JP6507336B2 - Ｃｂｐ／カテニン阻害剤を用いる肝線維症の治療 - Google Patents
Ｃｂｐ／カテニン阻害剤を用いる肝線維症の治療 Download PDFInfo
- Publication number
- JP6507336B2 JP6507336B2 JP2016548443A JP2016548443A JP6507336B2 JP 6507336 B2 JP6507336 B2 JP 6507336B2 JP 2016548443 A JP2016548443 A JP 2016548443A JP 2016548443 A JP2016548443 A JP 2016548443A JP 6507336 B2 JP6507336 B2 JP 6507336B2
- Authority
- JP
- Japan
- Prior art keywords
- liver
- compound
- group
- disease
- fibrosis
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Active
Links
- 208000019425 cirrhosis of liver Diseases 0.000 title description 41
- 239000003112 inhibitor Substances 0.000 title description 23
- 102000016362 Catenins Human genes 0.000 title description 2
- 108010067316 Catenins Proteins 0.000 title description 2
- 208000008338 non-alcoholic fatty liver disease Diseases 0.000 claims description 32
- 206010053219 non-alcoholic steatohepatitis Diseases 0.000 claims description 27
- 208000004930 Fatty Liver Diseases 0.000 claims description 7
- 239000008194 pharmaceutical composition Substances 0.000 claims description 6
- KLGHKOORFHZFGO-AZXNYEMZSA-N (6s,9s,9as)-n-benzyl-6-[(4-hydroxyphenyl)methyl]-2,9-dimethyl-4,7-dioxo-8-(quinolin-8-ylmethyl)-3,6,9,9a-tetrahydropyrazino[2,1-c][1,2,4]triazine-1-carboxamide Chemical compound C([C@@H]1N2[C@@H](N(N(C)CC2=O)C(=O)NCC=2C=CC=CC=2)[C@@H](N(C1=O)CC=1C2=NC=CC=C2C=CC=1)C)C1=CC=C(O)C=C1 KLGHKOORFHZFGO-AZXNYEMZSA-N 0.000 claims description 3
- 206010019668 Hepatic fibrosis Diseases 0.000 claims description 3
- VHOZWHQPEJGPCC-AZXNYEMZSA-N [4-[[(6s,9s,9as)-1-(benzylcarbamoyl)-2,9-dimethyl-4,7-dioxo-8-(quinolin-8-ylmethyl)-3,6,9,9a-tetrahydropyrazino[2,1-c][1,2,4]triazin-6-yl]methyl]phenyl] dihydrogen phosphate Chemical compound C([C@@H]1N2[C@@H](N(N(C)CC2=O)C(=O)NCC=2C=CC=CC=2)[C@@H](N(C1=O)CC=1C2=NC=CC=C2C=CC=1)C)C1=CC=C(OP(O)(O)=O)C=C1 VHOZWHQPEJGPCC-AZXNYEMZSA-N 0.000 claims description 2
- 229940126062 Compound A Drugs 0.000 description 71
- NLDMNSXOCDLTTB-UHFFFAOYSA-N Heterophylliin A Natural products O1C2COC(=O)C3=CC(O)=C(O)C(O)=C3C3=C(O)C(O)=C(O)C=C3C(=O)OC2C(OC(=O)C=2C=C(O)C(O)=C(O)C=2)C(O)C1OC(=O)C1=CC(O)=C(O)C(O)=C1 NLDMNSXOCDLTTB-UHFFFAOYSA-N 0.000 description 71
- RMMXLENWKUUMAY-UHFFFAOYSA-N telmisartan Chemical compound CCCC1=NC2=C(C)C=C(C=3N(C4=CC=CC=C4N=3)C)C=C2N1CC(C=C1)=CC=C1C1=CC=CC=C1C(O)=O RMMXLENWKUUMAY-UHFFFAOYSA-N 0.000 description 66
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 59
- 210000004185 liver Anatomy 0.000 description 58
- 201000010099 disease Diseases 0.000 description 57
- 239000003981 vehicle Substances 0.000 description 41
- 150000001875 compounds Chemical class 0.000 description 39
- 108060000903 Beta-catenin Proteins 0.000 description 35
- 102000015735 Beta-catenin Human genes 0.000 description 35
- 239000005537 C09CA07 - Telmisartan Substances 0.000 description 34
- 229960005187 telmisartan Drugs 0.000 description 33
- 206010016654 Fibrosis Diseases 0.000 description 21
- 230000014509 gene expression Effects 0.000 description 20
- 230000004761 fibrosis Effects 0.000 description 18
- 210000004024 hepatic stellate cell Anatomy 0.000 description 18
- 108050003627 Wnt Proteins 0.000 description 17
- 239000003814 drug Substances 0.000 description 17
- 239000000203 mixture Substances 0.000 description 16
- 102000013814 Wnt Human genes 0.000 description 15
- 208000006454 hepatitis Diseases 0.000 description 15
- -1 benzylcarbamoyl Chemical group 0.000 description 14
- 108090000623 proteins and genes Proteins 0.000 description 14
- PMMYEEVYMWASQN-DMTCNVIQSA-N Hydroxyproline Chemical compound O[C@H]1CN[C@H](C(O)=O)C1 PMMYEEVYMWASQN-DMTCNVIQSA-N 0.000 description 13
- 241000699670 Mus sp. Species 0.000 description 13
- 108020004999 messenger RNA Proteins 0.000 description 13
- 238000000034 method Methods 0.000 description 13
- 102000008186 Collagen Human genes 0.000 description 12
- 108010035532 Collagen Proteins 0.000 description 12
- 229920001436 collagen Polymers 0.000 description 12
- PMMYEEVYMWASQN-UHFFFAOYSA-N dl-hydroxyproline Natural products OC1C[NH2+]C(C([O-])=O)C1 PMMYEEVYMWASQN-UHFFFAOYSA-N 0.000 description 12
- 230000000694 effects Effects 0.000 description 12
- 230000011664 signaling Effects 0.000 description 12
- 210000001519 tissue Anatomy 0.000 description 12
- 206010061218 Inflammation Diseases 0.000 description 11
- 210000004369 blood Anatomy 0.000 description 11
- 239000008280 blood Substances 0.000 description 11
- 230000037396 body weight Effects 0.000 description 11
- 229960002591 hydroxyproline Drugs 0.000 description 11
- 230000004054 inflammatory process Effects 0.000 description 11
- 210000002966 serum Anatomy 0.000 description 11
- FGMPLJWBKKVCDB-UHFFFAOYSA-N trans-L-hydroxy-proline Natural products ON1CCCC1C(O)=O FGMPLJWBKKVCDB-UHFFFAOYSA-N 0.000 description 11
- 241001465754 Metazoa Species 0.000 description 10
- 239000000126 substance Substances 0.000 description 10
- 108010047761 Interferon-alpha Proteins 0.000 description 9
- 102000006992 Interferon-alpha Human genes 0.000 description 9
- IWUCXVSUMQZMFG-AFCXAGJDSA-N Ribavirin Chemical compound N1=C(C(=O)N)N=CN1[C@H]1[C@H](O)[C@H](O)[C@@H](CO)O1 IWUCXVSUMQZMFG-AFCXAGJDSA-N 0.000 description 9
- 108010016283 TCF Transcription Factors Proteins 0.000 description 9
- 102000000479 TCF Transcription Factors Human genes 0.000 description 9
- OHDXDNUPVVYWOV-UHFFFAOYSA-N n-methyl-1-(2-naphthalen-1-ylsulfanylphenyl)methanamine Chemical compound CNCC1=CC=CC=C1SC1=CC=CC2=CC=CC=C12 OHDXDNUPVVYWOV-UHFFFAOYSA-N 0.000 description 9
- 229960000329 ribavirin Drugs 0.000 description 9
- HZCAHMRRMINHDJ-DBRKOABJSA-N ribavirin Natural products O[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1N1N=CN=C1 HZCAHMRRMINHDJ-DBRKOABJSA-N 0.000 description 9
- 239000000243 solution Substances 0.000 description 9
- 210000004027 cell Anatomy 0.000 description 8
- 231100000283 hepatitis Toxicity 0.000 description 8
- 238000002360 preparation method Methods 0.000 description 8
- 235000018102 proteins Nutrition 0.000 description 8
- 102000004169 proteins and genes Human genes 0.000 description 8
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 7
- 230000004913 activation Effects 0.000 description 7
- 101710099518 Dickkopf-related protein 1 Proteins 0.000 description 6
- 102100030074 Dickkopf-related protein 1 Human genes 0.000 description 6
- 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 6
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 6
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 6
- 239000004480 active ingredient Substances 0.000 description 6
- 239000002775 capsule Substances 0.000 description 6
- 239000003795 chemical substances by application Substances 0.000 description 6
- 239000003937 drug carrier Substances 0.000 description 6
- 235000019441 ethanol Nutrition 0.000 description 6
- 230000003176 fibrotic effect Effects 0.000 description 6
- 239000008103 glucose Substances 0.000 description 6
- 230000008595 infiltration Effects 0.000 description 6
- 238000001764 infiltration Methods 0.000 description 6
- 230000002265 prevention Effects 0.000 description 6
- 231100000240 steatosis hepatitis Toxicity 0.000 description 6
- 210000004500 stellate cell Anatomy 0.000 description 6
- 238000012360 testing method Methods 0.000 description 6
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 6
- 125000003143 4-hydroxybenzyl group Chemical group [H]C([*])([H])C1=C([H])C([H])=C(O[H])C([H])=C1[H] 0.000 description 5
