CN110101703A - Application of the CDK7 inhibitor in preparation ulcerative colitis or colon cancer drug - Google Patents
Application of the CDK7 inhibitor in preparation ulcerative colitis or colon cancer drug Download PDFInfo
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Abstract
The present invention provides CDK7 inhibitor in the application for preparing ulcerative colitis or colon cancer drug.The present invention passes through the research of Experiment on therapy Ulcerative Colitis mouse and the research of Experiment on therapy Ulcerative Colitis correlation colon cancer mouse, CDK7 inhibitor is had found for the first time, especially THZ2 is able to suppress the adjoint bloody stool symptom of ulcerative colitis, and the adjoint symptom of diarrhea of ulcerative colitis can be reduced, ulcerative colitis and ulcerative colitis correlation colon cancer can effectively be treated, facilitate patient and reduces body fluid loss, effectively shorten the bloody stool period, alleviate the severity of bloody stool and the severity of diarrhea, weaken colon lymphocytic infiltration, it is horizontal to reduce inflammation related proteins, reduce Tumor incidence, shorten the treatment cycle of patient, improve cure rate, with positive medication guide meaning, the application range of THZ2 is further expanded, improve its application value.
Description
Technical field
The invention belongs to pharmaceutical technology fields, in particular to CDK7 inhibitor is in preparation ulcerative colitis or colon cancer medicine
The application of object.
Background technique
Inflammatory enteritis is broadly divided into ulcerative colitis (ulcerative colitis, UC) and Crohn disease
(Crohn's disease,CD).Wherein Ulcerative Colitis is unclear, and normal recurrent exerbation, is often accompanied by bloody stool, abdomen
The symptom such as rush down, the submucous layer of colon under pathology section examination there are a large amount of leukocyte infiltrations, if things go on like this will increase patient's hair
The incidence probability of raw colon cancer is a kind of disease for threatening health of people, and there is presently no a kind of specific drugs can cure all burst
The patient of ulcer enteritis.
Academic circles at present thinks that inflammation is one of them important inducement of cancer.The relevant colon of ulcerative colitis
Cancer is since ulcerative colitis cannot be cured in time mostly, and for a long time, ulcerative colitis further deteriorates.Colon
Cancer seriously threatens the life and health of people as a kind of cancer for a long time, but molecular mechanism of specifically falling ill, and arrives at present also not
It is clear.
Compound THZ2 belongs to the micromolecular inhibitor of Expression Vector Specific for Cyclin CDK7 a kind of, it can occur competing with ATP
It strives on the residue for the 312nd cysteine for being integrated to CDK7, so that selection inhibits the phosphorylation activity of CDK7 well.CDK1
It is related to CDK2 to inflammation, but activate the relationship of the active CDK7 of CDK1 and CDK2 and inflammation also indefinite, so far not yet
The research of CDK7 inhibitor THZ2 treatment of colon cancer relevant to inflammation treatment and ulcerative colitis is reported.
Summary of the invention
The purpose of the present invention is to overcome the shortcomings of the existing technology and deficiency, provides CDK7 inhibitor in preparation and prevents and treats ulcer
Application in property colitis and/or colon cancer drug.
The purpose of the invention is achieved by the following technical solution:
Application of the CDK7 inhibitor in preparation prevention and treatment ulcerative colitis and/or colon cancer drug.
The CDK7 inhibitor is preferably THZ2 (CAS:1604810-84-5), the structure of the THZ2 such as I institute of formula
Show.
Contain at least one in THZ2 and its pharmaceutical salts in the prevention and treatment ulcerative colitis and/or colon cancer drug
Kind.
The prevention and treatment ulcerative colitis and/or colon cancer drug contain one or more pharmaceutically acceptable auxiliary
Material.
The auxiliary material be preferably sustained release agent, excipient, filler, adhesive, wetting agent, disintegrating agent, sorbefacient,
Surfactant, antibacterial agent, aromatic, antioxidant, pH adjusting agent, protective agent, diluent, lubricant, solvent, matrix or carrier
At least one of material.
The prevention and treatment ulcerative colitis and/or colon cancer drug can be prepared into respectively using the conventional method of this field
Kind of dosage form, as injection, capsule, pill, tablet, granule, tincture, sucking preparation, oral solution, oral suspensions,
The dosage forms such as Orally taken emulsion.
