CA2289119C - Methods for treating inflammation and inflammatory diseases using padprt inhibitors - Google Patents

Info

Publication number

CA2289119C

CA2289119C CA2289119A CA2289119A CA2289119C CA 2289119 C CA2289119 C CA 2289119C CA 2289119 A CA2289119 A CA 2289119A CA 2289119 A CA2289119 A CA 2289119A CA 2289119 C CA2289119 C CA 2289119C

Authority

CA

Canada

Prior art keywords

lps

amino

compound

cells

induced

Prior art date

1997-05-13

Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)

Expired - Fee Related

Links

• Espacenet
• Global Dossier
• CIPO
• Discuss

• 230000004054 inflammatory process Effects 0.000 title abstract description 47
• 206010061218 Inflammation Diseases 0.000 title abstract description 38
• 238000000034 method Methods 0.000 title abstract description 37
• 208000027866 inflammatory disease Diseases 0.000 title abstract description 14
• 239000003112 inhibitor Substances 0.000 title description 24
• 150000001875 compounds Chemical class 0.000 claims abstract description 86
• 241001465754 Metazoa Species 0.000 claims abstract description 51
• 230000002401 inhibitory effect Effects 0.000 claims abstract description 45
• 239000002158 endotoxin Substances 0.000 claims description 135
• 229920006008 lipopolysaccharide Polymers 0.000 claims description 127
• 238000004519 manufacturing process Methods 0.000 claims description 54
• -1 hydroxy, amino Chemical group 0.000 claims description 32
• 125000003545 alkoxy group Chemical group 0.000 claims description 23
• 239000001257 hydrogen Substances 0.000 claims description 18
• 229910052739 hydrogen Inorganic materials 0.000 claims description 18
• 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 16
• 230000001580 bacterial effect Effects 0.000 claims description 16
• 239000000203 mixture Substances 0.000 claims description 16
• 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 16
• 150000002431 hydrogen Chemical class 0.000 claims description 14
• 125000000018 nitroso group Chemical group N(=O)* 0.000 claims description 13
• 150000003839 salts Chemical class 0.000 claims description 10
• 208000024891 symptom Diseases 0.000 claims description 10
• 125000001424 substituent group Chemical group 0.000 claims description 9
• 239000003814 drug Substances 0.000 claims description 8
• 239000008194 pharmaceutical composition Substances 0.000 claims description 6
• 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 5
• 239000000546 pharmaceutical excipient Substances 0.000 claims description 5
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 5
• 125000006272 (C3-C7) cycloalkyl group Chemical group 0.000 claims description 4
• UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 4
• 229910052736 halogen Inorganic materials 0.000 claims description 4
• 150000002367 halogens Chemical class 0.000 claims description 4
• 229940124531 pharmaceutical excipient Drugs 0.000 claims description 4
• 241000124008 Mammalia Species 0.000 abstract description 22
• MWUXSHHQAYIFBG-UHFFFAOYSA-N Nitric oxide Chemical compound O=[N] MWUXSHHQAYIFBG-UHFFFAOYSA-N 0.000 description 133
• WWRAFPGUBABZSD-UHFFFAOYSA-N 6-amino-5-iodochromen-2-one Chemical compound O1C(=O)C=CC2=C(I)C(N)=CC=C21 WWRAFPGUBABZSD-UHFFFAOYSA-N 0.000 description 78
• 210000004027 cell Anatomy 0.000 description 74
• QRXWMOHMRWLFEY-UHFFFAOYSA-N isoniazide Chemical compound NNC(=O)C1=CC=NC=C1 QRXWMOHMRWLFEY-UHFFFAOYSA-N 0.000 description 73
• 230000000694 effects Effects 0.000 description 64
• 230000006698 induction Effects 0.000 description 39
• 102000043136 MAP kinase family Human genes 0.000 description 38
• 108091054455 MAP kinase family Proteins 0.000 description 37
• 230000004913 activation Effects 0.000 description 32
• 206010003246 arthritis Diseases 0.000 description 31
• 230000005764 inhibitory process Effects 0.000 description 31
• 210000002540 macrophage Anatomy 0.000 description 30
• CMFNMSMUKZHDEY-UHFFFAOYSA-N peroxynitrous acid Chemical compound OON=O CMFNMSMUKZHDEY-UHFFFAOYSA-N 0.000 description 28
• 230000014509 gene expression Effects 0.000 description 25
• 108090000623 proteins and genes Proteins 0.000 description 24
• 108010057466 NF-kappa B Proteins 0.000 description 23
• 102000003945 NF-kappa B Human genes 0.000 description 23
• 241000699670 Mus sp. Species 0.000 description 22
• 210000002683 foot Anatomy 0.000 description 22
• 108010021487 Nitric Oxide Synthase Proteins 0.000 description 20
• 230000001404 mediated effect Effects 0.000 description 20
• 108060008682 Tumor Necrosis Factor Proteins 0.000 description 19
• 108020004414 DNA Proteins 0.000 description 18
• ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 18
• 102000012338 Poly(ADP-ribose) Polymerases Human genes 0.000 description 18
• 108010061844 Poly(ADP-ribose) Polymerases Proteins 0.000 description 18
• 210000002889 endothelial cell Anatomy 0.000 description 18
• 102000004169 proteins and genes Human genes 0.000 description 18
• 102000008299 Nitric Oxide Synthase Human genes 0.000 description 17
• IOVCWXUNBOPUCH-UHFFFAOYSA-M Nitrite anion Chemical compound [O-]N=O IOVCWXUNBOPUCH-UHFFFAOYSA-M 0.000 description 17
• 239000002502 liposome Substances 0.000 description 17
• DFPAKSUCGFBDDF-UHFFFAOYSA-N Nicotinamide Chemical compound NC(=O)C1=CC=CN=C1 DFPAKSUCGFBDDF-UHFFFAOYSA-N 0.000 description 16
• 229920000776 Poly(Adenosine diphosphate-ribose) polymerase Polymers 0.000 description 16
• 241000700159 Rattus Species 0.000 description 16
• 241000283690 Bos taurus Species 0.000 description 15
• 208000009386 Experimental Arthritis Diseases 0.000 description 15
• 239000005089 Luciferase Substances 0.000 description 15
• 102000000852 Tumor Necrosis Factor-alpha Human genes 0.000 description 15
• 230000027455 binding Effects 0.000 description 15
• 201000010099 disease Diseases 0.000 description 15
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 15
• 230000004048 modification Effects 0.000 description 15
• 238000012986 modification Methods 0.000 description 15
• 230000002829 reductive effect Effects 0.000 description 15
• 230000003110 anti-inflammatory effect Effects 0.000 description 14
• 230000002917 arthritic effect Effects 0.000 description 14
• 230000001413 cellular effect Effects 0.000 description 14
• 230000009483 enzymatic pathway Effects 0.000 description 14
• 230000012010 growth Effects 0.000 description 14
• 230000008569 process Effects 0.000 description 14
• 230000015572 biosynthetic process Effects 0.000 description 13
• 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 13
• 230000004044 response Effects 0.000 description 13
• 239000003981 vehicle Substances 0.000 description 13
• 102000003960 Ligases Human genes 0.000 description 12
• 108090000364 Ligases Proteins 0.000 description 12
• 108060001084 Luciferase Proteins 0.000 description 12
• 229920001525 carrageenan Polymers 0.000 description 12
• 238000011161 development Methods 0.000 description 12
• 230000018109 developmental process Effects 0.000 description 12
• 125000005843 halogen group Chemical group 0.000 description 12
• 238000000338 in vitro Methods 0.000 description 12
• 238000001727 in vivo Methods 0.000 description 12
• 230000002757 inflammatory effect Effects 0.000 description 12
• 230000037361 pathway Effects 0.000 description 12
• 102000004127 Cytokines Human genes 0.000 description 11
• 108090000695 Cytokines Proteins 0.000 description 11
• 102000004232 Mitogen-Activated Protein Kinase Kinases Human genes 0.000 description 11
• 206010030113 Oedema Diseases 0.000 description 11
• 230000033228 biological regulation Effects 0.000 description 11
• 201000011510 cancer Diseases 0.000 description 11
• 239000000679 carrageenan Substances 0.000 description 11
• 229940113118 carrageenan Drugs 0.000 description 11
• 239000003795 chemical substances by application Substances 0.000 description 11
• 239000000499 gel Substances 0.000 description 11
• 238000002347 injection Methods 0.000 description 11
• 239000007924 injection Substances 0.000 description 11
• 239000000047 product Substances 0.000 description 11
• 108090000174 Interleukin-10 Proteins 0.000 description 10
• 102000003814 Interleukin-10 Human genes 0.000 description 10
• 108090001005 Interleukin-6 Proteins 0.000 description 10
• 102000004889 Interleukin-6 Human genes 0.000 description 10
• 108090000744 Mitogen-Activated Protein Kinase Kinases Proteins 0.000 description 10
• 206010028980 Neoplasm Diseases 0.000 description 10
• 102000001253 Protein Kinase Human genes 0.000 description 10
• 230000009471 action Effects 0.000 description 10
• 235000010418 carrageenan Nutrition 0.000 description 10
• 125000002887 hydroxy group Chemical group [H]O* 0.000 description 10
• 229940076144 interleukin-10 Drugs 0.000 description 10
• 229940100601 interleukin-6 Drugs 0.000 description 10
• 239000003446 ligand Substances 0.000 description 10
• 230000003211 malignant effect Effects 0.000 description 10
• YBYRMVIVWMBXKQ-UHFFFAOYSA-N phenylmethanesulfonyl fluoride Chemical compound FS(=O)(=O)CC1=CC=CC=C1 YBYRMVIVWMBXKQ-UHFFFAOYSA-N 0.000 description 10
• 108060006633 protein kinase Proteins 0.000 description 10
