JP6653120B2 - Ikaros阻害に基づく抗炎症薬 - Google Patents
Ikaros阻害に基づく抗炎症薬 Download PDFInfo
- Publication number
- JP6653120B2 JP6653120B2 JP2015043590A JP2015043590A JP6653120B2 JP 6653120 B2 JP6653120 B2 JP 6653120B2 JP 2015043590 A JP2015043590 A JP 2015043590A JP 2015043590 A JP2015043590 A JP 2015043590A JP 6653120 B2 JP6653120 B2 JP 6653120B2
- Authority
- JP
- Japan
- Prior art keywords
- ikaros
- inflammatory
- cells
- gene
- expression
- 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.)
- Active
Links
- 101150016712 IKZF1 gene Proteins 0.000 title claims description 430
- 102100037799 DNA-binding protein Ikaros Human genes 0.000 title claims description 351
- 229940124599 anti-inflammatory drug Drugs 0.000 title description 18
- 230000005764 inhibitory process Effects 0.000 title description 4
- 238000000034 method Methods 0.000 claims description 198
- 210000004027 cell Anatomy 0.000 claims description 187
- 230000014509 gene expression Effects 0.000 claims description 163
- 239000000126 substance Substances 0.000 claims description 138
- 206010061218 Inflammation Diseases 0.000 claims description 129
- 230000004054 inflammatory process Effects 0.000 claims description 128
- 210000002919 epithelial cell Anatomy 0.000 claims description 114
- 150000007523 nucleic acids Chemical class 0.000 claims description 114
- 102000039446 nucleic acids Human genes 0.000 claims description 103
- 108020004707 nucleic acids Proteins 0.000 claims description 103
- 108090000623 proteins and genes Proteins 0.000 claims description 98
- 241000282414 Homo sapiens Species 0.000 claims description 70
- 238000012360 testing method Methods 0.000 claims description 69
- 239000002260 anti-inflammatory agent Substances 0.000 claims description 66
- 102000004169 proteins and genes Human genes 0.000 claims description 62
- 241001465754 Metazoa Species 0.000 claims description 52
- 210000001519 tissue Anatomy 0.000 claims description 49
- 108020004459 Small interfering RNA Proteins 0.000 claims description 41
- 238000012216 screening Methods 0.000 claims description 36
- 230000001965 increasing effect Effects 0.000 claims description 34
- 208000027866 inflammatory disease Diseases 0.000 claims description 31
- 101000599038 Homo sapiens DNA-binding protein Ikaros Proteins 0.000 claims description 30
- 108010013958 Ikaros Transcription Factor Proteins 0.000 claims description 29
- 102000017182 Ikaros Transcription Factor Human genes 0.000 claims description 29
- 230000028709 inflammatory response Effects 0.000 claims description 27
- 230000027455 binding Effects 0.000 claims description 25
- 229940121363 anti-inflammatory agent Drugs 0.000 claims description 23
- 238000011282 treatment Methods 0.000 claims description 23
- 239000000203 mixture Substances 0.000 claims description 22
- 230000000638 stimulation Effects 0.000 claims description 20
- 239000003112 inhibitor Substances 0.000 claims description 19
- 210000004400 mucous membrane Anatomy 0.000 claims description 18
- 230000001105 regulatory effect Effects 0.000 claims description 16
- 230000002401 inhibitory effect Effects 0.000 claims description 15
- 230000003110 anti-inflammatory effect Effects 0.000 claims description 14
- 206010042033 Stevens-Johnson syndrome Diseases 0.000 claims description 11
- 231100000168 Stevens-Johnson syndrome Toxicity 0.000 claims description 11
- 238000005259 measurement Methods 0.000 claims description 11
- 230000002265 prevention Effects 0.000 claims description 9
- 230000002829 reductive effect Effects 0.000 claims description 9
- 230000008595 infiltration Effects 0.000 claims description 8
- 238000001764 infiltration Methods 0.000 claims description 8
- 230000002103 transcriptional effect Effects 0.000 claims description 8
- 108060008682 Tumor Necrosis Factor Proteins 0.000 claims description 6
- 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 claims description 6
- 229960002986 dinoprostone Drugs 0.000 claims description 4
- XEYBRNLFEZDVAW-UHFFFAOYSA-N prostaglandin E2 Natural products CCCCCC(O)C=CC1C(O)CC(=O)C1CC=CCCCC(O)=O XEYBRNLFEZDVAW-UHFFFAOYSA-N 0.000 claims description 4
- 102000003390 tumor necrosis factor Human genes 0.000 claims description 4
- 230000001747 exhibiting effect Effects 0.000 claims description 3
- 239000003860 topical agent Substances 0.000 claims description 2
- 108020004999 messenger RNA Proteins 0.000 description 84
- 108091032973 (ribonucleotides)n+m Proteins 0.000 description 64
- 108020004414 DNA Proteins 0.000 description 63
- 239000002773 nucleotide Substances 0.000 description 61
- 125000003729 nucleotide group Chemical group 0.000 description 60
- 230000000694 effects Effects 0.000 description 58
- 235000018102 proteins Nutrition 0.000 description 57
- 230000006870 function Effects 0.000 description 56
- 125000003275 alpha amino acid group Chemical group 0.000 description 51
- 239000003814 drug Substances 0.000 description 50
- 230000000295 complement effect Effects 0.000 description 43
- 235000001014 amino acid Nutrition 0.000 description 39
- 229940024606 amino acid Drugs 0.000 description 37
- 150000001413 amino acids Chemical class 0.000 description 36
- 241000699666 Mus <mouse, genus> Species 0.000 description 35
- 150000001875 compounds Chemical class 0.000 description 35
- 108091034117 Oligonucleotide Proteins 0.000 description 34
- 210000000981 epithelium Anatomy 0.000 description 34
- 239000013604 expression vector Substances 0.000 description 34
- 102000040430 polynucleotide Human genes 0.000 description 34
- 108091033319 polynucleotide Proteins 0.000 description 34
- 239000002157 polynucleotide Substances 0.000 description 34
- 230000000692 anti-sense effect Effects 0.000 description 32
- 230000002757 inflammatory effect Effects 0.000 description 32
- 229940079593 drug Drugs 0.000 description 31
- 108090000765 processed proteins & peptides Proteins 0.000 description 28
- 238000002347 injection Methods 0.000 description 27
- 239000007924 injection Substances 0.000 description 27
- 230000008685 targeting Effects 0.000 description 26
- 239000013598 vector Substances 0.000 description 26
- 210000003491 skin Anatomy 0.000 description 25
- 241000699670 Mus sp. Species 0.000 description 23
- 102000008230 Toll-like receptor 3 Human genes 0.000 description 23
- 108010060885 Toll-like receptor 3 Proteins 0.000 description 23
- 239000003795 chemical substances by application Substances 0.000 description 21
- 102000004196 processed proteins & peptides Human genes 0.000 description 21
- 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 20
- 108091027967 Small hairpin RNA Proteins 0.000 description 19
- -1 aromatic amino acids Chemical class 0.000 description 19
- 238000001514 detection method Methods 0.000 description 19
- 210000001339 epidermal cell Anatomy 0.000 description 19
- 239000000523 sample Substances 0.000 description 19
- 239000004055 small Interfering RNA Substances 0.000 description 19
- 241000283707 Capra Species 0.000 description 17
- 102000053642 Catalytic RNA Human genes 0.000 description 17
- 108090000994 Catalytic RNA Proteins 0.000 description 17
- 239000002609 medium Substances 0.000 description 17
- 229920001184 polypeptide Polymers 0.000 description 17
- 108091092562 ribozyme Proteins 0.000 description 17
- 102000005705 Keratin-5 Human genes 0.000 description 16
- 108010070553 Keratin-5 Proteins 0.000 description 16
- 239000002299 complementary DNA Substances 0.000 description 16
- 238000011830 transgenic mouse model Methods 0.000 description 16
- 230000014616 translation Effects 0.000 description 15
- 238000007796 conventional method Methods 0.000 description 14
- 210000002865 immune cell Anatomy 0.000 description 14
- 230000001939 inductive effect Effects 0.000 description 14
- 239000012488 sample solution Substances 0.000 description 14
- 102000004190 Enzymes Human genes 0.000 description 13
- 108090000790 Enzymes Proteins 0.000 description 13
- 108091028043 Nucleic acid sequence Proteins 0.000 description 13
- 239000000427 antigen Substances 0.000 description 13
- 230000001276 controlling effect Effects 0.000 description 13
- 238000004519 manufacturing process Methods 0.000 description 13
- 230000004048 modification Effects 0.000 description 13
- 238000012986 modification Methods 0.000 description 13
- 238000013519 translation Methods 0.000 description 13
- 102000040650 (ribonucleotides)n+m Human genes 0.000 description 12
- 108700019146 Transgenes Proteins 0.000 description 12
- 108091007433 antigens Proteins 0.000 description 12
- 102000036639 antigens Human genes 0.000 description 12
- 238000005516 engineering process Methods 0.000 description 12
- 238000002474 experimental method Methods 0.000 description 12
- 238000002372 labelling Methods 0.000 description 12
- 239000003550 marker Substances 0.000 description 12
- 239000008194 pharmaceutical composition Substances 0.000 description 12
- 102000004127 Cytokines Human genes 0.000 description 11
- 108090000695 Cytokines Proteins 0.000 description 11
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 11
- 208000022559 Inflammatory bowel disease Diseases 0.000 description 11
- 206010028116 Mucosal inflammation Diseases 0.000 description 11
- 108010029485 Protein Isoforms Proteins 0.000 description 11
- 102000001708 Protein Isoforms Human genes 0.000 description 11
- 108700008625 Reporter Genes Proteins 0.000 description 11
- 238000007792 addition Methods 0.000 description 11
- 238000006243 chemical reaction Methods 0.000 description 11
- OPTASPLRGRRNAP-UHFFFAOYSA-N cytosine Chemical compound NC=1C=CNC(=O)N=1 OPTASPLRGRRNAP-UHFFFAOYSA-N 0.000 description 11
- 201000010099 disease Diseases 0.000 description 11
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 11
- 239000012634 fragment Substances 0.000 description 11
- 102000006602 glyceraldehyde-3-phosphate dehydrogenase Human genes 0.000 description 11
- 108020004445 glyceraldehyde-3-phosphate dehydrogenase Proteins 0.000 description 11
- 238000006467 substitution reaction Methods 0.000 description 11
- 229940124597 therapeutic agent Drugs 0.000 description 11
- 108091036414 Polyinosinic:polycytidylic acid Proteins 0.000 description 10
- 208000026935 allergic disease Diseases 0.000 description 10
- 238000001727 in vivo Methods 0.000 description 10
- 230000006698 induction Effects 0.000 description 10
- 239000007788 liquid Substances 0.000 description 10
- 210000000056 organ Anatomy 0.000 description 10
- 239000013612 plasmid Substances 0.000 description 10
- 229920000642 polymer Polymers 0.000 description 10
- 102000053602 DNA Human genes 0.000 description 9
- 241000700159 Rattus Species 0.000 description 9
- PYMYPHUHKUWMLA-LMVFSUKVSA-N Ribose Natural products OC[C@@H](O)[C@@H](O)[C@@H](O)C=O PYMYPHUHKUWMLA-LMVFSUKVSA-N 0.000 description 9
