SG176858A1 - Gip receptor-active glucagon compounds - Google Patents

Info

Publication number

SG176858A1

SG176858A1 SG2011092772A SG2011092772A SG176858A1 SG 176858 A1 SG176858 A1 SG 176858A1 SG 2011092772 A SG2011092772 A SG 2011092772A SG 2011092772 A SG2011092772 A SG 2011092772A SG 176858 A1 SG176858 A1 SG 176858A1

Authority

SG

Singapore

Prior art keywords

amino acid

analog

glucagon

seq

peptide

Prior art date

2009-06-16

Links

• Espacenet
• Global Dossier
• Discuss

• MASNOZXLGMXCHN-ZLPAWPGGSA-N glucagon Chemical class 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 title claims abstract description 299
• 150000001413 amino acids Chemical group 0.000 claims abstract description 466
• 108060003199 Glucagon Proteins 0.000 claims abstract description 401
• 102000051325 Glucagon Human genes 0.000 claims abstract description 258
• 229960004666 glucagon Drugs 0.000 claims abstract description 210
• 230000000694 effects Effects 0.000 claims abstract description 206
• 102100039994 Gastric inhibitory polypeptide Human genes 0.000 claims abstract 5
• 235000001014 amino acid Nutrition 0.000 claims description 598
• 125000006850 spacer group Chemical group 0.000 claims description 152
• 108010063919 Glucagon Receptors Proteins 0.000 claims description 127
• 108010086246 Glucagon-Like Peptide-1 Receptor Proteins 0.000 claims description 123
• 102100032882 Glucagon-like peptide 1 receptor Human genes 0.000 claims description 123
• 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 claims description 110
• 102100040918 Pro-glucagon Human genes 0.000 claims description 105
• 102100040890 Glucagon receptor Human genes 0.000 claims description 99
• 230000004048 modification Effects 0.000 claims description 96
• 238000012986 modification Methods 0.000 claims description 96
• 125000000217 alkyl group Chemical group 0.000 claims description 94
• FUOOLUPWFVMBKG-UHFFFAOYSA-N 2-Aminoisobutyric acid Chemical compound CC(C)(N)C(O)=O FUOOLUPWFVMBKG-UHFFFAOYSA-N 0.000 claims description 85
• 238000006467 substitution reaction Methods 0.000 claims description 81
• -1 aromatic amino acid Chemical class 0.000 claims description 75
• 210000004899 c-terminal region Anatomy 0.000 claims description 73
• WHUUTDBJXJRKMK-UHFFFAOYSA-N Glutamic acid Natural products OC(=O)C(N)CCC(O)=O WHUUTDBJXJRKMK-UHFFFAOYSA-N 0.000 claims description 72
• 125000002252 acyl group Chemical group 0.000 claims description 69
• 238000000034 method Methods 0.000 claims description 57
• 108010036598 gastric inhibitory polypeptide receptor Proteins 0.000 claims description 47
• 229920001223 polyethylene glycol Polymers 0.000 claims description 42
• 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 37
• DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 claims description 33
• 108010016626 Dipeptides Proteins 0.000 claims description 26
• 125000000291 glutamic acid group Chemical group N[C@@H](CCC(O)=O)C(=O)* 0.000 claims description 26
• 239000002202 Polyethylene glycol Substances 0.000 claims description 20
• 150000001408 amides Chemical group 0.000 claims description 19
• 206010012601 diabetes mellitus Diseases 0.000 claims description 19
• 125000000404 glutamine group Chemical group N[C@@H](CCC(N)=O)C(=O)* 0.000 claims description 19
• 125000003295 alanine group Chemical group N[C@@H](C)C(=O)* 0.000 claims description 17
• 208000013016 Hypoglycemia Diseases 0.000 claims description 16
• 230000002218 hypoglycaemic effect Effects 0.000 claims description 15
• 150000003839 salts Chemical class 0.000 claims description 14
• 239000000203 mixture Substances 0.000 claims description 13
• QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 12
• 239000004471 Glycine Substances 0.000 claims description 12
• 239000008194 pharmaceutical composition Substances 0.000 claims description 11
• KZSNJWFQEVHDMF-UHFFFAOYSA-N Valine Natural products CC(C)C(N)C(O)=O KZSNJWFQEVHDMF-UHFFFAOYSA-N 0.000 claims description 10
• 125000001924 fatty-acyl group Chemical group 0.000 claims description 10
• 125000001360 methionine group Chemical group N[C@@H](CCSC)C(=O)* 0.000 claims description 10
• 230000004580 weight loss Effects 0.000 claims description 10
• 125000003277 amino group Chemical group 0.000 claims description 8
• FFFHZYDWPBMWHY-VKHMYHEASA-N L-homocysteine Chemical group OC(=O)[C@@H](N)CCS FFFHZYDWPBMWHY-VKHMYHEASA-N 0.000 claims description 7
• 230000004584 weight gain Effects 0.000 claims description 7
• 235000019786 weight gain Nutrition 0.000 claims description 7
• SLXKOJJOQWFEFD-UHFFFAOYSA-N 6-aminohexanoic acid Chemical group NCCCCCC(O)=O SLXKOJJOQWFEFD-UHFFFAOYSA-N 0.000 claims description 6
• 230000004913 activation Effects 0.000 claims description 6
• 229930195711 D-Serine Natural products 0.000 claims description 5
• QNAYBMKLOCPYGJ-UWTATZPHSA-N D-alanine Chemical compound C[C@@H](N)C(O)=O QNAYBMKLOCPYGJ-UWTATZPHSA-N 0.000 claims description 5
• PSFABYLDRXJYID-VKHMYHEASA-N N-Methylserine Chemical compound CN[C@@H](CO)C(O)=O PSFABYLDRXJYID-VKHMYHEASA-N 0.000 claims description 5
• PSFABYLDRXJYID-UHFFFAOYSA-N N-methyl-DL-serine Natural products CNC(CO)C(O)=O PSFABYLDRXJYID-UHFFFAOYSA-N 0.000 claims description 5
• 108091005804 Peptidases Proteins 0.000 claims description 5
• 239000004365 Protease Substances 0.000 claims description 5
• 229960002684 aminocaproic acid Drugs 0.000 claims description 5
• 229910052739 hydrogen Inorganic materials 0.000 claims description 5
• 230000001939 inductive effect Effects 0.000 claims description 5
• 125000001493 tyrosinyl group Chemical group [H]OC1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])(N([H])[H])C(*)=O 0.000 claims description 5
• 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 claims description 4
• MTCFGRXMJLQNBG-UWTATZPHSA-N D-Serine Chemical compound OC[C@@H](N)C(O)=O MTCFGRXMJLQNBG-UWTATZPHSA-N 0.000 claims description 4
• 239000000539 dimer Substances 0.000 claims description 4
• SNRCMWGPCHPRBP-YFKPBYRVSA-N (2s)-2-(hydroxyamino)-3-(1h-imidazol-5-yl)propanoic acid Chemical compound ON[C@H](C(O)=O)CC1=CNC=N1 SNRCMWGPCHPRBP-YFKPBYRVSA-N 0.000 claims description 3
• PSWSDQRXCOJSFC-FJXQXJEOSA-N (2s)-2-acetamido-3-(1h-imidazol-5-yl)propanoic acid;hydrate Chemical compound O.CC(=O)N[C@H](C(O)=O)CC1=CN=CN1 PSWSDQRXCOJSFC-FJXQXJEOSA-N 0.000 claims description 3
• 229930195721 D-histidine Natural products 0.000 claims description 3
• DEFJQIDDEAULHB-IMJSIDKUSA-N L-alanyl-L-alanine Chemical compound C[C@H](N)C(=O)N[C@@H](C)C(O)=O DEFJQIDDEAULHB-IMJSIDKUSA-N 0.000 claims description 3
• KZSNJWFQEVHDMF-BYPYZUCNSA-N L-valine Chemical compound CC(C)[C@H](N)C(O)=O KZSNJWFQEVHDMF-BYPYZUCNSA-N 0.000 claims description 3
• LCPYQJIKPJDLLB-UWVGGRQHSA-N Leu-Leu Chemical compound CC(C)C[C@H](N)C(=O)N[C@H](C(O)=O)CC(C)C LCPYQJIKPJDLLB-UWVGGRQHSA-N 0.000 claims description 3
• CYZKJBZEIFWZSR-LURJTMIESA-N N(alpha)-methyl-L-histidine Chemical compound CN[C@H](C(O)=O)CC1=CNC=N1 CYZKJBZEIFWZSR-LURJTMIESA-N 0.000 claims description 3
• RWCOTTLHDJWHRS-YUMQZZPRSA-N Pro-Pro Chemical compound OC(=O)[C@@H]1CCCN1C(=O)[C@H]1NCCC1 RWCOTTLHDJWHRS-YUMQZZPRSA-N 0.000 claims description 3
• 108010056243 alanylalanine Proteins 0.000 claims description 3
• HRRYYCWYCMJNGA-ZETCQYMHSA-N alpha-methyl-L-histidine Chemical compound OC(=O)[C@](N)(C)CC1=CN=CN1 HRRYYCWYCMJNGA-ZETCQYMHSA-N 0.000 claims description 3
• ZCKYOWGFRHAZIQ-UHFFFAOYSA-N dihydrourocanic acid Chemical compound OC(=O)CCC1=CNC=N1 ZCKYOWGFRHAZIQ-UHFFFAOYSA-N 0.000 claims description 3
• 239000003937 drug carrier Substances 0.000 claims description 3
• PRJKNHOMHKJCEJ-UHFFFAOYSA-N imidazol-4-ylacetic acid Chemical compound OC(=O)CC1=CN=CN1 PRJKNHOMHKJCEJ-UHFFFAOYSA-N 0.000 claims description 3
• 108010091798 leucylleucine Proteins 0.000 claims description 3
• 108010077112 prolyl-proline Proteins 0.000 claims description 3
• 239000004474 valine Substances 0.000 claims description 3
• HNDVDQJCIGZPNO-RXMQYKEDSA-N D-histidine Chemical compound OC(=O)[C@H](N)CC1=CN=CN1 HNDVDQJCIGZPNO-RXMQYKEDSA-N 0.000 claims description 2
• GDFAOVXKHJXLEI-VKHMYHEASA-N N-methyl-L-alanine Chemical compound C[NH2+][C@@H](C)C([O-])=O GDFAOVXKHJXLEI-VKHMYHEASA-N 0.000 claims description 2
• 206010033799 Paralysis Diseases 0.000 claims description 2
• 235000004279 alanine Nutrition 0.000 claims description 2
• 210000001035 gastrointestinal tract Anatomy 0.000 claims description 2
• 101710198884 GATA-type zinc finger protein 1 Proteins 0.000 claims 4
• 241000024188 Andala Species 0.000 claims 1
• QNAYBMKLOCPYGJ-REOHCLBHSA-N L-alanine Chemical compound C[C@H](N)C(O)=O QNAYBMKLOCPYGJ-REOHCLBHSA-N 0.000 claims 1
• CBQJSKKFNMDLON-JTQLQIEISA-N N-acetyl-L-phenylalanine Chemical group CC(=O)N[C@H](C(O)=O)CC1=CC=CC=C1 CBQJSKKFNMDLON-JTQLQIEISA-N 0.000 claims 1
• 102100037486 Reverse transcriptase/ribonuclease H Human genes 0.000 claims 1
• 125000000753 cycloalkyl group Chemical group 0.000 claims 1
• 150000002308 glutamine derivatives Chemical group 0.000 claims 1
• 125000001072 heteroaryl group Chemical group 0.000 claims 1
• 125000000623 heterocyclic group Chemical group 0.000 claims 1
• 125000002883 imidazolyl group Chemical group 0.000 claims 1
• 230000001965 increasing effect Effects 0.000 abstract description 33
• 101001032756 Rattus norvegicus Granzyme-like protein 1 Proteins 0.000 abstract 1
• 229940024606 amino acid Drugs 0.000 description 511
• 108090000765 processed proteins & peptides Proteins 0.000 description 228
• 125000003275 alpha amino acid group Chemical group 0.000 description 163
• 101800000224 Glucagon-like peptide 1 Proteins 0.000 description 97
• 239000000556 agonist Substances 0.000 description 90
• KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 60
• 230000036515 potency Effects 0.000 description 56
• 125000004429 atom Chemical group 0.000 description 51
• WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 description 49
• 150000001335 aliphatic alkanes Chemical class 0.000 description 49
• 150000001412 amines Chemical class 0.000 description 49
• 150000003951 lactams Chemical group 0.000 description 48
• KDXKERNSBIXSRK-YFKPBYRVSA-N L-lysine Chemical compound NCCCC[C@H](N)C(O)=O KDXKERNSBIXSRK-YFKPBYRVSA-N 0.000 description 46
• 125000002887 hydroxy group Chemical group [H]O* 0.000 description 46
• 102000004196 processed proteins & peptides Human genes 0.000 description 46
• 230000001588 bifunctional effect Effects 0.000 description 44
• 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 43
• 239000008103 glucose Substances 0.000 description 41
• 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 37
• XUJNEKJLAYXESH-REOHCLBHSA-N L-Cysteine Chemical compound SC[C@H](N)C(O)=O XUJNEKJLAYXESH-REOHCLBHSA-N 0.000 description 35
• 150000003573 thiols Chemical class 0.000 description 35
• 210000004369 blood Anatomy 0.000 description 30
• 239000008280 blood Substances 0.000 description 30
• CKLJMWTZIZZHCS-REOHCLBHSA-N L-aspartic acid Chemical compound OC(=O)[C@@H](N)CC(O)=O CKLJMWTZIZZHCS-REOHCLBHSA-N 0.000 description 28
• 230000002209 hydrophobic effect Effects 0.000 description 28
• 230000010933 acylation Effects 0.000 description 26
• 238000005917 acylation reaction Methods 0.000 description 26
