JP6125610B2 - 代謝障害、高脂血症、糖尿病、脂肪性肝疾患及びアテローム性動脈硬化症の治療のための新規コレステロール代謝物、５−コレステン−３β，２５−ジオールジスルファート（２５ＨＣＤＳ） - Google Patents
代謝障害、高脂血症、糖尿病、脂肪性肝疾患及びアテローム性動脈硬化症の治療のための新規コレステロール代謝物、５−コレステン−３β，２５−ジオールジスルファート（２５ＨＣＤＳ） Download PDFInfo
- Publication number
- JP6125610B2 JP6125610B2 JP2015505762A JP2015505762A JP6125610B2 JP 6125610 B2 JP6125610 B2 JP 6125610B2 JP 2015505762 A JP2015505762 A JP 2015505762A JP 2015505762 A JP2015505762 A JP 2015505762A JP 6125610 B2 JP6125610 B2 JP 6125610B2
- Authority
- JP
- Japan
- Prior art keywords
- treatment
- 25hcds
- compound
- subject
- need
- 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.)
- Expired - Fee Related
Links
- 238000011282 treatment Methods 0.000 title claims description 100
- 208000031226 Hyperlipidaemia Diseases 0.000 title claims description 20
- 201000001320 Atherosclerosis Diseases 0.000 title claims description 16
- 208000010706 fatty liver disease Diseases 0.000 title claims description 15
- 206010012601 diabetes mellitus Diseases 0.000 title claims description 14
- INBGSXNNRGWLJU-ZHHJOTBYSA-N 25-hydroxycholesterol Chemical compound C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@@H](CCCC(C)(C)O)C)[C@@]1(C)CC2 INBGSXNNRGWLJU-ZHHJOTBYSA-N 0.000 title description 17
- 150000001841 cholesterols Chemical class 0.000 title description 11
- VFNGKCDDZUSWLR-UHFFFAOYSA-L disulfate(2-) Chemical compound [O-]S(=O)(=O)OS([O-])(=O)=O VFNGKCDDZUSWLR-UHFFFAOYSA-L 0.000 title description 5
- 208000030159 metabolic disease Diseases 0.000 title description 4
- 238000000034 method Methods 0.000 claims description 78
- 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 claims description 77
- 150000001875 compounds Chemical class 0.000 claims description 71
- 150000002632 lipids Chemical class 0.000 claims description 54
- 150000003839 salts Chemical class 0.000 claims description 39
- 239000000203 mixture Substances 0.000 claims description 37
- 230000009467 reduction Effects 0.000 claims description 36
- 230000015572 biosynthetic process Effects 0.000 claims description 35
- 235000012000 cholesterol Nutrition 0.000 claims description 35
- 239000008194 pharmaceutical composition Substances 0.000 claims description 35
- 230000004054 inflammatory process Effects 0.000 claims description 27
- 206010061218 Inflammation Diseases 0.000 claims description 26
- AKEJUJNQAAGONA-UHFFFAOYSA-N sulfur trioxide Chemical compound O=S(=O)=O AKEJUJNQAAGONA-UHFFFAOYSA-N 0.000 claims description 26
- 239000007788 liquid Substances 0.000 claims description 17
- 208000027866 inflammatory disease Diseases 0.000 claims description 16
- 239000007787 solid Substances 0.000 claims description 15
- 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 claims description 11
- 238000004519 manufacturing process Methods 0.000 claims description 11
- 239000002953 phosphate buffered saline Substances 0.000 claims description 11
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 11
- 230000037396 body weight Effects 0.000 claims description 10
- 239000000843 powder Substances 0.000 claims description 10
- 208000017170 Lipid metabolism disease Diseases 0.000 claims description 9
- 239000003708 ampul Substances 0.000 claims description 9
- 239000003085 diluting agent Substances 0.000 claims description 9
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 9
- -1 sulfur trioxide amine Chemical class 0.000 claims description 9
- 238000002347 injection Methods 0.000 claims description 8
- 239000007924 injection Substances 0.000 claims description 8
- 239000004067 bulking agent Substances 0.000 claims description 6
- DTGDZMYNKLTSKC-HKQCOZBKSA-N cholest-5-ene Chemical compound C1C=C2CCCC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CCCC(C)C)[C@@]1(C)CC2 DTGDZMYNKLTSKC-HKQCOZBKSA-N 0.000 claims description 6
- DTGDZMYNKLTSKC-UHFFFAOYSA-N cholest-5-ene Natural products C1C=C2CCCCC2(C)C2C1C1CCC(C(C)CCCC(C)C)C1(C)CC2 DTGDZMYNKLTSKC-UHFFFAOYSA-N 0.000 claims description 6
- 239000002775 capsule Substances 0.000 claims description 5
- 239000002552 dosage form Substances 0.000 claims description 5
- 238000010255 intramuscular injection Methods 0.000 claims description 5
- 239000007927 intramuscular injection Substances 0.000 claims description 5
- 238000007911 parenteral administration Methods 0.000 claims description 5
- 238000010254 subcutaneous injection Methods 0.000 claims description 5
- 239000007929 subcutaneous injection Substances 0.000 claims description 5
- 239000003826 tablet Substances 0.000 claims description 5
- 238000001990 intravenous administration Methods 0.000 claims description 4
- 239000008227 sterile water for injection Substances 0.000 claims description 4
- 230000014509 gene expression Effects 0.000 description 34
- 210000004185 liver Anatomy 0.000 description 24
- 208000008338 non-alcoholic fatty liver disease Diseases 0.000 description 22
- 210000004027 cell Anatomy 0.000 description 20
- 230000002829 reductive effect Effects 0.000 description 20
- 108020004999 messenger RNA Proteins 0.000 description 19
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 18
- 230000028709 inflammatory response Effects 0.000 description 17
- INBGSXNNRGWLJU-UHFFFAOYSA-N 25epsilon-Hydroxycholesterin Natural products C1C=C2CC(O)CCC2(C)C2C1C1CCC(C(CCCC(C)(C)O)C)C1(C)CC2 INBGSXNNRGWLJU-UHFFFAOYSA-N 0.000 description 16
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 16
- 108090000623 proteins and genes Proteins 0.000 description 16
- 108010016731 PPAR gamma Proteins 0.000 description 15
- 102100038825 Peroxisome proliferator-activated receptor gamma Human genes 0.000 description 15
- 210000003494 hepatocyte Anatomy 0.000 description 15
- 238000003786 synthesis reaction Methods 0.000 description 15
- 201000010099 disease Diseases 0.000 description 13
- 230000037356 lipid metabolism Effects 0.000 description 12
- PIUZYOCNZPYXOA-ZHHJOTBYSA-N [(3s,8s,9s,10r,13r,14s,17r)-17-[(2r)-6-hydroxy-6-methylheptan-2-yl]-10,13-dimethyl-2,3,4,7,8,9,11,12,14,15,16,17-dodecahydro-1h-cyclopenta[a]phenanthren-3-yl] hydrogen sulfate Chemical compound C1C=C2C[C@@H](OS(O)(=O)=O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@@H](CCCC(C)(C)O)C)[C@@]1(C)CC2 PIUZYOCNZPYXOA-ZHHJOTBYSA-N 0.000 description 11
- 239000003814 drug Substances 0.000 description 11
- 102000004169 proteins and genes Human genes 0.000 description 11
- 102000004190 Enzymes Human genes 0.000 description 10
- 108090000790 Enzymes Proteins 0.000 description 10
- 102000004286 Hydroxymethylglutaryl CoA Reductases Human genes 0.000 description 10
- 239000000047 product Substances 0.000 description 10
- 235000018102 proteins Nutrition 0.000 description 10
- 239000002904 solvent Substances 0.000 description 10
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 9
- 101001123331 Homo sapiens Peroxisome proliferator-activated receptor gamma coactivator 1-alpha Proteins 0.000 description 9
- 108090000895 Hydroxymethylglutaryl CoA Reductases Proteins 0.000 description 9
- 102100028960 Peroxisome proliferator-activated receptor gamma coactivator 1-alpha Human genes 0.000 description 9
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical group [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 9
- 230000000694 effects Effects 0.000 description 9
- 210000002540 macrophage Anatomy 0.000 description 9
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 9
- 230000001105 regulatory effect Effects 0.000 description 9
- 239000000126 substance Substances 0.000 description 9
- 150000003626 triacylglycerols Chemical class 0.000 description 9
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 8
- 241001465754 Metazoa Species 0.000 description 8
- 230000004913 activation Effects 0.000 description 8
- 235000009200 high fat diet Nutrition 0.000 description 8
- 239000000463 material Substances 0.000 description 8
- UFTFJSFQGQCHQW-UHFFFAOYSA-N triformin Chemical compound O=COCC(OC=O)COC=O UFTFJSFQGQCHQW-UHFFFAOYSA-N 0.000 description 8
- 102100022089 Acyl-[acyl-carrier-protein] hydrolase Human genes 0.000 description 7
- 108010039731 Fatty Acid Synthases Proteins 0.000 description 7
- 241000699670 Mus sp. Species 0.000 description 7
- 235000014113 dietary fatty acids Nutrition 0.000 description 7
- 229930195729 fatty acid Natural products 0.000 description 7
- 239000000194 fatty acid Substances 0.000 description 7
- 235000021588 free fatty acids Nutrition 0.000 description 7
