CN113952343A - Application of cryptotanshinone in inhibition of STAT5 protein phosphorylation - Google Patents
Application of cryptotanshinone in inhibition of STAT5 protein phosphorylation Download PDFInfo
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Abstract
The invention discloses application of cryptotanshinone in inhibiting STAT5 protein phosphorylation. The research of the invention finds that cryptotanshinone can effectively inhibit phosphorylation of intracellular STAT5 protein and expression of downstream protein regulated by phosphorylation STAT5 protein; the inhibition is specific, significant and rapid. Therefore, cryptotanshinone has obvious growth inhibition effect and apoptosis induction effect on cells with abnormal STAT5 protein phosphorylation, and based on the invention, cryptotanshinone can be used as a novel STAT5 protein phosphorylation inhibitor, and has important scientific significance and clinical application value in the aspects of high-efficiency STAT5 protein phosphorylation inhibitor preparation, disease treatment of STAT5 protein abnormal phosphorylation and the like.
Description
The application is a divisional application with application date of 2017, 12 and 11, application number of 201711306880.5 and invention name of application of cryptotanshinone in inhibiting STAT5 protein phosphorylation.
Technical Field
The invention belongs to the technical field of biological medicines. More particularly, relates to the application of cryptotanshinone in inhibiting STAT5 protein phosphorylation.
Background
STAT5 is a member of the Signal Transducer and Activator of Transcription (STAT) family, and it is phosphorylated by kinase and can be used as Transcription factor to play an important role in the transduction of cell Signal pathway, and phosphorylated STAT5 protein plays an important role in the physiological and pathological processes of growth and development, immune regulation, disease development and the like.
In diseases caused by abnormal phosphorylation of STAT5, the abnormally phosphorylated STAT5 protein can obviously up-regulate the expression of a plurality of proliferation-related proteins and apoptosis resistance-related proteins in downstream cell signal pathways, so that cells show the malignant change characteristics of rapid proliferation and difficult apoptosis. The effective inhibition of the abnormal phosphorylation of STAT5 protein can obviously inhibit the proliferation of malignant cells and effectively induce the apoptosis of the malignant cells.
Therefore, the development of new and more effective inhibitors of phosphorylation of STAT5 protein, as well as highly effective inhibitors of downstream proteins in pathways regulated by phosphorylated STAT5 protein, has become a hot spot of current diseased cell targeted drugs.
Disclosure of Invention
The technical problem to be solved by the invention is to overcome the defects and technical shortcomings of the prior art and provide a STAT5 protein phosphorylation inhibitor. The research of the invention finds that cryptotanshinone can effectively inhibit phosphorylation of intracellular STAT5 protein, is expected to be developed into a phosphorylation inhibitor of STAT5 protein, and is applied to reagent development, medicine preparation, pharmacodynamic analysis and evaluation and clinical examination.
In order to achieve the above purpose, the invention provides the following technical scheme:
the invention provides application of cryptotanshinone in preparing an inhibitor for STAT5 protein phosphorylation.
The research of the invention finds that cryptotanshinone can effectively inhibit phosphorylation of STAT5 protein under certain conditions, and further down-regulates expression of downstream protein of a signal channel regulated by phosphorylated STAT5 protein, thereby obviously inhibiting cell growth and effectively inducing apoptosis. In the experiment, the effective action concentration of the cryptotanshinone is more than or equal to 1 mu mol/L, and the optimal action concentration is more than or equal to 20 mu mol/L; the effective action time is more than or equal to 0.5 hour under the concentration of 20 mu mol/L cryptotanshinone, and the optimal action time is more than or equal to 4 hours. Through research, the cryptotanshinone is found to be a high-efficiency inhibitor for STAT5 protein phosphorylation and can be used for inhibiting the proliferation of STAT5 protein abnormal phosphorylation cells; the preparation containing cryptotanshinone is adopted or combined with other medicines to prepare the medicine for treating diseases (such as chronic myelogenous leukemia and the like) caused by abnormal phosphorylation of STAT5 protein.
Therefore, the following applications should be within the scope of the present invention:
the application of cryptotanshinone as or in preparing STAT5 protein phosphorylation inhibitor is characterized in that the cryptotanshinone also comprises pharmaceutically acceptable salts and esters thereof, selectively substituted analogues or a combination of one or more compounds containing the cryptotanshinone; also comprises a derivative of cryptotanshinone or a pharmaceutically acceptable salt or solvate of the salt of the derivative.
