CN113694187A - Pharmaceutical composition for inhibiting myocardial fibrosis - Google Patents
Pharmaceutical composition for inhibiting myocardial fibrosis Download PDFInfo
- Publication number
- CN113694187A CN113694187A CN202110818057.2A CN202110818057A CN113694187A CN 113694187 A CN113694187 A CN 113694187A CN 202110818057 A CN202110818057 A CN 202110818057A CN 113694187 A CN113694187 A CN 113694187A
- Authority
- CN
- China
- Prior art keywords
- myocardial
- fibrosis
- pharmaceutical composition
- inhibiting
- btk
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
Images
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/43—Enzymes; Proenzymes; Derivatives thereof
- A61K38/45—Transferases (2)
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/4985—Pyrazines or piperazines ortho- or peri-condensed with heterocyclic ring systems
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/04—Inotropic agents, i.e. stimulants of cardiac contraction; Drugs for heart failure
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/12—Antihypertensives
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12Y—ENZYMES
- C12Y207/00—Transferases transferring phosphorus-containing groups (2.7)
- C12Y207/10—Protein-tyrosine kinases (2.7.10)
- C12Y207/10001—Receptor protein-tyrosine kinase (2.7.10.1)
Landscapes
- Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Animal Behavior & Ethology (AREA)
- Medicinal Chemistry (AREA)
- Veterinary Medicine (AREA)
- Organic Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Cardiology (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Heart & Thoracic Surgery (AREA)
- Epidemiology (AREA)
- Urology & Nephrology (AREA)
- Genetics & Genomics (AREA)
- Wood Science & Technology (AREA)
- Zoology (AREA)
- General Engineering & Computer Science (AREA)
- Vascular Medicine (AREA)
- Hospice & Palliative Care (AREA)
- Biochemistry (AREA)
- Gastroenterology & Hepatology (AREA)
- Immunology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Abstract
The invention relates to a pharmaceutical composition for inhibiting myocardial fibrosis, and belongs to the technical field of biological medicines. Because the acatinib has higher kinase selectivity and better safety, and in a pathological state, BTK in myocardial fibroblasts can directly bind and phosphorylate TGF-beta receptor I (T beta RI), thereby promoting the activation of downstream SMAD classical and MAPK non-classical fibrosis signal pathways. The Acalabrutinib can inhibit the phosphorylation and activation of BTK in a targeted mode, reduce the activation of a fibrosis signal path in a pathological state and further prevent the occurrence of myocardial pathological fibrosis. Therefore, researches show that the BTK inhibitor acarabutinib can inhibit myocardial fibrosis reaction under myocardial pathological conditions (such as myocardial infarction, hypertension, chronic myocardial ischemia and other pathological conditions), so that the heart function is protected, poor cardiac remodeling is prevented, and the occurrence of heart failure is controlled.
Description
Technical Field
The invention relates to the technical field of biomedicine, in particular to a pharmaceutical composition for inhibiting myocardial fibrosis.
Background
In real life, myocardial fibrosis is observed to varying degrees in almost all heart diseases. Myocardial fibrosis is an important marker of poor cardiac remodeling under the pathological condition of the heart, and can lead to the occurrence of heart failure in severe cases. Although some approaches have been found in basic research to be potentially effective in controlling the development of pathologic myocardial fibrosis, there are still limited clinical approaches to treating myocardial fibrosis. Cardiac fibrosis is most typically characterized by excessive extracellular matrix (ECM) deposition and activation of fibroblasts. Accumulated ECM between myocardial tissues leads to cardiac stiffness, decreased ventricular compliance, impaired cardiac function, and ultimately heart failure. Therefore, innovative strategies and the development of new drugs are of great value for improving the therapeutic efficacy and prognosis of various heart disease-related cardiopathological fibrosis.
