SK5552002A3 - Pituitary adenylate cyclase activating peptide (PACAP) receptor 3 (R3) agonists and their pharmacological methods of use - Google Patents

Pituitary adenylate cyclase activating peptide (PACAP) receptor 3 (R3) agonists and their pharmacological methods of use Download PDF

Info

Publication number: SK5552002A3
Authority: SK; Slovakia
Prior art keywords: seq; polypeptide; nos; pacap; polypeptides
Prior art date: 1999-09-28

Application number

SK555-2002A

Other languages

English (en)

Slovak (sk)

Inventor

Clark Pan

Manami Tsutsumi

Armen B Shanafelt

Original Assignee

Bayer Ag

Priority date (The priority date 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 date listed.)

1999-09-28

Filing date

2000-09-27

Publication date

2003-05-02

2000-09-27 Application filed by Bayer Ag filed Critical Bayer Ag

2003-05-02 Publication of SK5552002A3 publication Critical patent/SK5552002A3/sk

Links

108090000765 processed proteins & peptides Proteins 0.000 title claims abstract description 345
238000000034 method Methods 0.000 title claims abstract description 63
239000000556 agonist Substances 0.000 title claims description 37
230000003213 activating effect Effects 0.000 title description 4
102000030621 adenylate cyclase Human genes 0.000 title description 3
108060000200 adenylate cyclase Proteins 0.000 title description 3
230000000144 pharmacologic effect Effects 0.000 title description 2
230000001817 pituitary effect Effects 0.000 title description 2
102000004196 processed proteins & peptides Human genes 0.000 claims abstract description 271
229920001184 polypeptide Polymers 0.000 claims abstract description 223
230000003914 insulin secretion Effects 0.000 claims abstract description 37
102000002808 Pituitary adenylate cyclase-activating polypeptide Human genes 0.000 claims abstract description 26
108010004684 Pituitary adenylate cyclase-activating polypeptide Proteins 0.000 claims abstract description 26
241000124008 Mammalia Species 0.000 claims abstract description 12
208000030159 metabolic disease Diseases 0.000 claims abstract description 5
108090000623 proteins and genes Proteins 0.000 claims description 56
108010003205 Vasoactive Intestinal Peptide Proteins 0.000 claims description 53
239000013598 vector Substances 0.000 claims description 53
102000055135 Vasoactive Intestinal Peptide Human genes 0.000 claims description 46
239000012634 fragment Substances 0.000 claims description 28
108091033319 polynucleotide Proteins 0.000 claims description 27
102000040430 polynucleotide Human genes 0.000 claims description 27
239000002157 polynucleotide Substances 0.000 claims description 27
239000000203 mixture Substances 0.000 claims description 18
238000001415 gene therapy Methods 0.000 claims description 16
208000001072 type 2 diabetes mellitus Diseases 0.000 claims description 12
230000004936 stimulating effect Effects 0.000 claims description 7
VBUWHHLIZKOSMS-RIWXPGAOSA-N invicorp Chemical compound C([C@@H](C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CO)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(N)=O)C(O)=O)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CCCCN)NC(=O)[C@@H](NC(=O)[C@H](C)NC(=O)[C@H](CCSC)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@@H](NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(O)=O)NC(=O)[C@@H](NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@@H](NC(=O)[C@H](C)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CO)NC(=O)[C@@H](N)CC=1NC=NC=1)C(C)C)[C@@H](C)O)[C@@H](C)O)C(C)C)C1=CC=C(O)C=C1 VBUWHHLIZKOSMS-RIWXPGAOSA-N 0.000 claims description 6
208000002705 Glucose Intolerance Diseases 0.000 claims description 5
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 5
239000008194 pharmaceutical composition Substances 0.000 claims description 5
201000009104 prediabetes syndrome Diseases 0.000 claims description 5
238000004113 cell culture Methods 0.000 claims description 4
206010018429 Glucose tolerance impaired Diseases 0.000 claims description 3
239000003937 drug carrier Substances 0.000 claims description 3
238000012258 culturing Methods 0.000 claims description 2
230000002503 metabolic effect Effects 0.000 claims description 2
208000023504 respiratory system disease Diseases 0.000 claims 1
WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 abstract description 80
239000008103 glucose Substances 0.000 abstract description 80
238000001727 in vivo Methods 0.000 abstract description 27
230000001419 dependent effect Effects 0.000 abstract description 20
238000002560 therapeutic procedure Methods 0.000 abstract description 10
238000000338 in vitro Methods 0.000 abstract description 9
210000002237 B-cell of pancreatic islet Anatomy 0.000 abstract description 6
210000004153 islets of langerhan Anatomy 0.000 abstract description 6
229940122199 Insulin secretagogue Drugs 0.000 abstract 2
230000003247 decreasing effect Effects 0.000 abstract 1
208000016097 disease of metabolism Diseases 0.000 abstract 1
NOESYZHRGYRDHS-UHFFFAOYSA-N insulin Chemical compound N1C(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(NC(=O)CN)C(C)CC)CSSCC(C(NC(CO)C(=O)NC(CC(C)C)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CCC(N)=O)C(=O)NC(CC(C)C)C(=O)NC(CCC(O)=O)C(=O)NC(CC(N)=O)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CSSCC(NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2C=CC(O)=CC=2)NC(=O)C(CC(C)C)NC(=O)C(C)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2NC=NC=2)NC(=O)C(CO)NC(=O)CNC2=O)C(=O)NCC(=O)NC(CCC(O)=O)C(=O)NC(CCCNC(N)=N)C(=O)NCC(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC(O)=CC=3)C(=O)NC(C(C)O)C(=O)N3C(CCC3)C(=O)NC(CCCCN)C(=O)NC(C)C(O)=O)C(=O)NC(CC(N)=O)C(O)=O)=O)NC(=O)C(C(C)CC)NC(=O)C(CO)NC(=O)C(C(C)O)NC(=O)C1CSSCC2NC(=O)C(CC(C)C)NC(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CC(N)=O)NC(=O)C(NC(=O)C(N)CC=1C=CC=CC=1)C(C)C)CC1=CN=CN1 NOESYZHRGYRDHS-UHFFFAOYSA-N 0.000 description 86
210000004027 cell Anatomy 0.000 description 61
230000000694 effects Effects 0.000 description 50
102000004877 Insulin Human genes 0.000 description 43
108090001061 Insulin Proteins 0.000 description 43
229940125396 insulin Drugs 0.000 description 43
238000011282 treatment Methods 0.000 description 29
241000700159 Rattus Species 0.000 description 27
102000005962 receptors Human genes 0.000 description 26
108020003175 receptors Proteins 0.000 description 26
108020004414 DNA Proteins 0.000 description 22
125000003275 alpha amino acid group Chemical group 0.000 description 22
229940024606 amino acid Drugs 0.000 description 21
235000001014 amino acid Nutrition 0.000 description 20
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 19
102400000322 Glucagon-like peptide 1 Human genes 0.000 description 18
150000001413 amino acids Chemical class 0.000 description 18
239000008280 blood Substances 0.000 description 18
210000004369 blood Anatomy 0.000 description 18
101710198884 GATA-type zinc finger protein 1 Proteins 0.000 description 17
DTHNMHAUYICORS-KTKZVXAJSA-N Glucagon-like peptide 1 Chemical compound C([C@@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](C)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CCCCN)C(=O)NCC(=O)N[C@@H](CCCNC(N)=N)C(N)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CCCCN)NC(=O)[C@H](C)NC(=O)[C@H](C)NC(=O)[C@H](CCC(N)=O)NC(=O)CNC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CO)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@@H](NC(=O)CNC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C)NC(=O)[C@@H](N)CC=1N=CNC=1)[C@@H](C)O)[C@@H](C)O)C(C)C)C1=CC=CC=C1 DTHNMHAUYICORS-KTKZVXAJSA-N 0.000 description 17
108091028043 Nucleic acid sequence Proteins 0.000 description 17
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 17
235000018102 proteins Nutrition 0.000 description 17
102000004169 proteins and genes Human genes 0.000 description 17
238000004519 manufacturing process Methods 0.000 description 16
230000008827 biological function Effects 0.000 description 14
206010012601 diabetes mellitus Diseases 0.000 description 14
239000000126 substance Substances 0.000 description 14
IVOMOUWHDPKRLL-KQYNXXCUSA-N Cyclic adenosine monophosphate Chemical compound C([C@H]1O2)OP(O)(=O)O[C@H]1[C@@H](O)[C@@H]2N1C(N=CN=C2N)=C2N=C1 IVOMOUWHDPKRLL-KQYNXXCUSA-N 0.000 description 13
125000000539 amino acid group Chemical group 0.000 description 13
239000013604 expression vector Substances 0.000 description 13
239000011780 sodium chloride Substances 0.000 description 13
241001465754 Metazoa Species 0.000 description 12
230000015572 biosynthetic process Effects 0.000 description 12
239000000872 buffer Substances 0.000 description 11
210000002216 heart Anatomy 0.000 description 11
230000001965 increasing effect Effects 0.000 description 11
230000001404 mediated effect Effects 0.000 description 11
239000013612 plasmid Substances 0.000 description 11
239000000047 product Substances 0.000 description 11
230000001177 retroviral effect Effects 0.000 description 11
230000004071 biological effect Effects 0.000 description 10
238000003776 cleavage reaction Methods 0.000 description 10
125000003729 nucleotide group Chemical group 0.000 description 10
230000007017 scission Effects 0.000 description 10
238000003786 synthesis reaction Methods 0.000 description 10
241000588724 Escherichia coli Species 0.000 description 9
108010074860 Factor Xa Proteins 0.000 description 9
DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 9
101710137651 Vasoactive intestinal polypeptide receptor 2 Proteins 0.000 description 9
102100038286 Vasoactive intestinal polypeptide receptor 2 Human genes 0.000 description 9
241000700605 Viruses Species 0.000 description 9
230000004913 activation Effects 0.000 description 9
210000000227 basophil cell of anterior lobe of hypophysis Anatomy 0.000 description 9
LOKCTEFSRHRXRJ-UHFFFAOYSA-I dipotassium trisodium dihydrogen phosphate hydrogen phosphate dichloride Chemical compound P(=O)(O)(O)[O-].[K+].P(=O)(O)([O-])[O-].[Na+].[Na+].[Cl-].[K+].[Cl-].[Na+] LOKCTEFSRHRXRJ-UHFFFAOYSA-I 0.000 description 9
230000004927 fusion Effects 0.000 description 9
239000002773 nucleotide Substances 0.000 description 9
239000002953 phosphate buffered saline Substances 0.000 description 9
238000006467 substitution reaction Methods 0.000 description 9
241000701161 unidentified adenovirus Species 0.000 description 9
ROHFNLRQFUQHCH-YFKPBYRVSA-N L-leucine Chemical compound CC(C)C[C@H](N)C(O)=O ROHFNLRQFUQHCH-YFKPBYRVSA-N 0.000 description 8
241000829100 Macaca mulatta polyomavirus 1 Species 0.000 description 8
230000001580 bacterial effect Effects 0.000 description 8
NZWOPGCLSHLLPA-UHFFFAOYSA-N methacholine Chemical compound C[N+](C)(C)CC(C)OC(C)=O NZWOPGCLSHLLPA-UHFFFAOYSA-N 0.000 description 8
229960002329 methacholine Drugs 0.000 description 8
238000010188 recombinant method Methods 0.000 description 8
239000000243 solution Substances 0.000 description 8
MTCFGRXMJLQNBG-REOHCLBHSA-N (2S)-2-Amino-3-hydroxypropansäure Chemical compound OC[C@H](N)C(O)=O MTCFGRXMJLQNBG-REOHCLBHSA-N 0.000 description 7
239000000427 antigen Substances 0.000 description 7
102000036639 antigens Human genes 0.000 description 7
108091007433 antigens Proteins 0.000 description 7
239000003814 drug Substances 0.000 description 7
239000003623 enhancer Substances 0.000 description 7
210000003527 eukaryotic cell Anatomy 0.000 description 7
230000006870 function Effects 0.000 description 7
230000004048 modification Effects 0.000 description 7
238000012986 modification Methods 0.000 description 7
150000007523 nucleic acids Chemical class 0.000 description 7
239000003981 vehicle Substances 0.000 description 7
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 6
108010011459 Exenatide Proteins 0.000 description 6
XUJNEKJLAYXESH-REOHCLBHSA-N L-Cysteine Chemical compound SC[C@H](N)C(O)=O XUJNEKJLAYXESH-REOHCLBHSA-N 0.000 description 6
AYFVYJQAPQTCCC-GBXIJSLDSA-N L-threonine Chemical compound C[C@@H](O)[C@H](N)C(O)=O AYFVYJQAPQTCCC-GBXIJSLDSA-N 0.000 description 6
102100034309 Pituitary adenylate cyclase-activating polypeptide type I receptor Human genes 0.000 description 6
102100038388 Vasoactive intestinal polypeptide receptor 1 Human genes 0.000 description 6
101710137655 Vasoactive intestinal polypeptide receptor 1 Proteins 0.000 description 6
210000003169 central nervous system Anatomy 0.000 description 6