Inventor has carried out the research and progress of Experiment on therapy Ulcerative Colitis mouse using compound THZ2
The research of Experiment on therapy Ulcerative Colitis correlation colon cancer mouse.The result shows that compound THZ2 can inhibit exedens
The adjoint bloody stool symptom of colitis, can reduce the adjoint symptom of diarrhea of ulcerative colitis.It therefore, can be by compound
THZ2 is used to prepare the drug for the treatment of ulcerative colitis and ulcerative colitis correlation colon cancer.
The present invention has the following advantages and effects with respect to the prior art:
On the one hand the adjoint bloody stool of ulcerative colitis and diarrhea lose patient's body fluid flow serious, body is more empty
It is weak, on the other hand further increase the treatment difficulty of the disease.Present invention firstly discovers that CDK7 inhibitor THZ2 can have
Effect treatment ulcerative colitis and ulcerative colitis correlation colon cancer are conducive to patient and reduce body fluid loss, shorten patient
Treatment cycle, improve cure rate, have positive medication guide meaning, further expanded the application range of THZ2, improve
Its application value.
Detailed description of the invention
Fig. 1 is that Mouse Ulcerative Colitis Model constructs schematic diagram.
Fig. 2 is that colitis in mice correlation model of colon cancer constructs schematic diagram.
Fig. 3 be colitis in mice experiment in, negative control group, 3 groups of mouse of positive controls and treatment group body
Weight result of variations analysis chart.
Fig. 4 is the bloody stool degree result analysis chart of mouse in colitis in mice experiment, shows controlling using THZ2
The bloody stool period for the treatment of group is shorter than the bloody stool period of positive controls and the bloody stool severity for the treatment of group also below positive control
Group bloody stool degree.
Fig. 5 is the diarrhoea degree result analysis chart of mouse in colitis in mice experiment, shows controlling using THZ2
Treatment group diarrhoea degree is lower than the diarrhoea degree of positive controls.
Fig. 6 be colitis in mice experiment in respectively at the 0th, 6 and 12 day negative control group, positive controls and
3 groups of mouse bloody stools for the treatment of group and diarrhea situation photographic examples figure.
Fig. 7 is the knot of three groups of negative control group in colitis in mice experiment, positive controls and treatment group mouse
The microscope mirror following figure of the intestinal tissue histotomy after HE dyeing；Wherein, the black scale in the lower right corner of three width figure of left side is 200
Micron, three width figure of right side is the partial enlarged view of corresponding left hand view respectively.
Fig. 8 is that the protein of inflammation related proteins matter level variation in mouse Colon in colitis in mice experiment is exempted from
Epidemic disease trace development figure and quantization histogram.
Fig. 9 is negative control group, positive controls and treatment group three in the experiment of colitis in mice correlation colon cancer
The weight result analysis chart of group mouse.
Figure 10 is negative control group, positive controls and treatment group three in the experiment of colitis in mice correlation colon cancer
The bloody stool degree result analysis chart of group mouse.
Figure 11 is negative control group, positive controls and treatment group three in the experiment of colitis in mice correlation colon cancer
The diarrhoea degree result analysis chart of group mouse.
Figure 12 is negative control group, positive controls and treatment group three in the experiment of colitis in mice correlation colon cancer
The colon anatomy figure of group mouse；Wherein, white scale is 1 centimetre in figure.
Figure 13 is negative control group, positive controls and treatment group three in the experiment of colitis in mice correlation colon cancer
The colon tumor number statistical chart of group mouse.
Figure 14 is negative control group, positive controls and treatment group three in the experiment of colitis in mice correlation colon cancer
The microscope mirror following figure of the colonic tissue slice of group mouse after HE dyeing；Wherein, the black mark in the lower right corner of three width figure of left side
Ruler is 200 microns, and three width figure of right side is the partial enlarged view of corresponding left hand view respectively.
Figure 15 is that inflammation related proteins matter level becomes in mouse Colon in the experiment of colitis in mice correlation colon cancer
The protein immunoblotting development figure and quantization histogram of change.
Specific embodiment
Present invention will now be described in further detail with reference to the embodiments and the accompanying drawings, but embodiments of the present invention are unlimited
In this.