- 238000001727 in vivo Methods 0.000 description 7
- 230000003834 intracellular effect Effects 0.000 description 7
- 239000003981 vehicle Substances 0.000 description 7
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 6
- 241000699666 Mus <mouse, genus> Species 0.000 description 6
- 229930182558 Sterol Natural products 0.000 description 6
- 108060008682 Tumor Necrosis Factor Proteins 0.000 description 6
- 102000000852 Tumor Necrosis Factor-alpha Human genes 0.000 description 6
- 230000035508 accumulation Effects 0.000 description 6
- 238000009825 accumulation Methods 0.000 description 6
- 238000004458 analytical method Methods 0.000 description 6
- 150000004665 fatty acids Chemical class 0.000 description 6
- 238000004128 high performance liquid chromatography Methods 0.000 description 6
- 230000002757 inflammatory effect Effects 0.000 description 6
- 230000004322 lipid homeostasis Effects 0.000 description 6
- 239000002609 medium Substances 0.000 description 6
- 238000003753 real-time PCR Methods 0.000 description 6
- 102000005962 receptors Human genes 0.000 description 6
- 108020003175 receptors Proteins 0.000 description 6
- 230000011664 signaling Effects 0.000 description 6
- 238000001228 spectrum Methods 0.000 description 6
- 150000003432 sterols Chemical class 0.000 description 6
- 235000003702 sterols Nutrition 0.000 description 6
- 230000009885 systemic effect Effects 0.000 description 6
- 210000001519 tissue Anatomy 0.000 description 6
- 239000013598 vector Substances 0.000 description 6
- 206010020751 Hypersensitivity Diseases 0.000 description 5
- 206010067125 Liver injury Diseases 0.000 description 5
- 208000008589 Obesity Diseases 0.000 description 5
- 238000006243 chemical reaction Methods 0.000 description 5
- 208000019425 cirrhosis of liver Diseases 0.000 description 5
- 230000006378 damage Effects 0.000 description 5
- 235000005911 diet Nutrition 0.000 description 5
- 230000037213 diet Effects 0.000 description 5
- 229940079593 drug Drugs 0.000 description 5
- 238000001035 drying Methods 0.000 description 5
- 231100000234 hepatic damage Toxicity 0.000 description 5
- 230000008818 liver damage Effects 0.000 description 5
- 210000005228 liver tissue Anatomy 0.000 description 5
- 235000020824 obesity Nutrition 0.000 description 5
- 230000003389 potentiating effect Effects 0.000 description 5
- 230000002265 prevention Effects 0.000 description 5
- 230000008569 process Effects 0.000 description 5
- 239000000523 sample Substances 0.000 description 5
- 239000000243 solution Substances 0.000 description 5
- 238000004809 thin layer chromatography Methods 0.000 description 5
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 4
- 206010016654 Fibrosis Diseases 0.000 description 4
- 206010019708 Hepatic steatosis Diseases 0.000 description 4
- 101000979342 Homo sapiens Nuclear factor NF-kappa-B p105 subunit Proteins 0.000 description 4
- 201000002481 Myositis Diseases 0.000 description 4
- 102100023050 Nuclear factor NF-kappa-B p105 subunit Human genes 0.000 description 4
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 4
- 241000700159 Rattus Species 0.000 description 4
- 108010074436 Sterol Regulatory Element Binding Protein 1 Proteins 0.000 description 4
- 108010074438 Sterol Regulatory Element Binding Protein 2 Proteins 0.000 description 4
- 102100026841 Sterol regulatory element-binding protein 2 Human genes 0.000 description 4
- MUMGGOZAMZWBJJ-DYKIIFRCSA-N Testostosterone Chemical compound O=C1CC[C@]2(C)[C@H]3CC[C@](C)([C@H](CC4)O)[C@@H]4[C@@H]3CCC2=C1 MUMGGOZAMZWBJJ-DYKIIFRCSA-N 0.000 description 4
- 230000002159 abnormal effect Effects 0.000 description 4
- QTBSBXVTEAMEQO-HQMMCQRPSA-N acetic acid Chemical compound C[14C](O)=O QTBSBXVTEAMEQO-HQMMCQRPSA-N 0.000 description 4
- 238000003556 assay Methods 0.000 description 4
- 230000001684 chronic effect Effects 0.000 description 4
- 230000007882 cirrhosis Effects 0.000 description 4
- 230000007423 decrease Effects 0.000 description 4
- 230000003247 decreasing effect Effects 0.000 description 4
- 238000009472 formulation Methods 0.000 description 4
- 208000006454 hepatitis Diseases 0.000 description 4
- 230000005764 inhibitory process Effects 0.000 description 4
- 150000002500 ions Chemical class 0.000 description 4
- 230000006372 lipid accumulation Effects 0.000 description 4
- 206010053219 non-alcoholic steatohepatitis Diseases 0.000 description 4
- 230000037361 pathway Effects 0.000 description 4
- 230000004044 response Effects 0.000 description 4
- 210000002966 serum Anatomy 0.000 description 4
- 230000019491 signal transduction Effects 0.000 description 4
- 239000011734 sodium Substances 0.000 description 4
- 159000000000 sodium salts Chemical class 0.000 description 4
- 239000007858 starting material Substances 0.000 description 4
- QAOWNCQODCNURD-UHFFFAOYSA-L sulfate group Chemical group S(=O)(=O)([O-])[O-] QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 4
- GPRLSGONYQIRFK-MNYXATJNSA-N triton Chemical compound [3H+] GPRLSGONYQIRFK-MNYXATJNSA-N 0.000 description 4
- 108091032973 (ribonucleotides)n+m Proteins 0.000 description 3
- 101710194665 1-aminocyclopropane-1-carboxylate synthase Proteins 0.000 description 3
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 3
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
- 102100036475 Alanine aminotransferase 1 Human genes 0.000 description 3
- 108010082126 Alanine transaminase Proteins 0.000 description 3
- 102000002260 Alkaline Phosphatase Human genes 0.000 description 3
- 108020004774 Alkaline Phosphatase Proteins 0.000 description 3
- 208000023275 Autoimmune disease Diseases 0.000 description 3
- 108010074051 C-Reactive Protein Proteins 0.000 description 3
- 102100032752 C-reactive protein Human genes 0.000 description 3
- 102000004127 Cytokines Human genes 0.000 description 3
- 108090000695 Cytokines Proteins 0.000 description 3
- 108010010234 HDL Lipoproteins Proteins 0.000 description 3
- 102000015779 HDL Lipoproteins Human genes 0.000 description 3
- 208000028782 Hereditary disease Diseases 0.000 description 3
- 208000035150 Hypercholesterolemia Diseases 0.000 description 3
- 208000026350 Inborn Genetic disease Diseases 0.000 description 3
- 108090001005 Interleukin-6 Proteins 0.000 description 3
- 102000004889 Interleukin-6 Human genes 0.000 description 3
- 208000024556 Mendelian disease Diseases 0.000 description 3
- 238000013232 NAFLD rodent model Methods 0.000 description 3
- 102100033457 NF-kappa-B inhibitor beta Human genes 0.000 description 3
- 101710204094 NF-kappa-B inhibitor beta Proteins 0.000 description 3
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
- QTBSBXVTEAMEQO-UHFFFAOYSA-N acetic acid Substances CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- 230000033228 biological regulation Effects 0.000 description 3
- 210000004369 blood Anatomy 0.000 description 3
- 239000008280 blood Substances 0.000 description 3
- 239000003153 chemical reaction reagent Substances 0.000 description 3
- 238000011161 development Methods 0.000 description 3
- 150000002009 diols Chemical class 0.000 description 3
- 208000035475 disorder Diseases 0.000 description 3
- 238000000132 electrospray ionisation Methods 0.000 description 3
- 235000019197 fats Nutrition 0.000 description 3
- 102000006602 glyceraldehyde-3-phosphate dehydrogenase Human genes 0.000 description 3
- 108020004445 glyceraldehyde-3-phosphate dehydrogenase Proteins 0.000 description 3
- 231100000283 hepatitis Toxicity 0.000 description 3
- 206010073071 hepatocellular carcinoma Diseases 0.000 description 3
- 231100000844 hepatocellular carcinoma Toxicity 0.000 description 3
- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 3
- 208000006575 hypertriglyceridemia Diseases 0.000 description 3
- 238000000338 in vitro Methods 0.000 description 3
- 230000036512 infertility Effects 0.000 description 3
- 208000014674 injury Diseases 0.000 description 3
- 229940100601 interleukin-6 Drugs 0.000 description 3
- 229920000136 polysorbate Polymers 0.000 description 3
- 238000012545 processing Methods 0.000 description 3
- 230000000750 progressive effect Effects 0.000 description 3
- 239000011541 reaction mixture Substances 0.000 description 3
- 231100000240 steatosis hepatitis Toxicity 0.000 description 3
- 230000019635 sulfation Effects 0.000 description 3
- 238000005670 sulfation reaction Methods 0.000 description 3
