TW201620938A - 雙特異性抗cgrp受體/pac1受體抗原結合蛋白質及其用途 - Google Patents

Info

Publication number

TW201620938A

TW201620938A TW104130488A TW104130488A TW201620938A TW 201620938 A TW201620938 A TW 201620938A TW 104130488 A TW104130488 A TW 104130488A TW 104130488 A TW104130488 A TW 104130488A TW 201620938 A TW201620938 A TW 201620938A

Authority

TW

Taiwan

Prior art keywords

ips

seq

sequence

antigen binding

binding protein

Prior art date

2014-09-15

Links

• Espacenet
• Global Dossier
• Discuss

• 102000025171 antigen binding proteins Human genes 0.000 title claims abstract description 386
• 108091000831 antigen binding proteins Proteins 0.000 title claims abstract description 386
• 102000005737 Type I Pituitary Adenylate Cyclase-Activating Polypeptide Receptors Human genes 0.000 title claims abstract description 115
• 108010045627 Type I Pituitary Adenylate Cyclase-Activating Polypeptide Receptors Proteins 0.000 title claims description 48
• 102000005962 receptors Human genes 0.000 title abstract description 260
• 108020003175 receptors Proteins 0.000 title abstract description 260
• 230000027455 binding Effects 0.000 claims abstract description 233
• 108010078311 Calcitonin Gene-Related Peptide Receptors Proteins 0.000 claims abstract description 128
• 238000000034 method Methods 0.000 claims abstract description 118
• 102000008323 calcitonin gene-related peptide receptor activity proteins Human genes 0.000 claims abstract description 115
• 206010027599 migraine Diseases 0.000 claims abstract description 102
• 208000019695 Migraine disease Diseases 0.000 claims abstract description 93
• 101100117763 Homo sapiens DUSP2 gene Proteins 0.000 claims abstract description 67
• DNKYDHSONDSTNJ-XJVRLEFXSA-N chembl1910953 Chemical compound C([C@@H](C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](C)C(=O)NCC(=O)N[C@@H](CC(C)C)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](CO)C(=O)NCC(=O)NCC(=O)N[C@@H](C(C)C)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](C(C)C)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](C(C)C)C(=O)NCC(=O)N[C@@H](CO)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](C)C(=O)N[C@@H](CC=1C=CC=CC=1)C(N)=O)NC(=O)[C@@H](NC(=O)[C@@H](NC(=O)[C@H](CS)NC(=O)[C@@H](NC(=O)[C@H](C)NC(=O)[C@@H](NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CS)NC(=O)[C@H](C)N)[C@@H](C)O)[C@@H](C)O)C(C)C)[C@@H](C)O)C1=CN=CN1 DNKYDHSONDSTNJ-XJVRLEFXSA-N 0.000 claims abstract description 64
• 208000002193 Pain Diseases 0.000 claims abstract description 37
• 208000006561 Cluster Headache Diseases 0.000 claims abstract description 21
• 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 14
• 208000000094 Chronic Pain Diseases 0.000 claims abstract description 12
• 235000001014 amino acid Nutrition 0.000 claims description 242
• 108090000765 processed proteins & peptides Proteins 0.000 claims description 213
• 150000001413 amino acids Chemical class 0.000 claims description 187
• 102000004196 processed proteins & peptides Human genes 0.000 claims description 151
• 229920001184 polypeptide Polymers 0.000 claims description 149
• 210000004027 cell Anatomy 0.000 claims description 130
• 241000282414 Homo sapiens Species 0.000 claims description 101
• 125000003275 alpha amino acid group Chemical group 0.000 claims description 100
• 150000007523 nucleic acids Chemical class 0.000 claims description 96
• 239000012634 fragment Substances 0.000 claims description 91
• 102000039446 nucleic acids Human genes 0.000 claims description 87
• 108020004707 nucleic acids Proteins 0.000 claims description 87
• 108090000623 proteins and genes Proteins 0.000 claims description 86
• 238000006467 substitution reaction Methods 0.000 claims description 73
• 206010019233 Headaches Diseases 0.000 claims description 51
• 102000004169 proteins and genes Human genes 0.000 claims description 50
• 210000004899 c-terminal region Anatomy 0.000 claims description 49
• 235000018102 proteins Nutrition 0.000 claims description 49
• 239000002253 acid Substances 0.000 claims description 46
• 231100000869 headache Toxicity 0.000 claims description 45
• 108060003951 Immunoglobulin Proteins 0.000 claims description 40
• 150000001412 amines Chemical class 0.000 claims description 40
• 102000018358 immunoglobulin Human genes 0.000 claims description 40
• 239000013598 vector Substances 0.000 claims description 40
• 230000035772 mutation Effects 0.000 claims description 36
• WHUUTDBJXJRKMK-UHFFFAOYSA-N Glutamic acid Natural products OC(=O)C(N)CCC(O)=O WHUUTDBJXJRKMK-UHFFFAOYSA-N 0.000 claims description 30
• 235000013922 glutamic acid Nutrition 0.000 claims description 30
• 239000004220 glutamic acid Substances 0.000 claims description 30
• 102000014914 Carrier Proteins Human genes 0.000 claims description 25
• 108091008324 binding proteins Proteins 0.000 claims description 25
• 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 25
• 238000011282 treatment Methods 0.000 claims description 23
• 230000014509 gene expression Effects 0.000 claims description 22
• CKLJMWTZIZZHCS-REOHCLBHSA-N aspartic acid group Chemical group N[C@@H](CC(=O)O)C(=O)O CKLJMWTZIZZHCS-REOHCLBHSA-N 0.000 claims description 21
• 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 21
• 239000012636 effector Substances 0.000 claims description 20
• 235000003704 aspartic acid Nutrition 0.000 claims description 19
• OQFSQFPPLPISGP-UHFFFAOYSA-N beta-carboxyaspartic acid Natural products OC(=O)C(N)C(C(O)=O)C(O)=O OQFSQFPPLPISGP-UHFFFAOYSA-N 0.000 claims description 19
• 230000013595 glycosylation Effects 0.000 claims description 18
• 238000006206 glycosylation reaction Methods 0.000 claims description 18
• 238000004519 manufacturing process Methods 0.000 claims description 15
• 108010067060 Immunoglobulin Variable Region Proteins 0.000 claims description 14
• 102000017727 Immunoglobulin Variable Region Human genes 0.000 claims description 14
• 239000003814 drug Substances 0.000 claims description 13
• 230000001314 paroxysmal effect Effects 0.000 claims description 13
• 208000018912 cluster headache syndrome Diseases 0.000 claims description 11
• 239000000546 pharmaceutical excipient Substances 0.000 claims description 11
• 125000000291 glutamic acid group Chemical group N[C@@H](CCC(O)=O)C(=O)* 0.000 claims description 10
• 238000011321 prophylaxis Methods 0.000 claims description 7
• 239000003085 diluting agent Substances 0.000 claims description 6
• 238000002360 preparation method Methods 0.000 claims description 5
• 102220283785 rs1344101243 Human genes 0.000 claims description 3
• FWMNVWWHGCHHJJ-SKKKGAJSSA-N 4-amino-1-[(2r)-6-amino-2-[[(2r)-2-[[(2r)-2-[[(2r)-2-amino-3-phenylpropanoyl]amino]-3-phenylpropanoyl]amino]-4-methylpentanoyl]amino]hexanoyl]piperidine-4-carboxylic acid Chemical compound C([C@H](C(=O)N[C@H](CC(C)C)C(=O)N[C@H](CCCCN)C(=O)N1CCC(N)(CC1)C(O)=O)NC(=O)[C@H](N)CC=1C=CC=CC=1)C1=CC=CC=C1 FWMNVWWHGCHHJJ-SKKKGAJSSA-N 0.000 claims description 2
• 238000012258 culturing Methods 0.000 claims description 2
• 229940099472 immunoglobulin a Drugs 0.000 claims 1
• 229940024606 amino acid Drugs 0.000 description 175
• 229960005552 PAC-1 Drugs 0.000 description 124
• 239000000427 antigen Substances 0.000 description 68
• 108091007433 antigens Proteins 0.000 description 68
• 102000036639 antigens Human genes 0.000 description 68
• 108010047041 Complementarity Determining Regions Proteins 0.000 description 61
• NFGXHKASABOEEW-UHFFFAOYSA-N 1-methylethyl 11-methoxy-3,7,11-trimethyl-2,4-dodecadienoate Chemical group COC(C)(C)CCCC(C)CC=CC(C)=CC(=O)OC(C)C NFGXHKASABOEEW-UHFFFAOYSA-N 0.000 description 37
• 108010054477 Immunoglobulin Fab Fragments Proteins 0.000 description 35
• 102000001706 Immunoglobulin Fab Fragments Human genes 0.000 description 35
• 108010004684 Pituitary adenylate cyclase-activating polypeptide Proteins 0.000 description 33
• 102000002808 Pituitary adenylate cyclase-activating polypeptide Human genes 0.000 description 32
• 239000000203 mixture Substances 0.000 description 31
• DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 30
• 229960002989 glutamic acid Drugs 0.000 description 30
• 239000002773 nucleotide Substances 0.000 description 29
• 125000003729 nucleotide group Chemical group 0.000 description 29
• 108020004414 DNA Proteins 0.000 description 28
• 108090000932 Calcitonin Gene-Related Peptide Proteins 0.000 description 26
• 102000004414 Calcitonin Gene-Related Peptide Human genes 0.000 description 26
• 230000004927 fusion Effects 0.000 description 25
• UFTCZKMBJOPXDM-XXFCQBPRSA-N pituitary adenylate cyclase-activating polypeptide Chemical compound C([C@H](N)C(=O)N[C@@H](CO)C(=O)N[C@@H](CC(O)=O)C(=O)NCC(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CO)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](C)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](C)C(=O)N[C@@H](C)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CC(C)C)C(=O)NCC(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CCCCN)C(N)=O)C1=CN=CN1 UFTCZKMBJOPXDM-XXFCQBPRSA-N 0.000 description 25
• WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 description 23
• 241000699666 Mus <mouse, genus> Species 0.000 description 22
• 238000009472 formulation Methods 0.000 description 22
• 230000006870 function Effects 0.000 description 22
• 206010057190 Respiratory tract infections Diseases 0.000 description 21
• 108010076504 Protein Sorting Signals Proteins 0.000 description 20
• KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 18
• 125000000539 amino acid group Chemical group 0.000 description 18
• 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 17
• 101000760563 Homo sapiens Calcitonin gene-related peptide type 1 receptor Proteins 0.000 description 17
• 101001139126 Homo sapiens Krueppel-like factor 6 Proteins 0.000 description 17
• 101001133600 Homo sapiens Pituitary adenylate cyclase-activating polypeptide type I receptor Proteins 0.000 description 17
• 101001080401 Homo sapiens Proteasome assembly chaperone 1 Proteins 0.000 description 17
• 102000008394 Immunoglobulin Fragments Human genes 0.000 description 17
• 108010021625 Immunoglobulin Fragments Proteins 0.000 description 17
• 241001465754 Metazoa Species 0.000 description 17
• 102100034309 Pituitary adenylate cyclase-activating polypeptide type I receptor Human genes 0.000 description 17
• 239000002585 base Substances 0.000 description 17
• 230000000694 effects Effects 0.000 description 17
• 239000013604 expression vector Substances 0.000 description 17
• 102100024654 Calcitonin gene-related peptide type 1 receptor Human genes 0.000 description 16
• 239000004472 Lysine Substances 0.000 description 16
• 108091028043 Nucleic acid sequence Proteins 0.000 description 16
• 238000012217 deletion Methods 0.000 description 16
• 230000037430 deletion Effects 0.000 description 16
• 238000003780 insertion Methods 0.000 description 16
• 230000037431 insertion Effects 0.000 description 16
• 235000018977 lysine Nutrition 0.000 description 16
• 108091026890 Coding region Proteins 0.000 description 15
• 238000003556 assay Methods 0.000 description 15
• 239000000243 solution Substances 0.000 description 15
• 108020001507 fusion proteins Proteins 0.000 description 14
• 102000037865 fusion proteins Human genes 0.000 description 14
• 239000003446 ligand Substances 0.000 description 14
• 102000014468 Calcitonin Gene-Related Peptide Receptors Human genes 0.000 description 13
• -1 amino acid amino acid Chemical class 0.000 description 13
• 239000003623 enhancer Substances 0.000 description 13
• 102000006496 Immunoglobulin Heavy Chains Human genes 0.000 description 12
• 108010019476 Immunoglobulin Heavy Chains Proteins 0.000 description 12
• KDXKERNSBIXSRK-YFKPBYRVSA-N L-lysine Chemical compound NCCCC[C@H](N)C(O)=O KDXKERNSBIXSRK-YFKPBYRVSA-N 0.000 description 12
