CN110522905A - 丝氨酸蛋白酶抑制剂在治疗皮肤病中的用途 - Google Patents
丝氨酸蛋白酶抑制剂在治疗皮肤病中的用途 Download PDFInfo
- Publication number
- CN110522905A CN110522905A CN201910841916.2A CN201910841916A CN110522905A CN 110522905 A CN110522905 A CN 110522905A CN 201910841916 A CN201910841916 A CN 201910841916A CN 110522905 A CN110522905 A CN 110522905A
- Authority
- CN
- China
- Prior art keywords
- serpin
- inhibitor
- recombinant
- kallikrein
- skin
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
- 239000003001 serine protease inhibitor Substances 0.000 title claims abstract description 142
- 238000011282 treatment Methods 0.000 title claims abstract description 19
- 208000017520 skin disease Diseases 0.000 title claims description 35
- 102000008847 Serpin Human genes 0.000 claims abstract description 96
- 108050000761 Serpin Proteins 0.000 claims abstract description 96
- 238000000034 method Methods 0.000 claims abstract description 36
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 12
- 101000605520 Homo sapiens Kallikrein-14 Proteins 0.000 claims description 172
- 102100038298 Kallikrein-14 Human genes 0.000 claims description 171
- 102000001399 Kallikrein Human genes 0.000 claims description 63
- 108060005987 Kallikrein Proteins 0.000 claims description 63
- 230000000694 effects Effects 0.000 claims description 48
- 108090000317 Chymotrypsin Proteins 0.000 claims description 39
- 229960002376 chymotrypsin Drugs 0.000 claims description 39
- 102000012479 Serine Proteases Human genes 0.000 claims description 38
- 108010022999 Serine Proteases Proteins 0.000 claims description 38
- 239000000203 mixture Substances 0.000 claims description 33
- 229940122055 Serine protease inhibitor Drugs 0.000 claims description 28
- 101710102218 Serine protease inhibitor Proteins 0.000 claims description 28
- 239000012634 fragment Substances 0.000 claims description 27
- 208000011219 Netherton syndrome Diseases 0.000 claims description 19
- 206010040844 Skin exfoliation Diseases 0.000 claims description 16
- 206010012438 Dermatitis atopic Diseases 0.000 claims description 15
- 201000008937 atopic dermatitis Diseases 0.000 claims description 15
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 15
- 108091006086 inhibitor proteins Proteins 0.000 claims description 15
- 108090000435 Urokinase-type plasminogen activator Proteins 0.000 claims description 14
- 239000002537 cosmetic Substances 0.000 claims description 13
- 201000010099 disease Diseases 0.000 claims description 13
- 238000002360 preparation method Methods 0.000 claims description 13
- 201000004681 Psoriasis Diseases 0.000 claims description 12
- 102000003990 Urokinase-type plasminogen activator Human genes 0.000 claims description 11
- 102100034867 Kallikrein-7 Human genes 0.000 claims description 10
- 241000124008 Mammalia Species 0.000 claims description 10
- 229960005356 urokinase Drugs 0.000 claims description 10
- 108010088842 Fibrinolysin Proteins 0.000 claims description 9
- 238000001514 detection method Methods 0.000 claims description 9
- 238000004519 manufacturing process Methods 0.000 claims description 9
- 229940012957 plasmin Drugs 0.000 claims description 9
- 208000011580 syndromic disease Diseases 0.000 claims description 8
- 239000003814 drug Substances 0.000 claims description 7
- 108010028275 Leukocyte Elastase Proteins 0.000 claims description 6
- 108060005989 Tryptase Proteins 0.000 claims description 6
- 102000001400 Tryptase Human genes 0.000 claims description 6
- 230000002411 adverse Effects 0.000 claims description 6
- 238000003556 assay Methods 0.000 claims description 4
- 239000003550 marker Substances 0.000 claims description 3
- 239000003153 chemical reaction reagent Substances 0.000 claims description 2
- 230000002265 prevention Effects 0.000 claims description 2
- 102100033174 Neutrophil elastase Human genes 0.000 claims 6
- 230000004071 biological effect Effects 0.000 claims 2
- 241001465754 Metazoa Species 0.000 abstract description 15
- 230000001225 therapeutic effect Effects 0.000 abstract description 8
- 150000001875 compounds Chemical class 0.000 abstract description 7
- 238000004393 prognosis Methods 0.000 abstract description 3
- 239000000758 substrate Substances 0.000 description 143
- 239000003112 inhibitor Substances 0.000 description 102
- 239000003541 chymotrypsin inhibitor Substances 0.000 description 86
- 101001050577 Homo sapiens Kinesin-like protein KIF2A Proteins 0.000 description 83
- 102100023426 Kinesin-like protein KIF2A Human genes 0.000 description 82
- 108090000765 processed proteins & peptides Proteins 0.000 description 69
- 108090000623 proteins and genes Proteins 0.000 description 60
- 108020004414 DNA Proteins 0.000 description 57
- 102000004169 proteins and genes Human genes 0.000 description 57
- 235000018102 proteins Nutrition 0.000 description 56
- 102000015395 alpha 1-Antitrypsin Human genes 0.000 description 51
- 108010050122 alpha 1-Antitrypsin Proteins 0.000 description 51
- 102000035195 Peptidases Human genes 0.000 description 49
- 108091005804 Peptidases Proteins 0.000 description 49
- 239000004365 Protease Substances 0.000 description 49
- 229940024142 alpha 1-antitrypsin Drugs 0.000 description 48
- 230000005764 inhibitory process Effects 0.000 description 45
- 102000004196 processed proteins & peptides Human genes 0.000 description 45
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 42
- 229940088598 enzyme Drugs 0.000 description 42
- 239000000137 peptide hydrolase inhibitor Substances 0.000 description 41
- 102000004190 Enzymes Human genes 0.000 description 39
- 108090000790 Enzymes Proteins 0.000 description 39
- 229940124158 Protease/peptidase inhibitor Drugs 0.000 description 38
- 230000002401 inhibitory effect Effects 0.000 description 34
- 238000006243 chemical reaction Methods 0.000 description 33
- 238000003776 cleavage reaction Methods 0.000 description 32
- 230000007017 scission Effects 0.000 description 32
- 102000004142 Trypsin Human genes 0.000 description 30
- 108090000631 Trypsin Proteins 0.000 description 30
- 239000012588 trypsin Substances 0.000 description 30
- 229960001322 trypsin Drugs 0.000 description 30
- 102000003827 Plasma Kallikrein Human genes 0.000 description 28
- 108090000113 Plasma Kallikrein Proteins 0.000 description 28
- 235000001014 amino acid Nutrition 0.000 description 28
- 210000003491 skin Anatomy 0.000 description 28
- 229940024606 amino acid Drugs 0.000 description 26
- 150000001413 amino acids Chemical class 0.000 description 26
- 210000004027 cell Anatomy 0.000 description 26
- 108091032973 (ribonucleotides)n+m Proteins 0.000 description 23
- 235000019419 proteases Nutrition 0.000 description 22
- 239000011780 sodium chloride Substances 0.000 description 21
- 230000001810 trypsinlike Effects 0.000 description 19
- 108010072866 Prostate-Specific Antigen Proteins 0.000 description 18
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 18
- 102100038358 Prostate-specific antigen Human genes 0.000 description 17
- 230000003902 lesion Effects 0.000 description 17
- 239000000047 product Substances 0.000 description 17
- 239000007983 Tris buffer Substances 0.000 description 16
- 125000003275 alpha amino acid group Chemical group 0.000 description 16
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 16
- 101000851058 Homo sapiens Neutrophil elastase Proteins 0.000 description 15
- 102100024078 Plasma serine protease inhibitor Human genes 0.000 description 15
- 108010001953 Protein C Inhibitor Proteins 0.000 description 15
- 102000052502 human ELANE Human genes 0.000 description 15
- 229920001184 polypeptide Polymers 0.000 description 15
- 238000004458 analytical method Methods 0.000 description 14
- 238000011534 incubation Methods 0.000 description 13
- 150000007523 nucleic acids Chemical class 0.000 description 13
- 238000002415 sodium dodecyl sulfate polyacrylamide gel electrophoresis Methods 0.000 description 13
- 101000856199 Homo sapiens Chymotrypsin-like protease CTRL-1 Proteins 0.000 description 12
- 102000016387 Pancreatic elastase Human genes 0.000 description 12
- 108010067372 Pancreatic elastase Proteins 0.000 description 12
- 229940122929 Protein C inhibitor Drugs 0.000 description 12
- 102000057032 Tissue Kallikreins Human genes 0.000 description 12
- 230000027455 binding Effects 0.000 description 12
- 102000039446 nucleic acids Human genes 0.000 description 12
- 108020004707 nucleic acids Proteins 0.000 description 12
- 101001091379 Homo sapiens Kallikrein-5 Proteins 0.000 description 11
- 101001091388 Homo sapiens Kallikrein-7 Proteins 0.000 description 11
- 102100034868 Kallikrein-5 Human genes 0.000 description 11
- -1 for example Chemical class 0.000 description 11
- 208000024891 symptom Diseases 0.000 description 11
- 102100025566 Chymotrypsin-like protease CTRL-1 Human genes 0.000 description 10
- KDXKERNSBIXSRK-YFKPBYRVSA-N L-lysine Chemical compound NCCCC[C@H](N)C(O)=O KDXKERNSBIXSRK-YFKPBYRVSA-N 0.000 description 10
- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 10
- 229920004890 Triton X-100 Polymers 0.000 description 10
- 230000014509 gene expression Effects 0.000 description 10
- 238000002823 phage display Methods 0.000 description 10
- 210000000434 stratum corneum Anatomy 0.000 description 10
- 102100022524 Alpha-1-antichymotrypsin Human genes 0.000 description 9
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 9
- 241000699670 Mus sp. Species 0.000 description 9
- 108090000190 Thrombin Proteins 0.000 description 9
- 239000013504 Triton X-100 Substances 0.000 description 9
- 108010091628 alpha 1-Antichymotrypsin Proteins 0.000 description 9
- 238000000338 in vitro Methods 0.000 description 9
- PXHVJJICTQNCMI-UHFFFAOYSA-N nickel Substances [Ni] PXHVJJICTQNCMI-UHFFFAOYSA-N 0.000 description 9
- 229960004072 thrombin Drugs 0.000 description 9
- 101001091371 Homo sapiens Kallikrein-8 Proteins 0.000 description 8
- 108091034117 Oligonucleotide Proteins 0.000 description 8
- 108700022175 Tissue Kallikreins Proteins 0.000 description 8
- 230000015572 biosynthetic process Effects 0.000 description 8
- 230000035618 desquamation Effects 0.000 description 8
- 238000011161 development Methods 0.000 description 8
- 230000018109 developmental process Effects 0.000 description 8
- 239000007850 fluorescent dye Substances 0.000 description 8
- 238000009472 formulation Methods 0.000 description 8
- 238000001727 in vivo Methods 0.000 description 8
- 230000003993 interaction Effects 0.000 description 8
- 239000000463 material Substances 0.000 description 8
- 230000008569 process Effects 0.000 description 8
- 239000011535 reaction buffer Substances 0.000 description 8
- 206010040882 skin lesion Diseases 0.000 description 8
- 231100000444 skin lesion Toxicity 0.000 description 8
- 238000001262 western blot Methods 0.000 description 8
- 241000588724 Escherichia coli Species 0.000 description 7
- 101000603877 Homo sapiens Nuclear receptor subfamily 1 group I member 2 Proteins 0.000 description 7
- 101001098560 Homo sapiens Proteinase-activated receptor 2 Proteins 0.000 description 7
- 101000713170 Homo sapiens Solute carrier family 52, riboflavin transporter, member 1 Proteins 0.000 description 7
- 229920000663 Hydroxyethyl cellulose Polymers 0.000 description 7
- 102100023012 Kallistatin Human genes 0.000 description 7
- 206010028980 Neoplasm Diseases 0.000 description 7
- 108091028043 Nucleic acid sequence Proteins 0.000 description 7
- 102100037132 Proteinase-activated receptor 2 Human genes 0.000 description 7
- 230000004913 activation Effects 0.000 description 7
