JP2013516170A - インターフェロンアナログ - Google Patents
インターフェロンアナログ Download PDFInfo
- Publication number
- JP2013516170A JP2013516170A JP2012547044A JP2012547044A JP2013516170A JP 2013516170 A JP2013516170 A JP 2013516170A JP 2012547044 A JP2012547044 A JP 2012547044A JP 2012547044 A JP2012547044 A JP 2012547044A JP 2013516170 A JP2013516170 A JP 2013516170A
- Authority
- JP
- Japan
- Prior art keywords
- receptor
- xaa
- analog
- amino acid
- ifnγ
- 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
- 102000014150 Interferons Human genes 0.000 title abstract description 41
- 108010050904 Interferons Proteins 0.000 title abstract description 41
- 229940079322 interferon Drugs 0.000 title abstract description 37
- 102000005962 receptors Human genes 0.000 claims abstract description 65
- 230000008685 targeting Effects 0.000 claims abstract description 61
- 230000000694 effects Effects 0.000 claims abstract description 43
- 230000011664 signaling Effects 0.000 claims abstract description 24
- 239000003814 drug Substances 0.000 claims abstract description 18
- 238000000034 method Methods 0.000 claims abstract description 17
- 230000001225 therapeutic effect Effects 0.000 claims abstract description 12
- 108010001857 Cell Surface Receptors Proteins 0.000 claims abstract description 7
- 230000003834 intracellular effect Effects 0.000 claims abstract description 6
- 210000004027 cell Anatomy 0.000 claims description 79
- 108020003175 receptors Proteins 0.000 claims description 63
- 125000003275 alpha amino acid group Chemical group 0.000 claims description 33
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 31
- 206010028980 Neoplasm Diseases 0.000 claims description 28
- 125000000539 amino acid group Chemical group 0.000 claims description 26
- 201000010099 disease Diseases 0.000 claims description 26
- 108091008606 PDGF receptors Proteins 0.000 claims description 25
- 102000011653 Platelet-Derived Growth Factor Receptors Human genes 0.000 claims description 25
- 206010016654 Fibrosis Diseases 0.000 claims description 23
- 102000001189 Cyclic Peptides Human genes 0.000 claims description 21
- 108010069514 Cyclic Peptides Proteins 0.000 claims description 21
- 210000002950 fibroblast Anatomy 0.000 claims description 20
- 238000011282 treatment Methods 0.000 claims description 20
- 230000004761 fibrosis Effects 0.000 claims description 18
- 208000019425 cirrhosis of liver Diseases 0.000 claims description 16
- 229920001223 polyethylene glycol Polymers 0.000 claims description 15
- 125000002619 bicyclic group Chemical group 0.000 claims description 14
- 150000001413 amino acids Chemical class 0.000 claims description 13
- 150000001875 compounds Chemical class 0.000 claims description 12
- 210000000651 myofibroblast Anatomy 0.000 claims description 12
- 108010074328 Interferon-gamma Proteins 0.000 claims description 10
- 150000007523 nucleic acids Chemical group 0.000 claims description 10
- 108010002913 Asialoglycoproteins Proteins 0.000 claims description 9
- 108091035707 Consensus sequence Proteins 0.000 claims description 9
- 108091028043 Nucleic acid sequence Proteins 0.000 claims description 9
- 102000008070 Interferon-gamma Human genes 0.000 claims description 8
- 108010077850 Nuclear Localization Signals Proteins 0.000 claims description 8
- 239000002202 Polyethylene glycol Substances 0.000 claims description 8
- 230000001684 chronic effect Effects 0.000 claims description 8
- 125000001165 hydrophobic group Chemical group 0.000 claims description 8
- 208000005069 pulmonary fibrosis Diseases 0.000 claims description 8
- 241000725643 Respiratory syncytial virus Species 0.000 claims description 7
- 230000001154 acute effect Effects 0.000 claims description 7
- 201000011510 cancer Diseases 0.000 claims description 7
- 229960003130 interferon gamma Drugs 0.000 claims description 7
- 238000004519 manufacturing process Methods 0.000 claims description 7
- 230000003612 virological effect Effects 0.000 claims description 7
- 102000000844 Cell Surface Receptors Human genes 0.000 claims description 6
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 claims description 6
- 108010051742 Platelet-Derived Growth Factor beta Receptor Proteins 0.000 claims description 6
- 102000018967 Platelet-Derived Growth Factor beta Receptor Human genes 0.000 claims description 6
- 230000004068 intracellular signaling Effects 0.000 claims description 6
- 239000008101 lactose Substances 0.000 claims description 6
- 208000019423 liver disease Diseases 0.000 claims description 6
- 229920001542 oligosaccharide Polymers 0.000 claims description 6
- 150000002482 oligosaccharides Chemical class 0.000 claims description 6
- 239000008194 pharmaceutical composition Substances 0.000 claims description 6
- NBSCHQHZLSJFNQ-QTVWNMPRSA-N D-Mannose-6-phosphate Chemical compound OC1O[C@H](COP(O)(O)=O)[C@@H](O)[C@H](O)[C@@H]1O NBSCHQHZLSJFNQ-QTVWNMPRSA-N 0.000 claims description 5
- WQZGKKKJIJFFOK-QTVWNMPRSA-N D-mannopyranose Chemical compound OC[C@H]1OC(O)[C@@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-QTVWNMPRSA-N 0.000 claims description 5
- 208000034189 Sclerosis Diseases 0.000 claims description 5
- 230000003176 fibrotic effect Effects 0.000 claims description 5
- 208000027866 inflammatory disease Diseases 0.000 claims description 5
- 229920000642 polymer Polymers 0.000 claims description 5
- 238000011321 prophylaxis Methods 0.000 claims description 5
- 239000013598 vector Substances 0.000 claims description 5
- 230000007781 signaling event Effects 0.000 claims description 4
- 201000001320 Atherosclerosis Diseases 0.000 claims description 3
- 206010009900 Colitis ulcerative Diseases 0.000 claims description 3
- 208000011231 Crohn disease Diseases 0.000 claims description 3
- 206010018364 Glomerulonephritis Diseases 0.000 claims description 3
- 108010031792 IGF Type 2 Receptor Proteins 0.000 claims description 3
- 102000038460 IGF Type 2 Receptor Human genes 0.000 claims description 3
- 108010031099 Mannose Receptor Proteins 0.000 claims description 3
- 206010040047 Sepsis Diseases 0.000 claims description 3
- 108091005735 TGF-beta receptors Proteins 0.000 claims description 3
- 201000006704 Ulcerative Colitis Diseases 0.000 claims description 3
- 230000001580 bacterial effect Effects 0.000 claims description 3
- 230000007882 cirrhosis Effects 0.000 claims description 3
- 239000013604 expression vector Substances 0.000 claims description 3
- 206010061989 glomerulosclerosis Diseases 0.000 claims description 3
- 206010039073 rheumatoid arthritis Diseases 0.000 claims description 3
- 102000009410 Chemokine receptor Human genes 0.000 claims description 2
- 108050000299 Chemokine receptor Proteins 0.000 claims description 2
- 102000002734 Collagen Type VI Human genes 0.000 claims description 2
- 108010043741 Collagen Type VI Proteins 0.000 claims description 2
- 102000003886 Glycoproteins Human genes 0.000 claims description 2
- 108090000288 Glycoproteins Proteins 0.000 claims description 2
- 102000009465 Growth Factor Receptors Human genes 0.000 claims description 2
- 108010009202 Growth Factor Receptors Proteins 0.000 claims description 2
- 102000016715 Transforming Growth Factor beta Receptors Human genes 0.000 claims description 2
- 108060008682 Tumor Necrosis Factor Proteins 0.000 claims description 2
- 102000000852 Tumor Necrosis Factor-alpha Human genes 0.000 claims description 2
- 108091008605 VEGF receptors Proteins 0.000 claims description 2
- 102000009484 Vascular Endothelial Growth Factor Receptors Human genes 0.000 claims description 2
- 239000000654 additive Substances 0.000 claims description 2
- 230000000890 antigenic effect Effects 0.000 claims description 2
- 102000003675 cytokine receptors Human genes 0.000 claims description 2
- 108010057085 cytokine receptors Proteins 0.000 claims description 2
- 239000003937 drug carrier Substances 0.000 claims description 2
- 210000003584 mesangial cell Anatomy 0.000 claims description 2
- 230000002685 pulmonary effect Effects 0.000 claims description 2
- 210000002536 stromal cell Anatomy 0.000 claims description 2
- 229910052717 sulfur Inorganic materials 0.000 claims description 2
- 241000712461 unidentified influenza virus Species 0.000 claims description 2
- 102100037182 Cation-independent mannose-6-phosphate receptor Human genes 0.000 claims 1
- 101001028831 Homo sapiens Cation-independent mannose-6-phosphate receptor Proteins 0.000 claims 1
- 102000003746 Insulin Receptor Human genes 0.000 claims 1
- 108010001127 Insulin Receptor Proteins 0.000 claims 1
- 229910019142 PO4 Inorganic materials 0.000 claims 1
- 230000000996 additive effect Effects 0.000 claims 1
- 239000002671 adjuvant Substances 0.000 claims 1
- 230000030648 nucleus localization Effects 0.000 claims 1
- 239000010452 phosphate Substances 0.000 claims 1
- 102000006240 membrane receptors Human genes 0.000 abstract 1