The experiment of 1 colitis in mice of embodiment
1. test medicine
THZ2 pulvis (is purchased from U.S. APExBIO, article No. A8717), is dissolved as 0.1g/mL mother liquor with DMSO solvent, then
It is injected 2 times daily with normal saline dilution to 1mg/mL by the dose intraperitoneal injection of 10mg/kg.
2. experimental animal
SPF grades of BABL/c male mice (6~7 week old, 17~19g), totally 13.Guangdong Medical Lab Animal Center
It provides, credit number: SCXK (Guangdong) 2013-0002.
3. the foundation of Mouse Ulcerative Colitis Model
DSS (dextran sodium sulfate, Dextran sulfate sodium), is widely used in murine lesion knot
In the animal model building of enteritis.
As shown in Figure 1, continuous 7 days with containing concentration be 2.5% DSS (be purchased from Shanghai Yi Sheng Biotechnology Co., Ltd,
Article No. is 60316ES76) sterile pure water feed experiment mice.When there are the main symptom such as bloody stool, diarrhea in mouse, it was demonstrated that small
Mouse Ulcerative Colitis Model is successfully established.Experiment mice is fed with the sterile pure water without DSS within 8th day and continue one week, prevent
Mouse leads to dead mouse because bloody stool diarrhea is serious.In the 14th day execution mouse, terminate experiment.
4. experimental group
Experiment is divided into following 3 groups:
(1) negative control group without DSS+ without THZ2 (3 mouse)；
(2) there are positive controls (5 mouse) of the DSS+ without THZ2；
(3) DSS+ has the treatment group (5 mouse) of THZ2.
Such as Fig. 1, positive controls are consistent with treatment group administration mode, dosage period and administration number of times.In treatment group, change
Conjunction object THZ2 gave according to 10mg/kg/ days dosage to be injected intraperitoneally, and injection 2 times daily, administration time is from daystart to reality
End is tested, totally 2 weeks；And positive controls then only inject the physiological saline for being free of compound THZ2；Observing time is 2 weeks.
The experiment of 2 colitis in mice correlation colon cancer of embodiment
1. test medicine
THZ2 pulvis (is purchased from U.S. APExBIO, article No. A8717), is dissolved as 0.1g/mL mother liquor with DMSO solvent, then
It is injected 2 times daily with normal saline dilution to 1mg/mL by the dose intraperitoneal injection of 10mg/kg.
2. experimental animal
SPF grades of BABL/c male mice (6~7 week old, 17~19g), totally 13.Guangdong Medical Lab Animal Center
It provides, credit number: SCXK (Guangdong) 2013-0002.
3. the foundation of colitis in mice correlation model of colon cancer
AOM (azoxymethane, oxidized azoethane) can in living organism intracellular metabolite at methyl azoxymethanol
Bases G in DNA is set to be transformed into base A, to play carcinogenesis.
As shown in Fig. 2, the 1st day intraperitoneal injection AOM (10mg/kg) (is purchased from Sigma-Aldrich, the U.S., article No. is
A5486) once, fed mouse one week with sterile water.Start within 8th day, recycled according to one every 3 weeks, carries out three circulations and feed
Experiment mice.The circulation the 1st week feeds experiment mice with the sterile pure water for the DSS for being 2.5% containing concentration, and then 2 weeks without DSS
Sterile water feed experiment mice.
4. experimental group
Experiment is divided into 3 groups:
(1) negative control group without DSS+ without THZ2 (3 mouse)；
(2) there are positive controls (5 mouse) of the DSS+ without THZ2；
(3) DSS+ has the treatment group (5 mouse) of THZ2.
Such as Fig. 2, positive controls are consistent with treatment group administration mode, dosage period and administration number of times.In treatment group, change
Conjunction object THZ2 gave according to 10mg/kg/ days dosage to be injected intraperitoneally, injection 2 times daily.Administration time since the 1st weekend to
The experiment of 10th weekend terminates, and totally 9 weeks.And positive controls then only inject the physiological saline for being free of compound THZ2.Observing time
It is 10 weeks.
