CN113563423A - 白细胞介素-23受体的口服肽抑制剂以及其治疗炎症性肠病的用途 - Google Patents
白细胞介素-23受体的口服肽抑制剂以及其治疗炎症性肠病的用途 Download PDFInfo
- Publication number
- CN113563423A CN113563423A CN202110848583.3A CN202110848583A CN113563423A CN 113563423 A CN113563423 A CN 113563423A CN 202110848583 A CN202110848583 A CN 202110848583A CN 113563423 A CN113563423 A CN 113563423A
- Authority
- CN
- China
- Prior art keywords
- phe
- lys
- nal
- amino acid
- glu
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
- 108090000765 processed proteins & peptides Proteins 0.000 title claims abstract description 325
- 239000003112 inhibitor Substances 0.000 title claims abstract description 232
- 102100036672 Interleukin-23 receptor Human genes 0.000 title claims abstract description 62
- 101710195550 Interleukin-23 receptor Proteins 0.000 title claims abstract description 61
- 208000022559 Inflammatory bowel disease Diseases 0.000 title claims abstract description 31
- 239000000539 dimer Substances 0.000 claims abstract description 36
- 238000000034 method Methods 0.000 claims abstract description 29
- 125000003275 alpha amino acid group Chemical group 0.000 claims abstract description 27
- 150000003839 salts Chemical class 0.000 claims abstract description 25
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 16
- 239000012453 solvate Substances 0.000 claims abstract description 6
- 239000003937 drug carrier Substances 0.000 claims abstract description 3
- COLNVLDHVKWLRT-QMMMGPOBSA-N L-phenylalanine Chemical class OC(=O)[C@@H](N)CC1=CC=CC=C1 COLNVLDHVKWLRT-QMMMGPOBSA-N 0.000 claims description 921
- -1 N-MeGln Chemical compound 0.000 claims description 465
- 150000001413 amino acids Chemical class 0.000 claims description 322
- WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 claims description 284
- KDXKERNSBIXSRK-YFKPBYRVSA-N L-lysine Chemical compound NCCCC[C@H](N)C(O)=O KDXKERNSBIXSRK-YFKPBYRVSA-N 0.000 claims description 281
- DCXYFEDJOCDNAF-REOHCLBHSA-N L-asparagine Chemical compound OC(=O)[C@@H](N)CC(N)=O DCXYFEDJOCDNAF-REOHCLBHSA-N 0.000 claims description 255
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 claims description 223
- ZDXPYRJPNDTMRX-VKHMYHEASA-N L-glutamine Chemical compound OC(=O)[C@@H](N)CCC(N)=O ZDXPYRJPNDTMRX-VKHMYHEASA-N 0.000 claims description 209
- OUYCCCASQSFEME-QMMMGPOBSA-N L-tyrosine Chemical class OC(=O)[C@@H](N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-QMMMGPOBSA-N 0.000 claims description 193
- ROHFNLRQFUQHCH-YFKPBYRVSA-N L-leucine Chemical compound CC(C)C[C@H](N)C(O)=O ROHFNLRQFUQHCH-YFKPBYRVSA-N 0.000 claims description 155
- AYFVYJQAPQTCCC-GBXIJSLDSA-N L-threonine Chemical compound C[C@@H](O)[C@H](N)C(O)=O AYFVYJQAPQTCCC-GBXIJSLDSA-N 0.000 claims description 142
- MTCFGRXMJLQNBG-REOHCLBHSA-N (2S)-2-Amino-3-hydroxypropansäure Chemical compound OC[C@H](N)C(O)=O MTCFGRXMJLQNBG-REOHCLBHSA-N 0.000 claims description 138
- FUOOLUPWFVMBKG-UHFFFAOYSA-N 2-Aminoisobutyric acid Chemical compound CC(C)(N)C(O)=O FUOOLUPWFVMBKG-UHFFFAOYSA-N 0.000 claims description 128
- ODKSFYDXXFIFQN-BYPYZUCNSA-N L-arginine Chemical compound OC(=O)[C@@H](N)CCCN=C(N)N ODKSFYDXXFIFQN-BYPYZUCNSA-N 0.000 claims description 125
- DTERQYGMUDWYAZ-UHFFFAOYSA-N N-acetyl-N-thioacetyl-Lysine Natural products CC(=O)NCCCCC(N)C(O)=O DTERQYGMUDWYAZ-UHFFFAOYSA-N 0.000 claims description 124
- KZSNJWFQEVHDMF-UHFFFAOYSA-N Valine Chemical compound CC(C)C(N)C(O)=O KZSNJWFQEVHDMF-UHFFFAOYSA-N 0.000 claims description 122
- CKLJMWTZIZZHCS-REOHCLBHSA-N L-aspartic acid Chemical compound OC(=O)[C@@H](N)CC(O)=O CKLJMWTZIZZHCS-REOHCLBHSA-N 0.000 claims description 113
- 240000002390 Pandanus odoratissimus Species 0.000 claims description 77
- 235000005311 Pandanus odoratissimus Nutrition 0.000 claims description 77
- ODKSFYDXXFIFQN-UHFFFAOYSA-N Arginine Chemical compound OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 claims description 69
- ROHFNLRQFUQHCH-UHFFFAOYSA-N Leucine Chemical compound CC(C)CC(N)C(O)=O ROHFNLRQFUQHCH-UHFFFAOYSA-N 0.000 claims description 69
- 108010065637 Interleukin-23 Proteins 0.000 claims description 64
- 102000013264 Interleukin-23 Human genes 0.000 claims description 64
- 229940124829 interleukin-23 Drugs 0.000 claims description 64
- QNAYBMKLOCPYGJ-UHFFFAOYSA-N D-alpha-Ala Natural products CC([NH3+])C([O-])=O QNAYBMKLOCPYGJ-UHFFFAOYSA-N 0.000 claims description 56
- UCMIRNVEIXFBKS-UHFFFAOYSA-N beta-alanine Chemical compound NCCC(O)=O UCMIRNVEIXFBKS-UHFFFAOYSA-N 0.000 claims description 56
- QWCKQJZIFLGMSD-UHFFFAOYSA-N alpha-aminobutyric acid Chemical compound CCC(N)C(O)=O QWCKQJZIFLGMSD-UHFFFAOYSA-N 0.000 claims description 55
- WHUUTDBJXJRKMK-GSVOUGTGSA-N D-glutamic acid Chemical compound OC(=O)[C@H](N)CCC(O)=O WHUUTDBJXJRKMK-GSVOUGTGSA-N 0.000 claims description 46
- 239000004471 Glycine Substances 0.000 claims description 40
- CKLJMWTZIZZHCS-UHFFFAOYSA-N D-OH-Asp Natural products OC(=O)C(N)CC(O)=O CKLJMWTZIZZHCS-UHFFFAOYSA-N 0.000 claims description 34
- CKLJMWTZIZZHCS-UWTATZPHSA-N D-aspartic acid Chemical compound OC(=O)[C@H](N)CC(O)=O CKLJMWTZIZZHCS-UWTATZPHSA-N 0.000 claims description 34
- DPDPQQHHTHKSRN-UHFFFAOYSA-N 4-aminooxane-4-carboxylic acid Chemical compound OC(=O)C1(N)CCOCC1 DPDPQQHHTHKSRN-UHFFFAOYSA-N 0.000 claims description 30
- XUJNEKJLAYXESH-UHFFFAOYSA-N Cysteine Chemical compound SCC(N)C(O)=O XUJNEKJLAYXESH-UHFFFAOYSA-N 0.000 claims description 30
- 125000000174 L-prolyl group Chemical group [H]N1C([H])([H])C([H])([H])C([H])([H])[C@@]1([H])C(*)=O 0.000 claims description 26
- 125000005647 linker group Chemical group 0.000 claims description 26
- 239000000178 monomer Substances 0.000 claims description 26
- QNAYBMKLOCPYGJ-UWTATZPHSA-N D-alanine Chemical compound C[C@@H](N)C(O)=O QNAYBMKLOCPYGJ-UWTATZPHSA-N 0.000 claims description 25
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 25
- XUJNEKJLAYXESH-UWTATZPHSA-N D-Cysteine Chemical compound SC[C@@H](N)C(O)=O XUJNEKJLAYXESH-UWTATZPHSA-N 0.000 claims description 23
- NTWVQPHTOUKMDI-YFKPBYRVSA-N N-Methyl-arginine Chemical compound CN[C@H](C(O)=O)CCCN=C(N)N NTWVQPHTOUKMDI-YFKPBYRVSA-N 0.000 claims description 22
- DCXYFEDJOCDNAF-UWTATZPHSA-N D-Asparagine Chemical compound OC(=O)[C@H](N)CC(N)=O DCXYFEDJOCDNAF-UWTATZPHSA-N 0.000 claims description 20
- PECYZEOJVXMISF-UWTATZPHSA-N 3-amino-D-alanine Chemical compound NC[C@@H](N)C(O)=O PECYZEOJVXMISF-UWTATZPHSA-N 0.000 claims description 19
- ODHCTXKNWHHXJC-VKHMYHEASA-N 5-oxo-L-proline Chemical compound OC(=O)[C@@H]1CCC(=O)N1 ODHCTXKNWHHXJC-VKHMYHEASA-N 0.000 claims description 19
- KDXKERNSBIXSRK-RXMQYKEDSA-N D-lysine Chemical compound NCCCC[C@@H](N)C(O)=O KDXKERNSBIXSRK-RXMQYKEDSA-N 0.000 claims description 19
- ODHCTXKNWHHXJC-GSVOUGTGSA-N Pyroglutamic acid Natural products OC(=O)[C@H]1CCC(=O)N1 ODHCTXKNWHHXJC-GSVOUGTGSA-N 0.000 claims description 19
- ODHCTXKNWHHXJC-UHFFFAOYSA-N acide pyroglutamique Natural products OC(=O)C1CCC(=O)N1 ODHCTXKNWHHXJC-UHFFFAOYSA-N 0.000 claims description 19
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 claims description 19
- 230000027455 binding Effects 0.000 claims description 19
- 150000001875 compounds Chemical class 0.000 claims description 18
- 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 claims description 17
- 125000000393 L-methionino group Chemical group [H]OC(=O)[C@@]([H])(N([H])[*])C([H])([H])C(SC([H])([H])[H])([H])[H] 0.000 claims description 17
- KDYFGRWQOYBRFD-UHFFFAOYSA-N succinic acid Chemical compound OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 claims description 17
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 16
- BXRLWGXPSRYJDZ-UHFFFAOYSA-N 3-cyanoalanine Chemical compound OC(=O)C(N)CC#N BXRLWGXPSRYJDZ-UHFFFAOYSA-N 0.000 claims description 15
- DGYHPLMPMRKMPD-UHFFFAOYSA-N L-propargyl glycine Natural products OC(=O)C(N)CC#C DGYHPLMPMRKMPD-UHFFFAOYSA-N 0.000 claims description 15
- AGPKZVBTJJNPAG-WHFBIAKZSA-N L-isoleucine Chemical compound CC[C@H](C)[C@H](N)C(O)=O AGPKZVBTJJNPAG-WHFBIAKZSA-N 0.000 claims description 14
- 201000004681 Psoriasis Diseases 0.000 claims description 13
- 239000000126 substance Chemical group 0.000 claims description 13
- 241000700159 Rattus Species 0.000 claims description 12
- RTBFRGCFXZNCOE-UHFFFAOYSA-N 1-methylsulfonylpiperidin-4-one Chemical compound CS(=O)(=O)N1CCC(=O)CC1 RTBFRGCFXZNCOE-UHFFFAOYSA-N 0.000 claims description 11
- 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 claims description 11
- DHXVGJBLRPWPCS-UHFFFAOYSA-N Tetrahydropyran Chemical compound C1CCOCC1 DHXVGJBLRPWPCS-UHFFFAOYSA-N 0.000 claims description 11
- JFCQEDHGNNZCLN-UHFFFAOYSA-N anhydrous glutaric acid Natural products OC(=O)CCCC(O)=O JFCQEDHGNNZCLN-UHFFFAOYSA-N 0.000 claims description 11
- 150000003568 thioethers Chemical class 0.000 claims description 11
- KGNUPTNIPHPWLT-LBPRGKRZSA-N (2s)-2-[(4-phenylphenyl)methylazaniumyl]propanoate Chemical compound C1=CC(C[NH2+][C@@H](C)C([O-])=O)=CC=C1C1=CC=CC=C1 KGNUPTNIPHPWLT-LBPRGKRZSA-N 0.000 claims description 10
- BGGHCRNCRWQABU-JTQLQIEISA-N (2s)-2-amino-5-oxo-5-phenylmethoxypentanoic acid Chemical compound OC(=O)[C@@H](N)CCC(=O)OCC1=CC=CC=C1 BGGHCRNCRWQABU-JTQLQIEISA-N 0.000 claims description 10
- YTEUDCIEJDRJTM-UHFFFAOYSA-N 2-(chloromethyl)benzoic acid Chemical compound OC(=O)C1=CC=CC=C1CCl YTEUDCIEJDRJTM-UHFFFAOYSA-N 0.000 claims description 10
- AWSSTZZQBPIWKZ-UHFFFAOYSA-N 3-chloro-2-methylpropanoic acid Chemical compound ClCC(C)C(O)=O AWSSTZZQBPIWKZ-UHFFFAOYSA-N 0.000 claims description 10
- QEYMMOKECZBKAC-UHFFFAOYSA-N 3-chloropropanoic acid Chemical compound OC(=O)CCCl QEYMMOKECZBKAC-UHFFFAOYSA-N 0.000 claims description 10
- IPLKGJHGWCVSOG-UHFFFAOYSA-N 4-chlorobutanoic acid Chemical compound OC(=O)CCCCl IPLKGJHGWCVSOG-UHFFFAOYSA-N 0.000 claims description 10
- 239000002253 acid Substances 0.000 claims description 10
- GWYFCOCPABKNJV-UHFFFAOYSA-N isovaleric acid Chemical compound CC(C)CC(O)=O GWYFCOCPABKNJV-UHFFFAOYSA-N 0.000 claims description 10
- CFPHMAVQAJGVPV-UHFFFAOYSA-N 2-sulfanylbutanoic acid Chemical compound CCC(S)C(O)=O CFPHMAVQAJGVPV-UHFFFAOYSA-N 0.000 claims description 9
- DKIDEFUBRARXTE-UHFFFAOYSA-N 3-mercaptopropanoic acid Chemical compound OC(=O)CCS DKIDEFUBRARXTE-UHFFFAOYSA-N 0.000 claims description 9
- 239000005711 Benzoic acid Substances 0.000 claims description 9
- 208000011231 Crohn disease Diseases 0.000 claims description 9
- 235000010233 benzoic acid Nutrition 0.000 claims description 9
- FOCAUTSVDIKZOP-UHFFFAOYSA-N chloroacetic acid Chemical compound OC(=O)CCl FOCAUTSVDIKZOP-UHFFFAOYSA-N 0.000 claims description 9
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 9
- 239000001384 succinic acid Substances 0.000 claims description 8
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 7
- 206010009900 Colitis ulcerative Diseases 0.000 claims description 7
- 201000006704 Ulcerative Colitis Diseases 0.000 claims description 7
- MJWFYRWQSQLDLH-XGNXJENSSA-N (2S)-2-[(4-phenylcyclohexyl)amino]propanoic acid Chemical compound C1(=CC=CC=C1)C1CCC(CC1)N[C@@H](C)C(=O)O MJWFYRWQSQLDLH-XGNXJENSSA-N 0.000 claims description 6
- 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 claims description 6
- 206010009887 colitis Diseases 0.000 claims description 6
- 208000027866 inflammatory disease Diseases 0.000 claims description 6
- KIDHWZJUCRJVML-UHFFFAOYSA-N putrescine Chemical compound NCCCCN KIDHWZJUCRJVML-UHFFFAOYSA-N 0.000 claims description 6
- KHABBYNLBYZCKP-UHFFFAOYSA-N 4-aminopiperidin-1-ium-4-carboxylate Chemical compound OC(=O)C1(N)CCNCC1 KHABBYNLBYZCKP-UHFFFAOYSA-N 0.000 claims description 5
- 230000001684 chronic effect Effects 0.000 claims description 5
- NBZBKCUXIYYUSX-UHFFFAOYSA-N iminodiacetic acid Chemical compound OC(=O)CNCC(O)=O NBZBKCUXIYYUSX-UHFFFAOYSA-N 0.000 claims description 5
- AXDLCFOOGCNDST-VIFPVBQESA-N (2s)-3-(4-hydroxyphenyl)-2-(methylamino)propanoic acid Chemical compound CN[C@H](C(O)=O)CC1=CC=C(O)C=C1 AXDLCFOOGCNDST-VIFPVBQESA-N 0.000 claims description 4
- 208000015943 Coeliac disease Diseases 0.000 claims description 4