229960001519 exenatide Drugs 0.000 description 6
238000002474 experimental method Methods 0.000 description 6
239000007924 injection Substances 0.000 description 6
238000002347 injection Methods 0.000 description 6
239000002609 medium Substances 0.000 description 6
238000002703 mutagenesis Methods 0.000 description 6
231100000350 mutagenesis Toxicity 0.000 description 6
WEXRUCMBJFQVBZ-UHFFFAOYSA-N pentobarbital Chemical compound CCCC(C)C1(CC)C(=O)NC(=O)NC1=O WEXRUCMBJFQVBZ-UHFFFAOYSA-N 0.000 description 6
238000012216 screening Methods 0.000 description 6
238000012546 transfer Methods 0.000 description 6
241000282472 Canis lupus familiaris Species 0.000 description 5
108020004705 Codon Proteins 0.000 description 5
241000701022 Cytomegalovirus Species 0.000 description 5
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 5
108010070675 Glutathione transferase Proteins 0.000 description 5
102000005720 Glutathione transferase Human genes 0.000 description 5
COLNVLDHVKWLRT-QMMMGPOBSA-N L-phenylalanine Chemical compound OC(=O)[C@@H](N)CC1=CC=CC=C1 COLNVLDHVKWLRT-QMMMGPOBSA-N 0.000 description 5
OUYCCCASQSFEME-QMMMGPOBSA-N L-tyrosine Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-QMMMGPOBSA-N 0.000 description 5
KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 5
241000700157 Rattus norvegicus Species 0.000 description 5
229940100389 Sulfonylurea Drugs 0.000 description 5
102000006601 Thymidine Kinase Human genes 0.000 description 5
108020004440 Thymidine kinase Proteins 0.000 description 5
239000002671 adjuvant Substances 0.000 description 5
230000003321 amplification Effects 0.000 description 5
239000002269 analeptic agent Substances 0.000 description 5
210000004899 c-terminal region Anatomy 0.000 description 5
125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 5
230000008859 change Effects 0.000 description 5
150000001875 compounds Chemical class 0.000 description 5
125000004122 cyclic group Chemical group 0.000 description 5
235000018417 cysteine Nutrition 0.000 description 5
XUJNEKJLAYXESH-UHFFFAOYSA-N cysteine Natural products SCC(N)C(O)=O XUJNEKJLAYXESH-UHFFFAOYSA-N 0.000 description 5
239000000839 emulsion Substances 0.000 description 5
238000005755 formation reaction Methods 0.000 description 5
238000009472 formulation Methods 0.000 description 5
230000002068 genetic effect Effects 0.000 description 5
239000002502 liposome Substances 0.000 description 5
210000004962 mammalian cell Anatomy 0.000 description 5
OETHQSJEHLVLGH-UHFFFAOYSA-N metformin hydrochloride Chemical compound Cl.CN(C)C(=N)N=C(N)N OETHQSJEHLVLGH-UHFFFAOYSA-N 0.000 description 5
XZWYZXLIPXDOLR-UHFFFAOYSA-N metformin hydrochloride Natural products CN(C)C(=N)NC(N)=N XZWYZXLIPXDOLR-UHFFFAOYSA-N 0.000 description 5
229930182817 methionine Natural products 0.000 description 5
238000003199 nucleic acid amplification method Methods 0.000 description 5
210000000496 pancreas Anatomy 0.000 description 5
238000010647 peptide synthesis reaction Methods 0.000 description 5
239000012071 phase Substances 0.000 description 5
239000013600 plasmid vector Substances 0.000 description 5
210000000813 small intestine Anatomy 0.000 description 5
230000001225 therapeutic effect Effects 0.000 description 5
238000013519 translation Methods 0.000 description 5
241001430294 unidentified retrovirus Species 0.000 description 5
108091032973 (ribonucleotides)n+m Proteins 0.000 description 4
RZVAJINKPMORJF-UHFFFAOYSA-N Acetaminophen Chemical compound CC(=O)NC1=CC=C(O)C=C1 RZVAJINKPMORJF-UHFFFAOYSA-N 0.000 description 4
108091006146 Channels Proteins 0.000 description 4
102000004190 Enzymes Human genes 0.000 description 4
108090000790 Enzymes Proteins 0.000 description 4
HTQBXNHDCUEHJF-XWLPCZSASA-N Exenatide Chemical compound C([C@@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(N)=O)C(=O)NCC(=O)NCC(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CO)C(=O)N[C@@H](CO)C(=O)NCC(=O)N[C@@H](C)C(=O)N1[C@@H](CCC1)C(=O)N1[C@@H](CCC1)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CO)C(N)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@@H](NC(=O)[C@H](C)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CCSC)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CO)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@@H](NC(=O)CNC(=O)[C@H](CCC(O)=O)NC(=O)CNC(=O)[C@@H](N)CC=1NC=NC=1)[C@@H](C)O)[C@@H](C)O)C(C)C)C1=CC=CC=C1 HTQBXNHDCUEHJF-XWLPCZSASA-N 0.000 description 4
-1 GLP-1 Chemical compound 0.000 description 4
WHUUTDBJXJRKMK-UHFFFAOYSA-N Glutamic acid Natural products OC(=O)C(N)CCC(O)=O WHUUTDBJXJRKMK-UHFFFAOYSA-N 0.000 description 4
102000008100 Human Serum Albumin Human genes 0.000 description 4
108091006905 Human Serum Albumin Proteins 0.000 description 4
206010020751 Hypersensitivity Diseases 0.000 description 4
208000013016 Hypoglycemia Diseases 0.000 description 4
WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 description 4
KDXKERNSBIXSRK-YFKPBYRVSA-N L-lysine Chemical compound NCCCC[C@H](N)C(O)=O KDXKERNSBIXSRK-YFKPBYRVSA-N 0.000 description 4
108091034117 Oligonucleotide Proteins 0.000 description 4
101710103249 Pituitary adenylate cyclase-activating polypeptide type I receptor Proteins 0.000 description 4
IVOMOUWHDPKRLL-UHFFFAOYSA-N UNPD107823 Natural products O1C2COP(O)(=O)OC2C(O)C1N1C(N=CN=C2N)=C2N=C1 IVOMOUWHDPKRLL-UHFFFAOYSA-N 0.000 description 4
KZSNJWFQEVHDMF-UHFFFAOYSA-N Valine Natural products CC(C)C(N)C(O)=O KZSNJWFQEVHDMF-UHFFFAOYSA-N 0.000 description 4
102400000015 Vasoactive intestinal peptide Human genes 0.000 description 4
239000002253 acid Substances 0.000 description 4
239000000443 aerosol Substances 0.000 description 4
208000026935 allergic disease Diseases 0.000 description 4
238000003556 assay Methods 0.000 description 4
208000006673 asthma Diseases 0.000 description 4
230000001413 cellular effect Effects 0.000 description 4
238000004587 chromatography analysis Methods 0.000 description 4
238000010367 cloning Methods 0.000 description 4
229940095074 cyclic amp Drugs 0.000 description 4
230000005714 functional activity Effects 0.000 description 4
230000002496 gastric effect Effects 0.000 description 4
229940095884 glucophage Drugs 0.000 description 4
ZDXPYRJPNDTMRX-UHFFFAOYSA-N glutamine Natural products OC(=O)C(N)CCC(N)=O ZDXPYRJPNDTMRX-UHFFFAOYSA-N 0.000 description 4
230000009610 hypersensitivity Effects 0.000 description 4
230000001939 inductive effect Effects 0.000 description 4
210000000936 intestine Anatomy 0.000 description 4
230000035772 mutation Effects 0.000 description 4
239000006199 nebulizer Substances 0.000 description 4
102000039446 nucleic acids Human genes 0.000 description 4
108020004707 nucleic acids Proteins 0.000 description 4
239000002245 particle Substances 0.000 description 4
229920001223 polyethylene glycol Polymers 0.000 description 4
230000008569 process Effects 0.000 description 4
238000012545 processing Methods 0.000 description 4
238000000746 purification Methods 0.000 description 4
230000009467 reduction Effects 0.000 description 4
230000002829 reductive effect Effects 0.000 description 4
230000010076 replication Effects 0.000 description 4
108091008146 restriction endonucleases Proteins 0.000 description 4
238000007920 subcutaneous administration Methods 0.000 description 4
238000012360 testing method Methods 0.000 description 4
230000003612 virological effect Effects 0.000 description 4
239000003643 water by type Substances 0.000 description 4
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
108091026890 Coding region Proteins 0.000 description 3
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 3
PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 3
DCXYFEDJOCDNAF-REOHCLBHSA-N L-asparagine Chemical compound OC(=O)[C@@H](N)CC(N)=O DCXYFEDJOCDNAF-REOHCLBHSA-N 0.000 description 3
CKLJMWTZIZZHCS-REOHCLBHSA-N L-aspartic acid Chemical compound OC(=O)[C@@H](N)CC(O)=O CKLJMWTZIZZHCS-REOHCLBHSA-N 0.000 description 3
AGPKZVBTJJNPAG-WHFBIAKZSA-N L-isoleucine Chemical compound CC[C@H](C)[C@H](N)C(O)=O AGPKZVBTJJNPAG-WHFBIAKZSA-N 0.000 description 3
FFEARJCKVFRZRR-BYPYZUCNSA-N L-methionine Chemical compound CSCC[C@H](N)C(O)=O FFEARJCKVFRZRR-BYPYZUCNSA-N 0.000 description 3
QIVBCDIJIAJPQS-VIFPVBQESA-N L-tryptophane Chemical compound C1=CC=C2C(C[C@H](N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-VIFPVBQESA-N 0.000 description 3
KZSNJWFQEVHDMF-BYPYZUCNSA-N L-valine Chemical compound CC(C)[C@H](N)C(O)=O KZSNJWFQEVHDMF-BYPYZUCNSA-N 0.000 description 3
241000283973 Oryctolagus cuniculus Species 0.000 description 3
229920001213 Polysorbate 20 Polymers 0.000 description 3
240000004808 Saccharomyces cerevisiae Species 0.000 description 3
AYFVYJQAPQTCCC-UHFFFAOYSA-N Threonine Natural products CC(O)C(N)C(O)=O AYFVYJQAPQTCCC-UHFFFAOYSA-N 0.000 description 3
239000004473 Threonine Substances 0.000 description 3
QIVBCDIJIAJPQS-UHFFFAOYSA-N Tryptophan Natural products C1=CC=C2C(CC(N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-UHFFFAOYSA-N 0.000 description 3
206010067584 Type 1 diabetes mellitus Diseases 0.000 description 3
208000003443 Unconsciousness Diseases 0.000 description 3
102100037790 VIP peptides Human genes 0.000 description 3
101710128740 VIP peptides Proteins 0.000 description 3
JLCPHMBAVCMARE-UHFFFAOYSA-N [3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-[[3-[[3-[[3-[[3-[[3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-hydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methyl [5-(6-aminopurin-9-yl)-2-(hydroxymethyl)oxolan-3-yl] hydrogen phosphate Polymers Cc1cn(C2CC(OP(O)(=O)OCC3OC(CC3OP(O)(=O)OCC3OC(CC3O)n3cnc4c3nc(N)[nH]c4=O)n3cnc4c3nc(N)[nH]c4=O)C(COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3CO)n3cnc4c(N)ncnc34)n3ccc(N)nc3=O)n3cnc4c(N)ncnc34)n3ccc(N)nc3=O)n3ccc(N)nc3=O)n3ccc(N)nc3=O)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cc(C)c(=O)[nH]c3=O)n3cc(C)c(=O)[nH]c3=O)n3ccc(N)nc3=O)n3cc(C)c(=O)[nH]c3=O)n3cnc4c3nc(N)[nH]c4=O)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)O2)c(=O)[nH]c1=O JLCPHMBAVCMARE-UHFFFAOYSA-N 0.000 description 3
239000013543 active substance Substances 0.000 description 3
229920001222 biopolymer Polymers 0.000 description 3
230000037396 body weight Effects 0.000 description 3
239000003795 chemical substances by application Substances 0.000 description 3
210000004978 chinese hamster ovary cell Anatomy 0.000 description 3
238000012217 deletion Methods 0.000 description 3
230000037430 deletion Effects 0.000 description 3
201000010099 disease Diseases 0.000 description 3
230000002526 effect on cardiovascular system Effects 0.000 description 3
238000004128 high performance liquid chromatography Methods 0.000 description 3
HNDVDQJCIGZPNO-UHFFFAOYSA-N histidine Natural products OC(=O)C(N)CC1=CN=CN1 HNDVDQJCIGZPNO-UHFFFAOYSA-N 0.000 description 3
238000009396 hybridization Methods 0.000 description 3
230000001771 impaired effect Effects 0.000 description 3
238000007689 inspection Methods 0.000 description 3
230000000968 intestinal effect Effects 0.000 description 3
238000007912 intraperitoneal administration Methods 0.000 description 3
108700025647 major vault Proteins 0.000 description 3
238000000816 matrix-assisted laser desorption--ionisation Methods 0.000 description 3
238000005259 measurement Methods 0.000 description 3
125000001360 methionine group Chemical group N[C@@H](CCSC)C(=O)* 0.000 description 3
238000004806 packaging method and process Methods 0.000 description 3
230000037361 pathway Effects 0.000 description 3
230000006320 pegylation Effects 0.000 description 3
229960001412 pentobarbital Drugs 0.000 description 3
COLNVLDHVKWLRT-UHFFFAOYSA-N phenylalanine Natural products OC(=O)C(N)CC1=CC=CC=C1 COLNVLDHVKWLRT-UHFFFAOYSA-N 0.000 description 3
229960005190 phenylalanine Drugs 0.000 description 3
239000000256 polyoxyethylene sorbitan monolaurate Substances 0.000 description 3
229920000136 polysorbate Polymers 0.000 description 3
230000001323 posttranslational effect Effects 0.000 description 3
230000001105 regulatory effect Effects 0.000 description 3
229920005989 resin Polymers 0.000 description 3
239000011347 resin Substances 0.000 description 3
230000000241 respiratory effect Effects 0.000 description 3
230000004044 response Effects 0.000 description 3
230000002441 reversible effect Effects 0.000 description 3
238000012552 review Methods 0.000 description 3
