EA031428B1 - Функционализированные производные эксендина-4 - Google Patents

Info

Publication number

EA031428B1

EA031428B1 EA201591174A EA201591174A EA031428B1 EA 031428 B1 EA031428 B1 EA 031428B1 EA 201591174 A EA201591174 A EA 201591174A EA 201591174 A EA201591174 A EA 201591174A EA 031428 B1 EA031428 B1 EA 031428B1

Authority

EA

Eurasian Patent Office

Prior art keywords

carboxy

ethoxy

butyryl

amino acid

acid residue

Prior art date

2012-12-21

Links

• Espacenet
• Global Dossier
• Discuss

• JUFFVKRROAPVBI-PVOYSMBESA-N chembl1210015 Chemical class 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 title abstract description 50
• 238000011282 treatment Methods 0.000 claims abstract description 57
• 208000008589 Obesity Diseases 0.000 claims abstract description 40
• 235000020824 obesity Nutrition 0.000 claims abstract description 38
• 235000012631 food intake Nutrition 0.000 claims abstract description 24
• 230000037406 food intake Effects 0.000 claims abstract description 20
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 17
• 208000001145 Metabolic Syndrome Diseases 0.000 claims abstract description 14
• 201000000690 abdominal obesity-metabolic syndrome Diseases 0.000 claims abstract description 14
• 108010033276 Peptide Fragments Proteins 0.000 claims abstract description 8
• 102000007079 Peptide Fragments Human genes 0.000 claims abstract description 8
• -1 4-hexadecanoyl-aminobutyryl- Chemical group 0.000 claims description 325
• 150000001875 compounds Chemical class 0.000 claims description 203
• 108090000765 processed proteins & peptides Proteins 0.000 claims description 157
• 125000000539 amino acid group Chemical group 0.000 claims description 150
• 125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 claims description 118
• 125000000738 acetamido group Chemical group [H]C([H])([H])C(=O)N([H])[*] 0.000 claims description 90
• 230000000694 effects Effects 0.000 claims description 69
• 150000003839 salts Chemical class 0.000 claims description 43
• 108010004460 Gastric Inhibitory Polypeptide Proteins 0.000 claims description 36
• 102100039994 Gastric inhibitory polypeptide Human genes 0.000 claims description 35
• 229960004666 glucagon Drugs 0.000 claims description 31
• 102000051325 Glucagon Human genes 0.000 claims description 28
• 108060003199 Glucagon Proteins 0.000 claims description 28
• 239000012453 solvate Substances 0.000 claims description 28
• 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 claims description 27
• 102100040890 Glucagon receptor Human genes 0.000 claims description 24
• 241000024188 Andala Species 0.000 claims description 23
• 108010063919 Glucagon Receptors Proteins 0.000 claims description 23
• 108010036598 gastric inhibitory polypeptide receptor Proteins 0.000 claims description 23
• 208000001072 type 2 diabetes mellitus Diseases 0.000 claims description 21
• 239000000556 agonist Substances 0.000 claims description 17
• 108010086246 Glucagon-Like Peptide-1 Receptor Proteins 0.000 claims description 15
• 102100032882 Glucagon-like peptide 1 receptor Human genes 0.000 claims description 15
• 125000004063 butyryl group Chemical group O=C([*])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 15
• AYFVYJQAPQTCCC-GBXIJSLDSA-N L-threonine Chemical compound C[C@@H](O)[C@H](N)C(O)=O AYFVYJQAPQTCCC-GBXIJSLDSA-N 0.000 claims description 13
• 201000010099 disease Diseases 0.000 claims description 13
• YSDQQAXHVYUZIW-QCIJIYAXSA-N Liraglutide Chemical compound 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 12
• 229960002701 liraglutide Drugs 0.000 claims description 12
• 108010019598 Liraglutide Proteins 0.000 claims description 11
• 201000009104 prediabetes syndrome Diseases 0.000 claims description 10
• 208000002705 Glucose Intolerance Diseases 0.000 claims description 9
• 230000002265 prevention Effects 0.000 claims description 8
• 206010020772 Hypertension Diseases 0.000 claims description 7
• 210000001035 gastrointestinal tract Anatomy 0.000 claims description 7
• 208000015122 neurodegenerative disease Diseases 0.000 claims description 7
• 230000004580 weight loss Effects 0.000 claims description 7
• QNAYBMKLOCPYGJ-UWTATZPHSA-N D-alanine Chemical compound C[C@@H](N)C(O)=O QNAYBMKLOCPYGJ-UWTATZPHSA-N 0.000 claims description 5
• 206010067584 Type 1 diabetes mellitus Diseases 0.000 claims description 5
• 208000029078 coronary artery disease Diseases 0.000 claims description 5
• 230000004584 weight gain Effects 0.000 claims description 5
• 235000019786 weight gain Nutrition 0.000 claims description 5
• 201000001320 Atherosclerosis Diseases 0.000 claims description 4
• 208000032928 Dyslipidaemia Diseases 0.000 claims description 4
• DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 claims description 4
• 208000017170 Lipid metabolism disease Diseases 0.000 claims description 4
• 206010033307 Overweight Diseases 0.000 claims description 4
• 201000001421 hyperglycemia Diseases 0.000 claims description 4
• 239000002876 beta blocker Substances 0.000 claims description 3
• 229940097320 beta blocking agent Drugs 0.000 claims description 3
• 210000004899 c-terminal region Anatomy 0.000 claims description 3
• 230000002441 reversible effect Effects 0.000 claims description 3
• NGJOFQZEYQGZMB-KTKZVXAJSA-N (4S)-5-[[2-[[(2S,3R)-1-[[(2S)-1-[[(2S,3R)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[2-[[(2S)-5-amino-1-[[(2S)-1-[[(2S)-1-[[(2S)-6-amino-1-[[(2S)-1-[[(2S)-1-[[(2S,3S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-6-amino-1-[[2-[[(1S)-4-carbamimidamido-1-carboxybutyl]amino]-2-oxoethyl]amino]-1-oxohexan-2-yl]amino]-3-methyl-1-oxobutan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-3-(1H-indol-3-yl)-1-oxopropan-2-yl]amino]-1-oxopropan-2-yl]amino]-3-methyl-1-oxopentan-2-yl]amino]-1-oxo-3-phenylpropan-2-yl]amino]-4-carboxy-1-oxobutan-2-yl]amino]-1-oxohexan-2-yl]amino]-1-oxopropan-2-yl]amino]-1-oxopropan-2-yl]amino]-1,5-dioxopentan-2-yl]amino]-2-oxoethyl]amino]-4-carboxy-1-oxobutan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-3-(4-hydroxyphenyl)-1-oxopropan-2-yl]amino]-3-hydroxy-1-oxopropan-2-yl]amino]-3-hydroxy-1-oxopropan-2-yl]amino]-3-methyl-1-oxobutan-2-yl]amino]-3-carboxy-1-oxopropan-2-yl]amino]-3-hydroxy-1-oxopropan-2-yl]amino]-3-hydroxy-1-oxobutan-2-yl]amino]-1-oxo-3-phenylpropan-2-yl]amino]-3-hydroxy-1-oxobutan-2-yl]amino]-2-oxoethyl]amino]-4-[[(2S)-2-[[(2S)-2-amino-3-(1H-imidazol-4-yl)propanoyl]amino]propanoyl]amino]-5-oxopentanoic acid 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)=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=1NC=NC=1)[C@@H](C)O)[C@@H](C)O)C(C)C)C1=CC=CC=C1 NGJOFQZEYQGZMB-KTKZVXAJSA-N 0.000 claims description 2
• 208000032841 Bulimia Diseases 0.000 claims description 2
• 206010006550 Bulimia nervosa Diseases 0.000 claims description 2
• 101800004295 Glucagon-like peptide 1(7-36) Proteins 0.000 claims description 2
• 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 2
• 230000006698 induction Effects 0.000 claims description 2
• 230000002401 inhibitory effect Effects 0.000 claims description 2
• 235000012054 meals Nutrition 0.000 claims description 2
• 231100000572 poisoning Toxicity 0.000 claims description 2
• 230000000607 poisoning effect Effects 0.000 claims description 2
• 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 2
• 230000003893 regulation of appetite Effects 0.000 claims description 2
• ZDFKJVWFYGHALK-UHFFFAOYSA-N 4-[[4-amino-5-(pyridine-3-carbonyl)-1,3-thiazol-2-yl]amino]benzenesulfonamide Chemical compound S1C(C(=O)C=2C=NC=CC=2)=C(N)N=C1NC1=CC=C(S(N)(=O)=O)C=C1 ZDFKJVWFYGHALK-UHFFFAOYSA-N 0.000 claims 1
• 208000019423 liver disease Diseases 0.000 claims 1
• 230000004899 motility Effects 0.000 claims 1
• 206010012601 diabetes mellitus Diseases 0.000 abstract description 42
• 230000009467 reduction Effects 0.000 abstract description 9
• 208000035475 disorder Diseases 0.000 abstract description 4
• KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 112
• KDXKERNSBIXSRK-YFKPBYRVSA-N L-lysine Chemical compound NCCCC[C@H](N)C(O)=O KDXKERNSBIXSRK-YFKPBYRVSA-N 0.000 description 88
• WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 87
• 241000699670 Mus sp. Species 0.000 description 87
• 239000008103 glucose Substances 0.000 description 87
• FUOOLUPWFVMBKG-UHFFFAOYSA-N 2-Aminoisobutyric acid Chemical compound CC(C)(N)C(O)=O FUOOLUPWFVMBKG-UHFFFAOYSA-N 0.000 description 67
• 210000004369 blood Anatomy 0.000 description 57
• 239000008280 blood Substances 0.000 description 57
• 238000000034 method Methods 0.000 description 56
• 102100040918 Pro-glucagon Human genes 0.000 description 55
• DTHNMHAUYICORS-KTKZVXAJSA-N Glucagon-like peptide 1 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(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@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 DTHNMHAUYICORS-KTKZVXAJSA-N 0.000 description 54
• 101800000224 Glucagon-like peptide 1 Proteins 0.000 description 52
• WHUUTDBJXJRKMK-UHFFFAOYSA-N Glutamic acid Natural products OC(=O)C(N)CCC(O)=O WHUUTDBJXJRKMK-UHFFFAOYSA-N 0.000 description 48
• 108010031719 prolyl-serine Proteins 0.000 description 46
• 230000037396 body weight Effects 0.000 description 44
• WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 description 43
• ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 40
• JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 39
• NOESYZHRGYRDHS-UHFFFAOYSA-N insulin Chemical compound N1C(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(NC(=O)CN)C(C)CC)CSSCC(C(NC(CO)C(=O)NC(CC(C)C)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CCC(N)=O)C(=O)NC(CC(C)C)C(=O)NC(CCC(O)=O)C(=O)NC(CC(N)=O)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CSSCC(NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2C=CC(O)=CC=2)NC(=O)C(CC(C)C)NC(=O)C(C)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2NC=NC=2)NC(=O)C(CO)NC(=O)CNC2=O)C(=O)NCC(=O)NC(CCC(O)=O)C(=O)NC(CCCNC(N)=N)C(=O)NCC(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC(O)=CC=3)C(=O)NC(C(C)O)C(=O)N3C(CCC3)C(=O)NC(CCCCN)C(=O)NC(C)C(O)=O)C(=O)NC(CC(N)=O)C(O)=O)=O)NC(=O)C(C(C)CC)NC(=O)C(CO)NC(=O)C(C(C)O)NC(=O)C1CSSCC2NC(=O)C(CC(C)C)NC(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CC(N)=O)NC(=O)C(NC(=O)C(N)CC=1C=CC=CC=1)C(C)C)CC1=CN=CN1 NOESYZHRGYRDHS-UHFFFAOYSA-N 0.000 description 39
• 229940024606 amino acid Drugs 0.000 description 37
• 235000001014 amino acid Nutrition 0.000 description 37
• 239000011347 resin Substances 0.000 description 37
• 229920005989 resin Polymers 0.000 description 37
• SBVPYBFMIGDIDX-SRVKXCTJSA-N Pro-Pro-Pro Chemical compound OC(=O)[C@@H]1CCCN1C(=O)[C@H]1N(C(=O)[C@H]2NCCC2)CCC1 SBVPYBFMIGDIDX-SRVKXCTJSA-N 0.000 description 36
• WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 33
• LLWQVJNHMYBLLK-CDMKHQONSA-N Gly-Thr-Phe Chemical compound [H]NCC(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC1=CC=CC=C1)C(O)=O LLWQVJNHMYBLLK-CDMKHQONSA-N 0.000 description 32
• 102000005962 receptors Human genes 0.000 description 32
• 108020003175 receptors Proteins 0.000 description 32
• IVDFVBVIVLJJHR-LKXGYXEUSA-N Thr-Ser-Asp Chemical compound [H]N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CO)C(=O)N[C@@H](CC(O)=O)C(O)=O IVDFVBVIVLJJHR-LKXGYXEUSA-N 0.000 description 31
• MTCFGRXMJLQNBG-REOHCLBHSA-N (2S)-2-Amino-3-hydroxypropansäure Chemical compound OC[C@H](N)C(O)=O MTCFGRXMJLQNBG-REOHCLBHSA-N 0.000 description 30
• 108010011459 Exenatide Proteins 0.000 description 30
• 150000001413 amino acids Chemical class 0.000 description 30
• ZDXPYRJPNDTMRX-VKHMYHEASA-N L-glutamine Chemical compound OC(=O)[C@@H](N)CCC(N)=O ZDXPYRJPNDTMRX-VKHMYHEASA-N 0.000 description 29
• UQFYNFTYDHUIMI-WHFBIAKZSA-N Ser-Gly-Ala Chemical compound OC(=O)[C@H](C)NC(=O)CNC(=O)[C@@H](N)CO UQFYNFTYDHUIMI-WHFBIAKZSA-N 0.000 description 29
• MVHXGBZUJLWZOH-BJDJZHNGSA-N Leu-Ser-Ile Chemical compound [H]N[C@@H](CC(C)C)C(=O)N[C@@H](CO)C(=O)N[C@@H]([C@@H](C)CC)C(O)=O MVHXGBZUJLWZOH-BJDJZHNGSA-N 0.000 description 27
• 229960001519 exenatide Drugs 0.000 description 24
• 230000015572 biosynthetic process Effects 0.000 description 23
• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 23
• 230000001965 increasing effect Effects 0.000 description 22
• IELISNUVHBKYBX-XDTLVQLUSA-N Tyr-Ala-Glu Chemical compound OC(=O)CC[C@@H](C(O)=O)NC(=O)[C@H](C)NC(=O)[C@@H](N)CC1=CC=C(O)C=C1 IELISNUVHBKYBX-XDTLVQLUSA-N 0.000 description 21
• 102000004196 processed proteins & peptides Human genes 0.000 description 21
• CKLJMWTZIZZHCS-REOHCLBHSA-N L-aspartic acid Chemical compound OC(=O)[C@@H](N)CC(O)=O CKLJMWTZIZZHCS-REOHCLBHSA-N 0.000 description 20
