SK284586B6 - Použitie alfa_v_beta3 antagonistu na prípravu liečiva - Google Patents
Použitie alfa_v_beta3 antagonistu na prípravu liečiva Download PDFInfo
- Publication number
- SK284586B6 SK284586B6 SK1190-96A SK119096A SK284586B6 SK 284586 B6 SK284586 B6 SK 284586B6 SK 119096 A SK119096 A SK 119096A SK 284586 B6 SK284586 B6 SK 284586B6
- Authority
- SK
- Slovakia
- Prior art keywords
- antagonist
- angiogenesis
- tumor
- cam
- medicament
- Prior art date
Links
- 239000003814 drug Substances 0.000 title claims abstract description 43
- HGFOOLONGOBCMP-IBGZPJMESA-N (3s)-3-(6-methoxypyridin-3-yl)-3-[2-oxo-3-[3-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)propyl]imidazolidin-1-yl]propanoic acid Chemical compound C1=NC(OC)=CC=C1[C@H](CC(O)=O)N1C(=O)N(CCCC=2N=C3NCCCC3=CC=2)CC1 HGFOOLONGOBCMP-IBGZPJMESA-N 0.000 title abstract 4
- 206010028980 Neoplasm Diseases 0.000 claims abstract description 204
- 230000033115 angiogenesis Effects 0.000 claims abstract description 187
- 238000011282 treatment Methods 0.000 claims abstract description 82
- 230000027455 binding Effects 0.000 claims abstract description 64
- 230000002401 inhibitory effect Effects 0.000 claims abstract description 47
- 229940012952 fibrinogen Drugs 0.000 claims abstract description 31
- 108010049003 Fibrinogen Proteins 0.000 claims abstract description 30
- 102000008946 Fibrinogen Human genes 0.000 claims abstract description 30
- 208000037803 restenosis Diseases 0.000 claims abstract description 14
- 206010012689 Diabetic retinopathy Diseases 0.000 claims abstract description 11
- 208000002780 macular degeneration Diseases 0.000 claims abstract description 9
- 206010003246 arthritis Diseases 0.000 claims abstract description 8
- 201000011066 hemangioma Diseases 0.000 claims abstract description 8
- 208000026310 Breast neoplasm Diseases 0.000 claims abstract description 7
- 210000000481 breast Anatomy 0.000 claims abstract description 7
- 210000001072 colon Anatomy 0.000 claims abstract description 6
- 210000004072 lung Anatomy 0.000 claims abstract description 6
- 210000001672 ovary Anatomy 0.000 claims abstract description 6
- 210000000496 pancreas Anatomy 0.000 claims abstract description 6
- 208000029742 colonic neoplasm Diseases 0.000 claims abstract description 5
- 210000000867 larynx Anatomy 0.000 claims abstract description 5
- 206010061535 Ovarian neoplasm Diseases 0.000 claims abstract description 4
- 206010061902 Pancreatic neoplasm Diseases 0.000 claims abstract description 4
- 238000002512 chemotherapy Methods 0.000 claims abstract description 4
- 206010023841 laryngeal neoplasm Diseases 0.000 claims abstract description 4
- 108090000765 processed proteins & peptides Proteins 0.000 claims description 224
- 239000005557 antagonist Substances 0.000 claims description 144
- 102000004196 processed proteins & peptides Human genes 0.000 claims description 124
- 229920001184 polypeptide Polymers 0.000 claims description 59
- 108010069514 Cyclic Peptides Proteins 0.000 claims description 31
- 102000001189 Cyclic Peptides Human genes 0.000 claims description 31
- 238000001990 intravenous administration Methods 0.000 claims description 24
- 150000003839 salts Chemical class 0.000 claims description 17
- 230000000699 topical effect Effects 0.000 claims description 15
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 14
- 238000004519 manufacturing process Methods 0.000 claims description 6
- 238000007887 coronary angioplasty Methods 0.000 claims description 3
- 206010039073 rheumatoid arthritis Diseases 0.000 claims description 3
- 230000005747 tumor angiogenesis Effects 0.000 claims description 3
- DTQVDTLACAAQTR-UHFFFAOYSA-M Trifluoroacetate Chemical compound [O-]C(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-M 0.000 claims description 2
- 238000007918 intramuscular administration Methods 0.000 claims description 2
- 238000007919 intrasynovial administration Methods 0.000 claims description 2
- 230000004263 retinal angiogenesis Effects 0.000 claims description 2
- 230000000694 effects Effects 0.000 abstract description 57
- 210000001519 tissue Anatomy 0.000 description 149
- 210000004027 cell Anatomy 0.000 description 98
- 210000004204 blood vessel Anatomy 0.000 description 83
- 108010044426 integrins Proteins 0.000 description 76
- 102000006495 integrins Human genes 0.000 description 76
- 238000000034 method Methods 0.000 description 72
- 238000003556 assay Methods 0.000 description 55
- 239000003446 ligand Substances 0.000 description 51
- 102000018233 Fibroblast Growth Factor Human genes 0.000 description 46
- 108050007372 Fibroblast Growth Factor Proteins 0.000 description 46
- 229940126864 fibroblast growth factor Drugs 0.000 description 46
- 210000002257 embryonic structure Anatomy 0.000 description 45
- 239000002953 phosphate buffered saline Substances 0.000 description 44
- 230000005764 inhibitory process Effects 0.000 description 42
- 150000001413 amino acids Chemical class 0.000 description 41
- 238000002360 preparation method Methods 0.000 description 38
- 235000001014 amino acid Nutrition 0.000 description 37
- 229940024606 amino acid Drugs 0.000 description 37
- 239000012634 fragment Substances 0.000 description 36
- 239000000203 mixture Substances 0.000 description 34
- 206010029113 Neovascularisation Diseases 0.000 description 33
- 125000000539 amino acid group Chemical group 0.000 description 29
- 230000012010 growth Effects 0.000 description 29
- IYMAXBFPHPZYIK-BQBZGAKWSA-N Arg-Gly-Asp Chemical compound NC(N)=NCCC[C@H](N)C(=O)NCC(=O)N[C@@H](CC(O)=O)C(O)=O IYMAXBFPHPZYIK-BQBZGAKWSA-N 0.000 description 28
- 241000283973 Oryctolagus cuniculus Species 0.000 description 28
- 241000287828 Gallus gallus Species 0.000 description 26
- 102000005962 receptors Human genes 0.000 description 26
- 108020003175 receptors Proteins 0.000 description 26
- 238000010186 staining Methods 0.000 description 26
- 201000001441 melanoma Diseases 0.000 description 25
- 239000003102 growth factor Substances 0.000 description 24
- 201000010099 disease Diseases 0.000 description 23
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 23
- 238000012360 testing method Methods 0.000 description 23
- 230000006907 apoptotic process Effects 0.000 description 22
- 238000001727 in vivo Methods 0.000 description 21
- 230000014399 negative regulation of angiogenesis Effects 0.000 description 21
- 239000000243 solution Substances 0.000 description 21
- 210000003491 skin Anatomy 0.000 description 20
- 108020004414 DNA Proteins 0.000 description 19
- 210000001161 mammalian embryo Anatomy 0.000 description 19
- 210000004087 cornea Anatomy 0.000 description 18
- 241000699666 Mus <mouse, genus> Species 0.000 description 17
- 210000004408 hybridoma Anatomy 0.000 description 17
- 239000008188 pellet Substances 0.000 description 17
