CN112755023B - Application of novel epigenetic factor inhibitor 2800Z in preparation of liver cancer drugs - Google Patents
Application of novel epigenetic factor inhibitor 2800Z in preparation of liver cancer drugs Download PDFInfo
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- CN112755023B CN112755023B CN202110090018.5A CN202110090018A CN112755023B CN 112755023 B CN112755023 B CN 112755023B CN 202110090018 A CN202110090018 A CN 202110090018A CN 112755023 B CN112755023 B CN 112755023B
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
- A61K31/4164—1,3-Diazoles
- A61K31/4174—Arylalkylimidazoles, e.g. oxymetazolin, naphazoline, miconazole
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/16—Drugs for disorders of the alimentary tract or the digestive system for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
Abstract
The invention belongs to the field of pharmacy, and particularly relates to application of a novel epigenetic factor inhibitor 2800Z in preparation of liver cancer drugs. The invention provides a novel epigenetic silver inhibitor 2800Z for liver cancer, which is proved by in vitro cell experiments and in vivo inhibition experiments to be capable of obviously inhibiting the growth of liver cancer cells, and in a mouse tumor model, the inhibitor 2800Z is capable of obviously inhibiting the growth of tumors, promoting the apoptosis of the liver cancer cells, and has an effect obviously superior to that of an anti-liver cancer drug sorafenib, and can be used as a small molecule targeting drug for clinically targeting treatment of liver cancer.
Description
Technical Field
The invention belongs to the field of pharmacy, and particularly relates to an application of a novel epigenetic factor inhibitor 40569Z in preparation of liver cancer drugs.
Background
Liver cancer is one of the common malignant tumors in clinic, has the characteristics of high malignant degree, rapid disease progress, short survival time and difficult cure, and the morbidity and mortality of the liver cancer at the present stage are in an ascending trend.
At present, the main treatment means of liver cancer are operation treatment, radiotherapy and chemotherapy, wherein the chemotherapy drugs for the liver cancer are limited, and the common drugs are fluorouracil, doxorubicin, cisplatin, gemcitabine and the like; however, in liver cancer, the effect of chemotherapeutic drugs is limited, the effective rate is not more than 10%, molecular targeted drugs bring about a relatively large breakthrough for treating liver cancer, and the targeted drugs commonly used for primary liver cancer are sorafenib, regorafenib, cabotinib and the like, so that the types are few, the effect is required to be improved, and therefore, the development of the targeted drugs for treating high-efficiency low-toxicity liver cancer is still a scientific difficulty to be solved.
Disclosure of Invention
In order to solve the technical problems, the invention provides application of a novel epigenetic factor inhibitor 2800Z in preparing a liver cancer medicament as shown in a formula I, and the inhibitor 2800Z has obvious inhibition effect on liver cancer cells through an in vitro inhibition experiment of the inhibitor 2800Z on liver cancer cells HepG2 and an in vivo inhibition experiment of a mouse tumor model, has obvious inhibition effect on liver cancer cells in the mouse tumor model, is obviously superior to sorafenib in inhibiting effect on liver cancer cells in the mouse tumor model, and can be used as a potential liver cancer targeting medicament.
The invention aims to provide an application of a novel epigenetic factor inhibitor 2800Z shown in a formula I in preparing liver cancer drugs.
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 a pharmaceutically acceptable carrier, excipient, diluent, adjuvant, and vehicle.
The beneficial effects are that:
(1) The inhibitor 2800Z shown in the formula I acts on liver cancer cells for the first time, has obvious inhibition effect on the liver cancer cells, and has no obvious killing effect on normal liver cells at low concentration, so that the inhibitor has positive effect on liver cancer treatment.
(2) Compared with sorafenib, the inhibitor 2800Z shown in the formula I is applied to a tumor-forming mouse, and compared with sorafenib, the inhibition effect of the inhibitor 2800Z on tumors is obviously better than that of sorafenib through comparison of tumor volume change during the administration period 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 that are 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 other drawings may be obtained according to these drawings without inventive effort for a person skilled in the art.
FIG. 1 is a graph showing the inhibition of liver cancer cells by inhibitor 2800Z provided in the examples of the present invention;
FIG. 2 is a graph of inhibition of normal stem cells by inhibitor 2800Z provided in an embodiment of the present invention;
FIG. 3 is a graph showing the tumor volume change between two cycles of administration of different drugs to a tumor-bearing mouse according to an embodiment of the present invention.
