EA036757B1 - Фармацевтические композиции для комбинированной терапии - Google Patents

Info

Publication number

EA036757B1

EA036757B1 EA201792203A EA201792203A EA036757B1 EA 036757 B1 EA036757 B1 EA 036757B1 EA 201792203 A EA201792203 A EA 201792203A EA 201792203 A EA201792203 A EA 201792203A EA 036757 B1 EA036757 B1 EA 036757B1

Authority

EA

Eurasian Patent Office

Prior art keywords

liver

dose

miu

oca

disease

Prior art date

2015-04-07

Links

• Espacenet
• Global Dossier
• Discuss

• 239000008194 pharmaceutical composition Substances 0.000 title claims abstract description 67
• 238000002648 combination therapy Methods 0.000 title description 8
• 239000003814 drug Substances 0.000 claims abstract description 146
• 229940124597 therapeutic agent Drugs 0.000 claims abstract description 118
• 208000008338 non-alcoholic fatty liver disease Diseases 0.000 claims abstract description 116
• 206010053219 non-alcoholic steatohepatitis Diseases 0.000 claims abstract description 94
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 80
• 201000010099 disease Diseases 0.000 claims abstract description 75
• 230000003914 insulin secretion Effects 0.000 claims abstract description 31
• 229940121360 farnesoid X receptor (fxr) agonists Drugs 0.000 claims abstract description 12
• 150000001875 compounds Chemical class 0.000 claims description 116
• 238000000034 method Methods 0.000 claims description 81
• YSDQQAXHVYUZIW-QCIJIYAXSA-N Liraglutide Chemical group C([C@@H](C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(O)=O)C(=O)NCC(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](C)C(=O)N[C@@H](C)C(=O)N[C@@H](CCCCNC(=O)CC[C@H](NC(=O)CCCCCCCCCCCCCCC)C(O)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](C)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)NCC(=O)N[C@@H](CCCNC(N)=N)C(=O)NCC(O)=O)NC(=O)[C@H](CO)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@@H](NC(=O)CNC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C)NC(=O)[C@@H](N)CC=1NC=NC=1)[C@@H](C)O)[C@@H](C)O)C(C)C)C1=CC=C(O)C=C1 YSDQQAXHVYUZIW-QCIJIYAXSA-N 0.000 claims description 52
• 108010019598 Liraglutide Proteins 0.000 claims description 51
• 229960002701 liraglutide Drugs 0.000 claims description 51
• 150000001413 amino acids Chemical class 0.000 claims description 30
• 150000003839 salts Chemical class 0.000 claims description 23
• 229910052739 hydrogen Inorganic materials 0.000 claims description 20
• 239000001257 hydrogen Substances 0.000 claims description 19
• 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 12
• 239000003937 drug carrier Substances 0.000 claims description 11
• 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 11
• 229940125904 compound 1 Drugs 0.000 claims description 7
• 150000002431 hydrogen Chemical group 0.000 claims description 7
• UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 6
• 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 6
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 6
• 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 6
• 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims 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 abstract description 86
• 239000008103 glucose Substances 0.000 abstract description 86
• 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 abstract description 64
• 210000004369 blood Anatomy 0.000 abstract description 52
• 239000008280 blood Substances 0.000 abstract description 52
• 206010022489 Insulin Resistance Diseases 0.000 abstract description 47
• 238000011282 treatment Methods 0.000 abstract description 39
• 230000001965 increasing effect Effects 0.000 abstract description 33
• 102000004877 Insulin Human genes 0.000 abstract description 31
• 108090001061 Insulin Proteins 0.000 abstract description 31
• 229940125396 insulin Drugs 0.000 abstract description 31
• 102100038495 Bile acid receptor Human genes 0.000 abstract description 29
• 230000003247 decreasing effect Effects 0.000 abstract description 27
• 208000001072 type 2 diabetes mellitus Diseases 0.000 abstract description 22
• 208000008589 Obesity Diseases 0.000 abstract description 17
• 206010012601 diabetes mellitus Diseases 0.000 abstract description 17
• 235000020824 obesity Nutrition 0.000 abstract description 17
• 201000001421 hyperglycemia Diseases 0.000 abstract description 14
• 230000001404 mediated effect Effects 0.000 abstract description 12
• 230000002265 prevention Effects 0.000 abstract description 9
• 230000004936 stimulating effect Effects 0.000 abstract description 6
• 230000028327 secretion Effects 0.000 abstract 1
• ZXERDUOLZKYMJM-ZWECCWDJSA-N obeticholic acid Chemical compound C([C@@]12C)C[C@@H](O)C[C@H]1[C@@H](CC)[C@@H](O)[C@@H]1[C@@H]2CC[C@]2(C)[C@@H]([C@H](C)CCC(O)=O)CC[C@H]21 ZXERDUOLZKYMJM-ZWECCWDJSA-N 0.000 description 136
• 229960001601 obeticholic acid Drugs 0.000 description 134
• 230000000694 effects Effects 0.000 description 95
• 210000004185 liver Anatomy 0.000 description 93
• 241000699670 Mus sp. Species 0.000 description 90
• 229960001031 glucose Drugs 0.000 description 85
• 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 83
• 239000002609 medium Substances 0.000 description 69
• 108090000623 proteins and genes Proteins 0.000 description 64
• 229960003105 metformin Drugs 0.000 description 56
• XZWYZXLIPXDOLR-UHFFFAOYSA-N metformin Chemical compound CN(C)C(=N)NC(N)=N XZWYZXLIPXDOLR-UHFFFAOYSA-N 0.000 description 56
• 210000004027 cell Anatomy 0.000 description 55
• HVYWMOMLDIMFJA-DPAQBDIFSA-N cholesterol Chemical compound C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CCCC(C)C)[C@@]1(C)CC2 HVYWMOMLDIMFJA-DPAQBDIFSA-N 0.000 description 52
• 230000014509 gene expression Effects 0.000 description 45
• 239000000203 mixture Substances 0.000 description 41
• 230000007423 decrease Effects 0.000 description 37
• 210000003494 hepatocyte Anatomy 0.000 description 37
• 241001465754 Metazoa Species 0.000 description 33
• 206010016654 Fibrosis Diseases 0.000 description 32
• 210000001519 tissue Anatomy 0.000 description 30
• 108010035532 Collagen Proteins 0.000 description 28
• 229940024606 amino acid Drugs 0.000 description 28
• 235000001014 amino acid Nutrition 0.000 description 28
• 230000004761 fibrosis Effects 0.000 description 26
• 241000283973 Oryctolagus cuniculus Species 0.000 description 24
• 206010061218 Inflammation Diseases 0.000 description 23
• 238000004458 analytical method Methods 0.000 description 23
• 239000003795 chemical substances by application Substances 0.000 description 23
• MFFMDFFZMYYVKS-SECBINFHSA-N sitagliptin Chemical compound C([C@H](CC(=O)N1CC=2N(C(=NN=2)C(F)(F)F)CC1)N)C1=CC(F)=C(F)C=C1F MFFMDFFZMYYVKS-SECBINFHSA-N 0.000 description 23
• 208000008439 Biliary Liver Cirrhosis Diseases 0.000 description 22
• 235000012000 cholesterol Nutrition 0.000 description 22
• 235000005911 diet Nutrition 0.000 description 22
• 230000037213 diet Effects 0.000 description 22
• 229940079593 drug Drugs 0.000 description 22
• -1 septagliptin Chemical compound 0.000 description 22
• 229960004034 sitagliptin Drugs 0.000 description 22
• 208000012654 Primary biliary cholangitis Diseases 0.000 description 21
• 230000004054 inflammatory process Effects 0.000 description 21
• 208000033222 Biliary cirrhosis primary Diseases 0.000 description 20
• 102000008186 Collagen Human genes 0.000 description 19
• 230000001587 cholestatic effect Effects 0.000 description 19
• 229920001436 collagen Polymers 0.000 description 19
• 230000001105 regulatory effect Effects 0.000 description 19
• IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 18
• 239000002775 capsule Substances 0.000 description 18
• 208000019425 cirrhosis of liver Diseases 0.000 description 18
• 108020004999 messenger RNA Proteins 0.000 description 18
• 230000007863 steatosis Effects 0.000 description 18
• 231100000240 steatosis hepatitis Toxicity 0.000 description 18
• 238000002474 experimental method Methods 0.000 description 17
• 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 16
• 208000001145 Metabolic Syndrome Diseases 0.000 description 16
• 201000000690 abdominal obesity-metabolic syndrome Diseases 0.000 description 16
• 239000002552 dosage form Substances 0.000 description 16
• 239000003826 tablet Substances 0.000 description 16
• 239000003925 fat Substances 0.000 description 15
• 239000001963 growth medium Substances 0.000 description 15
• 238000009097 single-agent therapy Methods 0.000 description 15
• 208000024891 symptom Diseases 0.000 description 15
• 238000012360 testing method Methods 0.000 description 15
• 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 14
• 229960003345 empagliflozin Drugs 0.000 description 14
• OBWASQILIWPZMG-QZMOQZSNSA-N empagliflozin Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@H]1C1=CC=C(Cl)C(CC=2C=CC(O[C@@H]3COCC3)=CC=2)=C1 OBWASQILIWPZMG-QZMOQZSNSA-N 0.000 description 14
• 235000019197 fats Nutrition 0.000 description 14
• 238000011534 incubation Methods 0.000 description 14
• 210000002966 serum Anatomy 0.000 description 14
• 239000000243 solution Substances 0.000 description 14
• 230000015572 biosynthetic process Effects 0.000 description 13
• 230000037396 body weight Effects 0.000 description 13
• 239000001768 carboxy methyl cellulose Substances 0.000 description 13
• 208000019423 liver disease Diseases 0.000 description 13
• 210000005228 liver tissue Anatomy 0.000 description 13
• 210000000056 organ Anatomy 0.000 description 13
• 230000010412 perfusion Effects 0.000 description 13
• 210000002381 plasma Anatomy 0.000 description 13
• 238000012545 processing Methods 0.000 description 13
• 150000003626 triacylglycerols Chemical class 0.000 description 13
• 102000004625 Aspartate Aminotransferases Human genes 0.000 description 12
• 108010003415 Aspartate Aminotransferases Proteins 0.000 description 12
• 239000000546 pharmaceutical excipient Substances 0.000 description 12
• 102000004169 proteins and genes Human genes 0.000 description 12
• 101710107035 Gamma-glutamyltranspeptidase Proteins 0.000 description 11
• 101710173228 Glutathione hydrolase proenzyme Proteins 0.000 description 11
• 235000013305 food Nutrition 0.000 description 11
• 102000006640 gamma-Glutamyltransferase Human genes 0.000 description 11
• 238000002955 isolation Methods 0.000 description 11
• 235000018102 proteins Nutrition 0.000 description 11
• 230000009467 reduction Effects 0.000 description 11
• 102100036475 Alanine aminotransferase 1 Human genes 0.000 description 10
• 108010082126 Alanine transaminase Proteins 0.000 description 10
• DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 10
• NPGIHFRTRXVWOY-UHFFFAOYSA-N Oil red O Chemical compound Cc1ccc(C)c(c1)N=Nc1cc(C)c(cc1C)N=Nc1c(O)ccc2ccccc12 NPGIHFRTRXVWOY-UHFFFAOYSA-N 0.000 description 10
• 238000009825 accumulation Methods 0.000 description 10
• 210000000013 bile duct Anatomy 0.000 description 10
• 235000020940 control diet Nutrition 0.000 description 10
• 239000003085 diluting agent Substances 0.000 description 10
• 238000009472 formulation Methods 0.000 description 10
• 239000007788 liquid Substances 0.000 description 10
• 235000015263 low fat diet Nutrition 0.000 description 10
• 210000004379 membrane Anatomy 0.000 description 10
• 239000012528 membrane Substances 0.000 description 10
• XOAAWQZATWQOTB-UHFFFAOYSA-N taurine Chemical group NCCS(O)(=O)=O XOAAWQZATWQOTB-UHFFFAOYSA-N 0.000 description 10
• 230000001225 therapeutic effect Effects 0.000 description 10
• LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 9
• OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 9
• 238000011161 development Methods 0.000 description 9
• 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 9
• 238000011156 evaluation Methods 0.000 description 9
• 229910052757 nitrogen Inorganic materials 0.000 description 9
• 238000007410 oral glucose tolerance test Methods 0.000 description 9
• 239000002953 phosphate buffered saline Substances 0.000 description 9
• 238000002360 preparation method Methods 0.000 description 9
• 108020003175 receptors Proteins 0.000 description 9
• 102000004008 5'-Nucleotidase Human genes 0.000 description 8
• 229920002134 Carboxymethyl cellulose Polymers 0.000 description 8
• 206010008635 Cholestasis Diseases 0.000 description 8
• 239000006144 Dulbecco’s modified Eagle's medium Substances 0.000 description 8
• 102000004190 Enzymes Human genes 0.000 description 8
• 108090000790 Enzymes Proteins 0.000 description 8
• RFSUNEUAIZKAJO-ARQDHWQXSA-N Fructose Chemical compound OC[C@H]1O[C@](O)(CO)[C@@H](O)[C@@H]1O RFSUNEUAIZKAJO-ARQDHWQXSA-N 0.000 description 8
• 239000004698 Polyethylene Substances 0.000 description 8
• 239000013543 active substance Substances 0.000 description 8
• 239000000872 buffer Substances 0.000 description 8
• 229940105329 carboxymethylcellulose Drugs 0.000 description 8
• 229940088598 enzyme Drugs 0.000 description 8
• 108010043671 prostatic acid phosphatase Proteins 0.000 description 8
• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 8
• 108091032973 (ribonucleotides)n+m Proteins 0.000 description 7
• 102000029816 Collagenase Human genes 0.000 description 7
• 229930091371 Fructose Natural products 0.000 description 7
• 239000005715 Fructose Substances 0.000 description 7
• 229920002527 Glycogen Polymers 0.000 description 7
• 206010067125 Liver injury Diseases 0.000 description 7
• 229930040373 Paraformaldehyde Natural products 0.000 description 7
• 239000002253 acid Substances 0.000 description 7
• 238000010171 animal model Methods 0.000 description 7
• 238000003556 assay Methods 0.000 description 7
• 235000010948 carboxy methyl cellulose Nutrition 0.000 description 7
• 239000008112 carboxymethyl-cellulose Substances 0.000 description 7
• 238000004113 cell culture Methods 0.000 description 7
• 229960002424 collagenase Drugs 0.000 description 7
• 230000001086 cytosolic effect Effects 0.000 description 7
• 230000004069 differentiation Effects 0.000 description 7
• 230000006870 function Effects 0.000 description 7
• 229940096919 glycogen Drugs 0.000 description 7
• 231100000234 hepatic damage Toxicity 0.000 description 7
• 239000003112 inhibitor Substances 0.000 description 7
• 150000002632 lipids Chemical class 0.000 description 7
• 238000012317 liver biopsy Methods 0.000 description 7
• 230000008818 liver damage Effects 0.000 description 7
• 239000012188 paraffin wax Substances 0.000 description 7
• 229920002866 paraformaldehyde Polymers 0.000 description 7
• 230000000291 postprandial effect Effects 0.000 description 7
• 230000000750 progressive effect Effects 0.000 description 7
• 102000005962 receptors Human genes 0.000 description 7
• 208000010157 sclerosing cholangitis Diseases 0.000 description 7
• 239000000126 substance Substances 0.000 description 7
• 230000002195 synergetic effect Effects 0.000 description 7
• 238000003786 synthesis reaction Methods 0.000 description 7
• 208000022309 Alcoholic Liver disease Diseases 0.000 description 6
• IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 6
• 108010067722 Dipeptidyl Peptidase 4 Proteins 0.000 description 6
• 102100025012 Dipeptidyl peptidase 4 Human genes 0.000 description 6
• 208000010334 End Stage Liver Disease Diseases 0.000 description 6
• KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 6
• 206010028980 Neoplasm Diseases 0.000 description 6
• JLRGJRBPOGGCBT-UHFFFAOYSA-N Tolbutamide Chemical compound CCCCNC(=O)NS(=O)(=O)C1=CC=C(C)C=C1 JLRGJRBPOGGCBT-UHFFFAOYSA-N 0.000 description 6
• 108060008682 Tumor Necrosis Factor Proteins 0.000 description 6
• DPXJVFZANSGRMM-UHFFFAOYSA-N acetic acid;2,3,4,5,6-pentahydroxyhexanal;sodium Chemical compound [Na].CC(O)=O.OCC(O)C(O)C(O)C(O)C=O DPXJVFZANSGRMM-UHFFFAOYSA-N 0.000 description 6
• 230000003213 activating effect Effects 0.000 description 6
• 230000004913 activation Effects 0.000 description 6
• 210000000577 adipose tissue Anatomy 0.000 description 6
• 230000008901 benefit Effects 0.000 description 6
• 239000003613 bile acid Substances 0.000 description 6
• 239000003153 chemical reaction reagent Substances 0.000 description 6
• 208000011444 chronic liver failure Diseases 0.000 description 6
• 230000007882 cirrhosis Effects 0.000 description 6
• 230000002503 metabolic effect Effects 0.000 description 6
• 230000000144 pharmacologic effect Effects 0.000 description 6
• 210000000229 preadipocyte Anatomy 0.000 description 6