- 238000002560 therapeutic procedure Methods 0.000 description 3
- FYHRJWMENCALJY-YSQMORBQSA-N (25R)-cholest-5-ene-3beta,26-diol 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)CCC[C@H](CO)C)[C@@]1(C)CC2 FYHRJWMENCALJY-YSQMORBQSA-N 0.000 description 2
- DKISDYAXCJJSLZ-UHFFFAOYSA-N 26-Hydroxy-cholesterin Natural products C1CC2CC(O)CCC2(C)C2C1C1CCC(C(C)CCCC(CO)C)C1(C)CC2 DKISDYAXCJJSLZ-UHFFFAOYSA-N 0.000 description 2
- 101150092476 ABCA1 gene Proteins 0.000 description 2
- 108700005241 ATP Binding Cassette Transporter 1 Proteins 0.000 description 2
- 102100039164 Acetyl-CoA carboxylase 1 Human genes 0.000 description 2
- 206010003210 Arteriosclerosis Diseases 0.000 description 2
- 108010003415 Aspartate Aminotransferases Proteins 0.000 description 2
- 102000004625 Aspartate Aminotransferases Human genes 0.000 description 2
- BPYKTIZUTYGOLE-IFADSCNNSA-N Bilirubin Chemical compound N1C(=O)C(C)=C(C=C)\C1=C\C1=C(C)C(CCC(O)=O)=C(CC2=C(C(C)=C(\C=C/3C(=C(C=C)C(=O)N\3)C)N2)CCC(O)=O)N1 BPYKTIZUTYGOLE-IFADSCNNSA-N 0.000 description 2
- 108010018763 Biotin carboxylase Proteins 0.000 description 2
- 208000024172 Cardiovascular disease Diseases 0.000 description 2
- 102000014914 Carrier Proteins Human genes 0.000 description 2
- 208000004930 Fatty Liver Diseases 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
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 2
- 206010020710 Hyperphagia Diseases 0.000 description 2
- 208000022559 Inflammatory bowel disease Diseases 0.000 description 2
- 102000003810 Interleukin-18 Human genes 0.000 description 2
- 108090000171 Interleukin-18 Proteins 0.000 description 2
- 102000004890 Interleukin-8 Human genes 0.000 description 2
- 108090001007 Interleukin-8 Proteins 0.000 description 2
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 2
- 108010007622 LDL Lipoproteins Proteins 0.000 description 2
- 102000007330 LDL Lipoproteins Human genes 0.000 description 2
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 2
- 102000004895 Lipoproteins Human genes 0.000 description 2
- 108090001030 Lipoproteins Proteins 0.000 description 2
- 241000124008 Mammalia Species 0.000 description 2
- 108010052419 NF-KappaB Inhibitor alpha Proteins 0.000 description 2
- 102100039337 NF-kappa-B inhibitor alpha Human genes 0.000 description 2
- 206010028980 Neoplasm Diseases 0.000 description 2
- 108020005497 Nuclear hormone receptor Proteins 0.000 description 2
- 239000012425 OXONE® Substances 0.000 description 2
- 241000283973 Oryctolagus cuniculus Species 0.000 description 2
- 239000002033 PVDF binder Substances 0.000 description 2
- 206010033645 Pancreatitis Diseases 0.000 description 2
- 206010033647 Pancreatitis acute Diseases 0.000 description 2
- 102100033616 Phospholipid-transporting ATPase ABCA1 Human genes 0.000 description 2
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 2
- PXIPVTKHYLBLMZ-UHFFFAOYSA-N Sodium azide Chemical compound [Na+].[N-]=[N+]=[N-] PXIPVTKHYLBLMZ-UHFFFAOYSA-N 0.000 description 2
- 102000008078 Sterol Regulatory Element Binding Protein 1 Human genes 0.000 description 2
- 102100026839 Sterol regulatory element-binding protein 1 Human genes 0.000 description 2
- NKANXQFJJICGDU-QPLCGJKRSA-N Tamoxifen Chemical compound C=1C=CC=CC=1C(/CC)=C(C=1C=CC(OCCN(C)C)=CC=1)/C1=CC=CC=C1 NKANXQFJJICGDU-QPLCGJKRSA-N 0.000 description 2
- 102000040945 Transcription factor Human genes 0.000 description 2
- 108091023040 Transcription factor Proteins 0.000 description 2
- 208000027418 Wounds and injury Diseases 0.000 description 2
- 229960000583 acetic acid Drugs 0.000 description 2
- 239000012190 activator Substances 0.000 description 2
- 201000003229 acute pancreatitis Diseases 0.000 description 2
- 239000000654 additive Substances 0.000 description 2
- 229910052783 alkali metal Inorganic materials 0.000 description 2
- 150000003863 ammonium salts Chemical class 0.000 description 2
- 230000003321 amplification Effects 0.000 description 2
- 238000010171 animal model Methods 0.000 description 2
- 239000005557 antagonist Substances 0.000 description 2
- 208000011775 arteriosclerosis disease Diseases 0.000 description 2
- 239000002585 base Substances 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
- 210000000013 bile duct Anatomy 0.000 description 2
- 108091008324 binding proteins Proteins 0.000 description 2
- 230000000903 blocking effect Effects 0.000 description 2
- 159000000007 calcium salts Chemical class 0.000 description 2
- 238000001460 carbon-13 nuclear magnetic resonance spectrum Methods 0.000 description 2
- 230000015556 catabolic process Effects 0.000 description 2
- 230000005779 cell damage Effects 0.000 description 2
- 208000037887 cell injury Diseases 0.000 description 2
- 239000003795 chemical substances by application Substances 0.000 description 2
- 238000012258 culturing Methods 0.000 description 2
- 238000006731 degradation reaction Methods 0.000 description 2
- 230000001419 dependent effect Effects 0.000 description 2
- 238000001514 detection method Methods 0.000 description 2
- 238000002474 experimental method Methods 0.000 description 2
- 238000013230 female C57BL/6J mice Methods 0.000 description 2
- 238000007710 freezing Methods 0.000 description 2
- 230000008014 freezing Effects 0.000 description 2
- 239000008103 glucose Substances 0.000 description 2
- 238000010438 heat treatment Methods 0.000 description 2
- 230000002440 hepatic effect Effects 0.000 description 2
- 210000000987 immune system Anatomy 0.000 description 2
- 208000026278 immune system disease Diseases 0.000 description 2
- 230000002401 inhibitory effect Effects 0.000 description 2
- NOESYZHRGYRDHS-UHFFFAOYSA-N insulin Chemical compound N1C(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(NC(=O)CN)C(C)CC)CSSCC(C(NC(CO)C(=O)NC(CC(C)C)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CCC(N)=O)C(=O)NC(CC(C)C)C(=O)NC(CCC(O)=O)C(=O)NC(CC(N)=O)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CSSCC(NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2C=CC(O)=CC=2)NC(=O)C(CC(C)C)NC(=O)C(C)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2NC=NC=2)NC(=O)C(CO)NC(=O)CNC2=O)C(=O)NCC(=O)NC(CCC(O)=O)C(=O)NC(CCCNC(N)=N)C(=O)NCC(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC(O)=CC=3)C(=O)NC(C(C)O)C(=O)N3C(CCC3)C(=O)NC(CCCCN)C(=O)NC(C)C(O)=O)C(=O)NC(CC(N)=O)C(O)=O)=O)NC(=O)C(C(C)CC)NC(=O)C(CO)NC(=O)C(C(C)O)NC(=O)C1CSSCC2NC(=O)C(CC(C)C)NC(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CC(N)=O)NC(=O)C(NC(=O)C(N)CC=1C=CC=CC=1)C(C)C)CC1=CN=CN1 NOESYZHRGYRDHS-UHFFFAOYSA-N 0.000 description 2
- XKTZWUACRZHVAN-VADRZIEHSA-N interleukin-8 Chemical compound C([C@H](NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC=1C2=CC=CC=C2NC=1)NC(=O)[C@@H](NC(C)=O)CCSC)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H]([C@@H](C)O)C(=O)NCC(=O)N[C@@H](CCSC)C(=O)N1[C@H](CCC1)C(=O)N1[C@H](CCC1)C(=O)N[C@@H](C)C(=O)N[C@H](CC(O)=O)C(=O)N[C@H](CCC(O)=O)C(=O)N[C@H](CC(O)=O)C(=O)N[C@H](CC=1C=CC(O)=CC=1)C(=O)N[C@H](CO)C(=O)N1[C@H](CCC1)C(N)=O)C1=CC=CC=C1 XKTZWUACRZHVAN-VADRZIEHSA-N 0.000 description 2
- 229940096397 interleukin-8 Drugs 0.000 description 2
- 239000008101 lactose Substances 0.000 description 2
- 239000003446 ligand Substances 0.000 description 2
- 229910003002 lithium salt Inorganic materials 0.000 description 2
- 159000000002 lithium salts Chemical class 0.000 description 2
- 230000001404 mediated effect Effects 0.000 description 2
- 239000012528 membrane Substances 0.000 description 2
- 230000004060 metabolic process Effects 0.000 description 2
- 239000002207 metabolite Substances 0.000 description 2
- LXCFILQKKLGQFO-UHFFFAOYSA-N methylparaben Chemical compound COC(=O)C1=CC=C(O)C=C1 LXCFILQKKLGQFO-UHFFFAOYSA-N 0.000 description 2
- 244000005700 microbiome Species 0.000 description 2
- 230000003228 microsomal effect Effects 0.000 description 2
- 210000001616 monocyte Anatomy 0.000 description 2
- DXASQZJWWGZNSF-UHFFFAOYSA-N n,n-dimethylmethanamine;sulfur trioxide Chemical compound CN(C)C.O=S(=O)=O DXASQZJWWGZNSF-UHFFFAOYSA-N 0.000 description 2
- 230000007935 neutral effect Effects 0.000 description 2
- 229910052757 nitrogen Inorganic materials 0.000 description 2
- 239000002736 nonionic surfactant Substances 0.000 description 2
- 102000006255 nuclear receptors Human genes 0.000 description 2
- 108020004017 nuclear receptors Proteins 0.000 description 2
- 238000003199 nucleic acid amplification method Methods 0.000 description 2
