WO2024035023A1 - Nouveau variant de bax et composition pharmaceutique le comprenant - Google Patents
Nouveau variant de bax et composition pharmaceutique le comprenant Download PDFInfo
- Publication number
- WO2024035023A1 WO2024035023A1 PCT/KR2023/011541 KR2023011541W WO2024035023A1 WO 2024035023 A1 WO2024035023 A1 WO 2024035023A1 KR 2023011541 W KR2023011541 W KR 2023011541W WO 2024035023 A1 WO2024035023 A1 WO 2024035023A1
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- bax
- seq
- bax protein
- lysine
- amino acid
- Prior art date
Links
- 239000008194 pharmaceutical composition Substances 0.000 title claims abstract description 11
- 108700000707 bcl-2-Associated X Proteins 0.000 claims abstract description 169
- 102000055102 bcl-2-Associated X Human genes 0.000 claims abstract description 169
- 235000018977 lysine Nutrition 0.000 claims abstract description 56
- 125000003588 lysine group Chemical group [H]N([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])(N([H])[H])C(*)=O 0.000 claims abstract description 48
- 239000004472 Lysine Substances 0.000 claims abstract description 39
- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 claims abstract description 39
- 239000004475 Arginine Substances 0.000 claims abstract description 29
- ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 claims abstract description 29
- 125000000637 arginyl group Chemical group N[C@@H](CCCNC(N)=N)C(=O)* 0.000 claims abstract description 23
- 238000000034 method Methods 0.000 claims abstract description 22
- 230000001965 increasing effect Effects 0.000 claims abstract description 11
- 239000000126 substance Substances 0.000 claims abstract description 10
- 238000012216 screening Methods 0.000 claims abstract description 9
- 230000001093 anti-cancer Effects 0.000 claims abstract description 7
- 125000003275 alpha amino acid group Chemical group 0.000 claims description 36
- 206010028980 Neoplasm Diseases 0.000 claims description 15
- 201000011510 cancer Diseases 0.000 claims description 13
- 230000030833 cell death Effects 0.000 claims description 7
- 239000007787 solid Substances 0.000 claims description 7
- 101000607909 Homo sapiens Ubiquitin carboxyl-terminal hydrolase 1 Proteins 0.000 claims description 6
- 101000760210 Homo sapiens Ubiquitin carboxyl-terminal hydrolase 12 Proteins 0.000 claims description 6
- 101000759935 Homo sapiens Ubiquitin carboxyl-terminal hydrolase 49 Proteins 0.000 claims description 6
- 101150020913 USP7 gene Proteins 0.000 claims description 6
- 102100024662 Ubiquitin carboxyl-terminal hydrolase 12 Human genes 0.000 claims description 6
- 102100025044 Ubiquitin carboxyl-terminal hydrolase 49 Human genes 0.000 claims description 6
- 102100021013 Ubiquitin carboxyl-terminal hydrolase 7 Human genes 0.000 claims description 6
- 108700011958 Ubiquitin-Specific Peptidase 7 Proteins 0.000 claims description 6
- 229940126752 Ubiquitin-specific protease 7 inhibitor Drugs 0.000 claims description 6
- 239000004480 active ingredient Substances 0.000 claims description 6
- 230000009504 deubiquitination Effects 0.000 claims description 4
- 206010006187 Breast cancer Diseases 0.000 claims description 3
- 208000026310 Breast neoplasm Diseases 0.000 claims description 3
- 206010009944 Colon cancer Diseases 0.000 claims description 3
- 206010058467 Lung neoplasm malignant Diseases 0.000 claims description 3
- 206010033128 Ovarian cancer Diseases 0.000 claims description 3
- 206010061535 Ovarian neoplasm Diseases 0.000 claims description 3
- 208000005718 Stomach Neoplasms Diseases 0.000 claims description 3
- 208000029742 colonic neoplasm Diseases 0.000 claims description 3
- 238000012258 culturing Methods 0.000 claims description 3
- 206010017758 gastric cancer Diseases 0.000 claims description 3
- 201000007270 liver cancer Diseases 0.000 claims description 3
- 208000014018 liver neoplasm Diseases 0.000 claims description 3
- 201000005202 lung cancer Diseases 0.000 claims description 3
- 208000020816 lung neoplasm Diseases 0.000 claims description 3