• 235000019812 sodium carboxymethyl cellulose Nutrition 0.000 description 6
• 238000010186 staining Methods 0.000 description 6
• UCSJYZPVAKXKNQ-HZYVHMACSA-N streptomycin Chemical compound CN[C@H]1[C@H](O)[C@@H](O)[C@H](CO)O[C@H]1O[C@@H]1[C@](C=O)(O)[C@H](C)O[C@H]1O[C@@H]1[C@@H](NC(N)=N)[C@H](O)[C@@H](NC(N)=N)[C@H](O)[C@H]1O UCSJYZPVAKXKNQ-HZYVHMACSA-N 0.000 description 6
• 239000012730 sustained-release form Substances 0.000 description 6
• 102000002260 Alkaline Phosphatase Human genes 0.000 description 5
• 108020004774 Alkaline Phosphatase Proteins 0.000 description 5
• 108060005980 Collagenase Proteins 0.000 description 5
• 208000004930 Fatty Liver Diseases 0.000 description 5
• 102000051325 Glucagon Human genes 0.000 description 5
• 108060003199 Glucagon Proteins 0.000 description 5
• 239000004471 Glycine Substances 0.000 description 5
• 206010020772 Hypertension Diseases 0.000 description 5
• 102000003855 L-lactate dehydrogenase Human genes 0.000 description 5
• 108700023483 L-lactate dehydrogenases Proteins 0.000 description 5
• 238000003559 RNA-seq method Methods 0.000 description 5
• 108010009583 Transforming Growth Factors Proteins 0.000 description 5
• 210000001789 adipocyte Anatomy 0.000 description 5
• 210000000941 bile Anatomy 0.000 description 5
• 238000001574 biopsy Methods 0.000 description 5
• 239000013078 crystal Substances 0.000 description 5
• 235000014113 dietary fatty acids Nutrition 0.000 description 5
• 208000035475 disorder Diseases 0.000 description 5
• 239000000194 fatty acid Substances 0.000 description 5
• 229930195729 fatty acid Natural products 0.000 description 5
• 239000000499 gel Substances 0.000 description 5
• MASNOZXLGMXCHN-ZLPAWPGGSA-N glucagon Chemical compound C([C@@H](C(=O)N[C@H](C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(O)=O)C(C)C)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](C)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CO)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CO)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@@H](NC(=O)CNC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CO)NC(=O)[C@@H](N)CC=1NC=NC=1)[C@@H](C)O)[C@@H](C)O)C1=CC=CC=C1 MASNOZXLGMXCHN-ZLPAWPGGSA-N 0.000 description 5
• 229960004666 glucagon Drugs 0.000 description 5
• 230000004153 glucose metabolism Effects 0.000 description 5
• 229960002449 glycine Drugs 0.000 description 5
• 206010073071 hepatocellular carcinoma Diseases 0.000 description 5
• 231100000844 hepatocellular carcinoma Toxicity 0.000 description 5
• 229940088597 hormone Drugs 0.000 description 5
• 239000005556 hormone Substances 0.000 description 5
• 230000006698 induction Effects 0.000 description 5
• 238000002347 injection Methods 0.000 description 5
• 239000007924 injection Substances 0.000 description 5
• 230000037353 metabolic pathway Effects 0.000 description 5
• 230000004060 metabolic process Effects 0.000 description 5
• 210000003240 portal vein Anatomy 0.000 description 5
• 229920001027 sodium carboxymethylcellulose Polymers 0.000 description 5
• 238000003860 storage Methods 0.000 description 5
• 238000001356 surgical procedure Methods 0.000 description 5
• 239000000725 suspension Substances 0.000 description 5
• 238000013268 sustained release Methods 0.000 description 5
• 229960003080 taurine Drugs 0.000 description 5
• 238000002560 therapeutic procedure Methods 0.000 description 5
• 229960005371 tolbutamide Drugs 0.000 description 5
• 238000001262 western blot Methods 0.000 description 5
• YKFCISHFRZHKHY-NGQGLHOPSA-N (2s)-2-amino-3-(3,4-dihydroxyphenyl)-2-methylpropanoic acid;trihydrate Chemical compound O.O.O.OC(=O)[C@](N)(C)CC1=CC=C(O)C(O)=C1.OC(=O)[C@](N)(C)CC1=CC=C(O)C(O)=C1 YKFCISHFRZHKHY-NGQGLHOPSA-N 0.000 description 4
• 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 4
• 206010059245 Angiopathy Diseases 0.000 description 4
• 102100021253 Antileukoproteinase Human genes 0.000 description 4
• 206010003827 Autoimmune hepatitis Diseases 0.000 description 4
• 208000007257 Budd-Chiari syndrome Diseases 0.000 description 4
• 238000011746 C57BL/6J (JAX™ mouse strain) Methods 0.000 description 4
• HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 4
• 206010008609 Cholangitis sclerosing Diseases 0.000 description 4
• 206010010356 Congenital anomaly Diseases 0.000 description 4
• 108090000738 Decorin Proteins 0.000 description 4
• 206010012735 Diarrhoea Diseases 0.000 description 4
• 108010011459 Exenatide Proteins 0.000 description 4
• WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 4
• 206010072104 Fructose intolerance Diseases 0.000 description 4
• 208000027472 Galactosemias Diseases 0.000 description 4
• 208000015872 Gaucher disease Diseases 0.000 description 4
• 208000018565 Hemochromatosis Diseases 0.000 description 4
• 208000002972 Hepatolenticular Degeneration Diseases 0.000 description 4
• 206010019878 Hereditary fructose intolerance Diseases 0.000 description 4
• 206010072877 Intestinal fibrosis Diseases 0.000 description 4
• XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 4
• 108060001084 Luciferase Proteins 0.000 description 4
• 239000005089 Luciferase Substances 0.000 description 4
• 241000124008 Mammalia Species 0.000 description 4
• 241000283984 Rodentia Species 0.000 description 4
• 102000009618 Transforming Growth Factors Human genes 0.000 description 4
• 208000012346 Venoocclusive disease Diseases 0.000 description 4
• 208000018839 Wilson disease Diseases 0.000 description 4
• 239000002671 adjuvant Substances 0.000 description 4
• 229960005260 amiodarone Drugs 0.000 description 4
• 229920000080 bile acid sequestrant Polymers 0.000 description 4
• 150000001720 carbohydrates Chemical class 0.000 description 4
• 235000014633 carbohydrates Nutrition 0.000 description 4
• 229940083181 centrally acting adntiadrenergic agent methyldopa Drugs 0.000 description 4
• ZPEIMTDSQAKGNT-UHFFFAOYSA-N chlorpromazine Chemical compound C1=C(Cl)C=C2N(CCCN(C)C)C3=CC=CC=C3SC2=C1 ZPEIMTDSQAKGNT-UHFFFAOYSA-N 0.000 description 4
• 229960001076 chlorpromazine Drugs 0.000 description 4
• 230000006378 damage Effects 0.000 description 4
• 238000010586 diagram Methods 0.000 description 4
• 239000012636 effector Substances 0.000 description 4
• 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 4
• 229960001519 exenatide Drugs 0.000 description 4
• 238000010195 expression analysis Methods 0.000 description 4
• 239000012634 fragment Substances 0.000 description 4
• 239000011521 glass Substances 0.000 description 4
• 238000007490 hematoxylin and eosin (H&E) staining Methods 0.000 description 4
• 208000006454 hepatitis Diseases 0.000 description 4
• 208000010710 hepatitis C virus infection Diseases 0.000 description 4
• 201000006846 hereditary fructose intolerance syndrome Diseases 0.000 description 4
• JYGXADMDTFJGBT-VWUMJDOOSA-N hydrocortisone Chemical compound O=C1CC[C@]2(C)[C@H]3[C@@H](O)C[C@](C)([C@@](CC4)(O)C(=O)CO)[C@@H]4[C@@H]3CCC2=C1 JYGXADMDTFJGBT-VWUMJDOOSA-N 0.000 description 4
• 230000006872 improvement Effects 0.000 description 4
• 238000001727 in vivo Methods 0.000 description 4
• 238000011065 in-situ storage Methods 0.000 description 4
• 230000002401 inhibitory effect Effects 0.000 description 4
• 230000005764 inhibitory process Effects 0.000 description 4
• 210000001596 intra-abdominal fat Anatomy 0.000 description 4
• 201000007270 liver cancer Diseases 0.000 description 4
• 230000007774 longterm Effects 0.000 description 4
• QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 4
• 239000005022 packaging material Substances 0.000 description 4
• 201000000742 primary sclerosing cholangitis Diseases 0.000 description 4
• 238000011002 quantification Methods 0.000 description 4
• 238000011160 research Methods 0.000 description 4
• 201000000306 sarcoidosis Diseases 0.000 description 4
• FSYKKLYZXJSNPZ-UHFFFAOYSA-N sarcosine Chemical compound C[NH2+]CC([O-])=O FSYKKLYZXJSNPZ-UHFFFAOYSA-N 0.000 description 4
• 201000005060 thrombophlebitis Diseases 0.000 description 4
• 235000010692 trans-unsaturated fatty acids Nutrition 0.000 description 4
• UFTFJSFQGQCHQW-UHFFFAOYSA-N triformin Chemical compound O=COCC(OC=O)COC=O UFTFJSFQGQCHQW-UHFFFAOYSA-N 0.000 description 4
• 201000011296 tyrosinemia Diseases 0.000 description 4
• 208000019553 vascular disease Diseases 0.000 description 4
• MZOFCQQQCNRIBI-VMXHOPILSA-N (3s)-4-[[(2s)-1-[[(2s)-1-[[(1s)-1-carboxy-2-hydroxyethyl]amino]-4-methyl-1-oxopentan-2-yl]amino]-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-3-[[2-[[(2s)-2,6-diaminohexanoyl]amino]acetyl]amino]-4-oxobutanoic acid Chemical compound OC[C@@H](C(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCN=C(N)N)NC(=O)[C@H](CC(O)=O)NC(=O)CNC(=O)[C@@H](N)CCCCN MZOFCQQQCNRIBI-VMXHOPILSA-N 0.000 description 3
• 206010063409 Acarodermatitis Diseases 0.000 description 3
• ACTIUHUUMQJHFO-UHFFFAOYSA-N Coenzym Q10 Natural products COC1=C(OC)C(=O)C(CC=C(C)CCC=C(C)CCC=C(C)CCC=C(C)CCC=C(C)CCC=C(C)CCC=C(C)CCC=C(C)CCC=C(C)CCC=C(C)C)=C(C)C1=O ACTIUHUUMQJHFO-UHFFFAOYSA-N 0.000 description 3
• 102000012422 Collagen Type I Human genes 0.000 description 3
• 108010022452 Collagen Type I Proteins 0.000 description 3
• 102000018832 Cytochromes Human genes 0.000 description 3
• 108010052832 Cytochromes Proteins 0.000 description 3
• 102000010170 Death domains Human genes 0.000 description 3
• 108050001718 Death domains Proteins 0.000 description 3
• RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 3
• LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 3
• 102000058061 Glucose Transporter Type 4 Human genes 0.000 description 3
• 208000005176 Hepatitis C Diseases 0.000 description 3
• 241000282412 Homo Species 0.000 description 3
• 229940123993 Incretin mimetic Drugs 0.000 description 3
• 108010041872 Islet Amyloid Polypeptide Proteins 0.000 description 3
• 102000036770 Islet Amyloid Polypeptide Human genes 0.000 description 3
• 208000008839 Kidney Neoplasms Diseases 0.000 description 3
• 108010085895 Laminin Proteins 0.000 description 3
• 102100031545 Microsomal triglyceride transfer protein large subunit Human genes 0.000 description 3
• 108090000854 Oxidoreductases Proteins 0.000 description 3
• 102000004316 Oxidoreductases Human genes 0.000 description 3
• 229930182555 Penicillin Natural products 0.000 description 3
• JGSARLDLIJGVTE-MBNYWOFBSA-N Penicillin G Chemical compound N([C@H]1[C@H]2SC([C@@H](N2C1=O)C(O)=O)(C)C)C(=O)CC1=CC=CC=C1 JGSARLDLIJGVTE-MBNYWOFBSA-N 0.000 description 3
• DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
• 208000003251 Pruritus Diseases 0.000 description 3
• 238000002123 RNA extraction Methods 0.000 description 3
• 208000015634 Rectal Neoplasms Diseases 0.000 description 3
• 206010038389 Renal cancer Diseases 0.000 description 3
• 108091006300 SLC2A4 Proteins 0.000 description 3
• 241000447727 Scabies Species 0.000 description 3
• FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 3
• HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
• 229940123518 Sodium/glucose cotransporter 2 inhibitor Drugs 0.000 description 3
• 208000005718 Stomach Neoplasms Diseases 0.000 description 3
• 241000282887 Suidae Species 0.000 description 3
• 229940100389 Sulfonylurea Drugs 0.000 description 3
• 229940123464 Thiazolidinedione Drugs 0.000 description 3
• GLNADSQYFUSGOU-GPTZEZBUSA-J Trypan blue Chemical compound [Na+].[Na+].[Na+].[Na+].C1=C(S([O-])(=O)=O)C=C2C=C(S([O-])(=O)=O)C(/N=N/C3=CC=C(C=C3C)C=3C=C(C(=CC=3)\N=N\C=3C(=CC4=CC(=CC(N)=C4C=3O)S([O-])(=O)=O)S([O-])(=O)=O)C)=C(O)C2=C1N GLNADSQYFUSGOU-GPTZEZBUSA-J 0.000 description 3
• 102000000852 Tumor Necrosis Factor-alpha Human genes 0.000 description 3
• 208000006682 alpha 1-Antitrypsin Deficiency Diseases 0.000 description 3
• 125000004429 atom Chemical group 0.000 description 3
• 210000003445 biliary tract Anatomy 0.000 description 3
• 208000020790 biliary tract neoplasm Diseases 0.000 description 3
• 238000012742 biochemical analysis Methods 0.000 description 3
• 230000033228 biological regulation Effects 0.000 description 3
• 239000006285 cell suspension Substances 0.000 description 3
• 230000007870 cholestasis Effects 0.000 description 3
• 231100000359 cholestasis Toxicity 0.000 description 3
• 208000019902 chronic diarrheal disease Diseases 0.000 description 3
• 230000001684 chronic effect Effects 0.000 description 3
• 235000017471 coenzyme Q10 Nutrition 0.000 description 3
• ACTIUHUUMQJHFO-UPTCCGCDSA-N coenzyme Q10 Chemical compound COC1=C(OC)C(=O)C(C\C=C(/C)CC\C=C(/C)CC\C=C(/C)CC\C=C(/C)CC\C=C(/C)CC\C=C(/C)CC\C=C(/C)CC\C=C(/C)CC\C=C(/C)CCC=C(C)C)=C(C)C1=O ACTIUHUUMQJHFO-UPTCCGCDSA-N 0.000 description 3
• 239000000512 collagen gel Substances 0.000 description 3
• 208000029742 colonic neoplasm Diseases 0.000 description 3
• 230000003111 delayed effect Effects 0.000 description 3
• 230000001419 dependent effect Effects 0.000 description 3
• 230000008021 deposition Effects 0.000 description 3
• 239000002270 dispersing agent Substances 0.000 description 3
• 239000000284 extract Substances 0.000 description 3
• 239000000796 flavoring agent Substances 0.000 description 3
• 230000002496 gastric effect Effects 0.000 description 3
• 210000001035 gastrointestinal tract Anatomy 0.000 description 3
• 238000003304 gavage Methods 0.000 description 3
• 210000002216 heart Anatomy 0.000 description 3
• 235000009200 high fat diet Nutrition 0.000 description 3
• 239000012729 immediate-release (IR) formulation Substances 0.000 description 3
• 230000001771 impaired effect Effects 0.000 description 3
• 230000000968 intestinal effect Effects 0.000 description 3
• 238000007912 intraperitoneal administration Methods 0.000 description 3
• 210000003734 kidney Anatomy 0.000 description 3
• 201000010982 kidney cancer Diseases 0.000 description 3
• 239000002523 lectin Substances 0.000 description 3
• 210000005229 liver cell Anatomy 0.000 description 3
• 208000014018 liver neoplasm Diseases 0.000 description 3
• 210000002540 macrophage Anatomy 0.000 description 3
• 239000000463 material Substances 0.000 description 3
• 230000007246 mechanism Effects 0.000 description 3
• 239000002207 metabolite Substances 0.000 description 3
• 108010038232 microsomal triglyceride transfer protein Proteins 0.000 description 3
• 230000000116 mitigating effect Effects 0.000 description 3
• 238000011294 monotherapeutic Methods 0.000 description 3
• 230000003204 osmotic effect Effects 0.000 description 3
• 239000008188 pellet Substances 0.000 description 3
• 229940049954 penicillin Drugs 0.000 description 3
• 208000007232 portal hypertension Diseases 0.000 description 3
• 239000013641 positive control Substances 0.000 description 3
• 239000003755 preservative agent Substances 0.000 description 3
• 238000000746 purification Methods 0.000 description 3
• NPCOQXAVBJJZBQ-UHFFFAOYSA-N reduced coenzyme Q9 Natural products COC1=C(O)C(C)=C(CC=C(C)CCC=C(C)CCC=C(C)CCC=C(C)CCC=C(C)CCC=C(C)CCC=C(C)CCC=C(C)CCC=C(C)C)C(O)=C1OC NPCOQXAVBJJZBQ-UHFFFAOYSA-N 0.000 description 3
• 230000002829 reductive effect Effects 0.000 description 3
• 201000002793 renal fibrosis Diseases 0.000 description 3
• 208000005687 scabies Diseases 0.000 description 3
• 231100000241 scar Toxicity 0.000 description 3
• 230000035945 sensitivity Effects 0.000 description 3
• 230000001568 sexual effect Effects 0.000 description 3
• 238000007619 statistical method Methods 0.000 description 3
• 230000000638 stimulation Effects 0.000 description 3
• 210000002784 stomach Anatomy 0.000 description 3
• 229960005322 streptomycin Drugs 0.000 description 3
• 238000007920 subcutaneous administration Methods 0.000 description 3
• 239000006228 supernatant Substances 0.000 description 3
• 239000007939 sustained release tablet Substances 0.000 description 3
• 150000001467 thiazolidinediones Chemical class 0.000 description 3
• 102000003390 tumor necrosis factor Human genes 0.000 description 3
• 229940035936 ubiquinone Drugs 0.000 description 3
• XUFXOAAUWZOOIT-SXARVLRPSA-N (2R,3R,4R,5S,6R)-5-[[(2R,3R,4R,5S,6R)-5-[[(2R,3R,4S,5S,6R)-3,4-dihydroxy-6-methyl-5-[[(1S,4R,5S,6S)-4,5,6-trihydroxy-3-(hydroxymethyl)-1-cyclohex-2-enyl]amino]-2-oxanyl]oxy]-3,4-dihydroxy-6-(hydroxymethyl)-2-oxanyl]oxy]-6-(hydroxymethyl)oxane-2,3,4-triol Chemical compound O([C@H]1O[C@H](CO)[C@H]([C@@H]([C@H]1O)O)O[C@H]1O[C@@H]([C@H]([C@H](O)[C@H]1O)N[C@@H]1[C@@H]([C@@H](O)[C@H](O)C(CO)=C1)O)C)[C@@H]1[C@@H](CO)O[C@@H](O)[C@H](O)[C@H]1O XUFXOAAUWZOOIT-SXARVLRPSA-N 0.000 description 2