3 effect example of embodiment
Reason group everywhere in embodiment 1, embodiment 2 is studied as follows:
1. protein immunoblotting is tested
Relevant to body inflammatory albumen, such as COX-2, IL-6, TNF-α etc., the expression energy one of this albuminoid
Determine to reflect that body inflammatory is horizontal in degree.This kind of protein level is higher, reflects that body inflammatory level is higher.
Cyclooxygenase (Cyclooxygenase, COX) is also known as prostaglandin endoperoxides synzyme
(Prostaglandin-endoperoxide synthase, PTGS), is a kind of bifunctional enzyme, has Cycloxygenase and peroxide
Change hydrogenase activity, is the key enzyme that conversion of arachidonic acid is converted into prostaglandin.Having now been found that Cycloxygenase, there are two types of COX-1
With COX-2 isodynamic enzyme, the former is structural type, is primarily present in the tissue such as blood vessel, stomach, kidney, participates in angiokinesis, platelet aggregation
The adjusting of collection, gastric mucosal blood flow, stomach mucilage secretion and renal function etc., function and protection gastrointestinal mucosa, adjust platelet aggregation,
It adjusts the resistance of peripheral blood vessel and adjusts renal blood flow and be distributed with.The latter is induction type, various damaging chemistry, physics and biology
Factor activator phospholipase A2 hydrolyzed cellular membrane phospholipid, generates arachidonic acid, and the latter generates prostate through COX-2 catalysis oxygenation
Element.
Interleukin-6 (interleukin 6), abbreviation interleukin 6 (IL-6) are a kind of cell factors, are belonged to white thin
One kind of born of the same parents' interleukin participates in acute and chronic inflammation reaction and organism fever process.It is monokaryon/macrophage by inflammation part
Produced by the various kinds of cell such as cell, T lymphocyte, bone-marrow-derived lymphocyte.
Tumor necrosis factor (tumor necrosis factor α, TNF-α) is a kind of multi-functional proinflammatory cytokine,
Belong to tumor necrosis factor (TNF) superfamily.This cell factor participates in adjusting extensive biology mainly by macrophages secrete
Process, including cell Proliferation, differentiation, apoptosis, lipid-metabolism and blood coagulation.The cell factor participates in a variety of diseases, including itself
Immunological diseases, insulin resistance and cancer.
Colon cancer related to the colitis in mice of embodiment 2 is tested in the colitis in mice of embodiment 1
In experiment, negative control group selects 1 mouse at random, and positive controls and treatment group respectively select 2 mouse at random, totally 5 mouse.
Then their colon cell protein cleavage liquid is extracted, protein immunoblotting experiment is carried out, to detect inflammation related proteins
Level variation.The antibody wherein used has 4, and COX-2 (is purchased from Wuhan Boster Biological Technology Co., Ltd., article No.
BA0738), IL-6 (being purchased from four Zheng Bai Biotechnology Co., Ltd of Beijing, article No. 4ab080344), TNF-α is (magnificent purchased from Wuhan
Bioengineering Co., Ltd www.cusabio.com, article No. PA07427A0Rb), β-tubulin (is purchased from three arrow biology skill of Tianjin
Art Co., Ltd, article No. KM9003T).
Colon cell protein cleavage liquid extraction step:
(1) colonic tissue of equivalent is cut, and grinds and is placed in EP pipe.
(2) tissue is cracked with 1% protein lysate of 200 μ L, cracking condition is 0 DEG C, 30 minutes.
(3) after cracking, 4 DEG C of centrifugations, revolving speed 12rpm.
(4) Aspirate supernatant is colon cell protein lysate.
The method and step of protein immunoblot experiment with reference to " fine works protein science experiment guide " (JE. Ke Lingen etc. writes,
Li Shentao etc. is translated).
2. colonic tissue is sliced HE dyeing (hematoxylin eosin staining) experiment
Colon cancer related to the colitis in mice of embodiment 2 is tested in the colitis in mice of embodiment 1
In experiment, 1 mouse is selected at random in negative control group, positive controls and treatment group respectively, dissection obtains colonic tissue, uses stone
Wax embedding, slice, then dyed with HE, finally observe under the microscope.