• UHVMMEOXYDMDKI-JKYCWFKZSA-L zinc;1-(5-cyanopyridin-2-yl)-3-[(1s,2s)-2-(6-fluoro-2-hydroxy-3-propanoylphenyl)cyclopropyl]urea;diacetate Chemical compound [Zn+2].CC([O-])=O.CC([O-])=O.CCC(=O)C1=CC=C(F)C([C@H]2[C@H](C2)NC(=O)NC=2N=CC(=CC=2)C#N)=C1O UHVMMEOXYDMDKI-JKYCWFKZSA-L 0.000 description 10
• 102000053602 DNA Human genes 0.000 description 9
• 241001529936 Murinae Species 0.000 description 9
• 125000000217 alkyl group Chemical group 0.000 description 9
• 230000004075 alteration Effects 0.000 description 9
• 230000005796 circulatory shock Effects 0.000 description 9
• 238000005259 measurement Methods 0.000 description 9
• 108020004999 messenger RNA Proteins 0.000 description 9
• 230000035939 shock Effects 0.000 description 9
• 239000000243 solution Substances 0.000 description 9
• 230000001629 suppression Effects 0.000 description 9
• 230000009466 transformation Effects 0.000 description 9
• 108091000080 Phosphotransferase Proteins 0.000 description 8
• 238000013459 approach Methods 0.000 description 8
• 239000000872 buffer Substances 0.000 description 8
• 238000006243 chemical reaction Methods 0.000 description 8
• 235000012000 cholesterol Nutrition 0.000 description 8
• 230000001965 increasing effect Effects 0.000 description 8
• 239000012528 membrane Substances 0.000 description 8
• 229960003966 nicotinamide Drugs 0.000 description 8
• 235000005152 nicotinamide Nutrition 0.000 description 8
• 239000011570 nicotinamide Substances 0.000 description 8
• 150000002828 nitro derivatives Chemical class 0.000 description 8
• 102000020233 phosphotransferase Human genes 0.000 description 8
• 230000000770 proinflammatory effect Effects 0.000 description 8
• 150000003180 prostaglandins Chemical class 0.000 description 8
• 238000003786 synthesis reaction Methods 0.000 description 8
• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 8
• KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 7
• 108010029485 Protein Isoforms Proteins 0.000 description 7
• 102000001708 Protein Isoforms Human genes 0.000 description 7
• 229940107161 cholesterol Drugs 0.000 description 7
• 238000002474 experimental method Methods 0.000 description 7
• 230000028709 inflammatory response Effects 0.000 description 7
• 230000005937 nuclear translocation Effects 0.000 description 7
• 150000003254 radicals Chemical class 0.000 description 7
• 230000004083 survival effect Effects 0.000 description 7
• 238000001262 western blot Methods 0.000 description 7
• 125000006552 (C3-C8) cycloalkyl group Chemical group 0.000 description 6
• QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 6
• 241000282414 Homo sapiens Species 0.000 description 6
• 229910002651 NO3 Inorganic materials 0.000 description 6
• NHNBFGGVMKEFGY-UHFFFAOYSA-N Nitrate Chemical compound [O-][N+]([O-])=O NHNBFGGVMKEFGY-UHFFFAOYSA-N 0.000 description 6
• 102100038280 Prostaglandin G/H synthase 2 Human genes 0.000 description 6
• 102000004005 Prostaglandin-endoperoxide synthases Human genes 0.000 description 6
• 108090000459 Prostaglandin-endoperoxide synthases Proteins 0.000 description 6
• FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 6
• 238000003556 assay Methods 0.000 description 6
• 208000037976 chronic inflammation Diseases 0.000 description 6
• 230000006020 chronic inflammation Effects 0.000 description 6
• 230000003013 cytotoxicity Effects 0.000 description 6
• 231100000135 cytotoxicity Toxicity 0.000 description 6
• 230000004069 differentiation Effects 0.000 description 6
• DEFVIWRASFVYLL-UHFFFAOYSA-N ethylene glycol bis(2-aminoethyl)tetraacetic acid Chemical compound OC(=O)CN(CC(O)=O)CCOCCOCCN(CC(O)=O)CC(O)=O DEFVIWRASFVYLL-UHFFFAOYSA-N 0.000 description 6
• 150000002632 lipids Chemical class 0.000 description 6
• 210000004962 mammalian cell Anatomy 0.000 description 6
• 230000007246 mechanism Effects 0.000 description 6
• 210000004379 membrane Anatomy 0.000 description 6
• 239000003226 mitogen Substances 0.000 description 6
• 239000007800 oxidant agent Substances 0.000 description 6
• 230000001590 oxidative effect Effects 0.000 description 6
• 230000003248 secreting effect Effects 0.000 description 6
• 210000002966 serum Anatomy 0.000 description 6
• 230000019491 signal transduction Effects 0.000 description 6
• PFNFFQXMRSDOHW-UHFFFAOYSA-N spermine Chemical compound NCCCNCCCCNCCCN PFNFFQXMRSDOHW-UHFFFAOYSA-N 0.000 description 6
• 230000035882 stress Effects 0.000 description 6
• DGVVWUTYPXICAM-UHFFFAOYSA-N β‐Mercaptoethanol Chemical compound OCCS DGVVWUTYPXICAM-UHFFFAOYSA-N 0.000 description 6
• 208000005623 Carcinogenesis Diseases 0.000 description 5
• 102000008186 Collagen Human genes 0.000 description 5
• 108010035532 Collagen Proteins 0.000 description 5
• 102000004190 Enzymes Human genes 0.000 description 5
• 108090000790 Enzymes Proteins 0.000 description 5
• 108010074328 Interferon-gamma Proteins 0.000 description 5
• 102000008070 Interferon-gamma Human genes 0.000 description 5
• 102000000589 Interleukin-1 Human genes 0.000 description 5
• 108050003267 Prostaglandin G/H synthase 2 Proteins 0.000 description 5
• 206010040070 Septic Shock Diseases 0.000 description 5
• 230000017531 blood circulation Effects 0.000 description 5
• 230000036952 cancer formation Effects 0.000 description 5
• 230000000711 cancerogenic effect Effects 0.000 description 5
• 231100000504 carcinogenesis Toxicity 0.000 description 5
• 231100000315 carcinogenic Toxicity 0.000 description 5
• 229920001436 collagen Polymers 0.000 description 5
• 230000006378 damage Effects 0.000 description 5
• 230000001419 dependent effect Effects 0.000 description 5
• 229940079593 drug Drugs 0.000 description 5
• 210000003038 endothelium Anatomy 0.000 description 5
• 229940088598 enzyme Drugs 0.000 description 5
• 230000001939 inductive effect Effects 0.000 description 5
• 229960003130 interferon gamma Drugs 0.000 description 5
• 239000007788 liquid Substances 0.000 description 5
• 229940094443 oxytocics prostaglandins Drugs 0.000 description 5
• 239000012660 pharmacological inhibitor Substances 0.000 description 5
• 230000003389 potentiating effect Effects 0.000 description 5
• 230000009467 reduction Effects 0.000 description 5
• 238000012552 review Methods 0.000 description 5
• 238000002415 sodium dodecyl sulfate polyacrylamide gel electrophoresis Methods 0.000 description 5
• 230000000638 stimulation Effects 0.000 description 5
• 230000005730 ADP ribosylation Effects 0.000 description 4
• 102000002260 Alkaline Phosphatase Human genes 0.000 description 4
• 108020004774 Alkaline Phosphatase Proteins 0.000 description 4
• HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 4
• 230000033616 DNA repair Effects 0.000 description 4
• 239000006144 Dulbecco’s modified Eagle's medium Substances 0.000 description 4
• BAWFJGJZGIEFAR-NNYOXOHSSA-O NAD(+) Chemical compound NC(=O)C1=CC=C[N+]([C@H]2[C@@H]([C@H](O)[C@@H](COP(O)(=O)OP(O)(=O)OC[C@@H]3[C@H]([C@@H](O)[C@@H](O3)N3C4=NC=NC(N)=C4N=C3)O)O2)O)=C1 BAWFJGJZGIEFAR-NNYOXOHSSA-O 0.000 description 4
• 108010025020 Nerve Growth Factor Proteins 0.000 description 4
• 102000015336 Nerve Growth Factor Human genes 0.000 description 4
• NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 4
• 206010063837 Reperfusion injury Diseases 0.000 description 4
• OUUQCZGPVNCOIJ-UHFFFAOYSA-M Superoxide Chemical compound [O-][O] OUUQCZGPVNCOIJ-UHFFFAOYSA-M 0.000 description 4
• 102100040247 Tumor necrosis factor Human genes 0.000 description 4
• 102000009270 Tumour necrosis factor alpha Human genes 0.000 description 4
• 108050000101 Tumour necrosis factor alpha Proteins 0.000 description 4
• 208000027418 Wounds and injury Diseases 0.000 description 4
• 229940124599 anti-inflammatory drug Drugs 0.000 description 4
• 210000004413 cardiac myocyte Anatomy 0.000 description 4
• 238000004113 cell culture Methods 0.000 description 4
• 239000012228 culture supernatant Substances 0.000 description 4
• 125000000753 cycloalkyl group Chemical group 0.000 description 4
• 239000000284 extract Substances 0.000 description 4
• 238000001125 extrusion Methods 0.000 description 4
• 230000006870 function Effects 0.000 description 4
• 238000011534 incubation Methods 0.000 description 4
• 208000015181 infectious disease Diseases 0.000 description 4
• 208000014674 injury Diseases 0.000 description 4
• 125000002346 iodo group Chemical group I* 0.000 description 4
• 210000000265 leukocyte Anatomy 0.000 description 4
• 210000004072 lung Anatomy 0.000 description 4
• 230000006540 mitochondrial respiration Effects 0.000 description 4
• 229940053128 nerve growth factor Drugs 0.000 description 4
• 230000007310 pathophysiology Effects 0.000 description 4
• 230000000144 pharmacologic effect Effects 0.000 description 4
• 239000011780 sodium chloride Substances 0.000 description 4
• 230000001988 toxicity Effects 0.000 description 4
• 231100000419 toxicity Toxicity 0.000 description 4
• 238000001890 transfection Methods 0.000 description 4
• 229940121358 tyrosine kinase inhibitor Drugs 0.000 description 4
• 239000005483 tyrosine kinase inhibitor Substances 0.000 description 4
• 238000011144 upstream manufacturing Methods 0.000 description 4
• DZUXGQBLFALXCR-UHFFFAOYSA-N (+)-(9alpha,11alpha,13E,15S)-9,11,15-trihydroxyprost-13-en-1-oic acid Natural products CCCCCC(O)C=CC1C(O)CC(O)C1CCCCCCC(O)=O DZUXGQBLFALXCR-UHFFFAOYSA-N 0.000 description 3