• GZCGUPFRVQAUEE-IFLZFJRASA-N (2R,3S,4R,5R)-2,3,4,5,6-pentahydroxy(114C)hexanal Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)[14CH]=O GZCGUPFRVQAUEE-IFLZFJRASA-N 0.000 description 2
• HSINOMROUCMIEA-FGVHQWLLSA-N (2s,4r)-4-[(3r,5s,6r,7r,8s,9s,10s,13r,14s,17r)-6-ethyl-3,7-dihydroxy-10,13-dimethyl-2,3,4,5,6,7,8,9,11,12,14,15,16,17-tetradecahydro-1h-cyclopenta[a]phenanthren-17-yl]-2-methylpentanoic acid Chemical compound C([C@@]12C)C[C@@H](O)C[C@H]1[C@@H](CC)[C@@H](O)[C@@H]1[C@@H]2CC[C@]2(C)[C@@H]([C@H](C)C[C@H](C)C(O)=O)CC[C@H]21 HSINOMROUCMIEA-FGVHQWLLSA-N 0.000 description 2
• GVJHHUAWPYXKBD-UHFFFAOYSA-N (±)-α-Tocopherol Chemical compound OC1=C(C)C(C)=C2OC(CCCC(C)CCCC(C)CCCC(C)C)(C)CCC2=C1C GVJHHUAWPYXKBD-UHFFFAOYSA-N 0.000 description 2
• SKUVJFHTKRTQQZ-UHFFFAOYSA-N 1-(2-nitroimidazol-1-yl)-3-piperidin-1-ylpropan-2-ol;hydrochloride Chemical compound Cl.C1=CN=C([N+]([O-])=O)N1CC(O)CN1CCCCC1 SKUVJFHTKRTQQZ-UHFFFAOYSA-N 0.000 description 2
• BOVGTQGAOIONJV-BETUJISGSA-N 1-[(3ar,6as)-3,3a,4,5,6,6a-hexahydro-1h-cyclopenta[c]pyrrol-2-yl]-3-(4-methylphenyl)sulfonylurea Chemical compound C1=CC(C)=CC=C1S(=O)(=O)NC(=O)NN1C[C@H]2CCC[C@H]2C1 BOVGTQGAOIONJV-BETUJISGSA-N 0.000 description 2
• IXPNQXFRVYWDDI-UHFFFAOYSA-N 1-methyl-2,4-dioxo-1,3-diazinane-5-carboximidamide Chemical compound CN1CC(C(N)=N)C(=O)NC1=O IXPNQXFRVYWDDI-UHFFFAOYSA-N 0.000 description 2
• VBICKXHEKHSIBG-UHFFFAOYSA-N 1-monostearoylglycerol Chemical compound CCCCCCCCCCCCCCCCCC(=O)OCC(O)CO VBICKXHEKHSIBG-UHFFFAOYSA-N 0.000 description 2
• IZHVBANLECCAGF-UHFFFAOYSA-N 2-hydroxy-3-(octadecanoyloxy)propyl octadecanoate Chemical compound CCCCCCCCCCCCCCCCCC(=O)OCC(O)COC(=O)CCCCCCCCCCCCCCCCC IZHVBANLECCAGF-UHFFFAOYSA-N 0.000 description 2
• 101710123832 2-hydroxyacyl-CoA lyase 1 Proteins 0.000 description 2
• APIXJSLKIYYUKG-UHFFFAOYSA-N 3 Isobutyl 1 methylxanthine Chemical compound O=C1N(C)C(=O)N(CC(C)C)C2=C1N=CN2 APIXJSLKIYYUKG-UHFFFAOYSA-N 0.000 description 2
• 101150090724 3 gene Proteins 0.000 description 2
• WTWSDDKGKIGSJE-UHFFFAOYSA-N 5-(4-aminophenyl)cyclohexa-2,4-diene-1,1,2-triamine;tetrahydrochloride Chemical compound Cl.Cl.Cl.Cl.C1C(N)(N)C(N)=CC=C1C1=CC=C(N)C=C1 WTWSDDKGKIGSJE-UHFFFAOYSA-N 0.000 description 2
• 244000215068 Acacia senegal Species 0.000 description 2
• IKHGUXGNUITLKF-UHFFFAOYSA-N Acetaldehyde Chemical compound CC=O IKHGUXGNUITLKF-UHFFFAOYSA-N 0.000 description 2
• 102100031786 Adiponectin Human genes 0.000 description 2
• 108010076365 Adiponectin Proteins 0.000 description 2
• 229940077274 Alpha glucosidase inhibitor Drugs 0.000 description 2
• 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 2
• CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 2
• 241000416162 Astragalus gummifer Species 0.000 description 2
• 241000271566 Aves Species 0.000 description 2
• 229940123208 Biguanide Drugs 0.000 description 2
• XNCOSPRUTUOJCJ-UHFFFAOYSA-N Biguanide Chemical compound NC(N)=NC(N)=N XNCOSPRUTUOJCJ-UHFFFAOYSA-N 0.000 description 2
• 108091003079 Bovine Serum Albumin Proteins 0.000 description 2
• 101100263837 Bovine ephemeral fever virus (strain BB7721) beta gene Proteins 0.000 description 2
• VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 description 2
• 241000282472 Canis lupus familiaris Species 0.000 description 2
• CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 2
• RKWGIWYCVPQPMF-UHFFFAOYSA-N Chloropropamide Chemical compound CCCNC(=O)NS(=O)(=O)C1=CC=C(Cl)C=C1 RKWGIWYCVPQPMF-UHFFFAOYSA-N 0.000 description 2
• 206010063209 Chronic allograft nephropathy Diseases 0.000 description 2
• 206010009900 Colitis ulcerative Diseases 0.000 description 2
• 102000009268 Collagen Receptors Human genes 0.000 description 2
• 108010048623 Collagen Receptors Proteins 0.000 description 2
• 206010009944 Colon cancer Diseases 0.000 description 2
• 229920002261 Corn starch Polymers 0.000 description 2
• 208000011231 Crohn disease Diseases 0.000 description 2
• 201000003883 Cystic fibrosis Diseases 0.000 description 2
• 102000052510 DNA-Binding Proteins Human genes 0.000 description 2
• 101710096438 DNA-binding protein Proteins 0.000 description 2
• 208000007342 Diabetic Nephropathies Diseases 0.000 description 2
• 238000002965 ELISA Methods 0.000 description 2
• 101100316840 Enterobacteria phage P4 Beta gene Proteins 0.000 description 2
• 101800003838 Epidermal growth factor Proteins 0.000 description 2
• 102400001368 Epidermal growth factor Human genes 0.000 description 2
• HTQBXNHDCUEHJF-XWLPCZSASA-N Exenatide Chemical compound C([C@@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(N)=O)C(=O)NCC(=O)NCC(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CO)C(=O)N[C@@H](CO)C(=O)NCC(=O)N[C@@H](C)C(=O)N1[C@@H](CCC1)C(=O)N1[C@@H](CCC1)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CO)C(N)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@@H](NC(=O)[C@H](C)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CCSC)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CO)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@@H](NC(=O)CNC(=O)[C@H](CCC(O)=O)NC(=O)CNC(=O)[C@@H](N)CC=1NC=NC=1)[C@@H](C)O)[C@@H](C)O)C(C)C)C1=CC=CC=C1 HTQBXNHDCUEHJF-XWLPCZSASA-N 0.000 description 2
• 101150108864 Ffar1 gene Proteins 0.000 description 2
• 108010067306 Fibronectins Proteins 0.000 description 2
• 102000016359 Fibronectins Human genes 0.000 description 2
• 102100026148 Free fatty acid receptor 1 Human genes 0.000 description 2
• 206010018367 Glomerulonephritis chronic Diseases 0.000 description 2
• 229940089838 Glucagon-like peptide 1 receptor agonist Drugs 0.000 description 2
• FAEKWTJYAYMJKF-QHCPKHFHSA-N GlucoNorm Chemical compound C1=C(C(O)=O)C(OCC)=CC(CC(=O)N[C@@H](CC(C)C)C=2C(=CC=CC=2)N2CCCCC2)=C1 FAEKWTJYAYMJKF-QHCPKHFHSA-N 0.000 description 2
• 239000004366 Glucose oxidase Substances 0.000 description 2
• 108010015776 Glucose oxidase Proteins 0.000 description 2
• 206010018691 Granuloma Diseases 0.000 description 2
• 108010009202 Growth Factor Receptors Proteins 0.000 description 2
• 102000009465 Growth Factor Receptors Human genes 0.000 description 2
• 229920000084 Gum arabic Polymers 0.000 description 2
• 206010019708 Hepatic steatosis Diseases 0.000 description 2
• 101000775558 Homo sapiens Cell death activator CIDE-3 Proteins 0.000 description 2
• 101000894525 Homo sapiens Transforming growth factor-beta-induced protein ig-h3 Proteins 0.000 description 2
• 108010001336 Horseradish Peroxidase Proteins 0.000 description 2
• 208000035150 Hypercholesterolemia Diseases 0.000 description 2
• 208000031226 Hyperlipidaemia Diseases 0.000 description 2
• 101150098499 III gene Proteins 0.000 description 2
• 101150101999 IL6 gene Proteins 0.000 description 2
• 108010089308 Insulin Detemir Proteins 0.000 description 2
• 108010057186 Insulin Glargine Proteins 0.000 description 2
• 108010065920 Insulin Lispro Proteins 0.000 description 2
• COCFEDIXXNGUNL-RFKWWTKHSA-N Insulin glargine Chemical compound C([C@@H](C(=O)N[C@@H](CC(C)C)C(=O)N[C@H]1CSSC[C@H]2C(=O)N[C@H](C(=O)N[C@@H](CO)C(=O)N[C@H](C(=O)N[C@H](C(N[C@@H](CO)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC=3C=CC(O)=CC=3)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC=3C=CC(O)=CC=3)C(=O)N[C@@H](CSSC[C@H](NC(=O)[C@H](C(C)C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC=3C=CC(O)=CC=3)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](C)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C(C)C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC=3NC=NC=3)NC(=O)[C@H](CO)NC(=O)CNC1=O)C(=O)NCC(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)NCC(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N[C@@H]([C@@H](C)O)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O)C(=O)NCC(O)=O)=O)CSSC[C@@H](C(N2)=O)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C(C)C)NC(=O)[C@@H](NC(=O)CN)[C@@H](C)CC)[C@@H](C)CC)[C@@H](C)O)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CC(N)=O)NC(=O)[C@@H](NC(=O)[C@@H](N)CC=1C=CC=CC=1)C(C)C)C1=CN=CN1 COCFEDIXXNGUNL-RFKWWTKHSA-N 0.000 description 2
• PIWKPBJCKXDKJR-UHFFFAOYSA-N Isoflurane Chemical compound FC(F)OC(Cl)C(F)(F)F PIWKPBJCKXDKJR-UHFFFAOYSA-N 0.000 description 2
• ZDXPYRJPNDTMRX-VKHMYHEASA-N L-glutamine Chemical compound OC(=O)[C@@H](N)CCC(N)=O ZDXPYRJPNDTMRX-VKHMYHEASA-N 0.000 description 2
• 229930182816 L-glutamine Natural products 0.000 description 2
• 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 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
• 108090001090 Lectins Proteins 0.000 description 2
• 102000004856 Lectins Human genes 0.000 description 2
• VTAJIXDZFCRWBR-UHFFFAOYSA-N Licoricesaponin B2 Natural products C1C(C2C(C3(CCC4(C)CCC(C)(CC4C3=CC2)C(O)=O)C)(C)CC2)(C)C2C(C)(C)CC1OC1OC(C(O)=O)C(O)C(O)C1OC1OC(C(O)=O)C(O)C(O)C1O VTAJIXDZFCRWBR-UHFFFAOYSA-N 0.000 description 2
• LTXREWYXXSTFRX-QGZVFWFLSA-N Linagliptin Chemical compound N=1C=2N(C)C(=O)N(CC=3N=C4C=CC=CC4=C(C)N=3)C(=O)C=2N(CC#CC)C=1N1CCC[C@@H](N)C1 LTXREWYXXSTFRX-QGZVFWFLSA-N 0.000 description 2
• 239000012097 Lipofectamine 2000 Substances 0.000 description 2
• IBAQFPQHRJAVAV-ULAWRXDQSA-N Miglitol Chemical group OCCN1C[C@H](O)[C@@H](O)[C@H](O)[C@H]1CO IBAQFPQHRJAVAV-ULAWRXDQSA-N 0.000 description 2
• 241000699666 Mus <mouse, genus> Species 0.000 description 2
• 101100273740 Mus musculus Cd68 gene Proteins 0.000 description 2
• 206010028813 Nausea Diseases 0.000 description 2
• 101710204575 Oxysterol-binding protein 3 Proteins 0.000 description 2
• 206010033645 Pancreatitis Diseases 0.000 description 2
• 208000037273 Pathologic Processes Diseases 0.000 description 2
• 235000019483 Peanut oil Nutrition 0.000 description 2
• 108050005456 Phosphatidate phosphatase LPIN1 Proteins 0.000 description 2
• 239000002202 Polyethylene glycol Substances 0.000 description 2
• 229920001214 Polysorbate 60 Polymers 0.000 description 2
• LCTONWCANYUPML-UHFFFAOYSA-M Pyruvate Chemical compound CC(=O)C([O-])=O LCTONWCANYUPML-UHFFFAOYSA-M 0.000 description 2
• 102000013009 Pyruvate Kinase Human genes 0.000 description 2
• 108020005115 Pyruvate Kinase Proteins 0.000 description 2
• 241000700159 Rattus Species 0.000 description 2
• YASAKCUCGLMORW-UHFFFAOYSA-N Rosiglitazone Chemical compound C=1C=CC=NC=1N(C)CCOC(C=C1)=CC=C1CC1SC(=O)NC1=O YASAKCUCGLMORW-UHFFFAOYSA-N 0.000 description 2
• 108010077895 Sarcosine Proteins 0.000 description 2
• 206010040047 Sepsis Diseases 0.000 description 2
• 235000021355 Stearic acid Nutrition 0.000 description 2
• 108700012920 TNF Proteins 0.000 description 2
• 229920001615 Tragacanth Polymers 0.000 description 2
• XLYOFNOQVPJJNP-PWCQTSIFSA-N Tritiated water Chemical compound [3H]O[3H] XLYOFNOQVPJJNP-PWCQTSIFSA-N 0.000 description 2
• 206010048302 Tubulointerstitial nephritis Diseases 0.000 description 2
• 201000006704 Ulcerative Colitis Diseases 0.000 description 2
• 206010047700 Vomiting Diseases 0.000 description 2
• 101100264077 Xenopus laevis wrn gene Proteins 0.000 description 2
• 201000004525 Zellweger Syndrome Diseases 0.000 description 2
• 210000000683 abdominal cavity Anatomy 0.000 description 2
• 235000010489 acacia gum Nutrition 0.000 description 2
• 239000000205 acacia gum Substances 0.000 description 2
• 229960001466 acetohexamide Drugs 0.000 description 2
• VGZSUPCWNCWDAN-UHFFFAOYSA-N acetohexamide Chemical compound C1=CC(C(=O)C)=CC=C1S(=O)(=O)NC(=O)NC1CCCCC1 VGZSUPCWNCWDAN-UHFFFAOYSA-N 0.000 description 2
• 239000000556 agonist Substances 0.000 description 2
• 239000003888 alpha glucosidase inhibitor Substances 0.000 description 2
• 239000003242 anti bacterial agent Substances 0.000 description 2
• 229940088710 antibiotic agent Drugs 0.000 description 2
• RCHHVVGSTHAVPF-ZPHPLDECSA-N apidra Chemical compound C([C@@H](C(=O)N[C@@H](CC(C)C)C(=O)N[C@H]1CSSC[C@H]2C(=O)N[C@H](C(=O)N[C@@H](CO)C(=O)N[C@H](C(=O)N[C@H](C(N[C@@H](CO)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC=3C=CC(O)=CC=3)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC=3C=CC(O)=CC=3)C(=O)N[C@@H](CSSC[C@H](NC(=O)[C@H](C(C)C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC=3C=CC(O)=CC=3)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](C)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C(C)C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC=3N=CNC=3)NC(=O)[C@H](CO)NC(=O)CNC1=O)C(=O)NCC(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)NCC(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N[C@@H]([C@@H](C)O)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H]([C@@H](C)O)C(O)=O)C(=O)N[C@@H](CC(N)=O)C(O)=O)=O)CSSC[C@@H](C(N2)=O)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C(C)C)NC(=O)[C@@H](NC(=O)CN)[C@@H](C)CC)[C@@H](C)CC)[C@@H](C)O)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CCCCN)NC(=O)[C@@H](NC(=O)[C@@H](N)CC=1C=CC=CC=1)C(C)C)C1=CNC=N1 RCHHVVGSTHAVPF-ZPHPLDECSA-N 0.000 description 2
• 238000011888 autopsy Methods 0.000 description 2
• 210000000227 basophil cell of anterior lobe of hypophysis Anatomy 0.000 description 2
• 230000009286 beneficial effect Effects 0.000 description 2
• 229940096699 bile acid sequestrants Drugs 0.000 description 2
• 201000009036 biliary tract cancer Diseases 0.000 description 2
• 239000011230 binding agent Substances 0.000 description 2
• 238000004422 calculation algorithm Methods 0.000 description 2
• 238000011088 calibration curve Methods 0.000 description 2
• 201000011510 cancer Diseases 0.000 description 2
• LEMUFSYUPGXXCM-JNEQYSBXSA-N caninsulin Chemical compound [Zn].C([C@@H](C(=O)N[C@@H](CC(C)C)C(=O)N[C@H]1CSSC[C@H]2C(=O)N[C@H](C(=O)N[C@@H](CO)C(=O)N[C@H](C(=O)N[C@H](C(N[C@@H](CO)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC=3C=CC(O)=CC=3)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC=3C=CC(O)=CC=3)C(=O)N[C@@H](CSSC[C@H](NC(=O)[C@H](C(C)C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC=3C=CC(O)=CC=3)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](C)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C(C)C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC3N=CN=C3)NC(=O)[C@H](CO)NC(=O)CNC1=O)C(=O)NCC(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)NCC(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N[C@@H]([C@@H](C)O)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](C(C)O)C(O)=O)C(=O)N[C@@H](CC(N)=O)C(O)=O)=O)CSSC[C@@H](C(N2)=O)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C(C)C)NC(=O)[C@@H](NC(=O)CN)[C@@H](C)CC)[C@@H](C)CC)[C@@H](C)O)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CC(N)=O)NC(=O)[C@@H](NC(=O)[C@@H](N)CC=1C=CC=CC=1)C(C)C)C1C=NC=N1 LEMUFSYUPGXXCM-JNEQYSBXSA-N 0.000 description 2
• 235000011089 carbon dioxide Nutrition 0.000 description 2
• VDTNNGKXZGSZIP-UHFFFAOYSA-N carbutamide Chemical compound CCCCNC(=O)NS(=O)(=O)C1=CC=C(N)C=C1 VDTNNGKXZGSZIP-UHFFFAOYSA-N 0.000 description 2
• 239000000969 carrier Substances 0.000 description 2
• 230000021164 cell adhesion Effects 0.000 description 2
• 230000030833 cell death Effects 0.000 description 2
• 230000003833 cell viability Effects 0.000 description 2
• 230000008859 change Effects 0.000 description 2
• JUFFVKRROAPVBI-PVOYSMBESA-N chembl1210015 Chemical compound C([C@@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(=O)N[C@H]1[C@@H]([C@@H](O)[C@H](O[C@H]2[C@@H]([C@@H](O)[C@@H](O)[C@@H](CO[C@]3(O[C@@H](C[C@H](O)[C@H](O)CO)[C@H](NC(C)=O)[C@@H](O)C3)C(O)=O)O2)O)[C@@H](CO)O1)NC(C)=O)C(=O)NCC(=O)NCC(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CO)C(=O)N[C@@H](CO)C(=O)NCC(=O)N[C@@H](C)C(=O)N1[C@@H](CCC1)C(=O)N1[C@@H](CCC1)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CO)C(N)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@@H](NC(=O)[C@H](C)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CCSC)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CO)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@@H](NC(=O)CNC(=O)[C@H](CCC(O)=O)NC(=O)CNC(=O)[C@@H](N)CC=1NC=NC=1)[C@@H](C)O)[C@@H](C)O)C(C)C)C1=CC=CC=C1 JUFFVKRROAPVBI-PVOYSMBESA-N 0.000 description 2
• 239000007795 chemical reaction product Substances 0.000 description 2
• 231100000850 chronic interstitial nephritis Toxicity 0.000 description 2
• 239000011248 coating agent Substances 0.000 description 2
• 206010009887 colitis Diseases 0.000 description 2
• 210000001072 colon Anatomy 0.000 description 2
• 239000008120 corn starch Substances 0.000 description 2