- JLCPHMBAVCMARE-UHFFFAOYSA-N [3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-[[3-[[3-[[3-[[3-[[3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-hydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methyl [5-(6-aminopurin-9-yl)-2-(hydroxymethyl)oxolan-3-yl] hydrogen phosphate Polymers Cc1cn(C2CC(OP(O)(=O)OCC3OC(CC3OP(O)(=O)OCC3OC(CC3O)n3cnc4c3nc(N)[nH]c4=O)n3cnc4c3nc(N)[nH]c4=O)C(COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3CO)n3cnc4c(N)ncnc34)n3ccc(N)nc3=O)n3cnc4c(N)ncnc34)n3ccc(N)nc3=O)n3ccc(N)nc3=O)n3ccc(N)nc3=O)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cc(C)c(=O)[nH]c3=O)n3cc(C)c(=O)[nH]c3=O)n3ccc(N)nc3=O)n3cc(C)c(=O)[nH]c3=O)n3cnc4c3nc(N)[nH]c4=O)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)O2)c(=O)[nH]c1=O JLCPHMBAVCMARE-UHFFFAOYSA-N 0.000 description 9
- 238000004458 analytical method Methods 0.000 description 9
- 230000037396 body weight Effects 0.000 description 9
- 210000000170 cell membrane Anatomy 0.000 description 9
- 239000003446 ligand Substances 0.000 description 9
- 102000005962 receptors Human genes 0.000 description 9
- 108020003175 receptors Proteins 0.000 description 9
- 230000009467 reduction Effects 0.000 description 9
- 239000007790 solid phase Substances 0.000 description 9
- 235000000346 sugar Nutrition 0.000 description 9
- 230000009261 transgenic effect Effects 0.000 description 9
- KDCGOANMDULRCW-UHFFFAOYSA-N 7H-purine Chemical compound N1=CNC2=NC=NC2=C1 KDCGOANMDULRCW-UHFFFAOYSA-N 0.000 description 8
- 241000282693 Cercopithecidae Species 0.000 description 8
- 201000004624 Dermatitis Diseases 0.000 description 8
- 241000124008 Mammalia Species 0.000 description 8
- 108091081021 Sense strand Proteins 0.000 description 8
- 238000004422 calculation algorithm Methods 0.000 description 8
- 210000002615 epidermis Anatomy 0.000 description 8
- 238000010195 expression analysis Methods 0.000 description 8
- 238000009396 hybridization Methods 0.000 description 8
- 238000003018 immunoassay Methods 0.000 description 8
- 229920001223 polyethylene glycol Polymers 0.000 description 8
- 239000002243 precursor Substances 0.000 description 8
- 108091008146 restriction endonucleases Proteins 0.000 description 8
- 150000003384 small molecules Chemical class 0.000 description 8
- 238000013518 transcription Methods 0.000 description 8
- 230000035897 transcription Effects 0.000 description 8
- 238000011144 upstream manufacturing Methods 0.000 description 8
- AUHDWARTFSKSAC-HEIFUQTGSA-N (2S,3R,4S,5R)-3,4-dihydroxy-5-(hydroxymethyl)-2-(6-oxo-1H-purin-9-yl)oxolane-2-carboxylic acid Chemical group [C@]1([C@H](O)[C@H](O)[C@@H](CO)O1)(N1C=NC=2C(O)=NC=NC12)C(=O)O AUHDWARTFSKSAC-HEIFUQTGSA-N 0.000 description 7
- 206010012438 Dermatitis atopic Diseases 0.000 description 7
- 239000002202 Polyethylene glycol Substances 0.000 description 7
- 238000012228 RNA interference-mediated gene silencing Methods 0.000 description 7
- 230000004913 activation Effects 0.000 description 7
- HMFHBZSHGGEWLO-UHFFFAOYSA-N alpha-D-Furanose-Ribose Natural products OCC1OC(O)C(O)C1O HMFHBZSHGGEWLO-UHFFFAOYSA-N 0.000 description 7
- 201000008937 atopic dermatitis Diseases 0.000 description 7
- 206010009887 colitis Diseases 0.000 description 7
- IERHLVCPSMICTF-XVFCMESISA-N cytidine 5'-monophosphate Chemical group O=C1N=C(N)C=CN1[C@H]1[C@H](O)[C@H](O)[C@@H](COP(O)(O)=O)O1 IERHLVCPSMICTF-XVFCMESISA-N 0.000 description 7
- 239000002552 dosage form Substances 0.000 description 7
- 230000009368 gene silencing by RNA Effects 0.000 description 7
- 238000010353 genetic engineering Methods 0.000 description 7
- 210000004962 mammalian cell Anatomy 0.000 description 7
- 239000000463 material Substances 0.000 description 7
- 238000002360 preparation method Methods 0.000 description 7
- 150000003180 prostaglandins Chemical class 0.000 description 7
- 239000000243 solution Substances 0.000 description 7
- WVDDGKGOMKODPV-UHFFFAOYSA-N Benzyl alcohol Chemical compound OCC1=CC=CC=C1 WVDDGKGOMKODPV-UHFFFAOYSA-N 0.000 description 6
- 241000283690 Bos taurus Species 0.000 description 6
- 241000282472 Canis lupus familiaris Species 0.000 description 6
- 206010010744 Conjunctivitis allergic Diseases 0.000 description 6
- HMFHBZSHGGEWLO-SOOFDHNKSA-N D-ribofuranose Chemical compound OC[C@H]1OC(O)[C@H](O)[C@@H]1O HMFHBZSHGGEWLO-SOOFDHNKSA-N 0.000 description 6
- GRSZFWQUAKGDAV-UHFFFAOYSA-N Inosinic acid Natural products OC1C(O)C(COP(O)(O)=O)OC1N1C(NC=NC2=O)=C2N=C1 GRSZFWQUAKGDAV-UHFFFAOYSA-N 0.000 description 6
- 241000283973 Oryctolagus cuniculus Species 0.000 description 6
- 241001494479 Pecora Species 0.000 description 6
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 6
- CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 description 6
- ISAKRJDGNUQOIC-UHFFFAOYSA-N Uracil Chemical group O=C1C=CNC(=O)N1 ISAKRJDGNUQOIC-UHFFFAOYSA-N 0.000 description 6
- 208000002205 allergic conjunctivitis Diseases 0.000 description 6
- 208000006673 asthma Diseases 0.000 description 6
- 208000024998 atopic conjunctivitis Diseases 0.000 description 6
- 230000015572 biosynthetic process Effects 0.000 description 6
- 210000004369 blood Anatomy 0.000 description 6
- 239000008280 blood Substances 0.000 description 6
- 239000000284 extract Substances 0.000 description 6
- 230000000984 immunochemical effect Effects 0.000 description 6
- 235000013902 inosinic acid Nutrition 0.000 description 6
- 239000004245 inosinic acid Substances 0.000 description 6
- 229940028843 inosinic acid Drugs 0.000 description 6
- 230000003993 interaction Effects 0.000 description 6
- 210000000440 neutrophil Anatomy 0.000 description 6
- 238000007911 parenteral administration Methods 0.000 description 6
- 239000000546 pharmaceutical excipient Substances 0.000 description 6
- 239000000829 suppository Substances 0.000 description 6
- 208000024891 symptom Diseases 0.000 description 6
- 239000003826 tablet Substances 0.000 description 6
- RYYWUUFWQRZTIU-UHFFFAOYSA-K thiophosphate Chemical compound [O-]P([O-])([O-])=S RYYWUUFWQRZTIU-UHFFFAOYSA-K 0.000 description 6
- 108020004705 Codon Proteins 0.000 description 5
- 206010009900 Colitis ulcerative Diseases 0.000 description 5
- 208000011231 Crohn disease Diseases 0.000 description 5
- 241000701022 Cytomegalovirus Species 0.000 description 5
- 101150074155 DHFR gene Proteins 0.000 description 5
- 241000282326 Felis catus Species 0.000 description 5
- 101710163270 Nuclease Proteins 0.000 description 5
- 238000012300 Sequence Analysis Methods 0.000 description 5
- 201000006704 Ulcerative Colitis Diseases 0.000 description 5
- 241000700605 Viruses Species 0.000 description 5
- 239000002253 acid Substances 0.000 description 5
- 230000001154 acute effect Effects 0.000 description 5
- 210000004102 animal cell Anatomy 0.000 description 5
- 230000008901 benefit Effects 0.000 description 5
- 230000004071 biological effect Effects 0.000 description 5
- 239000000872 buffer Substances 0.000 description 5
- 230000015556 catabolic process Effects 0.000 description 5
- 238000012790 confirmation Methods 0.000 description 5
- 238000010276 construction Methods 0.000 description 5
- 238000012258 culturing Methods 0.000 description 5
- 229940104302 cytosine Drugs 0.000 description 5
- 238000006731 degradation reaction Methods 0.000 description 5
- 229920003045 dextran sodium sulfate Polymers 0.000 description 5
- 235000013305 food Nutrition 0.000 description 5
- 238000007490 hematoxylin and eosin (H&E) staining Methods 0.000 description 5
- 238000000338 in vitro Methods 0.000 description 5
- 238000010253 intravenous injection Methods 0.000 description 5
- 210000004698 lymphocyte Anatomy 0.000 description 5
- 239000012528 membrane Substances 0.000 description 5
- 229940021182 non-steroidal anti-inflammatory drug Drugs 0.000 description 5
- 239000002777 nucleoside Substances 0.000 description 5
- 239000000047 product Substances 0.000 description 5
- 230000000069 prophylactic effect Effects 0.000 description 5
- 238000000746 purification Methods 0.000 description 5
- 238000003757 reverse transcription PCR Methods 0.000 description 5
- 206010039073 rheumatoid arthritis Diseases 0.000 description 5
- 239000002904 solvent Substances 0.000 description 5
- MTCFGRXMJLQNBG-REOHCLBHSA-N (2S)-2-Amino-3-hydroxypropansäure Chemical compound OC[C@H](N)C(O)=O MTCFGRXMJLQNBG-REOHCLBHSA-N 0.000 description 4
- NHJVRSWLHSJWIN-UHFFFAOYSA-N 2,4,6-trinitrobenzenesulfonic acid Chemical compound OS(=O)(=O)C1=C([N+]([O-])=O)C=C([N+]([O-])=O)C=C1[N+]([O-])=O NHJVRSWLHSJWIN-UHFFFAOYSA-N 0.000 description 4
- 206010012442 Dermatitis contact Diseases 0.000 description 4
- 241000588724 Escherichia coli Species 0.000 description 4
- 241000238631 Hexapoda Species 0.000 description 4
- 241000282412 Homo Species 0.000 description 4
- 101001056473 Homo sapiens Keratin, type II cytoskeletal 5 Proteins 0.000 description 4
- 102000014150 Interferons Human genes 0.000 description 4
- 108010050904 Interferons Proteins 0.000 description 4
- 108060001084 Luciferase Proteins 0.000 description 4
- 108700011259 MicroRNAs Proteins 0.000 description 4
- 241000699660 Mus musculus Species 0.000 description 4
- 101100452381 Mus musculus Ikzf1 gene Proteins 0.000 description 4
- 238000010222 PCR analysis Methods 0.000 description 4
- ALLWOAVDORUJLA-UHFFFAOYSA-N Rebamipida Chemical compound C=1C(=O)NC2=CC=CC=C2C=1CC(C(=O)O)NC(=O)C1=CC=C(Cl)C=C1 ALLWOAVDORUJLA-UHFFFAOYSA-N 0.000 description 4
- 108091081024 Start codon Proteins 0.000 description 4
- 230000009471 action Effects 0.000 description 4
- 239000004480 active ingredient Substances 0.000 description 4
- 125000000539 amino acid group Chemical group 0.000 description 4
- 206010069664 atopic keratoconjunctivitis Diseases 0.000 description 4
- 230000004888 barrier function Effects 0.000 description 4
- SESFRYSPDFLNCH-UHFFFAOYSA-N benzyl benzoate Chemical compound C=1C=CC=CC=1C(=O)OCC1=CC=CC=C1 SESFRYSPDFLNCH-UHFFFAOYSA-N 0.000 description 4
- 239000002775 capsule Substances 0.000 description 4
- 239000000969 carrier Substances 0.000 description 4
- 210000004978 chinese hamster ovary cell Anatomy 0.000 description 4
- HVYWMOMLDIMFJA-DPAQBDIFSA-N cholesterol Chemical compound C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CCCC(C)C)[C@@]1(C)CC2 HVYWMOMLDIMFJA-DPAQBDIFSA-N 0.000 description 4
- 208000010247 contact dermatitis Diseases 0.000 description 4
- 238000011161 development Methods 0.000 description 4
- 230000018109 developmental process Effects 0.000 description 4
- 239000003085 diluting agent Substances 0.000 description 4
- 235000013601 eggs Nutrition 0.000 description 4
- 238000011156 evaluation Methods 0.000 description 4
- 238000012239 gene modification Methods 0.000 description 4
- 230000005017 genetic modification Effects 0.000 description 4
- 235000013617 genetically modified food Nutrition 0.000 description 4
- 102000055354 human IKZF1 Human genes 0.000 description 4
- 102000057575 human KRT5 Human genes 0.000 description 4
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 4