• 108091032973 (ribonucleotides)n+m Proteins 0.000 description 3
• RNAMYOYQYRYFQY-UHFFFAOYSA-N 2-(4,4-difluoropiperidin-1-yl)-6-methoxy-n-(1-propan-2-ylpiperidin-4-yl)-7-(3-pyrrolidin-1-ylpropoxy)quinazolin-4-amine Chemical compound N1=C(N2CCC(F)(F)CC2)N=C2C=C(OCCCN3CCCC3)C(OC)=CC2=C1NC1CCN(C(C)C)CC1 RNAMYOYQYRYFQY-UHFFFAOYSA-N 0.000 description 3
• JKMHFZQWWAIEOD-UHFFFAOYSA-N 2-[4-(2-hydroxyethyl)piperazin-1-yl]ethanesulfonic acid Chemical compound OCC[NH+]1CCN(CCS([O-])(=O)=O)CC1 JKMHFZQWWAIEOD-UHFFFAOYSA-N 0.000 description 3
• GSCPDZHWVNUUFI-UHFFFAOYSA-N 3-aminobenzamide Chemical compound NC(=O)C1=CC=CC(N)=C1 GSCPDZHWVNUUFI-UHFFFAOYSA-N 0.000 description 3
• LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 3
• WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 3
• 102100029974 GTPase HRas Human genes 0.000 description 3
• 108700039691 Genetic Promoter Regions Proteins 0.000 description 3
• PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 3
• 101000584633 Homo sapiens GTPase HRas Proteins 0.000 description 3
• 108010002352 Interleukin-1 Proteins 0.000 description 3
• GDBQQVLCIARPGH-UHFFFAOYSA-N Leupeptin Natural products CC(C)CC(NC(C)=O)C(=O)NC(CC(C)C)C(=O)NC(C=O)CCCN=C(N)N GDBQQVLCIARPGH-UHFFFAOYSA-N 0.000 description 3
• 108060006687 MAP kinase kinase kinase Proteins 0.000 description 3
• 241000283973 Oryctolagus cuniculus Species 0.000 description 3
• DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
• 102000004022 Protein-Tyrosine Kinases Human genes 0.000 description 3
• 108090000412 Protein-Tyrosine Kinases Proteins 0.000 description 3
• 241000700157 Rattus norvegicus Species 0.000 description 3
• 208000025747 Rheumatic disease Diseases 0.000 description 3
• 102000040945 Transcription factor Human genes 0.000 description 3
• 108091023040 Transcription factor Proteins 0.000 description 3
• 230000005779 cell damage Effects 0.000 description 3
• 230000024245 cell differentiation Effects 0.000 description 3
• 230000036755 cellular response Effects 0.000 description 3
• 238000011278 co-treatment Methods 0.000 description 3
• RNPXCFINMKSQPQ-UHFFFAOYSA-N dicetyl hydrogen phosphate Chemical compound CCCCCCCCCCCCCCCCOP(O)(=O)OCCCCCCCCCCCCCCCC RNPXCFINMKSQPQ-UHFFFAOYSA-N 0.000 description 3
• 229940093541 dicetylphosphate Drugs 0.000 description 3
• 231100000673 dose–response relationship Toxicity 0.000 description 3
• 238000011156 evaluation Methods 0.000 description 3
• 230000007760 free radical scavenging Effects 0.000 description 3
• 238000004108 freeze drying Methods 0.000 description 3
• 239000003102 growth factor Substances 0.000 description 3
• 210000000987 immune system Anatomy 0.000 description 3
• 230000003053 immunization Effects 0.000 description 3
• 238000002649 immunization Methods 0.000 description 3
• 230000003308 immunostimulating effect Effects 0.000 description 3
• 230000006872 improvement Effects 0.000 description 3
• 230000002779 inactivation Effects 0.000 description 3
• 230000004968 inflammatory condition Effects 0.000 description 3
• 210000003127 knee Anatomy 0.000 description 3
• 231100000518 lethal Toxicity 0.000 description 3
• 230000001665 lethal effect Effects 0.000 description 3
• GDBQQVLCIARPGH-ULQDDVLXSA-N leupeptin Chemical compound CC(C)C[C@H](NC(C)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@H](C=O)CCCN=C(N)N GDBQQVLCIARPGH-ULQDDVLXSA-N 0.000 description 3
• 108010052968 leupeptin Proteins 0.000 description 3
• 239000012139 lysis buffer Substances 0.000 description 3
• 239000002207 metabolite Substances 0.000 description 3
• 238000012261 overproduction Methods 0.000 description 3
• 230000008506 pathogenesis Effects 0.000 description 3
• 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 3
• 230000004983 pleiotropic effect Effects 0.000 description 3
• 230000002265 prevention Effects 0.000 description 3
• 210000000329 smooth muscle myocyte Anatomy 0.000 description 3
• 229940063675 spermine Drugs 0.000 description 3
• 230000002269 spontaneous effect Effects 0.000 description 3
• 239000000126 substance Substances 0.000 description 3
• 210000001179 synovial fluid Anatomy 0.000 description 3
• 230000009885 systemic effect Effects 0.000 description 3
• 230000001225 therapeutic effect Effects 0.000 description 3
• 238000002560 therapeutic procedure Methods 0.000 description 3
• 210000001519 tissue Anatomy 0.000 description 3
• 230000014616 translation Effects 0.000 description 3
• GIANIJCPTPUNBA-QMMMGPOBSA-N (2s)-3-(4-hydroxyphenyl)-2-nitramidopropanoic acid Chemical compound [O-][N+](=O)N[C@H](C(=O)O)CC1=CC=C(O)C=C1 GIANIJCPTPUNBA-QMMMGPOBSA-N 0.000 description 2
• MZOFCQQQCNRIBI-VMXHOPILSA-N (3s)-4-[[(2s)-1-[[(2s)-1-[[(1s)-1-carboxy-2-hydroxyethyl]amino]-4-methyl-1-oxopentan-2-yl]amino]-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-3-[[2-[[(2s)-2,6-diaminohexanoyl]amino]acetyl]amino]-4-oxobutanoic acid Chemical compound OC[C@@H](C(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCN=C(N)N)NC(=O)[C@H](CC(O)=O)NC(=O)CNC(=O)[C@@H](N)CCCCN MZOFCQQQCNRIBI-VMXHOPILSA-N 0.000 description 2
• HTSGKJQDMSTCGS-UHFFFAOYSA-N 1,4-bis(4-chlorophenyl)-2-(4-methylphenyl)sulfonylbutane-1,4-dione Chemical compound C1=CC(C)=CC=C1S(=O)(=O)C(C(=O)C=1C=CC(Cl)=CC=1)CC(=O)C1=CC=C(Cl)C=C1 HTSGKJQDMSTCGS-UHFFFAOYSA-N 0.000 description 2
• OZUBORKYZRYLSQ-UHFFFAOYSA-N 3-nitrosobenzamide Chemical compound NC(=O)C1=CC=CC(N=O)=C1 OZUBORKYZRYLSQ-UHFFFAOYSA-N 0.000 description 2
• PWJFNRJRHXWEPT-UHFFFAOYSA-N ADP ribose Natural products C1=NC=2C(N)=NC=NC=2N1C1OC(COP(O)(=O)OP(O)(=O)OCC(O)C(O)C(O)C=O)C(O)C1O PWJFNRJRHXWEPT-UHFFFAOYSA-N 0.000 description 2
• SRNWOUGRCWSEMX-KEOHHSTQSA-N ADP-beta-D-ribose Chemical compound C([C@H]1O[C@H]([C@@H]([C@@H]1O)O)N1C=2N=CN=C(C=2N=C1)N)OP(O)(=O)OP(O)(=O)OC[C@H]1O[C@@H](O)[C@H](O)[C@@H]1O SRNWOUGRCWSEMX-KEOHHSTQSA-N 0.000 description 2
• 108010039627 Aprotinin Proteins 0.000 description 2
• 239000004475 Arginine Substances 0.000 description 2
• CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 2
• IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
• KXDAEFPNCMNJSK-UHFFFAOYSA-N Benzamide Chemical compound NC(=O)C1=CC=CC=C1 KXDAEFPNCMNJSK-UHFFFAOYSA-N 0.000 description 2
• 150000004006 C-nitroso compounds Chemical class 0.000 description 2
• 239000004215 Carbon black (E152) Substances 0.000 description 2
• 108010077544 Chromatin Proteins 0.000 description 2
• 102000000503 Collagen Type II Human genes 0.000 description 2
• 108010041390 Collagen Type II Proteins 0.000 description 2
• 125000000824 D-ribofuranosyl group Chemical group [H]OC([H])([H])[C@@]1([H])OC([H])(*)[C@]([H])(O[H])[C@]1([H])O[H] 0.000 description 2
• 102000003915 DNA Topoisomerases Human genes 0.000 description 2
• 108090000323 DNA Topoisomerases Proteins 0.000 description 2
• 230000004568 DNA-binding Effects 0.000 description 2
• 238000008157 ELISA kit Methods 0.000 description 2
• 208000037487 Endotoxemia Diseases 0.000 description 2
• 241000588724 Escherichia coli Species 0.000 description 2
• 108010010803 Gelatin Proteins 0.000 description 2
• WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 2
• 108010033040 Histones Proteins 0.000 description 2
• 102000006947 Histones Human genes 0.000 description 2
• VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
• 102000004157 Hydrolases Human genes 0.000 description 2
• 108090000604 Hydrolases Proteins 0.000 description 2
• 108091054729 IRF family Proteins 0.000 description 2
• 208000004575 Infectious Arthritis Diseases 0.000 description 2
• 102000016854 Interferon Regulatory Factors Human genes 0.000 description 2
• 108010082786 Interleukin-1alpha Proteins 0.000 description 2
• AHLPHDHHMVZTML-BYPYZUCNSA-N L-Ornithine Chemical compound NCCC[C@H](N)C(O)=O AHLPHDHHMVZTML-BYPYZUCNSA-N 0.000 description 2
• RHGKLRLOHDJJDR-BYPYZUCNSA-N L-citrulline Chemical compound NC(=O)NCCC[C@H]([NH3+])C([O-])=O RHGKLRLOHDJJDR-BYPYZUCNSA-N 0.000 description 2
• OUYCCCASQSFEME-QMMMGPOBSA-N L-tyrosine Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-QMMMGPOBSA-N 0.000 description 2
• AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 2
• 241000699666 Mus <mouse, genus> Species 0.000 description 2
• 150000004008 N-nitroso compounds Chemical class 0.000 description 2
• 206010028851 Necrosis Diseases 0.000 description 2
• 102000011779 Nitric Oxide Synthase Type II Human genes 0.000 description 2
• 108010076864 Nitric Oxide Synthase Type II Proteins 0.000 description 2
• 239000000020 Nitrocellulose Substances 0.000 description 2
• 238000000636 Northern blotting Methods 0.000 description 2
• 101710163270 Nuclease Proteins 0.000 description 2
• ZQPPMHVWECSIRJ-UHFFFAOYSA-N Oleic acid Natural products CCCCCCCCC=CCCCCCCCC(O)=O ZQPPMHVWECSIRJ-UHFFFAOYSA-N 0.000 description 2
• 229910019142 PO4 Inorganic materials 0.000 description 2
• 208000037581 Persistent Infection Diseases 0.000 description 2
• 108091026813 Poly(ADPribose) Proteins 0.000 description 2
• 102000003923 Protein Kinase C Human genes 0.000 description 2
• 108090000315 Protein Kinase C Proteins 0.000 description 2
• 230000006819 RNA synthesis Effects 0.000 description 2
• 208000019155 Radiation injury Diseases 0.000 description 2
• 108700008625 Reporter Genes Proteins 0.000 description 2
• QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
