CN114886895A - Application of small molecule inhibitor BAY87-2243 in preparing medicine for treating hepatitis B - Google Patents
Application of small molecule inhibitor BAY87-2243 in preparing medicine for treating hepatitis B Download PDFInfo
- Publication number
- CN114886895A CN114886895A CN202210576920.2A CN202210576920A CN114886895A CN 114886895 A CN114886895 A CN 114886895A CN 202210576920 A CN202210576920 A CN 202210576920A CN 114886895 A CN114886895 A CN 114886895A
- Authority
- CN
- China
- Prior art keywords
- bay87
- medicament
- hepatitis
- hbv
- cells
- 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.)
- Granted
Links
- CDJNNOJINJAXPV-UHFFFAOYSA-N 5-[1-[[2-(4-cyclopropylpiperazin-1-yl)pyridin-4-yl]methyl]-5-methylpyrazol-3-yl]-3-[4-(trifluoromethoxy)phenyl]-1,2,4-oxadiazole Chemical compound CC1=CC(C=2ON=C(N=2)C=2C=CC(OC(F)(F)F)=CC=2)=NN1CC(C=1)=CC=NC=1N(CC1)CCN1C1CC1 CDJNNOJINJAXPV-UHFFFAOYSA-N 0.000 title claims abstract description 54
- 239000003814 drug Substances 0.000 title claims abstract description 30
- 239000003112 inhibitor Substances 0.000 title claims abstract description 15
- 208000002672 hepatitis B Diseases 0.000 title claims abstract description 11
- 150000003384 small molecules Chemical class 0.000 title claims abstract description 8
- 241000700721 Hepatitis B virus Species 0.000 claims abstract description 50
- 230000010076 replication Effects 0.000 claims abstract description 14
- 238000013518 transcription Methods 0.000 claims abstract description 12
- 230000035897 transcription Effects 0.000 claims abstract description 12
- 108091036055 CccDNA Proteins 0.000 claims abstract 2
- 108020004414 DNA Proteins 0.000 claims description 10
- 239000000427 antigen Substances 0.000 claims description 8
- 108091007433 antigens Proteins 0.000 claims description 8
- 102000036639 antigens Human genes 0.000 claims description 8
- 239000000203 mixture Substances 0.000 claims description 8
- 238000009472 formulation Methods 0.000 claims description 5
- 230000002401 inhibitory effect Effects 0.000 claims description 5
- 208000006454 hepatitis Diseases 0.000 claims description 4
- 231100000283 hepatitis Toxicity 0.000 claims description 4
- 238000004519 manufacturing process Methods 0.000 claims description 4
- 238000002360 preparation method Methods 0.000 claims description 4
- 102100032742 Histone-lysine N-methyltransferase SETD2 Human genes 0.000 claims description 3
- 101000654725 Homo sapiens Histone-lysine N-methyltransferase SETD2 Proteins 0.000 claims description 3
- 239000004480 active ingredient Substances 0.000 claims description 2
- 239000008187 granular material Substances 0.000 claims description 2
- 239000004615 ingredient Substances 0.000 claims description 2
- 239000000463 material Substances 0.000 claims description 2
- 239000006072 paste Substances 0.000 claims description 2
- 239000006187 pill Substances 0.000 claims description 2
- 239000000243 solution Substances 0.000 claims description 2
- 239000003826 tablet Substances 0.000 claims description 2
- 210000004027 cell Anatomy 0.000 abstract description 44
- 201000007270 liver cancer Diseases 0.000 abstract description 2
- 208000014018 liver neoplasm Diseases 0.000 abstract description 2
- 238000000338 in vitro Methods 0.000 abstract 1
- 210000005229 liver cell Anatomy 0.000 abstract 1
- 230000000694 effects Effects 0.000 description 17
- 101710142246 External core antigen Proteins 0.000 description 10
- 230000028327 secretion Effects 0.000 description 10
- 238000011529 RT qPCR Methods 0.000 description 7
- 210000003494 hepatocyte Anatomy 0.000 description 7
- 229940079593 drug Drugs 0.000 description 6
- 230000003013 cytotoxicity Effects 0.000 description 5
- 231100000135 cytotoxicity Toxicity 0.000 description 5
- 230000003834 intracellular effect Effects 0.000 description 5
- 239000006228 supernatant Substances 0.000 description 5
- 238000002965 ELISA Methods 0.000 description 4
- 239000003153 chemical reaction reagent Substances 0.000 description 3