241000894007 species Species 0.000 description 3
238000013518 transcription Methods 0.000 description 3
230000035897 transcription Effects 0.000 description 3
238000001890 transfection Methods 0.000 description 3
230000009466 transformation Effects 0.000 description 3
GXPHKUHSUJUWKP-UHFFFAOYSA-N troglitazone Chemical compound C1CC=2C(C)=C(O)C(C)=C(C)C=2OC1(C)COC(C=C1)=CC=C1CC1SC(=O)NC1=O GXPHKUHSUJUWKP-UHFFFAOYSA-N 0.000 description 3
229960001641 troglitazone Drugs 0.000 description 3
OUYCCCASQSFEME-UHFFFAOYSA-N tyrosine Natural products OC(=O)C(N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-UHFFFAOYSA-N 0.000 description 3
239000004474 valine Substances 0.000 description 3
210000003462 vein Anatomy 0.000 description 3
230000004584 weight gain Effects 0.000 description 3
235000019786 weight gain Nutrition 0.000 description 3
125000003088 (fluoren-9-ylmethoxy)carbonyl group Chemical group 0.000 description 2
YQNRVGJCPCNMKT-JLPGSUDCSA-N 2-(4-benzylpiperazin-1-yl)-n-[(2-hydroxy-3-prop-2-enyl-phenyl)methylideneamino]acetamide Chemical compound OC1=C(CC=C)C=CC=C1\C=N/NC(=O)CN1CCN(CC=2C=CC=CC=2)CC1 YQNRVGJCPCNMKT-JLPGSUDCSA-N 0.000 description 2
102000007469 Actins Human genes 0.000 description 2
108010085238 Actins Proteins 0.000 description 2
102000009027 Albumins Human genes 0.000 description 2
108010088751 Albumins Proteins 0.000 description 2
229940077274 Alpha glucosidase inhibitor Drugs 0.000 description 2
206010002091 Anaesthesia Diseases 0.000 description 2
208000002267 Anti-neutrophil cytoplasmic antibody-associated vasculitis Diseases 0.000 description 2
239000004475 Arginine Substances 0.000 description 2
241000244188 Ascaris suum Species 0.000 description 2
DCXYFEDJOCDNAF-UHFFFAOYSA-N Asparagine Natural products OC(=O)C(N)CC(N)=O DCXYFEDJOCDNAF-UHFFFAOYSA-N 0.000 description 2
241000894006 Bacteria Species 0.000 description 2
241000700199 Cavia porcellus Species 0.000 description 2
241000282693 Cercopithecidae Species 0.000 description 2
241000450599 DNA viruses Species 0.000 description 2
241000702421 Dependoparvovirus Species 0.000 description 2
241000196324 Embryophyta Species 0.000 description 2
229920001917 Ficoll Polymers 0.000 description 2
ZHNUHDYFZUAESO-UHFFFAOYSA-N Formamide Chemical compound NC=O ZHNUHDYFZUAESO-UHFFFAOYSA-N 0.000 description 2
108060003199 Glucagon Proteins 0.000 description 2
239000004471 Glycine Substances 0.000 description 2
241000238631 Hexapoda Species 0.000 description 2
101001139126 Homo sapiens Krueppel-like factor 6 Proteins 0.000 description 2
101001133600 Homo sapiens Pituitary adenylate cyclase-activating polypeptide type I receptor Proteins 0.000 description 2
101001080401 Homo sapiens Proteasome assembly chaperone 1 Proteins 0.000 description 2
101001104570 Homo sapiens Proteasome assembly chaperone 2 Proteins 0.000 description 2
101000625842 Homo sapiens Tubulin-specific chaperone E Proteins 0.000 description 2
208000001953 Hypotension Diseases 0.000 description 2
QNAYBMKLOCPYGJ-REOHCLBHSA-N L-alanine Chemical compound C[C@H](N)C(O)=O QNAYBMKLOCPYGJ-REOHCLBHSA-N 0.000 description 2
HNDVDQJCIGZPNO-YFKPBYRVSA-N L-histidine Chemical compound OC(=O)[C@@H](N)CC1=CN=CN1 HNDVDQJCIGZPNO-YFKPBYRVSA-N 0.000 description 2
ROHFNLRQFUQHCH-UHFFFAOYSA-N Leucine Natural products CC(C)CC(N)C(O)=O ROHFNLRQFUQHCH-UHFFFAOYSA-N 0.000 description 2
239000004472 Lysine Substances 0.000 description 2
241000282567 Macaca fascicularis Species 0.000 description 2
241000713869 Moloney murine leukemia virus Species 0.000 description 2
MWUXSHHQAYIFBG-UHFFFAOYSA-N Nitric oxide Chemical compound O=[N] MWUXSHHQAYIFBG-UHFFFAOYSA-N 0.000 description 2
101710163270 Nuclease Proteins 0.000 description 2
229960005552 PAC-1 Drugs 0.000 description 2
108010025501 PG 97-269 Proteins 0.000 description 2
ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 2
102000014743 Pituitary Adenylate Cyclase-Activating Polypeptide Receptors Human genes 0.000 description 2
108010064032 Pituitary Adenylate Cyclase-Activating Polypeptide Receptors Proteins 0.000 description 2
239000002202 Polyethylene glycol Substances 0.000 description 2
241000288906 Primates Species 0.000 description 2
ONIBWKKTOPOVIA-UHFFFAOYSA-N Proline Natural products OC(=O)C1CCCN1 ONIBWKKTOPOVIA-UHFFFAOYSA-N 0.000 description 2
102100041008 Proteasome assembly chaperone 2 Human genes 0.000 description 2
241000125945 Protoparvovirus Species 0.000 description 2
241000293869 Salmonella enterica subsp. enterica serovar Typhimurium Species 0.000 description 2
BUGBHKTXTAQXES-UHFFFAOYSA-N Selenium Chemical compound [Se] BUGBHKTXTAQXES-UHFFFAOYSA-N 0.000 description 2
MTCFGRXMJLQNBG-UHFFFAOYSA-N Serine Natural products OCC(N)C(O)=O MTCFGRXMJLQNBG-UHFFFAOYSA-N 0.000 description 2
241000187747 Streptomyces Species 0.000 description 2
208000025865 Ulcer Diseases 0.000 description 2
150000007513 acids Chemical class 0.000 description 2
230000001154 acute effect Effects 0.000 description 2
230000010933 acylation Effects 0.000 description 2
238000005917 acylation reaction Methods 0.000 description 2
235000004279 alanine Nutrition 0.000 description 2
239000003888 alpha glucosidase inhibitor Substances 0.000 description 2
230000009435 amidation Effects 0.000 description 2
238000007112 amidation reaction Methods 0.000 description 2
229960000723 ampicillin Drugs 0.000 description 2
AVKUERGKIZMTKX-NJBDSQKTSA-N ampicillin Chemical compound C1([C@@H](N)C(=O)N[C@H]2[C@H]3SC([C@@H](N3C2=O)C(O)=O)(C)C)=CC=CC=C1 AVKUERGKIZMTKX-NJBDSQKTSA-N 0.000 description 2
230000037005 anaesthesia Effects 0.000 description 2
238000004458 analytical method Methods 0.000 description 2
ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 2
125000003118 aryl group Chemical group 0.000 description 2
235000009582 asparagine Nutrition 0.000 description 2
229960001230 asparagine Drugs 0.000 description 2
235000003704 aspartic acid Nutrition 0.000 description 2
210000003050 axon Anatomy 0.000 description 2
230000008901 benefit Effects 0.000 description 2
WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 2
OQFSQFPPLPISGP-UHFFFAOYSA-N beta-carboxyaspartic acid Natural products OC(=O)C(N)C(C(O)=O)C(O)=O OQFSQFPPLPISGP-UHFFFAOYSA-N 0.000 description 2
210000004556 brain Anatomy 0.000 description 2
230000011496 cAMP-mediated signaling Effects 0.000 description 2
239000011575 calcium Substances 0.000 description 2
230000005961 cardioprotection Effects 0.000 description 2
238000005119 centrifugation Methods 0.000 description 2
JUFFVKRROAPVBI-PVOYSMBESA-N chembl1210015 Chemical compound C([C@@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(=O)N[C@H]1[C@@H]([C@@H](O)[C@H](O[C@H]2[C@@H]([C@@H](O)[C@@H](O)[C@@H](CO[C@]3(O[C@@H](C[C@H](O)[C@H](O)CO)[C@H](NC(C)=O)[C@@H](O)C3)C(O)=O)O2)O)[C@@H](CO)O1)NC(C)=O)C(=O)NCC(=O)NCC(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CO)C(=O)N[C@@H](CO)C(=O)NCC(=O)N[C@@H](C)C(=O)N1[C@@H](CCC1)C(=O)N1[C@@H](CCC1)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CO)C(N)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@@H](NC(=O)[C@H](C)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CCSC)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CO)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@@H](NC(=O)CNC(=O)[C@H](CCC(O)=O)NC(=O)CNC(=O)[C@@H](N)CC=1NC=NC=1)[C@@H](C)O)[C@@H](C)O)C(C)C)C1=CC=CC=C1 JUFFVKRROAPVBI-PVOYSMBESA-N 0.000 description 2
239000012707 chemical precursor Substances 0.000 description 2
239000003153 chemical reaction reagent Substances 0.000 description 2
230000002759 chromosomal effect Effects 0.000 description 2
230000000295 complement effect Effects 0.000 description 2
239000002299 complementary DNA Substances 0.000 description 2
238000007796 conventional method Methods 0.000 description 2
238000001514 detection method Methods 0.000 description 2
238000011161 development Methods 0.000 description 2
230000018109 developmental process Effects 0.000 description 2
229940079593 drug Drugs 0.000 description 2
235000013601 eggs Nutrition 0.000 description 2
238000004520 electroporation Methods 0.000 description 2
239000003480 eluent Substances 0.000 description 2
238000005516 engineering process Methods 0.000 description 2
230000002708 enhancing effect Effects 0.000 description 2
230000002255 enzymatic effect Effects 0.000 description 2
230000028023 exocytosis Effects 0.000 description 2
239000000284 extract Substances 0.000 description 2
210000002950 fibroblast Anatomy 0.000 description 2
108020001507 fusion proteins Proteins 0.000 description 2
102000037865 fusion proteins Human genes 0.000 description 2
BRZYSWJRSDMWLG-CAXSIQPQSA-N geneticin Chemical compound O1C[C@@](O)(C)[C@H](NC)[C@@H](O)[C@H]1O[C@@H]1[C@@H](O)[C@H](O[C@@H]2[C@@H]([C@@H](O)[C@H](O)[C@@H](C(C)O)O2)N)[C@@H](N)C[C@H]1N BRZYSWJRSDMWLG-CAXSIQPQSA-N 0.000 description 2
210000004907 gland Anatomy 0.000 description 2
235000013922 glutamic acid Nutrition 0.000 description 2
239000004220 glutamic acid Substances 0.000 description 2
RWSXRVCMGQZWBV-WDSKDSINSA-N glutathione Chemical compound OC(=O)[C@@H](N)CCC(=O)N[C@@H](CS)C(=O)NCC(O)=O RWSXRVCMGQZWBV-WDSKDSINSA-N 0.000 description 2
230000013595 glycosylation Effects 0.000 description 2
238000006206 glycosylation reaction Methods 0.000 description 2
239000001963 growth medium Substances 0.000 description 2
210000003494 hepatocyte Anatomy 0.000 description 2
231100000304 hepatotoxicity Toxicity 0.000 description 2
230000036543 hypotension Effects 0.000 description 2
230000001976 improved effect Effects 0.000 description 2
230000006698 induction Effects 0.000 description 2
238000001802 infusion Methods 0.000 description 2
230000000977 initiatory effect Effects 0.000 description 2
230000003834 intracellular effect Effects 0.000 description 2
230000000302 ischemic effect Effects 0.000 description 2
238000002955 isolation Methods 0.000 description 2
210000003734 kidney Anatomy 0.000 description 2
JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 2
208000032839 leukemia Diseases 0.000 description 2
150000002632 lipids Chemical class 0.000 description 2
210000004185 liver Anatomy 0.000 description 2
210000004072 lung Anatomy 0.000 description 2
238000004949 mass spectrometry Methods 0.000 description 2
239000000463 material Substances 0.000 description 2
235000012054 meals Nutrition 0.000 description 2
239000012528 membrane Substances 0.000 description 2
108020004999 messenger RNA Proteins 0.000 description 2
235000013336 milk Nutrition 0.000 description 2
239000008267 milk Substances 0.000 description 2
210000004080 milk Anatomy 0.000 description 2
238000010369 molecular cloning Methods 0.000 description 2
UOJMTSCORVQOHS-UHFFFAOYSA-N pachypodol Natural products COc1cc(ccc1O)C2=C(C)C(=O)c3c(O)cc(C)cc3O2 UOJMTSCORVQOHS-UHFFFAOYSA-N 0.000 description 2
230000008488 polyadenylation Effects 0.000 description 2
235000010486 polyoxyethylene sorbitan monolaurate Nutrition 0.000 description 2
210000001236 prokaryotic cell Anatomy 0.000 description 2
230000001737 promoting effect Effects 0.000 description 2
230000001681 protective effect Effects 0.000 description 2
238000003259 recombinant expression Methods 0.000 description 2
238000011160 research Methods 0.000 description 2
238000004366 reverse phase liquid chromatography Methods 0.000 description 2
238000012106 screening analysis Methods 0.000 description 2
230000003248 secreting effect Effects 0.000 description 2
230000028327 secretion Effects 0.000 description 2
229910052711 selenium Inorganic materials 0.000 description 2
239000011669 selenium Substances 0.000 description 2
230000011664 signaling Effects 0.000 description 2
230000019100 sperm motility Effects 0.000 description 2
238000012453 sprague-dawley rat model Methods 0.000 description 2
230000002194 synthesizing effect Effects 0.000 description 2
238000010189 synthetic method Methods 0.000 description 2
230000008685 targeting Effects 0.000 description 2
210000001519 tissue Anatomy 0.000 description 2
208000035408 type 1 diabetes mellitus 1 Diseases 0.000 description 2
230000034512 ubiquitination Effects 0.000 description 2
238000010798 ubiquitination Methods 0.000 description 2
210000005253 yeast cell Anatomy 0.000 description 2