• 239000004098 Tetracycline Substances 0.000 description 2
• 102000018594 Tumour necrosis factor Human genes 0.000 description 2
• 108050007852 Tumour necrosis factor Proteins 0.000 description 2
• 102000007537 Type II DNA Topoisomerases Human genes 0.000 description 2
• 108010046308 Type II DNA Topoisomerases Proteins 0.000 description 2
• 241001492404 Woodchuck hepatitis virus Species 0.000 description 2
• HMNZFMSWFCAGGW-XPWSMXQVSA-N [3-[hydroxy(2-hydroxyethoxy)phosphoryl]oxy-2-[(e)-octadec-9-enoyl]oxypropyl] (e)-octadec-9-enoate Chemical compound CCCCCCCC\C=C\CCCCCCCC(=O)OCC(COP(O)(=O)OCCO)OC(=O)CCCCCCC\C=C\CCCCCCCC HMNZFMSWFCAGGW-XPWSMXQVSA-N 0.000 description 2
• 238000002679 ablation Methods 0.000 description 2
• 238000009825 accumulation Methods 0.000 description 2
• 239000002253 acid Substances 0.000 description 2
• 239000002671 adjuvant Substances 0.000 description 2
• 229910000147 aluminium phosphate Inorganic materials 0.000 description 2
• 238000010171 animal model Methods 0.000 description 2
• 239000000427 antigen Substances 0.000 description 2
• 108091007433 antigens Proteins 0.000 description 2
• 102000036639 antigens Human genes 0.000 description 2
• 210000003433 aortic smooth muscle cell Anatomy 0.000 description 2
• 229960004405 aprotinin Drugs 0.000 description 2
• 239000007864 aqueous solution Substances 0.000 description 2
• YZXBAPSDXZZRGB-DOFZRALJSA-N arachidonic acid Chemical compound CCCCC\C=C/C\C=C/C\C=C/C\C=C/CCCC(O)=O YZXBAPSDXZZRGB-DOFZRALJSA-N 0.000 description 2
• 210000001130 astrocyte Anatomy 0.000 description 2
• 230000003416 augmentation Effects 0.000 description 2
• 230000005784 autoimmunity Effects 0.000 description 2
• 230000009286 beneficial effect Effects 0.000 description 2
• 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 2
• 230000003115 biocidal effect Effects 0.000 description 2
• 210000004369 blood Anatomy 0.000 description 2
• 239000008280 blood Substances 0.000 description 2
• 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 2
• 229910052799 carbon Inorganic materials 0.000 description 2
• 230000004663 cell proliferation Effects 0.000 description 2
• 230000004715 cellular signal transduction Effects 0.000 description 2
• 210000001612 chondrocyte Anatomy 0.000 description 2
• 210000003483 chromatin Anatomy 0.000 description 2
• 229960002173 citrulline Drugs 0.000 description 2
• 210000004748 cultured cell Anatomy 0.000 description 2
• 230000003247 decreasing effect Effects 0.000 description 2
• 239000003937 drug carrier Substances 0.000 description 2
• 238000001962 electrophoresis Methods 0.000 description 2
• NLFBCYMMUAKCPC-KQQUZDAGSA-N ethyl (e)-3-[3-amino-2-cyano-1-[(e)-3-ethoxy-3-oxoprop-1-enyl]sulfanyl-3-oxoprop-1-enyl]sulfanylprop-2-enoate Chemical compound CCOC(=O)\C=C\SC(=C(C#N)C(N)=O)S\C=C\C(=O)OCC NLFBCYMMUAKCPC-KQQUZDAGSA-N 0.000 description 2
• 210000003527 eukaryotic cell Anatomy 0.000 description 2
• 238000009472 formulation Methods 0.000 description 2
• 239000008273 gelatin Substances 0.000 description 2
• 229920000159 gelatin Polymers 0.000 description 2
• 235000019322 gelatine Nutrition 0.000 description 2
• 235000011852 gelatine desserts Nutrition 0.000 description 2
• 210000002443 helper t lymphocyte Anatomy 0.000 description 2
• 230000004730 hepatocarcinogenesis Effects 0.000 description 2
• 210000003494 hepatocyte Anatomy 0.000 description 2
• 238000010562 histological examination Methods 0.000 description 2
• 230000005745 host immune response Effects 0.000 description 2
• 229930195733 hydrocarbon Natural products 0.000 description 2
• 206010020718 hyperplasia Diseases 0.000 description 2
• 230000004046 hyporesponsiveness Effects 0.000 description 2
• 230000001976 improved effect Effects 0.000 description 2
• 230000008595 infiltration Effects 0.000 description 2
• 238000001764 infiltration Methods 0.000 description 2
• 230000003960 inflammatory cascade Effects 0.000 description 2
• ZPNFWUPYTFPOJU-LPYSRVMUSA-N iniprol Chemical compound C([C@H]1C(=O)NCC(=O)NCC(=O)N[C@H]2CSSC[C@H]3C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@H](C(N[C@H](C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC=4C=CC(O)=CC=4)C(=O)N[C@@H](CC=4C=CC=CC=4)C(=O)N[C@@H](CC=4C=CC(O)=CC=4)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](C)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](C)C(=O)NCC(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CSSC[C@H](NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C)NC(=O)[C@H](CO)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CC=4C=CC=CC=4)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CCCCN)NC(=O)[C@H](C)NC(=O)[C@H](CCCNC(N)=N)NC2=O)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CSSC[C@H](NC(=O)[C@H](CC=2C=CC=CC=2)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H]2N(CCC2)C(=O)[C@@H](N)CCCNC(N)=N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(O)=O)C(=O)N2[C@@H](CCC2)C(=O)N2[C@@H](CCC2)C(=O)N[C@@H](CC=2C=CC(O)=CC=2)C(=O)N[C@@H]([C@@H](C)O)C(=O)NCC(=O)N2[C@@H](CCC2)C(=O)N3)C(=O)NCC(=O)NCC(=O)N[C@@H](C)C(O)=O)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@H](C(=O)N[C@@H](CC=2C=CC=CC=2)C(=O)N[C@H](C(=O)N1)C(C)C)[C@@H](C)O)[C@@H](C)CC)=O)[C@@H](C)CC)C1=CC=C(O)C=C1 ZPNFWUPYTFPOJU-LPYSRVMUSA-N 0.000 description 2
• 230000003834 intracellular effect Effects 0.000 description 2
• 230000006662 intracellular pathway Effects 0.000 description 2
• 230000006525 intracellular process Effects 0.000 description 2
• QXJSBBXBKPUZAA-UHFFFAOYSA-N isooleic acid Natural products CCCCCCCC=CCCCCCCCCC(O)=O QXJSBBXBKPUZAA-UHFFFAOYSA-N 0.000 description 2
• VDBNYAPERZTOOF-UHFFFAOYSA-N isoquinolin-1(2H)-one Chemical compound C1=CC=C2C(=O)NC=CC2=C1 VDBNYAPERZTOOF-UHFFFAOYSA-N 0.000 description 2
• 238000000021 kinase assay Methods 0.000 description 2
• 231100000636 lethal dose Toxicity 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
• 239000000463 material Substances 0.000 description 2
• 210000004925 microvascular endothelial cell Anatomy 0.000 description 2
• 210000001616 monocyte Anatomy 0.000 description 2
• 230000035772 mutation Effects 0.000 description 2
• 230000017074 necrotic cell death Effects 0.000 description 2
• 210000000440 neutrophil Anatomy 0.000 description 2
• 238000006396 nitration reaction Methods 0.000 description 2
• YBVAXJOZZAJCLA-UHFFFAOYSA-N nitric acid nitrous acid Chemical compound ON=O.O[N+]([O-])=O YBVAXJOZZAJCLA-UHFFFAOYSA-N 0.000 description 2
• 229960003753 nitric oxide Drugs 0.000 description 2
• 229920001220 nitrocellulos Polymers 0.000 description 2
• 230000000263 nonmitogenic effect Effects 0.000 description 2
• 231100000252 nontoxic Toxicity 0.000 description 2
• 230000003000 nontoxic effect Effects 0.000 description 2
• 230000004792 oxidative damage Effects 0.000 description 2
• 230000036542 oxidative stress Effects 0.000 description 2
• 229910052760 oxygen Inorganic materials 0.000 description 2
• SECPZKHBENQXJG-FPLPWBNLSA-N palmitoleic acid Chemical compound CCCCCC\C=C/CCCCCCCC(O)=O SECPZKHBENQXJG-FPLPWBNLSA-N 0.000 description 2
• 239000008188 pellet Substances 0.000 description 2
• 108010091212 pepstatin Proteins 0.000 description 2
• FAXGPCHRFPCXOO-LXTPJMTPSA-N pepstatin A Chemical compound OC(=O)C[C@H](O)[C@H](CC(C)C)NC(=O)[C@H](C)NC(=O)C[C@H](O)[C@H](CC(C)C)NC(=O)[C@H](C(C)C)NC(=O)[C@H](C(C)C)NC(=O)CC(C)C FAXGPCHRFPCXOO-LXTPJMTPSA-N 0.000 description 2
• 210000003024 peritoneal macrophage Anatomy 0.000 description 2
• CNVZJPUDSLNTQU-SEYXRHQNSA-N petroselinic acid Chemical compound CCCCCCCCCCC\C=C/CCCCC(O)=O CNVZJPUDSLNTQU-SEYXRHQNSA-N 0.000 description 2
• 230000009038 pharmacological inhibition Effects 0.000 description 2
• 239000010452 phosphate Substances 0.000 description 2
• 150000003904 phospholipids Chemical class 0.000 description 2
• 230000035790 physiological processes and functions Effects 0.000 description 2
• 229920000136 polysorbate Polymers 0.000 description 2
• 239000000843 powder Substances 0.000 description 2
• KIDHWZJUCRJVML-UHFFFAOYSA-N putrescine Chemical compound NCCCCN KIDHWZJUCRJVML-UHFFFAOYSA-N 0.000 description 2
• 102000016914 ras Proteins Human genes 0.000 description 2
• 108010014186 ras Proteins Proteins 0.000 description 2
• BOLDJAUMGUJJKM-LSDHHAIUSA-N renifolin D Natural products CC(=C)[C@@H]1Cc2c(O)c(O)ccc2[C@H]1CC(=O)c3ccc(O)cc3O BOLDJAUMGUJJKM-LSDHHAIUSA-N 0.000 description 2
• 206010039073 rheumatoid arthritis Diseases 0.000 description 2
• YGSDEFSMJLZEOE-UHFFFAOYSA-N salicylic acid Chemical compound OC(=O)C1=CC=CC=C1O YGSDEFSMJLZEOE-UHFFFAOYSA-N 0.000 description 2
• 230000036303 septic shock Effects 0.000 description 2
• 210000003491 skin Anatomy 0.000 description 2
• 239000006228 supernatant Substances 0.000 description 2
• 239000000829 suppository Substances 0.000 description 2
• 239000000725 suspension Substances 0.000 description 2
• 210000001258 synovial membrane Anatomy 0.000 description 2
• 238000012360 testing method Methods 0.000 description 2
• 229960002180 tetracycline Drugs 0.000 description 2
• 229930101283 tetracycline Natural products 0.000 description 2
• 235000019364 tetracycline Nutrition 0.000 description 2
• 150000003522 tetracyclines Chemical class 0.000 description 2
• 238000010257 thawing Methods 0.000 description 2