- 230000008569 process Effects 0.000 description 17
- 102100035140 Vitronectin Human genes 0.000 description 15
- 108010031318 Vitronectin Proteins 0.000 description 15
- 238000004458 analytical method Methods 0.000 description 15
- 150000008574 D-amino acids Chemical class 0.000 description 14
- 230000000692 anti-sense effect Effects 0.000 description 14
- 230000015572 biosynthetic process Effects 0.000 description 14
- 230000004614 tumor growth Effects 0.000 description 14
- 230000002491 angiogenic effect Effects 0.000 description 13
- 201000011510 cancer Diseases 0.000 description 13
- 239000003795 chemical substances by application Substances 0.000 description 13
- 238000009826 distribution Methods 0.000 description 13
- 230000001225 therapeutic effect Effects 0.000 description 13
- 239000012981 Hank's balanced salt solution Substances 0.000 description 12
- 239000007787 solid Substances 0.000 description 12
- 210000004881 tumor cell Anatomy 0.000 description 12
- 210000005167 vascular cell Anatomy 0.000 description 12
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 11
- 239000003112 inhibitor Substances 0.000 description 11
- 206010063560 Excessive granulation tissue Diseases 0.000 description 10
- 230000022131 cell cycle Effects 0.000 description 10
- 239000006285 cell suspension Substances 0.000 description 10
- 210000001126 granulation tissue Anatomy 0.000 description 10
- 238000010166 immunofluorescence Methods 0.000 description 10
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 9
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 9
- 102000004127 Cytokines Human genes 0.000 description 9
- 108090000695 Cytokines Proteins 0.000 description 9
- 108060003951 Immunoglobulin Proteins 0.000 description 9
- 150000008575 L-amino acids Chemical group 0.000 description 9
- 241000124008 Mammalia Species 0.000 description 9
- 206010027476 Metastases Diseases 0.000 description 9
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 9
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 9
- 108060008682 Tumor Necrosis Factor Proteins 0.000 description 9
- 102000000852 Tumor Necrosis Factor-alpha Human genes 0.000 description 9
- 239000004480 active ingredient Substances 0.000 description 9
- 230000000903 blocking effect Effects 0.000 description 9
- 239000000872 buffer Substances 0.000 description 9
- 102000018358 immunoglobulin Human genes 0.000 description 9
- 238000010253 intravenous injection Methods 0.000 description 9
- 235000018102 proteins Nutrition 0.000 description 9
- 102000004169 proteins and genes Human genes 0.000 description 9
- 108090000623 proteins and genes Proteins 0.000 description 9
- 239000000126 substance Substances 0.000 description 9
- 230000002792 vascular Effects 0.000 description 9
- 210000005166 vasculature Anatomy 0.000 description 9
- KDXKERNSBIXSRK-YFKPBYRVSA-N L-lysine Chemical compound NCCCC[C@H](N)C(O)=O KDXKERNSBIXSRK-YFKPBYRVSA-N 0.000 description 8
- 206010058467 Lung neoplasm malignant Diseases 0.000 description 8
- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 8
- 150000001875 compounds Chemical class 0.000 description 8
- 108010045325 cyclic arginine-glycine-aspartic acid peptide Proteins 0.000 description 8
- 210000002889 endothelial cell Anatomy 0.000 description 8
- 238000002474 experimental method Methods 0.000 description 8
- 230000006870 function Effects 0.000 description 8
- 230000006698 induction Effects 0.000 description 8
- 125000006239 protecting group Chemical group 0.000 description 8
- 229920006395 saturated elastomer Polymers 0.000 description 8
- 108010047303 von Willebrand Factor Proteins 0.000 description 8
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 7
- RPLLQZBOVIVGMX-QWRGUYRKSA-N Gly-Asp-Phe Chemical compound [H]NCC(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC1=CC=CC=C1)C(O)=O RPLLQZBOVIVGMX-QWRGUYRKSA-N 0.000 description 7
- 102000007547 Laminin Human genes 0.000 description 7
- 239000004472 Lysine Substances 0.000 description 7
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 7
- 239000004037 angiogenesis inhibitor Substances 0.000 description 7
- 229940098773 bovine serum albumin Drugs 0.000 description 7
- 230000001419 dependent effect Effects 0.000 description 7
- 235000018977 lysine Nutrition 0.000 description 7
- 230000009467 reduction Effects 0.000 description 7
- 102100036537 von Willebrand factor Human genes 0.000 description 7
- 229960001134 von willebrand factor Drugs 0.000 description 7
- 239000004475 Arginine Substances 0.000 description 6
- 201000009030 Carcinoma Diseases 0.000 description 6
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 6
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 6
- 102100024785 Fibroblast growth factor 2 Human genes 0.000 description 6
- 108090000379 Fibroblast growth factor 2 Proteins 0.000 description 6
- 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 6
- 102100022337 Integrin alpha-V Human genes 0.000 description 6
- 108010085895 Laminin Proteins 0.000 description 6
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 6
- SJRJJKPEHAURKC-UHFFFAOYSA-N N-Methylmorpholine Chemical compound CN1CCOCC1 SJRJJKPEHAURKC-UHFFFAOYSA-N 0.000 description 6
- 108010048673 Vitronectin Receptors Proteins 0.000 description 6
- -1 acetic Chemical class 0.000 description 6
- ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 6
- 210000004899 c-terminal region Anatomy 0.000 description 6
- 125000004122 cyclic group Chemical group 0.000 description 6
- 238000001514 detection method Methods 0.000 description 6
- 230000013020 embryo development Effects 0.000 description 6
- 210000003953 foreskin Anatomy 0.000 description 6
- 238000011534 incubation Methods 0.000 description 6
- 230000002757 inflammatory effect Effects 0.000 description 6
- 239000007788 liquid Substances 0.000 description 6
- 230000037311 normal skin Effects 0.000 description 6
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 6
- 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 6
- 229940124597 therapeutic agent Drugs 0.000 description 6
- 238000002560 therapeutic procedure Methods 0.000 description 6
- QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 description 5
- 108010067306 Fibronectins Proteins 0.000 description 5
- 102000016359 Fibronectins Human genes 0.000 description 5
- WHUUTDBJXJRKMK-UHFFFAOYSA-N Glutamic acid Natural products OC(=O)C(N)CCC(O)=O WHUUTDBJXJRKMK-UHFFFAOYSA-N 0.000 description 5
- JLXVRFDTDUGQEE-YFKPBYRVSA-N Gly-Arg Chemical compound NCC(=O)N[C@H](C(O)=O)CCCN=C(N)N JLXVRFDTDUGQEE-YFKPBYRVSA-N 0.000 description 5
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 5
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 5
- WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-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