- 238000012744 immunostaining Methods 0.000 description 4
- 150000002632 lipids Chemical class 0.000 description 4
- 239000007791 liquid phase Substances 0.000 description 4
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 4
- 230000007246 mechanism Effects 0.000 description 4
- 230000010534 mechanism of action Effects 0.000 description 4
- YACKEPLHDIMKIO-UHFFFAOYSA-N methylphosphonic acid Chemical compound CP(O)(O)=O YACKEPLHDIMKIO-UHFFFAOYSA-N 0.000 description 4
- 239000002679 microRNA Substances 0.000 description 4
- 238000010369 molecular cloning Methods 0.000 description 4
- 210000001616 monocyte Anatomy 0.000 description 4
- 229940094443 oxytocics prostaglandins Drugs 0.000 description 4
- 230000007170 pathology Effects 0.000 description 4
- 230000035699 permeability Effects 0.000 description 4
- 125000002467 phosphate group Chemical group [H]OP(=O)(O[H])O[*] 0.000 description 4
- 239000006187 pill Substances 0.000 description 4
- 230000001737 promoting effect Effects 0.000 description 4
- 238000011002 quantification Methods 0.000 description 4
- 238000003753 real-time PCR Methods 0.000 description 4
- 229950004535 rebamipide Drugs 0.000 description 4
- 238000011160 research Methods 0.000 description 4
- 150000003839 salts Chemical class 0.000 description 4
- 230000035945 sensitivity Effects 0.000 description 4
- 238000003786 synthesis reaction Methods 0.000 description 4
- 230000002194 synthesizing effect Effects 0.000 description 4
- 241000701161 unidentified adenovirus Species 0.000 description 4
- 230000003827 upregulation Effects 0.000 description 4
- 238000001262 western blot Methods 0.000 description 4
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 3
- 108010035563 Chloramphenicol O-acetyltransferase Proteins 0.000 description 3
- 241000196324 Embryophyta Species 0.000 description 3
- 108700039887 Essential Genes Proteins 0.000 description 3
- 208000009386 Experimental Arthritis Diseases 0.000 description 3
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 3
- 108010043121 Green Fluorescent Proteins Proteins 0.000 description 3
- 102000004144 Green Fluorescent Proteins Human genes 0.000 description 3
- 206010020751 Hypersensitivity Diseases 0.000 description 3
- 206010021118 Hypotonia Diseases 0.000 description 3
- UGQMRVRMYYASKQ-KQYNXXCUSA-N Inosine Chemical compound O[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1N1C2=NC=NC(O)=C2N=C1 UGQMRVRMYYASKQ-KQYNXXCUSA-N 0.000 description 3
- FBOZXECLQNJBKD-ZDUSSCGKSA-N L-methotrexate Chemical compound C=1N=C2N=C(N)N=C(N)C2=NC=1CN(C)C1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 FBOZXECLQNJBKD-ZDUSSCGKSA-N 0.000 description 3
- AYFVYJQAPQTCCC-GBXIJSLDSA-N L-threonine Chemical compound C[C@@H](O)[C@H](N)C(O)=O AYFVYJQAPQTCCC-GBXIJSLDSA-N 0.000 description 3
- 239000005089 Luciferase Substances 0.000 description 3
- 238000000636 Northern blotting Methods 0.000 description 3
- 108700026244 Open Reading Frames Proteins 0.000 description 3
- 238000011529 RT qPCR Methods 0.000 description 3
- 241000714474 Rous sarcoma virus Species 0.000 description 3
- 241000251131 Sphyrna Species 0.000 description 3
- 241000282898 Sus scrofa Species 0.000 description 3
- 239000002671 adjuvant Substances 0.000 description 3
- 239000000556 agonist Substances 0.000 description 3
- 230000007815 allergy Effects 0.000 description 3
- 238000000137 annealing Methods 0.000 description 3
- 238000013459 approach Methods 0.000 description 3
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 3
- 102000005936 beta-Galactosidase Human genes 0.000 description 3
- 108010005774 beta-Galactosidase Proteins 0.000 description 3
- 230000008827 biological function Effects 0.000 description 3
- 239000012472 biological sample Substances 0.000 description 3
- 238000004113 cell culture Methods 0.000 description 3
- 238000005859 coupling reaction Methods 0.000 description 3
- 238000012136 culture method Methods 0.000 description 3
- 230000016396 cytokine production Effects 0.000 description 3
- 230000002950 deficient Effects 0.000 description 3
- 230000002255 enzymatic effect Effects 0.000 description 3
- 239000003889 eye drop Substances 0.000 description 3
- 210000000744 eyelid Anatomy 0.000 description 3
- 208000017561 flaccidity Diseases 0.000 description 3
- 125000000524 functional group Chemical group 0.000 description 3
- 239000005090 green fluorescent protein Substances 0.000 description 3
- 239000003018 immunosuppressive agent Substances 0.000 description 3
- 238000010874 in vitro model Methods 0.000 description 3
- 208000015181 infectious disease Diseases 0.000 description 3
- 210000004969 inflammatory cell Anatomy 0.000 description 3
- 210000002490 intestinal epithelial cell Anatomy 0.000 description 3
- 210000002510 keratinocyte Anatomy 0.000 description 3
- 238000011813 knockout mouse model Methods 0.000 description 3
- 210000004379 membrane Anatomy 0.000 description 3
- 229910052751 metal Inorganic materials 0.000 description 3
- 239000002184 metal Substances 0.000 description 3
- 150000002739 metals Chemical class 0.000 description 3
- 229960000485 methotrexate Drugs 0.000 description 3
- 238000004848 nephelometry Methods 0.000 description 3
- 150000003833 nucleoside derivatives Chemical class 0.000 description 3
- 125000003835 nucleoside group Chemical group 0.000 description 3
- 229910052760 oxygen Inorganic materials 0.000 description 3
- 239000001301 oxygen Substances 0.000 description 3
- 239000013600 plasmid vector Substances 0.000 description 3
- 238000000926 separation method Methods 0.000 description 3
- 150000003431 steroids Chemical class 0.000 description 3
- 238000007920 subcutaneous administration Methods 0.000 description 3
- 238000001356 surgical procedure Methods 0.000 description 3
- 238000011200 topical administration Methods 0.000 description 3
- 241001430294 unidentified retrovirus Species 0.000 description 3
- 229940035893 uracil Drugs 0.000 description 3
- 108020004491 Antisense DNA Proteins 0.000 description 2
- 102100037435 Antiviral innate immune response receptor RIG-I Human genes 0.000 description 2
- 101710127675 Antiviral innate immune response receptor RIG-I Proteins 0.000 description 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- 102000014914 Carrier Proteins Human genes 0.000 description 2
- 102000000503 Collagen Type II Human genes 0.000 description 2
- 108010041390 Collagen Type II Proteins 0.000 description 2
- 108010047041 Complementarity Determining Regions Proteins 0.000 description 2
- 108020004635 Complementary DNA Proteins 0.000 description 2
- 206010010741 Conjunctivitis Diseases 0.000 description 2
- 241000699800 Cricetinae Species 0.000 description 2
- WCZDQPXNBJTKPI-UHFFFAOYSA-O Cyanidin 7-glucoside Chemical compound OC1C(O)C(O)C(CO)OC1OC1=CC(O)=C(C=C(O)C(=[O+]2)C=3C=C(O)C(O)=CC=3)C2=C1 WCZDQPXNBJTKPI-UHFFFAOYSA-O 0.000 description 2
- 229930183912 Cytidylic acid Natural products 0.000 description 2
- IGXWBGJHJZYPQS-SSDOTTSWSA-N D-Luciferin Chemical compound OC(=O)[C@H]1CSC(C=2SC3=CC=C(O)C=C3N=2)=N1 IGXWBGJHJZYPQS-SSDOTTSWSA-N 0.000 description 2
- 230000007018 DNA scission Effects 0.000 description 2
- CYCGRDQQIOGCKX-UHFFFAOYSA-N Dehydro-luciferin Natural products OC(=O)C1=CSC(C=2SC3=CC(O)=CC=C3N=2)=N1 CYCGRDQQIOGCKX-UHFFFAOYSA-N 0.000 description 2
- 239000006144 Dulbecco’s modified Eagle's medium Substances 0.000 description 2
- BJGNCJDXODQBOB-UHFFFAOYSA-N Fivefly Luciferin Natural products OC(=O)C1CSC(C=2SC3=CC(O)=CC=C3N=2)=N1 BJGNCJDXODQBOB-UHFFFAOYSA-N 0.000 description 2
- 108700039691 Genetic Promoter Regions Proteins 0.000 description 2
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 2
- 108010060309 Glucuronidase Proteins 0.000 description 2
- 102000053187 Glucuronidase Human genes 0.000 description 2
- WHUUTDBJXJRKMK-UHFFFAOYSA-N Glutamic acid Natural products OC(=O)C(N)CCC(O)=O WHUUTDBJXJRKMK-UHFFFAOYSA-N 0.000 description 2
- NYHBQMYGNKIUIF-UUOKFMHZSA-N Guanosine Chemical compound C1=NC=2C(=O)NC(N)=NC=2N1[C@@H]1O[C@H](CO)[C@@H](O)[C@H]1O NYHBQMYGNKIUIF-UUOKFMHZSA-N 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
- 101000953492 Homo sapiens Inositol hexakisphosphate and diphosphoinositol-pentakisphosphate kinase 1 Proteins 0.000 description 2
- 101001082073 Homo sapiens Interferon-induced helicase C domain-containing protein 1 Proteins 0.000 description 2
- 108010001336 Horseradish Peroxidase Proteins 0.000 description 2
- 102000004157 Hydrolases Human genes 0.000 description 2
- 108090000604 Hydrolases Proteins 0.000 description 2
- 229930010555 Inosine Natural products 0.000 description 2
- 102100037739 Inositol hexakisphosphate and diphosphoinositol-pentakisphosphate kinase 1 Human genes 0.000 description 2
- 102100027353 Interferon-induced helicase C domain-containing protein 1 Human genes 0.000 description 2
- 102000004890 Interleukin-8 Human genes 0.000 description 2
- 108090001007 Interleukin-8 Proteins 0.000 description 2
- 125000000998 L-alanino group Chemical group [H]N([*])[C@](C([H])([H])[H])([H])C(=O)O[H] 0.000 description 2
- DCXYFEDJOCDNAF-REOHCLBHSA-N L-asparagine Chemical compound OC(=O)[C@@H](N)CC(N)=O DCXYFEDJOCDNAF-REOHCLBHSA-N 0.000 description 2
- CKLJMWTZIZZHCS-REOHCLBHSA-N L-aspartic acid Chemical compound OC(=O)[C@@H](N)CC(O)=O CKLJMWTZIZZHCS-REOHCLBHSA-N 0.000 description 2
- WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-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
- ROHFNLRQFUQHCH-YFKPBYRVSA-N L-leucine Chemical compound CC(C)C[C@H](N)C(O)=O ROHFNLRQFUQHCH-YFKPBYRVSA-N 0.000 description 2
- KDXKERNSBIXSRK-YFKPBYRVSA-N L-lysine Chemical compound NCCCC[C@H](N)C(O)=O KDXKERNSBIXSRK-YFKPBYRVSA-N 0.000 description 2
- COLNVLDHVKWLRT-QMMMGPOBSA-N L-phenylalanine Chemical compound OC(=O)[C@@H](N)CC1=CC=CC=C1 COLNVLDHVKWLRT-QMMMGPOBSA-N 0.000 description 2
- OUYCCCASQSFEME-QMMMGPOBSA-N L-tyrosine Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-QMMMGPOBSA-N 0.000 description 2
- 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 description 2
- DDWFXDSYGUXRAY-UHFFFAOYSA-N Luciferin Natural products CCc1c(C)c(CC2NC(=O)C(=C2C=C)C)[nH]c1Cc3[nH]c4C(=C5/NC(CC(=O)O)C(C)C5CC(=O)O)CC(=O)c4c3C DDWFXDSYGUXRAY-UHFFFAOYSA-N 0.000 description 2
- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 2
- 241000713869 Moloney murine leukemia virus Species 0.000 description 2
- 101100442582 Neurospora crassa (strain ATCC 24698 / 74-OR23-1A / CBS 708.71 / DSM 1257 / FGSC 987) spe-1 gene Proteins 0.000 description 2
- 239000004677 Nylon Substances 0.000 description 2
- 108010038807 Oligopeptides Proteins 0.000 description 2
- 102000015636 Oligopeptides Human genes 0.000 description 2
- 229910019142 PO4 Inorganic materials 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- 229920003171 Poly (ethylene oxide) Polymers 0.000 description 2
- 108010039918 Polylysine Proteins 0.000 description 2