• 230000036962 time dependent Effects 0.000 description 2
• 238000013518 transcription Methods 0.000 description 2
• 230000035897 transcription Effects 0.000 description 2
• 238000003146 transient transfection Methods 0.000 description 2
• 239000003656 tris buffered saline Substances 0.000 description 2
• OUYCCCASQSFEME-UHFFFAOYSA-N tyrosine Natural products OC(=O)C(N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-UHFFFAOYSA-N 0.000 description 2
• 235000021122 unsaturated fatty acids Nutrition 0.000 description 2
• 150000004670 unsaturated fatty acids Chemical class 0.000 description 2
• 230000002792 vascular Effects 0.000 description 2
• 238000005406 washing Methods 0.000 description 2
• GWHCXVQVJPWHRF-KTKRTIGZSA-N (15Z)-tetracosenoic acid Chemical compound CCCCCCCC\C=C/CCCCCCCCCCCCCC(O)=O GWHCXVQVJPWHRF-KTKRTIGZSA-N 0.000 description 1
• HVJCKZFYZWPQOO-AXYOXNHISA-N (3s,8s,9s,10r,13r,14s,17r)-3-ethoxy-10,13-dimethyl-17-[(2r)-6-methylheptan-2-yl]-2,3,4,7,8,9,11,12,14,15,16,17-dodecahydro-1h-cyclopenta[a]phenanthrene Chemical compound C([C@@H]12)C[C@]3(C)[C@@H]([C@H](C)CCCC(C)C)CC[C@H]3[C@@H]1CC=C1[C@]2(C)CC[C@H](OCC)C1 HVJCKZFYZWPQOO-AXYOXNHISA-N 0.000 description 1
• OYHQOLUKZRVURQ-NTGFUMLPSA-N (9Z,12Z)-9,10,12,13-tetratritiooctadeca-9,12-dienoic acid Chemical compound C(CCCCCCC\C(=C(/C\C(=C(/CCCCC)\[3H])\[3H])\[3H])\[3H])(=O)O OYHQOLUKZRVURQ-NTGFUMLPSA-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
• 102000040650 (ribonucleotides)n+m Human genes 0.000 description 1
• ICLYJLBTOGPLMC-KVVVOXFISA-N (z)-octadec-9-enoate;tris(2-hydroxyethyl)azanium Chemical compound OCCN(CCO)CCO.CCCCCCCC\C=C/CCCCCCCC(O)=O ICLYJLBTOGPLMC-KVVVOXFISA-N 0.000 description 1
• OXEDXHIBHVMDST-UHFFFAOYSA-N 12Z-octadecenoic acid Natural products CCCCCC=CCCCCCCCCCCC(O)=O OXEDXHIBHVMDST-UHFFFAOYSA-N 0.000 description 1
• 108020004463 18S ribosomal RNA Proteins 0.000 description 1
• PXBFMLJZNCDSMP-UHFFFAOYSA-N 2-Aminobenzamide Chemical compound NC(=O)C1=CC=CC=C1N PXBFMLJZNCDSMP-UHFFFAOYSA-N 0.000 description 1
• KISWVXRQTGLFGD-UHFFFAOYSA-N 2-[[2-[[6-amino-2-[[2-[[2-[[5-amino-2-[[2-[[1-[2-[[6-amino-2-[(2,5-diamino-5-oxopentanoyl)amino]hexanoyl]amino]-5-(diaminomethylideneamino)pentanoyl]pyrrolidine-2-carbonyl]amino]-3-hydroxypropanoyl]amino]-5-oxopentanoyl]amino]-5-(diaminomethylideneamino)p Chemical compound C1CCN(C(=O)C(CCCN=C(N)N)NC(=O)C(CCCCN)NC(=O)C(N)CCC(N)=O)C1C(=O)NC(CO)C(=O)NC(CCC(N)=O)C(=O)NC(CCCN=C(N)N)C(=O)NC(CO)C(=O)NC(CCCCN)C(=O)NC(C(=O)NC(CC(C)C)C(O)=O)CC1=CC=C(O)C=C1 KISWVXRQTGLFGD-UHFFFAOYSA-N 0.000 description 1
• QKNYBSVHEMOAJP-UHFFFAOYSA-N 2-amino-2-(hydroxymethyl)propane-1,3-diol;hydron;chloride Chemical compound Cl.OCC(N)(CO)CO QKNYBSVHEMOAJP-UHFFFAOYSA-N 0.000 description 1
• LQJBNNIYVWPHFW-UHFFFAOYSA-N 20:1omega9c fatty acid Natural products CCCCCCCCCCC=CCCCCCCCC(O)=O LQJBNNIYVWPHFW-UHFFFAOYSA-N 0.000 description 1
• AZKSAVLVSZKNRD-UHFFFAOYSA-M 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide Chemical compound [Br-].S1C(C)=C(C)N=C1[N+]1=NC(C=2C=CC=CC=2)=NN1C1=CC=CC=C1 AZKSAVLVSZKNRD-UHFFFAOYSA-M 0.000 description 1
• BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 1
• XUGISPSHIFXEHZ-UHFFFAOYSA-N 3beta-acetoxy-cholest-5-ene Natural products C1C=C2CC(OC(C)=O)CCC2(C)C2C1C1CCC(C(C)CCCC(C)C)C1(C)CC2 XUGISPSHIFXEHZ-UHFFFAOYSA-N 0.000 description 1
• YEYCQJVCAMFWCO-UHFFFAOYSA-N 3beta-cholesteryl formate Natural products C1C=C2CC(OC=O)CCC2(C)C2C1C1CCC(C(C)CCCC(C)C)C1(C)CC2 YEYCQJVCAMFWCO-UHFFFAOYSA-N 0.000 description 1
• PRYIJAGAEJZDBO-ZEQHCUNVSA-N 5,6alpha-epoxy-5alpha-cholestan-3beta-ol Chemical compound C([C@]12O[C@H]1C1)[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 PRYIJAGAEJZDBO-ZEQHCUNVSA-N 0.000 description 1
• QRXMUCSWCMTJGU-UHFFFAOYSA-N 5-bromo-4-chloro-3-indolyl phosphate Chemical compound C1=C(Br)C(Cl)=C2C(OP(O)(=O)O)=CNC2=C1 QRXMUCSWCMTJGU-UHFFFAOYSA-N 0.000 description 1
• ZOJAINJCZSVZGW-UHFFFAOYSA-N 6-aminochromen-2-one Chemical compound O1C(=O)C=CC2=CC(N)=CC=C21 ZOJAINJCZSVZGW-UHFFFAOYSA-N 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
• UXMPRYSFGIABNF-UHFFFAOYSA-N 8-amino-2h-isoquinolin-1-one Chemical compound C1=CNC(=O)C2=C1C=CC=C2N UXMPRYSFGIABNF-UHFFFAOYSA-N 0.000 description 1
• QSBYPNXLFMSGKH-UHFFFAOYSA-N 9-Heptadecensaeure Natural products CCCCCCCC=CCCCCCCCC(O)=O QSBYPNXLFMSGKH-UHFFFAOYSA-N 0.000 description 1
• 102000009062 ADP Ribose Transferases Human genes 0.000 description 1
• 108010049290 ADP Ribose Transferases Proteins 0.000 description 1
• 230000002407 ATP formation Effects 0.000 description 1
• RSWGJHLUYNHPMX-UHFFFAOYSA-N Abietic-Saeure Natural products C12CCC(C(C)C)=CC2=CCC2C1(C)CCCC2(C)C(O)=O RSWGJHLUYNHPMX-UHFFFAOYSA-N 0.000 description 1
• 102000007698 Alcohol dehydrogenase Human genes 0.000 description 1
• 108010021809 Alcohol dehydrogenase Proteins 0.000 description 1
• 241000234282 Allium Species 0.000 description 1
• 235000002732 Allium cepa var. cepa Nutrition 0.000 description 1
• GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 1
• 206010002091 Anaesthesia Diseases 0.000 description 1
• 208000023275 Autoimmune disease Diseases 0.000 description 1
• 238000011725 BALB/c mouse Methods 0.000 description 1
• 102100026189 Beta-galactosidase Human genes 0.000 description 1
• 108091003079 Bovine Serum Albumin Proteins 0.000 description 1
• 238000009010 Bradford assay Methods 0.000 description 1
• DPUOLQHDNGRHBS-UHFFFAOYSA-N Brassidinsaeure Natural products CCCCCCCCC=CCCCCCCCCCCCC(O)=O DPUOLQHDNGRHBS-UHFFFAOYSA-N 0.000 description 1
• YDNKGFDKKRUKPY-JHOUSYSJSA-N C16 ceramide Natural products CCCCCCCCCCCCCCCC(=O)N[C@@H](CO)[C@H](O)C=CCCCCCCCCCCCCC YDNKGFDKKRUKPY-JHOUSYSJSA-N 0.000 description 1
• 101100459438 Caenorhabditis elegans nac-1 gene Proteins 0.000 description 1
• 101100361281 Caenorhabditis elegans rpm-1 gene Proteins 0.000 description 1
• 102000000584 Calmodulin Human genes 0.000 description 1
• 108010041952 Calmodulin Proteins 0.000 description 1
• 241000283707 Capra Species 0.000 description 1
• BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 description 1
• RMLFYKFCGMSLTB-ZBDFTZOCSA-N Cholesteryl laurate Chemical compound C([C@@H]12)C[C@]3(C)[C@@H]([C@H](C)CCCC(C)C)CC[C@H]3[C@@H]1CC=C1[C@]2(C)CC[C@H](OC(=O)CCCCCCCCCCC)C1 RMLFYKFCGMSLTB-ZBDFTZOCSA-N 0.000 description 1
• 208000037051 Chromosomal Instability Diseases 0.000 description 1
• 206010009900 Colitis ulcerative Diseases 0.000 description 1
• 102000029816 Collagenase Human genes 0.000 description 1
• 108060005980 Collagenase Proteins 0.000 description 1
• 206010009944 Colon cancer Diseases 0.000 description 1
• 208000001333 Colorectal Neoplasms Diseases 0.000 description 1
• 206010010144 Completed suicide Diseases 0.000 description 1
• 208000011231 Crohn disease Diseases 0.000 description 1
• 108010037462 Cyclooxygenase 2 Proteins 0.000 description 1
• 108010015742 Cytochrome P-450 Enzyme System Proteins 0.000 description 1
• 102000003849 Cytochrome P450 Human genes 0.000 description 1
• FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 1
• 102000011724 DNA Repair Enzymes Human genes 0.000 description 1
• 108010076525 DNA Repair Enzymes Proteins 0.000 description 1
• 231100001074 DNA strand break Toxicity 0.000 description 1
• 238000002965 ELISA Methods 0.000 description 1
• 102000016942 Elastin Human genes 0.000 description 1
• 108010014258 Elastin Proteins 0.000 description 1
• 206010014824 Endotoxic shock Diseases 0.000 description 1
• URXZXNYJPAJJOQ-UHFFFAOYSA-N Erucic acid Natural products CCCCCCC=CCCCCCCCCCCCC(O)=O URXZXNYJPAJJOQ-UHFFFAOYSA-N 0.000 description 1
• 108700039887 Essential Genes Proteins 0.000 description 1
• 241000206602 Eukaryota Species 0.000 description 1
• 206010016654 Fibrosis Diseases 0.000 description 1
• 229940123457 Free radical scavenger Drugs 0.000 description 1
• 206010018364 Glomerulonephritis Diseases 0.000 description 1
• 102000016354 Glucuronosyltransferase Human genes 0.000 description 1
• 108010092364 Glucuronosyltransferase Proteins 0.000 description 1
• 102000005720 Glutathione transferase Human genes 0.000 description 1
• 108010070675 Glutathione transferase Proteins 0.000 description 1
• 239000007995 HEPES buffer Substances 0.000 description 1
• 101710088172 HTH-type transcriptional regulator RipA Proteins 0.000 description 1
• 241000590002 Helicobacter pylori Species 0.000 description 1
• 241000282412 Homo Species 0.000 description 1
• 101000998969 Homo sapiens Inositol-3-phosphate synthase 1 Proteins 0.000 description 1
• 208000006142 Infectious Encephalitis Diseases 0.000 description 1
• 206010061217 Infestation Diseases 0.000 description 1
• 101150109636 Inos gene Proteins 0.000 description 1
• 102100036881 Inositol-3-phosphate synthase 1 Human genes 0.000 description 1
• 102100036981 Interferon regulatory factor 1 Human genes 0.000 description 1
• 108090000890 Interferon regulatory factor 1 Proteins 0.000 description 1
• 102000003816 Interleukin-13 Human genes 0.000 description 1
• 108090000176 Interleukin-13 Proteins 0.000 description 1
• KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 1
• LEVWYRKDKASIDU-IMJSIDKUSA-N L-cystine Chemical compound [O-]C(=O)[C@@H]([NH3+])CSSC[C@H]([NH3+])C([O-])=O LEVWYRKDKASIDU-IMJSIDKUSA-N 0.000 description 1
• 239000004158 L-cystine Substances 0.000 description 1