• LEHPJMKVGFPSSP-ZQINRCPSSA-N Ile-Glu-Trp Chemical compound C1=CC=C2C(C[C@H](NC(=O)[C@H](CCC(O)=O)NC(=O)[C@@H](N)[C@@H](C)CC)C(O)=O)=CNC2=C1 LEHPJMKVGFPSSP-ZQINRCPSSA-N 0.000 description 19
• 102000004877 Insulin Human genes 0.000 description 19
• 108090001061 Insulin Proteins 0.000 description 19
• 238000003786 synthesis reaction Methods 0.000 description 19
• 210000004027 cell Anatomy 0.000 description 18
• 229940125396 insulin Drugs 0.000 description 18
• OOBVTWHLKYJFJH-FXQIFTODSA-N Arg-Ala-Ala Chemical compound [H]N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](C)C(=O)N[C@@H](C)C(O)=O OOBVTWHLKYJFJH-FXQIFTODSA-N 0.000 description 17
• 108010076324 alanyl-glycyl-glycine Proteins 0.000 description 17
• 206010002022 amyloidosis Diseases 0.000 description 17
• DTQVDTLACAAQTR-UHFFFAOYSA-N trifluoroacetic acid Substances OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 17
• 230000004913 activation Effects 0.000 description 16
• ZRHDPZAAWLXXIR-SRVKXCTJSA-N Leu-Lys-Ala Chemical compound [H]N[C@@H](CC(C)C)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](C)C(O)=O ZRHDPZAAWLXXIR-SRVKXCTJSA-N 0.000 description 15
• 239000003814 drug Substances 0.000 description 15
• 239000003112 inhibitor Substances 0.000 description 15
• 238000010532 solid phase synthesis reaction Methods 0.000 description 15
• 210000002784 stomach Anatomy 0.000 description 15
• 239000003643 water by type Substances 0.000 description 15
• WXUOJXIGOPMDJM-SRVKXCTJSA-N Leu-Lys-Asn Chemical compound CC(C)C[C@H](N)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(N)=O)C(O)=O WXUOJXIGOPMDJM-SRVKXCTJSA-N 0.000 description 14
• 230000008859 change Effects 0.000 description 14
• 239000000203 mixture Substances 0.000 description 14
• 239000012071 phase Substances 0.000 description 14
• 239000000243 solution Substances 0.000 description 14
• 238000011785 NMRI mouse Methods 0.000 description 13
• 230000007423 decrease Effects 0.000 description 13
• 239000008194 pharmaceutical composition Substances 0.000 description 13
• 108090000623 proteins and genes Proteins 0.000 description 13
• 238000007920 subcutaneous administration Methods 0.000 description 13
• HPCOBEHVEHWREJ-DCAQKATOSA-N Gln-Lys-Glu Chemical compound [H]N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCC(O)=O)C(O)=O HPCOBEHVEHWREJ-DCAQKATOSA-N 0.000 description 12
• BUEFQXUHTUZXHR-LURJTMIESA-N Gly-Gly-Pro zwitterion Chemical compound NCC(=O)NCC(=O)N1CCC[C@H]1C(O)=O BUEFQXUHTUZXHR-LURJTMIESA-N 0.000 description 12
• DCXYFEDJOCDNAF-REOHCLBHSA-N L-asparagine Chemical compound OC(=O)[C@@H](N)CC(N)=O DCXYFEDJOCDNAF-REOHCLBHSA-N 0.000 description 12
• OUYCCCASQSFEME-QMMMGPOBSA-N L-tyrosine Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-QMMMGPOBSA-N 0.000 description 12
• 241001465754 Metazoa Species 0.000 description 12
• 239000013543 active substance Substances 0.000 description 12
• 125000003275 alpha amino acid group Chemical group 0.000 description 12
• 108010050025 alpha-glutamyltryptophan Proteins 0.000 description 12
• 125000003277 amino group Chemical group 0.000 description 12
• 239000000872 buffer Substances 0.000 description 12
• 235000018102 proteins Nutrition 0.000 description 12
• 102000004169 proteins and genes Human genes 0.000 description 12
• 238000012360 testing method Methods 0.000 description 12
• 239000003981 vehicle Substances 0.000 description 12
• 125000003088 (fluoren-9-ylmethoxy)carbonyl group Chemical group 0.000 description 11
• 239000004472 Lysine Substances 0.000 description 10
• TWIAMTNJOMRDAK-GUBZILKMSA-N Gln-Lys-Asp Chemical compound [H]N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(O)=O)C(O)=O TWIAMTNJOMRDAK-GUBZILKMSA-N 0.000 description 9
• ROHFNLRQFUQHCH-YFKPBYRVSA-N L-leucine Chemical compound CC(C)C[C@H](N)C(O)=O ROHFNLRQFUQHCH-YFKPBYRVSA-N 0.000 description 9
• XLMDWQNAOKLKCP-XDTLVQLUSA-N Tyr-Ala-Gln Chemical compound C[C@@H](C(=O)N[C@@H](CCC(=O)N)C(=O)O)NC(=O)[C@H](CC1=CC=C(C=C1)O)N XLMDWQNAOKLKCP-XDTLVQLUSA-N 0.000 description 9
• 235000013305 food Nutrition 0.000 description 9
• 230000000968 intestinal effect Effects 0.000 description 9
• 238000002953 preparative HPLC Methods 0.000 description 9
• 230000002829 reductive effect Effects 0.000 description 9
• 210000000813 small intestine Anatomy 0.000 description 9
• GNRMAQSIROFNMI-IXOXFDKPSA-N Phe-Thr-Ser Chemical compound [H]N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CO)C(O)=O GNRMAQSIROFNMI-IXOXFDKPSA-N 0.000 description 8
• NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 8
• 239000004480 active ingredient Substances 0.000 description 8
• 235000005911 diet Nutrition 0.000 description 8
• 229940079593 drug Drugs 0.000 description 8
• 108010089804 glycyl-threonine Proteins 0.000 description 8
• 235000009200 high fat diet Nutrition 0.000 description 8
• 238000005259 measurement Methods 0.000 description 8
• 239000002953 phosphate buffered saline Substances 0.000 description 8
• 125000006239 protecting group Chemical group 0.000 description 8
• 238000006722 reduction reaction Methods 0.000 description 8
• ZEQLLMOXFVKKCN-AWEZNQCLSA-N (2s)-2-[(2-methylpropan-2-yl)oxycarbonylamino]-3-[4-[(2-methylpropan-2-yl)oxy]phenyl]propanoic acid Chemical compound CC(C)(C)OC(=O)N[C@H](C(O)=O)CC1=CC=C(OC(C)(C)C)C=C1 ZEQLLMOXFVKKCN-AWEZNQCLSA-N 0.000 description 7
• 239000005485 Azilsartan Substances 0.000 description 7
• KZNQNBZMBZJQJO-UHFFFAOYSA-N N-glycyl-L-proline Natural products NCC(=O)N1CCCC1C(O)=O KZNQNBZMBZJQJO-UHFFFAOYSA-N 0.000 description 7
• MKGIILKDUGDRRO-FXQIFTODSA-N Pro-Ser-Ser Chemical compound OC[C@@H](C(O)=O)NC(=O)[C@H](CO)NC(=O)[C@@H]1CCCN1 MKGIILKDUGDRRO-FXQIFTODSA-N 0.000 description 7
• CJINPXGSKSZQNE-KBIXCLLPSA-N Ser-Ile-Gln Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CCC(N)=O)C(O)=O CJINPXGSKSZQNE-KBIXCLLPSA-N 0.000 description 7
• 239000002253 acid Substances 0.000 description 7
• 230000009471 action Effects 0.000 description 7
• 210000000577 adipose tissue Anatomy 0.000 description 7
• 150000001408 amides Chemical class 0.000 description 7
• KGSXMPPBFPAXLY-UHFFFAOYSA-N azilsartan Chemical compound CCOC1=NC2=CC=CC(C(O)=O)=C2N1CC(C=C1)=CC=C1C1=CC=CC=C1C1=NOC(=O)N1 KGSXMPPBFPAXLY-UHFFFAOYSA-N 0.000 description 7
• 229960002731 azilsartan Drugs 0.000 description 7
• 239000003153 chemical reaction reagent Substances 0.000 description 7
• 239000012043 crude product Substances 0.000 description 7
• 239000003937 drug carrier Substances 0.000 description 7
• 238000005516 engineering process Methods 0.000 description 7
• 238000002474 experimental method Methods 0.000 description 7
• 150000004665 fatty acids Chemical group 0.000 description 7
• 238000004128 high performance liquid chromatography Methods 0.000 description 7
• 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 7
• 230000014759 maintenance of location Effects 0.000 description 7
• 230000035764 nutrition Effects 0.000 description 7
• 235000016709 nutrition Nutrition 0.000 description 7
• 239000000018 receptor agonist Substances 0.000 description 7
• 229940044601 receptor agonist Drugs 0.000 description 7
• 239000002904 solvent Substances 0.000 description 7
• 238000010254 subcutaneous injection Methods 0.000 description 7
• 239000007929 subcutaneous injection Substances 0.000 description 7
• 239000000126 substance Substances 0.000 description 7
• 230000001225 therapeutic effect Effects 0.000 description 7
• 238000004704 ultra performance liquid chromatography Methods 0.000 description 7
• PAIHPOGPJVUFJY-WDSKDSINSA-N Ala-Glu-Gly Chemical compound C[C@H](N)C(=O)N[C@@H](CCC(O)=O)C(=O)NCC(O)=O PAIHPOGPJVUFJY-WDSKDSINSA-N 0.000 description 6
• 239000002947 C09CA04 - Irbesartan Substances 0.000 description 6
• YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 6
• 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 6
• LRQKBLKVPFOOQJ-YFKPBYRVSA-N L-norleucine Chemical compound CCCC[C@H]([NH3+])C([O-])=O LRQKBLKVPFOOQJ-YFKPBYRVSA-N 0.000 description 6
• 108010079364 N-glycylalanine Proteins 0.000 description 6
• 239000005480 Olmesartan Substances 0.000 description 6
• HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 6
• MSIYNSBKKVMGFO-BHNWBGBOSA-N Thr-Gly-Pro Chemical compound C[C@H]([C@@H](C(=O)NCC(=O)N1CCC[C@@H]1C(=O)O)N)O MSIYNSBKKVMGFO-BHNWBGBOSA-N 0.000 description 6
• 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 6
• 238000010511 deprotection reaction Methods 0.000 description 6
• 230000037213 diet Effects 0.000 description 6
• 235000014113 dietary fatty acids Nutrition 0.000 description 6
• 229930195729 fatty acid Natural products 0.000 description 6
• 239000000194 fatty acid Substances 0.000 description 6
• VPZXBVLAVMBEQI-UHFFFAOYSA-N glycyl-DL-alpha-alanine Natural products OC(=O)C(C)NC(=O)CN VPZXBVLAVMBEQI-UHFFFAOYSA-N 0.000 description 6
• 125000002887 hydroxy group Chemical group [H]O* 0.000 description 6
• 238000000338 in vitro Methods 0.000 description 6
• 238000001727 in vivo Methods 0.000 description 6
• 239000007924 injection Substances 0.000 description 6
• 238000002347 injection Methods 0.000 description 6
• 210000000936 intestine Anatomy 0.000 description 6
• 229960002198 irbesartan Drugs 0.000 description 6
• YCPOHTHPUREGFM-UHFFFAOYSA-N irbesartan Chemical compound O=C1N(CC=2C=CC(=CC=2)C=2C(=CC=CC=2)C=2[N]N=NN=2)C(CCCC)=NC21CCCC2 YCPOHTHPUREGFM-UHFFFAOYSA-N 0.000 description 6
• 108010009298 lysylglutamic acid Proteins 0.000 description 6
• BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 6
• 229960005117 olmesartan Drugs 0.000 description 6
• VTRAEEWXHOVJFV-UHFFFAOYSA-N olmesartan Chemical compound CCCC1=NC(C(C)(C)O)=C(C(O)=O)N1CC1=CC=C(C=2C(=CC=CC=2)C=2NN=NN=2)C=C1 VTRAEEWXHOVJFV-UHFFFAOYSA-N 0.000 description 6
• 238000010647 peptide synthesis reaction Methods 0.000 description 6
• NWZSZGALRFJKBT-KNIFDHDWSA-N (2s)-2,6-diaminohexanoic acid;(2s)-2-hydroxybutanedioic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O.NCCCC[C@H](N)C(O)=O NWZSZGALRFJKBT-KNIFDHDWSA-N 0.000 description 5
• SSHIXEILTLPAQT-WHFBIAKZSA-N Gln-Asp Chemical compound NC(=O)CC[C@H](N)C(=O)N[C@@H](CC(O)=O)C(O)=O SSHIXEILTLPAQT-WHFBIAKZSA-N 0.000 description 5
• XMBSYZWANAQXEV-UHFFFAOYSA-N N-alpha-L-glutamyl-L-phenylalanine Natural products OC(=O)CCC(N)C(=O)NC(C(O)=O)CC1=CC=CC=C1 XMBSYZWANAQXEV-UHFFFAOYSA-N 0.000 description 5
• KRYSMKKRRRWOCZ-QEWYBTABSA-N Phe-Ile-Glu Chemical compound [H]N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CCC(O)=O)C(O)=O KRYSMKKRRRWOCZ-QEWYBTABSA-N 0.000 description 5
• RRVUOLRWIZXBRQ-IHPCNDPISA-N Trp-Leu-Lys Chemical compound CC(C)C[C@@H](C(=O)N[C@@H](CCCCN)C(=O)O)NC(=O)[C@H](CC1=CNC2=CC=CC=C21)N RRVUOLRWIZXBRQ-IHPCNDPISA-N 0.000 description 5
• QTBSBXVTEAMEQO-UHFFFAOYSA-N acetic acid Substances CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 5
• 230000001154 acute effect Effects 0.000 description 5
• 238000004458 analytical method Methods 0.000 description 5
• 239000002585 base Substances 0.000 description 5
• 239000003795 chemical substances by application Substances 0.000 description 5
• 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 5
• 230000035611 feeding Effects 0.000 description 5
• BTCSSZJGUNDROE-UHFFFAOYSA-N gamma-aminobutyric acid Chemical compound NCCCC(O)=O BTCSSZJGUNDROE-UHFFFAOYSA-N 0.000 description 5
• IKDUDTNKRLTJSI-UHFFFAOYSA-N hydrazine monohydrate Substances O.NN IKDUDTNKRLTJSI-UHFFFAOYSA-N 0.000 description 5
• PBGKTOXHQIOBKM-FHFVDXKLSA-N insulin (human) 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)=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 5
• 125000003588 lysine group Chemical group [H]N([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])(N([H])[H])C(*)=O 0.000 description 5
• 229930182817 methionine Natural products 0.000 description 5
• 125000001360 methionine group Chemical group N[C@@H](CCSC)C(=O)* 0.000 description 5
• 230000004048 modification Effects 0.000 description 5
• 238000012986 modification Methods 0.000 description 5
• 210000000496 pancreas Anatomy 0.000 description 5
• 239000000047 product Substances 0.000 description 5
• 230000004044 response Effects 0.000 description 5
• 239000007787 solid Substances 0.000 description 5
• 239000007790 solid phase Substances 0.000 description 5
• 238000007619 statistical method Methods 0.000 description 5
• 108010061238 threonyl-glycine Proteins 0.000 description 5
• 210000001519 tissue Anatomy 0.000 description 5
• 238000007492 two-way ANOVA Methods 0.000 description 5
• 238000005303 weighing Methods 0.000 description 5