- 201000011510 cancer Diseases 0.000 description 7
- 239000002299 complementary DNA Substances 0.000 description 7
- 238000005516 engineering process Methods 0.000 description 7
- 230000002255 enzymatic effect Effects 0.000 description 7
- 235000019447 hydroxyethyl cellulose Nutrition 0.000 description 7
- 238000006467 substitution reaction Methods 0.000 description 7
- 239000006228 supernatant Substances 0.000 description 7
- 230000000699 topical effect Effects 0.000 description 7
- YBJHBAHKTGYVGT-ZKWXMUAHSA-N (+)-Biotin Chemical compound N1C(=O)N[C@@H]2[C@H](CCCCC(=O)O)SC[C@@H]21 YBJHBAHKTGYVGT-ZKWXMUAHSA-N 0.000 description 6
- 102000040650 (ribonucleotides)n+m Human genes 0.000 description 6
- 102000053602 DNA Human genes 0.000 description 6
- 201000004624 Dermatitis Diseases 0.000 description 6
- 235000010469 Glycine max Nutrition 0.000 description 6
- 101001091385 Homo sapiens Kallikrein-6 Proteins 0.000 description 6
- 101000975003 Homo sapiens Kallistatin Proteins 0.000 description 6
- 101001077723 Homo sapiens Serine protease inhibitor Kazal-type 6 Proteins 0.000 description 6
- 206010061218 Inflammation Diseases 0.000 description 6
- 229940122920 Kallikrein inhibitor Drugs 0.000 description 6
- 102100034870 Kallikrein-8 Human genes 0.000 description 6
- CKLJMWTZIZZHCS-REOHCLBHSA-N L-aspartic acid Chemical compound OC(=O)[C@@H](N)CC(O)=O CKLJMWTZIZZHCS-REOHCLBHSA-N 0.000 description 6
- ZDXPYRJPNDTMRX-VKHMYHEASA-N L-glutamine Chemical compound OC(=O)[C@@H](N)CCC(N)=O ZDXPYRJPNDTMRX-VKHMYHEASA-N 0.000 description 6
- OUYCCCASQSFEME-QMMMGPOBSA-N L-tyrosine Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-QMMMGPOBSA-N 0.000 description 6
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 6
- 108010005020 Serine Peptidase Inhibitor Kazal-Type 5 Proteins 0.000 description 6
- 102100025420 Serine protease inhibitor Kazal-type 5 Human genes 0.000 description 6
- 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 6
- 125000000539 amino acid group Chemical group 0.000 description 6
- 239000011324 bead Substances 0.000 description 6
- 230000015556 catabolic process Effects 0.000 description 6
- 230000006870 function Effects 0.000 description 6
- 230000004054 inflammatory process Effects 0.000 description 6
- 230000004048 modification Effects 0.000 description 6
- 238000012986 modification Methods 0.000 description 6
- 239000002953 phosphate buffered saline Substances 0.000 description 6
- 229920005989 resin Polymers 0.000 description 6
- 239000011347 resin Substances 0.000 description 6
- 239000000243 solution Substances 0.000 description 6
- 210000001519 tissue Anatomy 0.000 description 6
- GAWIXWVDTYZWAW-UHFFFAOYSA-N C[CH]O Chemical group C[CH]O GAWIXWVDTYZWAW-UHFFFAOYSA-N 0.000 description 5
- 101000605522 Homo sapiens Kallikrein-1 Proteins 0.000 description 5
- 239000004354 Hydroxyethyl cellulose Substances 0.000 description 5
- 102100034866 Kallikrein-6 Human genes 0.000 description 5
- 241000283891 Kobus Species 0.000 description 5
- WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 description 5
- 240000004808 Saccharomyces cerevisiae Species 0.000 description 5
- 229920002684 Sepharose Polymers 0.000 description 5
- 230000003197 catalytic effect Effects 0.000 description 5
- 229920002678 cellulose Polymers 0.000 description 5
- 239000001913 cellulose Substances 0.000 description 5
- 238000005119 centrifugation Methods 0.000 description 5
- 230000000295 complement effect Effects 0.000 description 5
- 238000006731 degradation reaction Methods 0.000 description 5
- 230000007062 hydrolysis Effects 0.000 description 5
- 238000006460 hydrolysis reaction Methods 0.000 description 5
- 230000004962 physiological condition Effects 0.000 description 5
- 239000002243 precursor Substances 0.000 description 5
- 230000002797 proteolythic effect Effects 0.000 description 5
- 238000000746 purification Methods 0.000 description 5
- 230000009467 reduction Effects 0.000 description 5
- 230000004044 response Effects 0.000 description 5
- 108091008146 restriction endonucleases Proteins 0.000 description 5
- 108010088201 squamous cell carcinoma-related antigen Proteins 0.000 description 5
- 238000012360 testing method Methods 0.000 description 5
- OUYCCCASQSFEME-UHFFFAOYSA-N tyrosine Natural products OC(=O)C(N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-UHFFFAOYSA-N 0.000 description 5
- 108091005957 yellow fluorescent proteins Proteins 0.000 description 5
- 108020004705 Codon Proteins 0.000 description 4
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 4
- 244000068988 Glycine max Species 0.000 description 4
- 229940127379 Kallikrein Inhibitors Drugs 0.000 description 4
- 102100027612 Kallikrein-11 Human genes 0.000 description 4
- 239000004472 Lysine Substances 0.000 description 4
- 241000699666 Mus <mouse, genus> Species 0.000 description 4
- 102000002020 Protease-activated receptors Human genes 0.000 description 4
- 108050009310 Protease-activated receptors Proteins 0.000 description 4
- 208000010668 atopic eczema Diseases 0.000 description 4
- 108010085937 benzyloxycarbonyl-phenylalanylarginine-4-methylcoumaryl-7-amide Proteins 0.000 description 4
- 230000023555 blood coagulation Effects 0.000 description 4
- 229940041514 candida albicans extract Drugs 0.000 description 4
- 230000001684 chronic effect Effects 0.000 description 4
- 230000037012 chymotrypsin-like activity Effects 0.000 description 4
- 239000003085 diluting agent Substances 0.000 description 4
- 238000006911 enzymatic reaction Methods 0.000 description 4
- 230000005284 excitation Effects 0.000 description 4
- 239000013604 expression vector Substances 0.000 description 4
- 239000000499 gel Substances 0.000 description 4
- 230000002068 genetic effect Effects 0.000 description 4
- 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 4
- 230000003301 hydrolyzing effect Effects 0.000 description 4
- 208000015181 infectious disease Diseases 0.000 description 4
- 208000014674 injury Diseases 0.000 description 4
- 230000007246 mechanism Effects 0.000 description 4
- CMEUDEVBFFPSEI-NFHWZJRKSA-N methyl 4-[[(2s)-1-[[(2s)-1-[(2s)-2-[[(2s)-3-methyl-1-[(4-methyl-2-oxochromen-7-yl)amino]-1-oxobutan-2-yl]carbamoyl]pyrrolidin-1-yl]-1-oxopropan-2-yl]amino]-1-oxopropan-2-yl]amino]-4-oxobutanoate Chemical compound COC(=O)CCC(=O)N[C@@H](C)C(=O)N[C@@H](C)C(=O)N1CCC[C@H]1C(=O)N[C@@H](C(C)C)C(=O)NC1=CC=C(C(C)=CC(=O)O2)C2=C1 CMEUDEVBFFPSEI-NFHWZJRKSA-N 0.000 description 4
- 238000010172 mouse model Methods 0.000 description 4
- 238000002703 mutagenesis Methods 0.000 description 4
- 231100000350 mutagenesis Toxicity 0.000 description 4
- UPSFMJHZUCSEHU-JYGUBCOQSA-N n-[(2s,3r,4r,5s,6r)-2-[(2r,3s,4r,5r,6s)-5-acetamido-4-hydroxy-2-(hydroxymethyl)-6-(4-methyl-2-oxochromen-7-yl)oxyoxan-3-yl]oxy-4,5-dihydroxy-6-(hydroxymethyl)oxan-3-yl]acetamide Chemical compound CC(=O)N[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@H]1O[C@H]1[C@H](O)[C@@H](NC(C)=O)[C@H](OC=2C=C3OC(=O)C=C(C)C3=CC=2)O[C@@H]1CO UPSFMJHZUCSEHU-JYGUBCOQSA-N 0.000 description 4
- 239000002773 nucleotide Substances 0.000 description 4
- 125000003729 nucleotide group Chemical group 0.000 description 4
- 102220024624 rs267607620 Human genes 0.000 description 4
- 238000012216 screening Methods 0.000 description 4
- 150000003431 steroids Chemical class 0.000 description 4
- 239000002753 trypsin inhibitor Substances 0.000 description 4
- 125000001493 tyrosinyl group Chemical group [H]OC1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])(N([H])[H])C(*)=O 0.000 description 4
- 239000013598 vector Substances 0.000 description 4
- 239000012138 yeast extract Substances 0.000 description 4
- 102000007469 Actins Human genes 0.000 description 3
- 108010085238 Actins Proteins 0.000 description 3
- 229920000936 Agarose Polymers 0.000 description 3
- WVDDGKGOMKODPV-UHFFFAOYSA-N Benzyl alcohol Chemical compound OCC1=CC=CC=C1 WVDDGKGOMKODPV-UHFFFAOYSA-N 0.000 description 3
- 108010076667 Caspases Proteins 0.000 description 3
- 102000011727 Caspases Human genes 0.000 description 3
- 238000001712 DNA sequencing Methods 0.000 description 3
- 206010012455 Dermatitis exfoliative Diseases 0.000 description 3
- 102100034579 Desmoglein-1 Human genes 0.000 description 3
- 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 3
- WHUUTDBJXJRKMK-UHFFFAOYSA-N Glutamic acid Natural products OC(=O)C(N)CCC(O)=O WHUUTDBJXJRKMK-UHFFFAOYSA-N 0.000 description 3
- 101000924316 Homo sapiens Desmoglein-1 Proteins 0.000 description 3
- 102100038297 Kallikrein-1 Human genes 0.000 description 3
- DCXYFEDJOCDNAF-REOHCLBHSA-N L-asparagine Chemical compound OC(=O)[C@@H](N)CC(N)=O DCXYFEDJOCDNAF-REOHCLBHSA-N 0.000 description 3
- 102000016799 Leukocyte elastase Human genes 0.000 description 3
- 108010070503 PAR-2 Receptor Proteins 0.000 description 3
- 102000032628 PAR-2 Receptor Human genes 0.000 description 3
- 101150030170 Paat gene Proteins 0.000 description 3
- 239000002202 Polyethylene glycol Substances 0.000 description 3
- 208000003251 Pruritus Diseases 0.000 description 3
- 102000007056 Recombinant Fusion Proteins Human genes 0.000 description 3
- 108010008281 Recombinant Fusion Proteins Proteins 0.000 description 3
- 102100036383 Serpin B3 Human genes 0.000 description 3
- 108090000787 Subtilisin Proteins 0.000 description 3
- 208000027418 Wounds and injury Diseases 0.000 description 3
- 239000002671 adjuvant Substances 0.000 description 3
- 238000001042 affinity chromatography Methods 0.000 description 3
- 150000003862 amino acid derivatives Chemical class 0.000 description 3
- 229960000723 ampicillin Drugs 0.000 description 3
- 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 3
- SXTGIAYWYXVNLT-NRFANRHFSA-N benzyl n-[2-[[2-[[(2s)-5-(diaminomethylideneamino)-1-[(4-methyl-2-oxochromen-7-yl)amino]-1-oxopentan-2-yl]amino]-2-oxoethyl]amino]-2-oxoethyl]carbamate Chemical compound N([C@@H](CCCNC(N)=N)C(=O)NC1=CC=2OC(=O)C=C(C=2C=C1)C)C(=O)CNC(=O)CNC(=O)OCC1=CC=CC=C1 SXTGIAYWYXVNLT-NRFANRHFSA-N 0.000 description 3
- 108010079115 benzyloxycarbonyl-glycyl-glycyl-arginine-4-methylcoumaryl-7-amide Proteins 0.000 description 3
- 229960002685 biotin Drugs 0.000 description 3
- 235000020958 biotin Nutrition 0.000 description 3
- 239000011616 biotin Substances 0.000 description 3
- 239000000872 buffer Substances 0.000 description 3
- 229940043292 chymotrypsin / trypsin Drugs 0.000 description 3
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
- 238000010276 construction Methods 0.000 description 3
- 208000010247 contact dermatitis Diseases 0.000 description 3
- 229920001577 copolymer Polymers 0.000 description 3
- 230000001086 cytosolic effect Effects 0.000 description 3
- 230000006378 damage Effects 0.000 description 3
- 239000002552 dosage form Substances 0.000 description 3
- 239000003937 drug carrier Substances 0.000 description 3
- 230000009977 dual effect Effects 0.000 description 3
- 230000008482 dysregulation Effects 0.000 description 3
- 230000002901 elastaselike Effects 0.000 description 3
- 230000007613 environmental effect Effects 0.000 description 3
- 125000003630 glycyl group Chemical group [H]N([H])C([H])([H])C(*)=O 0.000 description 3
- 206010021198 ichthyosis Diseases 0.000 description 3
- 230000002427 irreversible effect Effects 0.000 description 3
- 238000012417 linear regression Methods 0.000 description 3
- 239000011159 matrix material Substances 0.000 description 3
- 239000012528 membrane Substances 0.000 description 3
- 229920001223 polyethylene glycol Polymers 0.000 description 3
- 230000009257 reactivity Effects 0.000 description 3
