阅读说明：本技术 一种新型表观遗传因子抑制剂2800z在制备肝癌药物中的应用 (Application of novel epigenetic factor inhibitor 2800Z in preparation of liver cancer drugs ) 是由 李专 张晨 刘博豪 唐文斌 肖雅丹 李汇明 于 2021-01-22 设计创作，主要内容包括：本发明属于药学领域,具体涉及一种新型表观遗传因子抑制剂2800Z在制备肝癌药物中的应用。本发明提供了一种新型表观遗传银子抑制剂2800Z对肝癌的作用,通过体外细胞实验和体内抑制实验证实了抑制剂2800Z能明显抑制肝癌细胞的生长,在小鼠肿瘤模型中,明显抑制了肿瘤的生长,能够促进其肝癌细胞的凋亡,效果明显优于抗肝癌药物索拉菲尼,可作为临床靶向治疗肝癌的小分子靶向药物。(The invention belongs to the field of pharmacy, and particularly relates to application of a novel epigenetic factor inhibitor 2800Z in preparation of a liver cancer medicament. The invention provides the effect of a novel epigenetic silvern inhibitor 2800Z on liver cancer, and in vitro cell experiments and in vivo inhibition experiments prove that the inhibitor 2800Z can obviously inhibit the growth of liver cancer cells, obviously inhibit the growth of tumors in a mouse tumor model, promote the apoptosis of the liver cancer cells, has an effect obviously superior to that of an anti-liver cancer drug Sorafenib, and can be used as a small molecular targeted drug for clinically and targetedly treating the liver cancer.)

1. A novel epigenetic factor inhibitor 2800Z is the application in preparing liver cancer medicine as shown in formula I:

2. a pharmaceutical composition for treating liver cancer, which comprises an inhibitor 2800Z shown as a formula I.

3. The pharmaceutical composition for treating liver cancer according to claim 2, wherein the pharmaceutical composition further comprises at least one of pharmaceutically acceptable carriers, excipients, diluents, adjuvants and vehicles.

Technical Field

The invention belongs to the field of pharmacy, and particularly relates to application of a novel epigenetic factor inhibitor 40569Z in preparation of a liver cancer medicament.

Background

Liver cancer is one of the common malignant tumors in clinic, has the characteristics of high malignancy, fast disease progression, short life cycle and difficult cure, and the morbidity and mortality of liver cancer at the present stage are in an increasing trend.

At present, the main treatment means of liver cancer are surgical treatment, radiotherapy and chemotherapy, wherein the chemotherapy drugs for liver cancer are limited, and the commonly used drugs are fluorouracil, adriamycin, cisplatin, gemcitabine and the like; however, in liver cancer, the effects of chemotherapeutic drugs are relatively limited, the effective rate is not more than 10%, molecular targeted drugs bring a relatively large breakthrough for the treatment of liver cancer, and the targeted drugs commonly used for primary liver cancer include sorafenib, regorafenib, cabozantinib and the like, which are few in types and have to be improved in effect, so that the research and development of efficient and low-toxic targeted drugs for treating liver cancer still remain scientific problems to be solved urgently.

Disclosure of Invention

In order to solve the technical problems, the invention provides application of a novel epigenetic factor inhibitor 2800Z as formula I in preparation of a liver cancer medicament, the inhibitor 2800Z has an obvious inhibition effect on liver cancer cells through an inhibition experiment of the inhibitor 2800Z on liver cancer cells HepG2 in vitro and an inhibition experiment of the inhibitor 2800Z in a mouse tumor model in vivo, the inhibition effect on the liver cancer cells in the mouse tumor model is obviously superior to that of sorafenib, and the inhibitor can be used as a potential liver cancer targeted medicament.

The invention aims to provide application of a novel epigenetic factor inhibitor 2800Z as shown in formula I in preparation of a liver cancer medicament.

Based on the same inventive concept, the invention provides a pharmaceutical composition for treating liver cancer, which comprises an inhibitor 2800Z shown as a formula I.

Further, the pharmaceutical composition further comprises at least one of pharmaceutically acceptable carriers, excipients, diluents, adjuvants and vehicles.

Has the advantages that:

(1) the inhibitor 2800Z shown as the formula I acts on liver cancer cells for the first time, so that the inhibitor has an obvious inhibition effect on the liver cancer cells, and does not have an obvious killing effect on normal liver cells at low concentration, so that the inhibitor has a positive effect on liver cancer treatment.