- 102100024458 Cyclin-dependent kinase inhibitor 2A Human genes 0.000 claims description 4
- MTHSVFCYNBDYFN-UHFFFAOYSA-N anhydrous diethylene glycol Natural products OCCOCCO MTHSVFCYNBDYFN-UHFFFAOYSA-N 0.000 claims description 4
- 125000004177 diethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 4
- 239000002702 enteric coating Substances 0.000 claims description 4
- 238000009505 enteric coating Methods 0.000 claims description 4
- 239000001257 hydrogen Substances 0.000 claims description 4
- 229910052739 hydrogen Inorganic materials 0.000 claims description 4
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 claims description 4
- 108091033319 polynucleotide Proteins 0.000 claims description 4
- 102000040430 polynucleotide Human genes 0.000 claims description 4
- 239000002157 polynucleotide Substances 0.000 claims description 4
- 125000001425 triazolyl group Chemical group 0.000 claims description 4
- 239000003981 vehicle Substances 0.000 claims description 4
- SAAQPSNNIOGFSQ-LURJTMIESA-N (2s)-2-(pyridin-4-ylamino)propanoic acid Chemical compound OC(=O)[C@H](C)NC1=CC=NC=C1 SAAQPSNNIOGFSQ-LURJTMIESA-N 0.000 claims description 3
- 239000005700 Putrescine Substances 0.000 claims description 3
- 208000006673 asthma Diseases 0.000 claims description 3
- 125000006850 spacer group Chemical group 0.000 claims description 3
- 230000000699 topical effect Effects 0.000 claims description 3
- 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 claims description 2
- 206010006458 Bronchitis chronic Diseases 0.000 claims description 2
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 2
- 206010009137 Chronic sinusitis Diseases 0.000 claims description 2
- 208000031879 Chédiak-Higashi syndrome Diseases 0.000 claims description 2
- 206010017993 Gastrointestinal neoplasms Diseases 0.000 claims description 2
- 208000011476 Glycogen storage disease due to glucose-6-phosphatase deficiency type Ib Diseases 0.000 claims description 2
- 208000009329 Graft vs Host Disease Diseases 0.000 claims description 2
- 208000006933 Hermanski-Pudlak Syndrome Diseases 0.000 claims description 2
- 206010071775 Hermansky-Pudlak syndrome Diseases 0.000 claims description 2
- PQNASZJZHFPQLE-LURJTMIESA-N N(6)-methyl-L-lysine Chemical compound CNCCCC[C@H](N)C(O)=O PQNASZJZHFPQLE-LURJTMIESA-N 0.000 claims description 2
- 206010033645 Pancreatitis Diseases 0.000 claims description 2
- 208000002389 Pouchitis Diseases 0.000 claims description 2
- 206010062164 Seronegative arthritis Diseases 0.000 claims description 2
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 2
- 206010067584 Type 1 diabetes mellitus Diseases 0.000 claims description 2
- 125000002723 alicyclic group Chemical group 0.000 claims description 2
- 206010006451 bronchitis Diseases 0.000 claims description 2
- 238000002512 chemotherapy Methods 0.000 claims description 2
- 208000003167 cholangitis Diseases 0.000 claims description 2
- 201000001352 cholecystitis Diseases 0.000 claims description 2
- 208000007451 chronic bronchitis Diseases 0.000 claims description 2
- 208000027157 chronic rhinosinusitis Diseases 0.000 claims description 2
- 208000008609 collagenous colitis Diseases 0.000 claims description 2
- 235000014113 dietary fatty acids Nutrition 0.000 claims description 2
- 239000003085 diluting agent Substances 0.000 claims description 2
- 208000037902 enteropathy Diseases 0.000 claims description 2
- 201000001564 eosinophilic gastroenteritis Diseases 0.000 claims description 2
- 229930195729 fatty acid Chemical group 0.000 claims description 2
- 239000000194 fatty acid Chemical group 0.000 claims description 2
- 150000004665 fatty acids Chemical group 0.000 claims description 2
- 210000005095 gastrointestinal system Anatomy 0.000 claims description 2
- 208000005516 glycogen storage disease Ib Diseases 0.000 claims description 2
- 208000024908 graft versus host disease Diseases 0.000 claims description 2
- 208000026278 immune system disease Diseases 0.000 claims description 2
- 208000028774 intestinal disease Diseases 0.000 claims description 2
- 238000007918 intramuscular administration Methods 0.000 claims description 2
- 238000007913 intrathecal administration Methods 0.000 claims description 2
- 238000001990 intravenous administration Methods 0.000 claims description 2
- 201000008105 leukocyte adhesion deficiency 1 Diseases 0.000 claims description 2
- 208000004396 mastitis Diseases 0.000 claims description 2
- 208000008275 microscopic colitis Diseases 0.000 claims description 2
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 2
- 238000001959 radiotherapy Methods 0.000 claims description 2
- 150000003346 selenoethers Chemical class 0.000 claims description 2
- 238000007920 subcutaneous administration Methods 0.000 claims description 2
- 229910052717 sulfur Inorganic materials 0.000 claims description 2
- 239000011593 sulfur Substances 0.000 claims description 2
- 208000011580 syndromic disease Diseases 0.000 claims description 2
- 208000035408 type 1 diabetes mellitus 1 Diseases 0.000 claims description 2
- 238000009834 vaporization Methods 0.000 claims description 2
- 230000008016 vaporization Effects 0.000 claims description 2
- 239000013598 vector Substances 0.000 claims description 2
- 125000000998 L-alanino group Chemical group [H]N([*])[C@](C([H])([H])[H])([H])C(=O)O[H] 0.000 claims 7
- BLFLLBZGZJTVJG-UHFFFAOYSA-N benzocaine Chemical compound CCOC(=O)C1=CC=C(N)C=C1 BLFLLBZGZJTVJG-UHFFFAOYSA-N 0.000 claims 4
- 208000024891 symptom Diseases 0.000 claims 2
- XYHKNCXZYYTLRG-UHFFFAOYSA-N 1h-imidazole-2-carbaldehyde Chemical compound O=CC1=NC=CN1 XYHKNCXZYYTLRG-UHFFFAOYSA-N 0.000 claims 1
- GWYFCOCPABKNJV-UHFFFAOYSA-M 3-Methylbutanoic acid Natural products CC(C)CC([O-])=O GWYFCOCPABKNJV-UHFFFAOYSA-M 0.000 claims 1
- FFFHZYDWPBMWHY-VKHMYHEASA-N L-homocysteine Chemical compound OC(=O)[C@@H](N)CCS FFFHZYDWPBMWHY-VKHMYHEASA-N 0.000 claims 1
- 206010062067 Perichondritis Diseases 0.000 claims 1
- 201000001263 Psoriatic Arthritis Diseases 0.000 claims 1
- 208000036824 Psoriatic arthropathy Diseases 0.000 claims 1
- 150000002431 hydrogen Chemical class 0.000 claims 1
- 239000013641 positive control Substances 0.000 claims 1
- 230000005855 radiation Effects 0.000 claims 1
- 208000037765 diseases and disorders Diseases 0.000 abstract description 7
- 239000000203 mixture Substances 0.000 abstract description 4
- 229940024606 amino acid Drugs 0.000 description 323
- 235000001014 amino acid Nutrition 0.000 description 321
- WHUUTDBJXJRKMK-UHFFFAOYSA-N Glutamic acid Natural products OC(=O)C(N)CCC(O)=O WHUUTDBJXJRKMK-UHFFFAOYSA-N 0.000 description 251
- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 229
- 125000003295 alanine group Chemical group N[C@@H](C)C(=O)* 0.000 description 77
- 125000000539 amino acid group Chemical group 0.000 description 65
- XUJNEKJLAYXESH-REOHCLBHSA-N L-Cysteine Chemical compound SC[C@H](N)C(O)=O XUJNEKJLAYXESH-REOHCLBHSA-N 0.000 description 43
- COLNVLDHVKWLRT-MRVPVSSYSA-N D-phenylalanine Chemical compound OC(=O)[C@H](N)CC1=CC=CC=C1 COLNVLDHVKWLRT-MRVPVSSYSA-N 0.000 description 38
- AYFVYJQAPQTCCC-STHAYSLISA-N D-threonine Chemical compound C[C@H](O)[C@@H](N)C(O)=O AYFVYJQAPQTCCC-STHAYSLISA-N 0.000 description 37
- LJQLQCAXBUHEAZ-UWTATZPHSA-N 3-phospho-D-glyceroyl dihydrogen phosphate Chemical compound OP(=O)(O)OC[C@@H](O)C(=O)OP(O)(O)=O LJQLQCAXBUHEAZ-UWTATZPHSA-N 0.000 description 30
- 102000004196 processed proteins & peptides Human genes 0.000 description 28
- 125000000570 L-alpha-aspartyl group Chemical group [H]OC(=O)C([H])([H])[C@]([H])(N([H])[H])C(*)=O 0.000 description 25
- MTCFGRXMJLQNBG-UWTATZPHSA-N D-Serine Chemical compound OC[C@@H](N)C(O)=O MTCFGRXMJLQNBG-UWTATZPHSA-N 0.000 description 23
- ODKSFYDXXFIFQN-SCSAIBSYSA-N D-arginine Chemical compound OC(=O)[C@H](N)CCCNC(N)=N ODKSFYDXXFIFQN-SCSAIBSYSA-N 0.000 description 23
- ROHFNLRQFUQHCH-RXMQYKEDSA-N D-leucine Chemical compound CC(C)C[C@@H](N)C(O)=O ROHFNLRQFUQHCH-RXMQYKEDSA-N 0.000 description 23
- 125000000415 L-cysteinyl group Chemical group O=C([*])[C@@](N([H])[H])([H])C([H])([H])S[H] 0.000 description 23
- 238000011282 treatment Methods 0.000 description 19
- 206010061218 Inflammation Diseases 0.000 description 13
- 230000004054 inflammatory process Effects 0.000 description 13
- 238000006467 substitution reaction Methods 0.000 description 12
- 101000853012 Homo sapiens Interleukin-23 receptor Proteins 0.000 description 11
- 230000015556 catabolic process Effects 0.000 description 11
- 210000001072 colon Anatomy 0.000 description 11
- 238000006731 degradation reaction Methods 0.000 description 11
- 101000853010 Mus musculus Interleukin-23 receptor Proteins 0.000 description 10
- 230000002496 gastric effect Effects 0.000 description 10
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 9
- 108090000623 proteins and genes Proteins 0.000 description 9
- 210000001519 tissue Anatomy 0.000 description 9
- 238000003556 assay Methods 0.000 description 8
- 230000000968 intestinal effect Effects 0.000 description 8
- 230000001404 mediated effect Effects 0.000 description 8
- 235000018102 proteins Nutrition 0.000 description 8
- 102000004169 proteins and genes Human genes 0.000 description 8
- 150000008574 D-amino acids Chemical class 0.000 description 7
- HNDVDQJCIGZPNO-RXMQYKEDSA-N D-histidine Chemical compound OC(=O)[C@H](N)CC1=CN=CN1 HNDVDQJCIGZPNO-RXMQYKEDSA-N 0.000 description 7
- 210000001744 T-lymphocyte Anatomy 0.000 description 7
- 235000008206 alpha-amino acids Nutrition 0.000 description 7
- 210000004899 c-terminal region Anatomy 0.000 description 7
- 210000004027 cell Anatomy 0.000 description 7
- 201000010099 disease Diseases 0.000 description 7
- 210000000936 intestine Anatomy 0.000 description 7
- 238000007069 methylation reaction Methods 0.000 description 7
- 229920001184 polypeptide Polymers 0.000 description 7
- 108010035017 rat interleukin-23 receptor Proteins 0.000 description 7
- 102000004127 Cytokines Human genes 0.000 description 6
- 108090000695 Cytokines Proteins 0.000 description 6
- 241001465754 Metazoa Species 0.000 description 6
- KAFHLONDOVSENM-HNNXBMFYSA-N O-Benzyl-L-tyrosine Chemical compound C1=CC(C[C@H](N)C(O)=O)=CC=C1OCC1=CC=CC=C1 KAFHLONDOVSENM-HNNXBMFYSA-N 0.000 description 6
- 230000000694 effects Effects 0.000 description 6
- 230000011987 methylation Effects 0.000 description 6
- 150000007523 nucleic acids Chemical class 0.000 description 6
- 239000002773 nucleotide Substances 0.000 description 6
- 125000003729 nucleotide group Chemical group 0.000 description 6
- 230000037361 pathway Effects 0.000 description 6
- FSYKKLYZXJSNPZ-UHFFFAOYSA-N sarcosine Chemical compound C[NH2+]CC([O-])=O FSYKKLYZXJSNPZ-UHFFFAOYSA-N 0.000 description 6
- 230000011664 signaling Effects 0.000 description 6
- 239000004475 Arginine Substances 0.000 description 5
- ODKSFYDXXFIFQN-BYPYZUCNSA-P L-argininium(2+) Chemical compound NC(=[NH2+])NCCC[C@H]([NH3+])C(O)=O ODKSFYDXXFIFQN-BYPYZUCNSA-P 0.000 description 5
- 150000001370 alpha-amino acid derivatives Chemical class 0.000 description 5
- CDUUKBXTEOFITR-UHFFFAOYSA-N alpha-methylserine Natural products OCC([NH3+])(C)C([O-])=O CDUUKBXTEOFITR-UHFFFAOYSA-N 0.000 description 5
- 239000002585 base Substances 0.000 description 5
- 230000002401 inhibitory effect Effects 0.000 description 5
- 230000005764 inhibitory process Effects 0.000 description 5
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 5
- BWGNESOTFCXPMA-UHFFFAOYSA-N Dihydrogen disulfide Chemical compound SS BWGNESOTFCXPMA-UHFFFAOYSA-N 0.000 description 4
- 241000282412 Homo Species 0.000 description 4
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 4
- 102000013691 Interleukin-17 Human genes 0.000 description 4
- 108050003558 Interleukin-17 Proteins 0.000 description 4
- 101150009057 JAK2 gene Proteins 0.000 description 4
- 150000008575 L-amino acids Chemical class 0.000 description 4
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 4