- 238000012163 sequencing technique Methods 0.000 description 3
- 210000004927 skin cell Anatomy 0.000 description 3
- 208000010744 skin desquamation Diseases 0.000 description 3
- 239000000126 substance Substances 0.000 description 3
- 238000013268 sustained release Methods 0.000 description 3
- 239000012730 sustained-release form Substances 0.000 description 3
- 230000009885 systemic effect Effects 0.000 description 3
- 230000014616 translation Effects 0.000 description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 3
- RNAMYOYQYRYFQY-UHFFFAOYSA-N 2-(4,4-difluoropiperidin-1-yl)-6-methoxy-n-(1-propan-2-ylpiperidin-4-yl)-7-(3-pyrrolidin-1-ylpropoxy)quinazolin-4-amine Chemical compound N1=C(N2CCC(F)(F)CC2)N=C2C=C(OCCCN3CCCC3)C(OC)=CC2=C1NC1CCN(C(C)C)CC1 RNAMYOYQYRYFQY-UHFFFAOYSA-N 0.000 description 2
- QFVHZQCOUORWEI-UHFFFAOYSA-N 4-[(4-anilino-5-sulfonaphthalen-1-yl)diazenyl]-5-hydroxynaphthalene-2,7-disulfonic acid Chemical compound C=12C(O)=CC(S(O)(=O)=O)=CC2=CC(S(O)(=O)=O)=CC=1N=NC(C1=CC=CC(=C11)S(O)(=O)=O)=CC=C1NC1=CC=CC=C1 QFVHZQCOUORWEI-UHFFFAOYSA-N 0.000 description 2
- 108020004774 Alkaline Phosphatase Proteins 0.000 description 2
- 102000002260 Alkaline Phosphatase Human genes 0.000 description 2
- 108090000935 Antithrombin III Proteins 0.000 description 2
- 102100022977 Antithrombin-III Human genes 0.000 description 2
- 239000004475 Arginine Substances 0.000 description 2
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- 241000894006 Bacteria Species 0.000 description 2
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 2
- 241000283707 Capra Species 0.000 description 2
- 108090000426 Caspase-1 Proteins 0.000 description 2
- 108090000227 Chymases Proteins 0.000 description 2
- 102000003858 Chymases Human genes 0.000 description 2
- 108010028774 Complement C1 Proteins 0.000 description 2
- 238000011537 Coomassie blue staining Methods 0.000 description 2
- 102000005927 Cysteine Proteases Human genes 0.000 description 2
- 108010005843 Cysteine Proteases Proteins 0.000 description 2
- FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 2
- 102000012410 DNA Ligases Human genes 0.000 description 2
- 108010061982 DNA Ligases Proteins 0.000 description 2
- 206010012442 Dermatitis contact Diseases 0.000 description 2
- 102100021202 Desmocollin-1 Human genes 0.000 description 2
- KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 2
- 108010074860 Factor Xa Proteins 0.000 description 2
- 241000282326 Felis catus Species 0.000 description 2
- 241000282412 Homo Species 0.000 description 2
- 101000968043 Homo sapiens Desmocollin-1 Proteins 0.000 description 2
- 101000880960 Homo sapiens Desmocollin-3 Proteins 0.000 description 2
- 101001008922 Homo sapiens Kallikrein-11 Proteins 0.000 description 2
- 101001010513 Homo sapiens Leukocyte elastase inhibitor Proteins 0.000 description 2
- 101001098529 Homo sapiens Proteinase-activated receptor 1 Proteins 0.000 description 2
- 101000713169 Homo sapiens Solute carrier family 52, riboflavin transporter, member 2 Proteins 0.000 description 2
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 2
- 101710176219 Kallikrein-1 Proteins 0.000 description 2
- XUJNEKJLAYXESH-REOHCLBHSA-N L-Cysteine Chemical compound SC[C@H](N)C(O)=O XUJNEKJLAYXESH-REOHCLBHSA-N 0.000 description 2
- 102100030635 Leukocyte elastase inhibitor Human genes 0.000 description 2
- 239000007987 MES buffer Substances 0.000 description 2
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 2
- 239000001888 Peptone Substances 0.000 description 2
- 108010080698 Peptones Proteins 0.000 description 2
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- 241000235648 Pichia Species 0.000 description 2
- 102100035846 Pigment epithelium-derived factor Human genes 0.000 description 2
- 208000012641 Pigmentation disease Diseases 0.000 description 2
- 102100039419 Plasminogen activator inhibitor 2 Human genes 0.000 description 2
- 108010021757 Polynucleotide 5'-Hydroxyl-Kinase Proteins 0.000 description 2
- 102000008422 Polynucleotide 5'-hydroxyl-kinase Human genes 0.000 description 2
- 229920001213 Polysorbate 20 Polymers 0.000 description 2
- 101710115193 Protease inhibitor 4 Proteins 0.000 description 2
- 102100037136 Proteinase-activated receptor 1 Human genes 0.000 description 2
- MTCFGRXMJLQNBG-UHFFFAOYSA-N Serine Natural products OCC(N)C(O)=O MTCFGRXMJLQNBG-UHFFFAOYSA-N 0.000 description 2
- 102000005821 Serpin E2 Human genes 0.000 description 2
- 108010005113 Serpin E2 Proteins 0.000 description 2
- 244000061456 Solanum tuberosum Species 0.000 description 2
- 235000002595 Solanum tuberosum Nutrition 0.000 description 2
- 108010000259 Thyroxine-Binding Globulin Proteins 0.000 description 2
- 102100028709 Thyroxine-binding globulin Human genes 0.000 description 2
- 229940122618 Trypsin inhibitor Drugs 0.000 description 2
- 101710162629 Trypsin inhibitor Proteins 0.000 description 2
- 101710152431 Trypsin-like protease Proteins 0.000 description 2
- 241000700605 Viruses Species 0.000 description 2
- 230000003213 activating effect Effects 0.000 description 2
- 239000012190 activator Substances 0.000 description 2
- 239000013543 active substance Substances 0.000 description 2
- 239000011543 agarose gel Substances 0.000 description 2
- 125000001931 aliphatic group Chemical group 0.000 description 2
- 125000000217 alkyl group Chemical group 0.000 description 2
- 230000000172 allergic effect Effects 0.000 description 2
- 108090000183 alpha-2-Antiplasmin Proteins 0.000 description 2
- 229940125715 antihistaminic agent Drugs 0.000 description 2
- 239000000739 antihistaminic agent Substances 0.000 description 2
- 239000003963 antioxidant agent Substances 0.000 description 2
- 235000006708 antioxidants Nutrition 0.000 description 2
- 230000006907 apoptotic process Effects 0.000 description 2
- ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 2
- 206010003246 arthritis Diseases 0.000 description 2
- 125000003118 aryl group Chemical group 0.000 description 2
- 235000003704 aspartic acid Nutrition 0.000 description 2
- 208000006673 asthma Diseases 0.000 description 2
- 230000001580 bacterial effect Effects 0.000 description 2
- 239000008228 bacteriostatic water for injection Substances 0.000 description 2
- 230000004888 barrier function Effects 0.000 description 2
- 230000008901 benefit Effects 0.000 description 2
- 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 2
- AFYNADDZULBEJA-UHFFFAOYSA-N bicinchoninic acid Chemical compound C1=CC=CC2=NC(C=3C=C(C4=CC=CC=C4N=3)C(=O)O)=CC(C(O)=O)=C21 AFYNADDZULBEJA-UHFFFAOYSA-N 0.000 description 2
- 230000001851 biosynthetic effect Effects 0.000 description 2
- 210000004369 blood Anatomy 0.000 description 2
- 239000008280 blood Substances 0.000 description 2
- 229940098773 bovine serum albumin Drugs 0.000 description 2
- 210000004899 c-terminal region Anatomy 0.000 description 2
- 238000004364 calculation method Methods 0.000 description 2
- YCIMNLLNPGFGHC-UHFFFAOYSA-N catechol Chemical compound OC1=CC=CC=C1O YCIMNLLNPGFGHC-UHFFFAOYSA-N 0.000 description 2
- 230000004663 cell proliferation Effects 0.000 description 2
- 238000012512 characterization method Methods 0.000 description 2
- 239000003795 chemical substances by application Substances 0.000 description 2
- 230000002860 competitive effect Effects 0.000 description 2
- 230000009918 complex formation Effects 0.000 description 2
- 239000006071 cream Substances 0.000 description 2
- 230000003247 decreasing effect Effects 0.000 description 2
- 230000007547 defect Effects 0.000 description 2
- 238000012217 deletion Methods 0.000 description 2
- 230000037430 deletion Effects 0.000 description 2
- 238000000326 densiometry Methods 0.000 description 2
- 238000013461 design Methods 0.000 description 2
- 238000003745 diagnosis Methods 0.000 description 2
- 238000010790 dilution Methods 0.000 description 2
- 239000012895 dilution Substances 0.000 description 2
- 229940042399 direct acting antivirals protease inhibitors Drugs 0.000 description 2
- 208000035475 disorder Diseases 0.000 description 2
- 108010030074 endodeoxyribonuclease MluI Proteins 0.000 description 2
- 230000006862 enzymatic digestion Effects 0.000 description 2
- 210000002615 epidermis Anatomy 0.000 description 2
- ZMMJGEGLRURXTF-UHFFFAOYSA-N ethidium bromide Chemical compound [Br-].C12=CC(N)=CC=C2C2=CC=C(N)C=C2[N+](CC)=C1C1=CC=CC=C1 ZMMJGEGLRURXTF-UHFFFAOYSA-N 0.000 description 2
- 229960005542 ethidium bromide Drugs 0.000 description 2
- 238000011156 evaluation Methods 0.000 description 2
- 238000002474 experimental method Methods 0.000 description 2
- 230000000762 glandular Effects 0.000 description 2
- 239000011521 glass Substances 0.000 description 2
- 102000057705 human KLK8 Human genes 0.000 description 2
- 229960000890 hydrocortisone Drugs 0.000 description 2
- 239000000017 hydrogel Substances 0.000 description 2
- 230000003463 hyperproliferative effect Effects 0.000 description 2
- 230000002757 inflammatory effect Effects 0.000 description 2
- 238000001990 intravenous administration Methods 0.000 description 2
- 230000007803 itching Effects 0.000 description 2
- 230000002147 killing effect Effects 0.000 description 2
- RGLRXNKKBLIBQS-XNHQSDQCSA-N leuprolide acetate Chemical compound CC(O)=O.CCNC(=O)[C@@H]1CCCN1C(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](CC(C)C)NC(=O)[C@@H](NC(=O)[C@H](CO)NC(=O)[C@H](CC=1C2=CC=CC=C2NC=1)NC(=O)[C@H](CC=1N=CNC=1)NC(=O)[C@H]1NC(=O)CC1)CC1=CC=C(O)C=C1 RGLRXNKKBLIBQS-XNHQSDQCSA-N 0.000 description 2
- 230000001404 mediated effect Effects 0.000 description 2
- 210000004379 membrane Anatomy 0.000 description 2
- LXCFILQKKLGQFO-UHFFFAOYSA-N methylparaben Chemical compound COC(=O)C1=CC=C(O)C=C1 LXCFILQKKLGQFO-UHFFFAOYSA-N 0.000 description 2
- 239000013642 negative control Substances 0.000 description 2
- 239000002674 ointment Substances 0.000 description 2
- 238000002515 oligonucleotide synthesis Methods 0.000 description 2
- 230000036961 partial effect Effects 0.000 description 2
- 230000037361 pathway Effects 0.000 description 2
- AQIXEPGDORPWBJ-UHFFFAOYSA-N pentan-3-ol Chemical compound CCC(O)CC AQIXEPGDORPWBJ-UHFFFAOYSA-N 0.000 description 2
- 235000019319 peptone Nutrition 0.000 description 2
- 230000000144 pharmacologic effect Effects 0.000 description 2
- 150000004713 phosphodiesters Chemical group 0.000 description 2
- 239000013612 plasmid Substances 0.000 description 2
- 239000000256 polyoxyethylene sorbitan monolaurate Substances 0.000 description 2
- 235000010486 polyoxyethylene sorbitan monolaurate Nutrition 0.000 description 2
- 239000000843 powder Substances 0.000 description 2
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 2
- 238000012545 processing Methods 0.000 description 2
- 230000000069 prophylactic effect Effects 0.000 description 2
- QELSKZZBTMNZEB-UHFFFAOYSA-N propylparaben Chemical compound CCCOC(=O)C1=CC=C(O)C=C1 QELSKZZBTMNZEB-UHFFFAOYSA-N 0.000 description 2
- 230000001681 protective effect Effects 0.000 description 2
- 230000001823 pruritic effect Effects 0.000 description 2
- 230000002285 radioactive effect Effects 0.000 description 2
- 230000002829 reductive effect Effects 0.000 description 2
- 238000000611 regression analysis Methods 0.000 description 2
- 230000001105 regulatory effect Effects 0.000 description 2
- 238000007634 remodeling Methods 0.000 description 2
- 238000011160 research Methods 0.000 description 2
- GHMLBKRAJCXXBS-UHFFFAOYSA-N resorcinol Chemical compound OC1=CC=CC(O)=C1 GHMLBKRAJCXXBS-UHFFFAOYSA-N 0.000 description 2
- 210000000582 semen Anatomy 0.000 description 2
- 108010021648 semen liquefaction factor Proteins 0.000 description 2