- 102100039364 Metalloproteinase inhibitor 1 Human genes 0.000 description 5
- 108010031374 Tissue Inhibitor of Metalloproteinase-1 Proteins 0.000 description 5
- 238000009825 accumulation Methods 0.000 description 5
- 125000000217 alkyl group Chemical group 0.000 description 5
- 210000002808 connective tissue Anatomy 0.000 description 5
- 230000008021 deposition Effects 0.000 description 5
- 238000011161 development Methods 0.000 description 5
- 208000002672 hepatitis B Diseases 0.000 description 5
- 239000007788 liquid Substances 0.000 description 5
- 210000005228 liver tissue Anatomy 0.000 description 5
- 230000017074 necrotic cell death Effects 0.000 description 5
- 230000003204 osmotic effect Effects 0.000 description 5
- 231100000241 scar Toxicity 0.000 description 5
- 230000007863 steatosis Effects 0.000 description 5
- 230000008961 swelling Effects 0.000 description 5
- 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 4
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 4
- 241000700159 Rattus Species 0.000 description 4
- 125000002947 alkylene group Chemical group 0.000 description 4
- 230000003510 anti-fibrotic effect Effects 0.000 description 4
- 125000003118 aryl group Chemical group 0.000 description 4
- 125000002619 bicyclic group Chemical group 0.000 description 4
- 230000015572 biosynthetic process Effects 0.000 description 4
- 230000006378 damage Effects 0.000 description 4
- 230000034994 death Effects 0.000 description 4
- 231100000517 death Toxicity 0.000 description 4
- 230000018109 developmental process Effects 0.000 description 4
- 239000006185 dispersion Substances 0.000 description 4
- 230000002440 hepatic effect Effects 0.000 description 4
- 210000003494 hepatocyte Anatomy 0.000 description 4
- 125000001072 heteroaryl group Chemical group 0.000 description 4
- 208000015181 infectious disease Diseases 0.000 description 4
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 4
- 230000037361 pathway Effects 0.000 description 4
- 210000003240 portal vein Anatomy 0.000 description 4
- 230000002829 reductive effect Effects 0.000 description 4
- 239000007787 solid Substances 0.000 description 4
- 208000024891 symptom Diseases 0.000 description 4
- 230000001225 therapeutic effect Effects 0.000 description 4
- 238000013518 transcription Methods 0.000 description 4
- 230000035897 transcription Effects 0.000 description 4
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 3
- 206010008909 Chronic Hepatitis Diseases 0.000 description 3
- 241000700721 Hepatitis B virus Species 0.000 description 3
- 241000124008 Mammalia Species 0.000 description 3
- MHZGAVWIXHVIET-UHFFFAOYSA-N N1(NC=NC=C1)C(=O)N Chemical compound N1(NC=NC=C1)C(=O)N MHZGAVWIXHVIET-UHFFFAOYSA-N 0.000 description 3
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
- 231100000354 acute hepatitis Toxicity 0.000 description 3
- 229960000074 biopharmaceutical Drugs 0.000 description 3
- 230000001587 cholestatic effect Effects 0.000 description 3
- 208000037976 chronic inflammation Diseases 0.000 description 3
- 230000006020 chronic inflammation Effects 0.000 description 3
- 230000007882 cirrhosis Effects 0.000 description 3
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
- 239000002552 dosage form Substances 0.000 description 3
- 210000002865 immune cell Anatomy 0.000 description 3
- 238000001802 infusion Methods 0.000 description 3
- 230000002147 killing effect Effects 0.000 description 3
- 210000001865 kupffer cell Anatomy 0.000 description 3
- 208000019423 liver disease Diseases 0.000 description 3
- 230000003908 liver function Effects 0.000 description 3
- 210000004698 lymphocyte Anatomy 0.000 description 3
- 230000003278 mimic effect Effects 0.000 description 3
- 230000007170 pathology Effects 0.000 description 3
- 229940002988 pegasys Drugs 0.000 description 3
- 108010092853 peginterferon alfa-2a Proteins 0.000 description 3
- CMPQUABWPXYYSH-UHFFFAOYSA-N phenyl phosphate Chemical compound OP(O)(=O)OC1=CC=CC=C1 CMPQUABWPXYYSH-UHFFFAOYSA-N 0.000 description 3
- 208000001297 phlebitis Diseases 0.000 description 3
- 239000003755 preservative agent Substances 0.000 description 3
- 102000004196 processed proteins & peptides Human genes 0.000 description 3
- 108090000765 processed proteins & peptides Proteins 0.000 description 3
- 229940002612 prodrug Drugs 0.000 description 3
- 239000000651 prodrug Substances 0.000 description 3
- 238000003753 real-time PCR Methods 0.000 description 3
- 230000008929 regeneration Effects 0.000 description 3
- 238000011069 regeneration method Methods 0.000 description 3
- 230000002441 reversible effect Effects 0.000 description 3
- 230000037390 scarring Effects 0.000 description 3
- 239000006228 supernatant Substances 0.000 description 3
- 239000000725 suspension Substances 0.000 description 3
- BBAWEDCPNXPBQM-GDEBMMAJSA-N telaprevir Chemical compound N([C@H](C(=O)N[C@H](C(=O)N1C[C@@H]2CCC[C@@H]2[C@H]1C(=O)N[C@@H](CCC)C(=O)C(=O)NC1CC1)C(C)(C)C)C1CCCCC1)C(=O)C1=CN=CC=N1 BBAWEDCPNXPBQM-GDEBMMAJSA-N 0.000 description 3
- 108091032973 (ribonucleotides)n+m Proteins 0.000 description 2
- IWUCXVSUMQZMFG-RGDLXGNYSA-N 1-[(2s,3s,4r,5s)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]-1,2,4-triazole-3-carboxamide Chemical compound N1=C(C(=O)N)N=CN1[C@@H]1[C@@H](O)[C@@H](O)[C@H](CO)O1 IWUCXVSUMQZMFG-RGDLXGNYSA-N 0.000 description 2
- ABEXEQSGABRUHS-UHFFFAOYSA-N 16-methylheptadecyl 16-methylheptadecanoate Chemical compound CC(C)CCCCCCCCCCCCCCCOC(=O)CCCCCCCCCCCCCCC(C)C ABEXEQSGABRUHS-UHFFFAOYSA-N 0.000 description 2
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 2
- 208000000419 Chronic Hepatitis B Diseases 0.000 description 2
- 241000725101 Clea Species 0.000 description 2
- 229920002261 Corn starch Polymers 0.000 description 2
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 2
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 2
- 102000010834 Extracellular Matrix Proteins Human genes 0.000 description 2
- 108010037362 Extracellular Matrix Proteins Proteins 0.000 description 2
- 101710181403 Frizzled Proteins 0.000 description 2
- 206010019663 Hepatic failure Diseases 0.000 description 2
- 241000282412 Homo Species 0.000 description 2
- 101710200424 Inosine-5'-monophosphate dehydrogenase Proteins 0.000 description 2
- 102100026720 Interferon beta Human genes 0.000 description 2
- 108090000467 Interferon-beta Proteins 0.000 description 2
- 241000764238 Isis Species 0.000 description 2
- 206010028980 Neoplasm Diseases 0.000 description 2
- 241000288906 Primates Species 0.000 description 2
- 102000016611 Proteoglycans Human genes 0.000 description 2
- 108010067787 Proteoglycans Proteins 0.000 description 2
- 101150032199 Rplp0 gene Proteins 0.000 description 2
- 229940122055 Serine protease inhibitor Drugs 0.000 description 2
- 101710102218 Serine protease inhibitor Proteins 0.000 description 2
- ZSJLQEPLLKMAKR-UHFFFAOYSA-N Streptozotocin Natural products O=NN(C)C(=O)NC1C(O)OC(CO)C(O)C1O ZSJLQEPLLKMAKR-UHFFFAOYSA-N 0.000 description 2
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 2
- 229930006000 Sucrose Natural products 0.000 description 2
- 108010078233 Thymalfasin Proteins 0.000 description 2
- 230000001154 acute effect Effects 0.000 description 2
- 208000038016 acute inflammation Diseases 0.000 description 2
- 230000006022 acute inflammation Effects 0.000 description 2