- HNDVDQJCIGZPNO-YFKPBYRVSA-N L-histidine Chemical compound OC(=O)[C@@H](N)CC1=CN=CN1 HNDVDQJCIGZPNO-YFKPBYRVSA-N 0.000 description 5
- 206010035226 Plasma cell myeloma Diseases 0.000 description 5
- 238000011579 SCID mouse model Methods 0.000 description 5
- 238000007792 addition Methods 0.000 description 5
- 229940121369 angiogenesis inhibitor Drugs 0.000 description 5
- 239000000427 antigen Substances 0.000 description 5
- 102000036639 antigens Human genes 0.000 description 5
- 108091007433 antigens Proteins 0.000 description 5
- 230000001640 apoptogenic effect Effects 0.000 description 5
- 210000004369 blood Anatomy 0.000 description 5
- 239000008280 blood Substances 0.000 description 5
- 238000011161 development Methods 0.000 description 5
- 230000018109 developmental process Effects 0.000 description 5
- LOKCTEFSRHRXRJ-UHFFFAOYSA-I dipotassium trisodium dihydrogen phosphate hydrogen phosphate dichloride Chemical compound P(=O)(O)(O)[O-].[K+].P(=O)(O)([O-])[O-].[Na+].[Na+].[Cl-].[K+].[Cl-].[Na+] LOKCTEFSRHRXRJ-UHFFFAOYSA-I 0.000 description 5
- 229940079593 drug Drugs 0.000 description 5
- 208000021045 exocrine pancreatic carcinoma Diseases 0.000 description 5
- 238000013467 fragmentation Methods 0.000 description 5
- 238000006062 fragmentation reaction Methods 0.000 description 5
- HNDVDQJCIGZPNO-UHFFFAOYSA-N histidine Natural products OC(=O)C(N)CC1=CN=CN1 HNDVDQJCIGZPNO-UHFFFAOYSA-N 0.000 description 5
- 238000003364 immunohistochemistry Methods 0.000 description 5
- 238000000338 in vitro Methods 0.000 description 5
- 230000008595 infiltration Effects 0.000 description 5
- 238000001764 infiltration Methods 0.000 description 5
- 230000003993 interaction Effects 0.000 description 5
- 201000005264 laryngeal carcinoma Diseases 0.000 description 5
- 201000005296 lung carcinoma Diseases 0.000 description 5
- 230000001404 mediated effect Effects 0.000 description 5
- 239000002609 medium Substances 0.000 description 5
- 201000000050 myeloid neoplasm Diseases 0.000 description 5
- 208000008443 pancreatic carcinoma Diseases 0.000 description 5
- 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 5
- 210000000329 smooth muscle myocyte Anatomy 0.000 description 5
- 230000000638 stimulation Effects 0.000 description 5
- 230000001988 toxicity Effects 0.000 description 5
- 231100000419 toxicity Toxicity 0.000 description 5
- 230000006444 vascular growth Effects 0.000 description 5
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 5
- 230000029663 wound healing Effects 0.000 description 5
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 4
- 238000002965 ELISA Methods 0.000 description 4
- 108010054477 Immunoglobulin Fab Fragments Proteins 0.000 description 4
- 102000001706 Immunoglobulin Fab Fragments Human genes 0.000 description 4
- ODKSFYDXXFIFQN-BYPYZUCNSA-P L-argininium(2+) Chemical compound NC(=[NH2+])NCCC[C@H]([NH3+])C(O)=O ODKSFYDXXFIFQN-BYPYZUCNSA-P 0.000 description 4
- BAVYZALUXZFZLV-UHFFFAOYSA-N Methylamine Chemical compound NC BAVYZALUXZFZLV-UHFFFAOYSA-N 0.000 description 4
- 241000699670 Mus sp. Species 0.000 description 4
- 101000781681 Protobothrops flavoviridis Disintegrin triflavin Proteins 0.000 description 4
- PXIPVTKHYLBLMZ-UHFFFAOYSA-N Sodium azide Chemical compound [Na+].[N-]=[N+]=[N-] PXIPVTKHYLBLMZ-UHFFFAOYSA-N 0.000 description 4
- 206010052428 Wound Diseases 0.000 description 4
- 208000027418 Wounds and injury Diseases 0.000 description 4
- 125000003277 amino group Chemical group 0.000 description 4
- 108010072041 arginyl-glycyl-aspartic acid Proteins 0.000 description 4
- 230000008901 benefit Effects 0.000 description 4
- 238000001574 biopsy Methods 0.000 description 4
- 239000000969 carrier Substances 0.000 description 4
- 230000021164 cell adhesion Effects 0.000 description 4
- 230000002939 deleterious effect Effects 0.000 description 4
- 230000004069 differentiation Effects 0.000 description 4
- 239000002158 endotoxin Substances 0.000 description 4
- 238000001943 fluorescence-activated cell sorting Methods 0.000 description 4
- GPRLSGONYQIRFK-UHFFFAOYSA-N hydron Chemical compound [H+] GPRLSGONYQIRFK-UHFFFAOYSA-N 0.000 description 4
- 230000036046 immunoreaction Effects 0.000 description 4
- 238000001802 infusion Methods 0.000 description 4
- 238000002372 labelling Methods 0.000 description 4
- 239000000463 material Substances 0.000 description 4
- 230000009401 metastasis Effects 0.000 description 4
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 4
- 238000001000 micrograph Methods 0.000 description 4
- 230000036470 plasma concentration Effects 0.000 description 4
- 229920002338 polyhydroxyethylmethacrylate Polymers 0.000 description 4
- 230000035755 proliferation Effects 0.000 description 4
- 238000001525 receptor binding assay Methods 0.000 description 4
- 239000007790 solid phase Substances 0.000 description 4
- 238000010532 solid phase synthesis reaction Methods 0.000 description 4
- 238000006467 substitution reaction Methods 0.000 description 4
- 230000008467 tissue growth Effects 0.000 description 4
- 230000035899 viability Effects 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 3
- YOYAIZYFCNQIRF-UHFFFAOYSA-N 2,6-dichlorobenzonitrile Chemical compound ClC1=CC=CC(Cl)=C1C#N YOYAIZYFCNQIRF-UHFFFAOYSA-N 0.000 description 3
- 206010006187 Breast cancer Diseases 0.000 description 3
- 241000283707 Capra Species 0.000 description 3
- ODKSFYDXXFIFQN-SCSAIBSYSA-N D-arginine Chemical compound OC(=O)[C@H](N)CCCNC(N)=N ODKSFYDXXFIFQN-SCSAIBSYSA-N 0.000 description 3
- 102000002322 Egg Proteins Human genes 0.000 description 3
- 108010000912 Egg Proteins Proteins 0.000 description 3
- 108010073385 Fibrin Proteins 0.000 description 3
- 102000009123 Fibrin Human genes 0.000 description 3
- BWGVNKXGVNDBDI-UHFFFAOYSA-N Fibrin monomer Chemical compound CNC(=O)CNC(=O)CN BWGVNKXGVNDBDI-UHFFFAOYSA-N 0.000 description 3
- 101100058944 Gallus gallus CALM gene 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
- DCXYFEDJOCDNAF-REOHCLBHSA-N L-asparagine Chemical compound OC(=O)[C@@H](N)CC(N)=O DCXYFEDJOCDNAF-REOHCLBHSA-N 0.000 description 3
- CKLJMWTZIZZHCS-REOHCLBHSA-N L-aspartic acid Chemical compound OC(=O)[C@@H](N)CC(O)=O CKLJMWTZIZZHCS-REOHCLBHSA-N 0.000 description 3
- OFOBLEOULBTSOW-UHFFFAOYSA-N Malonic acid Chemical compound OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 3
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 3
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 3
- 108060008245 Thrombospondin Proteins 0.000 description 3
- 102000002938 Thrombospondin Human genes 0.000 description 3
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
- 239000002253 acid Substances 0.000 description 3
- 125000000637 arginyl group Chemical group N[C@@H](CCCNC(N)=N)C(=O)* 0.000 description 3
- 230000002917 arthritic effect Effects 0.000 description 3
