CN106540255A - Ring dinucleotide cGAMP combines application of the Avastin in antitumor - Google Patents
Ring dinucleotide cGAMP combines application of the Avastin in antitumor Download PDFInfo
- Publication number
- CN106540255A CN106540255A CN201510597098.8A CN201510597098A CN106540255A CN 106540255 A CN106540255 A CN 106540255A CN 201510597098 A CN201510597098 A CN 201510597098A CN 106540255 A CN106540255 A CN 106540255A
- Authority
- CN
- China
- Prior art keywords
- cgamp
- avastin
- tumor
- combines
- antitumor
- 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
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
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/7084—Compounds having two nucleosides or nucleotides, e.g. nicotinamide-adenine dinucleotide, flavine-adenine dinucleotide
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K16/00—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Medicinal Chemistry (AREA)
- Organic Chemistry (AREA)
- Molecular Biology (AREA)
- General Health & Medical Sciences (AREA)
- Biochemistry (AREA)
- Genetics & Genomics (AREA)
- Biophysics (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Immunology (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Abstract
The invention belongs to pharmaceutical technology field, specially ring dinucleotide cGAMP combine application of the Avastin in treatment tumor.Present invention research shows that cGAMP joint Avastins can significantly inhibit the growth of kinds of tumor cells, with obvious antitumor action, can be used to prepare antitumor drug.Jing C57BL/6 mouse subcutaneous transplanting tumor models show, cGAMP combines Avastin to adenocarcinoma cell strain MC38, lung cancer cell line LLC, melanoma cells line B16-F10, colon cancer cell MC38 has significant inhibitory action, and it is better than independent medication effect, therefore, cGAMP can combine Avastin for treating tumor.
Description
Technical field
The invention belongs to biomedicine technical field, and in particular to a kind of ring dinucleotide（cGAMP）Application of the joint Avastin in antitumor and in antitumor drug is prepared.
Background technology
Tumor, is currently the major disease of a class serious harm human life and health, and which is embodied in cell hyperproliferation and disdifferentiation, and is difficult to suppress.According to WHO scholarly forecasts, to the year two thousand twenty, the tumor invasion number of population in the world is up to 20,000,000 people, and death toll is up to 1 200 ten thousand people, therefore, tumor will become the first big killer of this century mankind, constitute the threat of most serious to human survival.In China, including the M ＆ M of pulmonary carcinoma, colorectal cancer, gastric cancer, hepatocarcinoma etc. occupies the prostatitis of all kinds of malignant tumor, according to (2012 China's tumour registration annual reports that national tumor Register issues》Statistics, annual kainogenesis tumor cases about 3,120,000, average daily 8 550 people, the whole nation is per minute to have 6 people to be diagnosed as cancer.From the point of view of disease, pulmonary carcinoma, gastric cancer, knot/rectal cancer, hepatocarcinoma and the esophageal carcinoma occupy first five position of national malignant tumor morbidity.With the increase year by year of Cancer Mortality and mortality rate, treating malignant tumor demand is increasing.Aging, fresh water food pollution, environmental pollution in particular with Chinese population etc., Chinese malignant tumor patient number will continue to increase.
At present, chemotherapy is to treat one of effective ways of tumor.The mechanism of action of classic chemotherapy medicine mainly prevents the synthesis of DNA (deoxyribonucleic acid) (DNA), ribonucleic acid (RNA) or protein, or directly these macromole are had an effect, and so as to suppress the division growth of tumor cell, is allowed to dead.Some medicines can also suppress tumour growth by changing hormone in vivo balance.Antitumor drug has developed to 6 big class at present：1. antimetabolite；2. alkylating agent；3. cytotoxin class antibiotic；4. plant alkaloid and other crude drugs；5. antitumor hormoness；6. platinum class and other antineoplastic agents.With the transformation and the discovery of some new antitumor drug target spots of clinical treatment pattern, the research and development of field of antineoplastic medicaments there occurs great variety：For the mechanism of action of medicine, the targeted drug exploitation of non-cytotoxicity class has been turned to from traditional nonspecific cytotoxic drug.In the antitumor drug of FDA approvals in 2012, small molecule tyrosine kinase inhibitors (TKI) become the most popular series antineoplastic medicament of research and development, especially act on the TKI (accounting for 3/4) of multiple target spots, by the U.S. FDA of in June, 2013 approval TKI up to 18 kinds.Additionally, other focus mechanism of action medicines include immunostimulant, angiogenesis inhibitor, cell cycle inhibitor, immunosuppressant and stimulant, kinases inhibitor etc..In recent years, more and more immunomodulators are used for clinic, and are used for oncotherapy.