- 230000003278 mimic effect Effects 0.000 description 36
- 241000699666 Mus <mouse, genus> Species 0.000 description 30
- 241000699670 Mus sp. Species 0.000 description 30
- 108090000765 processed proteins & peptides Proteins 0.000 description 29
- 230000014509 gene expression Effects 0.000 description 21
- 235000001014 amino acid Nutrition 0.000 description 16
- 229940024606 amino acid Drugs 0.000 description 16
- 238000004458 analytical method Methods 0.000 description 15
- 108090000623 proteins and genes Proteins 0.000 description 15
- 108010038512 Platelet-Derived Growth Factor Proteins 0.000 description 14
- 102000010780 Platelet-Derived Growth Factor Human genes 0.000 description 13
- XUJNEKJLAYXESH-REOHCLBHSA-N L-Cysteine Chemical compound SC[C@H](N)C(O)=O XUJNEKJLAYXESH-REOHCLBHSA-N 0.000 description 11
- 241001465754 Metazoa Species 0.000 description 11
- 101001044384 Mus musculus Interferon gamma Proteins 0.000 description 11
- 229940079593 drug Drugs 0.000 description 11
- 201000009794 Idiopathic Pulmonary Fibrosis Diseases 0.000 description 10
- 208000036971 interstitial lung disease 2 Diseases 0.000 description 10
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 9
- 210000001519 tissue Anatomy 0.000 description 9
- IYMAXBFPHPZYIK-BQBZGAKWSA-N Arg-Gly-Asp Chemical compound NC(N)=NCCC[C@H](N)C(=O)NCC(=O)N[C@@H](CC(O)=O)C(O)=O IYMAXBFPHPZYIK-BQBZGAKWSA-N 0.000 description 8
- 206010067125 Liver injury Diseases 0.000 description 8
- 102000004887 Transforming Growth Factor beta Human genes 0.000 description 8
- 230000003510 anti-fibrotic effect Effects 0.000 description 8
- 210000004185 liver Anatomy 0.000 description 8
- 239000004006 olive oil Substances 0.000 description 8
- 235000008390 olive oil Nutrition 0.000 description 8
- 238000010186 staining Methods 0.000 description 8
- 101000959820 Homo sapiens Interferon alpha-1/13 Proteins 0.000 description 7
- 102100040019 Interferon alpha-1/13 Human genes 0.000 description 7
- 108090001012 Transforming Growth Factor beta Proteins 0.000 description 7
- 238000002474 experimental method Methods 0.000 description 7
- 210000004024 hepatic stellate cell Anatomy 0.000 description 7
- 210000003494 hepatocyte Anatomy 0.000 description 7
- 239000003446 ligand Substances 0.000 description 7
- 210000004072 lung Anatomy 0.000 description 7
- 102000004196 processed proteins & peptides Human genes 0.000 description 7
- 102000004169 proteins and genes Human genes 0.000 description 7
- 230000002829 reductive effect Effects 0.000 description 7
- 125000006850 spacer group Chemical group 0.000 description 7
- 241000894007 species Species 0.000 description 7
- 108091032973 (ribonucleotides)n+m Proteins 0.000 description 6
- 102000008186 Collagen Human genes 0.000 description 6
- 108010035532 Collagen Proteins 0.000 description 6
- 102000004127 Cytokines Human genes 0.000 description 6
- 108090000695 Cytokines Proteins 0.000 description 6
- 102100036912 Desmin Human genes 0.000 description 6
- 108010044052 Desmin Proteins 0.000 description 6
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 6
- 108010064593 Intercellular Adhesion Molecule-1 Proteins 0.000 description 6
- 102100037877 Intercellular adhesion molecule 1 Human genes 0.000 description 6
- 231100000439 acute liver injury Toxicity 0.000 description 6
- 230000000840 anti-viral effect Effects 0.000 description 6
- 230000004071 biological effect Effects 0.000 description 6
- 230000015572 biosynthetic process Effects 0.000 description 6
- 238000004820 blood count Methods 0.000 description 6
- 229920001436 collagen Polymers 0.000 description 6
- 210000005045 desmin Anatomy 0.000 description 6
- 238000011534 incubation Methods 0.000 description 6
- 210000002540 macrophage Anatomy 0.000 description 6
- 238000010172 mouse model Methods 0.000 description 6
- 239000002773 nucleotide Substances 0.000 description 6
- 125000003729 nucleotide group Chemical group 0.000 description 6
- MTCFGRXMJLQNBG-REOHCLBHSA-N (2S)-2-Amino-3-hydroxypropansäure Chemical compound OC[C@H](N)C(O)=O MTCFGRXMJLQNBG-REOHCLBHSA-N 0.000 description 5
- KDXKERNSBIXSRK-YFKPBYRVSA-N L-lysine Chemical compound NCCCC[C@H](N)C(O)=O KDXKERNSBIXSRK-YFKPBYRVSA-N 0.000 description 5
- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 5
- 238000001727 in vivo Methods 0.000 description 5
- 210000000265 leukocyte Anatomy 0.000 description 5
- 235000018102 proteins Nutrition 0.000 description 5
- 102000012422 Collagen Type I Human genes 0.000 description 4
- 108010022452 Collagen Type I Proteins 0.000 description 4
- 101000599940 Homo sapiens Interferon gamma Proteins 0.000 description 4
- CKLJMWTZIZZHCS-REOHCLBHSA-N L-aspartic acid Chemical compound OC(=O)[C@@H](N)CC(O)=O CKLJMWTZIZZHCS-REOHCLBHSA-N 0.000 description 4
- 108091023040 Transcription factor Proteins 0.000 description 4
- 102000040945 Transcription factor Human genes 0.000 description 4
- 238000010276 construction Methods 0.000 description 4
- MHMNJMPURVTYEJ-UHFFFAOYSA-N fluorescein-5-isothiocyanate Chemical compound O1C(=O)C2=CC(N=C=S)=CC=C2C21C1=CC=C(O)C=C1OC1=CC(O)=CC=C21 MHMNJMPURVTYEJ-UHFFFAOYSA-N 0.000 description 4
- 239000012634 fragment Substances 0.000 description 4
- 230000004927 fusion Effects 0.000 description 4
- 125000003630 glycyl group Chemical group [H]N([H])C([H])([H])C(*)=O 0.000 description 4
- 238000000338 in vitro Methods 0.000 description 4
- 208000015181 infectious disease Diseases 0.000 description 4
- 239000002502 liposome Substances 0.000 description 4
- 230000037361 pathway Effects 0.000 description 4
- 230000002441 reversible effect Effects 0.000 description 4
- 238000003786 synthesis reaction Methods 0.000 description 4
- 210000004881 tumor cell Anatomy 0.000 description 4
- 102000009027 Albumins Human genes 0.000 description 3
- 108010088751 Albumins Proteins 0.000 description 3
- 206010001889 Alveolitis Diseases 0.000 description 3
- 241000282412 Homo Species 0.000 description 3
- 101000934372 Homo sapiens Macrosialin Proteins 0.000 description 3
- 101000692455 Homo sapiens Platelet-derived growth factor receptor beta Proteins 0.000 description 3
- DCXYFEDJOCDNAF-REOHCLBHSA-N L-asparagine Chemical compound OC(=O)[C@@H](N)CC(N)=O DCXYFEDJOCDNAF-REOHCLBHSA-N 0.000 description 3
- 102100025136 Macrosialin Human genes 0.000 description 3
- 102000002274 Matrix Metalloproteinases Human genes 0.000 description 3
- 108010000684 Matrix Metalloproteinases Proteins 0.000 description 3
- 108010047620 Phytohemagglutinins Proteins 0.000 description 3
- 102100026547 Platelet-derived growth factor receptor beta Human genes 0.000 description 3
- 102000007056 Recombinant Fusion Proteins Human genes 0.000 description 3
- 108010008281 Recombinant Fusion Proteins Proteins 0.000 description 3
- 241000700605 Viruses Species 0.000 description 3
- 230000033115 angiogenesis Effects 0.000 description 3
- 230000009286 beneficial effect Effects 0.000 description 3
- 230000037396 body weight Effects 0.000 description 3
- 238000010367 cloning Methods 0.000 description 3
- 239000002299 complementary DNA Substances 0.000 description 3
- 230000008878 coupling Effects 0.000 description 3
- 238000010168 coupling process Methods 0.000 description 3
- 238000005859 coupling reaction Methods 0.000 description 3
- 125000004122 cyclic group Chemical group 0.000 description 3
- 235000018417 cysteine Nutrition 0.000 description 3
- XUJNEKJLAYXESH-UHFFFAOYSA-N cysteine Natural products SCC(N)C(O)=O XUJNEKJLAYXESH-UHFFFAOYSA-N 0.000 description 3
- 239000000412 dendrimer Substances 0.000 description 3
- 229920000736 dendritic polymer Polymers 0.000 description 3
- 210000002889 endothelial cell Anatomy 0.000 description 3
- 201000001155 extrinsic allergic alveolitis Diseases 0.000 description 3
- 102000037865 fusion proteins Human genes 0.000 description 3
- 108020001507 fusion proteins Proteins 0.000 description 3
- 208000022098 hypersensitivity pneumonitis Diseases 0.000 description 3
- 210000000987 immune system Anatomy 0.000 description 3
- 230000008595 infiltration Effects 0.000 description 3
- 238000001764 infiltration Methods 0.000 description 3
- 210000004969 inflammatory cell Anatomy 0.000 description 3
- 229940047124 interferons Drugs 0.000 description 3
- 210000004698 lymphocyte Anatomy 0.000 description 3
- 239000003550 marker Substances 0.000 description 3
- 239000000463 material Substances 0.000 description 3
- 239000002609 medium Substances 0.000 description 3
- 239000000203 mixture Substances 0.000 description 3
- 125000002950 monocyclic group Chemical group 0.000 description 3
- 230000005937 nuclear translocation Effects 0.000 description 3
- 210000004940 nucleus Anatomy 0.000 description 3
- 230000001885 phytohemagglutinin Effects 0.000 description 3
- 238000003753 real-time PCR Methods 0.000 description 3
- 238000007363 ring formation reaction Methods 0.000 description 3
