NO330221B1 - Anvendelse av en antagonist for integrin <alfa>-4-subenheten for fremstilling av et medikament til behandling av fibrose - Google Patents

Info

Publication number

NO330221B1

NO330221B1 NO20015122A NO20015122A NO330221B1 NO 330221 B1 NO330221 B1 NO 330221B1 NO 20015122 A NO20015122 A NO 20015122A NO 20015122 A NO20015122 A NO 20015122A NO 330221 B1 NO330221 B1 NO 330221B1

Authority

NO

Norway

Prior art keywords

antibody

integrin

fibrosis

use according

antagonist

Prior art date

1999-04-22

Links

• Espacenet
• Global Dossier
• Discuss

• 108010044426 integrins Proteins 0.000 title claims abstract description 77
• 102000006495 integrins Human genes 0.000 title claims abstract description 77
• 206010016654 Fibrosis Diseases 0.000 title claims abstract description 21
• 230000004761 fibrosis Effects 0.000 title claims abstract description 21
• 239000005557 antagonist Substances 0.000 title claims description 68
• 238000011282 treatment Methods 0.000 title claims description 23
• 238000004519 manufacturing process Methods 0.000 title description 15
• 239000003814 drug Substances 0.000 title description 7
• 229940079593 drug Drugs 0.000 title description 5
• 210000004072 lung Anatomy 0.000 claims description 58
• 239000003446 ligand Substances 0.000 claims description 39
• 239000000203 mixture Substances 0.000 claims description 25
• 230000003993 interaction Effects 0.000 claims description 18
• 208000005069 pulmonary fibrosis Diseases 0.000 claims description 14
• 239000008194 pharmaceutical composition Substances 0.000 claims description 10
• 238000002360 preparation method Methods 0.000 claims description 9
• 230000037390 scarring Effects 0.000 claims description 7
• 210000003734 kidney Anatomy 0.000 claims description 4
• 210000001835 viscera Anatomy 0.000 claims description 4
• 208000032544 Cicatrix Diseases 0.000 claims description 3
• 208000002260 Keloid Diseases 0.000 claims description 3
• 208000000185 Localized scleroderma Diseases 0.000 claims description 3
• 206010027982 Morphoea Diseases 0.000 claims description 3
• 206010039710 Scleroderma Diseases 0.000 claims description 3
• 210000002808 connective tissue Anatomy 0.000 claims description 3
• 230000002500 effect on skin Effects 0.000 claims description 3
• 210000001117 keloid Anatomy 0.000 claims description 3
• 231100000241 scar Toxicity 0.000 claims description 3
• 230000037387 scars Effects 0.000 claims description 3
• 206010012689 Diabetic retinopathy Diseases 0.000 claims description 2
• 208000007256 Nevus Diseases 0.000 claims description 2
• 208000002158 Proliferative Vitreoretinopathy Diseases 0.000 claims description 2
• 206010038934 Retinopathy proliferative Diseases 0.000 claims description 2
• 208000019425 cirrhosis of liver Diseases 0.000 claims description 2
• 210000004185 liver Anatomy 0.000 claims description 2
• 201000008265 mesangial proliferative glomerulonephritis Diseases 0.000 claims description 2
• 206010028537 myelofibrosis Diseases 0.000 claims description 2
• 208000021971 neovascular inflammatory vitreoretinopathy Diseases 0.000 claims description 2
• 230000036470 plasma concentration Effects 0.000 claims description 2
• 230000006785 proliferative vitreoretinopathy Effects 0.000 claims description 2
• 208000032131 Diabetic Neuropathies Diseases 0.000 claims 1
• 208000009209 Familial cutaneous collagenoma Diseases 0.000 claims 1
• 206010018378 Glomerulonephritis rapidly progressive Diseases 0.000 claims 1
• 206010072877 Intestinal fibrosis Diseases 0.000 claims 1
• 201000005637 crescentic glomerulonephritis Diseases 0.000 claims 1
• 210000001035 gastrointestinal tract Anatomy 0.000 claims 1
• 201000001119 neuropathy Diseases 0.000 claims 1
• 230000007823 neuropathy Effects 0.000 claims 1
• 208000033808 peripheral neuropathy Diseases 0.000 claims 1
• 238000000034 method Methods 0.000 abstract description 52
• 239000012634 fragment Substances 0.000 abstract description 47
• 241001465754 Metazoa Species 0.000 abstract description 11
• 108090000623 proteins and genes Proteins 0.000 description 82
• 102000004169 proteins and genes Human genes 0.000 description 73
• 235000018102 proteins Nutrition 0.000 description 72
• 210000004027 cell Anatomy 0.000 description 68
• 108090000765 processed proteins & peptides Proteins 0.000 description 59
• 108010008212 Integrin alpha4beta1 Proteins 0.000 description 55
• OYVAGSVQBOHSSS-UAPAGMARSA-O bleomycin A2 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(N=1)C=1SC=C(N=1)C(=O)NCCC[S+](C)C)[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 OYVAGSVQBOHSSS-UAPAGMARSA-O 0.000 description 53
• 229920000642 polymer Polymers 0.000 description 48
• 102000004196 processed proteins & peptides Human genes 0.000 description 46
• 235000001014 amino acid Nutrition 0.000 description 40
• 108010000134 Vascular Cell Adhesion Molecule-1 Proteins 0.000 description 39
• 108010006654 Bleomycin Proteins 0.000 description 38
• 229920001184 polypeptide Polymers 0.000 description 38
• 229940024606 amino acid Drugs 0.000 description 37
• 229960001561 bleomycin Drugs 0.000 description 36
• 229940123038 Integrin antagonist Drugs 0.000 description 35
• 150000001413 amino acids Chemical class 0.000 description 35
• 150000007523 nucleic acids Chemical group 0.000 description 33
• 241001529936 Murinae Species 0.000 description 29
• 230000027455 binding Effects 0.000 description 27
• 102000039446 nucleic acids Human genes 0.000 description 23
• 108020004707 nucleic acids Proteins 0.000 description 23
• 108091033319 polynucleotide Proteins 0.000 description 23
• 102000040430 polynucleotide Human genes 0.000 description 23
• 239000002157 polynucleotide Substances 0.000 description 23
• 235000002639 sodium chloride Nutrition 0.000 description 23
• 108010047041 Complementarity Determining Regions Proteins 0.000 description 21
• 125000003275 alpha amino acid group Chemical group 0.000 description 21
• 108020004414 DNA Proteins 0.000 description 19
• 239000003795 chemical substances by application Substances 0.000 description 19
• 230000000694 effects Effects 0.000 description 19
• FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 18
• 230000014509 gene expression Effects 0.000 description 18
• 108010041012 Integrin alpha4 Proteins 0.000 description 17
• 108060003951 Immunoglobulin Proteins 0.000 description 16
• 230000003176 fibrotic effect Effects 0.000 description 16
• 102000018358 immunoglobulin Human genes 0.000 description 16
• 229940122414 Alpha4 integrin antagonist Drugs 0.000 description 15
• 239000002202 Polyethylene glycol Substances 0.000 description 15
• 229920001223 polyethylene glycol Polymers 0.000 description 15
• 238000006467 substitution reaction Methods 0.000 description 15
• -1 aromatic amino acids Chemical class 0.000 description 14
• 239000011230 binding agent Substances 0.000 description 14
• 108020001507 fusion proteins Proteins 0.000 description 14
• 102000037865 fusion proteins Human genes 0.000 description 14
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 13
• 241000699670 Mus sp. Species 0.000 description 12
• 150000001875 compounds Chemical class 0.000 description 12
• 210000004408 hybridoma Anatomy 0.000 description 12
• 210000001519 tissue Anatomy 0.000 description 12
• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 12
• 241000699666 Mus <mouse, genus> Species 0.000 description 11
• 125000000539 amino acid group Chemical group 0.000 description 11
• 238000006243 chemical reaction Methods 0.000 description 11
• 210000004969 inflammatory cell Anatomy 0.000 description 11
• 210000000265 leukocyte Anatomy 0.000 description 11
• 239000002502 liposome Substances 0.000 description 11
• 229920001515 polyalkylene glycol Polymers 0.000 description 11
• 239000011780 sodium chloride Substances 0.000 description 11
• 108010035532 Collagen Proteins 0.000 description 10
• 102000008186 Collagen Human genes 0.000 description 10
• 102000016359 Fibronectins Human genes 0.000 description 10
• 108010067306 Fibronectins Proteins 0.000 description 10
• 239000000427 antigen Substances 0.000 description 10
• 108091007433 antigens Proteins 0.000 description 10
• 102000036639 antigens Human genes 0.000 description 10
• 229920001436 collagen Polymers 0.000 description 10
• 230000001404 mediated effect Effects 0.000 description 10
• 230000002829 reductive effect Effects 0.000 description 10
• 239000000243 solution Substances 0.000 description 10
• 239000000126 substance Substances 0.000 description 10
• 238000009825 accumulation Methods 0.000 description 9
• 125000003277 amino group Chemical group 0.000 description 9
• 238000000338 in vitro Methods 0.000 description 9
• 235000018977 lysine Nutrition 0.000 description 9
• 230000004048 modification Effects 0.000 description 9
• 238000012986 modification Methods 0.000 description 9
• 230000008569 process Effects 0.000 description 9
• 150000003839 salts Chemical class 0.000 description 9
• PMMYEEVYMWASQN-DMTCNVIQSA-N Hydroxyproline Chemical compound O[C@H]1CN[C@H](C(O)=O)C1 PMMYEEVYMWASQN-DMTCNVIQSA-N 0.000 description 8
• KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 8
• 239000004472 Lysine Substances 0.000 description 8
• 108091028043 Nucleic acid sequence Proteins 0.000 description 8
• 102000004079 Prolyl Hydroxylases Human genes 0.000 description 8
• 108010043005 Prolyl Hydroxylases Proteins 0.000 description 8
• PMMYEEVYMWASQN-UHFFFAOYSA-N dl-hydroxyproline Natural products OC1C[NH2+]C(C([O-])=O)C1 PMMYEEVYMWASQN-UHFFFAOYSA-N 0.000 description 8
• 229960002591 hydroxyproline Drugs 0.000 description 8
• 238000001727 in vivo Methods 0.000 description 8
• 238000012360 testing method Methods 0.000 description 8
• FGMPLJWBKKVCDB-UHFFFAOYSA-N trans-L-hydroxy-proline Natural products ON1CCCC1C(O)=O FGMPLJWBKKVCDB-UHFFFAOYSA-N 0.000 description 8
• DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 7
• 208000029523 Interstitial Lung disease Diseases 0.000 description 7
• 108091005804 Peptidases Proteins 0.000 description 7
• 102000035195 Peptidases Human genes 0.000 description 7
• 230000037396 body weight Effects 0.000 description 7
• 238000000576 coating method Methods 0.000 description 7
• 208000035475 disorder Diseases 0.000 description 7
• 210000002950 fibroblast Anatomy 0.000 description 7
• 230000006870 function Effects 0.000 description 7
• PEDCQBHIVMGVHV-UHFFFAOYSA-N glycerol group Chemical group OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 7
• 238000009396 hybridization Methods 0.000 description 7
• 238000002703 mutagenesis Methods 0.000 description 7
• 231100000350 mutagenesis Toxicity 0.000 description 7
• 239000000047 product Substances 0.000 description 7
• 239000002904 solvent Substances 0.000 description 7
• 229940122379 Alpha integrin antagonist Drugs 0.000 description 6
• LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 6
• 230000008859 change Effects 0.000 description 6
• 239000003153 chemical reaction reagent Substances 0.000 description 6
• 238000003776 cleavage reaction Methods 0.000 description 6