- 239000000463 material Substances 0.000 claims description 3
- 201000011549 stomach cancer Diseases 0.000 claims description 3
- 230000034512 ubiquitination Effects 0.000 abstract description 16
- 238000010798 ubiquitination Methods 0.000 abstract description 15
- 230000007246 mechanism Effects 0.000 abstract description 2
- 230000017854 proteolysis Effects 0.000 abstract description 2
- 210000004027 cell Anatomy 0.000 description 31
- 108090000623 proteins and genes Proteins 0.000 description 25
- 102000004169 proteins and genes Human genes 0.000 description 19
- 235000018102 proteins Nutrition 0.000 description 17
- 230000006907 apoptotic process Effects 0.000 description 15
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 8
- YPHMISFOHDHNIV-FSZOTQKASA-N cycloheximide Chemical compound C1[C@@H](C)C[C@H](C)C(=O)[C@@H]1[C@H](O)CC1CC(=O)NC(=O)C1 YPHMISFOHDHNIV-FSZOTQKASA-N 0.000 description 8
- 238000001262 western blot Methods 0.000 description 8
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 6
- 239000012528 membrane Substances 0.000 description 6
- UCSJYZPVAKXKNQ-HZYVHMACSA-N streptomycin Chemical compound CN[C@H]1[C@H](O)[C@@H](O)[C@H](CO)O[C@H]1O[C@@H]1[C@](C=O)(O)[C@H](C)O[C@H]1O[C@@H]1[C@@H](NC(N)=N)[C@H](O)[C@@H](NC(N)=N)[C@H](O)[C@H]1O UCSJYZPVAKXKNQ-HZYVHMACSA-N 0.000 description 6
- FWMNVWWHGCHHJJ-SKKKGAJSSA-N 4-amino-1-[(2r)-6-amino-2-[[(2r)-2-[[(2r)-2-[[(2r)-2-amino-3-phenylpropanoyl]amino]-3-phenylpropanoyl]amino]-4-methylpentanoyl]amino]hexanoyl]piperidine-4-carboxylic acid Chemical compound C([C@H](C(=O)N[C@H](CC(C)C)C(=O)N[C@H](CCCCN)C(=O)N1CCC(N)(CC1)C(O)=O)NC(=O)[C@H](N)CC=1C=CC=CC=1)C1=CC=CC=C1 FWMNVWWHGCHHJJ-SKKKGAJSSA-N 0.000 description 5
- 229940123573 Protein synthesis inhibitor Drugs 0.000 description 5
- 239000000007 protein synthesis inhibitor Substances 0.000 description 5
- 238000001890 transfection Methods 0.000 description 5
- 239000012091 fetal bovine serum Substances 0.000 description 4
- 238000001114 immunoprecipitation Methods 0.000 description 4
- 230000002438 mitochondrial effect Effects 0.000 description 4
- 238000003752 polymerase chain reaction Methods 0.000 description 4
- 239000011780 sodium chloride Substances 0.000 description 4
- 239000013598 vector Substances 0.000 description 4
- QKNYBSVHEMOAJP-UHFFFAOYSA-N 2-amino-2-(hydroxymethyl)propane-1,3-diol;hydron;chloride Chemical compound Cl.OCC(N)(CO)CO QKNYBSVHEMOAJP-UHFFFAOYSA-N 0.000 description 3
- 229930182555 Penicillin Natural products 0.000 description 3
- JGSARLDLIJGVTE-MBNYWOFBSA-N Penicillin G Chemical compound N([C@H]1[C@H]2SC([C@@H](N2C1=O)C(O)=O)(C)C)C(=O)CC1=CC=CC=C1 JGSARLDLIJGVTE-MBNYWOFBSA-N 0.000 description 3
- 239000006146 Roswell Park Memorial Institute medium Substances 0.000 description 3
- 230000004913 activation Effects 0.000 description 3
- 125000000539 amino acid group Chemical group 0.000 description 3
- 239000002246 antineoplastic agent Substances 0.000 description 3
- 238000006243 chemical reaction Methods 0.000 description 3
- 239000012139 lysis buffer Substances 0.000 description 3
- 229940049954 penicillin Drugs 0.000 description 3
- 229960005322 streptomycin Drugs 0.000 description 3
- 102000010565 Apoptosis Regulatory Proteins Human genes 0.000 description 2
- 108010063104 Apoptosis Regulatory Proteins Proteins 0.000 description 2
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 2
- 102000011727 Caspases Human genes 0.000 description 2
- 108010076667 Caspases Proteins 0.000 description 2
- 102000018832 Cytochromes Human genes 0.000 description 2
- 108010052832 Cytochromes Proteins 0.000 description 2
- 239000006144 Dulbecco’s modified Eagle's medium Substances 0.000 description 2
- KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 2
- 102000004190 Enzymes Human genes 0.000 description 2
- 108090000790 Enzymes Proteins 0.000 description 2
- 101100202339 Mus musculus Slc6a13 gene Proteins 0.000 description 2
- 229920002873 Polyethylenimine Polymers 0.000 description 2