- 230000019491 signal transduction Effects 0.000 description 3
- 230000009885 systemic effect Effects 0.000 description 3
- 238000012360 testing method Methods 0.000 description 3
- ZRKFYGHZFMAOKI-QMGMOQQFSA-N tgfbeta Chemical compound C([C@H](NC(=O)[C@H](C(C)C)NC(=O)CNC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H]([C@@H](C)O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H]([C@@H](C)O)NC(=O)[C@H](CC(C)C)NC(=O)CNC(=O)[C@H](C)NC(=O)[C@H](CO)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@@H](NC(=O)[C@H](C)NC(=O)[C@H](C)NC(=O)[C@@H](NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](N)CCSC)C(C)C)[C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](C)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](C)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](C)C(=O)N[C@@H](CC(C)C)C(=O)N1[C@@H](CCC1)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(C)C)C(O)=O)C1=CC=C(O)C=C1 ZRKFYGHZFMAOKI-QMGMOQQFSA-N 0.000 description 3
- 230000003827 upregulation Effects 0.000 description 3
- 229960005486 vaccine Drugs 0.000 description 3
- 238000001262 western blot Methods 0.000 description 3
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 2
- 206010002091 Anaesthesia Diseases 0.000 description 2
- 102000019034 Chemokines Human genes 0.000 description 2
- 108010012236 Chemokines Proteins 0.000 description 2
- 108020004705 Codon Proteins 0.000 description 2
- BWGNESOTFCXPMA-UHFFFAOYSA-N Dihydrogen disulfide Chemical compound SS BWGNESOTFCXPMA-UHFFFAOYSA-N 0.000 description 2
- 102000010834 Extracellular Matrix Proteins Human genes 0.000 description 2
- 108010037362 Extracellular Matrix Proteins Proteins 0.000 description 2
- 102000016359 Fibronectins Human genes 0.000 description 2
- 108010067306 Fibronectins Proteins 0.000 description 2
- WZUVPPKBWHMQCE-UHFFFAOYSA-N Haematoxylin Chemical compound C12=CC(O)=C(O)C=C2CC2(O)C1C1=CC=C(O)C(O)=C1OC2 WZUVPPKBWHMQCE-UHFFFAOYSA-N 0.000 description 2
- 101000852870 Homo sapiens Interferon alpha/beta receptor 1 Proteins 0.000 description 2
- 101000669513 Homo sapiens Metalloproteinase inhibitor 1 Proteins 0.000 description 2
- 102100036714 Interferon alpha/beta receptor 1 Human genes 0.000 description 2
- 102100037850 Interferon gamma Human genes 0.000 description 2
- 108010047761 Interferon-alpha Proteins 0.000 description 2
- 102000006992 Interferon-alpha Human genes 0.000 description 2
- PIWKPBJCKXDKJR-UHFFFAOYSA-N Isoflurane Chemical compound FC(F)OC(Cl)C(F)(F)F PIWKPBJCKXDKJR-UHFFFAOYSA-N 0.000 description 2
- ZDXPYRJPNDTMRX-VKHMYHEASA-N L-glutamine Chemical compound OC(=O)[C@@H](N)CCC(N)=O ZDXPYRJPNDTMRX-VKHMYHEASA-N 0.000 description 2
- AYFVYJQAPQTCCC-GBXIJSLDSA-N L-threonine Chemical compound C[C@@H](O)[C@H](N)C(O)=O AYFVYJQAPQTCCC-GBXIJSLDSA-N 0.000 description 2
- 239000004472 Lysine Substances 0.000 description 2
- 102000043131 MHC class II family Human genes 0.000 description 2
- 108091054438 MHC class II family Proteins 0.000 description 2
- 102100039364 Metalloproteinase inhibitor 1 Human genes 0.000 description 2
- 102100024616 Platelet endothelial cell adhesion molecule Human genes 0.000 description 2
- 230000010799 Receptor Interactions Effects 0.000 description 2
- 102000006381 STAT1 Transcription Factor Human genes 0.000 description 2
- 108010044012 STAT1 Transcription Factor Proteins 0.000 description 2
- 102000004265 STAT2 Transcription Factor Human genes 0.000 description 2
- 108010081691 STAT2 Transcription Factor Proteins 0.000 description 2
- 230000004913 activation Effects 0.000 description 2
- 239000012190 activator Substances 0.000 description 2
- 230000002411 adverse Effects 0.000 description 2
- 230000037005 anaesthesia Effects 0.000 description 2
- 230000006907 apoptotic process Effects 0.000 description 2
- 238000013459 approach Methods 0.000 description 2
- 210000004369 blood Anatomy 0.000 description 2
- 239000008280 blood Substances 0.000 description 2
- 210000004899 c-terminal region Anatomy 0.000 description 2
- -1 carboxymethyl ester Chemical class 0.000 description 2
- 230000021164 cell adhesion Effects 0.000 description 2
- 230000004700 cellular uptake Effects 0.000 description 2
- 238000006243 chemical reaction Methods 0.000 description 2
- 239000003153 chemical reaction reagent Substances 0.000 description 2
- 239000003795 chemical substances by application Substances 0.000 description 2
- 238000004440 column chromatography Methods 0.000 description 2
- 230000021615 conjugation Effects 0.000 description 2
- 210000004443 dendritic cell Anatomy 0.000 description 2
- 238000003745 diagnosis Methods 0.000 description 2
- 238000010586 diagram Methods 0.000 description 2
- 238000000502 dialysis Methods 0.000 description 2
- 239000000539 dimer Substances 0.000 description 2
- 239000012636 effector Substances 0.000 description 2
- 210000003743 erythrocyte Anatomy 0.000 description 2
- 210000002744 extracellular matrix Anatomy 0.000 description 2
- 230000006870 function Effects 0.000 description 2
- 239000003102 growth factor Substances 0.000 description 2
- 239000001963 growth medium Substances 0.000 description 2
- 210000002865 immune cell Anatomy 0.000 description 2
- 230000000977 initiatory effect Effects 0.000 description 2
- 238000002347 injection Methods 0.000 description 2
- 239000007924 injection Substances 0.000 description 2
- NOESYZHRGYRDHS-UHFFFAOYSA-N insulin Chemical compound N1C(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(NC(=O)CN)C(C)CC)CSSCC(C(NC(CO)C(=O)NC(CC(C)C)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CCC(N)=O)C(=O)NC(CC(C)C)C(=O)NC(CCC(O)=O)C(=O)NC(CC(N)=O)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CSSCC(NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2C=CC(O)=CC=2)NC(=O)C(CC(C)C)NC(=O)C(C)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2NC=NC=2)NC(=O)C(CO)NC(=O)CNC2=O)C(=O)NCC(=O)NC(CCC(O)=O)C(=O)NC(CCCNC(N)=N)C(=O)NCC(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC(O)=CC=3)C(=O)NC(C(C)O)C(=O)N3C(CCC3)C(=O)NC(CCCCN)C(=O)NC(C)C(O)=O)C(=O)NC(CC(N)=O)C(O)=O)=O)NC(=O)C(C(C)CC)NC(=O)C(CO)NC(=O)C(C(C)O)NC(=O)C1CSSCC2NC(=O)C(CC(C)C)NC(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CC(N)=O)NC(=O)C(NC(=O)C(N)CC=1C=CC=CC=1)C(C)C)CC1=CN=CN1 NOESYZHRGYRDHS-UHFFFAOYSA-N 0.000 description 2
- 108010044426 integrins Proteins 0.000 description 2
- 102000006495 integrins Human genes 0.000 description 2
- 230000002452 interceptive effect Effects 0.000 description 2
- 238000001990 intravenous administration Methods 0.000 description 2
- 229960002725 isoflurane Drugs 0.000 description 2
- QWTDNUCVQCZILF-UHFFFAOYSA-N isopentane Chemical compound CCC(C)C QWTDNUCVQCZILF-UHFFFAOYSA-N 0.000 description 2
- 210000003734 kidney Anatomy 0.000 description 2
- 210000005228 liver tissue Anatomy 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- 210000000440 neutrophil Anatomy 0.000 description 2
- 201000004071 non-specific interstitial pneumonia Diseases 0.000 description 2
- 108020004707 nucleic acids Proteins 0.000 description 2
- 102000039446 nucleic acids Human genes 0.000 description 2
- 239000000816 peptidomimetic Substances 0.000 description 2
- 102000013415 peroxidase activity proteins Human genes 0.000 description 2
- 108040007629 peroxidase activity proteins Proteins 0.000 description 2
- 229920001184 polypeptide Polymers 0.000 description 2
- 238000010837 poor prognosis Methods 0.000 description 2
- 150000003180 prostaglandins Chemical class 0.000 description 2
- 238000011002 quantification Methods 0.000 description 2
- 239000000700 radioactive tracer Substances 0.000 description 2
- 230000009467 reduction Effects 0.000 description 2
- 230000004044 response Effects 0.000 description 2
- 238000012552 review Methods 0.000 description 2
- 210000004989 spleen cell Anatomy 0.000 description 2
- 238000010561 standard procedure Methods 0.000 description 2
- 238000007920 subcutaneous administration Methods 0.000 description 2
- 235000000346 sugar Nutrition 0.000 description 2
- 230000004083 survival effect Effects 0.000 description 2
- VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 description 2
- 238000013518 transcription Methods 0.000 description 2
- 230000035897 transcription Effects 0.000 description 2
- 230000009466 transformation Effects 0.000 description 2
- VHRUMKCAEVRUBK-GODQJPCRSA-N 15-deoxy-Delta(12,14)-prostaglandin J2 Chemical compound CCCCC\C=C\C=C1/[C@@H](C\C=C/CCCC(O)=O)C=CC1=O VHRUMKCAEVRUBK-GODQJPCRSA-N 0.000 description 1
- 108020004463 18S ribosomal RNA Proteins 0.000 description 1
- WLAMNBDJUVNPJU-UHFFFAOYSA-N 2-methylbutyric acid Chemical compound CCC(C)C(O)=O WLAMNBDJUVNPJU-UHFFFAOYSA-N 0.000 description 1
- FWBHETKCLVMNFS-UHFFFAOYSA-N 4',6-Diamino-2-phenylindol Chemical compound C1=CC(C(=N)N)=CC=C1C1=CC2=CC=C(C(N)=N)C=C2N1 FWBHETKCLVMNFS-UHFFFAOYSA-N 0.000 description 1
- 102000007469 Actins Human genes 0.000 description 1