• 239000011248 coating agent Substances 0.000 description 6
• 201000010099 disease Diseases 0.000 description 6
• 230000004927 fusion Effects 0.000 description 6
• 239000000463 material Substances 0.000 description 6
• 239000002773 nucleotide Substances 0.000 description 6
• 125000003729 nucleotide group Chemical group 0.000 description 6
• 230000007017 scission Effects 0.000 description 6
• 241000894007 species Species 0.000 description 6
• 235000000346 sugar Nutrition 0.000 description 6
• 239000004475 Arginine Substances 0.000 description 5
• 102000010834 Extracellular Matrix Proteins Human genes 0.000 description 5
• 108010037362 Extracellular Matrix Proteins Proteins 0.000 description 5
• 108700005091 Immunoglobulin Genes Proteins 0.000 description 5
• XUJNEKJLAYXESH-REOHCLBHSA-N L-Cysteine Chemical compound SC[C@H](N)C(O)=O XUJNEKJLAYXESH-REOHCLBHSA-N 0.000 description 5
• ODKSFYDXXFIFQN-BYPYZUCNSA-P L-argininium(2+) Chemical compound NC(=[NH2+])NCCC[C@H]([NH3+])C(O)=O ODKSFYDXXFIFQN-BYPYZUCNSA-P 0.000 description 5
• WSMYVTOQOOLQHP-UHFFFAOYSA-N Malondialdehyde Chemical compound O=CCC=O WSMYVTOQOOLQHP-UHFFFAOYSA-N 0.000 description 5
• 206010035226 Plasma cell myeloma Diseases 0.000 description 5
• 108020004511 Recombinant DNA Proteins 0.000 description 5
• 208000027418 Wounds and injury Diseases 0.000 description 5
• 239000004480 active ingredient Substances 0.000 description 5
• ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 5
• 210000003719 b-lymphocyte Anatomy 0.000 description 5
• 230000009286 beneficial effect Effects 0.000 description 5
• 230000000903 blocking effect Effects 0.000 description 5
• 230000006378 damage Effects 0.000 description 5
• 239000000539 dimer Substances 0.000 description 5
• 239000001963 growth medium Substances 0.000 description 5
• 229940072221 immunoglobulins Drugs 0.000 description 5
• 239000004615 ingredient Substances 0.000 description 5
• 125000005647 linker group Chemical group 0.000 description 5
• 229940118019 malondialdehyde Drugs 0.000 description 5
• 239000002609 medium Substances 0.000 description 5
• 239000000178 monomer Substances 0.000 description 5
• 201000000050 myeloid neoplasm Diseases 0.000 description 5
• 239000003642 reactive oxygen metabolite Substances 0.000 description 5
• 230000001105 regulatory effect Effects 0.000 description 5
• 239000006228 supernatant Substances 0.000 description 5
• 230000001225 therapeutic effect Effects 0.000 description 5
• 230000009261 transgenic effect Effects 0.000 description 5
• 102000004127 Cytokines Human genes 0.000 description 4
• 108090000695 Cytokines Proteins 0.000 description 4
• 102000006496 Immunoglobulin Heavy Chains Human genes 0.000 description 4
• 108010019476 Immunoglobulin Heavy Chains Proteins 0.000 description 4
• 102100025323 Integrin alpha-1 Human genes 0.000 description 4
• 108010041341 Integrin alpha1 Proteins 0.000 description 4
• 108010055795 Integrin alpha1beta1 Proteins 0.000 description 4
• KDXKERNSBIXSRK-YFKPBYRVSA-N L-lysine Chemical compound NCCCC[C@H](N)C(O)=O KDXKERNSBIXSRK-YFKPBYRVSA-N 0.000 description 4
• COLNVLDHVKWLRT-QMMMGPOBSA-N L-phenylalanine Chemical compound OC(=O)[C@@H](N)CC1=CC=CC=C1 COLNVLDHVKWLRT-QMMMGPOBSA-N 0.000 description 4
• OUYCCCASQSFEME-QMMMGPOBSA-N L-tyrosine Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-QMMMGPOBSA-N 0.000 description 4
• WCUXLLCKKVVCTQ-UHFFFAOYSA-M Potassium chloride Chemical compound [Cl-].[K+] WCUXLLCKKVVCTQ-UHFFFAOYSA-M 0.000 description 4
• 108010050808 Procollagen Proteins 0.000 description 4
• 108090000631 Trypsin Proteins 0.000 description 4
• 102000004142 Trypsin Human genes 0.000 description 4
• 238000004458 analytical method Methods 0.000 description 4
• 230000004071 biological effect Effects 0.000 description 4
• 230000015572 biosynthetic process Effects 0.000 description 4
• 239000000872 buffer Substances 0.000 description 4
• 238000001212 derivatisation Methods 0.000 description 4
• 239000003937 drug carrier Substances 0.000 description 4
• 239000003792 electrolyte Substances 0.000 description 4
• 238000005516 engineering process Methods 0.000 description 4
• 239000013604 expression vector Substances 0.000 description 4
• 239000012530 fluid Substances 0.000 description 4
• 150000002334 glycols Chemical class 0.000 description 4
• 230000002757 inflammatory effect Effects 0.000 description 4
• 230000004941 influx Effects 0.000 description 4
• 230000003859 lipid peroxidation Effects 0.000 description 4
• 150000002632 lipids Chemical class 0.000 description 4
• 210000004962 mammalian cell Anatomy 0.000 description 4
• 229930182817 methionine Natural products 0.000 description 4
• 230000035772 mutation Effects 0.000 description 4
• 210000000651 myofibroblast Anatomy 0.000 description 4
• 210000000440 neutrophil Anatomy 0.000 description 4
• 238000003752 polymerase chain reaction Methods 0.000 description 4
• 230000003405 preventing effect Effects 0.000 description 4
• 229940024999 proteolytic enzymes for treatment of wounds and ulcers Drugs 0.000 description 4
• 230000004044 response Effects 0.000 description 4
• 230000011664 signaling Effects 0.000 description 4
• 238000012546 transfer Methods 0.000 description 4
• 239000012588 trypsin Substances 0.000 description 4
• 229960001322 trypsin Drugs 0.000 description 4
• 230000002792 vascular Effects 0.000 description 4
• 238000005406 washing Methods 0.000 description 4
• 206010002091 Anaesthesia Diseases 0.000 description 3
• WVDDGKGOMKODPV-UHFFFAOYSA-N Benzyl alcohol Chemical compound OCC1=CC=CC=C1 WVDDGKGOMKODPV-UHFFFAOYSA-N 0.000 description 3
• 108020004705 Codon Proteins 0.000 description 3
• 102000004190 Enzymes Human genes 0.000 description 3
• 108090000790 Enzymes Proteins 0.000 description 3
• 239000004471 Glycine Substances 0.000 description 3
• 241000282412 Homo Species 0.000 description 3
• 102000013463 Immunoglobulin Light Chains Human genes 0.000 description 3
• 108010065825 Immunoglobulin Light Chains Proteins 0.000 description 3
• 108010067060 Immunoglobulin Variable Region Proteins 0.000 description 3
• 102000017727 Immunoglobulin Variable Region Human genes 0.000 description 3
• QNAYBMKLOCPYGJ-REOHCLBHSA-N L-alanine Chemical compound C[C@H](N)C(O)=O QNAYBMKLOCPYGJ-REOHCLBHSA-N 0.000 description 3
• CKLJMWTZIZZHCS-REOHCLBHSA-N L-aspartic acid Chemical compound OC(=O)[C@@H](N)CC(O)=O CKLJMWTZIZZHCS-REOHCLBHSA-N 0.000 description 3
• 108091034117 Oligonucleotide Proteins 0.000 description 3
• 241000276498 Pollachius virens Species 0.000 description 3
• DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
• XLYOFNOQVPJJNP-PWCQTSIFSA-N Tritiated water Chemical compound [3H]O[3H] XLYOFNOQVPJJNP-PWCQTSIFSA-N 0.000 description 3
• 230000004913 activation Effects 0.000 description 3
• 235000004279 alanine Nutrition 0.000 description 3
• 150000001299 aldehydes Chemical class 0.000 description 3
• 230000037005 anaesthesia Effects 0.000 description 3
• 230000003510 anti-fibrotic effect Effects 0.000 description 3
• 239000002585 base Substances 0.000 description 3
• 230000008901 benefit Effects 0.000 description 3
• WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 3
• 230000001588 bifunctional effect Effects 0.000 description 3
• 102000023732 binding proteins Human genes 0.000 description 3
• 108091008324 binding proteins Proteins 0.000 description 3
• 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 3
• 239000000969 carrier Substances 0.000 description 3
• 238000010367 cloning Methods 0.000 description 3
• 230000000295 complement effect Effects 0.000 description 3
• 230000021615 conjugation Effects 0.000 description 3
• 238000007796 conventional method Methods 0.000 description 3
• 238000004132 cross linking Methods 0.000 description 3
• 239000012228 culture supernatant Substances 0.000 description 3
• 235000018417 cysteine Nutrition 0.000 description 3
• 230000003247 decreasing effect Effects 0.000 description 3
• 238000012217 deletion Methods 0.000 description 3
• 230000037430 deletion Effects 0.000 description 3
• BFMYDTVEBKDAKJ-UHFFFAOYSA-L disodium;(2',7'-dibromo-3',6'-dioxido-3-oxospiro[2-benzofuran-1,9'-xanthene]-4'-yl)mercury;hydrate Chemical compound O.[Na+].[Na+].O1C(=O)C2=CC=CC=C2C21C1=CC(Br)=C([O-])C([Hg])=C1OC1=C2C=C(Br)C([O-])=C1 BFMYDTVEBKDAKJ-UHFFFAOYSA-L 0.000 description 3
• 210000002889 endothelial cell Anatomy 0.000 description 3
• 229940088598 enzyme Drugs 0.000 description 3
• 210000002744 extracellular matrix Anatomy 0.000 description 3
• 238000009472 formulation Methods 0.000 description 3
• 230000035876 healing Effects 0.000 description 3
• 230000007062 hydrolysis Effects 0.000 description 3
• 238000006460 hydrolysis reaction Methods 0.000 description 3
• QWPPOHNGKGFGJK-UHFFFAOYSA-N hypochlorous acid Chemical compound ClO QWPPOHNGKGFGJK-UHFFFAOYSA-N 0.000 description 3
• 210000002865 immune cell Anatomy 0.000 description 3
• 238000010348 incorporation Methods 0.000 description 3
• 230000002401 inhibitory effect Effects 0.000 description 3
• 208000014674 injury Diseases 0.000 description 3
• 210000004698 lymphocyte Anatomy 0.000 description 3
• 230000008506 pathogenesis Effects 0.000 description 3
• 210000003200 peritoneal cavity Anatomy 0.000 description 3
• 239000002831 pharmacologic agent Substances 0.000 description 3
• COLNVLDHVKWLRT-UHFFFAOYSA-N phenylalanine Natural products OC(=O)C(N)CC1=CC=CC=C1 COLNVLDHVKWLRT-UHFFFAOYSA-N 0.000 description 3
• 150000003904 phospholipids Chemical class 0.000 description 3
• 229920000036 polyvinylpyrrolidone Polymers 0.000 description 3
• 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 3
• 239000003755 preservative agent Substances 0.000 description 3
• 238000010188 recombinant method Methods 0.000 description 3
• 238000011160 research Methods 0.000 description 3
• 238000000926 separation method Methods 0.000 description 3
• 235000004400 serine Nutrition 0.000 description 3
• 210000004988 splenocyte Anatomy 0.000 description 3
• 239000000758 substrate Substances 0.000 description 3
• 239000000725 suspension Substances 0.000 description 3
• 210000003437 trachea Anatomy 0.000 description 3
• 235000002374 tyrosine Nutrition 0.000 description 3
• OUYCCCASQSFEME-UHFFFAOYSA-N tyrosine Natural products OC(=O)C(N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-UHFFFAOYSA-N 0.000 description 3
• 241001515965 unidentified phage Species 0.000 description 3
• PUPZLCDOIYMWBV-UHFFFAOYSA-N (+/-)-1,3-Butanediol Chemical compound CC(O)CCO PUPZLCDOIYMWBV-UHFFFAOYSA-N 0.000 description 2
• MTCFGRXMJLQNBG-REOHCLBHSA-N (2S)-2-Amino-3-hydroxypropansäure Chemical compound OC[C@H](N)C(O)=O MTCFGRXMJLQNBG-REOHCLBHSA-N 0.000 description 2
• 108091032973 (ribonucleotides)n+m Proteins 0.000 description 2
• IIZPXYDJLKNOIY-JXPKJXOSSA-N 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCC\C=C/C\C=C/C\C=C/C\C=C/CCCCC IIZPXYDJLKNOIY-JXPKJXOSSA-N 0.000 description 2
• 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 2
• KPGXRSRHYNQIFN-UHFFFAOYSA-N 2-oxoglutaric acid Chemical compound OC(=O)CCC(=O)C(O)=O KPGXRSRHYNQIFN-UHFFFAOYSA-N 0.000 description 2