DIGQNXIGRZPYDK-WKSCXVIASA-N (2R)-6-amino-2-[[2-[[(2S)-2-[[2-[[(2R)-2-[[(2S)-2-[[(2R,3S)-2-[[2-[[(2S)-2-[[2-[[(2S)-2-[[(2S)-2-[[(2R)-2-[[(2S,3S)-2-[[(2R)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[2-[[(2S)-2-[[(2R)-2-[[2-[[2-[[2-[(2-amino-1-hydroxyethylidene)amino]-3-carboxy-1-hydroxypropylidene]amino]-1-hydroxy-3-sulfanylpropylidene]amino]-1-hydroxyethylidene]amino]-1-hydroxy-3-sulfanylpropylidene]amino]-1,3-dihydroxypropylidene]amino]-1-hydroxyethylidene]amino]-1-hydroxypropylidene]amino]-1,3-dihydroxypropylidene]amino]-1,3-dihydroxypropylidene]amino]-1-hydroxy-3-sulfanylpropylidene]amino]-1,3-dihydroxybutylidene]amino]-1-hydroxy-3-sulfanylpropylidene]amino]-1-hydroxypropylidene]amino]-1,3-dihydroxypropylidene]amino]-1-hydroxyethylidene]amino]-1,5-dihydroxy-5-iminopentylidene]amino]-1-hydroxy-3-sulfanylpropylidene]amino]-1,3-dihydroxybutylidene]amino]-1-hydroxy-3-sulfanylpropylidene]amino]-1,3-dihydroxypropylidene]amino]-1-hydroxyethylidene]amino]-1-hydroxy-3-sulfanylpropylidene]amino]-1-hydroxyethylidene]amino]hexanoic acid Chemical compound C[C@@H]([C@@H](C(=N[C@@H](CS)C(=N[C@@H](C)C(=N[C@@H](CO)C(=NCC(=N[C@@H](CCC(=N)O)C(=NC(CS)C(=N[C@H]([C@H](C)O)C(=N[C@H](CS)C(=N[C@H](CO)C(=NCC(=N[C@H](CS)C(=NCC(=N[C@H](CCCCN)C(=O)O)O)O)O)O)O)O)O)O)O)O)O)O)O)N=C([C@H](CS)N=C([C@H](CO)N=C([C@H](CO)N=C([C@H](C)N=C(CN=C([C@H](CO)N=C([C@H](CS)N=C(CN=C(C(CS)N=C(C(CC(=O)O)N=C(CN)O)O)O)O)O)O)O)O)O)O)O)O DIGQNXIGRZPYDK-WKSCXVIASA-N 0.000 description 1
XUFXOAAUWZOOIT-SXARVLRPSA-N (2R,3R,4R,5S,6R)-5-[[(2R,3R,4R,5S,6R)-5-[[(2R,3R,4S,5S,6R)-3,4-dihydroxy-6-methyl-5-[[(1S,4R,5S,6S)-4,5,6-trihydroxy-3-(hydroxymethyl)-1-cyclohex-2-enyl]amino]-2-oxanyl]oxy]-3,4-dihydroxy-6-(hydroxymethyl)-2-oxanyl]oxy]-6-(hydroxymethyl)oxane-2,3,4-triol Chemical compound O([C@H]1O[C@H](CO)[C@H]([C@@H]([C@H]1O)O)O[C@H]1O[C@@H]([C@H]([C@H](O)[C@H]1O)N[C@@H]1[C@@H]([C@@H](O)[C@H](O)C(CO)=C1)O)C)[C@@H]1[C@@H](CO)O[C@@H](O)[C@H](O)[C@H]1O XUFXOAAUWZOOIT-SXARVLRPSA-N 0.000 description 1
HCXLBYNBTBNDQZ-KFHPIRAKSA-N (4S)-4-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(1aS,3S,4aS,6S,7aS,9S,10aS,12S,15S,16aS,18S,21S,24S,27S,30S,33S,36S,39S,42S,45S,48S,51S,54S,57S,60S,63S,66S,69S,72S,75S,78S,81S,84S,87R,92R,95S,98S)-87-[[(2S)-2-[[(2S)-2-[[(2S,3S)-2-[[(2S)-2-[[(2S)-6-amino-2-[[(2S)-2-[[(2S)-2-[[(2S)-5-amino-2-[[(4R,7S,10S,13S,16R)-16-amino-13-(carboxymethyl)-7-[(1R)-1-hydroxyethyl]-10-methyl-6,9,12,15-tetraoxo-1,2-dithia-5,8,11,14-tetrazacycloheptadecane-4-carbonyl]amino]-5-oxopentanoyl]amino]-3-phenylpropanoyl]amino]-5-carbamimidamidopentanoyl]amino]hexanoyl]amino]propanoyl]amino]-3-methylpentanoyl]amino]-3-carboxypropanoyl]amino]-3-carboxypropanoyl]amino]-81,98-bis(4-aminobutyl)-10a,63-bis(2-amino-2-oxoethyl)-6,42,54,78,84-pentakis(3-amino-3-oxopropyl)-1a,27-dibenzyl-95-(2-carboxyethyl)-15-(carboxymethyl)-12,24,30,36,39,51-hexakis[(1R)-1-hydroxyethyl]-7a,9,21,48,66-pentakis(hydroxymethyl)-69,72-bis(1H-imidazol-5-ylmethyl)-33,75-dimethyl-3,57-bis(2-methylpropyl)-18-(2-methylsulfanylethyl)-a,2,3a,5,6a,8,9a,11,12a,14,15a,17,20,23,26,29,32,35,38,41,44,47,50,53,56,59,62,65,68,71,74,77,80,83,86,94,97-heptatriacontaoxo-4a,45,60-tri(propan-2-yl)-89,90-dithia-1,2a,4,5a,7,8a,10,11a,13,14a,16,19,22,25,28,31,34,37,40,43,46,49,52,55,58,61,64,67,70,73,76,79,82,85,93,96,99-heptatriacontazabicyclo[114.3.0]nonadecahectane-92-carbonyl]amino]-4-methylsulfanylbutanoyl]amino]-6-aminohexanoyl]amino]-5-amino-5-oxopentanoyl]amino]-6-aminohexanoyl]amino]-6-aminohexanoyl]amino]-6-aminohexanoyl]amino]-5-[[(2S)-1-[[(2S)-6-amino-1-[[(1S)-1-carboxyethyl]amino]-1-oxohexan-2-yl]amino]-1-oxo-3-phenylpropan-2-yl]amino]-5-oxopentanoic acid Chemical compound CC[C@H](C)[C@H](NC(=O)[C@H](C)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](Cc1ccccc1)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@@H]1CSSC[C@H](N)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](C)C(=O)N[C@@H]([C@@H](C)O)C(=O)N1)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@H]1CSSC[C@H](NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CCCCN)NC(=O)[C@H](Cc2ccccc2)NC(=O)[C@@H](NC(=O)[C@H](CO)NC(=O)[C@H](CC(N)=O)NC(=O)CNC(=O)[C@@H]2CCCN2C(=O)[C@H](CC(C)C)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CCSC)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@H](Cc2ccccc2)NC(=O)[C@@H](NC(=O)[C@H](C)NC(=O)[C@@H](NC(=O)[C@@H](NC(=O)[C@H](CCC(N)=O)NC(=O)[C@@H](NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CO)NC(=O)[C@H](Cc2cnc[nH]2)NC(=O)[C@H](Cc2cnc[nH]2)NC(=O)[C@H](C)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CCC(N)=O)NC1=O)C(C)C)[C@@H](C)O)C(C)C)[C@@H](C)O)[C@@H](C)O)[C@@H](C)O)[C@@H](C)O)[C@@H](C)O)C(C)C)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](Cc1ccccc1)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](C)C(O)=O HCXLBYNBTBNDQZ-KFHPIRAKSA-N 0.000 description 1
108010091350 (VIP-neurotensin) hybrid antagonist Proteins 0.000 description 1
102000040650 (ribonucleotides)n+m Human genes 0.000 description 1
DHBXNPKRAUYBTH-UHFFFAOYSA-N 1,1-ethanedithiol Chemical compound CC(S)S DHBXNPKRAUYBTH-UHFFFAOYSA-N 0.000 description 1
GZCWLCBFPRFLKL-UHFFFAOYSA-N 1-prop-2-ynoxypropan-2-ol Chemical compound CC(O)COCC#C GZCWLCBFPRFLKL-UHFFFAOYSA-N 0.000 description 1
JKMHFZQWWAIEOD-UHFFFAOYSA-N 2-[4-(2-hydroxyethyl)piperazin-1-yl]ethanesulfonic acid Chemical compound OCC[NH+]1CCN(CCS([O-])(=O)=O)CC1 JKMHFZQWWAIEOD-UHFFFAOYSA-N 0.000 description 1
OSJPPGNTCRNQQC-UWTATZPHSA-N 3-phospho-D-glyceric acid Chemical compound OC(=O)[C@H](O)COP(O)(O)=O OSJPPGNTCRNQQC-UWTATZPHSA-N 0.000 description 1
XZKIHKMTEMTJQX-UHFFFAOYSA-N 4-Nitrophenyl Phosphate Chemical compound OP(O)(=O)OC1=CC=C([N+]([O-])=O)C=C1 XZKIHKMTEMTJQX-UHFFFAOYSA-N 0.000 description 1
FWMNVWWHGCHHJJ-SKKKGAJSSA-N 4-amino-1-[(2r)-6-amino-2-[[(2r)-2-[[(2r)-2-[[(2r)-2-amino-3-phenylpropanoyl]amino]-3-phenylpropanoyl]amino]-4-methylpentanoyl]amino]hexanoyl]piperidine-4-carboxylic acid Chemical compound C([C@H](C(=O)N[C@H](CC(C)C)C(=O)N[C@H](CCCCN)C(=O)N1CCC(N)(CC1)C(O)=O)NC(=O)[C@H](N)CC=1C=CC=CC=1)C1=CC=CC=C1 FWMNVWWHGCHHJJ-SKKKGAJSSA-N 0.000 description 1
ODHCTXKNWHHXJC-VKHMYHEASA-N 5-oxo-L-proline Chemical compound OC(=O)[C@@H]1CCC(=O)N1 ODHCTXKNWHHXJC-VKHMYHEASA-N 0.000 description 1
102000013563 Acid Phosphatase Human genes 0.000 description 1
108010051457 Acid Phosphatase Proteins 0.000 description 1
102000002260 Alkaline Phosphatase Human genes 0.000 description 1
108020004774 Alkaline Phosphatase Proteins 0.000 description 1
101100238293 Arabidopsis thaliana MOR1 gene Proteins 0.000 description 1
241000972773 Aulopiformes Species 0.000 description 1
241000713826 Avian leukosis virus Species 0.000 description 1
244000063299 Bacillus subtilis Species 0.000 description 1
235000014469 Bacillus subtilis Nutrition 0.000 description 1
108010001478 Bacitracin Proteins 0.000 description 1
229940123208 Biguanide Drugs 0.000 description 1
XNCOSPRUTUOJCJ-UHFFFAOYSA-N Biguanide Chemical compound NC(N)=NC(N)=N XNCOSPRUTUOJCJ-UHFFFAOYSA-N 0.000 description 1
206010006187 Breast cancer Diseases 0.000 description 1
206010006482 Bronchospasm Diseases 0.000 description 1
101150029409 CFTR gene Proteins 0.000 description 1
241000283707 Capra Species 0.000 description 1
201000009030 Carcinoma Diseases 0.000 description 1
208000024172 Cardiovascular disease Diseases 0.000 description 1
108091005462 Cation channels Proteins 0.000 description 1
206010008469 Chest discomfort Diseases 0.000 description 1
108091062157 Cis-regulatory element Proteins 0.000 description 1
102100022641 Coagulation factor IX Human genes 0.000 description 1
102000008130 Cyclic AMP-Dependent Protein Kinases Human genes 0.000 description 1
108010049894 Cyclic AMP-Dependent Protein Kinases Proteins 0.000 description 1
102000053602 DNA Human genes 0.000 description 1
102000004594 DNA Polymerase I Human genes 0.000 description 1
108010017826 DNA Polymerase I Proteins 0.000 description 1
230000006820 DNA synthesis Effects 0.000 description 1
108010054576 Deoxyribonuclease EcoRI Proteins 0.000 description 1
229920002307 Dextran Polymers 0.000 description 1
206010012735 Diarrhoea Diseases 0.000 description 1
BWGNESOTFCXPMA-UHFFFAOYSA-N Dihydrogen disulfide Chemical compound SS BWGNESOTFCXPMA-UHFFFAOYSA-N 0.000 description 1
241000255581 Drosophila <fruit fly, genus> Species 0.000 description 1
241000701959 Escherichia virus Lambda Species 0.000 description 1
241000206602 Eukaryota Species 0.000 description 1
102000020897 Formins Human genes 0.000 description 1
108091022623 Formins Proteins 0.000 description 1
102000030782 GTP binding Human genes 0.000 description 1
108091000058 GTP-Binding Proteins 0.000 description 1
208000018522 Gastrointestinal disease Diseases 0.000 description 1
108700028146 Genetic Enhancer Elements Proteins 0.000 description 1
108700039691 Genetic Promoter Regions Proteins 0.000 description 1
102000051325 Glucagon Human genes 0.000 description 1
108010024636 Glutathione Proteins 0.000 description 1
CLNSYANKYVMZNM-UWVGGRQHSA-N Gly-Lys-Arg Chemical compound NCCCC[C@H](NC(=O)CN)C(=O)N[C@H](C(O)=O)CCCN=C(N)N CLNSYANKYVMZNM-UWVGGRQHSA-N 0.000 description 1
244000068988 Glycine max Species 0.000 description 1
235000010469 Glycine max Nutrition 0.000 description 1
239000007995 HEPES buffer Substances 0.000 description 1
206010019233 Headaches Diseases 0.000 description 1
108010004889 Heat-Shock Proteins Proteins 0.000 description 1
102000002812 Heat-Shock Proteins Human genes 0.000 description 1
206010019851 Hepatotoxicity Diseases 0.000 description 1
208000009889 Herpes Simplex Diseases 0.000 description 1
108010033040 Histones Proteins 0.000 description 1
241000282412 Homo Species 0.000 description 1
101000886868 Homo sapiens Gastric inhibitory polypeptide Proteins 0.000 description 1
101001128500 Homo sapiens Marginal zone B- and B1-cell-specific protein Proteins 0.000 description 1
101000735539 Homo sapiens Pituitary adenylate cyclase-activating polypeptide Proteins 0.000 description 1
101000666868 Homo sapiens Vasoactive intestinal polypeptide receptor 2 Proteins 0.000 description 1
102000002265 Human Growth Hormone Human genes 0.000 description 1
108010000521 Human Growth Hormone Proteins 0.000 description 1
239000000854 Human Growth Hormone Substances 0.000 description 1
241000701024 Human betaherpesvirus 5 Species 0.000 description 1
241000702617 Human parvovirus B19 Species 0.000 description 1
AVXURJPOCDRRFD-UHFFFAOYSA-N Hydroxylamine Chemical compound ON AVXURJPOCDRRFD-UHFFFAOYSA-N 0.000 description 1
206010020772 Hypertension Diseases 0.000 description 1
229940122355 Insulin sensitizer Drugs 0.000 description 1
101710186630 Insulin-1 Proteins 0.000 description 1
102000036770 Islet Amyloid Polypeptide Human genes 0.000 description 1
108010041872 Islet Amyloid Polypeptide Proteins 0.000 description 1
YQEZLKZALYSWHR-UHFFFAOYSA-N Ketamine Chemical compound C=1C=CC=C(Cl)C=1C1(NC)CCCCC1=O YQEZLKZALYSWHR-UHFFFAOYSA-N 0.000 description 1
ONIBWKKTOPOVIA-BYPYZUCNSA-N L-Proline Chemical compound OC(=O)[C@@H]1CCCN1 ONIBWKKTOPOVIA-BYPYZUCNSA-N 0.000 description 1
125000000998 L-alanino group Chemical group [H]N([*])[C@](C([H])([H])[H])([H])C(=O)O[H] 0.000 description 1
ODKSFYDXXFIFQN-BYPYZUCNSA-P L-argininium(2+) Chemical compound NC(=[NH2+])NCCC[C@H]([NH3+])C(O)=O ODKSFYDXXFIFQN-BYPYZUCNSA-P 0.000 description 1
ZDXPYRJPNDTMRX-VKHMYHEASA-N L-glutamine Chemical compound OC(=O)[C@@H](N)CCC(N)=O ZDXPYRJPNDTMRX-VKHMYHEASA-N 0.000 description 1
108010052014 Liberase Proteins 0.000 description 1
NNJVILVZKWQKPM-UHFFFAOYSA-N Lidocaine Chemical compound CCN(CC)CC(=O)NC1=C(C)C=CC=C1C NNJVILVZKWQKPM-UHFFFAOYSA-N 0.000 description 1
208000007466 Male Infertility Diseases 0.000 description 1
PEEHTFAAVSWFBL-UHFFFAOYSA-N Maleimide Chemical compound O=C1NC(=O)C=C1 PEEHTFAAVSWFBL-UHFFFAOYSA-N 0.000 description 1
101710144475 Maxadilan Proteins 0.000 description 1
102000003792 Metallothionein Human genes 0.000 description 1
108090000157 Metallothionein Proteins 0.000 description 1
IBAQFPQHRJAVAV-ULAWRXDQSA-N Miglitol Chemical compound OCCN1C[C@H](O)[C@@H](O)[C@H](O)[C@H]1CO IBAQFPQHRJAVAV-ULAWRXDQSA-N 0.000 description 1
241000699666 Mus <mouse, genus> Species 0.000 description 1
241000699660 Mus musculus Species 0.000 description 1
101000969137 Mus musculus Metallothionein-1 Proteins 0.000 description 1
241000699670 Mus sp. Species 0.000 description 1
206010049816 Muscle tightness Diseases 0.000 description 1
241000713883 Myeloproliferative sarcoma virus Species 0.000 description 1
