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Application of CDK7 inhibitor in preparing drug for ulcerative colitis or colon cancer

An ulcerative colitis and inhibitor technology, applied in the field of medicine, can solve the problems of colon cancer treatment without CDK7 inhibitor and unclear relationship, and achieve the effects of increasing the difficulty of treatment, expanding the scope of application and shortening the treatment period

Active Publication Date: 2019-08-09
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 preparing drug for ulcerative colitis or colon cancer
  • Application of CDK7 inhibitor in preparing drug for ulcerative colitis or colon cancer
  • Application of CDK7 inhibitor in preparing drug 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] like 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 the...

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

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 application of a CDK7 inhibitor in preparing a drug for ulcerative colitis or colon cancer. Through the research of the treatment of an experimental ulcerative colitis mouse andthe research of the treatment of an experimental ulcerative colitis-associated colon cancer mouse, it is firstly discovered that the CDK7 inhibitor, especially THZ2, can inhibit bloody stool symptomsassociated with the ulcerative colitis, can also reduce diarrhea symptoms associated with the ulcerative colitis, can effectively treat the ulcerative colitis and the ulcerative colitis-associated colon cancer, helps a patient reduce body fluid loss, effectively shortens the bloody stool cycle, relieves the severity of bloody stools and the severity of diarrhea, weakens lymphocytic infiltration in the colon, reduces the inflammation-associated protein level, reduces the tumor incidence, shortens the treatment cycle of the patient, increases the cure rate, has positive guiding significance formedication, further expands the application range of the THZ2, and improves the application value of the CDK7 inhibitor.

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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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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