In the mammalian cell of infection, microorganism and viral DNA can be by stimulating the strong immunne response in interferon secretion induction Inner sources.Endoplasmic reticulum（ER）Receptor protein（STING）It is required factor to the immunne response of cytoplasmic DNA.It has recently been demonstrated that cyclisation cGMP-AMP dinucleotide synzyme（cGAS）Under activation condition after with reference to DNA, the synthesis of cGAMP is endogenously catalyzed.CGAMP is a kind of cytoplasmic DNA sensor, and it stimulates the sensing of INF- β as second message,second messenger by STING, mediates the activation of TBK1 and IRF-3, and then starts the transcription of INF- β genes.Report recently, recombinate cGAS catalytic cyclization cGMP-AMP dinucleotide GAMP under DNA conjugation conditions.CGAS has also been reported with reference to the crystal structure of the complex of 18bp dsDNA, and researchs of the cGAMP in terms of antiviral immunity has been found to.CGAMP combines STING, transcription factor IRF3 is activated and is produced interferon-β.By STING paths, cGAMP can be by as immunomodulator, for activating immune system antitumor.
VEGF, is called VEGF.Vegf protein is scientist's difference successful purification and the identification in the Liang Jia biotechnologies company by the U.S. in 1989, and clones and determine its gene order, it was demonstrated that VPF and VEGF is the same albumen of same gene coding.VEGF has the types such as six（isoforms）：VEGF-A ,-B ,-C ,-D, and-E；From 35 to 44kDa, each waits type specificity ground and three " vascular endothelial growth factor receptor " to its molecular weight（VEGFR-1, -2, and -3) particular combination combines.VEGF is highly conserved homodimer glycoprotein.Two molecular weight respectively constitutes dimer with disulfide bond for the single-stranded of 24kDa.The monomer that VEGF decomposes is inactive, removes N2 glycosyls to biological effect without impact, but may work in cell secretion.Due to the different cut modes of mRNA, produce at least 5 kinds protein forms such as VEGF121, VEGF145, VEGF165, VEGF185, VEGF206, wherein VEGF121, VEGF145, VEGF165 are secreting type soluble proteins, vascular endothelial cell can be directly acted on and promote vascular endothelial cell proliferation, increase vascular permeability.Nineteen ninety, Harvard University doctor Folkman propose that famous Folkman is theoretical, i.e. tumor tissue growth, it is necessary to generate to provide enough oxygen and nutrient substance to maintain by new vesselses.It is considered as the basis of VEGF clinical practices.
Avastin（Bevacizumab, trade name Avastin）It is a kind of VEGF monoclonal antibodies, VEGF can be suppressed, for treating all kinds of metastatic cancers, is the treatment of cancer well selling medicine of Roche Holding Ag.Arastin its sales volume in 2009 is up to 5,900,000,000 dollars.Avastin, is a kind of medicine of line artery generation, by suppressing blood supply of the hindrance blocks of VEGF to tumor, suppresses tumor to spread in vivo, strengthen chemotherapy effect.This medicine is ratified for treating pulmonary carcinoma, colon cancer and rectal cancer by pencil office of the U.S., and is approved for treating breast carcinoma in Europe.
The content of the invention
It is an object of the invention to provide cGAMP joint applications of the Avastin in antitumor.
Experimentation of the present invention shows, cGAMP joint Avastins can significantly inhibit the growth of kinds of tumor cells, with obvious antitumor action, and tumor is treated better than Avastin is used alone, therefore cGAMP can be used to prepare antitumor drug or combine for treating tumor.
In the present invention, the tumor includes but is not limited to adenocarcinoma, pulmonary carcinoma, colon cancer, melanoma etc..