- 229910019142 PO4 Inorganic materials 0.000 description 4
- 230000002378 acidificating effect Effects 0.000 description 4
- 150000007513 acids Chemical class 0.000 description 4
- 230000004913 activation Effects 0.000 description 4
- 230000015572 biosynthetic process Effects 0.000 description 4
- 239000000306 component Substances 0.000 description 4
- 230000001419 dependent effect Effects 0.000 description 4
- 239000003814 drug Substances 0.000 description 4
- 125000004435 hydrogen atom Chemical class [H]* 0.000 description 4
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 4
- 102000039446 nucleic acids Human genes 0.000 description 4
- 108020004707 nucleic acids Proteins 0.000 description 4
- 230000008506 pathogenesis Effects 0.000 description 4
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 4
- 239000010452 phosphate Substances 0.000 description 4
- LVTJOONKWUXEFR-FZRMHRINSA-N protoneodioscin Natural products O(C[C@@H](CC[C@]1(O)[C@H](C)[C@@H]2[C@]3(C)[C@H]([C@H]4[C@@H]([C@]5(C)C(=CC4)C[C@@H](O[C@@H]4[C@H](O[C@H]6[C@@H](O)[C@@H](O)[C@@H](O)[C@H](C)O6)[C@@H](O)[C@H](O[C@H]6[C@@H](O)[C@@H](O)[C@@H](O)[C@H](C)O6)[C@H](CO)O4)CC5)CC3)C[C@@H]2O1)C)[C@H]1[C@H](O)[C@H](O)[C@H](O)[C@@H](CO)O1 LVTJOONKWUXEFR-FZRMHRINSA-N 0.000 description 4
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 3
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- 241000206602 Eukaryota Species 0.000 description 3
- 108090001005 Interleukin-6 Proteins 0.000 description 3
- 102000004889 Interleukin-6 Human genes 0.000 description 3
- QNAYBMKLOCPYGJ-REOHCLBHSA-N L-alanine Chemical compound C[C@H](N)C(O)=O QNAYBMKLOCPYGJ-REOHCLBHSA-N 0.000 description 3
- 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 3
- LRQKBLKVPFOOQJ-YFKPBYRVSA-N L-norleucine Chemical group CCCC[C@H]([NH3+])C([O-])=O LRQKBLKVPFOOQJ-YFKPBYRVSA-N 0.000 description 3
- 108091028043 Nucleic acid sequence Proteins 0.000 description 3
- 239000002202 Polyethylene glycol Chemical group 0.000 description 3
- 101150099493 STAT3 gene Proteins 0.000 description 3
- 108010077895 Sarcosine Proteins 0.000 description 3
- 108060008682 Tumor Necrosis Factor Proteins 0.000 description 3
- 230000002776 aggregation Effects 0.000 description 3
- 238000004220 aggregation Methods 0.000 description 3
- 125000003277 amino group Chemical group 0.000 description 3
- LGEQQWMQCRIYKG-DOFZRALJSA-N anandamide Chemical group CCCCC\C=C/C\C=C/C\C=C/C\C=C/CCCC(=O)NCCO LGEQQWMQCRIYKG-DOFZRALJSA-N 0.000 description 3
- 230000001363 autoimmune Effects 0.000 description 3
- 230000008901 benefit Effects 0.000 description 3
- XMIIGOLPHOKFCH-UHFFFAOYSA-N beta-phenylpropanoic acid Natural products OC(=O)CCC1=CC=CC=C1 XMIIGOLPHOKFCH-UHFFFAOYSA-N 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
- 230000002950 deficient Effects 0.000 description 3
- 229940079593 drug Drugs 0.000 description 3
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 3
- 239000012530 fluid Substances 0.000 description 3
- 230000014509 gene expression Effects 0.000 description 3
- 230000002209 hydrophobic effect Effects 0.000 description 3
- 238000004519 manufacturing process Methods 0.000 description 3
- 210000004877 mucosa Anatomy 0.000 description 3
- 229920001223 polyethylene glycol Chemical group 0.000 description 3
- 229920006395 saturated elastomer Polymers 0.000 description 3
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 3
- 102000003390 tumor necrosis factor Human genes 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 2
- OGNSCSPNOLGXSM-UHFFFAOYSA-N 2,4-diaminobutyric acid Chemical compound NCCC(N)C(O)=O OGNSCSPNOLGXSM-UHFFFAOYSA-N 0.000 description 2
- HZAXFHJVJLSVMW-UHFFFAOYSA-N 2-Aminoethan-1-ol Chemical compound NCCO HZAXFHJVJLSVMW-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
- PECYZEOJVXMISF-UHFFFAOYSA-N 3-aminoalanine Chemical compound [NH3+]CC(N)C([O-])=O PECYZEOJVXMISF-UHFFFAOYSA-N 0.000 description 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- 241000283690 Bos taurus Species 0.000 description 2
- 125000000882 C2-C6 alkenyl group Chemical group 0.000 description 2
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 2
- 241000282465 Canis Species 0.000 description 2
- 108090000317 Chymotrypsin Proteins 0.000 description 2
- KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 description 2
- 206010009944 Colon cancer Diseases 0.000 description 2
- 238000012286 ELISA Assay Methods 0.000 description 2
- 102000004190 Enzymes Human genes 0.000 description 2
- 108090000790 Enzymes Proteins 0.000 description 2
- 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 2
- 102000008070 Interferon-gamma Human genes 0.000 description 2
- 108010074328 Interferon-gamma Proteins 0.000 description 2
- AHLPHDHHMVZTML-BYPYZUCNSA-N L-Ornithine Chemical compound NCCC[C@H](N)C(O)=O AHLPHDHHMVZTML-BYPYZUCNSA-N 0.000 description 2
- UKAUYVFTDYCKQA-VKHMYHEASA-N L-homoserine Chemical compound OC(=O)[C@@H](N)CCO UKAUYVFTDYCKQA-VKHMYHEASA-N 0.000 description 2
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 2
- 241000124008 Mammalia Species 0.000 description 2
- 241000699670 Mus sp. Species 0.000 description 2
- 102000003896 Myeloperoxidases Human genes 0.000 description 2
- 108090000235 Myeloperoxidases Proteins 0.000 description 2
- AHLPHDHHMVZTML-UHFFFAOYSA-N Orn-delta-NH2 Natural products NCCCC(N)C(O)=O AHLPHDHHMVZTML-UHFFFAOYSA-N 0.000 description 2
- UTJLXEIPEHZYQJ-UHFFFAOYSA-N Ornithine Natural products OC(=O)C(C)CCCN UTJLXEIPEHZYQJ-UHFFFAOYSA-N 0.000 description 2
- 108010067372 Pancreatic elastase Proteins 0.000 description 2
- 102000016387 Pancreatic elastase Human genes 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 2
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 2
- ONIBWKKTOPOVIA-UHFFFAOYSA-N Proline Natural products OC(=O)C1CCCN1 ONIBWKKTOPOVIA-UHFFFAOYSA-N 0.000 description 2
- 241000283984 Rodentia Species 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- DTQVDTLACAAQTR-UHFFFAOYSA-M Trifluoroacetate Chemical compound [O-]C(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-M 0.000 description 2
- 108090000631 Trypsin Proteins 0.000 description 2
- 102000004142 Trypsin Human genes 0.000 description 2
- 230000001154 acute effect Effects 0.000 description 2
- 235000004279 alanine Nutrition 0.000 description 2
- 150000001336 alkenes Chemical class 0.000 description 2
- 150000001371 alpha-amino acids Chemical class 0.000 description 2
- 125000000266 alpha-aminoacyl group Chemical group 0.000 description 2
- 238000004458 analytical method Methods 0.000 description 2
- 239000005557 antagonist Substances 0.000 description 2
- 125000003118 aryl group Chemical group 0.000 description 2
- 150000001649 bromium compounds Chemical class 0.000 description 2
- 229910052791 calcium Inorganic materials 0.000 description 2
- 239000011575 calcium Substances 0.000 description 2
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 description 2
- 239000013592 cell lysate Substances 0.000 description 2
- 229960002376 chymotrypsin Drugs 0.000 description 2
- 208000029742 colonic neoplasm Diseases 0.000 description 2
- 125000000753 cycloalkyl group Chemical group 0.000 description 2
- 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 2
- JBDSSBMEKXHSJF-UHFFFAOYSA-N cyclopentanecarboxylic acid Chemical compound OC(=O)C1CCCC1 JBDSSBMEKXHSJF-UHFFFAOYSA-N 0.000 description 2
- 125000000151 cysteine group Chemical class N[C@@H](CS)C(=O)* 0.000 description 2
- 238000011161 development Methods 0.000 description 2
- 208000035475 disorder Diseases 0.000 description 2
- 229940088598 enzyme Drugs 0.000 description 2
- 230000006870 function Effects 0.000 description 2
- BTCSSZJGUNDROE-UHFFFAOYSA-N gamma-aminobutyric acid Chemical compound NCCCC(O)=O BTCSSZJGUNDROE-UHFFFAOYSA-N 0.000 description 2
- 210000001035 gastrointestinal tract Anatomy 0.000 description 2
- 125000002795 guanidino group Chemical group C(N)(=N)N* 0.000 description 2
- 210000002443 helper t lymphocyte Anatomy 0.000 description 2
- 125000001183 hydrocarbyl group Chemical group 0.000 description 2
- 238000000338 in vitro Methods 0.000 description 2
- 229960003130 interferon gamma Drugs 0.000 description 2
- 150000004694 iodide salts Chemical class 0.000 description 2
- SUMDYPCJJOFFON-UHFFFAOYSA-N isethionic acid Chemical compound OCCS(O)(=O)=O SUMDYPCJJOFFON-UHFFFAOYSA-N 0.000 description 2
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 2
- 230000003902 lesion Effects 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- 244000144972 livestock Species 0.000 description 2
- 210000002540 macrophage Anatomy 0.000 description 2
- 229910052749 magnesium Inorganic materials 0.000 description 2
- 239000011777 magnesium Substances 0.000 description 2
- 229940091250 magnesium supplement Drugs 0.000 description 2
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 2
- 239000011159 matrix material Substances 0.000 description 2
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 2
- 230000019079 negative regulation of cytokine secretion Effects 0.000 description 2
- 230000011234 negative regulation of signal transduction Effects 0.000 description 2
- 230000007935 neutral effect Effects 0.000 description 2
- 150000002894 organic compounds Chemical class 0.000 description 2
- 229960003104 ornithine Drugs 0.000 description 2
- 229960003975 potassium Drugs 0.000 description 2
- 229910052700 potassium Inorganic materials 0.000 description 2
- 239000011591 potassium Substances 0.000 description 2
- 230000017854 proteolysis Effects 0.000 description 2
- 230000009467 reduction Effects 0.000 description 2
- 238000006798 ring closing metathesis reaction Methods 0.000 description 2
- 229940043230 sarcosine Drugs 0.000 description 2
- 230000028327 secretion Effects 0.000 description 2
- 230000019491 signal transduction Effects 0.000 description 2
- 229910052708 sodium Inorganic materials 0.000 description 2
- 229940083542 sodium Drugs 0.000 description 2
- 239000011734 sodium Substances 0.000 description 2
- 241000894007 species Species 0.000 description 2
- 210000004988 splenocyte Anatomy 0.000 description 2
- 238000010561 standard procedure Methods 0.000 description 2
- 238000003786 synthesis reaction Methods 0.000 description 2
- 230000009885 systemic effect Effects 0.000 description 2
- 230000001225 therapeutic effect Effects 0.000 description 2
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 2
- 239000012588 trypsin Substances 0.000 description 2
- QIVBCDIJIAJPQS-UHFFFAOYSA-N tryptophan Chemical compound C1=CC=C2C(CC(N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-UHFFFAOYSA-N 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- AIFRHYZBTHREPW-UHFFFAOYSA-N β-carboline Chemical compound N1=CC=C2C3=CC=CC=C3NC2=C1 AIFRHYZBTHREPW-UHFFFAOYSA-N 0.000 description 2
- LSPHULWDVZXLIL-UHFFFAOYSA-N (+/-)-Camphoric acid Chemical compound CC1(C)C(C(O)=O)CCC1(C)C(O)=O LSPHULWDVZXLIL-UHFFFAOYSA-N 0.000 description 1
- SAUDSWFPPKSVMK-LBPRGKRZSA-N (2s)-2-(n-phenylanilino)propanoic acid Chemical compound C=1C=CC=CC=1N([C@@H](C)C(O)=O)C1=CC=CC=C1 SAUDSWFPPKSVMK-LBPRGKRZSA-N 0.000 description 1
- OFVBLKINTLPEGH-VIFPVBQESA-N (3S)-3-Amino-4-phenylbutanoic acid Chemical compound OC(=O)C[C@@H](N)CC1=CC=CC=C1 OFVBLKINTLPEGH-VIFPVBQESA-N 0.000 description 1
- ODIGIKRIUKFKHP-UHFFFAOYSA-N (n-propan-2-yloxycarbonylanilino) acetate Chemical compound CC(C)OC(=O)N(OC(C)=O)C1=CC=CC=C1 ODIGIKRIUKFKHP-UHFFFAOYSA-N 0.000 description 1
- VFWCMGCRMGJXDK-UHFFFAOYSA-N 1-chlorobutane Chemical class CCCCCl VFWCMGCRMGJXDK-UHFFFAOYSA-N 0.000 description 1
- 125000006017 1-propenyl group Chemical group 0.000 description 1
- LXFQSRIDYRFTJW-UHFFFAOYSA-M 2,4,6-trimethylbenzenesulfonate Chemical compound CC1=CC(C)=C(S([O-])(=O)=O)C(C)=C1 LXFQSRIDYRFTJW-UHFFFAOYSA-M 0.000 description 1
- MGKPFALCNDRSQD-UHFFFAOYSA-N 2-(4-fluorophenyl)acetic acid Chemical compound OC(=O)CC1=CC=C(F)C=C1 MGKPFALCNDRSQD-UHFFFAOYSA-N 0.000 description 1
- KVVDRQDTODKIJD-UHFFFAOYSA-N 2-cyclopropylacetic acid Chemical compound OC(=O)CC1CC1 KVVDRQDTODKIJD-UHFFFAOYSA-N 0.000 description 1
