WO2023061515A1 - Nouvel analogue fgf pour traiter le cancer du foie et son utilisation - Google Patents

Nouvel analogue fgf pour traiter le cancer du foie et son utilisation Download PDF

Info

Publication number
WO2023061515A1
WO2023061515A1 PCT/CN2022/137532 CN2022137532W WO2023061515A1 WO 2023061515 A1 WO2023061515 A1 WO 2023061515A1 CN 2022137532 W CN2022137532 W CN 2022137532W WO 2023061515 A1 WO2023061515 A1 WO 2023061515A1
Authority
WO
WIPO (PCT)
Prior art keywords
fgf21
liver cancer
cancer
injection
tumor
Prior art date
Application number
PCT/CN2022/137532
Other languages
English (en)
Chinese (zh)
Inventor
朱升龙
陈永泉
王振
Original Assignee
江南大学
Priority date (The priority date 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 date listed.)
Filing date
Publication date
Application filed by 江南大学 filed Critical 江南大学
Publication of WO2023061515A1 publication Critical patent/WO2023061515A1/fr

Links

Images

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • C07K14/475—Growth factors; Growth regulators
    • C07K14/50—Fibroblast growth factor [FGF]
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/0012—Galenical forms characterised by the site of application
    • A61K9/0019—Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/0012—Galenical forms characterised by the site of application
    • A61K9/0053—Mouth and digestive tract, i.e. intraoral and peroral administration
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • A61P35/04—Antineoplastic agents specific for metastasis
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
    • C12Q1/00—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions
    • C12Q1/68—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving nucleic acids
    • C12Q1/6876—Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes
    • C12Q1/6883—Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for diseases caused by alterations of genetic material
    • C12Q1/6886—Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for diseases caused by alterations of genetic material for cancer
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
    • C12Q2600/00—Oligonucleotides characterized by their use
    • C12Q2600/136—Screening for pharmacological compounds
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
    • C12Q2600/00—Oligonucleotides characterized by their use
    • C12Q2600/158—Expression markers
    • Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
    • Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
    • Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
    • Y02A50/30—Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change