-.
Specific embodiment
Present disclosure is illustrated below by embodiment.In the present invention, it, in order to preferably illustrate the present invention, is not for limiting the scope of the present invention that embodiments discussed below is.
Embodiment
1
：
cGAMP
Preparation
cGAMP （Cyclisation-GMP-AMP）Under by activation condition of the literature method after with reference to DNA, by cyclisation cGMP-AMP dinucleotide synzyme（cGAS）Catalyze and synthesize.Purity is more than 98%.（Ping weiLi, et al., Immunity, 2013,
39(6), 1019-1031.）
Embodiment
2
：The preparation of Avastin
Avastin variable region and Mus IgG2b constant domains are hybrid antibody, and the gene is synthesized and is cloned in pTT3 plasmids by Nanjing Jin Sirui.Plasmid extraction test kit, Protein A chromatographic columns, molecular sieve and except the clear post of endotoxin, endotoxin measurement test kit are purchased from common therapy or Nanjing Jin Sirui.
Avastin is expressed in 293F cell transient transfections, after Protein A posts, molecular sieve and Endotoxin removal column purification, purity is 90%, endotoxin is less than 1 EU/ml, protein dissolution is preserved after PBS, lyophilizing.
Embodiment
3
：
cGAMP
（Cyclisation
-GMP-AMP
）Antitumor action detected using lotus knurl mouse model
cGAMP
Inhibitory action to the growth of animal subcutaneous transplantation tumor.
Test medicine
Title：cGAMP
Character：White powder
Solvent：Normal saline.
Compound method：It is configured to the solution of desired concn before use with normal saline solution.
Test drug concentrations：5 mg/ml、10 mg/ml、20 mg/ml..
Animal
Kind, strain, sex, body weight, source, the quality certification
C57BL/6 Mus, female, body weight 20g, 8 week old, SPF levels are purchased from Shanghai Slac Experimental Animal Co., Ltd.'s [Quality of Experimental Animals quality certification number：SCXK （Shanghai）2007-0005 ] .
Rearing conditions
All C57BL/6 Mus, freely look for food and drink water, in room temperature（23±2）DEG C, raise in army medical university of Chinese People's Liberation Army Experimental Animal Center.Feedstuff and the equal Jing autoclavings of water are processed, and all experimentss feeding process is SPF levels.
Dosage is arranged
CGAMP Tail Vein injection Mouses, arrange 3 dosage groups：5 mg/kg, 10 mg/kg, 20 mg/kg
Experimental control
Negative control：Normal saline solution
Positive control：Avastin, dosage 10mg/kg
Medication
Route of administration：Intravenous injection is administered
Avastin administration number of times：Per 4 days 1 time, it is administered 4 times.
Administered volume：10 ml/kg
CGAMP administration number of times：Once a day, continuous 14 days
Every group of number of animals：10
Tumor cell line
Adenocarcinoma cell strain MC38, lung cancer cell line LLC, melanoma cells line B16-F10, colon cancer cell MC38, purchased from Chinese Academy of Sciences's cell bank or ATCC.
Test key step
1. the foundation of lotus knurl mouse model and intervention
6 kinds of subcutaneous transplantation tumor models are prepared respectively：Adenocarcinoma cell strain MC38, lung cancer cell line LLC, melanoma cells line B16-F10, colon cancer cell MC38, and observe the effect that cGAMP combines Avastin.
Adenocarcinoma cell strain MC38, lung cancer cell line LLC, melanoma cells line B16-F10, colon cancer cell MC38 are cultivated, and are passed on.Cell is collected in the cell log phase, make the cell suspension that concentration is (5.0 × 106)/per milliliter of ml, inject 0.2 ml cell suspension in C57BL/6 Mus right fores oxter (cell number is 1.0 × 106 /), 7-10 days or so tumor length is to diameter about 3-6 mm, tumorigenesis success.