- GHCZTIFQWKKGSB-UHFFFAOYSA-N 2-hydroxypropane-1,2,3-tricarboxylic acid;phosphoric acid Chemical compound OP(O)(O)=O.OC(=O)CC(O)(C(O)=O)CC(O)=O GHCZTIFQWKKGSB-UHFFFAOYSA-N 0.000 description 1
- 229940080296 2-naphthalenesulfonate Drugs 0.000 description 1
- WMPPDTMATNBGJN-UHFFFAOYSA-N 2-phenylethylbromide Chemical class BrCCC1=CC=CC=C1 WMPPDTMATNBGJN-UHFFFAOYSA-N 0.000 description 1
- KSNKQSPJFRQSEI-UHFFFAOYSA-N 3,3,3-trifluoropropanoic acid Chemical compound OC(=O)CC(F)(F)F KSNKQSPJFRQSEI-UHFFFAOYSA-N 0.000 description 1
- JPZXHKDZASGCLU-GFCCVEGCSA-N 3-(2-Naphthyl)-D-Alanine Chemical compound C1=CC=CC2=CC(C[C@@H](N)C(O)=O)=CC=C21 JPZXHKDZASGCLU-GFCCVEGCSA-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
- XMIIGOLPHOKFCH-UHFFFAOYSA-M 3-phenylpropionate Chemical compound [O-]C(=O)CCC1=CC=CC=C1 XMIIGOLPHOKFCH-UHFFFAOYSA-M 0.000 description 1
- UADMTAKPNCQPNT-UHFFFAOYSA-N 4-fluoro-3-methylbutanoic acid Chemical compound FCC(C)CC(O)=O UADMTAKPNCQPNT-UHFFFAOYSA-N 0.000 description 1
- BBYDXOIZLAWGSL-UHFFFAOYSA-N 4-fluorobenzoic acid Chemical compound OC(=O)C1=CC=C(F)C=C1 BBYDXOIZLAWGSL-UHFFFAOYSA-N 0.000 description 1
- MJZJYWCQPMNPRM-UHFFFAOYSA-N 6,6-dimethyl-1-[3-(2,4,5-trichlorophenoxy)propoxy]-1,6-dihydro-1,3,5-triazine-2,4-diamine Chemical compound CC1(C)N=C(N)N=C(N)N1OCCCOC1=CC(Cl)=C(Cl)C=C1Cl MJZJYWCQPMNPRM-UHFFFAOYSA-N 0.000 description 1
- FHVDTGUDJYJELY-UHFFFAOYSA-N 6-{[2-carboxy-4,5-dihydroxy-6-(phosphanyloxy)oxan-3-yl]oxy}-4,5-dihydroxy-3-phosphanyloxane-2-carboxylic acid Chemical compound O1C(C(O)=O)C(P)C(O)C(O)C1OC1C(C(O)=O)OC(OP)C(O)C1O FHVDTGUDJYJELY-UHFFFAOYSA-N 0.000 description 1
- RZVAJINKPMORJF-UHFFFAOYSA-N Acetaminophen Chemical compound CC(=O)NC1=CC=C(O)C=C1 RZVAJINKPMORJF-UHFFFAOYSA-N 0.000 description 1
- DHMQDGOQFOQNFH-UHFFFAOYSA-M Aminoacetate Chemical compound NCC([O-])=O DHMQDGOQFOQNFH-UHFFFAOYSA-M 0.000 description 1
- 102000004400 Aminopeptidases Human genes 0.000 description 1
- 108090000915 Aminopeptidases Proteins 0.000 description 1
- 208000023275 Autoimmune disease Diseases 0.000 description 1
- 241000894006 Bacteria Species 0.000 description 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-M Bicarbonate Chemical compound OC([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-M 0.000 description 1
- 102000004506 Blood Proteins Human genes 0.000 description 1
- 108010017384 Blood Proteins Proteins 0.000 description 1
- FERIUCNNQQJTOY-UHFFFAOYSA-M Butyrate Chemical compound CCCC([O-])=O FERIUCNNQQJTOY-UHFFFAOYSA-M 0.000 description 1
- FERIUCNNQQJTOY-UHFFFAOYSA-N Butyric acid Natural products CCCC(O)=O FERIUCNNQQJTOY-UHFFFAOYSA-N 0.000 description 1
- 125000001433 C-terminal amino-acid group Chemical group 0.000 description 1
- 241000282472 Canis lupus familiaris Species 0.000 description 1
- 102000003670 Carboxypeptidase B Human genes 0.000 description 1
- 108090000087 Carboxypeptidase B Proteins 0.000 description 1
- 102000000496 Carboxypeptidases A Human genes 0.000 description 1
- 108010080937 Carboxypeptidases A Proteins 0.000 description 1
- 241000700198 Cavia Species 0.000 description 1
- 241000699800 Cricetinae Species 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
- 125000000030 D-alanine group Chemical group [H]N([H])[C@](C([H])([H])[H])(C(=O)[*])[H] 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
- SNRUBQQJIBEYMU-UHFFFAOYSA-N Dodecane Natural products CCCCCCCCCCCC SNRUBQQJIBEYMU-UHFFFAOYSA-N 0.000 description 1
- 238000002965 ELISA Methods 0.000 description 1
- 208000004232 Enteritis Diseases 0.000 description 1
- 241000282324 Felis Species 0.000 description 1
- 241000282326 Felis catus Species 0.000 description 1
- BDAGIHXWWSANSR-UHFFFAOYSA-M Formate Chemical compound [O-]C=O BDAGIHXWWSANSR-UHFFFAOYSA-M 0.000 description 1
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 1
- 102000016354 Glucuronosyltransferase Human genes 0.000 description 1
- 108010092364 Glucuronosyltransferase Proteins 0.000 description 1
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 1
- 101710103841 Interleukin-12 receptor subunit beta-1 Proteins 0.000 description 1
- 102100020790 Interleukin-12 receptor subunit beta-1 Human genes 0.000 description 1
- 102100037792 Interleukin-6 receptor subunit alpha Human genes 0.000 description 1
- 102000015696 Interleukins Human genes 0.000 description 1
- 108010063738 Interleukins Proteins 0.000 description 1
- 230000035986 JAK-STAT signaling Effects 0.000 description 1
- ONIBWKKTOPOVIA-BYPYZUCNSA-N L-Proline Chemical compound OC(=O)[C@@H]1CCCN1 ONIBWKKTOPOVIA-BYPYZUCNSA-N 0.000 description 1
- FSBIGDSBMBYOPN-VKHMYHEASA-N L-canavanine Chemical compound OC(=O)[C@@H](N)CCONC(N)=N FSBIGDSBMBYOPN-VKHMYHEASA-N 0.000 description 1
- ZFOMKMMPBOQKMC-KXUCPTDWSA-N L-pyrrolysine Chemical compound C[C@@H]1CC=N[C@H]1C(=O)NCCCC[C@H]([NH3+])C([O-])=O ZFOMKMMPBOQKMC-KXUCPTDWSA-N 0.000 description 1
- ZKZBPNGNEQAJSX-REOHCLBHSA-N L-selenocysteine Chemical compound [SeH]C[C@H](N)C(O)=O ZKZBPNGNEQAJSX-REOHCLBHSA-N 0.000 description 1
- GHSJKUNUIHUPDF-BYPYZUCNSA-N L-thialysine Chemical compound NCCSC[C@H](N)C(O)=O GHSJKUNUIHUPDF-BYPYZUCNSA-N 0.000 description 1
- JVTAAEKCZFNVCJ-UHFFFAOYSA-M Lactate Chemical compound CC(O)C([O-])=O JVTAAEKCZFNVCJ-UHFFFAOYSA-M 0.000 description 1
- 239000004472 Lysine Substances 0.000 description 1
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 1
- 206010067993 Mucosal necrosis Diseases 0.000 description 1
- PYUSHNKNPOHWEZ-YFKPBYRVSA-N N-formyl-L-methionine Chemical compound CSCC[C@@H](C(O)=O)NC=O PYUSHNKNPOHWEZ-YFKPBYRVSA-N 0.000 description 1
- MBBZMMPHUWSWHV-BDVNFPICSA-N N-methylglucamine Chemical compound CNC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO MBBZMMPHUWSWHV-BDVNFPICSA-N 0.000 description 1
- 125000001429 N-terminal alpha-amino-acid group Chemical group 0.000 description 1
- CPUKKZFITUMBIB-PIVQAISJSA-N NCCOC1(CC=C(CN[C@@H](C)C(=O)O)C=C1)C1=CC=CC=C1 Chemical compound NCCOC1(CC=C(CN[C@@H](C)C(=O)O)C=C1)C1=CC=CC=C1 CPUKKZFITUMBIB-PIVQAISJSA-N 0.000 description 1
- 206010028980 Neoplasm Diseases 0.000 description 1
- PVNIIMVLHYAWGP-UHFFFAOYSA-N Niacin Chemical compound OC(=O)C1=CC=CN=C1 PVNIIMVLHYAWGP-UHFFFAOYSA-N 0.000 description 1
- FSBIGDSBMBYOPN-UHFFFAOYSA-N O-guanidino-DL-homoserine Natural products OC(=O)C(N)CCON=C(N)N FSBIGDSBMBYOPN-UHFFFAOYSA-N 0.000 description 1
- 241000283973 Oryctolagus cuniculus Species 0.000 description 1
- 241000282577 Pan troglodytes Species 0.000 description 1
- 229920002230 Pectic acid Polymers 0.000 description 1
- 108090000284 Pepsin A Proteins 0.000 description 1
- 102000057297 Pepsin A Human genes 0.000 description 1
- 102000035195 Peptidases Human genes 0.000 description 1
- 108091005804 Peptidases Proteins 0.000 description 1
- 241000288906 Primates Species 0.000 description 1
- OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 1
- XBDQKXXYIPTUBI-UHFFFAOYSA-M Propionate Chemical compound CCC([O-])=O XBDQKXXYIPTUBI-UHFFFAOYSA-M 0.000 description 1
- 239000004365 Protease Substances 0.000 description 1
- 101100008569 Rattus norvegicus Cst4 gene Proteins 0.000 description 1
- MTCFGRXMJLQNBG-UHFFFAOYSA-N Serine Natural products OCC(N)C(O)=O MTCFGRXMJLQNBG-UHFFFAOYSA-N 0.000 description 1
- 108091081024 Start codon Proteins 0.000 description 1
- 238000000692 Student's t-test Methods 0.000 description 1
- 230000005867 T cell response Effects 0.000 description 1
- 210000000068 Th17 cell Anatomy 0.000 description 1
- 239000007983 Tris buffer Substances 0.000 description 1
- 159000000021 acetate salts Chemical class 0.000 description 1
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 1
- 125000002015 acyclic group Chemical group 0.000 description 1
- 230000010933 acylation Effects 0.000 description 1
- 238000005917 acylation reaction Methods 0.000 description 1
- 230000003044 adaptive effect Effects 0.000 description 1
- WNLRTRBMVRJNCN-UHFFFAOYSA-L adipate(2-) Chemical compound [O-]C(=O)CCCCC([O-])=O WNLRTRBMVRJNCN-UHFFFAOYSA-L 0.000 description 1
- 150000001294 alanine derivatives Chemical class 0.000 description 1
- 229940072056 alginate Drugs 0.000 description 1
- 235000010443 alginic acid Nutrition 0.000 description 1
- 229920000615 alginic acid Polymers 0.000 description 1
- 150000001338 aliphatic hydrocarbons Chemical class 0.000 description 1
- 229910052783 alkali metal Inorganic materials 0.000 description 1
- 150000001447 alkali salts Chemical class 0.000 description 1
- 229910052784 alkaline earth metal Inorganic materials 0.000 description 1
- 125000000217 alkyl group Chemical group 0.000 description 1
- 208000026935 allergic disease Diseases 0.000 description 1
- AEMOLEFTQBMNLQ-BKBMJHBISA-N alpha-D-galacturonic acid Chemical compound O[C@H]1O[C@H](C(O)=O)[C@H](O)[C@H](O)[C@H]1O AEMOLEFTQBMNLQ-BKBMJHBISA-N 0.000 description 1
- AWUCVROLDVIAJX-UHFFFAOYSA-N alpha-glycerophosphate Natural products OCC(O)COP(O)(O)=O AWUCVROLDVIAJX-UHFFFAOYSA-N 0.000 description 1
- 229910052782 aluminium Inorganic materials 0.000 description 1
- XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 description 1
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
- 125000003368 amide group Chemical group 0.000 description 1
- 150000001408 amides Chemical class 0.000 description 1
- 150000001412 amines Chemical class 0.000 description 1
- 150000003862 amino acid derivatives Chemical class 0.000 description 1
- 230000003872 anastomosis Effects 0.000 description 1
- 238000010171 animal model Methods 0.000 description 1
- 230000003042 antagnostic effect Effects 0.000 description 1
- 239000003242 anti bacterial agent Substances 0.000 description 1
- 229940088710 antibiotic agent Drugs 0.000 description 1
- 229940009098 aspartate Drugs 0.000 description 1
- 230000001580 bacterial effect Effects 0.000 description 1
- 230000004888 barrier function Effects 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- JUHORIMYRDESRB-UHFFFAOYSA-N benzathine Chemical compound C=1C=CC=CC=1CNCCNCC1=CC=CC=C1 JUHORIMYRDESRB-UHFFFAOYSA-N 0.000 description 1
- 229940077388 benzenesulfonate Drugs 0.000 description 1
- SRSXLGNVWSONIS-UHFFFAOYSA-M benzenesulfonate Chemical compound [O-]S(=O)(=O)C1=CC=CC=C1 SRSXLGNVWSONIS-UHFFFAOYSA-M 0.000 description 1
- 229940050390 benzoate Drugs 0.000 description 1
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 1
- ADSALMJPJUKESW-UHFFFAOYSA-N beta-Homoproline Chemical compound OC(=O)CC1CCCN1 ADSALMJPJUKESW-UHFFFAOYSA-N 0.000 description 1
- 150000001576 beta-amino acids Chemical class 0.000 description 1
- 230000033228 biological regulation Effects 0.000 description 1
- 239000000872 buffer Substances 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
- 238000004364 calculation method Methods 0.000 description 1
- MIOPJNTWMNEORI-UHFFFAOYSA-N camphorsulfonic acid Chemical compound C1CC2(CS(O)(=O)=O)C(=O)CC1C2(C)C MIOPJNTWMNEORI-UHFFFAOYSA-N 0.000 description 1
- 201000011510 cancer Diseases 0.000 description 1
- 125000004432 carbon atom Chemical group C* 0.000 description 1
- 125000006297 carbonyl amino group Chemical group [H]N([*:2])C([*:1])=O 0.000 description 1
- 150000001732 carboxylic acid derivatives Chemical group 0.000 description 1
- 206010061592 cardiac fibrillation Diseases 0.000 description 1
- 150000001768 cations Chemical class 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 150000003841 chloride salts Chemical class 0.000 description 1
- 150000001805 chlorine compounds Chemical class 0.000 description 1
- 210000003763 chloroplast Anatomy 0.000 description 1
- OEYIOHPDSNJKLS-UHFFFAOYSA-N choline Chemical compound C[N+](C)(C)CCO OEYIOHPDSNJKLS-UHFFFAOYSA-N 0.000 description 1
- 229960001231 choline Drugs 0.000 description 1
- 238000002983 circular dichroism Methods 0.000 description 1
- 229940001468 citrate Drugs 0.000 description 1
- 150000001860 citric acid derivatives Chemical class 0.000 description 1
- 230000000112 colonic effect Effects 0.000 description 1
