CN110101703B - Application of CDK7 inhibitor in preparation of medicine for treating ulcerative colitis or colon cancer - Google Patents
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Abstract
The invention provides application of a CDK7 inhibitor in preparation of a medicine for treating ulcerative colitis or colon cancer. According to the invention, through the research on the mice for treating experimental ulcerative colitis and the research on the mice for treating colon cancer related to experimental ulcerative colitis, a CDK7 inhibitor is found for the first time, particularly THZ2 can inhibit bloody stool symptoms accompanied by ulcerative colitis, can reduce diarrhea symptoms accompanied by ulcerative colitis, can effectively treat ulcerative colitis and colon cancer related to ulcerative colitis, is beneficial to reducing body fluid loss of patients, effectively shortens bloody stool periods, relieves the severity of bloody stool and the severity of diarrhea, weakens lymphocyte infiltration in colon, reduces the level of inflammation-related protein, reduces the tumor incidence rate, shortens the treatment period of patients, improves the cure rate, has positive medication guiding significance, further expands the application range of THZ2 and improves the application value of the THZ 2.
Description
Technical Field
The invention belongs to the technical field of medicines, and particularly relates to application of a CDK7 inhibitor in preparation of a medicine for treating ulcerative colitis or colon cancer.
Background
Inflammatory bowel disease is mainly classified into Ulcerative Colitis (UC) and Crohn's Disease (CD). The pathogenesis of the ulcerative colitis is unclear, the ulcerative colitis frequently attacks repeatedly, the symptoms such as bloody stool and diarrhea are often accompanied, large amount of white blood cells infiltrate into the colonic submucosa observed by pathological sections, the incidence rate of colon cancer of patients can be increased in the past, the colon cancer is a disease threatening to the health of people, and no specific medicine can cure all patients with the ulcerative enteritis at present.
Inflammation is currently considered by academia as one of the important causes of cancer. Ulcerative colitis is often associated with colon cancer that is not cured in time, and is further worsened in the past. Colon cancer, a cancer, has long been a serious threat to human health, but the specific molecular mechanisms of pathogenesis are not clear at present.
The compound THZ2 belongs to a small molecule inhibitor targeting cyclin CDK7, which competes with ATP for binding to the residue of cysteine 312 of CDK7, thereby giving a good choice for inhibiting the phosphorylation activity of CDK 7. CDK1 and CDK2 are associated with inflammation, but the relationship of CDK7 activating CDK1 and CDK2 activity to inflammation is not clear, and no studies of CDK7 inhibitor THZ2 to the treatment of inflammation and colon cancer associated with ulcerative colitis have been reported so far.
Disclosure of Invention
The invention aims to overcome the defects of the prior art and provides application of a CDK7 inhibitor in preparation of a medicament for preventing and treating ulcerative colitis and/or colon cancer.
The purpose of the invention is realized by the following technical scheme:
application of CDK7 inhibitor in preparing medicine for preventing and treating ulcerative colitis and/or colon cancer is provided.
The CDK7 inhibitor is preferably THZ2(CAS:1604810-84-5), and the structure of the THZ2 is shown as a formula I.
The medicine for preventing and treating ulcerative colitis and/or colon cancer contains at least one of THZ2 and medicinal salts thereof.
The medicine for preventing and treating ulcerative colitis and/or colon cancer contains one or more pharmaceutically acceptable auxiliary materials.
The auxiliary material is preferably at least one of sustained release agent, excipient, filler, adhesive, wetting agent, disintegrating agent, absorption enhancer, surfactant, antibacterial agent, aromatic agent, antioxidant, pH regulator, protective agent, diluent, lubricant, solvent, matrix or carrier material.
The medicine for preventing and treating ulcerative colitis and/or colon cancer can be prepared into various dosage forms by adopting a conventional method in the field, such as injection, capsules, pills, tablets, granules, tinctures, inhalation preparations, oral solutions, oral suspensions, oral emulsions and other dosage forms.
The inventors have conducted studies on the treatment of mice with experimental ulcerative colitis and on the treatment of mice with colon cancer associated with experimental ulcerative colitis using compound THZ 2. The results show that the compound THZ2 can inhibit bloody stool symptoms accompanied by ulcerative colitis and reduce diarrhea symptoms accompanied by ulcerative colitis. Therefore, the compound THZ2 can be used for preparing medicines for treating ulcerative colitis and colon cancer related to the ulcerative colitis.