- 235000003704 aspartic acid Nutrition 0.000 description 3
- 210000002469 basement membrane Anatomy 0.000 description 3
- OQFSQFPPLPISGP-UHFFFAOYSA-N beta-carboxyaspartic acid Natural products OC(=O)C(N)C(C(O)=O)C(O)=O OQFSQFPPLPISGP-UHFFFAOYSA-N 0.000 description 3
- 230000008827 biological function Effects 0.000 description 3
- 230000001413 cellular effect Effects 0.000 description 3
- 230000008859 change Effects 0.000 description 3
- 238000006243 chemical reaction Methods 0.000 description 3
- 210000003711 chorioallantoic membrane Anatomy 0.000 description 3
- 230000008045 co-localization Effects 0.000 description 3
- 239000000512 collagen gel Substances 0.000 description 3
- 230000003013 cytotoxicity Effects 0.000 description 3
- 231100000135 cytotoxicity Toxicity 0.000 description 3
- UAOMVDZJSHZZME-UHFFFAOYSA-N diisopropylamine Chemical compound CC(C)NC(C)C UAOMVDZJSHZZME-UHFFFAOYSA-N 0.000 description 3
- 210000003278 egg shell Anatomy 0.000 description 3
- YQGOJNYOYNNSMM-UHFFFAOYSA-N eosin Chemical compound [Na+].OC(=O)C1=CC=CC=C1C1=C2C=C(Br)C(=O)C(Br)=C2OC2=C(Br)C(O)=C(Br)C=C21 YQGOJNYOYNNSMM-UHFFFAOYSA-N 0.000 description 3
- 238000011156 evaluation Methods 0.000 description 3
- 238000001704 evaporation Methods 0.000 description 3
- 230000008020 evaporation Effects 0.000 description 3
- 229950003499 fibrin Drugs 0.000 description 3
- 238000009472 formulation Methods 0.000 description 3
- 235000013922 glutamic acid Nutrition 0.000 description 3
- 239000004220 glutamic acid 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
- 230000036541 health Effects 0.000 description 3
- 150000003840 hydrochlorides Chemical class 0.000 description 3
- 238000010185 immunofluorescence analysis Methods 0.000 description 3
- 238000002347 injection Methods 0.000 description 3
- 239000007924 injection Substances 0.000 description 3
- 230000002452 interceptive effect Effects 0.000 description 3
- 201000005202 lung cancer Diseases 0.000 description 3
- 208000020816 lung neoplasm Diseases 0.000 description 3
- 210000004379 membrane Anatomy 0.000 description 3
- 239000012528 membrane Substances 0.000 description 3
- 125000004492 methyl ester group Chemical group 0.000 description 3
- 210000004088 microvessel Anatomy 0.000 description 3
- 230000010807 negative regulation of binding Effects 0.000 description 3
- 230000017066 negative regulation of growth Effects 0.000 description 3
- 235000015097 nutrients Nutrition 0.000 description 3
- 238000010647 peptide synthesis reaction Methods 0.000 description 3
- 238000012342 propidium iodide staining Methods 0.000 description 3
- 238000011002 quantification Methods 0.000 description 3
- 230000002207 retinal effect Effects 0.000 description 3
- 239000002904 solvent Substances 0.000 description 3
- 238000001356 surgical procedure Methods 0.000 description 3
- 230000004083 survival effect Effects 0.000 description 3
- 208000024891 symptom Diseases 0.000 description 3
- 238000003786 synthesis reaction Methods 0.000 description 3
- 238000007910 systemic administration Methods 0.000 description 3
- 238000011191 terminal modification Methods 0.000 description 3
- 125000005931 tert-butyloxycarbonyl group Chemical group [H]C([H])([H])C(OC(*)=O)(C([H])([H])[H])C([H])([H])[H] 0.000 description 3
- 230000007998 vessel formation Effects 0.000 description 3
- MZOFCQQQCNRIBI-VMXHOPILSA-N (3s)-4-[[(2s)-1-[[(2s)-1-[[(1s)-1-carboxy-2-hydroxyethyl]amino]-4-methyl-1-oxopentan-2-yl]amino]-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-3-[[2-[[(2s)-2,6-diaminohexanoyl]amino]acetyl]amino]-4-oxobutanoic acid Chemical compound OC[C@@H](C(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCN=C(N)N)NC(=O)[C@H](CC(O)=O)NC(=O)CNC(=O)[C@@H](N)CCCCN MZOFCQQQCNRIBI-VMXHOPILSA-N 0.000 description 2
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 2
- ASOKPJOREAFHNY-UHFFFAOYSA-N 1-Hydroxybenzotriazole Chemical compound C1=CC=C2N(O)N=NC2=C1 ASOKPJOREAFHNY-UHFFFAOYSA-N 0.000 description 2
- HZAXFHJVJLSVMW-UHFFFAOYSA-N 2-Aminoethan-1-ol Chemical compound NCCO HZAXFHJVJLSVMW-UHFFFAOYSA-N 0.000 description 2
- HVBSAKJJOYLTQU-UHFFFAOYSA-N 4-aminobenzenesulfonic acid Chemical compound NC1=CC=C(S(O)(=O)=O)C=C1 HVBSAKJJOYLTQU-UHFFFAOYSA-N 0.000 description 2
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 2
- 208000003120 Angiofibroma Diseases 0.000 description 2
- 108010032595 Antibody Binding Sites Proteins 0.000 description 2
- MCYJBCKCAPERSE-FXQIFTODSA-N Arg-Ala-Asp Chemical compound OC(=O)C[C@@H](C(O)=O)NC(=O)[C@H](C)NC(=O)[C@@H](N)CCCN=C(N)N MCYJBCKCAPERSE-FXQIFTODSA-N 0.000 description 2
- DCXYFEDJOCDNAF-UHFFFAOYSA-N Asparagine Natural products OC(=O)C(N)CC(N)=O DCXYFEDJOCDNAF-UHFFFAOYSA-N 0.000 description 2
- 206010005003 Bladder cancer Diseases 0.000 description 2
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 2
- 208000013641 Cerebrofacial arteriovenous metameric syndrome Diseases 0.000 description 2
- 108010035532 Collagen Proteins 0.000 description 2
- 102000008186 Collagen Human genes 0.000 description 2
- 206010009944 Colon cancer Diseases 0.000 description 2
- ROSDSFDQCJNGOL-UHFFFAOYSA-N Dimethylamine Chemical compound CNC ROSDSFDQCJNGOL-UHFFFAOYSA-N 0.000 description 2
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 2
- 208000010412 Glaucoma Diseases 0.000 description 2
- 239000004471 Glycine Substances 0.000 description 2
- AEMRFAOFKBGASW-UHFFFAOYSA-N Glycolic acid Chemical compound OCC(O)=O AEMRFAOFKBGASW-UHFFFAOYSA-N 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
- 108010021625 Immunoglobulin Fragments Proteins 0.000 description 2
- 102000008394 Immunoglobulin Fragments Human genes 0.000 description 2
- 206010061218 Inflammation Diseases 0.000 description 2
- ONIBWKKTOPOVIA-BYPYZUCNSA-N L-Proline Chemical compound OC(=O)[C@@H]1CCCN1 ONIBWKKTOPOVIA-BYPYZUCNSA-N 0.000 description 2
- AGPKZVBTJJNPAG-WHFBIAKZSA-N L-isoleucine Chemical compound CC[C@H](C)[C@H](N)C(O)=O AGPKZVBTJJNPAG-WHFBIAKZSA-N 0.000 description 2
- ROHFNLRQFUQHCH-YFKPBYRVSA-N L-leucine Chemical compound CC(C)C[C@H](N)C(O)=O ROHFNLRQFUQHCH-YFKPBYRVSA-N 0.000 description 2
- FFEARJCKVFRZRR-BYPYZUCNSA-N L-methionine Chemical compound CSCC[C@H](N)C(O)=O FFEARJCKVFRZRR-BYPYZUCNSA-N 0.000 description 2
- OUYCCCASQSFEME-QMMMGPOBSA-N L-tyrosine Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-QMMMGPOBSA-N 0.000 description 2
- KZSNJWFQEVHDMF-BYPYZUCNSA-N L-valine Chemical compound CC(C)[C@H](N)C(O)=O KZSNJWFQEVHDMF-BYPYZUCNSA-N 0.000 description 2
- 108010000851 Laminin Receptors Proteins 0.000 description 2
- ROHFNLRQFUQHCH-UHFFFAOYSA-N Leucine Natural products CC(C)CC(N)C(O)=O ROHFNLRQFUQHCH-UHFFFAOYSA-N 0.000 description 2
- 238000000585 Mann–Whitney U test Methods 0.000 description 2
- 102100039364 Metalloproteinase inhibitor 1 Human genes 0.000 description 2