- 230000035945 sensitivity Effects 0.000 description 2
- 238000010008 shearing Methods 0.000 description 2
- 230000008591 skin barrier function Effects 0.000 description 2
- 206010040872 skin infection Diseases 0.000 description 2
- 239000007787 solid Substances 0.000 description 2
- 239000000600 sorbitol Substances 0.000 description 2
- 238000003756 stirring Methods 0.000 description 2
- 235000000346 sugar Nutrition 0.000 description 2
- 150000008163 sugars Chemical class 0.000 description 2
- 238000001356 surgical procedure Methods 0.000 description 2
- 230000008685 targeting Effects 0.000 description 2
- 238000012546 transfer Methods 0.000 description 2
- 230000009261 transgenic effect Effects 0.000 description 2
- LWIHDJKSTIGBAC-UHFFFAOYSA-K tripotassium phosphate Chemical compound [K+].[K+].[K+].[O-]P([O-])([O-])=O LWIHDJKSTIGBAC-UHFFFAOYSA-K 0.000 description 2
- 108010036927 trypsin-like serine protease Proteins 0.000 description 2
- 239000012137 tryptone Substances 0.000 description 2
- 238000011144 upstream manufacturing Methods 0.000 description 2
- 239000003981 vehicle Substances 0.000 description 2
- HDTRYLNUVZCQOY-UHFFFAOYSA-N α-D-glucopyranosyl-α-D-glucopyranoside Natural products OC1C(O)C(O)C(CO)OC1OC1C(O)C(O)C(O)C(CO)O1 HDTRYLNUVZCQOY-UHFFFAOYSA-N 0.000 description 1
- XMQUEQJCYRFIQS-YFKPBYRVSA-N (2s)-2-amino-5-ethoxy-5-oxopentanoic acid Chemical compound CCOC(=O)CC[C@H](N)C(O)=O XMQUEQJCYRFIQS-YFKPBYRVSA-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
- IGKPQFYMWKQDQS-KCXKOMAXSA-N 4-[[(2s)-1-[[(2s)-1-[(2s)-2-[[(2s)-2-[(4-methyl-2-oxochromen-7-yl)amino]-3-phenylpropanoyl]carbamoyl]pyrrolidin-1-yl]-1-oxopropan-2-yl]amino]-1-oxopropan-2-yl]amino]-4-oxobutanoic acid Chemical compound OC(=O)CCC(=O)N[C@@H](C)C(=O)N[C@@H](C)C(=O)N1CCC[C@H]1C(=O)NC(=O)[C@@H](NC=1C=C2OC(=O)C=C(C)C2=CC=1)CC1=CC=CC=C1 IGKPQFYMWKQDQS-KCXKOMAXSA-N 0.000 description 1
- LKDMKWNDBAVNQZ-UHFFFAOYSA-N 4-[[1-[[1-[2-[[1-(4-nitroanilino)-1-oxo-3-phenylpropan-2-yl]carbamoyl]pyrrolidin-1-yl]-1-oxopropan-2-yl]amino]-1-oxopropan-2-yl]amino]-4-oxobutanoic acid Chemical compound OC(=O)CCC(=O)NC(C)C(=O)NC(C)C(=O)N1CCCC1C(=O)NC(C(=O)NC=1C=CC(=CC=1)[N+]([O-])=O)CC1=CC=CC=C1 LKDMKWNDBAVNQZ-UHFFFAOYSA-N 0.000 description 1
- 102100040924 60S ribosomal protein L6 Human genes 0.000 description 1
- 206010000349 Acanthosis Diseases 0.000 description 1
- 208000002874 Acne Vulgaris Diseases 0.000 description 1
- HRPVXLWXLXDGHG-UHFFFAOYSA-N Acrylamide Chemical compound NC(=O)C=C HRPVXLWXLXDGHG-UHFFFAOYSA-N 0.000 description 1
- 206010067484 Adverse reaction Diseases 0.000 description 1
- 229920001817 Agar Polymers 0.000 description 1
- 108010039627 Aprotinin Proteins 0.000 description 1
- DCXYFEDJOCDNAF-UHFFFAOYSA-N Asparagine Natural products OC(=O)C(N)CC(N)=O DCXYFEDJOCDNAF-UHFFFAOYSA-N 0.000 description 1
- 201000001320 Atherosclerosis Diseases 0.000 description 1
- 208000012657 Atopic disease Diseases 0.000 description 1
- 206010003645 Atopy Diseases 0.000 description 1
- 108090001008 Avidin Proteins 0.000 description 1
- 208000035143 Bacterial infection Diseases 0.000 description 1
- 241000283690 Bos taurus Species 0.000 description 1
- 101000984722 Bos taurus Pancreatic trypsin inhibitor Proteins 0.000 description 1
- 238000009010 Bradford assay Methods 0.000 description 1
- 241000282472 Canis lupus familiaris Species 0.000 description 1
- 102000014914 Carrier Proteins Human genes 0.000 description 1
- 108090000397 Caspase 3 Proteins 0.000 description 1
- 102100035904 Caspase-1 Human genes 0.000 description 1
- 102100029855 Caspase-3 Human genes 0.000 description 1
- 102100025975 Cathepsin G Human genes 0.000 description 1
- 108090000617 Cathepsin G Proteins 0.000 description 1
- 108010084457 Cathepsins Proteins 0.000 description 1
- 102000005600 Cathepsins Human genes 0.000 description 1
- 241000282693 Cercopithecidae Species 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 1
- 208000017667 Chronic Disease Diseases 0.000 description 1
- 108020004638 Circular DNA Proteins 0.000 description 1
- 101800004419 Cleaved form Proteins 0.000 description 1
- 101710140722 Cocoonase Proteins 0.000 description 1
- 108091026890 Coding region Proteins 0.000 description 1
- 108010035532 Collagen Proteins 0.000 description 1
- 102000008186 Collagen Human genes 0.000 description 1
- 208000035473 Communicable disease Diseases 0.000 description 1
- 102000016917 Complement C1 Human genes 0.000 description 1
- 102000055157 Complement C1 Inhibitor Human genes 0.000 description 1
- 108700040183 Complement C1 Inhibitor Proteins 0.000 description 1
- 102100025406 Complement C1s subcomponent Human genes 0.000 description 1
- 102000010970 Connexin Human genes 0.000 description 1
- 108050001175 Connexin Proteins 0.000 description 1
- 108091035707 Consensus sequence Proteins 0.000 description 1
- 102000004127 Cytokines Human genes 0.000 description 1
- 108090000695 Cytokines Proteins 0.000 description 1
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 1
- FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 description 1
- WQZGKKKJIJFFOK-QTVWNMPRSA-N D-mannopyranose Chemical compound OC[C@H]1OC(O)[C@@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-QTVWNMPRSA-N 0.000 description 1
- 239000004375 Dextrin Substances 0.000 description 1
- 229920001353 Dextrin Polymers 0.000 description 1
- 206010013786 Dry skin Diseases 0.000 description 1
- 241000196324 Embryophyta Species 0.000 description 1
- 206010014561 Emphysema Diseases 0.000 description 1
- 201000009273 Endometriosis Diseases 0.000 description 1
- 102100031780 Endonuclease Human genes 0.000 description 1
- 102000005593 Endopeptidases Human genes 0.000 description 1
- 108010059378 Endopeptidases Proteins 0.000 description 1
- 102000010911 Enzyme Precursors Human genes 0.000 description 1
- 108010062466 Enzyme Precursors Proteins 0.000 description 1
- 241000283086 Equidae Species 0.000 description 1
- 229910052691 Erbium Inorganic materials 0.000 description 1
- 206010015150 Erythema Diseases 0.000 description 1
- 241000701533 Escherichia virus T4 Species 0.000 description 1
- 108700039887 Essential Genes Proteins 0.000 description 1
- 229910052693 Europium Inorganic materials 0.000 description 1
- 108010091443 Exopeptidases Proteins 0.000 description 1
- 102000018389 Exopeptidases Human genes 0.000 description 1
- 108010037362 Extracellular Matrix Proteins Proteins 0.000 description 1
- 102000010834 Extracellular Matrix Proteins Human genes 0.000 description 1
- 108010048049 Factor IXa Proteins 0.000 description 1
- 206010016654 Fibrosis Diseases 0.000 description 1
- 241000724791 Filamentous phage Species 0.000 description 1
- 102000003688 G-Protein-Coupled Receptors Human genes 0.000 description 1
- 108090000045 G-Protein-Coupled Receptors Proteins 0.000 description 1
- 229910052688 Gadolinium Inorganic materials 0.000 description 1
- 108010010803 Gelatin Proteins 0.000 description 1
- 208000034826 Genetic Predisposition to Disease Diseases 0.000 description 1
- 101710103262 Glandular kallikrein Proteins 0.000 description 1
- 206010018364 Glomerulonephritis Diseases 0.000 description 1
- 239000004471 Glycine Substances 0.000 description 1
- 108010043121 Green Fluorescent Proteins Proteins 0.000 description 1
- 108010051696 Growth Hormone Proteins 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
- 108090000481 Heparin Cofactor II Proteins 0.000 description 1
- 102100030500 Heparin cofactor 2 Human genes 0.000 description 1
- 208000028782 Hereditary disease Diseases 0.000 description 1
- 241000238631 Hexapoda Species 0.000 description 1
- 229910052689 Holmium Inorganic materials 0.000 description 1
- 101000673524 Homo sapiens 60S ribosomal protein L6 Proteins 0.000 description 1
- 101000678026 Homo sapiens Alpha-1-antichymotrypsin Proteins 0.000 description 1
- 101000823116 Homo sapiens Alpha-1-antitrypsin Proteins 0.000 description 1
- 101000757319 Homo sapiens Antithrombin-III Proteins 0.000 description 1
- 101000983528 Homo sapiens Caspase-8 Proteins 0.000 description 1
- 101000613565 Homo sapiens PRKC apoptosis WT1 regulator protein Proteins 0.000 description 1
- 101001073422 Homo sapiens Pigment epithelium-derived factor Proteins 0.000 description 1
- 101001091365 Homo sapiens Plasma kallikrein Proteins 0.000 description 1
- 101001081555 Homo sapiens Plasma protease C1 inhibitor Proteins 0.000 description 1
- 101000605403 Homo sapiens Plasminogen Proteins 0.000 description 1
- 101001113471 Homo sapiens Proteinase-activated receptor 4 Proteins 0.000 description 1
- 101000823100 Homo sapiens Putative alpha-1-antitrypsin-related protein Proteins 0.000 description 1
- 101000836383 Homo sapiens Serpin H1 Proteins 0.000 description 1
- 108010001336 Horseradish Peroxidase Proteins 0.000 description 1
- 206010020649 Hyperkeratosis Diseases 0.000 description 1
- 206010020751 Hypersensitivity Diseases 0.000 description 1
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical class C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
- 108060003951 Immunoglobulin Proteins 0.000 description 1
- 101710176220 Kallikrein-2 Proteins 0.000 description 1
- 229940124091 Keratolytic Drugs 0.000 description 1
- 102000002397 Kinins Human genes 0.000 description 1
- 108010093008 Kinins Proteins 0.000 description 1
- 241000235058 Komagataella pastoris Species 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
- FFEARJCKVFRZRR-BYPYZUCNSA-N L-methionine Chemical compound CSCC[C@H](N)C(O)=O FFEARJCKVFRZRR-BYPYZUCNSA-N 0.000 description 1
- 108010000817 Leuprolide Proteins 0.000 description 1
- 101001018085 Lysobacter enzymogenes Lysyl endopeptidase Proteins 0.000 description 1
- 229930195725 Mannitol Natural products 0.000 description 1
- 108010072582 Matrilin Proteins Proteins 0.000 description 1
- 102000055008 Matrilin Proteins Human genes 0.000 description 1
- 244000062730 Melissa officinalis Species 0.000 description 1
- 235000010654 Melissa officinalis Nutrition 0.000 description 1
- 239000004909 Moisturizer Substances 0.000 description 1
- 102000016943 Muramidase Human genes 0.000 description 1
- 108010014251 Muramidase Proteins 0.000 description 1
- 241000699660 Mus musculus Species 0.000 description 1
- 101000836058 Mus musculus Serine protease inhibitor A3C Proteins 0.000 description 1
- 108010062010 N-Acetylmuramoyl-L-alanine Amidase Proteins 0.000 description 1
- 206010028813 Nausea Diseases 0.000 description 1
- 206010061309 Neoplasm progression Diseases 0.000 description 1
- 101100007739 Neosartorya fumigata (strain ATCC MYA-4609 / Af293 / CBS 101355 / FGSC A1100) crmA gene Proteins 0.000 description 1
- 239000000020 Nitrocellulose Substances 0.000 description 1
- 108020004485 Nonsense Codon Proteins 0.000 description 1
- 108700026244 Open Reading Frames Proteins 0.000 description 1
- 241000283973 Oryctolagus cuniculus Species 0.000 description 1
- 208000001132 Osteoporosis Diseases 0.000 description 1
- 108010058846 Ovalbumin Proteins 0.000 description 1
- 238000012408 PCR amplification Methods 0.000 description 1
- 239000002033 PVDF binder Substances 0.000 description 1
- 206010033645 Pancreatitis Diseases 0.000 description 1
- 101000909992 Papio hamadryas Chymase Proteins 0.000 description 1
- GKZIWHRNKRBEOH-HOTGVXAUSA-N Phe-Phe Chemical compound C([C@H]([NH3+])C(=O)N[C@@H](CC=1C=CC=CC=1)C([O-])=O)C1=CC=CC=C1 GKZIWHRNKRBEOH-HOTGVXAUSA-N 0.000 description 1
- 102000004179 Plasminogen Activator Inhibitor 2 Human genes 0.000 description 1
- 108090000614 Plasminogen Activator Inhibitor 2 Proteins 0.000 description 1