- 230000002293 adipogenic effect Effects 0.000 description 2
- 230000002776 aggregation Effects 0.000 description 2
- 238000004220 aggregation Methods 0.000 description 2
- 125000003342 alkenyl group Chemical group 0.000 description 2
- 230000008485 antagonism Effects 0.000 description 2
- 230000003110 anti-inflammatory effect Effects 0.000 description 2
- 125000003710 aryl alkyl group Chemical group 0.000 description 2
- 239000011230 binding agent Substances 0.000 description 2
- 239000000872 buffer Substances 0.000 description 2
- 230000001684 chronic effect Effects 0.000 description 2
- 238000000576 coating method Methods 0.000 description 2
- 238000002648 combination therapy Methods 0.000 description 2
- 239000002299 complementary DNA Substances 0.000 description 2
- 230000001276 controlling effect Effects 0.000 description 2
- 239000008120 corn starch Substances 0.000 description 2
- 230000003247 decreasing effect Effects 0.000 description 2
- 208000035475 disorder Diseases 0.000 description 2
- 239000002612 dispersion medium Substances 0.000 description 2
- 239000003651 drinking water Substances 0.000 description 2
- 235000020188 drinking water Nutrition 0.000 description 2
- 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 2
- 210000002744 extracellular matrix Anatomy 0.000 description 2
- 208000010706 fatty liver disease Diseases 0.000 description 2
- 239000000796 flavoring agent Substances 0.000 description 2
- 235000003599 food sweetener Nutrition 0.000 description 2
- 230000006870 function Effects 0.000 description 2
- 230000005484 gravity Effects 0.000 description 2
- 230000012010 growth Effects 0.000 description 2
- 238000007490 hematoxylin and eosin (H&E) staining Methods 0.000 description 2
- 206010019692 hepatic necrosis Diseases 0.000 description 2
- 235000009200 high fat diet Nutrition 0.000 description 2
- 238000010562 histological examination Methods 0.000 description 2
- 238000005417 image-selected in vivo spectroscopy Methods 0.000 description 2
- 239000002955 immunomodulating agent Substances 0.000 description 2
- 229940121354 immunomodulator Drugs 0.000 description 2
- 230000002584 immunomodulator Effects 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
- 210000004969 inflammatory cell Anatomy 0.000 description 2
- 208000027866 inflammatory disease Diseases 0.000 description 2
- 239000004615 ingredient Substances 0.000 description 2
- 230000002401 inhibitory effect Effects 0.000 description 2
- 208000014674 injury Diseases 0.000 description 2
- 238000012739 integrated shape imaging system Methods 0.000 description 2
- 230000003993 interaction Effects 0.000 description 2
- 108010010648 interferon alfacon-1 Proteins 0.000 description 2
- 238000001990 intravenous administration Methods 0.000 description 2
- 229940065638 intron a Drugs 0.000 description 2
- 230000002045 lasting effect Effects 0.000 description 2
- 230000003902 lesion Effects 0.000 description 2
- 150000002632 lipids Chemical class 0.000 description 2
- 210000005229 liver cell Anatomy 0.000 description 2
- 231100000835 liver failure Toxicity 0.000 description 2
- 208000007903 liver failure Diseases 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
- 239000011159 matrix material Substances 0.000 description 2
- 244000005700 microbiome Species 0.000 description 2
- 210000005087 mononuclear cell Anatomy 0.000 description 2
- 235000021590 normal diet Nutrition 0.000 description 2
- 239000003921 oil Substances 0.000 description 2
- 235000019198 oils Nutrition 0.000 description 2
- 239000006186 oral dosage form Substances 0.000 description 2
- 210000000056 organ Anatomy 0.000 description 2
- 230000001575 pathological effect Effects 0.000 description 2
- 108010092851 peginterferon alfa-2b Proteins 0.000 description 2
- 229940106366 pegintron Drugs 0.000 description 2
- 229920001223 polyethylene glycol Polymers 0.000 description 2
- 239000000843 powder Substances 0.000 description 2
- 230000035755 proliferation Effects 0.000 description 2
- 108020003175 receptors Proteins 0.000 description 2
- 102000005962 receptors Human genes 0.000 description 2
- 230000000284 resting effect Effects 0.000 description 2
- 238000003757 reverse transcription PCR Methods 0.000 description 2
- 150000003839 salts Chemical class 0.000 description 2
- 239000003001 serine protease inhibitor Substances 0.000 description 2
- 230000019491 signal transduction Effects 0.000 description 2
- 239000002904 solvent Substances 0.000 description 2
- 238000007619 statistical method Methods 0.000 description 2
- 238000003860 storage Methods 0.000 description 2
- ZSJLQEPLLKMAKR-GKHCUFPYSA-N streptozocin Chemical compound O=NN(C)C(=O)N[C@H]1[C@@H](O)O[C@H](CO)[C@@H](O)[C@@H]1O ZSJLQEPLLKMAKR-GKHCUFPYSA-N 0.000 description 2
- 229960001052 streptozocin Drugs 0.000 description 2
- 239000005720 sucrose Substances 0.000 description 2
- 235000000346 sugar Nutrition 0.000 description 2
- 239000004094 surface-active agent Substances 0.000 description 2
- 230000004083 survival effect Effects 0.000 description 2
- 239000003765 sweetening agent Substances 0.000 description 2
- 238000003786 synthesis reaction Methods 0.000 description 2
- 239000003826 tablet Substances 0.000 description 2
- 229960002935 telaprevir Drugs 0.000 description 2
- 108010017101 telaprevir Proteins 0.000 description 2
- NZVYCXVTEHPMHE-ZSUJOUNUSA-N thymalfasin Chemical compound CC(=O)N[C@@H](CO)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](C)C(=O)N[C@@H](C)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CO)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(N)=O)C(O)=O NZVYCXVTEHPMHE-ZSUJOUNUSA-N 0.000 description 2
- 230000007704 transition Effects 0.000 description 2
- UFTFJSFQGQCHQW-UHFFFAOYSA-N triformin Chemical compound O=COCC(OC=O)COC=O UFTFJSFQGQCHQW-UHFFFAOYSA-N 0.000 description 2
- SCVHJVCATBPIHN-SJCJKPOMSA-N (3s)-3-[[(2s)-2-[[2-(2-tert-butylanilino)-2-oxoacetyl]amino]propanoyl]amino]-4-oxo-5-(2,3,5,6-tetrafluorophenoxy)pentanoic acid Chemical compound N([C@@H](C)C(=O)N[C@@H](CC(O)=O)C(=O)COC=1C(=C(F)C=C(F)C=1F)F)C(=O)C(=O)NC1=CC=CC=C1C(C)(C)C SCVHJVCATBPIHN-SJCJKPOMSA-N 0.000 description 1
- HQWTUOLCGKIECB-XZWHSSHBSA-N (6S,9aS)-6-[(4-hydroxyphenyl)methyl]-8-(1-naphthalenylmethyl)-4,7-dioxo-N-(phenylmethyl)-3,6,9,9a-tetrahydro-2H-pyrazino[1,2-a]pyrimidine-1-carboxamide Chemical compound C1=CC(O)=CC=C1C[C@H]1C(=O)N(CC=2C3=CC=CC=C3C=CC=2)C[C@H]2N1C(=O)CCN2C(=O)NCC1=CC=CC=C1 HQWTUOLCGKIECB-XZWHSSHBSA-N 0.000 description 1
- FIMMXHIGADWXKC-LCPXNYKMSA-N (6s,9s)-8-(1-benzothiophen-3-ylmethyl)-n-benzyl-6-[(4-hydroxyphenyl)methyl]-2,9-dimethyl-4,7-dioxo-3,6,9,9a-tetrahydropyrazino[2,1-c][1,2,4]triazine-1-carboxamide Chemical compound C([C@@H]1N2C(=O)CN(C)N(C2[C@@H](N(C1=O)CC=1C2=CC=CC=C2SC=1)C)C(=O)NCC=1C=CC=CC=1)C1=CC=C(O)C=C1 FIMMXHIGADWXKC-LCPXNYKMSA-N 0.000 description 1
- NDPMOEWIGDGDHW-NRBFQMLQSA-N (6s,9s)-8-(2,1,3-benzothiadiazol-4-ylmethyl)-n-benzyl-6-[(4-hydroxyphenyl)methyl]-2,9-dimethyl-4,7-dioxo-3,6,9,9a-tetrahydropyrazino[2,1-c][1,2,4]triazine-1-carboxamide Chemical compound C([C@@H]1N2C(N(N(C)CC2=O)C(=O)NCC=2C=CC=CC=2)[C@@H](N(C1=O)CC=1C2=NSN=C2C=CC=1)C)C1=CC=C(O)C=C1 NDPMOEWIGDGDHW-NRBFQMLQSA-N 0.000 description 1
- MRGJQBPNTMSCQL-OTAVPDNUSA-N (6s,9s)-8-[(2-amino-1,3-benzothiazol-4-yl)methyl]-n-benzyl-6-[(4-hydroxyphenyl)methyl]-2,9-dimethyl-4,7-dioxo-3,6,9,9a-tetrahydropyrazino[2,1-c][1,2,4]triazine-1-carboxamide Chemical compound C([C@@H]1N2C(=O)CN(C)N(C2[C@@H](N(C1=O)CC=1C=2N=C(N)SC=2C=CC=1)C)C(=O)NCC=1C=CC=CC=1)C1=CC=C(O)C=C1 MRGJQBPNTMSCQL-OTAVPDNUSA-N 0.000 description 1
