CA2618476A1 - Albumin fusion proteins - Google Patents

Info

Publication number

CA2618476A1

CA2618476A1 CA002618476A CA2618476A CA2618476A1 CA 2618476 A1 CA2618476 A1 CA 2618476A1 CA 002618476 A CA002618476 A CA 002618476A CA 2618476 A CA2618476 A CA 2618476A CA 2618476 A1 CA2618476 A1 CA 2618476A1

Authority

CA

Canada

Prior art keywords

albumin

variant

therapeutic

fragment

protein

Prior art date

2005-08-12

Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)

Abandoned

Links

• Espacenet
• Global Dossier
• CIPO
• Discuss

• 102000009027 Albumins Human genes 0.000 title claims abstract description 493
• 108010088751 Albumins Proteins 0.000 title claims abstract description 493
• 108020001507 fusion proteins Proteins 0.000 title claims abstract description 344
• 102000037865 fusion proteins Human genes 0.000 title claims abstract description 344
• 238000000034 method Methods 0.000 claims abstract description 128
• 150000007523 nucleic acids Chemical class 0.000 claims abstract description 48
• 102000039446 nucleic acids Human genes 0.000 claims abstract description 43
• 108020004707 nucleic acids Proteins 0.000 claims abstract description 43
• 239000013598 vector Substances 0.000 claims abstract description 37
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 27
• 201000010099 disease Diseases 0.000 claims abstract description 15
• 208000035475 disorder Diseases 0.000 claims abstract description 12
• 108090000623 proteins and genes Proteins 0.000 claims description 453
• 230000001225 therapeutic effect Effects 0.000 claims description 434
• 102000004169 proteins and genes Human genes 0.000 claims description 424
• 239000012634 fragment Substances 0.000 claims description 235
• 108090000765 processed proteins & peptides Proteins 0.000 claims description 154
• 102000040430 polynucleotide Human genes 0.000 claims description 117
• 108091033319 polynucleotide Proteins 0.000 claims description 117
• 239000002157 polynucleotide Substances 0.000 claims description 117
• 230000004927 fusion Effects 0.000 claims description 96
• 125000003275 alpha amino acid group Chemical group 0.000 claims description 81
• 230000004071 biological effect Effects 0.000 claims description 52
• 230000000694 effects Effects 0.000 claims description 52
• 101710173438 Late L2 mu core protein Proteins 0.000 claims description 50
• 101710188315 Protein X Proteins 0.000 claims description 50
• 150000001413 amino acids Chemical class 0.000 claims description 48
• 238000011282 treatment Methods 0.000 claims description 46
• 229940079322 interferon Drugs 0.000 claims description 44
• 102100040018 Interferon alpha-2 Human genes 0.000 claims description 16
• 240000004808 Saccharomyces cerevisiae Species 0.000 claims description 14
• 238000001727 in vivo Methods 0.000 claims description 14
• 208000005176 Hepatitis C Diseases 0.000 claims description 13
• 208000010710 hepatitis C virus infection Diseases 0.000 claims description 12
• 238000000338 in vitro Methods 0.000 claims description 12
• 210000002966 serum Anatomy 0.000 claims description 11
• 108010079944 Interferon-alpha2b Proteins 0.000 claims description 9
• IWUCXVSUMQZMFG-AFCXAGJDSA-N Ribavirin Chemical compound N1=C(C(=O)N)N=CN1[C@H]1[C@H](O)[C@H](O)[C@@H](CO)O1 IWUCXVSUMQZMFG-AFCXAGJDSA-N 0.000 claims description 9
• 239000000203 mixture Substances 0.000 claims description 9
• 229960000329 ribavirin Drugs 0.000 claims description 9
• HZCAHMRRMINHDJ-DBRKOABJSA-N ribavirin Natural products O[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1N1N=CN=C1 HZCAHMRRMINHDJ-DBRKOABJSA-N 0.000 claims description 9
• 230000028327 secretion Effects 0.000 claims description 5
• 230000001580 bacterial effect Effects 0.000 claims description 4
• 239000003937 drug carrier Substances 0.000 claims description 2
• 238000011284 combination treatment Methods 0.000 claims 1
• 239000008194 pharmaceutical composition Substances 0.000 abstract description 10
• 235000018102 proteins Nutrition 0.000 description 422
• 102000004196 processed proteins & peptides Human genes 0.000 description 142
• 229920001184 polypeptide Polymers 0.000 description 136
• 210000004027 cell Anatomy 0.000 description 91
• 235000001014 amino acid Nutrition 0.000 description 79
• 239000000427 antigen Substances 0.000 description 75
• 102000036639 antigens Human genes 0.000 description 75
• 108091007433 antigens Proteins 0.000 description 75
• 101800000407 Brain natriuretic peptide 32 Proteins 0.000 description 72
• 101800002247 Brain natriuretic peptide 45 Proteins 0.000 description 72
• 102400000667 Brain natriuretic peptide 32 Human genes 0.000 description 66
• 108091006905 Human Serum Albumin Proteins 0.000 description 61
• 102000008100 Human Serum Albumin Human genes 0.000 description 61
• 241000282414 Homo sapiens Species 0.000 description 59
• 230000027455 binding Effects 0.000 description 56
• 229940024606 amino acid Drugs 0.000 description 52
• 102000014150 Interferons Human genes 0.000 description 44
• 108010050904 Interferons Proteins 0.000 description 44
• 238000006467 substitution reaction Methods 0.000 description 40
• 238000003556 assay Methods 0.000 description 37
• 230000014509 gene expression Effects 0.000 description 35
• 241000711549 Hepacivirus C Species 0.000 description 32
• 238000012217 deletion Methods 0.000 description 29
• 230000037430 deletion Effects 0.000 description 29
• 108010047761 Interferon-alpha Proteins 0.000 description 27
• 229910052760 oxygen Inorganic materials 0.000 description 27
• 102000006992 Interferon-alpha Human genes 0.000 description 25
• 125000000539 amino acid group Chemical group 0.000 description 24
• 210000004899 c-terminal region Anatomy 0.000 description 24
• 102000007562 Serum Albumin Human genes 0.000 description 23
• 108010071390 Serum Albumin Proteins 0.000 description 23
• 125000003729 nucleotide group Chemical group 0.000 description 23
• 206010010099 Combined immunodeficiency Diseases 0.000 description 22
• 239000013604 expression vector Substances 0.000 description 22
• 239000002773 nucleotide Substances 0.000 description 22
• 239000003446 ligand Substances 0.000 description 19
• 102000005962 receptors Human genes 0.000 description 19
• 108020003175 receptors Proteins 0.000 description 19
• 230000013595 glycosylation Effects 0.000 description 16
• 238000006206 glycosylation reaction Methods 0.000 description 16
• 108020004414 DNA Proteins 0.000 description 15
• -1 antlbody Proteins 0.000 description 15
• 150000001875 compounds Chemical class 0.000 description 15
• 210000004408 hybridoma Anatomy 0.000 description 15
• 238000003018 immunoassay Methods 0.000 description 15
• 230000004048 modification Effects 0.000 description 15
• 238000012986 modification Methods 0.000 description 15
• 238000002965 ELISA Methods 0.000 description 14
• 108060003951 Immunoglobulin Proteins 0.000 description 14
• 108020001621 Natriuretic Peptide Proteins 0.000 description 14
• 102000004571 Natriuretic peptide Human genes 0.000 description 14
• 239000011324 bead Substances 0.000 description 14
• 102000018358 immunoglobulin Human genes 0.000 description 14
• 239000000692 natriuretic peptide Substances 0.000 description 14
• 210000002381 plasma Anatomy 0.000 description 14
• 230000015572 biosynthetic process Effects 0.000 description 13
• 230000000747 cardiac effect Effects 0.000 description 13
• 108010047041 Complementarity Determining Regions Proteins 0.000 description 12
• 206010019280 Heart failures Diseases 0.000 description 12
• 206010020772 Hypertension Diseases 0.000 description 12
• 235000014680 Saccharomyces cerevisiae Nutrition 0.000 description 12
• 238000005516 engineering process Methods 0.000 description 12
• 210000004379 membrane Anatomy 0.000 description 12
• 239000012528 membrane Substances 0.000 description 12
• 238000005406 washing Methods 0.000 description 12
• 102100040019 Interferon alpha-1/13 Human genes 0.000 description 11
• ZDXPYRJPNDTMRX-VKHMYHEASA-N L-glutamine Chemical compound OC(=O)[C@@H](N)CCC(N)=O ZDXPYRJPNDTMRX-VKHMYHEASA-N 0.000 description 11
• 241000699666 Mus <mouse, genus> Species 0.000 description 11
• 108091028043 Nucleic acid sequence Proteins 0.000 description 11
• 210000003719 b-lymphocyte Anatomy 0.000 description 11
• 230000005714 functional activity Effects 0.000 description 11
• 238000004519 manufacturing process Methods 0.000 description 11
• 239000000126 substance Substances 0.000 description 11
• 241000701044 Human gammaherpesvirus 4 Species 0.000 description 10
• 239000003443 antiviral agent Substances 0.000 description 10
• 239000003814 drug Substances 0.000 description 10
• 238000005755 formation reaction Methods 0.000 description 10
• 238000001990 intravenous administration Methods 0.000 description 10
• 238000003752 polymerase chain reaction Methods 0.000 description 10
• 238000009396 hybridization Methods 0.000 description 9
• 230000001965 increasing effect Effects 0.000 description 9
• 239000003550 marker Substances 0.000 description 9
• 238000012545 processing Methods 0.000 description 9
• 238000000746 purification Methods 0.000 description 9
• 238000001262 western blot Methods 0.000 description 9
• 101710106107 Interferon alpha-D Proteins 0.000 description 8
• 206010028980 Neoplasm Diseases 0.000 description 8
• 241000700605 Viruses Species 0.000 description 8
• 230000000903 blocking effect Effects 0.000 description 8
• 238000010494 dissociation reaction Methods 0.000 description 8
• 230000005593 dissociations Effects 0.000 description 8
• ZDXPYRJPNDTMRX-UHFFFAOYSA-N glutamine Natural products OC(=O)C(N)CCC(N)=O ZDXPYRJPNDTMRX-UHFFFAOYSA-N 0.000 description 8
• 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 8
• 239000000047 product Substances 0.000 description 8
• 239000000243 solution Substances 0.000 description 8
• 239000000758 substrate Substances 0.000 description 8
• 210000001519 tissue Anatomy 0.000 description 8
• ZOOGRGPOEVQQDX-UUOKFMHZSA-N 3',5'-cyclic GMP Chemical compound C([C@H]1O2)OP(O)(=O)O[C@H]1[C@@H](O)[C@@H]2N1C(N=C(NC2=O)N)=C2N=C1 ZOOGRGPOEVQQDX-UUOKFMHZSA-N 0.000 description 7
• 101800001288 Atrial natriuretic factor Proteins 0.000 description 7
• 101800001890 Atrial natriuretic peptide Proteins 0.000 description 7
• 206010007559 Cardiac failure congestive Diseases 0.000 description 7
• 108010001336 Horseradish Peroxidase Proteins 0.000 description 7
• 108010078049 Interferon alpha-2 Proteins 0.000 description 7
• 241001465754 Metazoa Species 0.000 description 7
• 241001529936 Murinae Species 0.000 description 7
• 108010076504 Protein Sorting Signals Proteins 0.000 description 7
• 230000004913 activation Effects 0.000 description 7
• 230000004872 arterial blood pressure Effects 0.000 description 7
• 230000008859 change Effects 0.000 description 7
• 238000006243 chemical reaction Methods 0.000 description 7
• 238000012875 competitive assay Methods 0.000 description 7
• 230000009260 cross reactivity Effects 0.000 description 7
• 239000000499 gel Substances 0.000 description 7
• 238000001114 immunoprecipitation Methods 0.000 description 7
• 208000017169 kidney disease Diseases 0.000 description 7
• 210000004962 mammalian cell Anatomy 0.000 description 7
• 239000000463 material Substances 0.000 description 7
• 239000011159 matrix material Substances 0.000 description 7
• 239000013612 plasmid Substances 0.000 description 7
• 239000003981 vehicle Substances 0.000 description 7
• MTCFGRXMJLQNBG-REOHCLBHSA-N (2S)-2-Amino-3-hydroxypropansäure Chemical compound OC[C@H](N)C(O)=O MTCFGRXMJLQNBG-REOHCLBHSA-N 0.000 description 6
• PQSUYGKTWSAVDQ-ZVIOFETBSA-N Aldosterone Chemical compound C([C@@]1([C@@H](C(=O)CO)CC[C@H]1[C@@H]1CC2)C=O)[C@H](O)[C@@H]1[C@]1(C)C2=CC(=O)CC1 PQSUYGKTWSAVDQ-ZVIOFETBSA-N 0.000 description 6
• PQSUYGKTWSAVDQ-UHFFFAOYSA-N Aldosterone Natural products C1CC2C3CCC(C(=O)CO)C3(C=O)CC(O)C2C2(C)C1=CC(=O)CC2 PQSUYGKTWSAVDQ-UHFFFAOYSA-N 0.000 description 6
• 102000002260 Alkaline Phosphatase Human genes 0.000 description 6
• 108020004774 Alkaline Phosphatase Proteins 0.000 description 6
• 102400001282 Atrial natriuretic peptide Human genes 0.000 description 6
• 108020004705 Codon Proteins 0.000 description 6
• 241000699670 Mus sp. Species 0.000 description 6
• 206010035226 Plasma cell myeloma Diseases 0.000 description 6
• 108020004511 Recombinant DNA Proteins 0.000 description 6
• 229960002478 aldosterone Drugs 0.000 description 6
• 238000004458 analytical method Methods 0.000 description 6
• 239000011575 calcium Substances 0.000 description 6
• 201000011510 cancer Diseases 0.000 description 6
• 239000013592 cell lysate Substances 0.000 description 6
• 239000003795 chemical substances by application Substances 0.000 description 6
• 239000011248 coating agent Substances 0.000 description 6
• 238000000576 coating method Methods 0.000 description 6
• 230000002255 enzymatic effect Effects 0.000 description 6
• 230000000670 limiting effect Effects 0.000 description 6
• 230000035772 mutation Effects 0.000 description 6
• 229920002401 polyacrylamide Polymers 0.000 description 6
• 238000003127 radioimmunoassay Methods 0.000 description 6
• 230000000717 retained effect Effects 0.000 description 6
• 238000012216 screening Methods 0.000 description 6
• 235000002639 sodium chloride Nutrition 0.000 description 6
• 230000035897 transcription Effects 0.000 description 6
• 238000013518 transcription Methods 0.000 description 6
• 239000011534 wash buffer Substances 0.000 description 6
• 102100039339 Atrial natriuretic peptide receptor 1 Human genes 0.000 description 5
• 101710102163 Atrial natriuretic peptide receptor 1 Proteins 0.000 description 5
• 208000024172 Cardiovascular disease Diseases 0.000 description 5
• 108091026890 Coding region Proteins 0.000 description 5
• 241000588724 Escherichia coli Species 0.000 description 5
• AYFVYJQAPQTCCC-GBXIJSLDSA-N L-threonine Chemical compound C[C@@H](O)[C@H](N)C(O)=O AYFVYJQAPQTCCC-GBXIJSLDSA-N 0.000 description 5
• 230000003213 activating effect Effects 0.000 description 5
• 230000001154 acute effect Effects 0.000 description 5
• 238000007792 addition Methods 0.000 description 5
• 239000000556 agonist Substances 0.000 description 5
• 230000004075 alteration Effects 0.000 description 5
• 229910052799 carbon Inorganic materials 0.000 description 5
• 230000001413 cellular effect Effects 0.000 description 5
• 231100000599 cytotoxic agent Toxicity 0.000 description 5
• 238000001514 detection method Methods 0.000 description 5
• 239000012530 fluid Substances 0.000 description 5
• 238000009472 formulation Methods 0.000 description 5
• 230000002068 genetic effect Effects 0.000 description 5
• 230000002163 immunogen Effects 0.000 description 5
• 201000000050 myeloid neoplasm Diseases 0.000 description 5
• 229910052757 nitrogen Inorganic materials 0.000 description 5
• 238000002823 phage display Methods 0.000 description 5
• 238000002360 preparation method Methods 0.000 description 5
• 239000007787 solid Substances 0.000 description 5
• 229940124597 therapeutic agent Drugs 0.000 description 5
• 230000009466 transformation Effects 0.000 description 5
• 238000013519 translation Methods 0.000 description 5
• 238000011144 upstream manufacturing Methods 0.000 description 5
• 230000003612 virological effect Effects 0.000 description 5
• 206010002383 Angina Pectoris Diseases 0.000 description 4
• 108010039627 Aprotinin Proteins 0.000 description 4
• 241000894006 Bacteria Species 0.000 description 4
• 102000004127 Cytokines Human genes 0.000 description 4
• 108090000695 Cytokines Proteins 0.000 description 4
• AOJJSUZBOXZQNB-TZSSRYMLSA-N Doxorubicin Chemical compound O([C@H]1C[C@@](O)(CC=2C(O)=C3C(=O)C=4C=CC=C(C=4C(=O)C3=C(O)C=21)OC)C(=O)CO)[C@H]1C[C@H](N)[C@H](O)[C@H](C)O1 AOJJSUZBOXZQNB-TZSSRYMLSA-N 0.000 description 4
• 208000000059 Dyspnea Diseases 0.000 description 4
• 206010013975 Dyspnoeas Diseases 0.000 description 4
• 102000004190 Enzymes Human genes 0.000 description 4
• 108090000790 Enzymes Proteins 0.000 description 4
• 206010016803 Fluid overload Diseases 0.000 description 4
• 208000022461 Glomerular disease Diseases 0.000 description 4
• 206010020880 Hypertrophy Diseases 0.000 description 4
• 208000001953 Hypotension Diseases 0.000 description 4
• 108010021625 Immunoglobulin Fragments Proteins 0.000 description 4
• 102000008394 Immunoglobulin Fragments Human genes 0.000 description 4
• 102000003996 Interferon-beta Human genes 0.000 description 4
• 108090000467 Interferon-beta Proteins 0.000 description 4
• 206010049694 Left Ventricular Dysfunction Diseases 0.000 description 4
• 241000699660 Mus musculus Species 0.000 description 4
• 208000007201 Myocardial reperfusion injury Diseases 0.000 description 4
• 125000000729 N-terminal amino-acid group Chemical group 0.000 description 4
• 208000013901 Nephropathies and tubular disease Diseases 0.000 description 4
• 102100028782 Neprilysin Human genes 0.000 description 4
• 108090000028 Neprilysin Proteins 0.000 description 4
• 108091034117 Oligonucleotide Proteins 0.000 description 4
• 241000700159 Rattus Species 0.000 description 4
• 229920002684 Sepharose Polymers 0.000 description 4
• FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 4
• 208000006011 Stroke Diseases 0.000 description 4
• 206010047139 Vasoconstriction Diseases 0.000 description 4
• 208000033774 Ventricular Remodeling Diseases 0.000 description 4
• 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 4
• 239000002253 acid Substances 0.000 description 4
• RJURFGZVJUQBHK-UHFFFAOYSA-N actinomycin D Natural products CC1OC(=O)C(C(C)C)N(C)C(=O)CN(C)C(=O)C2CCCN2C(=O)C(C(C)C)NC(=O)C1NC(=O)C1=C(N)C(=O)C(C)=C2OC(C(C)=CC=C3C(=O)NC4C(=O)NC(C(N5CCCC5C(=O)N(C)CC(=O)N(C)C(C(C)C)C(=O)OC4C)=O)C(C)C)=C3N=C21 RJURFGZVJUQBHK-UHFFFAOYSA-N 0.000 description 4
• 238000007818 agglutination assay Methods 0.000 description 4
• 230000008827 biological function Effects 0.000 description 4
• 239000000872 buffer Substances 0.000 description 4
• 208000020832 chronic kidney disease Diseases 0.000 description 4
• 208000022831 chronic renal failure syndrome Diseases 0.000 description 4
• 238000010367 cloning Methods 0.000 description 4
• 238000010790 dilution Methods 0.000 description 4
• 239000012895 dilution Substances 0.000 description 4
• 229940088598 enzyme Drugs 0.000 description 4
• 230000006870 function Effects 0.000 description 4
• 230000001434 glomerular Effects 0.000 description 4
• 231100000852 glomerular disease Toxicity 0.000 description 4
• 230000000004 hemodynamic effect Effects 0.000 description 4
• 230000036543 hypotension Effects 0.000 description 4
• 230000028993 immune response Effects 0.000 description 4
• 230000001771 impaired effect Effects 0.000 description 4
• 238000001802 infusion Methods 0.000 description 4
• 230000005764 inhibitory process Effects 0.000 description 4
• 238000003780 insertion Methods 0.000 description 4
• 230000037431 insertion Effects 0.000 description 4
• 230000003993 interaction Effects 0.000 description 4
• 238000012933 kinetic analysis Methods 0.000 description 4
• 125000005647 linker group Chemical group 0.000 description 4
• 239000012139 lysis buffer Substances 0.000 description 4
• 244000005700 microbiome Species 0.000 description 4
• 208000010125 myocardial infarction Diseases 0.000 description 4
• 150000002482 oligosaccharides Polymers 0.000 description 4
• 238000011275 oncology therapy Methods 0.000 description 4
• YBYRMVIVWMBXKQ-UHFFFAOYSA-N phenylmethanesulfonyl fluoride Chemical compound FS(=O)(=O)CC1=CC=CC=C1 YBYRMVIVWMBXKQ-UHFFFAOYSA-N 0.000 description 4
• 230000026731 phosphorylation Effects 0.000 description 4
• 238000006366 phosphorylation reaction Methods 0.000 description 4
• 239000013615 primer Substances 0.000 description 4
• 230000008569 process Effects 0.000 description 4
• 230000006337 proteolytic cleavage Effects 0.000 description 4
• 150000003839 salts Chemical class 0.000 description 4
• 241000894007 species Species 0.000 description 4
• 238000003860 storage Methods 0.000 description 4
• 230000035488 systolic blood pressure Effects 0.000 description 4
• 238000011830 transgenic mouse model Methods 0.000 description 4
• 241000701161 unidentified adenovirus Species 0.000 description 4
• 230000025033 vasoconstriction Effects 0.000 description 4
• 108091032973 (ribonucleotides)n+m Proteins 0.000 description 3
• STQGQHZAVUOBTE-UHFFFAOYSA-N 7-Cyan-hept-2t-en-4,6-diinsaeure Natural products C1=2C(O)=C3C(=O)C=4C(OC)=CC=CC=4C(=O)C3=C(O)C=2CC(O)(C(C)=O)CC1OC1CC(N)C(O)C(C)O1 STQGQHZAVUOBTE-UHFFFAOYSA-N 0.000 description 3
• 208000009304 Acute Kidney Injury Diseases 0.000 description 3
• 241000201370 Autographa californica nucleopolyhedrovirus Species 0.000 description 3
• 125000001433 C-terminal amino-acid group Chemical group 0.000 description 3
• 239000003155 DNA primer Substances 0.000 description 3
• 108010092160 Dactinomycin Proteins 0.000 description 3
• 108700039691 Genetic Promoter Regions Proteins 0.000 description 3
• 241000238631 Hexapoda Species 0.000 description 3
• 108700005091 Immunoglobulin Genes Proteins 0.000 description 3
• DCXYFEDJOCDNAF-REOHCLBHSA-N L-asparagine Chemical compound OC(=O)[C@@H](N)CC(N)=O DCXYFEDJOCDNAF-REOHCLBHSA-N 0.000 description 3
• FBOZXECLQNJBKD-ZDUSSCGKSA-N L-methotrexate Chemical compound C=1N=C2N=C(N)N=C(N)C2=NC=1CN(C)C1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 FBOZXECLQNJBKD-ZDUSSCGKSA-N 0.000 description 3
• OUYCCCASQSFEME-QMMMGPOBSA-N L-tyrosine Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-QMMMGPOBSA-N 0.000 description 3
• KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 3
• 241000124008 Mammalia Species 0.000 description 3
• 239000004677 Nylon Substances 0.000 description 3
• 241000283973 Oryctolagus cuniculus Species 0.000 description 3
• 208000033626 Renal failure acute Diseases 0.000 description 3
• 210000001744 T-lymphocyte Anatomy 0.000 description 3
• 229910052770 Uranium Inorganic materials 0.000 description 3
• 230000021736 acetylation Effects 0.000 description 3
• 238000006640 acetylation reaction Methods 0.000 description 3
• 201000011040 acute kidney failure Diseases 0.000 description 3
• 208000012998 acute renal failure Diseases 0.000 description 3
• 239000002671 adjuvant Substances 0.000 description 3
• 230000003321 amplification Effects 0.000 description 3
• 239000005557 antagonist Substances 0.000 description 3
• 230000000840 anti-viral effect Effects 0.000 description 3
• 238000013459 approach Methods 0.000 description 3
• 210000004369 blood Anatomy 0.000 description 3
• 239000008280 blood Substances 0.000 description 3
• 238000004113 cell culture Methods 0.000 description 3
• DQLATGHUWYMOKM-UHFFFAOYSA-L cisplatin Chemical compound N[Pt](N)(Cl)Cl DQLATGHUWYMOKM-UHFFFAOYSA-L 0.000 description 3
• 238000003776 cleavage reaction Methods 0.000 description 3
• 230000002860 competitive effect Effects 0.000 description 3
• 239000002299 complementary DNA Substances 0.000 description 3
• 230000021615 conjugation Effects 0.000 description 3
• 125000004122 cyclic group Chemical group 0.000 description 3
• 229940127089 cytotoxic agent Drugs 0.000 description 3
• 239000002254 cytotoxic agent Substances 0.000 description 3
• STQGQHZAVUOBTE-VGBVRHCVSA-N daunorubicin Chemical compound O([C@H]1C[C@@](O)(CC=2C(O)=C3C(=O)C=4C=CC=C(C=4C(=O)C3=C(O)C=21)OC)C(C)=O)[C@H]1C[C@H](N)[C@H](O)[C@H](C)O1 STQGQHZAVUOBTE-VGBVRHCVSA-N 0.000 description 3
• 230000007423 decrease Effects 0.000 description 3
• 206010012601 diabetes mellitus Diseases 0.000 description 3
• 238000011833 dog model Methods 0.000 description 3
• 231100000673 dose–response relationship Toxicity 0.000 description 3
• 229940079593 drug Drugs 0.000 description 3
• 210000001671 embryonic stem cell Anatomy 0.000 description 3
• 230000001747 exhibiting effect Effects 0.000 description 3
• 238000002347 injection Methods 0.000 description 3
• 239000007924 injection Substances 0.000 description 3
• 230000001404 mediated effect Effects 0.000 description 3
• 229910021645 metal ion Inorganic materials 0.000 description 3
• 229960000485 methotrexate Drugs 0.000 description 3
• 230000036963 noncompetitive effect Effects 0.000 description 3
• 238000003199 nucleic acid amplification method Methods 0.000 description 3
• 229920001778 nylon Polymers 0.000 description 3
• 229920001542 oligosaccharide Polymers 0.000 description 3
• 208000030613 peripheral artery disease Diseases 0.000 description 3
• 230000001323 posttranslational effect Effects 0.000 description 3
• 230000004853 protein function Effects 0.000 description 3
• 230000002285 radioactive effect Effects 0.000 description 3
• 239000000523 sample Substances 0.000 description 3
• 230000007017 scission Effects 0.000 description 3
• 238000002741 site-directed mutagenesis Methods 0.000 description 3
• 238000003786 synthesis reaction Methods 0.000 description 3
• 230000009885 systemic effect Effects 0.000 description 3
• 238000002560 therapeutic procedure Methods 0.000 description 3
• 230000001988 toxicity Effects 0.000 description 3
• 231100000419 toxicity Toxicity 0.000 description 3
• 230000002103 transcriptional effect Effects 0.000 description 3
• YBJHBAHKTGYVGT-ZKWXMUAHSA-N (+)-Biotin Chemical compound N1C(=O)N[C@@H]2[C@H](CCCCC(=O)O)SC[C@@H]21 YBJHBAHKTGYVGT-ZKWXMUAHSA-N 0.000 description 2
• 101710112752 Cytotoxin Proteins 0.000 description 2
• 208000007342 Diabetic Nephropathies Diseases 0.000 description 2
• BWGNESOTFCXPMA-UHFFFAOYSA-N Dihydrogen disulfide Chemical compound SS BWGNESOTFCXPMA-UHFFFAOYSA-N 0.000 description 2
• 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 2
• 241000196324 Embryophyta Species 0.000 description 2
• WHUUTDBJXJRKMK-UHFFFAOYSA-N Glutamic acid Natural products OC(=O)C(N)CCC(O)=O WHUUTDBJXJRKMK-UHFFFAOYSA-N 0.000 description 2
• DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 2
• 208000009329 Graft vs Host Disease Diseases 0.000 description 2
• 108010017080 Granulocyte Colony-Stimulating Factor Proteins 0.000 description 2
• 102100039619 Granulocyte colony-stimulating factor Human genes 0.000 description 2
• 108010017213 Granulocyte-Macrophage Colony-Stimulating Factor Proteins 0.000 description 2
• 102100039620 Granulocyte-macrophage colony-stimulating factor Human genes 0.000 description 2
• HVLSXIKZNLPZJJ-TXZCQADKSA-N HA peptide Chemical compound C([C@@H](C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](C(C)C)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N[C@@H](C)C(O)=O)NC(=O)[C@H]1N(CCC1)C(=O)[C@@H](N)CC=1C=CC(O)=CC=1)C1=CC=C(O)C=C1 HVLSXIKZNLPZJJ-TXZCQADKSA-N 0.000 description 2
• 101710154606 Hemagglutinin Proteins 0.000 description 2
• 241000282412 Homo Species 0.000 description 2
• 241000725303 Human immunodeficiency virus Species 0.000 description 2
• 241000701806 Human papillomavirus Species 0.000 description 2
• DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 2
• 108010054477 Immunoglobulin Fab Fragments Proteins 0.000 description 2
• 102000001706 Immunoglobulin Fab Fragments Human genes 0.000 description 2
• 206010022095 Injection Site reaction Diseases 0.000 description 2
• 102100039729 Interferon alpha-21 Human genes 0.000 description 2
• 102100036532 Interferon alpha-8 Human genes 0.000 description 2
• 101710106105 Interferon alpha-F Proteins 0.000 description 2
• 108010002350 Interleukin-2 Proteins 0.000 description 2
• 102000000588 Interleukin-2 Human genes 0.000 description 2
• 108090001005 Interleukin-6 Proteins 0.000 description 2
• 102000004889 Interleukin-6 Human genes 0.000 description 2
• CKLJMWTZIZZHCS-REOHCLBHSA-N L-aspartic acid Chemical compound OC(=O)[C@@H](N)CC(O)=O CKLJMWTZIZZHCS-REOHCLBHSA-N 0.000 description 2
• WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 description 2
• GQYIWUVLTXOXAJ-UHFFFAOYSA-N Lomustine Chemical compound ClCCN(N=O)C(=O)NC1CCCCC1 GQYIWUVLTXOXAJ-UHFFFAOYSA-N 0.000 description 2
• 239000007987 MES buffer Substances 0.000 description 2
• 241000282567 Macaca fascicularis Species 0.000 description 2
• 239000000020 Nitrocellulose Substances 0.000 description 2
• 108700026244 Open Reading Frames Proteins 0.000 description 2
• 101710093908 Outer capsid protein VP4 Proteins 0.000 description 2
• 101710135467 Outer capsid protein sigma-1 Proteins 0.000 description 2
• 238000012408 PCR amplification Methods 0.000 description 2
• 239000002033 PVDF binder Substances 0.000 description 2
• 241001494479 Pecora Species 0.000 description 2
• 108700019535 Phosphoprotein Phosphatases Proteins 0.000 description 2
• 102000045595 Phosphoprotein Phosphatases Human genes 0.000 description 2
• 101710182846 Polyhedrin Proteins 0.000 description 2
• 229920001213 Polysorbate 20 Polymers 0.000 description 2
• 101710176177 Protein A56 Proteins 0.000 description 2
• 239000012083 RIPA buffer Substances 0.000 description 2
• 108010008281 Recombinant Fusion Proteins Proteins 0.000 description 2
• 102000007056 Recombinant Fusion Proteins Human genes 0.000 description 2
• 108090000783 Renin Proteins 0.000 description 2
• 102100028255 Renin Human genes 0.000 description 2
• 208000007660 Residual Neoplasm Diseases 0.000 description 2
• MTCFGRXMJLQNBG-UHFFFAOYSA-N Serine Natural products OCC(N)C(O)=O MTCFGRXMJLQNBG-UHFFFAOYSA-N 0.000 description 2
• 108091081024 Start codon Proteins 0.000 description 2
• 241000723873 Tobacco mosaic virus Species 0.000 description 2
• 239000013504 Triton X-100 Substances 0.000 description 2
• 229920004890 Triton X-100 Polymers 0.000 description 2
• 108060008682 Tumor Necrosis Factor Proteins 0.000 description 2
• 102000000852 Tumor Necrosis Factor-alpha Human genes 0.000 description 2
• VGQOVCHZGQWAOI-UHFFFAOYSA-N UNPD55612 Natural products N1C(O)C2CC(C=CC(N)=O)=CN2C(=O)C2=CC=C(C)C(O)=C12 VGQOVCHZGQWAOI-UHFFFAOYSA-N 0.000 description 2
• 241000251539 Vertebrata <Metazoa> Species 0.000 description 2
• JXLYSJRDGCGARV-WWYNWVTFSA-N Vinblastine Natural products O=C(O[C@H]1[C@](O)(C(=O)OC)[C@@H]2N(C)c3c(cc(c(OC)c3)[C@]3(C(=O)OC)c4[nH]c5c(c4CCN4C[C@](O)(CC)C[C@H](C3)C4)cccc5)[C@@]32[C@H]2[C@@]1(CC)C=CCN2CC3)C JXLYSJRDGCGARV-WWYNWVTFSA-N 0.000 description 2
• 208000036142 Viral infection Diseases 0.000 description 2
• 230000002378 acidificating effect Effects 0.000 description 2
• RJURFGZVJUQBHK-IIXSONLDSA-N actinomycin D Chemical compound C[C@H]1OC(=O)[C@H](C(C)C)N(C)C(=O)CN(C)C(=O)[C@@H]2CCCN2C(=O)[C@@H](C(C)C)NC(=O)[C@H]1NC(=O)C1=C(N)C(=O)C(C)=C2OC(C(C)=CC=C3C(=O)N[C@@H]4C(=O)N[C@@H](C(N5CCC[C@H]5C(=O)N(C)CC(=O)N(C)[C@@H](C(C)C)C(=O)O[C@@H]4C)=O)C(C)C)=C3N=C21 RJURFGZVJUQBHK-IIXSONLDSA-N 0.000 description 2
• 230000002776 aggregation Effects 0.000 description 2
• 238000004220 aggregation Methods 0.000 description 2
• 125000001931 aliphatic group Chemical group 0.000 description 2
• 230000009435 amidation Effects 0.000 description 2
• 238000007112 amidation reaction Methods 0.000 description 2
• 150000001408 amides Chemical group 0.000 description 2
• VGQOVCHZGQWAOI-HYUHUPJXSA-N anthramycin Chemical compound N1[C@@H](O)[C@@H]2CC(\C=C\C(N)=O)=CN2C(=O)C2=CC=C(C)C(O)=C12 VGQOVCHZGQWAOI-HYUHUPJXSA-N 0.000 description 2
• 230000000340 anti-metabolite Effects 0.000 description 2
• 230000000890 antigenic effect Effects 0.000 description 2
• 229940100197 antimetabolite Drugs 0.000 description 2
• 239000002256 antimetabolite Substances 0.000 description 2
• 229960004405 aprotinin Drugs 0.000 description 2
• 125000003118 aryl group Chemical group 0.000 description 2
• 238000002869 basic local alignment search tool Methods 0.000 description 2
• 230000008901 benefit Effects 0.000 description 2
• 108010005774 beta-Galactosidase Proteins 0.000 description 2
• 230000001588 bifunctional effect Effects 0.000 description 2
• 239000012472 biological sample Substances 0.000 description 2
• 229960000074 biopharmaceutical Drugs 0.000 description 2
• 150000001720 carbohydrates Chemical class 0.000 description 2
• 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 2
• 238000007385 chemical modification Methods 0.000 description 2
• 239000003153 chemical reaction reagent Substances 0.000 description 2
• 210000004978 chinese hamster ovary cell Anatomy 0.000 description 2
• 238000004587 chromatography analysis Methods 0.000 description 2
• 210000000349 chromosome Anatomy 0.000 description 2
• 239000013599 cloning vector Substances 0.000 description 2
• 230000000295 complement effect Effects 0.000 description 2
• 238000004590 computer program Methods 0.000 description 2
• 230000001268 conjugating effect Effects 0.000 description 2
• 238000013270 controlled release Methods 0.000 description 2
• 238000007796 conventional method Methods 0.000 description 2
• 238000012937 correction Methods 0.000 description 2
• 230000001472 cytotoxic effect Effects 0.000 description 2
• 239000002619 cytotoxin Substances 0.000 description 2
• 229960000640 dactinomycin Drugs 0.000 description 2
• 238000013480 data collection Methods 0.000 description 2
• 229960000975 daunorubicin Drugs 0.000 description 2
• 230000003247 decreasing effect Effects 0.000 description 2
• 230000005860 defense response to virus Effects 0.000 description 2
• CFCUWKMKBJTWLW-UHFFFAOYSA-N deoliosyl-3C-alpha-L-digitoxosyl-MTM Natural products CC=1C(O)=C2C(O)=C3C(=O)C(OC4OC(C)C(O)C(OC5OC(C)C(O)C(OC6OC(C)C(O)C(C)(O)C6)C5)C4)C(C(OC)C(=O)C(O)C(C)O)CC3=CC2=CC=1OC(OC(C)C1O)CC1OC1CC(O)C(O)C(C)O1 CFCUWKMKBJTWLW-UHFFFAOYSA-N 0.000 description 2
• KXGVEGMKQFWNSR-LLQZFEROSA-N deoxycholic acid Chemical compound C([C@H]1CC2)[C@H](O)CC[C@]1(C)[C@@H]1[C@@H]2[C@@H]2CC[C@H]([C@@H](CCC(O)=O)C)[C@@]2(C)[C@@H](O)C1 KXGVEGMKQFWNSR-LLQZFEROSA-N 0.000 description 2
• 229960003964 deoxycholic acid Drugs 0.000 description 2
• 208000033679 diabetic kidney disease Diseases 0.000 description 2
• 238000002405 diagnostic procedure Methods 0.000 description 2
• 230000004069 differentiation Effects 0.000 description 2
• 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 2
• 229940042399 direct acting antivirals protease inhibitors Drugs 0.000 description 2
• 239000002934 diuretic Substances 0.000 description 2
• 229960004679 doxorubicin Drugs 0.000 description 2
• 238000012377 drug delivery Methods 0.000 description 2
• 238000001962 electrophoresis Methods 0.000 description 2
• 230000002708 enhancing effect Effects 0.000 description 2
• 238000013265 extended release Methods 0.000 description 2
• 235000013861 fat-free Nutrition 0.000 description 2
• GNBHRKFJIUUOQI-UHFFFAOYSA-N fluorescein Chemical compound O1C(=O)C2=CC=CC=C2C21C1=CC=C(O)C=C1OC1=CC(O)=CC=C21 GNBHRKFJIUUOQI-UHFFFAOYSA-N 0.000 description 2
• 230000022244 formylation Effects 0.000 description 2
• 238000006170 formylation reaction Methods 0.000 description 2
• 238000005227 gel permeation chromatography Methods 0.000 description 2
• 238000012817 gel-diffusion technique Methods 0.000 description 2
• 238000002873 global sequence alignment Methods 0.000 description 2
• RWSXRVCMGQZWBV-WDSKDSINSA-N glutathione Chemical compound OC(=O)[C@@H](N)CCC(=O)N[C@@H](CS)C(=O)NCC(O)=O RWSXRVCMGQZWBV-WDSKDSINSA-N 0.000 description 2
• 208000024908 graft versus host disease Diseases 0.000 description 2
• 239000003102 growth factor Substances 0.000 description 2
• 239000000122 growth hormone Substances 0.000 description 2
• 210000002216 heart Anatomy 0.000 description 2
• 208000006454 hepatitis Diseases 0.000 description 2
• 231100000283 hepatitis Toxicity 0.000 description 2
• 238000002744 homologous recombination Methods 0.000 description 2
• 230000006801 homologous recombination Effects 0.000 description 2
• 230000002209 hydrophobic effect Effects 0.000 description 2
• 125000002887 hydroxy group Chemical group [H]O* 0.000 description 2
• 230000006303 immediate early viral mRNA transcription Effects 0.000 description 2
• 230000000951 immunodiffusion Effects 0.000 description 2
• 239000012133 immunoprecipitate Substances 0.000 description 2
• 230000001976 improved effect Effects 0.000 description 2
• 238000011534 incubation Methods 0.000 description 2
• 230000001939 inductive effect Effects 0.000 description 2
• 239000003112 inhibitor Substances 0.000 description 2
• ZPNFWUPYTFPOJU-LPYSRVMUSA-N iniprol Chemical compound C([C@H]1C(=O)NCC(=O)NCC(=O)N[C@H]2CSSC[C@H]3C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@H](C(N[C@H](C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC=4C=CC(O)=CC=4)C(=O)N[C@@H](CC=4C=CC=CC=4)C(=O)N[C@@H](CC=4C=CC(O)=CC=4)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](C)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](C)C(=O)NCC(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CSSC[C@H](NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C)NC(=O)[C@H](CO)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CC=4C=CC=CC=4)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CCCCN)NC(=O)[C@H](C)NC(=O)[C@H](CCCNC(N)=N)NC2=O)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CSSC[C@H](NC(=O)[C@H](CC=2C=CC=CC=2)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H]2N(CCC2)C(=O)[C@@H](N)CCCNC(N)=N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(O)=O)C(=O)N2[C@@H](CCC2)C(=O)N2[C@@H](CCC2)C(=O)N[C@@H](CC=2C=CC(O)=CC=2)C(=O)N[C@@H]([C@@H](C)O)C(=O)NCC(=O)N2[C@@H](CCC2)C(=O)N3)C(=O)NCC(=O)NCC(=O)N[C@@H](C)C(O)=O)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@H](C(=O)N[C@@H](CC=2C=CC=CC=2)C(=O)N[C@H](C(=O)N1)C(C)C)[C@@H](C)O)[C@@H](C)CC)=O)[C@@H](C)CC)C1=CC=C(O)C=C1 ZPNFWUPYTFPOJU-LPYSRVMUSA-N 0.000 description 2
• 230000000977 initiatory effect Effects 0.000 description 2
• 108010010648 interferon alfacon-1 Proteins 0.000 description 2
• 108010047126 interferon-alpha 8 Proteins 0.000 description 2
• 229940047124 interferons Drugs 0.000 description 2
• 210000002490 intestinal epithelial cell Anatomy 0.000 description 2
• 238000010253 intravenous injection Methods 0.000 description 2
• 150000002632 lipids Chemical class 0.000 description 2
• 230000002934 lysing effect Effects 0.000 description 2
• 201000001441 melanoma Diseases 0.000 description 2
• GLVAUDGFNGKCSF-UHFFFAOYSA-N mercaptopurine Chemical compound S=C1NC=NC2=C1NC=N2 GLVAUDGFNGKCSF-UHFFFAOYSA-N 0.000 description 2
• 108020004999 messenger RNA Proteins 0.000 description 2
• 125000001360 methionine group Chemical group N[C@@H](CCSC)C(=O)* 0.000 description 2
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 2
• 235000013336 milk Nutrition 0.000 description 2
• 239000008267 milk Substances 0.000 description 2
• 210000004080 milk Anatomy 0.000 description 2
• CFCUWKMKBJTWLW-BKHRDMLASA-N mithramycin Chemical compound O([C@@H]1C[C@@H](O[C@H](C)[C@H]1O)OC=1C=C2C=C3C[C@H]([C@@H](C(=O)C3=C(O)C2=C(O)C=1C)O[C@@H]1O[C@H](C)[C@@H](O)[C@H](O[C@@H]2O[C@H](C)[C@H](O)[C@H](O[C@@H]3O[C@H](C)[C@@H](O)[C@@](C)(O)C3)C2)C1)[C@H](OC)C(=O)[C@@H](O)[C@@H](C)O)[C@H]1C[C@@H](O)[C@H](O)[C@@H](C)O1 CFCUWKMKBJTWLW-BKHRDMLASA-N 0.000 description 2
• 238000001823 molecular biology technique Methods 0.000 description 2
• 238000002703 mutagenesis Methods 0.000 description 2
• 231100000350 mutagenesis Toxicity 0.000 description 2
• 230000001452 natriuretic effect Effects 0.000 description 2
• 229920001220 nitrocellulos Polymers 0.000 description 2
• 230000006320 pegylation Effects 0.000 description 2
• 239000000137 peptide hydrolase inhibitor Substances 0.000 description 2
• 230000007030 peptide scission Effects 0.000 description 2
• 239000002953 phosphate buffered saline Substances 0.000 description 2
• 239000003934 phosphoprotein phosphatase inhibitor Substances 0.000 description 2
• 229960003171 plicamycin Drugs 0.000 description 2
• 239000000256 polyoxyethylene sorbitan monolaurate Substances 0.000 description 2
• 229920002981 polyvinylidene fluoride Polymers 0.000 description 2
• 238000001556 precipitation Methods 0.000 description 2
• 230000035755 proliferation Effects 0.000 description 2
• AQHHHDLHHXJYJD-UHFFFAOYSA-N propranolol Chemical compound C1=CC=C2C(OCC(O)CNC(C)C)=CC=CC2=C1 AQHHHDLHHXJYJD-UHFFFAOYSA-N 0.000 description 2
• 230000002685 pulmonary effect Effects 0.000 description 2
• RXWNCPJZOCPEPQ-NVWDDTSBSA-N puromycin Chemical compound C1=CC(OC)=CC=C1C[C@H](N)C(=O)N[C@H]1[C@@H](O)[C@H](N2C3=NC=NC(=C3N=C2)N(C)C)O[C@@H]1CO RXWNCPJZOCPEPQ-NVWDDTSBSA-N 0.000 description 2
• 239000012857 radioactive material Substances 0.000 description 2
• 238000003259 recombinant expression Methods 0.000 description 2
• 230000006798 recombination Effects 0.000 description 2
• 230000009467 reduction Effects 0.000 description 2
• 238000006722 reduction reaction Methods 0.000 description 2
• 230000010076 replication Effects 0.000 description 2
• 230000004044 response Effects 0.000 description 2
• 238000012552 review Methods 0.000 description 2
• 239000012723 sample buffer Substances 0.000 description 2
• 230000003248 secreting effect Effects 0.000 description 2
• 238000002864 sequence alignment Methods 0.000 description 2
• 229910052708 sodium Inorganic materials 0.000 description 2
• 239000011734 sodium Substances 0.000 description 2
• 239000011780 sodium chloride Substances 0.000 description 2
• 239000001509 sodium citrate Substances 0.000 description 2
• 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 2
• 238000002415 sodium dodecyl sulfate polyacrylamide gel electrophoresis Methods 0.000 description 2
• CMZUMMUJMWNLFH-UHFFFAOYSA-N sodium metavanadate Chemical compound [Na+].[O-][V](=O)=O CMZUMMUJMWNLFH-UHFFFAOYSA-N 0.000 description 2
• 210000000952 spleen Anatomy 0.000 description 2
• 210000004988 splenocyte Anatomy 0.000 description 2
• 238000010561 standard procedure Methods 0.000 description 2
• 229940126585 therapeutic drug Drugs 0.000 description 2
• WYWHKKSPHMUBEB-UHFFFAOYSA-N tioguanine Chemical compound N1C(N)=NC(=S)C2=C1N=CN2 WYWHKKSPHMUBEB-UHFFFAOYSA-N 0.000 description 2
• 229940108519 trasylol Drugs 0.000 description 2
• 238000011269 treatment regimen Methods 0.000 description 2
• 238000010798 ubiquitination Methods 0.000 description 2
• 230000034512 ubiquitination Effects 0.000 description 2
• 210000002700 urine Anatomy 0.000 description 2
• 229910052720 vanadium Inorganic materials 0.000 description 2
• 230000002861 ventricular Effects 0.000 description 2
• 229960003048 vinblastine Drugs 0.000 description 2
• JXLYSJRDGCGARV-XQKSVPLYSA-N vincaleukoblastine Chemical compound C([C@@H](C[C@]1(C(=O)OC)C=2C(=CC3=C([C@]45[C@H]([C@@]([C@H](OC(C)=O)[C@]6(CC)C=CCN([C@H]56)CC4)(O)C(=O)OC)N3C)C=2)OC)C[C@@](C2)(O)CC)N2CCC2=C1NC1=CC=CC=C21 JXLYSJRDGCGARV-XQKSVPLYSA-N 0.000 description 2
• OGWKCGZFUXNPDA-UHFFFAOYSA-N vincristine Natural products C1C(CC)(O)CC(CC2(C(=O)OC)C=3C(=CC4=C(C56C(C(C(OC(C)=O)C7(CC)C=CCN(C67)CC5)(O)C(=O)OC)N4C=O)C=3)OC)CN1CCC1=C2NC2=CC=CC=C12 OGWKCGZFUXNPDA-UHFFFAOYSA-N 0.000 description 2
• 229960004528 vincristine Drugs 0.000 description 2
• OGWKCGZFUXNPDA-XQKSVPLYSA-N vincristine Chemical compound C([N@]1C[C@@H](C[C@]2(C(=O)OC)C=3C(=CC4=C([C@]56[C@H]([C@@]([C@H](OC(C)=O)[C@]7(CC)C=CCN([C@H]67)CC5)(O)C(=O)OC)N4C=O)C=3)OC)C[C@@](C1)(O)CC)CC1=C2NC2=CC=CC=C12 OGWKCGZFUXNPDA-XQKSVPLYSA-N 0.000 description 2
• 230000009385 viral infection Effects 0.000 description 2
• 210000005253 yeast cell Anatomy 0.000 description 2
• 229910000166 zirconium phosphate Inorganic materials 0.000 description 2
• DIGQNXIGRZPYDK-WKSCXVIASA-N (2R)-6-amino-2-[[2-[[(2S)-2-[[2-[[(2R)-2-[[(2S)-2-[[(2R,3S)-2-[[2-[[(2S)-2-[[2-[[(2S)-2-[[(2S)-2-[[(2R)-2-[[(2S,3S)-2-[[(2R)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[2-[[(2S)-2-[[(2R)-2-[[2-[[2-[[2-[(2-amino-1-hydroxyethylidene)amino]-3-carboxy-1-hydroxypropylidene]amino]-1-hydroxy-3-sulfanylpropylidene]amino]-1-hydroxyethylidene]amino]-1-hydroxy-3-sulfanylpropylidene]amino]-1,3-dihydroxypropylidene]amino]-1-hydroxyethylidene]amino]-1-hydroxypropylidene]amino]-1,3-dihydroxypropylidene]amino]-1,3-dihydroxypropylidene]amino]-1-hydroxy-3-sulfanylpropylidene]amino]-1,3-dihydroxybutylidene]amino]-1-hydroxy-3-sulfanylpropylidene]amino]-1-hydroxypropylidene]amino]-1,3-dihydroxypropylidene]amino]-1-hydroxyethylidene]amino]-1,5-dihydroxy-5-iminopentylidene]amino]-1-hydroxy-3-sulfanylpropylidene]amino]-1,3-dihydroxybutylidene]amino]-1-hydroxy-3-sulfanylpropylidene]amino]-1,3-dihydroxypropylidene]amino]-1-hydroxyethylidene]amino]-1-hydroxy-3-sulfanylpropylidene]amino]-1-hydroxyethylidene]amino]hexanoic acid Chemical compound C[C@@H]([C@@H](C(=N[C@@H](CS)C(=N[C@@H](C)C(=N[C@@H](CO)C(=NCC(=N[C@@H](CCC(=N)O)C(=NC(CS)C(=N[C@H]([C@H](C)O)C(=N[C@H](CS)C(=N[C@H](CO)C(=NCC(=N[C@H](CS)C(=NCC(=N[C@H](CCCCN)C(=O)O)O)O)O)O)O)O)O)O)O)O)O)O)O)N=C([C@H](CS)N=C([C@H](CO)N=C([C@H](CO)N=C([C@H](C)N=C(CN=C([C@H](CO)N=C([C@H](CS)N=C(CN=C(C(CS)N=C(C(CC(=O)O)N=C(CN)O)O)O)O)O)O)O)O)O)O)O)O DIGQNXIGRZPYDK-WKSCXVIASA-N 0.000 description 1
• ASWBNKHCZGQVJV-UHFFFAOYSA-N (3-hexadecanoyloxy-2-hydroxypropyl) 2-(trimethylazaniumyl)ethyl phosphate Chemical compound CCCCCCCCCCCCCCCC(=O)OCC(O)COP([O-])(=O)OCC[N+](C)(C)C ASWBNKHCZGQVJV-UHFFFAOYSA-N 0.000 description 1
• CUKWUWBLQQDQAC-VEQWQPCFSA-N (3s)-3-amino-4-[[(2s)-1-[[(2s)-1-[[(2s)-1-[[(2s,3s)-1-[[(2s)-1-[(2s)-2-[[(1s)-1-carboxyethyl]carbamoyl]pyrrolidin-1-yl]-3-(1h-imidazol-5-yl)-1-oxopropan-2-yl]amino]-3-methyl-1-oxopentan-2-yl]amino]-3-(4-hydroxyphenyl)-1-oxopropan-2-yl]amino]-3-methyl-1-ox Chemical compound C([C@@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CC=1NC=NC=1)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](C)C(O)=O)NC(=O)[C@@H](NC(=O)[C@H](CCCN=C(N)N)NC(=O)[C@@H](N)CC(O)=O)C(C)C)C1=CC=C(O)C=C1 CUKWUWBLQQDQAC-VEQWQPCFSA-N 0.000 description 1
• MZOFCQQQCNRIBI-VMXHOPILSA-N (3s)-4-[[(2s)-1-[[(2s)-1-[[(1s)-1-carboxy-2-hydroxyethyl]amino]-4-methyl-1-oxopentan-2-yl]amino]-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-3-[[2-[[(2s)-2,6-diaminohexanoyl]amino]acetyl]amino]-4-oxobutanoic acid Chemical compound OC[C@@H](C(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCN=C(N)N)NC(=O)[C@H](CC(O)=O)NC(=O)CNC(=O)[C@@H](N)CCCCN MZOFCQQQCNRIBI-VMXHOPILSA-N 0.000 description 1
• FDKXTQMXEQVLRF-ZHACJKMWSA-N (E)-dacarbazine Chemical compound CN(C)\N=N\c1[nH]cnc1C(N)=O FDKXTQMXEQVLRF-ZHACJKMWSA-N 0.000 description 1
• IAKHMKGGTNLKSZ-INIZCTEOSA-N (S)-colchicine Chemical compound C1([C@@H](NC(C)=O)CC2)=CC(=O)C(OC)=CC=C1C1=C2C=C(OC)C(OC)=C1OC IAKHMKGGTNLKSZ-INIZCTEOSA-N 0.000 description 1
• VYEWZWBILJHHCU-OMQUDAQFSA-N (e)-n-[(2s,3r,4r,5r,6r)-2-[(2r,3r,4s,5s,6s)-3-acetamido-5-amino-4-hydroxy-6-(hydroxymethyl)oxan-2-yl]oxy-6-[2-[(2r,3s,4r,5r)-5-(2,4-dioxopyrimidin-1-yl)-3,4-dihydroxyoxolan-2-yl]-2-hydroxyethyl]-4,5-dihydroxyoxan-3-yl]-5-methylhex-2-enamide Chemical compound N1([C@@H]2O[C@@H]([C@H]([C@H]2O)O)C(O)C[C@@H]2[C@H](O)[C@H](O)[C@H]([C@@H](O2)O[C@@H]2[C@@H]([C@@H](O)[C@H](N)[C@@H](CO)O2)NC(C)=O)NC(=O)/C=C/CC(C)C)C=CC(=O)NC1=O VYEWZWBILJHHCU-OMQUDAQFSA-N 0.000 description 1
• NFGXHKASABOEEW-UHFFFAOYSA-N 1-methylethyl 11-methoxy-3,7,11-trimethyl-2,4-dodecadienoate Chemical compound COC(C)(C)CCCC(C)CC=CC(C)=CC(=O)OC(C)C NFGXHKASABOEEW-UHFFFAOYSA-N 0.000 description 1
• 108010041801 2',3'-Cyclic Nucleotide 3'-Phosphodiesterase Proteins 0.000 description 1
• UFBJCMHMOXMLKC-UHFFFAOYSA-N 2,4-dinitrophenol Chemical compound OC1=CC=C([N+]([O-])=O)C=C1[N+]([O-])=O UFBJCMHMOXMLKC-UHFFFAOYSA-N 0.000 description 1
• GOJUJUVQIVIZAV-UHFFFAOYSA-N 2-amino-4,6-dichloropyrimidine-5-carbaldehyde Chemical group NC1=NC(Cl)=C(C=O)C(Cl)=N1 GOJUJUVQIVIZAV-UHFFFAOYSA-N 0.000 description 1
• WOVKYSAHUYNSMH-RRKCRQDMSA-N 5-bromodeoxyuridine Chemical compound C1[C@H](O)[C@@H](CO)O[C@H]1N1C(=O)NC(=O)C(Br)=C1 WOVKYSAHUYNSMH-RRKCRQDMSA-N 0.000 description 1
• ODHCTXKNWHHXJC-VKHMYHEASA-N 5-oxo-L-proline Chemical compound OC(=O)[C@@H]1CCC(=O)N1 ODHCTXKNWHHXJC-VKHMYHEASA-N 0.000 description 1
• CJIJXIFQYOPWTF-UHFFFAOYSA-N 7-hydroxycoumarin Natural products O1C(=O)C=CC2=CC(O)=CC=C21 CJIJXIFQYOPWTF-UHFFFAOYSA-N 0.000 description 1
• 230000005730 ADP ribosylation Effects 0.000 description 1
• 208000030507 AIDS Diseases 0.000 description 1
• 108010066676 Abrin Proteins 0.000 description 1
• 240000005020 Acaciella glauca Species 0.000 description 1
• 108010022752 Acetylcholinesterase Proteins 0.000 description 1
• 102100033639 Acetylcholinesterase Human genes 0.000 description 1
• 101710170757 Acidic leucine-rich nuclear phosphoprotein 32 family member A Proteins 0.000 description 1
• 206010069754 Acquired gene mutation Diseases 0.000 description 1
• 102100029457 Adenine phosphoribosyltransferase Human genes 0.000 description 1
• 108010024223 Adenine phosphoribosyltransferase Proteins 0.000 description 1
• 101800004616 Adrenomedullin Proteins 0.000 description 1
• 102400001318 Adrenomedullin Human genes 0.000 description 1
• 108010000239 Aequorin Proteins 0.000 description 1
• 229920000936 Agarose Polymers 0.000 description 1
• 102400000068 Angiostatin Human genes 0.000 description 1
• 108010079709 Angiostatins Proteins 0.000 description 1
• 102400000345 Angiotensin-2 Human genes 0.000 description 1
• 101800000733 Angiotensin-2 Proteins 0.000 description 1
• 108010032595 Antibody Binding Sites Proteins 0.000 description 1
• 101001084702 Arabidopsis thaliana Histone H2B.10 Proteins 0.000 description 1
• 241000557639 Araucaria bidwillii Species 0.000 description 1
• 200000000007 Arterial disease Diseases 0.000 description 1
• 206010003445 Ascites Diseases 0.000 description 1
• DCXYFEDJOCDNAF-UHFFFAOYSA-N Asparagine Natural products OC(=O)C(N)CC(N)=O DCXYFEDJOCDNAF-UHFFFAOYSA-N 0.000 description 1
• 241000972773 Aulopiformes Species 0.000 description 1
• 241000271566 Aves Species 0.000 description 1
• 208000032791 BCR-ABL1 positive chronic myelogenous leukemia Diseases 0.000 description 1
• 235000014469 Bacillus subtilis Nutrition 0.000 description 1
• 101710125298 Beta-defensin 2 Proteins 0.000 description 1
• 102100038326 Beta-defensin 4A Human genes 0.000 description 1
• 101710176951 Beta-defensin 4A Proteins 0.000 description 1
• 102100026189 Beta-galactosidase Human genes 0.000 description 1
• 108010006654 Bleomycin Proteins 0.000 description 1
• 241000283690 Bos taurus Species 0.000 description 1
• 206010006187 Breast cancer Diseases 0.000 description 1
• 208000026310 Breast neoplasm Diseases 0.000 description 1
• 101000583086 Bunodosoma granuliferum Delta-actitoxin-Bgr2b Proteins 0.000 description 1
• COVZYZSDYWQREU-UHFFFAOYSA-N Busulfan Chemical compound CS(=O)(=O)OCCCCOS(C)(=O)=O COVZYZSDYWQREU-UHFFFAOYSA-N 0.000 description 1
• 108010053652 Butyrylcholinesterase Proteins 0.000 description 1
• YNXLOPYTAAFMTN-SBUIBGKBSA-N C([C@H](N)C(=O)N1CCC[C@H]1C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CCCCN)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](C)C(=O)N1[C@@H](CCC1)C(=O)NCC(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](C)C(=O)N[C@@H](CO)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N[C@@H](C)C(=O)N[C@@H](CO)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC=1NC=NC=1)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(N)=O)C1=CC=C(O)C=C1 Chemical compound C([C@H](N)C(=O)N1CCC[C@H]1C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CCCCN)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](C)C(=O)N1[C@@H](CCC1)C(=O)NCC(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](C)C(=O)N[C@@H](CO)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N[C@@H](C)C(=O)N[C@@H](CO)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC=1NC=NC=1)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(N)=O)C1=CC=C(O)C=C1 YNXLOPYTAAFMTN-SBUIBGKBSA-N 0.000 description 1
• 102100023705 C-C motif chemokine 14 Human genes 0.000 description 1
• 102100031478 C-type natriuretic peptide Human genes 0.000 description 1
• 101100494773 Caenorhabditis elegans ctl-2 gene Proteins 0.000 description 1
• 108090000932 Calcitonin Gene-Related Peptide Proteins 0.000 description 1
• 241000282836 Camelus dromedarius Species 0.000 description 1
• 241000283707 Capra Species 0.000 description 1
• DLGOEMSEDOSKAD-UHFFFAOYSA-N Carmustine Chemical compound ClCCNC(=O)N(N=O)CCCl DLGOEMSEDOSKAD-UHFFFAOYSA-N 0.000 description 1
• 241000701489 Cauliflower mosaic virus Species 0.000 description 1
• 241000700199 Cavia porcellus Species 0.000 description 1
• 101150015280 Cel gene Proteins 0.000 description 1
• 241000282693 Cercopithecidae Species 0.000 description 1
• 108010078239 Chemokine CX3CL1 Proteins 0.000 description 1
• 102100032404 Cholinesterase Human genes 0.000 description 1
• 208000006154 Chronic hepatitis C Diseases 0.000 description 1
• 208000010833 Chronic myeloid leukaemia Diseases 0.000 description 1
• 241000557626 Corvus corax Species 0.000 description 1
• 241000186216 Corynebacterium Species 0.000 description 1
• 241000699802 Cricetulus griseus Species 0.000 description 1
• PMATZTZNYRCHOR-CGLBZJNRSA-N Cyclosporin A Chemical compound CC[C@@H]1NC(=O)[C@H]([C@H](O)[C@H](C)C\C=C\C)N(C)C(=O)[C@H](C(C)C)N(C)C(=O)[C@H](CC(C)C)N(C)C(=O)[C@H](CC(C)C)N(C)C(=O)[C@@H](C)NC(=O)[C@H](C)NC(=O)[C@H](CC(C)C)N(C)C(=O)[C@H](C(C)C)NC(=O)[C@H](CC(C)C)N(C)C(=O)CN(C)C1=O PMATZTZNYRCHOR-CGLBZJNRSA-N 0.000 description 1
• 229930105110 Cyclosporin A Natural products 0.000 description 1
• 108010036949 Cyclosporine Proteins 0.000 description 1
• UHDGCWIWMRVCDJ-CCXZUQQUSA-N Cytarabine Chemical compound O=C1N=C(N)C=CN1[C@H]1[C@@H](O)[C@H](O)[C@@H](CO)O1 UHDGCWIWMRVCDJ-CCXZUQQUSA-N 0.000 description 1
• IGXWBGJHJZYPQS-SSDOTTSWSA-N D-Luciferin Chemical compound OC(=O)[C@H]1CSC(C=2SC3=CC=C(O)C=C3N=2)=N1 IGXWBGJHJZYPQS-SSDOTTSWSA-N 0.000 description 1
• 101150074155 DHFR gene Proteins 0.000 description 1
• 230000004544 DNA amplification Effects 0.000 description 1
• XPDXVDYUQZHFPV-UHFFFAOYSA-N Dansyl Chloride Chemical compound C1=CC=C2C(N(C)C)=CC=CC2=C1S(Cl)(=O)=O XPDXVDYUQZHFPV-UHFFFAOYSA-N 0.000 description 1
• WEAHRLBPCANXCN-UHFFFAOYSA-N Daunomycin Natural products CCC1(O)CC(OC2CC(N)C(O)C(C)O2)c3cc4C(=O)c5c(OC)cccc5C(=O)c4c(O)c3C1 WEAHRLBPCANXCN-UHFFFAOYSA-N 0.000 description 1
• CYCGRDQQIOGCKX-UHFFFAOYSA-N Dehydro-luciferin Natural products OC(=O)C1=CSC(C=2SC3=CC(O)=CC=C3N=2)=N1 CYCGRDQQIOGCKX-UHFFFAOYSA-N 0.000 description 1
• 102100024746 Dihydrofolate reductase Human genes 0.000 description 1
• 102000016607 Diphtheria Toxin Human genes 0.000 description 1
• 108010053187 Diphtheria Toxin Proteins 0.000 description 1
• 201000011001 Ebola Hemorrhagic Fever Diseases 0.000 description 1
• MBYXEBXZARTUSS-QLWBXOBMSA-N Emetamine Natural products O(C)c1c(OC)cc2c(c(C[C@@H]3[C@H](CC)CN4[C@H](c5c(cc(OC)c(OC)c5)CC4)C3)ncc2)c1 MBYXEBXZARTUSS-QLWBXOBMSA-N 0.000 description 1
• 102400001047 Endostatin Human genes 0.000 description 1
• 108010079505 Endostatins Proteins 0.000 description 1
• 102000002045 Endothelin Human genes 0.000 description 1
• 108050009340 Endothelin Proteins 0.000 description 1
• YQYJSBFKSSDGFO-UHFFFAOYSA-N Epihygromycin Natural products OC1C(O)C(C(=O)C)OC1OC(C(=C1)O)=CC=C1C=C(C)C(=O)NC1C(O)C(O)C2OCOC2C1O YQYJSBFKSSDGFO-UHFFFAOYSA-N 0.000 description 1
• 241000283074 Equus asinus Species 0.000 description 1
• 241000283073 Equus caballus Species 0.000 description 1
• 108010074860 Factor Xa Proteins 0.000 description 1
• 102100028071 Fibroblast growth factor 7 Human genes 0.000 description 1
• 108090000385 Fibroblast growth factor 7 Proteins 0.000 description 1
• 241000724791 Filamentous phage Species 0.000 description 1
• BJGNCJDXODQBOB-UHFFFAOYSA-N Fivefly Luciferin Natural products OC(=O)C1CSC(C=2SC3=CC(O)=CC=C3N=2)=N1 BJGNCJDXODQBOB-UHFFFAOYSA-N 0.000 description 1
• GHASVSINZRGABV-UHFFFAOYSA-N Fluorouracil Chemical compound FC1=CNC(=O)NC1=O GHASVSINZRGABV-UHFFFAOYSA-N 0.000 description 1
• 102000013818 Fractalkine Human genes 0.000 description 1
• 241000287828 Gallus gallus Species 0.000 description 1
• 102100028701 General vesicular transport factor p115 Human genes 0.000 description 1
• 108700028146 Genetic Enhancer Elements Proteins 0.000 description 1
• 101800001586 Ghrelin Proteins 0.000 description 1
• 102400000442 Ghrelin-28 Human genes 0.000 description 1
• 102100031132 Glucose-6-phosphate isomerase Human genes 0.000 description 1
• 108010070600 Glucose-6-phosphate isomerase Proteins 0.000 description 1
• 108010024636 Glutathione Proteins 0.000 description 1
• 108010026389 Gramicidin Proteins 0.000 description 1
• 208000031886 HIV Infections Diseases 0.000 description 1
• 208000002250 Hematologic Neoplasms Diseases 0.000 description 1
• 230000010556 Heparin Binding Activity Effects 0.000 description 1
• 108010093488 His-His-His-His-His-His Proteins 0.000 description 1
• 101000978381 Homo sapiens C-C motif chemokine 14 Proteins 0.000 description 1
• 101000767151 Homo sapiens General vesicular transport factor p115 Proteins 0.000 description 1
• 101000599951 Homo sapiens Insulin-like growth factor I Proteins 0.000 description 1
• 101000959820 Homo sapiens Interferon alpha-1/13 Proteins 0.000 description 1
• 101000830596 Homo sapiens Tumor necrosis factor ligand superfamily member 15 Proteins 0.000 description 1
• 101000818563 Homo sapiens Zinc finger and BTB domain-containing protein 25 Proteins 0.000 description 1
• 102000003839 Human Proteins Human genes 0.000 description 1
• 108090000144 Human Proteins Proteins 0.000 description 1
• 241000701024 Human betaherpesvirus 5 Species 0.000 description 1
• 101100321817 Human parvovirus B19 (strain HV) 7.5K gene Proteins 0.000 description 1
• 108010091358 Hypoxanthine Phosphoribosyltransferase Proteins 0.000 description 1
• 102100029098 Hypoxanthine-guanine phosphoribosyltransferase Human genes 0.000 description 1
• 108010009817 Immunoglobulin Constant Regions Proteins 0.000 description 1
• 102000009786 Immunoglobulin Constant Regions Human genes 0.000 description 1
• 108010067060 Immunoglobulin Variable Region Proteins 0.000 description 1
• 102000017727 Immunoglobulin Variable Region Human genes 0.000 description 1
• 102000016844 Immunoglobulin-like domains Human genes 0.000 description 1
• 108050006430 Immunoglobulin-like domains Proteins 0.000 description 1
• 206010061218 Inflammation Diseases 0.000 description 1
• 108020005350 Initiator Codon Proteins 0.000 description 1
• 108090000723 Insulin-Like Growth Factor I Proteins 0.000 description 1
• 102100037852 Insulin-like growth factor I Human genes 0.000 description 1
• 108010074328 Interferon-gamma Proteins 0.000 description 1
• 102000008070 Interferon-gamma Human genes 0.000 description 1
• 102000000589 Interleukin-1 Human genes 0.000 description 1
• 108010002352 Interleukin-1 Proteins 0.000 description 1
• 208000007766 Kaposi sarcoma Diseases 0.000 description 1
• 101710096444 Killer toxin Proteins 0.000 description 1
• QNAYBMKLOCPYGJ-REOHCLBHSA-N L-alanine Chemical compound C[C@H](N)C(O)=O QNAYBMKLOCPYGJ-REOHCLBHSA-N 0.000 description 1
• NNJVILVZKWQKPM-UHFFFAOYSA-N Lidocaine Chemical compound CCN(CC)CC(=O)NC1=C(C)C=CC=C1C NNJVILVZKWQKPM-UHFFFAOYSA-N 0.000 description 1
• 102400001283 Long-acting natriuretic peptide Human genes 0.000 description 1
• 108060001084 Luciferase Proteins 0.000 description 1
• 239000005089 Luciferase Substances 0.000 description 1
• DDWFXDSYGUXRAY-UHFFFAOYSA-N Luciferin Natural products CCc1c(C)c(CC2NC(=O)C(=C2C=C)C)[nH]c1Cc3[nH]c4C(=C5/NC(CC(=O)O)C(C)C5CC(=O)O)CC(=O)c4c3C DDWFXDSYGUXRAY-UHFFFAOYSA-N 0.000 description 1
• 102000008072 Lymphokines Human genes 0.000 description 1
• 108010074338 Lymphokines Proteins 0.000 description 1
• 108090000542 Lymphotoxin-alpha Proteins 0.000 description 1
• 102000004083 Lymphotoxin-alpha Human genes 0.000 description 1
• 102000018697 Membrane Proteins Human genes 0.000 description 1
• 108010052285 Membrane Proteins Proteins 0.000 description 1
• 102100024289 Metalloproteinase inhibitor 4 Human genes 0.000 description 1
• 108050006579 Metalloproteinase inhibitor 4 Proteins 0.000 description 1
• 102000003792 Metallothionein Human genes 0.000 description 1
• 108090000157 Metallothionein Proteins 0.000 description 1
• 229930192392 Mitomycin Natural products 0.000 description 1
• 208000034578 Multiple myelomas Diseases 0.000 description 1
• 208000033761 Myelogenous Chronic BCR-ABL Positive Leukemia Diseases 0.000 description 1
• 241001553014 Myrsine salicina Species 0.000 description 1
• NWIBSHFKIJFRCO-WUDYKRTCSA-N Mytomycin Chemical compound C1N2C(C(C(C)=C(N)C3=O)=O)=C3[C@@H](COC(N)=O)[C@@]2(OC)[C@@H]2[C@H]1N2 NWIBSHFKIJFRCO-WUDYKRTCSA-N 0.000 description 1
• SQVRNKJHWKZAKO-PFQGKNLYSA-N N-acetyl-beta-neuraminic acid Chemical compound CC(=O)N[C@@H]1[C@@H](O)C[C@@](O)(C(O)=O)O[C@H]1[C@H](O)[C@H](O)CO SQVRNKJHWKZAKO-PFQGKNLYSA-N 0.000 description 1
• 241001481166 Nautilus Species 0.000 description 1
• 108010006232 Neuraminidase Proteins 0.000 description 1
• 102000005348 Neuraminidase Human genes 0.000 description 1
• 108020005187 Oligonucleotide Probes Proteins 0.000 description 1
• 102400000319 Oxyntomodulin Human genes 0.000 description 1
• 101800001388 Oxyntomodulin Proteins 0.000 description 1
• 108090000526 Papain Proteins 0.000 description 1
• 241000237988 Patellidae Species 0.000 description 1
• 108090000284 Pepsin A Proteins 0.000 description 1
• 102000057297 Pepsin A Human genes 0.000 description 1
• 102100029909 Peptide YY Human genes 0.000 description 1
• 108010088847 Peptide YY Proteins 0.000 description 1
• 108010004729 Phycoerythrin Proteins 0.000 description 1
• 241000235648 Pichia Species 0.000 description 1
• 108010038512 Platelet-Derived Growth Factor Proteins 0.000 description 1
• 102000010780 Platelet-Derived Growth Factor Human genes 0.000 description 1
• 241000276498 Pollachius virens Species 0.000 description 1
• 239000002202 Polyethylene glycol Substances 0.000 description 1
• 239000004743 Polypropylene Substances 0.000 description 1
• 239000004793 Polystyrene Substances 0.000 description 1
• ONIBWKKTOPOVIA-UHFFFAOYSA-N Proline Natural products OC(=O)C1CCCN1 ONIBWKKTOPOVIA-UHFFFAOYSA-N 0.000 description 1
• 239000004365 Protease Substances 0.000 description 1
• 102100029812 Protein S100-A12 Human genes 0.000 description 1
• 101000762949 Pseudomonas aeruginosa (strain ATCC 15692 / DSM 22644 / CIP 104116 / JCM 14847 / LMG 12228 / 1C / PRS 101 / PAO1) Exotoxin A Proteins 0.000 description 1
• 208000006265 Renal cell carcinoma Diseases 0.000 description 1
• AUNGANRZJHBGPY-SCRDCRAPSA-N Riboflavin Chemical compound OC[C@@H](O)[C@@H](O)[C@@H](O)CN1C=2C=C(C)C(C)=CC=2N=C2C1=NC(=O)NC2=O AUNGANRZJHBGPY-SCRDCRAPSA-N 0.000 description 1
• 108010039491 Ricin Proteins 0.000 description 1
• 239000006146 Roswell Park Memorial Institute medium Substances 0.000 description 1
• AUVVAXYIELKVAI-UHFFFAOYSA-N SJ000285215 Natural products N1CCC2=CC(OC)=C(OC)C=C2C1CC1CC2C3=CC(OC)=C(OC)C=C3CCN2CC1CC AUVVAXYIELKVAI-UHFFFAOYSA-N 0.000 description 1
• 241000235070 Saccharomyces Species 0.000 description 1
• 108091058545 Secretory proteins Proteins 0.000 description 1
• 102000040739 Secretory proteins Human genes 0.000 description 1
• 241000700584 Simplexvirus Species 0.000 description 1
• 206010072610 Skeletal dysplasia Diseases 0.000 description 1
• 102220497176 Small vasohibin-binding protein_T47D_mutation Human genes 0.000 description 1
• 102000013275 Somatomedins Human genes 0.000 description 1
• 241000256248 Spodoptera Species 0.000 description 1
• 108010090804 Streptavidin Proteins 0.000 description 1
• ZSJLQEPLLKMAKR-UHFFFAOYSA-N Streptozotocin Natural products O=NN(C)C(=O)NC1C(O)OC(CO)C(O)C1O ZSJLQEPLLKMAKR-UHFFFAOYSA-N 0.000 description 1
• 241000282887 Suidae Species 0.000 description 1
• 241000282898 Sus scrofa Species 0.000 description 1
• 102100028644 Tenascin-R Human genes 0.000 description 1
• AYFVYJQAPQTCCC-UHFFFAOYSA-N Threonine Natural products CC(O)C(N)C(O)=O AYFVYJQAPQTCCC-UHFFFAOYSA-N 0.000 description 1
• 239000004473 Threonine Substances 0.000 description 1
• 108090000190 Thrombin Proteins 0.000 description 1
• 102000006601 Thymidine Kinase Human genes 0.000 description 1
• 108020004440 Thymidine kinase Proteins 0.000 description 1
• 108090000373 Tissue Plasminogen Activator Proteins 0.000 description 1
• 102000003978 Tissue Plasminogen Activator Human genes 0.000 description 1
• 101710120037 Toxin CcdB Proteins 0.000 description 1
• 108020004566 Transfer RNA Proteins 0.000 description 1
• 108700019146 Transgenes Proteins 0.000 description 1
• 102100024587 Tumor necrosis factor ligand superfamily member 15 Human genes 0.000 description 1
• 102100031988 Tumor necrosis factor ligand superfamily member 6 Human genes 0.000 description 1
• 108050002568 Tumor necrosis factor ligand superfamily member 6 Proteins 0.000 description 1
• YJQCOFNZVFGCAF-UHFFFAOYSA-N Tunicamycin II Natural products O1C(CC(O)C2C(C(O)C(O2)N2C(NC(=O)C=C2)=O)O)C(O)C(O)C(NC(=O)C=CCCCCCCCCC(C)C)C1OC1OC(CO)C(O)C(O)C1NC(C)=O YJQCOFNZVFGCAF-UHFFFAOYSA-N 0.000 description 1
• GBOGMAARMMDZGR-UHFFFAOYSA-N UNPD149280 Natural products N1C(=O)C23OC(=O)C=CC(O)CCCC(C)CC=CC3C(O)C(=C)C(C)C2C1CC1=CC=CC=C1 GBOGMAARMMDZGR-UHFFFAOYSA-N 0.000 description 1
• 241000700618 Vaccinia virus Species 0.000 description 1
• 208000003152 Yellow Fever Diseases 0.000 description 1
• 102100021127 Zinc finger and BTB domain-containing protein 25 Human genes 0.000 description 1
• 230000002159 abnormal effect Effects 0.000 description 1
• 229940022698 acetylcholinesterase Drugs 0.000 description 1
• 150000007513 acids Chemical class 0.000 description 1
• 229930183665 actinomycin Natural products 0.000 description 1
• 239000013543 active substance Substances 0.000 description 1
• 230000010933 acylation Effects 0.000 description 1
• 238000005917 acylation reaction Methods 0.000 description 1
• ULCUCJFASIJEOE-NPECTJMMSA-N adrenomedullin Chemical compound C([C@@H](C(=O)N[C@@H](CCC(N)=O)C(=O)NCC(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CO)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)NCC(=O)N[C@@H]1C(N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC=2C=CC=CC=2)C(=O)NCC(=O)N[C@H](C(=O)N[C@@H](CSSC1)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](C)C(=O)N[C@@H](CC=1NC=NC=1)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N[C@@H](CCC(N)=O)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](CCCCN)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](C)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCC(N)=O)C(=O)NCC(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(N)=O)[C@@H](C)O)=O)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CCSC)NC(=O)[C@H](CO)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@@H](N)CC=1C=CC(O)=CC=1)C1=CC=CC=C1 ULCUCJFASIJEOE-NPECTJMMSA-N 0.000 description 1
• 238000001042 affinity chromatography Methods 0.000 description 1
• 230000008484 agonism Effects 0.000 description 1
• 235000004279 alanine Nutrition 0.000 description 1
• 238000012867 alanine scanning Methods 0.000 description 1
• WNROFYMDJYEPJX-UHFFFAOYSA-K aluminium hydroxide Chemical compound [OH-].[OH-].[OH-].[Al+3] WNROFYMDJYEPJX-UHFFFAOYSA-K 0.000 description 1
• 230000001668 ameliorated effect Effects 0.000 description 1
• 229940126575 aminoglycoside Drugs 0.000 description 1
• 239000004037 angiogenesis inhibitor Substances 0.000 description 1
• 229950006323 angiotensin ii Drugs 0.000 description 1
• 238000000137 annealing Methods 0.000 description 1
• 230000008485 antagonism Effects 0.000 description 1
• MWPLVEDNUUSJAV-UHFFFAOYSA-N anthracene Chemical compound C1=CC=CC2=CC3=CC=CC=C3C=C21 MWPLVEDNUUSJAV-UHFFFAOYSA-N 0.000 description 1
• 229940045799 anthracyclines and related substance Drugs 0.000 description 1
• 239000003242 anti bacterial agent Substances 0.000 description 1
• 230000001028 anti-proliverative effect Effects 0.000 description 1
• 229940088710 antibiotic agent Drugs 0.000 description 1
• 238000011230 antibody-based therapy Methods 0.000 description 1
• 239000003080 antimitotic agent Substances 0.000 description 1
• 230000001640 apoptogenic effect Effects 0.000 description 1
• 230000036528 appetite Effects 0.000 description 1
• 235000019789 appetite Nutrition 0.000 description 1
• 239000007864 aqueous solution Substances 0.000 description 1
• 230000010516 arginylation Effects 0.000 description 1
• 208000028922 artery disease Diseases 0.000 description 1
• 235000009582 asparagine Nutrition 0.000 description 1
• 229960001230 asparagine Drugs 0.000 description 1
• 125000000613 asparagine group Chemical group N[C@@H](CC(N)=O)C(=O)* 0.000 description 1
• FZCSTZYAHCUGEM-UHFFFAOYSA-N aspergillomarasmine B Natural products OC(=O)CNC(C(O)=O)CNC(C(O)=O)CC(O)=O FZCSTZYAHCUGEM-UHFFFAOYSA-N 0.000 description 1
• 239000002585 base Substances 0.000 description 1
• 102000005936 beta-Galactosidase Human genes 0.000 description 1
• SQVRNKJHWKZAKO-UHFFFAOYSA-N beta-N-Acetyl-D-neuraminic acid Natural products CC(=O)NC1C(O)CC(O)(C(O)=O)OC1C(O)C(O)CO SQVRNKJHWKZAKO-UHFFFAOYSA-N 0.000 description 1
• 238000004166 bioassay Methods 0.000 description 1
• 230000033228 biological regulation Effects 0.000 description 1
• 230000008512 biological response Effects 0.000 description 1
• 238000001815 biotherapy Methods 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
• 210000002459 blastocyst Anatomy 0.000 description 1
• 229960001561 bleomycin Drugs 0.000 description 1
• OYVAGSVQBOHSSS-UAPAGMARSA-O bleomycin A2 Chemical compound N([C@H](C(=O)N[C@H](C)[C@@H](O)[C@H](C)C(=O)N[C@@H]([C@H](O)C)C(=O)NCCC=1SC=C(N=1)C=1SC=C(N=1)C(=O)NCCC[S+](C)C)[C@@H](O[C@H]1[C@H]([C@@H](O)[C@H](O)[C@H](CO)O1)O[C@@H]1[C@H]([C@@H](OC(N)=O)[C@H](O)[C@@H](CO)O1)O)C=1N=CNC=1)C(=O)C1=NC([C@H](CC(N)=O)NC[C@H](N)C(N)=O)=NC(N)=C1C OYVAGSVQBOHSSS-UAPAGMARSA-O 0.000 description 1
• 230000036772 blood pressure Effects 0.000 description 1
• RSIHSRDYCUFFLA-DYKIIFRCSA-N boldenone Chemical compound O=C1C=C[C@]2(C)[C@H]3CC[C@](C)([C@H](CC4)O)[C@@H]4[C@@H]3CCC2=C1 RSIHSRDYCUFFLA-DYKIIFRCSA-N 0.000 description 1
• 238000006664 bond formation reaction Methods 0.000 description 1
• 230000007883 bronchodilation Effects 0.000 description 1
• 229960002092 busulfan Drugs 0.000 description 1
• 235000014633 carbohydrates Nutrition 0.000 description 1
• 229960005243 carmustine Drugs 0.000 description 1
• 239000000969 carrier Substances 0.000 description 1
• 230000024245 cell differentiation Effects 0.000 description 1
• 239000006285 cell suspension Substances 0.000 description 1
• 229920002678 cellulose Polymers 0.000 description 1
• 239000001913 cellulose Substances 0.000 description 1
• 235000010980 cellulose Nutrition 0.000 description 1
• 238000005119 centrifugation Methods 0.000 description 1
• NDAYQJDHGXTBJL-MWWSRJDJSA-N chembl557217 Chemical compound C1=CC=C2C(C[C@H](NC(=O)[C@@H](CC(C)C)NC(=O)[C@H](CC=3C4=CC=CC=C4NC=3)NC(=O)[C@@H](CC(C)C)NC(=O)[C@H](CC=3C4=CC=CC=C4NC=3)NC(=O)[C@@H](CC(C)C)NC(=O)[C@H](CC=3C4=CC=CC=C4NC=3)NC(=O)[C@@H](C(C)C)NC(=O)[C@H](C(C)C)NC(=O)[C@@H](C(C)C)NC(=O)[C@H](C)NC(=O)[C@H](NC(=O)CNC(=O)[C@@H](NC=O)C(C)C)CC(C)C)C(=O)NCCO)=CNC2=C1 NDAYQJDHGXTBJL-MWWSRJDJSA-N 0.000 description 1
• 235000013330 chicken meat Nutrition 0.000 description 1
• 229960004630 chlorambucil Drugs 0.000 description 1
• JCKYGMPEJWAADB-UHFFFAOYSA-N chlorambucil Chemical compound OC(=O)CCCC1=CC=C(N(CCCl)CCCl)C=C1 JCKYGMPEJWAADB-UHFFFAOYSA-N 0.000 description 1
• 208000020403 chronic hepatitis C virus infection Diseases 0.000 description 1
• 229960001265 ciclosporin Drugs 0.000 description 1
• 229960004316 cisplatin Drugs 0.000 description 1
• 238000004440 column chromatography Methods 0.000 description 1
• 230000009137 competitive binding Effects 0.000 description 1
• 238000010276 construction Methods 0.000 description 1
• 239000000599 controlled substance Substances 0.000 description 1
• 239000013256 coordination polymer Substances 0.000 description 1
• 230000008878 coupling Effects 0.000 description 1
• 238000010168 coupling process Methods 0.000 description 1
• 238000005859 coupling reaction Methods 0.000 description 1
• 238000004132 cross linking Methods 0.000 description 1
• 238000012258 culturing Methods 0.000 description 1
• 208000035250 cutaneous malignant susceptibility to 1 melanoma Diseases 0.000 description 1
• XUJNEKJLAYXESH-UHFFFAOYSA-N cysteine Natural products SCC(N)C(O)=O XUJNEKJLAYXESH-UHFFFAOYSA-N 0.000 description 1
• 235000018417 cysteine Nutrition 0.000 description 1
• 125000000151 cysteine group Chemical group N[C@@H](CS)C(=O)* 0.000 description 1
• 229960000684 cytarabine Drugs 0.000 description 1
• GBOGMAARMMDZGR-TYHYBEHESA-N cytochalasin B Chemical compound C([C@H]1[C@@H]2[C@@H](C([C@@H](O)[C@@H]3/C=C/C[C@H](C)CCC[C@@H](O)/C=C/C(=O)O[C@@]23C(=O)N1)=C)C)C1=CC=CC=C1 GBOGMAARMMDZGR-TYHYBEHESA-N 0.000 description 1
• GBOGMAARMMDZGR-JREHFAHYSA-N cytochalasin B Natural products C[C@H]1CCC[C@@H](O)C=CC(=O)O[C@@]23[C@H](C=CC1)[C@H](O)C(=C)[C@@H](C)[C@@H]2[C@H](Cc4ccccc4)NC3=O GBOGMAARMMDZGR-JREHFAHYSA-N 0.000 description 1
• 231100000409 cytocidal Toxicity 0.000 description 1
• 230000000445 cytocidal effect Effects 0.000 description 1
• 239000000824 cytostatic agent Substances 0.000 description 1
• 230000001085 cytostatic effect Effects 0.000 description 1
• 231100000433 cytotoxic Toxicity 0.000 description 1
• 239000003145 cytotoxic factor Substances 0.000 description 1
• 230000002950 deficient Effects 0.000 description 1
• RSIHSRDYCUFFLA-UHFFFAOYSA-N dehydrotestosterone Natural products O=C1C=CC2(C)C3CCC(C)(C(CC4)O)C4C3CCC2=C1 RSIHSRDYCUFFLA-UHFFFAOYSA-N 0.000 description 1
• 230000017858 demethylation Effects 0.000 description 1
• 238000010520 demethylation reaction Methods 0.000 description 1
• 238000001212 derivatisation Methods 0.000 description 1
• 238000013461 design Methods 0.000 description 1
• 230000001627 detrimental effect Effects 0.000 description 1
• 238000011161 development Methods 0.000 description 1
• 230000018109 developmental process Effects 0.000 description 1
• 229940039227 diagnostic agent Drugs 0.000 description 1
• 239000000032 diagnostic agent Substances 0.000 description 1
• 230000035487 diastolic blood pressure Effects 0.000 description 1
• 230000003205 diastolic effect Effects 0.000 description 1
• 108020001096 dihydrofolate reductase Proteins 0.000 description 1
• 239000003085 diluting agent Substances 0.000 description 1
• 239000000539 dimer Substances 0.000 description 1
• 238000006471 dimerization reaction Methods 0.000 description 1
• 230000006334 disulfide bridging Effects 0.000 description 1
• 241001493065 dsRNA viruses Species 0.000 description 1
• 238000002592 echocardiography Methods 0.000 description 1
• 239000012636 effector Substances 0.000 description 1
• 238000010828 elution Methods 0.000 description 1
• AUVVAXYIELKVAI-CKBKHPSWSA-N emetine Chemical compound N1CCC2=CC(OC)=C(OC)C=C2[C@H]1C[C@H]1C[C@H]2C3=CC(OC)=C(OC)C=C3CCN2C[C@@H]1CC AUVVAXYIELKVAI-CKBKHPSWSA-N 0.000 description 1
• 229960002694 emetine Drugs 0.000 description 1
• AUVVAXYIELKVAI-UWBTVBNJSA-N emetine Natural products N1CCC2=CC(OC)=C(OC)C=C2[C@H]1C[C@H]1C[C@H]2C3=CC(OC)=C(OC)C=C3CCN2C[C@H]1CC AUVVAXYIELKVAI-UWBTVBNJSA-N 0.000 description 1
• 239000000839 emulsion Substances 0.000 description 1
• 239000006274 endogenous ligand Substances 0.000 description 1
• ZUBDGKVDJUIMQQ-UBFCDGJISA-N endothelin-1 Chemical compound C([C@@H](C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(O)=O)NC(=O)[C@H]1NC(=O)[C@H](CC=2C=CC=CC=2)NC(=O)[C@@H](CC=2C=CC(O)=CC=2)NC(=O)[C@H](C(C)C)NC(=O)[C@H]2CSSC[C@@H](C(N[C@H](CO)C(=O)N[C@@H](CO)C(=O)N[C@H](CC(C)C)C(=O)N[C@@H](CCSC)C(=O)N[C@H](CC(O)=O)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCC(O)=O)C(=O)N2)=O)NC(=O)[C@@H](CO)NC(=O)[C@H](N)CSSC1)C1=CNC=N1 ZUBDGKVDJUIMQQ-UBFCDGJISA-N 0.000 description 1
• 239000003623 enhancer Substances 0.000 description 1
• 238000001976 enzyme digestion Methods 0.000 description 1
• 230000008556 epithelial cell proliferation Effects 0.000 description 1
• 239000003797 essential amino acid Substances 0.000 description 1
• 235000020776 essential amino acid Nutrition 0.000 description 1
• ZMMJGEGLRURXTF-UHFFFAOYSA-N ethidium bromide Chemical compound [Br-].C12=CC(N)=CC=C2C2=CC=C(N)C=C2[N+](CC)=C1C1=CC=CC=C1 ZMMJGEGLRURXTF-UHFFFAOYSA-N 0.000 description 1
• 229960005542 ethidium bromide Drugs 0.000 description 1
• 229960005420 etoposide Drugs 0.000 description 1
• VJJPUSNTGOMMGY-MRVIYFEKSA-N etoposide Chemical compound COC1=C(O)C(OC)=CC([C@@H]2C3=CC=4OCOC=4C=C3[C@@H](O[C@H]3[C@@H]([C@@H](O)[C@@H]4O[C@H](C)OC[C@H]4O3)O)[C@@H]3[C@@H]2C(OC3)=O)=C1 VJJPUSNTGOMMGY-MRVIYFEKSA-N 0.000 description 1
• 210000003527 eukaryotic cell Anatomy 0.000 description 1
• 238000011156 evaluation Methods 0.000 description 1
• 230000007717 exclusion Effects 0.000 description 1
• 230000029142 excretion Effects 0.000 description 1
• 239000006277 exogenous ligand Substances 0.000 description 1
• 238000000605 extraction Methods 0.000 description 1
• 230000002349 favourable effect Effects 0.000 description 1
• 210000004700 fetal blood Anatomy 0.000 description 1
• 238000000684 flow cytometry Methods 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
• 229910052731 fluorine Inorganic materials 0.000 description 1
• 229960002949 fluorouracil Drugs 0.000 description 1
• 201000003444 follicular lymphoma Diseases 0.000 description 1
• 230000006251 gamma-carboxylation Effects 0.000 description 1
• 238000010353 genetic engineering Methods 0.000 description 1
• BGHSOEHUOOAYMY-JTZMCQEISA-N ghrelin Chemical compound C([C@@H](C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CO)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC=1N=CNC=1)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCCCN)C(=O)N1[C@@H](CCC1)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](C)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(N)=O)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O)NC(=O)[C@H](CO)NC(=O)[C@H](CO)NC(=O)CN)C1=CC=CC=C1 BGHSOEHUOOAYMY-JTZMCQEISA-N 0.000 description 1
• 239000011521 glass Substances 0.000 description 1
• 230000024924 glomerular filtration Effects 0.000 description 1
• 239000003862 glucocorticoid Substances 0.000 description 1
• 150000002308 glutamine derivatives Chemical class 0.000 description 1
• 229960003180 glutathione Drugs 0.000 description 1
• 150000002333 glycines Chemical class 0.000 description 1
• PCHJSUWPFVWCPO-UHFFFAOYSA-N gold Chemical compound [Au] PCHJSUWPFVWCPO-UHFFFAOYSA-N 0.000 description 1
• 239000001963 growth medium Substances 0.000 description 1
• 150000003278 haem Chemical group 0.000 description 1
• 230000035931 haemagglutination Effects 0.000 description 1
• 201000009277 hairy cell leukemia Diseases 0.000 description 1
• 230000036541 health Effects 0.000 description 1
• 239000000185 hemagglutinin Substances 0.000 description 1
• 210000003958 hematopoietic stem cell Anatomy 0.000 description 1
• 108060003552 hemocyanin Proteins 0.000 description 1
• 208000002672 hepatitis B Diseases 0.000 description 1
• 230000003054 hormonal effect Effects 0.000 description 1
• 231100000508 hormonal effect Toxicity 0.000 description 1
• 210000005260 human cell Anatomy 0.000 description 1
• 230000033444 hydroxylation Effects 0.000 description 1
• 238000005805 hydroxylation reaction Methods 0.000 description 1
• 201000010072 hypochondroplasia Diseases 0.000 description 1
• 230000001900 immune effect Effects 0.000 description 1
• 230000003053 immunization Effects 0.000 description 1
• 238000000760 immunoelectrophoresis Methods 0.000 description 1
• 238000010166 immunofluorescence Methods 0.000 description 1
• 230000005847 immunogenicity Effects 0.000 description 1
• 230000016784 immunoglobulin production Effects 0.000 description 1
• 239000000367 immunologic factor Substances 0.000 description 1
• 238000013394 immunophenotyping Methods 0.000 description 1
• 239000002596 immunotoxin Substances 0.000 description 1
• 238000003017 in situ immunoassay Methods 0.000 description 1
• 238000011065 in-situ storage Methods 0.000 description 1
• 238000010348 incorporation Methods 0.000 description 1
• 230000006698 induction Effects 0.000 description 1
• 208000015181 infectious disease Diseases 0.000 description 1
• 229940090438 infergen Drugs 0.000 description 1
• 230000004054 inflammatory process Effects 0.000 description 1
• 206010022000 influenza Diseases 0.000 description 1
• 229910052500 inorganic mineral Inorganic materials 0.000 description 1
• 230000003914 insulin secretion Effects 0.000 description 1
• 230000010354 integration Effects 0.000 description 1
• 229950000038 interferon alfa Drugs 0.000 description 1
• 108010055511 interferon alfa-2c Proteins 0.000 description 1
• 108010006088 interferon alfa-n1 Proteins 0.000 description 1
• 229960003358 interferon alfacon-1 Drugs 0.000 description 1
• 229960003130 interferon gamma Drugs 0.000 description 1
• 229960001388 interferon-beta Drugs 0.000 description 1
• 229940100601 interleukin-6 Drugs 0.000 description 1
• 230000026045 iodination Effects 0.000 description 1
• 238000006192 iodination reaction Methods 0.000 description 1
• 238000005342 ion exchange Methods 0.000 description 1
• 238000005304 joining Methods 0.000 description 1
• 229960004194 lidocaine Drugs 0.000 description 1
• 230000004807 localization Effects 0.000 description 1
• 229960002247 lomustine Drugs 0.000 description 1
• 230000005923 long-lasting effect Effects 0.000 description 1
• 230000007774 longterm Effects 0.000 description 1
• HWYHZTIRURJOHG-UHFFFAOYSA-N luminol Chemical compound O=C1NNC(=O)C2=C1C(N)=CC=C2 HWYHZTIRURJOHG-UHFFFAOYSA-N 0.000 description 1
• 210000001165 lymph node Anatomy 0.000 description 1
• 210000004698 lymphocyte Anatomy 0.000 description 1
• 230000005291 magnetic effect Effects 0.000 description 1
• 238000007885 magnetic separation Methods 0.000 description 1
• 238000009115 maintenance therapy Methods 0.000 description 1
• 210000005075 mammary gland Anatomy 0.000 description 1
• 230000035800 maturation Effects 0.000 description 1
• 230000007246 mechanism Effects 0.000 description 1
• 229960004961 mechlorethamine Drugs 0.000 description 1
• HAWPXGHAZFHHAD-UHFFFAOYSA-N mechlorethamine Chemical compound ClCCN(C)CCCl HAWPXGHAZFHHAD-UHFFFAOYSA-N 0.000 description 1
• 229960001924 melphalan Drugs 0.000 description 1
• SGDBTWWWUNNDEQ-LBPRGKRZSA-N melphalan Chemical compound OC(=O)[C@@H](N)CC1=CC=C(N(CCCl)CCCl)C=C1 SGDBTWWWUNNDEQ-LBPRGKRZSA-N 0.000 description 1
• 208000007106 menorrhagia Diseases 0.000 description 1
• 229960001428 mercaptopurine Drugs 0.000 description 1
• 230000002503 metabolic effect Effects 0.000 description 1
• 229910052751 metal Inorganic materials 0.000 description 1
• 239000002184 metal Substances 0.000 description 1
• 150000002739 metals Chemical class 0.000 description 1
• MYWUZJCMWCOHBA-VIFPVBQESA-N methamphetamine Chemical compound CN[C@@H](C)CC1=CC=CC=C1 MYWUZJCMWCOHBA-VIFPVBQESA-N 0.000 description 1
• SXTAYKAGBXMACB-UHFFFAOYSA-N methionine S-imide-S-oxide Natural products CS(=N)(=O)CCC(N)C(O)=O SXTAYKAGBXMACB-UHFFFAOYSA-N 0.000 description 1
• 230000011987 methylation Effects 0.000 description 1
• 238000007069 methylation reaction Methods 0.000 description 1
• HPNSFSBZBAHARI-UHFFFAOYSA-N micophenolic acid Natural products OC1=C(CC=C(C)CCC(O)=O)C(OC)=C(C)C2=C1C(=O)OC2 HPNSFSBZBAHARI-UHFFFAOYSA-N 0.000 description 1
• 235000010755 mineral Nutrition 0.000 description 1
• 239000011707 mineral Substances 0.000 description 1
• 229960004857 mitomycin Drugs 0.000 description 1
• KKZJGLLVHKMTCM-UHFFFAOYSA-N mitoxantrone Chemical compound O=C1C2=C(O)C=CC(O)=C2C(=O)C2=C1C(NCCNCCO)=CC=C2NCCNCCO KKZJGLLVHKMTCM-UHFFFAOYSA-N 0.000 description 1
• 229960001156 mitoxantrone Drugs 0.000 description 1
• 238000010369 molecular cloning Methods 0.000 description 1
• PXZWGQLGAKCNKD-DPNMSELWSA-N molport-023-276-326 Chemical compound C([C@@H](C(=O)N[C@H](C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@H](C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](C)C(O)=O)[C@@H](C)O)C(C)C)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](C)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CO)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CO)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@@H](NC(=O)CNC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CO)NC(=O)[C@@H](N)CC=1NC=NC=1)[C@@H](C)O)[C@@H](C)O)C1=CC=CC=C1 PXZWGQLGAKCNKD-DPNMSELWSA-N 0.000 description 1
• 201000006417 multiple sclerosis Diseases 0.000 description 1
• 230000000869 mutational effect Effects 0.000 description 1
• 229960000951 mycophenolic acid Drugs 0.000 description 1
• HPNSFSBZBAHARI-RUDMXATFSA-N mycophenolic acid Chemical compound OC1=C(C\C=C(/C)CCC(O)=O)C(OC)=C(C)C2=C1C(=O)OC2 HPNSFSBZBAHARI-RUDMXATFSA-N 0.000 description 1
• ZTLGJPIZUOVDMT-UHFFFAOYSA-N n,n-dichlorotriazin-4-amine Chemical compound ClN(Cl)C1=CC=NN=N1 ZTLGJPIZUOVDMT-UHFFFAOYSA-N 0.000 description 1
• 230000035407 negative regulation of cell proliferation Effects 0.000 description 1
• 210000005036 nerve Anatomy 0.000 description 1
• 210000002569 neuron Anatomy 0.000 description 1
• 230000007514 neuronal growth Effects 0.000 description 1
• 230000007935 neutral effect Effects 0.000 description 1
• PGSADBUBUOPOJS-UHFFFAOYSA-N neutral red Chemical compound Cl.C1=C(C)C(N)=CC2=NC3=CC(N(C)C)=CC=C3N=C21 PGSADBUBUOPOJS-UHFFFAOYSA-N 0.000 description 1
• 230000003472 neutralizing effect Effects 0.000 description 1
• 239000003921 oil Substances 0.000 description 1
• 235000019198 oils Nutrition 0.000 description 1
• 239000002751 oligonucleotide probe Substances 0.000 description 1
• 230000003204 osmotic effect Effects 0.000 description 1
• 230000011164 ossification Effects 0.000 description 1
• 210000001672 ovary Anatomy 0.000 description 1
• 230000003647 oxidation Effects 0.000 description 1
• 238000007254 oxidation reaction Methods 0.000 description 1
• 210000002741 palatine tonsil Anatomy 0.000 description 1
• 238000004091 panning Methods 0.000 description 1
• 229940055729 papain Drugs 0.000 description 1
• 235000019834 papain Nutrition 0.000 description 1
• 230000005298 paramagnetic effect Effects 0.000 description 1
• 239000002245 particle Substances 0.000 description 1
• 229940002988 pegasys Drugs 0.000 description 1
• 108010092853 peginterferon alfa-2a Proteins 0.000 description 1
• 108010092851 peginterferon alfa-2b Proteins 0.000 description 1
• 229940106366 pegintron Drugs 0.000 description 1
• 229940111202 pepsin Drugs 0.000 description 1
• 210000005259 peripheral blood Anatomy 0.000 description 1
• 239000011886 peripheral blood Substances 0.000 description 1
• 230000035699 permeability Effects 0.000 description 1
• 230000003285 pharmacodynamic effect Effects 0.000 description 1
• 239000012071 phase Substances 0.000 description 1
• 238000002135 phase contrast microscopy Methods 0.000 description 1
• 229910052698 phosphorus Inorganic materials 0.000 description 1
• 230000000704 physical effect Effects 0.000 description 1
• 229920001983 poloxamer Polymers 0.000 description 1
• 230000008488 polyadenylation Effects 0.000 description 1
• 229920000447 polyanionic polymer Polymers 0.000 description 1
• 229920001223 polyethylene glycol Polymers 0.000 description 1
• 229920005862 polyol Polymers 0.000 description 1
• 150000003077 polyols Chemical class 0.000 description 1
• 229920001155 polypropylene Polymers 0.000 description 1
• 229920002223 polystyrene Polymers 0.000 description 1
• 229920000915 polyvinyl chloride Polymers 0.000 description 1
• 239000004800 polyvinyl chloride Substances 0.000 description 1
• 238000002600 positron emission tomography Methods 0.000 description 1
• 229910052700 potassium Inorganic materials 0.000 description 1
• 230000003389 potentiating effect Effects 0.000 description 1
• 230000013823 prenylation Effects 0.000 description 1
• 230000002265 prevention Effects 0.000 description 1
• 229960004919 procaine Drugs 0.000 description 1
• MFDFERRIHVXMIY-UHFFFAOYSA-N procaine Chemical compound CCN(CC)CCOC(=O)C1=CC=C(N)C=C1 MFDFERRIHVXMIY-UHFFFAOYSA-N 0.000 description 1
• 230000002035 prolonged effect Effects 0.000 description 1
• 230000001737 promoting effect Effects 0.000 description 1
• 229960003712 propranolol Drugs 0.000 description 1
• 235000004252 protein component Nutrition 0.000 description 1
• 230000009145 protein modification Effects 0.000 description 1
• 230000002797 proteolythic effect Effects 0.000 description 1
• 229950010131 puromycin Drugs 0.000 description 1
• 229940043131 pyroglutamate Drugs 0.000 description 1
• 230000006340 racemization Effects 0.000 description 1
• 238000002708 random mutagenesis Methods 0.000 description 1
• 229940044601 receptor agonist Drugs 0.000 description 1
• 239000000018 receptor agonist Substances 0.000 description 1
• 238000005215 recombination Methods 0.000 description 1
• 235000003499 redwood Nutrition 0.000 description 1
• 230000029865 regulation of blood pressure Effects 0.000 description 1
• 230000021014 regulation of cell growth Effects 0.000 description 1
• 230000008327 renal blood flow Effects 0.000 description 1
• 208000015347 renal cell adenocarcinoma Diseases 0.000 description 1
• 238000009877 rendering Methods 0.000 description 1
• 108091008146 restriction endonucleases Proteins 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
• 238000007363 ring formation reaction Methods 0.000 description 1
• 102220126190 rs556840308 Human genes 0.000 description 1
• 235000019515 salmon Nutrition 0.000 description 1
• 239000006152 selective media Substances 0.000 description 1
• 238000004904 shortening Methods 0.000 description 1
• 239000013605 shuttle vector Substances 0.000 description 1
• SQVRNKJHWKZAKO-OQPLDHBCSA-N sialic acid Chemical compound CC(=O)N[C@@H]1[C@@H](O)C[C@@](O)(C(O)=O)OC1[C@H](O)[C@H](O)CO SQVRNKJHWKZAKO-OQPLDHBCSA-N 0.000 description 1
• 230000011664 signaling Effects 0.000 description 1
• 238000009097 single-agent therapy Methods 0.000 description 1
• 238000004513 sizing Methods 0.000 description 1
• 230000007958 sleep Effects 0.000 description 1
• 239000001488 sodium phosphate Substances 0.000 description 1
• 229910000162 sodium phosphate Inorganic materials 0.000 description 1
• 235000011008 sodium phosphates Nutrition 0.000 description 1
• 230000037439 somatic mutation Effects 0.000 description 1
• 238000001179 sorption measurement Methods 0.000 description 1
• 238000011699 spontaneously hypertensive rat Methods 0.000 description 1
• 230000000087 stabilizing effect Effects 0.000 description 1
• 230000010473 stable expression Effects 0.000 description 1
• 238000010186 staining Methods 0.000 description 1
• 238000011272 standard treatment Methods 0.000 description 1
• 210000000130 stem cell Anatomy 0.000 description 1
• 230000004936 stimulating effect Effects 0.000 description 1
• 230000000638 stimulation Effects 0.000 description 1
• 229960001052 streptozocin Drugs 0.000 description 1
• ZSJLQEPLLKMAKR-GKHCUFPYSA-N streptozocin Chemical compound O=NN(C)C(=O)N[C@H]1[C@@H](O)O[C@H](CO)[C@@H](O)[C@@H]1O ZSJLQEPLLKMAKR-GKHCUFPYSA-N 0.000 description 1
• 238000010254 subcutaneous injection Methods 0.000 description 1
• 239000007929 subcutaneous injection Substances 0.000 description 1
• 125000001424 substituent group Chemical group 0.000 description 1
• 230000019635 sulfation Effects 0.000 description 1
• 238000005670 sulfation reaction Methods 0.000 description 1
• 230000001629 suppression Effects 0.000 description 1
• 208000024891 symptom Diseases 0.000 description 1
• 238000010189 synthetic method Methods 0.000 description 1
• 229940037128 systemic glucocorticoids Drugs 0.000 description 1
• 239000001648 tannin Substances 0.000 description 1
• RCINICONZNJXQF-MZXODVADSA-N taxol Chemical compound O([C@@H]1[C@@]2(C[C@@H](C(C)=C(C2(C)C)[C@H](C([C@]2(C)[C@@H](O)C[C@H]3OC[C@]3([C@H]21)OC(C)=O)=O)OC(=O)C)OC(=O)[C@H](O)[C@@H](NC(=O)C=1C=CC=CC=1)C=1C=CC=CC=1)O)C(=O)C1=CC=CC=C1 RCINICONZNJXQF-MZXODVADSA-N 0.000 description 1
• 108010020387 tenascin R Proteins 0.000 description 1
• NRUKOCRGYNPUPR-QBPJDGROSA-N teniposide Chemical compound COC1=C(O)C(OC)=CC([C@@H]2C3=CC=4OCOC=4C=C3[C@@H](O[C@H]3[C@@H]([C@@H](O)[C@@H]4O[C@@H](OC[C@H]4O3)C=3SC=CC=3)O)[C@@H]3[C@@H]2C(OC3)=O)=C1 NRUKOCRGYNPUPR-QBPJDGROSA-N 0.000 description 1
• 229960001278 teniposide Drugs 0.000 description 1
• 238000012360 testing method Methods 0.000 description 1
• 238000012956 testing procedure Methods 0.000 description 1
• 229960002372 tetracaine Drugs 0.000 description 1
• GKCBAIGFKIBETG-UHFFFAOYSA-N tetracaine Chemical compound CCCCNC1=CC=C(C(=O)OCCN(C)C)C=C1 GKCBAIGFKIBETG-UHFFFAOYSA-N 0.000 description 1
• 201000003896 thanatophoric dysplasia Diseases 0.000 description 1
• 125000000341 threoninyl group Chemical group [H]OC([H])(C([H])([H])[H])C([H])(N([H])[H])C(*)=O 0.000 description 1
• 229960004072 thrombin Drugs 0.000 description 1
• 230000001732 thrombotic effect Effects 0.000 description 1
• 229960003087 tioguanine Drugs 0.000 description 1
• 229960000187 tissue plasminogen activator Drugs 0.000 description 1
• 239000010936 titanium Substances 0.000 description 1
• 231100000331 toxic Toxicity 0.000 description 1
• 230000002588 toxic effect Effects 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
• 238000012546 transfer Methods 0.000 description 1
• 230000009261 transgenic effect Effects 0.000 description 1
• 238000002054 transplantation Methods 0.000 description 1
• 230000032258 transport Effects 0.000 description 1
• RYFMWSXOAZQYPI-UHFFFAOYSA-K trisodium phosphate Chemical compound [Na+].[Na+].[Na+].[O-]P([O-])([O-])=O RYFMWSXOAZQYPI-UHFFFAOYSA-K 0.000 description 1
• 229910052721 tungsten Inorganic materials 0.000 description 1
• MEYZYGMYMLNUHJ-UHFFFAOYSA-N tunicamycin Natural products CC(C)CCCCCCCCCC=CC(=O)NC1C(O)C(O)C(CC(O)C2OC(C(O)C2O)N3C=CC(=O)NC3=O)OC1OC4OC(CO)C(O)C(O)C4NC(=O)C MEYZYGMYMLNUHJ-UHFFFAOYSA-N 0.000 description 1
• OUYCCCASQSFEME-UHFFFAOYSA-N tyrosine Natural products OC(=O)C(N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-UHFFFAOYSA-N 0.000 description 1
• ORHBXUUXSCNDEV-UHFFFAOYSA-N umbelliferone Chemical compound C1=CC(=O)OC2=CC(O)=CC=C21 ORHBXUUXSCNDEV-UHFFFAOYSA-N 0.000 description 1
• HFTAFOQKODTIJY-UHFFFAOYSA-N umbelliferone Natural products Cc1cc2C=CC(=O)Oc2cc1OCC=CC(C)(C)O HFTAFOQKODTIJY-UHFFFAOYSA-N 0.000 description 1
• 241000701447 unidentified baculovirus Species 0.000 description 1
• 241001515965 unidentified phage Species 0.000 description 1
• MYPYJXKWCTUITO-UHFFFAOYSA-N vancomycin Natural products O1C(C(=C2)Cl)=CC=C2C(O)C(C(NC(C2=CC(O)=CC(O)=C2C=2C(O)=CC=C3C=2)C(O)=O)=O)NC(=O)C3NC(=O)C2NC(=O)C(CC(N)=O)NC(=O)C(NC(=O)C(CC(C)C)NC)C(O)C(C=C3Cl)=CC=C3OC3=CC2=CC1=C3OC1OC(CO)C(O)C(O)C1OC1CC(C)(N)C(O)C(C)O1 MYPYJXKWCTUITO-UHFFFAOYSA-N 0.000 description 1
• 230000024883 vasodilation Effects 0.000 description 1
• 210000003462 vein Anatomy 0.000 description 1
• 229910001868 water Inorganic materials 0.000 description 1
• 230000003442 weekly effect Effects 0.000 description 1
• 229910052727 yttrium Inorganic materials 0.000 description 1