• WUIABRMSWOKTOF-OYALTWQYSA-N 3-[[2-[2-[2-[[(2s,3r)-2-[[(2s,3s,4r)-4-[[(2s,3r)-2-[[6-amino-2-[(1s)-3-amino-1-[[(2s)-2,3-diamino-3-oxopropyl]amino]-3-oxopropyl]-5-methylpyrimidine-4-carbonyl]amino]-3-[(2r,3s,4s,5s,6s)-3-[(2r,3s,4s,5r,6r)-4-carbamoyloxy-3,5-dihydroxy-6-(hydroxymethyl)ox Chemical compound OS([O-])(=O)=O.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(N=1)C=1SC=C(N=1)C(=O)NCCC[S+](C)C)[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=1NC=NC=1)C(=O)C1=NC([C@H](CC(N)=O)NC[C@H](N)C(N)=O)=NC(N)=C1C WUIABRMSWOKTOF-OYALTWQYSA-N 0.000 description 2
• FWMNVWWHGCHHJJ-SKKKGAJSSA-N 4-amino-1-[(2r)-6-amino-2-[[(2r)-2-[[(2r)-2-[[(2r)-2-amino-3-phenylpropanoyl]amino]-3-phenylpropanoyl]amino]-4-methylpentanoyl]amino]hexanoyl]piperidine-4-carboxylic acid Chemical compound C([C@H](C(=O)N[C@H](CC(C)C)C(=O)N[C@H](CCCCN)C(=O)N1CCC(N)(CC1)C(O)=O)NC(=O)[C@H](N)CC=1C=CC=CC=1)C1=CC=CC=C1 FWMNVWWHGCHHJJ-SKKKGAJSSA-N 0.000 description 2
• 206010003445 Ascites Diseases 0.000 description 2
• DCXYFEDJOCDNAF-UHFFFAOYSA-N Asparagine Natural products OC(=O)C(N)CC(N)=O DCXYFEDJOCDNAF-UHFFFAOYSA-N 0.000 description 2
• IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
• 108091003079 Bovine Serum Albumin Proteins 0.000 description 2
• 108090000317 Chymotrypsin Proteins 0.000 description 2
• 229920002261 Corn starch Polymers 0.000 description 2
• PMATZTZNYRCHOR-CGLBZJNRSA-N Cyclosporin A Chemical compound CC[C@@H]1NC(=O)[C@H]([C@H](O)[C@H](C)C\C=C\C)N(C)C(=O)[C@H](C(C)C)N(C)C(=O)[C@H](CC(C)C)N(C)C(=O)[C@H](CC(C)C)N(C)C(=O)[C@@H](C)NC(=O)[C@H](C)NC(=O)[C@H](CC(C)C)N(C)C(=O)[C@H](C(C)C)NC(=O)[C@H](CC(C)C)N(C)C(=O)CN(C)C1=O PMATZTZNYRCHOR-CGLBZJNRSA-N 0.000 description 2
• 108010036949 Cyclosporine Proteins 0.000 description 2
• 206010063560 Excessive granulation tissue Diseases 0.000 description 2
• 206010015719 Exsanguination Diseases 0.000 description 2
• WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 2
• 206010018364 Glomerulonephritis Diseases 0.000 description 2
• WHUUTDBJXJRKMK-UHFFFAOYSA-N Glutamic acid Natural products OC(=O)C(N)CCC(O)=O WHUUTDBJXJRKMK-UHFFFAOYSA-N 0.000 description 2
• 102000003886 Glycoproteins Human genes 0.000 description 2
• 108090000288 Glycoproteins Proteins 0.000 description 2
• WZUVPPKBWHMQCE-UHFFFAOYSA-N Haematoxylin Chemical compound C12=CC(O)=C(O)C=C2CC2(O)C1C1=CC=C(O)C(O)=C1OC2 WZUVPPKBWHMQCE-UHFFFAOYSA-N 0.000 description 2
• OAKJQQAXSVQMHS-UHFFFAOYSA-N Hydrazine Chemical compound NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 description 2
• VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
• 108010009817 Immunoglobulin Constant Regions Proteins 0.000 description 2
• 102000009786 Immunoglobulin Constant Regions Human genes 0.000 description 2
• 108010054477 Immunoglobulin Fab Fragments Proteins 0.000 description 2
• 102000001706 Immunoglobulin Fab Fragments Human genes 0.000 description 2
• 108010021625 Immunoglobulin Fragments Proteins 0.000 description 2
• 102000008394 Immunoglobulin Fragments Human genes 0.000 description 2
• XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 2
• 150000008575 L-amino acids Chemical class 0.000 description 2
• DCXYFEDJOCDNAF-REOHCLBHSA-N L-asparagine Chemical compound OC(=O)[C@@H](N)CC(N)=O DCXYFEDJOCDNAF-REOHCLBHSA-N 0.000 description 2
• WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 description 2
• ZDXPYRJPNDTMRX-VKHMYHEASA-N L-glutamine Chemical compound OC(=O)[C@@H](N)CCC(N)=O ZDXPYRJPNDTMRX-VKHMYHEASA-N 0.000 description 2
• AGPKZVBTJJNPAG-WHFBIAKZSA-N L-isoleucine Chemical compound CC[C@H](C)[C@H](N)C(O)=O AGPKZVBTJJNPAG-WHFBIAKZSA-N 0.000 description 2
• ROHFNLRQFUQHCH-YFKPBYRVSA-N L-leucine Chemical compound CC(C)C[C@H](N)C(O)=O ROHFNLRQFUQHCH-YFKPBYRVSA-N 0.000 description 2
• FFEARJCKVFRZRR-BYPYZUCNSA-N L-methionine Chemical compound CSCC[C@H](N)C(O)=O FFEARJCKVFRZRR-BYPYZUCNSA-N 0.000 description 2
• AYFVYJQAPQTCCC-GBXIJSLDSA-N L-threonine Chemical compound C[C@@H](O)[C@H](N)C(O)=O AYFVYJQAPQTCCC-GBXIJSLDSA-N 0.000 description 2
• QIVBCDIJIAJPQS-VIFPVBQESA-N L-tryptophane Chemical compound C1=CC=C2C(C[C@H](N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-VIFPVBQESA-N 0.000 description 2
• KZSNJWFQEVHDMF-BYPYZUCNSA-N L-valine Chemical compound CC(C)[C@H](N)C(O)=O KZSNJWFQEVHDMF-BYPYZUCNSA-N 0.000 description 2
• GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 2
• ROHFNLRQFUQHCH-UHFFFAOYSA-N Leucine Natural products CC(C)CC(N)C(O)=O ROHFNLRQFUQHCH-UHFFFAOYSA-N 0.000 description 2
• 102000003896 Myeloperoxidases Human genes 0.000 description 2
• 108090000235 Myeloperoxidases Proteins 0.000 description 2
• 108090000284 Pepsin A Proteins 0.000 description 2
• 102000057297 Pepsin A Human genes 0.000 description 2
• ONIBWKKTOPOVIA-UHFFFAOYSA-N Proline Natural products OC(=O)C1CCCN1 ONIBWKKTOPOVIA-UHFFFAOYSA-N 0.000 description 2
• 239000004365 Protease Substances 0.000 description 2
• 241000283984 Rodentia Species 0.000 description 2
• MTCFGRXMJLQNBG-UHFFFAOYSA-N Serine Natural products OCC(N)C(O)=O MTCFGRXMJLQNBG-UHFFFAOYSA-N 0.000 description 2
• AYFVYJQAPQTCCC-UHFFFAOYSA-N Threonine Natural products CC(O)C(N)C(O)=O AYFVYJQAPQTCCC-UHFFFAOYSA-N 0.000 description 2
• 239000004473 Threonine Substances 0.000 description 2
• IQFYYKKMVGJFEH-XLPZGREQSA-N Thymidine Chemical compound O=C1NC(=O)C(C)=CN1[C@@H]1O[C@H](CO)[C@@H](O)C1 IQFYYKKMVGJFEH-XLPZGREQSA-N 0.000 description 2
• QIVBCDIJIAJPQS-UHFFFAOYSA-N Tryptophan Natural products C1=CC=C2C(CC(N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-UHFFFAOYSA-N 0.000 description 2
• KZSNJWFQEVHDMF-UHFFFAOYSA-N Valine Natural products CC(C)C(N)C(O)=O KZSNJWFQEVHDMF-UHFFFAOYSA-N 0.000 description 2
• 206010052428 Wound Diseases 0.000 description 2
• 210000000683 abdominal cavity Anatomy 0.000 description 2
• 230000002159 abnormal effect Effects 0.000 description 2
• 230000009471 action Effects 0.000 description 2
• 238000007792 addition Methods 0.000 description 2
• 239000000654 additive Substances 0.000 description 2
• 229910052783 alkali metal Inorganic materials 0.000 description 2
• 229910052784 alkaline earth metal Inorganic materials 0.000 description 2
• AWUCVROLDVIAJX-UHFFFAOYSA-N alpha-glycerophosphate Natural products OCC(O)COP(O)(O)=O AWUCVROLDVIAJX-UHFFFAOYSA-N 0.000 description 2
• 238000010171 animal model Methods 0.000 description 2
• 239000002260 anti-inflammatory agent Substances 0.000 description 2
• 229940121363 anti-inflammatory agent Drugs 0.000 description 2
• 230000000340 anti-metabolite Effects 0.000 description 2
• 239000002256 antimetabolite Substances 0.000 description 2
• 229940100197 antimetabolite Drugs 0.000 description 2
• 210000000702 aorta abdominal Anatomy 0.000 description 2
• 239000007864 aqueous solution Substances 0.000 description 2
• 239000007900 aqueous suspension Substances 0.000 description 2
• 235000009582 asparagine Nutrition 0.000 description 2
• 229960001230 asparagine Drugs 0.000 description 2
• 235000003704 aspartic acid Nutrition 0.000 description 2
• UCMIRNVEIXFBKS-UHFFFAOYSA-N beta-alanine Chemical compound NCCC(O)=O UCMIRNVEIXFBKS-UHFFFAOYSA-N 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
• 229920001400 block copolymer Polymers 0.000 description 2
• 229940098773 bovine serum albumin Drugs 0.000 description 2
• 150000001649 bromium compounds Chemical class 0.000 description 2
• 239000002775 capsule Substances 0.000 description 2
• 125000000837 carbohydrate group Chemical group 0.000 description 2
• 230000021164 cell adhesion Effects 0.000 description 2
• 125000003636 chemical group Chemical group 0.000 description 2
• HVYWMOMLDIMFJA-DPAQBDIFSA-N cholesterol Chemical compound C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CCCC(C)C)[C@@]1(C)CC2 HVYWMOMLDIMFJA-DPAQBDIFSA-N 0.000 description 2
• 229960002376 chymotrypsin Drugs 0.000 description 2
• 229960001265 ciclosporin Drugs 0.000 description 2
• 239000002299 complementary DNA Substances 0.000 description 2
• 238000002591 computed tomography Methods 0.000 description 2
• 230000001268 conjugating effect Effects 0.000 description 2
• 239000008120 corn starch Substances 0.000 description 2
• 229930182912 cyclosporin Natural products 0.000 description 2
• XUJNEKJLAYXESH-UHFFFAOYSA-N cysteine Natural products SCC(N)C(O)=O XUJNEKJLAYXESH-UHFFFAOYSA-N 0.000 description 2
• 125000000151 cysteine group Chemical group N[C@@H](CS)C(=O)* 0.000 description 2
• GVJHHUAWPYXKBD-UHFFFAOYSA-N d-alpha-tocopherol Natural products OC1=C(C)C(C)=C2OC(CCCC(C)CCCC(C)CCCC(C)C)(C)CCC2=C1C GVJHHUAWPYXKBD-UHFFFAOYSA-N 0.000 description 2
• 238000013461 design Methods 0.000 description 2
• 238000011161 development Methods 0.000 description 2
• 229960000633 dextran sulfate Drugs 0.000 description 2
• 235000014113 dietary fatty acids Nutrition 0.000 description 2
• 239000003085 diluting agent Substances 0.000 description 2
• 239000002270 dispersing agent Substances 0.000 description 2
• 239000002552 dosage form Substances 0.000 description 2
• 230000029142 excretion Effects 0.000 description 2
• 238000002474 experimental method Methods 0.000 description 2
• 239000000194 fatty acid Substances 0.000 description 2
• 229930195729 fatty acid Natural products 0.000 description 2
• 150000004665 fatty acids Chemical class 0.000 description 2
• 239000010685 fatty oil Substances 0.000 description 2
• 230000003352 fibrogenic effect Effects 0.000 description 2
• 230000000893 fibroproliferative effect Effects 0.000 description 2
• 235000013922 glutamic acid Nutrition 0.000 description 2
• 239000004220 glutamic acid Substances 0.000 description 2
• ZDXPYRJPNDTMRX-UHFFFAOYSA-N glutamine Natural products OC(=O)C(N)CCC(N)=O ZDXPYRJPNDTMRX-UHFFFAOYSA-N 0.000 description 2
• 235000004554 glutamine Nutrition 0.000 description 2
• 125000005456 glyceride group Chemical group 0.000 description 2
• 150000002314 glycerols Polymers 0.000 description 2
• 230000013595 glycosylation Effects 0.000 description 2
• 238000006206 glycosylation reaction Methods 0.000 description 2
• 210000001126 granulation tissue Anatomy 0.000 description 2
• 239000003102 growth factor Substances 0.000 description 2
• HNDVDQJCIGZPNO-UHFFFAOYSA-N histidine Natural products OC(=O)C(N)CC1=CN=CN1 HNDVDQJCIGZPNO-UHFFFAOYSA-N 0.000 description 2
• 238000000265 homogenisation Methods 0.000 description 2
• 229920001519 homopolymer Polymers 0.000 description 2
• 125000001165 hydrophobic group Chemical group 0.000 description 2
• 125000002887 hydroxy group Chemical group [H]O* 0.000 description 2
• 230000001969 hypertrophic effect Effects 0.000 description 2
• FDGQSTZJBFJUBT-UHFFFAOYSA-N hypoxanthine Chemical compound O=C1NC=NC2=C1NC=N2 FDGQSTZJBFJUBT-UHFFFAOYSA-N 0.000 description 2
• 238000011532 immunohistochemical staining Methods 0.000 description 2
• 239000002955 immunomodulating agent Substances 0.000 description 2
• 229940121354 immunomodulator Drugs 0.000 description 2
• 238000012744 immunostaining Methods 0.000 description 2
• 229960003444 immunosuppressant agent Drugs 0.000 description 2