Definitions

  • the invention relates to a novel FGF analogue for treating liver cancer and its application, in particular to the application of a human FGF21 analogue in the preparation of drugs for treating liver cancer, and belongs to the field of medical technology.
  • Liver cancer is one of the common malignant tumors in my country, with a high incidence in the southeast coastal areas.
  • the median age of patients with liver cancer in my country is 40 to 50 years old, and it is more common in men than women. In recent years, its incidence has been increasing.
  • the annual mortality rate of liver cancer accounts for the second place in the death rate of tumors, and ranks the third place among malignant tumors of the digestive system, second only to gastric and esophageal cancer.
  • Hepatitis B, C, liver cirrhosis, hepatocyte necrosis accompanied by regeneration of liver cells are prone to malignant transformation.
  • liver cancer is mainly based on radical surgery, chemotherapy, radiotherapy, traditional Chinese medicine treatment and biological therapy as its auxiliary treatment means.
  • radical surgery Approximately two-thirds of patients diagnosed for the first time underwent radical surgery, and more than half of these patients developed recurrence or distant metastasis.
  • radical surgery cannot be performed, and comprehensive medical treatment is often used as the main treatment.
  • liver cancer still has a high recurrence rate after surgery.
  • the commonly used therapeutic drugs are usually broad-spectrum chemical drugs, which have more side effects. Therefore, it is an ideal goal of current research and development to develop a safe drug for the treatment of liver cancer that can inhibit tumor growth and recurrence and protect organs, and has no obvious side effects.
  • liver cancer In recent years, a large number of clinical investigations have shown that the occurrence and development of liver cancer are closely related to metabolic abnormalities.
  • metabolic pathways including glycolysis, tricarboxylic acid cycle, fatty acid metabolism, and glutamine metabolism, have undergone reprogramming changes in tumor cells.
  • Tumor cells can provide the necessary for proliferation through the coordination of various metabolic pathways.
  • metabolic abnormalities are not only the result of tumor occurrence and development, but may also be directly involved in the initiation process of tumors.
  • the present invention finds that human fibroblast growth factor 21, an important member involved in multiple links of the glucose and lipid metabolism network, can significantly inhibit the development and metastasis of liver cancer. Based on this, the present invention provides a new application of FGF21 analogues in the preparation of drugs for preventing, alleviating and/or treating liver cancer.
  • the present invention provides FGF21 analogues, and the amino acid sequence of the FGF21 protein analogues is any one of SEQ ID NO.1-3.
  • the present invention provides the gene encoding the FGF21 protein analogue.
  • the present invention provides vectors and/or microbial cells carrying the genes.
  • the microbial cells comprise E. coli or mammalian cells.
  • the mammalian cells comprise 293T cells or CHO cells.
  • the invention provides the application of the gene in screening drugs for treating liver cancer.
  • the FGF21 gene is used as a drug target.
  • nucleotide sequence of the FGF21 gene is shown in any one of SEQ ID NO.4-6.
  • the use is for screening small molecule activators of FGF21 protein.
  • the use is for screening agents that inhibit the expression of alpha-fetoprotein.
  • the present invention provides a medicament or a pharmaceutical composition, which contains the FGF21 analogue.
  • the drug or pharmaceutical composition further includes human acceptable modifications, pharmaceutical carriers and/or excipients.
  • the modification includes PEG modification and FC modification.
  • the pharmaceutical excipients include solvents, propellants, solubilizers, co-solvents, emulsifiers, colorants, binders, disintegrants, fillers, lubricants, wetting agents, osmotic pressure Regulators, stabilizers, glidants, flavoring agents, preservatives, suspending agents, coating materials, fragrances, anti-adhesives, integrating agents, penetration enhancers, pH regulators, buffers, plasticizers , Surfactants, foaming agents, defoamers, thickeners, inclusion agents, humectants, absorbents, diluents, flocculants and deflocculants, filter aids, release retardants.
  • the present invention provides the application of the FGF21 analog in the preparation of drugs or pharmaceutical compositions for preventing, alleviating and/or treating cancer.
  • the cancer includes but not limited to liver cancer, prostate cancer, breast cancer, esophageal cancer, colorectal adenocarcinoma, cervical cancer, endometrial cancer, ovarian cancer, pancreatic cancer, gallbladder cancer, clear cell renal cancer Carcinoma, melanoma, multiple myeloma.
  • the prevention, alleviation and/or treatment of liver cancer includes but not limited to (a)-(d):
  • the liver cancer factor is alpha-fetoprotein.
  • the effective dose of the FGF21 analog is 0.1-100 mg/kg.
  • the administration route of the drug or pharmaceutical composition includes intradermal injection, subcutaneous injection, intravenous injection, intramuscular injection, intraperitoneal injection, intravenous drip, arterial injection, intracavitary injection and/or oral administration.
  • the FGF21 fusion protein obtained in the present invention can be used in the treatment of liver cancer, and can significantly reduce the size of tumor lesions, so it can be used as an active ingredient of various dosage forms of drugs.