Transforming growth factor beta (TGF-beta) is the most common fibrosis promoting factor in myocardial fibrosis, and TGF-beta promotes the occurrence of myocardial fibrosis under pathological conditions by activating downstream SMAD-dependent and SMAD-independent signaling pathways through TGF-beta receptor I (TbetaRI). At the same time, activation of these signaling pathways may also promote fibroblast activation and transformation to myofibroblast phenotype. Previous studies have shown that activated TGF- β ligands interact with TGF- β receptor II (Tss RII) to recruit and phosphorylate several serine and threonine residues of the Tss RII. Subsequently, phosphorylated Tss RI transmits downstream signals via phosphorylated SMAD2/SMAD3 heterodimers. SMAD2/SMAD3 and SMAD4 assemble into a trimer, which then translocates to the nucleus, driving transcription of fibrosis-associated genes. Furthermore, activated T β R i also leads to activation of non-canonical mitogen-activated protein kinase (MAPK) signaling pathways including p38, JNK or ERK, however, the mechanism of activation of fibrosis-associated pathways, particularly the TGF- β receptor, remains to be fully explored.
Bruton's Tyrosine Kinase (BTK) belongs to a member of the TEC kinase family of non-receptor tyrosine kinases. BTK is as fine as BPlays a key role in the development and function of cells. BTK, a protein tyrosine kinase, exerts its regulatory function by catalyzing protein phosphorylation at tyrosine residues, thereby altering the activity of its substrate or its ability to interact with other proteins. BTK has been found to be associated with the development of a number of serious human diseases, including chronic lymphocytic leukemia and certain hyperactivated inflammatory responses following infection. To this end, clinically approved covalent specific BTK inhibitors such as Acarabutinib (Chinese name acacetib or acacetib) have been demonstrated in clinical trials for a variety of diseases such as chronic lymphocytic leukemia,
Has good therapeutic effect on macroglobulinemia and mantle cell lymphoma. However, little is known about the role of BTK in non-immune cells and other diseases.
BTK has long been an attractive molecular target for treating various diseases, and also promotes the development of specific targeted therapy of small molecule drugs. BTK inhibitors have found wide use in clinical trials and basic research. The current research shows that the BTK inhibitor has effective treatment effect on patients with hematological malignancies and solid tumors.
Acarabretinib is a second generation irreversible BTK inhibitor that has been approved by the FDA for the treatment of chronic lymphocytic leukemia. Compared with the first generation BTK inhibitor such as Ibrutinib which can cause atrial fibrillation, the Acaraburtinib has more specific kinase selectivity and higher safety. Nevertheless, the research of the BTK inhibitor acarabutinib is mainly focused on the field of oncology, and the inhibition effect of the BTK inhibitor acarabutinib on myocardial fibrosis response of myocardial pathological conditions (such as hypertension, myocardial infarction or chronic myocardial ischemia) other than oncology is not reported.
Disclosure of Invention
The present invention has been made to solve the above problems, and an object of the present invention is to provide a pharmaceutical composition for inhibiting myocardial fibrosis.
The invention provides a drug group for inhibiting myocardial fibrosisA compound having the characteristics comprising: BTK; and acatinib (aka acatinib), wherein the molecular formula of acatinib is C26H23N7O2。
In the pharmaceutical composition for inhibiting myocardial fibrosis provided by the invention, the pharmaceutical composition also has the following characteristics: wherein the pharmaceutical composition is used for inhibiting myocardial fibrosis response under the condition of myocardial pathology.
In the pharmaceutical composition for inhibiting myocardial fibrosis provided by the invention, the pharmaceutical composition also has the following characteristics: wherein the myocardial pathological condition is hypertension, myocardial infarction or chronic myocardial ischemia.
In the pharmaceutical composition for inhibiting myocardial fibrosis provided by the invention, the pharmaceutical composition also has the following characteristics: wherein, the pharmaceutical composition plays a role in resisting rational myocardial fibrosis by regulating and controlling the functions of myocardial fibroblasts.
In the pharmaceutical composition for inhibiting myocardial fibrosis provided by the invention, the pharmaceutical composition also has the following characteristics: the pharmaceutical composition can inhibit myocardial fibrosis under the myocardial pathological condition by inhibiting the function of BTK phosphorylation T beta RI in myocardial fibroblasts.