- 108010085238 Actins Proteins 0.000 description 1
- 239000004475 Arginine Substances 0.000 description 1
- DCXYFEDJOCDNAF-UHFFFAOYSA-N Asparagine Natural products OC(=O)C(N)CC(N)=O DCXYFEDJOCDNAF-UHFFFAOYSA-N 0.000 description 1
- 208000023275 Autoimmune disease Diseases 0.000 description 1
- 102000004506 Blood Proteins Human genes 0.000 description 1
- 108010017384 Blood Proteins Proteins 0.000 description 1
- 102100031650 C-X-C chemokine receptor type 4 Human genes 0.000 description 1
- 241000283707 Capra Species 0.000 description 1
- 102000016289 Cell Adhesion Molecules Human genes 0.000 description 1
- 108010067225 Cell Adhesion Molecules Proteins 0.000 description 1
- 102100027995 Collagenase 3 Human genes 0.000 description 1
- 108050005238 Collagenase 3 Proteins 0.000 description 1
- 208000035473 Communicable disease Diseases 0.000 description 1
- 102000002004 Cytochrome P-450 Enzyme System Human genes 0.000 description 1
- 108010015742 Cytochrome P-450 Enzyme System Proteins 0.000 description 1
- 238000001712 DNA sequencing Methods 0.000 description 1
- 102000016928 DNA-directed DNA polymerase Human genes 0.000 description 1
- 108010014303 DNA-directed DNA polymerase Proteins 0.000 description 1
- 101100364969 Dictyostelium discoideum scai gene Proteins 0.000 description 1
- 102400000686 Endothelin-1 Human genes 0.000 description 1
- 101800004490 Endothelin-1 Proteins 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- 241000588724 Escherichia coli Species 0.000 description 1
- 108010010803 Gelatin Proteins 0.000 description 1
- WHUUTDBJXJRKMK-UHFFFAOYSA-N Glutamic acid Natural products OC(=O)C(N)CCC(O)=O WHUUTDBJXJRKMK-UHFFFAOYSA-N 0.000 description 1
- 208000005176 Hepatitis C Diseases 0.000 description 1
- 101000922348 Homo sapiens C-X-C chemokine receptor type 4 Proteins 0.000 description 1
- 101000852865 Homo sapiens Interferon alpha/beta receptor 2 Proteins 0.000 description 1
- 101001001420 Homo sapiens Interferon gamma receptor 1 Proteins 0.000 description 1
- 101000617738 Homo sapiens Survival motor neuron protein Proteins 0.000 description 1
- 102000008100 Human Serum Albumin Human genes 0.000 description 1
- 108091006905 Human Serum Albumin Proteins 0.000 description 1
- 241000711920 Human orthopneumovirus Species 0.000 description 1
- 102100036186 Importin subunit alpha-5 Human genes 0.000 description 1
- 101710118220 Importin subunit alpha-5 Proteins 0.000 description 1
- 208000020060 Increased inflammatory response Diseases 0.000 description 1
- 206010022004 Influenza like illness Diseases 0.000 description 1
- 102000004877 Insulin Human genes 0.000 description 1
- 108090001061 Insulin Proteins 0.000 description 1
- 108010047852 Integrin alphaVbeta3 Proteins 0.000 description 1
- 108010054267 Interferon Receptors Proteins 0.000 description 1
- 102000001617 Interferon Receptors Human genes 0.000 description 1
- 108010014726 Interferon Type I Proteins 0.000 description 1
- 102000002227 Interferon Type I Human genes 0.000 description 1
- 102100036718 Interferon alpha/beta receptor 2 Human genes 0.000 description 1
- 102100026720 Interferon beta Human genes 0.000 description 1
- 102100035678 Interferon gamma receptor 1 Human genes 0.000 description 1
- 108090000467 Interferon-beta Proteins 0.000 description 1
- 102000004551 Interleukin-10 Receptors Human genes 0.000 description 1
- 108010017550 Interleukin-10 Receptors Proteins 0.000 description 1
- 102000008986 Janus Human genes 0.000 description 1
- 108050000950 Janus Proteins 0.000 description 1
- 206010023421 Kidney fibrosis Diseases 0.000 description 1
- ODKSFYDXXFIFQN-BYPYZUCNSA-P L-argininium(2+) Chemical compound NC(=[NH2+])NCCC[C@H]([NH3+])C(O)=O ODKSFYDXXFIFQN-BYPYZUCNSA-P 0.000 description 1
- LEVWYRKDKASIDU-IMJSIDKUSA-N L-cystine Chemical group [O-]C(=O)[C@@H]([NH3+])CSSC[C@H]([NH3+])C([O-])=O LEVWYRKDKASIDU-IMJSIDKUSA-N 0.000 description 1
- WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 description 1
- HNDVDQJCIGZPNO-YFKPBYRVSA-N L-histidine Chemical compound OC(=O)[C@@H](N)CC1=CN=CN1 HNDVDQJCIGZPNO-YFKPBYRVSA-N 0.000 description 1
- FFEARJCKVFRZRR-BYPYZUCNSA-N L-methionine Chemical compound CSCC[C@H](N)C(O)=O FFEARJCKVFRZRR-BYPYZUCNSA-N 0.000 description 1
- QIVBCDIJIAJPQS-VIFPVBQESA-N L-tryptophane Chemical compound C1=CC=C2C(C[C@H](N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-VIFPVBQESA-N 0.000 description 1
- OUYCCCASQSFEME-QMMMGPOBSA-N L-tyrosine Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-QMMMGPOBSA-N 0.000 description 1
- 108010063045 Lactoferrin Proteins 0.000 description 1
- 102000010445 Lactoferrin Human genes 0.000 description 1
- 206010024971 Lower respiratory tract infections Diseases 0.000 description 1
- 208000019693 Lung disease Diseases 0.000 description 1
- 241000124008 Mammalia Species 0.000 description 1
- 102000018697 Membrane Proteins Human genes 0.000 description 1
- 108010052285 Membrane Proteins Proteins 0.000 description 1
- 101100364971 Mus musculus Scai gene Proteins 0.000 description 1
- 208000000112 Myalgia Diseases 0.000 description 1
- 125000000729 N-terminal amino-acid group Chemical group 0.000 description 1
- 241000283973 Oryctolagus cuniculus Species 0.000 description 1
- 238000012408 PCR amplification Methods 0.000 description 1
- 229930040373 Paraformaldehyde Natural products 0.000 description 1
- 208000022553 Parenchymal lung disease Diseases 0.000 description 1
- 206010056342 Pulmonary mass Diseases 0.000 description 1
- 206010037660 Pyrexia Diseases 0.000 description 1
- 238000011530 RNeasy Mini Kit Methods 0.000 description 1
- 238000011529 RT qPCR Methods 0.000 description 1
- 101001044455 Rattus norvegicus Interferon gamma Proteins 0.000 description 1
- 108020004511 Recombinant DNA Proteins 0.000 description 1
- 206010061603 Respiratory syncytial virus infection Diseases 0.000 description 1
- 206010057190 Respiratory tract infections Diseases 0.000 description 1
- 108091027981 Response element Proteins 0.000 description 1
- 229920002684 Sepharose Polymers 0.000 description 1
- MTCFGRXMJLQNBG-UHFFFAOYSA-N Serine Natural products OCC(N)C(O)=O MTCFGRXMJLQNBG-UHFFFAOYSA-N 0.000 description 1
- 102000007562 Serum Albumin Human genes 0.000 description 1
- 108010071390 Serum Albumin Proteins 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 1
- 102100021947 Survival motor neuron protein Human genes 0.000 description 1
- 210000001744 T-lymphocyte Anatomy 0.000 description 1
- AYFVYJQAPQTCCC-UHFFFAOYSA-N Threonine Natural products CC(O)C(N)C(O)=O AYFVYJQAPQTCCC-UHFFFAOYSA-N 0.000 description 1
- 239000004473 Threonine Substances 0.000 description 1
- 208000007536 Thrombosis Diseases 0.000 description 1
- 108010005246 Tissue Inhibitor of Metalloproteinases Proteins 0.000 description 1
- 102000005876 Tissue Inhibitor of Metalloproteinases Human genes 0.000 description 1
- 102000004142 Trypsin Human genes 0.000 description 1
- 108090000631 Trypsin Proteins 0.000 description 1
- QIVBCDIJIAJPQS-UHFFFAOYSA-N Tryptophan Natural products C1=CC=C2C(CC(N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-UHFFFAOYSA-N 0.000 description 1
- 208000036142 Viral infection Diseases 0.000 description 1
- 238000009825 accumulation Methods 0.000 description 1
- 239000004480 active ingredient Substances 0.000 description 1
- 238000001042 affinity chromatography Methods 0.000 description 1
- 230000000172 allergic effect Effects 0.000 description 1
- 102000009899 alpha Karyopherins Human genes 0.000 description 1
- 108010077099 alpha Karyopherins Proteins 0.000 description 1
- 150000001412 amines Chemical group 0.000 description 1
- 230000003321 amplification Effects 0.000 description 1
- 230000003698 anagen phase Effects 0.000 description 1
- 230000001093 anti-cancer Effects 0.000 description 1
- 230000002300 anti-fibrosis Effects 0.000 description 1
- 230000030741 antigen processing and presentation Effects 0.000 description 1
- ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 1
- 108010072041 arginyl-glycyl-aspartic acid Proteins 0.000 description 1
- 235000009582 asparagine Nutrition 0.000 description 1
- 229960001230 asparagine Drugs 0.000 description 1
- 235000003704 aspartic acid Nutrition 0.000 description 1
- 238000003556 assay Methods 0.000 description 1
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
- 208000010668 atopic eczema Diseases 0.000 description 1
- 230000008901 benefit Effects 0.000 description 1
- OQFSQFPPLPISGP-UHFFFAOYSA-N beta-carboxyaspartic acid Natural products OC(=O)C(N)C(C(O)=O)C(O)=O OQFSQFPPLPISGP-UHFFFAOYSA-N 0.000 description 1
- 230000001588 bifunctional effect Effects 0.000 description 1
- 238000006664 bond formation reaction Methods 0.000 description 1
- 206010006451 bronchitis Diseases 0.000 description 1
- JEDYYFXHPAIBGR-UHFFFAOYSA-N butafenacil Chemical compound O=C1N(C)C(C(F)(F)F)=CC(=O)N1C1=CC=C(Cl)C(C(=O)OC(C)(C)C(=O)OCC=C)=C1 JEDYYFXHPAIBGR-UHFFFAOYSA-N 0.000 description 1