- 102000010752 Plasminogen Inactivators Human genes 0.000 description 1
- 108010077971 Plasminogen Inactivators Proteins 0.000 description 1
- 239000004372 Polyvinyl alcohol Substances 0.000 description 1
- 102000007066 Prostate-Specific Antigen Human genes 0.000 description 1
- 101710180012 Protease 7 Proteins 0.000 description 1
- 102100023710 Proteinase-activated receptor 4 Human genes 0.000 description 1
- 201000001263 Psoriatic Arthritis Diseases 0.000 description 1
- 208000036824 Psoriatic arthropathy Diseases 0.000 description 1
- 108010092799 RNA-directed DNA polymerase Proteins 0.000 description 1
- 101000836071 Rattus norvegicus Serine protease inhibitor A3K Proteins 0.000 description 1
- 108020004511 Recombinant DNA Proteins 0.000 description 1
- 206010063837 Reperfusion injury Diseases 0.000 description 1
- 241001303601 Rosacea Species 0.000 description 1
- 101150049485 SPINK5 gene Proteins 0.000 description 1
- 102000003667 Serine Endopeptidases Human genes 0.000 description 1
- 108090000083 Serine Endopeptidases Proteins 0.000 description 1
- 102100030326 Serpin B4 Human genes 0.000 description 1
- 102100025521 Serpin B7 Human genes 0.000 description 1
- 101710156145 Serpin B7 Proteins 0.000 description 1
- 102100027287 Serpin H1 Human genes 0.000 description 1
- 108010071390 Serum Albumin Proteins 0.000 description 1
- 102000007562 Serum Albumin Human genes 0.000 description 1
- 108020004682 Single-Stranded DNA Proteins 0.000 description 1
- 208000000453 Skin Neoplasms Diseases 0.000 description 1
- 206010040914 Skin reaction Diseases 0.000 description 1
- 102100038803 Somatotropin Human genes 0.000 description 1
- 108010090804 Streptavidin Proteins 0.000 description 1
- 241000187747 Streptomyces Species 0.000 description 1
- 241000187180 Streptomyces sp. Species 0.000 description 1
- 108700018667 Streptomyces subtilisin inhibitor Proteins 0.000 description 1
- 101710172711 Structural protein Proteins 0.000 description 1
- 101710174704 Subtilisin-like serine protease Proteins 0.000 description 1
- 229930006000 Sucrose Natural products 0.000 description 1
- 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 1
- 108700005078 Synthetic Genes Proteins 0.000 description 1
- 239000004098 Tetracycline Substances 0.000 description 1
- 208000007536 Thrombosis Diseases 0.000 description 1
- GYDJEQRTZSCIOI-UHFFFAOYSA-N Tranexamic acid Chemical compound NCC1CCC(C(O)=O)CC1 GYDJEQRTZSCIOI-UHFFFAOYSA-N 0.000 description 1
- HDTRYLNUVZCQOY-WSWWMNSNSA-N Trehalose Natural products O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@@H]1O[C@@H]1[C@H](O)[C@@H](O)[C@@H](O)[C@@H](CO)O1 HDTRYLNUVZCQOY-WSWWMNSNSA-N 0.000 description 1
- 108010084455 Zeocin Proteins 0.000 description 1
- 101150037054 aat gene Proteins 0.000 description 1
- 230000005856 abnormality Effects 0.000 description 1
- 238000005299 abrasion Methods 0.000 description 1
- 238000009825 accumulation Methods 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 206010000496 acne Diseases 0.000 description 1
- 239000004480 active ingredient Substances 0.000 description 1
- 108010016828 adenylyl sulfate-ammonia adenylyltransferase Proteins 0.000 description 1
- 230000006838 adverse reaction Effects 0.000 description 1
- 239000008272 agar Substances 0.000 description 1
- 238000013019 agitation Methods 0.000 description 1
- 230000007815 allergy Effects 0.000 description 1
- HDTRYLNUVZCQOY-LIZSDCNHSA-N alpha,alpha-trehalose Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@@H]1O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 HDTRYLNUVZCQOY-LIZSDCNHSA-N 0.000 description 1
- 102000003801 alpha-2-Antiplasmin Human genes 0.000 description 1
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
- 150000001408 amides Chemical class 0.000 description 1
- 229940093740 amino acid and derivative Drugs 0.000 description 1
- 239000003242 anti bacterial agent Substances 0.000 description 1
- 230000003712 anti-aging effect Effects 0.000 description 1
- 230000000845 anti-microbial effect Effects 0.000 description 1
- 229940088710 antibiotic agent Drugs 0.000 description 1
- 229940019748 antifibrinolytic proteinase inhibitors Drugs 0.000 description 1
- 229940121375 antifungal agent Drugs 0.000 description 1
- 239000000427 antigen Substances 0.000 description 1
- 108091007433 antigens Proteins 0.000 description 1
- 102000036639 antigens Human genes 0.000 description 1
- 229960005348 antithrombin iii Drugs 0.000 description 1
- 239000003443 antiviral agent Substances 0.000 description 1
- 229940121357 antivirals Drugs 0.000 description 1
- 235000010323 ascorbic acid Nutrition 0.000 description 1
- 229960005070 ascorbic acid Drugs 0.000 description 1
- 239000011668 ascorbic acid Substances 0.000 description 1
- 229960001230 asparagine Drugs 0.000 description 1
- 235000009582 asparagine Nutrition 0.000 description 1
- JPIYZTWMUGTEHX-UHFFFAOYSA-N auramine O free base Chemical compound C1=CC(N(C)C)=CC=C1C(=N)C1=CC=C(N(C)C)C=C1 JPIYZTWMUGTEHX-UHFFFAOYSA-N 0.000 description 1
- 230000001363 autoimmune Effects 0.000 description 1
- 208000022362 bacterial infectious disease Diseases 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 229960000686 benzalkonium chloride Drugs 0.000 description 1
- 229960001950 benzethonium chloride Drugs 0.000 description 1
- UREZNYTWGJKWBI-UHFFFAOYSA-M benzethonium chloride Chemical compound [Cl-].C1=CC(C(C)(C)CC(C)(C)C)=CC=C1OCCOCC[N+](C)(C)CC1=CC=CC=C1 UREZNYTWGJKWBI-UHFFFAOYSA-M 0.000 description 1
- 235000019445 benzyl alcohol Nutrition 0.000 description 1
- CADWTSSKOVRVJC-UHFFFAOYSA-N benzyl(dimethyl)azanium;chloride Chemical compound [Cl-].C[NH+](C)CC1=CC=CC=C1 CADWTSSKOVRVJC-UHFFFAOYSA-N 0.000 description 1
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 1
- 108091008324 binding proteins Proteins 0.000 description 1
- 239000013060 biological fluid Substances 0.000 description 1
- 230000031018 biological processes and functions Effects 0.000 description 1
- 229920001222 biopolymer Polymers 0.000 description 1
- 230000008499 blood brain barrier function Effects 0.000 description 1
- 230000017531 blood circulation Effects 0.000 description 1
- 210000001218 blood-brain barrier Anatomy 0.000 description 1
- 230000037396 body weight Effects 0.000 description 1
- DQXBYHZEEUGOBF-UHFFFAOYSA-N but-3-enoic acid;ethene Chemical compound C=C.OC(=O)CC=C DQXBYHZEEUGOBF-UHFFFAOYSA-N 0.000 description 1
- 235000014121 butter Nutrition 0.000 description 1
- 238000010804 cDNA synthesis Methods 0.000 description 1
- 238000011088 calibration curve Methods 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 238000006555 catalytic reaction Methods 0.000 description 1
- 102000014509 cathelicidin Human genes 0.000 description 1
- 108060001132 cathelicidin Proteins 0.000 description 1
- 238000005341 cation exchange Methods 0.000 description 1
- 238000004113 cell culture Methods 0.000 description 1
- 230000024245 cell differentiation Effects 0.000 description 1
- 230000033077 cellular process Effects 0.000 description 1
- 210000001638 cerebellum Anatomy 0.000 description 1
- 230000002490 cerebral effect Effects 0.000 description 1
- 239000002738 chelating agent Substances 0.000 description 1
- 238000001311 chemical methods and process Methods 0.000 description 1
- 239000007795 chemical reaction product Substances 0.000 description 1
- 238000004587 chromatography analysis Methods 0.000 description 1
- 230000007882 cirrhosis Effects 0.000 description 1
- 208000019425 cirrhosis of liver Diseases 0.000 description 1
- 239000011280 coal tar Substances 0.000 description 1
- 229920001436 collagen Polymers 0.000 description 1
- 238000013170 computed tomography imaging Methods 0.000 description 1
- 238000011970 concomitant therapy Methods 0.000 description 1
- 238000011109 contamination Methods 0.000 description 1
- 108010075231 contrapsin Proteins 0.000 description 1
- 150000003983 crown ethers Chemical class 0.000 description 1
- 238000002447 crystallographic data Methods 0.000 description 1
- VYQRBKCKQCRYEE-UHFFFAOYSA-N ctk1a7239 Chemical compound C12=CC=CC=C2N2CC=CC3=NC=CC1=C32 VYQRBKCKQCRYEE-UHFFFAOYSA-N 0.000 description 1
- 239000012228 culture supernatant Substances 0.000 description 1
- 238000009109 curative therapy Methods 0.000 description 1
- 108010082025 cyan fluorescent protein Proteins 0.000 description 1
- HPXRVTGHNJAIIH-UHFFFAOYSA-N cyclohexanol Chemical compound OC1CCCCC1 HPXRVTGHNJAIIH-UHFFFAOYSA-N 0.000 description 1
- 210000000805 cytoplasm Anatomy 0.000 description 1
- 230000007812 deficiency Effects 0.000 description 1
- 230000006735 deficit Effects 0.000 description 1
- 230000018044 dehydration Effects 0.000 description 1
- 238000006297 dehydration reaction Methods 0.000 description 1
- 239000002781 deodorant agent Substances 0.000 description 1
- 230000001419 dependent effect Effects 0.000 description 1
- 230000003831 deregulation Effects 0.000 description 1
- 230000001496 desquamative effect Effects 0.000 description 1
- 235000019425 dextrin Nutrition 0.000 description 1
- 239000008121 dextrose Substances 0.000 description 1
- 239000000032 diagnostic agent Substances 0.000 description 1
- 229940039227 diagnostic agent Drugs 0.000 description 1
- 238000002405 diagnostic procedure Methods 0.000 description 1
- 238000012631 diagnostic technique Methods 0.000 description 1
- 238000009792 diffusion process Methods 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
- 150000002016 disaccharides Chemical class 0.000 description 1
- 238000010494 dissociation reaction Methods 0.000 description 1
- 230000005593 dissociations Effects 0.000 description 1
- 208000002173 dizziness Diseases 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 230000037336 dry skin Effects 0.000 description 1
- 230000002497 edematous effect Effects 0.000 description 1
- 230000002500 effect on skin Effects 0.000 description 1
- 238000010828 elution Methods 0.000 description 1
- 230000003511 endothelial effect Effects 0.000 description 1
- 239000003623 enhancer Substances 0.000 description 1
- 230000006353 environmental stress Effects 0.000 description 1
- 239000002532 enzyme inhibitor Substances 0.000 description 1
- 229940125532 enzyme inhibitor Drugs 0.000 description 1
- 210000001339 epidermal cell Anatomy 0.000 description 1
- 239000006167 equilibration buffer Substances 0.000 description 1
- UYAHIZSMUZPPFV-UHFFFAOYSA-N erbium Chemical compound [Er] UYAHIZSMUZPPFV-UHFFFAOYSA-N 0.000 description 1
- 231100000321 erythema Toxicity 0.000 description 1
- 239000002329 esterase inhibitor Substances 0.000 description 1
- 239000005038 ethylene vinyl acetate Substances 0.000 description 1
- OGPBJKLSAFTDLK-UHFFFAOYSA-N europium atom Chemical compound [Eu] OGPBJKLSAFTDLK-UHFFFAOYSA-N 0.000 description 1
- 230000005713 exacerbation Effects 0.000 description 1
- 208000004526 exfoliative dermatitis Diseases 0.000 description 1
- 210000002744 extracellular matrix Anatomy 0.000 description 1
- 230000001815 facial effect Effects 0.000 description 1
- 230000002349 favourable effect Effects 0.000 description 1
- 230000004720 fertilization Effects 0.000 description 1
- 230000020764 fibrinolysis Effects 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- GNBHRKFJIUUOQI-UHFFFAOYSA-N fluorescein Chemical compound O1C(=O)C2=CC=CC=C2C21C1=CC=C(O)C=C1OC1=CC(O)=CC=C21 GNBHRKFJIUUOQI-UHFFFAOYSA-N 0.000 description 1
- 239000006260 foam Substances 0.000 description 1
- 230000037433 frameshift Effects 0.000 description 1
- 108020001507 fusion proteins Proteins 0.000 description 1