- YTRQFSDWAXHJCC-UHFFFAOYSA-N chloroform;phenol Chemical compound ClC(Cl)Cl.OC1=CC=CC=C1 YTRQFSDWAXHJCC-UHFFFAOYSA-N 0.000 description 3
- 208000015181 infectious disease Diseases 0.000 description 3
- 208000000419 Chronic Hepatitis B Diseases 0.000 description 2
- 238000009007 Diagnostic Kit Methods 0.000 description 2
- 108060002716 Exonuclease Proteins 0.000 description 2
- 241000700605 Viruses Species 0.000 description 2
- 230000000840 anti-viral effect Effects 0.000 description 2
- 230000001684 chronic effect Effects 0.000 description 2
- 150000001875 compounds Chemical class 0.000 description 2
- 238000001514 detection method Methods 0.000 description 2
- 230000008030 elimination Effects 0.000 description 2
- 238000003379 elimination reaction Methods 0.000 description 2
- 102000013165 exonuclease Human genes 0.000 description 2
- 238000002474 experimental method Methods 0.000 description 2
- 238000007747 plating Methods 0.000 description 2
- 238000003762 quantitative reverse transcription PCR Methods 0.000 description 2
- 238000011160 research Methods 0.000 description 2
- 239000000523 sample Substances 0.000 description 2
- 108020004638 Circular DNA Proteins 0.000 description 1
- 208000035473 Communicable disease Diseases 0.000 description 1
- 230000004543 DNA replication Effects 0.000 description 1
- 238000008157 ELISA kit Methods 0.000 description 1
- 206010053155 Epigastric discomfort Diseases 0.000 description 1
- 206010016654 Fibrosis Diseases 0.000 description 1
- 206010019670 Hepatic function abnormal Diseases 0.000 description 1
- 206010019705 Hepatic pain Diseases 0.000 description 1
- 206010019799 Hepatitis viral Diseases 0.000 description 1
- 206010019842 Hepatomegaly Diseases 0.000 description 1
- 208000006083 Hypokinesia Diseases 0.000 description 1
- 206010021143 Hypoxia Diseases 0.000 description 1
- 102000014150 Interferons Human genes 0.000 description 1
- 108010050904 Interferons Proteins 0.000 description 1
- 206010023126 Jaundice Diseases 0.000 description 1
- 206010058467 Lung neoplasm malignant Diseases 0.000 description 1
- 206010028813 Nausea Diseases 0.000 description 1
- 206010028980 Neoplasm Diseases 0.000 description 1
- 206010037660 Pyrexia Diseases 0.000 description 1
- 206010040047 Sepsis Diseases 0.000 description 1
- 238000002105 Southern blotting Methods 0.000 description 1
- 208000007271 Substance Withdrawal Syndrome Diseases 0.000 description 1
- 108700005077 Viral Genes Proteins 0.000 description 1
- 238000002835 absorbance Methods 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 208000022531 anorexia Diseases 0.000 description 1
- 230000004888 barrier function Effects 0.000 description 1
- 238000010609 cell counting kit-8 assay Methods 0.000 description 1
- 230000004663 cell proliferation Effects 0.000 description 1
- 208000016350 chronic hepatitis B virus infection Diseases 0.000 description 1
- 230000007882 cirrhosis Effects 0.000 description 1
- 208000019425 cirrhosis of liver Diseases 0.000 description 1
- 238000003776 cleavage reaction Methods 0.000 description 1
- 206010061428 decreased appetite Diseases 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 230000002255 enzymatic effect Effects 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 230000006870 function Effects 0.000 description 1
- 206010073071 hepatocellular carcinoma Diseases 0.000 description 1
- 230000002452 interceptive effect Effects 0.000 description 1
- 229940079322 interferon Drugs 0.000 description 1
- 210000004347 intestinal mucosa Anatomy 0.000 description 1
- 238000011835 investigation Methods 0.000 description 1
- 210000004185 liver Anatomy 0.000 description 1
- 208000019423 liver disease Diseases 0.000 description 1
- 201000005202 lung cancer Diseases 0.000 description 1
- 208000020816 lung neoplasm Diseases 0.000 description 1
- 230000002934 lysing effect Effects 0.000 description 1
- 238000000034 method Methods 0.000 description 1
- 230000004898 mitochondrial function Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 230000008693 nausea Effects 0.000 description 1
- 239000002777 nucleoside Substances 0.000 description 1