Preferably, the application of the medicinal salts and esters of cryptotanshinone or the medicinal salts and esters of cryptotanshinone combined with other substances in the preparation of STAT5 protein phosphorylation inhibitor is characterized in that the effective concentration of cryptotanshinone in the inhibitor is more than or equal to 1 mu mol/L; the other substances include one or more of cryptotanshinone, a derivative of cryptotanshinone, a pharmaceutically acceptable salt or solvate of salt of the derivative of cryptotanshinone, an analog of selective substitution of cryptotanshinone, and a compound containing cryptotanshinone.
Preferably, the subject of action of the STAT5 protein phosphorylation inhibitor does not include total STAT5 protein, but includes phosphorylated STAT5 protein and target molecules downstream of the signaling pathway regulated by phosphorylated STAT5 protein.
Preferably, the effective concentration of cryptotanshinone in the inhibitor is more than or equal to 20 mu mol/L; the effective time of the inhibitor for inhibiting the phosphorylation of STAT5 protein in human cells is more than or equal to 0.5 hour, and the optimal time is more than or equal to 4 hours.
Application of cryptotanshinone in preparation of drugs for inhibiting growth of STAT5 protein abnormal phosphorylation cells and/or treating STAT5 protein abnormal phosphorylation diseases.
Preferably, the medicinal salts and esters of cryptotanshinone or the medicinal salts and esters of cryptotanshinone combined with other substances are applied to the preparation of medicines for inhibiting the growth of cells abnormally phosphorylated by STAT5 protein and/or treating diseases caused by abnormal phosphorylation of STAT5 protein. The effective concentration of cryptotanshinone in the inhibitor is more than or equal to 1 mu mol/L; the other substances include one or more of cryptotanshinone, a derivative of cryptotanshinone, a pharmaceutically acceptable salt or solvate of salt of the derivative of cryptotanshinone, an analog of selective substitution of cryptotanshinone, and a compound containing cryptotanshinone.
Preferably, the STAT5 protein abnormal phosphorylation cell is a tumor cell, and the STAT5 protein abnormal phosphorylation disease is a tumor; the tumor is a blood tumor or a solid tumor.
Preferably, the tumor is chronic myelogenous leukemia, acute lymphocytic leukemia, acute myelogenous leukemia, glioma, breast cancer, colon cancer, liver cancer, cervical cancer, Burkitt's lymphoma or melanoma, and the like.
Preferably, the medicament can be orally administered or injected, and can be prepared into various pharmaceutically acceptable preparations, such as a needle or freeze-dried powder preparation, a pill, a decoction, a tablet, a granule, a hard capsule, a soft capsule, a controlled release preparation, a sustained release preparation, an injection or an oral preparation, by using an acceptable medicinal carrier, and also comprises more than one pharmaceutically acceptable excipient.
Preferably, the drug can be used alone or combined with other drugs for compatibility as a phosphorylation inhibitor of STAT5 protein.
Aiming at the diseases of abnormal phosphorylation of STAT5 protein, cryptotanshinone is used for preparing an inhibitor of STAT5 protein phosphorylation and a medicine and a health product for preventing, treating, assisting in treating and/or prognosing relapse of downstream protein regulated by inhibiting phosphorylated STAT5 protein in pharmacy and clinical treatment. The cryptotanshinone is applied to clinical examination and drug effect detection and evaluation aiming at diseases in which phosphorylated STAT5 protein and downstream protein thereof are abnormally expressed. The cryptotanshinone is applied to development and preparation of related inhibitors of phosphorylated STAT5 protein or development and preparation of analytical reagents or biochemical reagents or detection reagents for inhibiting phosphorylation of STAT5 protein. The cryptotanshinone is applied as a cell proliferation inhibitor or an apoptosis inducer for inhibiting phosphorylated STAT5 protein and interfering the expression of target protein thereof in basic research of cell and molecular biology.
The invention also provides application of cryptotanshinone serving as an STAT5 protein phosphorylation inhibitor in preparation of medicines, health-care medicines or health-care foods for improving the immunity of the organism.