Compared with the prior art, the invention has the following advantages and effects:
the bloody stool and diarrhea accompanied by ulcerative colitis cause serious loss of body fluid and weaker body of patients on one hand, and further increase the treatment difficulty of the disease on the other hand. The invention discovers for the first time that the CDK7 inhibitor THZ2 can effectively treat ulcerative colitis and colon cancer related to ulcerative colitis, is beneficial to reducing body fluid loss of a patient, shortens the treatment period of the patient, improves the cure rate, has positive medication guidance significance, further expands the application range of THZ2 and improves the application value of the THZ 2.
Drawings
FIG. 1 is a schematic diagram of mouse ulcerative colitis model construction.
FIG. 2 is a schematic diagram of the construction of a mouse ulcerative colitis-associated colon cancer model.
FIG. 3 is a graph showing the results of analyzing the body weight changes of mice in the negative control group, the positive control group and the treatment group 3 in the mouse ulcerative colitis test.
Fig. 4 is a graph for analyzing the results of the blood stool degree of the mice in the mouse ulcerative colitis test, showing that the blood stool period of the treatment group using THZ2 is shorter than that of the positive control group, and the severity of the blood stool of the treatment group is also lower than that of the positive control group.
FIG. 5 is a graph showing the result of analyzing the diarrhea degree of mice in the mouse ulcerative colitis test, which shows that the diarrhea degree of the treatment group using THZ2 is lower than that of the positive control group.
FIG. 6 is a photograph showing the bloody stool and diarrhea of 3 mice in the negative control group, the positive control group and the treatment group at 0, 6 and 12 days respectively in the mouse ulcerative colitis experiment.
FIG. 7 is a microscopic image of colon tissue sections of mice in three groups of a negative control group, a positive control group and a treatment group after HE staining in an experiment of mouse ulcerative colitis; the black scale at the lower right corner of the left three images is 200 microns, and the right three images are respectively partial enlarged views corresponding to the left images.
FIG. 8 is a development of Western immunoblots and a quantitative bar graph of changes in the levels of inflammation-associated proteins in the colon of mice in experiments with ulcerative colitis in mice.
FIG. 9 is a graph of the analysis of the body weight results of mice in three groups, negative control group, positive control group and treatment group, in the experiment of colon cancer associated with ulcerative colitis in mice.
FIG. 10 is a graph showing the analysis of the bloody stool level of mice in three groups, namely a negative control group, a positive control group and a treatment group in the experiment of colon cancer related to mouse ulcerative colitis.
FIG. 11 is a graph showing the result of diarrhea in mice of three groups, i.e., a negative control group, a positive control group and a treatment group in an experiment on colon cancer related to ulcerative colitis in mice.
FIG. 12 is a colon anatomy diagram of mice in three groups, negative control group, positive control group and treatment group in the experiment of colon cancer related to ulcerative colitis in mice; wherein the white scale in the figure is 1 cm.
FIG. 13 is a statistical chart of the number of tumors in colon of mice in three groups, namely a negative control group, a positive control group and a treatment group in the experiment of colon cancer related to mouse ulcerative colitis.
FIG. 14 is a microscopic image of colon tissue sections of three groups of mice, negative control group, positive control group and treatment group, after HE staining in a mouse ulcerative colitis-associated colon cancer experiment; the black scale at the lower right corner of the left three images is 200 microns, and the right three images are respectively partial enlarged views corresponding to the left images.
FIG. 15 is a development and quantification bar graph of Western immunoblots of changes in the levels of inflammation-associated proteins in the colon of mice in experiments with colon cancer associated with ulcerative colitis in mice.
Detailed Description
The present invention will be described in further detail with reference to examples and drawings, but the present invention is not limited thereto.
Example 1 mouse ulcerative colitis test
1. Test drug
THZ2 powder (purchased from APExBIO, USA, Cat. No. A8717) was dissolved in DMSO solvent to give 0.1g/mL stock solution, diluted with physiological saline to 1mg/mL, and administered by intraperitoneal injection at a dose of 10mg/kg for 2 times per day.
2. Laboratory animal
SPF-grade BABL/c male mice (6-7 weeks old, 17-19 g) were 13 in total. The license number is provided by the Guangdong province medical experimental animal center: SCXK (Yue) 2013-.
3. Establishment of mouse ulcerative colitis model
DSS (dextran sulfate) is widely used in the animal model construction of mouse ulcerative colitis.