• 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 26
• MTCFGRXMJLQNBG-REOHCLBHSA-N (2S)-2-Amino-3-hydroxypropansäure Chemical compound OC[C@H](N)C(O)=O MTCFGRXMJLQNBG-REOHCLBHSA-N 0.000 description 25
• 150000007942 carboxylates Chemical group 0.000 description 24
• ZDXPYRJPNDTMRX-VKHMYHEASA-N L-glutamine Chemical compound OC(=O)[C@@H](N)CCC(N)=O ZDXPYRJPNDTMRX-VKHMYHEASA-N 0.000 description 23
• 230000037396 body weight Effects 0.000 description 23
• 230000002378 acidificating effect Effects 0.000 description 22
• 230000029936 alkylation Effects 0.000 description 22
• 238000005804 alkylation reaction Methods 0.000 description 22
• 150000001875 compounds Chemical class 0.000 description 22
• 239000003981 vehicle Substances 0.000 description 22
• 102000005962 receptors Human genes 0.000 description 21
• 108020003175 receptors Proteins 0.000 description 21
• 230000006698 induction Effects 0.000 description 20
• 102000004877 Insulin Human genes 0.000 description 19
• 108090001061 Insulin Proteins 0.000 description 19
• 241000699670 Mus sp. Species 0.000 description 19
• 229940125396 insulin Drugs 0.000 description 19
• OYIFNHCXNCRBQI-BYPYZUCNSA-N L-2-aminoadipic acid Chemical compound OC(=O)[C@@H](N)CCCC(O)=O OYIFNHCXNCRBQI-BYPYZUCNSA-N 0.000 description 18
• 230000015572 biosynthetic process Effects 0.000 description 18
• 235000014113 dietary fatty acids Nutrition 0.000 description 18
• 229930195729 fatty acid Natural products 0.000 description 18
• 239000000194 fatty acid Substances 0.000 description 18
• VBOQYPQEPHKASR-VKHMYHEASA-N L-homocysteic acid Chemical compound OC(=O)[C@@H](N)CCS(O)(=O)=O VBOQYPQEPHKASR-VKHMYHEASA-N 0.000 description 17
• 239000004220 glutamic acid Substances 0.000 description 17
• 208000008338 non-alcoholic fatty liver disease Diseases 0.000 description 17
• COLNVLDHVKWLRT-QMMMGPOBSA-N L-phenylalanine Chemical compound OC(=O)[C@@H](N)CC1=CC=CC=C1 COLNVLDHVKWLRT-QMMMGPOBSA-N 0.000 description 16
• AYFVYJQAPQTCCC-GBXIJSLDSA-N L-threonine Chemical compound C[C@@H](O)[C@H](N)C(O)=O AYFVYJQAPQTCCC-GBXIJSLDSA-N 0.000 description 16
• 239000002253 acid Substances 0.000 description 16
• 235000013922 glutamic acid Nutrition 0.000 description 16
• 125000003396 thiol group Chemical group [H]S* 0.000 description 16
• 125000001433 C-terminal amino-acid group Chemical group 0.000 description 15
• 238000007792 addition Methods 0.000 description 15
• 235000004400 serine Nutrition 0.000 description 15
• MTCFGRXMJLQNBG-UHFFFAOYSA-N Serine Natural products OCC(N)C(O)=O MTCFGRXMJLQNBG-UHFFFAOYSA-N 0.000 description 14
• 230000009471 action Effects 0.000 description 14
• 125000005647 linker group Chemical group 0.000 description 14
• 229920000642 polymer Polymers 0.000 description 14
• DCXYFEDJOCDNAF-REOHCLBHSA-N L-asparagine Chemical compound OC(=O)[C@@H](N)CC(N)=O DCXYFEDJOCDNAF-REOHCLBHSA-N 0.000 description 13
• 230000027455 binding Effects 0.000 description 13
• 235000012000 cholesterol Nutrition 0.000 description 13
• 150000004665 fatty acids Chemical group 0.000 description 13
• XVOYSCVBGLVSOL-UHFFFAOYSA-N cysteic acid Chemical compound OC(=O)C(N)CS(O)(=O)=O XVOYSCVBGLVSOL-UHFFFAOYSA-N 0.000 description 12
• 230000037430 deletion Effects 0.000 description 12
• 238000012217 deletion Methods 0.000 description 12
• 238000001727 in vivo Methods 0.000 description 12
• 230000002829 reductive effect Effects 0.000 description 12
• 238000011282 treatment Methods 0.000 description 12
• 239000004472 Lysine Substances 0.000 description 11
• 208000001145 Metabolic Syndrome Diseases 0.000 description 11
• 125000002843 carboxylic acid group Chemical group 0.000 description 11
• 230000008859 change Effects 0.000 description 11
• 150000002148 esters Chemical class 0.000 description 11
• 201000001421 hyperglycemia Diseases 0.000 description 11
• 102100025012 Dipeptidyl peptidase 4 Human genes 0.000 description 10
• 206010016654 Fibrosis Diseases 0.000 description 10
• 201000000690 abdominal obesity-metabolic syndrome Diseases 0.000 description 10
• 235000019197 fats Nutrition 0.000 description 10
• 229920001184 polypeptide Polymers 0.000 description 10
• 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 10
• 235000018102 proteins Nutrition 0.000 description 10
• 102000004169 proteins and genes Human genes 0.000 description 10
• 108090000623 proteins and genes Proteins 0.000 description 10
• 125000003607 serino group Chemical group [H]N([H])[C@]([H])(C(=O)[*])C(O[H])([H])[H] 0.000 description 10
• 125000000539 amino acid group Chemical group 0.000 description 9
• 235000003704 aspartic acid Nutrition 0.000 description 9
• OQFSQFPPLPISGP-UHFFFAOYSA-N beta-carboxyaspartic acid Natural products OC(=O)C(N)C(C(O)=O)C(O)=O OQFSQFPPLPISGP-UHFFFAOYSA-N 0.000 description 9
• 235000012631 food intake Nutrition 0.000 description 9
• 230000037406 food intake Effects 0.000 description 9
• 230000001976 improved effect Effects 0.000 description 9
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 9
• 125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 description 9
• ODKSFYDXXFIFQN-BYPYZUCNSA-N L-arginine Chemical compound OC(=O)[C@@H](N)CCCN=C(N)N ODKSFYDXXFIFQN-BYPYZUCNSA-N 0.000 description 8
• LRQKBLKVPFOOQJ-YFKPBYRVSA-N L-norleucine Chemical compound CCCC[C@H]([NH3+])C([O-])=O LRQKBLKVPFOOQJ-YFKPBYRVSA-N 0.000 description 8
• OUYCCCASQSFEME-QMMMGPOBSA-N L-tyrosine Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-QMMMGPOBSA-N 0.000 description 8
• 125000003368 amide group Chemical group 0.000 description 8
• 150000001732 carboxylic acid derivatives Chemical class 0.000 description 8
• 238000006243 chemical reaction Methods 0.000 description 8
• 238000003776 cleavage reaction Methods 0.000 description 8
• 230000006870 function Effects 0.000 description 8
• 125000003827 glycol group Chemical group 0.000 description 8
• 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 8
• 230000001404 mediated effect Effects 0.000 description 8
• 206010053219 non-alcoholic steatohepatitis Diseases 0.000 description 8
• 238000007363 ring formation reaction Methods 0.000 description 8
• 230000007017 scission Effects 0.000 description 8
• 239000004475 Arginine Substances 0.000 description 7
• 108010067722 Dipeptidyl Peptidase 4 Proteins 0.000 description 7
• 108060003951 Immunoglobulin Proteins 0.000 description 7
• 206010061218 Inflammation Diseases 0.000 description 7
• ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 7
• 229960003121 arginine Drugs 0.000 description 7
• 239000003795 chemical substances by application Substances 0.000 description 7
• 239000003814 drug Substances 0.000 description 7
• 230000004927 fusion Effects 0.000 description 7
• ZDXPYRJPNDTMRX-UHFFFAOYSA-N glutamine Natural products OC(=O)C(N)CCC(N)=O ZDXPYRJPNDTMRX-UHFFFAOYSA-N 0.000 description 7
• 102000018358 immunoglobulin Human genes 0.000 description 7
• 230000004054 inflammatory process Effects 0.000 description 7
• 210000004185 liver Anatomy 0.000 description 7
• 231100000240 steatosis hepatitis Toxicity 0.000 description 7
• 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 6
• GOJUJUVQIVIZAV-UHFFFAOYSA-N 2-amino-4,6-dichloropyrimidine-5-carbaldehyde Chemical group NC1=NC(Cl)=C(C=O)C(Cl)=N1 GOJUJUVQIVIZAV-UHFFFAOYSA-N 0.000 description 6
• OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 6
• 208000004930 Fatty Liver Diseases 0.000 description 6
• 102100026120 IgG receptor FcRn large subunit p51 Human genes 0.000 description 6
• 101710177940 IgG receptor FcRn large subunit p51 Proteins 0.000 description 6
• ODKSFYDXXFIFQN-BYPYZUCNSA-P L-argininium(2+) Chemical compound NC(=[NH2+])NCCC[C@H]([NH3+])C(O)=O ODKSFYDXXFIFQN-BYPYZUCNSA-P 0.000 description 6
• ROHFNLRQFUQHCH-YFKPBYRVSA-N L-leucine Chemical compound CC(C)C[C@H](N)C(O)=O ROHFNLRQFUQHCH-YFKPBYRVSA-N 0.000 description 6
• 208000008589 Obesity Diseases 0.000 description 6
• 102400000319 Oxyntomodulin Human genes 0.000 description 6
• 101800001388 Oxyntomodulin Proteins 0.000 description 6
• 239000003613 bile acid Substances 0.000 description 6
• 230000007882 cirrhosis Effects 0.000 description 6
• 208000019425 cirrhosis of liver Diseases 0.000 description 6
• 230000003247 decreasing effect Effects 0.000 description 6
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 6
• 230000014509 gene expression Effects 0.000 description 6
• 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 6
• 235000020824 obesity Nutrition 0.000 description 6
• 230000003389 potentiating effect Effects 0.000 description 6
• 239000000243 solution Substances 0.000 description 6
• 230000006641 stabilisation Effects 0.000 description 6
• 238000011105 stabilization Methods 0.000 description 6
• LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 5
• 101000930822 Giardia intestinalis Dipeptidyl-peptidase 4 Proteins 0.000 description 5
• AHLPHDHHMVZTML-BYPYZUCNSA-N L-Ornithine Chemical compound NCCC[C@H](N)C(O)=O AHLPHDHHMVZTML-BYPYZUCNSA-N 0.000 description 5
• AGPKZVBTJJNPAG-WHFBIAKZSA-N L-isoleucine Chemical compound CC[C@H](C)[C@H](N)C(O)=O AGPKZVBTJJNPAG-WHFBIAKZSA-N 0.000 description 5
• DWPCPZJAHOETAG-IMJSIDKUSA-N L-lanthionine Chemical compound OC(=O)[C@@H](N)CSC[C@H](N)C(O)=O DWPCPZJAHOETAG-IMJSIDKUSA-N 0.000 description 5
• OFOBLEOULBTSOW-UHFFFAOYSA-N Malonic acid Chemical compound OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 5
• AHLPHDHHMVZTML-UHFFFAOYSA-N Orn-delta-NH2 Natural products NCCCC(N)C(O)=O AHLPHDHHMVZTML-UHFFFAOYSA-N 0.000 description 5
• UTJLXEIPEHZYQJ-UHFFFAOYSA-N Ornithine Natural products OC(=O)C(C)CCCN UTJLXEIPEHZYQJ-UHFFFAOYSA-N 0.000 description 5
• AYFVYJQAPQTCCC-UHFFFAOYSA-N Threonine Natural products CC(O)C(N)C(O)=O AYFVYJQAPQTCCC-UHFFFAOYSA-N 0.000 description 5
• 239000004473 Threonine Substances 0.000 description 5
• 230000035508 accumulation Effects 0.000 description 5
• 238000009825 accumulation Methods 0.000 description 5
• 230000008484 agonism Effects 0.000 description 5
• 239000007864 aqueous solution Substances 0.000 description 5
• 125000004432 carbon atom Chemical group C* 0.000 description 5
• 125000006297 carbonyl amino group Chemical group [H]N([*:2])C([*:1])=O 0.000 description 5
• KXGVEGMKQFWNSR-UHFFFAOYSA-N deoxycholic acid Natural products C1CC2CC(O)CCC2(C)C2C1C1CCC(C(CCC(O)=O)C)C1(C)C(O)C2 KXGVEGMKQFWNSR-UHFFFAOYSA-N 0.000 description 5
• 230000003993 interaction Effects 0.000 description 5
• DWPCPZJAHOETAG-UHFFFAOYSA-N meso-lanthionine Natural products OC(=O)C(N)CSCC(N)C(O)=O DWPCPZJAHOETAG-UHFFFAOYSA-N 0.000 description 5
• 229960003104 ornithine Drugs 0.000 description 5
• 230000002035 prolonged effect Effects 0.000 description 5
• 230000009467 reduction Effects 0.000 description 5
• 238000006722 reduction reaction Methods 0.000 description 5
• 230000037390 scarring Effects 0.000 description 5
• 230000000087 stabilizing effect Effects 0.000 description 5
• 208000001072 type 2 diabetes mellitus Diseases 0.000 description 5
• SCOZOHWKTFBYNS-UHFFFAOYSA-N 2,2-diamino-3-methyl-4-oxopentanoic acid Chemical compound CC(=O)C(C)C(N)(N)C(O)=O SCOZOHWKTFBYNS-UHFFFAOYSA-N 0.000 description 4
• ALYNCZNDIQEVRV-UHFFFAOYSA-N 4-aminobenzoic acid Chemical compound NC1=CC=C(C(O)=O)C=C1 ALYNCZNDIQEVRV-UHFFFAOYSA-N 0.000 description 4