- 150000003833 nucleoside derivatives Chemical class 0.000 description 1
- 239000002245 particle Substances 0.000 description 1
- 230000003389 potentiating effect Effects 0.000 description 1
- 238000003757 reverse transcription PCR Methods 0.000 description 1
- 238000011895 specific detection Methods 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- 210000004881 tumor cell Anatomy 0.000 description 1
- 201000001862 viral hepatitis Diseases 0.000 description 1
- 230000003612 virological effect Effects 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
Images
Classifications
-
- 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
- A61K31/496—Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene or sparfloxacin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/16—Drugs for disorders of the alimentary tract or the digestive system for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
- A61P31/20—Antivirals for DNA viruses
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Medicinal Chemistry (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Chemical & Material Sciences (AREA)
- Virology (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Molecular Biology (AREA)
- Communicable Diseases (AREA)
- Biotechnology (AREA)
- Oncology (AREA)
- Epidemiology (AREA)
- Gastroenterology & Hepatology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The invention provides application of a small molecule inhibitor BAY87-2243 in preparing a medicament for treating hepatitis B virus infection. The invention uses different liver cancer cell lines which can stably produce Hepatitis B Virus (HBV) or HBV-infected human primary liver cells to verify that BAY87-2243 can obviously inhibit HBV transcription and replication and effectively reduce cccDNA expression level through the in vitro treatment of BAY87-2243 with different concentrations.
Description
Technical Field
The invention relates to application of a small molecule inhibitor BAY87-2243 in preparing a medicament for treating hepatitis B
Background
Viral hepatitis B (viral hepatitis type B) is an infectious disease mainly caused by Hepatitis B Virus (HBV) and mainly characterized by liver disease. Clinically, the symptoms of anorexia, nausea, epigastric discomfort, liver pain and hypodynamia are mainly manifested. Some patients may have jaundice fever and hepatomegaly with impaired liver function. Some patients can become chronic, even develop cirrhosis of the liver, and a few can develop liver cancer.
At present, the effect of treating chronic HBV infection by nucleoside (acid) analogues and interferon is very limited, and only a few patients can realize 'functional cure'. The key to cure chronic hepatitis B virus infection is that covalently closed circular DNA (cccDNA) in host hepatocytes must be thoroughly eliminated, and the cccDNA is a template for HBV transcription and replication and a viral gene repository and is a key cause for relapse of patients with chronic hepatitis B after drug withdrawal. At present, the medicine for effectively removing cccDNA is still lacking clinically, so the search and development of the medicine for effectively removing the cccDNA of the hepatitis B virus have good clinical application prospect.
The small molecule inhibitor BAY87-2243 is a potent selective hypoxia-inhibitor factor-1(HIF-1) inhibitor. At present, research reports show that the compounds can inhibit tumor cell proliferation by interfering mitochondrial function, can be used for treating cancers such as lung cancer, also report research that the compounds have positive influence on Intestinal Mucosa Barrier (IMB) function, and can be used for treating sepsis. No BAY87-2243 is reported to be used for treating hepatitis B.
Disclosure of Invention
In order to solve the problems, the invention provides the application of a small molecule inhibitor BAY87-2243 in preparing a medicament for treating hepatitis B; the BAY87-2243 is a HIF-1 specific inhibitor.
Further, the drug is a drug that reduces the level of hepatitis b surface antigen production.