- 101100202330 Rattus norvegicus Slc6a11 gene Proteins 0.000 description 2
- 102000044159 Ubiquitin Human genes 0.000 description 2
- 108090000848 Ubiquitin Proteins 0.000 description 2
- 235000001014 amino acid Nutrition 0.000 description 2
- 238000004458 analytical method Methods 0.000 description 2
- 230000001640 apoptogenic effect Effects 0.000 description 2
- 101150024147 bax gene Proteins 0.000 description 2
- 239000003153 chemical reaction reagent Substances 0.000 description 2
- 239000002299 complementary DNA Substances 0.000 description 2
- 238000012790 confirmation Methods 0.000 description 2
- 210000000805 cytoplasm Anatomy 0.000 description 2
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 2
- 239000003937 drug carrier Substances 0.000 description 2
- 238000010195 expression analysis Methods 0.000 description 2
- 239000007924 injection Substances 0.000 description 2
- 238000002347 injection Methods 0.000 description 2
- 230000003993 interaction Effects 0.000 description 2
- 210000003470 mitochondria Anatomy 0.000 description 2
- 239000000203 mixture Substances 0.000 description 2
- YBYRMVIVWMBXKQ-UHFFFAOYSA-N phenylmethanesulfonyl fluoride Chemical compound FS(=O)(=O)CC1=CC=CC=C1 YBYRMVIVWMBXKQ-UHFFFAOYSA-N 0.000 description 2
- 230000035882 stress Effects 0.000 description 2
- 238000006467 substitution reaction Methods 0.000 description 2
- 239000006228 supernatant Substances 0.000 description 2
- 230000008685 targeting Effects 0.000 description 2
- 238000012360 testing method Methods 0.000 description 2
- GPRLSGONYQIRFK-MNYXATJNSA-N triton Chemical compound [3H+] GPRLSGONYQIRFK-MNYXATJNSA-N 0.000 description 2
- QAPSNMNOIOSXSQ-YNEHKIRRSA-N 1-[(2r,4s,5r)-4-[tert-butyl(dimethyl)silyl]oxy-5-(hydroxymethyl)oxolan-2-yl]-5-methylpyrimidine-2,4-dione Chemical compound O=C1NC(=O)C(C)=CN1[C@@H]1O[C@H](CO)[C@@H](O[Si](C)(C)C(C)(C)C)C1 QAPSNMNOIOSXSQ-YNEHKIRRSA-N 0.000 description 1
- BDLWRIAFNYVGTC-UHFFFAOYSA-N 2-[bis(2-chloroethyl)amino]ethyl 3-(acridin-9-ylamino)propanoate Chemical compound C1=CC=C2C(NCCC(=O)OCCN(CCCl)CCCl)=C(C=CC=C3)C3=NC2=C1 BDLWRIAFNYVGTC-UHFFFAOYSA-N 0.000 description 1
- 229920000936 Agarose Polymers 0.000 description 1
- 102000051485 Bcl-2 family Human genes 0.000 description 1
- 108700038897 Bcl-2 family Proteins 0.000 description 1
- 108090000397 Caspase 3 Proteins 0.000 description 1
- 102000004018 Caspase 6 Human genes 0.000 description 1
- 108090000425 Caspase 6 Proteins 0.000 description 1
- 108090000567 Caspase 7 Proteins 0.000 description 1
- 102100029855 Caspase-3 Human genes 0.000 description 1
- 102100038902 Caspase-7 Human genes 0.000 description 1
- 102000004039 Caspase-9 Human genes 0.000 description 1
- 108090000566 Caspase-9 Proteins 0.000 description 1
- 108020004414 DNA Proteins 0.000 description 1
- 231100000277 DNA damage Toxicity 0.000 description 1
- 102000009058 Death Domain Receptors Human genes 0.000 description 1
- 108010049207 Death Domain Receptors Proteins 0.000 description 1
- 108010093668 Deubiquitinating Enzymes Proteins 0.000 description 1
- 102000001477 Deubiquitinating Enzymes Human genes 0.000 description 1
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Natural products NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 1
- 239000004471 Glycine Substances 0.000 description 1
- 206010021143 Hypoxia Diseases 0.000 description 1
- 206010064912 Malignant transformation Diseases 0.000 description 1
- 206010027476 Metastases Diseases 0.000 description 1
- 206010061309 Neoplasm progression Diseases 0.000 description 1
- 229920001213 Polysorbate 20 Polymers 0.000 description 1
- 206010060862 Prostate cancer Diseases 0.000 description 1
- 208000000236 Prostatic Neoplasms Diseases 0.000 description 1
- 102000051619 SUMO-1 Human genes 0.000 description 1
- 108700038981 SUMO-1 Proteins 0.000 description 1
- 102100039865 Ubiquitin carboxyl-terminal hydrolase 1 Human genes 0.000 description 1
- 150000001413 amino acids Chemical class 0.000 description 1
- 238000003782 apoptosis assay Methods 0.000 description 1