• 238000002425 crystallisation Methods 0.000 description 2
• 230000008025 crystallization Effects 0.000 description 2
• 238000000432 density-gradient centrifugation Methods 0.000 description 2
• 238000013461 design Methods 0.000 description 2
• 238000001514 detection method Methods 0.000 description 2
• 230000014541 detection of hypoxia Effects 0.000 description 2
• 229960003957 dexamethasone Drugs 0.000 description 2
• UREBDLICKHMUKA-CXSFZGCWSA-N dexamethasone Chemical compound C1CC2=CC(=O)C=C[C@]2(C)[C@]2(F)[C@@H]1[C@@H]1C[C@@H](C)[C@@](C(=O)CO)(O)[C@@]1(C)C[C@@H]2O UREBDLICKHMUKA-CXSFZGCWSA-N 0.000 description 2
• 208000033679 diabetic kidney disease Diseases 0.000 description 2
• 238000003745 diagnosis Methods 0.000 description 2
• 230000009274 differential gene expression Effects 0.000 description 2
• 239000007884 disintegrant Substances 0.000 description 2
• 238000006073 displacement reaction Methods 0.000 description 2
• 238000009826 distribution Methods 0.000 description 2
• POULHZVOKOAJMA-UHFFFAOYSA-M dodecanoate Chemical compound CCCCCCCCCCCC([O-])=O POULHZVOKOAJMA-UHFFFAOYSA-M 0.000 description 2
• 239000003651 drinking water Substances 0.000 description 2
• 235000020188 drinking water Nutrition 0.000 description 2
• 238000001647 drug administration Methods 0.000 description 2
• 230000008030 elimination Effects 0.000 description 2
• 238000003379 elimination reaction Methods 0.000 description 2
• 239000003995 emulsifying agent Substances 0.000 description 2
• 239000000839 emulsion Substances 0.000 description 2
• 238000005516 engineering process Methods 0.000 description 2
• 229940116977 epidermal growth factor Drugs 0.000 description 2
• 108010038795 estrogen receptors Proteins 0.000 description 2
• 230000007717 exclusion Effects 0.000 description 2
• 230000029142 excretion Effects 0.000 description 2
• 208000009866 extrahepatic cholestasis Diseases 0.000 description 2
• 230000004438 eyesight Effects 0.000 description 2
• 150000004665 fatty acids Chemical class 0.000 description 2
• 239000012894 fetal calf serum Substances 0.000 description 2
• 238000000684 flow cytometry Methods 0.000 description 2
• 235000013355 food flavoring agent Nutrition 0.000 description 2
• 235000003599 food sweetener Nutrition 0.000 description 2
• 210000000232 gallbladder Anatomy 0.000 description 2
• 206010017758 gastric cancer Diseases 0.000 description 2
• 238000001879 gelation Methods 0.000 description 2
• ZJJXGWJIGJFDTL-UHFFFAOYSA-N glipizide Chemical compound C1=NC(C)=CN=C1C(=O)NCCC1=CC=C(S(=O)(=O)NC(=O)NC2CCCCC2)C=C1 ZJJXGWJIGJFDTL-UHFFFAOYSA-N 0.000 description 2
• 239000003877 glucagon like peptide 1 receptor agonist Substances 0.000 description 2
• 229940124828 glucokinase activator Drugs 0.000 description 2
• 229940116332 glucose oxidase Drugs 0.000 description 2
• 235000019420 glucose oxidase Nutrition 0.000 description 2
• 230000004190 glucose uptake Effects 0.000 description 2
• LPLVUJXQOOQHMX-UHFFFAOYSA-N glycyrrhetinic acid glycoside Natural products C1CC(C2C(C3(CCC4(C)CCC(C)(CC4C3=CC2=O)C(O)=O)C)(C)CC2)(C)C2C(C)(C)C1OC1OC(C(O)=O)C(O)C(O)C1OC1OC(C(O)=O)C(O)C(O)C1O LPLVUJXQOOQHMX-UHFFFAOYSA-N 0.000 description 2
• 239000001685 glycyrrhizic acid Substances 0.000 description 2
• 229960004949 glycyrrhizic acid Drugs 0.000 description 2
• UYRUBYNTXSDKQT-UHFFFAOYSA-N glycyrrhizic acid Natural products CC1(C)C(CCC2(C)C1CCC3(C)C2C(=O)C=C4C5CC(C)(CCC5(C)CCC34C)C(=O)O)OC6OC(C(O)C(O)C6OC7OC(O)C(O)C(O)C7C(=O)O)C(=O)O UYRUBYNTXSDKQT-UHFFFAOYSA-N 0.000 description 2
• 235000019410 glycyrrhizin Nutrition 0.000 description 2
• LPLVUJXQOOQHMX-QWBHMCJMSA-N glycyrrhizinic acid Chemical group O([C@@H]1[C@@H](O)[C@H](O)[C@H](O[C@@H]1O[C@@H]1C([C@H]2[C@]([C@@H]3[C@@]([C@@]4(CC[C@@]5(C)CC[C@@](C)(C[C@H]5C4=CC3=O)C(O)=O)C)(C)CC2)(C)CC1)(C)C)C(O)=O)[C@@H]1O[C@H](C(O)=O)[C@@H](O)[C@H](O)[C@H]1O LPLVUJXQOOQHMX-QWBHMCJMSA-N 0.000 description 2
• 230000036541 health Effects 0.000 description 2
• 238000010438 heat treatment Methods 0.000 description 2
• 208000002672 hepatitis B Diseases 0.000 description 2
• 208000006359 hepatoblastoma Diseases 0.000 description 2
• BXWNKGSJHAJOGX-UHFFFAOYSA-N hexadecan-1-ol Chemical compound CCCCCCCCCCCCCCCCO BXWNKGSJHAJOGX-UHFFFAOYSA-N 0.000 description 2
• 238000000265 homogenisation Methods 0.000 description 2
• WNRQPCUGRUFHED-DETKDSODSA-N humalog Chemical compound C([C@H](NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CO)NC(=O)[C@H](CS)NC(=O)[C@H]([C@@H](C)CC)NC(=O)[C@H](CO)NC(=O)[C@H]([C@@H](C)O)NC(=O)[C@H](CS)NC(=O)[C@H](CS)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C(C)C)NC(=O)[C@@H](NC(=O)CN)[C@@H](C)CC)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N[C@@H](CS)C(=O)N[C@@H](CC(N)=O)C(O)=O)C1=CC=C(O)C=C1.C([C@@H](C(=O)N[C@@H](CC(C)C)C(=O)N[C@H](C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](C)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CS)C(=O)NCC(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)NCC(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CCCCN)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H]([C@@H](C)O)C(O)=O)C(C)C)NC(=O)[C@H](CO)NC(=O)CNC(=O)[C@H](CS)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC=1NC=NC=1)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CC(N)=O)NC(=O)[C@@H](NC(=O)[C@@H](N)CC=1C=CC=CC=1)C(C)C)C1=CN=CN1 WNRQPCUGRUFHED-DETKDSODSA-N 0.000 description 2
• 229960000890 hydrocortisone Drugs 0.000 description 2
• 230000001631 hypertensive effect Effects 0.000 description 2
• 238000002991 immunohistochemical analysis Methods 0.000 description 2
• 230000002055 immunohistochemical effect Effects 0.000 description 2
• 238000010348 incorporation Methods 0.000 description 2
• 230000001939 inductive effect Effects 0.000 description 2
• 208000015181 infectious disease Diseases 0.000 description 2
• 239000004026 insulin derivative Substances 0.000 description 2
• 108700039926 insulin glulisine Proteins 0.000 description 2
• 210000000936 intestine Anatomy 0.000 description 2
• 208000001024 intrahepatic cholestasis Diseases 0.000 description 2
• 230000007872 intrahepatic cholestasis Effects 0.000 description 2
• 238000007918 intramuscular administration Methods 0.000 description 2
• 238000001990 intravenous administration Methods 0.000 description 2
• 229910052742 iron Inorganic materials 0.000 description 2
• 229960002725 isoflurane Drugs 0.000 description 2
• 229960003350 isoniazid Drugs 0.000 description 2
• QRXWMOHMRWLFEY-UHFFFAOYSA-N isoniazide Chemical compound NNC(=O)C1=CC=NC=C1 QRXWMOHMRWLFEY-UHFFFAOYSA-N 0.000 description 2
• 230000007803 itching Effects 0.000 description 2
• 239000008101 lactose Substances 0.000 description 2
• 229960001375 lactose Drugs 0.000 description 2
• 229940070765 laurate Drugs 0.000 description 2
• UGOZVNFCFYTPAZ-IOXYNQHNSA-N levemir Chemical compound CCCCCCCCCCCCCC(=O)NCCCC[C@@H](C(O)=O)NC(=O)[C@@H]1CCCN1C(=O)[C@H]([C@@H](C)O)NC(=O)[C@@H](NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)CNC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CCC(O)=O)NC(=O)CNC(=O)[C@H]1NC(=O)[C@H](C(C)C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC=2C=CC(O)=CC=2)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](C)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C(C)C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC=2N=CNC=2)NC(=O)[C@H](CO)NC(=O)CNC(=O)[C@@H](NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC=2N=CNC=2)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CC(N)=O)NC(=O)[C@@H](NC(=O)[C@@H](N)CC=2C=CC=CC=2)C(C)C)CSSC[C@@H]2NC(=O)[C@@H](NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@@H](NC(=O)[C@@H](NC(=O)CN)[C@@H](C)CC)C(C)C)CSSC[C@H](NC(=O)[C@H]([C@@H](C)CC)NC(=O)[C@H](CO)NC(=O)[C@H]([C@@H](C)O)NC2=O)C(=O)N[C@@H](CO)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC=2C=CC(O)=CC=2)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC=2C=CC(O)=CC=2)C(=O)N[C@@H](CSSC1)C(=O)N[C@@H](CC(N)=O)C(O)=O)CC1=CC=C(O)C=C1 UGOZVNFCFYTPAZ-IOXYNQHNSA-N 0.000 description 2
• 239000003446 ligand Substances 0.000 description 2
• 208000018191 liver inflammation Diseases 0.000 description 2
• 239000007937 lozenge Substances 0.000 description 2
• 239000000314 lubricant Substances 0.000 description 2
• 210000004072 lung Anatomy 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
• 239000003550 marker Substances 0.000 description 2
• 235000012054 meals Nutrition 0.000 description 2
• 210000000713 mesentery Anatomy 0.000 description 2
• 229960000485 methotrexate Drugs 0.000 description 2
• 229920000609 methyl cellulose Polymers 0.000 description 2
• 150000004702 methyl esters Chemical class 0.000 description 2
• 239000001923 methylcellulose Substances 0.000 description 2
• 235000010981 methylcellulose Nutrition 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
• 244000005706 microflora Species 0.000 description 2
• 208000008275 microscopic colitis Diseases 0.000 description 2
• 238000002156 mixing Methods 0.000 description 2
• 230000004048 modification Effects 0.000 description 2
• 238000012986 modification Methods 0.000 description 2
• VLAPMBHFAWRUQP-UHFFFAOYSA-L molybdic acid Chemical compound O[Mo](O)(=O)=O VLAPMBHFAWRUQP-UHFFFAOYSA-L 0.000 description 2
• 239000001788 mono and diglycerides of fatty acids Substances 0.000 description 2
• OELFLUMRDSZNSF-BRWVUGGUSA-N nateglinide Chemical compound C1C[C@@H](C(C)C)CC[C@@H]1C(=O)N[C@@H](C(O)=O)CC1=CC=CC=C1 OELFLUMRDSZNSF-BRWVUGGUSA-N 0.000 description 2
• 230000008693 nausea Effects 0.000 description 2
• 201000009925 nephrosclerosis Diseases 0.000 description 2
• 230000007935 neutral effect Effects 0.000 description 2
• 238000011587 new zealand white rabbit Methods 0.000 description 2
• 235000020925 non fasting Nutrition 0.000 description 2
• 238000010606 normalization Methods 0.000 description 2
• 235000015097 nutrients Nutrition 0.000 description 2
• OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 2
• 230000003647 oxidation Effects 0.000 description 2
• 238000007254 oxidation reaction Methods 0.000 description 2
• 238000006213 oxygenation reaction Methods 0.000 description 2
• 238000012856 packing Methods 0.000 description 2
• 210000000496 pancreas Anatomy 0.000 description 2
• 230000001717 pathogenic effect Effects 0.000 description 2
• 230000009054 pathological process Effects 0.000 description 2
• 238000003068 pathway analysis Methods 0.000 description 2
• 235000021400 peanut butter Nutrition 0.000 description 2
• 239000000312 peanut oil Substances 0.000 description 2
• WEXRUCMBJFQVBZ-UHFFFAOYSA-N pentobarbital Chemical compound CCCC(C)C1(CC)C(=O)NC(=O)NC1=O WEXRUCMBJFQVBZ-UHFFFAOYSA-N 0.000 description 2
• YBYRMVIVWMBXKQ-UHFFFAOYSA-N phenylmethanesulfonyl fluoride Chemical compound FS(=O)(=O)CC1=CC=CC=C1 YBYRMVIVWMBXKQ-UHFFFAOYSA-N 0.000 description 2
• IYDGMDWEHDFVQI-UHFFFAOYSA-N phosphoric acid;trioxotungsten Chemical compound O=[W](=O)=O.O=[W](=O)=O.O=[W](=O)=O.O=[W](=O)=O.O=[W](=O)=O.O=[W](=O)=O.O=[W](=O)=O.O=[W](=O)=O.O=[W](=O)=O.O=[W](=O)=O.O=[W](=O)=O.O=[W](=O)=O.OP(O)(O)=O IYDGMDWEHDFVQI-UHFFFAOYSA-N 0.000 description 2
• HYAFETHFCAUJAY-UHFFFAOYSA-N pioglitazone Chemical compound N1=CC(CC)=CC=C1CCOC(C=C1)=CC=C1CC1C(=O)NC(=O)S1 HYAFETHFCAUJAY-UHFFFAOYSA-N 0.000 description 2
• 229920001223 polyethylene glycol Polymers 0.000 description 2
• 239000001267 polyvinylpyrrolidone Substances 0.000 description 2
• 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 2
• 229920000036 polyvinylpyrrolidone Polymers 0.000 description 2
• 235000015277 pork Nutrition 0.000 description 2
• 239000000843 powder Substances 0.000 description 2
• 230000002035 prolonged effect Effects 0.000 description 2
• QELSKZZBTMNZEB-UHFFFAOYSA-N propylparaben Chemical compound CCCOC(=O)C1=CC=C(O)C=C1 QELSKZZBTMNZEB-UHFFFAOYSA-N 0.000 description 2
• 238000000751 protein extraction Methods 0.000 description 2
• 230000005855 radiation Effects 0.000 description 2
• 238000003753 real-time PCR Methods 0.000 description 2
• 210000000664 rectum Anatomy 0.000 description 2
• 230000004044 response Effects 0.000 description 2
• 238000003757 reverse transcription PCR Methods 0.000 description 2
• 229940043230 sarcosine Drugs 0.000 description 2
• QGJUIPDUBHWZPV-SGTAVMJGSA-N saxagliptin Chemical compound C1C(C2)CC(C3)CC2(O)CC13[C@H](N)C(=O)N1[C@H](C#N)C[C@@H]2C[C@@H]21 QGJUIPDUBHWZPV-SGTAVMJGSA-N 0.000 description 2
• 108010033693 saxagliptin Proteins 0.000 description 2
• 230000037390 scarring Effects 0.000 description 2
• 238000013515 script Methods 0.000 description 2
• 235000010413 sodium alginate Nutrition 0.000 description 2
• 239000000661 sodium alginate Substances 0.000 description 2
• 229940005550 sodium alginate Drugs 0.000 description 2
• 238000002415 sodium dodecyl sulfate polyacrylamide gel electrophoresis Methods 0.000 description 2
• 239000007787 solid Substances 0.000 description 2
• 239000002904 solvent Substances 0.000 description 2
• 238000004611 spectroscopical analysis Methods 0.000 description 2
• 239000008117 stearic acid Substances 0.000 description 2
• 239000008223 sterile water Substances 0.000 description 2
• 201000011549 stomach cancer Diseases 0.000 description 2
• YROXIXLRRCOBKF-UHFFFAOYSA-N sulfonylurea Chemical class OC(=N)N=S(=O)=O YROXIXLRRCOBKF-UHFFFAOYSA-N 0.000 description 2
• 239000000375 suspending agent Substances 0.000 description 2
• 238000004114 suspension culture Methods 0.000 description 2
• 239000003765 sweetening agent Substances 0.000 description 2
• 208000011580 syndromic disease Diseases 0.000 description 2
• 230000008685 targeting Effects 0.000 description 2
• OUDSBRTVNLOZBN-UHFFFAOYSA-N tolazamide Chemical compound C1=CC(C)=CC=C1S(=O)(=O)NC(=O)NN1CCCCCC1 OUDSBRTVNLOZBN-UHFFFAOYSA-N 0.000 description 2
• VBEQCZHXXJYVRD-GACYYNSASA-N uroanthelone Chemical compound C([C@@H](C(=O)N[C@H](C(=O)N[C@@H](CS)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CS)C(=O)N[C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)NCC(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N[C@@H](CO)C(=O)NCC(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CS)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O)C(C)C)[C@@H](C)O)NC(=O)[C@H](CO)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CO)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@@H](NC(=O)[C@H](CC=1NC=NC=1)NC(=O)[C@H](CCSC)NC(=O)[C@H](CS)NC(=O)[C@@H](NC(=O)CNC(=O)CNC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CS)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)CNC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CO)NC(=O)[C@H](CO)NC(=O)[C@H]1N(CCC1)C(=O)[C@H](CS)NC(=O)CNC(=O)[C@H]1N(CCC1)C(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CO)NC(=O)[C@@H](N)CC(N)=O)C(C)C)[C@@H](C)CC)C1=CC=C(O)C=C1 VBEQCZHXXJYVRD-GACYYNSASA-N 0.000 description 2
• 210000003462 vein Anatomy 0.000 description 2
• 229960001254 vildagliptin Drugs 0.000 description 2
• SYOKIDBDQMKNDQ-XWTIBIIYSA-N vildagliptin Chemical compound C1C(O)(C2)CC(C3)CC1CC32NCC(=O)N1CCC[C@H]1C#N SYOKIDBDQMKNDQ-XWTIBIIYSA-N 0.000 description 2
• 230000008673 vomiting Effects 0.000 description 2
• XOSXWYQMOYSSKB-LDKJGXKFSA-L water blue Chemical compound CC1=CC(/C(\C(C=C2)=CC=C2NC(C=C2)=CC=C2S([O-])(=O)=O)=C(\C=C2)/C=C/C\2=N\C(C=C2)=CC=C2S([O-])(=O)=O)=CC(S(O)(=O)=O)=C1N.[Na+].[Na+] XOSXWYQMOYSSKB-LDKJGXKFSA-L 0.000 description 2
• 230000004580 weight loss Effects 0.000 description 2
• ZWASRJHIEFYJGL-BFUOFWGJSA-N (2r)-1,1,1-trifluoro-2-[3-[(2r)-4-[4-fluoro-2-(trifluoromethyl)phenyl]-2-methylpiperazin-1-yl]sulfonylphenyl]propan-2-ol Chemical compound C([C@H]1C)N(C=2C(=CC(F)=CC=2)C(F)(F)F)CCN1S(=O)(=O)C1=CC=CC([C@@](C)(O)C(F)(F)F)=C1 ZWASRJHIEFYJGL-BFUOFWGJSA-N 0.000 description 1
• MSFZPBXAGPYVFD-NFBCFJMWSA-N (2r)-2-amino-3-[1-[3-[2-[2-[2-[4-[[(5s)-5,6-diamino-6-oxohexyl]amino]butylamino]-2-oxoethoxy]ethoxy]ethylamino]-3-oxopropyl]-2,5-dioxopyrrolidin-3-yl]sulfanylpropanoic acid Chemical compound NC(=O)[C@@H](N)CCCCNCCCCNC(=O)COCCOCCNC(=O)CCN1C(=O)CC(SC[C@H](N)C(O)=O)C1=O MSFZPBXAGPYVFD-NFBCFJMWSA-N 0.000 description 1
• LNAZSHAWQACDHT-XIYTZBAFSA-N (2r,3r,4s,5r,6s)-4,5-dimethoxy-2-(methoxymethyl)-3-[(2s,3r,4s,5r,6r)-3,4,5-trimethoxy-6-(methoxymethyl)oxan-2-yl]oxy-6-[(2r,3r,4s,5r,6r)-4,5,6-trimethoxy-2-(methoxymethyl)oxan-3-yl]oxyoxane Chemical compound CO[C@@H]1[C@@H](OC)[C@H](OC)[C@@H](COC)O[C@H]1O[C@H]1[C@H](OC)[C@@H](OC)[C@H](O[C@H]2[C@@H]([C@@H](OC)[C@H](OC)O[C@@H]2COC)OC)O[C@@H]1COC LNAZSHAWQACDHT-XIYTZBAFSA-N 0.000 description 1