• 230000015572 biosynthetic process Effects 0.000 description 12
• 238000009396 hybridization Methods 0.000 description 12
• 239000011159 matrix material Substances 0.000 description 12
• 208000024891 symptom Diseases 0.000 description 12
• MTCFGRXMJLQNBG-REOHCLBHSA-N (2S)-2-Amino-3-hydroxypropansäure Chemical compound OC[C@H](N)C(O)=O MTCFGRXMJLQNBG-REOHCLBHSA-N 0.000 description 11
• FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 11
• 239000000872 buffer Substances 0.000 description 11
• 230000000295 complement effect Effects 0.000 description 11
• 238000012360 testing method Methods 0.000 description 11
• 238000013518 transcription Methods 0.000 description 11
• 230000035897 transcription Effects 0.000 description 11
• 102000004190 Enzymes Human genes 0.000 description 10
• 108090000790 Enzymes Proteins 0.000 description 10
• 239000004471 Glycine Substances 0.000 description 10
• 206010028980 Neoplasm Diseases 0.000 description 10
• 230000010056 antibody-dependent cellular cytotoxicity Effects 0.000 description 10
• 229940088598 enzyme Drugs 0.000 description 10
• 238000002372 labelling Methods 0.000 description 10
• 108091032973 (ribonucleotides)n+m Proteins 0.000 description 9
• 239000003795 chemical substances by application Substances 0.000 description 9
• 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 description 9
• 230000004048 modification Effects 0.000 description 9
• 238000012986 modification Methods 0.000 description 9
• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 9
• 102000013463 Immunoglobulin Light Chains Human genes 0.000 description 8
• 108010065825 Immunoglobulin Light Chains Proteins 0.000 description 8
• 241000699670 Mus sp. Species 0.000 description 8
• MTCFGRXMJLQNBG-UHFFFAOYSA-N Serine Natural products OCC(N)C(O)=O MTCFGRXMJLQNBG-UHFFFAOYSA-N 0.000 description 8
• 150000001720 carbohydrates Chemical class 0.000 description 8
• 239000002299 complementary DNA Substances 0.000 description 8
• 229940079593 drug Drugs 0.000 description 8
• 230000003053 immunization Effects 0.000 description 8
• 238000002649 immunization Methods 0.000 description 8
• 230000001225 therapeutic effect Effects 0.000 description 8
• 241000894006 Bacteria Species 0.000 description 7
• 241000282412 Homo Species 0.000 description 7
• 241000829100 Macaca mulatta polyomavirus 1 Species 0.000 description 7
• 240000004808 Saccharomyces cerevisiae Species 0.000 description 7
• 235000014680 Saccharomyces cerevisiae Nutrition 0.000 description 7
• 239000005557 antagonist Substances 0.000 description 7
• 210000004978 chinese hamster ovary cell Anatomy 0.000 description 7
• 201000010099 disease Diseases 0.000 description 7
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 7
• 238000010494 dissociation reaction Methods 0.000 description 7
• 230000005593 dissociations Effects 0.000 description 7
• 210000004962 mammalian cell Anatomy 0.000 description 7
• 239000000463 material Substances 0.000 description 7
• 239000002609 medium Substances 0.000 description 7
• 102000040430 polynucleotide Human genes 0.000 description 7
• 108091033319 polynucleotide Proteins 0.000 description 7
• 239000002157 polynucleotide Substances 0.000 description 7
• 239000007790 solid phase Substances 0.000 description 7
• 241000894007 species Species 0.000 description 7
• 239000003381 stabilizer Substances 0.000 description 7
• 239000004094 surface-active agent Substances 0.000 description 7
• 108010001789 Calcitonin Receptors Proteins 0.000 description 6
• 102100038520 Calcitonin receptor Human genes 0.000 description 6
• FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 6
• FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 6
• FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 description 6
• 101000584583 Homo sapiens Receptor activity-modifying protein 1 Proteins 0.000 description 6
• 229930195725 Mannitol Natural products 0.000 description 6
• 108020000631 PAC1 receptors Proteins 0.000 description 6
• CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 6
• 229930006000 Sucrose Natural products 0.000 description 6
• VREFGVBLTWBCJP-UHFFFAOYSA-N alprazolam Chemical compound C12=CC(Cl)=CC=C2N2C(C)=NN=C2CN=C1C1=CC=CC=C1 VREFGVBLTWBCJP-UHFFFAOYSA-N 0.000 description 6
• 238000004458 analytical method Methods 0.000 description 6
• 238000004422 calculation algorithm Methods 0.000 description 6
• 235000014633 carbohydrates Nutrition 0.000 description 6
• 238000003776 cleavage reaction Methods 0.000 description 6
• 230000004540 complement-dependent cytotoxicity Effects 0.000 description 6
• XUJNEKJLAYXESH-UHFFFAOYSA-N cysteine Natural products SCC(N)C(O)=O XUJNEKJLAYXESH-UHFFFAOYSA-N 0.000 description 6
• 235000018417 cysteine Nutrition 0.000 description 6
• 125000000151 cysteine group Chemical group N[C@@H](CS)C(=O)* 0.000 description 6
• 102000050292 human RAMP1 Human genes 0.000 description 6
• 238000001802 infusion Methods 0.000 description 6
• 230000005764 inhibitory process Effects 0.000 description 6
• 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 6
• 125000003588 lysine group Chemical group [H]N([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])(N([H])[H])C(*)=O 0.000 description 6
• 239000000594 mannitol Substances 0.000 description 6
• 235000010355 mannitol Nutrition 0.000 description 6
• 230000001404 mediated effect Effects 0.000 description 6
• 238000002823 phage display Methods 0.000 description 6
• 238000003752 polymerase chain reaction Methods 0.000 description 6
• 229920005862 polyol Polymers 0.000 description 6
• 150000003077 polyols Chemical class 0.000 description 6
• 238000003127 radioimmunoassay Methods 0.000 description 6
• 230000007017 scission Effects 0.000 description 6
• 239000011780 sodium chloride Substances 0.000 description 6
• 239000000600 sorbitol Substances 0.000 description 6
• 235000010356 sorbitol Nutrition 0.000 description 6
• 239000005720 sucrose Substances 0.000 description 6
• 235000000346 sugar Nutrition 0.000 description 6
• 150000008163 sugars Chemical class 0.000 description 6
• 239000006228 supernatant Substances 0.000 description 6
• 210000001519 tissue Anatomy 0.000 description 6
• 210000004881 tumor cell Anatomy 0.000 description 6
• 239000004475 Arginine Substances 0.000 description 5
• KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 5
• 108700028146 Genetic Enhancer Elements Proteins 0.000 description 5
• PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 5
• XUJNEKJLAYXESH-REOHCLBHSA-N L-Cysteine Chemical compound SC[C@H](N)C(O)=O XUJNEKJLAYXESH-REOHCLBHSA-N 0.000 description 5
• 206010035226 Plasma cell myeloma Diseases 0.000 description 5
• 102100038388 Vasoactive intestinal polypeptide receptor 1 Human genes 0.000 description 5
• 101710137655 Vasoactive intestinal polypeptide receptor 1 Proteins 0.000 description 5
• 102100038286 Vasoactive intestinal polypeptide receptor 2 Human genes 0.000 description 5
• 230000004913 activation Effects 0.000 description 5
• 230000002411 adverse Effects 0.000 description 5
• 239000000556 agonist Substances 0.000 description 5
• 125000003277 amino group Chemical group 0.000 description 5
• 230000000890 antigenic effect Effects 0.000 description 5
• ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 5
• 235000009697 arginine Nutrition 0.000 description 5
• 230000004071 biological effect Effects 0.000 description 5
• 238000001035 drying Methods 0.000 description 5
• 238000005516 engineering process Methods 0.000 description 5
• 230000012010 growth Effects 0.000 description 5
• HNDVDQJCIGZPNO-UHFFFAOYSA-N histidine Natural products OC(=O)C(N)CC1=CN=CN1 HNDVDQJCIGZPNO-UHFFFAOYSA-N 0.000 description 5
• 230000006698 induction Effects 0.000 description 5
• 238000002347 injection Methods 0.000 description 5
• 239000007924 injection Substances 0.000 description 5
• 201000000050 myeloid neoplasm Diseases 0.000 description 5
• 229920001223 polyethylene glycol Polymers 0.000 description 5
• 239000003755 preservative agent Substances 0.000 description 5
• 230000002265 prevention Effects 0.000 description 5
• 239000000047 product Substances 0.000 description 5
• 238000000159 protein binding assay Methods 0.000 description 5
• 230000010076 replication Effects 0.000 description 5
• 229910001415 sodium ion Inorganic materials 0.000 description 5
• 238000003860 storage Methods 0.000 description 5
• UCTWMZQNUQWSLP-VIFPVBQESA-N (R)-adrenaline Chemical compound CNC[C@H](O)C1=CC=C(O)C(O)=C1 UCTWMZQNUQWSLP-VIFPVBQESA-N 0.000 description 4
• KRQUFUKTQHISJB-YYADALCUSA-N 2-[(E)-N-[2-(4-chlorophenoxy)propoxy]-C-propylcarbonimidoyl]-3-hydroxy-5-(thian-3-yl)cyclohex-2-en-1-one Chemical compound CCC\C(=N/OCC(C)OC1=CC=C(Cl)C=C1)C1=C(O)CC(CC1=O)C1CCCSC1 KRQUFUKTQHISJB-YYADALCUSA-N 0.000 description 4
• 108010088751 Albumins Proteins 0.000 description 4
• CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 4
• ZHNUHDYFZUAESO-UHFFFAOYSA-N Formamide Chemical compound NC=O ZHNUHDYFZUAESO-UHFFFAOYSA-N 0.000 description 4
• BDAGIHXWWSANSR-UHFFFAOYSA-N Formic acid Chemical compound OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 4
• WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 4
• 101000666868 Homo sapiens Vasoactive intestinal polypeptide receptor 2 Proteins 0.000 description 4
• 102000009786 Immunoglobulin Constant Regions Human genes 0.000 description 4
• 108010009817 Immunoglobulin Constant Regions Proteins 0.000 description 4
• 108020004684 Internal Ribosome Entry Sites Proteins 0.000 description 4
• QNAYBMKLOCPYGJ-REOHCLBHSA-N L-alanine Chemical compound C[C@H](N)C(O)=O QNAYBMKLOCPYGJ-REOHCLBHSA-N 0.000 description 4
• ODKSFYDXXFIFQN-BYPYZUCNSA-P L-argininium(2+) Chemical compound NC(=[NH2+])NCCC[C@H]([NH3+])C(O)=O ODKSFYDXXFIFQN-BYPYZUCNSA-P 0.000 description 4
• HNDVDQJCIGZPNO-YFKPBYRVSA-N L-histidine Chemical compound OC(=O)[C@@H](N)CC1=CN=CN1 HNDVDQJCIGZPNO-YFKPBYRVSA-N 0.000 description 4
• 230000004988 N-glycosylation Effects 0.000 description 4
• 108091034117 Oligonucleotide Proteins 0.000 description 4
• 229910019142 PO4 Inorganic materials 0.000 description 4
• 108091005804 Peptidases Proteins 0.000 description 4
• ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 4
• 241000283984 Rodentia Species 0.000 description 4
• FKNQFGJONOIPTF-UHFFFAOYSA-N Sodium cation Chemical compound [Na+] FKNQFGJONOIPTF-UHFFFAOYSA-N 0.000 description 4
• 235000004279 alanine Nutrition 0.000 description 4
• 230000005888 antibody-dependent cellular phagocytosis Effects 0.000 description 4
• 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 4
• 210000004556 brain Anatomy 0.000 description 4
• 238000013262 cAMP assay Methods 0.000 description 4
• 230000008859 change Effects 0.000 description 4
• 238000012875 competitive assay Methods 0.000 description 4
• 238000004590 computer program Methods 0.000 description 4
• 229920001577 copolymer Polymers 0.000 description 4
• 230000006378 damage Effects 0.000 description 4
• 230000029087 digestion Effects 0.000 description 4
• 150000002016 disaccharides Chemical class 0.000 description 4
• 238000001943 fluorescence-activated cell sorting Methods 0.000 description 4
• 238000004108 freeze drying Methods 0.000 description 4
• 239000008103 glucose Substances 0.000 description 4
• XKUKSGPZAADMRA-UHFFFAOYSA-N glycyl-glycyl-glycine Chemical compound NCC(=O)NCC(=O)NCC(O)=O XKUKSGPZAADMRA-UHFFFAOYSA-N 0.000 description 4
• 239000001963 growth medium Substances 0.000 description 4
• 230000036541 health Effects 0.000 description 4
• 210000000987 immune system Anatomy 0.000 description 4
• 230000002163 immunogen Effects 0.000 description 4
• 210000003292 kidney cell Anatomy 0.000 description 4
• 230000000670 limiting effect Effects 0.000 description 4
• 239000003550 marker Substances 0.000 description 4
• 230000007246 mechanism Effects 0.000 description 4