- 102000037865 fusion proteins Human genes 0.000 description 1
- UIWYJDYFSGRHKR-UHFFFAOYSA-N gadolinium atom Chemical compound [Gd] UIWYJDYFSGRHKR-UHFFFAOYSA-N 0.000 description 1
- 239000007789 gas Substances 0.000 description 1
- 238000001502 gel electrophoresis Methods 0.000 description 1
- 239000008273 gelatin Substances 0.000 description 1
- 229920000159 gelatin Polymers 0.000 description 1
- 235000019322 gelatine Nutrition 0.000 description 1
- 235000011852 gelatine desserts Nutrition 0.000 description 1
- 238000003208 gene overexpression Methods 0.000 description 1
- 230000009395 genetic defect Effects 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- 229960002989 glutamic acid Drugs 0.000 description 1
- ZDXPYRJPNDTMRX-UHFFFAOYSA-N glutamine Natural products OC(=O)C(N)CCC(N)=O ZDXPYRJPNDTMRX-UHFFFAOYSA-N 0.000 description 1
- YMAWOPBAYDPSLA-UHFFFAOYSA-N glycylglycine Chemical compound [NH3+]CC(=O)NCC([O-])=O YMAWOPBAYDPSLA-UHFFFAOYSA-N 0.000 description 1
- 230000012010 growth Effects 0.000 description 1
- 229940093915 gynecological organic acid Drugs 0.000 description 1
- 239000000118 hair dye Substances 0.000 description 1
- 210000004919 hair shaft Anatomy 0.000 description 1
- 239000008266 hair spray Substances 0.000 description 1
- 230000036541 health Effects 0.000 description 1
- 229960002897 heparin Drugs 0.000 description 1
- 229920000669 heparin Polymers 0.000 description 1
- 125000005842 heteroatom Chemical group 0.000 description 1
- 208000002557 hidradenitis Diseases 0.000 description 1
- 201000007162 hidradenitis suppurativa Diseases 0.000 description 1
- HNDVDQJCIGZPNO-UHFFFAOYSA-N histidine Natural products OC(=O)C(N)CC1=CN=CN1 HNDVDQJCIGZPNO-UHFFFAOYSA-N 0.000 description 1
- KJZYNXUDTRRSPN-UHFFFAOYSA-N holmium atom Chemical compound [Ho] KJZYNXUDTRRSPN-UHFFFAOYSA-N 0.000 description 1
- 230000006801 homologous recombination Effects 0.000 description 1
- 238000002744 homologous recombination Methods 0.000 description 1
- 102000048448 human CASP8 Human genes 0.000 description 1
- 102000045758 human HK2 Human genes 0.000 description 1
- 102000047743 human KLK14 Human genes 0.000 description 1
- 102000053974 human KLK6 Human genes 0.000 description 1
- 102000052834 human SERPINC1 Human genes 0.000 description 1
- 102000044507 human SERPING1 Human genes 0.000 description 1
- 229960004336 human antithrombin iii Drugs 0.000 description 1
- 229920001477 hydrophilic polymer Polymers 0.000 description 1
- 125000001165 hydrophobic group Chemical group 0.000 description 1
- 229920001600 hydrophobic polymer Polymers 0.000 description 1
- 239000012216 imaging agent Substances 0.000 description 1
- 230000001900 immune effect Effects 0.000 description 1
- 230000028993 immune response Effects 0.000 description 1
- 102000018358 immunoglobulin Human genes 0.000 description 1
- 229940072221 immunoglobulins Drugs 0.000 description 1
- 229940088592 immunologic factor Drugs 0.000 description 1
- 239000000367 immunologic factor Substances 0.000 description 1
- 239000002955 immunomodulating agent Substances 0.000 description 1
- 229940121354 immunomodulator Drugs 0.000 description 1
- 238000011503 in vivo imaging Methods 0.000 description 1
- 238000011065 in-situ storage Methods 0.000 description 1
- 230000002779 inactivation Effects 0.000 description 1
- 230000036512 infertility Effects 0.000 description 1
- 230000028709 inflammatory response Effects 0.000 description 1
- 238000001802 infusion Methods 0.000 description 1
- 239000004615 ingredient Substances 0.000 description 1
- ZPNFWUPYTFPOJU-LPYSRVMUSA-N iniprol Chemical compound C([C@H]1C(=O)NCC(=O)NCC(=O)N[C@H]2CSSC[C@H]3C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@H](C(N[C@H](C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC=4C=CC(O)=CC=4)C(=O)N[C@@H](CC=4C=CC=CC=4)C(=O)N[C@@H](CC=4C=CC(O)=CC=4)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](C)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](C)C(=O)NCC(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CSSC[C@H](NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C)NC(=O)[C@H](CO)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CC=4C=CC=CC=4)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CCCCN)NC(=O)[C@H](C)NC(=O)[C@H](CCCNC(N)=N)NC2=O)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CSSC[C@H](NC(=O)[C@H](CC=2C=CC=CC=2)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H]2N(CCC2)C(=O)[C@@H](N)CCCNC(N)=N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(O)=O)C(=O)N2[C@@H](CCC2)C(=O)N2[C@@H](CCC2)C(=O)N[C@@H](CC=2C=CC(O)=CC=2)C(=O)N[C@@H]([C@@H](C)O)C(=O)NCC(=O)N2[C@@H](CCC2)C(=O)N3)C(=O)NCC(=O)NCC(=O)N[C@@H](C)C(O)=O)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@H](C(=O)N[C@@H](CC=2C=CC=CC=2)C(=O)N[C@H](C(=O)N1)C(C)C)[C@@H](C)O)[C@@H](C)CC)=O)[C@@H](C)CC)C1=CC=C(O)C=C1 ZPNFWUPYTFPOJU-LPYSRVMUSA-N 0.000 description 1
- 238000013101 initial test Methods 0.000 description 1
- 238000003780 insertion Methods 0.000 description 1
- 230000037431 insertion Effects 0.000 description 1
- 238000007918 intramuscular administration Methods 0.000 description 1
- 238000007912 intraperitoneal administration Methods 0.000 description 1
- 239000002563 ionic surfactant Substances 0.000 description 1
- 150000002500 ions Chemical class 0.000 description 1
- 229910052742 iron Inorganic materials 0.000 description 1
- 230000007794 irritation Effects 0.000 description 1
- 108010050180 kallistatin Proteins 0.000 description 1
- 230000001530 keratinolytic effect Effects 0.000 description 1
- 239000003410 keratolytic agent Substances 0.000 description 1
- 210000003292 kidney cell Anatomy 0.000 description 1
- 238000012933 kinetic analysis Methods 0.000 description 1
- 108010038862 laminin 10 Proteins 0.000 description 1
- 229910052746 lanthanum Inorganic materials 0.000 description 1
- FZLIPJUXYLNCLC-UHFFFAOYSA-N lanthanum atom Chemical compound [La] FZLIPJUXYLNCLC-UHFFFAOYSA-N 0.000 description 1
- 229960004338 leuprorelin Drugs 0.000 description 1
- 239000000865 liniment Substances 0.000 description 1
- 150000002632 lipids Chemical class 0.000 description 1
- 230000007774 longterm Effects 0.000 description 1
- 239000006210 lotion Substances 0.000 description 1
- 239000007937 lozenge Substances 0.000 description 1
- DLBFLQKQABVKGT-UHFFFAOYSA-L lucifer yellow dye Chemical compound [Li+].[Li+].[O-]S(=O)(=O)C1=CC(C(N(C(=O)NN)C2=O)=O)=C3C2=CC(S([O-])(=O)=O)=CC3=C1N DLBFLQKQABVKGT-UHFFFAOYSA-L 0.000 description 1
- 230000002132 lysosomal effect Effects 0.000 description 1
- 239000004325 lysozyme Substances 0.000 description 1
- 229960000274 lysozyme Drugs 0.000 description 1
- 235000010335 lysozyme Nutrition 0.000 description 1
- RLSSMJSEOOYNOY-UHFFFAOYSA-N m-cresol Chemical compound CC1=CC=CC(O)=C1 RLSSMJSEOOYNOY-UHFFFAOYSA-N 0.000 description 1
- 229920002521 macromolecule Polymers 0.000 description 1
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 1
- 235000019341 magnesium sulphate Nutrition 0.000 description 1
- 238000002595 magnetic resonance imaging Methods 0.000 description 1
- WPBNNNQJVZRUHP-UHFFFAOYSA-L manganese(2+);methyl n-[[2-(methoxycarbonylcarbamothioylamino)phenyl]carbamothioyl]carbamate;n-[2-(sulfidocarbothioylamino)ethyl]carbamodithioate Chemical compound [Mn+2].[S-]C(=S)NCCNC([S-])=S.COC(=O)NC(=S)NC1=CC=CC=C1NC(=S)NC(=O)OC WPBNNNQJVZRUHP-UHFFFAOYSA-L 0.000 description 1
- 239000000594 mannitol Substances 0.000 description 1
- 235000010355 mannitol Nutrition 0.000 description 1
- 238000000691 measurement method Methods 0.000 description 1
- 201000001441 melanoma Diseases 0.000 description 1
- 108020004999 messenger RNA Proteins 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
- 239000002184 metal Chemical class 0.000 description 1
- 229930182817 methionine Natural products 0.000 description 1
- 235000010270 methyl p-hydroxybenzoate Nutrition 0.000 description 1
- 239000004292 methyl p-hydroxybenzoate Substances 0.000 description 1
- 229960002216 methylparaben Drugs 0.000 description 1
- 239000003094 microcapsule Substances 0.000 description 1
- 239000004005 microsphere Substances 0.000 description 1
- 230000005012 migration Effects 0.000 description 1
- 238000013508 migration Methods 0.000 description 1
- 230000001333 moisturizer Effects 0.000 description 1
- 210000001616 monocyte Anatomy 0.000 description 1
- 150000002772 monosaccharides Chemical class 0.000 description 1
- 210000002200 mouth mucosa Anatomy 0.000 description 1
- 230000035772 mutation Effects 0.000 description 1
- 210000000282 nail Anatomy 0.000 description 1
- 230000008693 nausea Effects 0.000 description 1
- 230000002232 neuromuscular Effects 0.000 description 1
- 229910052759 nickel Inorganic materials 0.000 description 1
- 229920001220 nitrocellulos Polymers 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- 230000037434 nonsense mutation Effects 0.000 description 1
- 231100000252 nontoxic Toxicity 0.000 description 1
- 230000003000 nontoxic effect Effects 0.000 description 1
- 230000037311 normal skin Effects 0.000 description 1
- 239000002777 nucleoside Substances 0.000 description 1
- 150000003833 nucleoside derivatives Chemical class 0.000 description 1
- 239000003921 oil Substances 0.000 description 1
- 210000000056 organ Anatomy 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 235000005985 organic acids Nutrition 0.000 description 1
- 229940092253 ovalbumin Drugs 0.000 description 1
- 230000002018 overexpression Effects 0.000 description 1
- 230000036407 pain Effects 0.000 description 1
- 230000037324 pain perception Effects 0.000 description 1
- 210000000496 pancreas Anatomy 0.000 description 1
- 238000004091 panning Methods 0.000 description 1
- 230000005298 paramagnetic effect Effects 0.000 description 1
- 239000002245 particle Substances 0.000 description 1
- 230000008506 pathogenesis Effects 0.000 description 1
- 230000001575 pathological effect Effects 0.000 description 1
- 230000007310 pathophysiology Effects 0.000 description 1
- 238000000059 patterning Methods 0.000 description 1
- 239000002304 perfume Substances 0.000 description 1
- 230000002572 peristaltic effect Effects 0.000 description 1
- 230000035699 permeability Effects 0.000 description 1
- 108010073025 phenylalanylphenylalanine Proteins 0.000 description 1
- CWCMIVBLVUHDHK-ZSNHEYEWSA-N phleomycin D1 Chemical compound N([C@H](C(=O)N[C@H](C)[C@@H](O)[C@H](C)C(=O)N[C@@H]([C@H](O)C)C(=O)NCCC=1SC[C@@H](N=1)C=1SC=C(N=1)C(=O)NCCCCNC(N)=N)[C@@H](O[C@H]1[C@H]([C@@H](O)[C@H](O)[C@H](CO)O1)O[C@@H]1[C@H]([C@@H](OC(N)=O)[C@H](O)[C@@H](CO)O1)O)C=1N=CNC=1)C(=O)C1=NC([C@H](CC(N)=O)NC[C@H](N)C(N)=O)=NC(N)=C1C CWCMIVBLVUHDHK-ZSNHEYEWSA-N 0.000 description 1
- 230000001766 physiological effect Effects 0.000 description 1
- 230000035479 physiological effects, processes and functions Effects 0.000 description 1
- 230000035790 physiological processes and functions Effects 0.000 description 1
- 235000017807 phytochemicals Nutrition 0.000 description 1
- 108090000102 pigment epithelium-derived factor Proteins 0.000 description 1
- 230000003169 placental effect Effects 0.000 description 1
- 229930000223 plant secondary metabolite Natural products 0.000 description 1
- 239000002797 plasminogen activator inhibitor Substances 0.000 description 1
- 229920003023 plastic Polymers 0.000 description 1
- 239000004033 plastic Substances 0.000 description 1
- 238000007747 plating Methods 0.000 description 1
- 229920001200 poly(ethylene-vinyl acetate) Polymers 0.000 description 1
- 229920000747 poly(lactic acid) Polymers 0.000 description 1
- 229920000768 polyamine Polymers 0.000 description 1