Further, the drug is a drug that reduces the level of hepatitis b e antigen production.
Further, the drug is a drug that inhibits transcription of hepatitis b virus.
Further, the medicament is a medicament for inhibiting the replication of hepatitis B virus DNA.
Further, the medicament is a medicament for reducing the expression level of hepatitis b virus cccDNA.
Furthermore, the medicine is a preparation prepared by taking a small molecular inhibitor BAY87-2243 as an active ingredient and adding pharmaceutically acceptable auxiliary materials or auxiliary ingredients.
Still further, the formulation is an oral formulation; the oral preparation is granule, solution, pill, paste or tablet.
Experiments prove that the small molecular inhibitor BAY87-2243 can obviously inhibit HBV transcription and replication and effectively reduce the cccDNA expression level, so that the complete elimination of the virus carrying state of a hepatitis B patient becomes possible, the aim of antiviral treatment is finally achieved, and the application has practical popularization and application prospects.
Obviously, many modifications, substitutions, and variations are possible in light of the above teachings of the invention, without departing from the basic technical spirit of the invention, as defined by the following claims.
The present invention will be described in further detail with reference to the following examples. This should not be understood as limiting the scope of the above-described subject matter of the present invention to the following examples. All the technologies realized based on the above contents of the present invention belong to the scope of the present invention.
Drawings
FIG. 1 statistical data of the study on HBsAg/HBeAg secretion by BAY87-2243 treatment (A: effect of different concentrations of BAY87-2243 treatment on HepAD38 cytotoxicity and HBsAg secretion, B: effect of different concentrations of BAY87-2243 treatment on HepG2.2.15 cytotoxicity and HBsAg secretion, C: effect of different concentrations of BAY87-2243 treatment on HepAD38 cytotoxicity and HBeAg secretion, D: effect of different concentrations of BAY87-2243 treatment on HepG2.2.15 cytotoxicity and HBeAg secretion)
FIG. 2 statistical data of the effects of BAY87-2243 treatment on HBV transcription and replication levels and HBV cccDNA expression levels (A: the effect of BAY87-2243 treatment on HBV total RNA expression level in HepAD38 cells, B: the effect of BAY87-2243 treatment on HBVpgRNA expression level in HepAD38 cells, C: the effect of BAY87-2243 treatment on HBVDNA replication level in HepAD38 cells, D: the effect of BAY87-2243 treatment on HBVccc DNA expression level in HepAD38 cells) FIG. 3 is a statistical plot of the effects of BAY87-2243 treatment on HBV transcription and replication levels and HBV cccDNA expression level in HBV infected human primary hepatocytes, B: BAY87-2243 treatment on HBeAg secretion, C: BAY87 treatment on HBeAg secretion, B: BAY87-2243 treatment on HBegRNA expression level in HBegRNA 633, effect of BAY87-2243 treatment on intracellular HBV cccDNA expression level
Detailed Description
Example 1 Effect of BAY87-2243 on HBsAg/HBeAg secretion in HBV-producing hepatoma cells
Firstly, mix 8 × 10 4 One/well hepg2.215 and HepAD38 cells were seeded in 48-well plates, respectively. The next day after cell plating, cells were treated with different concentration gradients (0.01-100nM) of BAY87-2243, respectively. After BAY87 treated the cells for 72h, Cell Counting Kit-8 reagent (MedChemexpress, HY-K0301) was added to the 48-well plate, and the change in absorbance of the cells was detected by a multifunctional microplate reader at a wavelength of 450 nm. In addition, the cell supernatant was collected and the levels of HBsAg and HBeAg secreted in the cell supernatant were measured using a hepatitis B virus surface antigen diagnostic kit (enzyme linked immunosorbent assay; Shanghai Kowa, SI0910113) and a hepatitis B virus E antigen detection kit (enzyme linked immunosorbent assay; Shanghai Kowa, 20163400144), respectively. The specific detection results of the microplate reader and the ELISA kit are shown in FIGS. 1A-D. From the results of the graphSee: BAY87-2243 concentrations had less effect on cytotoxicity at 100nM, and lower concentrations (<0.1nM) of BAY87-2243 is effective in inhibiting secretion of HBsAg and HBeAg.