• 235000019393 L-cystine Nutrition 0.000 description 1
• 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 1
• 239000000232 Lipid Bilayer Substances 0.000 description 1
• 102000001291 MAP Kinase Kinase Kinase Human genes 0.000 description 1
• 108091054438 MHC class II family Proteins 0.000 description 1
• 229930195725 Mannitol Natural products 0.000 description 1
• 238000000585 Mann–Whitney U test Methods 0.000 description 1
• 201000009906 Meningitis Diseases 0.000 description 1
• 108060004795 Methyltransferase Proteins 0.000 description 1
• 241000699660 Mus musculus Species 0.000 description 1
• 101710135898 Myc proto-oncogene protein Proteins 0.000 description 1
• 102100038895 Myc proto-oncogene protein Human genes 0.000 description 1
• 241000187479 Mycobacterium tuberculosis Species 0.000 description 1
• 241001049988 Mycobacterium tuberculosis H37Ra Species 0.000 description 1
• 102000047918 Myelin Basic Human genes 0.000 description 1
• 101710107068 Myelin basic protein Proteins 0.000 description 1
• NTNWOCRCBQPEKQ-YFKPBYRVSA-N N(omega)-methyl-L-arginine Chemical compound CN=C(N)NCCC[C@H](N)C(O)=O NTNWOCRCBQPEKQ-YFKPBYRVSA-N 0.000 description 1
• CRJGESKKUOMBCT-VQTJNVASSA-N N-acetylsphinganine Chemical compound CCCCCCCCCCCCCCC[C@@H](O)[C@H](CO)NC(C)=O CRJGESKKUOMBCT-VQTJNVASSA-N 0.000 description 1
• NTNWOCRCBQPEKQ-UHFFFAOYSA-N NG-mono-methyl-L-arginine Natural products CN=C(N)NCCCC(N)C(O)=O NTNWOCRCBQPEKQ-UHFFFAOYSA-N 0.000 description 1
• 229910019501 NaVO3 Inorganic materials 0.000 description 1
• XJXROGWVRIJYMO-SJDLZYGOSA-N Nervonic acid Natural products O=C(O)[C@@H](/C=C/CCCCCCCC)CCCCCCCCCCCC XJXROGWVRIJYMO-SJDLZYGOSA-N 0.000 description 1
• 241001077878 Neurolaena lobata Species 0.000 description 1
• 108090000913 Nitrate Reductases Proteins 0.000 description 1
• GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 1
• 101710089543 Nitric oxide synthase, inducible Proteins 0.000 description 1
• 102000007999 Nuclear Proteins Human genes 0.000 description 1
• 108010089610 Nuclear Proteins Proteins 0.000 description 1
• 239000004677 Nylon Substances 0.000 description 1
• 239000005642 Oleic acid Substances 0.000 description 1
• 108020005187 Oligonucleotide Probes Proteins 0.000 description 1
• 108700020796 Oncogene Proteins 0.000 description 1
• AHLPHDHHMVZTML-UHFFFAOYSA-N Orn-delta-NH2 Natural products NCCCC(N)C(O)=O AHLPHDHHMVZTML-UHFFFAOYSA-N 0.000 description 1
• 241000906034 Orthops Species 0.000 description 1
• 235000021319 Palmitoleic acid Nutrition 0.000 description 1
• CNVZJPUDSLNTQU-UHFFFAOYSA-N Petroselaidic acid Natural products CCCCCCCCCCCC=CCCCCC(O)=O CNVZJPUDSLNTQU-UHFFFAOYSA-N 0.000 description 1
• OAICVXFJPJFONN-UHFFFAOYSA-N Phosphorus Chemical compound [P] OAICVXFJPJFONN-UHFFFAOYSA-N 0.000 description 1
• ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
• 239000005700 Putrescine Substances 0.000 description 1
• 101150040459 RAS gene Proteins 0.000 description 1
• 108050002653 Retinoblastoma protein Proteins 0.000 description 1
• KHPCPRHQVVSZAH-HUOMCSJISA-N Rosin Natural products O(C/C=C/c1ccccc1)[C@H]1[C@H](O)[C@@H](O)[C@@H](O)[C@@H](CO)O1 KHPCPRHQVVSZAH-HUOMCSJISA-N 0.000 description 1
• 229940124639 Selective inhibitor Drugs 0.000 description 1
• 206010040844 Skin exfoliation Diseases 0.000 description 1
• VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 1
• 229920002472 Starch Polymers 0.000 description 1
• 208000006011 Stroke Diseases 0.000 description 1
• 229930006000 Sucrose Natural products 0.000 description 1
• CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 1
• 102000019197 Superoxide Dismutase Human genes 0.000 description 1
• 108010012715 Superoxide dismutase Proteins 0.000 description 1
• 101710150448 Transcriptional regulator Myc Proteins 0.000 description 1
• 102000004357 Transferases Human genes 0.000 description 1
• 108090000992 Transferases Proteins 0.000 description 1
• 239000007983 Tris buffer Substances 0.000 description 1
• 201000006704 Ulcerative Colitis Diseases 0.000 description 1
• 208000036142 Viral infection Diseases 0.000 description 1
• LJGMGXXCKVFFIS-IATSNXCDSA-N [(3s,8s,9s,10r,13r,14s,17r)-10,13-dimethyl-17-[(2r)-6-methylheptan-2-yl]-2,3,4,7,8,9,11,12,14,15,16,17-dodecahydro-1h-cyclopenta[a]phenanthren-3-yl] decanoate Chemical compound C([C@@H]12)C[C@]3(C)[C@@H]([C@H](C)CCCC(C)C)CC[C@H]3[C@@H]1CC=C1[C@]2(C)CC[C@H](OC(=O)CCCCCCCCC)C1 LJGMGXXCKVFFIS-IATSNXCDSA-N 0.000 description 1
• XJLXINKUBYWONI-DQQFMEOOSA-N [[(2r,3r,4r,5r)-5-(6-aminopurin-9-yl)-3-hydroxy-4-phosphonooxyoxolan-2-yl]methoxy-hydroxyphosphoryl] [(2s,3r,4s,5s)-5-(3-carbamoylpyridin-1-ium-1-yl)-3,4-dihydroxyoxolan-2-yl]methyl phosphate Chemical compound NC(=O)C1=CC=C[N+]([C@@H]2[C@H]([C@@H](O)[C@H](COP([O-])(=O)OP(O)(=O)OC[C@@H]3[C@H]([C@@H](OP(O)(O)=O)[C@@H](O3)N3C4=NC=NC(N)=C4N=C3)O)O2)O)=C1 XJLXINKUBYWONI-DQQFMEOOSA-N 0.000 description 1
• XLLNINGEDIOQGQ-UHFFFAOYSA-N [acetyloxy(hydroxy)phosphoryl] acetate Chemical compound CC(=O)OP(O)(=O)OC(C)=O XLLNINGEDIOQGQ-UHFFFAOYSA-N 0.000 description 1
• KPBYZDRYGZZKIG-UHFFFAOYSA-N [hexadecanoyloxy(hydroxy)phosphoryl] hexadecanoate Chemical compound CCCCCCCCCCCCCCCC(=O)OP(O)(=O)OC(=O)CCCCCCCCCCCCCCC KPBYZDRYGZZKIG-UHFFFAOYSA-N 0.000 description 1
• 239000004480 active ingredient Substances 0.000 description 1
• 239000011543 agarose gel 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
• MBMBGCFOFBJSGT-KUBAVDMBSA-N all-cis-docosa-4,7,10,13,16,19-hexaenoic acid Chemical compound CC\C=C/C\C=C/C\C=C/C\C=C/C\C=C/C\C=C/CCC(O)=O MBMBGCFOFBJSGT-KUBAVDMBSA-N 0.000 description 1
• 102000015395 alpha 1-Antitrypsin Human genes 0.000 description 1
• 108010050122 alpha 1-Antitrypsin Proteins 0.000 description 1
• DTOSIQBPPRVQHS-PDBXOOCHSA-N alpha-linolenic acid Chemical compound CC\C=C/C\C=C/C\C=C/CCCCCCCC(O)=O DTOSIQBPPRVQHS-PDBXOOCHSA-N 0.000 description 1
• 235000020661 alpha-linolenic acid Nutrition 0.000 description 1
• 230000037005 anaesthesia Effects 0.000 description 1
• 230000001093 anti-cancer Effects 0.000 description 1
• 229940121363 anti-inflammatory agent Drugs 0.000 description 1
• 239000002260 anti-inflammatory agent Substances 0.000 description 1
• 230000000845 anti-microbial effect Effects 0.000 description 1
• ZPNFWUPYTFPOJU-MPSLMFKFSA-N aprotinin Chemical compound CC[C@H](C)[C@@H]1NC(=O)[C@@H](CCCNC(N)=N)NC(=O)[C@@H](C)NC(=O)[C@H](CCCCN)NC(=O)[C@@H]2CSSC[C@H]3NC(=O)CNC(=O)CNC(=O)[C@H](Cc4ccc(O)cc4)NC(=O)[C@H](NC(=O)[C@H](Cc4ccccc4)NC(=O)[C@@H](NC(=O)[C@H](CCC(N)=O)NC(=O)[C@@H](CSSC[C@@H](NC(=O)[C@H](CC(O)=O)NC(=O)[C@@H](CCC(O)=O)NC(=O)[C@H](C)NC(=O)[C@@H](CO)NC(=O)[C@H](CCCCN)NC(=O)[C@@H](Cc4ccccc4)NC(=O)[C@H](CC(N)=O)NC(=O)[C@@H](CC(N)=O)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@@H](CCCCN)NC(=O)[C@H](C)NC(=O)[C@H](CCCNC(N)=N)NC3=O)C(=O)N[C@H](CCSC)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@H](CSSC[C@@H](NC(=O)[C@H](Cc3ccccc3)NC(=O)[C@@H](CC(O)=O)NC(=O)[C@H]3CCCN3C(=O)[C@H](N)CCCNC(N)=N)C(=O)N[C@H](CC(C)C)C(=O)N[C@@H](CCC(O)=O)C(=O)N3CCC[C@@H]3C(=O)N3CCC[C@H]3C(=O)N[C@H](Cc3ccc(O)cc3)C(=O)N[C@H]([C@H](C)O)C(=O)NCC(=O)N3CCC[C@H]3C(=O)N2)C(=O)NCC(=O)NCC(=O)N[C@H](C)C(O)=O)NC(=O)[C@@H](CC(C)C)NC(=O)CNC(=O)[C@@H](C)NC(=O)[C@H](CCCCN)NC(=O)[C@@H](C)NC(=O)[C@H](CC(N)=O)NC(=O)[C@@H](Cc2ccc(O)cc2)NC(=O)[C@H](Cc2ccccc2)NC(=O)[C@@H](Cc2ccc(O)cc2)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](NC1=O)[C@H](C)CC)[C@@H](C)O)C(C)C ZPNFWUPYTFPOJU-MPSLMFKFSA-N 0.000 description 1
• 229940114079 arachidonic acid Drugs 0.000 description 1
• 235000021342 arachidonic acid Nutrition 0.000 description 1
• ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 1
• 210000000544 articulatio talocruralis Anatomy 0.000 description 1
• 229960005070 ascorbic acid Drugs 0.000 description 1
• 235000010323 ascorbic acid Nutrition 0.000 description 1
• 239000011668 ascorbic acid Substances 0.000 description 1
• 230000003190 augmentative effect Effects 0.000 description 1
• 230000008901 benefit Effects 0.000 description 1
• 108010005774 beta-Galactosidase Proteins 0.000 description 1
• 230000000903 blocking effect Effects 0.000 description 1
• 230000037396 body weight Effects 0.000 description 1
• 238000009835 boiling Methods 0.000 description 1
• 210000000988 bone and bone Anatomy 0.000 description 1
• 125000001246 bromo group Chemical group Br* 0.000 description 1
• 239000007853 buffer solution Substances 0.000 description 1
• 239000006227 byproduct Substances 0.000 description 1
• 239000001506 calcium phosphate Substances 0.000 description 1
• 229910000389 calcium phosphate Inorganic materials 0.000 description 1
• 235000011010 calcium phosphates Nutrition 0.000 description 1
• 239000002775 capsule Substances 0.000 description 1
• 125000004432 carbon atom Chemical group C* 0.000 description 1
• 230000000747 cardiac effect Effects 0.000 description 1
• 230000001756 cardiomyopathic effect Effects 0.000 description 1
• 239000000969 carrier Substances 0.000 description 1
• 230000015556 catabolic process Effects 0.000 description 1
• 230000003197 catalytic effect Effects 0.000 description 1
• 125000002091 cationic group Chemical group 0.000 description 1
• 230000030833 cell death Effects 0.000 description 1