• YLTKNGYYPIWKHZ-ACZMJKKPSA-N Ala-Ala-Glu Chemical compound C[C@H](N)C(=O)N[C@@H](C)C(=O)N[C@H](C(O)=O)CCC(O)=O YLTKNGYYPIWKHZ-ACZMJKKPSA-N 0.000 description 4
• MKZCBYZBCINNJN-DLOVCJGASA-N Ala-Asp-Phe Chemical compound C[C@H](N)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@H](C(O)=O)CC1=CC=CC=C1 MKZCBYZBCINNJN-DLOVCJGASA-N 0.000 description 4
• 206010002091 Anaesthesia Diseases 0.000 description 4
• FMNBYVSGRCXWEK-FOHZUACHSA-N Asn-Thr-Gly Chemical compound [H]N[C@@H](CC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(=O)NCC(O)=O FMNBYVSGRCXWEK-FOHZUACHSA-N 0.000 description 4
• KXDHJXZQYSOELW-UHFFFAOYSA-N Carbamic acid Chemical class NC(O)=O KXDHJXZQYSOELW-UHFFFAOYSA-N 0.000 description 4
• OWOFCNWTMWOOJJ-WDSKDSINSA-N Gln-Glu Chemical compound NC(=O)CC[C@H](N)C(=O)N[C@@H](CCC(O)=O)C(O)=O OWOFCNWTMWOOJJ-WDSKDSINSA-N 0.000 description 4
• BBBXWRGITSUJPB-YUMQZZPRSA-N Glu-Lys Chemical compound NCCCC[C@@H](C(O)=O)NC(=O)[C@@H](N)CCC(O)=O BBBXWRGITSUJPB-YUMQZZPRSA-N 0.000 description 4
• JZJGEKDPWVJOLD-QEWYBTABSA-N Glu-Phe-Ile Chemical compound [H]N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H]([C@@H](C)CC)C(O)=O JZJGEKDPWVJOLD-QEWYBTABSA-N 0.000 description 4
• 101000886868 Homo sapiens Gastric inhibitory polypeptide Proteins 0.000 description 4
• 102000013266 Human Regular Insulin Human genes 0.000 description 4
• 108010090613 Human Regular Insulin Proteins 0.000 description 4
• OAKJQQAXSVQMHS-UHFFFAOYSA-N Hydrazine Chemical compound NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 description 4
• 208000013016 Hypoglycemia Diseases 0.000 description 4
• PQNASZJZHFPQLE-LURJTMIESA-N N(6)-methyl-L-lysine Chemical compound CNCCCC[C@H](N)C(O)=O PQNASZJZHFPQLE-LURJTMIESA-N 0.000 description 4
• ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 4
• 235000021355 Stearic acid Nutrition 0.000 description 4
• 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 4
• 238000007792 addition Methods 0.000 description 4
• 108010017893 alanyl-alanyl-alanine Proteins 0.000 description 4
• 230000037005 anaesthesia Effects 0.000 description 4
• 210000000227 basophil cell of anterior lobe of hypophysis Anatomy 0.000 description 4
• 230000001684 chronic effect Effects 0.000 description 4
• 230000006378 damage Effects 0.000 description 4
• 239000007857 degradation product Substances 0.000 description 4
• 230000001419 dependent effect Effects 0.000 description 4
• 229960003692 gamma aminobutyric acid Drugs 0.000 description 4
• 125000000404 glutamine group Chemical group N[C@@H](CCC(N)=O)C(=O)* 0.000 description 4
• IPCSVZSSVZVIGE-UHFFFAOYSA-N hexadecanoic acid Chemical compound CCCCCCCCCCCCCCCC(O)=O IPCSVZSSVZVIGE-UHFFFAOYSA-N 0.000 description 4
• 229940088597 hormone Drugs 0.000 description 4
• 239000005556 hormone Substances 0.000 description 4
• 102000050325 human granulocyte inhibitory Human genes 0.000 description 4
• 229940103471 humulin Drugs 0.000 description 4
• 230000002218 hypoglycaemic effect Effects 0.000 description 4
• 239000000859 incretin Substances 0.000 description 4
• 230000003914 insulin secretion Effects 0.000 description 4
• 150000002500 ions Chemical class 0.000 description 4
• 108020004707 nucleic acids Proteins 0.000 description 4
• 150000007523 nucleic acids Chemical class 0.000 description 4
• 102000039446 nucleic acids Human genes 0.000 description 4
• QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 4
• OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 4
• 238000001543 one-way ANOVA Methods 0.000 description 4
• 239000002464 receptor antagonist Substances 0.000 description 4
• 229940044551 receptor antagonist Drugs 0.000 description 4
• 239000000523 sample Substances 0.000 description 4
• 230000028327 secretion Effects 0.000 description 4
• 239000008117 stearic acid Substances 0.000 description 4
• GOPWHXPXSPIIQZ-FQEVSTJZSA-N (4s)-4-(9h-fluoren-9-ylmethoxycarbonylamino)-5-[(2-methylpropan-2-yl)oxy]-5-oxopentanoic acid Chemical compound C1=CC=C2C(COC(=O)N[C@@H](CCC(O)=O)C(=O)OC(C)(C)C)C3=CC=CC=C3C2=C1 GOPWHXPXSPIIQZ-FQEVSTJZSA-N 0.000 description 3
• HNSDLXPSAYFUHK-UHFFFAOYSA-N 1,4-bis(2-ethylhexyl) sulfosuccinate Chemical compound CCCCC(CC)COC(=O)CC(S(O)(=O)=O)C(=O)OCC(CC)CCCC HNSDLXPSAYFUHK-UHFFFAOYSA-N 0.000 description 3
• OGNSCSPNOLGXSM-UHFFFAOYSA-N 2,4-diaminobutyric acid Chemical compound NCCC(N)C(O)=O OGNSCSPNOLGXSM-UHFFFAOYSA-N 0.000 description 3
• SLXKOJJOQWFEFD-UHFFFAOYSA-N 6-aminohexanoic acid Chemical compound NCCCCCC(O)=O SLXKOJJOQWFEFD-UHFFFAOYSA-N 0.000 description 3
• 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 3
• 208000024827 Alzheimer disease Diseases 0.000 description 3
• PCJOFZYFFMBZKC-PCBIJLKTSA-N Asp-Phe-Ile Chemical compound [H]N[C@@H](CC(O)=O)C(=O)N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H]([C@@H](C)CC)C(O)=O PCJOFZYFFMBZKC-PCBIJLKTSA-N 0.000 description 3
• JKPGHIQCHIIRMS-AVGNSLFASA-N Gln-Asp-Phe Chemical compound C1=CC=C(C=C1)C[C@@H](C(=O)O)NC(=O)[C@H](CC(=O)O)NC(=O)[C@H](CCC(=O)N)N JKPGHIQCHIIRMS-AVGNSLFASA-N 0.000 description 3
• 239000007821 HATU Substances 0.000 description 3
• 241000282414 Homo sapiens Species 0.000 description 3
• 101001040075 Homo sapiens Glucagon receptor Proteins 0.000 description 3
• 101001015516 Homo sapiens Glucagon-like peptide 1 receptor Proteins 0.000 description 3
• 108010057186 Insulin Glargine Proteins 0.000 description 3
• 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 3
• ODKSFYDXXFIFQN-BYPYZUCNSA-N L-arginine Chemical compound OC(=O)[C@@H](N)CCCN=C(N)N ODKSFYDXXFIFQN-BYPYZUCNSA-N 0.000 description 3
• ROHFNLRQFUQHCH-UHFFFAOYSA-N Leucine Natural products CC(C)CC(N)C(O)=O ROHFNLRQFUQHCH-UHFFFAOYSA-N 0.000 description 3
• 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 3
• 208000016604 Lyme disease Diseases 0.000 description 3
• WXJKFRMKJORORD-DCAQKATOSA-N Lys-Arg-Ala Chemical compound NC(=N)NCCC[C@@H](C(=O)N[C@@H](C)C(O)=O)NC(=O)[C@@H](N)CCCCN WXJKFRMKJORORD-DCAQKATOSA-N 0.000 description 3
• 238000005481 NMR spectroscopy Methods 0.000 description 3
• 206010028813 Nausea Diseases 0.000 description 3
• 102000003729 Neprilysin Human genes 0.000 description 3
• 108090000028 Neprilysin Proteins 0.000 description 3
• PVNIIMVLHYAWGP-UHFFFAOYSA-N Niacin Chemical compound OC(=O)C1=CC=CN=C1 PVNIIMVLHYAWGP-UHFFFAOYSA-N 0.000 description 3
• 208000001132 Osteoporosis Diseases 0.000 description 3
• AFWBWPCXSWUCLB-WDSKDSINSA-N Pro-Ser Chemical compound OC[C@@H](C([O-])=O)NC(=O)[C@@H]1CCC[NH2+]1 AFWBWPCXSWUCLB-WDSKDSINSA-N 0.000 description 3
• 208000006011 Stroke Diseases 0.000 description 3
• 241000282887 Suidae Species 0.000 description 3
• KSCVLGXNQXKUAR-JYJNAYRXSA-N Tyr-Leu-Glu Chemical compound [H]N[C@@H](CC1=CC=C(O)C=C1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(O)=O)C(O)=O KSCVLGXNQXKUAR-JYJNAYRXSA-N 0.000 description 3
• 150000007513 acids Chemical class 0.000 description 3
• 230000008484 agonism Effects 0.000 description 3
• 108010044940 alanylglutamine Proteins 0.000 description 3
• 238000000540 analysis of variance Methods 0.000 description 3
• 238000010171 animal model Methods 0.000 description 3
• 239000005557 antagonist Substances 0.000 description 3
• 230000003178 anti-diabetic effect Effects 0.000 description 3
• 239000003472 antidiabetic agent Substances 0.000 description 3
• 238000013459 approach Methods 0.000 description 3
• 125000003118 aryl group Chemical group 0.000 description 3
• 230000004888 barrier function Effects 0.000 description 3
• 230000009286 beneficial effect Effects 0.000 description 3
• 210000004204 blood vessel Anatomy 0.000 description 3
• 210000004556 brain Anatomy 0.000 description 3
• 239000000969 carrier Substances 0.000 description 3
• 235000012000 cholesterol Nutrition 0.000 description 3
• KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
• 230000003247 decreasing effect Effects 0.000 description 3
• 230000007812 deficiency Effects 0.000 description 3
• 231100000673 dose–response relationship Toxicity 0.000 description 3
• 210000003890 endocrine cell Anatomy 0.000 description 3
• 239000013604 expression vector Substances 0.000 description 3
• 235000019253 formic acid Nutrition 0.000 description 3
• 125000000524 functional group Chemical group 0.000 description 3
• 210000003736 gastrointestinal content Anatomy 0.000 description 3
• 230000014509 gene expression Effects 0.000 description 3
• 239000004220 glutamic acid Substances 0.000 description 3
• ZDXPYRJPNDTMRX-UHFFFAOYSA-N glutamine Natural products OC(=O)C(N)CCC(N)=O ZDXPYRJPNDTMRX-UHFFFAOYSA-N 0.000 description 3
• YMAWOPBAYDPSLA-UHFFFAOYSA-N glycylglycine Chemical compound [NH3+]CC(=O)NCC([O-])=O YMAWOPBAYDPSLA-UHFFFAOYSA-N 0.000 description 3
• 210000002216 heart Anatomy 0.000 description 3
• 238000002868 homogeneous time resolved fluorescence Methods 0.000 description 3
• 239000012535 impurity Substances 0.000 description 3
• 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 3
• 230000003834 intracellular effect Effects 0.000 description 3
• 210000003734 kidney Anatomy 0.000 description 3
• 102000005861 leptin receptors Human genes 0.000 description 3
• 108010019813 leptin receptors Proteins 0.000 description 3
• 238000004811 liquid chromatography Methods 0.000 description 3
• 238000004949 mass spectrometry Methods 0.000 description 3
• 230000007246 mechanism Effects 0.000 description 3
• 239000002609 medium Substances 0.000 description 3
• 230000008693 nausea Effects 0.000 description 3
• 230000004770 neurodegeneration Effects 0.000 description 3
• 230000003647 oxidation Effects 0.000 description 3
• 238000007254 oxidation reaction Methods 0.000 description 3
• 244000052769 pathogen Species 0.000 description 3
• 239000000546 pharmaceutical excipient Substances 0.000 description 3
• 229920000642 polymer Polymers 0.000 description 3
• 238000004007 reversed phase HPLC Methods 0.000 description 3
• 210000000278 spinal cord Anatomy 0.000 description 3
• 230000000638 stimulation Effects 0.000 description 3
• 239000006228 supernatant Substances 0.000 description 3
• 229940124597 therapeutic agent Drugs 0.000 description 3
• JKMHFZQWWAIEOD-UHFFFAOYSA-N 2-[4-(2-hydroxyethyl)piperazin-1-yl]ethanesulfonic acid Chemical compound OCC[NH+]1CCN(CCS([O-])(=O)=O)CC1 JKMHFZQWWAIEOD-UHFFFAOYSA-N 0.000 description 2
• PECYZEOJVXMISF-UHFFFAOYSA-N 3-aminoalanine Chemical compound [NH3+]CC(N)C([O-])=O PECYZEOJVXMISF-UHFFFAOYSA-N 0.000 description 2
• OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 2
• 208000022385 ALys amyloidosis Diseases 0.000 description 2
• 108010088751 Albumins Proteins 0.000 description 2
• 102000009027 Albumins Human genes 0.000 description 2
• 206010003210 Arteriosclerosis Diseases 0.000 description 2
• DCXYFEDJOCDNAF-UHFFFAOYSA-N Asparagine Natural products OC(=O)C(N)CC(N)=O DCXYFEDJOCDNAF-UHFFFAOYSA-N 0.000 description 2
• 206010003591 Ataxia Diseases 0.000 description 2
• 208000006386 Bone Resorption Diseases 0.000 description 2
• 108091003079 Bovine Serum Albumin Proteins 0.000 description 2
• 208000024172 Cardiovascular disease Diseases 0.000 description 2
• VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 2
• KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 description 2
• 206010012289 Dementia Diseases 0.000 description 2
• 208000032131 Diabetic Neuropathies Diseases 0.000 description 2
• 102000016622 Dipeptidyl Peptidase 4 Human genes 0.000 description 2
• 108010067722 Dipeptidyl Peptidase 4 Proteins 0.000 description 2
• 239000006144 Dulbecco’s modified Eagle's medium Substances 0.000 description 2
• LCDDAGSJHKEABN-MLGOLLRUSA-N Evogliptin Chemical compound C1CNC(=O)[C@@H](COC(C)(C)C)N1C(=O)C[C@H](N)CC1=CC(F)=C(F)C=C1F LCDDAGSJHKEABN-MLGOLLRUSA-N 0.000 description 2
• CGOHAEBMDSEKFB-FXQIFTODSA-N Glu-Glu-Ala Chemical compound [H]N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](C)C(O)=O CGOHAEBMDSEKFB-FXQIFTODSA-N 0.000 description 2
• HGJREIGJLUQBTJ-SZMVWBNQSA-N Glu-Trp-Leu Chemical compound [H]N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC1=CNC2=C1C=CC=C2)C(=O)N[C@@H](CC(C)C)C(O)=O HGJREIGJLUQBTJ-SZMVWBNQSA-N 0.000 description 2
• 229940089838 Glucagon-like peptide 1 receptor agonist Drugs 0.000 description 2
• XTQFHTHIAKKCTM-YFKPBYRVSA-N Gly-Glu-Gly Chemical compound NCC(=O)N[C@@H](CCC(O)=O)C(=O)NCC(O)=O XTQFHTHIAKKCTM-YFKPBYRVSA-N 0.000 description 2
• 239000007995 HEPES buffer Substances 0.000 description 2
• 239000012981 Hank's balanced salt solution Substances 0.000 description 2
• 241000270431 Heloderma suspectum Species 0.000 description 2