• JJMDCOVWQOJGCB-UHFFFAOYSA-N 5-aminopentanoic acid Chemical compound [NH3+]CCCCC([O-])=O JJMDCOVWQOJGCB-UHFFFAOYSA-N 0.000 description 4
• XDOLZJYETYVRKV-UHFFFAOYSA-N 7-Aminoheptanoic acid Chemical compound NCCCCCCC(O)=O XDOLZJYETYVRKV-UHFFFAOYSA-N 0.000 description 4
• UQXNEWQGGVUVQA-UHFFFAOYSA-N 8-aminooctanoic acid Chemical compound NCCCCCCCC(O)=O UQXNEWQGGVUVQA-UHFFFAOYSA-N 0.000 description 4
• KDMSVYIHKLZKET-UHFFFAOYSA-N 8-hydroxyoctanoic acid Chemical compound OCCCCCCCC(O)=O KDMSVYIHKLZKET-UHFFFAOYSA-N 0.000 description 4
• 102000004506 Blood Proteins Human genes 0.000 description 4
• 108010017384 Blood Proteins Proteins 0.000 description 4
• QNAYBMKLOCPYGJ-UHFFFAOYSA-N D-alpha-Ala Chemical group CC([NH3+])C([O-])=O QNAYBMKLOCPYGJ-UHFFFAOYSA-N 0.000 description 4
• RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 4
• 102000004190 Enzymes Human genes 0.000 description 4
• 108090000790 Enzymes Proteins 0.000 description 4
• 101800004266 Glucagon-like peptide 1(7-37) Proteins 0.000 description 4
• 206010019708 Hepatic steatosis Diseases 0.000 description 4
• 206010022489 Insulin Resistance Diseases 0.000 description 4
• RHGKLRLOHDJJDR-BYPYZUCNSA-N L-citrulline Chemical compound NC(=O)NCCC[C@H]([NH3+])C([O-])=O RHGKLRLOHDJJDR-BYPYZUCNSA-N 0.000 description 4
• 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 description 4
• 108010019598 Liraglutide Proteins 0.000 description 4
• RHGKLRLOHDJJDR-UHFFFAOYSA-N Ndelta-carbamoyl-DL-ornithine Natural products OC(=O)C(N)CCCNC(N)=O RHGKLRLOHDJJDR-UHFFFAOYSA-N 0.000 description 4
• 102000035195 Peptidases Human genes 0.000 description 4
• 108010058003 Proglucagon Proteins 0.000 description 4
• 230000002159 abnormal effect Effects 0.000 description 4
• 150000001299 aldehydes Chemical class 0.000 description 4
• 238000005865 alkene metathesis reaction Methods 0.000 description 4
• QWCKQJZIFLGMSD-UHFFFAOYSA-N alpha-aminobutyric acid Chemical compound CCC(N)C(O)=O QWCKQJZIFLGMSD-UHFFFAOYSA-N 0.000 description 4
• 230000004071 biological effect Effects 0.000 description 4
• 239000000969 carrier Substances 0.000 description 4
• 230000015556 catabolic process Effects 0.000 description 4
• JUFFVKRROAPVBI-PVOYSMBESA-N chembl1210015 Chemical compound C([C@@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(=O)N[C@H]1[C@@H]([C@@H](O)[C@H](O[C@H]2[C@@H]([C@@H](O)[C@@H](O)[C@@H](CO[C@]3(O[C@@H](C[C@H](O)[C@H](O)CO)[C@H](NC(C)=O)[C@@H](O)C3)C(O)=O)O2)O)[C@@H](CO)O1)NC(C)=O)C(=O)NCC(=O)NCC(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CO)C(=O)N[C@@H](CO)C(=O)NCC(=O)N[C@@H](C)C(=O)N1[C@@H](CCC1)C(=O)N1[C@@H](CCC1)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CO)C(N)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@@H](NC(=O)[C@H](C)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CCSC)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CO)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@@H](NC(=O)CNC(=O)[C@H](CCC(O)=O)NC(=O)CNC(=O)[C@@H](N)CC=1NC=NC=1)[C@@H](C)O)[C@@H](C)O)C(C)C)C1=CC=CC=C1 JUFFVKRROAPVBI-PVOYSMBESA-N 0.000 description 4
• 229960002173 citrulline Drugs 0.000 description 4
• 235000013477 citrulline Nutrition 0.000 description 4
• 229920001577 copolymer Polymers 0.000 description 4
• 125000000151 cysteine group Chemical group N[C@@H](CS)C(=O)* 0.000 description 4
• 230000007423 decrease Effects 0.000 description 4
• 238000006731 degradation reaction Methods 0.000 description 4
• 239000010432 diamond Substances 0.000 description 4
• 238000013229 diet-induced obese mouse Methods 0.000 description 4
• XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 4
• 208000035475 disorder Diseases 0.000 description 4
• 229940079593 drug Drugs 0.000 description 4
• 208000010706 fatty liver disease Diseases 0.000 description 4
• 230000004761 fibrosis Effects 0.000 description 4
• 239000003877 glucagon like peptide 1 receptor agonist Substances 0.000 description 4
• 108010063245 glucagon-like peptide 1 (7-36)amide Proteins 0.000 description 4
• 208000006454 hepatitis Diseases 0.000 description 4
• 231100000283 hepatitis Toxicity 0.000 description 4
• HNDVDQJCIGZPNO-UHFFFAOYSA-N histidine Natural products OC(=O)C(N)CC1=CN=CN1 HNDVDQJCIGZPNO-UHFFFAOYSA-N 0.000 description 4
• 229940088597 hormone Drugs 0.000 description 4
• 239000005556 hormone Substances 0.000 description 4
• 239000001257 hydrogen Substances 0.000 description 4
• 229960002701 liraglutide Drugs 0.000 description 4
• 210000005229 liver cell Anatomy 0.000 description 4
• 229910052760 oxygen Inorganic materials 0.000 description 4
• 230000006320 pegylation Effects 0.000 description 4
• 239000005017 polysaccharide Substances 0.000 description 4
• 150000004804 polysaccharides Chemical class 0.000 description 4
• 230000001737 promoting effect Effects 0.000 description 4
• 239000011550 stock solution Substances 0.000 description 4
• HLZKNKRTKFSKGZ-UHFFFAOYSA-N tetradecan-1-ol Chemical compound CCCCCCCCCCCCCCO HLZKNKRTKFSKGZ-UHFFFAOYSA-N 0.000 description 4
• 125000000341 threoninyl group Chemical group [H]OC([H])(C([H])([H])[H])C([H])(N([H])[H])C(*)=O 0.000 description 4
• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 4
• QFQYGJMNIDGZSG-YFKPBYRVSA-N (2r)-3-(acetamidomethylsulfanyl)-2-azaniumylpropanoate Chemical compound CC(=O)NCSC[C@H]([NH3+])C([O-])=O QFQYGJMNIDGZSG-YFKPBYRVSA-N 0.000 description 3
• BHQCQFFYRZLCQQ-UHFFFAOYSA-N (3alpha,5alpha,7alpha,12alpha)-3,7,12-trihydroxy-cholan-24-oic acid Natural products OC1CC2CC(O)CCC2(C)C2C1C1CCC(C(CCC(O)=O)C)C1(C)C(O)C2 BHQCQFFYRZLCQQ-UHFFFAOYSA-N 0.000 description 3
• UKAUYVFTDYCKQA-UHFFFAOYSA-N -2-Amino-4-hydroxybutanoic acid Natural products OC(=O)C(N)CCO UKAUYVFTDYCKQA-UHFFFAOYSA-N 0.000 description 3
• 208000004611 Abdominal Obesity Diseases 0.000 description 3
• 208000022309 Alcoholic Liver disease Diseases 0.000 description 3
• 206010003210 Arteriosclerosis Diseases 0.000 description 3
• DCXYFEDJOCDNAF-UHFFFAOYSA-N Asparagine Natural products OC(=O)C(N)CC(N)=O DCXYFEDJOCDNAF-UHFFFAOYSA-N 0.000 description 3
• 201000001320 Atherosclerosis Diseases 0.000 description 3
• 239000004215 Carbon black (E152) Substances 0.000 description 3
• 206010065941 Central obesity Diseases 0.000 description 3
• 239000004380 Cholic acid Substances 0.000 description 3
• 229920002307 Dextran Polymers 0.000 description 3
• 108010011459 Exenatide Proteins 0.000 description 3
• 102400000324 Glucagon-like peptide 1(7-37) Human genes 0.000 description 3
• PMMYEEVYMWASQN-DMTCNVIQSA-N Hydroxyproline Chemical compound O[C@H]1CN[C@H](C(O)=O)C1 PMMYEEVYMWASQN-DMTCNVIQSA-N 0.000 description 3
• 206010020772 Hypertension Diseases 0.000 description 3
• QEFRNWWLZKMPFJ-ZXPFJRLXSA-N L-methionine (R)-S-oxide Chemical compound C[S@@](=O)CC[C@H]([NH3+])C([O-])=O QEFRNWWLZKMPFJ-ZXPFJRLXSA-N 0.000 description 3
• QEFRNWWLZKMPFJ-UHFFFAOYSA-N L-methionine sulphoxide Natural products CS(=O)CCC(N)C(O)=O QEFRNWWLZKMPFJ-UHFFFAOYSA-N 0.000 description 3
• 125000000174 L-prolyl group Chemical group [H]N1C([H])([H])C([H])([H])C([H])([H])[C@@]1([H])C(*)=O 0.000 description 3
• 125000000510 L-tryptophano group Chemical group [H]C1=C([H])C([H])=C2N([H])C([H])=C(C([H])([H])[C@@]([H])(C(O[H])=O)N([H])[*])C2=C1[H] 0.000 description 3
• MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 3
• 210000000577 adipose tissue Anatomy 0.000 description 3
• 239000005557 antagonist Substances 0.000 description 3
• 230000010056 antibody-dependent cellular cytotoxicity Effects 0.000 description 3
• 230000036528 appetite Effects 0.000 description 3
• 235000019789 appetite Nutrition 0.000 description 3
• 125000000637 arginyl group Chemical group N[C@@H](CCCNC(N)=N)C(=O)* 0.000 description 3
• 235000009582 asparagine Nutrition 0.000 description 3
• 229960001230 asparagine Drugs 0.000 description 3
• 238000003556 assay Methods 0.000 description 3
• 230000036772 blood pressure Effects 0.000 description 3
• 229910052799 carbon Inorganic materials 0.000 description 3
• 210000004027 cell Anatomy 0.000 description 3
• 239000003153 chemical reaction reagent Substances 0.000 description 3
• BHQCQFFYRZLCQQ-OELDTZBJSA-N cholic acid Chemical compound C([C@H]1C[C@H]2O)[C@H](O)CC[C@]1(C)[C@@H]1[C@@H]2[C@@H]2CC[C@H]([C@@H](CCC(O)=O)C)[C@@]2(C)[C@@H](O)C1 BHQCQFFYRZLCQQ-OELDTZBJSA-N 0.000 description 3
• 235000019416 cholic acid Nutrition 0.000 description 3
• 229960002471 cholic acid Drugs 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
• 230000004540 complement-dependent cytotoxicity Effects 0.000 description 3
• 238000004132 cross linking Methods 0.000 description 3
• 235000018417 cysteine Nutrition 0.000 description 3
• 230000001419 dependent effect Effects 0.000 description 3
• 229960001519 exenatide Drugs 0.000 description 3
• 230000001747 exhibiting effect Effects 0.000 description 3
• 108020001507 fusion proteins Proteins 0.000 description 3
• 102000037865 fusion proteins Human genes 0.000 description 3
• 125000003630 glycyl group Chemical group [H]N([H])C([H])([H])C(*)=O 0.000 description 3
• 125000004404 heteroalkyl group Chemical group 0.000 description 3
• 125000005842 heteroatom Chemical group 0.000 description 3
• IPCSVZSSVZVIGE-UHFFFAOYSA-N hexadecanoic acid Chemical compound CCCCCCCCCCCCCCCC(O)=O IPCSVZSSVZVIGE-UHFFFAOYSA-N 0.000 description 3
• 125000000487 histidyl group Chemical group [H]N([H])C(C(=O)O*)C([H])([H])C1=C([H])N([H])C([H])=N1 0.000 description 3
• 125000000717 hydrazino group Chemical group [H]N([*])N([H])[H] 0.000 description 3
• 229940072221 immunoglobulins Drugs 0.000 description 3
• 238000010348 incorporation Methods 0.000 description 3
• 238000002347 injection Methods 0.000 description 3
• 239000007924 injection Substances 0.000 description 3
• 150000002596 lactones Chemical class 0.000 description 3
• 239000003446 ligand Substances 0.000 description 3
• 230000006742 locomotor activity Effects 0.000 description 3
• 238000005259 measurement Methods 0.000 description 3
• 229910052751 metal Inorganic materials 0.000 description 3
• 239000002184 metal Substances 0.000 description 3
• 230000000269 nucleophilic effect Effects 0.000 description 3
• 238000010534 nucleophilic substitution reaction Methods 0.000 description 3
• 229920001282 polysaccharide Polymers 0.000 description 3
• 230000004044 response Effects 0.000 description 3
• 230000000717 retained effect Effects 0.000 description 3
• 230000007863 steatosis Effects 0.000 description 3
• 229910052717 sulfur Inorganic materials 0.000 description 3
• 238000003786 synthesis reaction Methods 0.000 description 3
• 238000002560 therapeutic procedure Methods 0.000 description 3
• 150000003568 thioethers Chemical class 0.000 description 3
• 210000001519 tissue Anatomy 0.000 description 3
• 150000003626 triacylglycerols Chemical class 0.000 description 3
• 208000019553 vascular disease Diseases 0.000 description 3
• 229920003169 water-soluble polymer Polymers 0.000 description 3
• KSZFSNZOGAXEGH-BYPYZUCNSA-N (2s)-5-amino-2-(methylamino)-5-oxopentanoic acid Chemical compound CN[C@H](C(O)=O)CCC(N)=O KSZFSNZOGAXEGH-BYPYZUCNSA-N 0.000 description 2