229930193140 Neomycin Natural products 0.000 description 1
206010028980 Neoplasm Diseases 0.000 description 1
108700020796 Oncogene Proteins 0.000 description 1
102000043276 Oncogene Human genes 0.000 description 1
206010031127 Orthostatic hypotension Diseases 0.000 description 1
102000003728 Peroxisome Proliferator-Activated Receptors Human genes 0.000 description 1
108090000029 Peroxisome Proliferator-Activated Receptors Proteins 0.000 description 1
108091000080 Phosphotransferase Proteins 0.000 description 1
229940124158 Protease/peptidase inhibitor Drugs 0.000 description 1
102000001708 Protein Isoforms Human genes 0.000 description 1
108010029485 Protein Isoforms Proteins 0.000 description 1
102220586011 Protein downstream neighbor of Son_Y22F_mutation Human genes 0.000 description 1
102220586173 Protein downstream neighbor of Son_Y22S_mutation Human genes 0.000 description 1
241000589516 Pseudomonas Species 0.000 description 1
239000012980 RPMI-1640 medium Substances 0.000 description 1
108010008281 Recombinant Fusion Proteins Proteins 0.000 description 1
102000007056 Recombinant Fusion Proteins Human genes 0.000 description 1
208000002200 Respiratory Hypersensitivity Diseases 0.000 description 1
AUNGANRZJHBGPY-SCRDCRAPSA-N Riboflavin Chemical compound OC[C@@H](O)[C@@H](O)[C@@H](O)CN1C=2C=C(C)C(C)=CC=2N=C2C1=NC(=O)NC2=O AUNGANRZJHBGPY-SCRDCRAPSA-N 0.000 description 1
241000714474 Rous sarcoma virus Species 0.000 description 1
101100379247 Salmo trutta apoa1 gene Proteins 0.000 description 1
206010039491 Sarcoma Diseases 0.000 description 1
102100037505 Secretin Human genes 0.000 description 1
108010086019 Secretin Proteins 0.000 description 1
229920002684 Sepharose Polymers 0.000 description 1
241000700584 Simplexvirus Species 0.000 description 1
108020004682 Single-Stranded DNA Proteins 0.000 description 1
241000713896 Spleen necrosis virus Species 0.000 description 1
241000256248 Spodoptera Species 0.000 description 1
241000191940 Staphylococcus Species 0.000 description 1
108700005078 Synthetic Genes Proteins 0.000 description 1
101150006914 TRP1 gene Proteins 0.000 description 1
208000001871 Tachycardia Diseases 0.000 description 1
239000004098 Tetracycline Substances 0.000 description 1
108010022394 Threonine synthase Proteins 0.000 description 1
102000004357 Transferases Human genes 0.000 description 1
108090000992 Transferases Proteins 0.000 description 1
239000007983 Tris buffer Substances 0.000 description 1
229940122618 Trypsin inhibitor Drugs 0.000 description 1
101710162629 Trypsin inhibitor Proteins 0.000 description 1
206010046865 Vaccinia virus infection Diseases 0.000 description 1
241000700647 Variola virus Species 0.000 description 1
108020005202 Viral DNA Proteins 0.000 description 1
FZNCGRZWXLXZSZ-CIQUZCHMSA-N Voglibose Chemical compound OCC(CO)N[C@H]1C[C@](O)(CO)[C@@H](O)[C@H](O)[C@H]1O FZNCGRZWXLXZSZ-CIQUZCHMSA-N 0.000 description 1
206010047700 Vomiting Diseases 0.000 description 1
IXKSXJFAGXLQOQ-XISFHERQSA-N WHWLQLKPGQPMY Chemical compound C([C@@H](C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC(C)C)C(=O)N1CCC[C@H]1C(=O)NCC(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC(O)=O)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(O)=O)NC(=O)[C@@H](N)CC=1C2=CC=CC=C2NC=1)C1=CNC=N1 IXKSXJFAGXLQOQ-XISFHERQSA-N 0.000 description 1
238000010521 absorption reaction Methods 0.000 description 1
238000009825 accumulation Methods 0.000 description 1
PBCJIPOGFJYBJE-UHFFFAOYSA-N acetonitrile;hydrate Chemical compound O.CC#N PBCJIPOGFJYBJE-UHFFFAOYSA-N 0.000 description 1
230000021736 acetylation Effects 0.000 description 1
238000006640 acetylation reaction Methods 0.000 description 1
230000002378 acidificating effect Effects 0.000 description 1
230000009471 action Effects 0.000 description 1
208000024716 acute asthma Diseases 0.000 description 1
230000002730 additional effect Effects 0.000 description 1
210000000577 adipose tissue Anatomy 0.000 description 1
238000001042 affinity chromatography Methods 0.000 description 1
150000001408 amides Chemical group 0.000 description 1
BFNBIHQBYMNNAN-UHFFFAOYSA-N ammonium sulfate Chemical compound N.N.OS(O)(=O)=O BFNBIHQBYMNNAN-UHFFFAOYSA-N 0.000 description 1
229910052921 ammonium sulfate Inorganic materials 0.000 description 1
238000012870 ammonium sulfate precipitation Methods 0.000 description 1
235000011130 ammonium sulphate Nutrition 0.000 description 1
210000004102 animal cell Anatomy 0.000 description 1
238000010171 animal model Methods 0.000 description 1
125000000129 anionic group Chemical group 0.000 description 1
239000005557 antagonist Substances 0.000 description 1
230000002424 anti-apoptotic effect Effects 0.000 description 1
230000000692 anti-sense effect Effects 0.000 description 1
239000003699 antiulcer agent Substances 0.000 description 1
238000013459 approach Methods 0.000 description 1
230000010516 arginylation Effects 0.000 description 1
229960003071 bacitracin Drugs 0.000 description 1
229930184125 bacitracin Natural products 0.000 description 1
CLKOFPXJLQSYAH-ABRJDSQDSA-N bacitracin A Chemical compound C1SC([C@@H](N)[C@@H](C)CC)=N[C@@H]1C(=O)N[C@@H](CC(C)C)C(=O)N[C@H](CCC(O)=O)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H]1C(=O)N[C@H](CCCN)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@H](CC=2C=CC=CC=2)C(=O)N[C@@H](CC=2N=CNC=2)C(=O)N[C@H](CC(O)=O)C(=O)N[C@@H](CC(N)=O)C(=O)NCCCC1 CLKOFPXJLQSYAH-ABRJDSQDSA-N 0.000 description 1
230000009286 beneficial effect Effects 0.000 description 1
108010005774 beta-Galactosidase Proteins 0.000 description 1
239000012620 biological material Substances 0.000 description 1
230000001851 biosynthetic effect Effects 0.000 description 1
230000004397 blinking Effects 0.000 description 1
210000000424 bronchial epithelial cell Anatomy 0.000 description 1
230000007885 bronchoconstriction Effects 0.000 description 1
239000006227 byproduct Substances 0.000 description 1
230000001593 cAMP accumulation Effects 0.000 description 1
239000001506 calcium phosphate Substances 0.000 description 1
229910000389 calcium phosphate Inorganic materials 0.000 description 1
235000011010 calcium phosphates Nutrition 0.000 description 1
244000309466 calf Species 0.000 description 1
230000015556 catabolic process Effects 0.000 description 1
238000005277 cation exchange chromatography Methods 0.000 description 1
125000002091 cationic group Chemical group 0.000 description 1
238000001311 chemical methods and process Methods 0.000 description 1
238000007385 chemical modification Methods 0.000 description 1
229960005091 chloramphenicol Drugs 0.000 description 1
239000013611 chromosomal DNA Substances 0.000 description 1
210000000349 chromosome Anatomy 0.000 description 1
239000013599 cloning vector Substances 0.000 description 1
239000011248 coating agent Substances 0.000 description 1
238000000576 coating method Methods 0.000 description 1
238000002742 combinatorial mutagenesis Methods 0.000 description 1
239000000356 contaminant Substances 0.000 description 1
238000012937 correction Methods 0.000 description 1
239000000287 crude extract Substances 0.000 description 1
239000013078 crystal Substances 0.000 description 1
125000000151 cysteine group Chemical group N[C@@H](CS)C(=O)* 0.000 description 1
230000007547 defect Effects 0.000 description 1
230000002950 deficient Effects 0.000 description 1
238000006731 degradation reaction Methods 0.000 description 1
238000004925 denaturation Methods 0.000 description 1
230000036425 denaturation Effects 0.000 description 1
238000001212 derivatisation Methods 0.000 description 1
229960002086 dextran Drugs 0.000 description 1
229960000633 dextran sulfate Drugs 0.000 description 1
239000008121 dextrose Substances 0.000 description 1
238000003745 diagnosis Methods 0.000 description 1
235000005911 diet Nutrition 0.000 description 1
230000037213 diet Effects 0.000 description 1
ZBCBWPMODOFKDW-UHFFFAOYSA-N diethanolamine Chemical compound OCCNCCO ZBCBWPMODOFKDW-UHFFFAOYSA-N 0.000 description 1
230000004069 differentiation Effects 0.000 description 1
102000004419 dihydrofolate reductase Human genes 0.000 description 1
238000010790 dilution Methods 0.000 description 1
239000012895 dilution Substances 0.000 description 1
208000035475 disorder Diseases 0.000 description 1
238000009826 distribution Methods 0.000 description 1
231100000673 dose–response relationship Toxicity 0.000 description 1
230000000667 effect on insulin Effects 0.000 description 1
239000012636 effector Substances 0.000 description 1
210000001671 embryonic stem cell Anatomy 0.000 description 1
210000002889 endothelial cell Anatomy 0.000 description 1
210000003158 enteroendocrine cell Anatomy 0.000 description 1
239000003797 essential amino acid Substances 0.000 description 1
235000020776 essential amino acid Nutrition 0.000 description 1
238000012869 ethanol precipitation Methods 0.000 description 1
238000011156 evaluation Methods 0.000 description 1
230000001747 exhibiting effect Effects 0.000 description 1
238000000605 extraction Methods 0.000 description 1
239000003885 eye ointment Substances 0.000 description 1
230000001815 facial effect Effects 0.000 description 1
239000012530 fluid Substances 0.000 description 1
235000013305 food Nutrition 0.000 description 1
238000013467 fragmentation Methods 0.000 description 1
238000006062 fragmentation reaction Methods 0.000 description 1
238000007710 freezing Methods 0.000 description 1
230000008014 freezing Effects 0.000 description 1
230000002538 fungal effect Effects 0.000 description 1
230000006251 gamma-carboxylation Effects 0.000 description 1
238000001502 gel electrophoresis Methods 0.000 description 1
101150056310 gem1 gene Proteins 0.000 description 1
238000001476 gene delivery Methods 0.000 description 1
102000018146 globin Human genes 0.000 description 1
108060003196 globin Proteins 0.000 description 1
MASNOZXLGMXCHN-ZLPAWPGGSA-N glucagon Chemical compound C([C@@H](C(=O)N[C@H](C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(O)=O)C(C)C)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](C)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CO)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CO)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@@H](NC(=O)CNC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CO)NC(=O)[C@@H](N)CC=1NC=NC=1)[C@@H](C)O)[C@@H](C)O)C1=CC=CC=C1 MASNOZXLGMXCHN-ZLPAWPGGSA-N 0.000 description 1
229960004666 glucagon Drugs 0.000 description 1
230000010030 glucose lowering effect Effects 0.000 description 1
230000004153 glucose metabolism Effects 0.000 description 1
238000007446 glucose tolerance test Methods 0.000 description 1
230000004190 glucose uptake Effects 0.000 description 1
229960003180 glutathione Drugs 0.000 description 1
230000002641 glycemic effect Effects 0.000 description 1
230000002414 glycolytic effect Effects 0.000 description 1
PCHJSUWPFVWCPO-UHFFFAOYSA-N gold Chemical compound [Au] PCHJSUWPFVWCPO-UHFFFAOYSA-N 0.000 description 1
239000010931 gold Substances 0.000 description 1
229910052737 gold Inorganic materials 0.000 description 1
239000008187 granular material Substances 0.000 description 1
230000012010 growth Effects 0.000 description 1
231100000869 headache Toxicity 0.000 description 1
108010007884 helospectin Proteins 0.000 description 1
239000002382 helospectin Substances 0.000 description 1
210000003958 hematopoietic stem cell Anatomy 0.000 description 1
208000009429 hemophilia B Diseases 0.000 description 1
230000002440 hepatic effect Effects 0.000 description 1
230000007686 hepatotoxicity Effects 0.000 description 1
238000013537 high throughput screening Methods 0.000 description 1
102000055955 human ADCYAP1 Human genes 0.000 description 1
210000003917 human chromosome Anatomy 0.000 description 1
238000004191 hydrophobic interaction chromatography Methods 0.000 description 1
229910052588 hydroxylapatite Inorganic materials 0.000 description 1
230000033444 hydroxylation Effects 0.000 description 1
238000005805 hydroxylation reaction Methods 0.000 description 1
238000002649 immunization Methods 0.000 description 1
230000003053 immunization Effects 0.000 description 1
230000005847 immunogenicity Effects 0.000 description 1
238000011534 incubation Methods 0.000 description 1
208000015181 infectious disease Diseases 0.000 description 1