• 239000012528 membrane Substances 0.000 description 4
• 239000003094 microcapsule Substances 0.000 description 4
• 230000003472 neutralizing effect Effects 0.000 description 4
• 230000007310 pathophysiology Effects 0.000 description 4
• 235000021317 phosphate Nutrition 0.000 description 4
• 210000002706 plastid Anatomy 0.000 description 4
• 229920000642 polymer Polymers 0.000 description 4
• 239000000843 powder Substances 0.000 description 4
• 238000009117 preventive therapy Methods 0.000 description 4
• 230000009467 reduction Effects 0.000 description 4
• 230000002829 reductive effect Effects 0.000 description 4
• 230000001953 sensory effect Effects 0.000 description 4
• 210000004988 splenocyte Anatomy 0.000 description 4
• 239000000126 substance Substances 0.000 description 4
• 238000013268 sustained release Methods 0.000 description 4
• 239000012730 sustained-release form Substances 0.000 description 4
• 238000003786 synthesis reaction Methods 0.000 description 4
• 238000013519 translation Methods 0.000 description 4
• 102000009027 Albumins Human genes 0.000 description 3
• UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
• WVDDGKGOMKODPV-UHFFFAOYSA-N Benzyl alcohol Chemical compound OCC1=CC=CC=C1 WVDDGKGOMKODPV-UHFFFAOYSA-N 0.000 description 3
• 102000053602 DNA Human genes 0.000 description 3
• 241000255925 Diptera Species 0.000 description 3
• 108010010803 Gelatin Proteins 0.000 description 3
• 101000998953 Homo sapiens Immunoglobulin heavy variable 1-2 Proteins 0.000 description 3
• 101100239636 Homo sapiens MYCBP gene Proteins 0.000 description 3
• 101000584590 Homo sapiens Receptor activity-modifying protein 2 Proteins 0.000 description 3
• 108700005091 Immunoglobulin Genes Proteins 0.000 description 3
• 102100036887 Immunoglobulin heavy variable 1-2 Human genes 0.000 description 3
• 108090001061 Insulin Proteins 0.000 description 3
• 102000004877 Insulin Human genes 0.000 description 3
• ROHFNLRQFUQHCH-UHFFFAOYSA-N Leucine Natural products CC(C)CC(N)C(O)=O ROHFNLRQFUQHCH-UHFFFAOYSA-N 0.000 description 3
• 206010028813 Nausea Diseases 0.000 description 3
• 208000007920 Neurogenic Inflammation Diseases 0.000 description 3
• 108700026244 Open Reading Frames Proteins 0.000 description 3
• 102000035195 Peptidases Human genes 0.000 description 3
• DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
• 239000004365 Protease Substances 0.000 description 3
• 241000700159 Rattus Species 0.000 description 3
• 108020004511 Recombinant DNA Proteins 0.000 description 3
• 241000607720 Serratia Species 0.000 description 3
• 241000187747 Streptomyces Species 0.000 description 3
• 239000004473 Threonine Substances 0.000 description 3
• 241000700605 Viruses Species 0.000 description 3
• 206010047700 Vomiting Diseases 0.000 description 3
• 238000012452 Xenomouse strains Methods 0.000 description 3
• 239000002671 adjuvant Substances 0.000 description 3
• 230000002776 aggregation Effects 0.000 description 3
• 238000004220 aggregation Methods 0.000 description 3
• 239000003242 anti bacterial agent Substances 0.000 description 3
• 208000022371 chronic pain syndrome Diseases 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
• 230000002255 enzymatic effect Effects 0.000 description 3
• 238000002474 experimental method Methods 0.000 description 3
• 238000007710 freezing Methods 0.000 description 3
• 230000008014 freezing Effects 0.000 description 3
• 230000033581 fucosylation Effects 0.000 description 3
• 238000002825 functional assay Methods 0.000 description 3
• 239000008273 gelatin Substances 0.000 description 3
• 229920000159 gelatin Polymers 0.000 description 3
• 235000019322 gelatine Nutrition 0.000 description 3
• 235000011852 gelatine desserts Nutrition 0.000 description 3
• 150000004676 glycans Chemical class 0.000 description 3
• 239000000833 heterodimer Substances 0.000 description 3
• 230000001900 immune effect Effects 0.000 description 3
• 238000003018 immunoassay Methods 0.000 description 3
• 238000001727 in vivo Methods 0.000 description 3
• 238000010348 incorporation Methods 0.000 description 3
• 230000001939 inductive effect Effects 0.000 description 3
• 229940125396 insulin Drugs 0.000 description 3
• 230000003993 interaction Effects 0.000 description 3
• 238000007912 intraperitoneal administration Methods 0.000 description 3
• 238000002955 isolation Methods 0.000 description 3
• 238000012004 kinetic exclusion assay Methods 0.000 description 3
• RGLRXNKKBLIBQS-XNHQSDQCSA-N leuprolide acetate Chemical compound CC(O)=O.CCNC(=O)[C@@H]1CCCN1C(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](CC(C)C)NC(=O)[C@@H](NC(=O)[C@H](CO)NC(=O)[C@H](CC=1C2=CC=CC=C2NC=1)NC(=O)[C@H](CC=1N=CNC=1)NC(=O)[C@H]1NC(=O)CC1)CC1=CC=C(O)C=C1 RGLRXNKKBLIBQS-XNHQSDQCSA-N 0.000 description 3
• 210000004185 liver Anatomy 0.000 description 3
• 108020004999 messenger RNA Proteins 0.000 description 3
• LXCFILQKKLGQFO-UHFFFAOYSA-N methylparaben Chemical compound COC(=O)C1=CC=C(O)C=C1 LXCFILQKKLGQFO-UHFFFAOYSA-N 0.000 description 3
• 150000002772 monosaccharides Chemical class 0.000 description 3
• 230000008693 nausea Effects 0.000 description 3
• 210000005036 nerve Anatomy 0.000 description 3
• 239000002858 neurotransmitter agent Substances 0.000 description 3
• 235000015097 nutrients Nutrition 0.000 description 3
• 150000007524 organic acids Chemical class 0.000 description 3
• 230000007170 pathology Effects 0.000 description 3
• NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 3
• 239000010452 phosphate Substances 0.000 description 3
• 229920000136 polysorbate Polymers 0.000 description 3
• 229920000036 polyvinylpyrrolidone Polymers 0.000 description 3
• 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 3
• 239000011148 porous material Substances 0.000 description 3
• 230000003449 preventive effect Effects 0.000 description 3
• 230000008569 process Effects 0.000 description 3
• 230000001737 promoting effect Effects 0.000 description 3
• QELSKZZBTMNZEB-UHFFFAOYSA-N propylparaben Chemical compound CCCOC(=O)C1=CC=C(O)C=C1 QELSKZZBTMNZEB-UHFFFAOYSA-N 0.000 description 3
• 235000019833 protease Nutrition 0.000 description 3
• 238000011160 research Methods 0.000 description 3
• 230000004044 response Effects 0.000 description 3
• 108091008146 restriction endonucleases Proteins 0.000 description 3
• 238000012216 screening Methods 0.000 description 3
• 230000028327 secretion Effects 0.000 description 3
• 239000006152 selective media Substances 0.000 description 3
• 230000035945 sensitivity Effects 0.000 description 3
• 210000002966 serum Anatomy 0.000 description 3
• 230000011664 signaling Effects 0.000 description 3
• 239000007787 solid Substances 0.000 description 3
• 230000009870 specific binding Effects 0.000 description 3
• 238000010561 standard procedure Methods 0.000 description 3
• 230000000638 stimulation Effects 0.000 description 3
• 238000007920 subcutaneous administration Methods 0.000 description 3
• 238000002198 surface plasmon resonance spectroscopy Methods 0.000 description 3
• 230000004083 survival effect Effects 0.000 description 3
• 125000000341 threoninyl group Chemical group [H]OC([H])(C([H])([H])[H])C([H])(N([H])[H])C(*)=O 0.000 description 3
• 239000012929 tonicity agent Substances 0.000 description 3
• 230000005030 transcription termination Effects 0.000 description 3
• 238000001890 transfection Methods 0.000 description 3
• 238000012546 transfer Methods 0.000 description 3
• 241000701161 unidentified adenovirus Species 0.000 description 3
• 230000002792 vascular Effects 0.000 description 3
• 230000024883 vasodilation Effects 0.000 description 3
• 230000003612 virological effect Effects 0.000 description 3
• 230000008673 vomiting Effects 0.000 description 3
• HDTRYLNUVZCQOY-UHFFFAOYSA-N &alpha;-D-glucopyranosyl-&alpha;-D-glucopyranoside Natural products OC1C(O)C(O)C(CO)OC1OC1C(O)C(O)C(O)C(CO)O1 HDTRYLNUVZCQOY-UHFFFAOYSA-N 0.000 description 2
• YBJHBAHKTGYVGT-ZKWXMUAHSA-N (+)-Biotin Chemical group N1C(=O)N[C@@H]2[C@H](CCCCC(=O)O)SC[C@@H]21 YBJHBAHKTGYVGT-ZKWXMUAHSA-N 0.000 description 2
• 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 2
• WRMNZCZEMHIOCP-UHFFFAOYSA-N 2-phenylethanol Chemical compound OCCC1=CC=CC=C1 WRMNZCZEMHIOCP-UHFFFAOYSA-N 0.000 description 2
• QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 2
• UCTWMZQNUQWSLP-UHFFFAOYSA-N Adrenaline Natural products CNCC(O)C1=CC=C(O)C(O)=C1 UCTWMZQNUQWSLP-UHFFFAOYSA-N 0.000 description 2
• 102400001014 Adrenomedullin-2 Human genes 0.000 description 2
• 229920000936 Agarose Polymers 0.000 description 2
• 241000228212 Aspergillus Species 0.000 description 2
• 241000193830 Bacillus <bacterium> Species 0.000 description 2
• 241000194108 Bacillus licheniformis Species 0.000 description 2
• 235000014469 Bacillus subtilis Nutrition 0.000 description 2
• 229940127597 CGRP antagonist Drugs 0.000 description 2
• 241000282836 Camelus dromedarius Species 0.000 description 2
• 241000222120 Candida <Saccharomycetales> Species 0.000 description 2
• 241000282693 Cercopithecidae Species 0.000 description 2
• VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 2
• 241000251730 Chondrichthyes Species 0.000 description 2
• 108020004705 Codon Proteins 0.000 description 2
• 241000699802 Cricetulus griseus Species 0.000 description 2
• 241000701022 Cytomegalovirus Species 0.000 description 2
• RGHNJXZEOKUKBD-SQOUGZDYSA-N D-gluconic acid Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C(O)=O RGHNJXZEOKUKBD-SQOUGZDYSA-N 0.000 description 2
• WQZGKKKJIJFFOK-QTVWNMPRSA-N D-mannopyranose Chemical compound OC[C@H]1OC(O)[C@@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-QTVWNMPRSA-N 0.000 description 2
• SRBFZHDQGSBBOR-IOVATXLUSA-N D-xylopyranose Chemical compound O[C@@H]1COC(O)[C@H](O)[C@H]1O SRBFZHDQGSBBOR-IOVATXLUSA-N 0.000 description 2
• 239000004375 Dextrin Substances 0.000 description 2
• 229920001353 Dextrin Polymers 0.000 description 2
• 238000002965 ELISA Methods 0.000 description 2
• 241000196324 Embryophyta Species 0.000 description 2
• 241000206602 Eukaryota Species 0.000 description 2
• 102000009109 Fc receptors Human genes 0.000 description 2
• 108010087819 Fc receptors Proteins 0.000 description 2
• 206010016825 Flushing Diseases 0.000 description 2
• 241000233866 Fungi Species 0.000 description 2
• 102000006395 Globulins Human genes 0.000 description 2
• 108010044091 Globulins Proteins 0.000 description 2
• 241000238631 Hexapoda Species 0.000 description 2
• 101000935587 Homo sapiens Flavin reductase (NADPH) Proteins 0.000 description 2
• 101001008255 Homo sapiens Immunoglobulin kappa variable 1D-8 Proteins 0.000 description 2
• 101001047628 Homo sapiens Immunoglobulin kappa variable 2-29 Proteins 0.000 description 2
• 101001008321 Homo sapiens Immunoglobulin kappa variable 2D-26 Proteins 0.000 description 2
• 101001047619 Homo sapiens Immunoglobulin kappa variable 3-20 Proteins 0.000 description 2
• 101001008263 Homo sapiens Immunoglobulin kappa variable 3D-15 Proteins 0.000 description 2
• 101000584593 Homo sapiens Receptor activity-modifying protein 3 Proteins 0.000 description 2
• MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 description 2
• 102100022964 Immunoglobulin kappa variable 3-20 Human genes 0.000 description 2
• 102000000704 Interleukin-7 Human genes 0.000 description 2
• 108010002586 Interleukin-7 Proteins 0.000 description 2
• 108010000817 Leuprolide Proteins 0.000 description 2
• 241000282553 Macaca Species 0.000 description 2
• 101710144475 Maxadilan Proteins 0.000 description 2
• 206010027603 Migraine headaches Diseases 0.000 description 2
• 108010021466 Mutant Proteins Proteins 0.000 description 2
• 102000008300 Mutant Proteins Human genes 0.000 description 2
• LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 2
• 241000221961 Neurospora crassa Species 0.000 description 2