- 235000020830 overeating Nutrition 0.000 description 2
- 102000044160 oxysterol binding protein Human genes 0.000 description 2
- 108010040421 oxysterol binding protein Proteins 0.000 description 2
- 230000008506 pathogenesis Effects 0.000 description 2
- 239000008188 pellet Substances 0.000 description 2
- 239000003614 peroxisome proliferator Substances 0.000 description 2
- 229920002981 polyvinylidene fluoride Polymers 0.000 description 2
- XAEFZNCEHLXOMS-UHFFFAOYSA-M potassium benzoate Chemical compound [K+].[O-]C(=O)C1=CC=CC=C1 XAEFZNCEHLXOMS-UHFFFAOYSA-M 0.000 description 2
- 238000000425 proton nuclear magnetic resonance spectrum Methods 0.000 description 2
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 2
- 239000003642 reactive oxygen metabolite Substances 0.000 description 2
- 230000028503 regulation of lipid metabolic process Effects 0.000 description 2
- 230000002441 reversible effect Effects 0.000 description 2
- 230000028327 secretion Effects 0.000 description 2
- 150000003431 steroids Chemical class 0.000 description 2
- 208000011580 syndromic disease Diseases 0.000 description 2
- 238000012360 testing method Methods 0.000 description 2
- 229960003604 testosterone Drugs 0.000 description 2
- 230000001225 therapeutic effect Effects 0.000 description 2
- 230000032258 transport Effects 0.000 description 2
- 208000019553 vascular disease Diseases 0.000 description 2
- 238000001262 western blot Methods 0.000 description 2
- QGVLYPPODPLXMB-UBTYZVCOSA-N (1aR,1bS,4aR,7aS,7bS,8R,9R,9aS)-4a,7b,9,9a-tetrahydroxy-3-(hydroxymethyl)-1,1,6,8-tetramethyl-1,1a,1b,4,4a,7a,7b,8,9,9a-decahydro-5H-cyclopropa[3,4]benzo[1,2-e]azulen-5-one Chemical compound C1=C(CO)C[C@]2(O)C(=O)C(C)=C[C@H]2[C@@]2(O)[C@H](C)[C@@H](O)[C@@]3(O)C(C)(C)[C@H]3[C@@H]21 QGVLYPPODPLXMB-UBTYZVCOSA-N 0.000 description 1
- IXRAQYMAEVFORF-UTLNTRLCSA-N (3S,8S,9S,10R,13S,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]phenanthrene-3,16-diol Chemical compound C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC(O)[C@H]([C@H](C)CCCC(C)C)[C@@]1(C)CC2 IXRAQYMAEVFORF-UTLNTRLCSA-N 0.000 description 1
- DRCWOKJLSQUJPZ-DZGCQCFKSA-N (4ar,9as)-n-ethyl-1,4,9,9a-tetrahydrofluoren-4a-amine Chemical compound C1C2=CC=CC=C2[C@]2(NCC)[C@H]1CC=CC2 DRCWOKJLSQUJPZ-DZGCQCFKSA-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
- KJTLQQUUPVSXIM-ZCFIWIBFSA-N (R)-mevalonic acid Chemical compound OCC[C@](O)(C)CC(O)=O KJTLQQUUPVSXIM-ZCFIWIBFSA-N 0.000 description 1
- NSYDOBYFTHLPFM-UHFFFAOYSA-N 2-(2,2-dimethyl-1,3,6,2-dioxazasilocan-6-yl)ethanol Chemical compound C[Si]1(C)OCCN(CCO)CCO1 NSYDOBYFTHLPFM-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
- QSBYPNXLFMSGKH-UHFFFAOYSA-N 9-Heptadecensaeure Natural products CCCCCCCC=CCCCCCCCC(O)=O QSBYPNXLFMSGKH-UHFFFAOYSA-N 0.000 description 1
- 208000002874 Acne Vulgaris Diseases 0.000 description 1
- 108010085238 Actins Proteins 0.000 description 1
- 102000007469 Actins Human genes 0.000 description 1
- 201000011374 Alagille syndrome Diseases 0.000 description 1
- 208000007848 Alcoholism Diseases 0.000 description 1
- 208000035285 Allergic Seasonal Rhinitis Diseases 0.000 description 1
- ITPDYQOUSLNIHG-UHFFFAOYSA-N Amiodarone hydrochloride Chemical compound [Cl-].CCCCC=1OC2=CC=CC=C2C=1C(=O)C1=CC(I)=C(OCC[NH+](CC)CC)C(I)=C1 ITPDYQOUSLNIHG-UHFFFAOYSA-N 0.000 description 1
- QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 description 1
- 206010002198 Anaphylactic reaction Diseases 0.000 description 1
- BSYNRYMUTXBXSQ-UHFFFAOYSA-N Aspirin Chemical compound CC(=O)OC1=CC=CC=C1C(O)=O BSYNRYMUTXBXSQ-UHFFFAOYSA-N 0.000 description 1
- 206010003827 Autoimmune hepatitis Diseases 0.000 description 1
- 241000894006 Bacteria Species 0.000 description 1
- 208000035143 Bacterial infection Diseases 0.000 description 1
- 206010004593 Bile duct cancer Diseases 0.000 description 1
- 208000008439 Biliary Liver Cirrhosis Diseases 0.000 description 1
- 208000033222 Biliary cirrhosis primary Diseases 0.000 description 1
- 208000007257 Budd-Chiari syndrome Diseases 0.000 description 1
- DDYBGACOJKQPEC-UHFFFAOYSA-N CC(C)=O.O=S(=O)=O Chemical compound CC(C)=O.O=S(=O)=O DDYBGACOJKQPEC-UHFFFAOYSA-N 0.000 description 1
- 0 CC(CCCC(C)(C)*)C(CC1)C(C)(CC2)C1C1C2C(C)(CCC(*)C2)C2=CC1 Chemical compound CC(CCCC(C)(C)*)C(CC1)C(C)(CC2)C1C1C2C(C)(CCC(*)C2)C2=CC1 0.000 description 1
- 206010006895 Cachexia Diseases 0.000 description 1
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
- 241000283707 Capra Species 0.000 description 1
- 206010008609 Cholangitis sclerosing Diseases 0.000 description 1
- 206010008635 Cholestasis Diseases 0.000 description 1
- 238000008620 Cholesterol Assay Methods 0.000 description 1
- 108010089254 Cholesterol oxidase Proteins 0.000 description 1
- 206010057573 Chronic hepatic failure Diseases 0.000 description 1
- 108010004103 Chylomicrons Proteins 0.000 description 1
- 208000015943 Coeliac disease Diseases 0.000 description 1
- RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 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
- KJTLQQUUPVSXIM-UHFFFAOYSA-N DL-mevalonic acid Natural products OCCC(O)(C)CC(O)=O KJTLQQUUPVSXIM-UHFFFAOYSA-N 0.000 description 1
- 102000016911 Deoxyribonucleases Human genes 0.000 description 1
- 108010053770 Deoxyribonucleases Proteins 0.000 description 1
- 208000035762 Disorder of lipid metabolism Diseases 0.000 description 1
- 206010014476 Elevated cholesterol Diseases 0.000 description 1
- 206010014486 Elevated triglycerides Diseases 0.000 description 1
- 208000010334 End Stage Liver Disease Diseases 0.000 description 1
- 238000005033 Fourier transform infrared spectroscopy Methods 0.000 description 1
- 241000233866 Fungi Species 0.000 description 1
- 208000009139 Gilbert Disease Diseases 0.000 description 1
- 208000022412 Gilbert syndrome Diseases 0.000 description 1
- 206010018364 Glomerulonephritis Diseases 0.000 description 1
- 239000004471 Glycine Substances 0.000 description 1
- 108010023302 HDL Cholesterol Proteins 0.000 description 1
- 208000018565 Hemochromatosis Diseases 0.000 description 1
- 206010019799 Hepatitis viral Diseases 0.000 description 1
- 208000002972 Hepatolenticular Degeneration Diseases 0.000 description 1
- 241000282412 Homo Species 0.000 description 1
- 101000988577 Homo sapiens 3-hydroxy-3-methylglutaryl-coenzyme A reductase Proteins 0.000 description 1
- 101001051093 Homo sapiens Low-density lipoprotein receptor Proteins 0.000 description 1
- 101001008429 Homo sapiens Nucleobindin-2 Proteins 0.000 description 1
- 101000875401 Homo sapiens Sterol 26-hydroxylase, mitochondrial Proteins 0.000 description 1
- 101000629597 Homo sapiens Sterol regulatory element-binding protein 1 Proteins 0.000 description 1
- 101000629605 Homo sapiens Sterol regulatory element-binding protein 2 Proteins 0.000 description 1
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
- 102000004877 Insulin Human genes 0.000 description 1
- 108090001061 Insulin Proteins 0.000 description 1
- 208000031773 Insulin resistance syndrome Diseases 0.000 description 1
- 208000005615 Interstitial Cystitis Diseases 0.000 description 1
- FBOZXECLQNJBKD-ZDUSSCGKSA-N L-methotrexate Chemical compound C=1N=C2N=C(N)N=C(N)C2=NC=1CN(C)C1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 FBOZXECLQNJBKD-ZDUSSCGKSA-N 0.000 description 1
- 102000016267 Leptin Human genes 0.000 description 1
- 108010092277 Leptin Proteins 0.000 description 1
- WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 1
- 102100024640 Low-density lipoprotein receptor Human genes 0.000 description 1
- 229930195725 Mannitol Natural products 0.000 description 1
- 108010090837 Member 5 Subfamily G ATP Binding Cassette Transporter Proteins 0.000 description 1
- 102000013436 Member 5 Subfamily G ATP Binding Cassette Transporter Human genes 0.000 description 1
- 108010052285 Membrane Proteins Proteins 0.000 description 1
- 102000018697 Membrane Proteins Human genes 0.000 description 1
- 208000001145 Metabolic Syndrome Diseases 0.000 description 1
- PCZOHLXUXFIOCF-UHFFFAOYSA-N Monacolin X Natural products C12C(OC(=O)C(C)CC)CC(C)C=C2C=CC(C)C1CCC1CC(O)CC(=O)O1 PCZOHLXUXFIOCF-UHFFFAOYSA-N 0.000 description 1
- 208000021642 Muscular disease Diseases 0.000 description 1
- 201000009623 Myopathy Diseases 0.000 description 1
- 101000915175 Nicotiana tabacum 5-epi-aristolochene synthase Proteins 0.000 description 1