As shown in FIG. 1, experimental mice were continuously fed with sterile, pure water containing DSS (purchased from Shanghai assist, Sheng Biotech Co., Ltd., cat # 60316ES76) at a concentration of 2.5% for 7 days. When the mice have main symptoms such as bloody stool, diarrhea and the like, the successful establishment of the mouse ulcerative colitis model is proved. The experimental mice were fed with sterile, pure water without DSS for one week on day 8, preventing the mice from dying due to severe diarrhea in bloody stools. Mice were sacrificed on day 14 and the experiment was ended.
4. Experiment grouping
The experiments were divided into 3 groups as follows:
(1) negative control group without DSS + without THZ2 (3 mice);
(2) positive control group with DSS + without THZ2 (5 mice);
(3) there was a DSS + treatment group with THZ2 (5 mice).
As shown in FIG. 1, the administration pattern, administration period and administration frequency of the positive control group were identical to those of the treatment group. In the treatment group, compound THZ2 was administered as a dose of 10 mg/kg/day for 2 injections per day for 2 weeks starting on the first day and ending the experiment; whereas the positive control group was injected with physiological saline only without compound THZ 2; the observation time was 2 weeks.
Example 2 mouse ulcerative colitis associated with colon cancer experiment
1. Test drug
THZ2 powder (purchased from APExBIO, USA, Cat. No. A8717) was dissolved in DMSO solvent to give 0.1g/mL stock solution, diluted with physiological saline to 1mg/mL, and administered by intraperitoneal injection at a dose of 10mg/kg for 2 times per day.
2. Laboratory animal
SPF-grade BABL/c male mice (6-7 weeks old, 17-19 g) were 13 in total. The license number is provided by the Guangdong province medical experimental animal center: SCXK (Yue) 2013-.
3. Establishment of mouse ulcerative colitis related colon cancer model
AOM (azoxymethane) is metabolized in the living body to methyl azoxymethanol, which converts base G in DNA to base a, thereby exerting carcinogenic effects.
As shown in FIG. 2, mice were fed with sterile water once on day 1 by intraperitoneal injection of AOM (10mg/kg) (purchased from Sigma Aldrich, USA, Cat. No. A5486). Starting on day 8, the experimental mice were fed for three cycles, one cycle every 3 weeks. The experimental mice were fed with sterile, pure water containing DSS at a concentration of 2.5% at week 1 of the cycle, followed by 2 weeks of DSS-free sterile water.
4. Experiment grouping
The experiments were divided into 3 groups:
(1) negative control group without DSS + without THZ2 (3 mice);
(2) positive control group with DSS + without THZ2 (5 mice);
(3) there was a DSS + treatment group with THZ2 (5 mice).
As shown in fig. 2, the administration pattern, administration period and administration frequency of the positive control group were consistent with those of the treatment group. In the treatment group, compound THZ2 was administered as an intraperitoneal injection at a dose of 10 mg/kg/day, 2 times daily. The dosing time was 9 weeks from the start of week 1 to the end of week 10. While the positive control group was injected with physiological saline only without compound THZ 2. The observation time was 10 weeks.
Example 3 effects example
The following studies were conducted for each treatment group of example 1 and example 2:
1. western blot experiment
The expression level of the protein related to the body inflammation, such as COX-2, IL-6, TNF-alpha and the like, can reflect the body inflammation level to a certain extent. The higher the level of such proteins, the higher the level of inflammation in the body is reflected.
Cyclooxygenase (COX), also known as Prostaglandin endoperoxide synthase (PTGS), is a bifunctional enzyme having Cyclooxygenase and catalase activities and is a key enzyme catalyzing the conversion of arachidonic acid to prostaglandins. At present, cyclooxygenase has been found to have two kinds of COX-1 and COX-2 isozymes, wherein the COX-1 is structural type, mainly exists in tissues such as blood vessels, stomach, kidney and the like, participates in the regulation of vasomotor, platelet aggregation, blood flow of gastric mucosa, gastric mucus secretion, renal function and the like, and has the functions of protecting gastrointestinal mucosa, regulating platelet aggregation, regulating resistance of peripheral blood vessels and regulating blood flow distribution of kidney. The latter is inducible, and various damaging chemical, physical and biological factors activate phospholipase A2 to hydrolyze cell membrane phospholipids to produce arachidonic acid, which is oxidized by COX-2 catalysis to produce prostaglandins.