• 230000004989 O-glycosylation Effects 0.000 description 2
• 108010067372 Pancreatic elastase Proteins 0.000 description 2
• 108090000526 Papain Proteins 0.000 description 2
• 241000228143 Penicillium Species 0.000 description 2
• 229940083963 Peptide antagonist Drugs 0.000 description 2
• 239000002202 Polyethylene glycol Substances 0.000 description 2
• 108010076039 Polyproteins Proteins 0.000 description 2
• 229920001213 Polysorbate 20 Polymers 0.000 description 2
• WCUXLLCKKVVCTQ-UHFFFAOYSA-M Potassium chloride Chemical compound [Cl-].[K+] WCUXLLCKKVVCTQ-UHFFFAOYSA-M 0.000 description 2
• ONIBWKKTOPOVIA-UHFFFAOYSA-N Proline Natural products OC(=O)C1CCCN1 ONIBWKKTOPOVIA-UHFFFAOYSA-N 0.000 description 2
• 241000589516 Pseudomonas Species 0.000 description 2
• 241000311088 Schwanniomyces Species 0.000 description 2
• 241001123650 Schwanniomyces occidentalis Species 0.000 description 2
• 238000012300 Sequence Analysis Methods 0.000 description 2
• 108010071390 Serum Albumin Proteins 0.000 description 2
• 102000007562 Serum Albumin Human genes 0.000 description 2
• 241000607768 Shigella Species 0.000 description 2
• 108010003723 Single-Domain Antibodies Proteins 0.000 description 2
• 208000037065 Subacute sclerosing leukoencephalitis Diseases 0.000 description 2
• 206010042297 Subacute sclerosing panencephalitis Diseases 0.000 description 2
• 239000004098 Tetracycline Substances 0.000 description 2
• AYFVYJQAPQTCCC-UHFFFAOYSA-N Threonine Natural products CC(O)C(N)C(O)=O AYFVYJQAPQTCCC-UHFFFAOYSA-N 0.000 description 2
• 108010022394 Threonine synthase Proteins 0.000 description 2
• IQFYYKKMVGJFEH-XLPZGREQSA-N Thymidine Chemical compound O=C1NC(=O)C(C)=CN1[C@@H]1O[C@H](CO)[C@@H](O)C1 IQFYYKKMVGJFEH-XLPZGREQSA-N 0.000 description 2
• 108020004440 Thymidine kinase Proteins 0.000 description 2
• 241001149964 Tolypocladium Species 0.000 description 2
• 101710120037 Toxin CcdB Proteins 0.000 description 2
• HDTRYLNUVZCQOY-WSWWMNSNSA-N Trehalose Natural products O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@@H]1O[C@@H]1[C@H](O)[C@@H](O)[C@@H](O)[C@@H](CO)O1 HDTRYLNUVZCQOY-WSWWMNSNSA-N 0.000 description 2
• 101710137651 Vasoactive intestinal polypeptide receptor 2 Proteins 0.000 description 2
• 241000251539 Vertebrata <Metazoa> Species 0.000 description 2
• 241000711975 Vesicular stomatitis virus Species 0.000 description 2
• 208000027418 Wounds and injury Diseases 0.000 description 2
• 241000235013 Yarrowia Species 0.000 description 2
• 230000001154 acute effect Effects 0.000 description 2
• OIRDTQYFTABQOQ-KQYNXXCUSA-N adenosine Chemical compound C1=NC=2C(N)=NC=NC=2N1[C@@H]1O[C@H](CO)[C@@H](O)[C@H]1O OIRDTQYFTABQOQ-KQYNXXCUSA-N 0.000 description 2
• 229940102884 adrenalin Drugs 0.000 description 2
• 238000001042 affinity chromatography Methods 0.000 description 2
• HDTRYLNUVZCQOY-LIZSDCNHSA-N alpha,alpha-trehalose Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@@H]1O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 HDTRYLNUVZCQOY-LIZSDCNHSA-N 0.000 description 2
• 108010026331 alpha-Fetoproteins Proteins 0.000 description 2
• 239000004178 amaranth Substances 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
• 230000003321 amplification Effects 0.000 description 2
• 230000003042 antagnostic effect Effects 0.000 description 2
• 229940088710 antibiotic agent Drugs 0.000 description 2
• 239000003963 antioxidant agent Substances 0.000 description 2
• 235000006708 antioxidants Nutrition 0.000 description 2
• 239000013011 aqueous formulation Substances 0.000 description 2
• KBZOIRJILGZLEJ-LGYYRGKSSA-N argipressin Chemical compound C([C@H]1C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CSSC[C@@H](C(N[C@@H](CC=2C=CC(O)=CC=2)C(=O)N1)=O)N)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCCN=C(N)N)C(=O)NCC(N)=O)C1=CC=CC=C1 KBZOIRJILGZLEJ-LGYYRGKSSA-N 0.000 description 2
• 230000002917 arthritic effect Effects 0.000 description 2
• 235000010323 ascorbic acid Nutrition 0.000 description 2
• 239000011668 ascorbic acid Substances 0.000 description 2
• 229960005070 ascorbic acid Drugs 0.000 description 2
• 230000008901 benefit Effects 0.000 description 2
• 229960000686 benzalkonium chloride Drugs 0.000 description 2
• WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 2
• CADWTSSKOVRVJC-UHFFFAOYSA-N benzyl(dimethyl)azanium;chloride Chemical compound [Cl-].C[NH+](C)CC1=CC=CC=C1 CADWTSSKOVRVJC-UHFFFAOYSA-N 0.000 description 2
• 230000001588 bifunctional effect Effects 0.000 description 2
• 230000008512 biological response Effects 0.000 description 2
• 230000000903 blocking effect Effects 0.000 description 2
• 238000006664 bond formation reaction Methods 0.000 description 2
• 210000000133 brain stem Anatomy 0.000 description 2
• DQXBYHZEEUGOBF-UHFFFAOYSA-N but-3-enoic acid;ethene Chemical compound C=C.OC(=O)CC=C DQXBYHZEEUGOBF-UHFFFAOYSA-N 0.000 description 2
• RYYVLZVUVIJVGH-UHFFFAOYSA-N caffeine Chemical compound CN1C(=O)N(C)C(=O)C2=C1N=CN2C RYYVLZVUVIJVGH-UHFFFAOYSA-N 0.000 description 2
• 238000004364 calculation method Methods 0.000 description 2
• YCIMNLLNPGFGHC-UHFFFAOYSA-N catechol Chemical compound OC1=CC=CC=C1O YCIMNLLNPGFGHC-UHFFFAOYSA-N 0.000 description 2
• 230000001413 cellular effect Effects 0.000 description 2
• 239000002738 chelating agent Substances 0.000 description 2
• 238000006243 chemical reaction Methods 0.000 description 2
• OSASVXMJTNOKOY-UHFFFAOYSA-N chlorobutanol Chemical compound CC(C)(O)C(Cl)(Cl)Cl OSASVXMJTNOKOY-UHFFFAOYSA-N 0.000 description 2
• HVYWMOMLDIMFJA-DPAQBDIFSA-N cholesterol Chemical compound C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CCCC(C)C)[C@@]1(C)CC2 HVYWMOMLDIMFJA-DPAQBDIFSA-N 0.000 description 2
• 238000004587 chromatography analysis Methods 0.000 description 2
• 230000001684 chronic effect Effects 0.000 description 2
• 238000004440 column chromatography Methods 0.000 description 2
• 230000009137 competitive binding Effects 0.000 description 2
• 150000001875 compounds Chemical class 0.000 description 2
• 230000007812 deficiency Effects 0.000 description 2
• 230000001419 dependent effect Effects 0.000 description 2
• 238000013461 design Methods 0.000 description 2
• 238000001514 detection method Methods 0.000 description 2
• 235000019425 dextrin Nutrition 0.000 description 2
• 102000004419 dihydrofolate reductase Human genes 0.000 description 2
• 239000000539 dimer Substances 0.000 description 2
• 238000006471 dimerization reaction Methods 0.000 description 2
• 239000003937 drug carrier Substances 0.000 description 2
• 239000005038 ethylene vinyl acetate Substances 0.000 description 2
• 210000003527 eukaryotic cell Anatomy 0.000 description 2
• 230000003203 everyday effect Effects 0.000 description 2
• 230000002068 genetic effect Effects 0.000 description 2
• 235000011187 glycerol Nutrition 0.000 description 2
• 229940093915 gynecological organic acid Drugs 0.000 description 2
• 210000003128 head Anatomy 0.000 description 2
• 239000000710 homodimer Substances 0.000 description 2
• 239000000017 hydrogel Substances 0.000 description 2
• 229920001477 hydrophilic polymer Polymers 0.000 description 2
• 229910052588 hydroxylapatite Inorganic materials 0.000 description 2
• 230000005847 immunogenicity Effects 0.000 description 2
• 230000006872 improvement Effects 0.000 description 2
• 238000000338 in vitro Methods 0.000 description 2
• 230000000977 initiatory effect Effects 0.000 description 2
• 208000014674 injury Diseases 0.000 description 2
• 229940100994 interleukin-7 Drugs 0.000 description 2
• 150000002500 ions Chemical class 0.000 description 2
• 210000003734 kidney Anatomy 0.000 description 2
• 125000001909 leucine group Chemical group [H]N(*)C(C(*)=O)C([H])([H])C(C([H])([H])[H])C([H])([H])[H] 0.000 description 2
• 229960004338 leuprorelin Drugs 0.000 description 2
• 239000007788 liquid Substances 0.000 description 2
• 239000012931 lyophilized formulation Substances 0.000 description 2
• 230000003340 mental effect Effects 0.000 description 2
• 229910052751 metal Inorganic materials 0.000 description 2
• 239000002184 metal Chemical class 0.000 description 2
• MYWUZJCMWCOHBA-VIFPVBQESA-N methamphetamine Chemical compound CN[C@@H](C)CC1=CC=CC=C1 MYWUZJCMWCOHBA-VIFPVBQESA-N 0.000 description 2
• 235000010270 methyl p-hydroxybenzoate Nutrition 0.000 description 2
• 239000004292 methyl p-hydroxybenzoate Substances 0.000 description 2
• 229960002216 methylparaben Drugs 0.000 description 2
• 244000005700 microbiome Species 0.000 description 2
• 239000011859 microparticle Substances 0.000 description 2
• 239000004005 microsphere Substances 0.000 description 2
• 238000010369 molecular cloning Methods 0.000 description 2
• 231100000350 mutagenesis Toxicity 0.000 description 2
• 239000002736 nonionic surfactant Substances 0.000 description 2
• 231100000252 nontoxic Toxicity 0.000 description 2
• 230000003000 nontoxic effect Effects 0.000 description 2
• 238000003199 nucleic acid amplification method Methods 0.000 description 2
• 238000001668 nucleic acid synthesis Methods 0.000 description 2
• 235000005985 organic acids Nutrition 0.000 description 2
• 201000008482 osteoarthritis Diseases 0.000 description 2
• 210000001672 ovary Anatomy 0.000 description 2
• 235000019834 papain Nutrition 0.000 description 2
• 229940055729 papain Drugs 0.000 description 2
• 230000009958 parasympathetic pathway Effects 0.000 description 2
• 230000037361 pathway Effects 0.000 description 2
• 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 2
• AQIXEPGDORPWBJ-UHFFFAOYSA-N pentan-3-ol Chemical compound CCC(O)CC AQIXEPGDORPWBJ-UHFFFAOYSA-N 0.000 description 2
• 238000010647 peptide synthesis reaction Methods 0.000 description 2
• 239000008177 pharmaceutical agent Substances 0.000 description 2
• 230000037081 physical activity Effects 0.000 description 2
• 229920001983 poloxamer Polymers 0.000 description 2
• 229920001200 poly(ethylene-vinyl acetate) Polymers 0.000 description 2
• 230000008488 polyadenylation Effects 0.000 description 2
• 239000000256 polyoxyethylene sorbitan monolaurate Substances 0.000 description 2
• 235000010486 polyoxyethylene sorbitan monolaurate Nutrition 0.000 description 2
• 239000000244 polyoxyethylene sorbitan monooleate Substances 0.000 description 2
• 235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 description 2
• 229940068977 polysorbate 20 Drugs 0.000 description 2
• 229940068968 polysorbate 80 Drugs 0.000 description 2
• 229920000053 polysorbate 80 Polymers 0.000 description 2
• 239000001267 polyvinylpyrrolidone Substances 0.000 description 2
• 230000002335 preservative effect Effects 0.000 description 2
• 230000000069 prophylactic effect Effects 0.000 description 2
• 235000010232 propyl p-hydroxybenzoate Nutrition 0.000 description 2
• 239000004405 propyl p-hydroxybenzoate Substances 0.000 description 2
• 238000012207 quantitative assay Methods 0.000 description 2
• 239000002287 radioligand Substances 0.000 description 2
• 229940044551 receptor antagonist Drugs 0.000 description 2
• 239000002464 receptor antagonist Substances 0.000 description 2
• 230000000306 recurrent effect Effects 0.000 description 2
• 230000022532 regulation of transcription, DNA-dependent Effects 0.000 description 2
• GHMLBKRAJCXXBS-UHFFFAOYSA-N resorcinol Chemical compound OC1=CC=CC(O)=C1 GHMLBKRAJCXXBS-UHFFFAOYSA-N 0.000 description 2
• 206010039073 rheumatoid arthritis Diseases 0.000 description 2
• YGSDEFSMJLZEOE-UHFFFAOYSA-N salicylic acid Chemical compound OC(=O)C1=CC=CC=C1O YGSDEFSMJLZEOE-UHFFFAOYSA-N 0.000 description 2
• 150000003839 salts Chemical class 0.000 description 2
• 239000000523 sample Substances 0.000 description 2
• 238000000926 separation method Methods 0.000 description 2
• QZAYGJVTTNCVMB-UHFFFAOYSA-N serotonin Chemical compound C1=C(O)C=C2C(CCN)=CNC2=C1 QZAYGJVTTNCVMB-UHFFFAOYSA-N 0.000 description 2