- 238000010805 cDNA synthesis kit Methods 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 238000004113 cell culture Methods 0.000 description 1
- 239000002771 cell marker Substances 0.000 description 1
- 210000003855 cell nucleus Anatomy 0.000 description 1
- 230000005754 cellular signaling Effects 0.000 description 1
- 210000003169 central nervous system Anatomy 0.000 description 1
- 238000005119 centrifugation Methods 0.000 description 1
- 150000005829 chemical entities Chemical class 0.000 description 1
- 230000000052 comparative effect Effects 0.000 description 1
- 230000009918 complex formation Effects 0.000 description 1
- 230000016396 cytokine production Effects 0.000 description 1
- 210000000805 cytoplasm Anatomy 0.000 description 1
- 230000006196 deacetylation Effects 0.000 description 1
- 238000003381 deacetylation reaction Methods 0.000 description 1
- 230000002950 deficient Effects 0.000 description 1
- 238000006731 degradation reaction Methods 0.000 description 1
- 230000002939 deleterious effect Effects 0.000 description 1
- 230000001419 dependent effect Effects 0.000 description 1
- 230000008021 deposition Effects 0.000 description 1
- 238000013461 design Methods 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 230000018109 developmental process Effects 0.000 description 1
- 238000002405 diagnostic procedure Methods 0.000 description 1
- AFABGHUZZDYHJO-UHFFFAOYSA-N dimethyl butane Natural products CCCC(C)C AFABGHUZZDYHJO-UHFFFAOYSA-N 0.000 description 1
- XEYBRNLFEZDVAW-ARSRFYASSA-N dinoprostone Chemical compound CCCCC[C@H](O)\C=C\[C@H]1[C@H](O)CC(=O)[C@@H]1C\C=C/CCCC(O)=O XEYBRNLFEZDVAW-ARSRFYASSA-N 0.000 description 1
- 229960002986 dinoprostone Drugs 0.000 description 1
- 238000009826 distribution Methods 0.000 description 1
- 238000001647 drug administration Methods 0.000 description 1
- 239000000806 elastomer Substances 0.000 description 1
- 229920001971 elastomer Polymers 0.000 description 1
- 230000001159 endocytotic effect Effects 0.000 description 1
- 230000003511 endothelial effect Effects 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 230000001747 exhibiting effect Effects 0.000 description 1
- 238000010195 expression analysis Methods 0.000 description 1
- 230000003352 fibrogenic effect Effects 0.000 description 1
- 239000007789 gas Substances 0.000 description 1
- 229920000159 gelatin Polymers 0.000 description 1
- 239000008273 gelatin Substances 0.000 description 1
- 235000019322 gelatine Nutrition 0.000 description 1
- 235000011852 gelatine desserts Nutrition 0.000 description 1
- 239000011521 glass Substances 0.000 description 1
- 235000013922 glutamic acid Nutrition 0.000 description 1
- 239000004220 glutamic acid Substances 0.000 description 1
- ZDXPYRJPNDTMRX-UHFFFAOYSA-N glutamine Natural products OC(=O)C(N)CCC(N)=O ZDXPYRJPNDTMRX-UHFFFAOYSA-N 0.000 description 1
- 108020004445 glyceraldehyde-3-phosphate dehydrogenase Proteins 0.000 description 1
- 230000012010 growth Effects 0.000 description 1
- 230000003862 health status Effects 0.000 description 1
- 231100000234 hepatic damage Toxicity 0.000 description 1
- 231100000753 hepatic injury Toxicity 0.000 description 1
- 208000002672 hepatitis B Diseases 0.000 description 1
- HNDVDQJCIGZPNO-UHFFFAOYSA-N histidine Natural products OC(=O)C(N)CC1=CN=CN1 HNDVDQJCIGZPNO-UHFFFAOYSA-N 0.000 description 1
- 229940088597 hormone Drugs 0.000 description 1
- 239000005556 hormone Substances 0.000 description 1
- 210000005260 human cell Anatomy 0.000 description 1
- 235000003642 hunger Nutrition 0.000 description 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 1
- 230000001900 immune effect Effects 0.000 description 1
- 238000002649 immunization Methods 0.000 description 1
- 230000003053 immunization Effects 0.000 description 1
- 238000003365 immunocytochemistry Methods 0.000 description 1
- 230000005847 immunogenicity Effects 0.000 description 1
- 230000002055 immunohistochemical effect Effects 0.000 description 1
- 238000003364 immunohistochemistry Methods 0.000 description 1
- 238000000099 in vitro assay Methods 0.000 description 1
- 230000006698 induction Effects 0.000 description 1
- 230000028709 inflammatory response Effects 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 230000005764 inhibitory process Effects 0.000 description 1
- 229940125396 insulin Drugs 0.000 description 1
- 230000003993 interaction Effects 0.000 description 1
- 230000008611 intercellular interaction Effects 0.000 description 1
- 238000007912 intraperitoneal administration Methods 0.000 description 1
- 239000007928 intraperitoneal injection Substances 0.000 description 1
- 230000009545 invasion Effects 0.000 description 1
- BPHPUYQFMNQIOC-NXRLNHOXSA-N isopropyl beta-D-thiogalactopyranoside Chemical compound CC(C)S[C@@H]1O[C@H](CO)[C@H](O)[C@H](O)[C@H]1O BPHPUYQFMNQIOC-NXRLNHOXSA-N 0.000 description 1
- CSSYQJWUGATIHM-IKGCZBKSSA-N l-phenylalanyl-l-lysyl-l-cysteinyl-l-arginyl-l-arginyl-l-tryptophyl-l-glutaminyl-l-tryptophyl-l-arginyl-l-methionyl-l-lysyl-l-lysyl-l-leucylglycyl-l-alanyl-l-prolyl-l-seryl-l-isoleucyl-l-threonyl-l-cysteinyl-l-valyl-l-arginyl-l-arginyl-l-alanyl-l-phenylal Chemical compound C([C@H](N)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CS)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(C)C)C(=O)NCC(=O)N[C@@H](C)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CO)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CS)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](C)C(=O)N[C@@H](CC=1C=CC=CC=1)C(O)=O)C1=CC=CC=C1 CSSYQJWUGATIHM-IKGCZBKSSA-N 0.000 description 1
- 229940078795 lactoferrin Drugs 0.000 description 1
- 235000021242 lactoferrin Nutrition 0.000 description 1
- 150000002605 large molecules Chemical class 0.000 description 1
- 230000000670 limiting effect Effects 0.000 description 1
- 150000002632 lipids Chemical class 0.000 description 1
- 230000008818 liver damage Effects 0.000 description 1
- 231100000516 lung damage Toxicity 0.000 description 1
- 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 description 1
- 229920002521 macromolecule Polymers 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- DWPCPZJAHOETAG-UHFFFAOYSA-N meso-lanthionine Chemical group OC(=O)C(N)CSCC(N)C(O)=O DWPCPZJAHOETAG-UHFFFAOYSA-N 0.000 description 1
- 108020004999 messenger RNA Proteins 0.000 description 1
- 229930182817 methionine Natural products 0.000 description 1
- 238000001000 micrograph Methods 0.000 description 1
- 239000004005 microsphere Substances 0.000 description 1
- OHDXDNUPVVYWOV-UHFFFAOYSA-N n-methyl-1-(2-naphthalen-1-ylsulfanylphenyl)methanamine Chemical compound CNCC1=CC=CC=C1SC1=CC=CC2=CC=CC=C12 OHDXDNUPVVYWOV-UHFFFAOYSA-N 0.000 description 1
- 210000000822 natural killer cell Anatomy 0.000 description 1
- 238000010606 normalization Methods 0.000 description 1
- 230000017111 nuclear migration Effects 0.000 description 1
- 238000003199 nucleic acid amplification method Methods 0.000 description 1
- 210000000056 organ Anatomy 0.000 description 1
- 229910052760 oxygen Inorganic materials 0.000 description 1
- 239000001301 oxygen Substances 0.000 description 1
- 229940094443 oxytocics prostaglandins Drugs 0.000 description 1
- 229920002866 paraformaldehyde Polymers 0.000 description 1
- 230000036961 partial effect Effects 0.000 description 1
- 230000006320 pegylation Effects 0.000 description 1
- 239000008188 pellet Substances 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 230000006461 physiological response Effects 0.000 description 1
- 230000004983 pleiotropic effect Effects 0.000 description 1
- 108010054442 polyalanine Proteins 0.000 description 1
- 230000003389 potentiating effect Effects 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 230000000750 progressive effect Effects 0.000 description 1
- 230000009465 prokaryotic expression Effects 0.000 description 1
- 230000035755 proliferation Effects 0.000 description 1
- 230000000069 prophylactic effect Effects 0.000 description 1
- XEYBRNLFEZDVAW-UHFFFAOYSA-N prostaglandin E2 Natural products CCCCCC(O)C=CC1C(O)CC(=O)C1CC=CCCCC(O)=O XEYBRNLFEZDVAW-UHFFFAOYSA-N 0.000 description 1
- 230000018883 protein targeting Effects 0.000 description 1
- 238000004445 quantitative analysis Methods 0.000 description 1
- 238000010188 recombinant method Methods 0.000 description 1
- 230000007115 recruitment Effects 0.000 description 1
- 230000008263 repair mechanism Effects 0.000 description 1
- 208000020029 respiratory tract infectious disease Diseases 0.000 description 1
- 238000010839 reverse transcription Methods 0.000 description 1
- 230000036573 scar formation Effects 0.000 description 1
- 230000002784 sclerotic effect Effects 0.000 description 1
- 150000003384 small molecules Chemical class 0.000 description 1
- 210000002460 smooth muscle Anatomy 0.000 description 1
