Application of compound Parimifasor in the preparation of anti-tumor drugs
Through in vitro antitumor activity screening, it was found that the compound Parimifasor has antitumor activity on a variety of tumor cell lines, which solved the problem of lack of effective antitumor drugs in the prior art and realized the possibility of preparing broad-spectrum antitumor drugs.
Patent Information
- Application Number
- CN202310619499.3
- Authority / Receiving Office
- CN · China
- Patent Type
- Patents(China)
- Current Assignee / Owner
- Filing Date
- 2023-05-30
- Publication Date
- 2025-02-11
- Estimated Expiration
- 2043-05-30
AI Technical Summary
The application of the compound Parimifasor in tumor treatment has not yet been explored in the prior art, and effective anti-tumor drugs are lacking.
Through in vitro antitumor activity screening, it was found that the compound Parimifasor has broad-spectrum antitumor activity against 15 different types of tumor cell lines, and antitumor drugs were prepared, including the treatment of multiple types of cancer drugs.
The compound Parimifasor showed strong inhibitory activity on a variety of tumor cell lines in vitro assays, with IC50 values distributed in the range of 0.07-3.24μM, and has good development prospects for broad-spectrum anti-tumor drugs.
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Abstract
Description
Technical Field
[0001] The invention belongs to the field of medicine, and specifically relates to the application of a compound Parimifasor in the preparation of anti-tumor drugs. Background Art
[0002] Malignant tumors are one of the main causes of death in patients, and their incidence rate is increasing year by year. The patients are getting younger and younger, which seriously threatens human health and also creates a huge burden on the country and society. At present, tumor treatment measures mainly include surgical treatment, radiotherapy, chemotherapy, targeted therapy and immunotherapy. In the clinical treatment of tumors, different treatment plans and drugs are often combined. Therefore, the continuous exploration of potential tumor treatment drugs is an important issue that needs to be solved urgently, and it also provides more possibilities for tumor patients.
[0003] Parimifasor is an immunomodulator with anti-inflammatory activity. There are no studies on Parimifasor and tumors. Summary of the invention
[0004] In order to make up for the deficiencies of the prior art, the present invention provides an application of a compound Parimifasor in the preparation of an anti-tumor drug.
[0005] The structural formula of the compound Parimifasor described in the present invention is as follows:
[0006]
[0007] The results of in vitro antitumor activity screening showed that the compound Parimifasor has a broad spectrum of antitumor activity, and exhibits strong inhibitory activity against human glioblastoma (LN229), colon cancer (HCT-116), lung adenocarcinoma (H1299), large cell lung cancer (NCI-H460), renal clear cell carcinoma (786-O), osteosarcoma (143B), esophageal cancer (KYSE140), pancreatic cancer (PANC-1), cholangiocarcinoma (HCCC-9810), cervical cancer (Hela), hepatocellular carcinoma (HepG2), fibrosarcoma (HT-1080), gastric cancer (HGC-27), bladder transitional cell carcinoma (UM-UC-3) and melanoma (A375) cell lines. Its IC 50The values are 0.07μM, 0.19μM, 0.30μM, 3.24μM, 0.43μM, 0.68μM, 0.23μM, 0.24μM, 0.41μM, 0.14μM, 1.67μM, 0.29μM, 1.30μM, 0.63μM, 0.21μM, respectively. Therefore, the compound Parimifasor or a pharmaceutically acceptable salt thereof has the application of preparing anti-tumor drugs, and more specifically, the anti-tumor drug is at least one of the following drugs: a drug for treating glioblastoma, a drug for treating colon cancer, a drug for treating lung adenocarcinoma, a drug for treating large cell lung cancer, a drug for treating renal clear cell carcinoma, a drug for treating osteosarcoma, a drug for treating esophageal cancer, a drug for treating pancreatic cancer, a drug for treating bile duct cell carcinoma, a drug for treating cervical cancer, a drug for treating hepatocellular carcinoma, a drug for treating fibrosarcoma, a drug for treating gastric cancer, a drug for treating bladder transitional cell carcinoma, and a drug for treating melanoma.
[0008] The anti-tumor drug comprises an effective dose of Parimifasor or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier, excipient and / or auxiliary material.
[0009] Pharmaceutically acceptable carriers are various carriers known in the art, prepared according to methods known in the art, such as diluents, excipients such as water, binders such as cellulose derivatives, gelatin, polyvinyl pyrrolidone, fillers such as starch, disintegrants such as calcium carbonate, sodium bicarbonate, etc.
[0010] Pharmaceutically acceptable excipients include various excipients conventionally used in the art, such as sweeteners, buffers, solubilizers, colorants, flavors or other materials.
[0011] The compound Parimifasor or a pharmaceutically acceptable salt thereof can be combined with one or more solid and / or liquid pharmaceutical excipients and / or auxiliary materials to prepare a suitable form of use or dosage form for human medicine.
[0012] The anti-tumor drug can be prepared into preparations in various dosage forms, for example, tablets, capsules, pills, injections, sustained-release preparations or controlled-release preparations.