• AFPFGFUGETYOSY-HGNGGELXSA-N His-Ala-Glu Chemical compound [H]N[C@@H](CC1=CNC=N1)C(=O)N[C@@H](C)C(=O)N[C@@H](CCC(O)=O)C(O)=O AFPFGFUGETYOSY-HGNGGELXSA-N 0.000 description 2
• 108091016366 Histone-lysine N-methyltransferase EHMT1 Proteins 0.000 description 2
• 241000282412 Homo Species 0.000 description 2
• VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
• 206010061218 Inflammation Diseases 0.000 description 2
• 206010022489 Insulin Resistance Diseases 0.000 description 2
• 108010041872 Islet Amyloid Polypeptide Proteins 0.000 description 2
• 102000036770 Islet Amyloid Polypeptide Human genes 0.000 description 2
• 102000016267 Leptin Human genes 0.000 description 2
• 108010092277 Leptin Proteins 0.000 description 2
• SYRTUBLKWNDSDK-DKIMLUQUSA-N Leu-Phe-Ile Chemical compound [H]N[C@@H](CC(C)C)C(=O)N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H]([C@@H](C)CC)C(O)=O SYRTUBLKWNDSDK-DKIMLUQUSA-N 0.000 description 2
• FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 2
• 241000699666 Mus <mouse, genus> Species 0.000 description 2
• NQTADLQHYWFPDB-UHFFFAOYSA-N N-Hydroxysuccinimide Chemical compound ON1C(=O)CCC1=O NQTADLQHYWFPDB-UHFFFAOYSA-N 0.000 description 2
• 102400000319 Oxyntomodulin Human genes 0.000 description 2
• 101800001388 Oxyntomodulin Proteins 0.000 description 2
• 229910019142 PO4 Inorganic materials 0.000 description 2
• 235000021314 Palmitic acid Nutrition 0.000 description 2
• 208000018737 Parkinson disease Diseases 0.000 description 2
• 101800001672 Peptide YY(3-36) Proteins 0.000 description 2
• 108010058003 Proglucagon Proteins 0.000 description 2
• 208000005587 Refsum Disease Diseases 0.000 description 2
• GXXTUIUYTWGPMV-FXQIFTODSA-N Ser-Arg-Ala Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](C)C(O)=O GXXTUIUYTWGPMV-FXQIFTODSA-N 0.000 description 2
• 208000027583 Serpinopathy Diseases 0.000 description 2
• PZTZYZUTCPZWJH-FXQIFTODSA-N Val-Ser-Ser Chemical compound CC(C)[C@@H](C(=O)N[C@@H](CO)C(=O)N[C@@H](CO)C(=O)O)N PZTZYZUTCPZWJH-FXQIFTODSA-N 0.000 description 2
• 239000002535 acidifier Substances 0.000 description 2
• 239000012190 activator Substances 0.000 description 2
• 230000010933 acylation Effects 0.000 description 2
• 238000005917 acylation reaction Methods 0.000 description 2
• 239000000654 additive Substances 0.000 description 2
• 230000000996 additive effect Effects 0.000 description 2
• 208000030597 adult Refsum disease Diseases 0.000 description 2
• 230000001270 agonistic effect Effects 0.000 description 2
• GZCGUPFRVQAUEE-SLPGGIOYSA-N aldehydo-D-glucose Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C=O GZCGUPFRVQAUEE-SLPGGIOYSA-N 0.000 description 2
• 125000001931 aliphatic group Chemical group 0.000 description 2
• 229910052784 alkaline earth metal Inorganic materials 0.000 description 2
• 230000003113 alkalizing effect Effects 0.000 description 2
• 229940125708 antidiabetic agent Drugs 0.000 description 2
• 239000003524 antilipemic agent Substances 0.000 description 2
• 239000003963 antioxidant agent Substances 0.000 description 2
• 208000011775 arteriosclerosis disease Diseases 0.000 description 2
• 229960001230 asparagine Drugs 0.000 description 2
• 235000009582 asparagine Nutrition 0.000 description 2
• 125000000613 asparagine group Chemical group N[C@@H](CC(N)=O)C(=O)* 0.000 description 2
• 238000003556 assay Methods 0.000 description 2
• 239000012131 assay buffer Substances 0.000 description 2
• 230000008901 benefit Effects 0.000 description 2
• UCMIRNVEIXFBKS-UHFFFAOYSA-N beta-alanine Chemical compound NCCC(O)=O UCMIRNVEIXFBKS-UHFFFAOYSA-N 0.000 description 2
• 238000010241 blood sampling Methods 0.000 description 2
• 210000000988 bone and bone Anatomy 0.000 description 2
• 230000024279 bone resorption Effects 0.000 description 2
• 239000007853 buffer solution Substances 0.000 description 2
• SNPPWIUOZRMYNY-UHFFFAOYSA-N bupropion Chemical compound CC(C)(C)NC(C)C(=O)C1=CC=CC(Cl)=C1 SNPPWIUOZRMYNY-UHFFFAOYSA-N 0.000 description 2
• 229960001058 bupropion Drugs 0.000 description 2
• 238000004364 calculation method Methods 0.000 description 2
• 239000002775 capsule Substances 0.000 description 2
• 150000003857 carboxamides Chemical class 0.000 description 2
• 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 2
• 230000001413 cellular effect Effects 0.000 description 2
• 238000004587 chromatography analysis Methods 0.000 description 2
• 238000003776 cleavage reaction Methods 0.000 description 2
• 238000002648 combination therapy Methods 0.000 description 2
• 230000000052 comparative effect Effects 0.000 description 2
• 208000012696 congenital leptin deficiency Diseases 0.000 description 2
• 125000004122 cyclic group Chemical group 0.000 description 2
• 230000006240 deamidation Effects 0.000 description 2
• 230000007850 degeneration Effects 0.000 description 2
• 230000000378 dietary effect Effects 0.000 description 2
• 238000009826 distribution Methods 0.000 description 2
• 239000002934 diuretic Substances 0.000 description 2
• 229940030606 diuretics Drugs 0.000 description 2
• 239000003480 eluent Substances 0.000 description 2
• 210000003743 erythrocyte Anatomy 0.000 description 2
• 229950011259 evogliptin Drugs 0.000 description 2
• 230000006870 function Effects 0.000 description 2
• 238000007306 functionalization reaction Methods 0.000 description 2
• 208000020694 gallbladder disease Diseases 0.000 description 2
• 230000002496 gastric effect Effects 0.000 description 2
• 230000030136 gastric emptying Effects 0.000 description 2
• 230000014101 glucose homeostasis Effects 0.000 description 2
• 235000013922 glutamic acid Nutrition 0.000 description 2
• 125000000291 glutamic acid group Chemical group N[C@@H](CCC(O)=O)C(=O)* 0.000 description 2
• 230000036541 health Effects 0.000 description 2
• 208000019622 heart disease Diseases 0.000 description 2
• NPZTUJOABDZTLV-UHFFFAOYSA-N hydroxybenzotriazole Substances O=C1C=CC=C2NNN=C12 NPZTUJOABDZTLV-UHFFFAOYSA-N 0.000 description 2
• 230000006872 improvement Effects 0.000 description 2
• 230000004054 inflammatory process Effects 0.000 description 2
• 239000004615 ingredient Substances 0.000 description 2
• 229960002869 insulin glargine Drugs 0.000 description 2
• 230000003993 interaction Effects 0.000 description 2
• 238000007918 intramuscular administration Methods 0.000 description 2
• 238000001990 intravenous administration Methods 0.000 description 2
• 210000004153 islets of langerhan Anatomy 0.000 description 2
• 238000006317 isomerization reaction Methods 0.000 description 2
• 229940039781 leptin Drugs 0.000 description 2
• NRYBAZVQPHGZNS-ZSOCWYAHSA-N leptin Chemical compound O=C([C@H](CO)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CC=1C2=CC=CC=C2NC=1)NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CO)NC(=O)CNC(=O)[C@H](CCC(N)=O)NC(=O)[C@@H](N)CC(C)C)CCSC)N1CCC[C@H]1C(=O)NCC(=O)N[C@@H](CS)C(O)=O NRYBAZVQPHGZNS-ZSOCWYAHSA-N 0.000 description 2
• 125000001909 leucine group Chemical group [H]N(*)C(C(*)=O)C([H])([H])C(C([H])([H])[H])C([H])([H])[H] 0.000 description 2
• 108010034529 leucyl-lysine Proteins 0.000 description 2
• 229960002397 linagliptin Drugs 0.000 description 2
• 210000004185 liver Anatomy 0.000 description 2
• 229910052749 magnesium Inorganic materials 0.000 description 2
• 239000011777 magnesium Substances 0.000 description 2
• 230000001404 mediated effect Effects 0.000 description 2
• 208000030159 metabolic disease Diseases 0.000 description 2
• 108010056582 methionylglutamic acid Proteins 0.000 description 2
• 238000002156 mixing Methods 0.000 description 2
• PXZWGQLGAKCNKD-DPNMSELWSA-N molport-023-276-326 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(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](C)C(O)=O)[C@@H](C)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 PXZWGQLGAKCNKD-DPNMSELWSA-N 0.000 description 2
• 208000001022 morbid obesity Diseases 0.000 description 2
• WQEPLUUGTLDZJY-UHFFFAOYSA-N n-Pentadecanoic acid Natural products CCCCCCCCCCCCCCC(O)=O WQEPLUUGTLDZJY-UHFFFAOYSA-N 0.000 description 2
• 230000000324 neuroprotective effect Effects 0.000 description 2
• 229960003512 nicotinic acid Drugs 0.000 description 2
• 235000001968 nicotinic acid Nutrition 0.000 description 2
• 239000011664 nicotinic acid Substances 0.000 description 2
• 238000013421 nuclear magnetic resonance imaging Methods 0.000 description 2
• 229940125395 oral insulin Drugs 0.000 description 2
• 230000011164 ossification Effects 0.000 description 2
• 201000008482 osteoarthritis Diseases 0.000 description 2
• 125000001312 palmitoyl group Chemical group O=C([*])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 2
• 239000000813 peptide hormone Substances 0.000 description 2
• 230000002093 peripheral effect Effects 0.000 description 2
• 239000008024 pharmaceutical diluent Substances 0.000 description 2
• 229940124531 pharmaceutical excipient Drugs 0.000 description 2
• DHHVAGZRUROJKS-UHFFFAOYSA-N phentermine Chemical compound CC(C)(N)CC1=CC=CC=C1 DHHVAGZRUROJKS-UHFFFAOYSA-N 0.000 description 2
• NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 2
• 239000010452 phosphate Substances 0.000 description 2
• 239000008363 phosphate buffer Substances 0.000 description 2
• 239000008055 phosphate buffer solution Substances 0.000 description 2
• 229920001223 polyethylene glycol Polymers 0.000 description 2
• 239000000843 powder Substances 0.000 description 2
• 108010029667 pramlintide Proteins 0.000 description 2
• 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 2
• 239000003755 preservative agent Substances 0.000 description 2
• 230000006920 protein precipitation Effects 0.000 description 2
• 238000000746 purification Methods 0.000 description 2
• 231100000272 reduced body weight Toxicity 0.000 description 2
• 235000018770 reduced food intake Nutrition 0.000 description 2
• 230000007017 scission Effects 0.000 description 2
• 239000013049 sediment Substances 0.000 description 2
• 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 2
• 201000002859 sleep apnea Diseases 0.000 description 2
• 239000003381 stabilizer Substances 0.000 description 2
• 238000003860 storage Methods 0.000 description 2
• 238000013517 stratification Methods 0.000 description 2
• 125000001424 substituent group Chemical group 0.000 description 2
• 239000004094 surface-active agent Substances 0.000 description 2
• 208000011580 syndromic disease Diseases 0.000 description 2
• 239000003826 tablet Substances 0.000 description 2
• RMMXLENWKUUMAY-UHFFFAOYSA-N telmisartan Chemical compound CCCC1=NC2=C(C)C=C(C=3N(C4=CC=CC=C4N=3)C)C=C2N1CC(C=C1)=CC=C1C1=CC=CC=C1C(O)=O RMMXLENWKUUMAY-UHFFFAOYSA-N 0.000 description 2
• 239000013559 triple agonist Substances 0.000 description 2
• 108010080629 tryptophan-leucine Proteins 0.000 description 2
• IBIDRSSEHFLGSD-UHFFFAOYSA-N valinyl-arginine Natural products CC(C)C(N)C(=O)NC(C(O)=O)CCCN=C(N)N IBIDRSSEHFLGSD-UHFFFAOYSA-N 0.000 description 2
• 238000005406 washing Methods 0.000 description 2
• 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 1
• 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
• REITVGIIZHFVGU-LJQANCHMSA-N (2r)-2-(9h-fluoren-9-ylmethoxycarbonylamino)-3-[(2-methylpropan-2-yl)oxy]propanoic acid Chemical compound C1=CC=C2C(COC(=O)N[C@H](COC(C)(C)C)C(O)=O)C3=CC=CC=C3C2=C1 REITVGIIZHFVGU-LJQANCHMSA-N 0.000 description 1
• KLBPUVPNPAJWHZ-UMSFTDKQSA-N (2r)-2-(9h-fluoren-9-ylmethoxycarbonylamino)-3-tritylsulfanylpropanoic acid Chemical compound C([C@@H](C(=O)O)NC(=O)OCC1C2=CC=CC=C2C2=CC=CC=C21)SC(C=1C=CC=CC=1)(C=1C=CC=CC=1)C1=CC=CC=C1 KLBPUVPNPAJWHZ-UMSFTDKQSA-N 0.000 description 1
• ZPGDWQNBZYOZTI-SFHVURJKSA-N (2s)-1-(9h-fluoren-9-ylmethoxycarbonyl)pyrrolidine-2-carboxylic acid Chemical compound OC(=O)[C@@H]1CCCN1C(=O)OCC1C2=CC=CC=C2C2=CC=CC=C21 ZPGDWQNBZYOZTI-SFHVURJKSA-N 0.000 description 1
• REITVGIIZHFVGU-IBGZPJMESA-N (2s)-2-(9h-fluoren-9-ylmethoxycarbonylamino)-3-[(2-methylpropan-2-yl)oxy]propanoic acid Chemical compound C1=CC=C2C(COC(=O)N[C@@H](COC(C)(C)C)C(O)=O)C3=CC=CC=C3C2=C1 REITVGIIZHFVGU-IBGZPJMESA-N 0.000 description 1
• ADOHASQZJSJZBT-SANMLTNESA-N (2s)-2-(9h-fluoren-9-ylmethoxycarbonylamino)-3-[1-[(2-methylpropan-2-yl)oxycarbonyl]indol-3-yl]propanoic acid Chemical compound C12=CC=CC=C2N(C(=O)OC(C)(C)C)C=C1C[C@@H](C(O)=O)NC(=O)OCC1C2=CC=CC=C2C2=CC=CC=C21 ADOHASQZJSJZBT-SANMLTNESA-N 0.000 description 1
• UGNIYGNGCNXHTR-SFHVURJKSA-N (2s)-2-(9h-fluoren-9-ylmethoxycarbonylamino)-3-methylbutanoic acid Chemical compound C1=CC=C2C(COC(=O)N[C@@H](C(C)C)C(O)=O)C3=CC=CC=C3C2=C1 UGNIYGNGCNXHTR-SFHVURJKSA-N 0.000 description 1