• GZCGUPFRVQAUEE-CPMQAFPASA-N (2r,3s,4s,5r)-2,3,4,5,6-pentahydroxy-5-tritiohexanal Chemical compound OC[C@](O)([3H])[C@@H](O)[C@H](O)[C@@H](O)C=O GZCGUPFRVQAUEE-CPMQAFPASA-N 0.000 description 1
• ZAZOPXOKXNYGDE-ZDUSSCGKSA-N (5s)-2-[2-(2-fluorophenyl)propan-2-ylamino]-5-methyl-5-(trifluoromethyl)-1,3-thiazol-4-one Chemical compound C=1C=CC=C(F)C=1C(C)(C)NC1=NC(=O)[C@@](C)(C(F)(F)F)S1 ZAZOPXOKXNYGDE-ZDUSSCGKSA-N 0.000 description 1
• YCNCXQNUXCHRRX-ZHPDPMBESA-N (5s)-2-[[(1r,3s,4s)-3-bicyclo[2.2.1]heptanyl]amino]-5-methyl-5-propan-2-yl-1,3-thiazol-4-one Chemical compound N([C@@H]1[C@@]2([H])CC[C@](C2)(C1)[H])C1=NC(=O)[C@](C)(C(C)C)S1 YCNCXQNUXCHRRX-ZHPDPMBESA-N 0.000 description 1
• GVJHHUAWPYXKBD-IEOSBIPESA-N (R)-alpha-Tocopherol Natural products OC1=C(C)C(C)=C2O[C@@](CCC[C@H](C)CCC[C@H](C)CCCC(C)C)(C)CCC2=C1C GVJHHUAWPYXKBD-IEOSBIPESA-N 0.000 description 1
• 101150084750 1 gene Proteins 0.000 description 1
• OAAZMUGLOXGVNH-UHFFFAOYSA-N 1-(3-hydroxyazetidin-1-yl)-2-(6-hydroxy-2-phenyl-2-adamantyl)ethanone Chemical compound C1C(O)CN1C(=O)CC1(C=2C=CC=CC=2)C2CC(C3O)CC1CC3C2 OAAZMUGLOXGVNH-UHFFFAOYSA-N 0.000 description 1
• LLJFMFZYVVLQKT-UHFFFAOYSA-N 1-cyclohexyl-3-[4-[2-(7-methoxy-4,4-dimethyl-1,3-dioxo-2-isoquinolinyl)ethyl]phenyl]sulfonylurea Chemical compound C=1C(OC)=CC=C(C(C2=O)(C)C)C=1C(=O)N2CCC(C=C1)=CC=C1S(=O)(=O)NC(=O)NC1CCCCC1 LLJFMFZYVVLQKT-UHFFFAOYSA-N 0.000 description 1
• IIZPXYDJLKNOIY-JXPKJXOSSA-N 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCC\C=C/C\C=C/C\C=C/C\C=C/CCCCC IIZPXYDJLKNOIY-JXPKJXOSSA-N 0.000 description 1
• MPDGHEJMBKOTSU-YKLVYJNSSA-N 18beta-glycyrrhetic acid Chemical compound C([C@H]1C2=CC(=O)[C@H]34)[C@@](C)(C(O)=O)CC[C@]1(C)CC[C@@]2(C)[C@]4(C)CC[C@@H]1[C@]3(C)CC[C@H](O)C1(C)C MPDGHEJMBKOTSU-YKLVYJNSSA-N 0.000 description 1
• 101150028074 2 gene Proteins 0.000 description 1
• RATZLMXRALDSJW-UHFFFAOYSA-N 2-(2-ethyl-3H-benzofuran-2-yl)-4,5-dihydro-1H-imidazole Chemical compound C1C2=CC=CC=C2OC1(CC)C1=NCCN1 RATZLMXRALDSJW-UHFFFAOYSA-N 0.000 description 1
• SMZOUWXMTYCWNB-UHFFFAOYSA-N 2-(2-methoxy-5-methylphenyl)ethanamine Chemical compound COC1=CC=C(C)C=C1CCN SMZOUWXMTYCWNB-UHFFFAOYSA-N 0.000 description 1
• NIXOWILDQLNWCW-UHFFFAOYSA-N 2-Propenoic acid Natural products OC(=O)C=C NIXOWILDQLNWCW-UHFFFAOYSA-N 0.000 description 1
• NCDZABJPWMBMIQ-INIZCTEOSA-N 2-[(3s)-1-[5-(cyclohexylcarbamoyl)-6-propylsulfanylpyridin-2-yl]piperidin-3-yl]acetic acid Chemical compound CCCSC1=NC(N2C[C@H](CC(O)=O)CCC2)=CC=C1C(=O)NC1CCCCC1 NCDZABJPWMBMIQ-INIZCTEOSA-N 0.000 description 1
• 101710186882 2-hydroxyacyl-CoA lyase Proteins 0.000 description 1
• ORQZQBUNAMJFCY-UHFFFAOYSA-N 3-[1-(3-ethylsulfonylpropyl)-4-bicyclo[2.2.2]octanyl]-4-methyl-5-[2-(trifluoromethyl)phenyl]-1,2,4-triazole Chemical compound C1CC(CCCS(=O)(=O)CC)(CC2)CCC12C(N1C)=NN=C1C1=CC=CC=C1C(F)(F)F ORQZQBUNAMJFCY-UHFFFAOYSA-N 0.000 description 1
• OGYZYOKAXYFLIU-UHFFFAOYSA-N 3-[1-(4-chlorophenyl)-3-fluorocyclobutyl]-4,5-dicyclopropyl-1,2,4-triazole Chemical compound C1C(F)CC1(C=1C=CC(Cl)=CC=1)C(N1C2CC2)=NN=C1C1CC1 OGYZYOKAXYFLIU-UHFFFAOYSA-N 0.000 description 1
• DGENZVKCTGIDRZ-UHFFFAOYSA-N 3-[4-[(3-phenoxyphenyl)methylamino]phenyl]propanoic acid Chemical compound C1=CC(CCC(=O)O)=CC=C1NCC1=CC=CC(OC=2C=CC=CC=2)=C1 DGENZVKCTGIDRZ-UHFFFAOYSA-N 0.000 description 1
• WZFZJEPHYDDFCT-UHFFFAOYSA-N 3-chloro-2-methyl-n-[4-[2-(3-oxomorpholin-4-yl)ethyl]-1,3-thiazol-2-yl]benzenesulfonamide Chemical compound CC1=C(Cl)C=CC=C1S(=O)(=O)NC1=NC(CCN2C(COCC2)=O)=CS1 WZFZJEPHYDDFCT-UHFFFAOYSA-N 0.000 description 1
• YDPRNGAPPNPYQQ-UHFFFAOYSA-N 3-chloro-2-methyl-n-[4-[2-(4-methylpiperazin-1-yl)-2-oxoethyl]-1,3-thiazol-2-yl]benzenesulfonamide Chemical compound C1CN(C)CCN1C(=O)CC1=CSC(NS(=O)(=O)C=2C(=C(Cl)C=CC=2)C)=N1 YDPRNGAPPNPYQQ-UHFFFAOYSA-N 0.000 description 1
• BTXXTMOWISPQSJ-UHFFFAOYSA-N 4,4,4-trifluorobutan-2-one Chemical compound CC(=O)CC(F)(F)F BTXXTMOWISPQSJ-UHFFFAOYSA-N 0.000 description 1
• SWLAMJPTOQZTAE-UHFFFAOYSA-N 4-[2-[(5-chloro-2-methoxybenzoyl)amino]ethyl]benzoic acid Chemical group COC1=CC=C(Cl)C=C1C(=O)NCCC1=CC=C(C(O)=O)C=C1 SWLAMJPTOQZTAE-UHFFFAOYSA-N 0.000 description 1
• XWBXJBSVYVJAMZ-UHFFFAOYSA-N 4-[4-(2-adamantylcarbamoyl)-5-tert-butylpyrazol-1-yl]benzoic acid Chemical compound CC(C)(C)C1=C(C(=O)NC2C3CC4CC(C3)CC2C4)C=NN1C1=CC=C(C(O)=O)C=C1 XWBXJBSVYVJAMZ-UHFFFAOYSA-N 0.000 description 1
• MVDXXGIBARMXSA-PYUWXLGESA-N 5-[[(2r)-2-benzyl-3,4-dihydro-2h-chromen-6-yl]methyl]-1,3-thiazolidine-2,4-dione Chemical compound S1C(=O)NC(=O)C1CC1=CC=C(O[C@@H](CC=2C=CC=CC=2)CC2)C2=C1 MVDXXGIBARMXSA-PYUWXLGESA-N 0.000 description 1
• IETKPTYAGKZLKY-UHFFFAOYSA-N 5-[[4-[(3-methyl-4-oxoquinazolin-2-yl)methoxy]phenyl]methyl]-1,3-thiazolidine-2,4-dione Chemical compound N=1C2=CC=CC=C2C(=O)N(C)C=1COC(C=C1)=CC=C1CC1SC(=O)NC1=O IETKPTYAGKZLKY-UHFFFAOYSA-N 0.000 description 1
• KPRGOTLNGIBVFL-GINZOMEDSA-N 7-ketodehydroepiandrosterone Chemical group C1[C@@H](O)CC[C@]2(C)[C@H]3CC[C@](C)(C(CC4)=O)[C@@H]4[C@@H]3C(=O)C=C21 KPRGOTLNGIBVFL-GINZOMEDSA-N 0.000 description 1
• HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 description 1
• 208000004998 Abdominal Pain Diseases 0.000 description 1
• BQACOLQNOUYJCE-FYZZASKESA-N Abietic acid Natural products CC(C)C1=CC2=CC[C@]3(C)[C@](C)(CCC[C@@]3(C)C(=O)O)[C@H]2CC1 BQACOLQNOUYJCE-FYZZASKESA-N 0.000 description 1
• RSWGJHLUYNHPMX-UHFFFAOYSA-N Abietic-Saeure Natural products C12CCC(C(C)C)=CC2=CCC2C1(C)CCCC2(C)C(O)=O RSWGJHLUYNHPMX-UHFFFAOYSA-N 0.000 description 1
• 102000007469 Actins Human genes 0.000 description 1
• 108010085238 Actins Proteins 0.000 description 1
• 229920001817 Agar Polymers 0.000 description 1
• 101710189683 Alkaline protease 1 Proteins 0.000 description 1
• 101710154562 Alkaline proteinase Proteins 0.000 description 1
• 239000005995 Aluminium silicate Substances 0.000 description 1
• APKFDSVGJQXUKY-KKGHZKTASA-N Amphotericin-B Natural products O[C@H]1[C@@H](N)[C@H](O)[C@@H](C)O[C@H]1O[C@H]1C=CC=CC=CC=CC=CC=CC=C[C@H](C)[C@@H](O)[C@@H](C)[C@H](C)OC(=O)C[C@H](O)C[C@H](O)CC[C@@H](O)[C@H](O)C[C@H](O)C[C@](O)(C[C@H](O)[C@H]2C(O)=O)O[C@H]2C1 APKFDSVGJQXUKY-KKGHZKTASA-N 0.000 description 1
• 206010002091 Anaesthesia Diseases 0.000 description 1
• 101710170876 Antileukoproteinase Proteins 0.000 description 1
• 101710081722 Antitrypsin Proteins 0.000 description 1
• 108010011485 Aspartame Proteins 0.000 description 1
• 101150042514 B1 gene Proteins 0.000 description 1
• 238000009020 BCA Protein Assay Kit Methods 0.000 description 1
• 208000035143 Bacterial infection Diseases 0.000 description 1
• SPFYMRJSYKOXGV-UHFFFAOYSA-N Baytril Chemical compound C1CN(CC)CCN1C(C(=C1)F)=CC2=C1C(=O)C(C(O)=O)=CN2C1CC1 SPFYMRJSYKOXGV-UHFFFAOYSA-N 0.000 description 1
• 206010004637 Bile duct stone Diseases 0.000 description 1
• 206010004659 Biliary cirrhosis Diseases 0.000 description 1
• 241000283690 Bos taurus Species 0.000 description 1
• 241000167854 Bourreria succulenta Species 0.000 description 1
• 101150111062 C gene Proteins 0.000 description 1
• 101710112538 C-C motif chemokine 27 Proteins 0.000 description 1
• OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 1
• OKTJSMMVPCPJKN-NJFSPNSNSA-N Carbon-14 Chemical compound [14C] OKTJSMMVPCPJKN-NJFSPNSNSA-N 0.000 description 1
• 208000005623 Carcinogenesis Diseases 0.000 description 1
• 208000024172 Cardiovascular disease Diseases 0.000 description 1
• GUYMHFIHHOEFOA-ZCPGHIKRSA-N Carmegliptin Chemical compound N1([C@H]2CN3CCC=4C=C(C(=CC=4[C@@H]3C[C@@H]2N)OC)OC)C[C@@H](CF)CC1=O GUYMHFIHHOEFOA-ZCPGHIKRSA-N 0.000 description 1
• 102000014914 Carrier Proteins Human genes 0.000 description 1
• 108010078791 Carrier Proteins Proteins 0.000 description 1
• VWDXGKUTGQJJHJ-UHFFFAOYSA-N Catenarin Natural products C1=C(O)C=C2C(=O)C3=C(O)C(C)=CC(O)=C3C(=O)C2=C1O VWDXGKUTGQJJHJ-UHFFFAOYSA-N 0.000 description 1
• 241000700198 Cavia Species 0.000 description 1
• 102000000844 Cell Surface Receptors Human genes 0.000 description 1
• 108010001857 Cell Surface Receptors Proteins 0.000 description 1
• 102100032137 Cell death activator CIDE-3 Human genes 0.000 description 1
• 239000005046 Chlorosilane Substances 0.000 description 1
• 206010049055 Cholestasis of pregnancy Diseases 0.000 description 1
• 229920001268 Cholestyramine Polymers 0.000 description 1
• 206010008909 Chronic Hepatitis Diseases 0.000 description 1
• 108091026890 Coding region Proteins 0.000 description 1
• 229920002911 Colestipol Polymers 0.000 description 1
• 208000001333 Colorectal Neoplasms Diseases 0.000 description 1
• 206010010317 Congenital absence of bile ducts Diseases 0.000 description 1
• 102000010831 Cytoskeletal Proteins Human genes 0.000 description 1
• 108010037414 Cytoskeletal Proteins Proteins 0.000 description 1
• RFSUNEUAIZKAJO-VRPWFDPXSA-N D-Fructose Natural products OC[C@H]1OC(O)(CO)[C@@H](O)[C@@H]1O RFSUNEUAIZKAJO-VRPWFDPXSA-N 0.000 description 1
• FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 1
• FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 1
• FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 description 1
• JVHXJTBJCFBINQ-ADAARDCZSA-N Dapagliflozin Chemical compound C1=CC(OCC)=CC=C1CC1=CC([C@H]2[C@@H]([C@@H](O)[C@H](O)[C@@H](CO)O2)O)=CC=C1Cl JVHXJTBJCFBINQ-ADAARDCZSA-N 0.000 description 1
• 102000004237 Decorin Human genes 0.000 description 1
• YZCKVEUIGOORGS-OUBTZVSYSA-N Deuterium Chemical compound [2H] YZCKVEUIGOORGS-OUBTZVSYSA-N 0.000 description 1
• 235000019739 Dicalciumphosphate Nutrition 0.000 description 1
• 229940124213 Dipeptidyl peptidase 4 (DPP IV) inhibitor Drugs 0.000 description 1
• 206010013530 Diverticula Diseases 0.000 description 1
• 206010013554 Diverticulum Diseases 0.000 description 1
• 208000030453 Drug-Related Side Effects and Adverse reaction Diseases 0.000 description 1
• 238000003718 Dual-Luciferase Reporter Assay System Methods 0.000 description 1
• KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 1
• 239000010282 Emodin Substances 0.000 description 1
• RBLJKYCRSCQLRP-UHFFFAOYSA-N Emodin-dianthron Natural products O=C1C2=CC(C)=CC(O)=C2C(=O)C2=C1CC(=O)C=C2O RBLJKYCRSCQLRP-UHFFFAOYSA-N 0.000 description 1
• 241000283086 Equidae Species 0.000 description 1
• MCIACXAZCBVDEE-CUUWFGFTSA-N Ertugliflozin Chemical compound C1=CC(OCC)=CC=C1CC1=CC([C@@]23O[C@@](CO)(CO2)[C@@H](O)[C@H](O)[C@H]3O)=CC=C1Cl MCIACXAZCBVDEE-CUUWFGFTSA-N 0.000 description 1
• 108010007005 Estrogen Receptor alpha Proteins 0.000 description 1
• 102100038595 Estrogen receptor Human genes 0.000 description 1
• 108010043222 Exubera Proteins 0.000 description 1
• 241000282326 Felis catus Species 0.000 description 1
• PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 1
• 101710142060 Free fatty acid receptor 1 Proteins 0.000 description 1
• 206010017533 Fungal infection Diseases 0.000 description 1
• 229940125827 GPR40 agonist Drugs 0.000 description 1
• 108010046569 Galectins Proteins 0.000 description 1
• 108010010803 Gelatin Proteins 0.000 description 1
• 102000007446 Glucagon-Like Peptide-1 Receptor Human genes 0.000 description 1
• 108010086246 Glucagon-Like Peptide-1 Receptor Proteins 0.000 description 1
• 108010068370 Glutens Proteins 0.000 description 1
• 244000148687 Glycosmis pentaphylla Species 0.000 description 1
• MPDGHEJMBKOTSU-UHFFFAOYSA-N Glycyrrhetinsaeure Natural products C12C(=O)C=C3C4CC(C)(C(O)=O)CCC4(C)CCC3(C)C1(C)CCC1C2(C)CCC(O)C1(C)C MPDGHEJMBKOTSU-UHFFFAOYSA-N 0.000 description 1
• 208000024815 Granulomatous liver disease Diseases 0.000 description 1
• 206010019233 Headaches Diseases 0.000 description 1
• YOOXNSPYGCZLAX-UHFFFAOYSA-N Helminthosporin Natural products C1=CC(O)=C2C(=O)C3=CC(C)=CC(O)=C3C(=O)C2=C1O YOOXNSPYGCZLAX-UHFFFAOYSA-N 0.000 description 1
• 102000001554 Hemoglobins Human genes 0.000 description 1
• 108010054147 Hemoglobins Proteins 0.000 description 1
• 229920002971 Heparan sulfate Polymers 0.000 description 1
• 208000027761 Hepatic autoimmune disease Diseases 0.000 description 1
• 206010019663 Hepatic failure Diseases 0.000 description 1
• 206010019728 Hepatitis alcoholic Diseases 0.000 description 1
• 101000912510 Homo sapiens Free fatty acid receptor 1 Proteins 0.000 description 1
• 101000983854 Homo sapiens Phosphatidate phosphatase LPIN1 Proteins 0.000 description 1
• 108010090613 Human Regular Insulin Proteins 0.000 description 1
• 102000013266 Human Regular Insulin Human genes 0.000 description 1
• 206010060378 Hyperinsulinaemia Diseases 0.000 description 1
• 206010020751 Hypersensitivity Diseases 0.000 description 1
• 208000013016 Hypoglycemia Diseases 0.000 description 1
• 206010021143 Hypoxia Diseases 0.000 description 1
• 108060003951 Immunoglobulin Proteins 0.000 description 1
• 108010073961 Insulin Aspart Proteins 0.000 description 1
• FYZPCMFQCNBYCY-WIWKJPBBSA-N Insulin degludec Chemical compound CC[C@H](C)[C@H](NC(=O)CN)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@H]1CSSC[C@@H]2NC(=O)[C@@H](NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@H](CSSC[C@H](NC(=O)[C@H](CC(C)C)NC(=O)[C@H](Cc3c[nH]cn3)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CC(N)=O)NC(=O)[C@@H](NC(=O)[C@@H](N)Cc3ccccc3)C(C)C)C(=O)NCC(=O)N[C@@H](CO)C(=O)N[C@@H](Cc3c[nH]cn3)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](C)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](Cc3ccc(O)cc3)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CSSC[C@H](NC(=O)[C@H](Cc3ccc(O)cc3)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](Cc3ccc(O)cc3)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CO)NC2=O)C(=O)N[C@@H](CC(N)=O)C(O)=O)C(=O)NCC(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)NCC(=O)N[C@@H](Cc2ccccc2)C(=O)N[C@@H](Cc2ccccc2)C(=O)N[C@@H](Cc2ccc(O)cc2)C(=O)N[C@@H]([C@@H](C)O)C(=O)N2CCC[C@H]2C(=O)N[C@@H](CCCCNC(=O)CC[C@H](NC(=O)CCCCCCCCCCCCCCC(O)=O)C(O)=O)C(O)=O)NC1=O)[C@@H](C)O)[C@@H](C)CC FYZPCMFQCNBYCY-WIWKJPBBSA-N 0.000 description 1
• 208000031773 Insulin resistance syndrome Diseases 0.000 description 1
• 229940122199 Insulin secretagogue Drugs 0.000 description 1
• 102000005237 Isophane Insulin Human genes 0.000 description 1
• 108010081368 Isophane Insulin Proteins 0.000 description 1
• 206010023421 Kidney fibrosis Diseases 0.000 description 1
• 238000008214 LDL Cholesterol Methods 0.000 description 1
• JVTAAEKCZFNVCJ-UHFFFAOYSA-M Lactate Chemical compound CC(O)C([O-])=O JVTAAEKCZFNVCJ-UHFFFAOYSA-M 0.000 description 1
• XVVOERDUTLJJHN-UHFFFAOYSA-N Lixisenatide Chemical compound C=1NC2=CC=CC=C2C=1CC(C(=O)NC(CC(C)C)C(=O)NC(CCCCN)C(=O)NC(CC(N)=O)C(=O)NCC(=O)NCC(=O)N1C(CCC1)C(=O)NC(CO)C(=O)NC(CO)C(=O)NCC(=O)NC(C)C(=O)N1C(CCC1)C(=O)N1C(CCC1)C(=O)NC(CO)C(=O)NC(CCCCN)C(=O)NC(CCCCN)C(=O)NC(CCCCN)C(=O)NC(CCCCN)C(=O)NC(CCCCN)C(=O)NC(CCCCN)C(N)=O)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)CC)NC(=O)C(NC(=O)C(CC(C)C)NC(=O)C(CCCNC(N)=N)NC(=O)C(NC(=O)C(C)NC(=O)C(CCC(O)=O)NC(=O)C(CCC(O)=O)NC(=O)C(CCC(O)=O)NC(=O)C(CCSC)NC(=O)C(CCC(N)=O)NC(=O)C(CCCCN)NC(=O)C(CO)NC(=O)C(CC(C)C)NC(=O)C(CC(O)=O)NC(=O)C(CO)NC(=O)C(NC(=O)C(CC=1C=CC=CC=1)NC(=O)C(NC(=O)CNC(=O)C(CCC(O)=O)NC(=O)CNC(=O)C(N)CC=1NC=NC=1)C(C)O)C(C)O)C(C)C)CC1=CC=CC=C1 XVVOERDUTLJJHN-UHFFFAOYSA-N 0.000 description 1
• 108010092217 Long-Acting Insulin Proteins 0.000 description 1
• 102000016261 Long-Acting Insulin Human genes 0.000 description 1
• 229940100066 Long-acting insulin Drugs 0.000 description 1
• 229930195725 Mannitol Natural products 0.000 description 1
• 208000037196 Medullary thyroid carcinoma Diseases 0.000 description 1
• CERQOIWHTDAKMF-UHFFFAOYSA-N Methacrylic acid Chemical compound CC(=C)C(O)=O CERQOIWHTDAKMF-UHFFFAOYSA-N 0.000 description 1
• 208000031888 Mycoses Diseases 0.000 description 1
• 102100031455 NAD-dependent protein deacetylase sirtuin-1 Human genes 0.000 description 1
• 102100030710 NAD-dependent protein deacetylase sirtuin-3, mitochondrial Human genes 0.000 description 1
• 238000012565 NMR experiment Methods 0.000 description 1
• CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 1
• 239000002033 PVDF binder Substances 0.000 description 1
• 208000002193 Pain Diseases 0.000 description 1
• 206010033647 Pancreatitis acute Diseases 0.000 description 1
• 206010033654 Pancreatitis necrotising Diseases 0.000 description 1
• 208000030601 Parasitic Liver disease Diseases 0.000 description 1
• 241001494479 Pecora Species 0.000 description 1