- 108091005804 Peptidases Proteins 0.000 description 2
- 102000035195 Peptidases Human genes 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- 239000002202 Polyethylene glycol Substances 0.000 description 2
- WCUXLLCKKVVCTQ-UHFFFAOYSA-M Potassium chloride Chemical compound [Cl-].[K+] WCUXLLCKKVVCTQ-UHFFFAOYSA-M 0.000 description 2
- ONIBWKKTOPOVIA-UHFFFAOYSA-N Proline Natural products OC(=O)C1CCCN1 ONIBWKKTOPOVIA-UHFFFAOYSA-N 0.000 description 2
- 229920002684 Sepharose Polymers 0.000 description 2
- MTCFGRXMJLQNBG-UHFFFAOYSA-N Serine Natural products OCC(N)C(O)=O MTCFGRXMJLQNBG-UHFFFAOYSA-N 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- IQFYYKKMVGJFEH-XLPZGREQSA-N Thymidine Chemical compound O=C1NC(=O)C(C)=CN1[C@@H]1O[C@H](CO)[C@@H](O)C1 IQFYYKKMVGJFEH-XLPZGREQSA-N 0.000 description 2
- 229920004890 Triton X-100 Polymers 0.000 description 2
- 239000013504 Triton X-100 Substances 0.000 description 2
- 208000007097 Urinary Bladder Neoplasms Diseases 0.000 description 2
- KZSNJWFQEVHDMF-UHFFFAOYSA-N Valine Natural products CC(C)C(N)C(O)=O KZSNJWFQEVHDMF-UHFFFAOYSA-N 0.000 description 2
- 230000002378 acidificating effect Effects 0.000 description 2
- 239000000654 additive Substances 0.000 description 2
- 239000011543 agarose gel Substances 0.000 description 2
- 230000004075 alteration Effects 0.000 description 2
- 238000002399 angioplasty Methods 0.000 description 2
- RWZYAGGXGHYGMB-UHFFFAOYSA-N anthranilic acid Chemical compound NC1=CC=CC=C1C(O)=O RWZYAGGXGHYGMB-UHFFFAOYSA-N 0.000 description 2
- 235000009582 asparagine Nutrition 0.000 description 2
- 229960001230 asparagine Drugs 0.000 description 2
- 230000001580 bacterial effect 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
- 230000004071 biological effect Effects 0.000 description 2
- 230000031018 biological processes and functions Effects 0.000 description 2
- 125000004744 butyloxycarbonyl group Chemical group 0.000 description 2
- 239000011575 calcium Substances 0.000 description 2
- 229910052791 calcium Inorganic materials 0.000 description 2
- 150000001732 carboxylic acid derivatives Chemical group 0.000 description 2
- 230000004663 cell proliferation Effects 0.000 description 2
- 230000036755 cellular response Effects 0.000 description 2
- 238000012512 characterization method Methods 0.000 description 2
- 238000004587 chromatography analysis Methods 0.000 description 2
- 230000001684 chronic effect Effects 0.000 description 2
- 238000003776 cleavage reaction Methods 0.000 description 2
- 229920001436 collagen Polymers 0.000 description 2
- 238000010226 confocal imaging Methods 0.000 description 2
- 210000002808 connective tissue Anatomy 0.000 description 2
- 108010050963 cyclo(arginyl-glycyl-aspartyl-phenylalanyl-valyl) Proteins 0.000 description 2
- 230000007423 decrease Effects 0.000 description 2
- 230000003247 decreasing effect Effects 0.000 description 2
- 238000012217 deletion Methods 0.000 description 2
- 230000037430 deletion Effects 0.000 description 2
- 239000008121 dextrose Substances 0.000 description 2
- 238000010790 dilution Methods 0.000 description 2
- 239000012895 dilution Substances 0.000 description 2
- XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 2
- 238000009510 drug design Methods 0.000 description 2
- 210000000981 epithelium Anatomy 0.000 description 2
- 239000012894 fetal calf serum Substances 0.000 description 2
- 239000000834 fixative Substances 0.000 description 2
- MHMNJMPURVTYEJ-UHFFFAOYSA-N fluorescein-5-isothiocyanate Chemical compound O1C(=O)C2=CC(N=C=S)=CC=C2C21C1=CC=C(O)C=C1OC1=CC(O)=CC=C21 MHMNJMPURVTYEJ-UHFFFAOYSA-N 0.000 description 2
- 235000011187 glycerol Nutrition 0.000 description 2
- 239000001963 growth medium Substances 0.000 description 2
- 210000000987 immune system Anatomy 0.000 description 2
- 238000002513 implantation Methods 0.000 description 2
- 239000000411 inducer Substances 0.000 description 2
- 230000006882 induction of apoptosis Effects 0.000 description 2
- 230000001939 inductive effect Effects 0.000 description 2
- 208000027866 inflammatory disease Diseases 0.000 description 2
- 230000004054 inflammatory process Effects 0.000 description 2
- 230000000977 initiatory effect Effects 0.000 description 2
- 150000007529 inorganic bases Chemical class 0.000 description 2
- AGPKZVBTJJNPAG-UHFFFAOYSA-N isoleucine Natural products CCC(C)C(N)C(O)=O AGPKZVBTJJNPAG-UHFFFAOYSA-N 0.000 description 2
- 229960000310 isoleucine Drugs 0.000 description 2
- JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 2
- 239000007791 liquid phase Substances 0.000 description 2
- 210000004698 lymphocyte Anatomy 0.000 description 2
- 239000011159 matrix material Substances 0.000 description 2
- 229930182817 methionine Natural products 0.000 description 2
- 230000005012 migration Effects 0.000 description 2
- 238000013508 migration Methods 0.000 description 2
- 150000007522 mineralic acids Chemical class 0.000 description 2
- 230000000394 mitotic effect Effects 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- 230000000877 morphologic effect Effects 0.000 description 2
- 238000010172 mouse model Methods 0.000 description 2
- 201000003142 neovascular glaucoma Diseases 0.000 description 2
- 229910052757 nitrogen Inorganic materials 0.000 description 2
- 230000009871 nonspecific binding Effects 0.000 description 2
- 150000007530 organic bases Chemical class 0.000 description 2
- VLTRZXGMWDSKGL-UHFFFAOYSA-N perchloric acid Chemical compound OCl(=O)(=O)=O VLTRZXGMWDSKGL-UHFFFAOYSA-N 0.000 description 2
- 239000000546 pharmaceutical excipient Substances 0.000 description 2
- 229920001223 polyethylene glycol Polymers 0.000 description 2
- 229920000642 polymer Polymers 0.000 description 2
- 230000003389 potentiating effect Effects 0.000 description 2
- 235000019833 protease Nutrition 0.000 description 2
- 230000004044 response Effects 0.000 description 2
- 238000007363 ring formation reaction Methods 0.000 description 2
- 230000007017 scission Effects 0.000 description 2
- 238000012216 screening Methods 0.000 description 2
- 230000011218 segmentation Effects 0.000 description 2
- 210000000998 shell membrane Anatomy 0.000 description 2
- 230000007781 signaling event Effects 0.000 description 2
- 239000011780 sodium chloride Substances 0.000 description 2
- 241000894007 species Species 0.000 description 2
- MNQYNQBOVCBZIQ-JQOFMKNESA-A sucralfate Chemical compound O[Al](O)OS(=O)(=O)O[C@@H]1[C@@H](OS(=O)(=O)O[Al](O)O)[C@H](OS(=O)(=O)O[Al](O)O)[C@@H](COS(=O)(=O)O[Al](O)O)O[C@H]1O[C@@]1(COS(=O)(=O)O[Al](O)O)[C@@H](OS(=O)(=O)O[Al](O)O)[C@H](OS(=O)(=O)O[Al](O)O)[C@@H](OS(=O)(=O)O[Al](O)O)O1 MNQYNQBOVCBZIQ-JQOFMKNESA-A 0.000 description 2
- 229960004291 sucralfate Drugs 0.000 description 2
- 239000000725 suspension Substances 0.000 description 2