• FODJWPHPWBKDON-IBGZPJMESA-N (2s)-2-(9h-fluoren-9-ylmethoxycarbonylamino)-4-[(2-methylpropan-2-yl)oxy]-4-oxobutanoic acid Chemical compound C1=CC=C2C(COC(=O)N[C@@H](CC(=O)OC(C)(C)C)C(O)=O)C3=CC=CC=C3C2=C1 FODJWPHPWBKDON-IBGZPJMESA-N 0.000 description 1
• CBPJQFCAFFNICX-IBGZPJMESA-N (2s)-2-(9h-fluoren-9-ylmethoxycarbonylamino)-4-methylpentanoic acid Chemical compound C1=CC=C2C(COC(=O)N[C@@H](CC(C)C)C(O)=O)C3=CC=CC=C3C2=C1 CBPJQFCAFFNICX-IBGZPJMESA-N 0.000 description 1
• BUBGAUHBELNDEW-SFHVURJKSA-N (2s)-2-(9h-fluoren-9-ylmethoxycarbonylamino)-4-methylsulfanylbutanoic acid Chemical compound C1=CC=C2C(COC(=O)N[C@@H](CCSC)C(O)=O)C3=CC=CC=C3C2=C1 BUBGAUHBELNDEW-SFHVURJKSA-N 0.000 description 1
• OTKXCALUHMPIGM-FQEVSTJZSA-N (2s)-2-(9h-fluoren-9-ylmethoxycarbonylamino)-5-[(2-methylpropan-2-yl)oxy]-5-oxopentanoic acid Chemical compound C1=CC=C2C(COC(=O)N[C@@H](CCC(=O)OC(C)(C)C)C(O)=O)C3=CC=CC=C3C2=C1 OTKXCALUHMPIGM-FQEVSTJZSA-N 0.000 description 1
• UMRUUWFGLGNQLI-QFIPXVFZSA-N (2s)-2-(9h-fluoren-9-ylmethoxycarbonylamino)-6-[(2-methylpropan-2-yl)oxycarbonylamino]hexanoic acid Chemical compound C1=CC=C2C(COC(=O)N[C@@H](CCCCNC(=O)OC(C)(C)C)C(O)=O)C3=CC=CC=C3C2=C1 UMRUUWFGLGNQLI-QFIPXVFZSA-N 0.000 description 1
• QWXZOFZKSQXPDC-NSHDSACASA-N (2s)-2-(9h-fluoren-9-ylmethoxycarbonylamino)propanoic acid Chemical compound C1=CC=C2C(COC(=O)N[C@@H](C)C(O)=O)C3=CC=CC=C3C2=C1 QWXZOFZKSQXPDC-NSHDSACASA-N 0.000 description 1
• VDWWLJRQDNTHJB-MXAMYCJDSA-N (2s)-2-[[(2s,3r)-2-[[2-[[(2s)-5-amino-2-[[(2s)-2-[[(2s)-2-amino-3-(1h-imidazol-5-yl)propanoyl]amino]-3-hydroxypropanoyl]amino]-5-oxopentanoyl]amino]acetyl]amino]-3-hydroxybutanoyl]amino]-3-phenylpropanoic acid Chemical compound C([C@H](N)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCC(N)=O)C(=O)NCC(=O)N[C@@H]([C@H](O)C)C(=O)N[C@@H](CC=1C=CC=CC=1)C(O)=O)C1=CN=CN1 VDWWLJRQDNTHJB-MXAMYCJDSA-N 0.000 description 1
• CNBUSIJNWNXLQQ-NSHDSACASA-N (2s)-3-(4-hydroxyphenyl)-2-[(2-methylpropan-2-yl)oxycarbonylamino]propanoic acid Chemical compound CC(C)(C)OC(=O)N[C@H](C(O)=O)CC1=CC=C(O)C=C1 CNBUSIJNWNXLQQ-NSHDSACASA-N 0.000 description 1
• HNICLNKVURBTKV-NDEPHWFRSA-N (2s)-5-[[amino-[(2,2,4,6,7-pentamethyl-3h-1-benzofuran-5-yl)sulfonylamino]methylidene]amino]-2-(9h-fluoren-9-ylmethoxycarbonylamino)pentanoic acid Chemical compound C12=CC=CC=C2C2=CC=CC=C2C1COC(=O)N[C@H](C(O)=O)CCCN=C(N)NS(=O)(=O)C1=C(C)C(C)=C2OC(C)(C)CC2=C1C HNICLNKVURBTKV-NDEPHWFRSA-N 0.000 description 1
• QXVFEIPAZSXRGM-DJJJIMSYSA-N (2s,3s)-2-(9h-fluoren-9-ylmethoxycarbonylamino)-3-methylpentanoic acid Chemical compound C1=CC=C2C(COC(=O)N[C@@H]([C@@H](C)CC)C(O)=O)C3=CC=CC=C3C2=C1 QXVFEIPAZSXRGM-DJJJIMSYSA-N 0.000 description 1
• 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 1
• JSYGLDMGERSRPC-FQUUOJAGSA-N (2s,4s)-4-fluoro-1-[2-[[(1r,3s)-3-(1,2,4-triazol-1-ylmethyl)cyclopentyl]amino]acetyl]pyrrolidine-2-carbonitrile Chemical compound C1[C@@H](F)C[C@@H](C#N)N1C(=O)CN[C@H]1C[C@@H](CN2N=CN=C2)CC1 JSYGLDMGERSRPC-FQUUOJAGSA-N 0.000 description 1
• GCERFBKFVDLDKD-NRYJBHHQSA-N (3r)-3-amino-1-[3-(trifluoromethyl)-6,8-dihydro-5h-[1,2,4]triazolo[4,3-a]pyrazin-7-yl]-4-(2,4,5-trifluorophenyl)butan-1-one;3-(diaminomethylidene)-1,1-dimethylguanidine;phosphoric acid;hydrochloride Chemical compound Cl.OP(O)(O)=O.CN(C)C(=N)N=C(N)N.C([C@H](CC(=O)N1CC=2N(C(=NN=2)C(F)(F)F)CC1)N)C1=CC(F)=C(F)C=C1F GCERFBKFVDLDKD-NRYJBHHQSA-N 0.000 description 1
• TXNPQZGSVXLGGP-MMTVBGGISA-N (6s)-6-(2-hydroxy-2-methylpropyl)-3-[(1s)-1-[4-(1-methyl-2-oxopyridin-4-yl)phenyl]ethyl]-6-phenyl-1,3-oxazinan-2-one Chemical compound C1([C@@]2(CC(C)(C)O)CCN(C(O2)=O)[C@@H](C)C=2C=CC(=CC=2)C2=CC(=O)N(C)C=C2)=CC=CC=C1 TXNPQZGSVXLGGP-MMTVBGGISA-N 0.000 description 1
• WRIDQFICGBMAFQ-UHFFFAOYSA-N (E)-8-Octadecenoic acid Natural products CCCCCCCCCC=CCCCCCCC(O)=O WRIDQFICGBMAFQ-UHFFFAOYSA-N 0.000 description 1
• BDNKZNFMNDZQMI-UHFFFAOYSA-N 1,3-diisopropylcarbodiimide Chemical compound CC(C)N=C=NC(C)C BDNKZNFMNDZQMI-UHFFFAOYSA-N 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
• ASOKPJOREAFHNY-UHFFFAOYSA-N 1-Hydroxybenzotriazole Chemical compound C1=CC=C2N(O)N=NC2=C1 ASOKPJOREAFHNY-UHFFFAOYSA-N 0.000 description 1
• DFPYXQYWILNVAU-UHFFFAOYSA-N 1-hydroxybenzotriazole Chemical compound C1=CC=C2N(O)N=NC2=C1.C1=CC=C2N(O)N=NC2=C1 DFPYXQYWILNVAU-UHFFFAOYSA-N 0.000 description 1
• HOZZVEPRYYCBTO-UHFFFAOYSA-N 2-(9h-fluoren-9-ylmethoxycarbonylamino)-2-methylpropanoic acid Chemical compound C1=CC=C2C(COC(=O)NC(C)(C)C(O)=O)C3=CC=CC=C3C2=C1 HOZZVEPRYYCBTO-UHFFFAOYSA-N 0.000 description 1
• NDKDFTQNXLHCGO-UHFFFAOYSA-N 2-(9h-fluoren-9-ylmethoxycarbonylamino)acetic acid Chemical compound C1=CC=C2C(COC(=O)NCC(=O)O)C3=CC=CC=C3C2=C1 NDKDFTQNXLHCGO-UHFFFAOYSA-N 0.000 description 1
• GXALXAKNHIROPE-UHFFFAOYSA-N 2-[4-[4-[5-[[6-(trifluoromethyl)pyridin-3-yl]amino]pyridin-2-yl]phenyl]cyclohexyl]acetic acid Chemical compound C1CC(CC(=O)O)CCC1C1=CC=C(C=2N=CC(NC=3C=NC(=CC=3)C(F)(F)F)=CC=2)C=C1 GXALXAKNHIROPE-UHFFFAOYSA-N 0.000 description 1
• AYKLXGCULGWUJX-UHFFFAOYSA-N 2-[5-chloro-2-[[1-[(3,4-difluorophenyl)methyl]-4-[(4-methylsulfonylphenyl)methyl]pyrrole-2-carbonyl]amino]-1,3-thiazol-4-yl]acetic acid Chemical compound C1=CC(S(=O)(=O)C)=CC=C1CC1=CN(CC=2C=C(F)C(F)=CC=2)C(C(=O)NC=2SC(Cl)=C(CC(O)=O)N=2)=C1 AYKLXGCULGWUJX-UHFFFAOYSA-N 0.000 description 1
• HPGJSAAUJGAMLV-UHFFFAOYSA-N 2-[[2-[[cyclohexyl-(4-propoxycyclohexyl)carbamoyl]amino]-1,3-thiazol-5-yl]sulfanyl]acetic acid Chemical compound C1CC(OCCC)CCC1N(C(=O)NC=1SC(SCC(O)=O)=CN=1)C1CCCCC1 HPGJSAAUJGAMLV-UHFFFAOYSA-N 0.000 description 1
• LQJBNNIYVWPHFW-UHFFFAOYSA-N 20:1omega9c fatty acid Natural products CCCCCCCCCCC=CCCCCCCCC(O)=O LQJBNNIYVWPHFW-UHFFFAOYSA-N 0.000 description 1
• FODHWOBAQBTTFS-UHFFFAOYSA-N 3-[4-[2-(2-methylphenyl)ethynyl]phenyl]propanoic acid Chemical compound CC1=CC=CC=C1C#CC1=CC=C(CCC(O)=O)C=C1 FODHWOBAQBTTFS-UHFFFAOYSA-N 0.000 description 1
• OCNBSSLDAIWTKS-UHFFFAOYSA-N 3-[[[3,5-bis(trifluoromethyl)phenyl]methyl-(2-methyltetrazol-5-yl)amino]methyl]-n,n-bis(cyclopropylmethyl)-8-methylquinolin-2-amine Chemical compound C1CC1CN(CC1CC1)C=1N=C2C(C)=CC=CC2=CC=1CN(C1=NN(C)N=N1)CC1=CC(C(F)(F)F)=CC(C(F)(F)F)=C1 OCNBSSLDAIWTKS-UHFFFAOYSA-N 0.000 description 1
• YDNMHDRXNOHCJH-UHFFFAOYSA-N 3-aminopyrrolidine-2,5-dione Chemical compound NC1CC(=O)NC1=O YDNMHDRXNOHCJH-UHFFFAOYSA-N 0.000 description 1
• SWLAMJPTOQZTAE-UHFFFAOYSA-N 4-[2-[(5-chloro-2-methoxybenzoyl)amino]ethyl]benzoic acid Chemical class 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
• FWMNVWWHGCHHJJ-SKKKGAJSSA-N 4-amino-1-[(2r)-6-amino-2-[[(2r)-2-[[(2r)-2-[[(2r)-2-amino-3-phenylpropanoyl]amino]-3-phenylpropanoyl]amino]-4-methylpentanoyl]amino]hexanoyl]piperidine-4-carboxylic acid Chemical compound C([C@H](C(=O)N[C@H](CC(C)C)C(=O)N[C@H](CCCCN)C(=O)N1CCC(N)(CC1)C(O)=O)NC(=O)[C@H](N)CC=1C=CC=CC=1)C1=CC=CC=C1 FWMNVWWHGCHHJJ-SKKKGAJSSA-N 0.000 description 1
• 102000006902 5-HT2C Serotonin Receptor Human genes 0.000 description 1
• 108010072553 5-HT2C Serotonin Receptor Proteins 0.000 description 1
• AYJRTVVIBJSSKN-UHFFFAOYSA-N 5-[4-[[6-(4-methylsulfonylphenyl)pyridin-3-yl]oxymethyl]piperidin-1-yl]-3-propan-2-yl-1,2,4-oxadiazole Chemical compound CC(C)C1=NOC(N2CCC(COC=3C=NC(=CC=3)C=3C=CC(=CC=3)S(C)(=O)=O)CC2)=N1 AYJRTVVIBJSSKN-UHFFFAOYSA-N 0.000 description 1
• QSBYPNXLFMSGKH-UHFFFAOYSA-N 9-Heptadecensaeure Natural products CCCCCCCC=CCCCCCCCC(O)=O QSBYPNXLFMSGKH-UHFFFAOYSA-N 0.000 description 1
• 208000023769 AA amyloidosis Diseases 0.000 description 1
• 208000004611 Abdominal Obesity Diseases 0.000 description 1
• QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
• BUANFPRKJKJSRR-ACZMJKKPSA-N Ala-Ala-Gln Chemical compound C[C@H]([NH3+])C(=O)N[C@@H](C)C(=O)N[C@H](C([O-])=O)CCC(N)=O BUANFPRKJKJSRR-ACZMJKKPSA-N 0.000 description 1
• ZODMADSIQZZBSQ-FXQIFTODSA-N Ala-Gln-Glu Chemical compound [H]N[C@@H](C)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCC(O)=O)C(O)=O ZODMADSIQZZBSQ-FXQIFTODSA-N 0.000 description 1
• VGPWRRFOPXVGOH-BYPYZUCNSA-N Ala-Gly-Gly Chemical compound C[C@H](N)C(=O)NCC(=O)NCC(O)=O VGPWRRFOPXVGOH-BYPYZUCNSA-N 0.000 description 1
• VHEVVUZDDUCAKU-FXQIFTODSA-N Ala-Met-Asp Chemical compound [H]N[C@@H](C)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CC(O)=O)C(O)=O VHEVVUZDDUCAKU-FXQIFTODSA-N 0.000 description 1
• 208000011403 Alexander disease Diseases 0.000 description 1
• 229940077274 Alpha glucosidase inhibitor Drugs 0.000 description 1
• 208000031277 Amaurotic familial idiocy Diseases 0.000 description 1
• 102000013455 Amyloid beta-Peptides Human genes 0.000 description 1
• 108010090849 Amyloid beta-Peptides Proteins 0.000 description 1
• 206010059245 Angiopathy Diseases 0.000 description 1
• 101100460776 Arabidopsis thaliana NPY2 gene Proteins 0.000 description 1
• 101100460788 Arabidopsis thaliana NPY5 gene Proteins 0.000 description 1
• KLKHFFMNGWULBN-VKHMYHEASA-N Asn-Gly Chemical compound NC(=O)C[C@H](N)C(=O)NCC(O)=O KLKHFFMNGWULBN-VKHMYHEASA-N 0.000 description 1
• IBLAOXSULLECQZ-IUKAMOBKSA-N Asn-Ile-Thr Chemical compound C[C@@H](O)[C@@H](C(O)=O)NC(=O)[C@H]([C@@H](C)CC)NC(=O)[C@@H](N)CC(N)=O IBLAOXSULLECQZ-IUKAMOBKSA-N 0.000 description 1
• JHFNSBBHKSZXKB-VKHMYHEASA-N Asp-Gly Chemical compound OC(=O)C[C@H](N)C(=O)NCC(O)=O JHFNSBBHKSZXKB-VKHMYHEASA-N 0.000 description 1
• DWBZEJHQQIURML-IMJSIDKUSA-N Asp-Ser Chemical compound OC(=O)C[C@H](N)C(=O)N[C@@H](CO)C(O)=O DWBZEJHQQIURML-IMJSIDKUSA-N 0.000 description 1
• CZIVKMOEXPILDK-SRVKXCTJSA-N Asp-Tyr-Ser Chemical compound [H]N[C@@H](CC(O)=O)C(=O)N[C@@H](CC1=CC=C(O)C=C1)C(=O)N[C@@H](CO)C(O)=O CZIVKMOEXPILDK-SRVKXCTJSA-N 0.000 description 1
• XUKUURHRXDUEBC-KAYWLYCHSA-N Atorvastatin Chemical compound C=1C=CC=CC=1C1=C(C=2C=CC(F)=CC=2)N(CC[C@@H](O)C[C@@H](O)CC(O)=O)C(C(C)C)=C1C(=O)NC1=CC=CC=C1 XUKUURHRXDUEBC-KAYWLYCHSA-N 0.000 description 1
• XUKUURHRXDUEBC-UHFFFAOYSA-N Atorvastatin Natural products C=1C=CC=CC=1C1=C(C=2C=CC(F)=CC=2)N(CCC(O)CC(O)CC(O)=O)C(C(C)C)=C1C(=O)NC1=CC=CC=C1 XUKUURHRXDUEBC-UHFFFAOYSA-N 0.000 description 1
• 102100022548 Beta-hexosaminidase subunit alpha Human genes 0.000 description 1
• 206010068597 Bulbospinal muscular atrophy congenital Diseases 0.000 description 1
• 102100031151 C-C chemokine receptor type 2 Human genes 0.000 description 1
• 101710149815 C-C chemokine receptor type 2 Proteins 0.000 description 1
• 239000002083 C09CA01 - Losartan Substances 0.000 description 1
• 239000002080 C09CA02 - Eprosartan Substances 0.000 description 1
• 239000004072 C09CA03 - Valsartan Substances 0.000 description 1
• 239000002053 C09CA06 - Candesartan Substances 0.000 description 1
• 239000005537 C09CA07 - Telmisartan Substances 0.000 description 1
• WEDIKSVWBUKTRA-WTKGVUNUSA-N 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)N[C@@H](CC(O)=O)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H]([C@@H](C)O)C(O)=O)NC1=O)[C@@H](C)O)[C@@H](C)CC 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)N[C@@H](CC(O)=O)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H]([C@@H](C)O)C(O)=O)NC1=O)[C@@H](C)O)[C@@H](C)CC WEDIKSVWBUKTRA-WTKGVUNUSA-N 0.000 description 1
• OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
• 229940127291 Calcium channel antagonist Drugs 0.000 description 1
• 241000283707 Capra Species 0.000 description 1
• KXDHJXZQYSOELW-UHFFFAOYSA-M Carbamate Chemical compound NC([O-])=O KXDHJXZQYSOELW-UHFFFAOYSA-M 0.000 description 1
• 206010007558 Cardiac failure chronic Diseases 0.000 description 1
• 206010065941 Central obesity Diseases 0.000 description 1
• 206010008111 Cerebral haemorrhage Diseases 0.000 description 1
• 206010010356 Congenital anomaly Diseases 0.000 description 1
• 208000011990 Corticobasal Degeneration Diseases 0.000 description 1
• 208000020406 Creutzfeldt Jacob disease Diseases 0.000 description 1
• 208000003407 Creutzfeldt-Jakob Syndrome Diseases 0.000 description 1
• 208000010859 Creutzfeldt-Jakob disease Diseases 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
• QNAYBMKLOCPYGJ-UHFFFAOYSA-N D-alpha-Ala Natural products CC([NH3+])C([O-])=O QNAYBMKLOCPYGJ-UHFFFAOYSA-N 0.000 description 1
• 108020004414 DNA Proteins 0.000 description 1
• 206010012689 Diabetic retinopathy Diseases 0.000 description 1
• 102100036869 Diacylglycerol O-acyltransferase 1 Human genes 0.000 description 1
• 108050004099 Diacylglycerol O-acyltransferase 1 Proteins 0.000 description 1
• 206010064553 Dialysis amyloidosis Diseases 0.000 description 1
• ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 description 1
• 108010016626 Dipeptides Proteins 0.000 description 1
• 241000289669 Erinaceus europaeus Species 0.000 description 1
• 235000005224 Eucalyptus bridgesiana Nutrition 0.000 description 1