  • drugs similar to FGF21 are injected into the body by injection, which can effectively reduce the expression level of liver cancer factors, alleviate the occurrence and development of liver cancer, and inhibit the generation and metastasis of liver cancer, which is extremely important for the treatment of liver cancer. meaning.
  • Figure 1 is the effect of FGF21 on the growth rate of human liver cancer xenograft tumor; wherein, A is the change of tumor volume; B is the change of tumor mass;
  • Figure 2 is the effect of FGF21 on carbon tetrachloride-induced liver cancer in mice; wherein, A is the content of alpha-fetoprotein; B is liver cancer slices.
  • mice and C57BL/6 mice were purchased from Jiangsu Jicui Yaokang Biotechnology Co., Ltd. They were raised in the Animal Center of Wuxi Medical College, Jiangnan University, under alternating lighting every 12 hours, and the temperature was 20 ⁇ 2°C.
  • liver cancer cell line HepG2 was provided by the Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences;
  • DMEM and 0.05% Trypsin were purchased from Boster Company; fetal bovine serum was purchased from Sijiqing Company. Other medicines were domestic analytically pure.
  • the hepatocarcinoma cell lines were grown adherently in DMEM medium containing 10% fetal bovine serum, cultured in a humidified incubator with 5% CO 2 at 37°C, and passaged once every other day.
  • mice were injected with 1 mg/kg, 5 mg/kg and 10 mg/kg of FGF21 protein, and the corresponding human doses were 0.1 mg/kg, 0.5 mg/kg and 1 mg/kg.
  • Example 1 Construction, expression and purification of recombinant proteins
  • the fusion FGF21 protein (amino acid sequence is shown in SEQ ID NO.1 ⁇ 3), according to the codon preference of Escherichia coli, the corresponding nucleotide sequence is designed, and its nucleotide sequence is respectively as FGF21-1 in the sequence list ( Nucleotide sequence as shown in SEQ ID NO.4), FGF21-2 (nucleotide sequence as shown in SEQ ID NO.5), FGF21-3 (nucleotide sequence as shown in SEQ ID NO.6) Show.
  • the three genes were sent to the company for synthesis, and the three genes were connected between the NdeI and BamHI restriction sites of the pET30a(+) vector, and the enzyme-ligated products were transformed into E.
  • coli DH5 ⁇ respectively.
  • the positive clones were picked and identified by restriction enzyme digestion, and three recombinant plasmids pET30a-FGF21-1, pET30a-FGF21-2 and pET30a-FGF21-3 were respectively constructed.
  • the recombinant plasmids containing the correct sequence obtained in step 1 were respectively transformed into competent cells of the expression strain Rosseta (DE3). Transformed single colonies were inoculated into 20 mL of LB medium containing Kan (50 ⁇ g/mL), cultured at 37 °C for 8 h, and inoculated into another 20 mL of LB medium containing Kan (50 ⁇ g/mL) at a volume ratio of 1:100 medium, cultured at 37°C, when A600 was around 0.35, IPTG was added to a final concentration of 0.25mmol/L for induction, the induction temperature was 30°C, and the cells were harvested after 5h, and Lysis buffer (20mmol/LTris, 150mmol/LNaCl, pH 8.0) to resuspend the bacteria, break the bacteria and centrifuge, take the supernatant and precipitate respectively for 12wt% SDS-PAGE electrophoresis analysis. And the bacteria were crushed, and the protein was purified to
  • the FGF21 protein whose amino acid sequence is shown in SEQ ID NO.1 is prepared according to the method of Example 1.
  • Human liver cancer cell HepG2 cells were inoculated under the skin of 6-week-old male nude mice according to 1 ⁇ 106 cells/only, and were randomly divided into four groups when the tumor grew to 200mm3 .
  • 1Normal saline group injected with an equal volume of normal saline;2 Low-dose group: inject 1 mg/kg FGF21; 3 medium-dose group: inject 5 mg/kg FGF21; 4 high-dose group: inject 10 mg/kg FGF21. Inject once a day for 15 consecutive days. Tumor volume was monitored daily, mice were sacrificed three weeks later, and tumor weight was measured. The results showed that three different doses of FGF21 could inhibit the transplanted tumor volume and final tumor weight in a dose-dependent manner.
  • FGF21 protein 10mg/kg
  • high-dose FGF21 protein 10mg/kg
  • it can completely inhibit tumor growth, keep the tumor at 250mm 3 , and the final volume is only 20% of that of the control group, and the tumor mass also decreased by about 70%.
  • 5mg/kg can reduce tumor mass by 45% and 53% respectively (as shown in Figure 1).
  • mice On the 14th day after birth, the mice were intraperitoneally injected with 2 mg/kg of diethylnitrosamine (DEN), and 2 weeks after the administration, 5 mL/kg of 20% carbon tetrachloride (CCI4) was injected intraperitoneally, 2 times a week. A total of 16 weeks. After 16 weeks of induction, they were divided into normal saline group and FGF21 injection group. The injection dose of FGF21 injection group was 10 mg/kg, and the normal saline group was injected with the same amount of normal saline once a day for 6 consecutive weeks.
  • DEN diethylnitrosamine
  • CCI4 20% carbon tetrachloride
  • Figure 2A shows the alpha-fetoprotein levels of the FGF21 treatment group and the control group, and the alpha-fetoprotein content is a characteristic marker of liver cancer, indicating that the amino acid sequence of the FGF21 protein shown in SEQ ID NO.1 significantly After reducing the content of liver cancer markers
  • Figure 2B shows the pathological section of the tumor, further illustrating the inhibitory effect of FGF21 protein on liver cancer.
  • the inventor also tried to study the effect of the fusion protein of FGF21 protein shown in SEQ ID NO.
  • the FGF21 protein shown in SEQ ID NO.1 had comparable effects.