- 238000002415 sodium dodecyl sulfate polyacrylamide gel electrophoresis Methods 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 239000000243 solution Substances 0.000 description 1
- 210000000952 spleen Anatomy 0.000 description 1
- 235000000891 standard diet Nutrition 0.000 description 1
- 230000037351 starvation Effects 0.000 description 1
- 230000000638 stimulation Effects 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- 150000008163 sugars Chemical class 0.000 description 1
- 230000003319 supportive effect Effects 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 229940124597 therapeutic agent Drugs 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 231100000167 toxic agent Toxicity 0.000 description 1
- 239000003440 toxic substance Substances 0.000 description 1
- 108091006106 transcriptional activators Proteins 0.000 description 1
- 230000014616 translation Effects 0.000 description 1
- 239000012588 trypsin Substances 0.000 description 1
- 230000004614 tumor growth Effects 0.000 description 1
- 230000007306 turnover Effects 0.000 description 1
- OUYCCCASQSFEME-UHFFFAOYSA-N tyrosine Natural products OC(=O)C(N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-UHFFFAOYSA-N 0.000 description 1
- 210000005166 vasculature Anatomy 0.000 description 1
- 239000003981 vehicle Substances 0.000 description 1
- 230000029812 viral genome replication Effects 0.000 description 1
- 230000009385 viral infection Effects 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
- 238000005303 weighing Methods 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
- C07K14/52—Cytokines; Lymphokines; Interferons
- C07K14/555—Interferons [IFN]
- C07K14/57—IFN-gamma
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/04—Peptides having up to 20 amino acids in a fully defined sequence; Derivatives thereof
- A61K38/12—Cyclic peptides, e.g. bacitracins; Polymyxins; Gramicidins S, C; Tyrocidins A, B or C
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- A61K38/18—Growth factors; Growth regulators
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- A61K38/19—Cytokines; Lymphokines; Interferons
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- A61K38/19—Cytokines; Lymphokines; Interferons
- A61K38/20—Interleukins [IL]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- A61K38/19—Cytokines; Lymphokines; Interferons
- A61K38/21—Interferons [IFN]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- A61K38/19—Cytokines; Lymphokines; Interferons
- A61K38/21—Interferons [IFN]
- A61K38/217—IFN-gamma
-
- 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
-
- 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
- A61P1/04—Drugs for disorders of the alimentary tract or the digestive system for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
-
- 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
- A61P11/00—Drugs for disorders of the respiratory system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P13/00—Drugs for disorders of the urinary system
- A61P13/12—Drugs for disorders of the urinary system of the kidneys
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P21/00—Drugs for disorders of the muscular or neuromuscular system
- A61P21/02—Muscle relaxants, e.g. for tetanus or cramps
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
-
- 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
-
- 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
- A61P31/14—Antivirals for RNA viruses
-
- 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
- A61P31/14—Antivirals for RNA viruses
- A61P31/16—Antivirals for RNA viruses for influenza or rhinoviruses
-
- 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
- A61P37/00—Drugs for immunological or allergic disorders
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
-
- 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
-
- 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
-
- 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
- C07K14/52—Cytokines; Lymphokines; Interferons
- C07K14/555—Interferons [IFN]
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
- C07K16/18—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
- C07K16/18—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
- C07K16/22—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against growth factors ; against growth regulators
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
- C07K5/04—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing only normal peptide links
- C07K5/08—Tripeptides
- C07K5/0802—Tripeptides with the first amino acid being neutral
- C07K5/0804—Tripeptides with the first amino acid being neutral and aliphatic
- C07K5/0808—Tripeptides with the first amino acid being neutral and aliphatic the side chain containing 2 to 4 carbon atoms, e.g. Val, Ile, Leu
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
- C07K5/04—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing only normal peptide links
- C07K5/08—Tripeptides
- C07K5/0802—Tripeptides with the first amino acid being neutral
- C07K5/0804—Tripeptides with the first amino acid being neutral and aliphatic
- C07K5/081—Tripeptides with the first amino acid being neutral and aliphatic the side chain containing O or S as heteroatoms, e.g. Cys, Ser
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
- C07K5/04—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing only normal peptide links
- C07K5/08—Tripeptides
- C07K5/0815—Tripeptides with the first amino acid being basic
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
- C07K5/04—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing only normal peptide links
- C07K5/08—Tripeptides
- C07K5/0815—Tripeptides with the first amino acid being basic
- C07K5/0817—Tripeptides with the first amino acid being basic the first amino acid being Arg
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
- C07K5/04—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing only normal peptide links
- C07K5/08—Tripeptides
- C07K5/0819—Tripeptides with the first amino acid being acidic
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K7/00—Peptides having 5 to 20 amino acids in a fully defined sequence; Derivatives thereof
- C07K7/04—Linear peptides containing only normal peptide links
- C07K7/06—Linear peptides containing only normal peptide links having 5 to 11 amino acids
-
- 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
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2319/00—Fusion polypeptide
- C07K2319/01—Fusion polypeptide containing a localisation/targetting motif
- C07K2319/09—Fusion polypeptide containing a localisation/targetting motif containing a nuclear localisation signal
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2319/00—Fusion polypeptide
- C07K2319/70—Fusion polypeptide containing domain for protein-protein interaction
- C07K2319/74—Fusion polypeptide containing domain for protein-protein interaction containing a fusion for binding to a cell surface receptor
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)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Molecular Biology (AREA)
- Biophysics (AREA)
- Genetics & Genomics (AREA)
- Biochemistry (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Gastroenterology & Hepatology (AREA)
- Zoology (AREA)
- Immunology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Epidemiology (AREA)
- Toxicology (AREA)
- Virology (AREA)
- Oncology (AREA)
- Communicable Diseases (AREA)
- Urology & Nephrology (AREA)
- Pain & Pain Management (AREA)
- Pulmonology (AREA)
- Diabetes (AREA)
- Physical Education & Sports Medicine (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Neurology (AREA)
- Rheumatology (AREA)
- Heart & Thoracic Surgery (AREA)
- Cardiology (AREA)
- Vascular Medicine (AREA)
- Hematology (AREA)
Abstract
【選択図】なし
Description
(d)(a)、(b)、又は(c)の配列の少なくも10、好ましくは少なくとも15、の連続したアミノ酸の一続き;
(e) a)又はb)又はc)と少なくとも70%、好ましくは少なくとも80%、より好ましくは少なくとも90%、の同一性を示すアミノ酸配列、ただし細胞内シグナリング活性が維持される; 及び
(f) 多くとも10、好ましくは多くとも8、より好ましくは多くとも5のアミノ酸残基が削除され、追加され、又は置換されている(a)又は(b)又は(c)のアミノ酸配列、ただし該シグナリング活性、例えば核移行、が維持される;
(g)コンセンサス配列VxxxxVQRxAxxELIxVxxxLxPxxxxxKRxRS、ここでxは任意のアミノ酸残基である;
(h)コンセンサス配列VxxxxxQxxAxxELIxVxxxLxPxxxxxKRKRS、ここでxは任意のアミノ酸残基である;
からなる群から選ばれる配列を含み又は当該配列からなる。
である。
ここで
Xaa1、Xaa2、Xaa3、Xaa4、Xaa6、Xaa11、Xaa13、Xaa14、Xaa16、Xaa17、Xaa18、Xaa19、Xaa20、Xaa21、Xaa22、Xaa23、Xaa24、及びXaa25は任意のアミノ酸残基であり、
Xaa5は極性の荷電されていない残基、たとえばAsn又はThrであり、
Xaa7は非極性の疎水性残基、例えばPro又はLeuであり、
Xaa8は極性の荷電されていない残基、例えばGln又はAsnであり、
Xaa9は非極性の疎水性残基、例えばVal、Ile、又はLeuであり、
Xaa10は極性の塩基性残基、例えばArg、His、又はLysであり、
Xaa12は非極性の疎水性残基、例えばPhe、Val、又はIleであり、
Xaa15は非極性の疎水性残基、例えばVal、Ile、Metである。
配列
からなる。
からなり又は当該配列を含む。
、を含み又は当該配列からなるペプチドを含む。他の例となる医薬組成物は、ターゲティングドメインに複合体化された生物学的に活性な分子を含む複合体を含み、該ターゲティングドメインは、アミノ酸配列CSRNLIDC-リンカー-CSRNLIDCSを含み、ここで該リンカーは2〜7、好ましくは3〜5、のアミノ酸残基のアミノ酸配列である。