- 238000011530 RNeasy Mini Kit Methods 0.000 description 2
- 241000283984 Rodentia Species 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- 229920002472 Starch Polymers 0.000 description 2
- 229930006000 Sucrose Natural products 0.000 description 2
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 2
- 241000282887 Suidae Species 0.000 description 2
- 102000000852 Tumor Necrosis Factor-alpha Human genes 0.000 description 2
- 108091023045 Untranslated Region Proteins 0.000 description 2
- DRTQHJPVMGBUCF-XVFCMESISA-N Uridine Chemical compound O[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1N1C(=O)NC(=O)C=C1 DRTQHJPVMGBUCF-XVFCMESISA-N 0.000 description 2
- 235000010724 Wisteria floribunda Nutrition 0.000 description 2
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 2
- 238000010521 absorption reaction Methods 0.000 description 2
- 230000002378 acidificating effect Effects 0.000 description 2
- DZBUGLKDJFMEHC-UHFFFAOYSA-N acridine Chemical compound C1=CC=CC2=CC3=CC=CC=C3N=C21 DZBUGLKDJFMEHC-UHFFFAOYSA-N 0.000 description 2
- UCTWMZQNUQWSLP-UHFFFAOYSA-N adrenaline Chemical compound CNCC(O)C1=CC=C(O)C(O)=C1 UCTWMZQNUQWSLP-UHFFFAOYSA-N 0.000 description 2
- 238000005273 aeration Methods 0.000 description 2
- 230000000172 allergic effect Effects 0.000 description 2
- 239000003708 ampul Substances 0.000 description 2
- 238000010171 animal model Methods 0.000 description 2
- RWZYAGGXGHYGMB-UHFFFAOYSA-N anthranilic acid Chemical compound NC1=CC=CC=C1C(O)=O RWZYAGGXGHYGMB-UHFFFAOYSA-N 0.000 description 2
- 239000003816 antisense DNA Substances 0.000 description 2
- 208000010668 atopic eczema Diseases 0.000 description 2
- 238000002869 basic local alignment search tool Methods 0.000 description 2
- 235000019445 benzyl alcohol Nutrition 0.000 description 2
- 229960002903 benzyl benzoate Drugs 0.000 description 2
- 108091008324 binding proteins Proteins 0.000 description 2
- 238000001574 biopsy Methods 0.000 description 2
- 229910052796 boron Inorganic materials 0.000 description 2
- 210000004556 brain Anatomy 0.000 description 2
- 210000004899 c-terminal region Anatomy 0.000 description 2
- 239000001506 calcium phosphate Substances 0.000 description 2
- 229910000389 calcium phosphate Inorganic materials 0.000 description 2
- 235000011010 calcium phosphates Nutrition 0.000 description 2
- 229910052799 carbon Inorganic materials 0.000 description 2
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 2
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 2
- 239000004359 castor oil Substances 0.000 description 2
- 235000019438 castor oil Nutrition 0.000 description 2
- 125000002091 cationic group Chemical group 0.000 description 2
- 238000005119 centrifugation Methods 0.000 description 2
- 230000008859 change Effects 0.000 description 2
- 238000007385 chemical modification Methods 0.000 description 2
- 239000003153 chemical reaction reagent Substances 0.000 description 2
- 235000012000 cholesterol Nutrition 0.000 description 2
- 238000003776 cleavage reaction Methods 0.000 description 2
- 238000000975 co-precipitation Methods 0.000 description 2
- 230000002860 competitive effect Effects 0.000 description 2
- 239000002537 cosmetic Substances 0.000 description 2
- IERHLVCPSMICTF-UHFFFAOYSA-N cytidine monophosphate Natural products O=C1N=C(N)C=CN1C1C(O)C(O)C(COP(O)(O)=O)O1 IERHLVCPSMICTF-UHFFFAOYSA-N 0.000 description 2
- 210000000805 cytoplasm Anatomy 0.000 description 2
- 230000007423 decrease Effects 0.000 description 2
- 238000013461 design Methods 0.000 description 2
- XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 2
- 238000009826 distribution Methods 0.000 description 2
- 239000008298 dragée Substances 0.000 description 2
- 238000009509 drug development Methods 0.000 description 2
- 238000001962 electrophoresis Methods 0.000 description 2
- 238000004520 electroporation Methods 0.000 description 2
- 230000001804 emulsifying effect Effects 0.000 description 2
- 239000000839 emulsion Substances 0.000 description 2
- 108010048367 enhanced green fluorescent protein Proteins 0.000 description 2
- 210000003386 epithelial cell of thymus gland Anatomy 0.000 description 2
- 210000005081 epithelial layer Anatomy 0.000 description 2
- 230000029142 excretion Effects 0.000 description 2
- 239000013613 expression plasmid Substances 0.000 description 2
- 229940012356 eye drops Drugs 0.000 description 2
- 239000007941 film coated tablet Substances 0.000 description 2
- 238000001914 filtration Methods 0.000 description 2
- 229910052731 fluorine Inorganic materials 0.000 description 2
- 125000001153 fluoro group Chemical group F* 0.000 description 2
- 238000009472 formulation Methods 0.000 description 2
- 230000002496 gastric effect Effects 0.000 description 2
- 210000001035 gastrointestinal tract Anatomy 0.000 description 2
- 230000002068 genetic effect Effects 0.000 description 2
- 208000016759 gingival fibromatosis-progressive deafness syndrome Diseases 0.000 description 2
- 239000008103 glucose Substances 0.000 description 2
- 150000004676 glycans Polymers 0.000 description 2
- ZEMPKEQAKRGZGQ-XOQCFJPHSA-N glycerol triricinoleate Natural products CCCCCC[C@@H](O)CC=CCCCCCCCC(=O)OC[C@@H](COC(=O)CCCCCCCC=CC[C@@H](O)CCCCCC)OC(=O)CCCCCCCC=CC[C@H](O)CCCCCC ZEMPKEQAKRGZGQ-XOQCFJPHSA-N 0.000 description 2
- 239000008187 granular material Substances 0.000 description 2
- 235000013402 health food Nutrition 0.000 description 2
- 125000000623 heterocyclic group Chemical group 0.000 description 2
- 238000004128 high performance liquid chromatography Methods 0.000 description 2
- 210000004408 hybridoma Anatomy 0.000 description 2
- JYGXADMDTFJGBT-VWUMJDOOSA-N hydrocortisone Chemical compound O=C1CC[C@]2(C)[C@H]3[C@@H](O)C[C@](C)([C@@](CC4)(O)C(=O)CO)[C@@H]4[C@@H]3CCC2=C1 JYGXADMDTFJGBT-VWUMJDOOSA-N 0.000 description 2
- 125000001165 hydrophobic group Chemical group 0.000 description 2
- 230000036039 immunity Effects 0.000 description 2
- 229940124589 immunosuppressive drug Drugs 0.000 description 2
- 230000006872 improvement Effects 0.000 description 2
- 238000011534 incubation Methods 0.000 description 2
- 230000002718 inhibitory effect on inflammation Effects 0.000 description 2
- 229960003786 inosine Drugs 0.000 description 2
- 238000003780 insertion Methods 0.000 description 2
- 230000037431 insertion Effects 0.000 description 2
- 229940079322 interferon Drugs 0.000 description 2
- 229940047124 interferons Drugs 0.000 description 2
- 230000003834 intracellular effect Effects 0.000 description 2
- 238000010255 intramuscular injection Methods 0.000 description 2
- 239000007927 intramuscular injection Substances 0.000 description 2
- 239000000644 isotonic solution Substances 0.000 description 2
- 239000008101 lactose Substances 0.000 description 2
- 230000000670 limiting effect Effects 0.000 description 2
- 239000002502 liposome Substances 0.000 description 2
- 238000009630 liquid culture Methods 0.000 description 2
- 239000008297 liquid dosage form Substances 0.000 description 2
- 231100000053 low toxicity Toxicity 0.000 description 2
- HWYHZTIRURJOHG-UHFFFAOYSA-N luminol Chemical compound O=C1NNC(=O)C2=C1C(N)=CC=C2 HWYHZTIRURJOHG-UHFFFAOYSA-N 0.000 description 2
- 210000002540 macrophage Anatomy 0.000 description 2
- 235000019359 magnesium stearate Nutrition 0.000 description 2
- 230000001404 mediated effect Effects 0.000 description 2
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 2
- 244000005700 microbiome Species 0.000 description 2
- 238000000520 microinjection Methods 0.000 description 2
- 239000007758 minimum essential medium Substances 0.000 description 2
- 238000002156 mixing Methods 0.000 description 2
- 238000004264 monolayer culture Methods 0.000 description 2
- 210000005087 mononuclear cell Anatomy 0.000 description 2
- 238000010172 mouse model Methods 0.000 description 2
- 210000004877 mucosa Anatomy 0.000 description 2
- 239000007923 nasal drop Substances 0.000 description 2
- 239000002736 nonionic surfactant Substances 0.000 description 2
- 229920001778 nylon Polymers 0.000 description 2
- 238000002515 oligonucleotide synthesis Methods 0.000 description 2
- 239000008203 oral pharmaceutical composition Substances 0.000 description 2
- 239000012071 phase Substances 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 2
- 239000010452 phosphate Substances 0.000 description 2
- 239000002504 physiological saline solution Substances 0.000 description 2
- 229920000656 polylysine Polymers 0.000 description 2
- 102000054765 polymorphisms of proteins Human genes 0.000 description 2
- 239000000244 polyoxyethylene sorbitan monooleate Substances 0.000 description 2
- 235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 description 2
- 229920001282 polysaccharide Polymers 0.000 description 2
- 239000005017 polysaccharide Substances 0.000 description 2
- 229940068968 polysorbate 80 Drugs 0.000 description 2
- 229920000053 polysorbate 80 Polymers 0.000 description 2
- 230000004481 post-translational protein modification Effects 0.000 description 2
- 239000000843 powder Substances 0.000 description 2
- 239000002244 precipitate Substances 0.000 description 2
- 210000000064 prostate epithelial cell Anatomy 0.000 description 2
- ZCCUUQDIBDJBTK-UHFFFAOYSA-N psoralen Chemical compound C1=C2OC(=O)C=CC2=CC2=C1OC=C2 ZCCUUQDIBDJBTK-UHFFFAOYSA-N 0.000 description 2
- 150000003212 purines Chemical class 0.000 description 2
- 150000003230 pyrimidines Chemical class 0.000 description 2
- 230000005855 radiation Effects 0.000 description 2
- 238000003127 radioimmunoassay Methods 0.000 description 2
- 108010054624 red fluorescent protein Proteins 0.000 description 2
- 230000004044 response Effects 0.000 description 2
- 230000000717 retained effect Effects 0.000 description 2
- 230000002441 reversible effect Effects 0.000 description 2
- 239000003161 ribonuclease inhibitor Substances 0.000 description 2
- 239000002342 ribonucleoside Substances 0.000 description 2
- YGSDEFSMJLZEOE-UHFFFAOYSA-N salicylic acid Chemical compound OC(=O)C1=CC=CC=C1O YGSDEFSMJLZEOE-UHFFFAOYSA-N 0.000 description 2
- 230000007017 scission Effects 0.000 description 2
- 238000010517 secondary reaction Methods 0.000 description 2
- 239000008159 sesame oil Substances 0.000 description 2
- 235000011803 sesame oil Nutrition 0.000 description 2
- 238000002741 site-directed mutagenesis Methods 0.000 description 2
- 210000004927 skin cell Anatomy 0.000 description 2
- 239000007901 soft capsule Substances 0.000 description 2
- 239000007787 solid Substances 0.000 description 2
- 239000007909 solid dosage form Substances 0.000 description 2
- 239000003549 soybean oil Substances 0.000 description 2
- 235000012424 soybean oil Nutrition 0.000 description 2
- 239000008107 starch Substances 0.000 description 2
- 235000019698 starch Nutrition 0.000 description 2
- 239000007929 subcutaneous injection Substances 0.000 description 2