- KLGHKOORFHZFGO-ISZZHBKVSA-N (6s,9s)-n-benzyl-6-[(4-hydroxyphenyl)methyl]-2,9-dimethyl-4,7-dioxo-8-(quinolin-8-ylmethyl)-3,6,9,9a-tetrahydropyrazino[2,1-c][1,2,4]triazine-1-carboxamide Chemical compound C([C@@H]1N2C(N(N(C)CC2=O)C(=O)NCC=2C=CC=CC=2)[C@@H](N(C1=O)CC=1C2=NC=CC=C2C=CC=1)C)C1=CC=C(O)C=C1 KLGHKOORFHZFGO-ISZZHBKVSA-N 0.000 description 1
- SZSTZUAUXBGXTG-BYKCBHBLSA-N (6s,9s)-n-benzyl-6-[(4-hydroxyphenyl)methyl]-2,9-dimethyl-8-(naphthalen-1-ylmethyl)-4,7-dioxo-3,6,9,9a-tetrahydropyrazino[2,1-c][1,2,4]triazine-1-carboxamide Chemical compound C([C@@H]1N2C(N(N(C)CC2=O)C(=O)NCC=2C=CC=CC=2)[C@@H](N(C1=O)CC=1C2=CC=CC=C2C=CC=1)C)C1=CC=C(O)C=C1 SZSTZUAUXBGXTG-BYKCBHBLSA-N 0.000 description 1
- ZTEKOFICBUNGTR-KYDHLMDCSA-N (6s,9s)-n-benzyl-6-[(4-hydroxyphenyl)methyl]-8-(isoquinolin-5-ylmethyl)-2,9-dimethyl-4,7-dioxo-3,6,9,9a-tetrahydropyrazino[2,1-c][1,2,4]triazine-1-carboxamide Chemical compound C([C@@H]1N2C(N(N(C)CC2=O)C(=O)NCC=2C=CC=CC=2)[C@@H](N(C1=O)CC=1C2=CC=NC=C2C=CC=1)C)C1=CC=C(O)C=C1 ZTEKOFICBUNGTR-KYDHLMDCSA-N 0.000 description 1
- BYZVWJMAWBQNPA-KYDHLMDCSA-N (6s,9s)-n-benzyl-6-[(4-hydroxyphenyl)methyl]-9-methyl-8-(naphthalen-1-ylmethyl)-4,7-dioxo-9,9a-dihydro-6h-pyrazino[2,1-c][1,2,4]oxadiazine-1-carboxamide Chemical compound C([C@@H]1N2C(=O)CON(C2[C@@H](N(C1=O)CC=1C2=CC=CC=C2C=CC=1)C)C(=O)NCC=1C=CC=CC=1)C1=CC=C(O)C=C1 BYZVWJMAWBQNPA-KYDHLMDCSA-N 0.000 description 1
- SFTZRFVZRUJWGB-OMHHUHBJSA-N (6s,9s)-n-benzyl-8-[(5-chlorothieno[3,2-b]pyridin-3-yl)methyl]-6-[(4-hydroxyphenyl)methyl]-2,9-dimethyl-4,7-dioxo-3,6,9,9a-tetrahydropyrazino[2,1-c][1,2,4]triazine-1-carboxamide Chemical compound C([C@@H]1N2C(=O)CN(C)N(C2[C@@H](N(C1=O)CC=1C2=NC(Cl)=CC=C2SC=1)C)C(=O)NCC=1C=CC=CC=1)C1=CC=C(O)C=C1 SFTZRFVZRUJWGB-OMHHUHBJSA-N 0.000 description 1
- FPIPGXGPPPQFEQ-UHFFFAOYSA-N 13-cis retinol Natural products OCC=C(C)C=CC=C(C)C=CC1=C(C)CCCC1(C)C FPIPGXGPPPQFEQ-UHFFFAOYSA-N 0.000 description 1
- 102100040881 60S acidic ribosomal protein P0 Human genes 0.000 description 1
- 102000007469 Actins Human genes 0.000 description 1
- 108010085238 Actins Proteins 0.000 description 1
- 206010059193 Acute hepatitis B Diseases 0.000 description 1
- 102100036774 Afamin Human genes 0.000 description 1
- 102100036475 Alanine aminotransferase 1 Human genes 0.000 description 1
- 108010082126 Alanine transaminase Proteins 0.000 description 1
- 208000007082 Alcoholic Fatty Liver Diseases 0.000 description 1
- 208000022309 Alcoholic Liver disease Diseases 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
- 241000416162 Astragalus gummifer Species 0.000 description 1
- 238000009020 BCA Protein Assay Kit Methods 0.000 description 1
- 241000894006 Bacteria Species 0.000 description 1
- 229940096888 Beta tubulin inhibitor Drugs 0.000 description 1
- 208000031648 Body Weight Changes Diseases 0.000 description 1
- 241000283690 Bos taurus Species 0.000 description 1
- 239000011547 Bouin solution Substances 0.000 description 1
- 241000167854 Bourreria succulenta Species 0.000 description 1
- 238000011746 C57BL/6J (JAX™ mouse strain) Methods 0.000 description 1
- 229940123169 Caspase inhibitor Drugs 0.000 description 1
- 102000053642 Catalytic RNA Human genes 0.000 description 1
- 108090000994 Catalytic RNA Proteins 0.000 description 1
- 241000282693 Cercopithecidae Species 0.000 description 1
- 206010008635 Cholestasis Diseases 0.000 description 1
- 208000032544 Cicatrix Diseases 0.000 description 1
- 108020004635 Complementary DNA Proteins 0.000 description 1
- 102000005636 Cyclic AMP Response Element-Binding Protein Human genes 0.000 description 1
- 108010045171 Cyclic AMP Response Element-Binding Protein Proteins 0.000 description 1
- 102000004127 Cytokines Human genes 0.000 description 1
- 108090000695 Cytokines Proteins 0.000 description 1
- 238000000018 DNA microarray Methods 0.000 description 1
- 230000004568 DNA-binding Effects 0.000 description 1
- 101100317380 Danio rerio wnt4a gene Proteins 0.000 description 1
- 206010061818 Disease progression Diseases 0.000 description 1
- 241000283073 Equus caballus Species 0.000 description 1
- 208000000624 Esophageal and Gastric Varices Diseases 0.000 description 1
- 241000282326 Felis catus Species 0.000 description 1
- 102000016359 Fibronectins Human genes 0.000 description 1
- 108010067306 Fibronectins Proteins 0.000 description 1
- 241000710831 Flavivirus Species 0.000 description 1
- 241000233866 Fungi Species 0.000 description 1
- 206010051012 Gastric varices Diseases 0.000 description 1
- 108010010803 Gelatin Proteins 0.000 description 1
- 102000003886 Glycoproteins Human genes 0.000 description 1
- 108090000288 Glycoproteins Proteins 0.000 description 1
- 206010019708 Hepatic steatosis Diseases 0.000 description 1
- 206010019755 Hepatitis chronic active Diseases 0.000 description 1
- 206010019759 Hepatitis chronic persistent Diseases 0.000 description 1
- 206010019799 Hepatitis viral Diseases 0.000 description 1
- 206010019837 Hepatocellular injury Diseases 0.000 description 1
- 101000673456 Homo sapiens 60S acidic ribosomal protein P0 Proteins 0.000 description 1
- 101000910825 Homo sapiens Protein chibby homolog 1 Proteins 0.000 description 1
- 101000976959 Homo sapiens Transcription factor 4 Proteins 0.000 description 1
- 101000596771 Homo sapiens Transcription factor 7-like 2 Proteins 0.000 description 1
- 229920002153 Hydroxypropyl cellulose Polymers 0.000 description 1
- 102100034343 Integrase Human genes 0.000 description 1
- 108010078049 Interferon alpha-2 Proteins 0.000 description 1
- 108010005716 Interferon beta-1a Proteins 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
- 240000007472 Leucaena leucocephala Species 0.000 description 1
- 235000010643 Leucaena leucocephala Nutrition 0.000 description 1
- 206010067125 Liver injury Diseases 0.000 description 1
- 208000002720 Malnutrition Diseases 0.000 description 1
- 102000019256 Metalloproteinase inhibitor 1 Human genes 0.000 description 1
- 108050006599 Metalloproteinase inhibitor 1 Proteins 0.000 description 1
- 229920000168 Microcrystalline cellulose Polymers 0.000 description 1
- 241000713869 Moloney murine leukemia virus Species 0.000 description 1
- 241000699666 Mus <mouse, genus> Species 0.000 description 1
- 244000061176 Nicotiana tabacum Species 0.000 description 1
- 235000002637 Nicotiana tabacum Nutrition 0.000 description 1
- 208000008589 Obesity Diseases 0.000 description 1
- 229910019142 PO4 Inorganic materials 0.000 description 1
- 108010016731 PPAR gamma Proteins 0.000 description 1
- 102000003728 Peroxisome Proliferator-Activated Receptors Human genes 0.000 description 1
- 108090000029 Peroxisome Proliferator-Activated Receptors Proteins 0.000 description 1
- 102100038825 Peroxisome proliferator-activated receptor gamma Human genes 0.000 description 1
- 241000009328 Perro Species 0.000 description 1
- 208000037581 Persistent Infection Diseases 0.000 description 1
- 239000002202 Polyethylene glycol Substances 0.000 description 1
- 239000004743 Polypropylene Substances 0.000 description 1
- 102100026774 Protein chibby homolog 1 Human genes 0.000 description 1
- 108010092799 RNA-directed DNA polymerase Proteins 0.000 description 1
- 101710118046 RNA-directed RNA polymerase Proteins 0.000 description 1