• UQWNNUPJBDWRHC-UWVGGRQHSA-N (3s,4s)-4-amino-5-cyclohexyl-3-hydroxypentanoic acid Chemical compound OC(=O)C[C@H](O)[C@@H](N)CC1CCCCC1 UQWNNUPJBDWRHC-UWVGGRQHSA-N 0.000 description 2
• SNPQRYOQWLOTFA-UHFFFAOYSA-N 2,2-dimethyl-1,3-thiazolidine Chemical compound CC1(C)NCCS1 SNPQRYOQWLOTFA-UHFFFAOYSA-N 0.000 description 2
• RUVRGYVESPRHSZ-UHFFFAOYSA-N 2-[2-(2-azaniumylethoxy)ethoxy]acetate Chemical compound NCCOCCOCC(O)=O RUVRGYVESPRHSZ-UHFFFAOYSA-N 0.000 description 2
• JAJQQUQHMLWDFB-UHFFFAOYSA-N 4-azaniumyl-3-hydroxy-5-phenylpentanoate Chemical compound OC(=O)CC(O)C(N)CC1=CC=CC=C1 JAJQQUQHMLWDFB-UHFFFAOYSA-N 0.000 description 2
• DFVFTMTWCUHJBL-UHFFFAOYSA-N 4-azaniumyl-3-hydroxy-6-methylheptanoate Chemical compound CC(C)CC(N)C(O)CC(O)=O DFVFTMTWCUHJBL-UHFFFAOYSA-N 0.000 description 2
• FYEMIKRWWMYBFG-UHFFFAOYSA-N 8-sulfanyloctanoic acid Chemical compound OC(=O)CCCCCCCS FYEMIKRWWMYBFG-UHFFFAOYSA-N 0.000 description 2
• 102000011690 Adiponectin Human genes 0.000 description 2
• 108010076365 Adiponectin Proteins 0.000 description 2
• 108010088751 Albumins Proteins 0.000 description 2
• 102000009027 Albumins Human genes 0.000 description 2
• BPYKTIZUTYGOLE-IFADSCNNSA-N Bilirubin Chemical compound N1C(=O)C(C)=C(C=C)\C1=C\C1=C(C)C(CCC(O)=O)=C(CC2=C(C(C)=C(\C=C/3C(=C(C=C)C(=O)N\3)C)N2)CCC(O)=O)N1 BPYKTIZUTYGOLE-IFADSCNNSA-N 0.000 description 2
• QSJXEFYPDANLFS-UHFFFAOYSA-N Diacetyl Chemical compound CC(=O)C(C)=O QSJXEFYPDANLFS-UHFFFAOYSA-N 0.000 description 2
• 108010049003 Fibrinogen Proteins 0.000 description 2
• 102000008946 Fibrinogen Human genes 0.000 description 2
• VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 2
• 229940089838 Glucagon-like peptide 1 receptor agonist Drugs 0.000 description 2
• 108010007979 Glycocholic Acid Proteins 0.000 description 2
• AEMRFAOFKBGASW-UHFFFAOYSA-N Glycolic acid Chemical compound OCC(O)=O AEMRFAOFKBGASW-UHFFFAOYSA-N 0.000 description 2
• 101000934372 Homo sapiens Macrosialin Proteins 0.000 description 2
• 108090000144 Human Proteins Proteins 0.000 description 2
• 102000003839 Human Proteins Human genes 0.000 description 2
• VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
• 208000031226 Hyperlipidaemia Diseases 0.000 description 2
• 108010091358 Hypoxanthine Phosphoribosyltransferase Proteins 0.000 description 2
• 102000018251 Hypoxanthine Phosphoribosyltransferase Human genes 0.000 description 2
• WTDRDQBEARUVNC-LURJTMIESA-N L-DOPA Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C(O)=C1 WTDRDQBEARUVNC-LURJTMIESA-N 0.000 description 2
• HNDVDQJCIGZPNO-YFKPBYRVSA-N L-histidine Chemical compound OC(=O)[C@@H](N)CC1=CN=CN1 HNDVDQJCIGZPNO-YFKPBYRVSA-N 0.000 description 2
• SNDPXSYFESPGGJ-UHFFFAOYSA-N L-norVal-OH Natural products CCCC(N)C(O)=O SNDPXSYFESPGGJ-UHFFFAOYSA-N 0.000 description 2
• ROHFNLRQFUQHCH-UHFFFAOYSA-N Leucine Natural products CC(C)CC(N)C(O)=O ROHFNLRQFUQHCH-UHFFFAOYSA-N 0.000 description 2
• 208000017170 Lipid metabolism disease Diseases 0.000 description 2
• SMEROWZSTRWXGI-UHFFFAOYSA-N Lithocholsaeure Natural products C1CC2CC(O)CCC2(C)C2C1C1CCC(C(CCC(O)=O)C)C1(C)CC2 SMEROWZSTRWXGI-UHFFFAOYSA-N 0.000 description 2
• 102100025136 Macrosialin Human genes 0.000 description 2
• 241001465754 Metazoa Species 0.000 description 2
• AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 2
• 238000006845 Michael addition reaction Methods 0.000 description 2
• 208000023178 Musculoskeletal disease Diseases 0.000 description 2
• NQTADLQHYWFPDB-UHFFFAOYSA-N N-Hydroxysuccinimide Chemical compound ON1C(=O)CCC1=O NQTADLQHYWFPDB-UHFFFAOYSA-N 0.000 description 2
• AKCRVYNORCOYQT-YFKPBYRVSA-N N-methyl-L-valine Chemical compound CN[C@@H](C(C)C)C(O)=O AKCRVYNORCOYQT-YFKPBYRVSA-N 0.000 description 2
• RFDAIACWWDREDC-UHFFFAOYSA-N Na salt-Glycocholic acid Natural products OC1CC2CC(O)CCC2(C)C2C1C1CCC(C(CCC(=O)NCC(O)=O)C)C1(C)C(O)C2 RFDAIACWWDREDC-UHFFFAOYSA-N 0.000 description 2
• REYJJPSVUYRZGE-UHFFFAOYSA-N Octadecylamine Chemical compound CCCCCCCCCCCCCCCCCCN REYJJPSVUYRZGE-UHFFFAOYSA-N 0.000 description 2
• 208000018262 Peripheral vascular disease Diseases 0.000 description 2
• NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
• RADKZDMFGJYCBB-UHFFFAOYSA-N Pyridoxal Chemical compound CC1=NC=C(CO)C(C=O)=C1O RADKZDMFGJYCBB-UHFFFAOYSA-N 0.000 description 2
• LCTONWCANYUPML-UHFFFAOYSA-N Pyruvic acid Chemical compound CC(=O)C(O)=O LCTONWCANYUPML-UHFFFAOYSA-N 0.000 description 2
• NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical class [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 2
• QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
• WBWWGRHZICKQGZ-UHFFFAOYSA-N Taurocholic acid Natural products OC1CC2CC(O)CCC2(C)C2C1C1CCC(C(CCC(=O)NCCS(O)(=O)=O)C)C1(C)C(O)C2 WBWWGRHZICKQGZ-UHFFFAOYSA-N 0.000 description 2
• NYTOUQBROMCLBJ-UHFFFAOYSA-N Tetranitromethane Chemical compound [O-][N+](=O)C([N+]([O-])=O)([N+]([O-])=O)[N+]([O-])=O NYTOUQBROMCLBJ-UHFFFAOYSA-N 0.000 description 2
• YRKCREAYFQTBPV-UHFFFAOYSA-N acetylacetone Chemical compound CC(=O)CC(C)=O YRKCREAYFQTBPV-UHFFFAOYSA-N 0.000 description 2
• 150000007513 acids Chemical class 0.000 description 2
• 230000001154 acute effect Effects 0.000 description 2
• 125000001931 aliphatic group Chemical group 0.000 description 2
• 230000009286 beneficial effect Effects 0.000 description 2
• WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 2
• 230000033228 biological regulation Effects 0.000 description 2
• 230000036765 blood level Effects 0.000 description 2
• 239000000872 buffer Substances 0.000 description 2
• 230000003491 cAMP production Effects 0.000 description 2
• VHRGRCVQAFMJIZ-UHFFFAOYSA-N cadaverine Chemical compound NCCCCCN VHRGRCVQAFMJIZ-UHFFFAOYSA-N 0.000 description 2
• 150000001718 carbodiimides Chemical class 0.000 description 2
• 230000001413 cellular effect Effects 0.000 description 2
• 238000007385 chemical modification Methods 0.000 description 2
• FOCAUTSVDIKZOP-UHFFFAOYSA-N chloroacetic acid Chemical compound OC(=O)CCl FOCAUTSVDIKZOP-UHFFFAOYSA-N 0.000 description 2
• 230000021615 conjugation Effects 0.000 description 2
• 208000029078 coronary artery disease Diseases 0.000 description 2
• 230000008878 coupling Effects 0.000 description 2
• 238000010168 coupling process Methods 0.000 description 2
• 238000005859 coupling reaction Methods 0.000 description 2
• DMEGYFMYUHOHGS-UHFFFAOYSA-N cycloheptane Chemical compound C1CCCCCC1 DMEGYFMYUHOHGS-UHFFFAOYSA-N 0.000 description 2
• XUJNEKJLAYXESH-UHFFFAOYSA-N cysteine Natural products SCC(N)C(O)=O XUJNEKJLAYXESH-UHFFFAOYSA-N 0.000 description 2
• 230000006240 deamidation Effects 0.000 description 2
• 230000003111 delayed effect Effects 0.000 description 2
• KXGVEGMKQFWNSR-LLQZFEROSA-N deoxycholic acid Chemical compound C([C@H]1CC2)[C@H](O)CC[C@]1(C)[C@@H]1[C@@H]2[C@@H]2CC[C@H]([C@@H](CCC(O)=O)C)[C@@]2(C)[C@@H](O)C1 KXGVEGMKQFWNSR-LLQZFEROSA-N 0.000 description 2
• 229960003964 deoxycholic acid Drugs 0.000 description 2
• 238000001212 derivatisation Methods 0.000 description 2
• 201000010099 disease Diseases 0.000 description 2
• PMMYEEVYMWASQN-UHFFFAOYSA-N dl-hydroxyproline Natural products OC1C[NH2+]C(C([O-])=O)C1 PMMYEEVYMWASQN-UHFFFAOYSA-N 0.000 description 2
• 238000012377 drug delivery Methods 0.000 description 2
• 239000000839 emulsion Substances 0.000 description 2
• 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 2
• 229940012952 fibrinogen Drugs 0.000 description 2
• 125000000524 functional group Chemical group 0.000 description 2
• BTCSSZJGUNDROE-UHFFFAOYSA-N gamma-aminobutyric acid Chemical compound NCCCC(O)=O BTCSSZJGUNDROE-UHFFFAOYSA-N 0.000 description 2
• 229940093181 glucose injection Drugs 0.000 description 2
• RFDAIACWWDREDC-FRVQLJSFSA-N glycocholic acid Chemical compound C([C@H]1C[C@H]2O)[C@H](O)CC[C@]1(C)[C@@H]1[C@@H]2[C@@H]2CC[C@H]([C@@H](CCC(=O)NCC(O)=O)C)[C@@]2(C)[C@@H](O)C1 RFDAIACWWDREDC-FRVQLJSFSA-N 0.000 description 2
• 229940099347 glycocholic acid Drugs 0.000 description 2
• 229940093915 gynecological organic acid Drugs 0.000 description 2
• 230000002440 hepatic effect Effects 0.000 description 2
• 210000003494 hepatocyte Anatomy 0.000 description 2
• ORTRWBYBJVGVQC-UHFFFAOYSA-N hexadecane-1-thiol Chemical compound CCCCCCCCCCCCCCCCS ORTRWBYBJVGVQC-UHFFFAOYSA-N 0.000 description 2
• 229920001519 homopolymer Polymers 0.000 description 2
• 229930195733 hydrocarbon Natural products 0.000 description 2
• 150000002430 hydrocarbons Chemical class 0.000 description 2
• 125000004435 hydrogen atom Chemical group [H]* 0.000 description 2
• 229960002591 hydroxyproline Drugs 0.000 description 2
• 230000001771 impaired effect Effects 0.000 description 2
• 230000008595 infiltration Effects 0.000 description 2
• 238000001764 infiltration Methods 0.000 description 2
• 229940090044 injection Drugs 0.000 description 2
• 150000007529 inorganic bases Chemical class 0.000 description 2
• 230000002427 irreversible effect Effects 0.000 description 2
• 229960004502 levodopa Drugs 0.000 description 2
• 150000002632 lipids Chemical class 0.000 description 2
• SMEROWZSTRWXGI-HVATVPOCSA-N lithocholic acid Chemical compound C([C@H]1CC2)[C@H](O)CC[C@]1(C)[C@@H]1[C@@H]2[C@@H]2CC[C@H]([C@@H](CCC(O)=O)C)[C@@]2(C)CC1 SMEROWZSTRWXGI-HVATVPOCSA-N 0.000 description 2
• 208000019423 liver disease Diseases 0.000 description 2
• 239000000463 material Substances 0.000 description 2
• 108020004999 messenger RNA Proteins 0.000 description 2
• 230000011987 methylation Effects 0.000 description 2
• 238000007069 methylation reaction Methods 0.000 description 2
• 150000007522 mineralic acids Chemical class 0.000 description 2
• 230000035772 mutation Effects 0.000 description 2
• SCIFESDRCALIIM-UHFFFAOYSA-N n-methylphenylalanine Chemical compound CNC(C(O)=O)CC1=CC=CC=C1 SCIFESDRCALIIM-UHFFFAOYSA-N 0.000 description 2
• 229910052757 nitrogen Inorganic materials 0.000 description 2
• 108020004707 nucleic acids Proteins 0.000 description 2
• 102000039446 nucleic acids Human genes 0.000 description 2
• 150000007523 nucleic acids Chemical class 0.000 description 2
• 239000003921 oil Substances 0.000 description 2
• 235000019198 oils Nutrition 0.000 description 2
• 150000007524 organic acids Chemical class 0.000 description 2
• 235000005985 organic acids Nutrition 0.000 description 2
• 150000007530 organic bases Chemical class 0.000 description 2
• 238000010525 oxidative degradation reaction Methods 0.000 description 2
• 108010091748 peptide A Proteins 0.000 description 2
• OJUGVDODNPJEEC-UHFFFAOYSA-N phenylglyoxal Chemical compound O=CC(=O)C1=CC=CC=C1 OJUGVDODNPJEEC-UHFFFAOYSA-N 0.000 description 2
• NMHMNPHRMNGLLB-UHFFFAOYSA-N phloretic acid Chemical compound OC(=O)CCC1=CC=C(O)C=C1 NMHMNPHRMNGLLB-UHFFFAOYSA-N 0.000 description 2
• 230000026731 phosphorylation Effects 0.000 description 2
• 238000006366 phosphorylation reaction Methods 0.000 description 2
• 108091033319 polynucleotide Proteins 0.000 description 2
• 102000040430 polynucleotide Human genes 0.000 description 2
• 239000002157 polynucleotide Substances 0.000 description 2
• 230000002265 prevention Effects 0.000 description 2
• 235000019260 propionic acid Nutrition 0.000 description 2
• 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 2