• 230000001861 immunosuppressant effect Effects 0.000 description 2
• 239000003018 immunosuppressive agent Substances 0.000 description 2
• 230000006872 improvement Effects 0.000 description 2
• 230000005764 inhibitory process Effects 0.000 description 2
• 238000002347 injection Methods 0.000 description 2
• 239000007924 injection Substances 0.000 description 2
• 238000003780 insertion Methods 0.000 description 2
• 230000037431 insertion Effects 0.000 description 2
• 238000001990 intravenous administration Methods 0.000 description 2
• 150000004694 iodide salts Chemical class 0.000 description 2
• 229960000310 isoleucine Drugs 0.000 description 2
• AGPKZVBTJJNPAG-UHFFFAOYSA-N isoleucine Natural products CCC(C)C(N)C(O)=O AGPKZVBTJJNPAG-UHFFFAOYSA-N 0.000 description 2
• 239000008101 lactose Substances 0.000 description 2
• 235000019388 lanolin Nutrition 0.000 description 2
• 239000000787 lecithin Substances 0.000 description 2
• 235000010445 lecithin Nutrition 0.000 description 2
• 229940067606 lecithin Drugs 0.000 description 2
• 230000003902 lesion Effects 0.000 description 2
• 230000033001 locomotion Effects 0.000 description 2
• HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
• 239000011159 matrix material Substances 0.000 description 2
• 229910052751 metal Inorganic materials 0.000 description 2
• 239000002184 metal Substances 0.000 description 2
• 125000001360 methionine group Chemical group N[C@@H](CCSC)C(=O)* 0.000 description 2
• 125000002496 methyl group Chemical group [H]C([H])([H])* 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
• 238000002156 mixing Methods 0.000 description 2
• 231100000252 nontoxic Toxicity 0.000 description 2
• 230000003000 nontoxic effect Effects 0.000 description 2
• 210000000056 organ Anatomy 0.000 description 2
• 238000012261 overproduction Methods 0.000 description 2
• 230000003647 oxidation Effects 0.000 description 2
• 238000007254 oxidation reaction Methods 0.000 description 2
• 230000036961 partial effect Effects 0.000 description 2
• WEXRUCMBJFQVBZ-UHFFFAOYSA-N pentobarbital Chemical compound CCCC(C)C1(CC)C(=O)NC(=O)NC1=O WEXRUCMBJFQVBZ-UHFFFAOYSA-N 0.000 description 2
• 229940111202 pepsin Drugs 0.000 description 2
• 229920000233 poly(alkylene oxides) Polymers 0.000 description 2
• 229920001583 poly(oxyethylated polyols) Polymers 0.000 description 2
• 229920002401 polyacrylamide Polymers 0.000 description 2
• 229920001451 polypropylene glycol Polymers 0.000 description 2
• 239000001267 polyvinylpyrrolidone Substances 0.000 description 2
• 239000001103 potassium chloride Substances 0.000 description 2
• 235000011164 potassium chloride Nutrition 0.000 description 2
• 230000035755 proliferation Effects 0.000 description 2
• 230000002035 prolonged 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
• 230000002685 pulmonary effect Effects 0.000 description 2
• 239000000700 radioactive tracer Substances 0.000 description 2
• 102000005962 receptors Human genes 0.000 description 2
• 108020003175 receptors Proteins 0.000 description 2
• 230000009467 reduction Effects 0.000 description 2
• 238000006722 reduction reaction Methods 0.000 description 2
• 238000012552 review Methods 0.000 description 2
• 210000002966 serum Anatomy 0.000 description 2
• 230000019491 signal transduction Effects 0.000 description 2
• 150000003384 small molecules Chemical class 0.000 description 2
• 239000001509 sodium citrate Substances 0.000 description 2
• NLJMYIDDQXHKNR-UHFFFAOYSA-K sodium citrate Chemical compound O.O.[Na+].[Na+].[Na+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O NLJMYIDDQXHKNR-UHFFFAOYSA-K 0.000 description 2
• JQWHASGSAFIOCM-UHFFFAOYSA-M sodium periodate Chemical compound [Na+].[O-]I(=O)(=O)=O JQWHASGSAFIOCM-UHFFFAOYSA-M 0.000 description 2
• 125000006850 spacer group Chemical group 0.000 description 2
• 150000008163 sugars Chemical class 0.000 description 2
• 238000001356 surgical procedure Methods 0.000 description 2
• 239000000375 suspending agent Substances 0.000 description 2
• 238000003786 synthesis reaction Methods 0.000 description 2
• 239000003826 tablet Substances 0.000 description 2
• QJJXYPPXXYFBGM-SHYZHZOCSA-N tacrolimus Natural products CO[C@H]1C[C@H](CC[C@@H]1O)C=C(C)[C@H]2OC(=O)[C@H]3CCCCN3C(=O)C(=O)[C@@]4(O)O[C@@H]([C@H](C[C@H]4C)OC)[C@@H](C[C@H](C)CC(=C[C@@H](CC=C)C(=O)C[C@H](O)[C@H]2C)C)OC QJJXYPPXXYFBGM-SHYZHZOCSA-N 0.000 description 2
• ZFXYFBGIUFBOJW-UHFFFAOYSA-N theophylline Chemical compound O=C1N(C)C(=O)N(C)C2=C1NC=N2 ZFXYFBGIUFBOJW-UHFFFAOYSA-N 0.000 description 2
• 125000003396 thiol group Chemical group [H]S* 0.000 description 2
• 235000008521 threonine Nutrition 0.000 description 2
• 235000010384 tocopherol Nutrition 0.000 description 2
• 239000011732 tocopherol Substances 0.000 description 2
• 229960001295 tocopherol Drugs 0.000 description 2
• 229930003799 tocopherol Natural products 0.000 description 2
• 230000000699 topical effect Effects 0.000 description 2
• VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 2
• 238000010361 transduction Methods 0.000 description 2
• 230000026683 transduction Effects 0.000 description 2
• 230000014616 translation Effects 0.000 description 2
• 102000027257 transmembrane receptors Human genes 0.000 description 2
• 108091008578 transmembrane receptors Proteins 0.000 description 2
• 238000002054 transplantation Methods 0.000 description 2
• YNJBWRMUSHSURL-UHFFFAOYSA-N trichloroacetic acid Chemical compound OC(=O)C(Cl)(Cl)Cl YNJBWRMUSHSURL-UHFFFAOYSA-N 0.000 description 2
• LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 2
• 239000004474 valine Substances 0.000 description 2
• 239000003981 vehicle Substances 0.000 description 2
• GVJHHUAWPYXKBD-IEOSBIPESA-N α-tocopherol Chemical compound OC1=C(C)C(C)=C2O[C@@](CCC[C@H](C)CCC[C@H](C)CCCC(C)C)(C)CCC2=C1C GVJHHUAWPYXKBD-IEOSBIPESA-N 0.000 description 2
• LSPHULWDVZXLIL-UHFFFAOYSA-N (+/-)-Camphoric acid Chemical compound CC1(C)C(C(O)=O)CCC1(C)C(O)=O LSPHULWDVZXLIL-UHFFFAOYSA-N 0.000 description 1
• OQANPHBRHBJGNZ-FYJGNVAPSA-N (3e)-6-oxo-3-[[4-(pyridin-2-ylsulfamoyl)phenyl]hydrazinylidene]cyclohexa-1,4-diene-1-carboxylic acid Chemical compound C1=CC(=O)C(C(=O)O)=C\C1=N\NC1=CC=C(S(=O)(=O)NC=2N=CC=CC=2)C=C1 OQANPHBRHBJGNZ-FYJGNVAPSA-N 0.000 description 1
• WRIDQFICGBMAFQ-UHFFFAOYSA-N (E)-8-Octadecenoic acid Natural products CCCCCCCCCC=CCCCCCCC(O)=O WRIDQFICGBMAFQ-UHFFFAOYSA-N 0.000 description 1
• PORPENFLTBBHSG-MGBGTMOVSA-N 1,2-dihexadecanoyl-sn-glycerol-3-phosphate Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP(O)(O)=O)OC(=O)CCCCCCCCCCCCCCC PORPENFLTBBHSG-MGBGTMOVSA-N 0.000 description 1
• TZCPCKNHXULUIY-RGULYWFUSA-N 1,2-distearoyl-sn-glycero-3-phosphoserine Chemical compound CCCCCCCCCCCCCCCCCC(=O)OC[C@H](COP(O)(=O)OC[C@H](N)C(O)=O)OC(=O)CCCCCCCCCCCCCCCCC TZCPCKNHXULUIY-RGULYWFUSA-N 0.000 description 1
• RYCNUMLMNKHWPZ-SNVBAGLBSA-N 1-acetyl-sn-glycero-3-phosphocholine Chemical compound CC(=O)OC[C@@H](O)COP([O-])(=O)OCC[N+](C)(C)C RYCNUMLMNKHWPZ-SNVBAGLBSA-N 0.000 description 1
• VFWCMGCRMGJXDK-UHFFFAOYSA-N 1-chlorobutane Chemical class CCCCCl VFWCMGCRMGJXDK-UHFFFAOYSA-N 0.000 description 1
• VUQPJRPDRDVQMN-UHFFFAOYSA-N 1-chlorooctadecane Chemical class CCCCCCCCCCCCCCCCCCCl VUQPJRPDRDVQMN-UHFFFAOYSA-N 0.000 description 1
• CHHHXKFHOYLYRE-UHFFFAOYSA-M 2,4-Hexadienoic acid, potassium salt (1:1), (2E,4E)- Chemical compound [K+].CC=CC=CC([O-])=O CHHHXKFHOYLYRE-UHFFFAOYSA-M 0.000 description 1
• LRYZPFWEZHSTHD-HEFFAWAOSA-O 2-[[(e,2s,3r)-2-formamido-3-hydroxyoctadec-4-enoxy]-hydroxyphosphoryl]oxyethyl-trimethylazanium Chemical class CCCCCCCCCCCCC\C=C\[C@@H](O)[C@@H](NC=O)COP(O)(=O)OCC[N+](C)(C)C LRYZPFWEZHSTHD-HEFFAWAOSA-O 0.000 description 1
• NBGAYCYFNGPNPV-UHFFFAOYSA-N 2-aminooxybenzoic acid Chemical class NOC1=CC=CC=C1C(O)=O NBGAYCYFNGPNPV-UHFFFAOYSA-N 0.000 description 1
• 229940080296 2-naphthalenesulfonate Drugs 0.000 description 1
• WMPPDTMATNBGJN-UHFFFAOYSA-N 2-phenylethylbromide Chemical class BrCCC1=CC=CC=C1 WMPPDTMATNBGJN-UHFFFAOYSA-N 0.000 description 1
• RVBUGGBMJDPOST-UHFFFAOYSA-N 2-thiobarbituric acid Chemical compound O=C1CC(=O)NC(=S)N1 RVBUGGBMJDPOST-UHFFFAOYSA-N 0.000 description 1
• LQJBNNIYVWPHFW-UHFFFAOYSA-N 20:1omega9c fatty acid Natural products CCCCCCCCCCC=CCCCCCCCC(O)=O LQJBNNIYVWPHFW-UHFFFAOYSA-N 0.000 description 1
• ZRPLANDPDWYOMZ-UHFFFAOYSA-N 3-cyclopentylpropionic acid Chemical compound OC(=O)CCC1CCCC1 ZRPLANDPDWYOMZ-UHFFFAOYSA-N 0.000 description 1
• XMIIGOLPHOKFCH-UHFFFAOYSA-M 3-phenylpropionate Chemical compound [O-]C(=O)CCC1=CC=CC=C1 XMIIGOLPHOKFCH-UHFFFAOYSA-M 0.000 description 1
• FHVDTGUDJYJELY-UHFFFAOYSA-N 6-{[2-carboxy-4,5-dihydroxy-6-(phosphanyloxy)oxan-3-yl]oxy}-4,5-dihydroxy-3-phosphanyloxane-2-carboxylic acid Chemical compound O1C(C(O)=O)C(P)C(O)C(O)C1OC1C(C(O)=O)OC(OP)C(O)C1O FHVDTGUDJYJELY-UHFFFAOYSA-N 0.000 description 1
• QSBYPNXLFMSGKH-UHFFFAOYSA-N 9-Heptadecensaeure Natural products CCCCCCCC=CCCCCCCCC(O)=O QSBYPNXLFMSGKH-UHFFFAOYSA-N 0.000 description 1
• 208000007122 AIDS-Associated Nephropathy Diseases 0.000 description 1
• QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
• 229930024421 Adenine Natural products 0.000 description 1
• GFFGJBXGBJISGV-UHFFFAOYSA-N Adenine Chemical compound NC1=NC=NC2=C1N=CN2 GFFGJBXGBJISGV-UHFFFAOYSA-N 0.000 description 1
• 208000006820 Arthralgia Diseases 0.000 description 1
• CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Natural products OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 1
• 241000972773 Aulopiformes Species 0.000 description 1
• 241000894006 Bacteria Species 0.000 description 1
• 239000005711 Benzoic acid Substances 0.000 description 1
• DWRXFEITVBNRMK-UHFFFAOYSA-N Beta-D-1-Arabinofuranosylthymine Natural products O=C1NC(=O)C(C)=CN1C1C(O)C(O)C(CO)O1 DWRXFEITVBNRMK-UHFFFAOYSA-N 0.000 description 1
• 102000004506 Blood Proteins Human genes 0.000 description 1
• 108010017384 Blood Proteins Proteins 0.000 description 1
• 239000004255 Butylated hydroxyanisole Substances 0.000 description 1
• 239000004322 Butylated hydroxytoluene Substances 0.000 description 1
• NLZUEZXRPGMBCV-UHFFFAOYSA-N Butylhydroxytoluene Chemical compound CC1=CC(C(C)(C)C)=C(O)C(C(C)(C)C)=C1 NLZUEZXRPGMBCV-UHFFFAOYSA-N 0.000 description 1
• FERIUCNNQQJTOY-UHFFFAOYSA-M Butyrate Chemical compound CCCC([O-])=O FERIUCNNQQJTOY-UHFFFAOYSA-M 0.000 description 1
• FERIUCNNQQJTOY-UHFFFAOYSA-N Butyric acid Natural products CCCC(O)=O FERIUCNNQQJTOY-UHFFFAOYSA-N 0.000 description 1
• 238000011740 C57BL/6 mouse Methods 0.000 description 1
• OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
• UXVMQQNJUSDDNG-UHFFFAOYSA-L Calcium chloride Chemical compound [Cl-].[Cl-].[Ca+2] UXVMQQNJUSDDNG-UHFFFAOYSA-L 0.000 description 1
• 108010067225 Cell Adhesion Molecules Proteins 0.000 description 1
• 102000016289 Cell Adhesion Molecules Human genes 0.000 description 1
• 102000000844 Cell Surface Receptors Human genes 0.000 description 1
• 108010001857 Cell Surface Receptors Proteins 0.000 description 1
• 101710104316 Cell surface-binding protein Proteins 0.000 description 1