• 210000000170 cell membrane Anatomy 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
• 238000005119 centrifugation Methods 0.000 description 1
• 229940106189 ceramide Drugs 0.000 description 1
• ZVEQCJWYRWKARO-UHFFFAOYSA-N ceramide Natural products CCCCCCCCCCCCCCC(O)C(=O)NC(CO)C(O)C=CCCC=C(C)CCCCCCCCC ZVEQCJWYRWKARO-UHFFFAOYSA-N 0.000 description 1
• 230000008859 change Effects 0.000 description 1
• 239000003153 chemical reaction reagent Substances 0.000 description 1
• 125000001309 chloro group Chemical group Cl* 0.000 description 1
• 150000001841 cholesterols Chemical class 0.000 description 1
• XUGISPSHIFXEHZ-VEVYEIKRSA-N cholesteryl acetate Chemical compound C1C=C2C[C@@H](OC(C)=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 XUGISPSHIFXEHZ-VEVYEIKRSA-N 0.000 description 1
• PPQNZVDOBYGOLY-BFGJSWSOSA-N cholesteryl heptadecanoate Chemical compound C([C@@H]12)C[C@]3(C)[C@@H]([C@H](C)CCCC(C)C)CC[C@H]3[C@@H]1CC=C1[C@]2(C)CC[C@H](OC(=O)CCCCCCCCCCCCCCCC)C1 PPQNZVDOBYGOLY-BFGJSWSOSA-N 0.000 description 1
• SECPZKHBENQXJG-UHFFFAOYSA-N cis-palmitoleic acid Natural products CCCCCCC=CCCCCCCCC(O)=O SECPZKHBENQXJG-UHFFFAOYSA-N 0.000 description 1
• GWHCXVQVJPWHRF-UHFFFAOYSA-N cis-tetracosenoic acid Natural products CCCCCCCCC=CCCCCCCCCCCCCCC(O)=O GWHCXVQVJPWHRF-UHFFFAOYSA-N 0.000 description 1
• 206010009887 colitis Diseases 0.000 description 1
• 229960002424 collagenase Drugs 0.000 description 1
• 239000002299 complementary DNA Substances 0.000 description 1
• 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
• 125000000582 cycloheptyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
• 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
• 125000000640 cyclooctyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 description 1
• 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
• 229960003067 cystine Drugs 0.000 description 1
• 230000009089 cytolysis Effects 0.000 description 1
• 230000001086 cytosolic effect Effects 0.000 description 1
• 231100000433 cytotoxic Toxicity 0.000 description 1
• 230000001472 cytotoxic effect Effects 0.000 description 1
• RGWHQCVHVJXOKC-SHYZEUOFSA-J dCTP(4-) Chemical compound O=C1N=C(N)C=CN1[C@@H]1O[C@H](COP([O-])(=O)OP([O-])(=O)OP([O-])([O-])=O)[C@@H](O)C1 RGWHQCVHVJXOKC-SHYZEUOFSA-J 0.000 description 1
• 238000007405 data analysis Methods 0.000 description 1
• 230000007423 decrease Effects 0.000 description 1
• 230000003111 delayed effect Effects 0.000 description 1
• 238000001514 detection method Methods 0.000 description 1
• 239000008121 dextrose Substances 0.000 description 1
• 206010012601 diabetes mellitus Diseases 0.000 description 1
• 235000014113 dietary fatty acids Nutrition 0.000 description 1
• 239000003085 diluting agent Substances 0.000 description 1
• 238000010790 dilution Methods 0.000 description 1
• 239000012895 dilution Substances 0.000 description 1
• 239000000539 dimer Substances 0.000 description 1
• 230000003292 diminished effect Effects 0.000 description 1
• ZGSPNIOCEDOHGS-UHFFFAOYSA-L disodium [3-[2,3-di(octadeca-9,12-dienoyloxy)propoxy-oxidophosphoryl]oxy-2-hydroxypropyl] 2,3-di(octadeca-9,12-dienoyloxy)propyl phosphate Chemical compound [Na+].[Na+].CCCCCC=CCC=CCCCCCCCC(=O)OCC(OC(=O)CCCCCCCC=CCC=CCCCCC)COP([O-])(=O)OCC(O)COP([O-])(=O)OCC(OC(=O)CCCCCCCC=CCC=CCCCCC)COC(=O)CCCCCCCC=CCC=CCCCCC ZGSPNIOCEDOHGS-UHFFFAOYSA-L 0.000 description 1
• 238000009826 distribution Methods 0.000 description 1
• 230000003828 downregulation Effects 0.000 description 1
• 238000001035 drying Methods 0.000 description 1
• 230000004064 dysfunction Effects 0.000 description 1
• ZQPPMHVWECSIRJ-MDZDMXLPSA-N elaidic acid Chemical compound CCCCCCCC\C=C\CCCCCCCC(O)=O ZQPPMHVWECSIRJ-MDZDMXLPSA-N 0.000 description 1
• 229920002549 elastin Polymers 0.000 description 1
• 239000003995 emulsifying agent Substances 0.000 description 1
• 230000002255 enzymatic effect Effects 0.000 description 1
• DPUOLQHDNGRHBS-KTKRTIGZSA-N erucic acid Chemical compound CCCCCCCC\C=C/CCCCCCCCCCCC(O)=O DPUOLQHDNGRHBS-KTKRTIGZSA-N 0.000 description 1
• 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
• 230000029142 excretion Effects 0.000 description 1
• 239000000194 fatty acid Substances 0.000 description 1
• 229930195729 fatty acid Natural products 0.000 description 1
• 239000012894 fetal calf serum Substances 0.000 description 1
• 210000002950 fibroblast Anatomy 0.000 description 1
• 230000004761 fibrosis Effects 0.000 description 1
• 238000001914 filtration Methods 0.000 description 1
• 125000001153 fluoro group Chemical group F* 0.000 description 1
• 235000013305 food Nutrition 0.000 description 1
• 238000002825 functional assay Methods 0.000 description 1
• BTCSSZJGUNDROE-UHFFFAOYSA-N gamma-aminobutyric acid Chemical compound NCCCC(O)=O BTCSSZJGUNDROE-UHFFFAOYSA-N 0.000 description 1
• 206010017758 gastric cancer Diseases 0.000 description 1
• 208000010749 gastric carcinoma Diseases 0.000 description 1
• 210000001035 gastrointestinal tract Anatomy 0.000 description 1
• 239000008103 glucose Substances 0.000 description 1
• 235000001727 glucose Nutrition 0.000 description 1
• 230000034659 glycolysis Effects 0.000 description 1
• 244000144993 groups of animals Species 0.000 description 1
• 229960000789 guanidine hydrochloride Drugs 0.000 description 1
• PJJJBBJSCAKJQF-UHFFFAOYSA-N guanidinium chloride Chemical compound [Cl-].NC(N)=[NH2+] PJJJBBJSCAKJQF-UHFFFAOYSA-N 0.000 description 1
• 229940037467 helicobacter pylori Drugs 0.000 description 1
• 125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
• 210000000548 hind-foot Anatomy 0.000 description 1
• 238000000265 homogenisation Methods 0.000 description 1
• 230000009848 hypophosphorylation Effects 0.000 description 1
• 230000036039 immunity Effects 0.000 description 1
• 239000003018 immunosuppressive agent Substances 0.000 description 1
• 229940125721 immunosuppressive agent Drugs 0.000 description 1
• 238000002513 implantation Methods 0.000 description 1
• 239000000411 inducer Substances 0.000 description 1
• 208000013256 infectious meningitis Diseases 0.000 description 1
• 238000001802 infusion Methods 0.000 description 1
• 239000004615 ingredient Substances 0.000 description 1
• 230000000977 initiatory effect Effects 0.000 description 1
• 239000007972 injectable composition Substances 0.000 description 1
• 229940102223 injectable solution Drugs 0.000 description 1
• 229940102213 injectable suspension Drugs 0.000 description 1
• 230000031261 interleukin-10 production Effects 0.000 description 1
• 230000017306 interleukin-6 production Effects 0.000 description 1
• 210000004347 intestinal mucosa Anatomy 0.000 description 1
• 238000010255 intramuscular injection Methods 0.000 description 1
• 238000010253 intravenous injection Methods 0.000 description 1
• 238000011835 investigation Methods 0.000 description 1
• 230000005865 ionizing radiation Effects 0.000 description 1
• 208000012947 ischemia reperfusion injury Diseases 0.000 description 1
• 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 1
• 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
• 238000002218 isotachophoresis Methods 0.000 description 1
• 229940043355 kinase inhibitor Drugs 0.000 description 1
• 239000008101 lactose Substances 0.000 description 1
• 230000000670 limiting effect Effects 0.000 description 1
• 229960004488 linolenic acid Drugs 0.000 description 1
• KQQKGWQCNNTQJW-UHFFFAOYSA-N linolenic acid Natural products CC=CCCC=CCC=CCCCCCCCC(O)=O KQQKGWQCNNTQJW-UHFFFAOYSA-N 0.000 description 1
• 239000008297 liquid dosage form Substances 0.000 description 1
• 239000006193 liquid solution Substances 0.000 description 1
• 239000006194 liquid suspension Substances 0.000 description 1
• 210000004185 liver Anatomy 0.000 description 1
• 210000004698 lymphocyte Anatomy 0.000 description 1
• ZLNQQNXFFQJAID-UHFFFAOYSA-L magnesium carbonate Chemical compound [Mg+2].[O-]C([O-])=O ZLNQQNXFFQJAID-UHFFFAOYSA-L 0.000 description 1
• 239000001095 magnesium carbonate Substances 0.000 description 1
• 229910000021 magnesium carbonate Inorganic materials 0.000 description 1
• 235000019359 magnesium stearate Nutrition 0.000 description 1
• 238000012423 maintenance Methods 0.000 description 1
• 239000000594 mannitol Substances 0.000 description 1
• 235000010355 mannitol Nutrition 0.000 description 1
• 239000002609 medium Substances 0.000 description 1
• 230000002503 metabolic effect Effects 0.000 description 1
• 229940098779 methanesulfonic acid Drugs 0.000 description 1
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
• 244000005700 microbiome Species 0.000 description 1
• 150000007522 mineralic acids Chemical class 0.000 description 1
• 230000002438 mitochondrial effect Effects 0.000 description 1
• 238000002156 mixing Methods 0.000 description 1
• 239000000178 monomer Substances 0.000 description 1
• 238000010172 mouse model Methods 0.000 description 1
• VMGAPWLDMVPYIA-HIDZBRGKSA-N n'-amino-n-iminomethanimidamide Chemical compound N\N=C\N=N VMGAPWLDMVPYIA-HIDZBRGKSA-N 0.000 description 1
• 230000007935 neutral effect Effects 0.000 description 1
• VVGIYYKRAMHVLU-UHFFFAOYSA-N newbouldiamide Natural products CCCCCCCCCCCCCCCCCCCC(O)C(O)C(O)C(CO)NC(=O)CCCCCCCCCCCCCCCCC VVGIYYKRAMHVLU-UHFFFAOYSA-N 0.000 description 1
• 229930027945 nicotinamide-adenine dinucleotide Natural products 0.000 description 1