(2) According to the invention, the inhibitor 2800Z shown as the formula I is applied to a tumor-forming mouse, and compared with sorafenib, the effect of the inhibitor 2800Z on tumor inhibition is obviously better than that of sorafenib through comparison of the change of tumor volume during administration after administration.

Drawings

In order to more clearly illustrate the embodiments of the present invention or the technical solutions in the prior art, the drawings needed in the embodiments will be briefly described below, and it is obvious that the drawings in the following description are only some embodiments of the present invention, and it is obvious for those skilled in the art to obtain other drawings without creative efforts.

FIG. 1 is a graph showing the inhibitory effect of inhibitor 2800Z on hepatoma cells according to the present invention;

FIG. 2 is a graph of the inhibitory effect of inhibitor 2800Z on normal stem cells provided by an example of the present invention;

FIG. 3 is a graph showing the change in tumor volume between two cycles of administration of different drugs to tumor-forming mice according to an embodiment of the present invention.

Detailed Description

In order to make the technical problems, technical solutions and advantages of the present invention more apparent, the following detailed description is given with reference to the accompanying drawings and specific embodiments, but the scope of the present invention is not limited to the following specific embodiments.

Unless otherwise defined, all terms of art used hereinafter have the same meaning as commonly understood by one of ordinary skill in the art. The terminology used herein is for the purpose of describing particular embodiments only and is not intended to limit the scope of the present invention.

Unless otherwise specifically stated, various raw materials, reagents, instruments, equipment and the like used in the present invention are commercially available or can be prepared by existing methods. The inhibitor 2800Z was purchased from ceramic Biotechnology, Inc.

Example 1

Inhibitor 2800Z has in vitro inhibitory activity on hepatocarcinoma cell as shown in formula I

Adding 10% fetal calf serum solution into DMEM medium, inoculating HEPG2 cells at 37 deg.C and 5% CO₂Culturing for one day under the condition, and culturing HEPG2 cells at 3 × 10⁴cells/ml are inoculated on a 96-well plate at a density, a certain concentration gradient of inhibitor 2800Z is added after 24h of culture, the activity of the cells is analyzed by a CCK8 experiment after continuous 48h of culture, normal hepatocytes are used as a control group, and the cells are processed and analyzed according to the same method to obtain cell activity diagrams shown in figures 1 and 2, wherein figure 1 shows the inhibition effect of the inhibitor 2800Z on liver cancer cells, figure 2 shows the inhibition effect of the inhibitor 2800Z on the normal hepatocytes, and figure 1 shows that the IC of the inhibitor 2800Z on the growth inhibition of the liver cancer cells is IC₅₀The value is 102uM, and the inhibition effect on normal liver cells is weaker and the toxicity is lower under the condition that the concentration is 102uM, namely the inhibitor 2800Z provided by the invention has stronger specificity on inhibition of liver cancer cells and can obviously inhibit the growth of the liver cancer cells.

Example 2

Inhibitory Activity of inhibitor 2800Z against tumors in vivo neoplastic mice

10 adult mice were injected subcutaneously with 1X 10⁶The cells of HEPG2 were cultured in nude mice for 2 weeks in SPF-grade environment to induce tumor formation, divided into two groups, each group was administered with different drugs (2800Z inhibitor and sorafenib (sor)) twice weekly by intraperitoneal injection at a dose of 5mg/kg, and the control group was administered without drug, and the tumor volume was measured at regular time intervals during the administration period, the results are shown in FIG. 3Shown in the figure. As can be seen from FIG. 3, in the mice administered with the inhibitor 2800Z, the increase in tumor volume was less than 250mm³In mice dosed with sorafenib, the tumor volume gradually increases with time, and the increase of the tumor volume is more than 1000mm compared with the tumor volume in the initial state³Namely, the inhibitor 2800Z and sorafenib adopted have obvious statistical difference on the inhibition effect on in-vivo tumors, and the anti-tumor effect of the inhibitor 2800Z provided by the invention is obviously better than that of sorafenib.

While the foregoing is directed to the preferred embodiment of the present invention, it will be understood by those skilled in the art that various changes and modifications may be made without departing from the spirit and scope of the invention as defined in the appended claims.