230000002458 infectious effect Effects 0.000 description 1
239000004615 ingredient Substances 0.000 description 1
230000005764 inhibitory process Effects 0.000 description 1
238000003780 insertion Methods 0.000 description 1
230000037431 insertion Effects 0.000 description 1
230000002473 insulinotropic effect Effects 0.000 description 1
230000010354 integration Effects 0.000 description 1
230000002452 interceptive effect Effects 0.000 description 1
239000007928 intraperitoneal injection Substances 0.000 description 1
230000026045 iodination Effects 0.000 description 1
238000006192 iodination reaction Methods 0.000 description 1
229960000310 isoleucine Drugs 0.000 description 1
AGPKZVBTJJNPAG-UHFFFAOYSA-N isoleucine Natural products CCC(C)C(N)C(O)=O AGPKZVBTJJNPAG-UHFFFAOYSA-N 0.000 description 1
BPHPUYQFMNQIOC-NXRLNHOXSA-N isopropyl beta-D-thiogalactopyranoside Chemical compound CC(C)S[C@@H]1O[C@H](CO)[C@H](O)[C@H](O)[C@H]1O BPHPUYQFMNQIOC-NXRLNHOXSA-N 0.000 description 1
210000002510 keratinocyte Anatomy 0.000 description 1
229960003299 ketamine Drugs 0.000 description 1
230000003907 kidney function Effects 0.000 description 1
101150066555 lacZ gene Proteins 0.000 description 1
239000004310 lactic acid Substances 0.000 description 1
235000014655 lactic acid Nutrition 0.000 description 1
210000000867 larynx Anatomy 0.000 description 1
229960004194 lidocaine Drugs 0.000 description 1
230000000670 limiting effect Effects 0.000 description 1
239000007788 liquid Substances 0.000 description 1
238000004811 liquid chromatography Methods 0.000 description 1
230000003908 liver function Effects 0.000 description 1
230000007056 liver toxicity Effects 0.000 description 1
230000007774 longterm Effects 0.000 description 1
230000002934 lysing effect Effects 0.000 description 1
230000014759 maintenance of location Effects 0.000 description 1
239000003550 marker Substances 0.000 description 1
239000011159 matrix material Substances 0.000 description 1
230000007246 mechanism Effects 0.000 description 1
201000001441 melanoma Diseases 0.000 description 1
230000028161 membrane depolarization Effects 0.000 description 1
230000004060 metabolic process Effects 0.000 description 1
229960003105 metformin Drugs 0.000 description 1
MYWUZJCMWCOHBA-VIFPVBQESA-N methamphetamine Chemical compound CN[C@@H](C)CC1=CC=CC=C1 MYWUZJCMWCOHBA-VIFPVBQESA-N 0.000 description 1
230000011987 methylation Effects 0.000 description 1
238000007069 methylation reaction Methods 0.000 description 1
230000000813 microbial effect Effects 0.000 description 1
229960001110 miglitol Drugs 0.000 description 1
108091005601 modified peptides Proteins 0.000 description 1
238000012544 monitoring process Methods 0.000 description 1
238000010172 mouse model Methods 0.000 description 1
210000003205 muscle Anatomy 0.000 description 1
210000003098 myoblast Anatomy 0.000 description 1
210000004165 myocardium Anatomy 0.000 description 1
230000007498 myristoylation Effects 0.000 description 1
229960004927 neomycin Drugs 0.000 description 1
230000000955 neuroendocrine Effects 0.000 description 1
210000002569 neuron Anatomy 0.000 description 1
239000004090 neuroprotective agent Substances 0.000 description 1
230000000324 neuroprotective effect Effects 0.000 description 1
239000002858 neurotransmitter agent Substances 0.000 description 1
231100001222 nononcogenic Toxicity 0.000 description 1
239000002777 nucleoside Substances 0.000 description 1
125000003835 nucleoside group Chemical group 0.000 description 1
235000015097 nutrients Nutrition 0.000 description 1
229940126701 oral medication Drugs 0.000 description 1
230000003647 oxidation Effects 0.000 description 1
238000007254 oxidation reaction Methods 0.000 description 1
108010042202 p66 - pituitary adenylate cyclase-activating peptide analog Proteins 0.000 description 1
TVIDEEHSOPHZBR-AWEZNQCLSA-N para-(benzoyl)-phenylalanine Chemical compound C1=CC(C[C@H](N)C(O)=O)=CC=C1C(=O)C1=CC=CC=C1 TVIDEEHSOPHZBR-AWEZNQCLSA-N 0.000 description 1
238000007911 parenteral administration Methods 0.000 description 1
230000036961 partial effect Effects 0.000 description 1
239000008188 pellet Substances 0.000 description 1
XYJRXVWERLGGKC-UHFFFAOYSA-D pentacalcium;hydroxide;triphosphate Chemical compound [OH-].[Ca+2].[Ca+2].[Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O XYJRXVWERLGGKC-UHFFFAOYSA-D 0.000 description 1
239000000813 peptide hormone Substances 0.000 description 1
239000000137 peptide hydrolase inhibitor Substances 0.000 description 1
230000002093 peripheral effect Effects 0.000 description 1
210000001322 periplasm Anatomy 0.000 description 1
238000002823 phage display Methods 0.000 description 1
239000000546 pharmaceutical excipient Substances 0.000 description 1
229940080469 phosphocellulose Drugs 0.000 description 1
230000026731 phosphorylation Effects 0.000 description 1
238000006366 phosphorylation reaction Methods 0.000 description 1
102000020233 phosphotransferase Human genes 0.000 description 1
238000005222 photoaffinity labeling Methods 0.000 description 1
230000036470 plasma concentration Effects 0.000 description 1
229920000642 polymer Polymers 0.000 description 1
229920005990 polystyrene resin Polymers 0.000 description 1
230000000291 postprandial effect Effects 0.000 description 1
239000002244 precipitate Substances 0.000 description 1
238000001556 precipitation Methods 0.000 description 1
229940095885 precose Drugs 0.000 description 1
239000002243 precursor Substances 0.000 description 1
230000013823 prenylation Effects 0.000 description 1
238000002360 preparation method Methods 0.000 description 1
238000002953 preparative HPLC Methods 0.000 description 1
238000004321 preservation Methods 0.000 description 1
230000002265 prevention Effects 0.000 description 1
125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 1
230000002035 prolonged effect Effects 0.000 description 1
238000011321 prophylaxis Methods 0.000 description 1
230000004224 protection Effects 0.000 description 1
230000004952 protein activity Effects 0.000 description 1
108020001580 protein domains Proteins 0.000 description 1
230000009145 protein modification Effects 0.000 description 1
230000030788 protein refolding Effects 0.000 description 1
230000017854 proteolysis Effects 0.000 description 1
230000002797 proteolythic effect Effects 0.000 description 1
230000002685 pulmonary effect Effects 0.000 description 1
229940043131 pyroglutamate Drugs 0.000 description 1
230000008707 rearrangement Effects 0.000 description 1
230000011514 reflex Effects 0.000 description 1
230000004648 relaxation of smooth muscle Effects 0.000 description 1
238000004153 renaturation Methods 0.000 description 1
230000001850 reproductive effect Effects 0.000 description 1
230000029058 respiratory gaseous exchange Effects 0.000 description 1
230000000717 retained effect Effects 0.000 description 1
102220091606 rs148701985 Human genes 0.000 description 1
102220278104 rs1554096640 Human genes 0.000 description 1
102220010000 rs397507367 Human genes 0.000 description 1
102220088154 rs869025539 Human genes 0.000 description 1
210000003079 salivary gland Anatomy 0.000 description 1
235000019515 salmon Nutrition 0.000 description 1
239000012266 salt solution Substances 0.000 description 1
229920006395 saturated elastomer Polymers 0.000 description 1
229960002101 secretin Drugs 0.000 description 1
OWMZNFCDEHGFEP-NFBCVYDUSA-N secretin human Chemical compound C([C@@H](C(=O)N[C@H](C(=O)N[C@@H](CO)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCC(O)=O)C(=O)NCC(=O)N[C@@H](C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(N)=O)C(=O)NCC(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](C(C)C)C(N)=O)[C@@H](C)O)NC(=O)[C@@H](NC(=O)CNC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CO)NC(=O)[C@@H](N)CC=1NC=NC=1)[C@@H](C)O)C1=CC=CC=C1 OWMZNFCDEHGFEP-NFBCVYDUSA-N 0.000 description 1
210000004739 secretory vesicle Anatomy 0.000 description 1
230000035945 sensitivity Effects 0.000 description 1
238000000926 separation method Methods 0.000 description 1
238000012163 sequencing technique Methods 0.000 description 1
210000002966 serum Anatomy 0.000 description 1
230000035939 shock Effects 0.000 description 1
238000002741 site-directed mutagenesis Methods 0.000 description 1
210000002027 skeletal muscle Anatomy 0.000 description 1
239000011734 sodium Substances 0.000 description 1
239000001509 sodium citrate Substances 0.000 description 1
NLJMYIDDQXHKNR-UHFFFAOYSA-K sodium citrate Chemical compound O.O.[Na+].[Na+].[Na+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O NLJMYIDDQXHKNR-UHFFFAOYSA-K 0.000 description 1
238000002415 sodium dodecyl sulfate polyacrylamide gel electrophoresis Methods 0.000 description 1
TXBNDGDMWKVRQW-UHFFFAOYSA-M sodium;2-[[1,3-dihydroxy-2-(hydroxymethyl)propan-2-yl]azaniumyl]acetate;dodecyl sulfate Chemical compound [Na+].OCC(CO)(CO)NCC(O)=O.CCCCCCCCCCCCOS([O-])(=O)=O TXBNDGDMWKVRQW-UHFFFAOYSA-M 0.000 description 1
239000007790 solid phase Substances 0.000 description 1
238000000527 sonication Methods 0.000 description 1
125000006850 spacer group Chemical group 0.000 description 1
230000006641 stabilisation Effects 0.000 description 1
238000011105 stabilization Methods 0.000 description 1
238000011301 standard therapy Methods 0.000 description 1
239000008223 sterile water Substances 0.000 description 1
230000000638 stimulation Effects 0.000 description 1
239000011550 stock solution Substances 0.000 description 1
210000002784 stomach Anatomy 0.000 description 1
125000001424 substituent group Chemical group 0.000 description 1
239000000758 substrate Substances 0.000 description 1
235000000346 sugar Nutrition 0.000 description 1
150000008163 sugars Chemical class 0.000 description 1
239000006228 supernatant Substances 0.000 description 1
239000000725 suspension Substances 0.000 description 1
230000002459 sustained effect Effects 0.000 description 1
230000009747 swallowing Effects 0.000 description 1
208000024891 symptom Diseases 0.000 description 1
230000006794 tachycardia Effects 0.000 description 1
125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
229960002180 tetracycline Drugs 0.000 description 1
229930101283 tetracycline Natural products 0.000 description 1
235000019364 tetracycline Nutrition 0.000 description 1
150000003522 tetracyclines Chemical class 0.000 description 1
238000010257 thawing Methods 0.000 description 1
229940124597 therapeutic agent Drugs 0.000 description 1
HNKJADCVZUBCPG-UHFFFAOYSA-N thioanisole Chemical compound CSC1=CC=CC=C1 HNKJADCVZUBCPG-UHFFFAOYSA-N 0.000 description 1
231100000419 toxicity Toxicity 0.000 description 1
230000001988 toxicity Effects 0.000 description 1
210000005090 tracheal smooth muscle Anatomy 0.000 description 1
230000005030 transcription termination Effects 0.000 description 1
230000002103 transcriptional effect Effects 0.000 description 1
238000010361 transduction Methods 0.000 description 1
230000026683 transduction Effects 0.000 description 1
230000001131 transforming effect Effects 0.000 description 1
238000011830 transgenic mouse model Methods 0.000 description 1
230000014621 translational initiation Effects 0.000 description 1
230000032258 transport Effects 0.000 description 1
ZGYICYBLPGRURT-UHFFFAOYSA-N tri(propan-2-yl)silicon Chemical compound CC(C)[Si](C(C)C)C(C)C ZGYICYBLPGRURT-UHFFFAOYSA-N 0.000 description 1
QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 description 1
RYFMWSXOAZQYPI-UHFFFAOYSA-K trisodium phosphate Chemical compound [Na+].[Na+].[Na+].[O-]P([O-])([O-])=O RYFMWSXOAZQYPI-UHFFFAOYSA-K 0.000 description 1
GXPHKUHSUJUWKP-NTKDMRAZSA-N troglitazone Natural products C([C@@]1(OC=2C(C)=C(C(=C(C)C=2CC1)O)C)C)OC(C=C1)=CC=C1C[C@H]1SC(=O)NC1=O GXPHKUHSUJUWKP-NTKDMRAZSA-N 0.000 description 1
239000002753 trypsin inhibitor Substances 0.000 description 1
108010029384 tryptophyl-histidine Proteins 0.000 description 1
231100000397 ulcer Toxicity 0.000 description 1
230000036269 ulceration Effects 0.000 description 1
241001529453 unidentified herpesvirus Species 0.000 description 1
208000007089 vaccinia Diseases 0.000 description 1
239000013603 viral vector Substances 0.000 description 1
BPICBUSOMSTKRF-UHFFFAOYSA-N xylazine Chemical compound CC1=CC=CC(C)=C1NC1=NCCCS1 BPICBUSOMSTKRF-UHFFFAOYSA-N 0.000 description 1
229960001600 xylazine Drugs 0.000 description 1