3. observation index
The colitis in mice of embodiment 1 is tested: observation index includes the weight of mouse, the serious journey of bloody stool of mouse
(" 0 point " represents does not have blood to degree in excrement, " 2 points ", which represent in excrement, a small amount of blood, and " 4 points " represent big bleeding, the bigger representative of score value
Degree of inflammation is more serious), (" 0 point " represents spherical molding excrement to diarrhea of mouse severity, and " 0.33 point " represents half-formed soft
Excrement, " 0.66 point " represents not molding soft excrement, and " 1.00 points " represent liquid excrement, and score value is bigger to represent degree of inflammation
It is more serious), (colon basilar memebrane lower layer lymphocyte quantity, quantity is more, generation for mouse Colon tissue medium size lymphocyte Infiltrating
Table degree of inflammation is more serious) and murine colonic inflammation protein level variation (COX-2, IL-6 and TNF-α protein expression level are got over
It is higher to represent degree of inflammation for height).
The colitis in mice correlation colon cancer of embodiment 2 is tested: observation index includes the weight of mouse, mouse
Bloody stool severity (" 0 point ", which represents, does not have blood in excrement, " 2 points ", which represent in excrement, a small amount of blood, and " 4 points " represent big bleeding, point
Value is bigger, and to represent degree of inflammation more serious), (" 0 point " represents spherical molding excrement to diarrhea of mouse severity, " 0.33 point " generation
The half-formed soft excrement of table, " 0.66 point " represents not molding soft excrement, and " 1 point " represents liquid excrement, score value bigger generation
Table degree of inflammation is more serious), tumor number (tumour quantity is more, represents the degree for suffering from cancer and gets over inflammation), mouse in mouse Colon
(colon basilar memebrane lower layer lymphocyte quantity, quantity is more, represents degree of inflammation and gets over for colonic tissue medium size lymphocyte Infiltrating
Seriously) and murine colonic inflammation protein level variation (COX-2, IL-6 and TNF-α protein expression level are higher, represent inflammation journey
It spends higher).
Specific observation, detection method part can refer to following document:
" 2 kinds of mass concentration DSS cause the building of acute ulcer Colitis rat model compared with " (Wang Qian, Bao Yongxin,
The 4th phase of volume 36 " Traditional Chinese Medicine University Of Guangzhou's journal " in April, 2019)
" Effect study of pearl ointment for treating scald intervention colitis in mice " (Dong Yuan etc., " world's traditional Chinese medicine " 2019
04 month the 3rd phase of volume 14).
4. experimental result
(1) weight is analyzed
As shown in figure 3, carrying out T inspection to 3 groups of mouse weights, P > 0.05 does not have in colitis in mice experiment
Statistical difference, it was demonstrated that THZ2 does not have apparent toxic side effect.
As shown in figure 9, T inspection is carried out to 3 groups of mouse weights in the experiment of colitis in mice correlation colon cancer,
Negative control group and positive controls carry out T inspection, and P < 0.01, difference is extremely significant, have statistical significance, it was demonstrated that exedens knot
Under enteritis correlation model of colon cancer constructs successfully, and ulcerative colitis correlation colon cancer can be such that the weight of mouse occurs obviously
Drop.Treatment group and positive controls carry out T inspection, P=0.04, and significant difference has statistical significance, it was demonstrated that THZ2 can be certain
Weaken the influence that ulcerative colitis correlation colon cancer declines mouse weight in degree.
(2) bloody stool period and bloody stool degree analyzing
As shown in figure 4, the treatment of THZ2 can shorten the period of bloody stool in colitis in mice experiment, treatment
The group bloody stool period two days fewer than the positive controls bloody stool period, THZ2 can be substantially reduced the bloody stool severity of mouse, will control
Treatment group and positive controls carry out T inspection, and P < 0.01, difference is extremely significant, have statistical significance.
As shown in Figure 10, in the experiment of colitis in mice correlation colon cancer, treatment group and positive controls are subjected to T
It examines, P < 0.01, difference is extremely significant, has statistical significance, the mouse bloody stool degree for the treatment of group is very low, with positive controls
The high bloody stool degree of mouse has significant difference.
Result above proves that CDK7 inhibitor THZ2 can alleviate ulcerative colitis and ulcerative colitis to a certain extent
The bloody stool degree of the mouse of scorching correlation colon cancer, and shorten the period of bloody stool.