• 229910017604 nitric acid Inorganic materials 0.000 description 1
• 229940074355 nitric acid Drugs 0.000 description 1
• 229910052757 nitrogen Inorganic materials 0.000 description 1
• 231100000065 noncytotoxic Toxicity 0.000 description 1
• 230000002020 noncytotoxic effect Effects 0.000 description 1
• 210000004940 nucleus Anatomy 0.000 description 1
• 229920001778 nylon Polymers 0.000 description 1
• QNDVLZJODHBUFM-WFXQOWMNSA-N okadaic acid Chemical compound C([C@H](O1)[C@H](C)/C=C/[C@H]2CC[C@@]3(CC[C@H]4O[C@@H](C([C@@H](O)[C@@H]4O3)=C)[C@@H](O)C[C@H](C)[C@@H]3[C@@H](CC[C@@]4(OCCCC4)O3)C)O2)C(C)=C[C@]21O[C@H](C[C@@](C)(O)C(O)=O)CC[C@H]2O QNDVLZJODHBUFM-WFXQOWMNSA-N 0.000 description 1
• VEFJHAYOIAAXEU-UHFFFAOYSA-N okadaic acid Natural products CC(CC(O)C1OC2CCC3(CCC(O3)C=CC(C)C4CC(=CC5(OC(CC(C)(O)C(=O)O)CCC5O)O4)C)OC2C(O)C1C)C6OC7(CCCCO7)CCC6C VEFJHAYOIAAXEU-UHFFFAOYSA-N 0.000 description 1
• ZQPPMHVWECSIRJ-KTKRTIGZSA-N oleic acid Chemical compound CCCCCCCC\C=C/CCCCCCCC(O)=O ZQPPMHVWECSIRJ-KTKRTIGZSA-N 0.000 description 1
• 239000002751 oligonucleotide probe Substances 0.000 description 1
• 230000003287 optical effect Effects 0.000 description 1
• 229960003104 ornithine Drugs 0.000 description 1
• 239000001301 oxygen Substances 0.000 description 1
• 239000006179 pH buffering agent Substances 0.000 description 1
• 230000000242 pagocytic effect Effects 0.000 description 1
• FJKROLUGYXJWQN-UHFFFAOYSA-N papa-hydroxy-benzoic acid Natural products OC(=O)C1=CC=C(O)C=C1 FJKROLUGYXJWQN-UHFFFAOYSA-N 0.000 description 1
• 238000007911 parenteral administration Methods 0.000 description 1
• 238000005192 partition Methods 0.000 description 1
• 230000001717 pathogenic effect Effects 0.000 description 1
• 230000001991 pathophysiological effect Effects 0.000 description 1
• 125000004115 pentoxy group Chemical group [*]OC([H])([H])C([H])([H])C([H])([H])C(C([H])([H])[H])([H])[H] 0.000 description 1
• 125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 1
• 239000000137 peptide hydrolase inhibitor Substances 0.000 description 1
• 239000003186 pharmaceutical solution Substances 0.000 description 1
• 230000002974 pharmacogenomic effect Effects 0.000 description 1
• DDBREPKUVSBGFI-UHFFFAOYSA-N phenobarbital Chemical compound C=1C=CC=CC=1C1(CC)C(=O)NC(=O)NC1=O DDBREPKUVSBGFI-UHFFFAOYSA-N 0.000 description 1
• 229960002695 phenobarbital Drugs 0.000 description 1
• NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
• 229960004838 phosphoric acid Drugs 0.000 description 1
• 230000026731 phosphorylation Effects 0.000 description 1
• 238000006366 phosphorylation reaction Methods 0.000 description 1
• 239000003757 phosphotransferase inhibitor Substances 0.000 description 1
• 239000006187 pill Substances 0.000 description 1
• 230000036470 plasma concentration Effects 0.000 description 1
• 229920001467 poly(styrenesulfonates) Polymers 0.000 description 1
• 229920001515 polyalkylene glycol Polymers 0.000 description 1
• 238000006116 polymerization reaction Methods 0.000 description 1
• 230000004481 post-translational protein modification Effects 0.000 description 1
• 239000011591 potassium Substances 0.000 description 1
• 229910052700 potassium Inorganic materials 0.000 description 1
• 230000003334 potential effect Effects 0.000 description 1
• 238000002360 preparation method Methods 0.000 description 1
• 230000037452 priming Effects 0.000 description 1
• 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
• 238000001243 protein synthesis Methods 0.000 description 1
• 230000002685 pulmonary effect Effects 0.000 description 1
• 239000002516 radical scavenger Substances 0.000 description 1
• 238000010814 radioimmunoprecipitation assay Methods 0.000 description 1
• 108700042226 ras Genes Proteins 0.000 description 1
• 238000011552 rat model Methods 0.000 description 1
• 239000011541 reaction mixture Substances 0.000 description 1
• 230000008707 rearrangement Effects 0.000 description 1
• 230000022532 regulation of transcription, DNA-dependent Effects 0.000 description 1
• 108091006091 regulatory enzymes Proteins 0.000 description 1
• 230000009711 regulatory function Effects 0.000 description 1
• CSYSULGPHGCBQD-UHFFFAOYSA-N s-ethylisothiouronium diethylphosphate Chemical class CCSC(N)=N.CCOP(O)(=O)OCC CSYSULGPHGCBQD-UHFFFAOYSA-N 0.000 description 1
• CVHZOJJKTDOEJC-UHFFFAOYSA-N saccharin Chemical compound C1=CC=C2C(=O)NS(=O)(=O)C2=C1 CVHZOJJKTDOEJC-UHFFFAOYSA-N 0.000 description 1
• 229960004889 salicylic acid Drugs 0.000 description 1
• 239000000523 sample Substances 0.000 description 1
• 239000012723 sample buffer Substances 0.000 description 1
• FNKQXYHWGSIFBK-RPDRRWSUSA-N sapropterin Chemical compound N1=C(N)NC(=O)C2=C1NC[C@H]([C@@H](O)[C@@H](O)C)N2 FNKQXYHWGSIFBK-RPDRRWSUSA-N 0.000 description 1
• 229960004617 sapropterin Drugs 0.000 description 1
• 229920006395 saturated elastomer Polymers 0.000 description 1
• 201000004409 schistosomiasis Diseases 0.000 description 1
• 238000003345 scintillation counting Methods 0.000 description 1
• 229940116351 sebacate Drugs 0.000 description 1
• CXMXRPHRNRROMY-UHFFFAOYSA-L sebacate(2-) Chemical compound [O-]C(=O)CCCCCCCCC([O-])=O CXMXRPHRNRROMY-UHFFFAOYSA-L 0.000 description 1
• 239000008299 semisolid dosage form Substances 0.000 description 1
• RYMZZMVNJRMUDD-HGQWONQESA-N simvastatin Chemical compound C([C@H]1[C@@H](C)C=CC2=C[C@H](C)C[C@@H]([C@H]12)OC(=O)C(C)(C)CC)C[C@@H]1C[C@@H](O)CC(=O)O1 RYMZZMVNJRMUDD-HGQWONQESA-N 0.000 description 1
• 230000005783 single-strand break Effects 0.000 description 1
• 239000001632 sodium acetate Substances 0.000 description 1
• 235000017281 sodium acetate Nutrition 0.000 description 1
• 239000001509 sodium citrate Substances 0.000 description 1
• NLJMYIDDQXHKNR-UHFFFAOYSA-K sodium citrate Chemical compound O.O.[Na+].[Na+].[Na+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O NLJMYIDDQXHKNR-UHFFFAOYSA-K 0.000 description 1
• CMZUMMUJMWNLFH-UHFFFAOYSA-N sodium metavanadate Chemical compound [Na+].[O-][V](=O)=O CMZUMMUJMWNLFH-UHFFFAOYSA-N 0.000 description 1
• 239000007787 solid Substances 0.000 description 1
• 239000007909 solid dosage form Substances 0.000 description 1
• 239000008247 solid mixture Substances 0.000 description 1
• 239000002904 solvent Substances 0.000 description 1
• 238000000527 sonication Methods 0.000 description 1
• 238000001228 spectrum Methods 0.000 description 1
• 239000008107 starch Substances 0.000 description 1
• 235000019698 starch Nutrition 0.000 description 1
• 238000010972 statistical evaluation Methods 0.000 description 1
• 230000001954 sterilising effect Effects 0.000 description 1
• 238000004659 sterilization and disinfection Methods 0.000 description 1
• 238000003756 stirring Methods 0.000 description 1
• 201000000498 stomach carcinoma Diseases 0.000 description 1
• 108010062541 styrene oxide hydratase Proteins 0.000 description 1
• 238000007920 subcutaneous administration Methods 0.000 description 1
• 238000010254 subcutaneous injection Methods 0.000 description 1
• 239000000758 substrate Substances 0.000 description 1
• 239000005720 sucrose Substances 0.000 description 1
• FDDDEECHVMSUSB-UHFFFAOYSA-N sulfanilamide Chemical compound NC1=CC=C(S(N)(=O)=O)C=C1 FDDDEECHVMSUSB-UHFFFAOYSA-N 0.000 description 1
• 229940124530 sulfonamide Drugs 0.000 description 1
• 229940032330 sulfuric acid Drugs 0.000 description 1
• 230000008961 swelling Effects 0.000 description 1
• 230000008718 systemic inflammatory response Effects 0.000 description 1
• 239000003826 tablet Substances 0.000 description 1
• 239000000454 talc Substances 0.000 description 1
• 235000012222 talc Nutrition 0.000 description 1
• 229910052623 talc Inorganic materials 0.000 description 1
• 125000003831 tetrazolyl group Chemical group 0.000 description 1
• 229940124597 therapeutic agent Drugs 0.000 description 1
• 238000011200 topical administration Methods 0.000 description 1
• 231100000331 toxic Toxicity 0.000 description 1
• 230000002588 toxic effect Effects 0.000 description 1
• AQWHMKSIVLSRNY-UHFFFAOYSA-N trans-Octadec-5-ensaeure Natural products CCCCCCCCCCCCC=CCCCC(O)=O AQWHMKSIVLSRNY-UHFFFAOYSA-N 0.000 description 1
• KHPCPRHQVVSZAH-UHFFFAOYSA-N trans-cinnamyl beta-D-glucopyranoside Natural products OC1C(O)C(O)C(CO)OC1OCC=CC1=CC=CC=C1 KHPCPRHQVVSZAH-UHFFFAOYSA-N 0.000 description 1
• 238000011830 transgenic mouse model Methods 0.000 description 1
• 230000001052 transient effect Effects 0.000 description 1
• 230000032258 transport Effects 0.000 description 1
• QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 description 1
• 229940117013 triethanolamine oleate Drugs 0.000 description 1
• 230000001960 triggered effect Effects 0.000 description 1
• LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 1
• 230000006433 tumor necrosis factor production Effects 0.000 description 1
• 238000011870 unpaired t-test Methods 0.000 description 1
• 230000003827 upregulation Effects 0.000 description 1
• 210000003932 urinary bladder Anatomy 0.000 description 1
• 230000002485 urinary effect Effects 0.000 description 1
• 230000009385 viral infection Effects 0.000 description 1
• 238000009736 wetting Methods 0.000 description 1
• 239000000080 wetting agent Substances 0.000 description 1