Example 2 Effect of BAY87-2243 on HBV transcription and replication levels and HBV cccDNA expression levels in HepAD38 cells
Will be 3X 10 5 One/well HepAD38 cells were seeded in 12-well plates, treated the following day with varying concentration gradients (1, 2 or 4nM) of BAY87 for 72h, followed by extraction of intracellular total RNA using Trizol reagent (Invitrogen, 15596026) and One-Step real RT-qPCR kit [ One Step TBPrimeScript TM RT-PCR Kit II(Perfect Real Time),TaKaRa,RR086]Expression levels of HBV total RNA (FIG. 2A) and pgRNA (FIG. 2B) in cells were examined. From the results of the figures, it can be seen that: treatment with different concentrations of BAY87-2243 can significantly reduce the expression levels of total HBV RNA and pgRNA in cells, indicating that BAY87-2243 can effectively inhibit HBV transcription in cells.
Will be 6X 10 5 The HepAD38 cells are inoculated in a 6-well plate, treated with BAY87-2243 with different concentration gradients (1, 2 or 4nM) for 72h the next day, the cells are lysed and the HBV DNA inside the cells, which is enveloped by nucleocapsid, is extracted, and the influence of BAY87-2243 on the replication level of the HBV DNA inside the cells is detected by a Southern blot method. The specific results are shown in FIG. 2C. From the results of the figures, it can be seen that: treatment with BAY87-2243 at different concentrations can significantly reduce the intracellular HBV DNA replication level, suggesting that BAY87-2243 can effectively inhibit the intracellular HBVDNA replication.
Will be 6X 10 5 Individual/well HepAD38 cells were seeded in 6-well plates and treated the following day with varying concentration gradients (1, 2 or 4nM) of BAY87-2243 for 96 h. Then washing the cells with PBS 2 times, lysing the cells overnight, extracting DNA with phenol chloroform, subjecting the cccDNA obtained to an enzymatic cleavage reaction with T5 exonuclease, and performing Realtime qPCR (Probe qPCR Master Mix, promega, a6101) to detect HBV cccDNA expression levels in cells. The specific results are shown in FIG. 2D. FromThe results of the graph show that: BAY87-2243 treatment at different concentrations can obviously reduce the expression level of HBV cccDNA in cells, and the BAY87-2243 is suggested to effectively reduce the expression level of HBVcccDNA in cells.
Example 3 investigation of the Effect of BAY87-2243 on HBV transcription and replication levels and HBV cccDNA expression levels in HBV-infected human primary hepatocytes
Commercial human primary cells were arranged at 5X 10 5 One/well was seeded in 12-well plates, and the next day after cell plating, cells were incubated with William's E complete medium containing HBV viral particles (MOI: 1000); 24h after HBV infection, cells were washed 3 times with PBS and then treated with BAY87-2243 at different concentration gradients (2nM and 4nM) for 6 consecutive days. Collecting cell supernatant, using (hepatitis B virus surface antigen diagnostic kit (enzyme-linked immunosorbent assay) and hepatitis B virus E antigen detection kit (enzyme-linked immunosorbent assay) to respectively collect cell supernatant, and detecting the levels of HBsAg and HBeAg secreted in the cell supernatant, wherein the specific results are shown in figures 3A-B, and the results are shown in that BAY87-2243 can effectively inhibit the secretion of HBsAg and HBeAg.
Cells treated as in FIGS. 3A-B were washed 2 times with PBS, total RNA in the cells was extracted using Trizol reagent, and expression levels of HBV total RNA (FIG. 3C) and pgRNA (FIG. 3D) in the cells were measured using One-step simple RT-qPCR kit. From the results of the figures, it can be seen that: BAY87-2243 treatment with different concentrations can obviously reduce the expression level of HBV total RNA and pgRNA in hepatocytes, which indicates that BAY87-2243 can effectively inhibit HBV transcription in human primary hepatocytes.