• NGVDGCNFYWLIFO-UHFFFAOYSA-N pyridoxal 5'-phosphate Chemical compound CC1=NC=C(COP(O)(O)=O)C(C=O)=C1O NGVDGCNFYWLIFO-UHFFFAOYSA-N 0.000 description 2
• IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical compound O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 0.000 description 2
• 238000004064 recycling Methods 0.000 description 2
• 238000005932 reductive alkylation reaction Methods 0.000 description 2
• 230000001105 regulatory effect Effects 0.000 description 2
• 230000000241 respiratory effect Effects 0.000 description 2
• YGSDEFSMJLZEOE-UHFFFAOYSA-N salicylic acid Chemical compound OC(=O)C1=CC=CC=C1O YGSDEFSMJLZEOE-UHFFFAOYSA-N 0.000 description 2
• FSYKKLYZXJSNPZ-UHFFFAOYSA-N sarcosine Chemical compound C[NH2+]CC([O-])=O FSYKKLYZXJSNPZ-UHFFFAOYSA-N 0.000 description 2
• 210000002966 serum Anatomy 0.000 description 2
• 238000001228 spectrum Methods 0.000 description 2
• 150000003431 steroids Chemical group 0.000 description 2
• 230000000638 stimulation Effects 0.000 description 2
• KZNICNPSHKQLFF-UHFFFAOYSA-N succinimide Chemical compound O=C1CCC(=O)N1 KZNICNPSHKQLFF-UHFFFAOYSA-N 0.000 description 2
• 208000024891 symptom Diseases 0.000 description 2
• 208000011580 syndromic disease Diseases 0.000 description 2
• WBWWGRHZICKQGZ-GIHLXUJPSA-N taurocholic acid Chemical compound C([C@@H]1C[C@H]2O)[C@@H](O)CC[C@]1(C)[C@@H]1[C@@H]2[C@@H]2CC[C@@H]([C@@H](CCC(=O)NCCS(O)(=O)=O)C)[C@@]2(C)[C@H](O)C1 WBWWGRHZICKQGZ-GIHLXUJPSA-N 0.000 description 2
• 230000001225 therapeutic effect Effects 0.000 description 2
• 150000007970 thio esters Chemical class 0.000 description 2
• JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 2
• FGMPLJWBKKVCDB-UHFFFAOYSA-N trans-L-hydroxy-proline Natural products ON1CCCC1C(O)=O FGMPLJWBKKVCDB-UHFFFAOYSA-N 0.000 description 2
• VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 2
• 238000002054 transplantation Methods 0.000 description 2
• UFTFJSFQGQCHQW-UHFFFAOYSA-N triformin Chemical compound O=COCC(OC=O)COC=O UFTFJSFQGQCHQW-UHFFFAOYSA-N 0.000 description 2
• QBYIENPQHBMVBV-HFEGYEGKSA-N (2R)-2-hydroxy-2-phenylacetic acid Chemical compound O[C@@H](C(O)=O)c1ccccc1.O[C@@H](C(O)=O)c1ccccc1 QBYIENPQHBMVBV-HFEGYEGKSA-N 0.000 description 1
• DNDVHMGBCGSRIY-ZCFIWIBFSA-N (2r)-2-amino-3-(1,3-benzothiazol-2-yl)propanoic acid Chemical compound C1=CC=C2SC(C[C@@H](N)C(O)=O)=NC2=C1 DNDVHMGBCGSRIY-ZCFIWIBFSA-N 0.000 description 1
• FDKWRPBBCBCIGA-REOHCLBHSA-N (2r)-2-azaniumyl-3-$l^{1}-selanylpropanoate Chemical compound [Se]C[C@H](N)C(O)=O FDKWRPBBCBCIGA-REOHCLBHSA-N 0.000 description 1
• XCKUCSJNPYTMAE-QMMMGPOBSA-N (2s)-2-(chloroamino)-3-phenylpropanoic acid Chemical compound OC(=O)[C@@H](NCl)CC1=CC=CC=C1 XCKUCSJNPYTMAE-QMMMGPOBSA-N 0.000 description 1
• WBNIBXIBXCPMOW-JTQLQIEISA-N (2s)-2-(ethoxyamino)-3-(4-hydroxyphenyl)propanoic acid Chemical compound CCON[C@H](C(O)=O)CC1=CC=C(O)C=C1 WBNIBXIBXCPMOW-JTQLQIEISA-N 0.000 description 1
• FPDYKABXINADKS-LURJTMIESA-N (2s)-2-(methylazaniumyl)hexanoate Chemical compound CCCC[C@H](NC)C(O)=O FPDYKABXINADKS-LURJTMIESA-N 0.000 description 1
• XQBUAEBDRUXSPI-ZETCQYMHSA-N (2s)-2-(piperidin-1-ylamino)propanoic acid Chemical compound OC(=O)[C@H](C)NN1CCCCC1 XQBUAEBDRUXSPI-ZETCQYMHSA-N 0.000 description 1
• WTYDPHLGAWMABS-LURJTMIESA-N (2s)-2-(pyrrolidin-1-ylamino)propanoic acid Chemical compound OC(=O)[C@H](C)NN1CCCC1 WTYDPHLGAWMABS-LURJTMIESA-N 0.000 description 1
• RROQYZJPOZVQTM-BQBZGAKWSA-N (2s)-2-[[(2s)-2,5-diaminopentanoyl]amino]pentanedioic acid Chemical compound NCCC[C@H](N)C(=O)N[C@H](C(O)=O)CCC(O)=O RROQYZJPOZVQTM-BQBZGAKWSA-N 0.000 description 1
• KWIPUXXIFQQMKN-VIFPVBQESA-N (2s)-2-amino-3-(4-cyanophenyl)propanoic acid Chemical compound OC(=O)[C@@H](N)CC1=CC=C(C#N)C=C1 KWIPUXXIFQQMKN-VIFPVBQESA-N 0.000 description 1
• CBNRCFKJVUHIRM-LBPRGKRZSA-N (2s)-2-amino-3-[4-[bis(dimethylaminooxy)phosphoryloxy]phenyl]propanoic acid Chemical compound CN(C)OP(=O)(ON(C)C)OC1=CC=C(C[C@H](N)C(O)=O)C=C1 CBNRCFKJVUHIRM-LBPRGKRZSA-N 0.000 description 1
• SJTPYAOZAPSOLO-REOHCLBHSA-N (2s)-2-hydrazinyl-3-hydroxypropanoic acid Chemical compound NN[C@@H](CO)C(O)=O SJTPYAOZAPSOLO-REOHCLBHSA-N 0.000 description 1
• UTEYHKAJNNCEDX-VIFPVBQESA-N (2s)-3-(4-hydroxyphenyl)-2-(methoxyamino)propanoic acid Chemical compound CON[C@H](C(O)=O)CC1=CC=C(O)C=C1 UTEYHKAJNNCEDX-VIFPVBQESA-N 0.000 description 1
• MCOLRSXARZXGCL-HNNXBMFYSA-N (2s)-3-(4-phenylmethoxyphenyl)-2-(phosphonoamino)propanoic acid Chemical compound C1=CC(C[C@@H](C(=O)O)NP(O)(O)=O)=CC=C1OCC1=CC=CC=C1 MCOLRSXARZXGCL-HNNXBMFYSA-N 0.000 description 1
• ARMHACFUZZJJSF-VIFPVBQESA-N (2s)-3-phenylmethoxy-2-(phosphonoamino)propanoic acid Chemical compound OP(=O)(O)N[C@H](C(=O)O)COCC1=CC=CC=C1 ARMHACFUZZJJSF-VIFPVBQESA-N 0.000 description 1
• XJODGRWDFZVTKW-LURJTMIESA-N (2s)-4-methyl-2-(methylamino)pentanoic acid Chemical compound CN[C@H](C(O)=O)CC(C)C XJODGRWDFZVTKW-LURJTMIESA-N 0.000 description 1
• WCYLQLNJSDTVPN-BQBZGAKWSA-N (2s,3s)-2-amino-n-methoxy-n,3-dimethylpentanamide Chemical compound CC[C@H](C)[C@H](N)C(=O)N(C)OC WCYLQLNJSDTVPN-BQBZGAKWSA-N 0.000 description 1
• LJRDOKAZOAKLDU-UDXJMMFXSA-N (2s,3s,4r,5r,6r)-5-amino-2-(aminomethyl)-6-[(2r,3s,4r,5s)-5-[(1r,2r,3s,5r,6s)-3,5-diamino-2-[(2s,3r,4r,5s,6r)-3-amino-4,5-dihydroxy-6-(hydroxymethyl)oxan-2-yl]oxy-6-hydroxycyclohexyl]oxy-4-hydroxy-2-(hydroxymethyl)oxolan-3-yl]oxyoxane-3,4-diol;sulfuric ac Chemical compound OS(O)(=O)=O.N[C@@H]1[C@@H](O)[C@H](O)[C@H](CN)O[C@@H]1O[C@H]1[C@@H](O)[C@H](O[C@H]2[C@@H]([C@@H](N)C[C@@H](N)[C@@H]2O)O[C@@H]2[C@@H]([C@@H](O)[C@H](O)[C@@H](CO)O2)N)O[C@@H]1CO LJRDOKAZOAKLDU-UDXJMMFXSA-N 0.000 description 1
• RUDATBOHQWOJDD-UHFFFAOYSA-N (3beta,5beta,7alpha)-3,7-Dihydroxycholan-24-oic acid Natural products OC1CC2CC(O)CCC2(C)C2C1C1CCC(C(CCC(O)=O)C)C1(C)CC2 RUDATBOHQWOJDD-UHFFFAOYSA-N 0.000 description 1
• LDXFNKACRSEQND-ULUSZKPHSA-N (5R)-1-azabicyclo[3.1.0]hexane-5-carboxylic acid Chemical compound C1CC[C@@]2(C(=O)O)N1C2 LDXFNKACRSEQND-ULUSZKPHSA-N 0.000 description 1
• IADUEWIQBXOCDZ-VKHMYHEASA-N (S)-azetidine-2-carboxylic acid Chemical compound OC(=O)[C@@H]1CCN1 IADUEWIQBXOCDZ-VKHMYHEASA-N 0.000 description 1
• BJEPYKJPYRNKOW-REOHCLBHSA-N (S)-malic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O BJEPYKJPYRNKOW-REOHCLBHSA-N 0.000 description 1
• WBYWAXJHAXSJNI-VOTSOKGWSA-M .beta-Phenylacrylic acid Natural products [O-]C(=O)\C=C\C1=CC=CC=C1 WBYWAXJHAXSJNI-VOTSOKGWSA-M 0.000 description 1
• WNXJIVFYUVYPPR-UHFFFAOYSA-N 1,3-dioxolane Chemical compound C1COCO1 WNXJIVFYUVYPPR-UHFFFAOYSA-N 0.000 description 1
• PJSQECUPWDUIBT-UHFFFAOYSA-N 1-azaniumylcyclooctane-1-carboxylate Chemical compound OC(=O)C1(N)CCCCCCC1 PJSQECUPWDUIBT-UHFFFAOYSA-N 0.000 description 1
• 125000003287 1H-imidazol-4-ylmethyl group Chemical group [H]N1C([H])=NC(C([H])([H])[*])=C1[H] 0.000 description 1
• DXOCWBGPOJKSBL-UHFFFAOYSA-N 2,2,4-triamino-4-oxobutanoic acid Chemical compound NC(=O)CC(N)(N)C(O)=O DXOCWBGPOJKSBL-UHFFFAOYSA-N 0.000 description 1
• BLCJBICVQSYOIF-UHFFFAOYSA-N 2,2-diaminobutanoic acid Chemical compound CCC(N)(N)C(O)=O BLCJBICVQSYOIF-UHFFFAOYSA-N 0.000 description 1
• NHJVRSWLHSJWIN-UHFFFAOYSA-N 2,4,6-trinitrobenzenesulfonic acid Chemical compound OS(=O)(=O)C1=C([N+]([O-])=O)C=C([N+]([O-])=O)C=C1[N+]([O-])=O NHJVRSWLHSJWIN-UHFFFAOYSA-N 0.000 description 1
• OMGHIGVFLOPEHJ-UHFFFAOYSA-N 2,5-dihydro-1h-pyrrol-1-ium-2-carboxylate Chemical compound OC(=O)C1NCC=C1 OMGHIGVFLOPEHJ-UHFFFAOYSA-N 0.000 description 1
• FALRKNHUBBKYCC-UHFFFAOYSA-N 2-(chloromethyl)pyridine-3-carbonitrile Chemical compound ClCC1=NC=CC=C1C#N FALRKNHUBBKYCC-UHFFFAOYSA-N 0.000 description 1
• BHANCCMWYDZQOR-UHFFFAOYSA-N 2-(methyldisulfanyl)pyridine Chemical compound CSSC1=CC=CC=N1 BHANCCMWYDZQOR-UHFFFAOYSA-N 0.000 description 1
• PRSWALMQXKFZFA-UHFFFAOYSA-N 2-(piperidin-1-ylamino)acetic acid Chemical compound OC(=O)CNN1CCCCC1 PRSWALMQXKFZFA-UHFFFAOYSA-N 0.000 description 1
• ICBKJQDJWHBQAX-UHFFFAOYSA-N 2-aminooxane-4-carboxylic acid Chemical compound NC1CC(C(O)=O)CCO1 ICBKJQDJWHBQAX-UHFFFAOYSA-N 0.000 description 1
• VRFJLUHAQPBTLE-UHFFFAOYSA-N 2-aminopiperidine-1-carboxylic acid Chemical compound NC1CCCCN1C(O)=O VRFJLUHAQPBTLE-UHFFFAOYSA-N 0.000 description 1
• WTOFYLAWDLQMBZ-UHFFFAOYSA-N 2-azaniumyl-3-thiophen-2-ylpropanoate Chemical compound OC(=O)C(N)CC1=CC=CS1 WTOFYLAWDLQMBZ-UHFFFAOYSA-N 0.000 description 1
• FKJSFKCZZIXQIP-UHFFFAOYSA-N 2-bromo-1-(4-bromophenyl)ethanone Chemical compound BrCC(=O)C1=CC=C(Br)C=C1 FKJSFKCZZIXQIP-UHFFFAOYSA-N 0.000 description 1
• 125000000143 2-carboxyethyl group Chemical group [H]OC(=O)C([H])([H])C([H])([H])* 0.000 description 1
• JQPFYXFVUKHERX-UHFFFAOYSA-N 2-hydroxy-2-cyclohexen-1-one Natural products OC1=CCCCC1=O JQPFYXFVUKHERX-UHFFFAOYSA-N 0.000 description 1
• VJINKBZUJYGZGP-UHFFFAOYSA-N 3-(1-aminopropylideneamino)propyl-trimethylazanium Chemical compound CCC(N)=NCCC[N+](C)(C)C VJINKBZUJYGZGP-UHFFFAOYSA-N 0.000 description 1
• YHFKJGZDKILHTL-UHFFFAOYSA-N 3-(aminomethyl)-1h-pyrrole-2-carboxylic acid Chemical compound NCC=1C=CNC=1C(O)=O YHFKJGZDKILHTL-UHFFFAOYSA-N 0.000 description 1
• PECYZEOJVXMISF-UHFFFAOYSA-N 3-aminoalanine Chemical compound [NH3+]CC(N)C([O-])=O PECYZEOJVXMISF-UHFFFAOYSA-N 0.000 description 1
• BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 1
• ONZQYZKCUHFORE-UHFFFAOYSA-N 3-bromo-1,1,1-trifluoropropan-2-one Chemical compound FC(F)(F)C(=O)CBr ONZQYZKCUHFORE-UHFFFAOYSA-N 0.000 description 1
• DKIDEFUBRARXTE-UHFFFAOYSA-N 3-mercaptopropanoic acid Chemical class OC(=O)CCS DKIDEFUBRARXTE-UHFFFAOYSA-N 0.000 description 1
• QHSXWDVVFHXHHB-UHFFFAOYSA-N 3-nitro-2-[(3-nitropyridin-2-yl)disulfanyl]pyridine Chemical compound [O-][N+](=O)C1=CC=CN=C1SSC1=NC=CC=C1[N+]([O-])=O QHSXWDVVFHXHHB-UHFFFAOYSA-N 0.000 description 1
• VOUAQYXWVJDEQY-QENPJCQMSA-N 33017-11-7 Chemical compound OC(=O)CC[C@H](N)C(=O)N[C@@H](C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](C(C)C)C(=O)NCC(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)NCC(=O)NCC(=O)NCC(=O)N1CCC[C@H]1C(=O)NCC(=O)N[C@@H](C)C(=O)NCC(=O)N[C@@H](CO)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(N)=O)C(=O)N1[C@H](C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](C)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(O)=O)C(=O)NCC(=O)N[C@@H](CO)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(N)=O)C(O)=O)CCC1 VOUAQYXWVJDEQY-QENPJCQMSA-N 0.000 description 1
• XWHHYOYVRVGJJY-QMMMGPOBSA-N 4-fluoro-L-phenylalanine Chemical compound OC(=O)[C@@H](N)CC1=CC=C(F)C=C1 XWHHYOYVRVGJJY-QMMMGPOBSA-N 0.000 description 1
• GTVVZTAFGPQSPC-UHFFFAOYSA-N 4-nitrophenylalanine Chemical compound OC(=O)C(N)CC1=CC=C([N+]([O-])=O)C=C1 GTVVZTAFGPQSPC-UHFFFAOYSA-N 0.000 description 1
• 101710129138 ATP synthase subunit 9, mitochondrial Proteins 0.000 description 1
• 101710168506 ATP synthase subunit C, plastid Proteins 0.000 description 1
• 101710114069 ATP synthase subunit c Proteins 0.000 description 1
• 101710197943 ATP synthase subunit c, chloroplastic Proteins 0.000 description 1
• 101710187091 ATP synthase subunit c, sodium ion specific Proteins 0.000 description 1
• 102100036475 Alanine aminotransferase 1 Human genes 0.000 description 1
• 108010082126 Alanine transaminase Proteins 0.000 description 1
• QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 description 1
• 108010003415 Aspartate Aminotransferases Proteins 0.000 description 1
• 102000004625 Aspartate Aminotransferases Human genes 0.000 description 1
• 239000005711 Benzoic acid Substances 0.000 description 1
• 108010075254 C-Peptide Proteins 0.000 description 1
• 108010074051 C-Reactive Protein Proteins 0.000 description 1
• 102100032752 C-reactive protein Human genes 0.000 description 1
• 101800001453 C-terminal extension peptide Proteins 0.000 description 1
• 125000006539 C12 alkyl group Chemical group [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])* 0.000 description 1
• WSNMPAVSZJSIMT-UHFFFAOYSA-N COc1c(C)c2COC(=O)c2c(O)c1CC(O)C1(C)CCC(=O)O1 Chemical compound COc1c(C)c2COC(=O)c2c(O)c1CC(O)C1(C)CCC(=O)O1 WSNMPAVSZJSIMT-UHFFFAOYSA-N 0.000 description 1
• 101100337060 Caenorhabditis elegans glp-1 gene Proteins 0.000 description 1
• OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
• 208000024172 Cardiovascular disease Diseases 0.000 description 1
• WBYWAXJHAXSJNI-SREVYHEPSA-N Cinnamic acid Chemical compound OC(=O)\C=C/C1=CC=CC=C1 WBYWAXJHAXSJNI-SREVYHEPSA-N 0.000 description 1
• 206010010071 Coma Diseases 0.000 description 1
• JPVYNHNXODAKFH-UHFFFAOYSA-N Cu2+ Chemical compound [Cu+2] JPVYNHNXODAKFH-UHFFFAOYSA-N 0.000 description 1
• FDKWRPBBCBCIGA-UWTATZPHSA-N D-Selenocysteine Natural products [Se]C[C@@H](N)C(O)=O FDKWRPBBCBCIGA-UWTATZPHSA-N 0.000 description 1
• 125000002437 D-histidyl group Chemical group N[C@@H](C(=O)*)CC=1N=CNC1 0.000 description 1
• 125000000734 D-serino group Chemical group [H]N([H])[C@@]([H])(C(=O)[*])C(O[H])([H])[H] 0.000 description 1
• 108020004414 DNA Proteins 0.000 description 1
• 206010012373 Depressed level of consciousness Diseases 0.000 description 1
• FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 1
• 108090000194 Dipeptidyl-peptidases and tripeptidyl-peptidases Proteins 0.000 description 1
• 102000003779 Dipeptidyl-peptidases and tripeptidyl-peptidases Human genes 0.000 description 1
• 101100338242 Drosophila virilis His1.1 gene Proteins 0.000 description 1
• 208000032928 Dyslipidaemia Diseases 0.000 description 1
• LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 1
• IAYPIBMASNFSPL-UHFFFAOYSA-N Ethylene oxide Chemical compound C1CO1 IAYPIBMASNFSPL-UHFFFAOYSA-N 0.000 description 1
• 206010061857 Fat necrosis Diseases 0.000 description 1
• 108010087819 Fc receptors Proteins 0.000 description 1
• 102000009109 Fc receptors Human genes 0.000 description 1
• 229920001917 Ficoll Polymers 0.000 description 1
• 208000034826 Genetic Predisposition to Disease Diseases 0.000 description 1
• 102000006395 Globulins Human genes 0.000 description 1
• 108010044091 Globulins Proteins 0.000 description 1
• 101800000221 Glucagon-like peptide 2 Proteins 0.000 description 1
• 208000002705 Glucose Intolerance Diseases 0.000 description 1
• 206010018429 Glucose tolerance impaired Diseases 0.000 description 1
• SXRSQZLOMIGNAQ-UHFFFAOYSA-N Glutaraldehyde Chemical compound O=CCCCC=O SXRSQZLOMIGNAQ-UHFFFAOYSA-N 0.000 description 1
• 229920002527 Glycogen Polymers 0.000 description 1
• 206010019728 Hepatitis alcoholic Diseases 0.000 description 1
• 102100026122 High affinity immunoglobulin gamma Fc receptor I Human genes 0.000 description 1
• 101710182312 High affinity immunoglobulin gamma Fc receptor I Proteins 0.000 description 1
• 241000282412 Homo Species 0.000 description 1
• 208000028958 Hyperferritinemia Diseases 0.000 description 1
• 108010042653 IgA receptor Proteins 0.000 description 1
• 108010073816 IgE Receptors Proteins 0.000 description 1
• 102000009438 IgE Receptors Human genes 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
• 108010021625 Immunoglobulin Fragments Proteins 0.000 description 1
• 102000008394 Immunoglobulin Fragments Human genes 0.000 description 1
• 102000006496 Immunoglobulin Heavy Chains Human genes 0.000 description 1
• 108010019476 Immunoglobulin Heavy Chains Proteins 0.000 description 1
• 208000031773 Insulin resistance syndrome Diseases 0.000 description 1
• 102000012411 Intermediate Filament Proteins Human genes 0.000 description 1
• 108010061998 Intermediate Filament Proteins Proteins 0.000 description 1
• SNDPXSYFESPGGJ-BYPYZUCNSA-N L-2-aminopentanoic acid Chemical compound CCC[C@H](N)C(O)=O SNDPXSYFESPGGJ-BYPYZUCNSA-N 0.000 description 1
• ONIBWKKTOPOVIA-BYPYZUCNSA-N L-Proline Chemical compound OC(=O)[C@@H]1CCCN1 ONIBWKKTOPOVIA-BYPYZUCNSA-N 0.000 description 1
• ZGUNAGUHMKGQNY-ZETCQYMHSA-N L-alpha-phenylglycine zwitterion Chemical compound OC(=O)[C@@H](N)C1=CC=CC=C1 ZGUNAGUHMKGQNY-ZETCQYMHSA-N 0.000 description 1
• 125000002059 L-arginyl group Chemical group O=C([*])[C@](N([H])[H])([H])C([H])([H])C([H])([H])C([H])([H])N([H])C(=N[H])N([H])[H] 0.000 description 1
• LEVWYRKDKASIDU-IMJSIDKUSA-N L-cystine Chemical compound [O-]C(=O)[C@@H]([NH3+])CSSC[C@H]([NH3+])C([O-])=O LEVWYRKDKASIDU-IMJSIDKUSA-N 0.000 description 1
• UKAUYVFTDYCKQA-VKHMYHEASA-N L-homoserine Chemical compound OC(=O)[C@@H](N)CCO UKAUYVFTDYCKQA-VKHMYHEASA-N 0.000 description 1
• QEFRNWWLZKMPFJ-YGVKFDHGSA-N L-methionine S-oxide Chemical compound CS(=O)CC[C@H](N)C(O)=O QEFRNWWLZKMPFJ-YGVKFDHGSA-N 0.000 description 1
• UCUNFLYVYCGDHP-BYPYZUCNSA-N L-methionine sulfone Chemical compound CS(=O)(=O)CC[C@H](N)C(O)=O UCUNFLYVYCGDHP-BYPYZUCNSA-N 0.000 description 1
• QIVBCDIJIAJPQS-VIFPVBQESA-N L-tryptophane Chemical compound C1=CC=C2C(C[C@H](N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-VIFPVBQESA-N 0.000 description 1
• 238000008214 LDL Cholesterol Methods 0.000 description 1
• 241000270322 Lepidosauria Species 0.000 description 1
• 102000016267 Leptin Human genes 0.000 description 1
• 108010092277 Leptin Proteins 0.000 description 1
• WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 1
• 108060001084 Luciferase Proteins 0.000 description 1
• CIOWSLJGLSUOME-BQBZGAKWSA-N Lys-Asp Chemical compound NCCCC[C@H](N)C(=O)N[C@H](C(O)=O)CC(O)=O CIOWSLJGLSUOME-BQBZGAKWSA-N 0.000 description 1
• UGTZHPSKYRIGRJ-YUMQZZPRSA-N Lys-Glu Chemical compound NCCCC[C@H](N)C(=O)N[C@H](C(O)=O)CCC(O)=O UGTZHPSKYRIGRJ-YUMQZZPRSA-N 0.000 description 1
• PEEHTFAAVSWFBL-UHFFFAOYSA-N Maleimide Chemical compound O=C1NC(=O)C=C1 PEEHTFAAVSWFBL-UHFFFAOYSA-N 0.000 description 1
• HDNOQCZWJGGHSS-VEVYYDQMSA-N Met-Asn-Thr Chemical compound CSCC[C@H](N)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(O)=O HDNOQCZWJGGHSS-VEVYYDQMSA-N 0.000 description 1
• 102100029820 Mitochondrial brown fat uncoupling protein 1 Human genes 0.000 description 1
• 108050002686 Mitochondrial brown fat uncoupling protein 1 Proteins 0.000 description 1
• OLYPWXRMOFUVGH-LURJTMIESA-N N(2)-methyl-L-lysine Chemical compound CN[C@H](C(O)=O)CCCCN OLYPWXRMOFUVGH-LURJTMIESA-N 0.000 description 1
• MXNRLFUSFKVQSK-QMMMGPOBSA-O N(6),N(6),N(6)-trimethyl-L-lysine Chemical compound C[N+](C)(C)CCCC[C@H]([NH3+])C([O-])=O MXNRLFUSFKVQSK-QMMMGPOBSA-O 0.000 description 1
• RYFOQDQDVYIEHN-ZETCQYMHSA-N N,N-Dimethyllysine Chemical compound CN(C)[C@H](C(O)=O)CCCCN RYFOQDQDVYIEHN-ZETCQYMHSA-N 0.000 description 1
• 230000004988 N-glycosylation Effects 0.000 description 1
• XGEGHDBEHXKFPX-UHFFFAOYSA-N N-methyl urea Chemical compound CNC(N)=O XGEGHDBEHXKFPX-UHFFFAOYSA-N 0.000 description 1
• KSPIYJQBLVDRRI-WDSKDSINSA-N N-methyl-L-isoleucine Chemical compound CC[C@H](C)[C@H](NC)C(O)=O KSPIYJQBLVDRRI-WDSKDSINSA-N 0.000 description 1
• 125000000729 N-terminal amino-acid group Chemical group 0.000 description 1
• 206010028851 Necrosis Diseases 0.000 description 1
• 206010028980 Neoplasm Diseases 0.000 description 1
• GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 1
• CIQHWLTYGMYQQR-QMMMGPOBSA-N O(4')-sulfo-L-tyrosine Chemical compound OC(=O)[C@@H](N)CC1=CC=C(OS(O)(=O)=O)C=C1 CIQHWLTYGMYQQR-QMMMGPOBSA-N 0.000 description 1
• 229910019142 PO4 Inorganic materials 0.000 description 1
• 101800005164 Peptide V Proteins 0.000 description 1
• 101710117971 Peptide Y Proteins 0.000 description 1
• 108090000472 Phosphoenolpyruvate carboxykinase (ATP) Proteins 0.000 description 1
• 102100034792 Phosphoenolpyruvate carboxykinase [GTP], mitochondrial Human genes 0.000 description 1
• 108010022233 Plasminogen Activator Inhibitor 1 Proteins 0.000 description 1
• 102100039418 Plasminogen activator inhibitor 1 Human genes 0.000 description 1
• 229920000805 Polyaspartic acid Polymers 0.000 description 1
• 239000004698 Polyethylene Substances 0.000 description 1
• 108010020346 Polyglutamic Acid Proteins 0.000 description 1
• 108010039918 Polylysine Proteins 0.000 description 1
• 229920001231 Polysaccharide peptide Polymers 0.000 description 1
• 239000004372 Polyvinyl alcohol Substances 0.000 description 1
• ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
• 102000035554 Proglucagon Human genes 0.000 description 1
• ONIBWKKTOPOVIA-UHFFFAOYSA-N Proline Natural products OC(=O)C1CCCN1 ONIBWKKTOPOVIA-UHFFFAOYSA-N 0.000 description 1
• 101710188315 Protein X Proteins 0.000 description 1
• IWYDHOAUDWTVEP-UHFFFAOYSA-N R-2-phenyl-2-hydroxyacetic acid Natural products OC(=O)C(O)C1=CC=CC=C1 IWYDHOAUDWTVEP-UHFFFAOYSA-N 0.000 description 1
• 241000700159 Rattus Species 0.000 description 1
• 102000007156 Resistin Human genes 0.000 description 1
• 108010047909 Resistin Proteins 0.000 description 1
• 208000017442 Retinal disease Diseases 0.000 description 1
• 206010038923 Retinopathy Diseases 0.000 description 1
• 108010077895 Sarcosine Proteins 0.000 description 1
• 102000000019 Sterol Esterase Human genes 0.000 description 1
• 108010055297 Sterol Esterase Proteins 0.000 description 1
• 208000006011 Stroke Diseases 0.000 description 1
• KDYFGRWQOYBRFD-UHFFFAOYSA-N Succinic acid Natural products OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 description 1
• 102220564325 TIR domain-containing adapter molecule 2_S16E_mutation Human genes 0.000 description 1
• FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 1
• 102000004408 Transcription factor TFIIB Human genes 0.000 description 1
• 108090000941 Transcription factor TFIIB Proteins 0.000 description 1
• 102000004887 Transforming Growth Factor beta Human genes 0.000 description 1
• 108090001012 Transforming Growth Factor beta Proteins 0.000 description 1
• RHQDFWAXVIIEBN-UHFFFAOYSA-N Trifluoroethanol Chemical compound OCC(F)(F)F RHQDFWAXVIIEBN-UHFFFAOYSA-N 0.000 description 1
• QIVBCDIJIAJPQS-UHFFFAOYSA-N Tryptophan Natural products C1=CC=C2C(CC(N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-UHFFFAOYSA-N 0.000 description 1
• QZOSVNLXLSNHQK-UWVGGRQHSA-N Tyr-Asp Chemical compound OC(=O)C[C@@H](C(O)=O)NC(=O)[C@@H](N)CC1=CC=C(O)C=C1 QZOSVNLXLSNHQK-UWVGGRQHSA-N 0.000 description 1
• PDSLRCZINIDLMU-QWRGUYRKSA-N Tyr-Glu Chemical compound OC(=O)CC[C@@H](C(O)=O)NC(=O)[C@@H](N)CC1=CC=C(O)C=C1 PDSLRCZINIDLMU-QWRGUYRKSA-N 0.000 description 1
• 244000000188 Vaccinium ovalifolium Species 0.000 description 1
• 238000006959 Williamson synthesis reaction Methods 0.000 description 1
• PTFCDOFLOPIGGS-UHFFFAOYSA-N Zinc dication Chemical compound [Zn+2] PTFCDOFLOPIGGS-UHFFFAOYSA-N 0.000 description 1
• 210000001015 abdomen Anatomy 0.000 description 1
• 201000010390 abdominal obesity-metabolic syndrome 1 Diseases 0.000 description 1