The invention also provides application of cryptotanshinone in designing, developing and preparing related inhibitor aiming at phosphorylated STAT5 protein or using the inhibitor as biochemical reagent, analytical reagent or detection reagent.
Preferably, the medicinal salt and ester of cryptotanshinone or the medicinal salt and ester of cryptotanshinone are combined with other substances to be applied to designing, developing and preparing related inhibitors aiming at phosphorylated STAT5 protein or to be used as biochemical reagents, analytical reagents or detection reagents; the other substances include one or more of cryptotanshinone, a derivative of cryptotanshinone, a pharmaceutically acceptable salt or solvate of salt of the derivative of cryptotanshinone, an analog of selective substitution of cryptotanshinone, and a compound containing cryptotanshinone.
The invention also provides application of cryptotanshinone serving as the STAT5 protein phosphorylation inhibitor in detection and evaluation of drug effect, clinical examination, and related pharmacology, drug effect and clinical research.
Preferably, the medicinal salt and ester of cryptotanshinone or the medicinal salt and ester of cryptotanshinone combined with other substances are used as STAT5 protein phosphorylation inhibitor in the application of detection and evaluation of drug effect, clinical examination and related pharmacology, drug effect and clinical research; the other substances include one or more of cryptotanshinone, a derivative of cryptotanshinone, a pharmaceutically acceptable salt or solvate of salt of the derivative of cryptotanshinone, an analog of selective substitution of cryptotanshinone, and a compound containing cryptotanshinone.
The invention also provides application of cryptotanshinone serving as a cell proliferation inhibitor and an apoptosis inducer for inhibiting phosphorylation of STAT5 protein, and provides new technology, new method and new means for researching phosphorylation and phosphorylation regulation processes of STAT5 protein, cell signal channels regulated by phosphorylated STAT5 protein and biological functions of the cell signal channels related to the channels.
Preferably, the application of the pharmaceutically acceptable salts and esters of cryptotanshinone or the pharmaceutically acceptable salts and esters of cryptotanshinone combined with other substances as a cell proliferation inhibitor and an apoptosis inducer for inhibiting the phosphorylation of STAT5 protein, and the new technology, the new method and the new means provided by the research on the phosphorylation and phosphorylation regulation process of STAT5 protein, a cell signal pathway regulated by the phosphorylated STAT5 protein and the biological functions of the cell signal pathway related to the pathway; the other substances include one or more of cryptotanshinone, a derivative of cryptotanshinone, a pharmaceutically acceptable salt or solvate of salt of the derivative of cryptotanshinone, an analog of selective substitution of cryptotanshinone, and a compound containing cryptotanshinone.
The invention has the following beneficial effects:
the invention discloses application of cryptotanshinone in preparation of an inhibitor for STAT5 protein phosphorylation. Based on the invention, the STAT5 protein phosphorylation inhibiting reagent is prepared from cryptotanshinone, which is a natural diterpene quinone compound, is mainly derived from the traditional Chinese herb salvia miltiorrhiza, is easy to prepare, has low toxicity to human bodies and strong applicability.
The inhibitor prepared by cryptotanshinone has high efficiency and low toxicity, and can inhibit a plurality of downstream target proteins regulated and controlled by phosphorylation STAT5 protein. The preparation has strong specificity, quick response and easy operation, provides a thought for targeted treatment of diseases, and provides a new technology, a new method and a new means for experimental study of STAT5 protein and phosphorylated protein thereof as well as biological functions of downstream target proteins regulated by the STAT5 protein and the phosphorylated protein.
In various diseases, an inhibitor prepared by cryptotanshinone can inhibit phosphorylation of STAT5 protein and a cell signal pathway network which is closely related to proliferation and apoptosis and is mediated by phosphorylated STAT5 protein, and can inhibit expression of a plurality of downstream proteins from a transcription level, so that cell growth is finally inhibited, and apoptosis is promoted. The characteristics of inhibiting proliferation and promoting apoptosis are particularly prominent in tumor treatment, and the anticancer activity of the compound has obvious effect on various tumor cells and individuals.
Drawings
FIG. 1 is a graph showing the effect of cryptotanshinone at various concentrations in example 1 on STAT5 total protein and STAT5 phosphorylated protein.
FIG. 2 is the effect of 20 μ M cryptotanshinone on STAT5 total protein and STAT5 phosphorylated protein at different time points in example 2.
