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Suppression of Pathological Ocular Neovascularization by a Small Molecular Multi-Targeting Kinase Inhibitor, DCZ19903

文献类型：期刊论文

作者Ding, Jingjuan1; Li, Bo2,3; Zhang, Huiying1; Xu, Zhijian2,3; Zhang, Qiuyang1; Ye, Rong1; Feng, Siguo1; Jiang, Qin1; Zhu, Weiliang2,3; Yan, Biao5,6
刊名TRANSLATIONAL VISION SCIENCE & TECHNOLOGY
出版日期2022-12-01
卷号11期号:12页码:15
ISSN号2164-2591
关键词ocular neovascularization DCZ19903 multitarget kinase inhibitor network pharmacology MAPK signaling pathway
DOI10.1167/tvst.11.12.8
通讯作者Zhu, Weiliang(wlzhu@simm.ac.cn) ; Yan, Biao(biao.yan@fdeent.org)
英文摘要Purpose: The administration of anti-vascular endothelial growth factor agents is the standard firs-line therapy for ocular vascular diseases, but some patients still have poor outcomes and drug resistance. This study investigated the role of DCZ19903, a small molecule multitarget kinase inhibitor, in ocular angiogenesis. Methods: The toxicity of DCZ19903 was evaluated by 3-(4, 5-dimethylthiazol-2-yl)2,5-diphenyltetrazolium bromide assays, flow cytometry, Calcein-AM/PI staining, and terminal uridine nick-end labeling staining. Oxygen-induced retinopathy and laser-induced choroidal neovascularization models were adopted to assess the antiangiogenic effects of DCZ19903 by Isolectin B4 (GS-IB4) and hematoxylin-eosin staining. EdU assays, transwell migration assays, tube formation, and choroid sprouting assays were performed to determine the antiangiogenic effects of DCZ19903. The antiangiogenic mechanism of DCZ19903 was determined using network pharmacology approach and western blots. Results: There was no obvious cytotoxicity or tissue toxicity after DCZ19903 treatment. DCZ19903 exerted the antiangiogenic effects in OIR model and choroidal neovascularization model. DCZ19903 inhibited the proliferation, tube formation, migration ability of endothelial cells, and choroidal explant sprouting. DCZ19903 plus ranibizumab achieved greater antiangiogenetic effects than DCZ19903 or ranibizumab alone. DCZ19903 exerted its antiangiogenic effects via affecting the activation of ERK1/2 and p38 signaling. Conclusions: DCZ19903 is a promising drug for antiangiogenic treatment in ocular vascular diseases. Translational Relevance: These findings suggest that DCZ19903 possesses great antiangiogenic potential for treating ocular vascular diseases.
WOS关键词ENDOTHELIAL GROWTH-FACTOR ; TUMOR-GROWTH ; ANTI-VEGF ; ANGIOGENESIS ; BEVACIZUMAB ; BLOCKADE
资助项目National Natural Science Foundation of China[81570859] ; National Natural Science Foundation of China[82070983] ; National Natural Science Foundation of China[81872797] ; National Natural Science Foundation of China[22077131]
WOS研究方向Ophthalmology
语种英语
出版者ASSOC RESEARCH VISION OPHTHALMOLOGY INC
WOS记录号WOS:001000743100016
源URL[http://119.78.100.183/handle/2S10ELR8/306680]  
专题新药研究国家重点实验室
通讯作者Zhu, Weiliang; Yan, Biao
作者单位1.Nanjing Med Univ, Affiliated Eye Hosp, Nanjing, Peoples R China
2.State Key Lab Drug Res, Shanghai, 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		 Ding, Jingjuan,Li, Bo,Zhang, Huiying,et al. Suppression of Pathological Ocular Neovascularization by a Small Molecular Multi-Targeting Kinase Inhibitor, DCZ19903[J]. TRANSLATIONAL VISION SCIENCE & TECHNOLOGY,2022,11(12):15.
APA Ding, Jingjuan.,Li, Bo.,Zhang, Huiying.,Xu, Zhijian.,Zhang, Qiuyang.,...&Yan, Biao.(2022).Suppression of Pathological Ocular Neovascularization by a Small Molecular Multi-Targeting Kinase Inhibitor, DCZ19903.TRANSLATIONAL VISION SCIENCE & TECHNOLOGY,11(12),15.
MLA Ding, Jingjuan,et al."Suppression of Pathological Ocular Neovascularization by a Small Molecular Multi-Targeting Kinase Inhibitor, DCZ19903".TRANSLATIONAL VISION SCIENCE & TECHNOLOGY 11.12(2022):15.

入库方式： OAI收割

来源：上海药物研究所

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