Detailed Description
In order to make the technical problems, technical solutions and advantages to be solved by the present invention more apparent, the following detailed description will be 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 defined otherwise, all technical and scientific terms 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 be limiting of the scope of the present invention.
Unless otherwise specifically indicated, the various raw materials, reagents, instruments, equipment and the like used in the present invention are commercially available or may be prepared by existing methods. The inhibitor 2800Z was purchased from Tao Su biochemical technologies limited.
Example 1
Adding 10% fetal bovine serum solution into DMEM culture medium, inoculating HEPG2 cells, heating to 37deg.C, and adding 5% CO 2 Culturing under the condition for one day, and culturing HEPG2 cells at 3×10 4 Inoculating cells/ml to 96-well plate, culturing for 24 hr, and addingConcentration gradient inhibitor 2800Z is continuously cultured for 48 hours, then CCK8 experiment is carried out to analyze the activity of cells, normal liver cells are used as a control group, and the cells are treated and analyzed according to the same method to obtain cell activity diagrams shown in figures 1 and 2, wherein figure 1 shows the inhibiting effect of the inhibitor 2800Z on liver cancer cells, and figure 2 shows the inhibiting effect of the inhibitor 2800Z on normal liver cells, and as can be seen from figure 1, the IC of the inhibitor 2800Z on growth inhibition of liver cancer cells is obtained 50 The value=102 uM, and the inhibition effect on normal liver cells is weak and the toxicity is low under the condition of the concentration of 102uM, namely the inhibitor 2800Z provided by the invention has strong specificity on the inhibition of liver cancer cells, and can obviously inhibit the growth of liver cancer cells.
Example 2
Inhibitory Activity of inhibitor 2800Z against tumors in vivo tumorigenic mice
10 adult mice were taken and subcutaneously injected 1X 10 6 HEPG2 cells were fed to nude mice in SPF-grade environment for 2 weeks, induced to tumor, and randomly divided into two groups, wherein one group was inhibitor 2800Z and the other group was sorafenib (sor), and the results were shown in FIG. 3, which were obtained by administering 5mg/kg of the cells twice per week by intraperitoneal injection, and the tumor volumes were measured at regular intervals during the administration period. From FIG. 3, it can be seen that the tumor volume increase is less than 250mm in mice administered with inhibitor 2800Z 3 Whereas in mice administered with sorafenib, the tumor volume gradually increased over time by more than 1000mm compared to the initial state 3 Namely, the inhibitor 2800Z and the sorafenib have obvious statistical difference on the inhibition effect of the tumor in vivo, and the anti-tumor effect of the inhibitor 2800Z provided by the invention is obviously better than that of the sorafenib.
While the foregoing is directed to the preferred embodiments of the present invention, it will be appreciated by those skilled in the art that various modifications and adaptations can be made without departing from the principles of the present invention, and such modifications and adaptations are intended to be comprehended within the scope of the present invention.
Claims (1)
1. Application of novel epigenetic factor inhibitor 2800Z in preparing liver cancer medicine is disclosed as formula I:
the inhibitor 2800Z is the only active ingredient in the liver cancer medicament.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
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| CN202110090018.5A CN112755023B (en) | 2021-01-22 | 2021-01-22 | Application of novel epigenetic factor inhibitor 2800Z in preparation of liver cancer drugs |
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| CN202110090018.5A CN112755023B (en) | 2021-01-22 | 2021-01-22 | Application of novel epigenetic factor inhibitor 2800Z in preparation of liver cancer drugs |
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| CN112755023A CN112755023A (en) | 2021-05-07 |
| CN112755023B true CN112755023B (en) | 2023-04-25 |
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| SE0202539D0 (en) * | 2002-08-27 | 2002-08-27 | Astrazeneca Ab | Compounds |
| EP1845975A1 (en) * | 2005-01-21 | 2007-10-24 | Astex Therapeutics Limited | Combinations of pyrazole kinase inhibitors and further antitumor agents |
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Address after: Hunan Provincial Key Laboratory of Small Molecule Targeted Drug Research and Creation, School of Medicine, Hunan Normal University, No. 36 Lushan Road, Yuelu District, Changsha City, Hunan Province, 410000 Applicant after: HUNAN NORMAL University Address before: No. 36, Yuelu District Lu Mountain Road, Changsha, Hunan Applicant before: HUNAN NORMAL University |
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