- 238000010254 subcutaneous injection Methods 0.000 description 2
- 239000000758 substrate Substances 0.000 description 2
- 239000005720 sucrose Substances 0.000 description 2
- 150000005846 sugar alcohols Polymers 0.000 description 2
- 239000007940 sugar coated tablet Substances 0.000 description 2
- 239000002511 suppository base Substances 0.000 description 2
- 230000001629 suppression Effects 0.000 description 2
- 239000000725 suspension Substances 0.000 description 2
- 235000020357 syrup Nutrition 0.000 description 2
- 239000006188 syrup Substances 0.000 description 2
- 238000007910 systemic administration Methods 0.000 description 2
- 125000002813 thiocarbonyl group Chemical group *C(*)=S 0.000 description 2
- RWQNBRDOKXIBIV-UHFFFAOYSA-N thymine Chemical compound CC1=CNC(=O)NC1=O RWQNBRDOKXIBIV-UHFFFAOYSA-N 0.000 description 2
- 238000001890 transfection Methods 0.000 description 2
- 238000012546 transfer Methods 0.000 description 2
- 230000001131 transforming effect Effects 0.000 description 2
- 230000014621 translational initiation Effects 0.000 description 2
- QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 description 2
- YNJBWRMUSHSURL-UHFFFAOYSA-N trichloroacetic acid Chemical compound OC(=O)C(Cl)(Cl)Cl YNJBWRMUSHSURL-UHFFFAOYSA-N 0.000 description 2
- 210000003932 urinary bladder Anatomy 0.000 description 2
- 239000013603 viral vector Substances 0.000 description 2
- 108091005957 yellow fluorescent proteins Proteins 0.000 description 2
- 229910052725 zinc Inorganic materials 0.000 description 2
- 239000011701 zinc Substances 0.000 description 2
- DVWJFTGEISXVSH-CWVFEVJCSA-N (1R,3S,5S,7Z,11R,12S,13Z,15Z,17Z,19Z,21R,23S,24R,25S)-21-[(2R,3S,4S,5S,6R)-4-amino-3,5-dihydroxy-6-methyloxan-2-yl]oxy-12-ethyl-1,3,5,25-tetrahydroxy-11-methyl-9-oxo-10,27-dioxabicyclo[21.3.1]heptacosa-7,13,15,17,19-pentaene-24-carboxylic acid Chemical compound CC[C@H]1\C=C/C=C\C=C/C=C\[C@@H](C[C@@H]2O[C@@](O)(C[C@H](O)[C@H]2C(O)=O)C[C@@H](O)C[C@@H](O)C\C=C/C(=O)O[C@@H]1C)O[C@@H]1O[C@H](C)[C@@H](O)[C@H](N)[C@@H]1O DVWJFTGEISXVSH-CWVFEVJCSA-N 0.000 description 1
- KIUKXJAPPMFGSW-DNGZLQJQSA-N (2S,3S,4S,5R,6R)-6-[(2S,3R,4R,5S,6R)-3-Acetamido-2-[(2S,3S,4R,5R,6R)-6-[(2R,3R,4R,5S,6R)-3-acetamido-2,5-dihydroxy-6-(hydroxymethyl)oxan-4-yl]oxy-2-carboxy-4,5-dihydroxyoxan-3-yl]oxy-5-hydroxy-6-(hydroxymethyl)oxan-4-yl]oxy-3,4,5-trihydroxyoxane-2-carboxylic acid Chemical compound CC(=O)N[C@H]1[C@H](O)O[C@H](CO)[C@@H](O)[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@H](O[C@H]2[C@@H]([C@@H](O[C@H]3[C@@H]([C@@H](O)[C@H](O)[C@H](O3)C(O)=O)O)[C@H](O)[C@@H](CO)O2)NC(C)=O)[C@@H](C(O)=O)O1 KIUKXJAPPMFGSW-DNGZLQJQSA-N 0.000 description 1
- BHQCQFFYRZLCQQ-UHFFFAOYSA-N (3alpha,5alpha,7alpha,12alpha)-3,7,12-trihydroxy-cholan-24-oic acid Natural products OC1CC2CC(O)CCC2(C)C2C1C1CCC(C(CCC(O)=O)C)C1(C)C(O)C2 BHQCQFFYRZLCQQ-UHFFFAOYSA-N 0.000 description 1
- GMVPRGQOIOIIMI-UHFFFAOYSA-N (8R,11R,12R,13E,15S)-11,15-Dihydroxy-9-oxo-13-prostenoic acid Natural products CCCCCC(O)C=CC1C(O)CC(=O)C1CCCCCCC(O)=O GMVPRGQOIOIIMI-UHFFFAOYSA-N 0.000 description 1
- JUDOLRSMWHVKGX-UHFFFAOYSA-N 1,1-dioxo-1$l^{6},2-benzodithiol-3-one Chemical compound C1=CC=C2C(=O)SS(=O)(=O)C2=C1 JUDOLRSMWHVKGX-UHFFFAOYSA-N 0.000 description 1
- VGONTNSXDCQUGY-RRKCRQDMSA-N 2'-deoxyinosine Chemical group C1[C@H](O)[C@@H](CO)O[C@H]1N1C(N=CNC2=O)=C2N=C1 VGONTNSXDCQUGY-RRKCRQDMSA-N 0.000 description 1
- NHBKXEKEPDILRR-UHFFFAOYSA-N 2,3-bis(butanoylsulfanyl)propyl butanoate Chemical compound CCCC(=O)OCC(SC(=O)CCC)CSC(=O)CCC NHBKXEKEPDILRR-UHFFFAOYSA-N 0.000 description 1
- JKMHFZQWWAIEOD-UHFFFAOYSA-N 2-[4-(2-hydroxyethyl)piperazin-1-yl]ethanesulfonic acid Chemical compound OCC[NH+]1CCN(CCS([O-])(=O)=O)CC1 JKMHFZQWWAIEOD-UHFFFAOYSA-N 0.000 description 1
- 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 1
- ASJSAQIRZKANQN-CRCLSJGQSA-N 2-deoxy-D-ribose Chemical compound OC[C@@H](O)[C@@H](O)CC=O ASJSAQIRZKANQN-CRCLSJGQSA-N 0.000 description 1
- 108020005345 3' Untranslated Regions Proteins 0.000 description 1
- VXGRJERITKFWPL-UHFFFAOYSA-N 4',5'-Dihydropsoralen Natural products C1=C2OC(=O)C=CC2=CC2=C1OCC2 VXGRJERITKFWPL-UHFFFAOYSA-N 0.000 description 1
- 108020003589 5' Untranslated Regions Proteins 0.000 description 1
- UJBCLAXPPIDQEE-UHFFFAOYSA-N 5-prop-1-ynyl-1h-pyrimidine-2,4-dione Chemical class CC#CC1=CNC(=O)NC1=O UJBCLAXPPIDQEE-UHFFFAOYSA-N 0.000 description 1
- 102100023990 60S ribosomal protein L17 Human genes 0.000 description 1
- WLCZTRVUXYALDD-IBGZPJMESA-N 7-[[(2s)-2,6-bis(2-methoxyethoxycarbonylamino)hexanoyl]amino]heptoxy-methylphosphinic acid Chemical compound COCCOC(=O)NCCCC[C@H](NC(=O)OCCOC)C(=O)NCCCCCCCOP(C)(O)=O WLCZTRVUXYALDD-IBGZPJMESA-N 0.000 description 1
- MROJXXOCABQVEF-UHFFFAOYSA-N Actarit Chemical compound CC(=O)NC1=CC=C(CC(O)=O)C=C1 MROJXXOCABQVEF-UHFFFAOYSA-N 0.000 description 1
- 229920000936 Agarose Polymers 0.000 description 1
- 241000589158 Agrobacterium Species 0.000 description 1
- 102000002260 Alkaline Phosphatase Human genes 0.000 description 1
- 108020004774 Alkaline Phosphatase Proteins 0.000 description 1
- 208000035285 Allergic Seasonal Rhinitis Diseases 0.000 description 1
- 108091023037 Aptamer 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
- 229930003347 Atropine Natural products 0.000 description 1
- 208000023275 Autoimmune disease Diseases 0.000 description 1
- 108090001008 Avidin Proteins 0.000 description 1
- 244000063299 Bacillus subtilis Species 0.000 description 1
- 235000014469 Bacillus subtilis Nutrition 0.000 description 1
- 208000009137 Behcet syndrome Diseases 0.000 description 1
- BTBUEUYNUDRHOZ-UHFFFAOYSA-N Borate Chemical compound [O-]B([O-])[O-] BTBUEUYNUDRHOZ-UHFFFAOYSA-N 0.000 description 1
- ZOXJGFHDIHLPTG-UHFFFAOYSA-N Boron Chemical compound [B] ZOXJGFHDIHLPTG-UHFFFAOYSA-N 0.000 description 1
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 1
- 102100021943 C-C motif chemokine 2 Human genes 0.000 description 1
- 102100032367 C-C motif chemokine 5 Human genes 0.000 description 1
- KXDHJXZQYSOELW-UHFFFAOYSA-M Carbamate Chemical compound NC([O-])=O KXDHJXZQYSOELW-UHFFFAOYSA-M 0.000 description 1
- 229920002134 Carboxymethyl cellulose Polymers 0.000 description 1
- 208000005024 Castleman disease Diseases 0.000 description 1
- 208000002177 Cataract Diseases 0.000 description 1
- 241000700198 Cavia Species 0.000 description 1
- 108010055166 Chemokine CCL5 Proteins 0.000 description 1
- 239000004380 Cholic acid Substances 0.000 description 1
- 208000035473 Communicable disease Diseases 0.000 description 1
- 241000699802 Cricetulus griseus Species 0.000 description 1
- PMATZTZNYRCHOR-CGLBZJNRSA-N Cyclosporin A Chemical compound CC[C@@H]1NC(=O)[C@H]([C@H](O)[C@H](C)C\C=C\C)N(C)C(=O)[C@H](C(C)C)N(C)C(=O)[C@H](CC(C)C)N(C)C(=O)[C@H](CC(C)C)N(C)C(=O)[C@@H](C)NC(=O)[C@H](C)NC(=O)[C@H](CC(C)C)N(C)C(=O)[C@H](C(C)C)NC(=O)[C@H](CC(C)C)N(C)C(=O)CN(C)C1=O PMATZTZNYRCHOR-CGLBZJNRSA-N 0.000 description 1
- 108010036949 Cyclosporine Proteins 0.000 description 1
- 230000006820 DNA synthesis Effects 0.000 description 1
- 102000052510 DNA-Binding Proteins Human genes 0.000 description 1
- 101710096438 DNA-binding protein Proteins 0.000 description 1
- 241000702421 Dependoparvovirus Species 0.000 description 1
- 229920002307 Dextran Polymers 0.000 description 1
- 101001048065 Drosophila melanogaster E3 ubiquitin-protein ligase HRD1 Proteins 0.000 description 1
- 241000283073 Equus caballus Species 0.000 description 1
- 241000701959 Escherichia virus Lambda Species 0.000 description 1
- 108091062183 EsiRNA Proteins 0.000 description 1
- 108010008165 Etanercept Proteins 0.000 description 1
- 108060002716 Exonuclease Proteins 0.000 description 1
- 206010063006 Facial spasm Diseases 0.000 description 1
- 108010000916 Fimbriae Proteins Proteins 0.000 description 1
- 241000233866 Fungi Species 0.000 description 1
- 241000287828 Gallus gallus Species 0.000 description 1
- 229940122498 Gene expression inhibitor Drugs 0.000 description 1
- 208000010412 Glaucoma Diseases 0.000 description 1
- 239000004471 Glycine Substances 0.000 description 1
- 239000007995 HEPES buffer Substances 0.000 description 1
- 208000004095 Hemifacial Spasm Diseases 0.000 description 1
- HTTJABKRGRZYRN-UHFFFAOYSA-N Heparin Chemical compound OC1C(NC(=O)C)C(O)OC(COS(O)(=O)=O)C1OC1C(OS(O)(=O)=O)C(O)C(OC2C(C(OS(O)(=O)=O)C(OC3C(C(O)C(O)C(O3)C(O)=O)OS(O)(=O)=O)C(CO)O2)NS(O)(=O)=O)C(C(O)=O)O1 HTTJABKRGRZYRN-UHFFFAOYSA-N 0.000 description 1
- 101001066129 Homo sapiens Glyceraldehyde-3-phosphate dehydrogenase Proteins 0.000 description 1
- 102000003839 Human Proteins Human genes 0.000 description 1
- 108090000144 Human Proteins Proteins 0.000 description 1
- RKUNBYITZUJHSG-UHFFFAOYSA-N Hyosciamin-hydrochlorid Natural products CN1C(C2)CCC1CC2OC(=O)C(CO)C1=CC=CC=C1 RKUNBYITZUJHSG-UHFFFAOYSA-N 0.000 description 1
- 208000008454 Hyperhidrosis Diseases 0.000 description 1
- 241000571697 Icarus Species 0.000 description 1
- 206010061598 Immunodeficiency Diseases 0.000 description 1
- 208000029462 Immunodeficiency disease Diseases 0.000 description 1
- 101710090028 Inositol-3-phosphate synthase 1 Proteins 0.000 description 1
- 102100026720 Interferon beta Human genes 0.000 description 1
- 108090000467 Interferon-beta Proteins 0.000 description 1
- 102000000588 Interleukin-2 Human genes 0.000 description 1
- 108010002350 Interleukin-2 Proteins 0.000 description 1
- 108090001005 Interleukin-6 Proteins 0.000 description 1
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 1
- 102000011782 Keratins Human genes 0.000 description 1
- 108010076876 Keratins Proteins 0.000 description 1
- 238000012218 Kunkel's method Methods 0.000 description 1
- XUJNEKJLAYXESH-REOHCLBHSA-N L-Cysteine Chemical compound SC[C@H](N)C(O)=O XUJNEKJLAYXESH-REOHCLBHSA-N 0.000 description 1
- ONIBWKKTOPOVIA-BYPYZUCNSA-N L-Proline Chemical compound OC(=O)[C@@H]1CCCN1 ONIBWKKTOPOVIA-BYPYZUCNSA-N 0.000 description 1
- QNAYBMKLOCPYGJ-REOHCLBHSA-N L-alanine Chemical compound C[C@H](N)C(O)=O QNAYBMKLOCPYGJ-REOHCLBHSA-N 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
- HNDVDQJCIGZPNO-YFKPBYRVSA-N L-histidine Chemical compound OC(=O)[C@@H](N)CC1=CN=CN1 HNDVDQJCIGZPNO-YFKPBYRVSA-N 0.000 description 1
- AGPKZVBTJJNPAG-WHFBIAKZSA-N L-isoleucine Chemical compound CC[C@H](C)[C@H](N)C(O)=O AGPKZVBTJJNPAG-WHFBIAKZSA-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
- 125000000393 L-methionino group Chemical group [H]OC(=O)[C@@]([H])(N([H])[*])C([H])([H])C(SC([H])([H])[H])([H])[H] 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
- 125000000510 L-tryptophano group Chemical group [H]C1=C([H])C([H])=C2N([H])C([H])=C(C([H])([H])[C@@]([H])(C(O[H])=O)N([H])[*])C2=C1[H] 0.000 description 1
- KZSNJWFQEVHDMF-BYPYZUCNSA-N L-valine Chemical compound CC(C)[C@H](N)C(O)=O KZSNJWFQEVHDMF-BYPYZUCNSA-N 0.000 description 1
- 241000713666 Lentivirus Species 0.000 description 1