- 102100027441 Nucleobindin-2 Human genes 0.000 description 1
- 206010061876 Obstruction Diseases 0.000 description 1
- 239000005642 Oleic acid Substances 0.000 description 1
- ZQPPMHVWECSIRJ-UHFFFAOYSA-N Oleic acid Natural products CCCCCCCCC=CCCCCCCCC(O)=O ZQPPMHVWECSIRJ-UHFFFAOYSA-N 0.000 description 1
- 239000012807 PCR reagent Substances 0.000 description 1
- 208000029082 Pelvic Inflammatory Disease Diseases 0.000 description 1
- 102000003992 Peroxidases Human genes 0.000 description 1
- 229940080774 Peroxisome proliferator-activated receptor gamma agonist Drugs 0.000 description 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
- 208000012654 Primary biliary cholangitis Diseases 0.000 description 1
- 238000010802 RNA extraction kit Methods 0.000 description 1
- 238000010240 RT-PCR analysis Methods 0.000 description 1
- 108020004511 Recombinant DNA Proteins 0.000 description 1
- 206010063837 Reperfusion injury Diseases 0.000 description 1
- 201000007981 Reye syndrome Diseases 0.000 description 1
- 229920002472 Starch Polymers 0.000 description 1
- 102100036325 Sterol 26-hydroxylase, mitochondrial Human genes 0.000 description 1
- 208000006011 Stroke Diseases 0.000 description 1
- 238000000692 Student's t-test Methods 0.000 description 1
- 102000004896 Sulfotransferases Human genes 0.000 description 1
- 108090001033 Sulfotransferases Proteins 0.000 description 1
- 201000009594 Systemic Scleroderma Diseases 0.000 description 1
- 206010042953 Systemic sclerosis Diseases 0.000 description 1
- 239000004098 Tetracycline Substances 0.000 description 1
- 206010052779 Transplant rejections Diseases 0.000 description 1
- 108010062497 VLDL Lipoproteins Proteins 0.000 description 1
- 206010047115 Vasculitis Diseases 0.000 description 1
- 206010058990 Venous occlusion Diseases 0.000 description 1
- 241000700605 Viruses Species 0.000 description 1
- 208000018839 Wilson disease Diseases 0.000 description 1
- 201000000690 abdominal obesity-metabolic syndrome Diseases 0.000 description 1
- 230000005856 abnormality Effects 0.000 description 1
- AOZUYISQWWJMJC-UHFFFAOYSA-N acetic acid;methanol;hydrate Chemical compound O.OC.CC(O)=O AOZUYISQWWJMJC-UHFFFAOYSA-N 0.000 description 1
- WDJHALXBUFZDSR-UHFFFAOYSA-N acetoacetic acid Chemical compound CC(=O)CC(O)=O WDJHALXBUFZDSR-UHFFFAOYSA-N 0.000 description 1
- 229960001138 acetylsalicylic acid Drugs 0.000 description 1
- 206010000496 acne Diseases 0.000 description 1
- 239000013543 active substance Substances 0.000 description 1
- 208000038016 acute inflammation Diseases 0.000 description 1
- 230000006022 acute inflammation Effects 0.000 description 1
- 230000000996 additive effect Effects 0.000 description 1
- 239000002671 adjuvant Substances 0.000 description 1
- 239000000443 aerosol Substances 0.000 description 1
- 201000007930 alcohol dependence Diseases 0.000 description 1
- 150000001298 alcohols Chemical class 0.000 description 1
- 229910052784 alkaline earth metal Inorganic materials 0.000 description 1
- 150000001342 alkaline earth metals Chemical class 0.000 description 1
- 239000013566 allergen Substances 0.000 description 1
- 208000030961 allergic reaction Diseases 0.000 description 1
- 208000006682 alpha 1-Antitrypsin Deficiency Diseases 0.000 description 1
- 230000004075 alteration Effects 0.000 description 1
- 229960005260 amiodarone Drugs 0.000 description 1
- 230000036783 anaphylactic response Effects 0.000 description 1
- 208000003455 anaphylaxis Diseases 0.000 description 1
- 150000001450 anions Chemical class 0.000 description 1
- 230000003466 anti-cipated effect Effects 0.000 description 1
- 239000003416 antiarrhythmic agent Substances 0.000 description 1
- 230000005875 antibody response Effects 0.000 description 1
- 239000003443 antiviral agent Substances 0.000 description 1
- 230000006907 apoptotic process Effects 0.000 description 1
- 208000006673 asthma Diseases 0.000 description 1
- 208000010216 atopic IgE responsiveness Diseases 0.000 description 1
- 230000001363 autoimmune Effects 0.000 description 1
- 230000006472 autoimmune response Effects 0.000 description 1
- 208000022362 bacterial infectious disease Diseases 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 230000008901 benefit Effects 0.000 description 1
- 229960000686 benzalkonium chloride Drugs 0.000 description 1
- CADWTSSKOVRVJC-UHFFFAOYSA-N benzyl(dimethyl)azanium;chloride Chemical compound [Cl-].C[NH+](C)CC1=CC=CC=C1 CADWTSSKOVRVJC-UHFFFAOYSA-N 0.000 description 1
- 208000026900 bile duct neoplasm Diseases 0.000 description 1
- 239000011230 binding agent Substances 0.000 description 1
- 230000008827 biological function Effects 0.000 description 1
- 230000008687 biosynthesis inhibition Effects 0.000 description 1
- 238000009534 blood test Methods 0.000 description 1
- 239000000872 buffer Substances 0.000 description 1
- 238000010804 cDNA synthesis Methods 0.000 description 1
- 229910052791 calcium Inorganic materials 0.000 description 1
- 239000011575 calcium Substances 0.000 description 1
- 235000019577 caloric intake Nutrition 0.000 description 1
- 201000011510 cancer Diseases 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 150000001768 cations Chemical class 0.000 description 1
- 238000004113 cell culture Methods 0.000 description 1
- 239000012578 cell culture reagent Substances 0.000 description 1
- 239000012592 cell culture supplement Substances 0.000 description 1
- 230000001413 cellular effect Effects 0.000 description 1
- 230000010001 cellular homeostasis Effects 0.000 description 1
- 238000005119 centrifugation Methods 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 150000001793 charged compounds Chemical class 0.000 description 1
- 239000013626 chemical specie Substances 0.000 description 1
- 208000006990 cholangiocarcinoma Diseases 0.000 description 1
- 201000001883 cholelithiasis Diseases 0.000 description 1
- 231100000359 cholestasis Toxicity 0.000 description 1
- 230000007870 cholestasis Effects 0.000 description 1
- 150000001840 cholesterol esters Chemical class 0.000 description 1
- 230000031154 cholesterol homeostasis Effects 0.000 description 1
- 208000037976 chronic inflammation Diseases 0.000 description 1
- 230000006020 chronic inflammation Effects 0.000 description 1
- 208000011444 chronic liver failure Diseases 0.000 description 1
- 208000013507 chronic prostatitis Diseases 0.000 description 1
- 238000000576 coating method Methods 0.000 description 1
- 230000019771 cognition Effects 0.000 description 1
- 239000003086 colorant Substances 0.000 description 1
- 230000000052 comparative effect Effects 0.000 description 1
- 239000002131 composite material Substances 0.000 description 1
- 229910052802 copper Inorganic materials 0.000 description 1
- 239000010949 copper Substances 0.000 description 1
- 208000029078 coronary artery disease Diseases 0.000 description 1
- 239000003246 corticosteroid Substances 0.000 description 1
- 229960001334 corticosteroids Drugs 0.000 description 1
- 210000000172 cytosol Anatomy 0.000 description 1
- 230000034994 death Effects 0.000 description 1
- 230000018044 dehydration Effects 0.000 description 1
- 238000006297 dehydration reaction Methods 0.000 description 1
- 201000001981 dermatomyositis Diseases 0.000 description 1
- 238000007865 diluting Methods 0.000 description 1
- XREKLQOUFWBSFH-UHFFFAOYSA-N dimethyl 2-acetylbutanedioate Chemical compound COC(=O)CC(C(C)=O)C(=O)OC XREKLQOUFWBSFH-UHFFFAOYSA-N 0.000 description 1
- 239000007884 disintegrant Substances 0.000 description 1
- 229920001971 elastomer Polymers 0.000 description 1
- 238000010828 elution Methods 0.000 description 1
- 210000002889 endothelial cell Anatomy 0.000 description 1
- 230000019439 energy homeostasis Effects 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 238000010195 expression analysis Methods 0.000 description 1
- 235000013861 fat-free Nutrition 0.000 description 1
- 230000004319 fatty acid homeostasis Effects 0.000 description 1
- 239000000796 flavoring agent Substances 0.000 description 1
- 238000004401 flow injection analysis Methods 0.000 description 1
- 235000013305 food Nutrition 0.000 description 1
- 235000013355 food flavoring agent Nutrition 0.000 description 1
- 238000004108 freeze drying Methods 0.000 description 1
- 239000012737 fresh medium Substances 0.000 description 1
- 230000006870 function Effects 0.000 description 1
- 208000001130 gallstones Diseases 0.000 description 1
- 210000001035 gastrointestinal tract Anatomy 0.000 description 1
- 238000003633 gene expression assay Methods 0.000 description 1
- 230000002068 genetic effect Effects 0.000 description 1
- 239000012362 glacial acetic acid Substances 0.000 description 1
- 208000007345 glycogen storage disease Diseases 0.000 description 1
- 230000036541 health Effects 0.000 description 1
- 231100000334 hepatotoxic Toxicity 0.000 description 1
- 230000003082 hepatotoxic effect Effects 0.000 description 1
- 210000003630 histaminocyte Anatomy 0.000 description 1
- 230000013632 homeostatic process Effects 0.000 description 1
- 102000049234 human SREBF1 Human genes 0.000 description 1
- 102000049151 human SREBF2 Human genes 0.000 description 1
- 230000036571 hydration Effects 0.000 description 1
- 238000006703 hydration reaction Methods 0.000 description 1
- 229910052739 hydrogen Inorganic materials 0.000 description 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 1
- 230000000640 hydroxylating effect Effects 0.000 description 1
- 230000033444 hydroxylation Effects 0.000 description 1
- 238000005805 hydroxylation reaction Methods 0.000 description 1
- 230000009610 hypersensitivity Effects 0.000 description 1
- 210000002865 immune cell Anatomy 0.000 description 1
- 230000028993 immune response Effects 0.000 description 1
- 208000016245 inborn errors of metabolism Diseases 0.000 description 1
- 201000008319 inclusion body myositis Diseases 0.000 description 1
- 238000011534 incubation Methods 0.000 description 1
- 239000011261 inert gas Substances 0.000 description 1
- 239000012442 inert solvent Substances 0.000 description 1
- 208000015181 infectious disease Diseases 0.000 description 1
- 238000002329 infrared spectrum Methods 0.000 description 1
- 239000004615 ingredient Substances 0.000 description 1
- 208000015978 inherited metabolic disease Diseases 0.000 description 1
- 239000007972 injectable composition Substances 0.000 description 1
- 229940030980 inova Drugs 0.000 description 1
- 229940125396 insulin Drugs 0.000 description 1
- 239000007928 intraperitoneal injection Substances 0.000 description 1
- 238000010253 intravenous injection Methods 0.000 description 1
- 229910052742 iron Inorganic materials 0.000 description 1
- QXJSBBXBKPUZAA-UHFFFAOYSA-N isooleic acid Natural products CCCCCCCC=CCCCCCCCCC(O)=O QXJSBBXBKPUZAA-UHFFFAOYSA-N 0.000 description 1
- NRYBAZVQPHGZNS-ZSOCWYAHSA-N leptin Chemical compound O=C([C@H](CO)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CC=1C2=CC=CC=C2NC=1)NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CO)NC(=O)CNC(=O)[C@H](CCC(N)=O)NC(=O)[C@@H](N)CC(C)C)CCSC)N1CCC[C@H]1C(=O)NCC(=O)N[C@@H](CS)C(O)=O NRYBAZVQPHGZNS-ZSOCWYAHSA-N 0.000 description 1
- 229940039781 leptin Drugs 0.000 description 1
- 210000000265 leukocyte Anatomy 0.000 description 1
- 230000000670 limiting effect Effects 0.000 description 1
- 230000013190 lipid storage Effects 0.000 description 1
- 239000002502 liposome Substances 0.000 description 1
- 230000000512 lipotoxic effect Effects 0.000 description 1
- 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 1
- 239000011344 liquid material Substances 0.000 description 1
- 229910052744 lithium Inorganic materials 0.000 description 1
- 102000004311 liver X receptors Human genes 0.000 description 1
- 108090000865 liver X receptors Proteins 0.000 description 1
- 238000012317 liver biopsy Methods 0.000 description 1
- 201000007270 liver cancer Diseases 0.000 description 1
- 208000019423 liver disease Diseases 0.000 description 1
- 230000003908 liver function Effects 0.000 description 1
- 208000018191 liver inflammation Diseases 0.000 description 1
- 208000014018 liver neoplasm Diseases 0.000 description 1
- 238000011866 long-term treatment Methods 0.000 description 1
- PCZOHLXUXFIOCF-BXMDZJJMSA-N lovastatin Chemical compound C([C@H]1[C@@H](C)C=CC2=C[C@H](C)C[C@@H]([C@H]12)OC(=O)[C@@H](C)CC)C[C@@H]1C[C@@H](O)CC(=O)O1 PCZOHLXUXFIOCF-BXMDZJJMSA-N 0.000 description 1
- QLJODMDSTUBWDW-UHFFFAOYSA-N lovastatin hydroxy acid Natural products C1=CC(C)C(CCC(O)CC(O)CC(O)=O)C2C(OC(=O)C(C)CC)CC(C)C=C21 QLJODMDSTUBWDW-UHFFFAOYSA-N 0.000 description 1
- 238000012792 lyophilization process Methods 0.000 description 1
- 239000000594 mannitol Substances 0.000 description 1
- 235000010355 mannitol Nutrition 0.000 description 1
- 238000004949 mass spectrometry Methods 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- 238000002483 medication Methods 0.000 description 1
- 208000037819 metastatic cancer Diseases 0.000 description 1
- 208000011575 metastatic malignant neoplasm Diseases 0.000 description 1
- 229960000485 methotrexate Drugs 0.000 description 1
- 239000004292 methyl p-hydroxybenzoate Substances 0.000 description 1
- 235000010270 methyl p-hydroxybenzoate Nutrition 0.000 description 1
- 229960002216 methylparaben Drugs 0.000 description 1
- 210000001589 microsome Anatomy 0.000 description 1
- 235000013336 milk Nutrition 0.000 description 1
- 239000008267 milk Substances 0.000 description 1
- 210000004080 milk Anatomy 0.000 description 1
- 210000003470 mitochondria Anatomy 0.000 description 1
- 230000002438 mitochondrial effect Effects 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 210000003205 muscle Anatomy 0.000 description 1
- 208000031225 myocardial ischemia Diseases 0.000 description 1
- YYHPEVZFVMVUNJ-UHFFFAOYSA-N n,n-diethylethanamine;sulfur trioxide Chemical compound O=S(=O)=O.CCN(CC)CC YYHPEVZFVMVUNJ-UHFFFAOYSA-N 0.000 description 1
- NJCILVSHKJZLRA-UHFFFAOYSA-N n,n-dimethylaniline;sulfur trioxide Chemical compound O=S(=O)=O.CN(C)C1=CC=CC=C1 NJCILVSHKJZLRA-UHFFFAOYSA-N 0.000 description 1
- 231100000956 nontoxicity Toxicity 0.000 description 1
- 102000039446 nucleic acids Human genes 0.000 description 1
- 108020004707 nucleic acids Proteins 0.000 description 1
- 150000007523 nucleic acids Chemical class 0.000 description 1
- 229940127073 nucleoside analogue Drugs 0.000 description 1
- 210000004940 nucleus Anatomy 0.000 description 1
- ZQPPMHVWECSIRJ-KTKRTIGZSA-N oleic acid Chemical compound CCCCCCCC\C=C/CCCCCCCC(O)=O ZQPPMHVWECSIRJ-KTKRTIGZSA-N 0.000 description 1
- 210000004789 organ system Anatomy 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 102000004164 orphan nuclear receptors Human genes 0.000 description 1
- 108090000629 orphan nuclear receptors Proteins 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- 230000007170 pathology Effects 0.000 description 1
- 108040007629 peroxidase activity proteins Proteins 0.000 description 1
- QGVLYPPODPLXMB-QXYKVGAMSA-N phorbol Natural products C[C@@H]1[C@@H](O)[C@]2(O)[C@H]([C@H]3C=C(CO)C[C@@]4(O)[C@H](C=C(C)C4=O)[C@@]13O)C2(C)C QGVLYPPODPLXMB-QXYKVGAMSA-N 0.000 description 1
- 229920002401 polyacrylamide Polymers 0.000 description 1
- 201000010065 polycystic ovary syndrome Diseases 0.000 description 1
- 208000005987 polymyositis Diseases 0.000 description 1
- 229920002717 polyvinylpyridine Polymers 0.000 description 1
- 230000002980 postoperative effect Effects 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- OKBMCNHOEMXPTM-UHFFFAOYSA-M potassium peroxymonosulfate Chemical compound [K+].OOS([O-])(=O)=O OKBMCNHOEMXPTM-UHFFFAOYSA-M 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 201000000742 primary sclerosing cholangitis Diseases 0.000 description 1
- 238000011321 prophylaxis Methods 0.000 description 1
- 201000007094 prostatitis Diseases 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 239000012264 purified product Substances 0.000 description 1
- 238000005173 quadrupole mass spectroscopy Methods 0.000 description 1
- 238000011002 quantification Methods 0.000 description 1
- 230000035484 reaction time Effects 0.000 description 1
- 238000012755 real-time RT-PCR analysis Methods 0.000 description 1
- 230000008844 regulatory mechanism Effects 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 230000000717 retained effect Effects 0.000 description 1
- 108090000064 retinoic acid receptors Proteins 0.000 description 1
- 102000003702 retinoic acid receptors Human genes 0.000 description 1
- 206010039073 rheumatoid arthritis Diseases 0.000 description 1
- 201000000306 sarcoidosis Diseases 0.000 description 1
- 230000036186 satiety Effects 0.000 description 1
- 235000019627 satiety Nutrition 0.000 description 1
- 235000021003 saturated fats Nutrition 0.000 description 1
- 231100000241 scar Toxicity 0.000 description 1