In the pharmaceutical composition for inhibiting myocardial fibrosis provided by the invention, the pharmaceutical composition also has the following characteristics: wherein, the pharmaceutical composition can inhibit myocardial fibrosis under the myocardial pathological condition by inhibiting the activation of a fibrosis signal channel in a cardiac fibroblast.
In the pharmaceutical composition for inhibiting myocardial fibrosis provided by the invention, the pharmaceutical composition also has the following characteristics: wherein the fibrotic signaling pathway is a downstream classical SMAD pathway or a downstream non-classical MAPK signaling pathway.
Action and Effect of the invention
According to the pharmaceutical composition for inhibiting myocardial fibrosis, which is provided by the invention, the composition comprises BTK and acanthinib (acalabretinib), because the acanthinib has better kinase selectivity and higher safety, and in a pathological state, BTK in myocardial fibroblasts can directly bind and phosphorylate TGF-beta receptor I (T beta RI), so that the activation of downstream classical and non-classical fibrosis signal pathways is promoted. The Acalabrutinib can target and inhibit the activity of BTK, inhibit the combination of BTK and TbetaRI, and inhibit the activation of a fibrosis signal channel in a pathological state, thereby inhibiting the occurrence of myocardial pathological fibrosis. Therefore, the BTK inhibitor acaraburtinib can inhibit the myocardial fibrosis reaction under the myocardial pathological conditions (such as the pathological conditions of hypertension, myocardial infarction or chronic myocardial ischemia) through research, thereby protecting the cardiac function, preventing the poor cardiac remodeling and reducing the occurrence of heart failure.
Drawings
FIG. 1 is a graph showing the results of experiments on the inhibition of pressure overload-induced myocardial fibrosis by Acaraburtinib in example two of the present invention;
FIG. 2 is a graph of the results of a myocardial tissue staining experiment in which Acaraburtinib inhibits the level of pressure overload-induced myocardial tissue fibrosis;
FIG. 3 is a graph of the results of an experiment in which Acalabastinib inhibited the expression of fibrotic molecules in cardiac fibroblasts;
FIG. 4 is a graph of the experimental results of Acaraburtinib inhibition of fibrotic signaling pathway activation in myocardial tissue in a pressure-loaded model;
FIG. 5 is a graph of the results of an experiment in which Acalabastinib inhibits activation of the fibrotic signaling pathway in cardiac fibroblasts; and
FIG. 6 is a graph showing the results of experiments in which Acalabastinib inhibits the level of tyrosine phosphorylation of TGF-beta receptor I.
Detailed Description
In order to make the technical means, creation features, achievement purposes and effects of the invention easy to understand, a pharmaceutical composition for inhibiting myocardial fibrosis is specifically described below with reference to the embodiments and the accompanying drawings.
< example one >
The present embodiment provides a pharmaceutical composition for inhibiting myocardial fibrosis, which includes BTK and acarabtinib (acaraburtinib). The chemical structural formula of the acatinib is as follows:
the molecular formula of the acatinib is C26H23N7O2And the molecular weight is 465.51.
The pharmaceutical composition provided in this example is useful for inhibiting a fibrotic response in a myocardium under a pathologic condition of the myocardium, the pathologic condition of the myocardium being hypertension, myocardial infarction or chronic myocardial ischemia. The pharmaceutical composition can inhibit the function of BTK phosphorylation T beta RI in myocardial fibroblasts by regulating the function of the myocardial fibroblasts, thereby playing a role in resisting pathological myocardial fibrosis. Wherein the fibrotic signaling pathway is a downstream classical SMAD pathway or a non-classical MAPK signaling pathway.
< example two >
This example is a pharmacodynamic study of myocardial fibrosis molecular expression using acaraburtinib on a cardiac pressure overload model.
2.1 materials of the experiment
Mice (strain C57, male 30, 8-10 weeks old, purchased from Shanghai Spure-Biky laboratory animals Co., Ltd.), Trizol reagent (purchased from Invitrogen Co.), SYBR Green RT-PCR kit (purchased from TOYOBO Co., Ltd.), ABI QuantStudio6 fluorescent quantitative PCR instrument (purchased from Applied Biosystems Co., Ltd.), Acarabutinib (purchased from MCE Co., Ltd.), isoproterenol.