- 229920000728 polyester Polymers 0.000 description 1
- 229920002338 polyhydroxyethylmethacrylate Polymers 0.000 description 1
- 229920002451 polyvinyl alcohol Polymers 0.000 description 1
- 229920002981 polyvinylidene fluoride Polymers 0.000 description 1
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 1
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
- 150000004032 porphyrins Chemical class 0.000 description 1
- 229910000160 potassium phosphate Inorganic materials 0.000 description 1
- 235000011009 potassium phosphates Nutrition 0.000 description 1
- 238000001556 precipitation Methods 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 230000003449 preventive effect Effects 0.000 description 1
- 108010090013 prohormone thiol protease Proteins 0.000 description 1
- 238000011321 prophylaxis Methods 0.000 description 1
- 235000010232 propyl p-hydroxybenzoate Nutrition 0.000 description 1
- 239000004405 propyl p-hydroxybenzoate Substances 0.000 description 1
- 229960003415 propylparaben Drugs 0.000 description 1
- 230000012846 protein folding Effects 0.000 description 1
- 238000001742 protein purification Methods 0.000 description 1
- 230000017854 proteolysis Effects 0.000 description 1
- 229940024999 proteolytic enzymes for treatment of wounds and ulcers Drugs 0.000 description 1
- 230000002685 pulmonary effect Effects 0.000 description 1
- 150000003254 radicals Chemical class 0.000 description 1
- 239000011541 reaction mixture Substances 0.000 description 1
- 230000008707 rearrangement Effects 0.000 description 1
- 238000010188 recombinant method Methods 0.000 description 1
- 230000012760 regulation of cell migration Effects 0.000 description 1
- 230000031567 regulation of fertilization Effects 0.000 description 1
- 230000031337 regulation of inflammatory response Effects 0.000 description 1
- 230000001718 repressive effect Effects 0.000 description 1
- 230000003938 response to stress Effects 0.000 description 1
- 208000037803 restenosis Diseases 0.000 description 1
- 238000003757 reverse transcription PCR Methods 0.000 description 1
- 238000012552 review Methods 0.000 description 1
- 229910052702 rhenium Inorganic materials 0.000 description 1
- WUAPFZMCVAUBPE-UHFFFAOYSA-N rhenium atom Chemical compound [Re] WUAPFZMCVAUBPE-UHFFFAOYSA-N 0.000 description 1
- PYWVYCXTNDRMGF-UHFFFAOYSA-N rhodamine B Chemical compound [Cl-].C=12C=CC(=[N+](CC)CC)C=C2OC2=CC(N(CC)CC)=CC=C2C=1C1=CC=CC=C1C(O)=O PYWVYCXTNDRMGF-UHFFFAOYSA-N 0.000 description 1
- 201000004700 rosacea Diseases 0.000 description 1
- 108010059841 serine carboxypeptidase Proteins 0.000 description 1
- UQDJGEHQDNVPGU-UHFFFAOYSA-N serine phosphoethanolamine Chemical compound [NH3+]CCOP([O-])(=O)OCC([NH3+])C([O-])=O UQDJGEHQDNVPGU-UHFFFAOYSA-N 0.000 description 1
- 125000003607 serino group Chemical group [H]N([H])[C@]([H])(C(=O)[*])C(O[H])([H])[H] 0.000 description 1
- 230000035939 shock Effects 0.000 description 1
- 230000037432 silent mutation Effects 0.000 description 1
- 201000000849 skin cancer Diseases 0.000 description 1
- 231100000430 skin reaction Toxicity 0.000 description 1
- 230000035483 skin reaction Effects 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 238000001179 sorption measurement Methods 0.000 description 1
- 235000020712 soy bean extract Nutrition 0.000 description 1
- 235000013322 soy milk Nutrition 0.000 description 1
- 241000894007 species Species 0.000 description 1
- 230000009870 specific binding Effects 0.000 description 1
- 238000004611 spectroscopical analysis Methods 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 238000010561 standard procedure Methods 0.000 description 1
- SFVFIFLLYFPGHH-UHFFFAOYSA-M stearalkonium chloride Chemical compound [Cl-].CCCCCCCCCCCCCCCCCC[N+](C)(C)CC1=CC=CC=C1 SFVFIFLLYFPGHH-UHFFFAOYSA-M 0.000 description 1
- 238000011146 sterile filtration Methods 0.000 description 1
- 230000003637 steroidlike Effects 0.000 description 1
- 230000035882 stress Effects 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- 108010043175 succinylalanylalanyl-prolyl-phenylalanine-4-methylcoumaryl-7-amide Proteins 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 239000004094 surface-active agent Substances 0.000 description 1
- 230000004083 survival effect Effects 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 238000001308 synthesis method Methods 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- 238000004885 tandem mass spectrometry Methods 0.000 description 1
- 229960002180 tetracycline Drugs 0.000 description 1
- 229930101283 tetracycline Natural products 0.000 description 1
- 235000019364 tetracycline Nutrition 0.000 description 1
- 150000003522 tetracyclines Chemical class 0.000 description 1
- MPLHNVLQVRSVEE-UHFFFAOYSA-N texas red Chemical compound [O-]S(=O)(=O)C1=CC(S(Cl)(=O)=O)=CC=C1C(C1=CC=2CCCN3CCCC(C=23)=C1O1)=C2C1=C(CCC1)C3=[N+]1CCCC3=C2 MPLHNVLQVRSVEE-UHFFFAOYSA-N 0.000 description 1
- 230000036962 time dependent Effects 0.000 description 1
- 230000000451 tissue damage Effects 0.000 description 1
- 231100000827 tissue damage Toxicity 0.000 description 1
- 230000007838 tissue remodeling Effects 0.000 description 1
- 238000000954 titration curve Methods 0.000 description 1
- 210000004906 toe nail Anatomy 0.000 description 1
- 238000011200 topical administration Methods 0.000 description 1
- 230000009466 transformation Effects 0.000 description 1
- 238000011830 transgenic mouse model Methods 0.000 description 1
- 230000008733 trauma Effects 0.000 description 1
- 239000001226 triphosphate Substances 0.000 description 1
- 235000011178 triphosphate Nutrition 0.000 description 1
- 125000002264 triphosphate group Chemical class [H]OP(=O)(O[H])OP(=O)(O[H])OP(=O)(O[H])O* 0.000 description 1
- GPRLSGONYQIRFK-MNYXATJNSA-N triton Chemical compound [3H+] GPRLSGONYQIRFK-MNYXATJNSA-N 0.000 description 1
- 210000004881 tumor cell Anatomy 0.000 description 1
- 230000005751 tumor progression Effects 0.000 description 1
- 230000005760 tumorsuppression Effects 0.000 description 1
- 230000007306 turnover Effects 0.000 description 1
- 238000000108 ultra-filtration Methods 0.000 description 1
- 238000009281 ultraviolet germicidal irradiation Methods 0.000 description 1
- 241000701447 unidentified baculovirus Species 0.000 description 1
- 230000003612 virological effect Effects 0.000 description 1
- 230000029302 virus maturation Effects 0.000 description 1
- 229940088594 vitamin Drugs 0.000 description 1
- 239000011782 vitamin Substances 0.000 description 1
- 235000013343 vitamin Nutrition 0.000 description 1
- 229930003231 vitamin Natural products 0.000 description 1
- 239000000341 volatile oil Substances 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/43—Enzymes; Proenzymes; Derivatives thereof
- A61K38/46—Hydrolases (3)
- A61K38/48—Hydrolases (3) acting on peptide bonds (3.4)
- A61K38/49—Urokinase; Tissue plasminogen activator
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/43—Enzymes; Proenzymes; Derivatives thereof
- A61K38/46—Hydrolases (3)
- A61K38/48—Hydrolases (3) acting on peptide bonds (3.4)
- A61K38/482—Serine endopeptidases (3.4.21)
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/43—Enzymes; Proenzymes; Derivatives thereof
- A61K38/46—Hydrolases (3)
- A61K38/48—Hydrolases (3) acting on peptide bonds (3.4)
- A61K38/482—Serine endopeptidases (3.4.21)
- A61K38/4826—Trypsin (3.4.21.4) Chymotrypsin (3.4.21.1)
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/43—Enzymes; Proenzymes; Derivatives thereof
- A61K38/46—Hydrolases (3)
- A61K38/48—Hydrolases (3) acting on peptide bonds (3.4)
- A61K38/482—Serine endopeptidases (3.4.21)
- A61K38/484—Plasmin (3.4.21.7)
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/43—Enzymes; Proenzymes; Derivatives thereof
- A61K38/46—Hydrolases (3)
- A61K38/48—Hydrolases (3) acting on peptide bonds (3.4)
- A61K38/482—Serine endopeptidases (3.4.21)
- A61K38/4853—Kallikrein (3.4.21.34 or 3.4.21.35)
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/43—Enzymes; Proenzymes; Derivatives thereof
- A61K38/46—Hydrolases (3)
- A61K38/48—Hydrolases (3) acting on peptide bonds (3.4)
- A61K38/482—Serine endopeptidases (3.4.21)
- A61K38/486—Elastase (3.4.21.36 or 3.4.21.37)
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/55—Protease inhibitors
- A61K38/57—Protease inhibitors from animals; from humans
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
- A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
- A61K8/64—Proteins; Peptides; Derivatives or degradation products thereof
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
- A61P17/02—Drugs for dermatological disorders for treating wounds, ulcers, burns, scars, keloids, or the like
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
- A61P17/04—Antipruritics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
- A61P17/06—Antipsoriatics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
- A61P17/10—Anti-acne agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/08—Antiallergic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
- A61Q19/00—Preparations for care of the skin
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
- C12Q1/00—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions
- C12Q1/34—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving hydrolase
- C12Q1/37—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving hydrolase involving peptidase or proteinase
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
- G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
- G01N33/5005—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving human or animal cells
- G01N33/5008—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving human or animal cells for testing or evaluating the effect of chemical or biological compounds, e.g. drugs, cosmetics
- G01N33/502—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving human or animal cells for testing or evaluating the effect of chemical or biological compounds, e.g. drugs, cosmetics for testing non-proliferative effects
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K2800/00—Properties of cosmetic compositions or active ingredients thereof or formulation aids used therein and process related aspects
- A61K2800/74—Biological properties of particular ingredients
- A61K2800/78—Enzyme modulators, e.g. Enzyme agonists
- A61K2800/782—Enzyme inhibitors; Enzyme antagonists
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N2333/00—Assays involving biological materials from specific organisms or of a specific nature
- G01N2333/90—Enzymes; Proenzymes
- G01N2333/914—Hydrolases (3)
- G01N2333/948—Hydrolases (3) acting on peptide bonds (3.4)
- G01N2333/95—Proteinases, i.e. endopeptidases (3.4.21-3.4.99)
- G01N2333/964—Proteinases, i.e. endopeptidases (3.4.21-3.4.99) derived from animal tissue
- G01N2333/96425—Proteinases, i.e. endopeptidases (3.4.21-3.4.99) derived from animal tissue from mammals
- G01N2333/96427—Proteinases, i.e. endopeptidases (3.4.21-3.4.99) derived from animal tissue from mammals in general
- G01N2333/9643—Proteinases, i.e. endopeptidases (3.4.21-3.4.99) derived from animal tissue from mammals in general with EC number
- G01N2333/96433—Serine endopeptidases (3.4.21)
- G01N2333/96441—Serine endopeptidases (3.4.21) with definite EC number
- G01N2333/96455—Kallikrein (3.4.21.34; 3.4.21.35)
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N2500/00—Screening for compounds of potential therapeutic value
- G01N2500/04—Screening involving studying the effect of compounds C directly on molecule A (e.g. C are potential ligands for a receptor A, or potential substrates for an enzyme A)