- ROHFNLRQFUQHCH-UHFFFAOYSA-N Leucine Natural products CC(C)CC(N)C(O)=O ROHFNLRQFUQHCH-UHFFFAOYSA-N 0.000 description 1
- 239000012098 Lipofectamine RNAiMAX Substances 0.000 description 1
- 239000004472 Lysine Substances 0.000 description 1
- 101710091439 Major capsid protein 1 Proteins 0.000 description 1
- 102000013460 Malate Dehydrogenase Human genes 0.000 description 1
- 108010026217 Malate Dehydrogenase Proteins 0.000 description 1
- 208000019695 Migraine disease Diseases 0.000 description 1
- 102100023727 Mitochondrial antiviral-signaling protein Human genes 0.000 description 1
- 101710142315 Mitochondrial antiviral-signaling protein Proteins 0.000 description 1
- 201000010927 Mucositis Diseases 0.000 description 1
- 241000711408 Murine respirovirus Species 0.000 description 1
- 229930182474 N-glycoside Natural products 0.000 description 1
- 241000244206 Nematoda Species 0.000 description 1
- 229930193140 Neomycin Natural products 0.000 description 1
- 208000001132 Osteoporosis Diseases 0.000 description 1
- 239000012807 PCR reagent Substances 0.000 description 1
- 241000282577 Pan troglodytes Species 0.000 description 1
- 108010043958 Peptoids Proteins 0.000 description 1
- 102000003992 Peroxidases Human genes 0.000 description 1
- 206010035226 Plasma cell myeloma Diseases 0.000 description 1
- 239000004793 Polystyrene Substances 0.000 description 1
- 241000288906 Primates Species 0.000 description 1
- 101710089372 Programmed cell death protein 1 Proteins 0.000 description 1
- ONIBWKKTOPOVIA-UHFFFAOYSA-N Proline Natural products OC(=O)C1CCCN1 ONIBWKKTOPOVIA-UHFFFAOYSA-N 0.000 description 1
- 101800001494 Protease 2A Proteins 0.000 description 1
- 101800001066 Protein 2A Proteins 0.000 description 1
- 101710149951 Protein Tat Proteins 0.000 description 1
- 108090000944 RNA Helicases Proteins 0.000 description 1
- 102000004409 RNA Helicases Human genes 0.000 description 1
- 239000012980 RPMI-1640 medium Substances 0.000 description 1
- 108700005075 Regulator Genes Proteins 0.000 description 1
- 108010022187 Rev peptide Proteins 0.000 description 1
- 102000006382 Ribonucleases Human genes 0.000 description 1
- 108010083644 Ribonucleases Proteins 0.000 description 1
- 240000004808 Saccharomyces cerevisiae Species 0.000 description 1
- 101100221606 Saccharomyces cerevisiae (strain ATCC 204508 / S288c) COS7 gene Proteins 0.000 description 1
- MTCFGRXMJLQNBG-UHFFFAOYSA-N Serine Natural products OCC(N)C(O)=O MTCFGRXMJLQNBG-UHFFFAOYSA-N 0.000 description 1
- 241000700584 Simplexvirus Species 0.000 description 1
- 108020004682 Single-Stranded DNA Proteins 0.000 description 1
- 208000007107 Stomach Ulcer Diseases 0.000 description 1
- 208000004350 Strabismus Diseases 0.000 description 1
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 1
- QJJXYPPXXYFBGM-LFZNUXCKSA-N Tacrolimus Chemical compound C1C[C@@H](O)[C@H](OC)C[C@@H]1\C=C(/C)[C@@H]1[C@H](C)[C@@H](O)CC(=O)[C@H](CC=C)/C=C(C)/C[C@H](C)C[C@H](OC)[C@H]([C@H](C[C@H]2C)OC)O[C@@]2(O)C(=O)C(=O)N2CCCC[C@H]2C(=O)O1 QJJXYPPXXYFBGM-LFZNUXCKSA-N 0.000 description 1
- 101000834248 Takifugu rubripes Actin, cytoplasmic 1 Proteins 0.000 description 1
- 108020005038 Terminator Codon Proteins 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
- 108010022394 Threonine synthase Proteins 0.000 description 1
- IQFYYKKMVGJFEH-XLPZGREQSA-N Thymidine Chemical group O=C1NC(=O)C(C)=CN1[C@@H]1O[C@H](CO)[C@@H](O)C1 IQFYYKKMVGJFEH-XLPZGREQSA-N 0.000 description 1
- 102000006601 Thymidine Kinase Human genes 0.000 description 1
- 108020004440 Thymidine kinase Proteins 0.000 description 1
- 206010044074 Torticollis Diseases 0.000 description 1
- 102000040945 Transcription factor Human genes 0.000 description 1
- 108091023040 Transcription factor 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
- 108010057266 Type A Botulinum Toxins Proteins 0.000 description 1
- 108091026822 U6 spliceosomal RNA Proteins 0.000 description 1
- 241000700618 Vaccinia virus Species 0.000 description 1
- KZSNJWFQEVHDMF-UHFFFAOYSA-N Valine Natural products CC(C)C(N)C(O)=O KZSNJWFQEVHDMF-UHFFFAOYSA-N 0.000 description 1
- 108010019530 Vascular Endothelial Growth Factors Proteins 0.000 description 1
- 102000005789 Vascular Endothelial Growth Factors Human genes 0.000 description 1
- 241000726445 Viroids Species 0.000 description 1
- QNEPTKZEXBPDLF-JDTILAPWSA-N [(3s,8s,9s,10r,13r,14s,17r)-10,13-dimethyl-17-[(2r)-6-methylheptan-2-yl]-2,3,4,7,8,9,11,12,14,15,16,17-dodecahydro-1h-cyclopenta[a]phenanthren-3-yl] carbonochloridate Chemical compound C1C=C2C[C@@H](OC(Cl)=O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CCCC(C)C)[C@@]1(C)CC2 QNEPTKZEXBPDLF-JDTILAPWSA-N 0.000 description 1
- 210000001015 abdomen Anatomy 0.000 description 1
- 239000008351 acetate buffer Substances 0.000 description 1
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 1
- 230000021736 acetylation Effects 0.000 description 1
- 238000006640 acetylation reaction Methods 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 229950003218 actarit Drugs 0.000 description 1
- 229960002964 adalimumab Drugs 0.000 description 1
- 239000011543 agarose gel Substances 0.000 description 1
- 206010064930 age-related macular degeneration Diseases 0.000 description 1
- 238000013019 agitation Methods 0.000 description 1
- 235000004279 alanine Nutrition 0.000 description 1
- 125000001931 aliphatic group Chemical group 0.000 description 1
- 239000002168 alkylating agent Substances 0.000 description 1
- 229940100198 alkylating agent Drugs 0.000 description 1
- 229960000711 alprostadil Drugs 0.000 description 1
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
- 150000001412 amines Chemical group 0.000 description 1
- 229960000723 ampicillin Drugs 0.000 description 1
- AVKUERGKIZMTKX-NJBDSQKTSA-N ampicillin Chemical compound C1([C@@H](N)C(=O)N[C@H]2[C@H]3SC([C@@H](N3C2=O)C(O)=O)(C)C)=CC=CC=C1 AVKUERGKIZMTKX-NJBDSQKTSA-N 0.000 description 1
- 239000003242 anti bacterial agent Substances 0.000 description 1
- 238000011861 anti-inflammatory therapy Methods 0.000 description 1
- 230000000840 anti-viral effect Effects 0.000 description 1
- 229940088710 antibiotic agent Drugs 0.000 description 1
- 239000003435 antirheumatic agent Substances 0.000 description 1
- 239000000074 antisense oligonucleotide Substances 0.000 description 1
- 238000012230 antisense oligonucleotides Methods 0.000 description 1
- PYMYPHUHKUWMLA-UHFFFAOYSA-N arabinose Natural products OCC(O)C(O)C(O)C=O PYMYPHUHKUWMLA-UHFFFAOYSA-N 0.000 description 1
- ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 1
- 125000003118 aryl group Chemical group 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
- RKUNBYITZUJHSG-SPUOUPEWSA-N atropine Chemical compound O([C@H]1C[C@H]2CC[C@@H](C1)N2C)C(=O)C(CO)C1=CC=CC=C1 RKUNBYITZUJHSG-SPUOUPEWSA-N 0.000 description 1
- 229960000396 atropine Drugs 0.000 description 1
- 150000001540 azides Chemical class 0.000 description 1
- 229940124748 beta 2 agonist Drugs 0.000 description 1
- SRBFZHDQGSBBOR-UHFFFAOYSA-N beta-D-Pyranose-Lyxose Natural products OC1COC(O)C(O)C1O SRBFZHDQGSBBOR-UHFFFAOYSA-N 0.000 description 1
- 102000006995 beta-Glucosidase Human genes 0.000 description 1
- 108010047754 beta-Glucosidase Proteins 0.000 description 1
- DRTQHJPVMGBUCF-PSQAKQOGSA-N beta-L-uridine Natural products O[C@H]1[C@@H](O)[C@H](CO)O[C@@H]1N1C(=O)NC(=O)C=C1 DRTQHJPVMGBUCF-PSQAKQOGSA-N 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
- 229960002537 betamethasone Drugs 0.000 description 1
- UREBDLICKHMUKA-DVTGEIKXSA-N betamethasone Chemical compound C1CC2=CC(=O)C=C[C@]2(C)[C@]2(F)[C@@H]1[C@@H]1C[C@H](C)[C@@](C(=O)CO)(O)[C@@]1(C)C[C@@H]2O UREBDLICKHMUKA-DVTGEIKXSA-N 0.000 description 1
- 238000002306 biochemical method Methods 0.000 description 1
- 239000012620 biological material Substances 0.000 description 1
- 230000033228 biological regulation Effects 0.000 description 1
- 208000010217 blepharitis Diseases 0.000 description 1
- 206010005159 blepharospasm Diseases 0.000 description 1
- 230000000744 blepharospasm Effects 0.000 description 1
- 230000000903 blocking effect Effects 0.000 description 1
- 108091005948 blue fluorescent proteins Proteins 0.000 description 1
- 238000006664 bond formation reaction Methods 0.000 description 1
- 229940089093 botox Drugs 0.000 description 1
- 108010006025 bovine growth hormone Proteins 0.000 description 1
- 238000009395 breeding Methods 0.000 description 1
- 230000001488 breeding effect Effects 0.000 description 1
- 244000309464 bull Species 0.000 description 1
- 102220354910 c.4C>G Human genes 0.000 description 1
- 238000004364 calculation method Methods 0.000 description 1
- 239000001768 carboxy methyl cellulose Substances 0.000 description 1
- 235000010948 carboxy methyl cellulose Nutrition 0.000 description 1
- 239000008112 carboxymethyl-cellulose Substances 0.000 description 1
- 230000012292 cell migration Effects 0.000 description 1
- 230000004700 cellular uptake Effects 0.000 description 1
- 239000001913 cellulose Substances 0.000 description 1
- 229920002678 cellulose Polymers 0.000 description 1
- 235000013330 chicken meat Nutrition 0.000 description 1
- 235000019416 cholic acid Nutrition 0.000 description 1
- BHQCQFFYRZLCQQ-OELDTZBJSA-N cholic acid Chemical compound C([C@H]1C[C@H]2O)[C@H](O)CC[C@]1(C)[C@@H]1[C@@H]2[C@@H]2CC[C@H]([C@@H](CCC(O)=O)C)[C@@]2(C)[C@@H](O)C1 BHQCQFFYRZLCQQ-OELDTZBJSA-N 0.000 description 1
- 229960002471 cholic acid Drugs 0.000 description 1
- 238000011210 chromatographic step Methods 0.000 description 1
- 238000004587 chromatography analysis Methods 0.000 description 1
- 230000002759 chromosomal effect Effects 0.000 description 1
- 210000000349 chromosome Anatomy 0.000 description 1
- 229960001265 ciclosporin Drugs 0.000 description 1
- 238000010367 cloning Methods 0.000 description 1
- 210000001072 colon Anatomy 0.000 description 1
- 238000006482 condensation reaction Methods 0.000 description 1
- 230000021615 conjugation Effects 0.000 description 1
- 239000005289 controlled pore glass Substances 0.000 description 1
- 239000003246 corticosteroid Substances 0.000 description 1
- 229960001334 corticosteroids Drugs 0.000 description 1
- 230000008878 coupling Effects 0.000 description 1
- 238000010168 coupling process Methods 0.000 description 1
- 238000004132 cross linking Methods 0.000 description 1
- 238000005138 cryopreservation Methods 0.000 description 1
- 239000012228 culture supernatant Substances 0.000 description 1
- 238000005520 cutting process Methods 0.000 description 1
- 125000004122 cyclic group Chemical group 0.000 description 1
- 229930182912 cyclosporin Natural products 0.000 description 1
- XUJNEKJLAYXESH-UHFFFAOYSA-N cysteine Natural products SCC(N)C(O)=O XUJNEKJLAYXESH-UHFFFAOYSA-N 0.000 description 1
- 235000018417 cysteine Nutrition 0.000 description 1
- 230000006378 damage Effects 0.000 description 1
- 230000007123 defense Effects 0.000 description 1