2.2 Experimental methods
2.1.1Acalabrutinib heart pressure overload model construction
A mouse hypertension model is constructed by using isoproterenol, heart pressure overload is mediated, and 30 mice are labeled and then randomly divided into three groups of 10 mice each. Three groups were saline group (NS), isoproterenol group (ISO), and Acalabrutinib + isoproterenol group (Acala + ISO). Wherein ISO group mice are injected with ISO (15mg/kg/d) for 28 days to induce myocardial fibrosis, NS group is given with normal saline with the same volume, and in (Acala + ISO) group, Acala is orally taken with 15mg/kg dose, and is respectively given on the day before ISO subcutaneous injection and 14 days after ISO subcutaneous injection. Mice were kept in 12h light/12 h dark, and were raised at room temperature with free access to water. After day 28, the mice were anesthetized with pentobarbital and the myocardial tissue was removed.
2.1.2 real-time fluorescent quantitative PCR
The expression of the fibrotic molecules (Cola1, Col3a1, Acta2 and Ccn2) in three groups of myocardial tissues was analyzed using a real-time quantitative reverse transcription PCR (qRT-PCR) method. Weighing a proper amount of three groups of myocardial tissues, adding 1mL of Trizol reagent after shearing, fully grinding, performing reverse transcription and amplification experiments in an ABI QuantStaudio 6 real-time quantitative PCR instrument according to the instructions of a SYBR Green RT-PCR kit, and extracting the total RNA of the three groups of myocardial tissues. Final results the amount of mRNA expressed was used 2-ΔΔCtThe relative expression level of the gene was calculated by the method, and GAPDH was used as an internal control for the calculation of the expression level of mRNA.
2.3 results of the experiment
FIG. 1 is a graph showing the results of experiments in which Acaraburtinib inhibits the expression of myocardial fibrosis molecules induced by pressure overload in example two of the present invention.
As shown in fig. 1, the (Acala + ISO) group significantly inhibited the expression of fibrotic molecules in pressure overload-induced myocardial tissues compared to the NS group and ISO group.
< example three >
This example is a pharmacodynamic study of myocardial tissue fibrotic molecule expression using acaraburtinib on a cardiac pressure overload model.
3.1 Experimental materials
Mice (strain C57, 30 males, 8-10 weeks old, purchased from Shanghai Sphere-Biky laboratory animals Co., Ltd.), Acaraburtinib (purchased from MCE), isoproterenol, and paraformaldehyde.
3.2 Experimental methods
The molding method of this embodiment is similar to that of the second embodiment, and is not described herein again. After the model fabrication was completed according to the method of example two, the mice were anesthetized with pentobarbital, the heart was harvested, and the left ventricular tissue was excised and Masson stained. Ventricular tissue was fixed in 4% paraformaldehyde for 48h, gradient alcohol dehydrated, paraffin embedded and cut into 4 μm sections, heated overnight in an incubator at 60 ℃, stained after deparaffinization, and the staining of the sections was observed under a microscope.
3.3 results of the experiment
FIG. 2 is a graph of the results of an experiment in which Acalabastinib inhibited the level of myocardial tissue fibrosis induced by pressure overload.
As shown in fig. 2, the fibrosis level induced by the (Acala + ISO) group was significantly reduced compared to the ISO group, indicating that the BTK inhibitor acarabutinib can significantly inhibit the level of myocardial fibrosis induced by stress overload.
< example four >
This example is a pharmacodynamic study of the inhibition of the expression of fibrotic molecules in cardiac fibroblasts by acarabretinib.
4.1 Experimental materials
Wild type mice (20, purchased from Shanghai Spiral-BiKai laboratory animals Co., Ltd.), DMSO, and Acaraburtinib.