• 208000018316 severe headache Diseases 0.000 description 2
• 230000019491 signal transduction Effects 0.000 description 2
• GEHJYWRUCIMESM-UHFFFAOYSA-L sodium sulfite Chemical compound [Na+].[Na+].[O-]S([O-])=O GEHJYWRUCIMESM-UHFFFAOYSA-L 0.000 description 2
• PFNFFQXMRSDOHW-UHFFFAOYSA-N spermine Chemical compound NCCCNCCCCNCCCN PFNFFQXMRSDOHW-UHFFFAOYSA-N 0.000 description 2
• 230000001954 sterilising effect Effects 0.000 description 2
• 238000004659 sterilization and disinfection Methods 0.000 description 2
• 239000004575 stone Substances 0.000 description 2
• 150000005846 sugar alcohols Chemical class 0.000 description 2
• 239000013589 supplement Substances 0.000 description 2
• 239000000725 suspension Substances 0.000 description 2
• 230000035900 sweating Effects 0.000 description 2
• 229960002180 tetracycline Drugs 0.000 description 2
• 229930101283 tetracycline Natural products 0.000 description 2
• 235000019364 tetracycline Nutrition 0.000 description 2
• 150000003522 tetracyclines Chemical class 0.000 description 2
• 238000011200 topical administration Methods 0.000 description 2
• 230000009261 transgenic effect Effects 0.000 description 2
• 238000011830 transgenic mouse model Methods 0.000 description 2
• 210000000427 trigeminal ganglion Anatomy 0.000 description 2
• LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 2
• OUYCCCASQSFEME-UHFFFAOYSA-N tyrosine Natural products OC(=O)C(N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-UHFFFAOYSA-N 0.000 description 2
• 238000011144 upstream manufacturing Methods 0.000 description 2
• 229940124549 vasodilator Drugs 0.000 description 2
• 239000003071 vasodilator agent Substances 0.000 description 2
• 239000011800 void material Substances 0.000 description 2
• IIZPXYDJLKNOIY-JXPKJXOSSA-N 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCC\C=C/C\C=C/C\C=C/C\C=C/CCCCC IIZPXYDJLKNOIY-JXPKJXOSSA-N 0.000 description 1
• 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
• QKNYBSVHEMOAJP-UHFFFAOYSA-N 2-amino-2-(hydroxymethyl)propane-1,3-diol;hydron;chloride Chemical compound Cl.OCC(N)(CO)CO QKNYBSVHEMOAJP-UHFFFAOYSA-N 0.000 description 1
• QTWJRLJHJPIABL-UHFFFAOYSA-N 2-methylphenol;3-methylphenol;4-methylphenol Chemical compound CC1=CC=C(O)C=C1.CC1=CC=CC(O)=C1.CC1=CC=CC=C1O QTWJRLJHJPIABL-UHFFFAOYSA-N 0.000 description 1
• 229940117976 5-hydroxylysine Drugs 0.000 description 1
• 102100027499 5-hydroxytryptamine receptor 1B Human genes 0.000 description 1
• 101710138639 5-hydroxytryptamine receptor 1B Proteins 0.000 description 1
• 241000238876 Acari Species 0.000 description 1
• 206010069754 Acquired gene mutation Diseases 0.000 description 1
• 102000007469 Actins Human genes 0.000 description 1
• 108010085238 Actins Proteins 0.000 description 1
• 101150027984 Adcyap1r1 gene Proteins 0.000 description 1
• 206010067484 Adverse reaction Diseases 0.000 description 1
• 241000256118 Aedes aegypti Species 0.000 description 1
• 241000256173 Aedes albopictus Species 0.000 description 1
• 102000002260 Alkaline Phosphatase Human genes 0.000 description 1
• 108020004774 Alkaline Phosphatase Proteins 0.000 description 1
• 102100033770 Alpha-amylase 1C Human genes 0.000 description 1
• NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 1
• 235000002198 Annona diversifolia Nutrition 0.000 description 1
• 108010032595 Antibody Binding Sites Proteins 0.000 description 1
• 108020005544 Antisense RNA Proteins 0.000 description 1
• FTCGGKNCJZOPNB-WHFBIAKZSA-N Asn-Gly-Ser Chemical compound NC(=O)C[C@H](N)C(=O)NCC(=O)N[C@@H](CO)C(O)=O FTCGGKNCJZOPNB-WHFBIAKZSA-N 0.000 description 1
• 241000351920 Aspergillus nidulans Species 0.000 description 1
• 241000228245 Aspergillus niger Species 0.000 description 1
• 241001203868 Autographa californica Species 0.000 description 1
• 241000713842 Avian sarcoma virus Species 0.000 description 1
• 210000002237 B-cell of pancreatic islet Anatomy 0.000 description 1
• 244000063299 Bacillus subtilis Species 0.000 description 1
• 239000005711 Benzoic acid Substances 0.000 description 1
• DWRXFEITVBNRMK-UHFFFAOYSA-N Beta-D-1-Arabinofuranosylthymine Natural products O=C1NC(=O)C(C)=CN1C1C(O)C(O)C(CO)O1 DWRXFEITVBNRMK-UHFFFAOYSA-N 0.000 description 1
• BVKZGUZCCUSVTD-UHFFFAOYSA-M Bicarbonate Chemical compound OC([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-M 0.000 description 1
• 241000255789 Bombyx mori Species 0.000 description 1
• 241000409811 Bombyx mori nucleopolyhedrovirus Species 0.000 description 1
• 208000010392 Bone Fractures Diseases 0.000 description 1
• BTBUEUYNUDRHOZ-UHFFFAOYSA-N Borate Chemical compound [O-]B([O-])[O-] BTBUEUYNUDRHOZ-UHFFFAOYSA-N 0.000 description 1
• 241000701822 Bovine papillomavirus Species 0.000 description 1
• 206010006187 Breast cancer Diseases 0.000 description 1
• 239000002126 C01EB10 - Adenosine Substances 0.000 description 1
• 102000055006 Calcitonin Human genes 0.000 description 1
• 108060001064 Calcitonin Proteins 0.000 description 1
• OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
• 241000282832 Camelidae Species 0.000 description 1
• 241000282465 Canis Species 0.000 description 1
• 208000024172 Cardiovascular disease Diseases 0.000 description 1
• 206010008342 Cervix carcinoma Diseases 0.000 description 1
• GHXZTYHSJHQHIJ-UHFFFAOYSA-N Chlorhexidine Chemical compound C=1C=C(Cl)C=CC=1NC(N)=NC(N)=NCCCCCCN=C(N)N=C(N)NC1=CC=C(Cl)C=C1 GHXZTYHSJHQHIJ-UHFFFAOYSA-N 0.000 description 1
• 241000282552 Chlorocebus aethiops Species 0.000 description 1
• 108091062157 Cis-regulatory element Proteins 0.000 description 1
• KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 description 1
• 241000252095 Congridae Species 0.000 description 1
• 206010010904 Convulsion Diseases 0.000 description 1
• 241000699800 Cricetinae Species 0.000 description 1
• 229920000858 Cyclodextrin Polymers 0.000 description 1
• RGHNJXZEOKUKBD-UHFFFAOYSA-N D-gluconic acid Natural products OCC(O)C(O)C(O)C(O)C(O)=O RGHNJXZEOKUKBD-UHFFFAOYSA-N 0.000 description 1
• 241000255581 Drosophila <fruit fly, genus> Species 0.000 description 1
• 241000255601 Drosophila melanogaster Species 0.000 description 1
• 239000006144 Dulbecco’s modified Eagle's medium Substances 0.000 description 1
• 238000012286 ELISA Assay Methods 0.000 description 1
• 102100031780 Endonuclease Human genes 0.000 description 1
• 108010042407 Endonucleases Proteins 0.000 description 1
• 241000588914 Enterobacter Species 0.000 description 1
• 241000588921 Enterobacteriaceae Species 0.000 description 1
• 102400001368 Epidermal growth factor Human genes 0.000 description 1
• 101800003838 Epidermal growth factor Proteins 0.000 description 1
• 241000588698 Erwinia Species 0.000 description 1
• 241000588722 Escherichia Species 0.000 description 1
• 241000588724 Escherichia coli Species 0.000 description 1
• CTKXFMQHOOWWEB-UHFFFAOYSA-N Ethylene oxide/propylene oxide copolymer Chemical compound CCCOC(C)COCCO CTKXFMQHOOWWEB-UHFFFAOYSA-N 0.000 description 1
• 239000001116 FEMA 4028 Substances 0.000 description 1
• 208000010541 Familial or sporadic hemiplegic migraine Diseases 0.000 description 1
• 108010008177 Fd immunoglobulins Proteins 0.000 description 1
• 241000700662 Fowlpox virus Species 0.000 description 1
• 208000003098 Ganglion Cysts Diseases 0.000 description 1
• 102000018899 Glutamate Receptors Human genes 0.000 description 1
• 108010027915 Glutamate Receptors Proteins 0.000 description 1
• 229940121672 Glycosylation inhibitor Drugs 0.000 description 1
• 239000007995 HEPES buffer Substances 0.000 description 1
• 101710154606 Hemagglutinin Proteins 0.000 description 1
• 206010019476 Hemiplegic migraine Diseases 0.000 description 1
• 108091005904 Hemoglobin subunit beta Proteins 0.000 description 1
• 241000700721 Hepatitis B virus Species 0.000 description 1
• 101500025150 Homo sapiens Adrenomedullin-2 Proteins 0.000 description 1
• 101000779871 Homo sapiens Alpha-amylase 1A Proteins 0.000 description 1
• 101000779870 Homo sapiens Alpha-amylase 1B Proteins 0.000 description 1
• 101000779869 Homo sapiens Alpha-amylase 1C Proteins 0.000 description 1
• 101000732641 Homo sapiens Alpha-amylase 2B Proteins 0.000 description 1
• 101000741445 Homo sapiens Calcitonin Proteins 0.000 description 1
• 101000741435 Homo sapiens Calcitonin receptor Proteins 0.000 description 1
• 101000693011 Homo sapiens Pancreatic alpha-amylase Proteins 0.000 description 1
• 101000735539 Homo sapiens Pituitary adenylate cyclase-activating polypeptide Proteins 0.000 description 1
• 101000666856 Homo sapiens Vasoactive intestinal polypeptide receptor 1 Proteins 0.000 description 1
• 108010001336 Horseradish Peroxidase Proteins 0.000 description 1
• 208000033830 Hot Flashes Diseases 0.000 description 1
• 206010060800 Hot flush Diseases 0.000 description 1
• 241000701109 Human adenovirus 2 Species 0.000 description 1
• 208000008454 Hyperhidrosis Diseases 0.000 description 1
• 206010020751 Hypersensitivity Diseases 0.000 description 1
• XQFRJNBWHJMXHO-RRKCRQDMSA-N IDUR Chemical compound C1[C@H](O)[C@@H](CO)O[C@H]1N1C(=O)NC(=O)C(I)=C1 XQFRJNBWHJMXHO-RRKCRQDMSA-N 0.000 description 1
• DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
• 108010091135 Immunoglobulin Fc Fragments Proteins 0.000 description 1
• 102000018071 Immunoglobulin Fc Fragments Human genes 0.000 description 1
• 102000012745 Immunoglobulin Subunits Human genes 0.000 description 1
• 108010079585 Immunoglobulin Subunits Proteins 0.000 description 1
• 238000012695 Interfacial polymerization Methods 0.000 description 1
• 102000019223 Interleukin-1 receptor Human genes 0.000 description 1
• 108050006617 Interleukin-1 receptor Proteins 0.000 description 1
• 102000010789 Interleukin-2 Receptors Human genes 0.000 description 1
• 108010038453 Interleukin-2 Receptors Proteins 0.000 description 1
• 102000010787 Interleukin-4 Receptors Human genes 0.000 description 1
• 108010038486 Interleukin-4 Receptors Proteins 0.000 description 1
• 102000015696 Interleukins Human genes 0.000 description 1
• 108010063738 Interleukins Proteins 0.000 description 1
• 108091092195 Intron Proteins 0.000 description 1
• LPHGQDQBBGAPDZ-UHFFFAOYSA-N Isocaffeine Natural products CN1C(=O)N(C)C(=O)C2=C1N(C)C=N2 LPHGQDQBBGAPDZ-UHFFFAOYSA-N 0.000 description 1
• 241000588748 Klebsiella Species 0.000 description 1
• 241000235649 Kluyveromyces Species 0.000 description 1
• 241000235058 Komagataella pastoris Species 0.000 description 1
• ONIBWKKTOPOVIA-BYPYZUCNSA-N L-Proline Chemical compound OC(=O)[C@@H]1CCCN1 ONIBWKKTOPOVIA-BYPYZUCNSA-N 0.000 description 1
• ROHFNLRQFUQHCH-YFKPBYRVSA-N L-leucine Chemical compound CC(C)C[C@H](N)C(O)=O ROHFNLRQFUQHCH-YFKPBYRVSA-N 0.000 description 1
• AYFVYJQAPQTCCC-GBXIJSLDSA-N L-threonine Chemical compound C[C@@H](O)[C@H](N)C(O)=O AYFVYJQAPQTCCC-GBXIJSLDSA-N 0.000 description 1
• QIVBCDIJIAJPQS-VIFPVBQESA-N L-tryptophane Chemical compound C1=CC=C2C(C[C@H](N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-VIFPVBQESA-N 0.000 description 1
• OUYCCCASQSFEME-QMMMGPOBSA-N L-tyrosine Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-QMMMGPOBSA-N 0.000 description 1
• KZSNJWFQEVHDMF-BYPYZUCNSA-N L-valine Chemical compound CC(C)[C@H](N)C(O)=O KZSNJWFQEVHDMF-BYPYZUCNSA-N 0.000 description 1
• 241000282838 Lama Species 0.000 description 1
• 108090001030 Lipoproteins Proteins 0.000 description 1
• 102000004895 Lipoproteins Human genes 0.000 description 1
• 108060001084 Luciferase Proteins 0.000 description 1
• 239000005089 Luciferase Substances 0.000 description 1
• NPBGTPKLVJEOBE-IUCAKERBSA-N Lys-Arg Chemical compound NCCCC[C@H](N)C(=O)N[C@H](C(O)=O)CCCNC(N)=N NPBGTPKLVJEOBE-IUCAKERBSA-N 0.000 description 1
• 239000004907 Macro-emulsion Substances 0.000 description 1
• FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
