CN-122005518-A - Application of neuropeptide Y1 receptor antagonist in preparation of medicines for treating hereditary polycystic kidney disease

Abstract

The invention relates to the technical field of medicines, in particular to application of a neuropeptide Y1 receptor antagonist in preparation of a hereditary polycystic kidney disease treatment medicine. The neuropeptide Y1 receptor antagonist is selected from the group consisting of a compound BIBO3304 which blocks neuropeptide Y (NPY) from binding to its Y1 receptor subtype and functioning. The invention provides a potential therapeutic effect of neuropeptide Y1 receptor antagonist on the preparation of medicines for treating hereditary polycystic kidney disease on the basis of early histopathology, high throughput sequencing, cell biology, molecular biology combined in vitro cell culture and in vivo animal experiments, and provides a new basis for treating hereditary polycystic kidney disease.

Inventors

• YANG FU
• HE CUITONG
• XIAO BANG
• SUN NINGXIA
• LIU MENG
• CHEN MEITING
• LI TIANYU
• Yin Haozan
• SU KE
• LIU HUANJU

Assignees

• 中国人民解放军海军军医大学

Dates

Publication Date

20260512

Application Date

20260206

Claims (8)

1. 1. The application of neuropeptide Y1 receptor antagonist in preparing medicine for treating hereditary polycystic kidney disease.
2. 2. The use of a neuropeptide Y1 receptor antagonist according to claim 1 for the preparation of a medicament for the treatment of hereditary polycystic kidney disease, wherein said hereditary polycystic kidney disease is autosomal dominant polycystic kidney disease.
3. 3. The use of a neuropeptide Y1 receptor antagonist according to claim 1 for the preparation of a medicament for the treatment of hereditary polycystic kidney disease, wherein said neuropeptide Y1 receptor antagonist is a substance which blocks the binding of neuropeptide Y to its Y1 receptor subtype.
4. 4. The use of a neuropeptide Y1 receptor antagonist according to claim 1 for the preparation of a medicament for the treatment of hereditary polycystic kidney disease, wherein said medicament is a medicament for reducing polycystic kidney volume and cystic index.
5. 5. The use of a neuropeptide Y1 receptor antagonist according to claim 1 for the preparation of a therapeutic agent for hereditary polycystic kidney disease comprising the neuropeptide Y1 receptor antagonist as the sole active monomer component or the neuropeptide Y1 receptor antagonist in combination with other agents.
6. 6. The use of a neuropeptide Y1 receptor antagonist according to claim 5 for the preparation of a medicament for the treatment of hereditary polycystic kidney disease, wherein said medicament further comprises a pharmaceutically acceptable carrier or adjuvant.
7. 7. The use of a neuropeptide Y1 receptor antagonist according to claim 1 for the preparation of a medicament for the treatment of hereditary polycystic kidney disease, wherein said neuropeptide Y1 receptor antagonist is BIBO3304.
8. 8. The use of a neuropeptide Y1 receptor antagonist according to claim 7 for the preparation of a medicament for the treatment of hereditary polycystic kidney disease, wherein the concentration of BIBO3304 in said medicament is 100-250 μm.

Description

Application of neuropeptide Y1 receptor antagonist in preparation of medicines for treating hereditary polycystic kidney disease Technical Field The invention relates to the technical field of medicines, in particular to application of a neuropeptide Y1 receptor antagonist in preparation of a hereditary polycystic kidney disease treatment medicine. Background Autosomal dominant polycystic kidney disease (autosomal dominant polycystic KIDNEY DISEASE, ADPKD) is a disease characterized mainly by multiple fluid vesicles of the double kidneys, and has a morbidity of 1/1000 to 1/400, which is the most common monogenic hereditary kidney disease. ADPKD is the fourth leading cause of end stage renal disease (END STAGE RENAL DISEASE, ESRD), and approximately half of patients progress to ESRD by age 60. Clinically ADPKD is mainly used for symptomatic treatment, and cannot change the natural course of the disease. Thus, the search for new therapeutic approaches has been the focus and difficulty of current ADPKD research. Most ADPKD is caused by mutations in the PKD1 or PKD2 genes, in proportions of 86% and 10% of ADPKD, respectively. The expression products of the PKD1 and PKD2 genes are referred to as polycystic protein 1 (polycystin, PC 1) and polycystic protein 2 (PC 2), respectively. PC1 and PC2 are mainly located on the primary cilia of cells, which are organelles present on most cell surfaces, and function as cell receptors that promote cell interactions with the surrounding environment. Therefore, polycystic kidney disease is considered to be a type of cilia-related disease, and structural or functional abnormalities of cilia play an important role in the formation and development of renal cysts. PC1 acts as a mechanical sensor and PC2 is a calcium-regulated, non-selective cation channel that together regulate intracellular calcium ion concentration. The ciliated polycystic protein complex, which is defective in tubular epithelial cells, is not able to sense fluid flow, which may reduce cellular calcium ion influx, thereby stimulating cAMP signaling, leading to cyst growth. However, the specific regulatory mechanisms for ADPKD development and progression are still not known. Neuropeptide Y (NPY) is a hormone that is widely present in the central and peripheral areas and maintains homeostasis. The role of NPY is mainly accomplished by binding to its receptor. The small molecule BIBO3304 serving as a specific neuropeptide Y1 receptor antagonist can block a series of reactions caused by the combination of NPY and the Y1 receptor subtype. At present, no relation between NPY and hereditary polycystic kidney disease treatment has been reported. Disclosure of Invention The invention aims at solving the above difficult problem of hereditary polycystic kidney disease treatment, provides a novel medical application of a neuropeptide Y1 receptor antagonist, simultaneously provides application of NPY serving as a target spot in hereditary polycystic kidney disease treatment, and particularly provides application of the neuropeptide Y1 receptor antagonist in preparation of hereditary polycystic kidney disease treatment medicines. In order to achieve the above purpose, the present invention adopts the following technical scheme: Firstly, the research shows that the expression of the epithelial cell NPY lining the capsule wall of a polycystic kidney patient is obviously up-regulated, a polycystic kidney mouse model is constructed, the administration of the neuropeptide Y1 receptor antagonist can obviously reduce the kidney-body ratio and the cystic index of the mouse, and no obvious side effect is found when the administration is carried out in a mouse model group. The invention discloses an action mechanism of a neuropeptide Y1 receptor antagonist in inhibiting polycystic kidney, and firstly discloses BIBO3304 to obviously inhibit the kidney-body ratio and cystic index of a polycystic kidney mouse, thereby providing a brand new view and target point for inhibiting the progress of the polycystic kidney. Based on the technical scheme, the first aspect of the invention provides application of the neuropeptide Y1 receptor antagonist in preparing a hereditary polycystic kidney disease treatment drug. Further, the neuropeptide Y1 receptor antagonist is a substance that blocks binding of neuropeptide Y (NPY) to its Y1 receptor subtype. Further, the hereditary polycystic kidney disease is Autosomal Dominant Polycystic Kidney Disease (ADPKD). Further, the hereditary polycystic kidney disease therapeutic agent is an agent for reducing polycystic kidney volume and cystic index. Further, the hereditary polycystic kidney disease therapeutic agent is a pharmaceutical composition comprising the neuropeptide Y1 receptor antagonist as the only active monomer component, or the neuropeptide Y1 receptor antagonist is used together with other drugs. Further, the medicine also comprises pharmaceutically acceptable carriers or auxiliary materials.