- 238000003345 scintillation counting Methods 0.000 description 1
- 208000010157 sclerosing cholangitis Diseases 0.000 description 1
- 238000007789 sealing Methods 0.000 description 1
- 238000004062 sedimentation Methods 0.000 description 1
- 239000000377 silicon dioxide Substances 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 238000002415 sodium dodecyl sulfate polyacrylamide gel electrophoresis Methods 0.000 description 1
- 239000007909 solid dosage form Substances 0.000 description 1
- 239000011343 solid material Substances 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 230000007863 steatosis Effects 0.000 description 1
- UDYFLDICVHJSOY-UHFFFAOYSA-N sulfur trioxide-pyridine complex Substances O=S(=O)=O.C1=CC=NC=C1 UDYFLDICVHJSOY-UHFFFAOYSA-N 0.000 description 1
- 229910021653 sulphate ion Inorganic materials 0.000 description 1
- 230000001629 suppression Effects 0.000 description 1
- 239000004094 surface-active agent Substances 0.000 description 1
- 238000001356 surgical procedure Methods 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 230000008718 systemic inflammatory response Effects 0.000 description 1
- 238000012353 t test Methods 0.000 description 1
- 229960001603 tamoxifen Drugs 0.000 description 1
- 235000013616 tea Nutrition 0.000 description 1
- 229960002180 tetracycline Drugs 0.000 description 1
- 229930101283 tetracycline Natural products 0.000 description 1
- 235000019364 tetracycline Nutrition 0.000 description 1
- 150000003522 tetracyclines Chemical class 0.000 description 1
- 230000036962 time dependent 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
- 230000002103 transcriptional effect Effects 0.000 description 1
- 230000037317 transdermal delivery Effects 0.000 description 1
- 230000008733 trauma Effects 0.000 description 1
- 238000011269 treatment regimen Methods 0.000 description 1
- 230000001960 triggered effect Effects 0.000 description 1
- 230000008601 triglyceride homeostasis Effects 0.000 description 1
- 241000701161 unidentified adenovirus Species 0.000 description 1
- 241001529453 unidentified herpesvirus Species 0.000 description 1
- 241001430294 unidentified retrovirus Species 0.000 description 1
- 230000002792 vascular Effects 0.000 description 1
- 201000001862 viral hepatitis Diseases 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
Images
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07J—STEROIDS
- C07J31/00—Normal steroids containing one or more sulfur atoms not belonging to a hetero ring
- C07J31/006—Normal steroids containing one or more sulfur atoms not belonging to a hetero ring not covered by C07J31/003
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61J—CONTAINERS SPECIALLY ADAPTED FOR MEDICAL OR PHARMACEUTICAL PURPOSES; DEVICES OR METHODS SPECIALLY ADAPTED FOR BRINGING PHARMACEUTICAL PRODUCTS INTO PARTICULAR PHYSICAL OR ADMINISTERING FORMS; DEVICES FOR ADMINISTERING FOOD OR MEDICINES ORALLY; BABY COMFORTERS; DEVICES FOR RECEIVING SPITTLE
- A61J1/00—Containers specially adapted for medical or pharmaceutical purposes
- A61J1/14—Details; Accessories therefor
-
- 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
-
- 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
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
-
- 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
-
- 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
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
- A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07J—STEROIDS
- C07J31/00—Normal steroids containing one or more sulfur atoms not belonging to a hetero ring
- C07J31/003—Normal steroids containing one or more sulfur atoms not belonging to a hetero ring the S atom directly linked to a ring carbon atom of the cyclopenta(a)hydrophenanthrene skeleton
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07J—STEROIDS
- C07J9/00—Normal steroids containing carbon, hydrogen, halogen or oxygen substituted in position 17 beta by a chain of more than two carbon atoms, e.g. cholane, cholestane, coprostane
Landscapes
- Health & Medical Sciences (AREA)
- Organic Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Animal Behavior & Ethology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Medicinal Chemistry (AREA)
- Engineering & Computer Science (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Diabetes (AREA)
- Hematology (AREA)
- Obesity (AREA)
- Heart & Thoracic Surgery (AREA)
- Cardiology (AREA)
- Vascular Medicine (AREA)
- Endocrinology (AREA)
- Urology & Nephrology (AREA)
- Emergency Medicine (AREA)
- Pain & Pain Management (AREA)
- Rheumatology (AREA)
- Gastroenterology & Hepatology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Steroid Compounds (AREA)
- Medicinal Preparation (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Applications Claiming Priority (5)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201261623203P | 2012-04-12 | 2012-04-12 | |
| US201261623414P | 2012-04-12 | 2012-04-12 | |
| US61/623,203 | 2012-04-12 | ||
| US61/623,414 | 2012-04-12 | ||
| PCT/US2013/031861 WO2013154752A1 (en) | 2012-04-12 | 2013-03-15 | A NOVEL CHOLESTEROL METABOLITE, 5-CHOLESTEN, 3β-25-DIOL, DISULFATE (25HCDS) FOR THERAPY OF METABOLIC DISORDERS, HYPERLIPIDEMIA, DIABETES, FATTY LIVER DISEASES AND ATHEROSCLEROSIS |
Related Child Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2017074866A Division JP2017160213A (ja) | 2012-04-12 | 2017-04-05 | 代謝障害、高脂血症、糖尿病、脂肪性肝疾患及びアテローム性動脈硬化症の治療のための新規コレステロール代謝物、５−コレステン−３β，２５−ジオールジスルファート（２５ＨＣＤＳ） |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| JP2015512937A JP2015512937A (ja) | 2015-04-30 |
| JP2015512937A5 JP2015512937A5 (https=) | 2016-12-15 |
| JP6125610B2 true JP6125610B2 (ja) | 2017-05-10 |
Family
ID=49328028
Family Applications (4)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2015505762A Expired - Fee Related JP6125610B2 (ja) | 2012-04-12 | 2013-03-15 | 代謝障害、高脂血症、糖尿病、脂肪性肝疾患及びアテローム性動脈硬化症の治療のための新規コレステロール代謝物、５−コレステン−３β，２５−ジオールジスルファート（２５ＨＣＤＳ） |
| JP2017074866A Pending JP2017160213A (ja) | 2012-04-12 | 2017-04-05 | 代謝障害、高脂血症、糖尿病、脂肪性肝疾患及びアテローム性動脈硬化症の治療のための新規コレステロール代謝物、５−コレステン−３β，２５−ジオールジスルファート（２５ＨＣＤＳ） |
| JP2019002297A Withdrawn JP2019089777A (ja) | 2012-04-12 | 2019-01-10 | 代謝障害、高脂血症、糖尿病、脂肪性肝疾患及びアテローム性動脈硬化症の治療のための新規コレステロール代謝物、５−コレステン−３β，２５−ジオールジスルファート（２５ＨＣＤＳ） |
| JP2021082520A Pending JP2021138713A (ja) | 2012-04-12 | 2021-05-14 | 代謝障害、高脂血症、糖尿病、脂肪性肝疾患及びアテローム性動脈硬化症の治療のための新規コレステロール代謝物、５−コレステン−３β，２５−ジオールジスルファート（２５ＨＣＤＳ） |
Family Applications After (3)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2017074866A Pending JP2017160213A (ja) | 2012-04-12 | 2017-04-05 | 代謝障害、高脂血症、糖尿病、脂肪性肝疾患及びアテローム性動脈硬化症の治療のための新規コレステロール代謝物、５−コレステン−３β，２５−ジオールジスルファート（２５ＨＣＤＳ） |
| JP2019002297A Withdrawn JP2019089777A (ja) | 2012-04-12 | 2019-01-10 | 代謝障害、高脂血症、糖尿病、脂肪性肝疾患及びアテローム性動脈硬化症の治療のための新規コレステロール代謝物、５−コレステン−３β，２５−ジオールジスルファート（２５ＨＣＤＳ） |
| JP2021082520A Pending JP2021138713A (ja) | 2012-04-12 | 2021-05-14 | 代謝障害、高脂血症、糖尿病、脂肪性肝疾患及びアテローム性動脈硬化症の治療のための新規コレステロール代謝物、５−コレステン−３β，２５−ジオールジスルファート（２５ＨＣＤＳ） |
Country Status (20)
| Country | Link |
|---|---|
| US (6) | US20150072962A1 (https=) |
| EP (2) | EP3239163A1 (https=) |
| JP (4) | JP6125610B2 (https=) |
| KR (1) | KR102180485B1 (https=) |
| CN (2) | CN106083976B (https=) |
| AU (2) | AU2013246435B2 (https=) |
| BR (1) | BR112014025081B1 (https=) |
| CA (1) | CA2867694C (https=) |
| DK (1) | DK2836502T3 (https=) |
| EA (1) | EA026683B1 (https=) |
| ES (1) | ES2641841T3 (https=) |
| HU (1) | HUE035073T2 (https=) |
| IL (1) | IL234892B (https=) |
| IN (1) | IN2014KN02366A (https=) |
| MX (1) | MX357046B (https=) |
| PL (1) | PL2836502T3 (https=) |
| PT (1) | PT2836502T (https=) |
| SI (1) | SI2836502T1 (https=) |
| WO (1) | WO2013154752A1 (https=) |
| ZA (1) | ZA201406981B (https=) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2019089777A (ja) * | 2012-04-12 | 2019-06-13 | ヴァージニア コモンウェルス ユニバーシティ | 代謝障害、高脂血症、糖尿病、脂肪性肝疾患及びアテローム性動脈硬化症の治療のための新規コレステロール代謝物、５−コレステン−３β，２５−ジオールジスルファート（２５ＨＣＤＳ） |
Families Citing this family (19)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2006047022A1 (en) | 2004-10-25 | 2006-05-04 | Virginia Commonwealth University | Nuclear sulfated oxysterol, potent regulator of cholesterol homeostasis, for therapy of hypercholesterolemia, hyperlipidemia, and atherosclerosis |