- 238000004132 cross linking Methods 0.000 description 1
- 125000004122 cyclic group Chemical group 0.000 description 1
- 125000000596 cyclohexenyl group Chemical group C1(=CCCCC1)* 0.000 description 1
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
- 125000002433 cyclopentenyl group Chemical group C1(=CCCC1)* 0.000 description 1
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 1
- 235000018417 cysteine Nutrition 0.000 description 1
- 230000003247 decreasing effect Effects 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
- 210000004443 dendritic cell Anatomy 0.000 description 1
- 238000013461 design Methods 0.000 description 1
- ZBCBWPMODOFKDW-UHFFFAOYSA-N diethanolamine Chemical compound OCCNCCO ZBCBWPMODOFKDW-UHFFFAOYSA-N 0.000 description 1
- HPNMFZURTQLUMO-UHFFFAOYSA-N diethylamine Chemical compound CCNCC HPNMFZURTQLUMO-UHFFFAOYSA-N 0.000 description 1
- 102000038379 digestive enzymes Human genes 0.000 description 1
- 108091007734 digestive enzymes Proteins 0.000 description 1
- 125000000118 dimethyl group Chemical group [H]C([H])([H])* 0.000 description 1
- GAFRWLVTHPVQGK-UHFFFAOYSA-N dipentyl sulfate Chemical class CCCCCOS(=O)(=O)OCCCCC GAFRWLVTHPVQGK-UHFFFAOYSA-N 0.000 description 1
- XIMIGUBYDJDCKI-UHFFFAOYSA-N diselenium Chemical compound [Se]=[Se] XIMIGUBYDJDCKI-UHFFFAOYSA-N 0.000 description 1
- 125000003438 dodecyl 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
- 231100000673 dose–response relationship Toxicity 0.000 description 1
- 238000002296 dynamic light scattering Methods 0.000 description 1
- 239000012636 effector Substances 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 230000007515 enzymatic degradation Effects 0.000 description 1
- 230000002255 enzymatic effect Effects 0.000 description 1
- 229940031098 ethanolamine Drugs 0.000 description 1
- 230000007717 exclusion Effects 0.000 description 1
- 239000000284 extract Substances 0.000 description 1
- 230000002600 fibrillogenic effect Effects 0.000 description 1
- 239000007850 fluorescent dye Substances 0.000 description 1
- 239000012634 fragment Substances 0.000 description 1
- 230000037433 frameshift Effects 0.000 description 1
- 229960003692 gamma aminobutyric acid Drugs 0.000 description 1
- 210000004475 gamma-delta t lymphocyte Anatomy 0.000 description 1
- 230000002068 genetic effect Effects 0.000 description 1
- 210000004907 gland Anatomy 0.000 description 1
- 229930195712 glutamate Natural products 0.000 description 1
- 239000004220 glutamic acid Substances 0.000 description 1
- 150000002332 glycine derivatives Chemical class 0.000 description 1
- ZRALSGWEFCBTJO-UHFFFAOYSA-N guanidine group Chemical group NC(=N)N ZRALSGWEFCBTJO-UHFFFAOYSA-N 0.000 description 1
- 229940093915 gynecological organic acid Drugs 0.000 description 1
- MNWFXJYAOYHMED-UHFFFAOYSA-N heptanoic acid Chemical compound CCCCCCC(O)=O MNWFXJYAOYHMED-UHFFFAOYSA-N 0.000 description 1
- FUZZWVXGSFPDMH-UHFFFAOYSA-N hexanoic acid Chemical compound CCCCCC(O)=O FUZZWVXGSFPDMH-UHFFFAOYSA-N 0.000 description 1
- 102000057111 human IL23R Human genes 0.000 description 1
- 210000005260 human cell Anatomy 0.000 description 1
- XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-M hydrogensulfate Chemical compound OS([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-M 0.000 description 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 1
- 210000002865 immune cell Anatomy 0.000 description 1
- 230000036039 immunity Effects 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 230000006698 induction Effects 0.000 description 1
- 230000008595 infiltration Effects 0.000 description 1
- 238000001764 infiltration Methods 0.000 description 1
- 230000002757 inflammatory effect Effects 0.000 description 1
- 230000028709 inflammatory response Effects 0.000 description 1
- 230000003993 interaction Effects 0.000 description 1
- 108040006858 interleukin-6 receptor activity proteins Proteins 0.000 description 1
- 229940047122 interleukins Drugs 0.000 description 1
- 230000004609 intestinal homeostasis Effects 0.000 description 1
- 210000004347 intestinal mucosa Anatomy 0.000 description 1
- 150000002500 ions Chemical class 0.000 description 1
- 230000007794 irritation Effects 0.000 description 1
- 238000002955 isolation Methods 0.000 description 1
- 125000001972 isopentyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])C([H])([H])* 0.000 description 1
- 238000005304 joining Methods 0.000 description 1
- 150000003951 lactams Chemical class 0.000 description 1
- 239000003446 ligand Substances 0.000 description 1
- 230000000670 limiting effect Effects 0.000 description 1
- 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 1
- 230000004807 localization Effects 0.000 description 1
- 230000005923 long-lasting effect Effects 0.000 description 1
- 210000004698 lymphocyte Anatomy 0.000 description 1
- 229960003646 lysine Drugs 0.000 description 1
- 239000011976 maleic acid Substances 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- 229960003194 meglumine Drugs 0.000 description 1
- 210000003071 memory t lymphocyte Anatomy 0.000 description 1
- 230000002503 metabolic effect Effects 0.000 description 1
- 230000004060 metabolic process Effects 0.000 description 1
- 230000000696 methanogenic effect Effects 0.000 description 1
- 125000000250 methylamino group Chemical group [H]N(*)C([H])([H])[H] 0.000 description 1
- 238000001000 micrograph Methods 0.000 description 1
- 210000000110 microvilli Anatomy 0.000 description 1
- 230000003278 mimic effect Effects 0.000 description 1
- 150000007522 mineralic acids Chemical class 0.000 description 1
- 210000003470 mitochondria Anatomy 0.000 description 1
- 238000010172 mouse model Methods 0.000 description 1
- 201000006417 multiple sclerosis Diseases 0.000 description 1
- 125000001421 myristyl 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])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 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
- 125000001280 n-hexyl group Chemical group C(CCCCC)* 0.000 description 1
- 125000000740 n-pentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- PSZYNBSKGUBXEH-UHFFFAOYSA-M naphthalene-1-sulfonate Chemical compound C1=CC=C2C(S(=O)(=O)[O-])=CC=CC2=C1 PSZYNBSKGUBXEH-UHFFFAOYSA-M 0.000 description 1
- KVBGVZZKJNLNJU-UHFFFAOYSA-M naphthalene-2-sulfonate Chemical compound C1=CC=CC2=CC(S(=O)(=O)[O-])=CC=C21 KVBGVZZKJNLNJU-UHFFFAOYSA-M 0.000 description 1
- 238000002663 nebulization Methods 0.000 description 1
- 230000001338 necrotic effect Effects 0.000 description 1
- 239000013642 negative control Substances 0.000 description 1
- 210000000440 neutrophil Anatomy 0.000 description 1
- 235000001968 nicotinic acid Nutrition 0.000 description 1
- 239000011664 nicotinic acid Substances 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 description 1
- 231100000252 nontoxic Toxicity 0.000 description 1
- 230000003000 nontoxic effect Effects 0.000 description 1
- 239000003921 oil Substances 0.000 description 1
- 235000019198 oils Nutrition 0.000 description 1
- 238000001543 one-way ANOVA Methods 0.000 description 1
- 210000000056 organ Anatomy 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 235000005985 organic acids Nutrition 0.000 description 1
- 235000006408 oxalic acid Nutrition 0.000 description 1
- AVPKHOTUOHDTLW-UHFFFAOYSA-N oxane-4-carboxylic acid Chemical compound OC(=O)C1CCOCC1 AVPKHOTUOHDTLW-UHFFFAOYSA-N 0.000 description 1
- 230000003647 oxidation Effects 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- 210000000496 pancreas Anatomy 0.000 description 1
- 230000036961 partial effect Effects 0.000 description 1
- 230000001717 pathogenic effect Effects 0.000 description 1
- 235000019371 penicillin G benzathine Nutrition 0.000 description 1
- 229940111202 pepsin Drugs 0.000 description 1
- 210000003819 peripheral blood mononuclear cell Anatomy 0.000 description 1
- JRKICGRDRMAZLK-UHFFFAOYSA-L peroxydisulfate Chemical compound [O-]S(=O)(=O)OOS([O-])(=O)=O JRKICGRDRMAZLK-UHFFFAOYSA-L 0.000 description 1
- COLNVLDHVKWLRT-UHFFFAOYSA-N phenylalanine Natural products OC(=O)C(N)CC1=CC=CC=C1 COLNVLDHVKWLRT-UHFFFAOYSA-N 0.000 description 1
- 150000002994 phenylalanines Chemical class 0.000 description 1
- 229940075930 picrate Drugs 0.000 description 1
- OXNIZHLAWKMVMX-UHFFFAOYSA-M picrate anion Chemical compound [O-]C1=C([N+]([O-])=O)C=C([N+]([O-])=O)C=C1[N+]([O-])=O OXNIZHLAWKMVMX-UHFFFAOYSA-M 0.000 description 1
- 229950010765 pivalate Drugs 0.000 description 1
- IUGYQRQAERSCNH-UHFFFAOYSA-N pivalic acid Chemical compound CC(C)(C)C(O)=O IUGYQRQAERSCNH-UHFFFAOYSA-N 0.000 description 1
- 230000036470 plasma concentration Effects 0.000 description 1
- 229920000642 polymer Polymers 0.000 description 1
- 102000054765 polymorphisms of proteins Human genes 0.000 description 1
- 238000001556 precipitation Methods 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- 229960002429 proline Drugs 0.000 description 1
- 230000001737 promoting effect Effects 0.000 description 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 230000002797 proteolythic effect Effects 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- JAEIBKXSIXOLOL-UHFFFAOYSA-N pyrrolidin-1-ium-3-carboxylate Chemical compound OC(=O)C1CCNC1 JAEIBKXSIXOLOL-UHFFFAOYSA-N 0.000 description 1
- 150000004728 pyruvic acid derivatives Chemical class 0.000 description 1
- 238000011552 rat model Methods 0.000 description 1
- 102000005962 receptors Human genes 0.000 description 1
- 108020003175 receptors Proteins 0.000 description 1
- 238000010188 recombinant method Methods 0.000 description 1
- 230000002829 reductive effect Effects 0.000 description 1
- 210000003289 regulatory T cell Anatomy 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 230000004044 response Effects 0.000 description 1
- 206010039073 rheumatoid arthritis Diseases 0.000 description 1
- 238000007363 ring formation reaction Methods 0.000 description 1
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 125000000467 secondary amino group Chemical group [H]N([*:1])[*:2] 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
- 230000035945 sensitivity Effects 0.000 description 1
- 210000002966 serum Anatomy 0.000 description 1
- 208000017520 skin disease Diseases 0.000 description 1
- 210000000813 small intestine Anatomy 0.000 description 1
- AWUCVROLDVIAJX-GSVOUGTGSA-N sn-glycerol 3-phosphate Chemical compound OC[C@@H](O)COP(O)(O)=O AWUCVROLDVIAJX-GSVOUGTGSA-N 0.000 description 1
- 230000006641 stabilisation Effects 0.000 description 1
- 238000011105 stabilization Methods 0.000 description 1
- 125000002328 sterol group Chemical group 0.000 description 1
- 210000002784 stomach Anatomy 0.000 description 1
- 229940086735 succinate Drugs 0.000 description 1
- KDYFGRWQOYBRFD-UHFFFAOYSA-L succinate(2-) Chemical compound [O-]C(=O)CCC([O-])=O KDYFGRWQOYBRFD-UHFFFAOYSA-L 0.000 description 1
- 230000008685 targeting Effects 0.000 description 1
- 229940095064 tartrate Drugs 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- 229940124597 therapeutic agent Drugs 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 229940066528 trichloroacetate Drugs 0.000 description 1
- YNJBWRMUSHSURL-UHFFFAOYSA-N trichloroacetic acid Chemical compound OC(=O)C(Cl)(Cl)Cl YNJBWRMUSHSURL-UHFFFAOYSA-N 0.000 description 1
- 229960000281 trometamol Drugs 0.000 description 1
- 229960001322 trypsin Drugs 0.000 description 1
- 150000003667 tyrosine derivatives Chemical class 0.000 description 1
- ZDPHROOEEOARMN-UHFFFAOYSA-N undecanoic acid Chemical compound CCCCCCCCCCC(O)=O ZDPHROOEEOARMN-UHFFFAOYSA-N 0.000 description 1
- 229960003824 ustekinumab Drugs 0.000 description 1
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 1
- 238000012800 visualization Methods 0.000 description 1
- 150000003751 zinc Chemical class 0.000 description 1
Images
