Application of compound in preparation of medicine for treating liver cancer
By using compound 2,4,7,8,9-penta-O-acetyl-N-acetyl neuraminine methyl ester and its combined immune checkpoint inhibitor, the problem of poor efficacy of existing liver cancer treatment drugs was solved, and significant tumor reduction and enhanced anti-PD-1 treatment effects were achieved in the animal model of liver cancer, providing a new liver cancer treatment plan.
Patent Information
- Application Number
- CN202510311985.8
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- Filing Date
- 2025-03-17
- Publication Date
- 2025-05-30
AI Technical Summary
The current liver cancer treatment drugs are not effective, especially the objective response rate of single-agent treatment of immune checkpoint inhibitors is low, and the effect of current mainstream system treatment plans is still insufficient to meet clinical needs.
Compound 2,4,7,8,9-penta-O-acetyl-N-acetyl neuraminine methyl ester (CAS No.: 73208-82-9) and its combined immune checkpoint inhibitor were used to prepare drugs for treating liver cancer, and the effect of anti-PD-1 immunotherapy was enhanced by supplementing sialic acid.
In an animal model of liver cancer, the use of this compound significantly reduces the tumor volume, shows good therapeutic effects, and is more effective after being combined with anti-PD-1 antibodies, providing a new liver cancer therapeutic drug with clinical application prospects.
Smart Images
Figure CN120053420A_ABST
Abstract
Description
Technical Field
[0001] The present invention relates to the use of a compound in the preparation of a drug for treating liver cancer, belonging to the technical field of biomedicine. Background Art
[0002] Primary liver cancer is the 4th most common malignant tumor and the 2nd leading cause of cancer death in China, and the 6th most common malignant tumor and the 4th leading cause of cancer death globally. More than 80% of it is hepatocellular carcinoma (HCC, hereinafter referred to as liver cancer for short). Surgical and ablation therapies are the preferred treatment methods for patients with early-stage liver cancer. However, a large number of liver cancer patients are already in the advanced stage when they are diagnosed, losing the opportunity for surgical resection. In addition, the high postoperative recurrence rate also limits the benefits that can be brought by surgical treatment. Therefore, it is urgent to develop effective systemic treatment methods. In recent years, immunotherapy regimens represented by immune checkpoint inhibitors have made breakthrough progress in various cancer types. However, the objective response rate (ORR) of monotherapy with immune checkpoint inhibitors for liver cancer immunotherapy is only 15%-20%. The objective response rate and survival benefit of the current mainstream systemic treatment regimens represented by atezolizumab combined with bevacizumab ("A+T regimen") and sintilimab combined with bevacizumab analogue ("Double-Da combination") are both unsatisfactory, and the highest objective response rate is still less than 40%. The exploration of systemic treatment for liver cancer is still a long way to go. Summary of the Invention
[0003] The object of the present invention is: aiming at the technical problem that the existing drugs for treating liver cancer have poor efficacy, the present invention provides the use of a compound in the preparation of a drug for treating liver cancer.
[0004] To achieve the above object of solving the technical problem, the technical solution adopted by the present invention is to provide the use of a compound or its combination with an immune checkpoint inhibitor in the preparation of a drug for treating liver cancer. The CAS No. of the compound is: 73208-82-9, and its chemical structural formula is as follows:
[0005]
[0006] The present invention also provides the use of a compound or its combination with an immune checkpoint inhibitor in the preparation of a drug for preventing and / or treating liver cancer metastasis or diseases related to liver cancer metastasis. The CAS No. of the compound is: 73208-82-9, and its chemical structural formula is as follows:
[0007]
[0008] Preferably, the drug comprises an active ingredient and a pharmaceutically acceptable carrier or excipient, and the active ingredient comprises at least the compound.
[0009] Preferably, the active ingredient further comprises an immune checkpoint inhibitor.
[0010] Preferably, the immune checkpoint inhibitor comprises a PD-1 inhibitor (anti-PD-1 antibody).
[0011] Preferably, the dosage form of the drug comprises tablets, powders, granules, capsules, oral liquids, injections or sustained-release agents.
[0012] The present invention also provides a pharmaceutical composition, which comprises a first active ingredient and a second active ingredient. The first active ingredient is a compound shown as follows:
[0013]
[0014] The second active ingredient is an immune checkpoint inhibitor.
[0015] Preferably, the immune checkpoint inhibitor is a PD-1 inhibitor (anti-PD-1 antibody).
[0016] Compared with the prior art, the present invention has the following beneficial effects:
[0017] The present invention provides a new drug. Administering this drug in a liver cancer animal model can significantly reduce the tumor volume, showing good therapeutic effects, and can sensitize anti-PD-1 immunotherapy; it provides a drug with clinical application prospects for the treatment of liver cancer. Description of the Drawings
[0018] Figure 1 is the chemical structural formula of methyl 2,4,7,8,9-penta-O-acetyl-N-acetylneuraminic acid (CAS No.: 73208-82-9);
[0019] Figure 2 shows that a liver cancer clinical cohort indicates a significant lack of sialic acid-modified N-glycans in liver cancer patients;
[0020] Figure 3 is that methyl 2,4,7,8,9-penta-O-acetyl-N-acetylneuraminic acid (CAS No.: 73208-82-9) inhibits the growth of liver cancer and sensitizes anti-PD-1 therapy. Detailed Embodiments
[0021] To make the present invention more obvious and understandable, preferred embodiments are provided below in conjunction with the accompanying drawings for detailed description as follows.