[0013] The present invention has the following beneficial effects: through in vitro anti-tumor tests, the present invention finds that the compound Parimifasor has good anti-tumor activity against 15 different types of tumor cell lines, can be used to prepare a broad-spectrum anti-tumor drug, and has good development prospects. DETAILED DESCRIPTION
[0014] The present invention will be further described in detail below in conjunction with the examples. The following examples are only used to illustrate the present invention and are not intended to limit the scope of the present invention.
[0015] Example 1
[0016] 1. Experimental Methods
[0017] 1. Cell Culture
[0018] When the cell confluence reaches 80-90%, the cells are subcultured. During subculture, the original culture medium is removed, the cells are washed with an appropriate amount of PBS, and then digested with 0.25% trypsin. At the end of digestion, the digestion is terminated with complete culture medium 5 times the volume of trypsin, the cells are collected, and centrifuged at 200g for 5 minutes. After centrifugation, the supernatant is discarded, the cells are resuspended with 1mL of fresh culture medium, and the cells are transferred to new culture dishes in appropriate proportions and cultured in a 37°C, 5% CO2 incubator.
[0019] 2. Preparation of compound working solution
[0020] First, the Parimifasor stock solution was diluted with DMSO to 500 times the maximum concentration required for each cell, and then 2 μL of the above compound dilution was added to 298 μL of complete culture medium to obtain 10 / 3 × working solution W1, and then gradient dilution was performed with culture medium containing 1 / 150 (v / v) DMSO according to the dilution ratio set for each cell to obtain working solutions W2-9. Finally, the DMSO content of all wells was uniformly controlled at 0.2%.
[0021] 3. Cell seeding and drug treatment
[0022] The cells in the logarithmic growth phase were collected, resuspended in complete medium, and 70 µL of cells were seeded into each well of a 96-well plate (plating density HCT-116: 3200 cells / well; KYSE140: 16000 cells / well; Hela: 1800 cells / well; A375: 1600 cells / well; PANC-1: 3200 cells / well; H1299: 2500 cells / well; LN229: 2400 cells / well; HepG2: 6000 cells / well; 786-O: 3000 cells / well; NCI-H460: 14000 cells / well; HCCC-9810: 1500 cells / well; 143B: 1600 cells / well) and allowed to adhere overnight in a 37°C, 5% CO2 incubator. After the cells are fully attached, 30 µL of the corresponding 2× compound working solution is added to each well and incubated for 72 hours. All compounds are set at 9 concentration points, and all groups are set up with 3 replicate wells. The medium wells without cells are blank controls, and the cell culture wells with only solvent added are negative controls.
[0023] 4. Cell proliferation detection and data processing
[0024] After the incubation, add 10 µL of CCK8 solution to each well and continue incubation for 2-4 hours. Then measure the absorbance at 450 nm on a microplate reader. % Inhibition rate = (1- (OD S -OD BLK ) / (OD NC –OD BLK ))×100%. Among them, OD S Indicates the absorbance value of the sample well (cells + test compound), OD NC Indicates the absorbance value of negative wells (cells + solvent), OD BLK Represents the absorbance value of the blank well (medium + solvent). PRISM software was used to fit the dose-effect curve and calculate the IC 50 value.
[0025] 2. Experimental Results
[0026] The anti-tumor activity test results of the compound Parimifasor against 15 tumor cell lines are shown in Table 1.
[0027] Table 1 In vitro antitumor activity of compound Parimifasor
[0028]
[0029] As shown in Table 1, the compound Parimifasor has a broad-spectrum anti-tumor activity and has a strong inhibitory effect on the proliferation of all tumor cell lines. 50 The IC values of 12 tumor cell lines were in the range of 0.07-3.24 μM. 50 Less than 1 μM, IC in 10 tumor cell lines 50 Less than 0.5 μM. Therefore, the compound Parimifasor is expected to be developed into a broad-spectrum anti-tumor drug.
[0030] Although the present invention has been disclosed as above in the form of a preferred embodiment, it is not intended to limit the present invention. Any person skilled in the art may make possible changes and modifications to the technical solution of the present invention by using the methods and technical contents disclosed above without departing from the spirit and scope of the present invention. Therefore, any simple modifications, equivalent changes and modifications made to the above embodiments based on the technical essence of the present invention without departing from the content of the technical solution of the present invention shall fall within the protection scope of the technical solution of the present invention.
Claims
1. Use of the compound Parimifasor or a pharmaceutically acceptable salt thereof in the preparation of an anti-tumor drug, characterized in that: The structural formula of the compound Parimifasor is shown in formula (I): （I） The anti-tumor drug is an anti-glioblastoma drug.
2. The use according to claim 1, characterized in that: The anti-tumor drug comprises an effective dose of Parimifasor or a pharmaceutically acceptable salt thereof.
3. The use according to claim 2, characterized in that: The anti-tumor drug also contains pharmaceutically acceptable excipients.
4. The use according to claim 1, characterized in that: The dosage form of the anti-tumor drug is tablet, capsule, pill, injection, sustained-release preparation or controlled-release preparation.
Citation Information
Patent Citations
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