• 102000001406 Perilipin Human genes 0.000 description 1
• 108060006002 Perilipin Proteins 0.000 description 1
• 229940080774 Peroxisome proliferator-activated receptor gamma agonist Drugs 0.000 description 1
• 102100025731 Phosphatidate phosphatase LPIN1 Human genes 0.000 description 1
• 229920003171 Poly (ethylene oxide) Polymers 0.000 description 1
• 102000016611 Proteoglycans Human genes 0.000 description 1
• 108010067787 Proteoglycans Proteins 0.000 description 1
• 108010026552 Proteome Proteins 0.000 description 1
• 206010056658 Pseudocyst Diseases 0.000 description 1
• 239000012980 RPMI-1640 medium Substances 0.000 description 1
• 238000011529 RT qPCR Methods 0.000 description 1
• 241000700157 Rattus norvegicus Species 0.000 description 1
• GSINGUMRKGRYJP-VZWAGXQNSA-N Remogliflozin Chemical compound C1=CC(OC(C)C)=CC=C1CC1=C(C)N(C(C)C)N=C1O[C@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 GSINGUMRKGRYJP-VZWAGXQNSA-N 0.000 description 1
• 108010052090 Renilla Luciferases Proteins 0.000 description 1
• 108700008625 Reporter Genes Proteins 0.000 description 1
• NTGIIKCGBNGQAR-UHFFFAOYSA-N Rheoemodin Natural products C1=C(O)C=C2C(=O)C3=CC(O)=CC(O)=C3C(=O)C2=C1O NTGIIKCGBNGQAR-UHFFFAOYSA-N 0.000 description 1
• 240000007651 Rubus glaucus Species 0.000 description 1
• 235000011034 Rubus glaucus Nutrition 0.000 description 1
• 235000009122 Rubus idaeus Nutrition 0.000 description 1
• 108091005770 SIRT3 Proteins 0.000 description 1
• 235000019485 Safflower oil Nutrition 0.000 description 1
• DLSWIYLPEUIQAV-UHFFFAOYSA-N Semaglutide Chemical compound CCC(C)C(NC(=O)C(Cc1ccccc1)NC(=O)C(CCC(O)=O)NC(=O)C(CCCCNC(=O)COCCOCCNC(=O)COCCOCCNC(=O)CCC(NC(=O)CCCCCCCCCCCCCCCCC(O)=O)C(O)=O)NC(=O)C(C)NC(=O)C(C)NC(=O)C(CCC(N)=O)NC(=O)CNC(=O)C(CCC(O)=O)NC(=O)C(CC(C)C)NC(=O)C(Cc1ccc(O)cc1)NC(=O)C(CO)NC(=O)C(CO)NC(=O)C(NC(=O)C(CC(O)=O)NC(=O)C(CO)NC(=O)C(NC(=O)C(Cc1ccccc1)NC(=O)C(NC(=O)CNC(=O)C(CCC(O)=O)NC(=O)C(C)(C)NC(=O)C(N)Cc1cnc[nH]1)C(C)O)C(C)O)C(C)C)C(=O)NC(C)C(=O)NC(Cc1c[nH]c2ccccc12)C(=O)NC(CC(C)C)C(=O)NC(C(C)C)C(=O)NC(CCCNC(N)=N)C(=O)NCC(=O)NC(CCCNC(N)=N)C(=O)NCC(O)=O DLSWIYLPEUIQAV-UHFFFAOYSA-N 0.000 description 1
• 229920001800 Shellac Polymers 0.000 description 1
• 208000032023 Signs and Symptoms Diseases 0.000 description 1
• 102000011990 Sirtuin Human genes 0.000 description 1
• 108050002485 Sirtuin Proteins 0.000 description 1
• 108010041191 Sirtuin 1 Proteins 0.000 description 1
• DWAQJAXMDSEUJJ-UHFFFAOYSA-M Sodium bisulfite Chemical compound [Na+].OS([O-])=O DWAQJAXMDSEUJJ-UHFFFAOYSA-M 0.000 description 1
• BCKXLBQYZLBQEK-KVVVOXFISA-M Sodium oleate Chemical compound [Na+].CCCCCCCC\C=C/CCCCCCCC([O-])=O BCKXLBQYZLBQEK-KVVVOXFISA-M 0.000 description 1
• 102100037202 Sodium/myo-inositol cotransporter 2 Human genes 0.000 description 1
• 101710090560 Sodium/myo-inositol cotransporter 2 Proteins 0.000 description 1
• CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 1
• 229930006000 Sucrose Natural products 0.000 description 1
• 235000019486 Sunflower oil Nutrition 0.000 description 1
• 241000282898 Sus scrofa Species 0.000 description 1
• 239000012163 TRI reagent Substances 0.000 description 1
• 241000053227 Themus Species 0.000 description 1
• 108020004440 Thymidine kinase Proteins 0.000 description 1
• ZXOCGDDVNPDRIW-NHFZGCSJSA-N Tofogliflozin Chemical compound O.C1=CC(CC)=CC=C1CC1=CC=C(CO[C@@]23[C@@H]([C@@H](O)[C@H](O)[C@@H](CO)O3)O)C2=C1 ZXOCGDDVNPDRIW-NHFZGCSJSA-N 0.000 description 1
• 206010070863 Toxicity to various agents Diseases 0.000 description 1
• 102100033663 Transforming growth factor beta receptor type 3 Human genes 0.000 description 1
• 101710132313 Transforming growth factor beta receptor type 3 Proteins 0.000 description 1
• YZCKVEUIGOORGS-NJFSPNSNSA-N Tritium Chemical compound [3H] YZCKVEUIGOORGS-NJFSPNSNSA-N 0.000 description 1
• 206010067584 Type 1 diabetes mellitus Diseases 0.000 description 1
• 101150060750 UQCRH gene Proteins 0.000 description 1
• 241000251539 Vertebrata <Metazoa> Species 0.000 description 1
• 208000036142 Viral infection Diseases 0.000 description 1
• 229930003427 Vitamin E Natural products 0.000 description 1
• FZNCGRZWXLXZSZ-CIQUZCHMSA-N Voglibose Chemical compound OCC(CO)N[C@H]1C[C@](O)(CO)[C@@H](O)[C@H](O)[C@H]1O FZNCGRZWXLXZSZ-CIQUZCHMSA-N 0.000 description 1
• 229920002494 Zein Polymers 0.000 description 1
• HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 1
• 210000001015 abdomen Anatomy 0.000 description 1
• 210000003815 abdominal wall Anatomy 0.000 description 1
• 230000002159 abnormal effect Effects 0.000 description 1
• 230000005856 abnormality Effects 0.000 description 1
• 230000009102 absorption Effects 0.000 description 1
• 238000010521 absorption reaction Methods 0.000 description 1
• 229960002632 acarbose Drugs 0.000 description 1
• XUFXOAAUWZOOIT-UHFFFAOYSA-N acarviostatin I01 Natural products OC1C(O)C(NC2C(C(O)C(O)C(CO)=C2)O)C(C)OC1OC(C(C1O)O)C(CO)OC1OC1C(CO)OC(O)C(O)C1O XUFXOAAUWZOOIT-UHFFFAOYSA-N 0.000 description 1
• 230000004308 accommodation Effects 0.000 description 1
• 239000003377 acid catalyst Substances 0.000 description 1
• 230000009471 action Effects 0.000 description 1
• 239000011149 active material Substances 0.000 description 1
• 239000012042 active reagent Substances 0.000 description 1
• 201000003229 acute pancreatitis Diseases 0.000 description 1
• 230000006978 adaptation Effects 0.000 description 1
• 239000000654 additive Substances 0.000 description 1
• 239000000443 aerosol Substances 0.000 description 1
• 229940078883 afrezza Drugs 0.000 description 1
• 239000008272 agar Substances 0.000 description 1
• 229940023476 agar Drugs 0.000 description 1
• 235000010419 agar Nutrition 0.000 description 1
• 229960004733 albiglutide Drugs 0.000 description 1
• OGWAVGNOAMXIIM-UHFFFAOYSA-N albiglutide Chemical compound O=C(O)C(NC(=O)CNC(=O)C(NC(=O)C(NC(=O)C(NC(=O)C(NC(=O)C(NC(=O)C(NC(=O)C(NC(=O)C(NC(=O)C(NC(=O)C(NC(=O)C(NC(=O)C(NC(=O)CNC(=O)C(NC(=O)C(NC(=O)C(NC(=O)C(NC(=O)C(NC(=O)C(NC(=O)C(NC(=O)C(NC(=O)C(NC(=O)C(NC(=O)C(NC(=O)CNC(=O)C(NC(=O)CNC(=O)C(N)CC=1(N=CNC=1))CCC(=O)O)C(O)C)CC2(=CC=CC=C2))C(O)C)CO)CC(=O)O)C(C)C)CO)CO)CC3(=CC=C(O)C=C3))CC(C)C)CCC(=O)O)CCC(=O)N)C)C)CCCCN)CCC(=O)O)CC4(=CC=CC=C4))C(CC)C)C)CC=6(C5(=C(C=CC=C5)NC=6)))CC(C)C)C(C)C)CCCCN)CCCNC(=N)N OGWAVGNOAMXIIM-UHFFFAOYSA-N 0.000 description 1
• 208000002353 alcoholic hepatitis Diseases 0.000 description 1
• 238000005882 aldol condensation reaction Methods 0.000 description 1
• 235000010443 alginic acid Nutrition 0.000 description 1
• 239000000783 alginic acid Substances 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
• 208000030961 allergic reaction Diseases 0.000 description 1
• 229960001667 alogliptin Drugs 0.000 description 1
• ZSBOMTDTBDDKMP-OAHLLOKOSA-N alogliptin Chemical compound C=1C=CC=C(C#N)C=1CN1C(=O)N(C)C(=O)C=C1N1CCC[C@@H](N)C1 ZSBOMTDTBDDKMP-OAHLLOKOSA-N 0.000 description 1
• 229940087168 alpha tocopherol Drugs 0.000 description 1
• 235000012211 aluminium silicate Nutrition 0.000 description 1
• 229940000806 amaryl Drugs 0.000 description 1
• APKFDSVGJQXUKY-INPOYWNPSA-N amphotericin B Chemical compound O[C@H]1[C@@H](N)[C@H](O)[C@@H](C)O[C@H]1O[C@H]1/C=C/C=C/C=C/C=C/C=C/C=C/C=C/[C@H](C)[C@@H](O)[C@@H](C)[C@H](C)OC(=O)C[C@H](O)C[C@H](O)CC[C@@H](O)[C@H](O)C[C@H](O)C[C@](O)(C[C@H](O)[C@H]2C(O)=O)O[C@H]2C1 APKFDSVGJQXUKY-INPOYWNPSA-N 0.000 description 1
• 229960003942 amphotericin b Drugs 0.000 description 1
• 230000003321 amplification Effects 0.000 description 1
• 230000037005 anaesthesia Effects 0.000 description 1
• LDXYBEHACFJIEL-HNNXBMFYSA-N anagliptin Chemical compound C=1N2N=C(C)C=C2N=CC=1C(=O)NCC(C)(C)NCC(=O)N1CCC[C@H]1C#N LDXYBEHACFJIEL-HNNXBMFYSA-N 0.000 description 1
• 229950009977 anagliptin Drugs 0.000 description 1
• 230000033115 angiogenesis Effects 0.000 description 1
• 239000003957 anion exchange resin Substances 0.000 description 1
• PYKYMHQGRFAEBM-UHFFFAOYSA-N anthraquinone Natural products CCC(=O)c1c(O)c2C(=O)C3C(C=CC=C3O)C(=O)c2cc1CC(=O)OC PYKYMHQGRFAEBM-UHFFFAOYSA-N 0.000 description 1
• 150000004056 anthraquinones Chemical class 0.000 description 1
• 230000003367 anti-collagen effect Effects 0.000 description 1
• 230000001475 anti-trypsic effect Effects 0.000 description 1
• 229940121375 antifungal agent Drugs 0.000 description 1
• 239000003429 antifungal agent Substances 0.000 description 1
• 239000000427 antigen Substances 0.000 description 1
• 108091007433 antigens Proteins 0.000 description 1
• 102000036639 antigens Human genes 0.000 description 1
• 229940112930 apidra Drugs 0.000 description 1
• 235000010323 ascorbic acid Nutrition 0.000 description 1
• 239000011668 ascorbic acid Substances 0.000 description 1
• 229960005070 ascorbic acid Drugs 0.000 description 1
• IAOZJIPTCAWIRG-QWRGUYRKSA-N aspartame Chemical compound OC(=O)C[C@H](N)C(=O)N[C@H](C(=O)OC)CC1=CC=CC=C1 IAOZJIPTCAWIRG-QWRGUYRKSA-N 0.000 description 1
• 239000000605 aspartame Substances 0.000 description 1
• 235000010357 aspartame Nutrition 0.000 description 1
• 229960003438 aspartame Drugs 0.000 description 1
• 238000003149 assay kit Methods 0.000 description 1
• 239000012298 atmosphere Substances 0.000 description 1
• QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
• 230000004900 autophagic degradation Effects 0.000 description 1
• 230000001580 bacterial effect Effects 0.000 description 1
• 208000022362 bacterial infectious disease Diseases 0.000 description 1
• 229950010663 balaglitazone Drugs 0.000 description 1
• 239000002585 base Substances 0.000 description 1
• 229960001264 benfluorex Drugs 0.000 description 1
• 239000000440 bentonite Substances 0.000 description 1
• 229910000278 bentonite Inorganic materials 0.000 description 1
• 229940092782 bentonite Drugs 0.000 description 1
• 235000012216 bentonite Nutrition 0.000 description 1
• SVPXDRXYRYOSEX-UHFFFAOYSA-N bentoquatam Chemical compound O.O=[Si]=O.O=[Al]O[Al]=O SVPXDRXYRYOSEX-UHFFFAOYSA-N 0.000 description 1
• CJAVTWRYCDNHSM-UHFFFAOYSA-N benzoic acid 2-[1-[3-(trifluoromethyl)phenyl]propan-2-ylamino]ethyl ester Chemical compound C=1C=CC=CC=1C(=O)OCCNC(C)CC1=CC=CC(C(F)(F)F)=C1 CJAVTWRYCDNHSM-UHFFFAOYSA-N 0.000 description 1
• 208000026900 bile duct neoplasm Diseases 0.000 description 1
• 201000005271 biliary atresia Diseases 0.000 description 1
• 230000027455 binding Effects 0.000 description 1
• 108091008324 binding proteins Proteins 0.000 description 1
• 238000007622 bioinformatic analysis Methods 0.000 description 1
• 238000003766 bioinformatics method Methods 0.000 description 1
• 230000004071 biological effect Effects 0.000 description 1
• 239000000090 biomarker Substances 0.000 description 1
• 229960000074 biopharmaceutical Drugs 0.000 description 1
• 230000036765 blood level Effects 0.000 description 1
• 238000009530 blood pressure measurement Methods 0.000 description 1
• 238000010241 blood sampling Methods 0.000 description 1
• 229960002802 bromocriptine Drugs 0.000 description 1
• OZVBMTJYIDMWIL-AYFBDAFISA-N bromocriptine Chemical group C1=CC(C=2[C@H](N(C)C[C@@H](C=2)C(=O)N[C@]2(C(=O)N3[C@H](C(N4CCC[C@H]4[C@]3(O)O2)=O)CC(C)C)C(C)C)C2)=C3C2=C(Br)NC3=C1 OZVBMTJYIDMWIL-AYFBDAFISA-N 0.000 description 1
• 229960004111 buformin Drugs 0.000 description 1
• XSEUMFJMFFMCIU-UHFFFAOYSA-N buformin Chemical compound CCCC\N=C(/N)N=C(N)N XSEUMFJMFFMCIU-UHFFFAOYSA-N 0.000 description 1
• 239000011575 calcium Substances 0.000 description 1
• 229910000019 calcium carbonate Inorganic materials 0.000 description 1
• 235000010216 calcium carbonate Nutrition 0.000 description 1
• 239000001506 calcium phosphate Substances 0.000 description 1
• 239000000378 calcium silicate Substances 0.000 description 1
• 229910052918 calcium silicate Inorganic materials 0.000 description 1
• 235000012241 calcium silicate Nutrition 0.000 description 1
• OYACROKNLOSFPA-UHFFFAOYSA-N calcium;dioxido(oxo)silane Chemical compound [Ca+2].[O-][Si]([O-])=O OYACROKNLOSFPA-UHFFFAOYSA-N 0.000 description 1
• 235000020827 calorie restriction Nutrition 0.000 description 1
• 229960001713 canagliflozin Drugs 0.000 description 1
• VHOFTEAWFCUTOS-TUGBYPPCSA-N canagliflozin hydrate Chemical compound O.CC1=CC=C([C@H]2[C@@H]([C@@H](O)[C@H](O)[C@@H](CO)O2)O)C=C1CC(S1)=CC=C1C1=CC=C(F)C=C1.CC1=CC=C([C@H]2[C@@H]([C@@H](O)[C@H](O)[C@@H](CO)O2)O)C=C1CC(S1)=CC=C1C1=CC=C(F)C=C1 VHOFTEAWFCUTOS-TUGBYPPCSA-N 0.000 description 1
• 230000036952 cancer formation Effects 0.000 description 1
• OBZHEBDUNPOCJG-SZTGPWMUSA-N carbenoxolone Chemical compound C([C@H]1C2=CC(=O)[C@@H]34)[C@](C)(C(O)=O)CC[C@@]1(C)CC[C@@]2(C)[C@]4(C)CC[C@H]1[C@@]3(C)CC[C@@H](OC(=O)CCC(O)=O)C1(C)C OBZHEBDUNPOCJG-SZTGPWMUSA-N 0.000 description 1
• 229960000530 carbenoxolone Drugs 0.000 description 1
• 229910052799 carbon Inorganic materials 0.000 description 1
• 125000004432 carbon atom Chemical group C* 0.000 description 1
• 229960003362 carbutamide Drugs 0.000 description 1
• 231100000504 carcinogenesis Toxicity 0.000 description 1
• 229950003594 carmegliptin Drugs 0.000 description 1
• IVUMCTKHWDRRMH-UHFFFAOYSA-N carprofen Chemical compound C1=CC(Cl)=C[C]2C3=CC=C(C(C(O)=O)C)C=C3N=C21 IVUMCTKHWDRRMH-UHFFFAOYSA-N 0.000 description 1
• 229960003184 carprofen Drugs 0.000 description 1
• 239000006143 cell culture medium Substances 0.000 description 1
• 239000008004 cell lysis buffer Substances 0.000 description 1
• 230000005754 cellular signaling Effects 0.000 description 1
• 229920002678 cellulose Polymers 0.000 description 1
• 239000001913 cellulose Substances 0.000 description 1
• 235000010980 cellulose Nutrition 0.000 description 1
• 238000005119 centrifugation Methods 0.000 description 1
• 229960000541 cetyl alcohol Drugs 0.000 description 1
• 238000012512 characterization method Methods 0.000 description 1
• 238000006243 chemical reaction Methods 0.000 description 1
• 231100000045 chemical toxicity Toxicity 0.000 description 1
• 230000003399 chemotactic effect Effects 0.000 description 1
• RUDATBOHQWOJDD-BSWAIDMHSA-N chenodeoxycholic acid Chemical compound C([C@H]1C[C@H]2O)[C@H](O)CC[C@]1(C)[C@@H]1[C@@H]2[C@@H]2CC[C@H]([C@@H](CCC(O)=O)C)[C@@]2(C)CC1 RUDATBOHQWOJDD-BSWAIDMHSA-N 0.000 description 1
• 235000019693 cherries Nutrition 0.000 description 1
• KOPOQZFJUQMUML-UHFFFAOYSA-N chlorosilane Chemical compound Cl[SiH3] KOPOQZFJUQMUML-UHFFFAOYSA-N 0.000 description 1
• 229960001761 chlorpropamide Drugs 0.000 description 1
• 230000031154 cholesterol homeostasis Effects 0.000 description 1
• 230000007012 clinical effect Effects 0.000 description 1
• 238000011260 co-administration Methods 0.000 description 1
• 230000015271 coagulation Effects 0.000 description 1
• 238000005345 coagulation Methods 0.000 description 1
• 239000003240 coconut oil Substances 0.000 description 1
• 235000019864 coconut oil Nutrition 0.000 description 1
• 229960002604 colestipol Drugs 0.000 description 1
• GMRWGQCZJGVHKL-UHFFFAOYSA-N colestipol Chemical compound ClCC1CO1.NCCNCCNCCNCCN GMRWGQCZJGVHKL-UHFFFAOYSA-N 0.000 description 1
• 229940096422 collagen type i Drugs 0.000 description 1
• 239000002299 complementary DNA Substances 0.000 description 1
• 238000007906 compression Methods 0.000 description 1
• 230000006835 compression Effects 0.000 description 1
• 238000004590 computer program Methods 0.000 description 1
• 210000002808 connective tissue Anatomy 0.000 description 1
• 230000001276 controlling effect Effects 0.000 description 1
• 238000007796 conventional method Methods 0.000 description 1
• 238000001816 cooling Methods 0.000 description 1
• 229920001577 copolymer Polymers 0.000 description 1
• 238000012937 correction Methods 0.000 description 1
• 239000006071 cream Substances 0.000 description 1
• 208000031513 cyst Diseases 0.000 description 1
• 230000009089 cytolysis Effects 0.000 description 1
• 229960003834 dapagliflozin Drugs 0.000 description 1
• 108010041738 decorin receptor Proteins 0.000 description 1
• 230000007812 deficiency Effects 0.000 description 1
• 230000002950 deficient Effects 0.000 description 1
• 238000000326 densiometry Methods 0.000 description 1
• 238000010217 densitometric analysis Methods 0.000 description 1
• 229910052805 deuterium Inorganic materials 0.000 description 1
• 239000008121 dextrose Substances 0.000 description 1
• NEFBYIFKOOEVPA-UHFFFAOYSA-K dicalcium phosphate Chemical compound [Ca+2].[Ca+2].[O-]P([O-])([O-])=O NEFBYIFKOOEVPA-UHFFFAOYSA-K 0.000 description 1