5 groups are divided at random, per group of 10 mices：
Negative control group（Intravenous injection physiological saline group）
Avastin administration group (10 mg/kg groups of vein note)
CGAMP low dosage joint groups (5 mg/kg of intravenous injection cGAMP add 10 mg/kg of Avastin)
CGAMP middle dosage joint groups (10 mg/kg of intravenous injection cGAMP add 10 mg/kg of Avastin)
CGAMP high dose joint groups (20 mg/kg of intravenous injection cGAMP add 10 mg/kg of Avastin).
CGAMP is administered once daily, successive administration 14 days.Avastin is administered once for 4 days, totally 4 times.After 14 days, put to death C57BL/6 mices and claim tumor weight, tumour inhibiting rate=[the average knurl weight of the average knurl weight/negative control group of 1- experimental grouies)] × 100%.
2. statistical analysiss
Data are represented with x ± s, are processed using SPSS10.0 softwares, using one factor analysis of variance（one-way ANOVA）The significance of each group knurl weight difference, significance level a=0.05 are compared in inspection.
As a result
Subcutaneous transplantation tumor model is successfully prepared after C57BL/6 mouse hypodermic inoculation tumor cells, cGAMP joint Avastins can substantially suppress tumour growth, and the knurl weight after being administered 14 days is substantially less than Avastin matched group（P<0.05, P<0.01）, show cGAMP joint Avastins better than exclusive use Avastin, therefore cGAMP can combine Avastin use, and there is notable antitumor action.Concrete outcome is shown in Table 1- tables 4.
Table 1 CGAMP combines inhibition of the Avastin to cell strain MC38 adenocarcinoma
（N=10, mean ± SD）
Group
Average knurl weight（g）
Average tumour inhibiting rate（%）
Negative control group
2.021±0.211 （g）
-
Avastin group
0.920±0.214 （g）
54.5
CGAMP joint Avastins low dose group 0.896 ± 0.205（g）
55.7
CGAMP joint Avastins middle dose group 0.692 ± 0.189（g）*
65.8
CGAMP joint Avastins high dose group 0.513 ± 0.197（g）**
74.6
Note：*P<0.05 vs Avastin groups；**P<0.01 vs Avastin groups.
Table 2CGAMP combines inhibition of the Avastin to cell LLC pulmonary carcinoma
（N=10, mean ± SD）
Group
Average knurl weight（g）
Average tumour inhibiting rate（%）
Negative control group
2.412±0.329 （g）
-
Avastin group
1.374±0.263 （g）
43.0
CGAMP joint Avastins low dose group 0.896 ± 0.276（g）**
62.9
CGAMP joint Avastins middle dose group 0.683 ± 0.356（g）**
71.7
CGAMP joint Avastins high dose group 0.498 ± 0.413（g）**
79.4
Note：*P<0.05 vs Avastin groups；**P<0.01 vs Avastin groups.
Table 3CGAMP combines inhibition of the Avastin to cell B16-F10 melanomas
（N=10, mean ± SD）
Group
Average knurl weight（g）Average tumour inhibiting rate（%）
Negative control group
2.460±0.220 （g）
-
Avastin group
0. 898±0.421 （g）
63.5
CGAMP joint Avastins low dose group 0.687 ± 0.167（g）*
72.1
CGAMP joint Avastins middle dose group 0.633 ± 0.276（g）**
74.3
CGAMP joint Avastins high dose group 0.594 ± 0.312（g）**
75.9
Note：*P<0.05 vs Avastin groups；**P<0.01 vs Avastin groups.
4 cGAMP of table combines inhibition of the Avastin to cell MC38 colon cancer
（N=10, mean ± SD）
Group
Average knurl weight（g）Average tumour inhibiting rate（%）Negative control group
2.433±0.218 （g）
-
Avastin group
1.143±0.299 （g）
53.0
CGAMP combines Avastin low dose group
0.932±0.264 （g）*
61.7
CGAMP combines Avastin middle dose group
0.776±0.295（g）**
68.1
CGAMP combines Avastin high dose group
0.562±0.312 （g）** 76.9
Note：*P<0.05 vs Avastin groups； **P<0.01 vs Avastin groups.
Claims (5)
1.cGAMP combines Avastin in the anti-application treated in tumor.
2.cGAMP combines application of the Avastin in antitumor drug is prepared.