• 244000239638 Eucalyptus bridgesiana Species 0.000 description 1
• 208000034846 Familial Amyloid Neuropathies Diseases 0.000 description 1
• 206010016202 Familial Amyloidosis Diseases 0.000 description 1
• BZCALJIHZVNMGJ-HSZRJFAPSA-N Fasiglifam Chemical compound CC1=CC(OCCCS(C)(=O)=O)=CC(C)=C1C1=CC=CC(COC=2C=C3OC[C@@H](CC(O)=O)C3=CC=2)=C1 BZCALJIHZVNMGJ-HSZRJFAPSA-N 0.000 description 1
• 208000004930 Fatty Liver Diseases 0.000 description 1
• 108010049003 Fibrinogen Proteins 0.000 description 1
• 102000008946 Fibrinogen Human genes 0.000 description 1
• 102100026148 Free fatty acid receptor 1 Human genes 0.000 description 1
• 208000002339 Frontotemporal Lobar Degeneration Diseases 0.000 description 1
• 102000027487 Fructose-Bisphosphatase Human genes 0.000 description 1
• 108010017464 Fructose-Bisphosphatase Proteins 0.000 description 1
• 229940100607 GPR119 agonist Drugs 0.000 description 1
• 108091007911 GSKs Proteins 0.000 description 1
• 102100039997 Gastric inhibitory polypeptide receptor Human genes 0.000 description 1
• 208000034826 Genetic Predisposition to Disease Diseases 0.000 description 1
• 101800001586 Ghrelin Proteins 0.000 description 1
• 102400000442 Ghrelin-28 Human genes 0.000 description 1
• 208000010412 Glaucoma Diseases 0.000 description 1
• YJIUYQKQBBQYHZ-ACZMJKKPSA-N Gln-Ala-Ala Chemical compound [H]N[C@@H](CCC(N)=O)C(=O)N[C@@H](C)C(=O)N[C@@H](C)C(O)=O YJIUYQKQBBQYHZ-ACZMJKKPSA-N 0.000 description 1
• LFIVHGMKWFGUGK-IHRRRGAJSA-N Gln-Glu-Phe Chemical compound C1=CC=C(C=C1)C[C@@H](C(=O)O)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CCC(=O)N)N LFIVHGMKWFGUGK-IHRRRGAJSA-N 0.000 description 1
• UQHGAYSULGRWRG-WHFBIAKZSA-N Glu-Ser Chemical compound OC(=O)CC[C@H](N)C(=O)N[C@@H](CO)C(O)=O UQHGAYSULGRWRG-WHFBIAKZSA-N 0.000 description 1
• 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 1
• 102000030595 Glucokinase Human genes 0.000 description 1
• 108010021582 Glucokinase Proteins 0.000 description 1
• 206010018429 Glucose tolerance impaired Diseases 0.000 description 1
• RJIVPOXLQFJRTG-LURJTMIESA-N Gly-Arg-Gly Chemical compound OC(=O)CNC(=O)[C@@H](NC(=O)CN)CCCN=C(N)N RJIVPOXLQFJRTG-LURJTMIESA-N 0.000 description 1
• 102000017011 Glycated Hemoglobin A Human genes 0.000 description 1
• 108010014663 Glycated Hemoglobin A Proteins 0.000 description 1
• 229920002527 Glycogen Polymers 0.000 description 1
• 102000007390 Glycogen Phosphorylase Human genes 0.000 description 1
• 108010046163 Glycogen Phosphorylase Proteins 0.000 description 1
• 102000004103 Glycogen Synthase Kinases Human genes 0.000 description 1
• 102100030488 HEAT repeat-containing protein 6 Human genes 0.000 description 1
• 229940121710 HMGCoA reductase inhibitor Drugs 0.000 description 1
• 102000001554 Hemoglobins Human genes 0.000 description 1
• 108010054147 Hemoglobins Proteins 0.000 description 1
• 102000005548 Hexokinase Human genes 0.000 description 1
• 108700040460 Hexokinases Proteins 0.000 description 1
• 101000912510 Homo sapiens Free fatty acid receptor 1 Proteins 0.000 description 1
• 101000788682 Homo sapiens GATA-type zinc finger protein 1 Proteins 0.000 description 1
• 101000886866 Homo sapiens Gastric inhibitory polypeptide receptor Proteins 0.000 description 1
• 101500028775 Homo sapiens Glucagon Proteins 0.000 description 1
• 101000990566 Homo sapiens HEAT repeat-containing protein 6 Proteins 0.000 description 1
• 101000801684 Homo sapiens Phospholipid-transporting ATPase ABCA1 Proteins 0.000 description 1
• 101001098868 Homo sapiens Proprotein convertase subtilisin/kexin type 9 Proteins 0.000 description 1
• 208000023105 Huntington disease Diseases 0.000 description 1
• 102100021102 Hyaluronidase PH-20 Human genes 0.000 description 1
• 208000031226 Hyperlipidaemia Diseases 0.000 description 1
• 206010020710 Hyperphagia Diseases 0.000 description 1
• 206010020880 Hypertrophy Diseases 0.000 description 1
• WZPIKDWQVRTATP-SYWGBEHUSA-N Ile-Ala-Trp Chemical compound C1=CC=C2C(C[C@H](NC(=O)[C@H](C)NC(=O)[C@@H](N)[C@@H](C)CC)C(O)=O)=CNC2=C1 WZPIKDWQVRTATP-SYWGBEHUSA-N 0.000 description 1
• KUHFPGIVBOCRMV-MNXVOIDGSA-N Ile-Gln-Leu Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H](CCC(=O)N)C(=O)N[C@@H](CC(C)C)C(=O)O)N KUHFPGIVBOCRMV-MNXVOIDGSA-N 0.000 description 1
• HYLIOBDWPQNLKI-HVTMNAMFSA-N Ile-His-Gln Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H](CC1=CN=CN1)C(=O)N[C@@H](CCC(=O)N)C(=O)O)N HYLIOBDWPQNLKI-HVTMNAMFSA-N 0.000 description 1
• JZNVOBUNTWNZPW-GHCJXIJMSA-N Ile-Ser-Asp Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H](CO)C(=O)N[C@@H](CC(=O)O)C(=O)O)N JZNVOBUNTWNZPW-GHCJXIJMSA-N 0.000 description 1
• DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
• 108010089308 Insulin Detemir Proteins 0.000 description 1
• 108010065920 Insulin Lispro Proteins 0.000 description 1
• 208000027747 Kennedy disease Diseases 0.000 description 1
• AHLPHDHHMVZTML-BYPYZUCNSA-N L-Ornithine Chemical compound NCCC[C@H](N)C(O)=O AHLPHDHHMVZTML-BYPYZUCNSA-N 0.000 description 1
• FFEARJCKVFRZRR-BYPYZUCNSA-N L-methionine Chemical compound CSCC[C@H](N)C(O)=O FFEARJCKVFRZRR-BYPYZUCNSA-N 0.000 description 1
• 238000008214 LDL Cholesterol Methods 0.000 description 1
• 241000270322 Lepidosauria Species 0.000 description 1
• MJOZZTKJZQFKDK-GUBZILKMSA-N Leu-Ala-Gln Chemical compound CC(C)C[C@H](N)C(=O)N[C@@H](C)C(=O)N[C@H](C(O)=O)CCC(N)=O MJOZZTKJZQFKDK-GUBZILKMSA-N 0.000 description 1
• FBNPMTNBFFAMMH-AVGNSLFASA-N Leu-Val-Arg Chemical compound CC(C)C[C@H](N)C(=O)N[C@@H](C(C)C)C(=O)N[C@H](C(O)=O)CCCN=C(N)N FBNPMTNBFFAMMH-AVGNSLFASA-N 0.000 description 1
• FBNPMTNBFFAMMH-UHFFFAOYSA-N Leu-Val-Arg Natural products CC(C)CC(N)C(=O)NC(C(C)C)C(=O)NC(C(O)=O)CCCN=C(N)N FBNPMTNBFFAMMH-UHFFFAOYSA-N 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
• XFIHDSBIPWEYJJ-YUMQZZPRSA-N Lys-Ala-Gly Chemical compound OC(=O)CNC(=O)[C@H](C)NC(=O)[C@@H](N)CCCCN XFIHDSBIPWEYJJ-YUMQZZPRSA-N 0.000 description 1
• BYPMOIFBQPEWOH-CIUDSAMLSA-N Lys-Asn-Asp Chemical compound C(CCN)C[C@@H](C(=O)N[C@@H](CC(=O)N)C(=O)N[C@@H](CC(=O)O)C(=O)O)N BYPMOIFBQPEWOH-CIUDSAMLSA-N 0.000 description 1
• 108010062166 Lys-Asn-Asp Proteins 0.000 description 1
• QUCDKEKDPYISNX-HJGDQZAQSA-N Lys-Asn-Thr Chemical compound [H]N[C@@H](CCCCN)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(O)=O QUCDKEKDPYISNX-HJGDQZAQSA-N 0.000 description 1
• DUTMKEAPLLUGNO-JYJNAYRXSA-N Lys-Glu-Phe Chemical compound [H]N[C@@H](CCCCN)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC1=CC=CC=C1)C(O)=O DUTMKEAPLLUGNO-JYJNAYRXSA-N 0.000 description 1
• GQZMPWBZQALKJO-UWVGGRQHSA-N Lys-Gly-Arg Chemical compound [H]N[C@@H](CCCCN)C(=O)NCC(=O)N[C@@H](CCCNC(N)=N)C(O)=O GQZMPWBZQALKJO-UWVGGRQHSA-N 0.000 description 1
• NKKFVJRLCCUJNA-QWRGUYRKSA-N Lys-Gly-Lys Chemical compound NCCCC[C@H](N)C(=O)NCC(=O)N[C@H](C(O)=O)CCCCN NKKFVJRLCCUJNA-QWRGUYRKSA-N 0.000 description 1
• MIMXMVDLMDMOJD-BZSNNMDCSA-N Lys-Tyr-Leu Chemical compound [H]N[C@@H](CCCCN)C(=O)N[C@@H](CC1=CC=C(O)C=C1)C(=O)N[C@@H](CC(C)C)C(O)=O MIMXMVDLMDMOJD-BZSNNMDCSA-N 0.000 description 1
• 206010054805 Macroangiopathy Diseases 0.000 description 1
• 241000124008 Mammalia Species 0.000 description 1
• 229930195725 Mannitol Natural products 0.000 description 1
• AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical class CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 1
• IBAQFPQHRJAVAV-ULAWRXDQSA-N Miglitol Chemical compound OCCN1C[C@H](O)[C@@H](O)[C@H](O)[C@H]1CO IBAQFPQHRJAVAV-ULAWRXDQSA-N 0.000 description 1
• 239000004909 Moisturizer Substances 0.000 description 1
• 208000001089 Multiple system atrophy Diseases 0.000 description 1
• 208000021642 Muscular disease Diseases 0.000 description 1
• 208000023178 Musculoskeletal disease Diseases 0.000 description 1
• 201000009623 Myopathy Diseases 0.000 description 1
• 206010068871 Myotonic dystrophy Diseases 0.000 description 1
• 101150111774 NPY5R gene Proteins 0.000 description 1
• 206010028980 Neoplasm Diseases 0.000 description 1
• 208000007125 Neurotoxicity Syndromes Diseases 0.000 description 1
• 108091028043 Nucleic acid sequence Proteins 0.000 description 1
• 108010036875 ORMD-0801 Proteins 0.000 description 1
• 239000005642 Oleic acid Substances 0.000 description 1
• ZQPPMHVWECSIRJ-UHFFFAOYSA-N Oleic acid Natural products CCCCCCCCC=CCCCCCCCC(O)=O ZQPPMHVWECSIRJ-UHFFFAOYSA-N 0.000 description 1
• AHLPHDHHMVZTML-UHFFFAOYSA-N Orn-delta-NH2 Natural products NCCCC(N)C(O)=O AHLPHDHHMVZTML-UHFFFAOYSA-N 0.000 description 1
• UTJLXEIPEHZYQJ-UHFFFAOYSA-N Ornithine Natural products OC(=O)C(C)CCCN UTJLXEIPEHZYQJ-UHFFFAOYSA-N 0.000 description 1
• 102000018886 Pancreatic Polypeptide Human genes 0.000 description 1
• 102000052651 Pancreatic hormone Human genes 0.000 description 1
• 108700020479 Pancreatic hormone Proteins 0.000 description 1
• 101800001268 Pancreatic hormone Proteins 0.000 description 1
• 208000018262 Peripheral vascular disease Diseases 0.000 description 1
• 102000045595 Phosphoprotein Phosphatases Human genes 0.000 description 1
• 108700019535 Phosphoprotein Phosphatases Proteins 0.000 description 1
• 102000004160 Phosphoric Monoester Hydrolases Human genes 0.000 description 1
• 108090000608 Phosphoric Monoester Hydrolases Proteins 0.000 description 1
• 208000005374 Poisoning Diseases 0.000 description 1
• 239000002202 Polyethylene glycol Substances 0.000 description 1
• ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
• 208000001280 Prediabetic State Diseases 0.000 description 1
• 208000032319 Primary lateral sclerosis Diseases 0.000 description 1
• 208000024777 Prion disease Diseases 0.000 description 1
• 108010076181 Proinsulin Proteins 0.000 description 1
• 102100038955 Proprotein convertase subtilisin/kexin type 9 Human genes 0.000 description 1
• LCTONWCANYUPML-UHFFFAOYSA-M Pyruvate Chemical compound CC(=O)C([O-])=O LCTONWCANYUPML-UHFFFAOYSA-M 0.000 description 1
• 241000283984 Rodentia Species 0.000 description 1
• RYMZZMVNJRMUDD-UHFFFAOYSA-N SJ000286063 Natural products C12C(OC(=O)C(C)(C)CC)CC(C)C=C2C=CC(C)C1CCC1CC(O)CC(=O)O1 RYMZZMVNJRMUDD-UHFFFAOYSA-N 0.000 description 1
• 101150055528 SPAM1 gene Proteins 0.000 description 1
• 101100379247 Salmo trutta apoa1 gene Proteins 0.000 description 1
• 208000021811 Sandhoff disease Diseases 0.000 description 1
• BYCVMHKULKRVPV-GUBZILKMSA-N Ser-Lys-Gln Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCC(N)=O)C(O)=O BYCVMHKULKRVPV-GUBZILKMSA-N 0.000 description 1
• 208000005716 Subacute Combined Degeneration Diseases 0.000 description 1
• QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 1
• 208000032859 Synucleinopathies Diseases 0.000 description 1
• 208000034799 Tauopathies Diseases 0.000 description 1
• 208000022292 Tay-Sachs disease Diseases 0.000 description 1
• 206010043189 Telangiectasia Diseases 0.000 description 1
• 206010044221 Toxic encephalopathy Diseases 0.000 description 1
• 231100000076 Toxic encephalopathy Toxicity 0.000 description 1
• YLGQHMHKAASRGJ-WDSOQIARSA-N Trp-Leu-Met Chemical compound CC(C)C[C@@H](C(=O)N[C@@H](CCSC)C(=O)O)NC(=O)[C@H](CC1=CNC2=CC=CC=C21)N YLGQHMHKAASRGJ-WDSOQIARSA-N 0.000 description 1
• OWSRIUBVJOQHNY-IHPCNDPISA-N Trp-Lys-His Chemical compound C1=CC=C2C(=C1)C(=CN2)C[C@@H](C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC3=CN=CN3)C(=O)O)N OWSRIUBVJOQHNY-IHPCNDPISA-N 0.000 description 1
• 102000008316 Type 4 Melanocortin Receptor Human genes 0.000 description 1
• 108010021436 Type 4 Melanocortin Receptor Proteins 0.000 description 1
• QPOUERMDWKKZEG-HJPIBITLSA-N Tyr-Ser-Ile Chemical compound CC[C@H](C)[C@@H](C(O)=O)NC(=O)[C@H](CO)NC(=O)[C@@H](N)CC1=CC=C(O)C=C1 QPOUERMDWKKZEG-HJPIBITLSA-N 0.000 description 1
• 206010046298 Upper motor neurone lesion Diseases 0.000 description 1
• NMPXRFYMZDIBRF-ZOBUZTSGSA-N Val-Asn-Trp Chemical compound CC(C)[C@@H](C(=O)N[C@@H](CC(=O)N)C(=O)N[C@@H](CC1=CNC2=CC=CC=C21)C(=O)O)N NMPXRFYMZDIBRF-ZOBUZTSGSA-N 0.000 description 1
• PGQUDQYHWICSAB-NAKRPEOUSA-N Val-Ser-Ile Chemical compound CC[C@H](C)[C@@H](C(=O)O)NC(=O)[C@H](CO)NC(=O)[C@H](C(C)C)N PGQUDQYHWICSAB-NAKRPEOUSA-N 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
• 239000003875 Wang resin Substances 0.000 description 1
• 208000006269 X-Linked Bulbo-Spinal Atrophy Diseases 0.000 description 1
• 102400000752 Xenin Human genes 0.000 description 1
• NERFNHBZJXXFGY-UHFFFAOYSA-N [4-[(4-methylphenyl)methoxy]phenyl]methanol Chemical compound C1=CC(C)=CC=C1COC1=CC=C(CO)C=C1 NERFNHBZJXXFGY-UHFFFAOYSA-N 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
• 108010076089 accutase Proteins 0.000 description 1