- 238000010240 RT-PCR analysis Methods 0.000 description 1
- 108091027981 Response element Proteins 0.000 description 1
- 229920001800 Shellac Polymers 0.000 description 1
- YIQKLZYTHXTDDT-UHFFFAOYSA-H Sirius red F3B Chemical compound C1=CC(=CC=C1N=NC2=CC(=C(C=C2)N=NC3=C(C=C4C=C(C=CC4=C3[O-])NC(=O)NC5=CC6=CC(=C(C(=C6C=C5)[O-])N=NC7=C(C=C(C=C7)N=NC8=CC=C(C=C8)S(=O)(=O)[O-])S(=O)(=O)[O-])S(=O)(=O)O)S(=O)(=O)O)S(=O)(=O)[O-])S(=O)(=O)[O-].[Na+].[Na+].[Na+].[Na+].[Na+].[Na+] YIQKLZYTHXTDDT-UHFFFAOYSA-H 0.000 description 1
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 1
- 229920002472 Starch Polymers 0.000 description 1
- 241000282898 Sus scrofa Species 0.000 description 1
- 229920001615 Tragacanth Polymers 0.000 description 1
- 102000040945 Transcription factor Human genes 0.000 description 1
- 108091023040 Transcription factor Proteins 0.000 description 1
- 102100023489 Transcription factor 4 Human genes 0.000 description 1
- 208000036142 Viral infection Diseases 0.000 description 1
- FPIPGXGPPPQFEQ-BOOMUCAASA-N Vitamin A Natural products OC/C=C(/C)\C=C\C=C(\C)/C=C/C1=C(C)CCCC1(C)C FPIPGXGPPPQFEQ-BOOMUCAASA-N 0.000 description 1
- 108010020277 WD repeat containing planar cell polarity effector Proteins 0.000 description 1
- 101150010310 WNT-4 gene Proteins 0.000 description 1
- 235000010724 Wisteria floribunda Nutrition 0.000 description 1
- 102000006757 Wnt Receptors Human genes 0.000 description 1
- 108010047118 Wnt Receptors Proteins 0.000 description 1
- 102000052547 Wnt-1 Human genes 0.000 description 1
- 108700020987 Wnt-1 Proteins 0.000 description 1
- 102000052548 Wnt-4 Human genes 0.000 description 1
- 108700020984 Wnt-4 Proteins 0.000 description 1
- 208000027418 Wounds and injury Diseases 0.000 description 1
- VHOZWHQPEJGPCC-ISZZHBKVSA-N [4-[[(6s,9s)-1-(benzylcarbamoyl)-2,9-dimethyl-4,7-dioxo-8-(quinolin-8-ylmethyl)-3,6,9,9a-tetrahydropyrazino[2,1-c][1,2,4]triazin-6-yl]methyl]phenyl] dihydrogen phosphate Chemical compound C([C@@H]1N2C(N(N(C)CC2=O)C(=O)NCC=2C=CC=CC=2)[C@@H](N(C1=O)CC=1C2=NC=CC=C2C=CC=1)C)C1=CC=C(OP(O)(O)=O)C=C1 VHOZWHQPEJGPCC-ISZZHBKVSA-N 0.000 description 1
- 230000001594 aberrant effect Effects 0.000 description 1
- 238000002835 absorbance Methods 0.000 description 1
- 239000003070 absorption delaying agent Substances 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 238000005903 acid hydrolysis reaction Methods 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 239000013543 active substance Substances 0.000 description 1
- 208000037628 acute hepatitis B virus infection Diseases 0.000 description 1
- 239000003470 adrenal cortex hormone Substances 0.000 description 1
- 239000000443 aerosol Substances 0.000 description 1
- 239000000556 agonist Substances 0.000 description 1
- 208000026594 alcoholic fatty liver disease Diseases 0.000 description 1
- 150000001298 alcohols Chemical class 0.000 description 1
- 239000000783 alginic acid Substances 0.000 description 1
- 235000010443 alginic acid Nutrition 0.000 description 1
- 229920000615 alginic acid Polymers 0.000 description 1
- 229960001126 alginic acid Drugs 0.000 description 1
- 150000004781 alginic acids Chemical class 0.000 description 1
- FPIPGXGPPPQFEQ-OVSJKPMPSA-N all-trans-retinol Chemical compound OC\C=C(/C)\C=C\C=C(/C)\C=C\C1=C(C)CCCC1(C)C FPIPGXGPPPQFEQ-OVSJKPMPSA-N 0.000 description 1
- 108010090535 alpha-albumin Proteins 0.000 description 1
- WOLHOYHSEKDWQH-UHFFFAOYSA-N amantadine hydrochloride Chemical compound [Cl-].C1C(C2)CC3CC2CC1([NH3+])C3 WOLHOYHSEKDWQH-UHFFFAOYSA-N 0.000 description 1
- 230000037005 anaesthesia Effects 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 230000019552 anatomical structure morphogenesis Effects 0.000 description 1
- 239000003242 anti bacterial agent Substances 0.000 description 1
- 230000000390 anti-adipogenic effect Effects 0.000 description 1
- 230000000844 anti-bacterial effect Effects 0.000 description 1
- 230000000692 anti-sense effect Effects 0.000 description 1
- 239000003146 anticoagulant agent Substances 0.000 description 1
- 229940127219 anticoagulant drug Drugs 0.000 description 1
- 229940121375 antifungal agent Drugs 0.000 description 1
- 239000003429 antifungal agent Substances 0.000 description 1
- 239000003443 antiviral agent Substances 0.000 description 1
- 230000006907 apoptotic process Effects 0.000 description 1
- 238000013459 approach Methods 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 239000000305 astragalus gummifer gum Substances 0.000 description 1
- 230000006399 behavior Effects 0.000 description 1
- AFYNADDZULBEJA-UHFFFAOYSA-N bicinchoninic acid Chemical compound C1=CC=CC2=NC(C=3C=C(C4=CC=CC=C4N=3)C(=O)O)=CC(C(O)=O)=C21 AFYNADDZULBEJA-UHFFFAOYSA-N 0.000 description 1
- 210000000741 bile canaliculi Anatomy 0.000 description 1
- 230000027455 binding Effects 0.000 description 1
- 230000000903 blocking effect Effects 0.000 description 1
- 230000017531 blood circulation Effects 0.000 description 1
- 230000004579 body weight change Effects 0.000 description 1
- 238000010804 cDNA synthesis Methods 0.000 description 1
- FUFJGUQYACFECW-UHFFFAOYSA-L calcium hydrogenphosphate Chemical compound [Ca+2].OP([O-])([O-])=O FUFJGUQYACFECW-UHFFFAOYSA-L 0.000 description 1
- 201000011510 cancer Diseases 0.000 description 1
- 238000012754 cardiac puncture Methods 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 230000015556 catabolic process Effects 0.000 description 1
- 230000020411 cell activation Effects 0.000 description 1
- 230000011712 cell development Effects 0.000 description 1
- 230000004663 cell proliferation Effects 0.000 description 1
- 230000001413 cellular effect Effects 0.000 description 1
- 238000005119 centrifugation Methods 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 235000019693 cherries Nutrition 0.000 description 1
- 239000007958 cherry flavor Substances 0.000 description 1
- VDQQXEISLMTGAB-UHFFFAOYSA-N chloramine T Chemical compound [Na+].CC1=CC=C(S(=O)(=O)[N-]Cl)C=C1 VDQQXEISLMTGAB-UHFFFAOYSA-N 0.000 description 1
- WORJEOGGNQDSOE-UHFFFAOYSA-N chloroform;methanol Chemical compound OC.ClC(Cl)Cl WORJEOGGNQDSOE-UHFFFAOYSA-N 0.000 description 1
- SIHHLZPXQLFPMC-UHFFFAOYSA-N chloroform;methanol;hydrate Chemical compound O.OC.ClC(Cl)Cl SIHHLZPXQLFPMC-UHFFFAOYSA-N 0.000 description 1
- 231100000359 cholestasis Toxicity 0.000 description 1
- 230000007870 cholestasis Effects 0.000 description 1
- 208000016350 chronic hepatitis B virus infection Diseases 0.000 description 1
- PJZPDFUUXKKDNB-KNINVFKUSA-N ciluprevir Chemical compound N([C@@H]1C(=O)N2[C@H](C(N[C@@]3(C[C@H]3\C=C/CCCCC1)C(O)=O)=O)C[C@H](C2)OC=1C2=CC=C(C=C2N=C(C=1)C=1N=C(NC(C)C)SC=1)OC)C(=O)OC1CCCC1 PJZPDFUUXKKDNB-KNINVFKUSA-N 0.000 description 1
- 238000005352 clarification Methods 0.000 description 1
- 230000006690 co-activation Effects 0.000 description 1
- 239000003086 colorant Substances 0.000 description 1
- 238000013329 compounding Methods 0.000 description 1
- 238000010276 construction Methods 0.000 description 1
- 238000011109 contamination Methods 0.000 description 1
- 230000008602 contraction Effects 0.000 description 1
- 208000029078 coronary artery disease Diseases 0.000 description 1
- 239000006071 cream Substances 0.000 description 1
- 125000001316 cycloalkyl alkyl group Chemical group 0.000 description 1