Classifications

- 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
- C07K14/575—Hormones
- C07K14/57563—Vasoactive intestinal peptide [VIP]; Related peptides
- 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
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides

Landscapes

Health & Medical Sciences (AREA)
Chemical & Material Sciences (AREA)
Life Sciences & Earth Sciences (AREA)
Organic Chemistry (AREA)
Diabetes (AREA)
General Health & Medical Sciences (AREA)
Endocrinology (AREA)
Medicinal Chemistry (AREA)
Animal Behavior & Ethology (AREA)
Toxicology (AREA)
General Chemical & Material Sciences (AREA)
Obesity (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Hematology (AREA)
Pharmacology & Pharmacy (AREA)
Bioinformatics & Cheminformatics (AREA)
Engineering & Computer Science (AREA)
Emergency Medicine (AREA)
Public Health (AREA)
Veterinary Medicine (AREA)
Vascular Medicine (AREA)
Chemical Kinetics & Catalysis (AREA)
Zoology (AREA)
Gastroenterology & Hepatology (AREA)
Biochemistry (AREA)
Biophysics (AREA)
Genetics & Genomics (AREA)
Molecular Biology (AREA)
Proteomics, Peptides & Aminoacids (AREA)
Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Peptides Or Proteins (AREA)
Micro-Organisms Or Cultivation Processes Thereof (AREA)
Preparation Of Compounds By Using Micro-Organisms (AREA)

SK555-2002A 1999-09-28 2000-09-27 Pituitary adenylate cyclase activating peptide (PACAP) receptor 3 (R3) agonists and their pharmacological methods of use SK5552002A3 (en)

Applications Claiming Priority (3)

Application Number	Priority Date	Filing Date	Title
US40783299A	1999-09-28	1999-09-28
US59528000A	2000-06-15	2000-06-15
PCT/US2000/026638 WO2001023420A2 (fr)	1999-09-28	2000-09-27	Recepteurs 3 agonistes (r3) pituitaire adenyl cyclase activateur de peptide (pacap) et leurs procedes pharmacologiques d'utilisation

Publications (1)

Publication Number	Publication Date
SK5552002A3 true SK5552002A3 (en)	2003-05-02

Family

ID=27020026

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
SK555-2002A SK5552002A3 (en)	1999-09-28	2000-09-27	Pituitary adenylate cyclase activating peptide (PACAP) receptor 3 (R3) agonists and their pharmacological methods of use

Country Status (19)

Country	Link
EP (1)	EP1192182B1 (fr)
AT (1)	ATE397625T1 (fr)
AU (1)	AU7726600A (fr)
CA (1)	CA2379604A1 (fr)
CO (1)	CO5280048A1 (fr)
CZ (1)	CZ296858B6 (fr)
DE (1)	DE60039111D1 (fr)
DO (1)	DOP2000000071A (fr)
ES (1)	ES2307534T3 (fr)
GT (1)	GT200000162A (fr)
HU (1)	HUP0202175A3 (fr)
MY (1)	MY131983A (fr)
PE (1)	PE20010612A1 (fr)
RU (1)	RU2269354C2 (fr)
SK (1)	SK5552002A3 (fr)
SV (1)	SV2002000184A (fr)
TW (1)	TWI264438B (fr)
UY (1)	UY26360A1 (fr)
WO (1)	WO2001023420A2 (fr)