- 238000012217 deletion Methods 0.000 description 1
- 230000037430 deletion Effects 0.000 description 1
- KXGVEGMKQFWNSR-UHFFFAOYSA-N deoxycholic acid Natural products C1CC2CC(O)CCC2(C)C2C1C1CCC(C(CCC(O)=O)C)C1(C)C(O)C2 KXGVEGMKQFWNSR-UHFFFAOYSA-N 0.000 description 1
- 238000010511 deprotection reaction Methods 0.000 description 1
- 229960003957 dexamethasone Drugs 0.000 description 1
- UREBDLICKHMUKA-CXSFZGCWSA-N dexamethasone Chemical compound C1CC2=CC(=O)C=C[C@]2(C)[C@]2(F)[C@@H]1[C@@H]1C[C@@H](C)[C@@](C(=O)CO)(O)[C@@]1(C)C[C@@H]2O UREBDLICKHMUKA-CXSFZGCWSA-N 0.000 description 1
- 206010012601 diabetes mellitus Diseases 0.000 description 1
- 238000010586 diagram Methods 0.000 description 1
- 230000004069 differentiation Effects 0.000 description 1
- 239000012895 dilution Substances 0.000 description 1
- 238000010790 dilution Methods 0.000 description 1
- NAGJZTKCGNOGPW-UHFFFAOYSA-K dioxido-sulfanylidene-sulfido-$l^{5}-phosphane Chemical compound [O-]P([O-])([S-])=S NAGJZTKCGNOGPW-UHFFFAOYSA-K 0.000 description 1
- LOKCTEFSRHRXRJ-UHFFFAOYSA-I dipotassium trisodium dihydrogen phosphate hydrogen phosphate dichloride Chemical compound P(=O)(O)(O)[O-].[K+].P(=O)(O)([O-])[O-].[Na+].[Na+].[Cl-].[K+].[Cl-].[Na+] LOKCTEFSRHRXRJ-UHFFFAOYSA-I 0.000 description 1
- 230000006806 disease prevention Effects 0.000 description 1
- 108010007093 dispase Proteins 0.000 description 1
- 239000012153 distilled water Substances 0.000 description 1
- 239000003651 drinking water Substances 0.000 description 1
- 235000020188 drinking water Nutrition 0.000 description 1
- 229940000406 drug candidate Drugs 0.000 description 1
- 238000012912 drug discovery process Methods 0.000 description 1
- 239000003596 drug target Substances 0.000 description 1
- 230000009977 dual effect Effects 0.000 description 1
- 230000005611 electricity Effects 0.000 description 1
- 239000003623 enhancer Substances 0.000 description 1
- YQGOJNYOYNNSMM-UHFFFAOYSA-N eosin Chemical compound [Na+].OC(=O)C1=CC=CC=C1C1=C2C=C(Br)C(=O)C(Br)=C2OC2=C(Br)C(O)=C(Br)C=C21 YQGOJNYOYNNSMM-UHFFFAOYSA-N 0.000 description 1
- 230000036566 epidermal hyperplasia Effects 0.000 description 1
- 210000005175 epidermal keratinocyte Anatomy 0.000 description 1
- 210000003560 epithelium corneal Anatomy 0.000 description 1
- 229960000403 etanercept Drugs 0.000 description 1
- 150000002170 ethers Chemical group 0.000 description 1
- 210000003527 eukaryotic cell Anatomy 0.000 description 1
- 230000005713 exacerbation Effects 0.000 description 1
- 230000003090 exacerbative effect Effects 0.000 description 1
- 102000013165 exonuclease Human genes 0.000 description 1
- 230000001815 facial effect Effects 0.000 description 1
- 238000000855 fermentation Methods 0.000 description 1
- 230000004151 fermentation Effects 0.000 description 1
- 239000012894 fetal calf serum Substances 0.000 description 1
- 210000002950 fibroblast Anatomy 0.000 description 1
- ZFKJVJIDPQDDFY-UHFFFAOYSA-N fluorescamine Chemical compound C12=CC=CC=C2C(=O)OC1(C1=O)OC=C1C1=CC=CC=C1 ZFKJVJIDPQDDFY-UHFFFAOYSA-N 0.000 description 1
- 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 1
- 230000004927 fusion Effects 0.000 description 1
- 201000005917 gastric ulcer Diseases 0.000 description 1
- 239000000499 gel Substances 0.000 description 1
- 238000001502 gel electrophoresis Methods 0.000 description 1
- 238000002523 gelfiltration Methods 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
- 150000002334 glycols Chemical class 0.000 description 1
- 230000013595 glycosylation Effects 0.000 description 1
- 238000006206 glycosylation reaction Methods 0.000 description 1
- 230000012010 growth Effects 0.000 description 1
- 239000003102 growth factor Substances 0.000 description 1
- 229910052736 halogen Inorganic materials 0.000 description 1
- 125000005843 halogen group Chemical group 0.000 description 1
- 230000036541 health Effects 0.000 description 1
- 230000011132 hemopoiesis Effects 0.000 description 1
- 229960002897 heparin Drugs 0.000 description 1
- 229920000669 heparin Polymers 0.000 description 1
- 239000000833 heterodimer Substances 0.000 description 1
- 229920000140 heteropolymer Polymers 0.000 description 1
- HNDVDQJCIGZPNO-UHFFFAOYSA-N histidine Natural products OC(=O)C(N)CC1=CN=CN1 HNDVDQJCIGZPNO-UHFFFAOYSA-N 0.000 description 1
- 238000007489 histopathology method Methods 0.000 description 1
- 239000000710 homodimer Substances 0.000 description 1
- 229920001519 homopolymer Polymers 0.000 description 1
- 229940088597 hormone Drugs 0.000 description 1
- 239000005556 hormone Substances 0.000 description 1
- 108091008039 hormone receptors Proteins 0.000 description 1
- 229920002674 hyaluronan Polymers 0.000 description 1
- 229960003160 hyaluronic acid Drugs 0.000 description 1
- 229960000890 hydrocortisone Drugs 0.000 description 1
- 239000000017 hydrogel Substances 0.000 description 1
- 230000002209 hydrophobic effect Effects 0.000 description 1
- 230000037315 hyperhidrosis Effects 0.000 description 1
- 230000003100 immobilizing effect Effects 0.000 description 1
- 230000003053 immunization Effects 0.000 description 1
- 230000007813 immunodeficiency Effects 0.000 description 1
- 230000002163 immunogen Effects 0.000 description 1
- 239000002955 immunomodulating agent Substances 0.000 description 1
- 229940121354 immunomodulator Drugs 0.000 description 1
- 230000002584 immunomodulator Effects 0.000 description 1
- 229960003444 immunosuppressant agent Drugs 0.000 description 1
- 230000001861 immunosuppressant effect Effects 0.000 description 1
- 239000000411 inducer Substances 0.000 description 1
- 230000002458 infectious effect Effects 0.000 description 1
- 208000030603 inherited susceptibility to asthma Diseases 0.000 description 1
- 208000018197 inherited torticollis Diseases 0.000 description 1
- 230000015788 innate immune response Effects 0.000 description 1
- 210000005007 innate immune system Anatomy 0.000 description 1
- 230000002452 interceptive effect Effects 0.000 description 1
- 210000004347 intestinal mucosa Anatomy 0.000 description 1
- 238000001361 intraarterial administration Methods 0.000 description 1
- 238000007912 intraperitoneal administration Methods 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- 238000005342 ion exchange Methods 0.000 description 1
- 238000004255 ion exchange chromatography Methods 0.000 description 1
- 208000001875 irritant dermatitis Diseases 0.000 description 1
- 238000002955 isolation Methods 0.000 description 1
- AGPKZVBTJJNPAG-UHFFFAOYSA-N isoleucine Natural products CCC(C)C(N)C(O)=O AGPKZVBTJJNPAG-UHFFFAOYSA-N 0.000 description 1
- 229960000310 isoleucine Drugs 0.000 description 1
- GGXICVAJURFBLW-CEYXHVGTSA-N latanoprost Chemical compound CC(C)OC(=O)CCC\C=C/C[C@H]1[C@@H](O)C[C@@H](O)[C@@H]1CC[C@@H](O)CCC1=CC=CC=C1 GGXICVAJURFBLW-CEYXHVGTSA-N 0.000 description 1
- 239000010410 layer Substances 0.000 description 1
- 230000029226 lipidation Effects 0.000 description 1
- 238000001638 lipofection Methods 0.000 description 1
- KNJDBYZZKAZQNG-UHFFFAOYSA-N lucigenin Chemical compound [O-][N+]([O-])=O.[O-][N+]([O-])=O.C12=CC=CC=C2[N+](C)=C(C=CC=C2)C2=C1C1=C(C=CC=C2)C2=[N+](C)C2=CC=CC=C12 KNJDBYZZKAZQNG-UHFFFAOYSA-N 0.000 description 1
- 238000004020 luminiscence type Methods 0.000 description 1
- 229940092110 macugen Drugs 0.000 description 1
- 208000002780 macular degeneration Diseases 0.000 description 1
- 238000012423 maintenance Methods 0.000 description 1
- 210000001161 mammalian embryo Anatomy 0.000 description 1
- 238000013507 mapping Methods 0.000 description 1
- 239000011159 matrix material Substances 0.000 description 1
- 238000000691 measurement method Methods 0.000 description 1
- KBOPZPXVLCULAV-UHFFFAOYSA-N mesalamine Chemical compound NC1=CC=C(O)C(C(O)=O)=C1 KBOPZPXVLCULAV-UHFFFAOYSA-N 0.000 description 1
- 229960004963 mesalazine Drugs 0.000 description 1
- 230000002503 metabolic effect Effects 0.000 description 1
- 230000004060 metabolic process Effects 0.000 description 1
- 229930182817 methionine Natural products 0.000 description 1
- 230000000813 microbial effect Effects 0.000 description 1
- 230000002906 microbiologic effect Effects 0.000 description 1
- 239000004005 microsphere Substances 0.000 description 1
- 206010027599 migraine Diseases 0.000 description 1
- 150000002772 monosaccharides Chemical class 0.000 description 1
- 210000000214 mouth Anatomy 0.000 description 1
- 230000008066 mucocutaneous inflammation Effects 0.000 description 1
- 238000002703 mutagenesis Methods 0.000 description 1
- 231100000350 mutagenesis Toxicity 0.000 description 1
- 230000035772 mutation Effects 0.000 description 1
- 201000000050 myeloid neoplasm Diseases 0.000 description 1
- 210000003928 nasal cavity Anatomy 0.000 description 1
- 229940100662 nasal drops Drugs 0.000 description 1
- 239000013642 negative control Substances 0.000 description 1
- 229960004927 neomycin Drugs 0.000 description 1
- 230000007935 neutral effect Effects 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- 210000004940 nucleus Anatomy 0.000 description 1
- 235000015097 nutrients Nutrition 0.000 description 1
- 229920001542 oligosaccharide Polymers 0.000 description 1
- 150000002482 oligosaccharides Chemical class 0.000 description 1
- 230000005868 ontogenesis Effects 0.000 description 1
- 230000002018 overexpression Effects 0.000 description 1
- FJKROLUGYXJWQN-UHFFFAOYSA-N papa-hydroxy-benzoic acid Natural products OC(=O)C1=CC=C(O)C=C1 FJKROLUGYXJWQN-UHFFFAOYSA-N 0.000 description 1
- 230000036961 partial effect Effects 0.000 description 1
- 239000002245 particle Substances 0.000 description 1
- 230000037361 pathway Effects 0.000 description 1
- 239000000816 peptidomimetic Substances 0.000 description 1
- 108040007629 peroxidase activity proteins Proteins 0.000 description 1
- 238000002823 phage display Methods 0.000 description 1
- 210000003800 pharynx Anatomy 0.000 description 1
- 238000005191 phase separation Methods 0.000 description 1
- COLNVLDHVKWLRT-UHFFFAOYSA-N phenylalanine Natural products OC(=O)C(N)CC1=CC=CC=C1 COLNVLDHVKWLRT-UHFFFAOYSA-N 0.000 description 1
- 239000008363 phosphate buffer Substances 0.000 description 1
- 239000002953 phosphate buffered saline Substances 0.000 description 1
- 150000003904 phospholipids Chemical class 0.000 description 1
- PTMHPRAIXMAOOB-UHFFFAOYSA-L phosphoramidate Chemical compound NP([O-])([O-])=O PTMHPRAIXMAOOB-UHFFFAOYSA-L 0.000 description 1
- 150000008300 phosphoramidites Chemical class 0.000 description 1
- 150000003013 phosphoric acid derivatives Chemical class 0.000 description 1
- 230000026731 phosphorylation Effects 0.000 description 1
- 238000006366 phosphorylation reaction Methods 0.000 description 1
- 230000004962 physiological condition Effects 0.000 description 1
- 239000000419 plant extract Substances 0.000 description 1
- 229920000729 poly(L-lysine) polymer Polymers 0.000 description 1