• 241000713333 Mouse mammary tumor virus Species 0.000 description 1
• 241001529936 Murinae Species 0.000 description 1
• 241000699660 Mus musculus Species 0.000 description 1
• 101710107068 Myelin basic protein Proteins 0.000 description 1
• OVRNDRQMDRJTHS-CBQIKETKSA-N N-Acetyl-D-Galactosamine Chemical compound CC(=O)N[C@H]1[C@@H](O)O[C@H](CO)[C@H](O)[C@@H]1O OVRNDRQMDRJTHS-CBQIKETKSA-N 0.000 description 1
• MBLBDJOUHNCFQT-UHFFFAOYSA-N N-acetyl-D-galactosamine Natural products CC(=O)NC(C=O)C(O)C(O)C(O)CO MBLBDJOUHNCFQT-UHFFFAOYSA-N 0.000 description 1
• 125000001429 N-terminal alpha-amino-acid group Chemical group 0.000 description 1
• 108091007491 NSP3 Papain-like protease domains Proteins 0.000 description 1
• 229930193140 Neomycin Natural products 0.000 description 1
• 206010029260 Neuroblastoma Diseases 0.000 description 1
• 241000221960 Neurospora Species 0.000 description 1
• 108020005187 Oligonucleotide Probes Proteins 0.000 description 1
• 108010038807 Oligopeptides Proteins 0.000 description 1
• 102000015636 Oligopeptides Human genes 0.000 description 1
• 241000283973 Oryctolagus cuniculus Species 0.000 description 1
• 240000007594 Oryza sativa Species 0.000 description 1
• 235000007164 Oryza sativa Nutrition 0.000 description 1
• 101710093908 Outer capsid protein VP4 Proteins 0.000 description 1
• 101710135467 Outer capsid protein sigma-1 Proteins 0.000 description 1
• 102100026367 Pancreatic alpha-amylase Human genes 0.000 description 1
• 102000016387 Pancreatic elastase Human genes 0.000 description 1
• 206010033645 Pancreatitis Diseases 0.000 description 1
• 206010033647 Pancreatitis acute Diseases 0.000 description 1
• 241001631646 Papillomaviridae Species 0.000 description 1
• 206010057249 Phagocytosis Diseases 0.000 description 1
• 206010034960 Photophobia Diseases 0.000 description 1
• 241000235648 Pichia Species 0.000 description 1
• 241000167562 Pittosporum tobira Species 0.000 description 1
• 102000014743 Pituitary Adenylate Cyclase-Activating Polypeptide Receptors Human genes 0.000 description 1
• 108010064032 Pituitary Adenylate Cyclase-Activating Polypeptide Receptors Proteins 0.000 description 1
• 229920000954 Polyglycolide Polymers 0.000 description 1
• 241001505332 Polyomavirus sp. Species 0.000 description 1
• 102000007327 Protamines Human genes 0.000 description 1
• 108010007568 Protamines Proteins 0.000 description 1
• 101710176177 Protein A56 Proteins 0.000 description 1
• 241000588769 Proteus <enterobacteria> Species 0.000 description 1
• 206010037213 Psychomotor retardation Diseases 0.000 description 1
• 239000012980 RPMI-1640 medium Substances 0.000 description 1
• 241000700157 Rattus norvegicus Species 0.000 description 1
• 108010064300 Receptor Activity-Modifying Proteins Proteins 0.000 description 1
• 102000015146 Receptor Activity-Modifying Proteins Human genes 0.000 description 1
• 102100030696 Receptor activity-modifying protein 2 Human genes 0.000 description 1
• 108020005091 Replication Origin Proteins 0.000 description 1
• 206010052784 Retinal migraine Diseases 0.000 description 1
• 102100037486 Reverse transcriptase/ribonuclease H Human genes 0.000 description 1
• 241000714474 Rous sarcoma virus Species 0.000 description 1
• 241000607142 Salmonella Species 0.000 description 1
• 241000293869 Salmonella enterica subsp. enterica serovar Typhimurium Species 0.000 description 1
• 241000235347 Schizosaccharomyces pombe Species 0.000 description 1
• 229920002684 Sepharose Polymers 0.000 description 1
• 108020004459 Small interfering RNA Proteins 0.000 description 1
• 108010052164 Sodium Channels Proteins 0.000 description 1
• 102000018674 Sodium Channels Human genes 0.000 description 1
• VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 1
• DWAQJAXMDSEUJJ-UHFFFAOYSA-M Sodium bisulfite Chemical compound [Na+].OS([O-])=O DWAQJAXMDSEUJJ-UHFFFAOYSA-M 0.000 description 1
• 241000256251 Spodoptera frugiperda Species 0.000 description 1
• 101000857870 Squalus acanthias Gonadoliberin Proteins 0.000 description 1
• 108091081024 Start codon Proteins 0.000 description 1
• 208000005400 Synovial Cyst Diseases 0.000 description 1
• 210000001744 T-lymphocyte Anatomy 0.000 description 1
• JZRWCGZRTZMZEH-UHFFFAOYSA-N Thiamine Natural products CC1=C(CCO)SC=[N+]1CC1=CN=C(C)N=C1N JZRWCGZRTZMZEH-UHFFFAOYSA-N 0.000 description 1
• 102000006601 Thymidine Kinase Human genes 0.000 description 1
• KJADKKWYZYXHBB-XBWDGYHZSA-N Topiramic acid Chemical compound C1O[C@@]2(COS(N)(=O)=O)OC(C)(C)O[C@H]2[C@@H]2OC(C)(C)O[C@@H]21 KJADKKWYZYXHBB-XBWDGYHZSA-N 0.000 description 1
• 102000004338 Transferrin Human genes 0.000 description 1
• 108090000901 Transferrin Proteins 0.000 description 1
• 108700019146 Transgenes Proteins 0.000 description 1
• 241000223259 Trichoderma Species 0.000 description 1
• 239000007983 Tris buffer Substances 0.000 description 1
• QIVBCDIJIAJPQS-UHFFFAOYSA-N Tryptophan Natural products C1=CC=C2C(CC(N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-UHFFFAOYSA-N 0.000 description 1
• 208000006105 Uterine Cervical Neoplasms Diseases 0.000 description 1
• 244000000188 Vaccinium ovalifolium Species 0.000 description 1
• KZSNJWFQEVHDMF-UHFFFAOYSA-N Valine Natural products CC(C)C(N)C(O)=O KZSNJWFQEVHDMF-UHFFFAOYSA-N 0.000 description 1
• 108010003205 Vasoactive Intestinal Peptide Proteins 0.000 description 1
• GXBMIBRIOWHPDT-UHFFFAOYSA-N Vasopressin Natural products N1C(=O)C(CC=2C=C(O)C=CC=2)NC(=O)C(N)CSSCC(C(=O)N2C(CCC2)C(=O)NC(CCCN=C(N)N)C(=O)NCC(N)=O)NC(=O)C(CC(N)=O)NC(=O)C(CCC(N)=O)NC(=O)C1CC1=CC=CC=C1 GXBMIBRIOWHPDT-UHFFFAOYSA-N 0.000 description 1
• 108010004977 Vasopressins Proteins 0.000 description 1
• 102000002852 Vasopressins Human genes 0.000 description 1
• 241001416177 Vicugna pacos Species 0.000 description 1
• 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 1
• 239000008351 acetate buffer Substances 0.000 description 1
• 239000003929 acidic solution Substances 0.000 description 1
• 230000009471 action Effects 0.000 description 1
• 230000003213 activating effect Effects 0.000 description 1
• 239000004480 active ingredient Substances 0.000 description 1
• 201000003229 acute pancreatitis Diseases 0.000 description 1
• 239000000654 additive Substances 0.000 description 1
• 229960005305 adenosine Drugs 0.000 description 1
• 230000006838 adverse reaction Effects 0.000 description 1
• 238000001261 affinity purification Methods 0.000 description 1
• 239000011543 agarose gel Substances 0.000 description 1
• 229910001508 alkali metal halide Inorganic materials 0.000 description 1
• 150000008045 alkali metal halides Chemical class 0.000 description 1
• 208000026935 allergic disease Diseases 0.000 description 1
• 208000030961 allergic reaction Diseases 0.000 description 1
• 108010050122 alpha 1-Antitrypsin Proteins 0.000 description 1
• WQZGKKKJIJFFOK-PHYPRBDBSA-N alpha-D-galactose Chemical compound OC[C@H]1O[C@H](O)[C@H](O)[C@@H](O)[C@H]1O WQZGKKKJIJFFOK-PHYPRBDBSA-N 0.000 description 1
• 102000013529 alpha-Fetoproteins Human genes 0.000 description 1
• 230000004075 alteration Effects 0.000 description 1
• 229940037003 alum Drugs 0.000 description 1
• 150000001408 amides Chemical group 0.000 description 1
• 239000003194 amino acid receptor blocking agent Substances 0.000 description 1
• 238000012870 ammonium sulfate precipitation Methods 0.000 description 1
• 101150062861 amy3 gene Proteins 0.000 description 1
• 229940035676 analgesics Drugs 0.000 description 1
• 238000005571 anion exchange chromatography Methods 0.000 description 1
• 208000022531 anorexia Diseases 0.000 description 1
• 230000008485 antagonism Effects 0.000 description 1
• 239000000730 antalgic agent Substances 0.000 description 1
• 230000001773 anti-convulsant effect Effects 0.000 description 1
• 239000001961 anticonvulsive agent Substances 0.000 description 1
• 229960003965 antiepileptics Drugs 0.000 description 1
• 239000004599 antimicrobial Substances 0.000 description 1
• 238000013459 approach Methods 0.000 description 1
• 239000008365 aqueous carrier Substances 0.000 description 1
• 239000007864 aqueous solution Substances 0.000 description 1
• PYMYPHUHKUWMLA-UHFFFAOYSA-N arabinose Natural products OCC(O)C(O)C(O)C=O PYMYPHUHKUWMLA-UHFFFAOYSA-N 0.000 description 1
• 230000002567 autonomic effect Effects 0.000 description 1
• 210000003403 autonomic nervous system Anatomy 0.000 description 1
• 210000003719 b-lymphocyte Anatomy 0.000 description 1
• 230000003385 bacteriostatic effect Effects 0.000 description 1
• LFYJSSARVMHQJB-QIXNEVBVSA-N bakuchiol Chemical compound CC(C)=CCC[C@@](C)(C=C)\C=C\C1=CC=C(O)C=C1 LFYJSSARVMHQJB-QIXNEVBVSA-N 0.000 description 1
• 230000009286 beneficial effect Effects 0.000 description 1
• 235000010233 benzoic acid Nutrition 0.000 description 1
• 229960004365 benzoic acid Drugs 0.000 description 1
• 235000019445 benzyl alcohol Nutrition 0.000 description 1
• SRBFZHDQGSBBOR-UHFFFAOYSA-N beta-D-Pyranose-Lyxose Natural products OC1COC(O)C(O)C1O SRBFZHDQGSBBOR-UHFFFAOYSA-N 0.000 description 1
• 102000005936 beta-Galactosidase Human genes 0.000 description 1
• 108010005774 beta-Galactosidase Proteins 0.000 description 1
• IQFYYKKMVGJFEH-UHFFFAOYSA-N beta-L-thymidine Natural products O=C1NC(=O)C(C)=CN1C1OC(CO)C(O)C1 IQFYYKKMVGJFEH-UHFFFAOYSA-N 0.000 description 1
• WHGYBXFWUBPSRW-FOUAGVGXSA-N beta-cyclodextrin Chemical compound OC[C@H]([C@H]([C@@H]([C@H]1O)O)O[C@H]2O[C@@H]([C@@H](O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O3)[C@H](O)[C@H]2O)CO)O[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@@H]3O[C@@H]1CO WHGYBXFWUBPSRW-FOUAGVGXSA-N 0.000 description 1
• 235000011175 beta-cyclodextrine Nutrition 0.000 description 1
• 229960004853 betadex Drugs 0.000 description 1
• 238000002306 biochemical method Methods 0.000 description 1
• 239000012472 biological sample Substances 0.000 description 1
• 229960000074 biopharmaceutical Drugs 0.000 description 1
• 229960002685 biotin Drugs 0.000 description 1
• 235000020958 biotin Nutrition 0.000 description 1
• 239000011616 biotin Substances 0.000 description 1
• 230000017531 blood circulation Effects 0.000 description 1
• 210000004204 blood vessel Anatomy 0.000 description 1
• 210000002798 bone marrow cell Anatomy 0.000 description 1
• 210000000481 breast Anatomy 0.000 description 1
• 239000008366 buffered solution Substances 0.000 description 1
• 230000003491 cAMP production Effects 0.000 description 1
• 229960001948 caffeine Drugs 0.000 description 1
• VJEONQKOZGKCAK-UHFFFAOYSA-N caffeine Natural products CN1C(=O)N(C)C(=O)C2=C1C=CN2C VJEONQKOZGKCAK-UHFFFAOYSA-N 0.000 description 1
• BBBFJLBPOGFECG-VJVYQDLKSA-N calcitonin Chemical compound N([C@H](C(=O)N[C@@H](CC(C)C)C(=O)NCC(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC=1NC=NC=1)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(=O)NCC(=O)N[C@@H](CO)C(=O)NCC(=O)N[C@@H]([C@@H](C)O)C(=O)N1[C@@H](CCC1)C(N)=O)C(C)C)C(=O)[C@@H]1CSSC[C@H](N)C(=O)N[C@@H](CO)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CO)C(=O)N[C@@H]([C@@H](C)O)C(=O)N1 BBBFJLBPOGFECG-VJVYQDLKSA-N 0.000 description 1
• 229960004015 calcitonin Drugs 0.000 description 1
• 239000003735 calcitonin gene related peptide receptor antagonist Substances 0.000 description 1
• 239000011575 calcium Substances 0.000 description 1
• 229910052791 calcium Inorganic materials 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
• 239000000969 carrier Substances 0.000 description 1
• 238000005277 cation exchange chromatography Methods 0.000 description 1
• 150000001768 cations Chemical class 0.000 description 1
• 210000001159 caudate nucleus Anatomy 0.000 description 1
• 238000004113 cell culture Methods 0.000 description 1
• 230000007910 cell fusion Effects 0.000 description 1
• 230000009028 cell transition Effects 0.000 description 1
• 210000003169 central nervous system Anatomy 0.000 description 1