- ZMZDMBWJUHKJPS-UHFFFAOYSA-N thiocyanic acid Chemical compound SC#N ZMZDMBWJUHKJPS-UHFFFAOYSA-N 0.000 description 2
- CWERGRDVMFNCDR-UHFFFAOYSA-N thioglycolic acid Chemical compound OC(=O)CS CWERGRDVMFNCDR-UHFFFAOYSA-N 0.000 description 2
- 231100000331 toxic Toxicity 0.000 description 2
- 230000002588 toxic effect Effects 0.000 description 2
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 2
- 238000002054 transplantation Methods 0.000 description 2
- GETQZCLCWQTVFV-UHFFFAOYSA-N trimethylamine Chemical compound CN(C)C GETQZCLCWQTVFV-UHFFFAOYSA-N 0.000 description 2
- OUYCCCASQSFEME-UHFFFAOYSA-N tyrosine Natural products OC(=O)C(N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-UHFFFAOYSA-N 0.000 description 2
- 235000002374 tyrosine Nutrition 0.000 description 2
- 201000005112 urinary bladder cancer Diseases 0.000 description 2
- 239000004474 valine Substances 0.000 description 2
- 210000003556 vascular endothelial cell Anatomy 0.000 description 2
- 230000004862 vasculogenesis Effects 0.000 description 2
- 210000003462 vein Anatomy 0.000 description 2
- 238000005406 washing Methods 0.000 description 2
- RDEIXVOBVLKYNT-VQBXQJRRSA-N (2r,3r,4r,5r)-2-[(1s,2s,3r,4s,6r)-4,6-diamino-3-[(2r,3r,6s)-3-amino-6-(1-aminoethyl)oxan-2-yl]oxy-2-hydroxycyclohexyl]oxy-5-methyl-4-(methylamino)oxane-3,5-diol;(2r,3r,4r,5r)-2-[(1s,2s,3r,4s,6r)-4,6-diamino-3-[(2r,3r,6s)-3-amino-6-(aminomethyl)oxan-2-yl]o Chemical compound OS(O)(=O)=O.O1C[C@@](O)(C)[C@H](NC)[C@@H](O)[C@H]1O[C@@H]1[C@@H](O)[C@H](O[C@@H]2[C@@H](CC[C@@H](CN)O2)N)[C@@H](N)C[C@H]1N.O1C[C@@](O)(C)[C@H](NC)[C@@H](O)[C@H]1O[C@@H]1[C@@H](O)[C@H](O[C@@H]2[C@@H](CC[C@H](O2)C(C)N)N)[C@@H](N)C[C@H]1N.O1[C@H](C(C)NC)CC[C@@H](N)[C@H]1O[C@H]1[C@H](O)[C@@H](O[C@@H]2[C@@H]([C@@H](NC)[C@@](C)(O)CO2)O)[C@H](N)C[C@@H]1N RDEIXVOBVLKYNT-VQBXQJRRSA-N 0.000 description 1
- OIXLLKLZKCBCPS-RZVRUWJTSA-N (2s)-2-azanyl-5-[bis(azanyl)methylideneamino]pentanoic acid Chemical compound OC(=O)[C@@H](N)CCCNC(N)=N.OC(=O)[C@@H](N)CCCNC(N)=N OIXLLKLZKCBCPS-RZVRUWJTSA-N 0.000 description 1
- VEEGZPWAAPPXRB-BJMVGYQFSA-N (3e)-3-(1h-imidazol-5-ylmethylidene)-1h-indol-2-one Chemical compound O=C1NC2=CC=CC=C2\C1=C/C1=CN=CN1 VEEGZPWAAPPXRB-BJMVGYQFSA-N 0.000 description 1
- RGNVSYKVCGAEHK-GUBZILKMSA-N (3s)-3-[[2-[[(2s)-2-[(2-aminoacetyl)amino]-5-(diaminomethylideneamino)pentanoyl]amino]acetyl]amino]-4-[[(1s)-1-carboxy-2-hydroxyethyl]amino]-4-oxobutanoic acid Chemical compound NC(N)=NCCC[C@H](NC(=O)CN)C(=O)NCC(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CO)C(O)=O RGNVSYKVCGAEHK-GUBZILKMSA-N 0.000 description 1
- UKAUYVFTDYCKQA-UHFFFAOYSA-N -2-Amino-4-hydroxybutanoic acid Natural products OC(=O)C(N)CCO UKAUYVFTDYCKQA-UHFFFAOYSA-N 0.000 description 1
- WBYWAXJHAXSJNI-VOTSOKGWSA-M .beta-Phenylacrylic acid Natural products [O-]C(=O)\C=C\C1=CC=CC=C1 WBYWAXJHAXSJNI-VOTSOKGWSA-M 0.000 description 1
- DFPYXQYWILNVAU-UHFFFAOYSA-N 1-hydroxybenzotriazole Chemical compound C1=CC=C2N(O)N=NC2=C1.C1=CC=C2N(O)N=NC2=C1 DFPYXQYWILNVAU-UHFFFAOYSA-N 0.000 description 1
- UEJJHQNACJXSKW-UHFFFAOYSA-N 2-(2,6-dioxopiperidin-3-yl)-1H-isoindole-1,3(2H)-dione Chemical compound O=C1C2=CC=CC=C2C(=O)N1C1CCC(=O)NC1=O UEJJHQNACJXSKW-UHFFFAOYSA-N 0.000 description 1
- MIJDSYMOBYNHOT-UHFFFAOYSA-N 2-(ethylamino)ethanol Chemical compound CCNCCO MIJDSYMOBYNHOT-UHFFFAOYSA-N 0.000 description 1
- YYQUWEHEBOMRPH-NYUBLWNDSA-N 2-[(2s,5r,8s,11s)-5-benzyl-11-[3-(diaminomethylideneamino)propyl]-3,6,9,12,15-pentaoxo-8-propan-2-yl-1,4,7,10,13-pentazacyclopentadec-2-yl]acetic acid Chemical compound N1C(=O)[C@H](CC(O)=O)NC(=O)CNC(=O)[C@H](CCCN=C(N)N)NC(=O)[C@H](C(C)C)NC(=O)[C@H]1CC1=CC=CC=C1 YYQUWEHEBOMRPH-NYUBLWNDSA-N 0.000 description 1
- YVOOPGWEIRIUOX-UHFFFAOYSA-N 2-azanyl-3-sulfanyl-propanoic acid Chemical compound SCC(N)C(O)=O.SCC(N)C(O)=O YVOOPGWEIRIUOX-UHFFFAOYSA-N 0.000 description 1
- 238000005084 2D-nuclear magnetic resonance Methods 0.000 description 1
- BRMWTNUJHUMWMS-UHFFFAOYSA-N 3-Methylhistidine Natural products CN1C=NC(CC(N)C(O)=O)=C1 BRMWTNUJHUMWMS-UHFFFAOYSA-N 0.000 description 1
- BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 1
- 229940117976 5-hydroxylysine Drugs 0.000 description 1
- QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 description 1
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 1
- RVDVDRUZWZIBJQ-CIUDSAMLSA-N Arg-Asn-Glu Chemical compound [H]N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CCC(O)=O)C(O)=O RVDVDRUZWZIBJQ-CIUDSAMLSA-N 0.000 description 1
- SFJUYBCDQBAYAJ-YDHLFZDLSA-N Asp-Val-Phe Chemical compound OC(=O)C[C@H](N)C(=O)N[C@@H](C(C)C)C(=O)N[C@H](C(O)=O)CC1=CC=CC=C1 SFJUYBCDQBAYAJ-YDHLFZDLSA-N 0.000 description 1
- 208000037260 Atherosclerotic Plaque Diseases 0.000 description 1
- DWRXFEITVBNRMK-UHFFFAOYSA-N Beta-D-1-Arabinofuranosylthymine Natural products O=C1NC(=O)C(C)=CN1C1C(O)C(O)C(CO)O1 DWRXFEITVBNRMK-UHFFFAOYSA-N 0.000 description 1
- 101000645291 Bos taurus Metalloproteinase inhibitor 2 Proteins 0.000 description 1
- 206010007559 Cardiac failure congestive Diseases 0.000 description 1
- 241000499489 Castor canadensis Species 0.000 description 1
- 108010077544 Chromatin Proteins 0.000 description 1
- WBYWAXJHAXSJNI-SREVYHEPSA-N Cinnamic acid Chemical compound OC(=O)\C=C/C1=CC=CC=C1 WBYWAXJHAXSJNI-SREVYHEPSA-N 0.000 description 1
- QAQZXBKUPLZACV-UHFFFAOYSA-N Cl.OC(=O)C(F)(F)F.FC(C(=O)O)(F)F Chemical compound Cl.OC(=O)C(F)(F)F.FC(C(=O)O)(F)F QAQZXBKUPLZACV-UHFFFAOYSA-N 0.000 description 1
- 108010048623 Collagen Receptors Proteins 0.000 description 1
- 102000029816 Collagenase Human genes 0.000 description 1
- 108060005980 Collagenase Proteins 0.000 description 1
- 229940122097 Collagenase inhibitor Drugs 0.000 description 1
- XMVZMBGFIOQONW-GARJFASQSA-N Cys-Lys-Pro Chemical compound C1C[C@@H](N(C1)C(=O)[C@H](CCCCN)NC(=O)[C@H](CS)N)C(=O)O XMVZMBGFIOQONW-GARJFASQSA-N 0.000 description 1
- 239000006144 Dulbecco’s modified Eagle's medium Substances 0.000 description 1
- 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 1
- 238000012286 ELISA Assay Methods 0.000 description 1
- 102000010834 Extracellular Matrix Proteins Human genes 0.000 description 1
- 108010037362 Extracellular Matrix Proteins Proteins 0.000 description 1
- 102000009109 Fc receptors Human genes 0.000 description 1
- 108010087819 Fc receptors Proteins 0.000 description 1
- 108010012088 Fibrinogen Receptors Proteins 0.000 description 1
- 238000012413 Fluorescence activated cell sorting analysis Methods 0.000 description 1
- 241000233866 Fungi Species 0.000 description 1
- 230000010337 G2 phase Effects 0.000 description 1
- KSOBNUBCYHGUKH-UWVGGRQHSA-N Gly-Val-Val Chemical compound CC(C)[C@@H](C(O)=O)NC(=O)[C@H](C(C)C)NC(=O)CN KSOBNUBCYHGUKH-UWVGGRQHSA-N 0.000 description 1
- 102000003886 Glycoproteins Human genes 0.000 description 1
- 108090000288 Glycoproteins Proteins 0.000 description 1
- 206010019280 Heart failures Diseases 0.000 description 1