FIG. 3 is the effect of cryptotanshinone in example 3 on the inhibition of proliferation of K562 cells.
Detailed Description
The present invention is further illustrated by the following specific examples, which are not intended to limit the invention in any way. Reagents, methods and apparatus used in the present invention are conventional in the art unless otherwise indicated. Unless otherwise indicated, reagents and materials used in the present invention are commercially available.
The reagents used in the following examples are as follows:
cryptotanshinone: purchased from Selleck Chemicals, and having a purity of greater than 99% as determined by High Performance Liquid Chromatography (HPLC). Dimethylmaple (DMSO) was used as a stock solution at 5. mu. mol/L, frozen at-80 ℃ and diluted with medium to working concentration for each use.
K562 cell line: purchased from cell resource center of Shanghai Life sciences research institute of Chinese academy of sciences.
Antibody: both p-STAT5(Tyr694) and GAPDH antibodies were purchased from CellSignaling technology, USA.
Example 1
The cryptotanshinone is dose-dependent on the inhibition of phosphorylated STAT5 protein
1. Experimental methods
(1) Obtaining cells
Collecting cultured chronic myelogenous leukemia K562 cells of logarithmic growth phase, centrifuging at 750rpm for 3 minutes, suspending the cells in RPMI-1640 containing only 10% Fetal Bovine Serum (FBS), and adjusting the concentration of the cell suspension to 3X 105The cell suspension was inoculated into a 48-well plate at a concentration of 500. mu.L/well and placed at 37 ℃ in 5% CO2Culturing in an incubator for 24 hours;
(2) adding chemicals for treatment
The prepared 5mM cryptotanshinone mother liquor was diluted with DMSO solution to 100 times of the working concentration (0. mu.M, 1. mu.M, 2.5. mu.M, 5. mu.M, 7.5. mu.M, 10. mu.M, 15. mu.M, 20. mu.M and 30. mu.M) so that the preparation concentrations were 0mM, 0.1mM, 0.25mM, 0.5mM, 0.75mM, 1mM, 1.5mM, 2mM and 3mM, respectively, and was pipetted into wells of the respective concentrations. The cell culture plates were then placed at 37 ℃ in 5% CO2Culturing in an incubator for 24 hours;
(3) collecting cells, and performing Westernblotting experiment
Centrifuging at 3000rpm for 5 min to collect cells, adding 1 xSDS Loading Buffer with corresponding amount according to the amount of cell sediment, boiling at 99 ℃ for 10 min, cracking protein, and detecting the expression of phosphorylated STAT5 protein by Western blotting experiment.
2. The experimental results are as follows:
with the increase of the concentration, cryptotanshinone can gradually inhibit the phosphorylation of STAT5 protein. When the concentration of the drug reaches 20 mu mol/L, the inhibition efficiency is obviously improved, and the inhibition effect is further enhanced along with the increase of the concentration of the drug.
Example 2
The cryptotanshinone is time-dependent on the inhibition of phosphorylated STAT5 protein
1. Experimental methods
(1) Obtaining cells
Collecting cultured chronic myelogenous leukemia K562 cells of logarithmic growth phase, centrifuging at 750rpm for 3 minutes, suspending the cells in RPMI-1640 containing only 10% Fetal Bovine Serum (FBS), and adjusting the concentration of the cell suspension to 3X 105The cell suspension was inoculated into a 48-well plate at a concentration of 500. mu.L/well and placed at 37 ℃ in 5% CO2Culturing in an incubator for 24 hours;
(2) adding chemicals for treatment
Diluting the prepared 5mM cryptotanshinone mother liquor with DMSO solution to 100 times of working concentration 20 μ M, namely 2mM, blowing, mixing well, and adding into each well; control group (0 μ M cryptotanshinone) was added with a corresponding amount of DMSO. The cell culture plates were then placed at 37 ℃ in 5% CO2Culturing in an incubator;
(3) collecting cells, and performing Westernblotting experiment
Cells of the corresponding group were collected by centrifugation at 3000rpm for 5 minutes at 0.5, 1, 2, 4, 6, 12 and 24 hours after the drug addition, respectively, and a control group (0 μ M cryptotanshinone) was collected together with the samples of the 24-hour group. Adding a corresponding amount of 1 xSDS Loading Buffer according to the amount of the cell sediment, boiling for 10 minutes at 99 ℃, cracking the protein, and detecting the expression condition of the phosphorylated STAT5 protein through a Westernblotting experiment.