Landscapes

  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Organic Chemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • Animal Behavior & Ethology (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Genetics & Genomics (AREA)
  • Zoology (AREA)
  • Biochemistry (AREA)
  • Wood Science & Technology (AREA)
  • Pathology (AREA)
  • Epidemiology (AREA)
  • Engineering & Computer Science (AREA)
  • Biophysics (AREA)
  • Analytical Chemistry (AREA)
  • Oncology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Molecular Biology (AREA)
  • Immunology (AREA)
  • Hospice & Palliative Care (AREA)
  • Toxicology (AREA)
  • Physics & Mathematics (AREA)
  • Gastroenterology & Hepatology (AREA)
  • Biotechnology (AREA)
  • Microbiology (AREA)
  • Dermatology (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • General Engineering & Computer Science (AREA)
  • Nutrition Science (AREA)
  • Physiology (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Peptides Or Proteins (AREA)

Abstract

L'invention concerne un nouvel analogue FGF pour traiter le cancer du foie et son utilisation, se rapportant au domaine technique de la médecine. La protéine FGF21 fournie par la présente invention est une protéine sécrétée composée de 428 acides aminés. La présente invention montre par des expériences cytologiques et des expériences animales que le nouvel analogue FGF21 préparé peut inhiber la prolifération, l'invasion et la migration de lignées cellulaires du cancer du foie, et peut réduire de manière significative la taille de lésions tumorales dans un modèle de souris. Un médicament thérapeutique pour le cancer du foie préparé à l'aide de FGF21 en tant que substance active a les effets d'une bonne innocuité et d'une longue durée d'effet de médicament, le médicament thérapeutique préparé protège les organes contre les lésions et améliore les troubles du métabolisme lipidique.
PCT/CN2022/137532 2021-10-14 2022-12-08 Nouvel analogue fgf pour traiter le cancer du foie et son utilisation WO2023061515A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
CN202111199341.2A CN113956344A (zh) 2021-10-14 2021-10-14 一种新型治疗肝癌的fgf类似物及其应用
CN202111199341.2 2021-10-14

Publications (1)

Publication Number Publication Date
WO2023061515A1 true WO2023061515A1 (fr) 2023-04-20

Family

ID=79464584

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/CN2022/137532 WO2023061515A1 (fr) 2021-10-14 2022-12-08 Nouvel analogue fgf pour traiter le cancer du foie et son utilisation

Country Status (2)

Country Link
CN (1) CN113956344A (fr)
WO (1) WO2023061515A1 (fr)

Families Citing this family (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN113956344A (zh) * 2021-10-14 2022-01-21 江南大学 一种新型治疗肝癌的fgf类似物及其应用

Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
AU2012268895A1 (en) * 2007-03-30 2013-01-24 Ambrx, Inc. Modified FGF-21 polypeptides and their uses
CN110913886A (zh) * 2017-05-24 2020-03-24 巴塞罗那自治大学 包含成纤维细胞生长因子21(fgf21)编码序列的病毒表达构建体
CN113265007A (zh) * 2021-06-10 2021-08-17 江南大学 一种治疗代谢疾病的融合蛋白及其制备方法和应用
CN113956344A (zh) * 2021-10-14 2022-01-21 江南大学 一种新型治疗肝癌的fgf类似物及其应用