• 159000000021 acetate salts Chemical class 0.000 description 1
• 230000002378 acidificating effect Effects 0.000 description 1
• 125000002015 acyclic group Chemical group 0.000 description 1
• 125000002252 acyl group Chemical group 0.000 description 1
• 230000002730 additional effect Effects 0.000 description 1
• 102000030621 adenylate cyclase Human genes 0.000 description 1
• 108060000200 adenylate cyclase Proteins 0.000 description 1
• 210000001789 adipocyte Anatomy 0.000 description 1
• 239000002671 adjuvant Substances 0.000 description 1
• 210000004404 adrenal cortex Anatomy 0.000 description 1
• 210000004100 adrenal gland Anatomy 0.000 description 1
• 239000000670 adrenergic alpha-2 receptor antagonist Substances 0.000 description 1
• 239000000674 adrenergic antagonist Substances 0.000 description 1
• 229940078883 afrezza Drugs 0.000 description 1
• 230000002776 aggregation Effects 0.000 description 1
• 238000004220 aggregation Methods 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
• DAYKLWSKQJBGCS-NRFANRHFSA-N aleglitazar Chemical compound C1=2C=CSC=2C(C[C@H](OC)C(O)=O)=CC=C1OCCC(=C(O1)C)N=C1C1=CC=CC=C1 DAYKLWSKQJBGCS-NRFANRHFSA-N 0.000 description 1
• 229950010157 aleglitazar Drugs 0.000 description 1
• 239000003513 alkali Substances 0.000 description 1
• 150000001447 alkali salts Chemical class 0.000 description 1
• 230000029936 alkylation Effects 0.000 description 1
• 238000005804 alkylation reaction Methods 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
• 239000003888 alpha glucosidase inhibitor Substances 0.000 description 1
• 102000030484 alpha-2 Adrenergic Receptor Human genes 0.000 description 1
• 108020004101 alpha-2 Adrenergic Receptor Proteins 0.000 description 1
• 206010002026 amyotrophic lateral sclerosis Diseases 0.000 description 1
• 208000007502 anemia Diseases 0.000 description 1
• 239000002333 angiotensin II receptor antagonist Substances 0.000 description 1
• 238000005571 anion exchange chromatography Methods 0.000 description 1
• 230000006909 anti-apoptosis Effects 0.000 description 1
• 230000003276 anti-hypertensive effect Effects 0.000 description 1
• 239000003529 anticholesteremic agent Substances 0.000 description 1
• 239000002220 antihypertensive agent Substances 0.000 description 1
• 229940127088 antihypertensive drug Drugs 0.000 description 1
• 229940112930 apidra Drugs 0.000 description 1
• 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 1
• 235000019789 appetite Nutrition 0.000 description 1
• 230000036528 appetite Effects 0.000 description 1
• 235000021407 appetite control Nutrition 0.000 description 1
• 108010047857 aspartylglycine Proteins 0.000 description 1
• 108010092854 aspartyllysine Proteins 0.000 description 1
• 108010068265 aspartyltyrosine Proteins 0.000 description 1
• 230000000923 atherogenic effect Effects 0.000 description 1
• 230000003143 atherosclerotic effect Effects 0.000 description 1
• 125000004429 atom Chemical group 0.000 description 1
• 229960005370 atorvastatin Drugs 0.000 description 1
• 229940090047 auto-injector Drugs 0.000 description 1
• 230000006399 behavior Effects 0.000 description 1
• WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 1
• 229940000635 beta-alanine Drugs 0.000 description 1
• 229960000516 bezafibrate Drugs 0.000 description 1
• IIBYAHWJQTYFKB-UHFFFAOYSA-N bezafibrate Chemical compound C1=CC(OC(C)(C)C(O)=O)=CC=C1CCNC(=O)C1=CC=C(Cl)C=C1 IIBYAHWJQTYFKB-UHFFFAOYSA-N 0.000 description 1
• 230000001588 bifunctional effect Effects 0.000 description 1
• 239000003613 bile acid Substances 0.000 description 1
• 230000004071 biological effect Effects 0.000 description 1
• 230000008827 biological function Effects 0.000 description 1
• 230000033228 biological regulation Effects 0.000 description 1
• 239000000090 biomarker Substances 0.000 description 1
• 230000000903 blocking effect Effects 0.000 description 1
• 229940098773 bovine serum albumin Drugs 0.000 description 1
• NOJMTMIRQRDZMT-GSPXQYRGSA-N bromocriptine methanesulfonate Chemical compound CS(O)(=O)=O.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 NOJMTMIRQRDZMT-GSPXQYRGSA-N 0.000 description 1
• 229940012191 bupropion / naltrexone Drugs 0.000 description 1
• 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
• 239000011575 calcium Substances 0.000 description 1
• 229910052791 calcium Inorganic materials 0.000 description 1
• 159000000007 calcium salts Chemical class 0.000 description 1
• 244000309466 calf Species 0.000 description 1
• 235000019577 caloric intake Nutrition 0.000 description 1
• 201000011510 cancer Diseases 0.000 description 1
• 229960000932 candesartan Drugs 0.000 description 1
• SGZAIDDFHDDFJU-UHFFFAOYSA-N candesartan Chemical compound CCOC1=NC2=CC=CC(C(O)=O)=C2N1CC(C=C1)=CC=C1C1=CC=CC=C1C1=NN=N[N]1 SGZAIDDFHDDFJU-UHFFFAOYSA-N 0.000 description 1
• 239000003555 cannabinoid 1 receptor antagonist Substances 0.000 description 1
• 230000023852 carbohydrate metabolic process Effects 0.000 description 1
• 150000001720 carbohydrates Chemical class 0.000 description 1
• 235000014633 carbohydrates Nutrition 0.000 description 1
• 150000001735 carboxylic acids Chemical class 0.000 description 1
• 230000003293 cardioprotective effect Effects 0.000 description 1
• 150000001767 cationic compounds Chemical class 0.000 description 1
• 238000000423 cell based assay Methods 0.000 description 1
• 238000005119 centrifugation Methods 0.000 description 1
• 208000011142 cerebral arteriopathy, autosomal dominant, with subcortical infarcts and leukoencephalopathy, type 1 Diseases 0.000 description 1
• 230000002490 cerebral effect Effects 0.000 description 1
• WGEWUYACXPEFPO-AULYBMBSSA-N chembl2016681 Chemical compound C1C[C@@H](NS(=O)(=O)C(C)(C)C)CC[C@@H]1C(=O)NC1=CC=C(C(F)(F)F)C=N1 WGEWUYACXPEFPO-AULYBMBSSA-N 0.000 description 1
• 230000001906 cholesterol absorption Effects 0.000 description 1
• 239000003354 cholesterol ester transfer protein inhibitor Substances 0.000 description 1
• 208000010877 cognitive disease Diseases 0.000 description 1
• 235000020940 control diet Nutrition 0.000 description 1
• 239000006184 cosolvent Substances 0.000 description 1
• 238000004132 cross linking Methods 0.000 description 1
• 239000013058 crude material Substances 0.000 description 1
• 230000001186 cumulative effect Effects 0.000 description 1
• 229940015838 cycloset Drugs 0.000 description 1
• 230000034994 death Effects 0.000 description 1
• 238000000354 decomposition reaction Methods 0.000 description 1
• 230000002950 deficient Effects 0.000 description 1
• 230000003111 delayed effect Effects 0.000 description 1
• 125000004177 diethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
• UXGNZZKBCMGWAZ-UHFFFAOYSA-N dimethylformamide dmf Chemical compound CN(C)C=O.CN(C)C=O UXGNZZKBCMGWAZ-UHFFFAOYSA-N 0.000 description 1
• 229940090124 dipeptidyl peptidase 4 (dpp-4) inhibitors for blood glucose lowering Drugs 0.000 description 1
• 230000006806 disease prevention Effects 0.000 description 1
• 238000002224 dissection Methods 0.000 description 1
• 230000009977 dual effect Effects 0.000 description 1
• 229960005175 dulaglutide Drugs 0.000 description 1
• 108010005794 dulaglutide Proteins 0.000 description 1
• 230000002526 effect on cardiovascular system Effects 0.000 description 1
• 230000002900 effect on cell Effects 0.000 description 1
• 238000002330 electrospray ionisation mass spectrometry Methods 0.000 description 1
• 230000008030 elimination Effects 0.000 description 1
• 238000003379 elimination reaction Methods 0.000 description 1
• 238000010828 elution Methods 0.000 description 1
• 210000002889 endothelial cell Anatomy 0.000 description 1
• 238000005265 energy consumption Methods 0.000 description 1
• 239000002792 enkephalinase inhibitor Substances 0.000 description 1
• 210000003158 enteroendocrine cell Anatomy 0.000 description 1
• 230000007515 enzymatic degradation Effects 0.000 description 1
• 230000002255 enzymatic effect Effects 0.000 description 1
• 229960004563 eprosartan Drugs 0.000 description 1
• OROAFUQRIXKEMV-LDADJPATSA-N eprosartan Chemical compound C=1C=C(C(O)=O)C=CC=1CN1C(CCCC)=NC=C1\C=C(C(O)=O)/CC1=CC=CS1 OROAFUQRIXKEMV-LDADJPATSA-N 0.000 description 1
• 238000011156 evaluation Methods 0.000 description 1
• OLNTVTPDXPETLC-XPWALMASSA-N ezetimibe Chemical class N1([C@@H]([C@H](C1=O)CC[C@H](O)C=1C=CC(F)=CC=1)C=1C=CC(O)=CC=1)C1=CC=C(F)C=C1 OLNTVTPDXPETLC-XPWALMASSA-N 0.000 description 1
• 229960002297 fenofibrate Drugs 0.000 description 1
• YMTINGFKWWXKFG-UHFFFAOYSA-N fenofibrate Chemical compound C1=CC(OC(C)(C)C(=O)OC(C)C)=CC=C1C(=O)C1=CC=C(Cl)C=C1 YMTINGFKWWXKFG-UHFFFAOYSA-N 0.000 description 1
• 239000012894 fetal calf serum Substances 0.000 description 1
• 229940125753 fibrate Drugs 0.000 description 1
• 229940012952 fibrinogen Drugs 0.000 description 1
• 238000002825 functional assay Methods 0.000 description 1
• ZZUFCTLCJUWOSV-UHFFFAOYSA-N furosemide Chemical compound C1=C(Cl)C(S(=O)(=O)N)=CC(C(O)=O)=C1NCC1=CC=CO1 ZZUFCTLCJUWOSV-UHFFFAOYSA-N 0.000 description 1
• 230000005176 gastrointestinal motility Effects 0.000 description 1
• 238000001415 gene therapy Methods 0.000 description 1
• 238000007429 general method Methods 0.000 description 1
• 208000004104 gestational diabetes Diseases 0.000 description 1
• GNKDKYIHGQKHHM-RJKLHVOGSA-N ghrelin Chemical compound C([C@H](NC(=O)[C@@H](NC(=O)[C@H](CO)NC(=O)CN)COC(=O)CCCCCCC)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CO)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC=1N=CNC=1)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCCCN)C(=O)N1[C@@H](CCC1)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](C)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(N)=O)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O)C1=CC=CC=C1 GNKDKYIHGQKHHM-RJKLHVOGSA-N 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
• 229960004346 glimepiride Drugs 0.000 description 1
• 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 1
• 229960001381 glipizide Drugs 0.000 description 1
• 239000003877 glucagon like peptide 1 receptor agonist Substances 0.000 description 1
• 108010063245 glucagon-like peptide 1 (7-36)amide Proteins 0.000 description 1
• 230000009229 glucose formation Effects 0.000 description 1
• 230000002641 glycemic effect Effects 0.000 description 1
• 229940096919 glycogen Drugs 0.000 description 1
• 108010051307 glycyl-glycyl-proline Proteins 0.000 description 1
• 239000008187 granular material Substances 0.000 description 1
• 210000003128 head Anatomy 0.000 description 1
• 125000000623 heterocyclic group Chemical group 0.000 description 1
• 102000034345 heterotrimeric G proteins Human genes 0.000 description 1
• 108091006093 heterotrimeric G proteins Proteins 0.000 description 1
• 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 1
• 229940038661 humalog Drugs 0.000 description 1
• 235000003642 hunger Nutrition 0.000 description 1
• 239000000017 hydrogel Substances 0.000 description 1
• QAOWNCQODCNURD-UHFFFAOYSA-M hydrogensulfate Chemical compound OS([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-M 0.000 description 1
• 125000004356 hydroxy functional group Chemical group O* 0.000 description 1
• 239000002471 hydroxymethylglutaryl coenzyme A reductase inhibitor Substances 0.000 description 1
• 230000001771 impaired effect Effects 0.000 description 1
• 239000005414 inactive ingredient Substances 0.000 description 1
• 238000011534 incubation Methods 0.000 description 1
• 238000001802 infusion Methods 0.000 description 1
• 230000005764 inhibitory process Effects 0.000 description 1
• 229910001411 inorganic cation Inorganic materials 0.000 description 1
• 229960004717 insulin aspart Drugs 0.000 description 1
• 239000004026 insulin derivative Substances 0.000 description 1
• 108700039926 insulin glulisine Proteins 0.000 description 1
• 230000006362 insulin response pathway Effects 0.000 description 1
• 230000002473 insulinotropic effect Effects 0.000 description 1
• 230000031146 intracellular signal transduction Effects 0.000 description 1
• 238000011835 investigation Methods 0.000 description 1
• 238000004255 ion exchange chromatography Methods 0.000 description 1
• 229960000310 isoleucine Drugs 0.000 description 1
• AGPKZVBTJJNPAG-UHFFFAOYSA-N isoleucine Natural products CCC(C)C(N)C(O)=O AGPKZVBTJJNPAG-UHFFFAOYSA-N 0.000 description 1
• 125000000741 isoleucyl group Chemical group [H]N([H])C(C(C([H])([H])[H])C([H])([H])C([H])([H])[H])C(=O)O* 0.000 description 1
• 108010044374 isoleucyl-tyrosine Proteins 0.000 description 1