ヌクレオチド配列:マウスインターフェロンガンマ(NCBI参照配列: NM_008337.3)
マウスIFNガンマについてのアミノ酸配列
融合タンパク質(BiPPB-IFNγ)のヌクレオチド配列
BiPPB-IFNγについてのアミノ酸配列
イタリックはBiPPBを示す、通常のテキストがIFNγ模倣物を示す、太字はリンカー又はスペーサーを示す。図4も参照されたい。
融合タンパク質(BiPPB-IFNγ模倣物)のヌクレオチド配列
BiPPB-IFNγ模倣物についてのアミノ酸配列
イタリックはBiPPBを示す、通常テキストがIFNγ模倣物を示す、太字はリンカー又はスペーサーを示す。図5も参照されたい。
我々は、免疫−細胞化学により評価されたときの(α−SMA染色)、マウスNIH3T3線維芽細胞における開裂したIFNγ模倣ペプチドの抗線維効果を評価した。簡潔に言うと、3T3線維芽細胞が、24ウェルプレート中に6x104細胞/ウェルの密度で蒔かれ、24時間後、細胞が0.5% FBS含有培地で一晩飢餓状態にされた。その後、細胞が、種々の化合物(PDGF 50 ng/ml、TGFβ 10 ng/ml、模倣IFNγ 1μg/ml、50ng/mlのPDGF + 1μg/mlの模倣IFNγ、及び10 ng/mlのTGFβ+1μg/mlの模倣IFNγ)を有する飢餓培地中でインキュベートされた。48時間のインキュベーション後、細胞が洗浄され、エタノール:アセトン(1:1)により固定され、そして、α−SMA(活性化した線維芽細胞のマーカー)について染色された。
我々は、LX2細胞(ヒトHSC)におけるBiPPB及び模倣-BiPPBの結合を決定した。簡潔に言うと、LX2細胞が、48ウェルプレート中に、3x104細胞/ウェルの細胞密度でプレートされた。24時間後、細胞が培地(−FBS)中で一晩飢餓状態にされた。次に、結合の為に、細胞が種々の化合物(BiPPB、PPB-HAS、及びBiPPB-模倣IFNγ)と、2時間室温でインキュベートされた。結合後、細胞がPBSにより強く洗浄され、エタノール:アセトン(1:1)により固定化され、そして、PPBについて染色された。結果が図7に示される。
組み換えIFNγ、模倣IFNγ、組み換え融合タンパク質IFNγ−BiPPB、及び組み換え融合タンパク質模倣IFNγ−BiPPBが、CCl4誘発急性肝臓損傷マウスモデルにおける抗線維効果について試験された。1日目で、該動物は、オリーブ油中の四塩化炭素(CCl4)又はオリーブ油(対照n=6)の1回の腹腔内投与量(1ml/kg)を与えられた。CCl4注入の24時間後、2及び3日目で、動物が、PBS (n=6)、50,000 U/マウスのIFNγ (n=6)、50,000 U/マウスの模倣IFNγ(n=5)、50,000 U/マウスのIFNγ-BiPPB (n=6)、50,000 U/マウスの模倣IFNγ-BiPPB (n=6)のいずれかにより処置された。その後、4日目で、動物は犠牲にされ、そして、血球計数が実施され、及び、抗線維症効果(Hemmann S, Graf J, Roderfeld M, Roeb. J Hepatol. 2007 May;46(5):955-75を参照)が定量的PCRを用いて評価された。結果が図8及び9に提示される。
肝損傷を誘発する為に、マウスが腹腔内にCCl4を1日目に注入された。2及び3日目で、マウスは、IFNγ(5 ug/投与量)、模倣IFNg-PEG、模倣IFNg-PEG-BiPPB (5μg/投与量)、又はPBS単独により処置された。4日目で、動物が犠牲にされ、肝臓及び種々の臓器がさらなる分析の為に集められた。肝臓切片がアセトンにより固定化され、乾燥され、そしてPBSにより再水和された。次に、該切片が、一次抗体(コラーゲン、SMA、及びデスミン)と一緒に1時間インキュベートされた。その後、該切片が、内因性ペルオキシダーゼ活性に対する0.03%のH2O2により30分間ブロックされた。その後、切片が二次抗体HRP結合ウサギ抗ヤギ抗体(1:100、DAKO)、次にHRP結合ヤギ抗ウサギ抗体(1:100、DAKO)と、30分間インキュベートされた。ペルオキシダーゼ活性が、AEC(Sigma)を用いて20分間発現され、そして、核がヘマトキシリン(Fluka)により対比染色された。該切片は、カイザーゼラチンを載せられ、そして、光学顕微鏡(Olympus)下で可視化された。定量的分析の為に、27の顕微鏡写真が撮られ、そして、陽性に染色した領域がコンピュータ化オリンパスCell Dイメージングソフトウェアを用いて定量された。結果が図10に示される。
肝臓組織からの全RNAが、製造者の指示に従いRNeasyミニキット(Qiagen)を用いて単離された。RNA濃度は、UVスペクトロメーター(NanoDrop Technologies、ウィルミントン、デラウェア州)により定量された。全RNA(1.6 mg)が、cDNA合成キット(Promega)を用いた全量50 μlでの逆転写の為に用いられた。全てのプライマーは、Sigma-Genosys(Haverhill、英国)から購入された。10ngのcDNAが、定量的リアルタイムPCR分析の為に用いられた。反応は、製造者の指示に従いSYBRグリーンPCRミックス(Applied Biosystems)を用いて実施された。試料は、ABI7900HTシークエンス検出システム(Applied Biosystems)により分析された。最後に、閾値サイクル数(threshold cycle number、Ct)が、それぞれの遺伝子について計算され、そして、相対的な遺伝子発現が、参照遺伝子GAPDHの発現についての正規化後に計算された。結果が図11に示される。副作用の分析が図12に示される。
オスのbalb/cマウス(20-22g)が、オリーブ油又は増加する用量のCCl4 (1週目: 0.5 ml/kg; 2週目: 0.8 ml/kg、及び3〜8週目: 1 ml/kg、オリーブ油中に調製された)により週2回、8週間の腹腔内注入で処理された。7及び8週目において、マウスは、静脈内に、PBS、模倣IFNγ-PEG、又は模倣IFNγ-PEG-BiPPB (5μg/マウス、週当たり3回)により処置された。全てのマウスが8週目で犠牲にされ、血液及び肝臓試料が次の測定の為に集められた。肝臓切片は、コラーゲンI及びデスミン、CD68、33D1、及びMHCクラスIIについて染色された。標的とされた切り取られた形のIFNγ(模倣IFNγ-biPPB)が、マウスにおけるこの慢性肝臓線維症における線維症パラメータの実質的な減少を誘発することが発見され、コラーゲンI及びデスミン両方の染色が、処理されていないCCl4-マウスと比較して、模倣IFNγ-biPPBにより処理されたCCl4マウスにおいて顕著に減少された。対照的に、レセプター結合部位を欠くターゲティングされていない模倣IFNγによる処理は、これらのパラメータに対する効果を何も誘発しない一方で完全長マウスIFNγはコラーゲンI及びデスミン染色における少しの減少だけを誘発した。天然(マウス)IFNγは、炎症細胞(CD68+マクロファージ、好中球、33D1+樹状細胞)の浸潤を誘発し、及び、増加したMHCII発現を誘発した。対照的に、模倣IFNγ-BiPPBは、肝臓におけるこの増加した炎症応答を誘発しなかった。
20〜25gの重さの正常なオスのC57BL/6及びBalb/cマウスがHarlan (Zeist、オランダ)から得られた。それらは、12:12時間の明/暗サイクルで維持され、及び、自由に標準的な食餌を受けた。動物研究についての全ての実験プロトコルは、グローニンゲン大学の動物倫理委員会により承認された。皮下腫瘍を誘発する為に、C26細胞が、それらを増殖フェーズに維持する為に、動物における注入の1日前に、125-mm3フラスコにおいて培養された。細胞がトリプシン処理により脱着され、そして、トリプシンが遠心により除去された。細胞ペレットがPBS中に再懸濁された。100μlのPBS中に懸濁された1 × 106の細胞 (B16及びC26細胞)の全部がBalb/cマウスの脇腹に皮下注入された。腫瘍成長が、デジタルVernierカリパー(a digital Vernier caliper)を用いて腫瘍サイズを測定することにより追跡された。腫瘍体積が式:a × b2 / 2、を用いて確立され、ここでaは腫瘍長さを示し、そして、bは腫瘍幅を示す。C26腫瘍が、記載されたとおりに、マウスにおいて誘発された。処置が、腫瘍体積が50〜100mm3に達した5日目に開始された。というのも、この腫瘍サイズが該処置の開始のための最適な腫瘍サイズとして示されているからである。動物(群当たりn=4)が、麻酔(O2/イソフルラン)下で1日おきに、ビヒクル(PBS)、模倣IFNγ-PEG (5μg/投与)、又は模倣IFNγ-PEG-BiPPB (5 μg/投与)の6の用量を静脈内に注入された。腫瘍サイズは麻酔科で測定された。C26腫瘍を有する動物が、20日目で殺された。というのも、該処置の効果が観察されなかったからである。動物は、ガス麻酔(O2/イソフルラン)下で殺され、そして腫瘍が分離され、そして、凍結切片の為に冷たいイソペンタン中に固定化された。
Cys(1)-Cys(1)及びCys(2)-Cys(2) ジスルフィド架橋環状化
Claims (29)
- インターフェロンガンマ(IFNγ)のアナログであって、その天然のレセプターへの結合を媒介する部分が少なくとも機能的に破壊され、且つ、該アナログが細胞内のIFNγ活性を媒介することができるシグナリング部分を含み、該シグナリング部分がそのN末端で、任意的にリンカーを介して、該IFNγレセプター以外の細胞表面レセプターへ結合することができる少なくとも1つのターゲティングドメインを備えられている、前記アナログ。
- 細胞内活性を媒介する該シグナリング部分が、多塩基性核局在シグナル(NLS)モチーフを含む、請求項1に記載のアナログ。
- 該多塩基性NLSモチーフがアミノ酸配列(R)KRXRS(R)を含み、Xが任意のアミノ酸残基であり、好ましくはXがR、K、S、又はTであるところの(R)KRXRS(R)を含む、請求項2に記載のアナログ。
- 該シグナリング部分が、
(d) (a)、(b)、又は(c)における配列の少なくとも10、好ましくは少なくとも15、の連続したアミノ酸の一続き;
(e) (a)又は(b)又は(c)と少なくとも70%、好ましくは少なくとも80%、より好ましくは少なくとも90%の同一性を示すアミノ酸配列、ただし該細胞内シグナリング活性が維持されている; 及び
(f) 多くとも10、好ましくは多くとも8、より好ましくは多くとも5のアミノ酸残基が削除され、追加され、又は置換されている(a)又は(b)又は(c)下のアミノ酸配列、ただし該シグナリング活性、例えば核局在、が維持されている
(g) コンセンサス配列VxxxxVQRxAxxELIxVxxxLxPxxxxxKRxRS、ここでxは任意のアミノ酸残基である;
(h) コンセンサス配列VxxxxxQxxAxxELIxVxxxLxPxxxxxKRKRS、ここでxは任意のアミノ酸残基である; 及び
(i) コンセンサス配列Vxxx[Q/N][F/V/I]Q[R/H][Q/K]A[F/V/I][N/H]ELI[R/Q]Vx[H/A][Q/E]L[L/S]P[E/A][S/A][S/A][L/K]xxKRKRS、ここでxは任意のアミノ酸残基である;
からなる群から選ばれる配列を含む、請求項1〜3のいずれか1項に記載のアナログ。 - 配列:
ここで
Xaa1、Xaa2、Xaa3、Xaa4、Xaa6、Xaa11、Xaa13、Xaa14、Xaa16、Xaa17、Xaa18、Xaa19、Xaa20、Xaa21、Xaa22、Xaa23、Xaa24、及びXaa25が任意のアミノ酸残基であり、
Xaa5が極性の、荷電していない残基であり、例えばAsn又はThrなど、
Xaa7が非極性の、疎水性残基であり、例えばPro又はLeuなど、
Xaa8が極性の、荷電していない残基であり、例えばGln又はAsnなど、
Xaa9が非極性の、疎水性残基であり、例えばVal、Ile、又はLeuなど、
Xaa10が極性の、塩基性残基であり、例えばArg、His、又はLysなど、
Xaa12が非極性の、疎水性残基であり、例えばPhe、Val、又はIleなど、
Xaa15が非極性の、疎水性残基である、例えばVal、Ile、又はMetなど、
に従うシグナリング部分を含む、請求項4に記載のアナログ。 - 該ターゲティングドメインが、線維芽細胞及び線維芽細胞様細胞、好ましくは筋線維芽細胞、門脈線維芽細胞、メサンギウム細胞、間質線維芽細胞、肺胞線維芽細胞、及び/又は間質細胞に特異的であるレセプターに結合することができる、請求項1〜5のいずれか1項に記載のアナログ。
- 該ターゲティングドメインが、オリゴ糖又は糖タンパク質に対するレセプター、好ましくはマンノース6-ホスフェート/インスリン様成長因子IIレセプター(M6P/IGF2R)、アシアログリコプロテイン(ASGP)レセプター、又はマンノースレセプター(CD 206)、に結合することができる、請求項1〜6のいずれか1項に記載のアナログ。
- 該ターゲティングドメインが、キャリア分子と複合体化されたオリゴ糖、好ましくはマンノース(-6-ホスフェート)又はラクトースである、請求項7に記載のアナログ。
- 該レセプターが、PDGFレセプター、コラーゲンVI型レセプター、並びに、TGFβレセプター、TNFαレセプター、インスリン成長因子レセプター、VEGFレセプター、ケモカインレセプター、及びIL1βレセプターを包含するサイトカインレセプターからなる群から選ばれるものである、請求項1〜6のいずれか1項に記載のアナログ。
- レセプターがPDGFレセプター、好ましくはPDGFβレセプターである、請求項9に記載のアナログ。
- 該ターゲティングドメインが少なくとも1つの環状ペプチド部分を含む、請求項1〜10のいずれか1項に記載のアナログ。
- 該ターゲティングドメインが、環状ペプチド部分の少なくとも1つのタンデムリピート、好ましくは同一の環状ペプチド部分、を含む、請求項11に記載のアナログ。
- タンデムリピート内の該2つの環状ペプチド部分が2〜7のアミノ酸のリンカーを介して連結されている、請求項11に記載のアナログ。
- 該リンカーが、(i)配列K(GS)mGG、ここでmは1又は2である、及び(ii)一般式 [G n D m]の配列、ここでn+mが4〜7であり、n ≧ 4且つmが0〜3の整数である、からなる群から選ばれるものである、請求項13に記載のアナログ。
- 該ターゲティングドメインが、少なくともアミノ酸配列RGD、KPT、SRN、NLI、及び/又はLIDを含む、請求項1〜14のいずれか1項に記載のアナログ。
- 該ターゲティングドメインが、アミノ酸配列CSRNLIDC-リンカー-CSRNLIDCSを含み、該リンカーが3〜7、好ましくは4又は5、のアミノ酸残基のアミノ酸配列である、請求項15に記載のアナログ。
- ターゲティングドメインに複合体化された関心のある化合物を含む複合体であって、該ターゲティングドメインが、アミノ酸配列X1SRNLIDX2-リンカー-X3SRNLIDX4を含み、ここで、X1及びX2の対及びX3及びX4の対が、二環構造が形成され、配列SRNLIDが環のそれぞれの部分であるように、結合、好ましくはペプチド結合、を形成でき、且つ、該リンカーが2〜7、好ましくは3〜5、のアミノ酸残基のアミノ酸配列である、前記複合体。
- 好ましくはポリエチレングリコール及びその誘導体からなる群から選ばれる、少なくとも1つの非抗原性ポリマーを備えられた、請求項1〜17のいずれか1項に記載のアナログ又は複合体。
- 請求項1〜18のいずれか1項に記載のタンパク質性アナログ又は複合体をコードする、分離された核酸配列。
- 請求項19に記載の分離された核酸配列を含む発現ベクター。
- 請求項18に記載の核酸配列又は請求項20に記載のベクターを含む宿主細胞であって、好ましくは該宿主細胞がバクテリア宿主細胞又は哺乳類宿主細胞である、前記宿主細胞。
- 請求項1〜18のいずれか1項に記載のアナログ又は複合体と、医薬的に許容できるキャリア、アジュバント、及び/又は添加物とを含む医薬組成物。
- ガン、ウィルス性疾患、線維性疾患、硬化性疾患、及び慢性又は急性の炎症疾患から選ばれる疾患の治療的又は予防的処置の為の医薬の製造の為に、請求項1〜18のいずれか1項に記載のアナログ又は複合体を使用する方法。
- ガン、ウィルス性疾患、線維性疾患、硬化性疾患、及び慢性又は急性の炎症疾患から選ばれる疾患の治療的又は予防的処置の為の、請求項1〜18のいずれか1項に記載のアナログ又は複合体。
- 肝臓疾患、好ましくは慢性の肝臓疾患、例えば肝硬変など、の処置の為の、請求項24に記載のアナログ又は複合体。
- ウィルス性疾患、好ましくはインフルエンザウィルス又は呼吸器合胞体ウィルス(RSV)により引き起こされる疾患、の処置の為の、請求項24に記載のアナログ又は複合体。
- ガン、ウィルス性疾患、線維性疾患、硬化性疾患、及び慢性又は急性の炎症疾患から選ばれる疾患の治療的又は予防的処置の為の方法であって、その必要がある対象に、請求項1〜18のいずれか1項に記載のアナログ又は複合体の有効量を投与することを含む、前記方法。
- 該疾患が、糸球体硬化症、間質性線維症、肺線維症、アテローム性動脈硬化症、関節リウマチ、クローン病、潰瘍性大腸炎、糸球体腎炎、及び敗血症からなる群から選ばれるものであり、好ましくは該疾患が肝臓疾患であり、より好ましくは慢性肝臓疾患、例えば肝硬変である、請求項27に記載の方法。
- 該投与が、粘膜投与を含み、好ましくは肺内投与を含む、請求項27又は28に記載の方法。
Applications Claiming Priority (5)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
EP09181049A EP2343081A1 (en) | 2009-12-31 | 2009-12-31 | Interferon analogs |
EP09181049.9 | 2009-12-31 | ||
US30297310P | 2010-02-10 | 2010-02-10 | |
US61/302,973 | 2010-02-10 | ||
PCT/NL2010/050897 WO2011081523A1 (en) | 2009-12-31 | 2010-12-30 | Interferon analogs |
Publications (2)
Publication Number | Publication Date |
---|---|
JP2013516170A true JP2013516170A (ja) | 2013-05-13 |
JP5914356B2 JP5914356B2 (ja) | 2016-05-11 |
Family
ID=42174637
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2012547044A Expired - Fee Related JP5914356B2 (ja) | 2009-12-31 | 2010-12-30 | インターフェロンアナログ |
Country Status (11)
Country | Link |
---|---|
US (4) | US9381230B2 (ja) |
EP (2) | EP2343081A1 (ja) |
JP (1) | JP5914356B2 (ja) |
KR (1) | KR20120107000A (ja) |
CN (1) | CN102917726B (ja) |
BR (1) | BR112012016396A2 (ja) |
CA (1) | CA2786090A1 (ja) |
DK (1) | DK2519250T3 (ja) |
ES (1) | ES2588436T3 (ja) |
PL (1) | PL2519250T3 (ja) |
WO (1) | WO2011081523A1 (ja) |
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2019534002A (ja) * | 2016-10-24 | 2019-11-28 | オリオニス バイオサイエンシズ エヌブイ | 標的変異インターフェロン−ガンマおよびその使用 |