Families Citing this family (36)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
UA74912C2 (en)	2001-07-06	2006-02-15	Merck & Co Inc	Beta-aminotetrahydroimidazo-(1,2-a)-pyrazines and tetratriazolo-(4,3-a)-pyrazines as inhibitors of dipeptylpeptidase for the treatment or prevention of diabetes
JP2006514914A (ja) *	2002-02-14	2006-05-18	バイエル・フアーマシユーチカルズ・コーポレーシヨン	有機溶媒中および乾燥状態のペプチドの安定化における製剤の戦略
US7615219B2 (en)	2003-01-16	2009-11-10	Life Sciences Research Partners Vzw	Inhibition of PACAP signalling for the prevention and treatment of thrombocytopenia
TR201907313T4 (tr)	2003-05-23	2019-06-21	Nektar Therapeutics	İki PEG zinciri içeren PEG türevleri.
US7947261B2 (en)	2003-05-23	2011-05-24	Nektar Therapeutics	Conjugates formed from polymer derivatives having particular atom arrangements
BRPI0507177A (pt) *	2004-01-27	2007-06-26	Bayer Pharmaceuticals Corp	agonistas (vpac2) do receptor peptìdico de ativação de adenilato ciclase pituitários (pacap) e seus métodos farmacológicos de uso
CA2567635A1 (fr) *	2004-05-21	2005-12-01	Eli Lilly And Company	Agonistes peptidiques selectifs du recepteur vpac2
US20080026996A1 (en) *	2004-05-21	2008-01-31	Eli Lilly And Company	Selective Vpac2 Receptor Reptide Agonists
WO2005123109A2 (fr) *	2004-06-12	2005-12-29	Bayer Pharmaceuticals Corporation	Pegylation d'agonistes vis-a-vis du recepteur 2 (vpac2) de peptide intestinal vaso-actif (vip)/peptide d'activation d'adenylate cyclase pituitaire (pacap) et procedes d'utilisation
CA2576755A1 (fr) *	2004-08-18	2006-03-02	Eli Lilly And Company	Agonistes peptidiques selectifs du recepteur vpac2
US7595294B2 (en) *	2004-10-08	2009-09-29	Transition Therapeutics, Inc.	Vasoactive intestinal polypeptide pharmaceuticals
BRPI0516126A (pt)	2004-10-08	2008-08-26	Forbes Medi Tech Res Inc	produtos farmacêuticos de polipeptìdeos intestinais vasoativos
ES2377526T3 (es)	2005-01-10	2012-03-28	Cortendo Ab (Publ)	2S,4R ketoconazol para el tratamiento de la diabetes, el síndrome metabólico y otras afecciones
EP1896048A4 (fr) *	2005-05-06	2010-11-03	Bayer Pharmaceuticals Corp	Agonistes du recepteur (vpac2) du peptide activant l'adenylate cyclase hypophysaire (pacap) et leurs procedes pharmacologiques d'utilisation
CA2618740A1 (fr) *	2005-08-11	2007-02-22	Eli Lilly And Company	Agonistes peptidiques selectifs du recepteur vpac2
KR101057284B1 (ko)	2005-10-26	2011-08-16	일라이 릴리 앤드 캄파니	선택적 ｖｐａｃ２ 수용체 펩티드 작동제
EP1801098A1 (fr)	2005-12-16	2007-06-27	Merck Sante	Dérivés de 2-Adamantylurea comme inhibiteurs de 11B-HSD1
TW200745163A (en) *	2006-02-17	2007-12-16	Syntonix Pharmaceuticals Inc	Peptides that block the binding of IgG to FcRn
EP2076265A4 (fr)	2006-10-02	2010-09-22	Cortendo Invest Ab	Énantiomère de cétoconazole chez les êtres humains
EP1935420A1 (fr)	2006-12-21	2008-06-25	Merck Sante	Dérivés du 2-adamantyl-butyramide en tant qu'inhibiteurs selectifs de la 11beta-HSD1
EP2110374A1 (fr)	2008-04-18	2009-10-21	Merck Sante	Dérivés de benzofurane, benzothiophène, benzothiazol en tant que modulateurs FXR
AU2009264242A1 (en)	2008-06-27	2009-12-30	Novartis Ag	Organic compounds
AU2009314200B2 (en)	2008-11-17	2011-11-17	Merck Sharp & Dohme Corp.	Substituted bicyclic amines for the treatment of diabetes
WO2010112520A1 (fr)	2009-04-01	2010-10-07	Novartis Ag	Dérivés spiro pour la modulation de la stéaroyl-coa désaturase
US20120220567A1 (en)	2009-07-23	2012-08-30	Shipps Jr Gerald W	Benzo-fused oxazepine compounds as stearoyl-coenzyme a delta-9 desaturase inhibitors
WO2011011506A1 (fr)	2009-07-23	2011-01-27	Schering Corporation	Composés oxazépine spirocyclique en tant qu'inhibiteurs de la stéaroyl-coenzyme a delta-9 désaturase
BR112012007509A2 (pt)	2009-10-01	2016-11-22	Novartis Ag	derivados pirazóis que modulam estearoil-coa dessaturase
EP2501685A1 (fr)	2009-11-16	2012-09-26	Mellitech	Dérivés de [1,5]-diazocine
CN102791701B (zh)	2009-12-30	2014-02-12	深圳信立泰药业股份有限公司	作为二肽基肽酶iv(dpp-iv)抑制剂的3-(3-氨基哌啶-1-基)-5-氧代-1,2,4-三嗪衍生物
CU24075B1 (es) *	2011-08-26	2015-01-29	Ct De Ingeniería Genética Y Biotecnología	Composición vacunal que comprende el péptido activador de la adenilato ciclasa de pituitaria como adyuvante molecular.
WO2013155600A1 (fr)	2012-04-16	2013-10-24	Kaneq Pharma	Dérivés de phosphonates aromatiques fusionnés utilisés comme précurseurs d'inhibiteurs de ptp-1b
EP3035950A4 (fr) *	2013-08-14	2017-05-03	The Arizona Board Of Regents On Behalf Of The University Of Arizona	Analogues de pacap/vip glycosylés avec pénétration du snc augmentée pour le traitement de maladies neurodégénératives
CN106456998B (zh)	2014-04-17	2020-07-28	默沙东公司	西格列汀丹宁酸盐复合物
US10844116B2 (en)	2015-04-16	2020-11-24	The University Of Iowa Research Foundation	Use of anti-pacap antibodies and antigen binding fragments thereof for treatment, prevention, or inhibition of photophobia
AU2017250815B2 (en)	2016-04-15	2023-11-23	H. Lundbeck A/S.	Humanized anti-PACAP antibodies and uses thereof
EP3863634A1 (fr)	2018-10-12	2021-08-18	Strongbridge Dublin Limited	Lévokétoconazole pour le traitement de l'hyperplasie surrénale congénitale et de l'aldostéronisme primaire

Family Cites Families (6)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
CA2077764C (fr) *	1990-03-17	2002-12-10	Nobuhiro Suzuki	Anticorps contre la peptide activant l'adenylate-cyclase de l'hypophyse, et son utilisation
AU656230B2 (en) *	1991-10-11	1995-01-27	F. Hoffmann-La Roche Ag	Cyclic vasoactive peptides
AU682638B2 (en) *	1995-06-09	1997-10-09	ILS, Inc.	Peptide, bronchodilator and blood flow ameliorant
WO1998002453A2 (fr) *	1996-07-15	1998-01-22	Universite Libre De Bruxelles	Ligands peptidiques possedant une selectivite plus elevee pour le recepteur vip1 que pour le recepteur vip¿2?
FR2775902B1 (fr) *	1998-03-13	2001-05-11	Assist Publ Hopitaux De Paris	Utilisation d'analogues du vip dans la prevention et le traitement des lesions cerebrales du nouveau-ne humain
CZ2001253A3 (cs) *	1998-07-20	2001-11-14	Societe De Conseils De Recherches Et D'application	Peptidové analogy PACAP

2000
- 2000-09-27 ES ES00967002T patent/ES2307534T3/es not_active Expired - Lifetime
- 2000-09-27 WO PCT/US2000/026638 patent/WO2001023420A2/fr not_active Ceased
- 2000-09-27 PE PE2000001015A patent/PE20010612A1/es not_active Application Discontinuation
- 2000-09-27 EP EP00967002A patent/EP1192182B1/fr not_active Expired - Lifetime
- 2000-09-27 CZ CZ20021085A patent/CZ296858B6/cs not_active IP Right Cessation
- 2000-09-27 RU RU2001136014/15A patent/RU2269354C2/ru active
- 2000-09-27 CA CA002379604A patent/CA2379604A1/fr not_active Abandoned
- 2000-09-27 HU HU0202175A patent/HUP0202175A3/hu unknown
- 2000-09-27 DE DE60039111T patent/DE60039111D1/de not_active Expired - Lifetime
- 2000-09-27 AU AU77266/00A patent/AU7726600A/en not_active Abandoned
- 2000-09-27 SK SK555-2002A patent/SK5552002A3/sk unknown
- 2000-09-27 AT AT00967002T patent/ATE397625T1/de not_active IP Right Cessation
- 2000-09-28 SV SV2000000184A patent/SV2002000184A/es not_active Application Discontinuation
- 2000-09-28 UY UY26360A patent/UY26360A1/es unknown
- 2000-09-28 DO DO2000000071A patent/DOP2000000071A/es unknown
- 2000-09-28 CO CO00073865A patent/CO5280048A1/es active IP Right Grant
- 2000-09-28 MY MYPI20004551A patent/MY131983A/en unknown
- 2000-09-28 GT GT200000162A patent/GT200000162A/es unknown
- 2000-09-28 TW TW089120330A patent/TWI264438B/zh not_active IP Right Cessation

Also Published As

Publication number	Publication date
PE20010612A1 (es)	2001-07-12
SV2002000184A (es)	2002-06-07
ES2307534T3 (es)	2008-12-01
WO2001023420A3 (fr)	2001-08-30
EP1192182A2 (fr)	2002-04-03
HUP0202175A3 (en)	2005-01-28
AU7726600A (en)	2001-04-30
ATE397625T1 (de)	2008-06-15
CZ20021085A3 (cs)	2003-01-15
MY131983A (en)	2007-09-28
RU2269354C2 (ru)	2006-02-10
HUP0202175A2 (en)	2002-10-28
DOP2000000071A (es)	2002-02-28
CA2379604A1 (fr)	2001-04-05
EP1192182B1 (fr)	2008-06-04
DE60039111D1 (de)	2008-07-17
WO2001023420A2 (fr)	2001-04-05
GT200000162A (es)	2002-03-22
CO5280048A1 (es)	2003-05-30
UY26360A1 (es)	2001-04-30
TWI264438B (en)	2006-10-21
CZ296858B6 (cs)	2006-07-12

Publication	Publication Date	Title
SK5552002A3 (en)	2003-05-02	Pituitary adenylate cyclase activating peptide (PACAP) receptor 3 (R3) agonists and their pharmacological methods of use
US7488716B2 (en)	2009-02-10	Peptides acting as both GLP-1 receptor agonists and glucagon receptor antagonists and their pharmacological methods of use
CN108348583B (zh)	2022-06-03	胰高血糖素受体激动剂
US7507714B2 (en)	2009-03-24	Pituitary adenylate cyclase activating peptide (PACAP) receptor 3 (R3) agonists and their pharmacological methods of use
US7378494B2 (en)	2008-05-27	Pituitary adenylate cyclase activating peptide (PACAP) receptor (VPAC2) agonist peptide
US20040002442A1 (en)	2004-01-01	Peptides acting as both GLP-1 receptor agonists and glucagon receptor antagonists and their pharmacological methods of use
US20030124669A1 (en)	2003-07-03	Peptides acting as both GLP-1 receptor agonists and glucagon receptor antagonists and their pharmacological methods of use
US6972319B1 (en)	2005-12-06	Pituitary adenylate cyclase activating peptide (PACAP)receptor 3 (R3) agonists and their pharmacological methods of use
US10968266B2 (en)	2021-04-06	GIP peptide analogues
AU2002341961A1 (en)	2003-05-19	Peptides acting as both GLP-1 receptor agonists and glucagon receptor antagonists and their pharmacological methods of use
HK1131161A (en)	2010-01-15	Pituitary adenylate cyclase activating peptide (pacap) receptor (vpac2) agonists and their pharmacological methods of use

Legal Events

Date	Code	Title	Description
2010-12-07	FB9A	Suspension of patent application procedure