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/04—Drugs for disorders of the alimentary tract or the digestive system for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/16—Drugs for disorders of the alimentary tract or the digestive system for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/18—Drugs for disorders of the alimentary tract or the digestive system for pancreatic disorders, e.g. pancreatic enzymes
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
- A61P11/02—Nasal agents, e.g. decongestants
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
- A61P11/06—Antiasthmatics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P15/00—Drugs for genital or sexual disorders; Contraceptives
- A61P15/14—Drugs for genital or sexual disorders; Contraceptives for lactation disorders, e.g. galactorrhoea
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
- A61P17/06—Antipsoriatics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/02—Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
- A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
- A61P37/06—Immunosuppressants, e.g. drugs for graft rejection
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P5/00—Drugs for disorders of the endocrine system
- A61P5/48—Drugs for disorders of the endocrine system of the pancreatic hormones
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- C07K14/52—Cytokines; Lymphokines; Interferons
- C07K14/54—Interleukins [IL]
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K7/00—Peptides having 5 to 20 amino acids in a fully defined sequence; Derivatives thereof
- C07K7/02—Linear peptides containing at least one abnormal peptide link
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K7/00—Peptides having 5 to 20 amino acids in a fully defined sequence; Derivatives thereof
- C07K7/04—Linear peptides containing only normal peptide links
- C07K7/08—Linear peptides containing only normal peptide links having 12 to 20 amino acids
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K7/00—Peptides having 5 to 20 amino acids in a fully defined sequence; Derivatives thereof
- C07K7/50—Cyclic peptides containing at least one abnormal peptide link
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K7/00—Peptides having 5 to 20 amino acids in a fully defined sequence; Derivatives thereof
- C07K7/64—Cyclic peptides containing only normal peptide links
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N2333/00—Assays involving biological materials from specific organisms or of a specific nature
- G01N2333/435—Assays involving biological materials from specific organisms or of a specific nature from animals; from humans
- G01N2333/52—Assays involving cytokines
- G01N2333/54—Interleukins [IL]
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N2800/00—Detection or diagnosis of diseases
- G01N2800/06—Gastro-intestinal diseases
- G01N2800/065—Bowel diseases, e.g. Crohn, ulcerative colitis, IBS
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
- G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
- G01N33/5005—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving human or animal cells
- G01N33/5008—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving human or animal cells for testing or evaluating the effect of chemical or biological compounds, e.g. drugs, cosmetics
- G01N33/5082—Supracellular entities, e.g. tissue, organisms
- G01N33/5088—Supracellular entities, e.g. tissue, organisms of vertebrates
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- Medicinal Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Veterinary Medicine (AREA)
- Pharmacology & Pharmacy (AREA)
- Public Health (AREA)
- Animal Behavior & Ethology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Molecular Biology (AREA)
- Biochemistry (AREA)
- Genetics & Genomics (AREA)
- Biophysics (AREA)
- Immunology (AREA)
- Diabetes (AREA)
- Pulmonology (AREA)
- Endocrinology (AREA)
- Gastroenterology & Hepatology (AREA)
- Toxicology (AREA)
- Zoology (AREA)
- Epidemiology (AREA)
- Hematology (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Rheumatology (AREA)
- Physical Education & Sports Medicine (AREA)
- Dermatology (AREA)
- Otolaryngology (AREA)
- Reproductive Health (AREA)
- Pregnancy & Childbirth (AREA)
- Gynecology & Obstetrics (AREA)
- Transplantation (AREA)
- Obesity (AREA)
- Emergency Medicine (AREA)
Applications Claiming Priority (7)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201462025899P | 2014-07-17 | 2014-07-17 | |
| US62/025,899 | 2014-07-17 | ||
| US201562119685P | 2015-02-23 | 2015-02-23 | |
| US201562119688P | 2015-02-23 | 2015-02-23 | |
| US62/119,685 | 2015-02-23 | ||
| US62/119,688 | 2015-02-23 | ||
| CN201580047898.0A CN107206254B (zh) | 2014-07-17 | 2015-07-15 | 白细胞介素-23受体的口服肽抑制剂以及其治疗炎症性肠病的用途 |
Related Parent Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201580047898.0A Division CN107206254B (zh) | 2014-07-17 | 2015-07-15 | 白细胞介素-23受体的口服肽抑制剂以及其治疗炎症性肠病的用途 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN113563423A true CN113563423A (zh) | 2021-10-29 |
Family
ID=55079037
Family Applications (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202110848583.3A Pending CN113563423A (zh) | 2014-07-17 | 2015-07-15 | 白细胞介素-23受体的口服肽抑制剂以及其治疗炎症性肠病的用途 |
| CN201580047898.0A Active CN107206254B (zh) | 2014-07-17 | 2015-07-15 | 白细胞介素-23受体的口服肽抑制剂以及其治疗炎症性肠病的用途 |
Family Applications After (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201580047898.0A Active CN107206254B (zh) | 2014-07-17 | 2015-07-15 | 白细胞介素-23受体的口服肽抑制剂以及其治疗炎症性肠病的用途 |
Country Status (14)
| Country | Link |
|---|---|
| US (7) | US9624268B2 (enExample) |
| EP (2) | EP4378536A3 (enExample) |
| JP (2) | JP2017530090A (enExample) |
| KR (1) | KR102482790B1 (enExample) |
| CN (2) | CN113563423A (enExample) |
| AU (1) | AU2015289642B2 (enExample) |
| BR (1) | BR112017001010A2 (enExample) |
| CA (1) | CA2955460A1 (enExample) |
| DK (1) | DK3169403T5 (enExample) |
| ES (1) | ES2977537T3 (enExample) |
| IL (2) | IL250111B (enExample) |
| RU (1) | RU2736637C9 (enExample) |
| SG (2) | SG11201700327WA (enExample) |
| WO (1) | WO2016011208A1 (enExample) |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2024114762A1 (zh) * | 2022-11-30 | 2024-06-06 | 上海翰森生物医药科技有限公司 | 一种多肽抑制剂、其制备方法和应用 |
| WO2024227437A1 (zh) * | 2023-05-04 | 2024-11-07 | 西藏海思科制药有限公司 | 白介素-23受体的肽抑制剂制备及其用途 |
Families Citing this family (45)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| USRE49026E1 (en) | 2011-06-14 | 2022-04-12 | Medical Diagnostic Laboratories, Llc | Polypeptides that bound to IL-23 receptor and inhibit binding of IL-23 and cell signaling thereof |
| PT2968443T (pt) | 2013-03-15 | 2021-12-28 | Protagonist Therapeutics Inc | Análogos de hepcidina e seus usos |
| SG10201810321PA (en) | 2014-05-16 | 2018-12-28 | Protagonist Therapeutics Inc | α4β7 INTEGRIN THIOETHER PEPTIDE ANTAGONISTS |
| ES2977537T3 (es) | 2014-07-17 | 2024-08-26 | Protagonist Therapeutics Inc | Inhibidores peptídicos orales del receptor de interleucina-23 y su uso para tratar enfermedades inflamatorias intestinales |
| US10301371B2 (en) | 2014-10-01 | 2019-05-28 | Protagonist Therapeutics, Inc. | Cyclic monomer and dimer peptides having integrin antagonist activity |
| SG11201702553RA (en) | 2014-10-01 | 2017-04-27 | Protagonist Therapeutics Inc | NOVEL α4β7 PEPTIDE MONOMER AND DIMER ANTAGONISTS |
| US10787490B2 (en) | 2015-07-15 | 2020-09-29 | Protaganist Therapeutics, Inc. | Peptide inhibitors of interleukin-23 receptor and their use to treat inflammatory diseases |
| CN108348580B (zh) * | 2015-07-15 | 2022-05-10 | 领导医疗有限公司 | 白细胞介素-23受体的肽抑制剂以及其治疗炎症性疾病的用途 |
| WO2017117411A1 (en) | 2015-12-30 | 2017-07-06 | Protagonist Therapeutics, Inc. | Analogues of hepcidin mimetics with improved in vivo half lives |
| US10407468B2 (en) | 2016-03-23 | 2019-09-10 | Protagonist Therapeutics, Inc. | Methods for synthesizing α4β7 peptide antagonists |
| WO2018022937A1 (en) * | 2016-07-27 | 2018-02-01 | Protagonist Therapeutics, Inc. | Peptide inhibitors of interleukin-23 and their use to treat inflammatory diseases |
| WO2018136646A1 (en) | 2017-01-18 | 2018-07-26 | Protagonist Therapeutics, Inc. | Peptide inhibitors of interleukin-23 receptor and their use to treat inflammatory diseases |
| EP4092038A1 (en) | 2017-09-11 | 2022-11-23 | Protagonist Therapeutics, Inc. | Opioid agonist peptides and uses thereof |
| EP4501952A3 (en) | 2018-02-08 | 2025-04-16 | Protagonist Therapeutics, Inc. | Conjugated hepcidin mimetics |
| WO2019207427A2 (en) * | 2018-04-25 | 2019-10-31 | Janssen Pharmaceutica Nv | Thioether cyclic peptide amylin receptor modulators |
| WO2019215701A1 (en) | 2018-05-11 | 2019-11-14 | Janssen Biotech, Inc. | Methods of treating depression using il-23 antibodies |
| US12171764B2 (en) | 2018-06-20 | 2024-12-24 | Biora Therapeutics, Inc. | Treatment of a disease of the gastrointestinal tract with a JAK or other kinase inhibitor |
| WO2019246455A1 (en) | 2018-06-20 | 2019-12-26 | Progenity, Inc. | Treatment of a disease of the gastrointestinal tract with an integrin inhibitor |
| WO2019246313A1 (en) | 2018-06-20 | 2019-12-26 | Progenity, Inc. | Treatment of a disease of the gastrointestinal tract with a tnf inhibitor |
| EP3810268A1 (en) | 2018-06-20 | 2021-04-28 | Progenity, Inc. | Treatment of a disease of the gastrointestinal tract with an il-12/il-23 inhibitor |
| US20230041197A1 (en) | 2018-06-20 | 2023-02-09 | Progenity, Inc. | Treatment of a disease of the gastrointestinal tract with an immunomodulator |
| WO2020014646A1 (en) * | 2018-07-12 | 2020-01-16 | Protagonist Therapeutics, Inc. | Peptide inhibitors of interleukin-23 receptor and their use to treat inflammatory diseases |
| CN111040020B (zh) * | 2018-12-28 | 2022-04-12 | 中国人民解放军军事科学院军事医学研究院 | 一种烯烃硫醚类订书肽及其制备方法与应用 |
| CN110015978B (zh) * | 2019-04-29 | 2021-03-19 | 康化（上海）新药研发有限公司 | O-[2-[[叔丁氧羰基]氨基]乙基]-n-[芴甲氧羰基]-l-酪氨酸的合成方法 |
| TW202116793A (zh) * | 2019-07-10 | 2021-05-01 | 美商領導醫療有限公司 | 介白素-23受體之肽抑制劑及其於治療發炎疾病的用途 |
| EP3997105A4 (en) * | 2019-07-10 | 2023-09-13 | Protagonist Therapeutics, Inc. | PEPTIDE INHIBITORS OF THE INTERLEUKIN-23 RECEPTOR AND THEIR USE TO TREAT INFLAMMATORY DISEASES |
| CN110790763A (zh) * | 2019-11-24 | 2020-02-14 | 烟台大学 | 吡啶并二嘧啶及吡啶并二吡唑衍生物的制备方法 |
| CN115279782A (zh) | 2020-01-15 | 2022-11-01 | 詹森生物科技公司 | 白介素-23受体的肽抑制剂及其用于治疗炎性疾病的用途 |
| WO2021146458A1 (en) * | 2020-01-15 | 2021-07-22 | Protagonist Therapeutics, Inc. | Peptide inhibitors of interleukin-23 receptor and their use to treat inflammatory diseases |
| IL294680A (en) | 2020-01-15 | 2022-09-01 | Janssen Biotech Inc | Peptide inhibitors of the interleukin-23 receptor and their use for the treatment of inflammatory diseases |
| MX2022016012A (es) * | 2020-06-29 | 2023-03-10 | Univ Washington | Polipéptidos de unión al receptor de la il-23 humana. |
| JP2023145581A (ja) * | 2020-11-20 | 2023-10-11 | ヤンセン ファーマシューティカ エヌ．ベー． | インターロイキン－２３受容体のペプチド阻害剤の組成物 |
| IL302996B2 (en) * | 2020-11-20 | 2025-04-01 | Janssen Pharmaceutica Nv | Compositions of interleukin-23 receptor peptide inhibitors |
| AU2022249097A1 (en) * | 2021-04-01 | 2023-10-12 | Protagonist Therapeutics, Inc. | Conjugated hepcidin mimetics |
| MX2024000761A (es) * | 2021-07-14 | 2024-04-18 | Janssen Biotech Inc | Inhibidores peptidicos biciclicos del receptor de interleucina-23. |
| AU2022311814A1 (en) | 2021-07-14 | 2024-02-29 | Janssen Biotech, Inc. | Lipidated peptide inhibitors of interleukin-23 receptor |
| EP4370531A4 (en) * | 2021-07-14 | 2025-09-03 | Janssen Biotech Inc | PEPTIDE INHIBITORS OF THE INTERLEUKIN-23 RECEPTOR |
| CA3240982A1 (en) | 2021-12-01 | 2023-06-08 | Zealand Pharma A/S | Peptide inhibitors of interleukin-23 receptor |
| KR20230112549A (ko) | 2022-01-20 | 2023-07-27 | 한국과학기술연구원 | 로세부리아 속 또는 비피도박테리움 속 유래 세포외소포체를 포함하는, 염증성 질환의 예방, 개선, 또는 치료용 조성물 |
| TW202400659A (zh) * | 2022-05-04 | 2024-01-01 | 美商詹努克斯治療有限公司 | 經腫瘤活化之靶向ｃｄ２８及ｐｄ－ｌ１之多特異性抗體及其使用方法 |
| JP2025521647A (ja) | 2022-06-30 | 2025-07-10 | サノフイ | 選択的ｉｌ－２３受容体アンタゴニストとしての新規ペプチド |
| EP4471048A1 (en) | 2023-06-01 | 2024-12-04 | Zealand Pharma A/S | Peptide inhibitors of interleukin-23 receptor |