- 230000001086 cytosolic effect Effects 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 238000006731 degradation reaction Methods 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 230000006866 deterioration Effects 0.000 description 1
- 206010012601 diabetes mellitus Diseases 0.000 description 1
- 235000019700 dicalcium phosphate Nutrition 0.000 description 1
- 229940095079 dicalcium phosphate anhydrous Drugs 0.000 description 1
- 230000004069 differentiation Effects 0.000 description 1
- 239000003085 diluting agent Substances 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
- 231100000676 disease causative agent Toxicity 0.000 description 1
- 230000005750 disease progression Effects 0.000 description 1
- 239000007884 disintegrant Substances 0.000 description 1
- VHJLVAABSRFDPM-QWWZWVQMSA-N dithiothreitol Chemical compound SC[C@@H](O)[C@H](O)CS VHJLVAABSRFDPM-QWWZWVQMSA-N 0.000 description 1
- 230000007783 downstream signaling Effects 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 238000001647 drug administration Methods 0.000 description 1
- 241001493065 dsRNA viruses Species 0.000 description 1
- 230000013020 embryo development Effects 0.000 description 1
- 230000017793 embryonic organ development Effects 0.000 description 1
- 229950000234 emricasan Drugs 0.000 description 1
- 230000002327 eosinophilic effect Effects 0.000 description 1
- 238000013401 experimental design Methods 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 238000010195 expression analysis Methods 0.000 description 1
- 239000010685 fatty oil Substances 0.000 description 1
- 208000036449 fibrotic liver disease Diseases 0.000 description 1
- 235000019634 flavors Nutrition 0.000 description 1
- 239000012530 fluid Substances 0.000 description 1
- 235000013355 food flavoring agent Nutrition 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 101150082773 fz gene Proteins 0.000 description 1
- 229920000159 gelatin Polymers 0.000 description 1
- 239000008273 gelatin Substances 0.000 description 1
- 235000019322 gelatine Nutrition 0.000 description 1
- 235000011852 gelatine desserts Nutrition 0.000 description 1
- 210000000224 granular leucocyte Anatomy 0.000 description 1
- 239000003979 granulating agent Substances 0.000 description 1
- 239000003102 growth factor Substances 0.000 description 1
- 229910052736 halogen Inorganic materials 0.000 description 1
- 125000005843 halogen group Chemical group 0.000 description 1
- 239000007902 hard capsule Substances 0.000 description 1
- 230000035876 healing Effects 0.000 description 1
- 230000036541 health Effects 0.000 description 1
- 231100000234 hepatic damage Toxicity 0.000 description 1
- 231100000844 hepatocellular carcinoma Toxicity 0.000 description 1
- 206010073071 hepatocellular carcinoma Diseases 0.000 description 1
- 125000004446 heteroarylalkyl group Chemical group 0.000 description 1
- 125000005885 heterocycloalkylalkyl group Chemical group 0.000 description 1
- 230000002962 histologic effect Effects 0.000 description 1
- 238000007489 histopathology method Methods 0.000 description 1
- 230000013632 homeostatic process Effects 0.000 description 1
- KIUKXJAPPMFGSW-MNSSHETKSA-N hyaluronan Chemical compound CC(=O)N[C@H]1[C@H](O)O[C@H](CO)[C@@H](O)C1O[C@H]1[C@H](O)[C@@H](O)[C@H](O[C@H]2[C@@H](C(O[C@H]3[C@@H]([C@@H](O)[C@H](O)[C@H](O3)C(O)=O)O)[C@H](O)[C@@H](CO)O2)NC(C)=O)[C@@H](C(O)=O)O1 KIUKXJAPPMFGSW-MNSSHETKSA-N 0.000 description 1
- 229920002674 hyaluronan Polymers 0.000 description 1
- 229940099552 hyaluronan Drugs 0.000 description 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 1
- WGCNASOHLSPBMP-UHFFFAOYSA-N hydroxyacetaldehyde Natural products OCC=O WGCNASOHLSPBMP-UHFFFAOYSA-N 0.000 description 1
- 239000001863 hydroxypropyl cellulose Substances 0.000 description 1
- 235000010977 hydroxypropyl cellulose Nutrition 0.000 description 1
- 206010020718 hyperplasia Diseases 0.000 description 1
- 210000000987 immune system Anatomy 0.000 description 1
- 230000001771 impaired effect Effects 0.000 description 1
- 230000001976 improved effect Effects 0.000 description 1
- 230000006698 induction Effects 0.000 description 1
- 230000001939 inductive effect Effects 0.000 description 1
- 230000002458 infectious effect Effects 0.000 description 1
- 229940090438 infergen Drugs 0.000 description 1
- 230000002757 inflammatory effect Effects 0.000 description 1
- 230000000977 initiatory effect Effects 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 230000005732 intercellular adhesion Effects 0.000 description 1
- 238000007918 intramuscular administration Methods 0.000 description 1
- 239000007951 isotonicity adjuster Substances 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- XMGQYMWWDOXHJM-UHFFFAOYSA-N limonene Chemical compound CC(=C)C1CCC(C)=CC1 XMGQYMWWDOXHJM-UHFFFAOYSA-N 0.000 description 1
- 239000002502 liposome Substances 0.000 description 1
- 201000007270 liver cancer Diseases 0.000 description 1
- 230000008818 liver damage Effects 0.000 description 1
- 208000018191 liver inflammation Diseases 0.000 description 1
- 231100000149 liver necrosis Toxicity 0.000 description 1
- 208000014018 liver neoplasm Diseases 0.000 description 1
- 150000004668 long chain fatty acids Chemical class 0.000 description 1
- 239000000314 lubricant Substances 0.000 description 1
- 210000004072 lung Anatomy 0.000 description 1
- 239000011777 magnesium Substances 0.000 description 1
- 235000019359 magnesium stearate Nutrition 0.000 description 1
- 238000012423 maintenance Methods 0.000 description 1
- 230000001071 malnutrition Effects 0.000 description 1
- 235000000824 malnutrition Nutrition 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 235000012054 meals Nutrition 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 239000002609 medium Substances 0.000 description 1
- 150000004667 medium chain fatty acids Chemical class 0.000 description 1
- 230000002503 metabolic effect Effects 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- 235000010270 methyl p-hydroxybenzoate Nutrition 0.000 description 1
- 229940016286 microcrystalline cellulose Drugs 0.000 description 1
- 235000019813 microcrystalline cellulose Nutrition 0.000 description 1
- 239000008108 microcrystalline cellulose Substances 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 239000003607 modifier Substances 0.000 description 1
- 238000012544 monitoring process Methods 0.000 description 1
- 210000003205 muscle Anatomy 0.000 description 1
- 210000000651 myofibroblast Anatomy 0.000 description 1
- 230000001338 necrotic effect Effects 0.000 description 1
- 235000020925 non fasting Nutrition 0.000 description 1
- 239000002773 nucleotide Substances 0.000 description 1
- 125000003729 nucleotide group Chemical group 0.000 description 1
- 208000015380 nutritional deficiency disease Diseases 0.000 description 1
- 235000020824 obesity Nutrition 0.000 description 1
- 239000002674 ointment Substances 0.000 description 1
- 239000007968 orange flavor Substances 0.000 description 1
- 230000036542 oxidative stress Effects 0.000 description 1
- 239000012188 paraffin wax Substances 0.000 description 1
- 244000052769 pathogen Species 0.000 description 1
- 230000008506 pathogenesis Effects 0.000 description 1
- 230000001717 pathogenic effect Effects 0.000 description 1
- 239000003614 peroxisome proliferator Substances 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
- 239000010452 phosphate Substances 0.000 description 1