• 230000005856 abnormality Effects 0.000 description 1
• 230000021736 acetylation Effects 0.000 description 1
• 238000006640 acetylation reaction Methods 0.000 description 1
• 230000003213 activating effect Effects 0.000 description 1
• 150000001263 acyl chlorides Chemical class 0.000 description 1
• 239000000654 additive Substances 0.000 description 1
• 230000000996 additive effect Effects 0.000 description 1
• 210000001789 adipocyte Anatomy 0.000 description 1
• 210000000593 adipose tissue white Anatomy 0.000 description 1
• 230000002776 aggregation Effects 0.000 description 1
• 238000004220 aggregation Methods 0.000 description 1
• 230000032683 aging Effects 0.000 description 1
• 230000001476 alcoholic effect Effects 0.000 description 1
• 208000002353 alcoholic hepatitis Diseases 0.000 description 1
• 150000001350 alkyl halides Chemical class 0.000 description 1
• BJEPYKJPYRNKOW-UHFFFAOYSA-N alpha-hydroxysuccinic acid Natural products OC(=O)C(O)CC(O)=O BJEPYKJPYRNKOW-UHFFFAOYSA-N 0.000 description 1
• 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
• 230000009435 amidation Effects 0.000 description 1
• 238000007112 amidation reaction Methods 0.000 description 1
• 229940124277 aminobutyric acid Drugs 0.000 description 1
• 150000008064 anhydrides Chemical class 0.000 description 1
• 230000003042 antagnostic effect Effects 0.000 description 1
• 230000003466 anti-cipated effect Effects 0.000 description 1
• 230000003178 anti-diabetic effect Effects 0.000 description 1
• 230000003579 anti-obesity Effects 0.000 description 1
• 239000003472 antidiabetic agent Substances 0.000 description 1
• 210000001367 artery Anatomy 0.000 description 1
• 125000003118 aryl group Chemical group 0.000 description 1
• 125000000613 asparagine group Chemical group N[C@@H](CC(N)=O)C(=O)* 0.000 description 1
• 229940009098 aspartate Drugs 0.000 description 1
• 230000000923 atherogenic effect Effects 0.000 description 1
• 230000008901 benefit Effects 0.000 description 1
• 235000010233 benzoic acid Nutrition 0.000 description 1
• 239000003833 bile salt Substances 0.000 description 1
• 230000023555 blood coagulation Effects 0.000 description 1
• KDPAWGWELVVRCH-UHFFFAOYSA-N bromoacetic acid Chemical compound OC(=O)CBr KDPAWGWELVVRCH-UHFFFAOYSA-N 0.000 description 1
• 239000007853 buffer solution Substances 0.000 description 1
• 244000309464 bull Species 0.000 description 1
• KDYFGRWQOYBRFD-NUQCWPJISA-N butanedioic acid Chemical compound O[14C](=O)CC[14C](O)=O KDYFGRWQOYBRFD-NUQCWPJISA-N 0.000 description 1
• 238000013262 cAMP assay Methods 0.000 description 1
• 239000011575 calcium Substances 0.000 description 1
• 229910052791 calcium Inorganic materials 0.000 description 1
• 239000004202 carbamide Substances 0.000 description 1
• 150000001720 carbohydrates Chemical class 0.000 description 1
• 235000014633 carbohydrates Nutrition 0.000 description 1
• 125000004112 carboxyamino group Chemical group [H]OC(=O)N([H])[*] 0.000 description 1
• 150000001244 carboxylic acid anhydrides Chemical class 0.000 description 1
• 125000002057 carboxymethyl group Chemical group [H]OC(=O)C([H])([H])[*] 0.000 description 1
• 239000003054 catalyst Substances 0.000 description 1
• 238000006555 catalytic reaction Methods 0.000 description 1
• 238000012512 characterization method Methods 0.000 description 1
• 125000003636 chemical group Chemical group 0.000 description 1
• RUDATBOHQWOJDD-BSWAIDMHSA-N chenodeoxycholic acid Chemical compound C([C@H]1C[C@H]2O)[C@H](O)CC[C@]1(C)[C@@H]1[C@@H]2[C@@H]2CC[C@H]([C@@H](CCC(O)=O)C)[C@@]2(C)CC1 RUDATBOHQWOJDD-BSWAIDMHSA-N 0.000 description 1
• 229960001091 chenodeoxycholic acid Drugs 0.000 description 1
• VIMWCINSBRXAQH-UHFFFAOYSA-M chloro-(2-hydroxy-5-nitrophenyl)mercury Chemical compound OC1=CC=C([N+]([O-])=O)C=C1[Hg]Cl VIMWCINSBRXAQH-UHFFFAOYSA-M 0.000 description 1
• VXIVSQZSERGHQP-UHFFFAOYSA-N chloroacetamide Chemical compound NC(=O)CCl VXIVSQZSERGHQP-UHFFFAOYSA-N 0.000 description 1
• 229940106681 chloroacetic acid Drugs 0.000 description 1
• 235000013985 cinnamic acid Nutrition 0.000 description 1
• 229930016911 cinnamic acid Natural products 0.000 description 1
• 229960004106 citric acid Drugs 0.000 description 1
• 235000015165 citric acid Nutrition 0.000 description 1
• 238000011260 co-administration Methods 0.000 description 1
• 230000000112 colonic effect Effects 0.000 description 1
• 238000009833 condensation Methods 0.000 description 1
• 230000005494 condensation Effects 0.000 description 1
• 239000000356 contaminant Substances 0.000 description 1
• 239000003431 cross linking reagent Substances 0.000 description 1
• 125000004122 cyclic group Chemical group 0.000 description 1
• OILAIQUEIWYQPH-UHFFFAOYSA-N cyclohexane-1,2-dione Chemical compound O=C1CCCCC1=O OILAIQUEIWYQPH-UHFFFAOYSA-N 0.000 description 1
• WJTCGQSWYFHTAC-UHFFFAOYSA-N cyclooctane Chemical compound C1CCCCCCC1 WJTCGQSWYFHTAC-UHFFFAOYSA-N 0.000 description 1
• 239000004914 cyclooctane Substances 0.000 description 1
• 229960003067 cystine Drugs 0.000 description 1
• 235000021316 daily nutritional intake Nutrition 0.000 description 1
• 125000002704 decyl group Chemical group [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])* 0.000 description 1
• 230000007812 deficiency Effects 0.000 description 1
• 230000007850 degeneration Effects 0.000 description 1
• 230000018044 dehydration Effects 0.000 description 1
• 238000006297 dehydration reaction Methods 0.000 description 1
• 229940039227 diagnostic agent Drugs 0.000 description 1
• 239000000032 diagnostic agent Substances 0.000 description 1
• 125000001142 dicarboxylic acid group Chemical group 0.000 description 1
• FFYPMLJYZAEMQB-UHFFFAOYSA-N diethyl pyrocarbonate Chemical compound CCOC(=O)OC(=O)OCC FFYPMLJYZAEMQB-UHFFFAOYSA-N 0.000 description 1
• 230000001079 digestive effect Effects 0.000 description 1
• 239000003085 diluting agent Substances 0.000 description 1
• LOKCTEFSRHRXRJ-UHFFFAOYSA-I dipotassium trisodium dihydrogen phosphate hydrogen phosphate dichloride Chemical compound P(=O)(O)(O)[O-].[K+].P(=O)(O)([O-])[O-].[Na+].[Na+].[Cl-].[K+].[Cl-].[Na+] LOKCTEFSRHRXRJ-UHFFFAOYSA-I 0.000 description 1
• 238000009826 distribution Methods 0.000 description 1
• POULHZVOKOAJMA-UHFFFAOYSA-N dodecanoic acid Chemical compound CCCCCCCCCCCC(O)=O POULHZVOKOAJMA-UHFFFAOYSA-N 0.000 description 1
• 230000002708 enhancing effect Effects 0.000 description 1
• 230000002255 enzymatic effect Effects 0.000 description 1
• 210000003238 esophagus Anatomy 0.000 description 1
• 125000004185 ester group Chemical group 0.000 description 1
• 230000032050 esterification Effects 0.000 description 1
• 238000005886 esterification reaction Methods 0.000 description 1
• CCIVGXIOQKPBKL-UHFFFAOYSA-M ethanesulfonate Chemical compound CCS([O-])(=O)=O CCIVGXIOQKPBKL-UHFFFAOYSA-M 0.000 description 1
• 235000019441 ethanol Nutrition 0.000 description 1
• 229940093476 ethylene glycol Drugs 0.000 description 1
• 150000002190 fatty acyls Chemical group 0.000 description 1
• 239000012634 fragment Substances 0.000 description 1
• 239000001530 fumaric acid Substances 0.000 description 1
• 235000011087 fumaric acid Nutrition 0.000 description 1
• 229940083124 ganglion-blocking antiadrenergic secondary and tertiary amines Drugs 0.000 description 1
• 230000030136 gastric emptying Effects 0.000 description 1
• 238000010353 genetic engineering Methods 0.000 description 1
• 208000004104 gestational diabetes Diseases 0.000 description 1
• TWSALRJGPBVBQU-PKQQPRCHSA-N glucagon-like peptide 2 Chemical compound C([C@@H](C(=O)N[C@H](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]([C@@H](C)CC)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC(O)=O)C(O)=O)[C@@H](C)CC)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](C)NC(=O)[C@H](C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](NC(=O)[C@@H](NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CCSC)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CO)NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@H](CO)NC(=O)CNC(=O)[C@H](CC(O)=O)NC(=O)[C@H](C)NC(=O)[C@@H](N)CC=1NC=NC=1)[C@@H](C)O)[C@@H](C)CC)C1=CC=CC=C1 TWSALRJGPBVBQU-PKQQPRCHSA-N 0.000 description 1
• 230000014101 glucose homeostasis Effects 0.000 description 1
• 229940096919 glycogen Drugs 0.000 description 1
• 229930182470 glycoside Natural products 0.000 description 1
• 150000002338 glycosides Chemical class 0.000 description 1
• HHLFWLYXYJOTON-UHFFFAOYSA-N glyoxylic acid Chemical compound OC(=O)C=O HHLFWLYXYJOTON-UHFFFAOYSA-N 0.000 description 1
• 230000012010 growth Effects 0.000 description 1
• ZRALSGWEFCBTJO-UHFFFAOYSA-N guanidine group Chemical group NC(=N)N ZRALSGWEFCBTJO-UHFFFAOYSA-N 0.000 description 1
• 125000005179 haloacetyl group Chemical group 0.000 description 1
• 229910052736 halogen Inorganic materials 0.000 description 1
• 150000002367 halogens Chemical class 0.000 description 1
• 230000036541 health Effects 0.000 description 1
• 231100000844 hepatocellular carcinoma Toxicity 0.000 description 1
• 206010073071 hepatocellular carcinoma Diseases 0.000 description 1
• 239000000833 heterodimer Substances 0.000 description 1
• 238000005734 heterodimerization reaction Methods 0.000 description 1
• 125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
• 238000004128 high performance liquid chromatography Methods 0.000 description 1
• 239000000710 homodimer Substances 0.000 description 1
• 230000003054 hormonal effect Effects 0.000 description 1
• 150000002431 hydrogen Chemical class 0.000 description 1
• 230000003301 hydrolyzing effect Effects 0.000 description 1
• WGCNASOHLSPBMP-UHFFFAOYSA-N hydroxyacetaldehyde Natural products OCC=O WGCNASOHLSPBMP-UHFFFAOYSA-N 0.000 description 1
• 230000033444 hydroxylation Effects 0.000 description 1
• 238000005805 hydroxylation reaction Methods 0.000 description 1
• 150000002463 imidates Chemical class 0.000 description 1
• RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Substances C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 1
• 230000001900 immune effect Effects 0.000 description 1
• 230000005847 immunogenicity Effects 0.000 description 1
• 230000006872 improvement Effects 0.000 description 1
• 238000000338 in vitro Methods 0.000 description 1
• 238000000099 in vitro assay Methods 0.000 description 1
• 238000010874 in vitro model Methods 0.000 description 1
• 210000004969 inflammatory cell Anatomy 0.000 description 1
• 230000005764 inhibitory process Effects 0.000 description 1
• 238000003780 insertion Methods 0.000 description 1
• 230000037431 insertion Effects 0.000 description 1
• 230000003914 insulin secretion Effects 0.000 description 1
• 230000000968 intestinal effect Effects 0.000 description 1
• 238000007918 intramuscular administration Methods 0.000 description 1
• 238000001990 intravenous administration Methods 0.000 description 1
• JDNTWHVOXJZDSN-UHFFFAOYSA-N iodoacetic acid Chemical compound OC(=O)CI JDNTWHVOXJZDSN-UHFFFAOYSA-N 0.000 description 1
• 208000028867 ischemia Diseases 0.000 description 1
• 238000002955 isolation Methods 0.000 description 1
• 238000006317 isomerization reaction Methods 0.000 description 1