(3) diarrhoea degree is analyzed
As shown in figure 5, in colitis in mice experiment, treatment group and positive controls are subjected to T inspection, P <
0.01, difference is extremely significant, has statistical significance, it was demonstrated that the treatment of CDK7 inhibitor THZ2 can alleviate the serious of diarrhea of mouse
Degree.
As shown in fig. 6, the bloody stool of the mouse for the treatment of group and diarrhea situation are eased in embodiment 1.At the 0th day, at DSS
Before reason, 3 groups of stool in mice is molding spherical shape, and perianal villus is clean, without blood in excrement.At the 6th day, negative control
Group stool in mice is molding spherical shape, and perianal villus is clean, and excrement does not have blood；Positive controls stool in mice be it is liquid,
A large amount of villus of perianal are stained with excrement, with big bleeding；Treatment group's stool in mice is not molding soft excrement, perianal
A small amount of villus speckles with excrement, with a small amount of bleeding.At the 12nd day, negative control group stool in mice was molding spherical shape, anus week
It is clean to enclose villus, excrement does not have blood；Positive controls stool in mice is not form soft excrement, and a small amount of villus of perianal speckles with excrement
Just, there is no blood in excrement；Treatment group's stool in mice is between the spherical and half-formed soft excrement of molding, perianal stem of villus
Only, there is no blood in excrement.Prove that CDK7 inhibitor THZ2 can alleviate abdomen caused by colitis in mice to a certain extent
It rushes down and bloody stool situation.
As shown in figure 11, in the experiment of colitis in mice correlation colon cancer, by treatment group and positive controls into
Row T is examined, and P < 0.01, difference is extremely significant, has statistical significance, and treatment group's diarrhea of mouse degree is lower than positive controls diarrhea
Degree.
Result above proves that CDK7 inhibitor THZ2 can alleviate mouse and the ulcer of ulcerative colitis to a certain extent
Property colitis correlation colon cancer mouse diarrhoea degree and shorten diarrhea period.
(4) colonic lymph cellular infiltration situation analysis
As shown in fig. 7, in colitis in mice experiment, the colonic tissue and negative control group colon group for the treatment of group
Knit similar, too not big variation, lymphocytic infiltration degree is low, and positive controls colonic tissue has a large amount of lymphatic infiltration.
As shown in figure 14, in the experiment of colitis in mice correlation colon cancer, the colonic tissue and feminine gender for the treatment of group
Control group colonic tissue is similar, and too not big variation, lymphocytic infiltration degree is low, and positive controls colonic tissue has largely
Lymphatic infiltration.
Result above proves that CDK7 inhibitor THZ2 can alleviate mouse and the ulcer of ulcerative colitis to a certain extent
The colonic lymph Infiltrating of the mouse of property colitis correlation colon cancer.
(5) colon tumor number is analyzed
As shown in Figure 12 and Figure 13, in the experiment of colitis in mice correlation colon cancer, negative control group colon does not have
Tumour, positive controls colon have massive tumor, and the tumour quantity for the treatment of group is few more many than the tumour quantity of positive controls, sun
Property control group and treatment group carry out T inspection, P < 0.01, difference is extremely significant, have statistical significance.Prove CDK7 inhibitor THZ2
The Tumor incidence of the mouse of ulcerative colitis correlation colon cancer can be reduced to a certain extent.
(5) inflammation related proteins horizontal analysis: (as shown in Figure 8) and murine lesion in colitis in mice experiment
Property colitis correlation colon cancer experiment in (shown in Figure 15), inflammation related proteins COX-2, IL-6, TNF-α protein level is in feminine gender
All low expression in control group, all high expression in positive controls, expression all has dropped in treatment group, by positive control
Group and treatment group carry out T inspection, and P < 0.01, difference is extremely significant, have statistical significance.Prove that CDK7 inhibitor THZ2 can be one
The colon inflammation for determining the mouse of the mouse that ulcerative colitis is reduced in degree and ulcerative colitis correlation colon cancer is related
The level of albumen alleviates inflammatory reaction.