• 238000005119 centrifugation Methods 0.000 description 1
• 230000002490 cerebral effect Effects 0.000 description 1
• 201000010881 cervical cancer Diseases 0.000 description 1
• 239000013522 chelant Substances 0.000 description 1
• 229960003260 chlorhexidine Drugs 0.000 description 1
• 229960004926 chlorobutanol Drugs 0.000 description 1
• 229940107161 cholesterol Drugs 0.000 description 1
• 235000012000 cholesterol Nutrition 0.000 description 1
• 238000011098 chromatofocusing Methods 0.000 description 1
• 210000000349 chromosome Anatomy 0.000 description 1
• 150000001860 citric acid derivatives Chemical class 0.000 description 1
• 238000010367 cloning Methods 0.000 description 1
• 238000000975 co-precipitation Methods 0.000 description 1
• 238000005354 coacervation Methods 0.000 description 1
• 230000001149 cognitive effect Effects 0.000 description 1
• 239000003086 colorant Substances 0.000 description 1
• 238000004891 communication Methods 0.000 description 1
• 230000002860 competitive effect Effects 0.000 description 1
• 230000006957 competitive inhibition Effects 0.000 description 1
• 230000004154 complement system Effects 0.000 description 1
• 239000003184 complementary RNA Substances 0.000 description 1
• 239000008139 complexing agent Substances 0.000 description 1
• 239000000470 constituent Substances 0.000 description 1
• 230000008602 contraction Effects 0.000 description 1
• 238000013270 controlled release Methods 0.000 description 1
• 238000007796 conventional method Methods 0.000 description 1
• 230000036461 convulsion Effects 0.000 description 1
• 210000004351 coronary vessel Anatomy 0.000 description 1
• 229930003836 cresol Natural products 0.000 description 1
• 239000013078 crystal Substances 0.000 description 1
• HPXRVTGHNJAIIH-UHFFFAOYSA-N cyclohexanol Chemical compound OC1CCCCC1 HPXRVTGHNJAIIH-UHFFFAOYSA-N 0.000 description 1
• 230000007423 decrease Effects 0.000 description 1
• 206010061428 decreased appetite Diseases 0.000 description 1
• 230000003247 decreasing effect Effects 0.000 description 1
• 230000007850 degeneration Effects 0.000 description 1
• 230000001934 delay Effects 0.000 description 1
• YSMODUONRAFBET-UHFFFAOYSA-N delta-DL-hydroxylysine Natural products NCC(O)CCC(N)C(O)=O YSMODUONRAFBET-UHFFFAOYSA-N 0.000 description 1
• 230000001066 destructive effect Effects 0.000 description 1
• 238000000502 dialysis Methods 0.000 description 1
• 235000005911 diet Nutrition 0.000 description 1
• 230000037213 diet Effects 0.000 description 1
• LOKCTEFSRHRXRJ-UHFFFAOYSA-I dipotassium trisodium dihydrogen phosphate hydrogen phosphate dichloride Chemical compound P(=O)(O)(O)[O-].[K+].P(=O)(O)([O-])[O-].[Na+].[Na+].[Cl-].[K+].[Cl-].[Na+] LOKCTEFSRHRXRJ-UHFFFAOYSA-I 0.000 description 1
• 238000004090 dissolution Methods 0.000 description 1
• DLAHAXOYRFRPFQ-UHFFFAOYSA-N dodecyl benzoate Chemical compound CCCCCCCCCCCCOC(=O)C1=CC=CC=C1 DLAHAXOYRFRPFQ-UHFFFAOYSA-N 0.000 description 1
• 239000002552 dosage form Substances 0.000 description 1
• 231100000673 dose–response relationship Toxicity 0.000 description 1
• 238000012377 drug delivery Methods 0.000 description 1
• 238000009509 drug development Methods 0.000 description 1
• 230000009977 dual effect Effects 0.000 description 1
• 210000001951 dura mater Anatomy 0.000 description 1
• 230000008482 dysregulation Effects 0.000 description 1
• 238000004520 electroporation Methods 0.000 description 1
• 230000009881 electrostatic interaction Effects 0.000 description 1
• 239000005712 elicitor Substances 0.000 description 1
• 230000008030 elimination Effects 0.000 description 1
• 238000003379 elimination reaction Methods 0.000 description 1
• 230000008451 emotion Effects 0.000 description 1
• 238000004945 emulsification Methods 0.000 description 1
• 239000003995 emulsifying agent Substances 0.000 description 1
• 239000000839 emulsion Substances 0.000 description 1
• 230000002708 enhancing effect Effects 0.000 description 1
• 238000001976 enzyme digestion Methods 0.000 description 1
• 229940116977 epidermal growth factor Drugs 0.000 description 1
• 238000011067 equilibration Methods 0.000 description 1
• YSMODUONRAFBET-UHNVWZDZSA-N erythro-5-hydroxy-L-lysine Chemical compound NC[C@H](O)CC[C@H](N)C(O)=O YSMODUONRAFBET-UHNVWZDZSA-N 0.000 description 1
• 238000012869 ethanol precipitation Methods 0.000 description 1
• BEFDCLMNVWHSGT-UHFFFAOYSA-N ethenylcyclopentane Chemical compound C=CC1CCCC1 BEFDCLMNVWHSGT-UHFFFAOYSA-N 0.000 description 1
• 230000029142 excretion Effects 0.000 description 1
• 239000000945 filler Substances 0.000 description 1
• 238000001914 filtration Methods 0.000 description 1
• 239000000796 flavoring agent Substances 0.000 description 1
• MHMNJMPURVTYEJ-UHFFFAOYSA-N fluorescein-5-isothiocyanate Chemical compound O1C(=O)C2=CC(N=C=S)=CC=C2C21C1=CC=C(O)C=C1OC1=CC(O)=CC=C21 MHMNJMPURVTYEJ-UHFFFAOYSA-N 0.000 description 1
• 235000013355 food flavoring agent Nutrition 0.000 description 1
• 230000002538 fungal effect Effects 0.000 description 1
• 229930182830 galactose Natural products 0.000 description 1
• 238000001502 gel electrophoresis Methods 0.000 description 1
• 210000004602 germ cell Anatomy 0.000 description 1
• 239000011521 glass Substances 0.000 description 1
• 239000000174 gluconic acid Substances 0.000 description 1
• 235000012208 gluconic acid Nutrition 0.000 description 1
• ZDXPYRJPNDTMRX-UHFFFAOYSA-N glutamine Natural products OC(=O)C(N)CCC(N)=O ZDXPYRJPNDTMRX-UHFFFAOYSA-N 0.000 description 1
• 125000003630 glycyl group Chemical group [H]N([H])C([H])([H])C(*)=O 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
• 239000003102 growth factor Substances 0.000 description 1
• 238000003306 harvesting Methods 0.000 description 1
• 239000000185 hemagglutinin Substances 0.000 description 1
• 206010073071 hepatocellular carcinoma Diseases 0.000 description 1
• 238000005734 heterodimerization reaction Methods 0.000 description 1
• 210000003630 histaminocyte Anatomy 0.000 description 1
• 229940088597 hormone Drugs 0.000 description 1
• 239000005556 hormone Substances 0.000 description 1
• 102000050254 human CALCRL Human genes 0.000 description 1
• 102000056275 human VIPR1 Human genes 0.000 description 1
• 102000056273 human VIPR2 Human genes 0.000 description 1
• 229940045644 human calcitonin Drugs 0.000 description 1
• 239000003906 humectant Substances 0.000 description 1
• 229960002163 hydrogen peroxide Drugs 0.000 description 1
• 229920001600 hydrophobic polymer Polymers 0.000 description 1
• 229920003063 hydroxymethyl cellulose Polymers 0.000 description 1
• 229940031574 hydroxymethyl cellulose Drugs 0.000 description 1
• 210000003016 hypothalamus Anatomy 0.000 description 1
• 230000003100 immobilizing effect Effects 0.000 description 1
• 230000016784 immunoglobulin production Effects 0.000 description 1
• 229940072221 immunoglobulins Drugs 0.000 description 1
• 230000002055 immunohistochemical effect Effects 0.000 description 1
• 239000003018 immunosuppressive agent Substances 0.000 description 1
• 229940125721 immunosuppressive agent Drugs 0.000 description 1
• 230000001976 improved effect Effects 0.000 description 1
• 208000015181 infectious disease Diseases 0.000 description 1
• 230000036512 infertility Effects 0.000 description 1
• 230000002757 inflammatory effect Effects 0.000 description 1
• 230000002401 inhibitory effect Effects 0.000 description 1
• 150000002484 inorganic compounds Chemical class 0.000 description 1
• 229910010272 inorganic material Inorganic materials 0.000 description 1
• 230000002452 interceptive effect Effects 0.000 description 1
• 210000000936 intestine Anatomy 0.000 description 1
• 238000001361 intraarterial administration Methods 0.000 description 1
• 238000007918 intramuscular administration Methods 0.000 description 1
• 238000007913 intrathecal administration Methods 0.000 description 1
• 238000001990 intravenous administration Methods 0.000 description 1
• 238000010253 intravenous injection Methods 0.000 description 1
• 238000005304 joining Methods 0.000 description 1
• 229960000318 kanamycin Drugs 0.000 description 1
• SBUJHOSQTJFQJX-NOAMYHISSA-N kanamycin Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CN)O[C@@H]1O[C@H]1[C@H](O)[C@@H](O[C@@H]2[C@@H]([C@@H](N)[C@H](O)[C@@H](CO)O2)O)[C@H](N)C[C@@H]1N SBUJHOSQTJFQJX-NOAMYHISSA-N 0.000 description 1
• 229930027917 kanamycin Natural products 0.000 description 1
• 229930182823 kanamycin A Natural products 0.000 description 1
• 229910052747 lanthanoid Inorganic materials 0.000 description 1
• 150000002602 lanthanoids Chemical class 0.000 description 1
• 239000000787 lecithin Substances 0.000 description 1
• 235000010445 lecithin Nutrition 0.000 description 1
• 229940067606 lecithin Drugs 0.000 description 1
• 238000001638 lipofection Methods 0.000 description 1
• 239000002502 liposome Substances 0.000 description 1
• 210000005229 liver cell Anatomy 0.000 description 1
• 230000004807 localization Effects 0.000 description 1
• 230000033001 locomotion Effects 0.000 description 1
• 230000005923 long-lasting effect Effects 0.000 description 1
• 230000007774 longterm Effects 0.000 description 1
• 210000005265 lung cell Anatomy 0.000 description 1
• 210000002751 lymph Anatomy 0.000 description 1
• 210000001165 lymph node Anatomy 0.000 description 1
• 210000004698 lymphocyte Anatomy 0.000 description 1
• RLSSMJSEOOYNOY-UHFFFAOYSA-N m-cresol Chemical compound CC1=CC=CC(O)=C1 RLSSMJSEOOYNOY-UHFFFAOYSA-N 0.000 description 1
• 239000011777 magnesium Substances 0.000 description 1
• 229910052749 magnesium Inorganic materials 0.000 description 1
• 238000012423 maintenance Methods 0.000 description 1
• 238000013178 mathematical model Methods 0.000 description 1
• 230000008018 melting Effects 0.000 description 1
• 238000002844 melting Methods 0.000 description 1
• 230000009245 menopause Effects 0.000 description 1
• 230000036997 mental performance Effects 0.000 description 1
• LVWZTYCIRDMTEY-UHFFFAOYSA-N metamizole Chemical compound O=C1C(N(CS(O)(=O)=O)C)=C(C)N(C)N1C1=CC=CC=C1 LVWZTYCIRDMTEY-UHFFFAOYSA-N 0.000 description 1
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
• 239000004530 micro-emulsion Substances 0.000 description 1
• 238000000520 microinjection Methods 0.000 description 1
• 230000000116 mitigating effect Effects 0.000 description 1
• 102000035118 modified proteins Human genes 0.000 description 1
• 108091005573 modified proteins Proteins 0.000 description 1
• 239000003607 modifier Substances 0.000 description 1
• 229940126619 mouse monoclonal antibody Drugs 0.000 description 1
• 239000002088 nanocapsule Substances 0.000 description 1
• 239000002105 nanoparticle Substances 0.000 description 1
• 201000003631 narcolepsy Diseases 0.000 description 1
• 235000010298 natamycin Nutrition 0.000 description 1
• 229960003255 natamycin Drugs 0.000 description 1
• 239000004311 natamycin Substances 0.000 description 1
• NCXMLFZGDNKEPB-FFPOYIOWSA-N natamycin Chemical compound O[C@H]1[C@@H](N)[C@H](O)[C@@H](C)O[C@H]1O[C@H]1/C=C/C=C/C=C/C=C/C[C@@H](C)OC(=O)/C=C/[C@H]2O[C@@H]2C[C@H](O)C[C@](O)(C[C@H](O)[C@H]2C(O)=O)O[C@H]2C1 NCXMLFZGDNKEPB-FFPOYIOWSA-N 0.000 description 1
• 230000022128 negative regulation of vasodilation Effects 0.000 description 1
• 229960004927 neomycin Drugs 0.000 description 1
• 230000001537 neural effect Effects 0.000 description 1
• 230000000926 neurological effect Effects 0.000 description 1
• 206010029410 night sweats Diseases 0.000 description 1
• 230000036565 night sweats Effects 0.000 description 1
• 239000002777 nucleoside Substances 0.000 description 1
• 125000003835 nucleoside group Chemical group 0.000 description 1
• 210000004248 oligodendroglia Anatomy 0.000 description 1
• 239000002751 oligonucleotide probe Substances 0.000 description 1