3. cGAMP according to claim 2 combines application of the Avastin in antitumor drug is prepared, and the tumor is adenocarcinoma, pulmonary carcinoma, colon cancer, breast carcinoma, melanoma.
4. using cGAMP joint Avastin treatment tumors.
5. one or more in various dosage forms made by the combination medicine routinely pharmaceuticss according to claim 1 and 2, including tablet, capsule, granule, suspensoid, Emulsion, solution, syrup or injection etc., takes oral or injection（Including one or more in intravenous injection, intravenous drip, intramuscular injection or subcutaneous injection etc.）One or more route of administration in carries out prevention, protection or the treatment of tumor and its directly related disease.
Priority Applications (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201510597098.8A CN106540255A (en) | 2015-09-18 | 2015-09-18 | Ring dinucleotide cGAMP combines application of the Avastin in antitumor |
| PCT/CN2016/098931 WO2017045595A1 (en) | 2015-09-18 | 2016-09-13 | Application of cyclic gmp-amp (cgamp) in combination with bevacizumab in tumor resistance |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201510597098.8A CN106540255A (en) | 2015-09-18 | 2015-09-18 | Ring dinucleotide cGAMP combines application of the Avastin in antitumor |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN106540255A true CN106540255A (en) | 2017-03-29 |
Family
ID=58288031
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201510597098.8A Pending CN106540255A (en) | 2015-09-18 | 2015-09-18 | Ring dinucleotide cGAMP combines application of the Avastin in antitumor |
Country Status (2)
| Country | Link |
|---|---|
| CN (1) | CN106540255A (en) |
| WO (1) | WO2017045595A1 (en) |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN113546172A (en) * | 2020-04-24 | 2021-10-26 | 山东大学齐鲁医院 | Application of VEGF inhibitor in preparation of medicament for treating hypoxia-related diseases |
| CN117144004A (en) * | 2023-07-21 | 2023-12-01 | 中山大学附属第六医院 | Application of 14-3-3σ in colon cancer treatment |
Families Citing this family (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN117018011A (en) * | 2023-06-16 | 2023-11-10 | 桂林医学院 | Use of 2,3,-cyclic guanosine monophosphate sodium nucleotide in the preparation of anti-tumor drugs |
| CN117427070A (en) * | 2023-12-07 | 2024-01-23 | 中国人民解放军陆军特色医学中心 | Application of AF38469 in the preparation of anti-tumor angiogenesis drugs or health products |
Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103417964A (en) * | 2012-05-17 | 2013-12-04 | 江苏先声药物研究有限公司 | Application of anti-VEGF antibody |
| WO2013185052A1 (en) * | 2012-06-08 | 2013-12-12 | Aduro Biotech | Compostions and methods for cancer immunotherapy |
| CN103987405A (en) * | 2011-11-28 | 2014-08-13 | 默克专利股份公司 | Anti-PD-L1 antibodies and uses thereof |
| WO2014189805A1 (en) * | 2013-05-18 | 2014-11-27 | Auro Biotech, Inc. | Compositions and methods for activating "stimulator of interferon gene"-dependent signalling |
Family Cites Families (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| PT2934598T (en) * | 2012-12-19 | 2018-07-24 | Univ Texas | Pharmaceutical targeting of a mammalian cyclic di-nucleotide signaling pathway |
| WO2014179760A1 (en) * | 2013-05-03 | 2014-11-06 | The Regents Of The University Of California | Cyclic di-nucleotide induction of type i interferon |
| CN103908468B (en) * | 2014-04-21 | 2017-02-08 | 上海捌加壹医药科技有限公司 | Application of cyclic dinucleotide cGAMP in preparing anti-tumor medicaments |
-
2015
- 2015-09-18 CN CN201510597098.8A patent/CN106540255A/en active Pending
-
2016
- 2016-09-13 WO PCT/CN2016/098931 patent/WO2017045595A1/en not_active Ceased
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103987405A (en) * | 2011-11-28 | 2014-08-13 | 默克专利股份公司 | Anti-PD-L1 antibodies and uses thereof |
| CN103417964A (en) * | 2012-05-17 | 2013-12-04 | 江苏先声药物研究有限公司 | Application of anti-VEGF antibody |