- 239000002953 phosphate buffered saline Substances 0.000 description 1
- 230000035479 physiological effects, processes and functions Effects 0.000 description 1
- 230000035790 physiological processes and functions Effects 0.000 description 1
- 239000006187 pill Substances 0.000 description 1
- 210000004180 plasmocyte Anatomy 0.000 description 1
- 239000004417 polycarbonate Substances 0.000 description 1
- 229920000515 polycarbonate Polymers 0.000 description 1
- 229920005862 polyol Polymers 0.000 description 1
- 150000003077 polyols Chemical class 0.000 description 1
- 239000000244 polyoxyethylene sorbitan monooleate Substances 0.000 description 1
- 235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 description 1
- 229920001155 polypropylene Polymers 0.000 description 1
- 229940068968 polysorbate 80 Drugs 0.000 description 1
- 229920000053 polysorbate 80 Polymers 0.000 description 1
- 229920001592 potato starch Polymers 0.000 description 1
- 230000003389 potentiating effect Effects 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- 239000002243 precursor Substances 0.000 description 1
- 230000035935 pregnancy Effects 0.000 description 1
- 230000002335 preservative effect Effects 0.000 description 1
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- 238000004393 prognosis Methods 0.000 description 1
- 230000000750 progressive effect Effects 0.000 description 1
- 235000010232 propyl p-hydroxybenzoate Nutrition 0.000 description 1
- 230000002685 pulmonary effect Effects 0.000 description 1
- 238000004445 quantitative analysis Methods 0.000 description 1
- 238000013235 rat NASH model Methods 0.000 description 1
- 239000011541 reaction mixture Substances 0.000 description 1
- 239000002464 receptor antagonist Substances 0.000 description 1
- 229940044551 receptor antagonist Drugs 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 201000002793 renal fibrosis Diseases 0.000 description 1
- 230000008439 repair process Effects 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 230000008458 response to injury Effects 0.000 description 1
- 239000003161 ribonuclease inhibitor Substances 0.000 description 1
- 108091092562 ribozyme Proteins 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
- 229940081974 saccharin Drugs 0.000 description 1
- 235000019204 saccharin Nutrition 0.000 description 1
- 239000000901 saccharin and its Na,K and Ca salt Substances 0.000 description 1
- 230000037387 scars Effects 0.000 description 1
- 238000013207 serial dilution Methods 0.000 description 1
- ZLGIYFNHBLSMPS-ATJNOEHPSA-N shellac Chemical compound OCCCCCC(O)C(O)CCCCCCCC(O)=O.C1C23[C@H](C(O)=O)CCC2[C@](C)(CO)[C@@H]1C(C(O)=O)=C[C@@H]3O ZLGIYFNHBLSMPS-ATJNOEHPSA-N 0.000 description 1
- 239000004208 shellac Substances 0.000 description 1
- 229940113147 shellac Drugs 0.000 description 1
- 235000013874 shellac Nutrition 0.000 description 1
- 231100000161 signs of toxicity Toxicity 0.000 description 1
- 238000013424 sirius red staining Methods 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 239000007901 soft capsule Substances 0.000 description 1
- 239000007921 spray Substances 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- 125000001424 substituent group Chemical group 0.000 description 1
- 125000003107 substituted aryl group Chemical group 0.000 description 1
- 230000008093 supporting effect Effects 0.000 description 1
- 238000013268 sustained release Methods 0.000 description 1
- 239000012730 sustained-release form Substances 0.000 description 1
- 230000002195 synergetic effect Effects 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- NHKZSTHOYNWEEZ-AFCXAGJDSA-N taribavirin Chemical compound N1=C(C(=N)N)N=CN1[C@H]1[C@H](O)[C@H](O)[C@@H](CO)O1 NHKZSTHOYNWEEZ-AFCXAGJDSA-N 0.000 description 1
- 229950006081 taribavirin Drugs 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 229960004231 thymalfasin Drugs 0.000 description 1
- 230000000699 topical effect Effects 0.000 description 1
- 239000003053 toxin Substances 0.000 description 1
- 231100000765 toxin Toxicity 0.000 description 1
- 108700012359 toxins Proteins 0.000 description 1
- PMMYEEVYMWASQN-IMJSIDKUSA-N trans-4-Hydroxy-L-proline Natural products O[C@@H]1CN[C@H](C(O)=O)C1 PMMYEEVYMWASQN-IMJSIDKUSA-N 0.000 description 1
- 230000005945 translocation Effects 0.000 description 1
- 230000008733 trauma Effects 0.000 description 1
- 230000003827 upregulation Effects 0.000 description 1
- 239000013598 vector Substances 0.000 description 1
- 235000015112 vegetable and seed oil Nutrition 0.000 description 1
- 239000008158 vegetable oil Substances 0.000 description 1
- 210000003462 vein Anatomy 0.000 description 1
- 238000009423 ventilation Methods 0.000 description 1
- 201000001862 viral hepatitis Diseases 0.000 description 1
- 230000009385 viral infection Effects 0.000 description 1
- 235000019155 vitamin A Nutrition 0.000 description 1
- 239000011719 vitamin A Substances 0.000 description 1
- 229940045997 vitamin a Drugs 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
- 230000004580 weight loss Effects 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/4985—Pyrazines or piperazines ortho- or peri-condensed with heterocyclic ring systems
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/66—Phosphorus compounds
- A61K31/675—Phosphorus compounds having nitrogen as a ring hetero atom, e.g. pyridoxal phosphate
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/16—Drugs for disorders of the alimentary tract or the digestive system for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/06—Antihyperlipidemics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
- A61P31/20—Antivirals for DNA viruses
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Epidemiology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Engineering & Computer Science (AREA)
- Organic Chemistry (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Virology (AREA)
- Molecular Biology (AREA)
- Biotechnology (AREA)
- Diabetes (AREA)
- Hematology (AREA)
- Communicable Diseases (AREA)
- Oncology (AREA)
- Gastroenterology & Hepatology (AREA)
- Obesity (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201361892606P | 2013-10-18 | 2013-10-18 | |
| US61/892,606 | 2013-10-18 | ||
| PCT/IB2014/002846 WO2015056104A2 (en) | 2013-10-18 | 2014-10-17 | Treatment of hepatic fibrosis using an inhibitor of cbp/catenin |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| JP2016535082A JP2016535082A (ja) | 2016-11-10 |
| JP2016535082A5 JP2016535082A5 (OSRAM) | 2017-12-28 |
| JP6507336B2 true JP6507336B2 (ja) | 2019-05-08 |
Family
ID=52828810
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2016548443A Active JP6507336B2 (ja) | 2013-10-18 | 2014-10-17 | Ｃｂｐ／カテニン阻害剤を用いる肝線維症の治療 |
Country Status (5)
| Country | Link |
|---|---|
| US (1) | US20160263131A1 (OSRAM) |
| EP (1) | EP3057590B1 (OSRAM) |
| JP (1) | JP6507336B2 (OSRAM) |
| CN (1) | CN105899211A (OSRAM) |
| WO (1) | WO2015056104A2 (OSRAM) |
Families Citing this family (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US9700569B2 (en) * | 2012-12-12 | 2017-07-11 | Prism Pharma Co., Ltd. | Prevention or treatment agent for hepatic fibrosis |
| CN110240596B (zh) * | 2016-07-29 | 2020-09-11 | 新波制药有限公司 | 用于治疗hbv感染的治疗剂 |
| KR20180045213A (ko) * | 2016-10-25 | 2018-05-04 | 경상대학교산학협력단 | Icg-001을 함유하는 섬유증의 예방 또는 치료용 약학 조성물 |
| CN110691777B (zh) * | 2017-03-15 | 2024-03-01 | 诺和诺德牛津研究中心有限公司 | 大环化合物 |
