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Application of ANGPT2 inhibitor in preparation of drug for treating hemangiomas

A technology of hemangioma and inhibitor, applied in the direction of anti-tumor drugs, drug combinations, pharmaceutical formulations, etc., to achieve the effect of improving cerebral hemorrhage and reducing the number of cerebral hemorrhages

Inactive Publication Date: 2016-11-09
广州道瑞医药科技有限公司
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Problems solved by technology

In view of the lack of effective therapeutic drugs at present, surgical resection is the only treatment for CCM. Therefore, studying the pathogenesis of CCM and finding new effective drugs or treatments are current research hotspots.

Method used

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  • Application of ANGPT2 inhibitor in preparation of drug for treating hemangiomas
  • Application of ANGPT2 inhibitor in preparation of drug for treating hemangiomas
  • Application of ANGPT2 inhibitor in preparation of drug for treating hemangiomas

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Embodiment

[0029] 1. Materials and methods

[0030] 1.1 Tamoxifen-induced vascular endothelial cell-specific Ccm3 knockout mouse (Ccm3-iecKO) model Establish

[0031] To facilitate the study of the function of Ccm3 in vascular endothelial cells via the Cre-LoxP system, we used Cdh5-CreERT2 transgenic mice. The principle of Cdh5-CreERT2 transgenic technology is to firstly mutate the ligand-binding domain (LBD) of estrogen receptor (ER), and then fuse it with Cre recombinase to generate a chimeric recombinase (Cre-ER). Relies on the presence of tamoxifen without the influence of estrogen in the body. The expression of Cre recombinase gene in vascular endothelial cells is driven by the promoter of Cdh5 gene. If the transgenic mouse takes tamoxifen, the activity of Cre recombinase is activated, which can lead to Cre-mediated recombination within a predetermined time and on specific tissue cell types (here, vascular endothelial cells). The acquisition of Cdh5-CreERT2 transgenic mice ca...

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Abstract

The invention discloses application of an ANGPT2 inhibitor in preparation of a drug for treating hemangiomas. The application provided by the invention proves for the first time that ANGPT2 is significantly up-regulated in a mouse CCM3 model and a human CCM3 cerebrovascular tissue, and the cerebral hemorrhage situation caused by blood vessel leakage can be significantly improved and the focus number of vascular malformations can be significantly reduced by applying an ANGPT2 neutralizing antibody to a mouse CCM3 knockout model. Thus, ANGPT2 plays an important regulating role in vascular abnormalities, and the application of the ANGPT2 neutralizing antibody and other inhibitors can provide a basis for preparing the drug related to vascular abnormalities.

Description

technical field [0001] The invention belongs to the technical field of biomedicine, and in particular relates to the application of ANGPT2 inhibitors in the preparation of medicines for treating hemangiomas. Background technique [0002] Cerebral carvernous malformation (CCM) is a kind of vascular malformation that occurs in the central nervous system. The disease rate is about 0.1% to 4%. [0003] CCM is composed of cavernous sinuses of various sizes lacking muscular layer and elastic fibers, clusters of telangiectasia, and the inner wall is a single layer of flattened endothelial cells (ECs), lacking pericyte (PCs) coverage, There is no normal vascular basement membrane. Changes in the vascular endothelial barrier lead to increased vascular permeability, red blood cell extravasation, and secondary brain parenchymal inflammation, which significantly increases the risk of stroke, epilepsy, and neurological deficit. [0004] CCM is divided into sporadic and autosomal domin...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K45/00A61K39/395A61P35/00
CPCA61K45/00A61K39/3955
Inventor 王敏周焕娇
Owner 广州道瑞医药科技有限公司
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