| WO2013185052A1 (en) * | 2012-06-08 | 2013-12-12 | Aduro Biotech | Compostions and methods for cancer immunotherapy |
| WO2014189805A1 (en) * | 2013-05-18 | 2014-11-27 | Auro Biotech, Inc. | Compositions and methods for activating "stimulator of interferon gene"-dependent signalling |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN113546172A (en) * | 2020-04-24 | 2021-10-26 | 山东大学齐鲁医院 | Application of VEGF inhibitor in preparation of medicament for treating hypoxia-related diseases |
| CN117144004A (en) * | 2023-07-21 | 2023-12-01 | 中山大学附属第六医院 | Application of 14-3-3σ in colon cancer treatment |
| CN117144004B (en) * | 2023-07-21 | 2024-08-30 | 中山大学附属第六医院 | Use of 14-3-3 sigma in the treatment of colon cancer |
Also Published As
| Publication number | Publication date |
|---|---|
| WO2017045595A1 (en) | 2017-03-23 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| US10092592B2 (en) | Application of cyclic dinucleotide (cGAMP) in anti-tumor field | |
| CN106539757A (en) | Application of the ring dinucleotide cGAMP- liposomees in antitumor | |
| CN111420025B (en) | Application of rubiaceae cyclic peptide compound in preparation of medicine of cGAS-STING signal pathway activator | |
| CN106540255A (en) | Ring dinucleotide cGAMP combines application of the Avastin in antitumor | |
| CN108892700A (en) | A kind of new antitumoral compounds and its application in preparation of anti-tumor drugs | |
| AU2006257286B2 (en) | Uses of recombinant super-compound interferons | |
| Karp et al. | AIDS-related Kaposi's sarcoma: A template for the translation of molecular pathogenesis into targeted therapeutic approaches | |
| CN116212030A (en) | Antineoplastic pharmaceutical composition containing azvudine | |
| CN106692967A (en) | Application of cyclic dinucleotide cGAMP combined PD1 antibody (Nivolumab) in preparation of antitumor drugs | |
| CN106540253A (en) | The application of cGAMP and its derivant in anti-tumor vaccine is prepared | |
| CN108042526B (en) | Application of imperatorin in the preparation of drugs for inhibiting esophageal cancer tumors | |
| CN106928298B (en) | Structural composition, preparation method and application of cyclic dinucleotide cGAMP derivatives in anti-tumor | |
| CN102319260A (en) | The application of cisplatin combined itraconazole isomer in preparation treatment lung-cancer medicament | |
| CN116549455A (en) | Application of PLK4 inhibitor Centrinone in the preparation of medicines for treating echinococcosis | |
| CN113827603B (en) | Application of adefovir in preparing medicine for treating glioma | |
| CN111840541A (en) | Application of polyinosinic acid cytidylic acid combined with anti-CD47 antibody in tumor therapy | |
| CN113827604B (en) | Application of adefovir in preparing medicine for treating tumor or resisting tumor metastasis | |
| US10736873B2 (en) | Medical uses of N-(2-aminoethyl)-N-(4-benzyloxy)-3-methoxybenzyl)thiophene-2-formamide hydrochloride | |
| TR2022020067A2 (en) | USE OF SARS COV-2 VIRUS IN MELANOMA TREATMENT | |
| CN119326894A (en) | Use of GSDME inhibitors for manufacturing drugs for preventing and treating peripheral nerve damage during chemotherapy | |
| CN101642462B (en) | Tumor inhibitor NRN1SR42 | |
| CN100503825C (en) | Nucleic acid molecule RTN4BSR4 and its application in the preparation of anticancer drugs | |
| CN118976012A (en) | Use of a GSDMD inhibitor to prevent peripheral nerve damage during chemotherapy | |
| KR101658593B1 (en) | Composition for enhancing radiation sensitivity comprising PI4K isozyme inhibitor | |
| CN121154782A (en) | Application of small molecular compound DRP-104 in preparation of medicine for treating uveal melanoma |
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 | ||
| RJ01 | Rejection of invention patent application after publication |
Application publication date: 20170329 |
|
| RJ01 | Rejection of invention patent application after publication |