Cells treated as in FIGS. 3A-B were washed 2 times with PBS, lysed and nucleocapsid-encapsulated HBV DNA extracted from cells with phenol-chloroform, and subjected to Realtime qPCR (TB)Premix Ex Taq TM II (Tli RNaseH plus), TaKaRa, RR820) to test the effect of BAY87-2243 on the intracellular HBV DNA expression level. The specific results are shown in FIG. 3E. From the results of the figures, it can be seen that: BAY87-2243 treatment can obviously reduce the expression level of HBV DNA in cells, and the BAY87-2243 is suggested to be capable of effectively inhibiting the replication of HBVDNA in primary human hepatocytes.
Cells treated in the same manner as in FIGS. 3A-B were washed 2 times with PBS, lysed and then DNA was extracted with phenol chloroform, and finally the cccDNA obtained was digested with T5 exonuclease by Realtime qPCR (Probe qPCR Master Mix, promega, a6101) to detect HBV cccDNA expression levels in cells. The specific results are shown in FIG. 3F. From the results of the figures, it can be seen that: BAY87-2243 treatment can significantly reduce the expression level of HBV cccDNA in cells, and suggests that BAY87-2243 can effectively reduce the expression level of HBV cccDNA in human primary hepatocytes.
In conclusion, a series of experiments prove that the small molecular inhibitor BAY87-2243 can obviously inhibit HBV transcription and replication, effectively reduce the cccDNA expression level, enable complete elimination of the virus carrying state of a hepatitis B patient to be possible, finally realize the aim of antiviral treatment, and have practical popularization and application prospects.
Claims (9)
1. The use of small molecule inhibitor BAY87-2243 in the preparation of medicine for treating hepatitis B; the BAY87-2243 is a HIF-1 specific inhibitor.
2. The use of claim 1, wherein the medicament is a medicament that reduces the level of hepatitis b surface antigen production.
3. The use of claim 1, wherein the medicament is a medicament that reduces the level of hepatitis b e antigen production.
4. The use according to claim 1, wherein the medicament is a medicament for inhibiting transcription of hepatitis b virus.
5. The use according to claim 1, wherein the medicament is a medicament for inhibiting replication of hepatitis b virus DNA.
6. The use of claim 1, wherein the medicament is a medicament that reduces the expression level of hepatitis b virus cccDNA.
7. The use of any one of claims 1 to 6, wherein the medicament is a preparation prepared by taking a small molecule inhibitor BAY87-2243 as an active ingredient and adding pharmaceutically acceptable auxiliary materials or auxiliary ingredients.
8. Use according to claim 7, wherein the formulation is an oral formulation.
9. Use according to claim 8, characterized in that the oral formulation is a granule, solution, pill, paste or tablet.
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN202210529236 | 2022-05-16 | ||
CN2022105292369 | 2022-05-16 |
Publications (2)
Publication Number | Publication Date |
---|---|
CN114886895A true CN114886895A (en) | 2022-08-12 |
CN114886895B CN114886895B (en) | 2023-02-03 |
Family
ID=82726225
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CN202210576920.2A Active CN114886895B (en) | 2022-05-16 | 2022-05-25 | Application of small molecule inhibitor BAY87-2243 in preparing medicine for treating hepatitis B |
Country Status (2)
Country | Link |
---|---|
CN (1) | CN114886895B (en) |
WO (1) | WO2023221361A1 (en) |
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2023221361A1 (en) * | 2022-05-16 | 2023-11-23 | 重庆医科大学 | Use of small-molecule inhibitor bay87-2243 in preparing drug for treating hepatitis b |
Citations (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2022093770A1 (en) * | 2020-10-27 | 2022-05-05 | Memorial Sloan Kettering Cancer Center | Combination therapy with pi3k-akt-mtor inhibitors and ferroptosis inducing agents to treat cancer |
Family Cites Families (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN109381463A (en) * | 2017-08-08 | 2019-02-26 | 复旦大学 | Application of the tazarotene in preparation treatment hepatitis B virus infection drug |