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Engineering & Computer Science (AREA)
- Chemical & Material Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Immunology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Epidemiology (AREA)
- Gastroenterology & Hepatology (AREA)
- Organic Chemistry (AREA)
- Dermatology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Biomedical Technology (AREA)
- Zoology (AREA)
- Molecular Biology (AREA)
- Biotechnology (AREA)
- Hematology (AREA)
- Microbiology (AREA)
- Urology & Nephrology (AREA)
- Wood Science & Technology (AREA)
- Physics & Mathematics (AREA)
- Analytical Chemistry (AREA)
- Biochemistry (AREA)
- Birds (AREA)
- Tropical Medicine & Parasitology (AREA)
- Genetics & Genomics (AREA)
- Cell Biology (AREA)
- Toxicology (AREA)
- Pathology (AREA)
- General Physics & Mathematics (AREA)
- Biophysics (AREA)
- Food Science & Technology (AREA)
Applications Claiming Priority (5)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US2238608P | 2008-01-21 | 2008-01-21 | |
| US61/022,386 | 2008-01-21 | ||
| US657608P | 2008-01-22 | 2008-01-22 | |
| US61/006,576 | 2008-01-22 | ||
| CN2009801099736A CN101977626A (zh) | 2008-01-21 | 2009-01-21 | 丝氨酸蛋白酶抑制剂在治疗皮肤病中的用途 |
Related Parent Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN2009801099736A Division CN101977626A (zh) | 2008-01-21 | 2009-01-21 | 丝氨酸蛋白酶抑制剂在治疗皮肤病中的用途 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN110522905A true CN110522905A (zh) | 2019-12-03 |
Family
ID=40901490
Family Applications (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201910841916.2A Pending CN110522905A (zh) | 2008-01-21 | 2009-01-21 | 丝氨酸蛋白酶抑制剂在治疗皮肤病中的用途 |
| CN2009801099736A Pending CN101977626A (zh) | 2008-01-21 | 2009-01-21 | 丝氨酸蛋白酶抑制剂在治疗皮肤病中的用途 |
Family Applications After (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN2009801099736A Pending CN101977626A (zh) | 2008-01-21 | 2009-01-21 | 丝氨酸蛋白酶抑制剂在治疗皮肤病中的用途 |
Country Status (8)
| Country | Link |
|---|---|
| US (3) | US20110130338A1 (https=) |
| EP (1) | EP2244728B1 (https=) |
| JP (2) | JP5615184B2 (https=) |
| CN (2) | CN110522905A (https=) |
| AU (1) | AU2009207394B2 (https=) |
| BR (1) | BRPI0906167A2 (https=) |
| CA (1) | CA2712512C (https=) |
| WO (1) | WO2009093119A2 (https=) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN113768865A (zh) * | 2020-11-04 | 2021-12-10 | 深圳前海鹰岗生物科技有限公司 | 一种抑制炎症因子释放治疗痛风急性发作的聚合物微针及制备方法 |
Families Citing this family (28)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN110522905A (zh) | 2008-01-21 | 2019-12-03 | 德莫迪斯公司 | 丝氨酸蛋白酶抑制剂在治疗皮肤病中的用途 |
| EP2405925B1 (en) * | 2009-03-10 | 2015-01-14 | Med Discovery Sa | Kallikrein inhibitors for the treatment of neutropenia |
| WO2013084425A1 (ja) | 2011-12-09 | 2013-06-13 | モメンティブ・パフォーマンス・マテリアルズ・ジャパン合同会社 | シリコーンゴム発泡体用組成物、シリコーンゴム発泡体の製造方法およびシリコーンゴム発泡体 |
| DK2883954T3 (da) | 2012-08-08 | 2020-09-28 | Daiichi Sankyo Co Ltd | Peptidbibliotek og anvendelse deraf |
| JP6484174B2 (ja) * | 2012-09-19 | 2019-03-20 | マクカイ メモリアル ホスピタル | 皮膚老化を予防及び／又は改善するためのｐｅｄｆ−由来ポリペプチドの使用 |
| KR101437408B1 (ko) | 2012-11-05 | 2014-09-05 | 동아대학교 산학협력단 | 플라스민 및 엘라스타아제 저해 활성을 갖는 산왕거미 유래의 쿠니츠 타입 세린 프로테아제 저해 단백질 및 이를 유효성분으로 포함하는 염증 억제 및 항섬유소용해용 조성물 |
| US10807805B2 (en) | 2013-05-17 | 2020-10-20 | Intelligrated Headquarters, Llc | Robotic carton unloader |
| EP3495293B1 (en) | 2013-05-17 | 2023-05-03 | Intelligrated Headquarters LLC | Robotic carton unloader |
| GB201322091D0 (en) * | 2013-12-13 | 2014-01-29 | Cambridge Entpr Ltd | Modified serpins for the treatment of bleeding disorders |
| WO2015114144A1 (en) * | 2014-02-03 | 2015-08-06 | INSERM (Institut National de la Santé et de la Recherche Médicale) | Methods and pharmaceutical compositions for the treatment of netherton syndrome |
| EP3113849B1 (en) * | 2014-02-26 | 2019-06-12 | Luma Therapeutics, Inc. | Ultraviolet phototherapy apparatus |
| JP6738280B2 (ja) * | 2014-10-24 | 2020-08-12 | 株式会社 資生堂 | 角層剥離の抑制又は亢進に起因する肌状態を改善するための美容方法及び評価方法 |
| MA40998A (fr) | 2014-11-21 | 2017-09-26 | Ophirex Inc | Thérapies contre une envenimation, ainsi que compositions, systèmes et kits pharmaceutiques associés |
| US10597235B2 (en) | 2016-10-20 | 2020-03-24 | Intelligrated Headquarters, Llc | Carton unloader tool for jam recovery |
| CN106478812B (zh) * | 2016-10-21 | 2020-11-20 | 沈阳药科大学 | 丝氨酸蛋白酶抑制剂-3及其功能、制备方法和应用 |
| TW202313978A (zh) * | 2016-11-23 | 2023-04-01 | 美商阿尼拉製藥公司 | 絲胺酸蛋白酶抑制因子Ａ１ ｉＲＮＡ組成物及其使用方法 |
| SG11201909048TA (en) * | 2017-04-21 | 2019-11-28 | Genentech Inc | Use of klk5 antagonists for treatment of a disease |
| WO2018232300A1 (en) * | 2017-06-16 | 2018-12-20 | Azitra Inc | Compositions and methods for treatment of netherton syndrome with lekti expressing recombinant microbes |
| US20200040103A1 (en) | 2018-03-14 | 2020-02-06 | Genentech, Inc. | Anti-klk5 antibodies and methods of use |
| EP3856761A1 (en) | 2018-09-24 | 2021-08-04 | Krystal Biotech, Inc. | Compositions and methods for the treatment of netherton syndrome |
| PE20221906A1 (es) | 2019-09-18 | 2022-12-23 | Genentech Inc | Anticuerpos anti-klk7, anticuerpos anti-klk5, anticuerpos multiespecificos anti-klk5/klk7 y metodos de uso |
| CN114867865A (zh) * | 2019-11-21 | 2022-08-05 | 密执安大学评议会 | 中性粒细胞弹性蛋白酶活性的多肽抑制剂及其用途 |
| US20230099101A1 (en) * | 2020-03-06 | 2023-03-30 | The Regents Of The University Of Michigan | Serine protease inhibitors for suppressing or preventing anaphylactic reaction |
| EP4466008A4 (en) * | 2022-01-18 | 2025-08-20 | Univ California | METHOD FOR INHIBITING PROTEASE ACTIVITY IN DEGRADATION DURING AGING |
| JP7820193B2 (ja) * | 2022-03-04 | 2026-02-25 | 株式会社ナリス化粧品 | 角層剥離改善剤 |
| WO2024159008A1 (en) * | 2023-01-25 | 2024-08-02 | Quoin Pharmaceuticals, Inc. | Combination treatment for netherton syndrome |
| CN117084936A (zh) * | 2023-09-22 | 2023-11-21 | 南京盛德生物科技研究院有限公司 | 多萜类化合物作为激肽释放酶抑制剂在化妆品中的应用 |
| WO2026021603A1 (zh) * | 2024-07-25 | 2026-01-29 | 吉林大学第一医院 | Serpina3蛋白变异体或其编码序列以及它们的应用 |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1356907A (zh) * | 1999-06-18 | 2002-07-03 | 布亚纳森·乔·布拉吉 | 鱼丝氨酸蛋白酶及其在制药和化妆品上的应用 |
| CN1798838A (zh) * | 2003-04-04 | 2006-07-05 | 洛桑大学 | 一种蛋白酶的抑制剂蛋白及其用途 |
Family Cites Families (15)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5079336A (en) * | 1989-06-23 | 1992-01-07 | The Trustees Of The University Of Pennsylvania | α-1-antichymotrypsin, analogues and methods of production |
| US5252725A (en) * | 1989-06-23 | 1993-10-12 | The Trustees Of The University Of Pennsylvania | α-1-antichymotrypsin, analogues and methods of production |
| DE4214215A1 (de) * | 1992-04-30 | 1993-11-04 | Behringwerke Ag | Verwendung von inhibitoren von plasminogenaktivatoren zur behandlung von entzuendungen |
| AUPP508798A0 (en) * | 1998-08-05 | 1998-08-27 | Biotech Australia Pty Limited | Method of treating psoriasis |
| US7105172B1 (en) * | 1999-11-18 | 2006-09-12 | Bolla John D | Treatment of rosacea |
| WO2002040654A2 (en) * | 2000-11-14 | 2002-05-23 | Bristol-Myers Squibb Company | A human serpin secreted from lymphoid cells lsi-01 |
| US20040097481A1 (en) * | 2002-11-20 | 2004-05-20 | Benjamin Levinson | Water-soluble mesoporphyrin compounds and methods of preparation |
| AU2003286258B2 (en) * | 2002-11-20 | 2006-12-21 | Arriva-Prometic Inc. | Composition and method for treating inflammatory diseases using protease inhibitors |
| WO2005117955A1 (en) * | 2004-05-19 | 2005-12-15 | Arriva Pharmaceuticals, Inc. | Treatment of atopic dermatitis with unglycosylated alpha one-antitrypsin |
| EP1666075A1 (en) * | 2004-10-04 | 2006-06-07 | Switch Biotech Aktiengesellschaft | Wound dressing compositions, especially for delivery of protease inhibitors |
| WO2006090282A2 (en) * | 2005-02-28 | 2006-08-31 | Universite De Lausanne | Recombinant inhibitor proteins of an hk14 protease and use thereof |
| GB0525999D0 (en) * | 2005-12-21 | 2006-02-01 | Ares Trading Sa | Novel members of the kazal family of serine protease inhibitors |
| WO2009000878A1 (en) * | 2007-06-28 | 2008-12-31 | Novartis Ag | Kallikrein 7 modulators |
| WO2009024528A1 (en) * | 2007-08-17 | 2009-02-26 | Novartis Ag | Use of cyclic depsipeptides to inhibit kallikrein 7 |
| CN110522905A (zh) | 2008-01-21 | 2019-12-03 | 德莫迪斯公司 | 丝氨酸蛋白酶抑制剂在治疗皮肤病中的用途 |
-
2009
- 2009-01-21 CN CN201910841916.2A patent/CN110522905A/zh active Pending
- 2009-01-21 WO PCT/IB2009/000089 patent/WO2009093119A2/en not_active Ceased
- 2009-01-21 JP JP2010542703A patent/JP5615184B2/ja not_active Expired - Fee Related
- 2009-01-21 BR BRPI0906167-3A patent/BRPI0906167A2/en not_active IP Right Cessation
- 2009-01-21 EP EP09703640.4A patent/EP2244728B1/en active Active
- 2009-01-21 AU AU2009207394A patent/AU2009207394B2/en not_active Ceased
- 2009-01-21 CN CN2009801099736A patent/CN101977626A/zh active Pending
- 2009-01-21 CA CA2712512A patent/CA2712512C/en active Active
- 2009-01-21 US US12/863,651 patent/US20110130338A1/en not_active Abandoned
-
2014
- 2014-06-25 JP JP2014130313A patent/JP5891266B2/ja not_active Expired - Fee Related
- 2014-07-30 US US14/447,317 patent/US20140341881A1/en not_active Abandoned
-
2018
- 2018-12-12 US US16/217,957 patent/US11793864B2/en active Active
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1356907A (zh) * | 1999-06-18 | 2002-07-03 | 布亚纳森·乔·布拉吉 | 鱼丝氨酸蛋白酶及其在制药和化妆品上的应用 |
| CN1798838A (zh) * | 2003-04-04 | 2006-07-05 | 洛桑大学 | 一种蛋白酶的抑制剂蛋白及其用途 |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN113768865A (zh) * | 2020-11-04 | 2021-12-10 | 深圳前海鹰岗生物科技有限公司 | 一种抑制炎症因子释放治疗痛风急性发作的聚合物微针及制备方法 |
Also Published As
| Publication number | Publication date |
|---|---|
| CA2712512C (en) | 2018-08-28 |
| WO2009093119A3 (en) | 2009-11-26 |
| AU2009207394A1 (en) | 2009-07-30 |
| CA2712512A1 (en) | 2009-07-30 |
| US11793864B2 (en) | 2023-10-24 |
| AU2009207394B2 (en) | 2015-01-22 |
| EP2244728A2 (en) | 2010-11-03 |
| JP5891266B2 (ja) | 2016-03-22 |
| JP5615184B2 (ja) | 2014-10-29 |
| JP2011511766A (ja) | 2011-04-14 |
| CN101977626A (zh) | 2011-02-16 |
| WO2009093119A2 (en) | 2009-07-30 |
| JP2014240389A (ja) | 2014-12-25 |
| US20140341881A1 (en) | 2014-11-20 |
| US20110130338A1 (en) | 2011-06-02 |
| EP2244728B1 (en) | 2016-08-31 |
| US20190183989A1 (en) | 2019-06-20 |
| BRPI0906167A2 (en) | 2018-05-22 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN110522905A (zh) | 丝氨酸蛋白酶抑制剂在治疗皮肤病中的用途 | |
| CA2184908C (en) | Human osteoclast-derived cathepsin | |
| US5633227A (en) | Secretory leukocyte protease inhibitor as an inhibitor of tryptase | |
| CA2765423A1 (en) | Casein derived protease inhibitory peptides | |
| Guyot et al. | Proteolytic susceptibility of the serine protease inhibitor trappin-2 (pre-elafin): evidence for tryptase-mediated generation of elafin. | |
| CN104159915A (zh) | 牙龈蛋白酶抑制前肽 | |
| CA2521410C (en) | Inhibitor proteins of a protease and use thereof | |
| US9642898B2 (en) | Use of serine protease inhibitors in the treatment of neutropenia | |
| HK1151236A (en) | Use of serine protease inhibitors in the treatment of skin diseases | |
| US6207419B1 (en) | Thrombin inhibitory agents and methods of using same | |
| ES2604215T3 (es) | Uso de inhibidores de serina proteasas en el tratamiento de enfermedades de la piel | |
| Jayakumar et al. | Molecular and biochemical properties of lympho-epithelial kazal-type-inhibitor (LEKTI) |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| WD01 | Invention patent application deemed withdrawn after publication |
Application publication date: 20191203 |
|
| WD01 | Invention patent application deemed withdrawn after publication |