• 208000014085 Chronic respiratory disease Diseases 0.000 description 1
• KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 description 1
• 108010068426 Contractile Proteins Proteins 0.000 description 1
• 102000002585 Contractile Proteins Human genes 0.000 description 1
• CMSMOCZEIVJLDB-UHFFFAOYSA-N Cyclophosphamide Chemical compound ClCCN(CCCl)P1(=O)NCCCO1 CMSMOCZEIVJLDB-UHFFFAOYSA-N 0.000 description 1
• XUJNEKJLAYXESH-UWTATZPHSA-N D-Cysteine Chemical compound SC[C@@H](N)C(O)=O XUJNEKJLAYXESH-UWTATZPHSA-N 0.000 description 1
• AHLPHDHHMVZTML-SCSAIBSYSA-N D-Ornithine Chemical compound NCCC[C@@H](N)C(O)=O AHLPHDHHMVZTML-SCSAIBSYSA-N 0.000 description 1
• QNAYBMKLOCPYGJ-UWTATZPHSA-N D-alanine Chemical compound C[C@@H](N)C(O)=O QNAYBMKLOCPYGJ-UWTATZPHSA-N 0.000 description 1
• QNAYBMKLOCPYGJ-UHFFFAOYSA-N D-alpha-Ala Natural products CC([NH3+])C([O-])=O QNAYBMKLOCPYGJ-UHFFFAOYSA-N 0.000 description 1
• 150000008574 D-amino acids Chemical class 0.000 description 1
• ODKSFYDXXFIFQN-SCSAIBSYSA-N D-arginine Chemical compound OC(=O)[C@H](N)CCCNC(N)=N ODKSFYDXXFIFQN-SCSAIBSYSA-N 0.000 description 1
• 229930028154 D-arginine Natural products 0.000 description 1
• FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Polymers OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 description 1
• KDXKERNSBIXSRK-RXMQYKEDSA-N D-lysine Chemical compound NCCCC[C@@H](N)C(O)=O KDXKERNSBIXSRK-RXMQYKEDSA-N 0.000 description 1
• FFEARJCKVFRZRR-SCSAIBSYSA-N D-methionine Chemical compound CSCC[C@@H](N)C(O)=O FFEARJCKVFRZRR-SCSAIBSYSA-N 0.000 description 1
• 229930182818 D-methionine Natural products 0.000 description 1
• 229920002307 Dextran Polymers 0.000 description 1
• 208000007342 Diabetic Nephropathies Diseases 0.000 description 1
• XBPCUCUWBYBCDP-UHFFFAOYSA-N Dicyclohexylamine Chemical class C1CCCCC1NC1CCCCC1 XBPCUCUWBYBCDP-UHFFFAOYSA-N 0.000 description 1
• 201000003066 Diffuse Scleroderma Diseases 0.000 description 1
• 229930195710 D‐cysteine Natural products 0.000 description 1
• 102000004533 Endonucleases Human genes 0.000 description 1
• 108010042407 Endonucleases Proteins 0.000 description 1
• 206010014954 Eosinophilic fasciitis Diseases 0.000 description 1
• 108010008655 Epstein-Barr Virus Nuclear Antigens Proteins 0.000 description 1
• 241000588724 Escherichia coli Species 0.000 description 1
• 241000206602 Eukaryota Species 0.000 description 1
• 229920001917 Ficoll Polymers 0.000 description 1
• 241000287828 Gallus gallus Species 0.000 description 1
• 208000010412 Glaucoma Diseases 0.000 description 1
• 102000006395 Globulins Human genes 0.000 description 1
• 108010044091 Globulins Proteins 0.000 description 1
• 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 1
• JZNWSCPGTDBMEW-UHFFFAOYSA-N Glycerophosphorylethanolamin Natural products NCCOP(O)(=O)OCC(O)CO JZNWSCPGTDBMEW-UHFFFAOYSA-N 0.000 description 1
• ZWZWYGMENQVNFU-UHFFFAOYSA-N Glycerophosphorylserin Natural products OC(=O)C(N)COP(O)(=O)OCC(O)CO ZWZWYGMENQVNFU-UHFFFAOYSA-N 0.000 description 1
• 244000060234 Gmelina philippensis Species 0.000 description 1
• 108060003393 Granulin Proteins 0.000 description 1
• 206010070737 HIV associated nephropathy Diseases 0.000 description 1
• 208000032843 Hemorrhage Diseases 0.000 description 1
• 241000238631 Hexapoda Species 0.000 description 1
• 101000998953 Homo sapiens Immunoglobulin heavy variable 1-2 Proteins 0.000 description 1
• 101001008255 Homo sapiens Immunoglobulin kappa variable 1D-8 Proteins 0.000 description 1
• 101001047628 Homo sapiens Immunoglobulin kappa variable 2-29 Proteins 0.000 description 1
• 101001008321 Homo sapiens Immunoglobulin kappa variable 2D-26 Proteins 0.000 description 1
• 101001047619 Homo sapiens Immunoglobulin kappa variable 3-20 Proteins 0.000 description 1
• 101001008263 Homo sapiens Immunoglobulin kappa variable 3D-15 Proteins 0.000 description 1
• 101001063392 Homo sapiens Lymphocyte function-associated antigen 3 Proteins 0.000 description 1
• 108091006905 Human Serum Albumin Proteins 0.000 description 1
• 102000008100 Human Serum Albumin Human genes 0.000 description 1
• 241000701044 Human gammaherpesvirus 4 Species 0.000 description 1
• CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 1
• 229920002153 Hydroxypropyl cellulose Polymers 0.000 description 1
• 206010020751 Hypersensitivity Diseases 0.000 description 1
• UGQMRVRMYYASKQ-UHFFFAOYSA-N Hypoxanthine nucleoside Natural products OC1C(O)C(CO)OC1N1C(NC=NC2=O)=C2N=C1 UGQMRVRMYYASKQ-UHFFFAOYSA-N 0.000 description 1
• DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound 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
• 102100036887 Immunoglobulin heavy variable 1-2 Human genes 0.000 description 1
• 102100022964 Immunoglobulin kappa variable 3-20 Human genes 0.000 description 1
• 206010061216 Infarction Diseases 0.000 description 1
• 102000014150 Interferons Human genes 0.000 description 1
• 108010050904 Interferons Proteins 0.000 description 1
• UETNIIAIRMUTSM-UHFFFAOYSA-N Jacareubin Natural products CC1(C)OC2=CC3Oc4c(O)c(O)ccc4C(=O)C3C(=C2C=C1)O UETNIIAIRMUTSM-UHFFFAOYSA-N 0.000 description 1
• YQEZLKZALYSWHR-UHFFFAOYSA-N Ketamine Chemical compound C=1C=CC=C(Cl)C=1C1(NC)CCCCC1=O YQEZLKZALYSWHR-UHFFFAOYSA-N 0.000 description 1
• 206010023421 Kidney fibrosis Diseases 0.000 description 1
• QUOGESRFPZDMMT-UHFFFAOYSA-N L-Homoarginine Natural products OC(=O)C(N)CCCCNC(N)=N QUOGESRFPZDMMT-UHFFFAOYSA-N 0.000 description 1
• AHLPHDHHMVZTML-BYPYZUCNSA-N L-Ornithine Chemical compound NCCC[C@H](N)C(O)=O AHLPHDHHMVZTML-BYPYZUCNSA-N 0.000 description 1
• ONIBWKKTOPOVIA-BYPYZUCNSA-N L-Proline Chemical compound OC(=O)[C@@H]1CCCN1 ONIBWKKTOPOVIA-BYPYZUCNSA-N 0.000 description 1
• 239000011786 L-ascorbyl-6-palmitate Substances 0.000 description 1
• QAQJMLQRFWZOBN-LAUBAEHRSA-N L-ascorbyl-6-palmitate Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](O)[C@H]1OC(=O)C(O)=C1O QAQJMLQRFWZOBN-LAUBAEHRSA-N 0.000 description 1
• 239000004201 L-cysteine Substances 0.000 description 1
• 235000013878 L-cysteine Nutrition 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
• QUOGESRFPZDMMT-YFKPBYRVSA-N L-homoarginine Chemical compound OC(=O)[C@@H](N)CCCCNC(N)=N QUOGESRFPZDMMT-YFKPBYRVSA-N 0.000 description 1
• FBOZXECLQNJBKD-ZDUSSCGKSA-N L-methotrexate Chemical compound C=1N=C2N=C(N)N=C(N)C2=NC=1CN(C)C1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 FBOZXECLQNJBKD-ZDUSSCGKSA-N 0.000 description 1
• FEWJPZIEWOKRBE-JCYAYHJZSA-L L-tartrate(2-) Chemical compound [O-]C(=O)[C@H](O)[C@@H](O)C([O-])=O FEWJPZIEWOKRBE-JCYAYHJZSA-L 0.000 description 1
• 208000034693 Laceration Diseases 0.000 description 1
• JVTAAEKCZFNVCJ-UHFFFAOYSA-M Lactate Chemical compound CC(O)C([O-])=O JVTAAEKCZFNVCJ-UHFFFAOYSA-M 0.000 description 1
• 239000004166 Lanolin Substances 0.000 description 1
• 239000000232 Lipid Bilayer Substances 0.000 description 1
• 208000004852 Lung Injury Diseases 0.000 description 1
• 208000019693 Lung disease Diseases 0.000 description 1
• 102100030984 Lymphocyte function-associated antigen 3 Human genes 0.000 description 1
• PEEHTFAAVSWFBL-UHFFFAOYSA-N Maleimide Chemical compound O=C1NC(=O)C=C1 PEEHTFAAVSWFBL-UHFFFAOYSA-N 0.000 description 1
• 241000124008 Mammalia Species 0.000 description 1
• 206010027145 Melanocytic naevus Diseases 0.000 description 1
• 102000018697 Membrane Proteins Human genes 0.000 description 1
• 108010052285 Membrane Proteins Proteins 0.000 description 1
• AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 1
• 101710139349 Mucosal addressin cell adhesion molecule 1 Proteins 0.000 description 1
• 102100028793 Mucosal addressin cell adhesion molecule 1 Human genes 0.000 description 1
• 108010021466 Mutant Proteins Proteins 0.000 description 1
• 102000008300 Mutant Proteins Human genes 0.000 description 1
• MBBZMMPHUWSWHV-BDVNFPICSA-N N-methylglucamine Chemical compound CNC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO MBBZMMPHUWSWHV-BDVNFPICSA-N 0.000 description 1
• 125000000729 N-terminal amino-acid group Chemical group 0.000 description 1
• PVNIIMVLHYAWGP-UHFFFAOYSA-N Niacin Chemical compound OC(=O)C1=CC=CN=C1 PVNIIMVLHYAWGP-UHFFFAOYSA-N 0.000 description 1
• IOVCWXUNBOPUCH-UHFFFAOYSA-M Nitrite anion Chemical compound [O-]N=O IOVCWXUNBOPUCH-UHFFFAOYSA-M 0.000 description 1
• REYJJPSVUYRZGE-UHFFFAOYSA-N Octadecylamine Chemical compound CCCCCCCCCCCCCCCCCCN REYJJPSVUYRZGE-UHFFFAOYSA-N 0.000 description 1
• 206010030113 Oedema Diseases 0.000 description 1
• 239000005642 Oleic acid Substances 0.000 description 1
• ZQPPMHVWECSIRJ-UHFFFAOYSA-N Oleic acid Natural products CCCCCCCCC=CCCCCCCCC(O)=O ZQPPMHVWECSIRJ-UHFFFAOYSA-N 0.000 description 1
• 206010053159 Organ failure Diseases 0.000 description 1
• AHLPHDHHMVZTML-UHFFFAOYSA-N Orn-delta-NH2 Natural products NCCCC(N)C(O)=O AHLPHDHHMVZTML-UHFFFAOYSA-N 0.000 description 1
• UTJLXEIPEHZYQJ-UHFFFAOYSA-N Ornithine Natural products OC(=O)C(C)CCCN UTJLXEIPEHZYQJ-UHFFFAOYSA-N 0.000 description 1
• MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 1
• 229910019142 PO4 Inorganic materials 0.000 description 1
• 241001494479 Pecora Species 0.000 description 1
• 229920003171 Poly (ethylene oxide) Polymers 0.000 description 1
• 239000004698 Polyethylene Substances 0.000 description 1
• 229920002535 Polyethylene Glycol 1500 Polymers 0.000 description 1
• 206010036346 Posterior capsule opacification Diseases 0.000 description 1
• XBDQKXXYIPTUBI-UHFFFAOYSA-M Propionate Chemical compound CCC([O-])=O XBDQKXXYIPTUBI-UHFFFAOYSA-M 0.000 description 1
• 102000007327 Protamines Human genes 0.000 description 1
• 108010007568 Protamines Proteins 0.000 description 1
• 206010061924 Pulmonary toxicity Diseases 0.000 description 1
• 208000003782 Raynaud disease Diseases 0.000 description 1
• 208000012322 Raynaud phenomenon Diseases 0.000 description 1
• 241000235070 Saccharomyces Species 0.000 description 1
• 240000004808 Saccharomyces cerevisiae Species 0.000 description 1
• VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 1
• FBPFZTCFMRRESA-NQAPHZHOSA-N Sorbitol Polymers OCC(O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-NQAPHZHOSA-N 0.000 description 1
• 238000003639 Student–Newman–Keuls (SNK) method Methods 0.000 description 1
• 208000002847 Surgical Wound Diseases 0.000 description 1
• 201000009594 Systemic Scleroderma Diseases 0.000 description 1
• 206010042953 Systemic sclerosis Diseases 0.000 description 1
• 210000001744 T-lymphocyte Anatomy 0.000 description 1
• QJJXYPPXXYFBGM-LFZNUXCKSA-N Tacrolimus Chemical compound C1C[C@@H](O)[C@H](OC)C[C@@H]1\C=C(/C)[C@@H]1[C@H](C)[C@@H](O)CC(=O)[C@H](CC=C)/C=C(C)/C[C@H](C)C[C@H](OC)[C@H]([C@H](C[C@H]2C)OC)O[C@@]2(O)C(=O)C(=O)N2CCCC[C@H]2C(=O)O1 QJJXYPPXXYFBGM-LFZNUXCKSA-N 0.000 description 1
• ZMZDMBWJUHKJPS-UHFFFAOYSA-M Thiocyanate anion Chemical compound [S-]C#N ZMZDMBWJUHKJPS-UHFFFAOYSA-M 0.000 description 1
• 108090000190 Thrombin Proteins 0.000 description 1
• 108700019146 Transgenes Proteins 0.000 description 1
• 206010069363 Traumatic lung injury Diseases 0.000 description 1
• 239000007983 Tris buffer Substances 0.000 description 1
• HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 1
• JPBAVLUULZJFFO-JENHRLMUSA-N [(2s)-2-[(2r)-3,4-dihydroxy-5-oxo-2h-furan-2-yl]-2-hydroxyethyl] (z)-octadec-9-enoate Chemical compound CCCCCCCC\C=C/CCCCCCCC(=O)OC[C@H](O)[C@H]1OC(=O)C(O)=C1O JPBAVLUULZJFFO-JENHRLMUSA-N 0.000 description 1
• ATBOMIWRCZXYSZ-XZBBILGWSA-N [1-[2,3-dihydroxypropoxy(hydroxy)phosphoryl]oxy-3-hexadecanoyloxypropan-2-yl] (9e,12e)-octadeca-9,12-dienoate Chemical compound CCCCCCCCCCCCCCCC(=O)OCC(COP(O)(=O)OCC(O)CO)OC(=O)CCCCCCC\C=C\C\C=C\CCCCC ATBOMIWRCZXYSZ-XZBBILGWSA-N 0.000 description 1
• 230000003187 abdominal effect Effects 0.000 description 1
• 230000001594 aberrant effect Effects 0.000 description 1
• 238000010521 absorption reaction Methods 0.000 description 1
• DPXJVFZANSGRMM-UHFFFAOYSA-N acetic acid;2,3,4,5,6-pentahydroxyhexanal;sodium Chemical compound [Na].CC(O)=O.OCC(O)C(O)C(O)C(O)C=O DPXJVFZANSGRMM-UHFFFAOYSA-N 0.000 description 1
• 230000021736 acetylation Effects 0.000 description 1
• 238000006640 acetylation reaction Methods 0.000 description 1
• 239000002253 acid Substances 0.000 description 1
• 230000002378 acidificating effect Effects 0.000 description 1
• 239000012190 activator Substances 0.000 description 1
• 239000011149 active material Substances 0.000 description 1
• 229960000643 adenine Drugs 0.000 description 1
• WNLRTRBMVRJNCN-UHFFFAOYSA-L adipate(2-) Chemical compound [O-]C(=O)CCCCC([O-])=O WNLRTRBMVRJNCN-UHFFFAOYSA-L 0.000 description 1
• 239000002671 adjuvant Substances 0.000 description 1
• 230000002411 adverse Effects 0.000 description 1
• 239000000556 agonist Substances 0.000 description 1
• 229940072056 alginate Drugs 0.000 description 1
• 235000010443 alginic acid Nutrition 0.000 description 1
• 229920000615 alginic acid Polymers 0.000 description 1
• 150000001340 alkali metals Chemical class 0.000 description 1
• 125000000217 alkyl group Chemical group 0.000 description 1
• 150000001350 alkyl halides Chemical class 0.000 description 1
• 230000029936 alkylation Effects 0.000 description 1
• 238000005804 alkylation reaction Methods 0.000 description 1
• HWXBTNAVRSUOJR-UHFFFAOYSA-N alpha-hydroxyglutaric acid Natural products OC(=O)C(O)CCC(O)=O HWXBTNAVRSUOJR-UHFFFAOYSA-N 0.000 description 1
• 229940009533 alpha-ketoglutaric acid Drugs 0.000 description 1
• CEGOLXSVJUTHNZ-UHFFFAOYSA-K aluminium tristearate Chemical compound [Al+3].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O CEGOLXSVJUTHNZ-UHFFFAOYSA-K 0.000 description 1
• 229940063655 aluminum stearate Drugs 0.000 description 1
• 230000009435 amidation Effects 0.000 description 1
• 238000007112 amidation reaction Methods 0.000 description 1
• 150000003863 ammonium salts Chemical class 0.000 description 1
• 230000003042 antagnostic effect Effects 0.000 description 1
• 230000003367 anti-collagen effect Effects 0.000 description 1
• 230000003064 anti-oxidating effect Effects 0.000 description 1
• 230000000692 anti-sense effect Effects 0.000 description 1
• 230000000890 antigenic effect Effects 0.000 description 1
• 239000008346 aqueous phase Substances 0.000 description 1
• 210000001367 artery Anatomy 0.000 description 1
• 206010003246 arthritis Diseases 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
• 235000010385 ascorbyl palmitate Nutrition 0.000 description 1
• 229940009098 aspartate Drugs 0.000 description 1
• 238000003556 assay Methods 0.000 description 1
• 230000002238 attenuated effect Effects 0.000 description 1
• 239000003637 basic solution Substances 0.000 description 1
• 229940077388 benzenesulfonate Drugs 0.000 description 1
• SRSXLGNVWSONIS-UHFFFAOYSA-M benzenesulfonate Chemical compound [O-]S(=O)(=O)C1=CC=CC=C1 SRSXLGNVWSONIS-UHFFFAOYSA-M 0.000 description 1
• 229940050390 benzoate Drugs 0.000 description 1
• 235000010233 benzoic acid Nutrition 0.000 description 1
• 229960004365 benzoic acid Drugs 0.000 description 1
• 235000019445 benzyl alcohol Nutrition 0.000 description 1
• 229960004217 benzyl alcohol Drugs 0.000 description 1
• 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 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
• IQFYYKKMVGJFEH-UHFFFAOYSA-N beta-L-thymidine Natural products O=C1NC(=O)C(C)=CN1C1OC(CO)C(O)C1 IQFYYKKMVGJFEH-UHFFFAOYSA-N 0.000 description 1
• 229940000635 beta-alanine Drugs 0.000 description 1
• XMIIGOLPHOKFCH-UHFFFAOYSA-N beta-phenylpropanoic acid Natural products OC(=O)CCC1=CC=CC=C1 XMIIGOLPHOKFCH-UHFFFAOYSA-N 0.000 description 1
• 238000011325 biochemical measurement Methods 0.000 description 1
• 238000006065 biodegradation reaction Methods 0.000 description 1
• 230000033228 biological regulation Effects 0.000 description 1
• 238000001574 biopsy Methods 0.000 description 1
• 229960004395 bleomycin sulfate Drugs 0.000 description 1
• 230000017531 blood circulation Effects 0.000 description 1
• 238000009534 blood test Methods 0.000 description 1
• 210000004204 blood vessel Anatomy 0.000 description 1
• 208000029028 brain injury Diseases 0.000 description 1
• 238000013276 bronchoscopy Methods 0.000 description 1
• 235000019282 butylated hydroxyanisole Nutrition 0.000 description 1
• CZBZUDVBLSSABA-UHFFFAOYSA-N butylated hydroxyanisole Chemical compound COC1=CC=C(O)C(C(C)(C)C)=C1.COC1=CC=C(O)C=C1C(C)(C)C CZBZUDVBLSSABA-UHFFFAOYSA-N 0.000 description 1
• 229940043253 butylated hydroxyanisole Drugs 0.000 description 1
• 235000010354 butylated hydroxytoluene Nutrition 0.000 description 1
• 229940095259 butylated hydroxytoluene Drugs 0.000 description 1
• 210000004899 c-terminal region Anatomy 0.000 description 1
• 229910052791 calcium Inorganic materials 0.000 description 1
• 239000011575 calcium Substances 0.000 description 1
• 239000001110 calcium chloride Substances 0.000 description 1
• 229910001628 calcium chloride Inorganic materials 0.000 description 1
• MIOPJNTWMNEORI-UHFFFAOYSA-N camphorsulfonic acid Chemical compound C1CC2(CS(O)(=O)=O)C(=O)CC1C2(C)C MIOPJNTWMNEORI-UHFFFAOYSA-N 0.000 description 1
• 150000001720 carbohydrates Chemical class 0.000 description 1
• 235000014633 carbohydrates Nutrition 0.000 description 1
• 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 1
• 239000001768 carboxy methyl cellulose Substances 0.000 description 1
• 230000021523 carboxylation Effects 0.000 description 1
• 238000006473 carboxylation reaction Methods 0.000 description 1
• 230000009787 cardiac fibrosis Effects 0.000 description 1
• 239000012876 carrier material Substances 0.000 description 1
• 238000012219 cassette mutagenesis Methods 0.000 description 1
• 239000004359 castor oil Substances 0.000 description 1
• 235000019438 castor oil Nutrition 0.000 description 1
• 230000015556 catabolic process Effects 0.000 description 1
• 238000004113 cell culture Methods 0.000 description 1
• 239000013592 cell lysate Substances 0.000 description 1
• 230000001413 cellular effect Effects 0.000 description 1
• 230000007541 cellular toxicity Effects 0.000 description 1
• 239000001913 cellulose Substances 0.000 description 1
• 229920002678 cellulose Polymers 0.000 description 1
• 235000010980 cellulose Nutrition 0.000 description 1
• 238000010382 chemical cross-linking Methods 0.000 description 1
• 238000007385 chemical modification Methods 0.000 description 1
• 238000002512 chemotherapy Methods 0.000 description 1
• 238000011976 chest X-ray Methods 0.000 description 1
• 235000012000 cholesterol Nutrition 0.000 description 1
• 229940107161 cholesterol Drugs 0.000 description 1
• 230000001684 chronic effect Effects 0.000 description 1
• 238000004040 coloring Methods 0.000 description 1
• 238000002648 combination therapy Methods 0.000 description 1
• 238000002742 combinatorial mutagenesis Methods 0.000 description 1
• 230000002860 competitive effect Effects 0.000 description 1
• 238000009833 condensation Methods 0.000 description 1
• 230000005494 condensation Effects 0.000 description 1
• 230000001143 conditioned effect Effects 0.000 description 1
• 239000000470 constituent Substances 0.000 description 1
• 230000001276 controlling effect Effects 0.000 description 1
• 229920001577 copolymer Polymers 0.000 description 1
• 238000007887 coronary angioplasty Methods 0.000 description 1
• 239000003246 corticosteroid Substances 0.000 description 1
• 229960001334 corticosteroids Drugs 0.000 description 1
• 238000011461 current therapy Methods 0.000 description 1
• ATDGTVJJHBUTRL-UHFFFAOYSA-N cyanogen bromide Chemical compound BrC#N ATDGTVJJHBUTRL-UHFFFAOYSA-N 0.000 description 1
• 125000004122 cyclic group Chemical group 0.000 description 1
• 229960004397 cyclophosphamide Drugs 0.000 description 1
• OOTFVKOQINZBBF-UHFFFAOYSA-N cystamine Chemical compound CCSSCCN OOTFVKOQINZBBF-UHFFFAOYSA-N 0.000 description 1
• 229940099500 cystamine Drugs 0.000 description 1
• 150000001945 cysteines Chemical class 0.000 description 1
• 125000002704 decyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
• 230000006735 deficit Effects 0.000 description 1
• 238000006731 degradation reaction Methods 0.000 description 1
• 230000003111 delayed effect Effects 0.000 description 1
• 230000001419 dependent effect Effects 0.000 description 1
• 201000001981 dermatomyositis Diseases 0.000 description 1
• 238000001514 detection method Methods 0.000 description 1
• 230000006866 deterioration Effects 0.000 description 1
• 229960002086 dextran Drugs 0.000 description 1
• 229940000986 dextran 110 Drugs 0.000 description 1
• 239000008121 dextrose Substances 0.000 description 1
• 208000033679 diabetic kidney disease Diseases 0.000 description 1
• 150000008050 dialkyl sulfates Chemical class 0.000 description 1
• 235000005911 diet Nutrition 0.000 description 1
• 230000037213 diet Effects 0.000 description 1
• 125000004177 diethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
• 230000004069 differentiation Effects 0.000 description 1
• GXGAKHNRMVGRPK-UHFFFAOYSA-N dimagnesium;dioxido-bis[[oxido(oxo)silyl]oxy]silane Chemical compound [Mg+2].[Mg+2].[O-][Si](=O)O[Si]([O-])([O-])O[Si]([O-])=O GXGAKHNRMVGRPK-UHFFFAOYSA-N 0.000 description 1
• 125000000118 dimethyl group Chemical group [H]C([H])([H])* 0.000 description 1
• GAFRWLVTHPVQGK-UHFFFAOYSA-N dipentyl sulfate Chemical class CCCCCOS(=O)(=O)OCCCCC GAFRWLVTHPVQGK-UHFFFAOYSA-N 0.000 description 1
• ZPWVASYFFYYZEW-UHFFFAOYSA-L dipotassium hydrogen phosphate Chemical compound [K+].[K+].OP([O-])([O-])=O ZPWVASYFFYYZEW-UHFFFAOYSA-L 0.000 description 1
• 229910000396 dipotassium phosphate Inorganic materials 0.000 description 1
• 235000019797 dipotassium phosphate Nutrition 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
• 229940042399 direct acting antivirals protease inhibitors Drugs 0.000 description 1
• BNIILDVGGAEEIG-UHFFFAOYSA-L disodium hydrogen phosphate Chemical compound [Na+].[Na+].OP([O-])([O-])=O BNIILDVGGAEEIG-UHFFFAOYSA-L 0.000 description 1
• 238000009826 distribution Methods 0.000 description 1
• AFOSIXZFDONLBT-UHFFFAOYSA-N divinyl sulfone Chemical compound C=CS(=O)(=O)C=C AFOSIXZFDONLBT-UHFFFAOYSA-N 0.000 description 1
• 125000003438 dodecyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
