Application of cdk7 inhibitor in preparation of medicine for ulcerative colitis or colon cancer

A colon cancer and inhibitor technology, applied in the application field of preparing ulcerative colitis or colon cancer drugs, can solve the problems of unclear relationship, no CDK7 inhibitor colon cancer treatment, etc., to expand the scope of application and increase the difficulty of treatment , the effect of improving the cure rate

Active Publication Date: 2021-06-11
JINAN UNIVERSITY
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

CDK1 and CDK2 are related to inflammation, but the relationship between CDK7, which activates the activity of CDK1 and CDK2, and inflammation is still unclear. So far, there is no research report on the treatment of inflammation and colon cancer related to the treatment of CDK7 inhibitor THZ2 and ulcerative colitis

Method used

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  • Application of cdk7 inhibitor in preparation of medicine for ulcerative colitis or colon cancer
  • Application of cdk7 inhibitor in preparation of medicine for ulcerative colitis or colon cancer
  • Application of cdk7 inhibitor in preparation of medicine for ulcerative colitis or colon cancer

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0033] Embodiment 1 mouse ulcerative colitis experiment

[0034] 1. Test drug

[0035] THZ2 powder (purchased from APExBIO in the United States, product number A8717), dissolved in DMSO solvent to 0.1g / mL mother solution, then diluted to 1mg / mL with normal saline, administered by intraperitoneal injection at a dose of 10mg / kg, twice a day.

[0036] 2. Experimental animals

[0037] There were 13 SPF grade BABL / c male mice (6-7 weeks old, 17-19 g). Provided by the Guangdong Medical Experimental Animal Center, license number: SCXK (Guangdong) 2013-0002.

[0038] 3. Establishment of mouse ulcerative colitis model

[0039] DSS (dextran sodium sulfate, dextran sodium sulfate) is widely used in the construction of animal models of mouse ulcerative colitis.

[0040] Such as figure 1 As shown, the experimental mice were fed with sterile pure water containing 2.5% DSS (purchased from Shanghai Yisheng Biotechnology Co., Ltd., product number: 60316ES76) for 7 consecutive days. When ...

Embodiment 2

[0047] Example 2 Mouse ulcerative colitis related colon cancer experiment

[0048] 1. Test drug

[0049] THZ2 powder (purchased from APExBIO in the United States, product number A8717), dissolved in DMSO solvent to 0.1g / mL mother solution, then diluted to 1mg / mL with normal saline, administered by intraperitoneal injection at a dose of 10mg / kg, twice a day.

[0050] 2. Experimental animals

[0051]There were 13 SPF grade BABL / c male mice (6-7 weeks old, 17-19 g). Provided by the Guangdong Medical Experimental Animal Center, license number: SCXK (Guangdong) 2013-0002.

[0052] 3. Establishment of mouse ulcerative colitis-associated colon cancer model

[0053] AOM (azoxymethane, azoxymethane) is metabolized into methyl azoxymethanol in the organism, which can convert the base G in DNA into base A, thereby exerting carcinogenesis.

[0054] Such as figure 2 As indicated, AOM (10 mg / kg) (purchased from Sigma-Aldrich, USA, product number: A5486) was intraperitoneally injected ...

Embodiment 3

[0061] Embodiment 3 Effect embodiment

[0062] Each treatment group of embodiment 1, embodiment 2 is carried out following research:

[0063] 1. Western blotting

[0064] Proteins related to inflammation in the body, such as COX-2, IL-6, TNF-α, etc., the expression level of these proteins can reflect the level of inflammation in the body to a certain extent. Higher levels of these proteins reflect higher levels of inflammation in the body.

[0065] Cyclooxygenase (Cyclooxygenase, COX), also known as prostaglandin-endoperoxide synthase (PTGS), is a dual-functional enzyme with cyclooxygenase and catalase activities, and is a catalyst for peanut A key enzyme in the conversion of tetraenoic acid to prostaglandins. At present, it has been found that cyclooxygenase has two isoenzymes, COX-1 and COX-2. The former is a structural type, which mainly exists in blood vessels, stomach, kidney and other tissues, and is involved in vasomotor, platelet aggregation, gastric mucosal blood f...

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Abstract

The invention provides the application of the CDK7 inhibitor in the preparation of medicine for ulcerative colitis or colon cancer. Through the research on the treatment of mice with experimental ulcerative colitis and the research on the treatment of mice with colon cancer related to experimental ulcerative colitis, the present invention found for the first time that CDK7 inhibitors, especially THZ2, can inhibit the bloody stools accompanied by ulcerative colitis Symptoms, and can reduce the symptoms of diarrhea associated with ulcerative colitis, can effectively treat ulcerative colitis and ulcerative colitis-related colon cancer, help patients reduce body fluid loss, effectively shorten the bloody stool cycle, relieve the severity of bloody stool and The severity of diarrhea can reduce the infiltration of lymphocytes in the colon, reduce the level of inflammation-related proteins, reduce the incidence of tumors, shorten the treatment cycle of patients, and improve the cure rate. its application value.

Description

technical field [0001] The invention belongs to the technical field of medicine, and particularly relates to the application of a CDK7 inhibitor in the preparation of ulcerative colitis or colon cancer medicine. Background technique [0002] Inflammatory bowel disease is mainly divided into ulcerative colitis (UC) and Crohn's disease (CD). Among them, the pathogenesis of ulcerative colitis is unclear, and it often recurs. It is often accompanied by symptoms such as bloody stools and diarrhea. The submucosa of the colon under pathological section observation has a large number of leukocytes infiltrated, which will increase the incidence of colon cancer in the long run. A class of diseases that threaten people's health. At present, there is no specific drug that can cure all patients with ulcerative enteritis. [0003] At present, the academic circles believe that inflammation is one of the important causes of cancer. Colon cancer associated with ulcerative colitis is mostly...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): A61K31/506A61P1/00A61P1/04A61P35/00
CPCA61K31/506A61P1/00A61P1/04A61P35/00
Inventor 石智黄家荣
Owner JINAN UNIVERSITY
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