4.2 Experimental methods
20 wild-type mice are randomly divided into two groups after being labeled, 10 mice are taken, mouse cells are cultured to obtain cardiac fibroblasts, the cardiac fibroblasts of the two groups of mice are respectively pretreated with DMSO and Acalabastib (16 mu mol/L) for 24 hours, and then the fibroblasts are induced to generate a fibrosis reaction by TGF-beta (10ng/ml), and the result is shown in figure 3.
4.3 results of the experiment
FIG. 3 is a graph of the results of an experiment in which Acalabastinib inhibited the expression of fibrotic molecules in cardiac fibroblasts.
As shown in fig. 3, compared with the DMSO pretreatment group, the acarabutinib pretreatment group significantly reduced the expression of fibrotic molecules, indicating that the BTK inhibitor acarabutinib can significantly inhibit the cardiac fibroblast fibrotic response induced by ISO.
< example five >
This example is a pharmacodynamic study using acarabretinib to inhibit activation of fibrotic signaling pathways in myocardial tissue in a pressure-loaded model.
The experimental materials, grouping method and modeling method provided in this embodiment are similar to those in the second embodiment, and are not described herein again.
In this example, after modeling, mouse myocardial tissues were removed and proteins were extracted, and myocardial fibrosis effector proteins were detected by Western Blot technique.
Fig. 4 is a graph of experimental results of acarabretinib inhibiting activation of fibrotic signaling pathways in myocardial tissue in a pressure-loaded model.
FIG. 4a is a Western Blot assay of the proteins p-SMAD2, p-SMAD3 and GAPDH; FIG. 4b is a Western Blot detection of the proteins p-ERK, p-JNK, p-p38 and GAPDH.
As can be seen from fig. 4a and 4b, compared to the NS group and the ISO group, the acarabutinib group or (acarabutinib + ISO) group can significantly inhibit activation of the fibrosis signaling pathway (classical SMAD and non-classical MAPK signaling pathway) in the myocardial tissue induced by ISO.
< example six >
This example is a pharmacodynamic study of inhibition of activation of the fibrotic signaling pathway in cardiac fibroblasts using acaraburtinib.
The experimental materials and grouping method used in this embodiment are similar to those in the fourth embodiment, and are not described herein again. After wild-type mice are treated with DMSO and Acalabastinib for 24 hours, TGF-beta is utilized to induce the activation of a fibroblast fibrosis signal channel, and Western Blot technology is adopted to detect myocardial fibrosis effector protein.
The results of the experiment are shown in FIG. 5.
FIG. 5 is a graph of the results of Acaraburtinib inhibiting activation of the fibrotic signaling pathway in cardiac fibroblasts. FIG. 5a is a Western Blot assay of the proteins p-SMAD2, p-SMAD3 and GAPDH; FIG. 5b is a Werstern Blot assay of the proteins p-ERK, p-JNK, p-p38 and GAPDH.
As can be seen from FIG. 5a and FIG. 5b, compared with the DMSO group, the activation of the classical and non-classical signaling pathways of the Acaraburtinib group is significantly reduced, which indicates that the Acaraburtinib can significantly inhibit the activation of the TGF-beta-induced fibroblast fibrosis signaling pathway.
< example seven >
This example is a pharmacodynamic study of acarabretinib inhibiting TGF-beta receptor I tyrosine phosphorylation.
The experimental materials and grouping method used in this embodiment are similar to those in the fourth embodiment, and are not described herein again. After wild mouse myocardial fibroblasts are separated and cultured, the wild mouse myocardial fibroblasts are respectively pretreated by DMSO and Acalabastinib for 24 hours, and then the fibroblasts are treated by TGF-beta for 30-60 minutes. Immunoprecipitation was performed using TGF- β receptor I (T β RI) antibody, followed by detection of phosphorylation levels of T β RI using tyrosine phosphorylation (p-Tyr) antibody, and the results are shown in FIG. 6.
FIG. 6 is a graph showing the results of experiments in which Acalabastinib inhibits the level of tyrosine phosphorylation of TGF-beta receptor I.
As can be seen from FIG. 6, compared with the DMSO group, the p-Tyr level of the Acarabutinib pretreatment group is significantly reduced, indicating that Acarabutinib can significantly inhibit tyrosine phosphorylation of T beta RI.
