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4-（2-丁基-6,7-二氯-2-环戊基茚满-1-酮-5-基）氧代丁酸抑制血管生成 对血管内皮生长因子受体2信号通路的调节作用

4-(2-Butyl-6,7-dichloro-2-cyclopentyl-indan-1-on-5-yl) oxobutyric acid inhibits angiogenesis modulation of vascular endothelial growth factor receptor 2 signaling pathway.

作者信息

Zhou Tianli, Li Yunda, Zhang Heqiang, Pan Lei, Pang Jinglong, Yuan Qian, Li Guiyang, Jie Lingjun, Wang Yan, Zhang Yanhui

机构信息

Institute of Cardiovascular Diseases, Xiamen Cardiovascular Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, China.

Department of Cardiology, Xiamen Cardiovascular Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, China.

出版信息

Front Cardiovasc Med. 2022 Sep 23;9:969616. doi: 10.3389/fcvm.2022.969616. eCollection 2022.

DOI:10.3389/fcvm.2022.969616
PMID:36211567
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9537693/
Abstract

4-(2-Butyl-6,7-dichloro-2-cyclopentyl-indan-1-on-5-yl) oxobutyric acid (DCPIB), was discovered to be a potent and specific antagonist of volume-regulated anion channel that is closely linked to angiogenesis. However, the effect of DCPIB on angiogenesis remains unclear. Here, we found that DCPIB inhibited angiogenesis in the corneal suture and myocardial infarction model. In addition, DCPIB inhibited human umbilical vein endothelial cell migration, tube formation and proliferation . Moreover, DCPIB repressed the activation and expression of vascular endothelial growth factor receptor 2 (VEGFR2) and its downstream signaling pathway. Computer modeling further confirmed that DCPIB binds with high affinity to VEGFR2. Collectively, we present evidence supporting an antiangiogenic role of DCPIB by targeting VEGFR2 signaling pathway, which suggests that DCPIB is a valuable lead compound for the treatment of angiogenesis-related diseases.

摘要

4-（2-丁基-6,7-二氯-2-环戊基茚满-1-酮-5-基）氧代丁酸（DCPIB），被发现是一种与血管生成密切相关的容积调节性阴离子通道的强效特异性拮抗剂。然而，DCPIB对血管生成的影响仍不清楚。在此，我们发现DCPIB在角膜缝线和心肌梗死模型中抑制血管生成。此外，DCPIB抑制人脐静脉内皮细胞迁移、管腔形成和增殖。而且，DCPIB抑制血管内皮生长因子受体2（VEGFR2）的激活和表达及其下游信号通路。计算机建模进一步证实DCPIB与VEGFR2具有高亲和力结合。总体而言，我们提供的证据支持DCPIB通过靶向VEGFR2信号通路发挥抗血管生成作用，这表明DCPIB是治疗血管生成相关疾病的一种有价值的先导化合物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6fa3/9537693/ef1483b2c7c3/fcvm-09-969616-g0008.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6fa3/9537693/5cc3cb300c99/fcvm-09-969616-g0006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6fa3/9537693/8ffcd0258757/fcvm-09-969616-g0007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6fa3/9537693/ef1483b2c7c3/fcvm-09-969616-g0008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6fa3/9537693/4f690873717a/fcvm-09-969616-g0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6fa3/9537693/46a1ebc1f939/fcvm-09-969616-g0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6fa3/9537693/89115a402afd/fcvm-09-969616-g0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6fa3/9537693/213677fc7c07/fcvm-09-969616-g0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6fa3/9537693/a693454b95b1/fcvm-09-969616-g0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6fa3/9537693/5cc3cb300c99/fcvm-09-969616-g0006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6fa3/9537693/8ffcd0258757/fcvm-09-969616-g0007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6fa3/9537693/ef1483b2c7c3/fcvm-09-969616-g0008.jpg

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