[0022] The technical solution adopted by the present invention is to provide a chemical structural formula as Figure 1Use of the shown compound (CAS No.: 73208-82-9) in the preparation of a medicament for treating liver cancer.
[0023] Dosage forms of the said medicament include tablets, powders, granules, capsules, oral liquids, injections or sustained-release agents.
[0024] The present invention also provides the use of a compound with a chemical structural formula as Figure 1 shown (CAS No.: 73208-82-9) in the preparation of a medicament for treating diseases related to liver cancer metastasis.
[0025] The present invention also provides the use of an active ingredient or a preparation containing the said active ingredient, where the active ingredient is a compound as Figure 1 shown (methyl 2,4,7,8,9-penta-O-acetyl-N-acetylneuraminic acid, CAS No.: 73208-82-9) or a pharmaceutically acceptable salt thereof; and, the preparation of the said active ingredient is used for preparing an inhibitor for treating liver cancer; a synergistic drug in combination with anti-PD-1 liver cancer immunotherapy; and / or a medicament for treating and / or preventing and alleviating related diseases caused by liver cancer.
[0026] The related diseases caused by the above-mentioned liver cancer are liver cancer metastasis.
[0027] The above-mentioned inhibitor or medicament includes: oral preparations and non-oral preparations.
[0028] The above-mentioned compound or its pharmaceutically acceptable salt is used for preparing an anti-liver cancer drug.
[0029] For the experimental methods without specific conditions in the following examples, they are carried out according to conventional methods and conditions, or selected according to the product instructions; the materials, reagents, etc. used, unless otherwise specified, are all conventional commercially available products.
[0030] Examples
[0031] Use liver cancer clinical cohorts and animal models to study compounds effective against liver cancer;
[0032] 1. Glycoproteomics of liver cancer clinical cohorts
[0033] Add sample lysis buffer to cancer and adjacent tissues, lyse on a shaker at 4°C, centrifuge at 11000 rpm for 30 min, and collect the supernatant protein lysis solution. After protein denaturation and reduction alkylation, add trypsin to the protein solution and digest overnight on a shaker. Desalt the digested peptides with C18 and perform gradient elution, vacuum concentrate to dryness, then perform hydrophilic enrichment and vacuum concentrate to dryness for liquid chromatography-mass spectrometry analysis.
[0034] 2. Study the efficacy of compounds in liver cancer animal models
[0035] The Hepal-6 murine hepatoma cell line was injected subcutaneously into C57BL / 6 mice at a dose of 10 7 / mouse to establish a tumor-bearing model, which was divided into 4 groups: (1) Intraperitoneal injection of IgG as a control; (2) Intraperitoneal injection of methyl 2,4,7,8,9-penta-O-acetylneuraminic acid (CAS No.: 73208-82-9); (3) Intraperitoneal injection of anti-PD-1 antibody (Anti-mouse PD-1 antibody was used in the animal model); (4) Intraperitoneal injection of methyl 2,4,7,8,9-penta-O-acetylneuraminic acid (CAS No.: 73208-82-9) and anti-PD-1 antibody (Anti-mouse PD-1 antibody was used in the animal model).
[0036] Experimental results:
[0037] As Figure 2 shown, Figure 2 which are the glycoproteomics results of the clinical cohort of liver cancer, indicating a significant loss of sialic acid-modified N-glycans in liver cancer patients.
[0038] As Figure 3 shown, Figure 3 after supplementing the sialic acid methyl 2,4,7,8,9-penta-O-acetylneuraminic acid (CAS No.: 73208-82-9) in the liver cancer animal model, the tumor volume was significantly reduced, and the effect was better when combined with anti-PD-1 antibody.
[0039] Therefore, the results of the present invention show that the compound methyl 2,4,7,8,9-penta-O-acetylneuraminic acid (CAS No.: 73208-82-9) or its pharmaceutically acceptable salt, or a composition thereof combined with other drugs for treating liver cancer (such as anti-PD-1 antibody) is expected to become a new drug for treating liver cancer.
[0040] The above is only a preferred embodiment of the present invention, and does not limit the present invention in any form and substance. It should be noted that for those of ordinary skill in the art of this technology, without departing from the premise of the present invention, several improvements and supplements can still be made, and these improvements and supplements should also be regarded as the protection scope of the present invention.
Claims
1. Use of a compound or a combination thereof with an immune checkpoint inhibitor in the preparation of a drug for treating liver cancer, wherein the CAS No. of the compound is 73208-82-9 and its chemical structure is as follows:
2. Use of a compound or a combination thereof with an immune checkpoint inhibitor in the preparation of a drug for preventing and / or treating liver cancer metastasis or diseases related to liver cancer metastasis, wherein the compound has a CAS No. of 73208-82-9 and a chemical structure as shown below:
3. The use according to claim 1 or 2, characterized in that: The medicine comprises an active ingredient and a pharmaceutically acceptable carrier or excipient, wherein the active ingredient at least comprises the compound.
4. The use according to claim 3, characterized in that: The active ingredients also include immune checkpoint inhibitors.
5. The use according to claim 4, characterized in that: The immune checkpoint inhibitors include PD-1 inhibitors.
6. The use according to claim 1 or 2, characterized in that: The dosage form of the drug includes tablets, powders, granules, capsules, oral liquids, injections or sustained-release preparations.
7. A pharmaceutical composition, characterized in that The pharmaceutical composition comprises a first active ingredient and a second active ingredient, wherein the first active ingredient is a compound as shown below: The second active ingredient is an immune checkpoint inhibitor.
8. The composition according to claim 7, characterized in that The immune checkpoint inhibitor is a PD-1 inhibitor.