- 229920002401 polyacrylamide Polymers 0.000 description 1
- 108010011110 polyarginine Proteins 0.000 description 1
- 229940115272 polyinosinic:polycytidylic acid Drugs 0.000 description 1
- 150000004804 polysaccharides Polymers 0.000 description 1
- 229920002223 polystyrene Polymers 0.000 description 1
- 230000029279 positive regulation of transcription, DNA-dependent Effects 0.000 description 1
- 230000001124 posttranscriptional effect Effects 0.000 description 1
- 238000001556 precipitation Methods 0.000 description 1
- 229960005205 prednisolone Drugs 0.000 description 1
- OIGNJSKKLXVSLS-VWUMJDOOSA-N prednisolone Chemical compound O=C1C=C[C@]2(C)[C@H]3[C@@H](O)C[C@](C)([C@@](CC4)(O)C(=O)CO)[C@@H]4[C@@H]3CCC2=C1 OIGNJSKKLXVSLS-VWUMJDOOSA-N 0.000 description 1
- 230000035935 pregnancy Effects 0.000 description 1
- 230000003449 preventive effect Effects 0.000 description 1
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 1
- 238000012545 processing Methods 0.000 description 1
- 210000001236 prokaryotic cell Anatomy 0.000 description 1
- 238000011321 prophylaxis Methods 0.000 description 1
- 235000019260 propionic acid Nutrition 0.000 description 1
- GMVPRGQOIOIIMI-DWKJAMRDSA-N prostaglandin E1 Chemical compound CCCCC[C@H](O)\C=C\[C@H]1[C@H](O)CC(=O)[C@@H]1CCCCCCC(O)=O GMVPRGQOIOIIMI-DWKJAMRDSA-N 0.000 description 1
- 125000006239 protecting group Chemical group 0.000 description 1
- 238000001243 protein synthesis Methods 0.000 description 1
- 210000001938 protoplast Anatomy 0.000 description 1
- 239000012264 purified product Substances 0.000 description 1
- IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical compound O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 0.000 description 1
- 230000002285 radioactive effect Effects 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- 238000011084 recovery Methods 0.000 description 1
- 230000022532 regulation of transcription, DNA-dependent Effects 0.000 description 1
- 230000010076 replication Effects 0.000 description 1
- 238000003571 reporter gene assay Methods 0.000 description 1
- 238000012552 review Methods 0.000 description 1
- 239000002336 ribonucleotide Substances 0.000 description 1
- 229960004889 salicylic acid Drugs 0.000 description 1
- 238000013515 script Methods 0.000 description 1
- 239000013049 sediment Substances 0.000 description 1
- 230000008684 selective degradation Effects 0.000 description 1
- 238000002864 sequence alignment Methods 0.000 description 1
- 230000008142 sex development Effects 0.000 description 1
- 238000004904 shortening Methods 0.000 description 1
- 229910052710 silicon Inorganic materials 0.000 description 1
- 239000010703 silicon Substances 0.000 description 1
- 238000001542 size-exclusion chromatography Methods 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 239000001509 sodium citrate Substances 0.000 description 1
- NLJMYIDDQXHKNR-UHFFFAOYSA-K sodium citrate Chemical compound O.O.[Na+].[Na+].[Na+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O NLJMYIDDQXHKNR-UHFFFAOYSA-K 0.000 description 1
- 238000001179 sorption measurement Methods 0.000 description 1
- 125000006850 spacer group Chemical group 0.000 description 1
- 230000001148 spastic effect Effects 0.000 description 1
- 239000007921 spray Substances 0.000 description 1
- 230000000087 stabilizing effect Effects 0.000 description 1
- 238000010186 staining Methods 0.000 description 1
- 238000010561 standard procedure Methods 0.000 description 1
- 239000012086 standard solution Substances 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 239000011550 stock solution Substances 0.000 description 1
- 150000008163 sugars Chemical class 0.000 description 1
- NCEXYHBECQHGNR-QZQOTICOSA-N sulfasalazine Chemical compound C1=C(O)C(C(=O)O)=CC(\N=N\C=2C=CC(=CC=2)S(=O)(=O)NC=2N=CC=CC=2)=C1 NCEXYHBECQHGNR-QZQOTICOSA-N 0.000 description 1
- 229960001940 sulfasalazine Drugs 0.000 description 1
- 229910052717 sulfur Inorganic materials 0.000 description 1
- 239000011593 sulfur Substances 0.000 description 1
- 210000005222 synovial tissue Anatomy 0.000 description 1
- 210000002437 synoviocyte Anatomy 0.000 description 1
- 229920003002 synthetic resin Polymers 0.000 description 1
- 239000000057 synthetic resin Substances 0.000 description 1
- 239000013076 target substance Substances 0.000 description 1
- UWHCKJMYHZGTIT-UHFFFAOYSA-N tetraethylene glycol Chemical compound OCCOCCOCCOCCO UWHCKJMYHZGTIT-UHFFFAOYSA-N 0.000 description 1
- 229930183279 tetramycin Natural products 0.000 description 1
- 229940126585 therapeutic drug Drugs 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 230000008719 thickening Effects 0.000 description 1
- 150000007970 thio esters Chemical class 0.000 description 1
- 230000002992 thymic effect Effects 0.000 description 1
- 229940113082 thymine Drugs 0.000 description 1
- 230000000699 topical effect Effects 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 239000003053 toxin Substances 0.000 description 1
- 231100000765 toxin Toxicity 0.000 description 1
- 108700012359 toxins Proteins 0.000 description 1
- 210000003437 trachea Anatomy 0.000 description 1
- 230000005030 transcription termination Effects 0.000 description 1
- 230000009466 transformation 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
- 241001529453 unidentified herpesvirus Species 0.000 description 1
- 241001515965 unidentified phage Species 0.000 description 1
- DRTQHJPVMGBUCF-UHFFFAOYSA-N uracil arabinoside Natural products OC1C(O)C(CO)OC1N1C(=O)NC(=O)C=C1 DRTQHJPVMGBUCF-UHFFFAOYSA-N 0.000 description 1
- 210000003708 urethra Anatomy 0.000 description 1
- 229940045145 uridine Drugs 0.000 description 1
- 210000001215 vagina Anatomy 0.000 description 1
- 239000004474 valine Substances 0.000 description 1
- 210000003501 vero cell Anatomy 0.000 description 1
- 230000003612 virological effect Effects 0.000 description 1
- 239000011782 vitamin Substances 0.000 description 1
- 235000013343 vitamin Nutrition 0.000 description 1
- 229940088594 vitamin Drugs 0.000 description 1
- 229930003231 vitamin Natural products 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
- 230000029663 wound healing Effects 0.000 description 1
- 229940002639 xalatan Drugs 0.000 description 1
Landscapes
- Measuring Or Testing Involving Enzymes Or Micro-Organisms (AREA)
- Micro-Organisms Or Cultivation Processes Thereof (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Peptides Or Proteins (AREA)
- Investigating Or Analysing Biological Materials (AREA)
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
JP2014223295 | 2014-10-31 | ||
JP2014223295 | 2014-10-31 |
Publications (3)
Publication Number | Publication Date |
---|---|
JP2016088926A JP2016088926A (ja) | 2016-05-23 |
JP2016088926A5 JP2016088926A5 (enrdf_load_stackoverflow) | 2018-03-22 |
JP6653120B2 true JP6653120B2 (ja) | 2020-02-26 |
Family
ID=56017549
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2015043590A Active JP6653120B2 (ja) | 2014-10-31 | 2015-03-05 | Ikaros阻害に基づく抗炎症薬 |
Country Status (1)
Country | Link |
---|---|
JP (1) | JP6653120B2 (enrdf_load_stackoverflow) |
Families Citing this family (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
PL3797772T3 (pl) | 2019-09-03 | 2024-05-06 | Square Power Ltd | Rebamipid do zastosowania w zapobieganiu i leczeniu choroby Leśniowskiego-Crohna |
CN111961702A (zh) * | 2020-07-22 | 2020-11-20 | 上海珈蓓生物科技有限公司 | 植提物抗皮肤感染性炎症反应的细胞学评价方法及其应用 |
Family Cites Families (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP3562528B2 (ja) * | 1992-09-14 | 2004-09-08 | ザ ジェネラル ホスピタル コーポレイション | Ikaros:t細胞経路調節遺伝子 |
JPH1029942A (ja) * | 1996-04-02 | 1998-02-03 | Yoichi Ichikawa | 慢性関節リウマチ治療剤 |
JP2011530596A (ja) * | 2008-08-11 | 2011-12-22 | プレジデント アンド フェロウズ オブ ハーバード カレッジ | tRNA合成酵素の阻害のためのハロフジノン類似体およびそれらの使用 |
JP6318152B2 (ja) * | 2012-06-29 | 2018-04-25 | セルジーン コーポレイション | セレブロン関連タンパク質を利用して薬物効能を決定する方法 |
JP6870988B2 (ja) * | 2014-02-24 | 2021-05-19 | セルジーン コーポレイション | 神経細胞増幅及び中枢神経系障害治療のためのセレブロンの活性化因子の使用方法 |
-
2015
- 2015-03-05 JP JP2015043590A patent/JP6653120B2/ja active Active
Also Published As
Publication number | Publication date |
---|---|
JP2016088926A (ja) | 2016-05-23 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
JP5847590B2 (ja) | 生体材料およびその使用 | |
EP1923072A1 (en) | Prophylactic/therapeutic agent for cancer | |
WO2006093337A1 (ja) | 癌の予防・治療剤 | |
JP6653120B2 (ja) | Ikaros阻害に基づく抗炎症薬 | |
JP7175526B2 (ja) | 細胞遊走調節に関する疾患の予防・治療剤および肺間質の疾患の疾患活動性判定・予後評価 | |
JP5794514B2 (ja) | 腫瘍血管新生阻害剤 | |
JP2011032236A (ja) | 腫瘍血管新生阻害剤 | |
JP6029019B2 (ja) | 細胞接着阻害剤、細胞増殖阻害剤、並びに癌の検査方法および検査用キット | |
JP2017505763A (ja) | 生物学的材料およびその治療用途 | |
WO2009084668A1 (ja) | 癌細胞増殖阻害方法、増殖阻害剤及びスクリーニング方法 | |
WO2016031996A1 (ja) | 関節炎の予防·治療剤、検査キット、並びに関節炎予防·治療薬のスクリーニング方法 | |
JP6226315B2 (ja) | 炎症性疾患の予防・治療剤、並びに炎症性疾患予防・治療薬のスクリーニング方法 | |
JP5378202B2 (ja) | 脳・神経に特異的あるいは神経分化に特異的なバイオマーカー | |
JP5669271B2 (ja) | 腫瘍血管新生阻害剤 | |
EP2016949A1 (en) | Novel use of g-protein-conjugated receptor and ligand thereof | |
JP2006129724A (ja) | ラクリチン活性を有する化合物のスクリーニング方法 | |
WO2011115271A1 (ja) | 腫瘍血管新生阻害剤 | |
JPWO2008102777A1 (ja) | インスリン抵抗性改善剤 | |
JP2014014368A (ja) | がんに特異的なバイオマーカー | |
JP5451376B2 (ja) | 血球系に特異的あるいは破骨細胞分化に特異的なバイオマーカー | |
WO2011115268A1 (ja) | 腫瘍血管新生阻害剤 | |
WO2011019065A1 (ja) | 腫瘍血管新生阻害剤 | |
JP2011105669A (ja) | 抗腫瘍剤および抗腫瘍剤のスクリーニング方法 | |
KR20170049024A (ko) | ANKs1a 단백질 발현 또는 활성 억제제를 유효성분으로 포함하는 암 예방 또는 치료용 조성물 및 이의 스크리닝 방법 |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
A80 | Written request to apply exceptions to lack of novelty of invention |
Free format text: JAPANESE INTERMEDIATE CODE: A80 Effective date: 20150403 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20180205 |
|
A621 | Written request for application examination |
Free format text: JAPANESE INTERMEDIATE CODE: A621 Effective date: 20180205 |
|
A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20181024 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20181211 |
|
A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20190402 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20190529 |
|
A02 | Decision of refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A02 Effective date: 20191015 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20191203 |
|
A911 | Transfer to examiner for re-examination before appeal (zenchi) |
Free format text: JAPANESE INTERMEDIATE CODE: A911 Effective date: 20191211 |
|
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: 20200106 |
|
A61 | First payment of annual fees (during grant procedure) |
Free format text: JAPANESE INTERMEDIATE CODE: A61 Effective date: 20200127 |
|
R150 | Certificate of patent or registration of utility model |
Ref document number: 6653120 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 |
|
RD04 | Notification of resignation of power of attorney |
Free format text: JAPANESE INTERMEDIATE CODE: R3D04 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |