Shanghai, Peoples R China
4.Fudan Univ, Eye & ENT Hosp, State Key Lab Med Neurobiol, Shanghai, Peoples R China
5.Shanghai Key Lab Visual Impairment & Restorat, Shanghai, Peoples R China
6.Fudan Univ, Natl Hlth Commiss NHC, Key Lab Myopia, Shanghai, Peoples R China
推荐引用方式
GB/T 7714		 Zhang, Huiying,Li, Bo,Ding, Jingjuan,et al. DCZ19931, a novel multi-targeting kinase inhibitor, inhibits ocular neovascularization[J]. SCIENTIFIC REPORTS,2022,12(1):15.
APA Zhang, Huiying.,Li, Bo.,Ding, Jingjuan.,Ye, Rong.,Xu, Zhijian.,...&Yan, Biao.(2022).DCZ19931, a novel multi-targeting kinase inhibitor, inhibits ocular neovascularization.SCIENTIFIC REPORTS,12(1),15.
MLA Zhang, Huiying,et al."DCZ19931, a novel multi-targeting kinase inhibitor, inhibits ocular neovascularization".SCIENTIFIC REPORTS 12.1(2022):15.

入库方式： OAI收割

来源：上海药物研究所

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