| US9034859B2 (en) | 2011-04-06 | 2015-05-19 | Virginia Commonwealth University | Sulfated oxysterol and oxysterol sulfation by hydroxysterol sulfotransferase promote lipid homeostasis and liver proliferation |
| PL3639828T3 (pl) * | 2013-12-24 | 2022-05-02 | Virginia Commonwealth University | Zastosowanie utlenowanych siarczanów cholesterolu (ocs) w leczeniu ostrej niewydolności wątroby |
| TWI547280B (zh) * | 2014-04-24 | 2016-09-01 | 長弘生物科技股份有限公司 | 穩定醫藥組合物 |
| US10238664B2 (en) | 2014-07-09 | 2019-03-26 | Duke University | Compositions and methods for the repair of myelin |
| CN107106576A (zh) * | 2014-10-10 | 2017-08-29 | 弗吉尼亚联邦大学 | 用于因减弱的瘦蛋白活性和脂质贮积障碍中的至少一种导致的障碍的疗法的氧化胆固醇硫酸酯类 |
| JP6784963B2 (ja) * | 2014-12-24 | 2020-11-18 | 国立大学法人京都大学 | ビタミンｄ３誘導体及びその薬学的用途 |
| US20200222430A1 (en) * | 2016-08-02 | 2020-07-16 | Durect Corporation | Compositions comprising oxygenated cholesterol sulfate and at least one of polyalkylene glycol, carboxymethyl cellulose and polyoxylglyceride |
| EP3494125B1 (en) | 2016-08-02 | 2022-06-22 | Virginia Commonwealth University | Compositions comprising 5-cholesten-3, 25-diol, 3-sulfate (25hc3s) or pharmaceutically acceptable salt thereof and at least one cyclic oligosaccharide |
| CA3031211A1 (en) * | 2016-08-02 | 2018-02-08 | Virginia Commonwealth University | Use of oxygenated cholesterol sulfates (ocs) to treat inflammatory skin disease and skin lesions |
| US11458146B2 (en) | 2017-01-13 | 2022-10-04 | Duke University | Compositions and methods for the treatment of myelin related and inflammation related diseases or disorders |
| KR101892577B1 (ko) | 2017-04-21 | 2018-08-28 | 부산대학교 산학협력단 | 레블라스타틴 유도체 또는 이의 약학적으로 허용가능한 염을 유효성분으로 포함하는 죽상동맥경화증 예방 또는 치료용 조성물 |
| CN107286160A (zh) * | 2017-06-05 | 2017-10-24 | 毛佳婧 | 一种抗肝炎药物的哌啶并吡啶并吡唑‑锌配合物的制备方法 |
| RU2020110253A (ru) * | 2017-08-31 | 2021-09-30 | Ариэль Сайентифик Инновейшнз Лтд | Экстракт s. spinosum для лечения жировой болезни печени |
| BR112022005039A2 (pt) * | 2019-09-30 | 2022-06-21 | Durect Corp | Tratamento de hepatite alcoólica |
| EP4171573A4 (en) * | 2020-06-26 | 2025-04-09 | Durect Corporation | USE OF OXYGENATED CHOLESTEROL SULFATES FOR THE TREATMENT OF NEUROLOGICAL CONDITIONS, NEURODEGENERATIVE DISEASES AND ADDICTION |
| CN112294827B (zh) * | 2020-11-12 | 2021-12-24 | 四川大学华西医院 | 5-胆甾烯 -3β-醇硫酸酯盐的用途 |
| KR102732697B1 (ko) | 2021-10-29 | 2024-11-25 | 부산대학교 산학협력단 | 크산틴 유도체를 유효성분으로 포함하는 죽상동맥경화증 예방 또는 치료용 약학적 조성물 |
| WO2024008614A1 (en) * | 2022-07-08 | 2024-01-11 | Société des Produits Nestlé S.A. | Use of 25-hydroxycholesterol for diabetic treatment and/or prevention |
Family Cites Families (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| IL146223A0 (en) * | 1999-04-30 | 2002-07-25 | Arch Dev Corp | Steroid derivatives |
| WO2006047022A1 (en) | 2004-10-25 | 2006-05-04 | Virginia Commonwealth University | Nuclear sulfated oxysterol, potent regulator of cholesterol homeostasis, for therapy of hypercholesterolemia, hyperlipidemia, and atherosclerosis |
| CA2637884A1 (en) | 2006-02-13 | 2007-08-23 | Wellstat Therapeutics Corporation | Compounds for the treatment of metabolic disorders |
| US8003795B2 (en) | 2007-06-22 | 2011-08-23 | Cvi Pharmaceuticals Limited | Compounds and compositions for reducing lipid levels |
| WO2011077245A2 (en) * | 2009-12-23 | 2011-06-30 | Fondazione Centro San Raffaele Del Monte Tabor | Compositions |
| EA026683B1 (ru) * | 2012-04-12 | 2017-05-31 | Вирджиния Коммонвелт Юниверсити | МЕТАБОЛИТ ХОЛЕСТЕРИНА ДИСУЛЬФАТ 5-ХОЛЕСТЕН-3β,25-ДИОЛА (25HCDS) ДЛЯ ТЕРАПИИ НАРУШЕНИЙ ОБМЕНА ВЕЩЕСТВ, ГИПЕРЛИПИДЕМИИ, ДИАБЕТА, ЖИРОВЫХ БОЛЕЗНЕЙ ПЕЧЕНИ И АТЕРОСКЛЕРОЗА |
-
2013
- 2013-03-15 EA EA201491859A patent/EA026683B1/ru unknown
- 2013-03-15 MX MX2014012324A patent/MX357046B/es active IP Right Grant
- 2013-03-15 CN CN201610412359.9A patent/CN106083976B/zh not_active Expired - Fee Related
- 2013-03-15 PL PL13775974T patent/PL2836502T3/pl unknown
- 2013-03-15 SI SI201330794T patent/SI2836502T1/sl unknown
- 2013-03-15 PT PT137759742T patent/PT2836502T/pt unknown
- 2013-03-15 BR BR112014025081-2A patent/BR112014025081B1/pt not_active IP Right Cessation
- 2013-03-15 HU HUE13775974A patent/HUE035073T2/en unknown
- 2013-03-15 KR KR1020147031567A patent/KR102180485B1/ko not_active Expired - Fee Related
- 2013-03-15 EP EP17167122.5A patent/EP3239163A1/en not_active Withdrawn
- 2013-03-15 DK DK13775974.2T patent/DK2836502T3/en active
- 2013-03-15 JP JP2015505762A patent/JP6125610B2/ja not_active Expired - Fee Related
- 2013-03-15 CA CA2867694A patent/CA2867694C/en active Active
- 2013-03-15 AU AU2013246435A patent/AU2013246435B2/en not_active Ceased
- 2013-03-15 US US14/391,929 patent/US20150072962A1/en not_active Abandoned
- 2013-03-15 CN CN201380019476.3A patent/CN104220450B/zh not_active Expired - Fee Related
- 2013-03-15 WO PCT/US2013/031861 patent/WO2013154752A1/en not_active Ceased
- 2013-03-15 ES ES13775974.2T patent/ES2641841T3/es active Active
- 2013-03-15 EP EP13775974.2A patent/EP2836502B1/en active Active
-
2014
- 2014-09-25 ZA ZA2014/06981A patent/ZA201406981B/en unknown
- 2014-09-28 IL IL234892A patent/IL234892B/en active IP Right Grant
- 2014-10-27 IN IN2366KON2014 patent/IN2014KN02366A/en unknown
-
2016
- 2016-08-19 US US15/241,171 patent/US20160355544A1/en not_active Abandoned
-
2017
- 2017-04-05 JP JP2017074866A patent/JP2017160213A/ja active Pending
- 2017-10-10 US US15/728,827 patent/US20180127457A1/en not_active Abandoned
- 2017-11-30 AU AU2017268646A patent/AU2017268646B2/en not_active Ceased
-
2018
- 2018-09-25 US US16/140,964 patent/US20190135856A1/en not_active Abandoned
-
2019
- 2019-01-10 JP JP2019002297A patent/JP2019089777A/ja not_active Withdrawn
- 2019-10-10 US US16/599,044 patent/US20200157140A1/en not_active Abandoned
-
2020
- 2020-12-15 US US17/122,647 patent/US20210238219A1/en not_active Abandoned
-
2021
- 2021-05-14 JP JP2021082520A patent/JP2021138713A/ja active Pending
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2019089777A (ja) * | 2012-04-12 | 2019-06-13 | ヴァージニア コモンウェルス ユニバーシティ | 代謝障害、高脂血症、糖尿病、脂肪性肝疾患及びアテローム性動脈硬化症の治療のための新規コレステロール代謝物、５−コレステン−３β，２５−ジオールジスルファート（２５ＨＣＤＳ） |
Also Published As
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| JP6125610B2 (ja) | 代謝障害、高脂血症、糖尿病、脂肪性肝疾患及びアテローム性動脈硬化症の治療のための新規コレステロール代謝物、５−コレステン−３β，２５−ジオールジスルファート（２５ＨＣＤＳ） | |
| US11384115B2 (en) | Nuclear sulfated oxysterol, potent regulator of lipid homeostasis, for therapy of hypercholesterolemia, hypertriglycerides, fatty liver diseases, and atherosclerosis | |
| US20210101927A1 (en) | 3-desoxy derivative and pharmaceutical compositions thereof | |
| US8399441B2 (en) | Nuclear sulfated oxysterol, potent regulator of lipid homeostasis, for therapy of hypercholesterolemia, hypertriglycerides, fatty liver diseases, and atherosclerosis | |
| HK1202294B (en) | A novel cholesterol metabolite, 5-cholesten, 3beta-25-diol, disulfate (25hcds) for therapy of metabolic disorders, hyperlipidemia, diabetes, fatty liver diseases and atherosclerosis | |
| WO2015034010A1 (ja) | 核内受容体肝臓ｘ受容体アゴニスト |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| RD01 | Notification of change of attorney |
Free format text: JAPANESE INTERMEDIATE CODE: A7426 Effective date: 20150408 |
|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A821 Effective date: 20150408 |
|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20160223 |
|
| A621 | Written request for application examination |
Free format text: JAPANESE INTERMEDIATE CODE: A621 Effective date: 20160223 |
|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20161026 |
|
| A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20161122 |
|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20170203 |
|
| TRDD | Decision of grant or rejection written | ||
| A01 | Written decision to grant a patent or to grant a registration (utility model) |
Free format text: JAPANESE INTERMEDIATE CODE: A01 Effective date: 20170307 |
|
| A61 | First payment of annual fees (during grant procedure) |
Free format text: JAPANESE INTERMEDIATE CODE: A61 Effective date: 20170405 |
|
| R150 | Certificate of patent or registration of utility model |
Ref document number: 6125610 Country of ref document: JP Free format text: JAPANESE INTERMEDIATE CODE: R150 |
|
| R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
| R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
| R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
| LAPS | Cancellation because of no payment of annual fees |