• MOTZDAYCYVMXPC-UHFFFAOYSA-N dodecyl hydrogen sulfate Chemical compound CCCCCCCCCCCCOS(O)(=O)=O MOTZDAYCYVMXPC-UHFFFAOYSA-N 0.000 description 1
• 229940043264 dodecyl sulfate Drugs 0.000 description 1
• 229940112141 dry powder inhaler Drugs 0.000 description 1
• 230000002526 effect on cardiovascular system Effects 0.000 description 1
• 210000002257 embryonic structure Anatomy 0.000 description 1
• 239000003995 emulsifying agent Substances 0.000 description 1
• 230000001804 emulsifying effect Effects 0.000 description 1
• 210000003038 endothelium Anatomy 0.000 description 1
• 238000006911 enzymatic reaction Methods 0.000 description 1
• 238000001952 enzyme assay Methods 0.000 description 1
• YQGOJNYOYNNSMM-UHFFFAOYSA-N eosin Chemical compound [Na+].OC(=O)C1=CC=CC=C1C1=C2C=C(Br)C(=O)C(Br)=C2OC2=C(Br)C(O)=C(Br)C=C21 YQGOJNYOYNNSMM-UHFFFAOYSA-N 0.000 description 1
• 210000003979 eosinophil Anatomy 0.000 description 1
• 230000002327 eosinophilic effect Effects 0.000 description 1
• CCIVGXIOQKPBKL-UHFFFAOYSA-M ethanesulfonate Chemical compound CCS([O-])(=O)=O CCIVGXIOQKPBKL-UHFFFAOYSA-M 0.000 description 1
• 150000002169 ethanolamines Chemical class 0.000 description 1
• BEFDCLMNVWHSGT-UHFFFAOYSA-N ethenylcyclopentane Chemical compound C=CC1CCCC1 BEFDCLMNVWHSGT-UHFFFAOYSA-N 0.000 description 1
• 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
• 238000011156 evaluation Methods 0.000 description 1
• 239000000284 extract Substances 0.000 description 1
• IMBKASBLAKCLEM-UHFFFAOYSA-L ferrous ammonium sulfate (anhydrous) Chemical compound [NH4+].[NH4+].[Fe+2].[O-]S([O-])(=O)=O.[O-]S([O-])(=O)=O IMBKASBLAKCLEM-UHFFFAOYSA-L 0.000 description 1
• 239000000835 fiber Substances 0.000 description 1
• 230000009795 fibrotic process Effects 0.000 description 1
• 239000002657 fibrous material Substances 0.000 description 1
• 238000001914 filtration Methods 0.000 description 1
• 238000000684 flow cytometry Methods 0.000 description 1
• 239000007850 fluorescent dye Substances 0.000 description 1
• 235000013305 food Nutrition 0.000 description 1
• 235000003599 food sweetener Nutrition 0.000 description 1
• 125000002485 formyl group Chemical group [H]C(*)=O 0.000 description 1
• VZCYOOQTPOCHFL-OWOJBTEDSA-L fumarate(2-) Chemical compound [O-]C(=O)\C=C\C([O-])=O VZCYOOQTPOCHFL-OWOJBTEDSA-L 0.000 description 1
• 125000000524 functional group Chemical group 0.000 description 1
• 239000007789 gas Substances 0.000 description 1
• 210000005095 gastrointestinal system Anatomy 0.000 description 1
• 230000002068 genetic effect Effects 0.000 description 1
• 238000010353 genetic engineering Methods 0.000 description 1
• 150000002303 glucose derivatives Polymers 0.000 description 1
• 150000002304 glucoses Polymers 0.000 description 1
• 125000002791 glucosyl group Polymers C1([C@H](O)[C@@H](O)[C@H](O)[C@H](O1)CO)* 0.000 description 1
• ZEMPKEQAKRGZGQ-XOQCFJPHSA-N glycerol triricinoleate Natural products CCCCCC[C@@H](O)CC=CCCCCCCCC(=O)OC[C@@H](COC(=O)CCCCCCCC=CC[C@@H](O)CCCCCC)OC(=O)CCCCCCCC=CC[C@H](O)CCCCCC ZEMPKEQAKRGZGQ-XOQCFJPHSA-N 0.000 description 1
• 150000002321 glycerophosphoglycerophosphoglycerols Chemical class 0.000 description 1
• 229960002449 glycine Drugs 0.000 description 1
• 125000003827 glycol group Chemical group 0.000 description 1
• 210000004837 gut-associated lymphoid tissue Anatomy 0.000 description 1
• 229940093915 gynecological organic acid Drugs 0.000 description 1
• 150000004820 halides Chemical class 0.000 description 1
• 230000036541 health Effects 0.000 description 1
• 230000023597 hemostasis Effects 0.000 description 1
• MNWFXJYAOYHMED-UHFFFAOYSA-N heptanoic acid Chemical compound CCCCCCC(O)=O MNWFXJYAOYHMED-UHFFFAOYSA-N 0.000 description 1
• FUZZWVXGSFPDMH-UHFFFAOYSA-N hexanoic acid Chemical compound CCCCCC(O)=O FUZZWVXGSFPDMH-UHFFFAOYSA-N 0.000 description 1
• 238000010562 histological examination Methods 0.000 description 1
• 238000007489 histopathology method Methods 0.000 description 1
• 239000005556 hormone Substances 0.000 description 1
• 229940088597 hormone Drugs 0.000 description 1
• 239000001257 hydrogen Substances 0.000 description 1
• 229910052739 hydrogen Inorganic materials 0.000 description 1
• XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 1
• ZMZDMBWJUHKJPS-UHFFFAOYSA-N hydrogen thiocyanate Natural products SC#N ZMZDMBWJUHKJPS-UHFFFAOYSA-N 0.000 description 1
• QAOWNCQODCNURD-UHFFFAOYSA-M hydrogensulfate Chemical compound OS([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-M 0.000 description 1
• 230000003301 hydrolyzing effect Effects 0.000 description 1
• 230000002209 hydrophobic effect Effects 0.000 description 1
• 230000033444 hydroxylation Effects 0.000 description 1
• 238000005805 hydroxylation reaction Methods 0.000 description 1
• 239000001863 hydroxypropyl cellulose Substances 0.000 description 1
• 235000010977 hydroxypropyl cellulose Nutrition 0.000 description 1
• 239000001866 hydroxypropyl methyl cellulose Substances 0.000 description 1
• 235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 description 1
• 229920003088 hydroxypropyl methyl cellulose Polymers 0.000 description 1
• UFVKGYZPFZQRLF-UHFFFAOYSA-N hydroxypropyl methyl cellulose Chemical compound OC1C(O)C(OC)OC(CO)C1OC1C(O)C(O)C(OC2C(C(O)C(OC3C(C(O)C(O)C(CO)O3)O)C(CO)O2)O)C(CO)O1 UFVKGYZPFZQRLF-UHFFFAOYSA-N 0.000 description 1
• 230000003463 hyperproliferative effect Effects 0.000 description 1
• 230000028993 immune response Effects 0.000 description 1
• 230000036039 immunity Effects 0.000 description 1
• 230000009851 immunogenic response Effects 0.000 description 1
• 229940099472 immunoglobulin a Drugs 0.000 description 1
• 230000016784 immunoglobulin production Effects 0.000 description 1
• 238000002991 immunohistochemical analysis Methods 0.000 description 1
• 230000002055 immunohistochemical effect Effects 0.000 description 1
• 238000001114 immunoprecipitation Methods 0.000 description 1
• 238000011534 incubation Methods 0.000 description 1
• 230000007574 infarction Effects 0.000 description 1
• 208000015181 infectious disease Diseases 0.000 description 1
• 230000008595 infiltration Effects 0.000 description 1
• 238000001764 infiltration Methods 0.000 description 1
• 230000006749 inflammatory damage Effects 0.000 description 1
• 208000027866 inflammatory disease Diseases 0.000 description 1
• 238000001802 infusion Methods 0.000 description 1
• 239000003112 inhibitor Substances 0.000 description 1
• 230000000977 initiatory effect Effects 0.000 description 1
• 229940102223 injectable solution Drugs 0.000 description 1
• 229940102213 injectable suspension Drugs 0.000 description 1
• 229910052500 inorganic mineral Inorganic materials 0.000 description 1
• 230000008611 intercellular interaction Effects 0.000 description 1
• 230000002452 interceptive effect Effects 0.000 description 1
• 229940047124 interferons Drugs 0.000 description 1
• 238000007917 intracranial administration Methods 0.000 description 1
• 238000007918 intramuscular administration Methods 0.000 description 1
• 238000007919 intrasynovial administration Methods 0.000 description 1
• 238000007913 intrathecal administration Methods 0.000 description 1
• 150000002500 ions Chemical class 0.000 description 1
• 229910052742 iron Inorganic materials 0.000 description 1
• SUMDYPCJJOFFON-UHFFFAOYSA-N isethionic acid Chemical compound OCCS(O)(=O)=O SUMDYPCJJOFFON-UHFFFAOYSA-N 0.000 description 1
• QXJSBBXBKPUZAA-UHFFFAOYSA-N isooleic acid Natural products CCCCCCCC=CCCCCCCCCC(O)=O QXJSBBXBKPUZAA-UHFFFAOYSA-N 0.000 description 1
• 229960003299 ketamine Drugs 0.000 description 1
• 150000002576 ketones Chemical class 0.000 description 1
• TYQCGQRIZGCHNB-JLAZNSOCSA-N l-ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(O)=C(O)C1=O TYQCGQRIZGCHNB-JLAZNSOCSA-N 0.000 description 1
• 238000002372 labelling Methods 0.000 description 1
• 229940039717 lanolin Drugs 0.000 description 1
• 239000007788 liquid Substances 0.000 description 1
• 239000004973 liquid crystal related substance Substances 0.000 description 1
• 239000000314 lubricant Substances 0.000 description 1
• 231100000516 lung damage Toxicity 0.000 description 1
• 230000032646 lung growth Effects 0.000 description 1
• 231100000515 lung injury Toxicity 0.000 description 1
• 125000003588 lysine group Chemical group [H]N([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])(N([H])[H])C(*)=O 0.000 description 1
• 150000002669 lysines Chemical class 0.000 description 1
• 229920002521 macromolecule Polymers 0.000 description 1
• 210000002540 macrophage Anatomy 0.000 description 1
• 159000000003 magnesium salts Chemical class 0.000 description 1
• 239000000391 magnesium silicate Substances 0.000 description 1
• 235000019359 magnesium stearate Nutrition 0.000 description 1
• 235000019793 magnesium trisilicate Nutrition 0.000 description 1
• 229940099273 magnesium trisilicate Drugs 0.000 description 1
• 229910000386 magnesium trisilicate Inorganic materials 0.000 description 1
• VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
• 238000005259 measurement Methods 0.000 description 1
• 230000007246 mechanism Effects 0.000 description 1
• 239000012528 membrane Substances 0.000 description 1
• 210000004379 membrane Anatomy 0.000 description 1
• 230000002503 metabolic effect Effects 0.000 description 1
• 229940071648 metered dose inhaler Drugs 0.000 description 1
• 229960000485 methotrexate Drugs 0.000 description 1
• 235000010270 methyl p-hydroxybenzoate Nutrition 0.000 description 1
• 239000004292 methyl p-hydroxybenzoate Substances 0.000 description 1
• 230000011987 methylation Effects 0.000 description 1
• 238000007069 methylation reaction Methods 0.000 description 1
• 229960002216 methylparaben Drugs 0.000 description 1
• 230000005012 migration Effects 0.000 description 1
• 238000013508 migration Methods 0.000 description 1
• 235000010755 mineral Nutrition 0.000 description 1
• 239000011707 mineral Substances 0.000 description 1
• 150000007522 mineralic acids Chemical class 0.000 description 1
• 238000006011 modification reaction Methods 0.000 description 1
• 239000003607 modifier Substances 0.000 description 1
• 230000009149 molecular binding Effects 0.000 description 1
• 210000002433 mononuclear leukocyte Anatomy 0.000 description 1
• 125000001421 myristyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
• KVBGVZZKJNLNJU-UHFFFAOYSA-M naphthalene-2-sulfonate Chemical compound C1=CC=CC2=CC(S(=O)(=O)[O-])=CC=C21 KVBGVZZKJNLNJU-UHFFFAOYSA-M 0.000 description 1
• 239000007922 nasal spray Substances 0.000 description 1
• 210000000822 natural killer cell Anatomy 0.000 description 1
• 239000006199 nebulizer Substances 0.000 description 1
• 230000007935 neutral effect Effects 0.000 description 1
• 235000001968 nicotinic acid Nutrition 0.000 description 1
• 239000011664 nicotinic acid Substances 0.000 description 1
• 229910052757 nitrogen Inorganic materials 0.000 description 1
• QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 description 1
• 235000015097 nutrients Nutrition 0.000 description 1