• SRJOCJYGOFTFLH-UHFFFAOYSA-N isonipecotic acid Chemical compound OC(=O)C1CCNCC1 SRJOCJYGOFTFLH-UHFFFAOYSA-N 0.000 description 1
• 208000017169 kidney disease Diseases 0.000 description 1
• 238000011813 knockout mouse model Methods 0.000 description 1
• NRYBAZVQPHGZNS-ZSOCWYAHSA-N leptin Chemical compound O=C([C@H](CO)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CC=1C2=CC=CC=C2NC=1)NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CO)NC(=O)CNC(=O)[C@H](CCC(N)=O)NC(=O)[C@@H](N)CC(C)C)CCSC)N1CCC[C@H]1C(=O)NCC(=O)N[C@@H](CS)C(O)=O NRYBAZVQPHGZNS-ZSOCWYAHSA-N 0.000 description 1
• 229940039781 leptin Drugs 0.000 description 1
• 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 1
• 102000019758 lipid binding proteins Human genes 0.000 description 1
• 229910052744 lithium Inorganic materials 0.000 description 1
• 231100000832 liver cell necrosis Toxicity 0.000 description 1
• 239000008176 lyophilized powder Substances 0.000 description 1
• 229960003646 lysine Drugs 0.000 description 1
• 108010003700 lysyl aspartic acid Proteins 0.000 description 1
• 108010009298 lysylglutamic acid Proteins 0.000 description 1
• 238000005710 macrocyclization reaction Methods 0.000 description 1
• 159000000003 magnesium salts Chemical class 0.000 description 1
• VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
• 239000011976 maleic acid Substances 0.000 description 1
• 125000005439 maleimidyl group Chemical group C1(C=CC(N1*)=O)=O 0.000 description 1
• 239000001630 malic acid Substances 0.000 description 1
• 235000011090 malic acid Nutrition 0.000 description 1
• 229960002510 mandelic acid Drugs 0.000 description 1
• 235000012054 meals Nutrition 0.000 description 1
• 238000002483 medication Methods 0.000 description 1
• 230000002503 metabolic effect Effects 0.000 description 1
• 208000011661 metabolic syndrome X Diseases 0.000 description 1
• 229940098779 methanesulfonic acid Drugs 0.000 description 1
• 229930182817 methionine Natural products 0.000 description 1
• WBYWAXJHAXSJNI-UHFFFAOYSA-N methyl p-hydroxycinnamate Natural products OC(=O)C=CC1=CC=CC=C1 WBYWAXJHAXSJNI-UHFFFAOYSA-N 0.000 description 1
• NEGQCMNHXHSFGU-UHFFFAOYSA-N methyl pyridine-2-carboximidate Chemical compound COC(=N)C1=CC=CC=N1 NEGQCMNHXHSFGU-UHFFFAOYSA-N 0.000 description 1
• KRKPYFLIYNGWTE-UHFFFAOYSA-N n,o-dimethylhydroxylamine Chemical compound CNOC KRKPYFLIYNGWTE-UHFFFAOYSA-N 0.000 description 1
• 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
• 230000017074 necrotic cell death Effects 0.000 description 1
• 230000023187 negative regulation of glucagon secretion Effects 0.000 description 1
• 230000007935 neutral effect Effects 0.000 description 1
• 210000000440 neutrophil Anatomy 0.000 description 1
• FEMOMIGRRWSMCU-UHFFFAOYSA-N ninhydrin Chemical compound C1=CC=C2C(=O)C(O)(O)C(=O)C2=C1 FEMOMIGRRWSMCU-UHFFFAOYSA-N 0.000 description 1
• 229910017604 nitric acid Inorganic materials 0.000 description 1
• 231100000252 nontoxic Toxicity 0.000 description 1
• 230000003000 nontoxic effect Effects 0.000 description 1
• 102000044158 nucleic acid binding protein Human genes 0.000 description 1
• 108700020942 nucleic acid binding protein Proteins 0.000 description 1
• TWHMVKPVFOOAMY-UHFFFAOYSA-N octanedioic acid Chemical compound OC(=O)CCCCCCC(O)=O.OC(=O)CCCCCCC(O)=O TWHMVKPVFOOAMY-UHFFFAOYSA-N 0.000 description 1
• 125000002347 octyl group Chemical group [H]C([*])([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
• 210000000056 organ Anatomy 0.000 description 1
• 230000008520 organization Effects 0.000 description 1
• 235000006408 oxalic acid Nutrition 0.000 description 1
• 230000036542 oxidative stress Effects 0.000 description 1
• YFZOUMNUDGGHIW-UHFFFAOYSA-M p-chloromercuribenzoic acid Chemical compound OC(=O)C1=CC=C([Hg]Cl)C=C1 YFZOUMNUDGGHIW-UHFFFAOYSA-M 0.000 description 1
• 101800002712 p27 Proteins 0.000 description 1
• 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 1
• 210000000496 pancreas Anatomy 0.000 description 1
• FJKROLUGYXJWQN-UHFFFAOYSA-N papa-hydroxy-benzoic acid Natural products OC(=O)C1=CC=C(O)C=C1 FJKROLUGYXJWQN-UHFFFAOYSA-N 0.000 description 1
• 230000003950 pathogenic mechanism Effects 0.000 description 1
• 229960001639 penicillamine Drugs 0.000 description 1
• 239000000816 peptidomimetic Substances 0.000 description 1
• 239000000546 pharmaceutical excipient Substances 0.000 description 1
• 239000010452 phosphate Substances 0.000 description 1
• NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
• 239000002953 phosphate buffered saline Substances 0.000 description 1
• HMFAQQIORZDPJG-UHFFFAOYSA-N phosphono 2-chloroacetate Chemical compound OP(O)(=O)OC(=O)CCl HMFAQQIORZDPJG-UHFFFAOYSA-N 0.000 description 1
• DCWXELXMIBXGTH-QMMMGPOBSA-N phosphonotyrosine Chemical compound OC(=O)[C@@H](N)CC1=CC=C(OP(O)(O)=O)C=C1 DCWXELXMIBXGTH-QMMMGPOBSA-N 0.000 description 1
• 229910052698 phosphorus Inorganic materials 0.000 description 1
• 230000004962 physiological condition Effects 0.000 description 1
• 230000035790 physiological processes and functions Effects 0.000 description 1
• 229920000191 poly(N-vinyl pyrrolidone) Polymers 0.000 description 1
• 108010064470 polyaspartate Proteins 0.000 description 1
• 229920000573 polyethylene Polymers 0.000 description 1
• 229920002643 polyglutamic acid Polymers 0.000 description 1
• 229920000656 polylysine Polymers 0.000 description 1
• 238000006116 polymerization reaction Methods 0.000 description 1
• 229920001451 polypropylene glycol Polymers 0.000 description 1
• 108010022457 polysaccharide peptide Proteins 0.000 description 1
• 229920002451 polyvinyl alcohol Polymers 0.000 description 1
• 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
• 229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
• 239000001267 polyvinylpyrrolidone Substances 0.000 description 1
• 230000004481 post-translational protein modification Effects 0.000 description 1
• 239000011591 potassium Substances 0.000 description 1
• 229960003975 potassium Drugs 0.000 description 1
• 229910052700 potassium Inorganic materials 0.000 description 1
• 239000002243 precursor Substances 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
• 150000003141 primary amines Chemical class 0.000 description 1
• 239000000047 product Substances 0.000 description 1
• 230000000770 proinflammatory effect Effects 0.000 description 1
• 238000011321 prophylaxis Methods 0.000 description 1
• 230000003331 prothrombotic effect Effects 0.000 description 1
• 230000005180 public health Effects 0.000 description 1
• 229960003581 pyridoxal Drugs 0.000 description 1
• 235000008164 pyridoxal Nutrition 0.000 description 1
• 239000011674 pyridoxal Substances 0.000 description 1
• 235000007682 pyridoxal 5'-phosphate Nutrition 0.000 description 1
• 239000011589 pyridoxal 5'-phosphate Substances 0.000 description 1
• 229960001327 pyridoxal phosphate Drugs 0.000 description 1
• 229940107700 pyruvic acid Drugs 0.000 description 1
• 229920005604 random copolymer Polymers 0.000 description 1
• 238000003753 real-time PCR Methods 0.000 description 1
• 230000010410 reperfusion Effects 0.000 description 1
• 238000006798 ring closing metathesis reaction Methods 0.000 description 1
• XMVJITFPVVRMHC-UHFFFAOYSA-N roxarsone Chemical group OC1=CC=C([As](O)(O)=O)C=C1[N+]([O-])=O XMVJITFPVVRMHC-UHFFFAOYSA-N 0.000 description 1
• 102200082889 rs63750840 Human genes 0.000 description 1
• 102220058219 rs730881936 Human genes 0.000 description 1
• 229960004889 salicylic acid Drugs 0.000 description 1
• 229940043230 sarcosine Drugs 0.000 description 1
• 230000028327 secretion Effects 0.000 description 1
• 229940055619 selenocysteine Drugs 0.000 description 1
• 235000016491 selenocysteine Nutrition 0.000 description 1
• ZKZBPNGNEQAJSX-UHFFFAOYSA-N selenocysteine Natural products [SeH]CC(N)C(O)=O ZKZBPNGNEQAJSX-UHFFFAOYSA-N 0.000 description 1
• 210000000813 small intestine Anatomy 0.000 description 1
• 239000011734 sodium Substances 0.000 description 1
• 229910052708 sodium Inorganic materials 0.000 description 1
• IHQKEDIOMGYHEB-UHFFFAOYSA-M sodium dimethylarsinate Chemical compound [Na+].C[As](C)([O-])=O IHQKEDIOMGYHEB-UHFFFAOYSA-M 0.000 description 1
• 241000894007 species Species 0.000 description 1
• 230000003595 spectral effect Effects 0.000 description 1
• 238000003860 storage Methods 0.000 description 1
• 208000023516 stroke disease Diseases 0.000 description 1
• 238000007920 subcutaneous administration Methods 0.000 description 1
• 239000000126 substance Substances 0.000 description 1
• 239000000758 substrate Substances 0.000 description 1
• 229940014800 succinic anhydride Drugs 0.000 description 1
• 229960002317 succinimide Drugs 0.000 description 1
• 235000000346 sugar Nutrition 0.000 description 1
• 229940124530 sulfonamide Drugs 0.000 description 1
• 150000003871 sulfonates Chemical class 0.000 description 1
• 150000003457 sulfones Chemical class 0.000 description 1
• 125000000542 sulfonic acid group Chemical group 0.000 description 1
• 150000003463 sulfur Chemical class 0.000 description 1
• 239000011593 sulfur Substances 0.000 description 1
• 125000004434 sulfur atom Chemical group 0.000 description 1
• 230000002195 synergetic effect Effects 0.000 description 1
• 230000008685 targeting Effects 0.000 description 1
• 235000002906 tartaric acid Nutrition 0.000 description 1
• 239000011975 tartaric acid Substances 0.000 description 1
• ZRKFYGHZFMAOKI-QMGMOQQFSA-N tgfbeta Chemical compound C([C@H](NC(=O)[C@H](C(C)C)NC(=O)CNC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H]([C@@H](C)O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H]([C@@H](C)O)NC(=O)[C@H](CC(C)C)NC(=O)CNC(=O)[C@H](C)NC(=O)[C@H](CO)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@@H](NC(=O)[C@H](C)NC(=O)[C@H](C)NC(=O)[C@@H](NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](N)CCSC)C(C)C)[C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](C)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](CCC(O)=O)C(=O)N[C@@H](C)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](C)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](CCCNC(N)=N)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(C)C)C(O)=O)C1=CC=C(O)C=C1 ZRKFYGHZFMAOKI-QMGMOQQFSA-N 0.000 description 1
• ITMCEJHCFYSIIV-UHFFFAOYSA-M triflate Chemical compound [O-]S(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-M 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
• 230000034512 ubiquitination Effects 0.000 description 1
• 238000010798 ubiquitination Methods 0.000 description 1
• 229910052720 vanadium Inorganic materials 0.000 description 1
• 230000002792 vascular Effects 0.000 description 1
• 230000024883 vasodilation Effects 0.000 description 1
• 239000002435 venom Substances 0.000 description 1
• 210000001048 venom Anatomy 0.000 description 1
• 231100000611 venom Toxicity 0.000 description 1
• 239000000080 wetting agent Substances 0.000 description 1
• 238000002424 x-ray crystallography Methods 0.000 description 1
• 229910052727 yttrium Inorganic materials 0.000 description 1
• ORQXBVXKBGUSBA-QMMMGPOBSA-N β-cyclohexyl-alanine Chemical compound OC(=O)[C@@H](N)CC1CCCCC1 ORQXBVXKBGUSBA-QMMMGPOBSA-N 0.000 description 1