• 229940038472 dicalcium phosphate Drugs 0.000 description 1
• 229910000390 dicalcium phosphate Inorganic materials 0.000 description 1
• 238000007865 diluting Methods 0.000 description 1
• 229940090124 dipeptidyl peptidase 4 (dpp-4) inhibitors for blood glucose lowering Drugs 0.000 description 1
• 239000003603 dipeptidyl peptidase IV inhibitor Substances 0.000 description 1
• 229940042399 direct acting antivirals protease inhibitors Drugs 0.000 description 1
• 238000011549 displacement method Methods 0.000 description 1
• 208000002173 dizziness Diseases 0.000 description 1
• 239000012154 double-distilled water Substances 0.000 description 1
• 230000003828 downregulation Effects 0.000 description 1
• 230000035622 drinking Effects 0.000 description 1
• 238000007580 dry-mixing Methods 0.000 description 1
• 229960005175 dulaglutide Drugs 0.000 description 1
• 108010005794 dulaglutide Proteins 0.000 description 1
• 230000004064 dysfunction Effects 0.000 description 1
• 230000008482 dysregulation Effects 0.000 description 1
• 229950001765 efaroxan Drugs 0.000 description 1
• 230000002900 effect on cell Effects 0.000 description 1
• 230000001819 effect on gene Effects 0.000 description 1
• 230000002884 effect on inflammation Effects 0.000 description 1
• 238000001378 electrochemiluminescence detection Methods 0.000 description 1
• RHMXXJGYXNZAPX-UHFFFAOYSA-N emodin Chemical compound C1=C(O)C=C2C(=O)C3=CC(C)=CC(O)=C3C(=O)C2=C1O RHMXXJGYXNZAPX-UHFFFAOYSA-N 0.000 description 1
• VASFLQKDXBAWEL-UHFFFAOYSA-N emodin Natural products OC1=C(OC2=C(C=CC(=C2C1=O)O)O)C1=CC=C(C=C1)O VASFLQKDXBAWEL-UHFFFAOYSA-N 0.000 description 1
• 230000001804 emulsifying effect Effects 0.000 description 1
• 230000019439 energy homeostasis Effects 0.000 description 1
• 229950002375 englitazone Drugs 0.000 description 1
• 229960003720 enoxolone Drugs 0.000 description 1
• 229960000740 enrofloxacin Drugs 0.000 description 1
• 230000006862 enzymatic digestion Effects 0.000 description 1
• SEACYXSIPDVVMV-UHFFFAOYSA-L eosin Y Chemical compound [Na+].[Na+].[O-]C(=O)C1=CC=CC=C1C1=C2C=C(Br)C(=O)C(Br)=C2OC2=C(Br)C([O-])=C(Br)C=C21 SEACYXSIPDVVMV-UHFFFAOYSA-L 0.000 description 1
• 229950006535 ertugliflozin Drugs 0.000 description 1
• 210000003743 erythrocyte Anatomy 0.000 description 1
• 230000032050 esterification Effects 0.000 description 1
• 238000005886 esterification reaction Methods 0.000 description 1
• 150000002148 esters Chemical class 0.000 description 1
• 229940011871 estrogen Drugs 0.000 description 1
• 239000000262 estrogen Substances 0.000 description 1
• 230000003631 expected effect Effects 0.000 description 1
• 231100000573 exposure to toxins Toxicity 0.000 description 1
• 238000013265 extended release Methods 0.000 description 1
• 238000000605 extraction Methods 0.000 description 1
• 229940012151 exubera Drugs 0.000 description 1
• 235000013861 fat-free Nutrition 0.000 description 1
• 206010016256 fatigue Diseases 0.000 description 1
• 150000002191 fatty alcohols Chemical class 0.000 description 1
• 208000010706 fatty liver disease Diseases 0.000 description 1
• 230000001605 fetal effect Effects 0.000 description 1
• 239000000945 filler Substances 0.000 description 1
• 238000001914 filtration Methods 0.000 description 1
• 229930003935 flavonoid Natural products 0.000 description 1
• 235000017173 flavonoids Nutrition 0.000 description 1
• 235000019634 flavors Nutrition 0.000 description 1
• 239000012530 fluid Substances 0.000 description 1
• 229910052731 fluorine Inorganic materials 0.000 description 1
• 239000011737 fluorine Substances 0.000 description 1
• XSOUHEXVEOQRKJ-IUCAKERBSA-N fluparoxan Chemical compound O1[C@H]2CNC[C@@H]2OC2=C1C=CC=C2F XSOUHEXVEOQRKJ-IUCAKERBSA-N 0.000 description 1
• 229950006702 fluparoxan Drugs 0.000 description 1
• 239000012458 free base Substances 0.000 description 1
• 239000012737 fresh medium Substances 0.000 description 1
• 229930182830 galactose Natural products 0.000 description 1
• 108010090623 galactose binding protein Proteins 0.000 description 1
• 102000021529 galactose binding proteins Human genes 0.000 description 1
• WIGCFUFOHFEKBI-UHFFFAOYSA-N gamma-tocopherol Natural products CC(C)CCCC(C)CCCC(C)CCCC1CCC2C(C)C(O)C(C)C(C)C2O1 WIGCFUFOHFEKBI-UHFFFAOYSA-N 0.000 description 1
• 239000008273 gelatin Substances 0.000 description 1
• 229920000159 gelatin Polymers 0.000 description 1
• 235000019322 gelatine Nutrition 0.000 description 1
• 235000011852 gelatine desserts Nutrition 0.000 description 1
• 238000011223 gene expression profiling Methods 0.000 description 1
• 229960001764 glibornuride Drugs 0.000 description 1
• RMTYNAPTNBJHQI-LLDVTBCESA-N glibornuride Chemical compound C1=CC(C)=CC=C1S(=O)(=O)NC(=O)N[C@H]1[C@H](C2(C)C)CC[C@@]2(C)[C@H]1O RMTYNAPTNBJHQI-LLDVTBCESA-N 0.000 description 1
• 229960000346 gliclazide Drugs 0.000 description 1
• 229960004346 glimepiride Drugs 0.000 description 1
• WIGIZIANZCJQQY-RUCARUNLSA-N glimepiride Chemical compound O=C1C(CC)=C(C)CN1C(=O)NCCC1=CC=C(S(=O)(=O)NC(=O)N[C@@H]2CC[C@@H](C)CC2)C=C1 WIGIZIANZCJQQY-RUCARUNLSA-N 0.000 description 1
• 229960001381 glipizide Drugs 0.000 description 1
• 229960003468 gliquidone Drugs 0.000 description 1
• 229960003236 glisoxepide Drugs 0.000 description 1
• ZKUDBRCEOBOWLF-UHFFFAOYSA-N glisoxepide Chemical compound O1C(C)=CC(C(=O)NCCC=2C=CC(=CC=2)S(=O)(=O)NC(=O)NN2CCCCCC2)=N1 ZKUDBRCEOBOWLF-UHFFFAOYSA-N 0.000 description 1
• 239000003862 glucocorticoid Substances 0.000 description 1
• 230000001890 gluconeogenic effect Effects 0.000 description 1
• 235000001727 glucose Nutrition 0.000 description 1
• 230000014101 glucose homeostasis Effects 0.000 description 1
• 229940088991 glucotrol Drugs 0.000 description 1
• 235000021312 gluten Nutrition 0.000 description 1
• 150000002313 glycerolipids Chemical class 0.000 description 1
• 229940074045 glyceryl distearate Drugs 0.000 description 1
• 229940075507 glyceryl monostearate Drugs 0.000 description 1
• 229940084937 glyset Drugs 0.000 description 1
• 239000008187 granular material Substances 0.000 description 1
• 239000003102 growth factor Substances 0.000 description 1
• 231100000869 headache Toxicity 0.000 description 1
• 229960002897 heparin Drugs 0.000 description 1
• 229920000669 heparin Polymers 0.000 description 1
• 230000002440 hepatic effect Effects 0.000 description 1
• 210000005161 hepatic lobe Anatomy 0.000 description 1
• 231100000283 hepatitis Toxicity 0.000 description 1
• 230000013632 homeostatic process Effects 0.000 description 1
• 238000002868 homogeneous time resolved fluorescence Methods 0.000 description 1
• 229940038661 humalog Drugs 0.000 description 1
• 229940103471 humulin Drugs 0.000 description 1
• 239000008172 hydrogenated vegetable oil Substances 0.000 description 1
• 238000005984 hydrogenation reaction Methods 0.000 description 1
• 239000001866 hydroxypropyl methyl cellulose Substances 0.000 description 1
• 235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 description 1
• 229920003088 hydroxypropyl methyl cellulose Polymers 0.000 description 1
• UFVKGYZPFZQRLF-UHFFFAOYSA-N hydroxypropyl methyl cellulose Chemical compound OC1C(O)C(OC)OC(CO)C1OC1C(O)C(O)C(OC2C(C(O)C(OC3C(C(O)C(O)C(CO)O3)O)C(CO)O2)O)C(CO)O1 UFVKGYZPFZQRLF-UHFFFAOYSA-N 0.000 description 1
• 230000003451 hyperinsulinaemic effect Effects 0.000 description 1
• 201000008980 hyperinsulinism Diseases 0.000 description 1
• 230000007954 hypoxia Effects 0.000 description 1
• 208000030200 icteric eyes Diseases 0.000 description 1
• 208000030180 icteric skin Diseases 0.000 description 1
• HPMRFMKYPGXPEP-UHFFFAOYSA-N idazoxan Chemical compound N1CCN=C1C1OC2=CC=CC=C2OC1 HPMRFMKYPGXPEP-UHFFFAOYSA-N 0.000 description 1
• 229950001476 idazoxan Drugs 0.000 description 1
• 102000018358 immunoglobulin Human genes 0.000 description 1
• 238000003364 immunohistochemistry Methods 0.000 description 1
• 238000002513 implantation Methods 0.000 description 1
• 230000001976 improved effect Effects 0.000 description 1
• MGXWVYUBJRZYPE-YUGYIWNOSA-N incretin Chemical class C([C@@H](C(=O)N[C@@H](CO)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](C)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CC=1NC=NC=1)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](C)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCCCN)C(=O)NCC(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC=1NC=NC=1)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CCC(N)=O)C(O)=O)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@@H](NC(=O)CNC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C)NC(=O)[C@@H](N)CC=1C=CC(O)=CC=1)[C@@H](C)O)[C@@H](C)CC)C1=CC=C(O)C=C1 MGXWVYUBJRZYPE-YUGYIWNOSA-N 0.000 description 1
• 239000000859 incretin Substances 0.000 description 1
• 230000008595 infiltration Effects 0.000 description 1
• 238000001764 infiltration Methods 0.000 description 1
• 230000006749 inflammatory damage Effects 0.000 description 1
• 238000002329 infrared spectrum Methods 0.000 description 1
• 238000001802 infusion Methods 0.000 description 1
• 208000014674 injury Diseases 0.000 description 1
• 239000002198 insoluble material Substances 0.000 description 1
• PBGKTOXHQIOBKM-FHFVDXKLSA-N insulin (human) Chemical group C([C@@H](C(=O)N[C@@H](CC(C)C)C(=O)N[C@H]1CSSC[C@H]2C(=O)N[C@H](C(=O)N[C@@H](CO)C(=O)N[C@H](C(=O)N[C@H](C(N[C@@H](CO)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC=3C=CC(O)=CC=3)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC=3C=CC(O)=CC=3)C(=O)N[C@@H](CSSC[C@H](NC(=O)[C@H](C(C)C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC=3C=CC(O)=CC=3)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](C)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C(C)C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC=3NC=NC=3)NC(=O)[C@H](CO)NC(=O)CNC1=O)C(=O)NCC(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)NCC(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N[C@@H]([C@@H](C)O)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H]([C@@H](C)O)C(O)=O)C(=O)N[C@@H](CC(N)=O)C(O)=O)=O)CSSC[C@@H](C(N2)=O)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C(C)C)NC(=O)[C@@H](NC(=O)CN)[C@@H](C)CC)[C@@H](C)CC)[C@@H](C)O)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CC(N)=O)NC(=O)[C@@H](NC(=O)[C@@H](N)CC=1C=CC=CC=1)C(C)C)C1=CN=CN1 PBGKTOXHQIOBKM-FHFVDXKLSA-N 0.000 description 1
• 229960004717 insulin aspart Drugs 0.000 description 1
• 108010050259 insulin degludec Proteins 0.000 description 1
• 229960004225 insulin degludec Drugs 0.000 description 1
• 229960003948 insulin detemir Drugs 0.000 description 1
• 229960002869 insulin glargine Drugs 0.000 description 1
• 229960000696 insulin glulisine Drugs 0.000 description 1
• 229960002068 insulin lispro Drugs 0.000 description 1
• 230000003993 interaction Effects 0.000 description 1
• 230000031891 intestinal absorption Effects 0.000 description 1
• 230000003834 intracellular effect Effects 0.000 description 1
• 210000005024 intraepithelial lymphocyte Anatomy 0.000 description 1
• 201000002161 intrahepatic cholestasis of pregnancy Diseases 0.000 description 1
• 238000007913 intrathecal administration Methods 0.000 description 1
• AHFWIQIYAXSLBA-RQXATKFSSA-N ipragliflozin Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@H]1C1=CC=C(F)C(CC=2SC3=CC=CC=C3C=2)=C1 AHFWIQIYAXSLBA-RQXATKFSSA-N 0.000 description 1
• 229950000991 ipragliflozin Drugs 0.000 description 1
• 230000007794 irritation Effects 0.000 description 1
• 229940006445 isophane insulin Drugs 0.000 description 1
• 229940090473 januvia Drugs 0.000 description 1
• NLYAJNPCOHFWQQ-UHFFFAOYSA-N kaolin Chemical compound O.O.O=[Al]O[Si](=O)O[Si](=O)O[Al]=O NLYAJNPCOHFWQQ-UHFFFAOYSA-N 0.000 description 1
• 208000017169 kidney disease Diseases 0.000 description 1
• 238000009533 lab test Methods 0.000 description 1
• 108010057670 laminin 1 Proteins 0.000 description 1
• 229940060975 lantus Drugs 0.000 description 1
• 239000000787 lecithin Substances 0.000 description 1
• 235000010445 lecithin Nutrition 0.000 description 1
• 229940067606 lecithin Drugs 0.000 description 1
• 231100000636 lethal dose Toxicity 0.000 description 1
• 229940102988 levemir Drugs 0.000 description 1
• 238000011694 lewis rat Methods 0.000 description 1
• 230000000670 limiting effect Effects 0.000 description 1
• 229960002397 linagliptin Drugs 0.000 description 1
• 238000012417 linear regression Methods 0.000 description 1
• 229940057995 liquid paraffin Drugs 0.000 description 1
• 208000007903 liver failure Diseases 0.000 description 1
• 231100000835 liver failure Toxicity 0.000 description 1
• 229960001093 lixisenatide Drugs 0.000 description 1
• 108010004367 lixisenatide Proteins 0.000 description 1
• 238000011068 loading method Methods 0.000 description 1
• CHHXEZSCHQVSRE-UHFFFAOYSA-N lobeglitazone Chemical compound C1=CC(OC)=CC=C1OC1=CC(N(C)CCOC=2C=CC(CC3C(NC(=O)S3)=O)=CC=2)=NC=N1 CHHXEZSCHQVSRE-UHFFFAOYSA-N 0.000 description 1
• 229950007685 lobeglitazone Drugs 0.000 description 1
• 239000006210 lotion Substances 0.000 description 1
• 210000004698 lymphocyte Anatomy 0.000 description 1
• 239000008176 lyophilized powder Substances 0.000 description 1
• 239000006166 lysate Substances 0.000 description 1
• 239000012139 lysis buffer Substances 0.000 description 1
• 235000019359 magnesium stearate Nutrition 0.000 description 1
• 239000000594 mannitol Substances 0.000 description 1
• 235000010355 mannitol Nutrition 0.000 description 1
• 238000004519 manufacturing process Methods 0.000 description 1
• 239000011159 matrix material Substances 0.000 description 1
• 238000005259 measurement Methods 0.000 description 1
• 238000010339 medical test Methods 0.000 description 1
• 238000002483 medication Methods 0.000 description 1
• 208000023356 medullary thyroid gland carcinoma Diseases 0.000 description 1
• 229950004994 meglitinide Drugs 0.000 description 1
• DRLFMBDRBRZALE-UHFFFAOYSA-N melatonin Chemical compound COC1=CC=C2NC=C(CCNC(C)=O)C2=C1 DRLFMBDRBRZALE-UHFFFAOYSA-N 0.000 description 1
• 238000002844 melting Methods 0.000 description 1
• 230000008018 melting Effects 0.000 description 1
• 239000001525 mentha piperita l. herb oil Substances 0.000 description 1
• 208000030159 metabolic disease Diseases 0.000 description 1
• 208000037819 metastatic cancer Diseases 0.000 description 1
• 208000011575 metastatic malignant neoplasm Diseases 0.000 description 1
• 235000010270 methyl p-hydroxybenzoate Nutrition 0.000 description 1
• 239000004292 methyl p-hydroxybenzoate Substances 0.000 description 1
• OSWPMRLSEDHDFF-UHFFFAOYSA-N methyl salicylate Chemical compound COC(=O)C1=CC=CC=C1O OSWPMRLSEDHDFF-UHFFFAOYSA-N 0.000 description 1
• 229960002216 methylparaben Drugs 0.000 description 1
• 244000005700 microbiome Species 0.000 description 1
• 229960001110 miglitol Drugs 0.000 description 1
• 238000003801 milling Methods 0.000 description 1
• 229960003365 mitiglinide Drugs 0.000 description 1
• WPGGHFDDFPHPOB-BBWFWOEESA-N mitiglinide Chemical compound C([C@@H](CC(=O)N1C[C@@H]2CCCC[C@@H]2C1)C(=O)O)C1=CC=CC=C1 WPGGHFDDFPHPOB-BBWFWOEESA-N 0.000 description 1
• 230000002438 mitochondrial effect Effects 0.000 description 1
• 238000012544 monitoring process Methods 0.000 description 1
• 210000001616 monocyte Anatomy 0.000 description 1
• 239000012452 mother liquor Substances 0.000 description 1
• 238000010172 mouse model Methods 0.000 description 1
• 238000000491 multivariate analysis Methods 0.000 description 1
• BDQCDIWFPIDPQU-NDEPHWFRSA-N n-methyl-5-[4-[1-[(1r)-3-oxospiro[2-benzofuran-1,3'-pyrrolidine]-1'-carbonyl]cyclopropyl]phenyl]pyridine-2-carboxamide Chemical compound C1=NC(C(=O)NC)=CC=C1C1=CC=C(C2(CC2)C(=O)N2C[C@@]3(CC2)C2=CC=CC=C2C(=O)O3)C=C1 BDQCDIWFPIDPQU-NDEPHWFRSA-N 0.000 description 1
• WGEYAGZBLYNDFV-UHFFFAOYSA-N naringenin Natural products C1(=O)C2=C(O)C=C(O)C=C2OC(C1)C1=CC=C(CC1)O WGEYAGZBLYNDFV-UHFFFAOYSA-N 0.000 description 1
• 229940117954 naringenin Drugs 0.000 description 1
• 235000007625 naringenin Nutrition 0.000 description 1
• 229960000698 nateglinide Drugs 0.000 description 1
• 229920001206 natural gum Polymers 0.000 description 1
• PKWDZWYVIHVNKS-UHFFFAOYSA-N netoglitazone Chemical compound FC1=CC=CC=C1COC1=CC=C(C=C(CC2C(NC(=O)S2)=O)C=C2)C2=C1 PKWDZWYVIHVNKS-UHFFFAOYSA-N 0.000 description 1
• 229950001628 netoglitazone Drugs 0.000 description 1
• 231100000252 nontoxic Toxicity 0.000 description 1