• 239000003921 oil Substances 0.000 description 1
• 235000019198 oils Nutrition 0.000 description 1
• ZQPPMHVWECSIRJ-KTKRTIGZSA-N oleic acid Chemical compound CCCCCCCC\C=C/CCCCCCCC(O)=O ZQPPMHVWECSIRJ-KTKRTIGZSA-N 0.000 description 1
• 229920001542 oligosaccharide Polymers 0.000 description 1
• 239000004006 olive oil Substances 0.000 description 1
• 235000008390 olive oil Nutrition 0.000 description 1
• 238000005457 optimization Methods 0.000 description 1
• 150000007524 organic acids Chemical class 0.000 description 1
• 235000005985 organic acids Nutrition 0.000 description 1
• 150000007530 organic bases Chemical class 0.000 description 1
• 229960003104 ornithine Drugs 0.000 description 1
• 239000012188 paraffin wax Substances 0.000 description 1
• 230000007170 pathology Effects 0.000 description 1
• 229960001412 pentobarbital Drugs 0.000 description 1
• 239000000137 peptide hydrolase inhibitor Substances 0.000 description 1
• 102000013415 peroxidase activity proteins Human genes 0.000 description 1
• 108040007629 peroxidase activity proteins Proteins 0.000 description 1
• JRKICGRDRMAZLK-UHFFFAOYSA-L peroxydisulfate Chemical compound [O-]S(=O)(=O)OOS([O-])(=O)=O JRKICGRDRMAZLK-UHFFFAOYSA-L 0.000 description 1
• 239000000546 pharmaceutical excipient Substances 0.000 description 1
• 239000000825 pharmaceutical preparation Substances 0.000 description 1
• 235000021317 phosphate Nutrition 0.000 description 1
• 239000002953 phosphate buffered saline Substances 0.000 description 1
• 150000008103 phosphatidic acids Chemical class 0.000 description 1
• WTJKGGKOPKCXLL-RRHRGVEJSA-N phosphatidylcholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCCCCCCC=CCCCCCCCC WTJKGGKOPKCXLL-RRHRGVEJSA-N 0.000 description 1
• 150000008105 phosphatidylcholines Chemical class 0.000 description 1
• 150000008104 phosphatidylethanolamines Chemical class 0.000 description 1
• 150000003905 phosphatidylinositols Chemical class 0.000 description 1
• 150000003013 phosphoric acid derivatives Chemical class 0.000 description 1
• 230000026731 phosphorylation Effects 0.000 description 1
• 238000006366 phosphorylation reaction Methods 0.000 description 1
• 230000006461 physiological response Effects 0.000 description 1
• 229940075930 picrate Drugs 0.000 description 1
• OXNIZHLAWKMVMX-UHFFFAOYSA-M picrate anion Chemical compound [O-]C1=C([N+]([O-])=O)C=C([N+]([O-])=O)C=C1[N+]([O-])=O OXNIZHLAWKMVMX-UHFFFAOYSA-M 0.000 description 1
• IUGYQRQAERSCNH-UHFFFAOYSA-M pivalate Chemical compound CC(C)(C)C([O-])=O IUGYQRQAERSCNH-UHFFFAOYSA-M 0.000 description 1
• 229950010765 pivalate Drugs 0.000 description 1
• 239000013612 plasmid Substances 0.000 description 1
• 210000004224 pleura Anatomy 0.000 description 1
• 231100000374 pneumotoxicity Toxicity 0.000 description 1
• 229920000058 polyacrylate Polymers 0.000 description 1
• 229920001281 polyalkylene Polymers 0.000 description 1
• 229920000573 polyethylene Polymers 0.000 description 1
• 208000005987 polymyositis Diseases 0.000 description 1
• 208000015768 polyposis Diseases 0.000 description 1
• 229920002451 polyvinyl alcohol Polymers 0.000 description 1
• 235000019422 polyvinyl alcohol Nutrition 0.000 description 1
• 159000000001 potassium salts Chemical class 0.000 description 1
• 235000010241 potassium sorbate Nutrition 0.000 description 1
• 239000004302 potassium sorbate Substances 0.000 description 1
• 229940069338 potassium sorbate Drugs 0.000 description 1
• 239000002244 precipitate Substances 0.000 description 1
• 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 1
• 230000000770 proinflammatory effect Effects 0.000 description 1
• 230000002062 proliferating effect Effects 0.000 description 1
• 125000001500 prolyl group Chemical group [H]N1C([H])(C(=O)[*])C([H])([H])C([H])([H])C1([H])[H] 0.000 description 1
• 230000000069 prophylactic effect Effects 0.000 description 1
• 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 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
• 229950008679 protamine sulfate Drugs 0.000 description 1
• 238000002731 protein assay Methods 0.000 description 1
• 230000004853 protein function Effects 0.000 description 1
• 230000009145 protein modification Effects 0.000 description 1
• 201000001474 proteinuria Diseases 0.000 description 1
• 230000006337 proteolytic cleavage Effects 0.000 description 1
• 238000009613 pulmonary function test Methods 0.000 description 1
• 230000007047 pulmonary toxicity Effects 0.000 description 1
• 238000002708 random mutagenesis Methods 0.000 description 1
• ZAHRKKWIAAJSAO-UHFFFAOYSA-N rapamycin Natural products COCC(O)C(=C/C(C)C(=O)CC(OC(=O)C1CCCCN1C(=O)C(=O)C2(O)OC(CC(OC)C(=CC=CC=CC(C)CC(C)C(=O)C)C)CCC2C)C(C)CC3CCC(O)C(C3)OC)C ZAHRKKWIAAJSAO-UHFFFAOYSA-N 0.000 description 1
• 239000011541 reaction mixture Substances 0.000 description 1
• 230000009257 reactivity Effects 0.000 description 1
• 230000007115 recruitment Effects 0.000 description 1
• 238000005932 reductive alkylation reaction Methods 0.000 description 1
• 201000002793 renal fibrosis Diseases 0.000 description 1
• 230000008439 repair process Effects 0.000 description 1
• 230000002441 reversible effect Effects 0.000 description 1
• 238000011808 rodent model Methods 0.000 description 1
• VGGUKFAVHPGNBF-UHFFFAOYSA-N s-ethyl 2,2,2-trifluoroethanethioate Chemical compound CCSC(=O)C(F)(F)F VGGUKFAVHPGNBF-UHFFFAOYSA-N 0.000 description 1
• 235000019515 salmon Nutrition 0.000 description 1
• 229920006395 saturated elastomer Polymers 0.000 description 1
• 230000028327 secretion Effects 0.000 description 1
• 150000003355 serines Chemical class 0.000 description 1
• 229910052814 silicon oxide Inorganic materials 0.000 description 1
• 229960002930 sirolimus Drugs 0.000 description 1
• QFJCIRLUMZQUOT-HPLJOQBZSA-N sirolimus Chemical compound C1C[C@@H](O)[C@H](OC)C[C@@H]1C[C@@H](C)[C@H]1OC(=O)[C@@H]2CCCCN2C(=O)C(=O)[C@](O)(O2)[C@H](C)CC[C@H]2C[C@H](OC)/C(C)=C/C=C/C=C/[C@@H](C)C[C@@H](C)C(=O)[C@H](OC)[C@H](O)/C(C)=C/[C@@H](C)C(=O)C1 QFJCIRLUMZQUOT-HPLJOQBZSA-N 0.000 description 1
• 238000002741 site-directed mutagenesis Methods 0.000 description 1
• 208000017520 skin disease Diseases 0.000 description 1
• 210000002460 smooth muscle Anatomy 0.000 description 1
• 210000000329 smooth muscle myocyte Anatomy 0.000 description 1
• AWUCVROLDVIAJX-GSVOUGTGSA-N sn-glycerol 3-phosphate Chemical compound OC[C@@H](O)COP(O)(O)=O AWUCVROLDVIAJX-GSVOUGTGSA-N 0.000 description 1
• 229910052708 sodium Inorganic materials 0.000 description 1
• 239000011734 sodium Substances 0.000 description 1
• 235000019812 sodium carboxymethyl cellulose Nutrition 0.000 description 1
• 229920001027 sodium carboxymethylcellulose Polymers 0.000 description 1
• FQENQNTWSFEDLI-UHFFFAOYSA-J sodium diphosphate Chemical compound [Na+].[Na+].[Na+].[Na+].[O-]P([O-])(=O)OP([O-])([O-])=O FQENQNTWSFEDLI-UHFFFAOYSA-J 0.000 description 1
• 229940048086 sodium pyrophosphate Drugs 0.000 description 1
• 239000007790 solid phase Substances 0.000 description 1
• 230000003381 solubilizing effect Effects 0.000 description 1
• 239000002195 soluble material Substances 0.000 description 1
• 235000010199 sorbic acid Nutrition 0.000 description 1
• 239000004334 sorbic acid Substances 0.000 description 1
• 229940075582 sorbic acid Drugs 0.000 description 1
• 230000002269 spontaneous effect Effects 0.000 description 1
• 239000007858 starting material Substances 0.000 description 1
• 238000007619 statistical method Methods 0.000 description 1
• 150000003431 steroids Chemical class 0.000 description 1
• 230000000638 stimulation Effects 0.000 description 1
• 238000007920 subcutaneous administration Methods 0.000 description 1
• KDYFGRWQOYBRFD-UHFFFAOYSA-L succinate(2-) Chemical compound [O-]C(=O)CCC([O-])=O KDYFGRWQOYBRFD-UHFFFAOYSA-L 0.000 description 1
• 229960001940 sulfasalazine Drugs 0.000 description 1
• NCEXYHBECQHGNR-UHFFFAOYSA-N sulfasalazine Natural products C1=C(O)C(C(=O)O)=CC(N=NC=2C=CC(=CC=2)S(=O)(=O)NC=2N=CC=CC=2)=C1 NCEXYHBECQHGNR-UHFFFAOYSA-N 0.000 description 1
• 239000003765 sweetening agent Substances 0.000 description 1
• 230000008961 swelling Effects 0.000 description 1
• 229960001967 tacrolimus Drugs 0.000 description 1
• 230000008685 targeting Effects 0.000 description 1
• 229940095064 tartrate Drugs 0.000 description 1
• 125000005931 tert-butyloxycarbonyl group Chemical group [H]C([H])([H])C(OC(*)=O)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
• 235000019818 tetrasodium diphosphate Nutrition 0.000 description 1
• 239000001577 tetrasodium phosphonato phosphate Substances 0.000 description 1
• VUYXVWGKCKTUMF-UHFFFAOYSA-N tetratriacontaethylene glycol monomethyl ether Chemical compound COCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCO VUYXVWGKCKTUMF-UHFFFAOYSA-N 0.000 description 1
• 229960000278 theophylline Drugs 0.000 description 1
• 238000002560 therapeutic procedure Methods 0.000 description 1
• 239000002562 thickening agent Substances 0.000 description 1
• RSPCKAHMRANGJZ-UHFFFAOYSA-N thiohydroxylamine Chemical compound SN RSPCKAHMRANGJZ-UHFFFAOYSA-N 0.000 description 1
• 210000000115 thoracic cavity Anatomy 0.000 description 1
• 229960004072 thrombin Drugs 0.000 description 1
• 229940104230 thymidine Drugs 0.000 description 1
• 210000002303 tibia Anatomy 0.000 description 1
• 238000012090 tissue culture technique Methods 0.000 description 1
• JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 1
• 238000011200 topical administration Methods 0.000 description 1
• 239000012049 topical pharmaceutical composition Substances 0.000 description 1
• 238000013518 transcription Methods 0.000 description 1
• 230000035897 transcription Effects 0.000 description 1
• 238000013519 translation Methods 0.000 description 1
• 230000000472 traumatic effect Effects 0.000 description 1
• 150000003626 triacylglycerols Chemical class 0.000 description 1
• 238000007492 two-way ANOVA Methods 0.000 description 1
• ZDPHROOEEOARMN-UHFFFAOYSA-N undecanoic acid Chemical compound CCCCCCCCCCC(O)=O ZDPHROOEEOARMN-UHFFFAOYSA-N 0.000 description 1
• 238000005292 vacuum distillation Methods 0.000 description 1
• 239000013598 vector Substances 0.000 description 1
• 235000013311 vegetables Nutrition 0.000 description 1
• 239000001993 wax Substances 0.000 description 1
• 238000005303 weighing Methods 0.000 description 1
• 239000000080 wetting agent Substances 0.000 description 1
• 230000029663 wound healing Effects 0.000 description 1
• 238000002424 x-ray crystallography Methods 0.000 description 1
• 239000000230 xanthan gum Substances 0.000 description 1
• 229920001285 xanthan gum Polymers 0.000 description 1
• 235000010493 xanthan gum Nutrition 0.000 description 1
• 229940082509 xanthan gum Drugs 0.000 description 1
• BPICBUSOMSTKRF-UHFFFAOYSA-N xylazine Chemical compound CC1=CC=CC(C)=C1NC1=NCCCS1 BPICBUSOMSTKRF-UHFFFAOYSA-N 0.000 description 1
• 229960001600 xylazine Drugs 0.000 description 1
• 150000003751 zinc Chemical class 0.000 description 1
• 229910052725 zinc Inorganic materials 0.000 description 1
• 239000011701 zinc Substances 0.000 description 1