- 241000282412 Homo Species 0.000 description 1
- 101000669513 Homo sapiens Metalloproteinase inhibitor 1 Proteins 0.000 description 1
- PMMYEEVYMWASQN-DMTCNVIQSA-N Hydroxyproline Chemical compound O[C@H]1CN[C@H](C(O)=O)C1 PMMYEEVYMWASQN-DMTCNVIQSA-N 0.000 description 1
- 206010051151 Hyperviscosity syndrome Diseases 0.000 description 1
- 102100025305 Integrin alpha-2 Human genes 0.000 description 1
- 108010042918 Integrin alpha5beta1 Proteins 0.000 description 1
- XUJNEKJLAYXESH-REOHCLBHSA-N L-Cysteine Chemical compound SC[C@H](N)C(O)=O XUJNEKJLAYXESH-REOHCLBHSA-N 0.000 description 1
- QNAYBMKLOCPYGJ-REOHCLBHSA-N L-alanine Chemical compound C[C@H](N)C(O)=O QNAYBMKLOCPYGJ-REOHCLBHSA-N 0.000 description 1
- 229930182816 L-glutamine Natural products 0.000 description 1
- UKAUYVFTDYCKQA-VKHMYHEASA-N L-homoserine Chemical compound OC(=O)[C@@H](N)CCO UKAUYVFTDYCKQA-VKHMYHEASA-N 0.000 description 1
- COLNVLDHVKWLRT-QMMMGPOBSA-N L-phenylalanine Chemical compound OC(=O)[C@@H](N)CC1=CC=CC=C1 COLNVLDHVKWLRT-QMMMGPOBSA-N 0.000 description 1
- QIVBCDIJIAJPQS-VIFPVBQESA-N L-tryptophane Chemical compound C1=CC=C2C(C[C@H](N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-VIFPVBQESA-N 0.000 description 1
- 238000011050 LAL assay Methods 0.000 description 1
- 102000002297 Laminin Receptors Human genes 0.000 description 1
- 206010023825 Laryngeal cancer Diseases 0.000 description 1
- LJHGALIOHLRRQN-DCAQKATOSA-N Leu-Ala-Arg Chemical compound CC(C)C[C@H](N)C(=O)N[C@@H](C)C(=O)N[C@H](C(O)=O)CCCN=C(N)N LJHGALIOHLRRQN-DCAQKATOSA-N 0.000 description 1
- FMEICTQWUKNAGC-YUMQZZPRSA-N Leu-Gly-Asn Chemical compound [H]N[C@@H](CC(C)C)C(=O)NCC(=O)N[C@@H](CC(N)=O)C(O)=O FMEICTQWUKNAGC-YUMQZZPRSA-N 0.000 description 1
- 235000011779 Menyanthes trifoliata Nutrition 0.000 description 1
- LSDPWZHWYPCBBB-UHFFFAOYSA-N Methanethiol Chemical compound SC LSDPWZHWYPCBBB-UHFFFAOYSA-N 0.000 description 1
- 241001529936 Murinae Species 0.000 description 1
- JDHILDINMRGULE-LURJTMIESA-N N(pros)-methyl-L-histidine Chemical compound CN1C=NC=C1C[C@H](N)C(O)=O JDHILDINMRGULE-LURJTMIESA-N 0.000 description 1
- 238000005481 NMR spectroscopy Methods 0.000 description 1
- 206010028813 Nausea Diseases 0.000 description 1
- 206010028851 Necrosis Diseases 0.000 description 1
- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 1
- 108010081689 Osteopontin Proteins 0.000 description 1
- 102000004264 Osteopontin Human genes 0.000 description 1
- 208000001132 Osteoporosis Diseases 0.000 description 1
- 108090000526 Papain Proteins 0.000 description 1
- 229930040373 Paraformaldehyde Natural products 0.000 description 1
- 102000057297 Pepsin A Human genes 0.000 description 1
- 108090000284 Pepsin A Proteins 0.000 description 1
- 229940083963 Peptide antagonist Drugs 0.000 description 1
- 102000004211 Platelet factor 4 Human genes 0.000 description 1
- 108090000778 Platelet factor 4 Proteins 0.000 description 1
- 241000276498 Pollachius virens Species 0.000 description 1
- 229920002535 Polyethylene Glycol 1500 Polymers 0.000 description 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
- 239000004365 Protease Substances 0.000 description 1
- 201000004681 Psoriasis Diseases 0.000 description 1
- 206010037423 Pulmonary oedema Diseases 0.000 description 1
- 239000012980 RPMI-1640 medium Substances 0.000 description 1
- 108020004511 Recombinant DNA Proteins 0.000 description 1
- 208000007135 Retinal Neovascularization Diseases 0.000 description 1
- 206010038933 Retinopathy of prematurity Diseases 0.000 description 1
- 102000006382 Ribonucleases Human genes 0.000 description 1
- 108010083644 Ribonucleases Proteins 0.000 description 1
- 206010039491 Sarcoma Diseases 0.000 description 1
- 208000000453 Skin Neoplasms Diseases 0.000 description 1
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 1
- KDYFGRWQOYBRFD-UHFFFAOYSA-N Succinic acid Natural products OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 description 1
- FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric Acid Chemical compound [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 1
- 239000004809 Teflon Substances 0.000 description 1
- 229920006362 Teflon® Polymers 0.000 description 1
- HYLXOQURIOCKIH-VQVTYTSYSA-N Thr-Arg Chemical compound C[C@@H](O)[C@H](N)C(=O)N[C@H](C(O)=O)CCCNC(N)=N HYLXOQURIOCKIH-VQVTYTSYSA-N 0.000 description 1
- AYFVYJQAPQTCCC-UHFFFAOYSA-N Threonine Natural products CC(O)C(N)C(O)=O AYFVYJQAPQTCCC-UHFFFAOYSA-N 0.000 description 1
- 239000004473 Threonine Substances 0.000 description 1
- QIVBCDIJIAJPQS-UHFFFAOYSA-N Tryptophan Natural products C1=CC=C2C(CC(N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-UHFFFAOYSA-N 0.000 description 1
- XUIOBCQESNDTDE-FQPOAREZSA-N Tyr-Thr-Ala Chemical compound C[C@H]([C@@H](C(=O)N[C@@H](C)C(=O)O)NC(=O)[C@H](CC1=CC=C(C=C1)O)N)O XUIOBCQESNDTDE-FQPOAREZSA-N 0.000 description 1
- MNSSBIHFEUUXNW-RCWTZXSCSA-N Val-Thr-Arg Chemical compound CC(C)[C@H](N)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@H](C(O)=O)CCCN=C(N)N MNSSBIHFEUUXNW-RCWTZXSCSA-N 0.000 description 1
- ZHWZDZFWBXWPDW-GUBZILKMSA-N Val-Val-Cys Chemical compound CC(C)[C@H](N)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CS)C(O)=O ZHWZDZFWBXWPDW-GUBZILKMSA-N 0.000 description 1
- 108010019530 Vascular Endothelial Growth Factors Proteins 0.000 description 1
- 102000005789 Vascular Endothelial Growth Factors Human genes 0.000 description 1
- JOOSFXXMIOXKAZ-UHFFFAOYSA-H [Au+3].[Au+3].[O-]C(=O)CC(S)C([O-])=O.[O-]C(=O)CC(S)C([O-])=O.[O-]C(=O)CC(S)C([O-])=O Chemical compound [Au+3].[Au+3].[O-]C(=O)CC(S)C([O-])=O.[O-]C(=O)CC(S)C([O-])=O.[O-]C(=O)CC(S)C([O-])=O JOOSFXXMIOXKAZ-UHFFFAOYSA-H 0.000 description 1
- GELXFVQAWNTGPQ-UHFFFAOYSA-N [N].C1=CNC=N1 Chemical compound [N].C1=CNC=N1 GELXFVQAWNTGPQ-UHFFFAOYSA-N 0.000 description 1
- 230000003187 abdominal effect Effects 0.000 description 1
- 230000021736 acetylation Effects 0.000 description 1
- 238000006640 acetylation reaction Methods 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 239000012190 activator Substances 0.000 description 1
- 239000013543 active substance Substances 0.000 description 1
- 230000010933 acylation Effects 0.000 description 1
- 238000005917 acylation reaction Methods 0.000 description 1
- 230000000996 additive effect Effects 0.000 description 1
- 102000019997 adhesion receptor Human genes 0.000 description 1
- 108010013985 adhesion receptor Proteins 0.000 description 1
- 239000000853 adhesive Substances 0.000 description 1
- 230000001070 adhesive effect Effects 0.000 description 1
- 238000001042 affinity chromatography Methods 0.000 description 1
- 210000004712 air sac Anatomy 0.000 description 1
- 235000004279 alanine Nutrition 0.000 description 1
- 108010005233 alanylglutamic acid Proteins 0.000 description 1
- 230000029936 alkylation Effects 0.000 description 1