| WO2020122022A1 (ja) * | 2018-12-10 | 2020-06-18 | 東京都 | 肝機能改善剤 |
| US12404284B2 (en) * | 2020-02-11 | 2025-09-02 | Ospedale San Raffaele S.R.L. | Spirocyclic inhibitors of hepatitis B virus |
| KR20210153908A (ko) * | 2020-06-11 | 2021-12-20 | 제이더블유중외제약 주식회사 | 코로나바이러스감염증-19(covid-19) 치료용 조성물 |
| CN113730403A (zh) * | 2021-09-26 | 2021-12-03 | 中山大学肿瘤防治中心（中山大学附属肿瘤医院、中山大学肿瘤研究所） | 化合物kya1797k制备抗hbv病毒药物中的应用 |
Family Cites Families (16)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| AU1570292A (en) | 1991-02-07 | 1992-09-07 | Board Of Trustees Of The University Of Illinois, The | Conformationally restricted mimetics of beta turns and beta bulges and peptides containing the same |
| CA2141447A1 (en) | 1992-08-06 | 1994-02-17 | Michael Kahn | Conformationally restricted mimetics of reverse turns and peptides containing the same |
| US5929237A (en) | 1995-10-27 | 1999-07-27 | Molecumetics Ltd. | Reverse-turn mimetics and methods relating thereto |
| US6184223B1 (en) | 1995-10-27 | 2001-02-06 | Molecumetics Ltd. | Reverse-turn mimetics and methods relating thereto |
| US6013458A (en) * | 1995-10-27 | 2000-01-11 | Molecumetics, Ltd. | Reverse-turn mimetics and methods relating thereto |
| US6294525B1 (en) | 1999-09-01 | 2001-09-25 | Molecumetics Ltd. | Reverse-turn mimetics and methods relating thereto |
| US7566711B2 (en) * | 2001-10-12 | 2009-07-28 | Choongwae Pharma Corporation | Reverse-turn mimetics and method relating thereto |
| AU2006227776A1 (en) * | 2005-03-18 | 2006-09-28 | Institute For Chemical Genomics | Alpha-helix mimetics and methods relating to the treatment of fibrosis |
| AU2006311433B2 (en) | 2005-11-08 | 2012-06-28 | Choongwae Pharma Corporation | Alpha-helix mimetics and method relating to the treatment of cancer stem cells |
| US20080009500A1 (en) | 2005-11-08 | 2008-01-10 | Michael Kahn | Alpha-helix mimetics and methods relating to the treatment of fibrotic disorders |
| AU2009255042B2 (en) * | 2008-06-06 | 2014-05-15 | Prism Biolab Corporation | Alpha helix mimetics and methods relating thereto |
| WO2010044485A1 (en) | 2008-10-14 | 2010-04-22 | Prism Biolab Corporation | Alpha helix mimetics in the treatment of cancer |
| US9040531B2 (en) | 2009-05-07 | 2015-05-26 | Prism BioLab Co., Ltd. | Alpha helix mimetics and methods relating thereto |
| US20130274215A1 (en) * | 2010-04-08 | 2013-10-17 | Fate Therapeutics, Inc. | Pharmaceutical compositions to treat fibrosis |
| EP2678341A1 (en) * | 2011-02-25 | 2014-01-01 | PRISM Pharma Co., Ltd. | Alpha helix mimetics and methods relating thereto |
| US9700569B2 (en) * | 2012-12-12 | 2017-07-11 | Prism Pharma Co., Ltd. | Prevention or treatment agent for hepatic fibrosis |
-
2014
- 2014-10-17 EP EP14853712.9A patent/EP3057590B1/en active Active
- 2014-10-17 CN CN201480057194.7A patent/CN105899211A/zh active Pending
- 2014-10-17 WO PCT/IB2014/002846 patent/WO2015056104A2/en not_active Ceased
- 2014-10-17 US US15/030,095 patent/US20160263131A1/en not_active Abandoned
- 2014-10-17 JP JP2016548443A patent/JP6507336B2/ja active Active
Also Published As
| Publication number | Publication date |
|---|---|
| CN105899211A (zh) | 2016-08-24 |
| WO2015056104A3 (en) | 2015-06-18 |
| EP3057590B1 (en) | 2019-11-27 |
| WO2015056104A2 (en) | 2015-04-23 |
| EP3057590A2 (en) | 2016-08-24 |
| EP3057590A4 (en) | 2017-06-07 |
| US20160263131A1 (en) | 2016-09-15 |
| JP2016535082A (ja) | 2016-11-10 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| JP6507336B2 (ja) | Ｃｂｐ／カテニン阻害剤を用いる肝線維症の治療 | |
| Ryu et al. | Dasatinib regulates LPS-induced microglial and astrocytic neuroinflammatory responses by inhibiting AKT/STAT3 signaling | |
| McCollum et al. | Angiotensin-(1–7) attenuates angiotensin II-induced cardiac remodeling associated with upregulation of dual-specificity phosphatase 1 | |
| Seo et al. | Genipin protects d-galactosamine and lipopolysaccharide-induced hepatic injury through suppression of the necroptosis-mediated inflammasome signaling | |
| JP2013529627A (ja) | ヒドロキシクロロキンまたはヒドロキシクロロキンおよび抗ウイルス剤の組合せを使用するｃ型肝炎ウイルス関連疾患の処置 | |
| JP2010520200A (ja) | 特定のマトリックスメタロプロテイナーゼ（ｍｍｐ）阻害剤を使用する肝疾患を治療する方法 | |
| Mo et al. | NLRP3 inflammasome in cardiovascular diseases: an update | |
| Guan et al. | Dysregulated chemokine signaling in cystic fibrosis lung disease: A potential therapeutic target | |
| Lei et al. | Synergistic neuroprotective effect of rasagiline and idebenone against retinal ischemia-reperfusion injury via the Lin28-let-7-Dicer pathway | |
| Niina et al. | A sustained prostacyclin analog, ONO-1301, attenuates pancreatic fibrosis in experimental chronic pancreatitis induced by dibutyltin dichloride in rats | |
| Benitez et al. | Cortistatin regulates fibrosis and myofibroblast activation in experimental hepatotoxic‐and cholestatic‐induced liver injury | |
| WO2014093711A1 (en) | Methods of treating hepatic fibrosis and associated diseases by regulating rev-erb activity | |
| Cheon et al. | Niclosamide suppresses RANKL-induced osteoclastogenesis and prevents LPS-induced bone loss | |
| JP2021527669A (ja) | 線維症の軽減又は治療のための組成物及び方法 | |
| US20150038674A1 (en) | Use of glp-2 analogues in pulmonary diseases for therapeutic purpose | |
| Chen et al. | PK2/PKR1 signaling regulates bladder function and sensation in rats with cyclophosphamide‐induced cystitis | |
| WO2019103984A1 (en) | Compositions including fatp1, fatp3, fatp4, fatp5, and/or fatp6 inhibitors and uses thereof | |
| US20220372169A1 (en) | Inhibition of the ve-ptp phosphatase protects the kidney from ischemia-reperfusion injury | |
| US20160166577A1 (en) | Treatment of pulmonary fibrosis using an inhibitor of cbp/catenin | |
| TW201813640A (zh) | 含ｓｒｃ同源區２蛋白酪胺酸磷酸酶－１增效劑用於改善纖維化之用途 | |
| JP2006504769A (ja) | 病理学的プロセスに関する遺伝子発現を制御するためのキナゾリノン組成物 | |
| US20130040899A1 (en) | Use of PEDF-Derived Polypeptides for Treating Liver Cirrhosis | |
| WO2023230593A1 (en) | Ptp1b inhibitors for treating lung injury | |
| Jangra et al. | Recent Advancements in Antifibrotic Therapies for Regression of Liver Fibrosis. Cells 2022, 11, 1500 | |
| KR20230137078A (ko) | 카테콜아민/adrb2 매개 간질환 치료제 스크리닝 방법 |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A821 Effective date: 20160517 |
|
| RD01 | Notification of change of attorney |
Free format text: JAPANESE INTERMEDIATE CODE: A7426 Effective date: 20160517 |
|
| A711 | Notification of change in applicant |
Free format text: JAPANESE INTERMEDIATE CODE: A711 Effective date: 20171013 |
|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20171016 |
|
| A621 | Written request for application examination |
Free format text: JAPANESE INTERMEDIATE CODE: A621 Effective date: 20171016 |
|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A821 Effective date: 20171013 |
|
| A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20180619 |
|
| A01 | Written decision to grant a patent or to grant a registration (utility model) |
Free format text: JAPANESE INTERMEDIATE CODE: A01 Effective date: 20181120 |
|
| A711 | Notification of change in applicant |
Free format text: JAPANESE INTERMEDIATE CODE: A712 Effective date: 20181121 |
|
| A61 | First payment of annual fees (during grant procedure) |
Free format text: JAPANESE INTERMEDIATE CODE: A61 Effective date: 20181220 |
|
| R150 | Certificate of patent or registration of utility model |
Ref document number: 6507336 Country of ref document: JP Free format text: JAPANESE INTERMEDIATE CODE: R150 |