It is above-mentioned the results showed that ulcerative colitis and ulcerative colitis correlation colon cancer are along with bloody stool and diarrhea
Symptom, compound THZ2 treatment can effectively shorten the bloody stool period, alleviate the severity of bloody stool and the severity of diarrhea, weaken
Colon lymphocytic infiltration reduces inflammation related proteins level, reduces Tumor incidence；Illustrate that CDK7 inhibitor THZ2 can have
Effect treatment ulcerative colitis, and the relevant colon cancer of effective treatment ulcerative colitis.
The above embodiment is a preferred embodiment of the present invention, but embodiments of the present invention are not by above-described embodiment
Limitation, other any changes, modifications, substitutions, combinations, simplifications made without departing from the spirit and principles of the present invention,
It should be equivalent substitute mode, be included within the scope of the present invention.
Claims (7)
- Application of the 1.CDK7 inhibitor in preparation prevention and treatment ulcerative colitis and/or colon cancer drug.
- 2. CDK7 inhibitor according to claim 1 is in preparation prevention and treatment ulcerative colitis and/or colon cancer drug Using, it is characterised in that:The CDK7 inhibitor is THZ2, and the chemical substance accession number CAS of the THZ2 is 1604810-84-5.
- 3. CDK7 inhibitor according to claim 1 is in preparation prevention and treatment ulcerative colitis and/or colon cancer drug Using, it is characterised in that:Contain at least one of THZ2 and its pharmaceutical salts in the prevention and treatment ulcerative colitis and/or colon cancer drug.
- 4. described in any item CDK7 inhibitor are in preparation prevention and treatment ulcerative colitis and/or colon cancer according to claim 1~3 Application in drug, it is characterised in that:The prevention and treatment ulcerative colitis and/or colon cancer drug contain one or more pharmaceutically acceptable auxiliary materials.
- 5. CDK7 inhibitor according to claim 4 is in preparation prevention and treatment ulcerative colitis and/or colon cancer drug Using, it is characterised in that:The auxiliary material is sustained release agent, excipient, filler, adhesive, wetting agent, disintegrating agent, sorbefacient, surface-active In agent, antibacterial agent, aromatic, antioxidant, pH adjusting agent, protective agent, diluent, lubricant, solvent, matrix or carrier material It is at least one.
- 6. described in any item CDK7 inhibitor are in preparation prevention and treatment ulcerative colitis and/or colon cancer according to claim 1~3 Application in drug, it is characterised in that:The prevention and treatment ulcerative colitis and/or colon cancer drug use the conventional method of this field to be prepared into pharmaceutical dosage form.
- 7. CDK7 inhibitor according to claim 6 is in preparation prevention and treatment ulcerative colitis and/or colon cancer drug Using, it is characterised in that:The pharmaceutical preparation be injection, capsule, pill, tablet, granule, tincture, sucking preparation, oral solution, Oral suspensions, Orally taken emulsion.
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN110940816A (en) * | 2019-12-19 | 2020-03-31 | 广西中医药大学附属瑞康医院 | Detection method for prevention and treatment of ulceration, nodule and canceration mechanism by spleen-tonifying, heat-clearing and blood-activating prescription |
| CN111803618A (en) * | 2020-06-03 | 2020-10-23 | 桂林医学院附属医院 | Application of GPRP acetate in preparation of medicine for treating ulcerative colitis |
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| WO2013128028A1 (en) * | 2012-03-01 | 2013-09-06 | Lead Discovery Center Gmbh | Pyrazolo - triazine derivatives as selective cyclin- dependent kinase inhinitors |
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| WO2013128028A1 (en) * | 2012-03-01 | 2013-09-06 | Lead Discovery Center Gmbh | Pyrazolo - triazine derivatives as selective cyclin- dependent kinase inhinitors |
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Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN110940816A (en) * | 2019-12-19 | 2020-03-31 | 广西中医药大学附属瑞康医院 | Detection method for prevention and treatment of ulceration, nodule and canceration mechanism by spleen-tonifying, heat-clearing and blood-activating prescription |
| CN111803618A (en) * | 2020-06-03 | 2020-10-23 | 桂林医学院附属医院 | Application of GPRP acetate in preparation of medicine for treating ulcerative colitis |
| CN111803618B (en) * | 2020-06-03 | 2023-05-05 | 桂林医学院附属医院 | Application of GPRP acetate in preparation of medicines for treating ulcerative colitis |
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| CN110101703B (en) | 2021-06-11 |
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