Interleukin-6 (Interleukin 6), interleukin 6(IL-6) for short, is a cytokine, belongs to one of interleukins, and participates in acute and chronic inflammatory reactions and body fever. It is produced by a variety of cells such as monocytes/macrophages, T lymphocytes, B lymphocytes, etc. at the site of inflammation.
Tumor necrosis factor (TNF- α), a multifunctional proinflammatory cytokine, belongs to the Tumor Necrosis Factor (TNF) superfamily. This cytokine is secreted primarily by macrophages and is involved in regulating a wide range of biological processes including cell proliferation, differentiation, apoptosis, lipid metabolism and coagulation. The cytokine is involved in a variety of diseases, including autoimmune diseases, insulin resistance and cancer.
In the experiment of ulcerative colitis in mice of example 1 and the experiment of colon cancer associated with ulcerative colitis in mice of example 2, 1 mouse was randomly selected for the negative control group, and 2 mice were randomly selected for each of the positive control group and the treatment group, for a total of 5 mice. Then, the protein lysate of the colon cells is extracted and subjected to a western blot experiment to detect the protein level change related to the inflammation. Among the antibodies used were 4, COX-2 (purchased from Baker bioengineering, Inc., Wuhan, Inc., Cat. No. BA0738), IL-6 (purchased from Sizhenbai Biotech, Inc., Beijing, Cat. 4ab080344), TNF-alpha (purchased from www.cusabio.com, Cat. Huamei bioengineering, Inc., Cat. PA07427A0Rb), beta-tubulin (purchased from Tianjin three arrow biotechnologies, Inc., Cat. No. KM 9003T).
Extracting colon cell protein lysate:
(1) equal amounts of colon tissue were excised and placed in an EP tube by grinding.
(2) The tissue was lysed with 200. mu.L of 1% protein lysate at 0 ℃ for 30 min.
(3) After the cleavage, the mixture was centrifuged at 4 ℃ and the rotation speed was 12 rpm.
(4) And (4) sucking the supernatant fluid to obtain the colon cell protein lysate.
The procedures of Western blotting experiments are referred to "the Proc. protein science and Experimental guidelines for protein science", edited by JE. Kelin Gen et al, Li Cai Tao et al.
2. Colon tissue section HE staining (hematoxylin-eosin staining) experiment
In the experiment of ulcerative colitis in mice of example 1 and the experiment of colon cancer related to ulcerative colitis in mice of example 2, 1 mouse was randomly selected from the negative control group, the positive control group and the treatment group, respectively, and colon tissue was dissected, embedded with paraffin, sectioned, stained with HE, and finally observed under a microscope.
3. Observation index
Mouse ulcerative colitis experiment of example 1: the observation criteria included mouse body weight, mouse bloody stool severity ("score 0" for no blood in stool, "score 2" for small amount of blood in stool, "score 4" for large amount of bleeding, and score larger for greater inflammation), mouse diarrhea severity ("score 0" for globular formed stool, "score 0.33" for semi-formed soft stool, "score 0.66" for unformed soft stool, "score 1.00" for liquid stool, and score larger for greater inflammation), lymphocyte infiltration in mouse colon tissue (greater numbers of lymphocytes in the lower layer of the colon basement membrane, representing greater inflammation), and changes in mouse colon inflammatory protein levels (greater expression levels of COX-2, IL-6, and TNF- α proteins, representing greater inflammation).
Mouse ulcerative colitis associated colon cancer experiment of example 2: the observation indexes include the body weight of the mouse, the severity of bloody stool of the mouse ("0 point" represents no blood in the stool, "2 point" represents a small amount of blood in the stool, "4 point" represents a large amount of bleeding, the larger the score represents the more severe the degree of inflammation), the severity of diarrhea of the mouse ("0 point" represents a globular formed stool, "0.33 point" represents a semi-formed soft stool, "0.66 point" represents an unformed soft stool, "1 point" represents a liquid stool, the larger the score represents the more severe the degree of inflammation), the number of tumors in the colon of the mouse (the larger the number of tumors represents the more severe the degree of inflammation of the cancer), the infiltration of lymphocytes in the colon tissue of the mouse (the number of lymphocytes under the basement membrane of the colon, the larger the number represents the more severe the degree of inflammation), and the changes in the levels of inflammatory proteins of the colon of the mouse (the COX-2, IL-6 and TNF-, representing a higher degree of inflammation).