2. The experimental results are as follows:
20 mu M cryptotanshinone can inhibit phosphorylation of STAT5 protein within 0.5 hour; with the prolonged action time, cryptotanshinone can remarkably inhibit phosphorylation of STAT5 protein and empty the protein after 12 hours.
Example 3
Cryptotanshinone obviously inhibits proliferation of K562 cells
1. Experimental methods
(1) Obtaining cells
Chronic myelogenous leukemia K562 cells cultured to the logarithmic growth phase were collected by centrifugation at 750rpm for 3 minutes, and the cells were collected from a cell culture containing only 10% Fetal Bovine Serum (total Bovine Serum,FBS) and adjusting the concentration of the cell suspension to 3X 105The cell suspension was inoculated into a 96-well plate at a concentration of 100. mu.L/well, and the plate was incubated at 37 ℃ under 5% CO2The culture was carried out in an incubator for 24 hours.
(2) Adding chemicals for treatment
The prepared 5mM cryptotanshinone mother liquor was diluted with DMSO solution to 100 times of the working concentration (0. mu.M, 1. mu.M, 2.5. mu.M, 5. mu.M, 7.5. mu.M, 10. mu.M, 15. mu.M, 20. mu.M and 30. mu.M) so that the preparation concentrations were 0mM, 0.1mM, 0.25mM, 0.5mM, 0.75mM, 1mM, 1.5mM, 2mM and 3mM, respectively, and was pipetted into wells of the respective concentrations. Then, the cell culture plate is placed in an incubator with 37 ℃ and 5% CO2 for 24 hours;
(3) mu.L of MTT solution (MTT kit available from Promega, USA) was added to each cell culture well, and the mixture was incubated at 37 ℃ with 5% CO2Culturing for 4 hours in an incubator;
(4) add 100. mu.L STOP solution to each well in (3) and place at 37 ℃ with 5% CO2Culturing in an incubator for 24 hours;
(5) and taking out the culture plate with 96 wells, detecting the light absorption value of each well under the excitation light with the wavelength of 570nm and the wavelength of 630nm respectively, wherein A570-A630 is the real light absorption value of each well, and the survival rate of the cells in each well is reacted, so that the proliferation inhibition condition of the cells in each well under the action of the medicament can be calculated.
2. The experimental results are as follows:
the result is shown in figure 3, cryptotanshinone can obviously inhibit the proliferation of K562 cells, and the semilethal dose is about 15-20 mu M.
The results show that the research of the invention finds that cryptotanshinone has obvious inhibition effect on phosphorylation of STAT5 protein in cells, and the inhibition effect presents obvious dose dependence and time dependence. When the concentration of the cryptotanshinone is greater than or equal to 1 mu mol/L, the inhibition effect can be shown, the inhibition effect is continuously enhanced along with the increase of the drug concentration, when the drug concentration is greater than or equal to 20 mu mol/L, the inhibition efficiency is obviously improved, and the inhibition effect is further enhanced along with the increase of the drug concentration. The inhibition effect of cryptotanshinone on the phosphorylation of STAT5 protein can be shown after 0.5 hour of drug treatment, the inhibition effect can be continuously carried out along with the prolonging of the action time, and the effect is more obvious after the action time is longer than 4 hours. The phosphorylation inhibitor of STAT5 protein prepared by cryptotanshinone also has good effect on inhibiting downstream target protein of phosphorylated STAT5 protein.
Thus the following can be applied: application of cryptotanshinone in preparing medicine for treating STAT5 protein abnormal phosphorylation diseases, such as: preparing medicaments for inhibiting tumor cell proliferation and resisting tumors (including blood tumors and solid tumors); the cryptotanshinone is applied to designing, developing and preparing a STAT5 protein phosphorylation related inhibitor or using the same as a biochemical reagent, an analytical reagent or a detection reagent; the cryptotanshinone is used as an inhibitor of STAT5 protein phosphorylation in drug effect detection evaluation, clinical examination and related pharmacology, drug effect and clinical research; the application of cryptotanshinone as a cell proliferation inhibitor and an apoptosis inducer for inhibiting the phosphorylation of STAT5 protein in basic research of biology and medicine, and the new technology, the new method and the new means for researching the biological functions of the STAT5 protein and the phosphorylation protein thereof as well as related target proteins in cell signal paths regulated by the STAT5 protein and the phosphorylation protein.