Families Citing this family (11)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
PL2908837T3 (pl) * | 2012-10-19 | 2019-08-30 | Vect-Horus | Kompozycje do dostarczania leku |
US11867701B2 (en) | 2016-04-27 | 2024-01-09 | Washington University | Methods for prognosing crohn's disease comprising human defensin 5 (HD5) |
WO2018081388A1 (en) * | 2016-10-26 | 2018-05-03 | Washington University | Compositions comprising desaminotyrosine and uses thereof to enhance type i interferon stimulation |
EP3565638B8 (en) * | 2017-01-06 | 2024-04-10 | BicycleRD Limited | Bicycle conjugate for treating cancer |
CN108219003A (zh) * | 2018-01-26 | 2018-06-29 | 南华大学 | 融合蛋白及其制备方法和应用 |
CN108285490A (zh) * | 2018-01-26 | 2018-07-17 | 西南交通大学 | 一种高亲和性结合i型胶原蛋白的gst融合蛋白制备及其应用 |
EP3773674A4 (en) * | 2018-03-28 | 2022-05-25 | Orionis Biosciences, Inc. | BIFUNCTIONAL PROTEINS AND THEIR CONSTRUCTION |
US11180531B2 (en) | 2018-06-22 | 2021-11-23 | Bicycletx Limited | Bicyclic peptide ligands specific for Nectin-4 |
CA3123086A1 (en) | 2018-12-19 | 2020-06-25 | The Board Of Trustees Of The Leland Stanford Junior University | Bifunctional molecules for lysosomal targeting and related compositions and methods |
WO2020181130A2 (en) * | 2019-03-05 | 2020-09-10 | MiRagen Therapeutics, Inc. | Polynucleotide conjugates and uses thereof |
CA3133643A1 (en) | 2019-03-28 | 2020-10-01 | Orionis Biosciences, Inc. | Therapeutic interferon alpha 1 proteins |
Citations (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US5770191A (en) * | 1995-05-24 | 1998-06-23 | University Of Florida | Active C-terminal peptides of interferon--gamma and their use |
JP2002532384A (ja) * | 1998-10-08 | 2002-10-02 | ステイヒテイング・ボール・デ・テヒニシエ・ベテンシヤツペン | 星状細胞のためのペプチドを基剤としたキャリヤーデバイス |
JP2004510709A (ja) * | 2000-09-08 | 2004-04-08 | アンスティトゥー パストゥール ド リール | ペプチドと親油性ベクターとを溶液中で結合するための方法およびその使用 |
JP2009508947A (ja) * | 2005-09-20 | 2009-03-05 | ニューヨーク・ユニバーシティ | インターフェロンを用いる肺疾患の処置方法 |
WO2010151495A2 (en) * | 2009-06-26 | 2010-12-29 | University Of Florida Research Foundation Inc. | Materials and methods for treating and preventing viral infections |
Family Cites Families (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
EP0844252A3 (en) | 1996-11-15 | 1998-07-08 | Remacle, José | Cyclic peptides bearing a tail designed for subsequent chemical coupling and process for preparing same |
AU2003239774A1 (en) * | 2002-07-03 | 2004-01-23 | Maxygen Holdings Ltd. | Full-length interferon gamma polypeptide variants |
GB0624308D0 (en) | 2006-12-05 | 2007-01-17 | Molmed Spa | Combination product |
US20100028297A1 (en) * | 2006-12-19 | 2010-02-04 | Stewart Edward J | Coadministration of alpha-fetoprotein and an immunomodulatory agent to treat multiple sclerosis |
-
2009
- 2009-12-31 EP EP09181049A patent/EP2343081A1/en not_active Ceased
-
2010
- 2010-12-30 JP JP2012547044A patent/JP5914356B2/ja not_active Expired - Fee Related
- 2010-12-30 KR KR1020127020081A patent/KR20120107000A/ko not_active Application Discontinuation
- 2010-12-30 EP EP10807562.3A patent/EP2519250B1/en not_active Not-in-force
- 2010-12-30 WO PCT/NL2010/050897 patent/WO2011081523A1/en active Application Filing
- 2010-12-30 US US13/519,808 patent/US9381230B2/en active Active
- 2010-12-30 CA CA2786090A patent/CA2786090A1/en not_active Abandoned
- 2010-12-30 ES ES10807562.3T patent/ES2588436T3/es active Active
- 2010-12-30 CN CN201080062942.2A patent/CN102917726B/zh not_active Expired - Fee Related
- 2010-12-30 DK DK10807562.3T patent/DK2519250T3/en active
- 2010-12-30 BR BR112012016396A patent/BR112012016396A2/pt not_active Application Discontinuation
- 2010-12-30 PL PL10807562.3T patent/PL2519250T3/pl unknown
-
2016
- 2016-06-09 US US15/177,663 patent/US20160297861A1/en not_active Abandoned
-
2018
- 2018-04-11 US US15/950,512 patent/US10442845B2/en not_active Expired - Fee Related
-
2019
- 2019-09-09 US US16/565,079 patent/US20190389923A1/en not_active Abandoned
Patent Citations (6)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US5770191A (en) * | 1995-05-24 | 1998-06-23 | University Of Florida | Active C-terminal peptides of interferon--gamma and their use |
US6120762A (en) * | 1995-05-24 | 2000-09-19 | University Of Florida | C-terminal peptides of interferon γ |
JP2002532384A (ja) * | 1998-10-08 | 2002-10-02 | ステイヒテイング・ボール・デ・テヒニシエ・ベテンシヤツペン | 星状細胞のためのペプチドを基剤としたキャリヤーデバイス |
JP2004510709A (ja) * | 2000-09-08 | 2004-04-08 | アンスティトゥー パストゥール ド リール | ペプチドと親油性ベクターとを溶液中で結合するための方法およびその使用 |
JP2009508947A (ja) * | 2005-09-20 | 2009-03-05 | ニューヨーク・ユニバーシティ | インターフェロンを用いる肺疾患の処置方法 |
WO2010151495A2 (en) * | 2009-06-26 | 2010-12-29 | University Of Florida Research Foundation Inc. | Materials and methods for treating and preventing viral infections |
Non-Patent Citations (1)
Title |
---|
JPN6015000056; TAMURA, R. et al.: '"Fibroblasts as target and effector cells in Japanese patients with sarcoidosis."' LUNG Vol.176, No.2, 19980226, P.75-87 * |
Cited By (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2019534002A (ja) * | 2016-10-24 | 2019-11-28 | オリオニス バイオサイエンシズ エヌブイ | 標的変異インターフェロン−ガンマおよびその使用 |
JP7204643B2 (ja) | 2016-10-24 | 2023-01-16 | オリオニス バイオサイエンシズ ビーブイ | 標的変異インターフェロン-ガンマおよびその使用 |
Also Published As
Publication number | Publication date |
---|---|
US20130064791A1 (en) | 2013-03-14 |
BR112012016396A2 (pt) | 2017-07-04 |
CN102917726A (zh) | 2013-02-06 |
EP2519250B1 (en) | 2016-06-01 |
WO2011081523A1 (en) | 2011-07-07 |
KR20120107000A (ko) | 2012-09-27 |
US9381230B2 (en) | 2016-07-05 |
US20180298075A1 (en) | 2018-10-18 |
ES2588436T3 (es) | 2016-11-02 |
CN102917726B (zh) | 2015-03-25 |
EP2343081A1 (en) | 2011-07-13 |
JP5914356B2 (ja) | 2016-05-11 |
PL2519250T3 (pl) | 2016-12-30 |
CA2786090A1 (en) | 2011-07-07 |
US20160297861A1 (en) | 2016-10-13 |
EP2519250A1 (en) | 2012-11-07 |
US20190389923A1 (en) | 2019-12-26 |
DK2519250T3 (en) | 2016-09-05 |
US10442845B2 (en) | 2019-10-15 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
JP5914356B2 (ja) | インターフェロンアナログ | |
Bansal et al. | Novel engineered targeted interferon‐gamma blocks hepatic fibrogenesis in mice | |
JP5670875B2 (ja) | カーゴ分子の送達ビヒクルおよび炎症反応を免疫調節するための生物学的治療剤としてのYopM | |
US9790286B2 (en) | Stereoisomer peptides, their polymer conjugates, their encapsulation into nanoparticles, and uses thereof for the treatment of diseases caused by abnormal angiogenesis | |
US8906355B2 (en) | Synthetic stereoisomer peptides in the retro-inverso and inverso configuration, and with cyclic and linear structure, their polymer conjugates, their encapsulation in polymer particles, and uses thereof | |
JP2013538564A (ja) | 抗ウイルス剤 | |
JP6158097B2 (ja) | 炎症を抑制するためのペプチド | |
Rachmawati et al. | Chemical modification of interleukin-10 with mannose 6-phosphate groups yields a liver-selective cytokine | |
US8715986B2 (en) | Stereoisomer peptides, ligand-targeted multi- stereoisomer peptide polymer conjugates, and uses thereof | |
US11352404B2 (en) | Phosphatidylserine targeting fusion molecules and methods for their use | |
JP2023540486A (ja) | 免疫原性コロナウイルス融合タンパク質および関連方法 | |
JP2022545265A (ja) | 筋萎縮を治療するためのペプチド | |
JP2023145635A (ja) | 免疫調節特性を有するペプチド | |
Wan et al. | Optimizing size and copy number for PEG-fMLF (N-formyl-methionyl-leucyl-phenylalanine) nanocarrier uptake by macrophages | |
JP5666110B2 (ja) | 高機能化hvj−eの開発 | |
JP2023518954A (ja) | Ngrコンジュゲート及びその使用 | |
EP2081952B1 (en) | Peptides | |
JP2022553367A (ja) | 非アルコール性脂肪肝の治療 | |
JP2020518588A (ja) | I型およびiii型インターフェロン融合分子ならびにこれらの使用のための方法 |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
A621 | Written request for application examination |
Free format text: JAPANESE INTERMEDIATE CODE: A621 Effective date: 20131225 |
|
A977 | Report on retrieval |
Free format text: JAPANESE INTERMEDIATE CODE: A971007 Effective date: 20141224 |
|
A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20150109 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20150409 |
|
A02 | Decision of refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A02 Effective date: 20150825 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20151208 |
|
A911 | Transfer to examiner for re-examination before appeal (zenchi) |
Free format text: JAPANESE INTERMEDIATE CODE: A911 Effective date: 20160125 |
|
TRDD | Decision of grant or rejection written | ||
A01 | Written decision to grant a patent or to grant a registration (utility model) |
Free format text: JAPANESE INTERMEDIATE CODE: A01 Effective date: 20160307 |
|
A61 | First payment of annual fees (during grant procedure) |
Free format text: JAPANESE INTERMEDIATE CODE: A61 Effective date: 20160404 |
|
R150 | Certificate of patent or registration of utility model |
Ref document number: 5914356 Country of ref document: JP Free format text: JAPANESE INTERMEDIATE CODE: R150 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
LAPS | Cancellation because of no payment of annual fees |