Family Cites Families (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2010139741A1 (fr) * 2009-06-04 2010-12-09 Novartis Ag Fgf-21 pour traiter le cancer
KR102086788B1 (ko) * 2014-07-02 2020-03-09 드래곤 빅토리 디벨롭먼트 리미티드 간암의 비-침습성 진단을 위한 특이적 바이오마커 세트
BR112019009581A2 (pt) * 2016-11-10 2019-10-08 Yuhan Corp composição farmacêutica para evitar ou tratar hepatite, fibrose hepática, e cirrose hepática que compreende proteínas de fusão
CN115109166A (zh) * 2017-11-24 2022-09-27 浙江道尔生物科技有限公司 一种治疗代谢疾病的多结构域活性蛋白
US11679143B2 (en) * 2018-02-08 2023-06-20 Sunshine Lake Pharma Co., Ltd. FGF21 variant, fusion protein and application thereof
US20220153864A1 (en) * 2019-02-26 2022-05-19 Pieris Pharmaceuticals Gmbh Novel Fusion Proteins Specific for CD137 and GPC3
CN111420030B (zh) * 2020-05-12 2021-01-29 江南大学 Fgf21在制备用于治疗结直肠癌药物中的应用

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
AU2012268895A1 (en) * 2007-03-30 2013-01-24 Ambrx, Inc. Modified FGF-21 polypeptides and their uses
CN110913886A (zh) * 2017-05-24 2020-03-24 巴塞罗那自治大学 包含成纤维细胞生长因子21(fgf21)编码序列的病毒表达构建体
CN113265007A (zh) * 2021-06-10 2021-08-17 江南大学 一种治疗代谢疾病的融合蛋白及其制备方法和应用
CN113956344A (zh) * 2021-10-14 2022-01-21 江南大学 一种新型治疗肝癌的fgf类似物及其应用

Also Published As

Publication number Publication date
CN113956344A (zh) 2022-01-21

Similar Documents

Publication Publication Date Title
CN111420030B (zh) Fgf21在制备用于治疗结直肠癌药物中的应用
WO2023061515A1 (fr) Nouvel analogue fgf pour traiter le cancer du foie et son utilisation
CN111714629A (zh) 一种药物组合在制备对pd-1抗体免疫治疗不敏感肿瘤的治疗药物中的应用
WO2022188444A1 (fr) Analogue fgf de type nouveau contre des troubles du métabolisme et son utilisation
JP3725473B2 (ja) 新規血管形成阻害剤
JP2688180B2 (ja) スーパーオキシドジスムターゼアナログの産生方法
CN113755495A (zh) 基因编辑技术在治疗癌症中的应用
CN1526012A (zh) 一种高效表达抗癌基因的肿瘤细胞内特异性增殖的病毒及其用途
JPH0723309B2 (ja) 癌治療薬剤
US7589062B2 (en) Two synthetic peptides for treatment and prevention of cancers
JP3319597B2 (ja) 細胞培養及び治療に有用なβ―アレチン
EP3354268B1 (fr) 8-oxo-dgtp pur la prévention et le traitement de tumeur et ses applications
JP2006232761A (ja) 制癌剤
JP7229519B2 (ja) 血管新生促進剤
US9321820B2 (en) Compositions and methods for treating bladder cancer
EP0806477B1 (fr) Utilisation, pour la fabrication d'un medicament, d'un adn recombinant comprenant un adn codant pour la proteine isoforme sm1 de la chaine lourde de la myosine de type muscle lisse
CN113912699A (zh) 一种新型治疗乳腺癌的fgf类似物及其应用
WO2010095422A1 (fr) Agent thérapeutique pour tumeur maligne
US9371523B2 (en) Cell migration regulator
WO2004091650A1 (fr) Utilisation de la troponine i cardiaque pour preparer des medicaments antitumoraux
CN114316018A (zh) 一种fgf21蛋白类似物及其应用
KR102473666B1 (ko) Hoxa9 단백질 c-말단부위의 hadp 펩티드를 포함하는 폐암의 예방, 개선 또는 치료용 약학적 조성물
CN111494604B (zh) 蓝藻抗病毒蛋白n在制备抗炎药物中的应用
CN113827731B (zh) Vegf抑制剂和pd-1单克隆抗体在制备用于抑制卵巢癌的药盒中的用途
KR100733889B1 (ko) 187 트레오닌 변이 ｐ27 단백질을 코딩하는 유전자를포함하는 재조합 아데노바이러스 및 그 제조방법

Legal Events

Date Code Title Description
121 Ep: the epo has been informed by wipo that ep was designated in this application

Ref document number: 22880451

Country of ref document: EP

Kind code of ref document: A1