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 (10)
1. The application of the medicinal salt and ester of cryptotanshinone or the medicinal salt and ester of cryptotanshinone combined with other substances in the preparation of STAT5 protein phosphorylation inhibitor is characterized in that the effective concentration of cryptotanshinone in the inhibitor is more than or equal to 1 mu mol/L;
the other substances include one or more of cryptotanshinone, a derivative of cryptotanshinone, a pharmaceutically acceptable salt or solvate of salt of the derivative of cryptotanshinone, an analog of selective substitution of cryptotanshinone, and a compound containing cryptotanshinone.
2. The application of the medicinal salts and esters of cryptotanshinone or the medicinal salts and esters of cryptotanshinone combined with other substances in the preparation of inhibitors for inhibiting target molecules at the downstream of a signal path regulated by phosphorylated STAT5 protein and phosphorylated STAT5 protein is characterized in that the effective concentration of cryptotanshinone in the inhibitors is more than or equal to 1 mu mol/L;
the other substances include one or more of cryptotanshinone, a derivative of cryptotanshinone, a pharmaceutically acceptable salt or solvate of salt of the derivative of cryptotanshinone, an analog of selective substitution of cryptotanshinone, and a compound containing cryptotanshinone.
3. The application of the medicinal salts and esters of cryptotanshinone or the medicinal salts and esters of cryptotanshinone combined with other substances in the preparation of the medicine for inhibiting the growth of STAT5 protein abnormal phosphorylation cells is characterized in that the effective concentration of cryptotanshinone in the inhibitor is more than or equal to 1 mu mol/L;
the other substances include one or more of cryptotanshinone, a derivative of cryptotanshinone, a pharmaceutically acceptable salt or solvate of salt of the derivative of cryptotanshinone, an analog of selective substitution of cryptotanshinone, and a compound containing cryptotanshinone.
4. The use according to claim 3, wherein the cells aberrantly phosphorylated on STAT5 protein are tumor cells.
5. The application of the medicinal salts and esters of cryptotanshinone or the medicinal salts and esters of cryptotanshinone combined with other substances in the preparation of the medicines for inhibiting the growth of STAT5 protein abnormal phosphorylation cells and/or treating STAT5 protein abnormal phosphorylation diseases is characterized in that the effective concentration of cryptotanshinone in the inhibitor is more than or equal to 1 mu mol/L;
the other substances include one or more of cryptotanshinone, a derivative of cryptotanshinone, a pharmaceutically acceptable salt or solvate of salt of the derivative of cryptotanshinone, an analog of selective substitution of cryptotanshinone, and a compound containing cryptotanshinone.
6. The use according to claim 5, wherein the STAT5 protein abnormal phosphorylation disease is a tumor; the tumor is a blood tumor or a solid tumor.
7. The use of claim 6, wherein the tumor is chronic myelogenous leukemia, acute lymphocytic leukemia, acute myelogenous leukemia, glioma, breast cancer, colon cancer, liver cancer, cervical cancer, Burkitt's lymphoma or melanoma.
8. The use of claim 3 or 5, wherein the medicament is for use alone or in combination with other medicaments.
9. Application of cryptotanshinone as STAT5 protein phosphorylation inhibitor in preparing medicine, health medicine or health food for improving immunity is provided.
10. The application of the medicinal salt and ester of cryptotanshinone or the medicinal salt and ester of cryptotanshinone combined with other substances in designing, developing and preparing related inhibitor aiming at phosphorylated STAT5 protein or using the inhibitor as biochemical reagent, analytical reagent or detection reagent; or medicinal salts and esters of cryptotanshinone combined with other substances are used as a new method and technical application for researching cell signal pathways regulated by phosphorylated STAT5 protein and related target protein biological functions;
the other substances include one or more of cryptotanshinone, a derivative of cryptotanshinone, a pharmaceutically acceptable salt or solvate of salt of the derivative of cryptotanshinone, an analog of selective substitution of cryptotanshinone, and a compound containing cryptotanshinone.
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