• QXJSBBXBKPUZAA-UHFFFAOYSA-N isooleic acid Natural products CCCCCCCC=CCCCCCCCCC(O)=O QXJSBBXBKPUZAA-UHFFFAOYSA-N 0.000 description 1
• 229940090473 januvia Drugs 0.000 description 1
• 229940043355 kinase inhibitor Drugs 0.000 description 1
• 229940060975 lantus Drugs 0.000 description 1
• 201000010901 lateral sclerosis Diseases 0.000 description 1
• 229940102988 levemir Drugs 0.000 description 1
• 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 1
• 239000003446 ligand Substances 0.000 description 1
• 230000000670 limiting effect Effects 0.000 description 1
• 230000037356 lipid metabolism Effects 0.000 description 1
• 150000002632 lipids Chemical class 0.000 description 1
• 239000007788 liquid Substances 0.000 description 1
• 229960001093 lixisenatide Drugs 0.000 description 1
• 108010004367 lixisenatide Proteins 0.000 description 1
• 230000007774 longterm Effects 0.000 description 1
• 229960004773 losartan Drugs 0.000 description 1
• KJJZZJSZUJXYEA-UHFFFAOYSA-N losartan Chemical compound CCCCC1=NC(Cl)=C(CO)N1CC1=CC=C(C=2C(=CC=CC=2)C=2[N]N=NN=2)C=C1 KJJZZJSZUJXYEA-UHFFFAOYSA-N 0.000 description 1
• 210000004072 lung Anatomy 0.000 description 1
• 230000002101 lytic effect Effects 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
• 239000000463 material Substances 0.000 description 1
• 229950004994 meglitinide Drugs 0.000 description 1
• 229950009585 melogliptin Drugs 0.000 description 1
• 108700008455 metreleptin Proteins 0.000 description 1
• 229960000668 metreleptin Drugs 0.000 description 1
• 229960001110 miglitol Drugs 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
• 230000001333 moisturizer Effects 0.000 description 1
• 238000012544 monitoring process Methods 0.000 description 1
• 208000005264 motor neuron disease Diseases 0.000 description 1
• 208000010125 myocardial infarction Diseases 0.000 description 1
• 125000001419 myristoyl group Chemical group O=C([*])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
• CMWYAOXYQATXSI-UHFFFAOYSA-N n,n-dimethylformamide;piperidine Chemical compound CN(C)C=O.C1CCNCC1 CMWYAOXYQATXSI-UHFFFAOYSA-N 0.000 description 1
• BNPZTRDIESRGTC-IXYVTWBDSA-N n-[2-(dimethylamino)ethyl]-2-methyl-2-[4-[4-[[2-methyl-5-[(2s,3r,4r,5s,6r)-3,4,5-trihydroxy-6-methylsulfanyloxan-2-yl]phenyl]methyl]phenyl]butanoylamino]propanamide Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](SC)O[C@H]1C1=CC=C(C)C(CC=2C=CC(CCCC(=O)NC(C)(C)C(=O)NCCN(C)C)=CC=2)=C1 BNPZTRDIESRGTC-IXYVTWBDSA-N 0.000 description 1
• 230000009707 neogenesis Effects 0.000 description 1
• 230000001607 nephroprotective effect Effects 0.000 description 1
• 235000020925 non fasting Nutrition 0.000 description 1
• 231100000252 nontoxic Toxicity 0.000 description 1
• 230000003000 nontoxic effect Effects 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
• 230000000269 nucleophilic effect Effects 0.000 description 1
• 230000000050 nutritive effect Effects 0.000 description 1
• 239000007764 o/w emulsion Substances 0.000 description 1
• 208000001797 obstructive sleep apnea Diseases 0.000 description 1
• ZQPPMHVWECSIRJ-KTKRTIGZSA-N oleic acid Chemical compound CCCCCCCC\C=C/CCCCCCCC(O)=O ZQPPMHVWECSIRJ-KTKRTIGZSA-N 0.000 description 1
• 235000021313 oleic acid Nutrition 0.000 description 1
• MKMPWKUAHLTIBJ-ISTRZQFTSA-N omarigliptin Chemical compound C1([C@H]2OC[C@@H](C[C@@H]2N)N2CC3=CN(N=C3C2)S(=O)(=O)C)=CC(F)=CC=C1F MKMPWKUAHLTIBJ-ISTRZQFTSA-N 0.000 description 1
• 230000003287 optical effect Effects 0.000 description 1
• 238000007410 oral glucose tolerance test Methods 0.000 description 1
• 150000002892 organic cations Chemical class 0.000 description 1
• 239000003960 organic solvent Substances 0.000 description 1
• AHLBNYSZXLDEJQ-FWEHEUNISA-N orlistat Chemical compound CCCCCCCCCCC[C@H](OC(=O)[C@H](CC(C)C)NC=O)C[C@@H]1OC(=O)[C@H]1CCCCCC AHLBNYSZXLDEJQ-FWEHEUNISA-N 0.000 description 1
• 229960001243 orlistat Drugs 0.000 description 1
• 229960003104 ornithine Drugs 0.000 description 1
• 235000020830 overeating Nutrition 0.000 description 1
• 239000004025 pancreas hormone Substances 0.000 description 1
• 229940032957 pancreatic hormone Drugs 0.000 description 1
• 230000001575 pathological effect Effects 0.000 description 1
• 229940090048 pen injector Drugs 0.000 description 1
• 208000030613 peripheral artery disease Diseases 0.000 description 1
• 229960003562 phentermine Drugs 0.000 description 1
• 101150041492 phospho2 gene Proteins 0.000 description 1
• 229930029653 phosphoenolpyruvate Natural products 0.000 description 1
• DTBNBXWJWCWCIK-UHFFFAOYSA-N phosphoenolpyruvic acid Chemical compound OC(=O)C(=C)OP(O)(O)=O DTBNBXWJWCWCIK-UHFFFAOYSA-N 0.000 description 1
• 239000003757 phosphotransferase inhibitor Substances 0.000 description 1
• 230000004962 physiological condition Effects 0.000 description 1
• 239000002504 physiological saline solution Substances 0.000 description 1
• 230000001817 pituitary effect Effects 0.000 description 1
• 229940096701 plain lipid modifying drug hmg coa reductase inhibitors Drugs 0.000 description 1
• 229940068918 polyethylene glycol 400 Drugs 0.000 description 1
• 108700002854 polyethylene glycol(B1)- insulin Proteins 0.000 description 1
• 229920001184 polypeptide Polymers 0.000 description 1
• 230000029537 positive regulation of insulin secretion Effects 0.000 description 1
• 230000000291 postprandial effect Effects 0.000 description 1
• 239000011591 potassium Substances 0.000 description 1
• 229910052700 potassium Inorganic materials 0.000 description 1
• 230000003389 potentiating effect Effects 0.000 description 1
• 229960003611 pramlintide Drugs 0.000 description 1
• 239000002243 precursor Substances 0.000 description 1
• 230000035935 pregnancy Effects 0.000 description 1
• 238000002360 preparation method Methods 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
• 230000008569 process Effects 0.000 description 1
• 230000035755 proliferation Effects 0.000 description 1
• WPDCHTSXOPUOII-UHFFFAOYSA-N propan-2-yl 4-[5-methoxy-6-[(2-methyl-6-methylsulfonylpyridin-3-yl)amino]pyrimidin-4-yl]oxypiperidine-1-carboxylate Chemical compound N1=CN=C(OC2CCN(CC2)C(=O)OC(C)C)C(OC)=C1NC1=CC=C(S(C)(=O)=O)N=C1C WPDCHTSXOPUOII-UHFFFAOYSA-N 0.000 description 1
• 238000011321 prophylaxis Methods 0.000 description 1
• 239000012264 purified product Substances 0.000 description 1
• 108700027806 rGLP-1 Proteins 0.000 description 1
• 238000006268 reductive amination reaction Methods 0.000 description 1
• 229960002354 repaglinide Drugs 0.000 description 1
• 230000003979 response to food Effects 0.000 description 1
• 210000001525 retina Anatomy 0.000 description 1
• 210000003994 retinal ganglion cell Anatomy 0.000 description 1
• 210000003079 salivary gland Anatomy 0.000 description 1
• 230000036186 satiety Effects 0.000 description 1
• 235000019627 satiety Nutrition 0.000 description 1
• 210000003786 sclera Anatomy 0.000 description 1
• 238000012216 screening Methods 0.000 description 1
• 230000035945 sensitivity Effects 0.000 description 1
• UNAANXDKBXWMLN-UHFFFAOYSA-N sibutramine Chemical compound C=1C=C(Cl)C=CC=1C1(C(N(C)C)CC(C)C)CCC1 UNAANXDKBXWMLN-UHFFFAOYSA-N 0.000 description 1
• 229960004425 sibutramine Drugs 0.000 description 1
• 230000011664 signaling Effects 0.000 description 1
• 229960002855 simvastatin Drugs 0.000 description 1
• RYMZZMVNJRMUDD-HGQWONQESA-N simvastatin Chemical compound C([C@H]1[C@@H](C)C=CC2=C[C@H](C)C[C@@H]([C@H]12)OC(=O)C(C)(C)CC)C[C@@H]1C[C@@H](O)CC(=O)O1 RYMZZMVNJRMUDD-HGQWONQESA-N 0.000 description 1
• 229960004034 sitagliptin Drugs 0.000 description 1
• 239000011734 sodium Substances 0.000 description 1
• 229910052708 sodium Inorganic materials 0.000 description 1
• 239000011780 sodium chloride Substances 0.000 description 1
• 208000002320 spinal muscular atrophy Diseases 0.000 description 1
• 210000000952 spleen Anatomy 0.000 description 1
• 235000000891 standard diet Nutrition 0.000 description 1
• 208000023516 stroke disease Diseases 0.000 description 1
• 238000006467 substitution reaction Methods 0.000 description 1
• 229940124530 sulfonamide Drugs 0.000 description 1
• PVEFEIWVJKUCLJ-UHFFFAOYSA-N sulfuric acid;toluene Chemical compound OS(O)(=O)=O.CC1=CC=CC=C1 PVEFEIWVJKUCLJ-UHFFFAOYSA-N 0.000 description 1
• 230000001629 suppression Effects 0.000 description 1
• 238000001356 surgical procedure Methods 0.000 description 1
• 239000000725 suspension Substances 0.000 description 1
• 229940099093 symlin Drugs 0.000 description 1
• 230000002195 synergetic effect Effects 0.000 description 1
• 230000008685 targeting Effects 0.000 description 1
• 208000009056 telangiectasis Diseases 0.000 description 1
• 229960005187 telmisartan Drugs 0.000 description 1
• WGRQANOPCQRCME-PMACEKPBSA-N teneligliptin Chemical compound O=C([C@H]1NC[C@H](C1)N1CCN(CC1)C1=CC(=NN1C=1C=CC=CC=1)C)N1CCSC1 WGRQANOPCQRCME-PMACEKPBSA-N 0.000 description 1
• 229950000034 teneligliptin Drugs 0.000 description 1
• 150000003512 tertiary amines Chemical class 0.000 description 1
• 210000001550 testis Anatomy 0.000 description 1
• TUNFSRHWOTWDNC-HKGQFRNVSA-N tetradecanoic acid Chemical compound CCCCCCCCCCCCC[14C](O)=O TUNFSRHWOTWDNC-HKGQFRNVSA-N 0.000 description 1
• WROMPOXWARCANT-UHFFFAOYSA-N tfa trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.OC(=O)C(F)(F)F WROMPOXWARCANT-UHFFFAOYSA-N 0.000 description 1
• 238000002560 therapeutic procedure Methods 0.000 description 1
• 230000035924 thermogenesis Effects 0.000 description 1
• HNKJADCVZUBCPG-UHFFFAOYSA-N thioanisole Chemical compound CSC1=CC=CC=C1 HNKJADCVZUBCPG-UHFFFAOYSA-N 0.000 description 1
• 210000001541 thymus gland Anatomy 0.000 description 1
• 210000001685 thyroid gland Anatomy 0.000 description 1
• JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 1
• 230000000699 topical effect Effects 0.000 description 1
• CMSGWTNRGKRWGS-NQIIRXRSSA-N torcetrapib Chemical compound COC(=O)N([C@H]1C[C@@H](CC)N(C2=CC=C(C=C21)C(F)(F)F)C(=O)OCC)CC1=CC(C(F)(F)F)=CC(C(F)(F)F)=C1 CMSGWTNRGKRWGS-NQIIRXRSSA-N 0.000 description 1
• 229950004514 torcetrapib Drugs 0.000 description 1
• 239000003053 toxin Substances 0.000 description 1
• 231100000765 toxin Toxicity 0.000 description 1
• 108700012359 toxins Proteins 0.000 description 1
• 210000003437 trachea Anatomy 0.000 description 1
• 238000013518 transcription Methods 0.000 description 1
• 230000035897 transcription Effects 0.000 description 1
• 230000032258 transport Effects 0.000 description 1
• IWYJYHUNXVAVAA-OAHLLOKOSA-N trelagliptin Chemical compound C=1C(F)=CC=C(C#N)C=1CN1C(=O)N(C)C(=O)C=C1N1CCC[C@@H](N)C1 IWYJYHUNXVAVAA-OAHLLOKOSA-N 0.000 description 1
• 229950010728 trelagliptin Drugs 0.000 description 1
• 150000003626 triacylglycerols Chemical class 0.000 description 1
• 125000002221 trityl group Chemical group [H]C1=C([H])C([H])=C([H])C([H])=C1C([*])(C1=C(C(=C(C(=C1[H])[H])[H])[H])[H])C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 1
• OUYCCCASQSFEME-UHFFFAOYSA-N tyrosine Natural products OC(=O)C(N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-UHFFFAOYSA-N 0.000 description 1
• 210000002700 urine Anatomy 0.000 description 1
• 229960004699 valsartan Drugs 0.000 description 1
• SJSNUMAYCRRIOM-QFIPXVFZSA-N valsartan Chemical compound C1=CC(CN(C(=O)CCCC)[C@@H](C(C)C)C(O)=O)=CC=C1C1=CC=CC=C1C1=NN=N[N]1 SJSNUMAYCRRIOM-QFIPXVFZSA-N 0.000 description 1
• 208000019553 vascular disease Diseases 0.000 description 1
• 229950006508 velneperit Drugs 0.000 description 1
• 239000002435 venom Substances 0.000 description 1
• 231100000611 venom Toxicity 0.000 description 1
• 210000001048 venom Anatomy 0.000 description 1
• 229960001729 voglibose Drugs 0.000 description 1
• 239000007762 w/o emulsion Substances 0.000 description 1
• 208000027121 wild type ATTR amyloidosis Diseases 0.000 description 1
• IDHVLSACPFUBDY-QCDLPZBNSA-N xenin Chemical compound C([C@@H](C(=O)N1CCC[C@H]1C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CC(C)C)C(O)=O)NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@H](CO)NC(=O)[C@H](CC(C)C)NC(=O)CNC(=O)[C@H](CCCCN)NC(=O)[C@@H](NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](C)NC(=O)[C@H](CO)NC(=O)[C@H](CCCCN)NC(=O)[C@@H](NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@H](CCCCN)NC(=O)[C@@H](NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](N)CCSC)[C@@H](C)O)[C@@H](C)O)C(C)C)C1=CN=CN1 IDHVLSACPFUBDY-QCDLPZBNSA-N 0.000 description 1
• 108010006643 xenin 25 Proteins 0.000 description 1
• UBQNRHZMVUUOMG-UHFFFAOYSA-N zonisamide Chemical compound C1=CC=C2C(CS(=O)(=O)N)=NOC2=C1 UBQNRHZMVUUOMG-UHFFFAOYSA-N 0.000 description 1
• 229960002911 zonisamide Drugs 0.000 description 1