Effects and effects of the embodiments
According to the pharmaceutical composition for inhibiting myocardial fibrosis, which is related in the embodiment, the composition comprises BTK and acanthinib (acarabutinib), because acanthinib has better kinase selectivity and higher safety, and in a pathological state, BTK in myocardial fibroblasts can directly bind and phosphorylate TGF-beta type receptor I (T β RI), and further promote the activation of downstream classical and non-classical fiber signaling pathways. The Acalabrutinib can target and inhibit the activity of BTK, inhibit the combination of BTK and TbetaRI, and inhibit the activation of a fibrosis signal channel in a pathological state, thereby inhibiting the occurrence of myocardial pathological fibrosis. Therefore, the BTK inhibitor acaraburtinib can inhibit the myocardial fibrosis reaction under the myocardial pathological conditions (such as the pathological conditions of hypertension, myocardial infarction or chronic myocardial ischemia) through research, thereby protecting the cardiac function, preventing the poor cardiac remodeling and controlling the occurrence of heart failure.
Claims (7)
1. A pharmaceutical composition for inhibiting myocardial fibrosis, comprising:
BTK; and
the content of the acatinib is shown in the specification,
wherein the molecular formula of the acatinib is C26H23N7O2。
2. The pharmaceutical composition for inhibiting myocardial fibrosis according to claim 1, wherein:
wherein, the pharmaceutical composition is used for inhibiting the myocardial fibrosis reaction under the myocardial pathological condition.
3. The pharmaceutical composition for inhibiting myocardial fibrosis according to claim 2, wherein:
wherein the myocardial pathological condition is hypertension, myocardial infarction or chronic myocardial ischemia.
4. The pharmaceutical composition for inhibiting myocardial fibrosis according to claim 1, wherein:
the pharmaceutical composition plays a role in resisting pathological myocardial fibrosis by regulating and controlling the functions of myocardial fibroblasts.
5. The pharmaceutical composition for inhibiting myocardial fibrosis according to claim 4, wherein:
wherein, the pharmaceutical composition plays a role in inhibiting myocardial fibrosis under myocardial pathological conditions by inhibiting the function of BTK phosphorylation T beta RI in myocardial fibroblasts.
6. The pharmaceutical composition for inhibiting myocardial fibrosis according to claim 4, wherein:
wherein, the pharmaceutical composition can inhibit myocardial fibrosis under the myocardial pathological condition by inhibiting the activation of a fibrosis signal channel in a cardiac fibroblast.
7. The pharmaceutical composition for inhibiting myocardial fibrosis according to claim 6, wherein:
wherein the fibrotic signaling pathway is a downstream classical SMAD signaling pathway or a downstream non-classical MAPK signaling pathway.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202110818057.2A CN113694187A (en) | 2021-07-20 | 2021-07-20 | Pharmaceutical composition for inhibiting myocardial fibrosis |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202110818057.2A CN113694187A (en) | 2021-07-20 | 2021-07-20 | Pharmaceutical composition for inhibiting myocardial fibrosis |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN113694187A true CN113694187A (en) | 2021-11-26 |
Family
ID=78649053
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202110818057.2A Pending CN113694187A (en) | 2021-07-20 | 2021-07-20 | Pharmaceutical composition for inhibiting myocardial fibrosis |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN113694187A (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN114259565A (en) * | 2021-12-28 | 2022-04-01 | 广州市妇女儿童医疗中心 | Application of Wnt4 in preparing medicament for treating fibrosis |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN106999482A (en) * | 2014-12-03 | 2017-08-01 | 药品循环有限责任公司 | The method for treating fibrosis |