For the specific observation and detection methods, reference may be made in part to the following documents:
construction and comparison of 2 Mass concentration DSS-induced acute ulcerative colitis rat model (Royal, Bayongxin, proceedings of Guangzhou university of traditional Chinese medicine, 2019, No. 4 of 4 months, 36 th volume, No. 4)
Research on the effect of pearl scald ointment on the treatment of ulcerative colitis in mice (Dongyuan et al, world medicine, 14 th volume in 04/2019, 3 rd volume).
4. Results of the experiment
(1) Body weight analysis
As shown in fig. 3, in the mouse ulcerative colitis test, the body weight of 3 groups of mice was subjected to T test, P is greater than 0.05, and no statistical difference exists, which proves that THZ2 has no obvious toxic and side effect.
As shown in fig. 9, in the experiment of colon cancer related to ulcerative colitis in mice, the weights of 3 groups of mice were subjected to T test, and the negative control group and the positive control group were subjected to T test, wherein P is less than 0.01, the difference is very significant, and the statistical significance is provided, which proves that the model of colon cancer related to ulcerative colitis was successfully constructed, and the weight of mice is significantly reduced by colon cancer related to ulcerative colitis. T test is carried out on the treatment group and the positive control group, the difference is obvious and has statistical significance, and the THZ2 can weaken the influence of colon cancer related to ulcerative colitis on the weight reduction of mice to a certain extent.
(2) Analysis of bloody stool period and bloody stool degree
As shown in fig. 4, in the mouse ulcerative colitis experiment, the treatment of THZ2 can shorten the bloody stool period, the bloody stool period of the treatment group is two days less than that of the positive control group, the THZ2 can obviously reduce the severity of the bloody stool of the mouse, the treatment group and the positive control group are subjected to T test, P is less than 0.01, the difference is very significant, and the statistical significance is achieved.
As shown in fig. 10, in the experiment of colon cancer related to ulcerative colitis in mice, when T test is performed on the treatment group and the positive control group, P is less than 0.01, the difference is very significant and has statistical significance, and the degree of bloody stool of the mice in the treatment group is very low and is obviously different from the degree of bloody stool of the mice in the positive control group.
The results prove that the THZ2 inhibitor CDK7 can relieve the bloody stool degree of mice with ulcerative colitis and colon cancer related to the ulcerative colitis to a certain extent and shorten the bloody stool period.
(3) Analysis of degree of diarrhea
As shown in fig. 5, in the mouse ulcerative colitis experiment, the treatment group and the positive control group are subjected to a T test, P is less than 0.01, the difference is very significant and has statistical significance, and the treatment of the CDK7 inhibitor THZ2 is proved to relieve the severity of diarrhea of mice.
As shown in fig. 6, the mice of the treatment group in example 1 were relieved of bloody stools and diarrhea. On day 0, before DSS treatment, the feces of the mice in group 3 were formed spherical, with clean perianal villi and no blood in the feces. On day 6, the feces of the mice in the negative control group are shaped spheres, the villi around the anus are clean, and the feces have no blood; the excrement of the positive control group mouse is liquid, and a large amount of villi around the anus is stained with the excrement and accompanied with heavy bleeding; the feces of the mice in the treatment group are unformed soft feces, and a small amount of fluff around the anus is stained with the feces accompanied with a small amount of bleeding. On day 12, the feces of the mice in the negative control group are shaped spheres, the villi around the anus are clean, and the feces have no blood; the feces of the positive control group mice are unformed soft feces, a small amount of fluff around the anus is stained with the feces, and the feces have no blood; the feces of the mice in the treatment group are between the formed spherical feces and the semi-formed soft feces, the villi around the anus are clean, and the feces have no blood. The THZ2 inhibitor CDK7 is proved to relieve diarrhea and bloody stool caused by ulcerative colitis of mice to a certain extent.
As shown in fig. 11, in the experiment of colon cancer related to ulcerative colitis in mice, the treatment group and the positive control group were subjected to T test, P is less than 0.01, the difference is very significant, and the statistical significance is achieved, and the diarrhea degree of the mice in the treatment group is lower than that of the positive control group.
The results prove that the THZ2 inhibitor CDK7 can relieve the diarrhea degree and shorten the diarrhea period of mice with ulcerative colitis and mice with colon cancer related to ulcerative colitis to a certain extent.
(4) Colonic lymphocyte infiltration analysis
As shown in fig. 7, in the mouse ulcerative colitis experiment, the colon tissue of the treated group was similar to the colon tissue of the negative control group, and was not changed much, and the infiltration degree of lymphocytes was low, while the colon tissue of the positive control group had a large amount of lymphatic infiltration.
As shown in fig. 14, in the colon cancer experiment related to mouse ulcerative colitis, the colon tissue of the treated group was similar to the colon tissue of the negative control group, and was not changed much, and the infiltration degree of lymphocytes was low, while the colon tissue of the positive control group had a large amount of lymphatic infiltration.
The results prove that the THZ2 inhibitor CDK7 can relieve the colonic lymphatic infiltration condition of mice with ulcerative colitis and colon cancer related to ulcerative colitis to a certain extent.
(5) Colon tumor number analysis
As shown in fig. 12 and fig. 13, in the experiment of colon cancer related to mouse ulcerative colitis, the colon of the negative control group had no tumor, the colon of the positive control group had a large number of tumors, the number of tumors of the treatment group was much smaller than that of the positive control group, and the positive control group and the treatment group were subjected to T test, and P was less than 0.01, and the difference was very significant and had statistical significance. THZ2, an inhibitor of CDK7, was shown to reduce to some extent the incidence of tumors in mice with colon cancer associated with ulcerative colitis.
(5) Inflammation-related protein level analysis: in the mouse ulcerative colitis experiment (shown in figure 8) and the mouse ulcerative colitis-related colon cancer experiment (shown in figure 15), the levels of inflammation-related proteins COX-2, IL-6 and TNF-alpha are low expressed in a negative control group, high expressed in a positive control group and low expressed in a treatment group, and the positive control group and the treatment group are subjected to T test, wherein P is less than 0.01, the difference is very significant, and the statistical significance is achieved. The THZ2 inhibitor CDK7 is proved to reduce the level of intracolonic inflammation related protein of mice with ulcerative colitis and colon cancer related to ulcerative colitis to a certain extent and relieve inflammatory reaction.
The above experimental results show that: the compound THZ2 can effectively shorten the bloody stool period, relieve the severity of bloody stool and diarrhea, weaken the lymphocyte infiltration in colon, reduce the level of inflammation-related protein and reduce the incidence of tumors when being used for treating ulcerative colitis and colon cancer related to ulcerative colitis with the symptoms of bloody stool and diarrhea; it is shown that the inhibitor THZ2 of CDK7 is effective in the treatment of ulcerative colitis, as well as in the treatment of colon cancer associated with ulcerative colitis.
The above embodiments are preferred embodiments of the present invention, but the present invention is not limited to the above embodiments, and any other changes, modifications, substitutions, combinations, and simplifications which do not depart from the spirit and principle of the present invention should be construed as equivalents thereof, and all such changes, modifications, substitutions, combinations, and simplifications are intended to be included in the scope of the present invention.
Claims (6)
- Use of a CDK7 inhibitor in the preparation of a medicament for the prevention and treatment of colon cancer, characterized by:the CDK7 inhibitor is THZ2, and the chemical substance accession number CAS of the THZ2 is 1604810-84-5.
- 2. Use of an inhibitor of CDK7 in the preparation of a medicament according to claim 1, wherein:the medicine for preventing and treating colon cancer contains at least one of THZ2 and medicinal salts thereof.
- 3. Use of a CDK7 inhibitor according to any one of claims 1-2 in the preparation of a medicament for the prevention and treatment of colon cancer, wherein:the medicine for preventing and treating colon cancer contains one or more pharmaceutically acceptable auxiliary materials.
- 4. Use of an inhibitor of CDK7 in the preparation of a medicament according to claim 3, wherein:the adjuvant is at least one of sustained release agent, filler, binder, humectant, disintegrating agent, absorption enhancer, surfactant, antibacterial agent, aromatic, antioxidant, pH regulator, protectant, diluent, lubricant, and solvent.
- 5. Use of a CDK7 inhibitor according to any one of claims 1-2 in the preparation of a medicament for the prevention and treatment of colon cancer, wherein:the medicine for preventing and treating colon cancer is prepared into a pharmaceutical dosage form by adopting a conventional method in the field.
- 6. Use of an inhibitor of CDK7 in the preparation of a medicament according to claim 5, wherein:the pharmaceutical preparation is injection, capsule, pill, tablet, granule, tincture, inhalation preparation, oral solution, oral suspension, and oral emulsion.
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