| EP4471049A1 (en) | 2023-06-01 | 2024-12-04 | Zealand Pharma A/S | Peptide inhibitors of interleukin-23 receptor |
| WO2025051912A1 (en) | 2023-09-08 | 2025-03-13 | Sanofi | New peptides as selective il-23 receptor inhibitors |
| WO2025051920A1 (en) | 2023-09-08 | 2025-03-13 | Sanofi | New peptides as selective il-23 receptor inhibitors |
Family Cites Families (153)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4684620A (en) | 1984-09-04 | 1987-08-04 | Gibson-Stephens Neuropharmaceuticals, Inc. | Cyclic polypeptides having mu-receptor specificity |
| US4724229A (en) | 1986-09-30 | 1988-02-09 | Smithkline Beckman Corporation | Arg-arg-arg-vasopressin antagonists |
| JPH02306947A (ja) | 1989-05-01 | 1990-12-20 | Monsanto Co | キラルβ―アミノ酸の製造方法 |
| US5192746A (en) | 1990-07-09 | 1993-03-09 | Tanabe Seiyaku Co., Ltd. | Cyclic cell adhesion modulation compounds |
| DE69226077T2 (de) | 1991-04-05 | 1998-12-03 | Genentech, Inc., South San Francisco, Calif. | PLAETTCHENAGGREGATIONSINHIBITOREN MIT HOHER SPEZIFIZITAET ZUM GP IIbIIIa |
| US5569741A (en) | 1992-07-27 | 1996-10-29 | Biomeasure, Inc. | Cyclic octapeptide neuromedin B receptor antagonists |
| WO1994011018A1 (en) | 1992-11-12 | 1994-05-26 | Biomeasure, Inc. | Opioid peptides |
| US5293050A (en) | 1993-03-25 | 1994-03-08 | International Business Machines Corporation | Semiconductor quantum dot light emitting/detecting devices |
| AU673731B2 (en) | 1993-06-03 | 1996-11-21 | Banyu Pharmaceutical Co., Ltd. | Novel endothelin antagonistic peptide |
| GB9516994D0 (en) | 1995-08-18 | 1995-10-18 | Iaf Biochem Int | Solution synthesis of peripheral acting analgestic opioid tetrapeptides |
| US6037324A (en) | 1996-01-04 | 2000-03-14 | Leukosite, Inc. | Inhibitors of MAdCAM-1-mediated interactions and methods of use therefor |
| US5990084A (en) | 1996-04-19 | 1999-11-23 | Novo Nordisk A/S | Compounds with growth hormone releasing properties |
| GB9613112D0 (en) | 1996-06-21 | 1996-08-28 | Zeneca Ltd | Chemical compounds |
| US7122623B2 (en) | 1996-07-12 | 2006-10-17 | Adherex Technologies, Inc. | Compounds and methods for modulating cell adhesion |
| ES2283025T3 (es) | 1996-08-30 | 2007-10-16 | Novo Nordisk A/S | Derivados de glp-1.1. |
| US5942492A (en) | 1996-11-12 | 1999-08-24 | Angstrom Pharmaceuticals, Inc. | Cyclic peptides that bind to urokinase-type plasminogen activator receptor |
| US5993811A (en) | 1997-02-03 | 1999-11-30 | Biology Associates, Llc | Method and compositions for preventing and treating the systemic inflammatory response syndrome including sepsis |
| CA2206028C (en) | 1997-06-04 | 2006-10-03 | Frantisek Ziak | Fitness-balance board |
| EP0998309A1 (en) | 1997-07-11 | 2000-05-10 | Innerdyne Medical, Inc. | Methods and systems for preparing and sealing radiation delivery structures |
| US6818617B1 (en) | 1997-08-15 | 2004-11-16 | Temple University- Of The Commonwealth System Of Higher Education | EC-3, an inhibitor of α4β1 and α4β7 integrins |
| CA2309338A1 (en) | 1997-11-24 | 1999-06-03 | Merck & Co., Inc. | Cyclic amino acid derivatives as cell adhesion inhibitors |
| US8038984B2 (en) | 1998-06-20 | 2011-10-18 | Washington University | Membrane-permeant peptide complexes for treatment of sepsis |
| JP2002524108A (ja) | 1998-07-28 | 2002-08-06 | インナーダイン， インコーポレイテッド | 吸収性近接照射療法および化学療法送達デバイスならびに方法 |
| CA2341029A1 (en) | 1998-08-17 | 2000-02-24 | Abgenix, Inc. | Generation of modified molecules with increased serum half-lives |
| US6087334A (en) | 1998-08-21 | 2000-07-11 | Amylin Pharmaceuticals, Inc. | Anti-diabetic peptides |
| AUPP616498A0 (en) | 1998-09-25 | 1998-10-15 | University Of Queensland, The | Synthesis of cyclic peptides |
| AUPP616598A0 (en) | 1998-09-25 | 1998-10-15 | University Of Queensland, The | Auxiliary for amide bond formation |
| AUPP660698A0 (en) | 1998-10-21 | 1998-11-12 | University Of Queensland, The | A method of protein engineering |
| US6451987B1 (en) | 1999-03-15 | 2002-09-17 | Novo Nordisk A/S | Ion exchange chromatography of proteins and peptides |
| HUP0200297A3 (en) | 1999-03-17 | 2002-09-30 | Novo Nordisk As | Method for acylating peptides and the glutaminic acid derivatives as acylating agents |
| NZ514602A (en) | 1999-04-12 | 2003-06-30 | Aventis Pharma Ltd | Substituted bicyclic heteroaryl compounds as integrin antagonists |
| WO2001068586A2 (en) | 2000-03-14 | 2001-09-20 | Novartis Ag | α4β1 AND α4β7 INTEGRIN INHIBITORS |
| US20110131679A2 (en) | 2000-04-19 | 2011-06-02 | Thomas La Rosa | Rice Nucleic Acid Molecules and Other Molecules Associated with Plants and Uses Thereof for Plant Improvement |
| RU2292904C2 (ru) | 2001-01-09 | 2007-02-10 | Мерк Патент Гмбх | Комбинированная терапия, использующая ингибиторы рецептора тирозинкиназы и ингибиторы ангиогенезиса |
| DE10107707A1 (de) | 2001-02-19 | 2002-08-29 | Wilex Biotechnology Gmbh | Antagonisten für alpha¶4¶beta¶7¶-Integrin |
| AUPS039702A0 (en) | 2002-02-08 | 2002-03-07 | University Of Queensland, The | Common protein surface shapes and uses therefor |
| US20030166138A1 (en) | 2002-02-21 | 2003-09-04 | Todd Kinsella | Cyclic peptides and analogs useful to treat allergies |
| AU2003254585A1 (en) | 2002-07-24 | 2004-02-16 | Intercell Ag | Antigens encoded by alternative reading frame from pathogenic viruses |
| AU2003301059A1 (en) | 2002-12-18 | 2004-07-22 | Wyeth | Methods for screening, treating and diagnosing inflammatory bowel disease and compositions thereof |
| US20070032417A1 (en) | 2002-12-24 | 2007-02-08 | Walter And Eliza Hall Institute Of Medical Research | Peptides and therapeutic uses thereof |
| EP2006298A3 (en) | 2003-04-15 | 2009-04-22 | Xenon Pharmaceuticals Inc. | Juvenile hemochromatosis gene (HFE2A), expression products and uses thereof |
| PT2332968T (pt) | 2003-11-05 | 2016-08-17 | Harvard College | Péptidos alfa-helicoidais adequados para a activação ou inibição da morte celular |
| WO2005064345A2 (en) | 2003-12-19 | 2005-07-14 | Applera Corporation | Methods and systems for protein and peptide evidence assembly |
| CN1956738B (zh) | 2004-01-09 | 2013-05-29 | 辉瑞大药厂 | MAdCAM抗体 |
| US8536140B2 (en) | 2004-03-12 | 2013-09-17 | Mti Meta Tech Inc. | Methods for treating inflammatory bowel disease |
| WO2006000034A1 (en) | 2004-06-24 | 2006-01-05 | The Walter And Eliza Hall Institute Of Medical Research | Conjugates and therapeutic uses thereof |
| WO2006032104A1 (en) | 2004-09-23 | 2006-03-30 | The University Of Melbourne | Antigenic complex for the diagnosis and treatment of porphyromonas gingivalis infection |
| WO2006062685A2 (en) | 2004-11-11 | 2006-06-15 | Affymax, Inc. | Novel peptides that bind to the erythropoietin receptor |
| JP2008521840A (ja) | 2004-11-30 | 2008-06-26 | ガストロテック・ファルマ・アクティーゼルスカブ | 成長ホルモン分泌促進物質レセプター１ａリガンド |
| CN101163971B (zh) | 2004-12-20 | 2013-03-20 | 免疫体公司 | 测定作为肾病诊断标记物的嗜中性粒细胞明胶酶相关性脂笼蛋白 |
| US20100183617A1 (en) | 2005-02-23 | 2010-07-22 | University Of Virginia Patent Foundation | Compositions and methods for regulating sas1r |
| CA2549477A1 (en) | 2005-06-29 | 2006-12-29 | The Regents Of The University Of California | Competitive regulation of hepcidin mrna by soluble and cell-associated hemojuvelin |
| US20070212703A1 (en) | 2005-09-27 | 2007-09-13 | Stemmer Willem P | Proteinaceous pharmaceuticals and uses thereof |
| TW200744634A (en) * | 2006-02-21 | 2007-12-16 | Wyeth Corp | Methods of using antibodies against human IL-22 |
| EP2371957A1 (en) | 2006-04-12 | 2011-10-05 | Isis Pharmaceuticals, Inc. | Compositions and their uses directed to hepcidin |
| BRPI0713098A2 (pt) | 2006-05-22 | 2012-10-16 | Clinical Genomics Pty Ltd | método para determinar a origem anatÈmica de uma célula ou população celular derivada do intestino grosso de um indivìduo, método de detecção para determinar a origem anatÈmica de uma célula ou população celular derivada do intestino grosso de um indivìduo, sistema de detecção, meio de armazenagem legìvel por computador, arranjo de ácido nucleico, uso de um arranjo, método para determinar o inìcio ou predisposição para o inìcio de uma anormalidade celular ou uma condição destinguida por uma anormalidade celular no intestino grosso, kit de diagnóstico para ensaiar amostras biológicas |
| GB0610395D0 (en) | 2006-05-25 | 2006-07-05 | Ge Healthcare Ltd | Novel imaging agents |
| WO2007147019A2 (en) * | 2006-06-13 | 2007-12-21 | Zymogenetics, Inc. | Il-17 and il-23 antagonists and methods of using the same |
| US20080019913A1 (en) | 2006-07-07 | 2008-01-24 | University Of Arizona Office Of Technology Transfer | Enkepahlin analogs with improved bioavailability |
| CA2657338C (en) | 2006-07-21 | 2013-10-22 | Cristalia Produtos Quimicos Farmaceuticos Ltda. | Anti-inflammatory and antiallergic cyclic peptides |
| WO2008045252A2 (en) | 2006-10-04 | 2008-04-17 | The Board Of Trustees Of The Leland Stanford Junior University | Engineered integrin binding peptides |
| US7713937B2 (en) | 2006-11-10 | 2010-05-11 | Cara Therapeutics, Inc. | Synthetic peptide amides and dimeric forms thereof |
| WO2008140602A2 (en) | 2006-12-07 | 2008-11-20 | The Govenment Of The Usa As Represented By The Secretary Of The Dept. Of Health And Human Services | USE OF ANTAGONISTS OF THE INTERACTION BETWEEN HIV GP120 AND α4β7 INTEGRIN |
| PE20090722A1 (es) | 2007-02-02 | 2009-07-13 | Amgen Inc | Hepcidina, antagonistas de la hepcidina y metodos de uso |
| EA017849B1 (ru) | 2007-02-15 | 2013-03-29 | Индиана Юниверсити Рисерч Энд Текнолоджи Корпорейшн | Соагонисты глюкагоновых/glp-1-рецепторов |
| MX2009009079A (es) * | 2007-02-23 | 2009-08-31 | Schering Corp | Anticuerpos anti-il-23p19 de ingenieria. |
| US20080260820A1 (en) | 2007-04-19 | 2008-10-23 | Gilles Borrelly | Oral dosage formulations of protease-resistant polypeptides |
| WO2008134659A2 (en) | 2007-04-27 | 2008-11-06 | Zymogenetics, Inc. | Antagonists to il-17a, il-17f, and il-23p19 and methods of use |
| WO2008144041A1 (en) | 2007-05-21 | 2008-11-27 | The Ohio State University Research Foundation | Hepcidins as biomarkers for impending lupus nephritis flare |
| US20090131317A1 (en) | 2007-06-22 | 2009-05-21 | Affymax, Inc. | Compounds and peptides that bind the trail receptor |
| CN101990547A (zh) | 2007-07-06 | 2011-03-23 | 瓦勒瑞萨欣Hsj有限合伙公司 | Il-23受体拮抗剂以及其应用 |
| CN101358201A (zh) | 2007-07-31 | 2009-02-04 | 钱忠明 | 重组人铁调素腺病毒、其制备方法及应用 |
| CN101307085B (zh) | 2007-08-01 | 2012-06-13 | 香港理工大学深圳研究院 | 抑制铁调素调节蛋白的siRNA、重组慢病毒及其应用 |
| CA2707840A1 (en) | 2007-08-20 | 2009-02-26 | Allozyne, Inc. | Amino acid substituted molecules |
| GR1006896B (el) | 2007-08-24 | 2010-07-20 | Ελληνικο Ινστιτουτο Παστερ, | Μεθοδος παραγωγης μιας πεπτιδικης ορμονης |
| WO2009039185A1 (en) | 2007-09-17 | 2009-03-26 | The Trustees Of Columbia University In The City Of New York | Uses of immunologically modified scaffold for tissue prevascularization and cell transplantation |
| US20100280098A1 (en) | 2007-10-05 | 2010-11-04 | Juliano Rudolph L | Receptor targeted oligonucleotides |
| JP2012507723A (ja) | 2008-11-03 | 2012-03-29 | シェーリング コーポレイション | 炎症性腸疾患生物マーカーおよび関連治療方法 |
| CN102245626A (zh) | 2008-12-05 | 2011-11-16 | 加利福尼亚大学董事会 | 微型铁调素肽及其使用方法 |
| DE102009007381A1 (de) | 2009-01-29 | 2010-08-05 | Amp-Therapeutics Gmbh & Co. Kg | Antibiotische Peptide |
| US8999935B2 (en) | 2009-02-11 | 2015-04-07 | New York University | Treatment of osteoporosis in peri- and post-menopausal women with hepcidin |
| WO2010116752A1 (ja) | 2009-04-08 | 2010-10-14 | 武田薬品工業株式会社 | ニューロメジンｕ誘導体 |
| TWI578992B (zh) | 2009-04-30 | 2017-04-21 | 諾克森製藥股份有限公司 | 與鐵調節激素（ｈｅｐｃｉｄｉｎ）結合之核酸類 |
| US20110142889A1 (en) | 2009-12-16 | 2011-06-16 | Nod Pharmaceuticals, Inc. | Compositions and methods for oral drug delivery |
| CN104725472A (zh) | 2010-01-25 | 2015-06-24 | 康奈尔大学 | 芳香族阳离子肽及其用途 |
| US9523073B2 (en) * | 2010-03-31 | 2016-12-20 | Medical Diagnostic Laboratories, Llc | Elisa for a naturally-occurring soluble truncated form of IL-23 receptor |
| JP2011231085A (ja) | 2010-04-30 | 2011-11-17 | Osaka Prefecture Univ | 環状ペプチド |