• 230000003000 nontoxic effect Effects 0.000 description 1
• 229940112879 novolog Drugs 0.000 description 1
• VOMXSOIBEJBQNF-UTTRGDHVSA-N novorapid Chemical compound C([C@H](NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CO)NC(=O)[C@H](CS)NC(=O)[C@H]([C@@H](C)CC)NC(=O)[C@H](CO)NC(=O)[C@H]([C@@H](C)O)NC(=O)[C@H](CS)NC(=O)[C@H](CS)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C(C)C)NC(=O)[C@@H](NC(=O)CN)[C@@H](C)CC)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N[C@@H](CS)C(=O)N[C@@H](CC(N)=O)C(O)=O)C1=CC=C(O)C=C1.C([C@@H](C(=O)N[C@@H](CC(C)C)C(=O)N[C@H](C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](C)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CS)C(=O)NCC(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)NCC(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H]([C@@H](C)O)C(O)=O)C(C)C)NC(=O)[C@H](CO)NC(=O)CNC(=O)[C@H](CS)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC=1NC=NC=1)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CC(N)=O)NC(=O)[C@@H](NC(=O)[C@@H](N)CC=1C=CC=CC=1)C(C)C)C1=CN=CN1 VOMXSOIBEJBQNF-UTTRGDHVSA-N 0.000 description 1
• 238000003199 nucleic acid amplification method Methods 0.000 description 1
• 239000003921 oil Substances 0.000 description 1
• 235000019198 oils Nutrition 0.000 description 1
• 239000002674 ointment Substances 0.000 description 1
• 239000004006 olive oil Substances 0.000 description 1
• 235000008390 olive oil Nutrition 0.000 description 1
• 238000001543 one-way ANOVA Methods 0.000 description 1
• 229940001450 onglyza Drugs 0.000 description 1
• 230000003287 optical effect Effects 0.000 description 1
• 238000003305 oral gavage Methods 0.000 description 1
• 230000008816 organ damage Effects 0.000 description 1
• 230000008520 organization Effects 0.000 description 1
• AICOOMRHRUFYCM-ZRRPKQBOSA-N oxazine, 1 Chemical compound C([C@@H]1[C@H](C(C[C@]2(C)[C@@H]([C@H](C)N(C)C)[C@H](O)C[C@]21C)=O)CC1=CC2)C[C@H]1[C@@]1(C)[C@H]2N=C(C(C)C)OC1 AICOOMRHRUFYCM-ZRRPKQBOSA-N 0.000 description 1
• 239000001301 oxygen Substances 0.000 description 1
• 229910052760 oxygen Inorganic materials 0.000 description 1
• 102000044160 oxysterol binding protein Human genes 0.000 description 1
• 108010040421 oxysterol binding protein Proteins 0.000 description 1
• 230000036407 pain Effects 0.000 description 1
• 235000016236 parenteral nutrition Nutrition 0.000 description 1
• 230000036961 partial effect Effects 0.000 description 1
• 239000002245 particle Substances 0.000 description 1
• 238000005192 partition Methods 0.000 description 1
• 239000006072 paste Substances 0.000 description 1
• 230000007170 pathology Effects 0.000 description 1
• 230000035515 penetration Effects 0.000 description 1
• 229960001412 pentobarbital Drugs 0.000 description 1
• 235000019477 peppermint oil Nutrition 0.000 description 1
• 239000000137 peptide hydrolase inhibitor Substances 0.000 description 1
• 230000000858 peroxisomal effect Effects 0.000 description 1
• 239000003614 peroxisome proliferator Substances 0.000 description 1
• 229940124531 pharmaceutical excipient Drugs 0.000 description 1
• 229960003243 phenformin Drugs 0.000 description 1
• ICFJFFQQTFMIBG-UHFFFAOYSA-N phenformin Chemical compound NC(=N)NC(=N)NCCC1=CC=CC=C1 ICFJFFQQTFMIBG-UHFFFAOYSA-N 0.000 description 1
• 239000008363 phosphate buffer Substances 0.000 description 1
• 229910052698 phosphorus Inorganic materials 0.000 description 1
• 230000026731 phosphorylation Effects 0.000 description 1
• 238000006366 phosphorylation reaction Methods 0.000 description 1
• PKUBGLYEOAJPEG-UHFFFAOYSA-N physcion Natural products C1=C(C)C=C2C(=O)C3=CC(C)=CC(O)=C3C(=O)C2=C1O PKUBGLYEOAJPEG-UHFFFAOYSA-N 0.000 description 1
• 230000004962 physiological condition Effects 0.000 description 1
• 239000006187 pill Substances 0.000 description 1
• 229960005095 pioglitazone Drugs 0.000 description 1
• 230000036470 plasma concentration Effects 0.000 description 1
• 239000013612 plasmid Substances 0.000 description 1
• 208000030761 polycystic kidney disease Diseases 0.000 description 1
• 229920000642 polymer Polymers 0.000 description 1
• 238000003752 polymerase chain reaction Methods 0.000 description 1
• 229920002981 polyvinylidene fluoride Polymers 0.000 description 1
• 230000003389 potentiating effect Effects 0.000 description 1
• 244000144977 poultry Species 0.000 description 1
• 229960003611 pramlintide Drugs 0.000 description 1
• 108010029667 pramlintide Proteins 0.000 description 1
• NRKVKVQDUCJPIZ-MKAGXXMWSA-N pramlintide acetate Chemical compound C([C@@H](C(=O)NCC(=O)N1CCC[C@H]1C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CC(C)C)C(=O)N1[C@@H](CCC1)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](C(C)C)C(=O)NCC(=O)N[C@@H](CO)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(N)=O)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CO)NC(=O)[C@H](CO)NC(=O)[C@H](CC=1NC=NC=1)NC(=O)[C@@H](NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@@H](NC(=O)[C@H](C)NC(=O)[C@H](CS)NC(=O)[C@@H](NC(=O)[C@H](C)NC(=O)[C@@H](NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CS)NC(=O)[C@@H](N)CCCCN)[C@@H](C)O)[C@@H](C)O)[C@@H](C)O)C(C)C)C1=CC=CC=C1 NRKVKVQDUCJPIZ-MKAGXXMWSA-N 0.000 description 1
• 229940096058 prandin Drugs 0.000 description 1
• 238000011533 pre-incubation Methods 0.000 description 1
• 239000002244 precipitate Substances 0.000 description 1
• 229940095885 precose Drugs 0.000 description 1
• GCYXWQUSHADNBF-AAEALURTSA-N preproglucagon 78-108 Chemical compound C([C@@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](C)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CCCCN)C(=O)NCC(=O)N[C@@H](CCCNC(N)=N)C(=O)NCC(O)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CCCCN)NC(=O)[C@H](C)NC(=O)[C@H](C)NC(=O)[C@H](CCC(N)=O)NC(=O)CNC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CO)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@@H](NC(=O)CNC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C)NC(=O)[C@@H](N)CC=1N=CNC=1)[C@@H](C)O)[C@@H](C)O)C(C)C)C1=CC=CC=C1 GCYXWQUSHADNBF-AAEALURTSA-N 0.000 description 1
• 238000000513 principal component analysis Methods 0.000 description 1
• 230000008569 process Effects 0.000 description 1
• 108090000765 processed proteins & peptides Proteins 0.000 description 1
• 239000000047 product Substances 0.000 description 1
• 230000035755 proliferation Effects 0.000 description 1
• BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 1
• 239000003380 propellant Substances 0.000 description 1
• 235000010232 propyl p-hydroxybenzoate Nutrition 0.000 description 1
• 239000004405 propyl p-hydroxybenzoate Substances 0.000 description 1
• 229960003415 propylparaben Drugs 0.000 description 1
• 210000002307 prostate Anatomy 0.000 description 1
• 230000001681 protective effect Effects 0.000 description 1
• 238000002731 protein assay Methods 0.000 description 1
• 230000000541 pulsatile effect Effects 0.000 description 1
• 238000003908 quality control method Methods 0.000 description 1
• 150000003856 quaternary ammonium compounds Chemical class 0.000 description 1
• 108700027806 rGLP-1 Proteins 0.000 description 1
• 230000002285 radioactive effect Effects 0.000 description 1
• 238000011084 recovery Methods 0.000 description 1
• 238000001953 recrystallisation Methods 0.000 description 1
• 206010038038 rectal cancer Diseases 0.000 description 1
• 201000001275 rectum cancer Diseases 0.000 description 1
• 238000007634 remodeling Methods 0.000 description 1
• 229940126844 remogliflozin Drugs 0.000 description 1
• 230000030558 renal glucose absorption Effects 0.000 description 1
• 229960002354 repaglinide Drugs 0.000 description 1
• 238000010839 reverse transcription Methods 0.000 description 1
• 238000012502 risk assessment Methods 0.000 description 1
• 238000013349 risk mitigation Methods 0.000 description 1
• XMSXOLDPMGMWTH-UHFFFAOYSA-N rivoglitazone Chemical compound CN1C2=CC(OC)=CC=C2N=C1COC(C=C1)=CC=C1CC1SC(=O)NC1=O XMSXOLDPMGMWTH-UHFFFAOYSA-N 0.000 description 1
• 229950010764 rivoglitazone Drugs 0.000 description 1
• 229960004586 rosiglitazone Drugs 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
• 235000019204 saccharin Nutrition 0.000 description 1
• 229940081974 saccharin Drugs 0.000 description 1
• 239000000901 saccharin and its Na,K and Ca salt Substances 0.000 description 1
• 235000005713 safflower oil Nutrition 0.000 description 1
• 239000003813 safflower oil Substances 0.000 description 1
• 238000007127 saponification reaction Methods 0.000 description 1
• 229960004937 saxagliptin Drugs 0.000 description 1
• 238000002821 scintillation proximity assay Methods 0.000 description 1
• 239000013049 sediment Substances 0.000 description 1
• 229950011186 semaglutide Drugs 0.000 description 1
• 108010060325 semaglutide Proteins 0.000 description 1
• 238000000926 separation method Methods 0.000 description 1
• 238000012163 sequencing technique Methods 0.000 description 1
• HFLCZNNDZKKXCS-OUUBHVDSSA-N sergliflozin Chemical compound C1=CC(OC)=CC=C1CC1=CC=CC=C1O[C@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 HFLCZNNDZKKXCS-OUUBHVDSSA-N 0.000 description 1
• 229940126842 sergliflozin Drugs 0.000 description 1
• 239000008159 sesame oil Substances 0.000 description 1
• 235000011803 sesame oil Nutrition 0.000 description 1
• 239000004208 shellac Substances 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
• 229940113147 shellac Drugs 0.000 description 1
• 235000013874 shellac Nutrition 0.000 description 1
• 238000004904 shortening Methods 0.000 description 1
• 210000000813 small intestine Anatomy 0.000 description 1
• 239000011734 sodium Substances 0.000 description 1
• WXMKPNITSTVMEF-UHFFFAOYSA-M sodium benzoate Chemical compound [Na+].[O-]C(=O)C1=CC=CC=C1 WXMKPNITSTVMEF-UHFFFAOYSA-M 0.000 description 1
• 235000010234 sodium benzoate Nutrition 0.000 description 1
• 239000004299 sodium benzoate Substances 0.000 description 1
• 229960003885 sodium benzoate Drugs 0.000 description 1
• 229940001607 sodium bisulfite Drugs 0.000 description 1
• 239000011780 sodium chloride Substances 0.000 description 1
• 235000010267 sodium hydrogen sulphite Nutrition 0.000 description 1
• 239000000600 sorbitol Substances 0.000 description 1
• 238000001228 spectrum Methods 0.000 description 1
• 238000013222 sprague-dawley male rat Methods 0.000 description 1
• 239000007921 spray Substances 0.000 description 1
• 238000010561 standard procedure Methods 0.000 description 1
• 229940110862 starlix Drugs 0.000 description 1
• WNIFXKPDILJURQ-UHFFFAOYSA-N stearyl glycyrrhizinate Natural products C1CC(O)C(C)(C)C2CCC3(C)C4(C)CCC5(C)CCC(C(=O)OCCCCCCCCCCCCCCCCCC)(C)CC5C4=CC(=O)C3C21C WNIFXKPDILJURQ-UHFFFAOYSA-N 0.000 description 1
• 150000003431 steroids Chemical class 0.000 description 1
• 201000000498 stomach carcinoma Diseases 0.000 description 1
• 238000013517 stratification Methods 0.000 description 1
• 238000006467 substitution reaction Methods 0.000 description 1
• 239000000758 substrate Substances 0.000 description 1
• 239000005720 sucrose Substances 0.000 description 1
• 229960004793 sucrose Drugs 0.000 description 1
• 239000002600 sunflower oil Substances 0.000 description 1
• 239000013589 supplement Substances 0.000 description 1
• 239000006188 syrup Substances 0.000 description 1
• 235000020357 syrup Nutrition 0.000 description 1
• 229940037128 systemic glucocorticoids Drugs 0.000 description 1
• 239000000454 talc Substances 0.000 description 1
• 229910052623 talc Inorganic materials 0.000 description 1
• 239000008399 tap water Substances 0.000 description 1
• 235000020679 tap water Nutrition 0.000 description 1
• WRGVLTAWMNZWGT-VQSPYGJZSA-N taspoglutide Chemical compound C([C@@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](C)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CCCCN)C(=O)NC(C)(C)C(=O)N[C@@H](CCCNC(N)=N)C(N)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CCCCN)NC(=O)[C@H](C)NC(=O)[C@H](C)NC(=O)[C@H](CCC(N)=O)NC(=O)CNC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CO)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@@H](NC(=O)CNC(=O)[C@H](CCC(O)=O)NC(=O)C(C)(C)NC(=O)[C@@H](N)CC=1NC=NC=1)[C@@H](C)O)[C@@H](C)O)C(C)C)C1=CC=CC=C1 WRGVLTAWMNZWGT-VQSPYGJZSA-N 0.000 description 1
• 229950007151 taspoglutide Drugs 0.000 description 1
• 108010048573 taspoglutide Proteins 0.000 description 1
• WBWWGRHZICKQGZ-HZAMXZRMSA-N taurocholic acid Chemical compound C([C@H]1C[C@H]2O)[C@H](O)CC[C@]1(C)[C@@H]1[C@@H]2[C@@H]2CC[C@H]([C@@H](CCC(=O)NCCS(O)(=O)=O)C)[C@@]2(C)[C@@H](O)C1 WBWWGRHZICKQGZ-HZAMXZRMSA-N 0.000 description 1
• 238000012956 testing procedure Methods 0.000 description 1
• 208000013818 thyroid gland medullary carcinoma Diseases 0.000 description 1
• 229940098465 tincture Drugs 0.000 description 1
• 230000000451 tissue damage Effects 0.000 description 1
• 231100000827 tissue damage Toxicity 0.000 description 1
• 238000003354 tissue distribution assay Methods 0.000 description 1
• 229960000984 tocofersolan Drugs 0.000 description 1
• AOBORMOPSGHCAX-DGHZZKTQSA-N tocofersolan Chemical compound OCCOC(=O)CCC(=O)OC1=C(C)C(C)=C2O[C@](CCC[C@H](C)CCC[C@H](C)CCCC(C)C)(C)CCC2=C1C AOBORMOPSGHCAX-DGHZZKTQSA-N 0.000 description 1
• 229950006667 tofogliflozin Drugs 0.000 description 1
• 229960002277 tolazamide Drugs 0.000 description 1
• 229940035266 tolinase Drugs 0.000 description 1
• 229960003069 tolrestat Drugs 0.000 description 1
• LUBHDINQXIHVLS-UHFFFAOYSA-N tolrestat Chemical compound OC(=O)CN(C)C(=S)C1=CC=CC2=C(C(F)(F)F)C(OC)=CC=C21 LUBHDINQXIHVLS-UHFFFAOYSA-N 0.000 description 1
• 230000000699 topical effect Effects 0.000 description 1
• 235000021476 total parenteral nutrition Nutrition 0.000 description 1
• 231100000419 toxicity Toxicity 0.000 description 1
• 230000001988 toxicity Effects 0.000 description 1
• 229940049667 tradjenta Drugs 0.000 description 1
• 230000037317 transdermal delivery Effects 0.000 description 1
• 238000001890 transfection Methods 0.000 description 1
• 230000001052 transient effect Effects 0.000 description 1
• 238000003146 transient transfection Methods 0.000 description 1
• 238000002054 transplantation Methods 0.000 description 1
• 230000032258 transport Effects 0.000 description 1
• 230000008733 trauma Effects 0.000 description 1
• 229910052722 tritium Inorganic materials 0.000 description 1
• 229960001641 troglitazone Drugs 0.000 description 1
• GXPHKUHSUJUWKP-UHFFFAOYSA-N troglitazone Chemical compound C1CC=2C(C)=C(O)C(C)=C(C)C=2OC1(C)COC(C=C1)=CC=C1CC1SC(=O)NC1=O GXPHKUHSUJUWKP-UHFFFAOYSA-N 0.000 description 1
• GXPHKUHSUJUWKP-NTKDMRAZSA-N troglitazone Natural products C([C@@]1(OC=2C(C)=C(C(=C(C)C=2CC1)O)C)C)OC(C=C1)=CC=C1C[C@H]1SC(=O)NC1=O GXPHKUHSUJUWKP-NTKDMRAZSA-N 0.000 description 1
• 239000002753 trypsin inhibitor Substances 0.000 description 1
• 210000005239 tubule Anatomy 0.000 description 1
• 230000005760 tumorsuppression Effects 0.000 description 1
• 210000002700 urine Anatomy 0.000 description 1
• 238000010200 validation analysis Methods 0.000 description 1
• 239000003981 vehicle Substances 0.000 description 1
• 230000035899 viability Effects 0.000 description 1
• 108700026220 vif Genes Proteins 0.000 description 1
• 230000003612 virological effect Effects 0.000 description 1
• 230000009278 visceral effect Effects 0.000 description 1
• 235000019165 vitamin E Nutrition 0.000 description 1
• 229940046009 vitamin E Drugs 0.000 description 1
• 239000011709 vitamin E Substances 0.000 description 1
• 229960001729 voglibose Drugs 0.000 description 1
• 239000001993 wax Substances 0.000 description 1
• 230000003442 weekly effect Effects 0.000 description 1
• 238000005303 weighing Methods 0.000 description 1
• 239000009637 wintergreen oil Substances 0.000 description 1
• 239000000230 xanthan gum Substances 0.000 description 1
• 229920001285 xanthan gum Polymers 0.000 description 1
• 235000010493 xanthan gum Nutrition 0.000 description 1
• 229940082509 xanthan gum Drugs 0.000 description 1
• 239000008096 xylene Substances 0.000 description 1
• 229940093612 zein Drugs 0.000 description 1
• 239000005019 zein Substances 0.000 description 1
• 239000011701 zinc Substances 0.000 description 1
• 229910052725 zinc Inorganic materials 0.000 description 1
• 239000002076 α-tocopherol Substances 0.000 description 1
• 235000004835 α-tocopherol Nutrition 0.000 description 1
• 230000003820 β-cell dysfunction Effects 0.000 description 1