- 230000005775 apoptotic pathway Effects 0.000 description 1
- 238000013459 approach Methods 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 239000003125 aqueous solvent Substances 0.000 description 1
- 239000011324 bead Substances 0.000 description 1
- 238000003766 bioinformatics method Methods 0.000 description 1
- 230000000903 blocking effect Effects 0.000 description 1
- 229940098773 bovine serum albumin Drugs 0.000 description 1
- 230000015556 catabolic process Effects 0.000 description 1
- 238000010367 cloning Methods 0.000 description 1
- 238000010835 comparative analysis Methods 0.000 description 1
- 230000006378 damage Effects 0.000 description 1
- 230000007423 decrease Effects 0.000 description 1
- 238000006731 degradation reaction Methods 0.000 description 1
- 238000010217 densitometric analysis Methods 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 239000013604 expression vector Substances 0.000 description 1
- 230000006624 extrinsic pathway Effects 0.000 description 1
- 230000006832 extrinsic signaling Effects 0.000 description 1
- 125000003630 glycyl group Chemical group [H]N([H])C([H])([H])C(*)=O 0.000 description 1
- 239000001963 growth medium Substances 0.000 description 1
- 230000036541 health Effects 0.000 description 1
- 230000007954 hypoxia Effects 0.000 description 1
- 230000001939 inductive effect Effects 0.000 description 1
- 239000003999 initiator Substances 0.000 description 1
- 230000034727 intrinsic apoptotic signaling pathway Effects 0.000 description 1
- 230000006623 intrinsic pathway Effects 0.000 description 1
- 230000006831 intrinsic signaling Effects 0.000 description 1
- 239000007951 isotonicity adjuster Substances 0.000 description 1
- 239000012160 loading buffer Substances 0.000 description 1
- 230000036212 malign transformation Effects 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 239000002609 medium Substances 0.000 description 1
- 230000009401 metastasis Effects 0.000 description 1
- 230000004987 nonapoptotic effect Effects 0.000 description 1
- 238000006384 oligomerization reaction Methods 0.000 description 1
- 230000008789 oxidative DNA damage Effects 0.000 description 1
- 230000036542 oxidative stress Effects 0.000 description 1
- 230000037361 pathway Effects 0.000 description 1
- 230000035699 permeability Effects 0.000 description 1
- 239000002504 physiological saline solution Substances 0.000 description 1
- 239000000256 polyoxyethylene sorbitan monolaurate Substances 0.000 description 1
- 235000010486 polyoxyethylene sorbitan monolaurate Nutrition 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 230000005522 programmed cell death Effects 0.000 description 1
- 230000001737 promoting effect Effects 0.000 description 1
- 238000007634 remodeling Methods 0.000 description 1
- 230000003252 repetitive effect Effects 0.000 description 1
- 235000020183 skimmed milk Nutrition 0.000 description 1
- 238000002415 sodium dodecyl sulfate polyacrylamide gel electrophoresis Methods 0.000 description 1
- 239000000243 solution Substances 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 238000007619 statistical method Methods 0.000 description 1
- 238000012916 structural analysis Methods 0.000 description 1
- 238000010998 test method Methods 0.000 description 1
- 230000005945 translocation Effects 0.000 description 1
- 230000005751 tumor progression Effects 0.000 description 1
- 238000011144 upstream manufacturing Methods 0.000 description 1
- 239000011534 wash buffer Substances 0.000 description 1
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
- C07K14/46—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates
- C07K14/47—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates from mammals
- C07K14/4701—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates from mammals not used
- C07K14/4747—Apoptosis related proteins
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- 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
- C07K14/46—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates
- C07K14/47—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates from mammals
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
- G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
- G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
- G01N33/5005—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving human or animal cells
- G01N33/5008—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving human or animal cells for testing or evaluating the effect of chemical or biological compounds, e.g. drugs, cosmetics
- G01N33/5011—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving human or animal cells for testing or evaluating the effect of chemical or biological compounds, e.g. drugs, cosmetics for testing antineoplastic activity
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Engineering & Computer Science (AREA)
- Medicinal Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Immunology (AREA)
- Molecular Biology (AREA)
- Organic Chemistry (AREA)
- Biomedical Technology (AREA)
- Urology & Nephrology (AREA)
- Hematology (AREA)
- Biochemistry (AREA)
- Public Health (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Toxicology (AREA)
- Pharmacology & Pharmacy (AREA)
- Veterinary Medicine (AREA)
- Animal Behavior & Ethology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Biotechnology (AREA)
- Gastroenterology & Hepatology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Genetics & Genomics (AREA)
- Pathology (AREA)
- Biophysics (AREA)
- Cell Biology (AREA)
- General Physics & Mathematics (AREA)
- Microbiology (AREA)
- Zoology (AREA)
- Food Science & Technology (AREA)
- Physics & Mathematics (AREA)
- Analytical Chemistry (AREA)
- Epidemiology (AREA)
- Tropical Medicine & Parasitology (AREA)
- Peptides Or Proteins (AREA)
Abstract
La présente invention concerne : un variant de protéine Bax dont la lysine en position 128, la lysine en position 190 ou les lysines en positions 128 et 190 dans une protéine Bax sont substituées par l'arginine ; un procédé permettant d'augmenter la demi-vie d'une protéine Bax, le procédé comprenant la substitution de la lysine en position 128, de la lysine en position 190, ou des lysines aux positions 128 et 190 dans la protéine Bax avec l'arginine ; une composition pharmaceutique comprenant le variant de protéine Bax ; et un procédé de criblage d'une substance anticancéreuse. Le variant de protéine Bax selon la présente invention peut inhiber un mécanisme de dégradation de protéine par ubiquitination et présente une demi-vie plus longue que le Bax de type sauvage.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| KR1020220098471A KR20240020743A (ko) | 2022-08-08 | 2022-08-08 | 신규의 Bax 변이체 및 이를 포함한 약학 조성물 |
| KR10-2022-0098471 | 2022-08-08 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| WO2024035023A1 true WO2024035023A1 (fr) | 2024-02-15 |
Family
ID=89852156
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| PCT/KR2023/011541 WO2024035023A1 (fr) | 2022-08-08 | 2023-08-07 | Nouveau variant de bax et composition pharmaceutique le comprenant |
Country Status (2)
| Country | Link |
|---|---|
| KR (1) | KR20240020743A (fr) |
| WO (1) | WO2024035023A1 (fr) |
Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5691179A (en) * | 1993-08-26 | 1997-11-25 | Washington University | Cell death regulators |
| US5702897A (en) * | 1994-04-13 | 1997-12-30 | The Burnham Institute | Interaction of proteins involved in a cell death pathway |
| US20020052316A1 (en) * | 1998-10-05 | 2002-05-02 | Shore Gordon C. | Bax-mediated apoptosis modulating reagents and methods |
| KR20190016263A (ko) * | 2017-08-08 | 2019-02-18 | 차의과학대학교 산학협력단 | 효모 이중 혼성 스크리닝을 위한 벡터 라이브러리 및 이를 이용한 표적 단백질에 결합하는 탈유비퀴틴화 효소의 동정방법 |
-
2022
- 2022-08-08 KR KR1020220098471A patent/KR20240020743A/ko unknown
-
2023
- 2023-08-07 WO PCT/KR2023/011541 patent/WO2024035023A1/fr unknown
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5691179A (en) * | 1993-08-26 | 1997-11-25 | Washington University | Cell death regulators |