| CN108721294A (en) * | 2017-04-25 | 2018-11-02 | 复旦大学 | Compound EPZ5676 and its related inhibitors are preparing the purposes in treating myocardial fibrosis disease medicament |
-
2021
- 2021-07-20 CN CN202110818057.2A patent/CN113694187A/en active Pending
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN106999482A (en) * | 2014-12-03 | 2017-08-01 | 药品循环有限责任公司 | The method for treating fibrosis |
| CN108721294A (en) * | 2017-04-25 | 2018-11-02 | 复旦大学 | Compound EPZ5676 and its related inhibitors are preparing the purposes in treating myocardial fibrosis disease medicament |
Non-Patent Citations (1)
| Title |
|---|
| 周文慧: "酪氨酸激酶BTK对心脏纤维化的调控作用及机制研究", 中国优秀硕士学位论文全文数据库 医药卫生科技辑, no. 2 * |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN114259565A (en) * | 2021-12-28 | 2022-04-01 | 广州市妇女儿童医疗中心 | Application of Wnt4 in preparing medicament for treating fibrosis |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| Jakubik et al. | MicroRNAs and long non-coding RNAs in the pathophysiological processes of diabetic cardiomyopathy: emerging biomarkers and potential therapeutics | |
| Jin et al. | Molecular mechanism of pancreatic stellate cells activation in chronic pancreatitis and pancreatic cancer | |
| Singh et al. | Resistin induces cardiac fibroblast-myofibroblast differentiation through JAK/STAT3 and JNK/c-Jun signaling | |
| Holmquist et al. | Phenotypic persistence after reoxygenation of hypoxic neuroblastoma cells | |
| KR101339489B1 (en) | New use of periostin | |
| US20220008420A1 (en) | Calmodulin inhibitors, chk2 inhibitors and rsk inhibitors for the treatment of ribosomal disorders and ribosomapathies | |
| Bai et al. | Anti-psoriatic properties of paeoniflorin: suppression of the NF-kappaB pathway and Keratin 17 | |
| US11820981B2 (en) | Modulation of TJP1 expression to regulate regeneration of heart cells | |
| CN113694187A (en) | Pharmaceutical composition for inhibiting myocardial fibrosis | |
| Iwasaki et al. | Regulation of cellular senescence in type 2 diabetes mellitus: From mechanisms to clinical applications | |
| Zhou et al. | Human Umbilical Cord Mesenchymal Stem Cells Ameliorate Hepatic Stellate Cell Activation and Liver Fibrosis by Upregulating MicroRNA‐455‐3p through Suppression of p21‐Activated Kinase‐2 | |
| Xu et al. | Immediate early response protein 2 promotes the migration and invasion of hepatocellular carcinoma cells via regulating the activity of Rho GTPases. | |
| Sang et al. | Ras-AKT signaling represses the phosphorylation of histone H1. 5 at threonine 10 via GSK3 to promote the progression of glioma | |
| Ji et al. | Molecular Mechanism of HSF1‐Upregulated ALDH2 by PKC in Ameliorating Pressure Overload‐Induced Heart Failure in Mice | |
| Chen et al. | Expression of SGTA correlates with neuronal apoptosis and reactive gliosis after spinal cord injury | |
| US20180221369A1 (en) | Compositions and methods for treating fibrosing disorders and cancer | |
| US11077110B2 (en) | Compositions and methods for treating and preventing metabolic disorders | |
| Huang et al. | ATF3 affects myocardial fibrosis remodeling after myocardial infarction by regulating autophagy and its mechanism of action | |
| TWI827190B (en) | Target therapy composition and its use for suppressing breast cancer cells proliferation, migration or invasion | |
| CN106906217A (en) | Suppress siRNA and its application of Kdm6a gene expressions | |
| Sidhu et al. | Rosiglitazone promotes pancreatic regeneration in experimental model of acute pancreatitis | |
| Li et al. | RETRACTED ARTICLE: Long Noncoding RNA H19 Induces Neuropathic Pain by Upregulating Cyclin-Dependent Kinase 5-Mediated Phosphorylation of cAMP Response Element Binding Protein | |
| CN112618527B (en) | Application of small molecule in preparation of mutant type uveal melanoma medicine | |
| Yao et al. | Roles of non-coding RNA in diabetic cardiomyopathy | |
| Li et al. | Effects of suppressing Smads expression on wound healing in Hyriopsis cumingii |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination |