ES2295202T3 - Utilizacion de un antagonista especifico de erbb4 para el tratamiento de la estenosis. - Google Patents
Utilizacion de un antagonista especifico de erbb4 para el tratamiento de la estenosis. Download PDFInfo
- Publication number
- ES2295202T3 ES2295202T3 ES01966399T ES01966399T ES2295202T3 ES 2295202 T3 ES2295202 T3 ES 2295202T3 ES 01966399 T ES01966399 T ES 01966399T ES 01966399 T ES01966399 T ES 01966399T ES 2295202 T3 ES2295202 T3 ES 2295202T3
- Authority
- ES
- Spain
- Prior art keywords
- use according
- antibody
- erbb4
- cells
- receptor
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired - Lifetime
Links
- 238000011282 treatment Methods 0.000 title claims description 46
- 229940123852 ERbB-4 antagonist Drugs 0.000 title description 28
- 101710100963 Receptor tyrosine-protein kinase erbB-4 Proteins 0.000 claims abstract description 86
- 102000044591 ErbB-4 Receptor Human genes 0.000 claims abstract description 71
- 210000000329 smooth muscle myocyte Anatomy 0.000 claims abstract description 63
- 230000035755 proliferation Effects 0.000 claims abstract description 45
- 208000031481 Pathologic Constriction Diseases 0.000 claims abstract description 44
- 230000036262 stenosis Effects 0.000 claims abstract description 43
- 208000037804 stenosis Diseases 0.000 claims abstract description 43
- 239000005557 antagonist Substances 0.000 claims abstract description 39
- 238000013508 migration Methods 0.000 claims abstract description 25
- 230000005012 migration Effects 0.000 claims abstract description 24
- 210000004027 cell Anatomy 0.000 claims description 231
- 241000282414 Homo sapiens Species 0.000 claims description 89
- 230000027455 binding Effects 0.000 claims description 77
- 102000005962 receptors Human genes 0.000 claims description 58
- 108020003175 receptors Proteins 0.000 claims description 58
- 108060003951 Immunoglobulin Proteins 0.000 claims description 57
- 102000018358 immunoglobulin Human genes 0.000 claims description 57
- 239000003446 ligand Substances 0.000 claims description 40
- 150000007523 nucleic acids Chemical class 0.000 claims description 37
- 108020004707 nucleic acids Proteins 0.000 claims description 35
- 102000039446 nucleic acids Human genes 0.000 claims description 35
- 108090000556 Neuregulin-1 Proteins 0.000 claims description 33
- 208000037803 restenosis Diseases 0.000 claims description 28
- 239000012634 fragment Substances 0.000 claims description 27
- 210000004408 hybridoma Anatomy 0.000 claims description 24
- 239000003814 drug Substances 0.000 claims description 21
- 229940079593 drug Drugs 0.000 claims description 20
- 210000003932 urinary bladder Anatomy 0.000 claims description 19
- 108010021625 Immunoglobulin Fragments Proteins 0.000 claims description 17
- 102000008394 Immunoglobulin Fragments Human genes 0.000 claims description 17
- 230000005764 inhibitory process Effects 0.000 claims description 17
- 238000004519 manufacturing process Methods 0.000 claims description 17
- 230000026731 phosphorylation Effects 0.000 claims description 16
- 238000006366 phosphorylation reaction Methods 0.000 claims description 16
- OUYCCCASQSFEME-QMMMGPOBSA-N L-tyrosine Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-QMMMGPOBSA-N 0.000 claims description 15
- 102100029981 Receptor tyrosine-protein kinase erbB-4 Human genes 0.000 claims description 15
- 238000001727 in vivo Methods 0.000 claims description 14
- OUYCCCASQSFEME-UHFFFAOYSA-N tyrosine Natural products OC(=O)C(N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-UHFFFAOYSA-N 0.000 claims description 14
- 230000002792 vascular Effects 0.000 claims description 13
- 230000003472 neutralizing effect Effects 0.000 claims description 12
- 206010057469 Vascular stenosis Diseases 0.000 claims description 11
- 230000008719 thickening Effects 0.000 claims description 11
- 206010020772 Hypertension Diseases 0.000 claims description 10
- 210000000709 aorta Anatomy 0.000 claims description 10
- 230000002265 prevention Effects 0.000 claims description 10
- 239000002253 acid Substances 0.000 claims description 9
- 210000002460 smooth muscle Anatomy 0.000 claims description 9
- 201000000660 Pyloric Stenosis Diseases 0.000 claims description 7
- 210000000663 muscle cell Anatomy 0.000 claims description 7
- 229940044551 receptor antagonist Drugs 0.000 claims description 7
- 239000002464 receptor antagonist Substances 0.000 claims description 7
- 210000002889 endothelial cell Anatomy 0.000 claims description 6
- 238000002347 injection Methods 0.000 claims description 6
- 239000007924 injection Substances 0.000 claims description 6
- 230000000241 respiratory effect Effects 0.000 claims description 6
- 230000002485 urinary effect Effects 0.000 claims description 6
- FWMNVWWHGCHHJJ-SKKKGAJSSA-N 4-amino-1-[(2r)-6-amino-2-[[(2r)-2-[[(2r)-2-[[(2r)-2-amino-3-phenylpropanoyl]amino]-3-phenylpropanoyl]amino]-4-methylpentanoyl]amino]hexanoyl]piperidine-4-carboxylic acid Chemical compound C([C@H](C(=O)N[C@H](CC(C)C)C(=O)N[C@H](CCCCN)C(=O)N1CCC(N)(CC1)C(O)=O)NC(=O)[C@H](N)CC=1C=CC=CC=1)C1=CC=CC=C1 FWMNVWWHGCHHJJ-SKKKGAJSSA-N 0.000 claims description 5
- 210000004509 vascular smooth muscle cell Anatomy 0.000 claims description 5
- 238000001802 infusion Methods 0.000 claims description 4
- 102000006496 Immunoglobulin Heavy Chains Human genes 0.000 claims description 3
- 108010019476 Immunoglobulin Heavy Chains Proteins 0.000 claims description 3
- 208000023504 respiratory system disease Diseases 0.000 claims description 3
- 230000003449 preventive effect Effects 0.000 claims description 2
- 102000048238 Neuregulin-1 Human genes 0.000 claims 2
- 238000000034 method Methods 0.000 abstract description 130
- 230000002401 inhibitory effect Effects 0.000 abstract description 4
- 239000000556 agonist Substances 0.000 abstract 1
- 230000002708 enhancing effect Effects 0.000 abstract 1
- 108090000623 proteins and genes Proteins 0.000 description 89
- 108090000765 processed proteins & peptides Proteins 0.000 description 67
- 102000004196 processed proteins & peptides Human genes 0.000 description 62
- 229920001184 polypeptide Polymers 0.000 description 58
- 235000018102 proteins Nutrition 0.000 description 48
- 102000004169 proteins and genes Human genes 0.000 description 48
- 230000014509 gene expression Effects 0.000 description 41
- 239000013598 vector Substances 0.000 description 38
- 108020004414 DNA Proteins 0.000 description 35
- 102400000058 Neuregulin-1 Human genes 0.000 description 32
- 235000001014 amino acid Nutrition 0.000 description 29
- 229940024606 amino acid Drugs 0.000 description 27
- 150000001413 amino acids Chemical class 0.000 description 27
- 125000003275 alpha amino acid group Chemical group 0.000 description 26
- 239000000427 antigen Substances 0.000 description 23
- 108091007433 antigens Proteins 0.000 description 23
- 102000036639 antigens Human genes 0.000 description 23
- 230000004663 cell proliferation Effects 0.000 description 21
- 230000004927 fusion Effects 0.000 description 21
- 102000004190 Enzymes Human genes 0.000 description 20
- 108090000790 Enzymes Proteins 0.000 description 20
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 20
- 230000000694 effects Effects 0.000 description 20
- 229940088598 enzyme Drugs 0.000 description 20
- 238000006467 substitution reaction Methods 0.000 description 20
- 206010028980 Neoplasm Diseases 0.000 description 19
- 240000004808 Saccharomyces cerevisiae Species 0.000 description 18
- 235000014680 Saccharomyces cerevisiae Nutrition 0.000 description 18
- 101800001649 Heparin-binding EGF-like growth factor Proteins 0.000 description 17
- 102400001369 Heparin-binding EGF-like growth factor Human genes 0.000 description 17
- 230000004913 activation Effects 0.000 description 17
- 238000012360 testing method Methods 0.000 description 17
- 241000899864 Cherry mottle leaf virus Species 0.000 description 16
- 238000010276 construction Methods 0.000 description 16
- 239000002502 liposome Substances 0.000 description 16
- 201000010099 disease Diseases 0.000 description 15
- 238000000338 in vitro Methods 0.000 description 15
- 238000002360 preparation method Methods 0.000 description 15
- 206010006187 Breast cancer Diseases 0.000 description 14
- 238000011534 incubation Methods 0.000 description 14
- 235000002374 tyrosine Nutrition 0.000 description 14
- 208000026310 Breast neoplasm Diseases 0.000 description 13
- 102100030086 Receptor tyrosine-protein kinase erbB-2 Human genes 0.000 description 13
- 238000003556 assay Methods 0.000 description 13
- 230000015572 biosynthetic process Effects 0.000 description 13
- 239000000872 buffer Substances 0.000 description 13
- 201000011510 cancer Diseases 0.000 description 13
- 230000001965 increasing effect Effects 0.000 description 13
- 210000004962 mammalian cell Anatomy 0.000 description 13
- 238000013459 approach Methods 0.000 description 12
- 239000012528 membrane Substances 0.000 description 12
- 239000000203 mixture Substances 0.000 description 12
- 230000004048 modification Effects 0.000 description 12
- 238000012986 modification Methods 0.000 description 12
- 230000001225 therapeutic effect Effects 0.000 description 12
- 102000001301 EGF receptor Human genes 0.000 description 11
- 241000588724 Escherichia coli Species 0.000 description 11
- 101001012157 Homo sapiens Receptor tyrosine-protein kinase erbB-2 Proteins 0.000 description 11
- 239000003795 chemical substances by application Substances 0.000 description 11
- 238000010367 cloning Methods 0.000 description 11
- -1 glycine Chemical class 0.000 description 11
- 108010037896 heparin-binding hemagglutinin Proteins 0.000 description 11
- 239000002609 medium Substances 0.000 description 11
- 238000000746 purification Methods 0.000 description 11
- 239000007790 solid phase Substances 0.000 description 11
- 241000124008 Mammalia Species 0.000 description 10
- 206010035226 Plasma cell myeloma Diseases 0.000 description 10
- 102100024952 Protein CBFA2T1 Human genes 0.000 description 10
- 108010076504 Protein Sorting Signals Proteins 0.000 description 10
- 239000003153 chemical reaction reagent Substances 0.000 description 10
- 238000012217 deletion Methods 0.000 description 10
- 230000037430 deletion Effects 0.000 description 10
- 230000006870 function Effects 0.000 description 10
- 239000003102 growth factor Substances 0.000 description 10
- 238000002703 mutagenesis Methods 0.000 description 10
- 231100000350 mutagenesis Toxicity 0.000 description 10
- 201000000050 myeloid neoplasm Diseases 0.000 description 10
- 238000012216 screening Methods 0.000 description 10
- 238000003786 synthesis reaction Methods 0.000 description 10
- 108060006698 EGF receptor Proteins 0.000 description 9
- 241000699670 Mus sp. Species 0.000 description 9
- 239000002202 Polyethylene glycol Substances 0.000 description 9
- 238000004587 chromatography analysis Methods 0.000 description 9
- 238000010790 dilution Methods 0.000 description 9
- 239000012895 dilution Substances 0.000 description 9
- 238000005516 engineering process Methods 0.000 description 9
- 239000013604 expression vector Substances 0.000 description 9
- 230000016784 immunoglobulin production Effects 0.000 description 9
- 229940072221 immunoglobulins Drugs 0.000 description 9
- 238000010348 incorporation Methods 0.000 description 9
- 238000003780 insertion Methods 0.000 description 9
- 230000037431 insertion Effects 0.000 description 9
- 239000000463 material Substances 0.000 description 9
- 230000035772 mutation Effects 0.000 description 9
- 229920001223 polyethylene glycol Polymers 0.000 description 9
- 229940002612 prodrug Drugs 0.000 description 9
- 239000000651 prodrug Substances 0.000 description 9
- 239000000047 product Substances 0.000 description 9
- 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 8
- 241000894006 Bacteria Species 0.000 description 8
- 241001465754 Metazoa Species 0.000 description 8
- 241001529936 Murinae Species 0.000 description 8
- 241000699666 Mus <mouse, genus> Species 0.000 description 8
- 241000283984 Rodentia Species 0.000 description 8
- 238000002399 angioplasty Methods 0.000 description 8
- 239000012636 effector Substances 0.000 description 8
- 230000012010 growth Effects 0.000 description 8
- 239000013612 plasmid Substances 0.000 description 8
- 230000008569 process Effects 0.000 description 8
- 210000002966 serum Anatomy 0.000 description 8
- 210000001519 tissue Anatomy 0.000 description 8
- 230000009466 transformation Effects 0.000 description 8
- 241000283707 Capra Species 0.000 description 7
- 108091026890 Coding region Proteins 0.000 description 7
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 7
- 108091005804 Peptidases Proteins 0.000 description 7
- 239000004365 Protease Substances 0.000 description 7
- 102220497176 Small vasohibin-binding protein_T47D_mutation Human genes 0.000 description 7
- 108010022394 Threonine synthase Proteins 0.000 description 7
- 108090000190 Thrombin Proteins 0.000 description 7
- 238000004458 analytical method Methods 0.000 description 7
- 230000004071 biological effect Effects 0.000 description 7
- 210000004204 blood vessel Anatomy 0.000 description 7
- 238000004113 cell culture Methods 0.000 description 7
- 238000012512 characterization method Methods 0.000 description 7
- 238000011161 development Methods 0.000 description 7
- 230000018109 developmental process Effects 0.000 description 7
- 102000004419 dihydrofolate reductase Human genes 0.000 description 7
- 239000003085 diluting agent Substances 0.000 description 7
- 239000001963 growth medium Substances 0.000 description 7
- 206010020718 hyperplasia Diseases 0.000 description 7
- 230000007170 pathology Effects 0.000 description 7
- 239000012071 phase Substances 0.000 description 7
- 238000011160 research Methods 0.000 description 7
- 238000001890 transfection Methods 0.000 description 7
- 239000002699 waste material Substances 0.000 description 7
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 6
- 241000699802 Cricetulus griseus Species 0.000 description 6
- WQZGKKKJIJFFOK-QTVWNMPRSA-N D-mannopyranose Chemical compound OC[C@H]1OC(O)[C@@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-QTVWNMPRSA-N 0.000 description 6
- 108091034117 Oligonucleotide Proteins 0.000 description 6
- 108700020796 Oncogene Proteins 0.000 description 6
- 102000003992 Peroxidases Human genes 0.000 description 6
- 102000004022 Protein-Tyrosine Kinases Human genes 0.000 description 6
- 108090000412 Protein-Tyrosine Kinases Proteins 0.000 description 6
- 101710100969 Receptor tyrosine-protein kinase erbB-3 Proteins 0.000 description 6
- 108020004511 Recombinant DNA Proteins 0.000 description 6
- IQFYYKKMVGJFEH-XLPZGREQSA-N Thymidine Chemical compound O=C1NC(=O)C(C)=CN1[C@@H]1O[C@H](CO)[C@@H](O)C1 IQFYYKKMVGJFEH-XLPZGREQSA-N 0.000 description 6
- 125000000539 amino acid group Chemical group 0.000 description 6
- 150000001720 carbohydrates Chemical class 0.000 description 6
- 235000014633 carbohydrates Nutrition 0.000 description 6
- 239000013592 cell lysate Substances 0.000 description 6
- 238000006243 chemical reaction Methods 0.000 description 6
- HVYWMOMLDIMFJA-DPAQBDIFSA-N cholesterol Chemical compound C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CCCC(C)C)[C@@]1(C)CC2 HVYWMOMLDIMFJA-DPAQBDIFSA-N 0.000 description 6
- 150000001875 compounds Chemical class 0.000 description 6
- 108020001507 fusion proteins Proteins 0.000 description 6
- 102000037865 fusion proteins Human genes 0.000 description 6
- 230000013595 glycosylation Effects 0.000 description 6
- 238000006206 glycosylation reaction Methods 0.000 description 6
- 230000006698 induction Effects 0.000 description 6
- 239000003550 marker Substances 0.000 description 6
- 230000001404 mediated effect Effects 0.000 description 6
- 239000003226 mitogen Substances 0.000 description 6
- 239000002773 nucleotide Substances 0.000 description 6
- 125000003729 nucleotide group Chemical group 0.000 description 6
- 239000002245 particle Substances 0.000 description 6
- 108040007629 peroxidase activity proteins Proteins 0.000 description 6
- 230000003389 potentiating effect Effects 0.000 description 6
- 230000002829 reductive effect Effects 0.000 description 6
- 230000004044 response Effects 0.000 description 6
- 241000894007 species Species 0.000 description 6
- 239000000126 substance Substances 0.000 description 6
- 229960004072 thrombin Drugs 0.000 description 6
- 238000012546 transfer Methods 0.000 description 6
- 241000701161 unidentified adenovirus Species 0.000 description 6
- 101100285680 Caenorhabditis elegans hrg-1 gene Proteins 0.000 description 5
- 201000009030 Carcinoma Diseases 0.000 description 5
- 101150004694 Erbb4 gene Proteins 0.000 description 5
- 241000282412 Homo Species 0.000 description 5
- DCXYFEDJOCDNAF-REOHCLBHSA-N L-asparagine Chemical compound OC(=O)[C@@H](N)CC(N)=O DCXYFEDJOCDNAF-REOHCLBHSA-N 0.000 description 5
- ZDXPYRJPNDTMRX-VKHMYHEASA-N L-glutamine Chemical compound OC(=O)[C@@H](N)CCC(N)=O ZDXPYRJPNDTMRX-VKHMYHEASA-N 0.000 description 5
- 108091000080 Phosphotransferase Proteins 0.000 description 5
- 229920001213 Polysorbate 20 Polymers 0.000 description 5
- 102100029986 Receptor tyrosine-protein kinase erbB-3 Human genes 0.000 description 5
- 241000700605 Viruses Species 0.000 description 5
- 230000001464 adherent effect Effects 0.000 description 5
- 230000003305 autocrine Effects 0.000 description 5
- 230000017531 blood circulation Effects 0.000 description 5
- 210000004899 c-terminal region Anatomy 0.000 description 5
- 239000001506 calcium phosphate Substances 0.000 description 5
- 229910000389 calcium phosphate Inorganic materials 0.000 description 5
- 235000011010 calcium phosphates Nutrition 0.000 description 5
- 230000001413 cellular effect Effects 0.000 description 5
- 230000035605 chemotaxis Effects 0.000 description 5
- 230000003247 decreasing effect Effects 0.000 description 5
- 208000035475 disorder Diseases 0.000 description 5
- 230000002526 effect on cardiovascular system Effects 0.000 description 5
- 230000003511 endothelial effect Effects 0.000 description 5
- 239000003623 enhancer Substances 0.000 description 5
- 230000002255 enzymatic effect Effects 0.000 description 5
- 230000003993 interaction Effects 0.000 description 5
- 238000002955 isolation Methods 0.000 description 5
- 150000002632 lipids Chemical class 0.000 description 5
- 238000012423 maintenance Methods 0.000 description 5
- 239000000178 monomer Substances 0.000 description 5
- 210000000056 organ Anatomy 0.000 description 5
- 230000037361 pathway Effects 0.000 description 5
- 102000020233 phosphotransferase Human genes 0.000 description 5
- 239000000256 polyoxyethylene sorbitan monolaurate Substances 0.000 description 5
- 235000010486 polyoxyethylene sorbitan monolaurate Nutrition 0.000 description 5
- 238000000159 protein binding assay Methods 0.000 description 5
- 230000002285 radioactive effect Effects 0.000 description 5
- 230000010076 replication Effects 0.000 description 5
- 239000000243 solution Substances 0.000 description 5
- 238000013518 transcription Methods 0.000 description 5
- 230000035897 transcription Effects 0.000 description 5
- QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 description 5
- 239000003981 vehicle Substances 0.000 description 5
- 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 4
- MTCFGRXMJLQNBG-REOHCLBHSA-N (2S)-2-Amino-3-hydroxypropansäure Chemical compound OC[C@H](N)C(O)=O MTCFGRXMJLQNBG-REOHCLBHSA-N 0.000 description 4
- 102000002260 Alkaline Phosphatase Human genes 0.000 description 4
- 108020004774 Alkaline Phosphatase Proteins 0.000 description 4
- DCXYFEDJOCDNAF-UHFFFAOYSA-N Asparagine Natural products OC(=O)C(N)CC(N)=O DCXYFEDJOCDNAF-UHFFFAOYSA-N 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
- 102400001329 Epiregulin Human genes 0.000 description 4
- 101800000155 Epiregulin Proteins 0.000 description 4
- 108010008165 Etanercept Proteins 0.000 description 4
- 102000013463 Immunoglobulin Light Chains Human genes 0.000 description 4
- 108010065825 Immunoglobulin Light Chains Proteins 0.000 description 4
- QNAYBMKLOCPYGJ-REOHCLBHSA-N L-alanine Chemical compound C[C@H](N)C(O)=O QNAYBMKLOCPYGJ-REOHCLBHSA-N 0.000 description 4
- WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 description 4
- KDXKERNSBIXSRK-YFKPBYRVSA-N L-lysine Chemical compound NCCCC[C@H](N)C(O)=O KDXKERNSBIXSRK-YFKPBYRVSA-N 0.000 description 4
- AYFVYJQAPQTCCC-GBXIJSLDSA-N L-threonine Chemical compound C[C@@H](O)[C@H](N)C(O)=O AYFVYJQAPQTCCC-GBXIJSLDSA-N 0.000 description 4
- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 4
- 108091028043 Nucleic acid sequence Proteins 0.000 description 4
- 102000035195 Peptidases Human genes 0.000 description 4
- 108010029485 Protein Isoforms Proteins 0.000 description 4
- 102000001708 Protein Isoforms Human genes 0.000 description 4
- 239000012980 RPMI-1640 medium Substances 0.000 description 4
- 102000004278 Receptor Protein-Tyrosine Kinases Human genes 0.000 description 4
- 108090000873 Receptor Protein-Tyrosine Kinases Proteins 0.000 description 4
- 239000004473 Threonine Substances 0.000 description 4
- 108060008682 Tumor Necrosis Factor Proteins 0.000 description 4
- 239000002671 adjuvant Substances 0.000 description 4
- 235000004279 alanine Nutrition 0.000 description 4
- 239000002246 antineoplastic agent Substances 0.000 description 4
- 235000009582 asparagine Nutrition 0.000 description 4
- 229960001230 asparagine Drugs 0.000 description 4
- 239000012148 binding buffer Substances 0.000 description 4
- 210000000481 breast Anatomy 0.000 description 4
- 230000012292 cell migration Effects 0.000 description 4
- 230000036755 cellular response Effects 0.000 description 4
- 230000008859 change Effects 0.000 description 4
- 229940127089 cytotoxic agent Drugs 0.000 description 4
- 230000006378 damage Effects 0.000 description 4
- 230000007423 decrease Effects 0.000 description 4
- 238000004520 electroporation Methods 0.000 description 4
- 230000008472 epithelial growth Effects 0.000 description 4
- 210000004602 germ cell Anatomy 0.000 description 4
- 230000002209 hydrophobic effect Effects 0.000 description 4
- FDGQSTZJBFJUBT-UHFFFAOYSA-N hypoxanthine Chemical compound O=C1NC=NC2=C1NC=N2 FDGQSTZJBFJUBT-UHFFFAOYSA-N 0.000 description 4
- 230000002163 immunogen Effects 0.000 description 4
- 239000007943 implant Substances 0.000 description 4
- 230000000670 limiting effect Effects 0.000 description 4
- 210000004698 lymphocyte Anatomy 0.000 description 4
- 238000013507 mapping Methods 0.000 description 4
- 239000003094 microcapsule Substances 0.000 description 4
- 210000003205 muscle Anatomy 0.000 description 4
- 239000000523 sample Substances 0.000 description 4
- 230000028327 secretion Effects 0.000 description 4
- 230000019491 signal transduction Effects 0.000 description 4
- 238000010186 staining Methods 0.000 description 4
- 239000000758 substrate Substances 0.000 description 4
- 239000006228 supernatant Substances 0.000 description 4
- 230000004083 survival effect Effects 0.000 description 4
- 102000003390 tumor necrosis factor Human genes 0.000 description 4
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 3
- 206010003445 Ascites Diseases 0.000 description 3
- 201000001320 Atherosclerosis Diseases 0.000 description 3
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
- DWRXFEITVBNRMK-UHFFFAOYSA-N Beta-D-1-Arabinofuranosylthymine Natural products O=C1NC(=O)C(C)=CN1C1C(O)C(O)C(CO)O1 DWRXFEITVBNRMK-UHFFFAOYSA-N 0.000 description 3
- 241000283690 Bos taurus Species 0.000 description 3
- 241000222120 Candida <Saccharomycetales> Species 0.000 description 3
- BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 description 3
- 241000701022 Cytomegalovirus Species 0.000 description 3
- 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 3
- 241000196324 Embryophyta Species 0.000 description 3
- 102100038132 Endogenous retrovirus group K member 6 Pro protein Human genes 0.000 description 3
- 101100390711 Escherichia coli (strain K12) fhuA gene Proteins 0.000 description 3
- 241000233866 Fungi Species 0.000 description 3
- 108010010803 Gelatin Proteins 0.000 description 3
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 3
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 3
- 239000004471 Glycine Substances 0.000 description 3
- 108010092694 L-Selectin Proteins 0.000 description 3
- ROHFNLRQFUQHCH-YFKPBYRVSA-N L-leucine Chemical compound CC(C)C[C@H](N)C(O)=O ROHFNLRQFUQHCH-YFKPBYRVSA-N 0.000 description 3
- 102100033467 L-selectin Human genes 0.000 description 3
- QIVBCDIJIAJPQS-VIFPVBQESA-N L-tryptophane Chemical compound C1=CC=C2C(C[C@H](N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-VIFPVBQESA-N 0.000 description 3
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- 101100178822 Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv) htrA1 gene Proteins 0.000 description 3
- 101800000675 Neuregulin-2 Proteins 0.000 description 3
- 101100407828 Neurospora crassa (strain ATCC 24698 / 74-OR23-1A / CBS 708.71 / DSM 1257 / FGSC 987) ptr-3 gene Proteins 0.000 description 3
- 230000004989 O-glycosylation Effects 0.000 description 3
- 229910019142 PO4 Inorganic materials 0.000 description 3
- 102100022668 Pro-neuregulin-2, membrane-bound isoform Human genes 0.000 description 3
- 241000700159 Rattus Species 0.000 description 3
- 101710100968 Receptor tyrosine-protein kinase erbB-2 Proteins 0.000 description 3
- 101100277437 Rhizobium meliloti (strain 1021) degP1 gene Proteins 0.000 description 3
- 206010040070 Septic Shock Diseases 0.000 description 3
- MTCFGRXMJLQNBG-UHFFFAOYSA-N Serine Natural products OCC(N)C(O)=O MTCFGRXMJLQNBG-UHFFFAOYSA-N 0.000 description 3
- 241000607720 Serratia Species 0.000 description 3
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 3
- AYFVYJQAPQTCCC-UHFFFAOYSA-N Threonine Natural products CC(O)C(N)C(O)=O AYFVYJQAPQTCCC-UHFFFAOYSA-N 0.000 description 3
- QIVBCDIJIAJPQS-UHFFFAOYSA-N Tryptophan Natural products C1=CC=C2C(CC(N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-UHFFFAOYSA-N 0.000 description 3
- 108060008683 Tumor Necrosis Factor Receptor Proteins 0.000 description 3
- 208000027418 Wounds and injury Diseases 0.000 description 3
- JLCPHMBAVCMARE-UHFFFAOYSA-N [3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-[[3-[[3-[[3-[[3-[[3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-hydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methyl [5-(6-aminopurin-9-yl)-2-(hydroxymethyl)oxolan-3-yl] hydrogen phosphate Polymers Cc1cn(C2CC(OP(O)(=O)OCC3OC(CC3OP(O)(=O)OCC3OC(CC3O)n3cnc4c3nc(N)[nH]c4=O)n3cnc4c3nc(N)[nH]c4=O)C(COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3CO)n3cnc4c(N)ncnc34)n3ccc(N)nc3=O)n3cnc4c(N)ncnc34)n3ccc(N)nc3=O)n3ccc(N)nc3=O)n3ccc(N)nc3=O)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cc(C)c(=O)[nH]c3=O)n3cc(C)c(=O)[nH]c3=O)n3ccc(N)nc3=O)n3cc(C)c(=O)[nH]c3=O)n3cnc4c3nc(N)[nH]c4=O)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)O2)c(=O)[nH]c1=O JLCPHMBAVCMARE-UHFFFAOYSA-N 0.000 description 3
- 230000002378 acidificating effect Effects 0.000 description 3
- 230000004075 alteration Effects 0.000 description 3
- 230000003321 amplification Effects 0.000 description 3
- 229960005070 ascorbic acid Drugs 0.000 description 3
- 235000010323 ascorbic acid Nutrition 0.000 description 3
- 239000011668 ascorbic acid Substances 0.000 description 3
- 239000012131 assay buffer Substances 0.000 description 3
- 230000035578 autophosphorylation Effects 0.000 description 3
- IQFYYKKMVGJFEH-UHFFFAOYSA-N beta-L-thymidine Natural products O=C1NC(=O)C(C)=CN1C1OC(CO)C(O)C1 IQFYYKKMVGJFEH-UHFFFAOYSA-N 0.000 description 3
- 230000033228 biological regulation Effects 0.000 description 3
- 230000000903 blocking effect Effects 0.000 description 3
- 210000004369 blood Anatomy 0.000 description 3
- 239000008280 blood Substances 0.000 description 3
- 201000008275 breast carcinoma Diseases 0.000 description 3
- 230000010261 cell growth Effects 0.000 description 3
- 238000002512 chemotherapy Methods 0.000 description 3
- 235000012000 cholesterol Nutrition 0.000 description 3
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
- 230000000295 complement effect Effects 0.000 description 3
- 229920001577 copolymer Polymers 0.000 description 3
- 101150018266 degP gene Proteins 0.000 description 3
- 229940073621 enbrel Drugs 0.000 description 3
- 210000003527 eukaryotic cell Anatomy 0.000 description 3
- 238000001943 fluorescence-activated cell sorting Methods 0.000 description 3
- 230000002496 gastric effect Effects 0.000 description 3
- 239000000499 gel Substances 0.000 description 3
- 229920000159 gelatin Polymers 0.000 description 3
- 235000019322 gelatine Nutrition 0.000 description 3
- 235000011852 gelatine desserts Nutrition 0.000 description 3
- 239000008103 glucose Substances 0.000 description 3
- ZDXPYRJPNDTMRX-UHFFFAOYSA-N glutamine Natural products OC(=O)C(N)CCC(N)=O ZDXPYRJPNDTMRX-UHFFFAOYSA-N 0.000 description 3
- 229940022353 herceptin Drugs 0.000 description 3
- 208000009322 hypertrophic pyloric stenosis Diseases 0.000 description 3
- 229940124452 immunizing agent Drugs 0.000 description 3
- 230000008676 import Effects 0.000 description 3
- 230000028709 inflammatory response Effects 0.000 description 3
- 239000003112 inhibitor Substances 0.000 description 3
- 208000014674 injury Diseases 0.000 description 3
- 230000003834 intracellular effect Effects 0.000 description 3
- 210000003734 kidney Anatomy 0.000 description 3
- 210000004072 lung Anatomy 0.000 description 3
- 108020004999 messenger RNA Proteins 0.000 description 3
- 210000004165 myocardium Anatomy 0.000 description 3
- 230000007935 neutral effect Effects 0.000 description 3
- 238000003199 nucleic acid amplification method Methods 0.000 description 3
- 235000015097 nutrients Nutrition 0.000 description 3
- 230000002611 ovarian Effects 0.000 description 3
- 210000001672 ovary Anatomy 0.000 description 3
- 230000001575 pathological effect Effects 0.000 description 3
- 238000010647 peptide synthesis reaction Methods 0.000 description 3
- 239000000546 pharmaceutical excipient Substances 0.000 description 3
- 235000021317 phosphate Nutrition 0.000 description 3
- 229920001451 polypropylene glycol Polymers 0.000 description 3
- 238000001556 precipitation Methods 0.000 description 3
- 210000001236 prokaryotic cell Anatomy 0.000 description 3
- 235000019419 proteases Nutrition 0.000 description 3
- 230000008707 rearrangement Effects 0.000 description 3
- 230000009467 reduction Effects 0.000 description 3
- 210000002345 respiratory system Anatomy 0.000 description 3
- 238000012552 review Methods 0.000 description 3
- 230000003248 secreting effect Effects 0.000 description 3
- 238000000926 separation method Methods 0.000 description 3
- 230000036303 septic shock Effects 0.000 description 3
- 238000002415 sodium dodecyl sulfate polyacrylamide gel electrophoresis Methods 0.000 description 3
- 239000003381 stabilizer Substances 0.000 description 3
- 230000000638 stimulation Effects 0.000 description 3
- 238000001356 surgical procedure Methods 0.000 description 3
- 208000011580 syndromic disease Diseases 0.000 description 3
- 229940104230 thymidine Drugs 0.000 description 3
- 230000014616 translation Effects 0.000 description 3
- 102000003298 tumor necrosis factor receptor Human genes 0.000 description 3
- 210000001635 urinary tract Anatomy 0.000 description 3
- 230000003612 virological effect Effects 0.000 description 3
- 239000011534 wash buffer Substances 0.000 description 3
- 238000005406 washing Methods 0.000 description 3
- IQFYYKKMVGJFEH-OFKYTIFKSA-N 1-[(2r,4s,5r)-4-hydroxy-5-(tritiooxymethyl)oxolan-2-yl]-5-methylpyrimidine-2,4-dione Chemical compound C1[C@H](O)[C@@H](CO[3H])O[C@H]1N1C(=O)NC(=O)C(C)=C1 IQFYYKKMVGJFEH-OFKYTIFKSA-N 0.000 description 2
- GZCWLCBFPRFLKL-UHFFFAOYSA-N 1-prop-2-ynoxypropan-2-ol Chemical compound CC(O)COCC#C GZCWLCBFPRFLKL-UHFFFAOYSA-N 0.000 description 2
- JKMHFZQWWAIEOD-UHFFFAOYSA-N 2-[4-(2-hydroxyethyl)piperazin-1-yl]ethanesulfonic acid Chemical compound OCC[NH+]1CCN(CCS([O-])(=O)=O)CC1 JKMHFZQWWAIEOD-UHFFFAOYSA-N 0.000 description 2
- OSJPPGNTCRNQQC-UWTATZPHSA-N 3-phospho-D-glyceric acid Chemical compound OC(=O)[C@H](O)COP(O)(O)=O OSJPPGNTCRNQQC-UWTATZPHSA-N 0.000 description 2
- KKJUPNGICOCCDW-UHFFFAOYSA-N 7-N,N-Dimethylamino-1,2,3,4,5-pentathiocyclooctane Chemical compound CN(C)C1CSSSSSC1 KKJUPNGICOCCDW-UHFFFAOYSA-N 0.000 description 2
- 102000013563 Acid Phosphatase Human genes 0.000 description 2
- 108010051457 Acid Phosphatase Proteins 0.000 description 2
- 229920000936 Agarose Polymers 0.000 description 2
- 108010088751 Albumins Proteins 0.000 description 2
- 102000009027 Albumins Human genes 0.000 description 2
- 101100067974 Arabidopsis thaliana POP2 gene Proteins 0.000 description 2
- 239000004475 Arginine Substances 0.000 description 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- 102100022717 Atypical chemokine receptor 1 Human genes 0.000 description 2
- 241000194108 Bacillus licheniformis Species 0.000 description 2
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 2
- 235000011960 Brassica ruvo Nutrition 0.000 description 2
- 206010006482 Bronchospasm Diseases 0.000 description 2
- 108010041884 CD4 Immunoadhesins Proteins 0.000 description 2
- 102000005600 Cathepsins Human genes 0.000 description 2
- 108010084457 Cathepsins Proteins 0.000 description 2
- 229920002157 Cellulin Polymers 0.000 description 2
- 108020004705 Codon Proteins 0.000 description 2
- 108020004635 Complementary DNA Proteins 0.000 description 2
- 108091035707 Consensus sequence Proteins 0.000 description 2
- FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 2
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 2
- FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 description 2
- SRBFZHDQGSBBOR-IOVATXLUSA-N D-xylopyranose Chemical compound O[C@@H]1COC(O)[C@H](O)[C@H]1O SRBFZHDQGSBBOR-IOVATXLUSA-N 0.000 description 2
- 230000004544 DNA amplification Effects 0.000 description 2
- 229920002307 Dextran Polymers 0.000 description 2
- 239000004375 Dextrin Substances 0.000 description 2
- 229920001353 Dextrin Polymers 0.000 description 2
- 239000006144 Dulbecco’s modified Eagle's medium Substances 0.000 description 2
- 241000588921 Enterobacteriaceae Species 0.000 description 2
- 241001302584 Escherichia coli str. K-12 substr. W3110 Species 0.000 description 2
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 2
- 241000206602 Eukaryota Species 0.000 description 2
- 241000724791 Filamentous phage Species 0.000 description 2
- 238000012413 Fluorescence activated cell sorting analysis Methods 0.000 description 2
- 108091006027 G proteins Proteins 0.000 description 2
- 102000030782 GTP binding Human genes 0.000 description 2
- 108091000058 GTP-Binding Proteins 0.000 description 2
- 108700028146 Genetic Enhancer Elements Proteins 0.000 description 2
- 108010070600 Glucose-6-phosphate isomerase Proteins 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
- JZNWSCPGTDBMEW-UHFFFAOYSA-N Glycerophosphorylethanolamin Natural products NCCOP(O)(=O)OCC(O)CO JZNWSCPGTDBMEW-UHFFFAOYSA-N 0.000 description 2
- 102000009465 Growth Factor Receptors Human genes 0.000 description 2
- 108010009202 Growth Factor Receptors Proteins 0.000 description 2
- 239000007995 HEPES buffer Substances 0.000 description 2
- WZUVPPKBWHMQCE-UHFFFAOYSA-N Haematoxylin Chemical compound C12=CC(O)=C(O)C=C2CC2(O)C1C1=CC=C(O)C(O)=C1OC2 WZUVPPKBWHMQCE-UHFFFAOYSA-N 0.000 description 2
- HTTJABKRGRZYRN-UHFFFAOYSA-N Heparin Chemical compound OC1C(NC(=O)C)C(O)OC(COS(O)(=O)=O)C1OC1C(OS(O)(=O)=O)C(O)C(OC2C(C(OS(O)(=O)=O)C(OC3C(C(O)C(O)C(O3)C(O)=O)OS(O)(=O)=O)C(CO)O2)NS(O)(=O)=O)C(C(O)=O)O1 HTTJABKRGRZYRN-UHFFFAOYSA-N 0.000 description 2
- 241000238631 Hexapoda Species 0.000 description 2
- 101000678879 Homo sapiens Atypical chemokine receptor 1 Proteins 0.000 description 2
- 101100118549 Homo sapiens EGFR gene Proteins 0.000 description 2
- 206010020880 Hypertrophy Diseases 0.000 description 2
- 108010091358 Hypoxanthine Phosphoribosyltransferase Proteins 0.000 description 2
- UGQMRVRMYYASKQ-UHFFFAOYSA-N Hypoxanthine nucleoside Natural products OC1C(O)C(CO)OC1N1C(NC=NC2=O)=C2N=C1 UGQMRVRMYYASKQ-UHFFFAOYSA-N 0.000 description 2
- 102100029098 Hypoxanthine-guanine phosphoribosyltransferase Human genes 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
- 206010061218 Inflammation Diseases 0.000 description 2
- 241000235649 Kluyveromyces Species 0.000 description 2
- 244000285963 Kluyveromyces fragilis Species 0.000 description 2
- 241001138401 Kluyveromyces lactis Species 0.000 description 2
- 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 2
- ROHFNLRQFUQHCH-UHFFFAOYSA-N Leucine Natural products CC(C)CC(N)C(O)=O ROHFNLRQFUQHCH-UHFFFAOYSA-N 0.000 description 2
- 239000004472 Lysine Substances 0.000 description 2
- 229930195725 Mannitol Natural products 0.000 description 2
- 102000018697 Membrane Proteins Human genes 0.000 description 2
- 108010052285 Membrane Proteins Proteins 0.000 description 2
- 230000004988 N-glycosylation Effects 0.000 description 2
- SEQKRHFRPICQDD-UHFFFAOYSA-N N-tris(hydroxymethyl)methylglycine Chemical compound OCC(CO)(CO)[NH2+]CC([O-])=O SEQKRHFRPICQDD-UHFFFAOYSA-N 0.000 description 2
- 206010028851 Necrosis Diseases 0.000 description 2
- 101800002648 Neuregulin-1 Proteins 0.000 description 2
- 102400000054 Neuregulin-3 Human genes 0.000 description 2
- 101800000673 Neuregulin-3 Proteins 0.000 description 2
- 241000283973 Oryctolagus cuniculus Species 0.000 description 2
- 239000002033 PVDF binder Substances 0.000 description 2
- 108090000526 Papain Proteins 0.000 description 2
- 241001494479 Pecora Species 0.000 description 2
- 241000235648 Pichia Species 0.000 description 2
- 229920000362 Polyethylene-block-poly(ethylene glycol) Polymers 0.000 description 2
- 241000589516 Pseudomonas Species 0.000 description 2
- 241000235070 Saccharomyces Species 0.000 description 2
- 101100123851 Saccharomyces cerevisiae (strain ATCC 204508 / S288c) HER1 gene Proteins 0.000 description 2
- 108010071390 Serum Albumin Proteins 0.000 description 2
- 102000007562 Serum Albumin Human genes 0.000 description 2
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 2
- BQCADISMDOOEFD-UHFFFAOYSA-N Silver Chemical compound [Ag] BQCADISMDOOEFD-UHFFFAOYSA-N 0.000 description 2
- 108010090804 Streptavidin Proteins 0.000 description 2
- 101150006914 TRP1 gene Proteins 0.000 description 2
- 208000007536 Thrombosis Diseases 0.000 description 2
- 239000007983 Tris buffer Substances 0.000 description 2
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 2
- 244000000188 Vaccinium ovalifolium Species 0.000 description 2
- 150000007513 acids Chemical class 0.000 description 2
- 230000003213 activating effect Effects 0.000 description 2
- 238000001042 affinity chromatography Methods 0.000 description 2
- WQZGKKKJIJFFOK-PHYPRBDBSA-N alpha-D-galactose Chemical compound OC[C@H]1O[C@H](O)[C@H](O)[C@@H](O)[C@H]1O WQZGKKKJIJFFOK-PHYPRBDBSA-N 0.000 description 2
- 230000001093 anti-cancer Effects 0.000 description 2
- 238000010913 antigen-directed enzyme pro-drug therapy Methods 0.000 description 2
- 230000000890 antigenic effect Effects 0.000 description 2
- 239000003963 antioxidant agent Substances 0.000 description 2
- 235000006708 antioxidants Nutrition 0.000 description 2
- 239000007864 aqueous solution Substances 0.000 description 2
- ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 2
- 208000006673 asthma Diseases 0.000 description 2
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 2
- 244000052616 bacterial pathogen Species 0.000 description 2
- 230000009286 beneficial effect Effects 0.000 description 2
- 230000008901 benefit Effects 0.000 description 2
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 2
- 239000011230 binding agent Substances 0.000 description 2
- 229920001222 biopolymer Polymers 0.000 description 2
- 229960002685 biotin Drugs 0.000 description 2
- 235000020958 biotin Nutrition 0.000 description 2
- 239000011616 biotin Substances 0.000 description 2
- 230000007885 bronchoconstriction Effects 0.000 description 2
- 238000012219 cassette mutagenesis Methods 0.000 description 2
- 239000002738 chelating agent Substances 0.000 description 2
- 230000000973 chemotherapeutic effect Effects 0.000 description 2
- 239000002299 complementary DNA Substances 0.000 description 2
- 230000021615 conjugation Effects 0.000 description 2
- 238000007887 coronary angioplasty Methods 0.000 description 2
- 210000004351 coronary vessel Anatomy 0.000 description 2
- 238000012258 culturing Methods 0.000 description 2
- 238000005520 cutting process Methods 0.000 description 2
- OPTASPLRGRRNAP-UHFFFAOYSA-N cytosine Chemical compound NC=1C=CNC(=O)N=1 OPTASPLRGRRNAP-UHFFFAOYSA-N 0.000 description 2
- 235000013365 dairy product Nutrition 0.000 description 2
- 230000002950 deficient Effects 0.000 description 2
- 230000001419 dependent effect Effects 0.000 description 2
- 230000008021 deposition Effects 0.000 description 2
- 238000001514 detection method Methods 0.000 description 2
- 235000019425 dextrin Nutrition 0.000 description 2
- 150000002016 disaccharides Chemical class 0.000 description 2
- 125000002228 disulfide group Chemical group 0.000 description 2
- 229960004679 doxorubicin Drugs 0.000 description 2
- 238000001704 evaporation Methods 0.000 description 2
- 230000008020 evaporation Effects 0.000 description 2
- 239000013613 expression plasmid Substances 0.000 description 2
- 239000012091 fetal bovine serum Substances 0.000 description 2
- 210000002950 fibroblast Anatomy 0.000 description 2
- 238000001914 filtration Methods 0.000 description 2
- 239000012530 fluid Substances 0.000 description 2
- 238000009472 formulation Methods 0.000 description 2
- 238000005194 fractionation Methods 0.000 description 2
- 229930182830 galactose Natural products 0.000 description 2
- 238000001502 gel electrophoresis Methods 0.000 description 2
- 239000008273 gelatin Substances 0.000 description 2
- 102000006602 glyceraldehyde-3-phosphate dehydrogenase Human genes 0.000 description 2
- 108020004445 glyceraldehyde-3-phosphate dehydrogenase Proteins 0.000 description 2
- 208000035474 group of disease Diseases 0.000 description 2
- UYTPUPDQBNUYGX-UHFFFAOYSA-N guanine Chemical compound O=C1NC(N)=NC2=C1N=CN2 UYTPUPDQBNUYGX-UHFFFAOYSA-N 0.000 description 2
- 229940093915 gynecological organic acid Drugs 0.000 description 2
- 229960002897 heparin Drugs 0.000 description 2
- 229920000669 heparin Polymers 0.000 description 2
- 239000000833 heterodimer Substances 0.000 description 2
- 229920001477 hydrophilic polymer Polymers 0.000 description 2
- 230000003053 immunization Effects 0.000 description 2
- 238000002649 immunization Methods 0.000 description 2
- 238000003119 immunoblot Methods 0.000 description 2
- 238000001114 immunoprecipitation Methods 0.000 description 2
- 230000004054 inflammatory process Effects 0.000 description 2
- NOESYZHRGYRDHS-UHFFFAOYSA-N insulin Chemical compound N1C(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(NC(=O)CN)C(C)CC)CSSCC(C(NC(CO)C(=O)NC(CC(C)C)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CCC(N)=O)C(=O)NC(CC(C)C)C(=O)NC(CCC(O)=O)C(=O)NC(CC(N)=O)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CSSCC(NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2C=CC(O)=CC=2)NC(=O)C(CC(C)C)NC(=O)C(C)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2NC=NC=2)NC(=O)C(CO)NC(=O)CNC2=O)C(=O)NCC(=O)NC(CCC(O)=O)C(=O)NC(CCCNC(N)=N)C(=O)NCC(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC(O)=CC=3)C(=O)NC(C(C)O)C(=O)N3C(CCC3)C(=O)NC(CCCCN)C(=O)NC(C)C(O)=O)C(=O)NC(CC(N)=O)C(O)=O)=O)NC(=O)C(C(C)CC)NC(=O)C(CO)NC(=O)C(C(C)O)NC(=O)C1CSSCC2NC(=O)C(CC(C)C)NC(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CC(N)=O)NC(=O)C(NC(=O)C(N)CC=1C=CC=CC=1)C(C)C)CC1=CN=CN1 NOESYZHRGYRDHS-UHFFFAOYSA-N 0.000 description 2
- 238000007912 intraperitoneal administration Methods 0.000 description 2
- 238000001990 intravenous administration Methods 0.000 description 2
- 238000005342 ion exchange Methods 0.000 description 2
- 150000002500 ions Chemical class 0.000 description 2
- 210000003292 kidney cell Anatomy 0.000 description 2
- RGLRXNKKBLIBQS-XNHQSDQCSA-N leuprolide acetate Chemical compound CC(O)=O.CCNC(=O)[C@@H]1CCCN1C(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](CC(C)C)NC(=O)[C@@H](NC(=O)[C@H](CO)NC(=O)[C@H](CC=1C2=CC=CC=C2NC=1)NC(=O)[C@H](CC=1N=CNC=1)NC(=O)[C@H]1NC(=O)CC1)CC1=CC=C(O)C=C1 RGLRXNKKBLIBQS-XNHQSDQCSA-N 0.000 description 2
- 239000000594 mannitol Substances 0.000 description 2
- 235000010355 mannitol Nutrition 0.000 description 2
- 239000011159 matrix material Substances 0.000 description 2
- 230000007246 mechanism Effects 0.000 description 2
- 125000001360 methionine group Chemical group N[C@@H](CCSC)C(=O)* 0.000 description 2
- 229960000485 methotrexate Drugs 0.000 description 2
- 244000005700 microbiome Species 0.000 description 2
- 238000000520 microinjection Methods 0.000 description 2
- 239000004005 microsphere Substances 0.000 description 2
- 238000002156 mixing Methods 0.000 description 2
- 238000010369 molecular cloning Methods 0.000 description 2
- 150000002772 monosaccharides Chemical class 0.000 description 2
- 210000002464 muscle smooth vascular Anatomy 0.000 description 2
- 208000010125 myocardial infarction Diseases 0.000 description 2
- 230000017074 necrotic cell death Effects 0.000 description 2
- 230000008692 neointimal formation Effects 0.000 description 2
- 230000009871 nonspecific binding Effects 0.000 description 2
- 231100000252 nontoxic Toxicity 0.000 description 2
- 230000003000 nontoxic effect Effects 0.000 description 2
- 101150093139 ompT gene Proteins 0.000 description 2
- 150000007524 organic acids Chemical class 0.000 description 2
- 235000005985 organic acids Nutrition 0.000 description 2
- 230000002018 overexpression Effects 0.000 description 2
- 239000001301 oxygen Substances 0.000 description 2
- 229910052760 oxygen Inorganic materials 0.000 description 2
- 229940055729 papain Drugs 0.000 description 2
- 235000019834 papain Nutrition 0.000 description 2
- 230000036961 partial effect Effects 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 2
- 239000010452 phosphate Substances 0.000 description 2
- WTJKGGKOPKCXLL-RRHRGVEJSA-N phosphatidylcholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCCCCCCC=CCCCCCCCC WTJKGGKOPKCXLL-RRHRGVEJSA-N 0.000 description 2
- 150000008104 phosphatidylethanolamines Chemical class 0.000 description 2
- 238000003566 phosphorylation assay Methods 0.000 description 2
- 229920001983 poloxamer Polymers 0.000 description 2
- 229920000642 polymer Polymers 0.000 description 2
- 229920000136 polysorbate Polymers 0.000 description 2
- 229920002981 polyvinylidene fluoride Polymers 0.000 description 2
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 2
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 2
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 2
- 239000011148 porous material Substances 0.000 description 2
- 239000002244 precipitate Substances 0.000 description 2
- 239000002243 precursor Substances 0.000 description 2
- 238000001243 protein synthesis Methods 0.000 description 2
- 229940024999 proteolytic enzymes for treatment of wounds and ulcers Drugs 0.000 description 2
- 238000003127 radioimmunoassay Methods 0.000 description 2
- 102000027426 receptor tyrosine kinases Human genes 0.000 description 2
- 108091008598 receptor tyrosine kinases Proteins 0.000 description 2
- 238000003757 reverse transcription PCR Methods 0.000 description 2
- 230000002441 reversible effect Effects 0.000 description 2
- 206010039073 rheumatoid arthritis Diseases 0.000 description 2
- 230000011664 signaling Effects 0.000 description 2
- 229910052709 silver Inorganic materials 0.000 description 2
- 239000004332 silver Substances 0.000 description 2
- 150000003384 small molecules Chemical class 0.000 description 2
- 230000015590 smooth muscle cell migration Effects 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
- 239000000600 sorbitol Substances 0.000 description 2
- 238000010561 standard procedure Methods 0.000 description 2
- 230000004936 stimulating effect Effects 0.000 description 2
- 238000003756 stirring Methods 0.000 description 2
- 210000002784 stomach Anatomy 0.000 description 2
- UCSJYZPVAKXKNQ-HZYVHMACSA-N streptomycin Chemical compound CN[C@H]1[C@H](O)[C@@H](O)[C@H](CO)O[C@H]1O[C@@H]1[C@](C=O)(O)[C@H](C)O[C@H]1O[C@@H]1[C@@H](NC(N)=N)[C@H](O)[C@@H](NC(N)=N)[C@H](O)[C@H]1O UCSJYZPVAKXKNQ-HZYVHMACSA-N 0.000 description 2
- 150000005846 sugar alcohols Chemical class 0.000 description 2
- 238000013268 sustained release Methods 0.000 description 2
- 239000012730 sustained-release form Substances 0.000 description 2
- 208000024891 symptom Diseases 0.000 description 2
- 238000002560 therapeutic procedure Methods 0.000 description 2
- 230000019432 tissue death Effects 0.000 description 2
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 2
- 210000004881 tumor cell Anatomy 0.000 description 2
- 210000003708 urethra Anatomy 0.000 description 2
- DGVVWUTYPXICAM-UHFFFAOYSA-N β‐Mercaptoethanol Chemical compound OCCS DGVVWUTYPXICAM-UHFFFAOYSA-N 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
- XMQUEQJCYRFIQS-YFKPBYRVSA-N (2s)-2-amino-5-ethoxy-5-oxopentanoic acid Chemical compound CCOC(=O)CC[C@H](N)C(O)=O XMQUEQJCYRFIQS-YFKPBYRVSA-N 0.000 description 1
- KYBXNPIASYUWLN-WUCPZUCCSA-N (2s)-5-hydroxypyrrolidine-2-carboxylic acid Chemical compound OC1CC[C@@H](C(O)=O)N1 KYBXNPIASYUWLN-WUCPZUCCSA-N 0.000 description 1
- NMWKYTGJWUAZPZ-WWHBDHEGSA-N (4S)-4-[[(4R,7S,10S,16S,19S,25S,28S,31R)-31-[[(2S)-2-[[(1R,6R,9S,12S,18S,21S,24S,27S,30S,33S,36S,39S,42R,47R,53S,56S,59S,62S,65S,68S,71S,76S,79S,85S)-47-[[(2S)-2-[[(2S)-4-amino-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-amino-3-methylbutanoyl]amino]-3-methylbutanoyl]amino]-3-hydroxypropanoyl]amino]-3-(1H-imidazol-4-yl)propanoyl]amino]-3-phenylpropanoyl]amino]-4-oxobutanoyl]amino]-3-carboxypropanoyl]amino]-18-(4-aminobutyl)-27,68-bis(3-amino-3-oxopropyl)-36,71,76-tribenzyl-39-(3-carbamimidamidopropyl)-24-(2-carboxyethyl)-21,56-bis(carboxymethyl)-65,85-bis[(1R)-1-hydroxyethyl]-59-(hydroxymethyl)-62,79-bis(1H-imidazol-4-ylmethyl)-9-methyl-33-(2-methylpropyl)-8,11,17,20,23,26,29,32,35,38,41,48,54,57,60,63,66,69,72,74,77,80,83,86-tetracosaoxo-30-propan-2-yl-3,4,44,45-tetrathia-7,10,16,19,22,25,28,31,34,37,40,49,55,58,61,64,67,70,73,75,78,81,84,87-tetracosazatetracyclo[40.31.14.012,16.049,53]heptaoctacontane-6-carbonyl]amino]-3-methylbutanoyl]amino]-7-(3-carbamimidamidopropyl)-25-(hydroxymethyl)-19-[(4-hydroxyphenyl)methyl]-28-(1H-imidazol-4-ylmethyl)-10-methyl-6,9,12,15,18,21,24,27,30-nonaoxo-16-propan-2-yl-1,2-dithia-5,8,11,14,17,20,23,26,29-nonazacyclodotriacontane-4-carbonyl]amino]-5-[[(2S)-1-[[(2S)-1-[[(2S)-3-carboxy-1-[[(2S)-1-[[(2S)-1-[[(1S)-1-carboxyethyl]amino]-4-methyl-1-oxopentan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-1-oxopropan-2-yl]amino]-1-oxopropan-2-yl]amino]-3-(1H-imidazol-4-yl)-1-oxopropan-2-yl]amino]-5-oxopentanoic acid Chemical compound CC(C)C[C@H](NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](C)NC(=O)[C@H](Cc1c[nH]cn1)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@@H]1CSSC[C@H](NC(=O)[C@@H](NC(=O)[C@@H]2CSSC[C@@H]3NC(=O)[C@H](Cc4ccccc4)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@@H](NC(=O)[C@H](Cc4c[nH]cn4)NC(=O)[C@H](CO)NC(=O)[C@H](CC(O)=O)NC(=O)[C@@H]4CCCN4C(=O)[C@H](CSSC[C@H](NC(=O)[C@@H](NC(=O)CNC(=O)[C@H](Cc4c[nH]cn4)NC(=O)[C@H](Cc4ccccc4)NC3=O)[C@@H](C)O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](Cc3ccccc3)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CCCCN)C(=O)N3CCC[C@H]3C(=O)N[C@@H](C)C(=O)N2)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](Cc2ccccc2)NC(=O)[C@H](Cc2c[nH]cn2)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@@H](N)C(C)C)C(C)C)[C@@H](C)O)C(C)C)C(=O)N[C@@H](Cc2c[nH]cn2)C(=O)N[C@@H](CO)C(=O)NCC(=O)N[C@@H](Cc2ccc(O)cc2)C(=O)N[C@@H](C(C)C)C(=O)NCC(=O)N[C@@H](C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N1)C(=O)N[C@@H](C)C(O)=O NMWKYTGJWUAZPZ-WWHBDHEGSA-N 0.000 description 1
- IEUUDEWWMRQUDS-UHFFFAOYSA-N (6-azaniumylidene-1,6-dimethoxyhexylidene)azanium;dichloride Chemical compound Cl.Cl.COC(=N)CCCCC(=N)OC IEUUDEWWMRQUDS-UHFFFAOYSA-N 0.000 description 1
- 108091032973 (ribonucleotides)n+m Proteins 0.000 description 1
- NWUYHJFMYQTDRP-UHFFFAOYSA-N 1,2-bis(ethenyl)benzene;1-ethenyl-2-ethylbenzene;styrene Chemical compound C=CC1=CC=CC=C1.CCC1=CC=CC=C1C=C.C=CC1=CC=CC=C1C=C NWUYHJFMYQTDRP-UHFFFAOYSA-N 0.000 description 1
- GEYOCULIXLDCMW-UHFFFAOYSA-N 1,2-phenylenediamine Chemical compound NC1=CC=CC=C1N GEYOCULIXLDCMW-UHFFFAOYSA-N 0.000 description 1
- VILFTWLXLYIEMV-UHFFFAOYSA-N 1,5-difluoro-2,4-dinitrobenzene Chemical compound [O-][N+](=O)C1=CC([N+]([O-])=O)=C(F)C=C1F VILFTWLXLYIEMV-UHFFFAOYSA-N 0.000 description 1
- OWEGMIWEEQEYGQ-UHFFFAOYSA-N 100676-05-9 Natural products OC1C(O)C(O)C(CO)OC1OCC1C(O)C(O)C(O)C(OC2C(OC(O)C(O)C2O)CO)O1 OWEGMIWEEQEYGQ-UHFFFAOYSA-N 0.000 description 1
- LDGWQMRUWMSZIU-LQDDAWAPSA-M 2,3-bis[(z)-octadec-9-enoxy]propyl-trimethylazanium;chloride Chemical compound [Cl-].CCCCCCCC\C=C/CCCCCCCCOCC(C[N+](C)(C)C)OCCCCCCCC\C=C/CCCCCCCC LDGWQMRUWMSZIU-LQDDAWAPSA-M 0.000 description 1
- XMGJGSKRRWXOIF-UHFFFAOYSA-N 2-(azepan-1-yl)ethyl 2-cyclohexyl-2-thiophen-3-ylacetate;2-hydroxypropane-1,2,3-tricarboxylic acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O.C1CCCCC1C(C1=CSC=C1)C(=O)OCCN1CCCCCC1 XMGJGSKRRWXOIF-UHFFFAOYSA-N 0.000 description 1
- QFVHZQCOUORWEI-UHFFFAOYSA-N 4-[(4-anilino-5-sulfonaphthalen-1-yl)diazenyl]-5-hydroxynaphthalene-2,7-disulfonic acid Chemical compound C=12C(O)=CC(S(O)(=O)=O)=CC2=CC(S(O)(=O)=O)=CC=1N=NC(C1=CC=CC(=C11)S(O)(=O)=O)=CC=C1NC1=CC=CC=C1 QFVHZQCOUORWEI-UHFFFAOYSA-N 0.000 description 1
- TVZGACDUOSZQKY-LBPRGKRZSA-N 4-aminofolic acid Chemical compound C1=NC2=NC(N)=NC(N)=C2N=C1CNC1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 TVZGACDUOSZQKY-LBPRGKRZSA-N 0.000 description 1
- SLFZWKBTTILTLU-UHFFFAOYSA-N 4-sulfanylbutanamide Chemical compound NC(=O)CCCS SLFZWKBTTILTLU-UHFFFAOYSA-N 0.000 description 1
- 229940117976 5-hydroxylysine Drugs 0.000 description 1
- NIXOWILDQLNWCW-UHFFFAOYSA-N Acrylic acid Chemical compound OC(=O)C=C NIXOWILDQLNWCW-UHFFFAOYSA-N 0.000 description 1
- 102000007469 Actins Human genes 0.000 description 1
- 108010085238 Actins Proteins 0.000 description 1
- 241000589155 Agrobacterium tumefaciens Species 0.000 description 1
- 101710187573 Alcohol dehydrogenase 2 Proteins 0.000 description 1
- 101710133776 Alcohol dehydrogenase class-3 Proteins 0.000 description 1
- 102400000345 Angiotensin-2 Human genes 0.000 description 1
- 101800000733 Angiotensin-2 Proteins 0.000 description 1
- 101100107610 Arabidopsis thaliana ABCF4 gene Proteins 0.000 description 1
- 208000002109 Argyria Diseases 0.000 description 1
- 102000009133 Arylsulfatases Human genes 0.000 description 1
- 241000228212 Aspergillus Species 0.000 description 1
- 241000351920 Aspergillus nidulans Species 0.000 description 1
- 241000228245 Aspergillus niger Species 0.000 description 1
- 206010063836 Atrioventricular septal defect Diseases 0.000 description 1
- 241000271566 Aves Species 0.000 description 1
- 241000713842 Avian sarcoma virus Species 0.000 description 1
- 102100038080 B-cell receptor CD22 Human genes 0.000 description 1
- 101150042514 B1 gene Proteins 0.000 description 1
- WOVKYSAHUYNSMH-UHFFFAOYSA-N BROMODEOXYURIDINE Natural products C1C(O)C(CO)OC1N1C(=O)NC(=O)C(Br)=C1 WOVKYSAHUYNSMH-UHFFFAOYSA-N 0.000 description 1
- 241000193830 Bacillus <bacterium> Species 0.000 description 1
- 235000014469 Bacillus subtilis Nutrition 0.000 description 1
- 102400001242 Betacellulin Human genes 0.000 description 1
- 101800001382 Betacellulin Proteins 0.000 description 1
- 241000701822 Bovine papillomavirus Species 0.000 description 1
- 102100032912 CD44 antigen Human genes 0.000 description 1
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
- UXVMQQNJUSDDNG-UHFFFAOYSA-L Calcium chloride Chemical compound [Cl-].[Cl-].[Ca+2] UXVMQQNJUSDDNG-UHFFFAOYSA-L 0.000 description 1
- 241000222122 Candida albicans Species 0.000 description 1
- 241000282472 Canis lupus familiaris Species 0.000 description 1
- 108090000565 Capsid Proteins Proteins 0.000 description 1
- 102000005367 Carboxypeptidases Human genes 0.000 description 1
- 108010006303 Carboxypeptidases Proteins 0.000 description 1
- 102000000844 Cell Surface Receptors Human genes 0.000 description 1
- 108010001857 Cell Surface Receptors Proteins 0.000 description 1
- 241000282693 Cercopithecidae Species 0.000 description 1
- 102100023321 Ceruloplasmin Human genes 0.000 description 1
- KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 description 1
- 238000011537 Coomassie blue staining Methods 0.000 description 1
- 241000699800 Cricetinae Species 0.000 description 1
- QNAYBMKLOCPYGJ-UWTATZPHSA-N D-alanine Chemical compound C[C@@H](N)C(O)=O QNAYBMKLOCPYGJ-UWTATZPHSA-N 0.000 description 1
- QNAYBMKLOCPYGJ-UHFFFAOYSA-N D-alpha-Ala Natural products CC([NH3+])C([O-])=O QNAYBMKLOCPYGJ-UHFFFAOYSA-N 0.000 description 1
- 150000008574 D-amino acids Chemical class 0.000 description 1
- 102000053602 DNA Human genes 0.000 description 1
- 230000006820 DNA synthesis Effects 0.000 description 1
- 108090000204 Dipeptidase 1 Proteins 0.000 description 1
- 102000016607 Diphtheria Toxin Human genes 0.000 description 1
- 108010053187 Diphtheria Toxin Proteins 0.000 description 1
- 206010061818 Disease progression Diseases 0.000 description 1
- 241000255581 Drosophila <fruit fly, genus> Species 0.000 description 1
- 108010024212 E-Selectin Proteins 0.000 description 1
- 102100023471 E-selectin Human genes 0.000 description 1
- 238000002965 ELISA Methods 0.000 description 1
- 101000633756 Echis pyramidum leakeyi Snaclec 4 Proteins 0.000 description 1
- 102400000686 Endothelin-1 Human genes 0.000 description 1
- 101800004490 Endothelin-1 Proteins 0.000 description 1
- 241000588914 Enterobacter Species 0.000 description 1
- 101710146739 Enterotoxin Proteins 0.000 description 1
- 101710091045 Envelope protein Proteins 0.000 description 1
- 241000283086 Equidae Species 0.000 description 1
- 102000056372 ErbB-3 Receptor Human genes 0.000 description 1
- 241000588698 Erwinia Species 0.000 description 1
- 241000588722 Escherichia Species 0.000 description 1
- 241001646716 Escherichia coli K-12 Species 0.000 description 1
- PIICEJLVQHRZGT-UHFFFAOYSA-N Ethylenediamine Chemical compound NCCN PIICEJLVQHRZGT-UHFFFAOYSA-N 0.000 description 1
- 206010063560 Excessive granulation tissue Diseases 0.000 description 1
- 108010037362 Extracellular Matrix Proteins Proteins 0.000 description 1
- 102000010834 Extracellular Matrix Proteins Human genes 0.000 description 1
- 108010087819 Fc receptors Proteins 0.000 description 1
- 102000009109 Fc receptors Human genes 0.000 description 1
- 241000282326 Felis catus Species 0.000 description 1
- GHASVSINZRGABV-UHFFFAOYSA-N Fluorouracil Chemical compound FC1=CNC(=O)NC1=O GHASVSINZRGABV-UHFFFAOYSA-N 0.000 description 1
- 108010093031 Galactosidases Proteins 0.000 description 1
- 102000002464 Galactosidases Human genes 0.000 description 1
- 206010064571 Gene mutation Diseases 0.000 description 1
- 108700007698 Genetic Terminator Regions Proteins 0.000 description 1
- 102000006395 Globulins Human genes 0.000 description 1
- 108010044091 Globulins Proteins 0.000 description 1
- 108010073178 Glucan 1,4-alpha-Glucosidase Proteins 0.000 description 1
- 102100022624 Glucoamylase Human genes 0.000 description 1
- 102000030595 Glucokinase Human genes 0.000 description 1
- 108010021582 Glucokinase Proteins 0.000 description 1
- 239000004366 Glucose oxidase Substances 0.000 description 1
- 108010015776 Glucose oxidase Proteins 0.000 description 1
- 102100031132 Glucose-6-phosphate isomerase Human genes 0.000 description 1
- 102000005731 Glucose-6-phosphate isomerase Human genes 0.000 description 1
- SXRSQZLOMIGNAQ-UHFFFAOYSA-N Glutaraldehyde Chemical compound O=CCCCC=O SXRSQZLOMIGNAQ-UHFFFAOYSA-N 0.000 description 1
- 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 1
- 208000031886 HIV Infections Diseases 0.000 description 1
- 208000037357 HIV infectious disease Diseases 0.000 description 1
- 241001149669 Hanseniaspora Species 0.000 description 1
- 102100027618 Heme transporter HRG1 Human genes 0.000 description 1
- 241000700721 Hepatitis B virus Species 0.000 description 1
- 102100031000 Hepatoma-derived growth factor Human genes 0.000 description 1
- 208000028523 Hereditary Complement Deficiency disease Diseases 0.000 description 1
- 208000009889 Herpes Simplex Diseases 0.000 description 1
- 229920000209 Hexadimethrine bromide Polymers 0.000 description 1
- 102000005548 Hexokinase Human genes 0.000 description 1
- 108700040460 Hexokinases Proteins 0.000 description 1
- 101000884305 Homo sapiens B-cell receptor CD22 Proteins 0.000 description 1
- 101000868273 Homo sapiens CD44 antigen Proteins 0.000 description 1
- 101000935587 Homo sapiens Flavin reductase (NADPH) Proteins 0.000 description 1
- 101001081412 Homo sapiens Heme transporter HRG1 Proteins 0.000 description 1
- 101001083798 Homo sapiens Hepatoma-derived growth factor Proteins 0.000 description 1
- 101000840258 Homo sapiens Immunoglobulin J chain Proteins 0.000 description 1
- 101100405240 Homo sapiens NRG1 gene Proteins 0.000 description 1
- 101000914514 Homo sapiens T-cell-specific surface glycoprotein CD28 Proteins 0.000 description 1
- 108010001336 Horseradish Peroxidase Proteins 0.000 description 1
- 108090000144 Human Proteins Proteins 0.000 description 1
- 102000003839 Human Proteins Human genes 0.000 description 1
- 241000701109 Human adenovirus 2 Species 0.000 description 1
- 241000700588 Human alphaherpesvirus 1 Species 0.000 description 1
- 102000009438 IgE Receptors Human genes 0.000 description 1
- 108010073816 IgE Receptors Proteins 0.000 description 1
- CZGUSIXMZVURDU-JZXHSEFVSA-N Ile(5)-angiotensin II 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](CC=1C=CC=CC=1)C([O-])=O)NC(=O)[C@@H](NC(=O)[C@H](CCCNC(N)=[NH2+])NC(=O)[C@@H]([NH3+])CC([O-])=O)C(C)C)C1=CC=C(O)C=C1 CZGUSIXMZVURDU-JZXHSEFVSA-N 0.000 description 1
- 108010058683 Immobilized Proteins Proteins 0.000 description 1
- 108010009817 Immunoglobulin Constant Regions Proteins 0.000 description 1
- 102000009786 Immunoglobulin Constant Regions Human genes 0.000 description 1
- 108700005091 Immunoglobulin Genes Proteins 0.000 description 1
- 102100029571 Immunoglobulin J chain Human genes 0.000 description 1
- 102000012745 Immunoglobulin Subunits Human genes 0.000 description 1
- 108010079585 Immunoglobulin Subunits Proteins 0.000 description 1
- 238000012404 In vitro experiment Methods 0.000 description 1
- 108090001061 Insulin Proteins 0.000 description 1
- 102000004877 Insulin Human genes 0.000 description 1
- 102000001617 Interferon Receptors Human genes 0.000 description 1
- 108010054267 Interferon Receptors Proteins 0.000 description 1
- 241000588748 Klebsiella Species 0.000 description 1
- 241000235058 Komagataella pastoris Species 0.000 description 1
- ODKSFYDXXFIFQN-BYPYZUCNSA-P L-argininium(2+) Chemical compound NC(=[NH2+])NCCC[C@H]([NH3+])C(O)=O ODKSFYDXXFIFQN-BYPYZUCNSA-P 0.000 description 1
- 229930182816 L-glutamine Natural products 0.000 description 1
- LRQKBLKVPFOOQJ-YFKPBYRVSA-N L-norleucine Chemical compound CCCC[C@H]([NH3+])C([O-])=O LRQKBLKVPFOOQJ-YFKPBYRVSA-N 0.000 description 1
- 241000481961 Lachancea thermotolerans Species 0.000 description 1
- 241000235651 Lachancea waltii Species 0.000 description 1
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 1
- 108010000817 Leuprolide Proteins 0.000 description 1
- 101001133631 Lysinibacillus sphaericus Penicillin acylase Proteins 0.000 description 1
- 241000282553 Macaca Species 0.000 description 1
- 239000004907 Macro-emulsion Substances 0.000 description 1
- GUBGYTABKSRVRQ-PICCSMPSSA-N Maltose Natural products O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@@H]1O[C@@H]1[C@@H](CO)OC(O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-PICCSMPSSA-N 0.000 description 1
- 102000003792 Metallothionein Human genes 0.000 description 1
- 108090000157 Metallothionein Proteins 0.000 description 1
- 241000699660 Mus musculus Species 0.000 description 1
- 101710135898 Myc proto-oncogene protein Proteins 0.000 description 1
- 102100038895 Myc proto-oncogene protein Human genes 0.000 description 1
- OVRNDRQMDRJTHS-CBQIKETKSA-N N-Acetyl-D-Galactosamine Chemical compound CC(=O)N[C@H]1[C@@H](O)O[C@H](CO)[C@H](O)[C@@H]1O OVRNDRQMDRJTHS-CBQIKETKSA-N 0.000 description 1
- MBLBDJOUHNCFQT-UHFFFAOYSA-N N-acetyl-D-galactosamine Natural products CC(=O)NC(C=O)C(O)C(O)C(O)CO MBLBDJOUHNCFQT-UHFFFAOYSA-N 0.000 description 1
- 229930193140 Neomycin Natural products 0.000 description 1
- 108010006232 Neuraminidase Proteins 0.000 description 1
- 102000005348 Neuraminidase Human genes 0.000 description 1
- 101800002641 Neuregulin-4 Proteins 0.000 description 1
- 206010029260 Neuroblastoma Diseases 0.000 description 1
- 241000221960 Neurospora Species 0.000 description 1
- 241000221961 Neurospora crassa Species 0.000 description 1
- 101100438748 Neurospora crassa (strain ATCC 24698 / 74-OR23-1A / CBS 708.71 / DSM 1257 / FGSC 987) cyt-2 gene Proteins 0.000 description 1
- 108091093105 Nuclear DNA Proteins 0.000 description 1
- 208000027771 Obstructive airways disease Diseases 0.000 description 1
- 108020005187 Oligonucleotide Probes Proteins 0.000 description 1
- 206010033128 Ovarian cancer Diseases 0.000 description 1
- 206010061535 Ovarian neoplasm Diseases 0.000 description 1
- 108010035766 P-Selectin Proteins 0.000 description 1
- 102100023472 P-selectin Human genes 0.000 description 1
- 108010067372 Pancreatic elastase Proteins 0.000 description 1
- 102000016387 Pancreatic elastase Human genes 0.000 description 1
- 206010061902 Pancreatic neoplasm Diseases 0.000 description 1
- 229930182555 Penicillin Natural products 0.000 description 1
- 108010073038 Penicillin Amidase Proteins 0.000 description 1
- JGSARLDLIJGVTE-MBNYWOFBSA-N Penicillin G Chemical compound N([C@H]1[C@H]2SC([C@@H](N2C1=O)C(O)=O)(C)C)C(=O)CC1=CC=CC=C1 JGSARLDLIJGVTE-MBNYWOFBSA-N 0.000 description 1
- 101710123388 Penicillin G acylase Proteins 0.000 description 1
- 108010087702 Penicillinase Proteins 0.000 description 1
- 241000228143 Penicillium Species 0.000 description 1
- 102000007079 Peptide Fragments Human genes 0.000 description 1
- 108010033276 Peptide Fragments Proteins 0.000 description 1
- 102000001105 Phosphofructokinases Human genes 0.000 description 1
- 108010069341 Phosphofructokinases Proteins 0.000 description 1
- 239000004698 Polyethylene Substances 0.000 description 1
- 102100022661 Pro-neuregulin-1, membrane-bound isoform Human genes 0.000 description 1
- 102100022658 Pro-neuregulin-4, membrane-bound isoform Human genes 0.000 description 1
- ONIBWKKTOPOVIA-UHFFFAOYSA-N Proline Natural products OC(=O)C1CCCN1 ONIBWKKTOPOVIA-UHFFFAOYSA-N 0.000 description 1
- XBDQKXXYIPTUBI-UHFFFAOYSA-M Propionate Chemical compound CCC([O-])=O XBDQKXXYIPTUBI-UHFFFAOYSA-M 0.000 description 1
- 102000001253 Protein Kinase Human genes 0.000 description 1
- 101710188315 Protein X Proteins 0.000 description 1
- 241000588769 Proteus <enterobacteria> Species 0.000 description 1
- 108010011939 Pyruvate Decarboxylase Proteins 0.000 description 1
- 102000013009 Pyruvate Kinase Human genes 0.000 description 1
- 108020005115 Pyruvate Kinase Proteins 0.000 description 1
- 102000004879 Racemases and epimerases Human genes 0.000 description 1
- 108090001066 Racemases and epimerases Proteins 0.000 description 1
- 101001081402 Rattus norvegicus Histidine-rich glycoprotein Proteins 0.000 description 1
- 108091005682 Receptor kinases Proteins 0.000 description 1
- 241000223252 Rhodotorula Species 0.000 description 1
- 230000018199 S phase Effects 0.000 description 1
- 239000012722 SDS sample buffer Substances 0.000 description 1
- 101100068078 Saccharomyces cerevisiae (strain ATCC 204508 / S288c) GCN4 gene Proteins 0.000 description 1
- 241000607142 Salmonella Species 0.000 description 1
- 241000293869 Salmonella enterica subsp. enterica serovar Typhimurium Species 0.000 description 1
- 241000311088 Schwanniomyces Species 0.000 description 1
- 241001123650 Schwanniomyces occidentalis Species 0.000 description 1
- 102000003800 Selectins Human genes 0.000 description 1
- 108090000184 Selectins Proteins 0.000 description 1
- 229920002684 Sepharose Polymers 0.000 description 1
- 108010022999 Serine Proteases Proteins 0.000 description 1
- 102000012479 Serine Proteases Human genes 0.000 description 1
- 241000607768 Shigella Species 0.000 description 1
- 241000700584 Simplexvirus Species 0.000 description 1
- 108020004682 Single-Stranded DNA Proteins 0.000 description 1
- 241000256248 Spodoptera Species 0.000 description 1
- 241000187747 Streptomyces Species 0.000 description 1
- 108090000787 Subtilisin Proteins 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 1
- UZMAPBJVXOGOFT-UHFFFAOYSA-N Syringetin Natural products COC1=C(O)C(OC)=CC(C2=C(C(=O)C3=C(O)C=C(O)C=C3O2)O)=C1 UZMAPBJVXOGOFT-UHFFFAOYSA-N 0.000 description 1
- 108091008874 T cell receptors Proteins 0.000 description 1
- 102000016266 T-Cell Antigen Receptors Human genes 0.000 description 1
- 102100027213 T-cell-specific surface glycoprotein CD28 Human genes 0.000 description 1
- 239000004098 Tetracycline Substances 0.000 description 1
- 108090001109 Thermolysin Proteins 0.000 description 1
- 101710109570 Thymidine kinase a Proteins 0.000 description 1
- 241001149964 Tolypocladium Species 0.000 description 1
- 101710150448 Transcriptional regulator Myc Proteins 0.000 description 1
- 102000004357 Transferases Human genes 0.000 description 1
- 108090000992 Transferases Proteins 0.000 description 1
- 102000009618 Transforming Growth Factors Human genes 0.000 description 1
- 108010009583 Transforming Growth Factors Proteins 0.000 description 1
- 102400001320 Transforming growth factor alpha Human genes 0.000 description 1
- 101800004564 Transforming growth factor alpha Proteins 0.000 description 1
- 241000223259 Trichoderma Species 0.000 description 1
- 239000007997 Tricine buffer Substances 0.000 description 1
- 108090000631 Trypsin Proteins 0.000 description 1
- 102000004142 Trypsin Human genes 0.000 description 1
- 101150117115 V gene Proteins 0.000 description 1
- 241000700647 Variola virus Species 0.000 description 1
- 102000005789 Vascular Endothelial Growth Factors Human genes 0.000 description 1
- 108010019530 Vascular Endothelial Growth Factors Proteins 0.000 description 1
- 208000032594 Vascular Remodeling Diseases 0.000 description 1
- 241000251539 Vertebrata <Metazoa> Species 0.000 description 1
- 108020005202 Viral DNA Proteins 0.000 description 1
- IXKSXJFAGXLQOQ-XISFHERQSA-N WHWLQLKPGQPMY Chemical compound C([C@@H](C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC(C)C)C(=O)N1CCC[C@H]1C(=O)NCC(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC(O)=O)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(O)=O)NC(=O)[C@@H](N)CC=1C2=CC=CC=C2NC=1)C1=CNC=N1 IXKSXJFAGXLQOQ-XISFHERQSA-N 0.000 description 1
- 241000235013 Yarrowia Species 0.000 description 1
- HIHOWBSBBDRPDW-PTHRTHQKSA-N [(3s,8s,9s,10r,13r,14s,17r)-10,13-dimethyl-17-[(2r)-6-methylheptan-2-yl]-2,3,4,7,8,9,11,12,14,15,16,17-dodecahydro-1h-cyclopenta[a]phenanthren-3-yl] n-[2-(dimethylamino)ethyl]carbamate Chemical compound C1C=C2C[C@@H](OC(=O)NCCN(C)C)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CCCC(C)C)[C@@]1(C)CC2 HIHOWBSBBDRPDW-PTHRTHQKSA-N 0.000 description 1
- 230000001594 aberrant effect Effects 0.000 description 1
- 230000005856 abnormality Effects 0.000 description 1
- QPMSXSBEVQLBIL-CZRHPSIPSA-N ac1mix0p Chemical compound C1=CC=C2N(C[C@H](C)CN(C)C)C3=CC(OC)=CC=C3SC2=C1.O([C@H]1[C@]2(OC)C=CC34C[C@@H]2[C@](C)(O)CCC)C2=C5[C@]41CCN(C)[C@@H]3CC5=CC=C2O QPMSXSBEVQLBIL-CZRHPSIPSA-N 0.000 description 1
- 238000009825 accumulation Methods 0.000 description 1
- 208000038016 acute inflammation Diseases 0.000 description 1
- 230000006022 acute inflammation Effects 0.000 description 1
- 230000006978 adaptation Effects 0.000 description 1
- 238000001261 affinity purification Methods 0.000 description 1
- 238000013019 agitation Methods 0.000 description 1
- 150000001299 aldehydes Chemical class 0.000 description 1
- 108010026331 alpha-Fetoproteins Proteins 0.000 description 1
- 102000013529 alpha-Fetoproteins Human genes 0.000 description 1
- 229960003896 aminopterin Drugs 0.000 description 1
- BFNBIHQBYMNNAN-UHFFFAOYSA-N ammonium sulfate Chemical compound N.N.OS(O)(=O)=O BFNBIHQBYMNNAN-UHFFFAOYSA-N 0.000 description 1
- 229960000723 ampicillin Drugs 0.000 description 1
- AVKUERGKIZMTKX-NJBDSQKTSA-N ampicillin Chemical compound C1([C@@H](N)C(=O)N[C@H]2[C@H]3SC([C@@H](N3C2=O)C(O)=O)(C)C)=CC=CC=C1 AVKUERGKIZMTKX-NJBDSQKTSA-N 0.000 description 1
- 239000002870 angiogenesis inducing agent Substances 0.000 description 1
- 229950006323 angiotensin ii Drugs 0.000 description 1
- 238000010171 animal model Methods 0.000 description 1
- 230000003042 antagnostic effect Effects 0.000 description 1
- 239000003242 anti bacterial agent Substances 0.000 description 1
- 230000001028 anti-proliverative effect Effects 0.000 description 1
- 230000002785 anti-thrombosis Effects 0.000 description 1
- 229940088710 antibiotic agent Drugs 0.000 description 1
- 230000005875 antibody response Effects 0.000 description 1
- 238000011319 anticancer therapy Methods 0.000 description 1
- 239000003146 anticoagulant agent Substances 0.000 description 1
- 230000007503 antigenic stimulation Effects 0.000 description 1
- 229940127218 antiplatelet drug Drugs 0.000 description 1
- PYMYPHUHKUWMLA-UHFFFAOYSA-N arabinose Natural products OCC(O)C(O)C(O)C=O PYMYPHUHKUWMLA-UHFFFAOYSA-N 0.000 description 1
- 210000001367 artery Anatomy 0.000 description 1
- 125000003118 aryl group Chemical group 0.000 description 1
- 238000000376 autoradiography Methods 0.000 description 1
- 210000003719 b-lymphocyte Anatomy 0.000 description 1
- 239000011324 bead Substances 0.000 description 1
- SRBFZHDQGSBBOR-UHFFFAOYSA-N beta-D-Pyranose-Lyxose Natural products OC1COC(O)C(O)C1O SRBFZHDQGSBBOR-UHFFFAOYSA-N 0.000 description 1
- 108010051210 beta-Fructofuranosidase Proteins 0.000 description 1
- 102000006635 beta-lactamase Human genes 0.000 description 1
- GUBGYTABKSRVRQ-QUYVBRFLSA-N beta-maltose Chemical compound OC[C@H]1O[C@H](O[C@H]2[C@H](O)[C@@H](O)[C@H](O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@@H]1O GUBGYTABKSRVRQ-QUYVBRFLSA-N 0.000 description 1
- 230000001588 bifunctional effect Effects 0.000 description 1
- 230000003115 biocidal effect Effects 0.000 description 1
- 230000036770 blood supply Effects 0.000 description 1
- 230000037396 body weight Effects 0.000 description 1
- 201000008274 breast adenocarcinoma Diseases 0.000 description 1
- 210000000621 bronchi Anatomy 0.000 description 1
- DQXBYHZEEUGOBF-UHFFFAOYSA-N but-3-enoic acid;ethene Chemical compound C=C.OC(=O)CC=C DQXBYHZEEUGOBF-UHFFFAOYSA-N 0.000 description 1
- 229910052791 calcium Inorganic materials 0.000 description 1
- 239000011575 calcium Substances 0.000 description 1
- 239000001110 calcium chloride Substances 0.000 description 1
- 229910001628 calcium chloride Inorganic materials 0.000 description 1
- 239000004202 carbamide Substances 0.000 description 1
- 230000022131 cell cycle Effects 0.000 description 1
- 230000024245 cell differentiation Effects 0.000 description 1
- 230000007910 cell fusion Effects 0.000 description 1
- 210000000170 cell membrane Anatomy 0.000 description 1
- 238000001516 cell proliferation assay Methods 0.000 description 1
- 230000010307 cell transformation Effects 0.000 description 1
- 210000002421 cell wall Anatomy 0.000 description 1
- 108091092356 cellular DNA Proteins 0.000 description 1
- 238000005119 centrifugation Methods 0.000 description 1
- 235000013339 cereals Nutrition 0.000 description 1
- 230000003196 chaotropic effect Effects 0.000 description 1
- 229920001429 chelating resin Polymers 0.000 description 1
- 230000007073 chemical hydrolysis Effects 0.000 description 1
- 239000002975 chemoattractant Substances 0.000 description 1
- 230000003399 chemotactic effect Effects 0.000 description 1
- 239000005482 chemotactic factor Substances 0.000 description 1
- 229960001231 choline Drugs 0.000 description 1
- OEYIOHPDSNJKLS-UHFFFAOYSA-N choline Chemical compound C[N+](C)(C)CCO OEYIOHPDSNJKLS-UHFFFAOYSA-N 0.000 description 1
- 230000001684 chronic effect Effects 0.000 description 1
- 230000004087 circulation Effects 0.000 description 1
- 150000001860 citric acid derivatives Chemical class 0.000 description 1
- 230000004186 co-expression Effects 0.000 description 1
- 238000005354 coacervation Methods 0.000 description 1
- 239000011248 coating agent Substances 0.000 description 1
- 238000000576 coating method Methods 0.000 description 1
- 210000001072 colon Anatomy 0.000 description 1
- 230000009137 competitive binding Effects 0.000 description 1
- 230000002860 competitive effect Effects 0.000 description 1
- 230000024203 complement activation Effects 0.000 description 1
- 230000004154 complement system Effects 0.000 description 1
- 238000004590 computer program Methods 0.000 description 1
- 239000012141 concentrate Substances 0.000 description 1
- 239000003636 conditioned culture medium Substances 0.000 description 1
- 108091036078 conserved sequence Proteins 0.000 description 1
- 238000011109 contamination Methods 0.000 description 1
- 230000008602 contraction Effects 0.000 description 1
- 239000005289 controlled pore glass 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
- 239000013078 crystal Substances 0.000 description 1
- 239000012531 culture fluid Substances 0.000 description 1
- 210000004748 cultured cell Anatomy 0.000 description 1
- 235000018417 cysteine Nutrition 0.000 description 1
- XUJNEKJLAYXESH-UHFFFAOYSA-N cysteine Natural products SCC(N)C(O)=O XUJNEKJLAYXESH-UHFFFAOYSA-N 0.000 description 1
- 125000000151 cysteine group Chemical group N[C@@H](CS)C(=O)* 0.000 description 1
- 229940104302 cytosine Drugs 0.000 description 1
- 230000001086 cytosolic effect Effects 0.000 description 1
- 231100000433 cytotoxic Toxicity 0.000 description 1
- 230000001472 cytotoxic effect Effects 0.000 description 1
- 230000000593 degrading effect Effects 0.000 description 1
- 239000003405 delayed action preparation Substances 0.000 description 1
- YSMODUONRAFBET-UHFFFAOYSA-N delta-DL-hydroxylysine Natural products NCC(O)CCC(N)C(O)=O YSMODUONRAFBET-UHFFFAOYSA-N 0.000 description 1
- 238000000326 densiometry Methods 0.000 description 1
- 239000003599 detergent Substances 0.000 description 1
- 238000002405 diagnostic procedure Methods 0.000 description 1
- 238000000502 dialysis Methods 0.000 description 1
- 239000012954 diazonium Substances 0.000 description 1
- CGMRCMMOCQYHAD-UHFFFAOYSA-J dicalcium hydroxide phosphate Chemical compound [OH-].[Ca++].[Ca++].[O-]P([O-])([O-])=O CGMRCMMOCQYHAD-UHFFFAOYSA-J 0.000 description 1
- 230000004069 differentiation Effects 0.000 description 1
- 230000029087 digestion Effects 0.000 description 1
- KCFYHBSOLOXZIF-UHFFFAOYSA-N dihydrochrysin Natural products COC1=C(O)C(OC)=CC(C2OC3=CC(O)=CC(O)=C3C(=O)C2)=C1 KCFYHBSOLOXZIF-UHFFFAOYSA-N 0.000 description 1
- 125000005442 diisocyanate group Chemical group 0.000 description 1
- 230000010339 dilation Effects 0.000 description 1
- 239000000539 dimer Substances 0.000 description 1
- 238000006471 dimerization reaction Methods 0.000 description 1
- 230000005750 disease progression Effects 0.000 description 1
- 238000006073 displacement reaction Methods 0.000 description 1
- 150000002019 disulfides Chemical class 0.000 description 1
- 210000001198 duodenum Anatomy 0.000 description 1
- 238000001211 electron capture detection Methods 0.000 description 1
- 230000008030 elimination Effects 0.000 description 1
- 238000003379 elimination reaction Methods 0.000 description 1
- 230000012202 endocytosis Effects 0.000 description 1
- 210000004696 endometrium Anatomy 0.000 description 1
- 231100000655 enterotoxin Toxicity 0.000 description 1
- 239000000147 enterotoxin Substances 0.000 description 1
- 239000003344 environmental pollutant Substances 0.000 description 1
- 238000007824 enzymatic assay Methods 0.000 description 1
- 230000007071 enzymatic hydrolysis Effects 0.000 description 1
- 238000006047 enzymatic hydrolysis reaction Methods 0.000 description 1
- 238000006911 enzymatic reaction Methods 0.000 description 1
- 210000002919 epithelial cell Anatomy 0.000 description 1
- 108700021032 erbB Genes Proteins 0.000 description 1
- 108700020302 erbB-2 Genes Proteins 0.000 description 1
- YSMODUONRAFBET-UHNVWZDZSA-N erythro-5-hydroxy-L-lysine Chemical compound NC[C@H](O)CC[C@H](N)C(O)=O YSMODUONRAFBET-UHNVWZDZSA-N 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- 229960000403 etanercept Drugs 0.000 description 1
- 238000012869 ethanol precipitation Methods 0.000 description 1
- 239000005038 ethylene vinyl acetate Substances 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 210000002744 extracellular matrix Anatomy 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 230000002349 favourable effect Effects 0.000 description 1
- 238000000855 fermentation Methods 0.000 description 1
- 230000004151 fermentation Effects 0.000 description 1
- 230000001605 fetal effect Effects 0.000 description 1
- 238000011049 filling Methods 0.000 description 1
- XRECTZIEBJDKEO-UHFFFAOYSA-N flucytosine Chemical compound NC1=NC(=O)NC=C1F XRECTZIEBJDKEO-UHFFFAOYSA-N 0.000 description 1
- 229960004413 flucytosine Drugs 0.000 description 1
- 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 1
- 239000007850 fluorescent dye Substances 0.000 description 1
- 150000002222 fluorine compounds Chemical class 0.000 description 1
- 229960002949 fluorouracil Drugs 0.000 description 1
- 238000004108 freeze drying Methods 0.000 description 1
- 206010017758 gastric cancer Diseases 0.000 description 1
- 208000010749 gastric carcinoma Diseases 0.000 description 1
- 238000005227 gel permeation chromatography Methods 0.000 description 1
- 239000007903 gelatin capsule Substances 0.000 description 1
- 238000002523 gelfiltration Methods 0.000 description 1
- 238000001415 gene therapy Methods 0.000 description 1
- 102000054767 gene variant Human genes 0.000 description 1
- 230000007274 generation of a signal involved in cell-cell signaling Effects 0.000 description 1
- 230000002068 genetic effect Effects 0.000 description 1
- 230000002518 glial effect Effects 0.000 description 1
- 102000018146 globin Human genes 0.000 description 1
- 108060003196 globin Proteins 0.000 description 1
- 229940116332 glucose oxidase Drugs 0.000 description 1
- 235000019420 glucose oxidase Nutrition 0.000 description 1
- 229960002989 glutamic acid Drugs 0.000 description 1
- 230000002414 glycolytic effect Effects 0.000 description 1
- 210000001126 granulation tissue Anatomy 0.000 description 1
- 125000005842 heteroatom Chemical group 0.000 description 1
- 238000005734 heterodimerization reaction Methods 0.000 description 1
- SYECJBOWSGTPLU-UHFFFAOYSA-N hexane-1,1-diamine Chemical compound CCCCCC(N)N SYECJBOWSGTPLU-UHFFFAOYSA-N 0.000 description 1
- 230000001744 histochemical effect Effects 0.000 description 1
- 239000000710 homodimer Substances 0.000 description 1
- 229940088597 hormone Drugs 0.000 description 1
- 239000005556 hormone Substances 0.000 description 1
- 210000005260 human cell Anatomy 0.000 description 1
- 208000033519 human immunodeficiency virus infectious disease Diseases 0.000 description 1
- 239000000017 hydrogel Substances 0.000 description 1
- 238000006460 hydrolysis reaction Methods 0.000 description 1
- 229920001600 hydrophobic polymer Polymers 0.000 description 1
- WGCNASOHLSPBMP-UHFFFAOYSA-N hydroxyacetaldehyde Natural products OCC=O WGCNASOHLSPBMP-UHFFFAOYSA-N 0.000 description 1
- 125000002349 hydroxyamino group Chemical group [H]ON([H])[*] 0.000 description 1
- 229920003063 hydroxymethyl cellulose Polymers 0.000 description 1
- 229940031574 hydroxymethyl cellulose Drugs 0.000 description 1
- 101150020087 ilvG gene Proteins 0.000 description 1
- 150000002463 imidates Chemical class 0.000 description 1
- 230000014726 immortalization of host cell Effects 0.000 description 1
- 230000028993 immune response Effects 0.000 description 1
- 210000000987 immune system Anatomy 0.000 description 1
- 238000003018 immunoassay Methods 0.000 description 1
- 229940127121 immunoconjugate Drugs 0.000 description 1
- 230000005847 immunogenicity Effects 0.000 description 1
- 238000003364 immunohistochemistry Methods 0.000 description 1
- 229940051026 immunotoxin Drugs 0.000 description 1
- 239000002596 immunotoxin Substances 0.000 description 1
- 231100000608 immunotoxin Toxicity 0.000 description 1
- 230000002637 immunotoxin Effects 0.000 description 1
- 230000001976 improved effect Effects 0.000 description 1
- 230000006872 improvement Effects 0.000 description 1
- 239000012535 impurity Substances 0.000 description 1
- 238000000099 in vitro assay Methods 0.000 description 1
- 238000005462 in vivo assay Methods 0.000 description 1
- 238000011065 in-situ storage Methods 0.000 description 1
- 230000001939 inductive effect Effects 0.000 description 1
- 208000015181 infectious disease Diseases 0.000 description 1
- 230000000977 initiatory effect Effects 0.000 description 1
- 238000007689 inspection Methods 0.000 description 1
- 229940125396 insulin Drugs 0.000 description 1
- 230000010354 integration Effects 0.000 description 1
- 239000000543 intermediate Substances 0.000 description 1
- 238000001361 intraarterial administration Methods 0.000 description 1
- 230000031146 intracellular signal transduction Effects 0.000 description 1
- 238000007918 intramuscular administration Methods 0.000 description 1
- 239000001573 invertase Substances 0.000 description 1
- 235000011073 invertase Nutrition 0.000 description 1
- 239000003456 ion exchange resin Substances 0.000 description 1
- 229920003303 ion-exchange polymer Polymers 0.000 description 1
- 150000002540 isothiocyanates Chemical class 0.000 description 1
- 238000005304 joining Methods 0.000 description 1
- 229960000318 kanamycin Drugs 0.000 description 1
- 229930027917 kanamycin Natural products 0.000 description 1
- SBUJHOSQTJFQJX-NOAMYHISSA-N kanamycin Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CN)O[C@@H]1O[C@H]1[C@H](O)[C@@H](O[C@@H]2[C@@H]([C@@H](N)[C@H](O)[C@@H](CO)O2)O)[C@H](N)C[C@@H]1N SBUJHOSQTJFQJX-NOAMYHISSA-N 0.000 description 1
- 229930182823 kanamycin A Natural products 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 238000011031 large-scale manufacturing process Methods 0.000 description 1
- 230000003902 lesion Effects 0.000 description 1
- 229960004338 leuprorelin Drugs 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 210000005229 liver cell Anatomy 0.000 description 1
- 230000004807 localization Effects 0.000 description 1
- 210000005265 lung cell Anatomy 0.000 description 1
- 210000001165 lymph node Anatomy 0.000 description 1
- 239000012139 lysis buffer Substances 0.000 description 1
- 230000012976 mRNA stabilization Effects 0.000 description 1
- 229920002521 macromolecule Polymers 0.000 description 1
- 208000015486 malignant pancreatic neoplasm Diseases 0.000 description 1
- 230000035800 maturation Effects 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 230000004060 metabolic process Effects 0.000 description 1
- 229910021645 metal ion Inorganic materials 0.000 description 1
- 230000001394 metastastic effect Effects 0.000 description 1
- 206010061289 metastatic neoplasm Diseases 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
- 239000004530 micro-emulsion Substances 0.000 description 1
- 238000012737 microarray-based gene expression Methods 0.000 description 1
- 238000007814 microscopic assay Methods 0.000 description 1
- 238000010232 migration assay Methods 0.000 description 1
- 235000013336 milk Nutrition 0.000 description 1
- 239000008267 milk Substances 0.000 description 1
- 210000004080 milk Anatomy 0.000 description 1
- 230000000394 mitotic effect Effects 0.000 description 1
- 238000001009 modulus addition using spatially separated echo spectroscopy Methods 0.000 description 1
- 238000012544 monitoring process Methods 0.000 description 1
- 210000002161 motor neuron Anatomy 0.000 description 1
- 238000012243 multiplex automated genomic engineering Methods 0.000 description 1
- 210000000066 myeloid cell Anatomy 0.000 description 1
- 210000003098 myoblast Anatomy 0.000 description 1
- 239000002088 nanocapsule Substances 0.000 description 1
- 239000002105 nanoparticle Substances 0.000 description 1
- 239000013642 negative control Substances 0.000 description 1
- 230000017095 negative regulation of cell growth Effects 0.000 description 1
- 230000017066 negative regulation of growth Effects 0.000 description 1
- 229960004927 neomycin Drugs 0.000 description 1
- 230000001613 neoplastic effect Effects 0.000 description 1
- 210000000440 neutrophil Anatomy 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- 239000002736 nonionic surfactant Substances 0.000 description 1
- 239000002751 oligonucleotide probe Substances 0.000 description 1
- 229940043515 other immunoglobulins in atc Drugs 0.000 description 1
- 230000001590 oxidative effect Effects 0.000 description 1
- 239000006174 pH buffer Substances 0.000 description 1
- 210000000496 pancreas Anatomy 0.000 description 1
- 201000002528 pancreatic cancer Diseases 0.000 description 1
- 208000008443 pancreatic carcinoma Diseases 0.000 description 1
- 230000003076 paracrine Effects 0.000 description 1
- 230000008506 pathogenesis Effects 0.000 description 1
- 229940049954 penicillin Drugs 0.000 description 1
- 229950009506 penicillinase Drugs 0.000 description 1
- 125000001151 peptidyl group Chemical group 0.000 description 1
- 230000002093 peripheral effect Effects 0.000 description 1
- 238000002823 phage display Methods 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 238000009520 phase I clinical trial Methods 0.000 description 1
- 150000003013 phosphoric acid derivatives Chemical class 0.000 description 1
- 230000004962 physiological condition Effects 0.000 description 1
- 230000035790 physiological processes and functions Effects 0.000 description 1
- 229920003023 plastic Polymers 0.000 description 1
- 239000004033 plastic Substances 0.000 description 1
- 239000000106 platelet aggregation inhibitor Substances 0.000 description 1
- 108010017843 platelet-derived growth factor A Proteins 0.000 description 1
- 231100000719 pollutant Toxicity 0.000 description 1
- 229920001200 poly(ethylene-vinyl acetate) Polymers 0.000 description 1
- 229920000747 poly(lactic acid) Polymers 0.000 description 1
- 229920003229 poly(methyl methacrylate) Polymers 0.000 description 1
- 229920002401 polyacrylamide Polymers 0.000 description 1
- 229920000728 polyester Polymers 0.000 description 1
- 229920000573 polyethylene Polymers 0.000 description 1
- 229920002338 polyhydroxyethylmethacrylate Polymers 0.000 description 1
- 238000006116 polymerization reaction Methods 0.000 description 1
- 239000004926 polymethyl methacrylate Substances 0.000 description 1
- 229920002451 polyvinyl alcohol Polymers 0.000 description 1
- 239000013641 positive control Substances 0.000 description 1
- 230000036515 potency Effects 0.000 description 1
- 238000012545 processing Methods 0.000 description 1
- 238000004393 prognosis Methods 0.000 description 1
- 230000000770 proinflammatory effect Effects 0.000 description 1
- 230000002062 proliferating effect Effects 0.000 description 1
- 230000009696 proliferative response Effects 0.000 description 1
- 230000002035 prolonged effect Effects 0.000 description 1
- 230000000644 propagated effect Effects 0.000 description 1
- 238000011321 prophylaxis Methods 0.000 description 1
- XJMOSONTPMZWPB-UHFFFAOYSA-M propidium iodide Chemical compound [I-].[I-].C12=CC(N)=CC=C2C2=CC=C(N)C=C2[N+](CCC[N+](C)(CC)CC)=C1C1=CC=CC=C1 XJMOSONTPMZWPB-UHFFFAOYSA-M 0.000 description 1
- 108060006633 protein kinase Proteins 0.000 description 1
- 230000002797 proteolythic effect Effects 0.000 description 1
- 210000001938 protoplast Anatomy 0.000 description 1
- 230000005180 public health Effects 0.000 description 1
- 210000001187 pylorus Anatomy 0.000 description 1
- 238000011002 quantification Methods 0.000 description 1
- 238000002708 random mutagenesis Methods 0.000 description 1
- 239000011541 reaction mixture Substances 0.000 description 1
- 230000009257 reactivity Effects 0.000 description 1
- 230000010837 receptor-mediated endocytosis Effects 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 238000007634 remodeling Methods 0.000 description 1
- 229920005989 resin Polymers 0.000 description 1
- 239000011347 resin Substances 0.000 description 1
- 108091008146 restriction endonucleases Proteins 0.000 description 1
- 230000001177 retroviral effect Effects 0.000 description 1
- 230000000250 revascularization Effects 0.000 description 1
- 238000004007 reversed phase HPLC Methods 0.000 description 1
- PYWVYCXTNDRMGF-UHFFFAOYSA-N rhodamine B Chemical compound [Cl-].C=12C=CC(=[N+](CC)CC)C=C2OC2=CC(N(CC)CC)=CC=C2C=1C1=CC=CC=C1C(O)=O PYWVYCXTNDRMGF-UHFFFAOYSA-N 0.000 description 1
- 210000003079 salivary gland Anatomy 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- 239000012723 sample buffer Substances 0.000 description 1
- 238000013391 scatchard analysis Methods 0.000 description 1
- 210000004116 schwann cell Anatomy 0.000 description 1
- 230000035945 sensitivity Effects 0.000 description 1
- 230000001953 sensory effect Effects 0.000 description 1
- 210000001044 sensory neuron Anatomy 0.000 description 1
- 210000000717 sertoli cell Anatomy 0.000 description 1
- 239000012679 serum free medium Substances 0.000 description 1
- 208000037974 severe injury Diseases 0.000 description 1
- 230000009528 severe injury Effects 0.000 description 1
- 230000035939 shock Effects 0.000 description 1
- 239000000377 silicon dioxide Substances 0.000 description 1
- 210000002027 skeletal muscle Anatomy 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 230000000392 somatic effect Effects 0.000 description 1
- 229940043517 specific immunoglobulins Drugs 0.000 description 1
- 210000000952 spleen Anatomy 0.000 description 1
- 208000010110 spontaneous platelet aggregation Diseases 0.000 description 1
- 230000006641 stabilisation Effects 0.000 description 1
- 238000011105 stabilization Methods 0.000 description 1
- 238000003153 stable transfection Methods 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 238000011146 sterile filtration Methods 0.000 description 1
- 201000000498 stomach carcinoma Diseases 0.000 description 1
- 238000003860 storage Methods 0.000 description 1
- 229960005322 streptomycin Drugs 0.000 description 1
- 238000010254 subcutaneous injection Methods 0.000 description 1
- 239000007929 subcutaneous injection Substances 0.000 description 1
- TYFQFVWCELRYAO-UHFFFAOYSA-L suberate(2-) Chemical compound [O-]C(=O)CCCCCCC([O-])=O TYFQFVWCELRYAO-UHFFFAOYSA-L 0.000 description 1
- 125000001424 substituent group Chemical group 0.000 description 1
- 235000000346 sugar Nutrition 0.000 description 1
- 150000008163 sugars Chemical class 0.000 description 1
- 108060007951 sulfatase Proteins 0.000 description 1
- 230000008093 supporting effect Effects 0.000 description 1
- 239000004094 surface-active agent Substances 0.000 description 1
- 238000004114 suspension culture Methods 0.000 description 1
- 229960002180 tetracycline Drugs 0.000 description 1
- 229930101283 tetracycline Natural products 0.000 description 1
- 235000019364 tetracycline Nutrition 0.000 description 1
- 150000003522 tetracyclines Chemical class 0.000 description 1
- MPLHNVLQVRSVEE-UHFFFAOYSA-N texas red Chemical compound [O-]S(=O)(=O)C1=CC(S(Cl)(=O)=O)=CC=C1C(C1=CC=2CCCN3CCCC(C=23)=C1O1)=C2C1=C(CCC1)C3=[N+]1CCCC3=C2 MPLHNVLQVRSVEE-UHFFFAOYSA-N 0.000 description 1
- CNHYKKNIIGEXAY-UHFFFAOYSA-N thiolan-2-imine Chemical compound N=C1CCCS1 CNHYKKNIIGEXAY-UHFFFAOYSA-N 0.000 description 1
- 150000003573 thiols Chemical class 0.000 description 1
- 229960003766 thrombin (human) Drugs 0.000 description 1
- 210000001685 thyroid gland Anatomy 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
- 210000003437 trachea Anatomy 0.000 description 1
- 238000010361 transduction Methods 0.000 description 1
- 230000026683 transduction Effects 0.000 description 1
- 238000000844 transformation Methods 0.000 description 1
- 230000009261 transgenic effect Effects 0.000 description 1
- 238000011830 transgenic mouse model Methods 0.000 description 1
- 238000003146 transient transfection Methods 0.000 description 1
- 238000013519 translation Methods 0.000 description 1
- 239000012588 trypsin Substances 0.000 description 1
- 150000003668 tyrosines Chemical class 0.000 description 1
- 125000001493 tyrosinyl group Chemical group [H]OC1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])(N([H])[H])C(*)=O 0.000 description 1
- 238000005199 ultracentrifugation Methods 0.000 description 1
- 241001430294 unidentified retrovirus Species 0.000 description 1
- 238000011144 upstream manufacturing Methods 0.000 description 1
- 210000000626 ureter Anatomy 0.000 description 1
- 210000005167 vascular cell Anatomy 0.000 description 1
- 210000003556 vascular endothelial cell Anatomy 0.000 description 1
- 230000025033 vasoconstriction Effects 0.000 description 1
- 210000000264 venule Anatomy 0.000 description 1
- 239000013603 viral vector Substances 0.000 description 1
- 238000001262 western blot Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/82—Translation products from oncogenes
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P13/00—Drugs for disorders of the urinary system
- A61P13/10—Drugs for disorders of the urinary system of the bladder
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P21/00—Drugs for disorders of the muscular or neuromuscular system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/12—Antihypertensives
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- C07K14/475—Growth factors; Growth regulators
- C07K14/4756—Neuregulins, i.e. p185erbB2 ligands, glial growth factor, heregulin, ARIA, neu differentiation factor
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
- C07K16/18—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
- C07K16/32—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against translation products of oncogenes
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
- G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
- G01N33/5005—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving human or animal cells
- G01N33/5008—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving human or animal cells for testing or evaluating the effect of chemical or biological compounds, e.g. drugs, cosmetics
- G01N33/5044—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving human or animal cells for testing or evaluating the effect of chemical or biological compounds, e.g. drugs, cosmetics involving specific cell types
- G01N33/5061—Muscle cells
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/70—Immunoglobulins specific features characterized by effect upon binding to a cell or to an antigen
- C07K2317/73—Inducing cell death, e.g. apoptosis, necrosis or inhibition of cell proliferation
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/70—Immunoglobulins specific features characterized by effect upon binding to a cell or to an antigen
- C07K2317/76—Antagonist effect on antigen, e.g. neutralization or inhibition of binding
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/90—Immunoglobulins specific features characterized by (pharmaco)kinetic aspects or by stability of the immunoglobulin
- C07K2317/92—Affinity (KD), association rate (Ka), dissociation rate (Kd) or EC50 value
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2319/00—Fusion polypeptide
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2319/00—Fusion polypeptide
- C07K2319/30—Non-immunoglobulin-derived peptide or protein having an immunoglobulin constant or Fc region, or a fragment thereof, attached thereto
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Organic Chemistry (AREA)
- Engineering & Computer Science (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Molecular Biology (AREA)
- Biochemistry (AREA)
- Immunology (AREA)
- Biophysics (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Genetics & Genomics (AREA)
- Biomedical Technology (AREA)
- Cell Biology (AREA)
- Urology & Nephrology (AREA)
- Pharmacology & Pharmacy (AREA)
- Gastroenterology & Hepatology (AREA)
- Veterinary Medicine (AREA)
- Hematology (AREA)
- Oncology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Toxicology (AREA)
- Public Health (AREA)
- General Chemical & Material Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Physics & Mathematics (AREA)
- Pathology (AREA)
- Heart & Thoracic Surgery (AREA)
- Tropical Medicine & Parasitology (AREA)
- Biotechnology (AREA)
- Zoology (AREA)
- Microbiology (AREA)
- Food Science & Technology (AREA)
- Physics & Mathematics (AREA)
- Analytical Chemistry (AREA)
- Cardiology (AREA)
- Orthopedic Medicine & Surgery (AREA)
Applications Claiming Priority (6)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US940101 | 1997-09-29 | ||
| US22967900P | 2000-09-01 | 2000-09-01 | |
| US229679P | 2000-09-01 | ||
| US26551601P | 2001-01-31 | 2001-01-31 | |
| US265516P | 2001-01-31 | ||
| US09/940,101 US20020119148A1 (en) | 2000-09-01 | 2001-08-27 | ErbB4 antagonists |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| ES2295202T3 true ES2295202T3 (es) | 2008-04-16 |
Family
ID=27397993
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| ES01966399T Expired - Lifetime ES2295202T3 (es) | 2000-09-01 | 2001-08-29 | Utilizacion de un antagonista especifico de erbb4 para el tratamiento de la estenosis. |
Country Status (11)
| Country | Link |
|---|---|
| US (6) | US20020119148A1 (enExample) |
| EP (1) | EP1351744B1 (enExample) |
| JP (1) | JP2004507559A (enExample) |
| AT (1) | ATE374642T1 (enExample) |
| AU (2) | AU8691801A (enExample) |
| CA (1) | CA2420062C (enExample) |
| DE (1) | DE60130797T2 (enExample) |
| DK (1) | DK1351744T3 (enExample) |
| ES (1) | ES2295202T3 (enExample) |
| IL (2) | IL154495A0 (enExample) |
| WO (1) | WO2002018444A2 (enExample) |
Families Citing this family (34)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20020119148A1 (en) * | 2000-09-01 | 2002-08-29 | Gerritsen Mary E. | ErbB4 antagonists |
| US20040156835A1 (en) * | 2001-05-30 | 2004-08-12 | Taiji Imoto | Protein preparation |
| US7198899B2 (en) * | 2002-06-03 | 2007-04-03 | Chiron Corporation | Use of NRG4, or inhibitors thereof, in the treatment of colon and pancreatic cancers |
| EP2263691B1 (en) | 2002-07-15 | 2012-08-29 | F.Hoffmann-La Roche Ag | Treatment of cancer with the recombinant humanized monoclonal anti-erbb2 antibody 2C4 (rhuMAb 2C4) |
| TWI229650B (en) * | 2002-11-19 | 2005-03-21 | Sharp Kk | Substrate accommodating tray |
| JP4527388B2 (ja) * | 2003-12-11 | 2010-08-18 | 東洋鋼鈑株式会社 | ポリペプチドとレセプターとの相互作用を検出する方法、該検出する方法を用いてリガンドまたはリガンド変異体をスクリーニングする方法および該検出する方法を用いる診断方法 |
| MXPA06014065A (es) | 2004-06-01 | 2007-01-31 | Genentech Inc | Conjugados de droga-anticuerpo y metodos. |
| US20100111856A1 (en) | 2004-09-23 | 2010-05-06 | Herman Gill | Zirconium-radiolabeled, cysteine engineered antibody conjugates |
| ES2579805T3 (es) | 2004-09-23 | 2016-08-16 | Genentech, Inc. | Anticuerpos y conjugados modificados por ingeniería genética con cisteína |
| CA2600375A1 (en) * | 2005-03-07 | 2006-09-14 | Targeted Molecular Diagnostics, Llc | Tyrosine kinase inhibitor compositions and methods for manufacturing and using them in the treatment of disease |
| HRP20131113T1 (hr) * | 2007-02-16 | 2014-01-17 | Merrimack Pharmaceuticals, Inc. | Protutijela protiv erbb3 i njihova uporaba |
| EP2698380A1 (en) | 2008-03-28 | 2014-02-19 | Sea Lane Biotechnologies, LLC | Neutralizing molecules to viral antigens |
| BRPI0917871A2 (pt) * | 2008-08-15 | 2017-06-20 | Merrimack Pharmaceuticals Inc | agente terapêutico anti-erbb3 para uso em terapia de um tumor, métodos para predizer responsividade de um tumor de um agente terapêutco anti-erbb3, para selecionar terapia anti-erbb3 para um paciente, para predizer a resposta de células ao tratamento com um agente terapêutico, para identificar um biomarcador, e para evitar administração de uma droga para câncer anti-erbb3, e, kit para predizer a resposta das células ao tratamento com um agente terapêutico |
| AU2009324939B2 (en) | 2008-11-25 | 2015-07-09 | Genentech, Inc. | Isoform specific anti-HER4 antibodies |
| CN102356092B (zh) * | 2009-03-20 | 2014-11-05 | 霍夫曼-拉罗奇有限公司 | 双特异性抗-her抗体 |
| JP6184695B2 (ja) | 2009-12-04 | 2017-08-23 | ジェネンテック, インコーポレイテッド | 多重特異性抗体、抗体アナログ、組成物、及び方法 |
| US20130045492A1 (en) | 2010-02-08 | 2013-02-21 | Regeneron Pharmaceuticals, Inc. | Methods For Making Fully Human Bispecific Antibodies Using A Common Light Chain |
| SMT201900372T1 (it) | 2010-02-08 | 2019-09-09 | Regeneron Pharma | Topo con catena leggera comune |
| US9796788B2 (en) | 2010-02-08 | 2017-10-24 | Regeneron Pharmaceuticals, Inc. | Mice expressing a limited immunoglobulin light chain repertoire |
| WO2011107100A1 (en) | 2010-03-03 | 2011-09-09 | Aarhus Universitet | Methods and compositions for regulation of herv4 |
| JP2013522237A (ja) | 2010-03-11 | 2013-06-13 | メリマック ファーマシューティカルズ インコーポレーティッド | トリプルネガティブおよび基底様乳癌の治療におけるerbb3阻害剤の使用 |
| WO2012099566A1 (en) | 2010-11-17 | 2012-07-26 | Sea Lane Biotechnologies, Llc | Influenza virus neutralizing agents that mimic the binding site of an influenza neutralizing antibody |
| HUE068728T2 (hu) | 2011-08-05 | 2025-01-28 | Regeneron Pharma | Humanizált univerzális könnyûláncú egerek |
| WO2013033008A2 (en) | 2011-08-26 | 2013-03-07 | Merrimack Pharmaceuticals, Inc. | Tandem fc bispecific antibodies |
| EA201500503A1 (ru) * | 2012-11-08 | 2015-10-30 | Ф.Хоффманн-Ля Рош Аг | Анти-her3/her4 антигенсвязывающие белки, связывающиеся с бета-шпилькой her3 и бета-шпилькой her4 |
| US9725512B2 (en) | 2012-11-08 | 2017-08-08 | Hoffmann-La Roche Inc. | HER3 antibodies binding to the beta-hairpin of HER3 |
| MX2015011712A (es) | 2013-03-06 | 2016-04-04 | Merrimack Pharmaceuticals Inc | Anticerpos biespecificos fc en fila anti-c-met. |
| WO2015100459A2 (en) | 2013-12-27 | 2015-07-02 | Merrimack Pharmaceuticals, Inc. | Biomarker profiles for predicting outcomes of cancer therapy with erbb3 inhibitors and/or chemotherapies |
| RU2016141307A (ru) | 2014-03-21 | 2018-04-24 | Регенерон Фармасьютикалз, Инк. | Отличные от человека животные, которые вырабатывают однодоменные связывающие белки |
| FR3020063A1 (fr) * | 2014-04-16 | 2015-10-23 | Gamamabs Pharma | Anticorps humain anti-her4 |
| BR112016024457A2 (pt) | 2014-05-14 | 2018-01-23 | Hoffmann La Roche | anticorpo isolado, imunoconjugado, uso do anticorpo, formulação farmacêutica, ácido nucleico isolado, célula hospedeira e método de produção de um anticorpo |
| US11111314B2 (en) | 2015-03-19 | 2021-09-07 | Regeneron Pharmaceuticals, Inc. | Non-human animals that select for light chain variable regions that bind antigen |
| US10184006B2 (en) | 2015-06-04 | 2019-01-22 | Merrimack Pharmaceuticals, Inc. | Biomarkers for predicting outcomes of cancer therapy with ErbB3 inhibitors |
| US20230040928A1 (en) * | 2019-12-09 | 2023-02-09 | INSERM (Institut National de la Santé et de la Recherche Médicale) | Antibodies having specificity to her4 and uses thereof |
Family Cites Families (21)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4968603A (en) * | 1986-12-31 | 1990-11-06 | The Regents Of The University Of California | Determination of status in neoplastic disease |
| US5116964A (en) * | 1989-02-23 | 1992-05-26 | Genentech, Inc. | Hybrid immunoglobulins |
| US5183884A (en) * | 1989-12-01 | 1993-02-02 | United States Of America | Dna segment encoding a gene for a receptor related to the epidermal growth factor receptor |
| US5859205A (en) * | 1989-12-21 | 1999-01-12 | Celltech Limited | Humanised antibodies |
| CA2037440A1 (en) | 1990-03-02 | 1991-09-03 | Gregory D. Plowman | Her3: a novel egf receptor homolog |
| IL101943A0 (en) * | 1991-05-24 | 1992-12-30 | Genentech Inc | Structure,production and use of heregulin |
| EP0590058B1 (en) * | 1991-06-14 | 2003-11-26 | Genentech, Inc. | HUMANIZED Heregulin ANTIBODy |
| CA2103323A1 (en) | 1992-11-24 | 1994-05-25 | Gregory D. Plowman | Her4 human receptor tyrosine kinase |
| US5811098A (en) * | 1992-11-24 | 1998-09-22 | Bristol-Myers Squibb Company | Antibodies to HER4, human receptor tyrosine kinase |
| ATE190978T1 (de) | 1994-11-14 | 2000-04-15 | Warner Lambert Co | 6-aryl-pyrido(2,3-d)pyrimidine und -naphthyridine zur hemmung der durch protein-tyrosin-kinase hervorgerufenen zellvermehrung |
| US5770567A (en) * | 1994-11-14 | 1998-06-23 | Genentech, Inc. | Sensory and motor neuron derived factor (SMDF) |
| US5968511A (en) * | 1996-03-27 | 1999-10-19 | Genentech, Inc. | ErbB3 antibodies |
| IL127892A0 (en) * | 1996-07-12 | 1999-10-28 | Genentech Inc | Gamma-heregulin |
| DE69740038D1 (enExample) * | 1996-07-12 | 2010-12-16 | Genentech Inc | |
| JP4031049B2 (ja) * | 1996-11-27 | 2008-01-09 | ジェネンテック,インコーポレーテッド | タンパク質精製 |
| US6121415A (en) | 1997-07-09 | 2000-09-19 | Genentech, Inc. | ErbB4 receptor-specific neuregolin related ligands and uses therefor |
| US6994856B1 (en) * | 1997-07-24 | 2006-02-07 | Genentech, Inc. | ErbB4 receptor-specific neuregulin related ligands and uses therefor |
| AU9805398A (en) | 1997-10-15 | 1999-05-03 | Children's Medical Center Corporation | Novel human egf receptors and use thereof |
| WO2000031048A1 (en) * | 1998-11-19 | 2000-06-02 | Warner-Lambert Company | N-[4-(3-chloro-4-fluoro-phenylamino)-7-(3-morpholin-4-yl-propoxy)-quinazolin-6-yl]-acrylamide, an irreversible inhibitor of tyrosine kinases |
| US6965018B2 (en) * | 2000-06-06 | 2005-11-15 | Bristol-Myers Squibb Company | Antibodies directed to B7-related polypeptide, BSL-2 |
| US20020119148A1 (en) * | 2000-09-01 | 2002-08-29 | Gerritsen Mary E. | ErbB4 antagonists |
-
2001
- 2001-08-27 US US09/940,101 patent/US20020119148A1/en not_active Abandoned
- 2001-08-29 AU AU8691801A patent/AU8691801A/xx active Pending
- 2001-08-29 EP EP01966399A patent/EP1351744B1/en not_active Expired - Lifetime
- 2001-08-29 WO PCT/US2001/026984 patent/WO2002018444A2/en not_active Ceased
- 2001-08-29 AU AU2001286918A patent/AU2001286918B2/en not_active Ceased
- 2001-08-29 JP JP2002523958A patent/JP2004507559A/ja active Pending
- 2001-08-29 CA CA2420062A patent/CA2420062C/en not_active Expired - Fee Related
- 2001-08-29 ES ES01966399T patent/ES2295202T3/es not_active Expired - Lifetime
- 2001-08-29 AT AT01966399T patent/ATE374642T1/de active
- 2001-08-29 US US10/362,380 patent/US7332579B2/en not_active Expired - Fee Related
- 2001-08-29 IL IL15449501A patent/IL154495A0/xx unknown
- 2001-08-29 DE DE60130797T patent/DE60130797T2/de not_active Expired - Lifetime
- 2001-08-29 DK DK01966399T patent/DK1351744T3/da active
-
2003
- 2003-02-17 IL IL154495A patent/IL154495A/en not_active IP Right Cessation
-
2005
- 2005-10-11 US US11/248,122 patent/US20060093603A1/en not_active Abandoned
-
2006
- 2006-10-13 US US11/581,221 patent/US20070092513A1/en not_active Abandoned
-
2008
- 2008-06-24 US US12/215,200 patent/US7704498B2/en not_active Expired - Fee Related
-
2010
- 2010-04-02 US US12/753,792 patent/US20100190964A1/en not_active Abandoned
Also Published As
| Publication number | Publication date |
|---|---|
| AU8691801A (en) | 2002-03-13 |
| IL154495A0 (en) | 2003-09-17 |
| DK1351744T3 (da) | 2008-02-11 |
| DE60130797T2 (de) | 2008-08-07 |
| DE60130797D1 (de) | 2007-11-15 |
| US7704498B2 (en) | 2010-04-27 |
| US20100190964A1 (en) | 2010-07-29 |
| CA2420062A1 (en) | 2002-03-07 |
| HK1059404A1 (en) | 2004-07-02 |
| EP1351744A2 (en) | 2003-10-15 |
| EP1351744B1 (en) | 2007-10-03 |
| CA2420062C (en) | 2014-04-01 |
| US20040052786A1 (en) | 2004-03-18 |
| US20060093603A1 (en) | 2006-05-04 |
| AU2001286918B2 (en) | 2006-12-21 |
| US7332579B2 (en) | 2008-02-19 |
| WO2002018444A2 (en) | 2002-03-07 |
| US20070092513A1 (en) | 2007-04-26 |
| JP2004507559A (ja) | 2004-03-11 |
| IL154495A (en) | 2009-12-24 |
| WO2002018444A3 (en) | 2003-07-31 |
| ATE374642T1 (de) | 2007-10-15 |
| US20090068205A1 (en) | 2009-03-12 |
| US20020119148A1 (en) | 2002-08-29 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| ES2295202T3 (es) | Utilizacion de un antagonista especifico de erbb4 para el tratamiento de la estenosis. | |
| AU2001286918A1 (en) | ErbB4 antagonists | |
| ES2264127T3 (es) | Ligando de htk. | |
| ES2355952T3 (es) | PROTEÍNA DE FUSIÓN QUE COMPRENDE bpTK7. | |
| TWI527830B (zh) | 介白素-17a/f(il-17a/f)異源多肽及治療用途 | |
| ES2268538T3 (es) | Homologo nl3 del ligando del receptor trirosina quinasa tie. | |
| ES2240981T3 (es) | Citocina denominada lerk-7. | |
| ES2751414T5 (es) | Anticuerpos antagonistas a polipéptidos heterólogos IL-17 A/F | |
| US7084257B2 (en) | Fully human antibody Fab fragments with human interferon-gamma neutralizing activity | |
| ES2391334T3 (es) | Anticuerpos y fragmentos de los mismos que se unen a la IL-1beta | |
| ES2206448T3 (es) | Heregulinas (hrgs), proteinas de union de p185?erb2. | |
| ES2287020T3 (es) | Procedimiento y composiciones para inhibir el crecimiento de celulas neoplasicas. | |
| KR101078459B1 (ko) | 항 수초 관련 당단백질 항체 | |
| ES2264929T3 (es) | Acidos nucleicos y polipeptidos del factor 19 de crecimiento fibroblastico (fgf-19) y procedimientos de utilizacion para el tratamiento de la obesidad. | |
| US20100119523A1 (en) | Vascular endothelial cell growth factor antagonists | |
| MX2011000233A (es) | Agentes de union del receptor notch1 y metodos para su uso. | |
| ES2319202T3 (es) | Polipeptidos transmembrana secretados y acidos nucleicos que los codifican. | |
| CN102762220A (zh) | 人抗淀粉样蛋白抗体、组合物、方法和用途发明背景 | |
| ES2291626T3 (es) | Anticuerpos humanos de ligando anti-hfas antagonista y fragmentos asociados. | |
| US20030023046A1 (en) | Vascular endothelial cell growth factor antagonists | |
| CN113045659B (zh) | 抗cd73人源化抗体 | |
| ES2865303T3 (es) | Ligante de adrenomedulina para su uso en la terapia del cáncer | |
| HK1059404B (en) | Use of specific erbb4 antagonists for treating stenosis | |
| ES2371335T3 (es) | Identificación y modificación de epítopos inmunodominantes en polipéptidos. | |
| ES2333876T3 (es) | Polipeptidos secretados y transmembrana y acidos nucleicos que los codifican. |