| WO2011149942A2 (en) | 2010-05-24 | 2011-12-01 | Children's Medical Center Corporation | Compositions and methods for plasma peptide analysis |
| IT1406051B1 (it) | 2010-08-05 | 2014-02-06 | D M G Italia S R L | Uso di hmgb1 come marcatore biologico di infiammazione intestinale umana, metodo non invasivo per la sua rilevazione in campioni fecali e kit relativo. |
| EP3626253B8 (en) | 2010-08-11 | 2022-04-20 | Ironwood Pharmaceuticals, Inc. | Stable formulations of linaclotide |
| EP2444101A1 (en) | 2010-10-21 | 2012-04-25 | Universitätsklinikum Freiburg | Selective targeting of the CD40L/Mac-1 interaction by small peptide inhibitors and its use for the treatment of inflammation and atherogenesis |
| US9243034B2 (en) | 2011-01-27 | 2016-01-26 | Ramot At Tel-Aviv University Ltd. | Glycogen synthase kinase-3 inhibitors |
| CN103764159A (zh) | 2011-06-14 | 2014-04-30 | 康肽德生物医药技术有限公司 | 芳香族阳离子肽及其用途 |
| US9169292B2 (en) * | 2011-06-14 | 2015-10-27 | Medical Diagnostic Laboratories, Llc | Polypeptides that bound to IL-23 receptor and inhibit binding of IL-23 and cell signaling thereof |
| US9605027B2 (en) | 2011-06-14 | 2017-03-28 | Medical Diagnostic Laboratories, Llc | Polypeptides that bound to IL-23 receptor and inhibit binding of IL-23 and cell signaling thereof |
| US8946150B2 (en) * | 2011-06-14 | 2015-02-03 | Medical Diagnostic Laboratories, LLC. | Polypeptides that bound to IL-23 receptor and inhibit binding of IL-23 and cell signaling thereof |
| CA2855122A1 (en) | 2011-12-09 | 2013-06-13 | The Regents Of The University Of California | Modified mini-hepcidin peptides and methods of using thereof |
| WO2013177432A1 (en) | 2012-05-23 | 2013-11-28 | The University Of Chicago | Methods of treating obesity |
| US9024044B2 (en) | 2012-06-14 | 2015-05-05 | Ajinomoto Co., Inc. | Heteroarylcarboxylic acid ester derivative |
| US9273093B2 (en) | 2012-10-11 | 2016-03-01 | Protagonist Therapeutics, Inc. | α4β7 peptide dimer antagonists |
| HK1219048A1 (zh) | 2013-02-15 | 2017-03-24 | Srx Cardio, Llc | 前蛋白转化酶枯草杆菌蛋白酶/kexin 9型(pcsk9)变构结合配体来调节低密度脂蛋白(ldl)血清水平 |
| PT2968443T (pt) | 2013-03-15 | 2021-12-28 | Protagonist Therapeutics Inc | Análogos de hepcidina e seus usos |
| US20140294901A1 (en) | 2013-04-02 | 2014-10-02 | Protagonist Therapeutics, Inc. | Novel a4b7 peptide dimer antagonists |
| US20140294902A1 (en) | 2013-04-02 | 2014-10-02 | Protagonist Therapeutics, Inc. | Novel a4b7 peptide antagonists |
| JP6401255B2 (ja) | 2013-06-24 | 2018-10-10 | 株式会社 キャンバス | ペプチド及びペプチド模倣物の併用並びに癌患者亜集団の処置 |
| CA2916492A1 (en) | 2013-06-27 | 2014-12-31 | Stealth Biotherapeutics Corp | Peptide therapeutics and methods for using same |
| EP3065757A4 (en) | 2013-10-09 | 2017-08-23 | Synergy Pharmaceuticals Inc. | Agonists of guanylate cyclase useful for downregulation of pro-inflammatory cytokines |
| US9284362B2 (en) | 2014-01-22 | 2016-03-15 | Wisconsin Alumni Research Foundation | α/β-peptide mimics of Z-domain peptides |
| WO2015157283A1 (en) | 2014-04-07 | 2015-10-15 | Merganser Biotech Llc | Hepdicin mimetic peptides and uses thereof |
| SG10201810321PA (en) | 2014-05-16 | 2018-12-28 | Protagonist Therapeutics Inc | α4β7 INTEGRIN THIOETHER PEPTIDE ANTAGONISTS |
| WO2015183963A2 (en) | 2014-05-28 | 2015-12-03 | Stealth Peptides International, Inc. | Therapeutic compositions including redox-active parabenzoquinones and uses thereof |
| CA2953721A1 (en) | 2014-06-27 | 2015-12-30 | Protagonist Therapeutics, Inc. | Hepcidin and mini-hepcidin analogues and uses therof |
| WO2016004093A2 (en) | 2014-07-01 | 2016-01-07 | Stealth Biotherapeutics Corp | Therapeutic compositions including galectin-3 inhibitors and uses thereof |
| ES2977537T3 (es) | 2014-07-17 | 2024-08-26 | Protagonist Therapeutics Inc | Inhibidores peptídicos orales del receptor de interleucina-23 y su uso para tratar enfermedades inflamatorias intestinales |
| US10301371B2 (en) | 2014-10-01 | 2019-05-28 | Protagonist Therapeutics, Inc. | Cyclic monomer and dimer peptides having integrin antagonist activity |
| SG11201702553RA (en) | 2014-10-01 | 2017-04-27 | Protagonist Therapeutics Inc | NOVEL α4β7 PEPTIDE MONOMER AND DIMER ANTAGONISTS |
| US20170362292A1 (en) | 2014-12-29 | 2017-12-21 | The Regents Of The University Of California | S-Alkylated Hepcidin Peptides and Methods of Making and Using Thereof |
| US20160199437A1 (en) | 2015-01-08 | 2016-07-14 | D. Travis Wilson | Therapeutic compositions including iron chelators and uses thereof |
| WO2016115168A1 (en) | 2015-01-12 | 2016-07-21 | Synthorx, Inc. | Incorporation of unnatural nucleotides and methods thereof |
| US20160228491A1 (en) | 2015-02-09 | 2016-08-11 | Stealth Biotherapeutics Corp | Therapeutic compositions including phenazine-3-one and phenothiazine-3-one derivatives and uses thereof |
| WO2016195663A1 (en) | 2015-06-02 | 2016-12-08 | Stealth Peptides International, Inc. | Therapeutic compositions including bpm 31510, variants and analogues thereof, and uses thereof |
| WO2016200364A1 (en) | 2015-06-08 | 2016-12-15 | Stealth Peptides International, Inc. | THERAPEUTIC COMPOSITIONS INCLUDING SkQ COMPOUNDS AND USES THEREOF |
| CN108348580B (zh) | 2015-07-15 | 2022-05-10 | 领导医疗有限公司 | 白细胞介素-23受体的肽抑制剂以及其治疗炎症性疾病的用途 |
| US10787490B2 (en) | 2015-07-15 | 2020-09-29 | Protaganist Therapeutics, Inc. | Peptide inhibitors of interleukin-23 receptor and their use to treat inflammatory diseases |
| WO2017117411A1 (en) | 2015-12-30 | 2017-07-06 | Protagonist Therapeutics, Inc. | Analogues of hepcidin mimetics with improved in vivo half lives |
| US10407468B2 (en) | 2016-03-23 | 2019-09-10 | Protagonist Therapeutics, Inc. | Methods for synthesizing α4β7 peptide antagonists |
| WO2018022917A1 (en) | 2016-07-27 | 2018-02-01 | Protagonist Therapeutics, Inc. | Disulfide-rich peptide libraries and methods of use thereof |
| WO2018022937A1 (en) | 2016-07-27 | 2018-02-01 | Protagonist Therapeutics, Inc. | Peptide inhibitors of interleukin-23 and their use to treat inflammatory diseases |
| WO2018089693A2 (en) | 2016-11-09 | 2018-05-17 | Protagonist Therapeutics, Inc. | Methods for determining and monitoring gastrointestinal inflammation |
| US11192918B2 (en) | 2016-12-06 | 2021-12-07 | Stichting Voor De Technische Wetenschappen | Multicyclic peptides and methods for their preparation |
| WO2018136646A1 (en) | 2017-01-18 | 2018-07-26 | Protagonist Therapeutics, Inc. | Peptide inhibitors of interleukin-23 receptor and their use to treat inflammatory diseases |
| EP4092038A1 (en) | 2017-09-11 | 2022-11-23 | Protagonist Therapeutics, Inc. | Opioid agonist peptides and uses thereof |
| EP4501952A3 (en) | 2018-02-08 | 2025-04-16 | Protagonist Therapeutics, Inc. | Conjugated hepcidin mimetics |
| US12171764B2 (en) * | 2018-06-20 | 2024-12-24 | Biora Therapeutics, Inc. | Treatment of a disease of the gastrointestinal tract with a JAK or other kinase inhibitor |
| JOP20190150A1 (ar) | 2018-06-21 | 2019-12-21 | Merck Sharp & Dohme | مركبات مناهضة لـ pcsk9 |
| WO2020014646A1 (en) | 2018-07-12 | 2020-01-16 | Protagonist Therapeutics, Inc. | Peptide inhibitors of interleukin-23 receptor and their use to treat inflammatory diseases |
| WO2020198682A1 (en) | 2019-03-28 | 2020-10-01 | Protagonist Therapeutics, Inc. | METHODS FOR SYNTHESIZING β-HOMOAMINO ACIDS |
| EP3997105A4 (en) | 2019-07-10 | 2023-09-13 | Protagonist Therapeutics, Inc. | PEPTIDE INHIBITORS OF THE INTERLEUKIN-23 RECEPTOR AND THEIR USE TO TREAT INFLAMMATORY DISEASES |
| TW202116793A (zh) | 2019-07-10 | 2021-05-01 | 美商領導醫療有限公司 | 介白素-23受體之肽抑制劑及其於治療發炎疾病的用途 |
| BR112022003999A2 (pt) | 2019-09-03 | 2022-05-31 | Protagonist Therapeutics Inc | Miméticos de hepcidina conjugados |
| US20230063321A1 (en) | 2020-01-10 | 2023-03-02 | Suneel Kumar Gupta | Methods for Treating Inflammatory Bowel Diseases with alpha4beta7 Integrin Antagonists |
| IL294680A (en) | 2020-01-15 | 2022-09-01 | Janssen Biotech Inc | Peptide inhibitors of the interleukin-23 receptor and their use for the treatment of inflammatory diseases |
| CN115279782A (zh) | 2020-01-15 | 2022-11-01 | 詹森生物科技公司 | 白介素-23受体的肽抑制剂及其用于治疗炎性疾病的用途 |
| WO2021146458A1 (en) | 2020-01-15 | 2021-07-22 | Protagonist Therapeutics, Inc. | Peptide inhibitors of interleukin-23 receptor and their use to treat inflammatory diseases |
| AU2021315564A1 (en) | 2020-07-28 | 2023-02-09 | Protagonist Therapeutics, Inc. | Conjugated hepcidin mimetics |
| IL302996B2 (en) | 2020-11-20 | 2025-04-01 | Janssen Pharmaceutica Nv | Compositions of interleukin-23 receptor peptide inhibitors |
| AU2022249097A1 (en) | 2021-04-01 | 2023-10-12 | Protagonist Therapeutics, Inc. | Conjugated hepcidin mimetics |
| CA3213688A1 (en) | 2021-04-01 | 2022-10-06 | Ashok Bhandari | Conjugated hepcidin mimetics |
| US20240226225A1 (en) | 2021-04-01 | 2024-07-11 | Protagonist Therapeutics, Inc. | Conjugated hepcidin mimetics |
| KR20240021833A (ko) | 2021-06-14 | 2024-02-19 | 프로타고니스트 테라퓨틱스, 인코포레이티드 | 유전성 혈색소 침착증의 치료를 위한 헵시딘 모방체 |
| EP4370531A4 (en) | 2021-07-14 | 2025-09-03 | Janssen Biotech Inc | PEPTIDE INHIBITORS OF THE INTERLEUKIN-23 RECEPTOR |
| MX2024000761A (es) | 2021-07-14 | 2024-04-18 | Janssen Biotech Inc | Inhibidores peptidicos biciclicos del receptor de interleucina-23. |
| AU2022311814A1 (en) | 2021-07-14 | 2024-02-29 | Janssen Biotech, Inc. | Lipidated peptide inhibitors of interleukin-23 receptor |
-
2015
- 2015-07-15 ES ES15821351T patent/ES2977537T3/es active Active
- 2015-07-15 SG SG11201700327WA patent/SG11201700327WA/en unknown
- 2015-07-15 EP EP24156804.7A patent/EP4378536A3/en active Pending
- 2015-07-15 KR KR1020177004395A patent/KR102482790B1/ko active Active
- 2015-07-15 JP JP2017502701A patent/JP2017530090A/ja not_active Withdrawn
- 2015-07-15 AU AU2015289642A patent/AU2015289642B2/en active Active
- 2015-07-15 RU RU2017105115A patent/RU2736637C9/ru active
- 2015-07-15 EP EP15821351.2A patent/EP3169403B9/en active Active
- 2015-07-15 CN CN202110848583.3A patent/CN113563423A/zh active Pending
- 2015-07-15 US US14/800,627 patent/US9624268B2/en active Active
- 2015-07-15 BR BR112017001010A patent/BR112017001010A2/pt not_active IP Right Cessation
- 2015-07-15 CA CA2955460A patent/CA2955460A1/en active Pending
- 2015-07-15 SG SG10201810154WA patent/SG10201810154WA/en unknown
- 2015-07-15 CN CN201580047898.0A patent/CN107206254B/zh active Active
- 2015-07-15 DK DK15821351.2T patent/DK3169403T5/da active
- 2015-07-15 WO PCT/US2015/040658 patent/WO2016011208A1/en not_active Ceased
-
2017
- 2017-01-15 IL IL250111A patent/IL250111B/en unknown
- 2017-02-24 US US15/442,229 patent/US10196424B2/en active Active
- 2017-12-04 US US15/831,100 patent/US10023614B2/en active Active
- 2017-12-04 US US15/831,087 patent/US10035824B2/en active Active
-
2018
- 2018-12-12 US US16/217,864 patent/US10941183B2/en active Active
-
2020
- 2020-06-08 JP JP2020099144A patent/JP6995933B2/ja active Active
-
2021
- 2021-01-28 US US17/161,370 patent/US11884748B2/en active Active
- 2021-08-15 IL IL285614A patent/IL285614A/en unknown
-
2023
- 2023-12-01 US US18/527,006 patent/US20240199700A1/en active Pending
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2024114762A1 (zh) * | 2022-11-30 | 2024-06-06 | 上海翰森生物医药科技有限公司 | 一种多肽抑制剂、其制备方法和应用 |
| WO2024227437A1 (zh) * | 2023-05-04 | 2024-11-07 | 西藏海思科制药有限公司 | 白介素-23受体的肽抑制剂制备及其用途 |
Also Published As
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN107206254B (zh) | 白细胞介素-23受体的口服肽抑制剂以及其治疗炎症性肠病的用途 | |
| AU2016293619B2 (en) | Peptide inhibitors of interleukin-23 receptor and their use to treat inflammatory diseases | |
| US10787490B2 (en) | Peptide inhibitors of interleukin-23 receptor and their use to treat inflammatory diseases | |
| AU2018210174B2 (en) | Peptide inhibitors of interleukin-23 receptor and their use to treat inflammatory diseases | |
| WO2018022937A1 (en) | Peptide inhibitors of interleukin-23 and their use to treat inflammatory diseases | |
| HK1259149B (en) | Peptide inhibitors of interleukin-23 receptor and their use to treat inflammatory diseases |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination |