CN-121971450-A - Application of histone methyltransferase inhibitor BIX-0194 in preparation of medicines for treating echinococcosis

Abstract

The invention discloses an application of a histone methyltransferase inhibitor BIX-0194 in preparing a medicine for treating echinococcosis, belonging to the field of biomedicine. The technical problem solved by the invention is how to treat and/or prevent the echinococcosis acinosa. The BIX-0194 can treat and/or prevent echinococcosis, has remarkable killing effect on the original head and the vesicle of the echinococcosis in the taenia multicamera larva in vitro and can damage the tissue structures of the head and the head, the sucking disc, microvilli and the like, so that the vesicle collapse in the taenia continuous period is caused. In addition, BIX-0194 treatment can inhibit the capability of echinococcus multilocularis protobasal ganglia to develop into cysts in the body of a secondary infection model of a mouse, and the infection rate and liver transfer rate are reduced. It is explained that BIX-0194 can be used as a medicine for treating echinococcosis.

Inventors

• ZHANG CHUANSHAN
• WANG HUI
• Ge Conghui
• Adilai Dolikun
• LI JING
• XIAO WENYING
• GAO YI
• WANG MENGYING

Assignees

• 新疆医科大学第一附属医院

Dates

Publication Date

20260505

Application Date

20260317

Claims (10)

1. 1. Use of a histone methyltransferase inhibitor in the manufacture of a product for the treatment and/or prophylaxis of echinococcosis bullosa, or in the treatment and/or prophylaxis of echinococcosis bullosa.
2. 2. The method according to claim 1, wherein the histone methyltransferase inhibitor is a G9a or GLP histone methyltransferase inhibitor.
3. 3. The method according to claim 2, wherein the G9a and GLP histone methyltransferase inhibitor is BIX-0194.
4. 4. The application of histone methyltransferase inhibitor in preparing a product for killing echinococcus multilocularis protoknob or vesicle or in killing echinococcus multilocularis protoknob or vesicle.
5. 5. Use of a histone methyltransferase inhibitor in the preparation of a product that inhibits the growth or development of echinococcus multilocularis, or in inhibiting the growth or development of echinococcus multilocularis.
6. 6. Use of a histone methyltransferase inhibitor in the preparation of a product that reduces the pathogenicity of echinococcus multinomial, or in reducing the pathogenicity of echinococcus multinomial.
7. 7. Use of a histone methyltransferase inhibitor in the manufacture of a product for inhibiting infection of a human or animal with echinococcus multinomis or in inhibiting infection of a human or animal with echinococcus multinomis.
8. 8. Use of a histone methyltransferase inhibitor in the preparation of a product for inhibiting the metastasis of human or animal echinococcosis lesions, or in inhibiting the metastasis of human or animal echinococcosis lesions.
9. 9. Use of a histone methyltransferase inhibitor in the preparation of a product for inhibiting growth of a human or animal echinococcosis focus, or in inhibiting growth of a human or animal echinococcosis focus.
10. 10. The use according to any one of claims 4 to 9, characterized in that the histone methyltransferase inhibitors are G9a and GLP histone methyltransferase inhibitors; further, the G9a and GLP histone methyltransferase inhibitor is BIX-0194.

Description

Application of histone methyltransferase inhibitor BIX-0194 in preparation of medicines for treating echinococcosis Technical Field The invention belongs to the field of biomedicine, and particularly relates to application of a histone methyltransferase inhibitor BIX-0194 in preparation of a medicine for treating echinococcosis. Background The echinococcosis (Alveolar echinococcosis, AE) is a serious lethal parasitic disease caused by the parasitic of echinococcosis (Echinococcus multilocularis, E.m) larvae on human organs, and is a malignant invasive growth commonly called as 'insect cancer'. AE is highly frequent in western China, severely threatening the health of people and public health safety. Currently, surgical excision is the first method of clinical treatment of AE, but for patients with AE at end-stage or without surgical indications, oral albendazole tablets or liposomes are required for drug treatment. However, the bioavailability of albendazole drugs in vivo is less than 5%, the clinical administration oral dosage is large, patients need to take the drugs for a long time, and the target point of the drugs is the worm microtubulin (beta-tubulin), and the homology with the host beta-tubulin is as high as 94%, so that various adverse toxic and side effects can be generated, the compliance of the patients on taking the drugs is poor, and the clinical cure rate is only 30%. Therefore, there is an urgent need to discover or develop new AE-accurate, targeted therapeutic drugs. In recent years, the development of specific epigenetic regulation drugs to achieve accurate treatment of tumors, dysplasia, neurodegenerative diseases and the like has become one of the main directions of current drug development. Histone methyltransferase (Histone Methyltransferases, HMTs) uses S-adenosylmethionine (SAM) as a methyl donor, and transfers methyl to histone lysine or arginine residues to carry out methylation modification on histone, and the expression of genes is regulated by changing the tightness degree of chromatin structure so as to influence the fate of cells. The degree of methylation (mono/di/trimethylation) of different lysine/arginine sites of histones will produce different regulatory effects. BIX-0194 is a quinazoline-4-amine derivative, inhibits the activity of G9a/GLP enzyme by competing with and combining with the amino acid at the N end of a substrate lysine residue, thereby reducing the methylation level of histone H3K9 (especially H3K9me 2), inhibiting the epigenetic silencing of related genes, becoming a reversible and highly selective G9a and GLP histone methyltransferase inhibitor, and showing anti-tumor effect in various cancers such as esophageal squamous cell carcinoma, lung adenocarcinoma, kidney cancer, colorectal cancer and the like. In the parasite field, BIX-0194 is found to inhibit plasmodium falciparum histone methyltransferase, thereby leading to rapid and irreversible death of plasmodium, and is hopeful to be developed into a brand new therapeutic drug which is needed for prevention and control of malaria. In addition, BIX-0194 can also reduce the formation of cyst of human bud cyst, and has inhibiting effect on the in vitro growth of Babesia. However, there is no report on the use of BIX-0194 in the preparation of a medicament for treating echinococcosis bullosa. Disclosure of Invention The invention aims to solve the technical problem of how to treat and/or prevent the echinococcosis acinosa. To solve the above technical problems, the present invention provides, first, any one of the following applications of histone methyltransferase inhibitors: 1. Preparing a product for treating and/or preventing echinococcosis; 2. treating and/or preventing echinococcosis; 3. preparing a product for killing echinococcus multilocularis protohead segments or vesicles; 4. Killing Echinococcus multilocularis protohead segments or vesicles; 5. Preparing a product for inhibiting the growth or development of echinococcus multinomial; 6. Inhibiting growth or development of echinococcus multinomial; 7. preparing a product for reducing pathogenicity of echinococcus multinomis; 8. Reduce the pathogenicity of echinococcus multinomis; 9. preparing a product for inhibiting infection of human or animal by echinococcus multilocularis; 10. Inhibiting infection of humans or animals with echinococcus multilocularis; 11. preparing a product for inhibiting the metastasis of human or animal echinococcosis focus; 12. inhibiting echinococcosis focus metastasis in human or animal; 13. preparing a product for inhibiting growth of human or animal echinococcosis focus; 14. inhibit growth of human or animal echinococcosis focus. Specifically, the pathogenicity of Echinococcus multilocularis is the pathogenicity of the original head segment of Echinococcus multilocularis. In particular, the animal is a mammal. In one embodiment of the invention, the animal is a mouse. Specifically, the focal metastasis of echinococcosis