• 230000003204 osmotic effect Effects 0.000 description 1
• IWVCMVBTMGNXQD-PXOLEDIWSA-N oxytetracycline Chemical compound C1=CC=C2[C@](O)(C)[C@H]3[C@H](O)[C@H]4[C@H](N(C)C)C(O)=C(C(N)=O)C(=O)[C@@]4(O)C(O)=C3C(=O)C2=C1O IWVCMVBTMGNXQD-PXOLEDIWSA-N 0.000 description 1
• 239000003002 pH adjusting agent Substances 0.000 description 1
• 238000004091 panning Methods 0.000 description 1
• FJKROLUGYXJWQN-UHFFFAOYSA-N papa-hydroxy-benzoic acid Natural products OC(=O)C1=CC=C(O)C=C1 FJKROLUGYXJWQN-UHFFFAOYSA-N 0.000 description 1
• 210000001002 parasympathetic nervous system Anatomy 0.000 description 1
• 238000007911 parenteral administration Methods 0.000 description 1
• 208000035824 paresthesia Diseases 0.000 description 1
• 230000008506 pathogenesis Effects 0.000 description 1
• 230000000149 penetrating effect Effects 0.000 description 1
• 210000001428 peripheral nervous system Anatomy 0.000 description 1
• 210000001322 periplasm Anatomy 0.000 description 1
• 230000008782 phagocytosis Effects 0.000 description 1
• 239000012071 phase Substances 0.000 description 1
• WVDDGKGOMKODPV-ZQBYOMGUSA-N phenyl(114C)methanol Chemical compound O[14CH2]C1=CC=CC=C1 WVDDGKGOMKODPV-ZQBYOMGUSA-N 0.000 description 1
• 229940067107 phenylethyl alcohol Drugs 0.000 description 1
• 239000002953 phosphate buffered saline Substances 0.000 description 1
• 150000003013 phosphoric acid derivatives Chemical class 0.000 description 1
• 230000026731 phosphorylation Effects 0.000 description 1
• 238000006366 phosphorylation reaction Methods 0.000 description 1
• 230000036314 physical performance Effects 0.000 description 1
• 229940068196 placebo Drugs 0.000 description 1
• 239000000902 placebo Substances 0.000 description 1
• 210000000557 podocyte Anatomy 0.000 description 1
• 229920001993 poloxamer 188 Polymers 0.000 description 1
• 229940044519 poloxamer 188 Drugs 0.000 description 1
• 108010087782 poly(glycyl-alanyl) Proteins 0.000 description 1
• 229920000747 poly(lactic acid) Polymers 0.000 description 1
• 229920003229 poly(methyl methacrylate) Polymers 0.000 description 1
• 108010054442 polyalanine Proteins 0.000 description 1
• 229920000728 polyester Polymers 0.000 description 1
• 239000004633 polyglycolic acid Substances 0.000 description 1
• 229920002338 polyhydroxyethylmethacrylate Polymers 0.000 description 1
• 239000004626 polylactic acid Substances 0.000 description 1
• 239000004926 polymethyl methacrylate Substances 0.000 description 1
• 229920001282 polysaccharide Polymers 0.000 description 1
• 239000005017 polysaccharide Substances 0.000 description 1
• 229950008882 polysorbate Drugs 0.000 description 1
• 229940068965 polysorbates Drugs 0.000 description 1
• 229920002451 polyvinyl alcohol Polymers 0.000 description 1
• 239000004175 ponceau 4R Substances 0.000 description 1
• 230000004481 post-translational protein modification Effects 0.000 description 1
• 230000001323 posttranslational effect Effects 0.000 description 1
• 239000001103 potassium chloride Substances 0.000 description 1
• 235000011164 potassium chloride Nutrition 0.000 description 1
• 239000002244 precipitate Substances 0.000 description 1
• 238000012545 processing Methods 0.000 description 1
• 210000001236 prokaryotic cell Anatomy 0.000 description 1
• 230000009465 prokaryotic expression Effects 0.000 description 1
• 230000002035 prolonged effect Effects 0.000 description 1
• 229960003415 propylparaben Drugs 0.000 description 1
• 229940048914 protamine Drugs 0.000 description 1
• 235000019419 proteases Nutrition 0.000 description 1
• 238000001742 protein purification Methods 0.000 description 1
• 238000000734 protein sequencing Methods 0.000 description 1
• 230000000541 pulsatile effect Effects 0.000 description 1
• 238000000746 purification Methods 0.000 description 1
• 239000000018 receptor agonist Substances 0.000 description 1
• 229940044601 receptor agonist Drugs 0.000 description 1
• 238000003259 recombinant expression Methods 0.000 description 1
• 230000001105 regulatory effect Effects 0.000 description 1
• 229920005989 resin Polymers 0.000 description 1
• 239000011347 resin Substances 0.000 description 1
• 230000000979 retarding effect Effects 0.000 description 1
• 238000003757 reverse transcription PCR Methods 0.000 description 1
• 238000004007 reversed phase HPLC Methods 0.000 description 1
• PYWVYCXTNDRMGF-UHFFFAOYSA-N rhodamine B Chemical compound [Cl-].C=12C=CC(=[N+](CC)CC)C=C2OC2=CC(N(CC)CC)=CC=C2C=1C1=CC=CC=C1C(O)=O PYWVYCXTNDRMGF-UHFFFAOYSA-N 0.000 description 1
• 235000009566 rice Nutrition 0.000 description 1
• 102200087972 rs1042821 Human genes 0.000 description 1
• 238000007665 sagging Methods 0.000 description 1
• 229960004889 salicylic acid Drugs 0.000 description 1
• 230000009155 sensory pathway Effects 0.000 description 1
• 238000002864 sequence alignment Methods 0.000 description 1
• 238000012163 sequencing technique Methods 0.000 description 1
• 125000003607 serino group Chemical group [H]N([H])[C@]([H])(C(=O)[*])C(O[H])([H])[H] 0.000 description 1
• 229940076279 serotonin Drugs 0.000 description 1
• 230000035939 shock Effects 0.000 description 1
• 210000002027 skeletal muscle Anatomy 0.000 description 1
• 150000003384 small molecules Chemical class 0.000 description 1
• 239000011734 sodium Substances 0.000 description 1
• 229910052708 sodium Inorganic materials 0.000 description 1
• 239000001632 sodium acetate Substances 0.000 description 1
• 235000017281 sodium acetate Nutrition 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
• 235000010267 sodium hydrogen sulphite Nutrition 0.000 description 1
• 229940074404 sodium succinate Drugs 0.000 description 1
• ZDQYSKICYIVCPN-UHFFFAOYSA-L sodium succinate (anhydrous) Chemical compound [Na+].[Na+].[O-]C(=O)CCC([O-])=O ZDQYSKICYIVCPN-UHFFFAOYSA-L 0.000 description 1
• 235000010265 sodium sulphite Nutrition 0.000 description 1
• 239000001433 sodium tartrate Substances 0.000 description 1
• 239000002904 solvent Substances 0.000 description 1
• 230000037439 somatic mutation Effects 0.000 description 1
• 235000010199 sorbic acid Nutrition 0.000 description 1
• 239000004334 sorbic acid Substances 0.000 description 1
• 229940075582 sorbic acid Drugs 0.000 description 1
• 238000001179 sorption measurement Methods 0.000 description 1
• 125000006850 spacer group Chemical group 0.000 description 1
• 229940063675 spermine Drugs 0.000 description 1
• 210000000952 spleen Anatomy 0.000 description 1
• 210000004989 spleen cell Anatomy 0.000 description 1
• 230000000087 stabilizing effect Effects 0.000 description 1
• 238000010186 staining Methods 0.000 description 1
• SFVFIFLLYFPGHH-UHFFFAOYSA-M stearalkonium chloride Chemical compound [Cl-].CCCCCCCCCCCCCCCCCC[N+](C)(C)CC1=CC=CC=C1 SFVFIFLLYFPGHH-UHFFFAOYSA-M 0.000 description 1
• 238000011146 sterile filtration Methods 0.000 description 1
• 239000008174 sterile solution Substances 0.000 description 1
• 238000010254 subcutaneous injection Methods 0.000 description 1
• 239000007929 subcutaneous injection Substances 0.000 description 1
• 239000000758 substrate Substances 0.000 description 1
• KDYFGRWQOYBRFD-UHFFFAOYSA-L succinate(2-) Chemical compound [O-]C(=O)CCC([O-])=O KDYFGRWQOYBRFD-UHFFFAOYSA-L 0.000 description 1
• 230000001629 suppression Effects 0.000 description 1
• 238000001356 surgical procedure Methods 0.000 description 1
• 239000000375 suspending agent Substances 0.000 description 1
• 238000004114 suspension culture Methods 0.000 description 1
• 230000008961 swelling Effects 0.000 description 1
• 230000005062 synaptic transmission Effects 0.000 description 1
• 230000002195 synergetic effect Effects 0.000 description 1
• 210000001550 testis Anatomy 0.000 description 1
• 229940124597 therapeutic agent Drugs 0.000 description 1
• 238000002560 therapeutic procedure Methods 0.000 description 1
• 235000019157 thiamine Nutrition 0.000 description 1
• KYMBYSLLVAOCFI-UHFFFAOYSA-N thiamine Chemical compound CC1=C(CCO)SCN1CC1=CN=C(C)N=C1N KYMBYSLLVAOCFI-UHFFFAOYSA-N 0.000 description 1
• 229960003495 thiamine Drugs 0.000 description 1
• 239000011721 thiamine Substances 0.000 description 1
• RTKIYNMVFMVABJ-UHFFFAOYSA-L thimerosal Chemical compound [Na+].CC[Hg]SC1=CC=CC=C1C([O-])=O RTKIYNMVFMVABJ-UHFFFAOYSA-L 0.000 description 1
• 229940033663 thimerosal Drugs 0.000 description 1
• 125000003396 thiol group Chemical group [H]S* 0.000 description 1
• 229940104230 thymidine Drugs 0.000 description 1
• 230000000699 topical effect Effects 0.000 description 1
• 229960004394 topiramate Drugs 0.000 description 1
• 239000003053 toxin Substances 0.000 description 1
• 231100000765 toxin Toxicity 0.000 description 1
• 108700012359 toxins Proteins 0.000 description 1
• 235000013619 trace mineral Nutrition 0.000 description 1
• 239000011573 trace mineral Substances 0.000 description 1
• 230000002103 transcriptional effect Effects 0.000 description 1
• 239000012581 transferrin Substances 0.000 description 1
• 230000009466 transformation Effects 0.000 description 1
• ODLHGICHYURWBS-LKONHMLTSA-N trappsol cyclo Chemical compound CC(O)COC[C@H]([C@H]([C@@H]([C@H]1O)O)O[C@H]2O[C@@H]([C@@H](O[C@H]3O[C@H](COCC(C)O)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](COCC(C)O)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](COCC(C)O)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](COCC(C)O)[C@H]([C@@H]([C@H]3O)O)O3)[C@H](O)[C@H]2O)COCC(O)C)O[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@@H]3O[C@@H]1COCC(C)O ODLHGICHYURWBS-LKONHMLTSA-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
• GPRLSGONYQIRFK-MNYXATJNSA-N triton Chemical compound [3H+] GPRLSGONYQIRFK-MNYXATJNSA-N 0.000 description 1
• 229960000281 trometamol Drugs 0.000 description 1
• 125000001493 tyrosinyl group Chemical group [H]OC1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])(N([H])[H])C(*)=O 0.000 description 1
• 238000000108 ultra-filtration Methods 0.000 description 1
• 241000701447 unidentified baculovirus Species 0.000 description 1
• 241000712461 unidentified influenza virus Species 0.000 description 1
• 241001430294 unidentified retrovirus Species 0.000 description 1
• VBEQCZHXXJYVRD-GACYYNSASA-N uroanthelone Chemical compound C([C@@H](C(=O)N[C@H](C(=O)N[C@@H](CS)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CS)C(=O)N[C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)NCC(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N[C@@H](CO)C(=O)NCC(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CS)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O)C(C)C)[C@@H](C)O)NC(=O)[C@H](CO)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CO)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@@H](NC(=O)[C@H](CC=1NC=NC=1)NC(=O)[C@H](CCSC)NC(=O)[C@H](CS)NC(=O)[C@@H](NC(=O)CNC(=O)CNC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CS)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)CNC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CO)NC(=O)[C@H](CO)NC(=O)[C@H]1N(CCC1)C(=O)[C@H](CS)NC(=O)CNC(=O)[C@H]1N(CCC1)C(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CO)NC(=O)[C@@H](N)CC(N)=O)C(C)C)[C@@H](C)CC)C1=CC=C(O)C=C1 VBEQCZHXXJYVRD-GACYYNSASA-N 0.000 description 1
• 239000004474 valine Substances 0.000 description 1
• 235000014393 valine Nutrition 0.000 description 1
• 208000019553 vascular disease Diseases 0.000 description 1
• 230000006442 vascular tone Effects 0.000 description 1
• 210000005166 vasculature Anatomy 0.000 description 1
• 230000000304 vasodilatating effect Effects 0.000 description 1
• 229960003726 vasopressin Drugs 0.000 description 1
• 239000003981 vehicle Substances 0.000 description 1
• 239000013603 viral vector Substances 0.000 description 1
• 239000011534 wash buffer Substances 0.000 description 1
• 238000005406 washing Methods 0.000 description 1
• 229920003169 water-soluble polymer Polymers 0.000 description 1