EP3676379A1 (en) * | 2017-09-01 | 2020-07-08 | Institut National de la Sante et de la Recherche Medicale (INSERM) | An inhibitor for use for preventing and/or treating an infection with hepatitis b virus |
CN113337602A (en) * | 2020-03-02 | 2021-09-03 | 苏州亚盛药业有限公司 | Methods of treatment and biomarkers for MDM2 inhibitors |
CN114886895B (en) * | 2022-05-16 | 2023-02-03 | 重庆医科大学 | Application of small molecule inhibitor BAY87-2243 in preparing medicine for treating hepatitis B |
-
2022
- 2022-05-25 CN CN202210576920.2A patent/CN114886895B/en active Active
- 2022-09-27 WO PCT/CN2022/121759 patent/WO2023221361A1/en unknown
Patent Citations (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2022093770A1 (en) * | 2020-10-27 | 2022-05-05 | Memorial Sloan Kettering Cancer Center | Combination therapy with pi3k-akt-mtor inhibitors and ferroptosis inducing agents to treat cancer |
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2023221361A1 (en) * | 2022-05-16 | 2023-11-23 | 重庆医科大学 | Use of small-molecule inhibitor bay87-2243 in preparing drug for treating hepatitis b |
Also Published As
Publication number | Publication date |
---|---|
WO2023221361A1 (en) | 2023-11-23 |
CN114886895B (en) | 2023-02-03 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
Huang et al. | Anti-hepatitis B virus effects of wogonin isolated from Scutellaria baicalensis | |
Shin et al. | A flavonoid from medicinal plants blocks hepatitis B virus-e antigen secretion in HBV-infected hepatocytes | |
US8895725B2 (en) | Use of 9, 10-anthraquinone compounds | |
CN114886895B (en) | Application of small molecule inhibitor BAY87-2243 in preparing medicine for treating hepatitis B | |
CN103458913A (en) | Treatment for infection with Hepatitis B virus alone or in combination with Hepatitis Delta virus and associated liver diseases | |
CN114832023B (en) | Application of herba Erodii seu Geranii effective component in treating or preventing viral hepatitis | |
CN109364074B (en) | Application of 6-aminonicotinamide as effective component in preparing medicament for treating hepatitis B | |
CN102631384B (en) | Application of pomegranate in preparing medicament for treating or preventing hepatitis B virus infection | |
CN113304165B (en) | Application of monomeric compound Ciliaoside A in preparation of hepatitis B treatment drug | |
CN115105519A (en) | Pharmaceutical composition for treating hepatitis B and preparation method thereof | |
CN112294823B (en) | Application of harringtonine or analogue thereof and prepared preparation | |
CN105031613B (en) | A kind of human beta-defensin 1 is preparing the application in treating or preventing hepatitis B virus infective medicament | |
CN114246847A (en) | Application of chalcone compound in treatment of coronavirus infection | |
CN113502288A (en) | Antisense oligonucleotide and application thereof in inhibiting new coronavirus | |
CN109811030B (en) | Application of antazoline hydrochloride derivative as HBV inhibitor | |
CN104758282B (en) | Berberine is for preparing the purposes of the medicine of viral myocarditis disease caused by treatment Coxsackie B virus 3 | |
CN109248202A (en) | A kind of serviceberry and its extract are preparing the application in medicine resisting viral hepatitis | |
CN113975267B (en) | Application of 6 alpha-hydroxyeyeurycommactone in preparation of anti-dengue virus drugs | |
CN114246858A (en) | Application of artemisinin compound in treatment and prevention of coronavirus infection | |
CN112618661A (en) | Antiviral traditional Chinese medicine composition and preparation method and application thereof | |
CN117281800A (en) | Application of niclosamide in preparing medicine for treating hepatitis B | |
CN114515338B (en) | Pharmaceutical composition for treating viral hepatitis | |
CN111803492B (en) | Application of coumarin compound in preparation of medicine for treating hepatitis B | |
CN102048716A (en) | New application of hydroquinone compound | |
CN111228245A (en) | Application of phenolic compound and pharmaceutically acceptable salt thereof in preparation of anti-hepatitis B virus medicine |
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 | ||
GR01 | Patent grant | ||
GR01 | Patent grant |