| US5702897A (en) * | 1994-04-13 | 1997-12-30 | The Burnham Institute | Interaction of proteins involved in a cell death pathway |
| US20020052316A1 (en) * | 1998-10-05 | 2002-05-02 | Shore Gordon C. | Bax-mediated apoptosis modulating reagents and methods |
| KR20190016263A (ko) * | 2017-08-08 | 2019-02-18 | 차의과학대학교 산학협력단 | 효모 이중 혼성 스크리닝을 위한 벡터 라이브러리 및 이를 이용한 표적 단백질에 결합하는 탈유비퀴틴화 효소의 동정방법 |
Non-Patent Citations (1)
| Title |
|---|
| DATABASE Protein 19 March 2015 (2015-03-19), ANONYMOUS : "BAX, partial [synthetic construct]", XP093138235, retrieved from NCBI Database accession no. AIC48347.1 * |
Also Published As
| Publication number | Publication date |
|---|---|
| KR20240020743A (ko) | 2024-02-16 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| Collette et al. | Physical and Functional Interaction of Nef with Lck: HIV-1 Nef-INDUCED T-CELL SIGNALING DEFECTS (∗) | |
| RU2577971C2 (ru) | Система для увеличения экспрессии генов и вектор, содержащий указанную систему | |
| Runnegar et al. | In vivo and in vitro binding of microcystin to protein phosphatase 1 and 2A | |
| Yang et al. | Phosphorylation of Vif and Its Role in HIV-1 Replication (∗) | |
| Sawai et al. | A Conserved Domain and Membrane Targeting of Nef from HIV and SIV Are Required for Association with a Cellular Serine Kinase Activity (∗) | |
| DeTomaso et al. | Expression, targeting, and assembly of functional Na, K-ATPase polypeptides in baculovirus-infected insect cells. | |
| Hayashi et al. | Accumulation of mtDNA with a mutation at position 3271 in tRNALeu (UUR) gene introduced from a MELAS patient to HeLa cells lacking mtDNA results in progressive inhibition of mitochondrial respiratory function | |
| JP2005139121A (ja) | ｐ３８／ＪＴＶ−１を有効成分とする癌治療用薬学的組成物及び癌治療用薬学的組成物のスクリーニング方法 | |
| CA2263744A1 (fr) | Procede permettant d'identifier des genes codant des proteines possedant une activite favorisant la proliferation cellulaire | |
| EA004309B1 (ru) | Модуляторы связанного с рецептором tnf фактора (traf), их получение и применение | |
| JP4742345B2 (ja) | カルシウムチャネルを遮断するグラモストラ・スパチュラタ由来のポリペプチドおよびその遺伝子 | |
| WO2012064146A9 (fr) | Composition anticancéreuse contenant gkn 1 | |
| US5717058A (en) | Peptide inhibitors of tax-dependent transcription | |
| Kanno et al. | Expression of Kaposi's sarcoma-associated herpesvirus-encoded K10/10.1 protein in tissues and its interaction with poly (A)-binding protein | |
| WO2024035023A1 (fr) | Nouveau variant de bax et composition pharmaceutique le comprenant | |
| Chevalier et al. | Presence of a functional but dispensable nuclear export signal in the HTLV-2 Tax protein | |
| US7700754B1 (en) | Polypeptide for unstabilizing protein in cells under aerobic conditions and DNA encoding the same | |
| Collombet et al. | Eukaryotic DING proteins are endogenous: an immunohistological study in mouse tissues | |
| Sarin et al. | Comparison of a human T-cell lymphotropic virus type I strain from cerebrospinal fluid of a Jamaican patient with tropical spastic paraparesis with a prototype human T-cell lymphotropic virus type I. | |
| EA004658B1 (ru) | Белок b1, способный модулировать внутриклеточные каскады воспаления, клеточной гибели или клеточного выживания, кодирующая его молекула днк, вектор, содержащий указанную молекулу днк, штамм клеток, содержащий данный вектор, способы их использования и фармацевтическая композиция | |
| Shima et al. | Identification of p26xb and p24xb of human T-cell leukemia virus type II | |
| EA004062B1 (ru) | Модуляторы функций рецепторов семейства рецепторов tnf/ngf и других белков | |
| KR101480365B1 (ko) | Ｍｇ53 저해제를 포함하는 브로디병과 브로디신드롬의 예방 또는 치료용 조성물 | |
| WO1999061467A2 (fr) | Agents interferant avec la liaison de typrosine-phosphatase pest a des domaines de proteines de signalisation en tant qu'inhibiteurs de migration cellulaire et/ou d'adhesion focale | |
| US8440804B2 (en) | Polypeptides having modulatory effects on cells |
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: 23852903 Country of ref document: EP Kind code of ref document: A1 |