- 238000005804 alkylation reaction Methods 0.000 description 1
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
- 230000001668 ameliorated effect Effects 0.000 description 1
- 230000009435 amidation Effects 0.000 description 1
- 238000007112 amidation reaction Methods 0.000 description 1
- 150000001412 amines Chemical group 0.000 description 1
- 150000003862 amino acid derivatives Chemical class 0.000 description 1
- 229960003896 aminopterin Drugs 0.000 description 1
- 229910021529 ammonia Inorganic materials 0.000 description 1
- 239000000908 ammonium hydroxide Substances 0.000 description 1
- 239000002870 angiogenesis inducing agent Substances 0.000 description 1
- 230000000964 angiostatic effect Effects 0.000 description 1
- 230000001772 anti-angiogenic effect Effects 0.000 description 1
- 210000000628 antibody-producing cell Anatomy 0.000 description 1
- 210000000709 aorta Anatomy 0.000 description 1
- 238000003782 apoptosis assay Methods 0.000 description 1
- 239000008365 aqueous carrier Substances 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 239000003125 aqueous solvent Substances 0.000 description 1
- 108010091818 arginyl-glycyl-aspartyl-valine Proteins 0.000 description 1
- 150000004982 aromatic amines Chemical class 0.000 description 1
- 108010077245 asparaginyl-proline Proteins 0.000 description 1
- 210000000270 basal cell Anatomy 0.000 description 1
- 239000011324 bead Substances 0.000 description 1
- IQFYYKKMVGJFEH-UHFFFAOYSA-N beta-L-thymidine Natural products O=C1NC(=O)C(C)=CN1C1OC(CO)C(O)C1 IQFYYKKMVGJFEH-UHFFFAOYSA-N 0.000 description 1
- 239000013060 biological fluid Substances 0.000 description 1
- 230000033228 biological regulation Effects 0.000 description 1
- 230000036770 blood supply Effects 0.000 description 1
- 230000015624 blood vessel development Effects 0.000 description 1
- 230000037396 body weight Effects 0.000 description 1
- 210000000988 bone and bone Anatomy 0.000 description 1
- 201000009378 breast hemangioma Diseases 0.000 description 1
- 239000000337 buffer salt Substances 0.000 description 1
- KDYFGRWQOYBRFD-NUQCWPJISA-N butanedioic acid Chemical compound O[14C](=O)CC[14C](O)=O KDYFGRWQOYBRFD-NUQCWPJISA-N 0.000 description 1
- 239000006227 byproduct Substances 0.000 description 1
- 229940087373 calcium oxide Drugs 0.000 description 1
- 230000036952 cancer formation Effects 0.000 description 1
- 150000007942 carboxylates Chemical group 0.000 description 1
- 230000034303 cell budding Effects 0.000 description 1
- 238000004113 cell culture Methods 0.000 description 1
- 239000013592 cell lysate Substances 0.000 description 1
- 230000008614 cellular interaction Effects 0.000 description 1
- 230000006364 cellular survival Effects 0.000 description 1
- 238000009104 chemotherapy regimen Methods 0.000 description 1
- 210000003837 chick embryo Anatomy 0.000 description 1
- 125000002668 chloroacetyl group Chemical group ClCC(=O)* 0.000 description 1
- 210000003483 chromatin Anatomy 0.000 description 1
- 230000010428 chromatin condensation Effects 0.000 description 1
- 239000013611 chromosomal DNA Substances 0.000 description 1
- 235000013985 cinnamic acid Nutrition 0.000 description 1
- 229930016911 cinnamic acid Natural products 0.000 description 1
- 239000011248 coating agent Substances 0.000 description 1
- 238000000576 coating method Methods 0.000 description 1
- 229960002424 collagenase Drugs 0.000 description 1
- 239000002442 collagenase inhibitor Substances 0.000 description 1
- 238000012875 competitive assay Methods 0.000 description 1
- 238000009833 condensation Methods 0.000 description 1
- 230000005494 condensation Effects 0.000 description 1
- 238000011254 conventional chemotherapy Methods 0.000 description 1
- 210000004246 corpus luteum Anatomy 0.000 description 1
- 239000006184 cosolvent Substances 0.000 description 1
- 235000012343 cottonseed oil Nutrition 0.000 description 1
- 239000002385 cottonseed oil 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
- WZHCOOQXZCIUNC-UHFFFAOYSA-N cyclandelate Chemical compound C1C(C)(C)CC(C)CC1OC(=O)C(O)C1=CC=CC=C1 WZHCOOQXZCIUNC-UHFFFAOYSA-N 0.000 description 1
- 108010083321 cyclic(arginyl-alanyl-aspartyl-phenylalanyl-valyl) Proteins 0.000 description 1
- 230000001351 cycling effect Effects 0.000 description 1
- XUJNEKJLAYXESH-UHFFFAOYSA-N cysteine Natural products SCC(N)C(O)=O XUJNEKJLAYXESH-UHFFFAOYSA-N 0.000 description 1
- 235000018417 cysteine Nutrition 0.000 description 1
- 230000009089 cytolysis Effects 0.000 description 1
- 238000004163 cytometry Methods 0.000 description 1
- 230000006378 damage Effects 0.000 description 1
- 230000034994 death Effects 0.000 description 1
- 238000002716 delivery method Methods 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
- 210000004207 dermis Anatomy 0.000 description 1
- 238000013461 design Methods 0.000 description 1
- 230000006866 deterioration Effects 0.000 description 1
- ZBCBWPMODOFKDW-UHFFFAOYSA-N diethanolamine Chemical compound OCCNCCO ZBCBWPMODOFKDW-UHFFFAOYSA-N 0.000 description 1
- 229940043279 diisopropylamine Drugs 0.000 description 1
- 238000007865 diluting Methods 0.000 description 1
- UXGNZZKBCMGWAZ-UHFFFAOYSA-N dimethylformamide dmf Chemical compound CN(C)C=O.CN(C)C=O UXGNZZKBCMGWAZ-UHFFFAOYSA-N 0.000 description 1
- 208000002173 dizziness Diseases 0.000 description 1
- PMMYEEVYMWASQN-UHFFFAOYSA-N dl-hydroxyproline Natural products OC1C[NH2+]C(C([O-])=O)C1 PMMYEEVYMWASQN-UHFFFAOYSA-N 0.000 description 1
- 238000004043 dyeing Methods 0.000 description 1
- 238000001962 electrophoresis Methods 0.000 description 1
- 239000003995 emulsifying agent Substances 0.000 description 1
- 230000010595 endothelial cell migration Effects 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
- 150000002169 ethanolamines Chemical class 0.000 description 1
- ZMMJGEGLRURXTF-UHFFFAOYSA-N ethidium bromide Chemical compound [Br-].C12=CC(N)=CC=C2C2=CC=C(N)C=C2[N+](CC)=C1C1=CC=CC=C1 ZMMJGEGLRURXTF-UHFFFAOYSA-N 0.000 description 1
- 229960005542 ethidium bromide Drugs 0.000 description 1
- 125000004494 ethyl ester group Chemical group 0.000 description 1
- DNJIEGIFACGWOD-UHFFFAOYSA-N ethyl mercaptane Natural products CCS DNJIEGIFACGWOD-UHFFFAOYSA-N 0.000 description 1
- 210000003195 fascia Anatomy 0.000 description 1
- 229960004887 ferric hydroxide Drugs 0.000 description 1
- 210000002950 fibroblast Anatomy 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 125000002485 formyl group Chemical group [H]C(*)=O 0.000 description 1
- 239000001530 fumaric acid Substances 0.000 description 1
- 230000004927 fusion Effects 0.000 description 1
- 230000002496 gastric effect Effects 0.000 description 1
- 239000000499 gel Substances 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- 108010049041 glutamylalanine Proteins 0.000 description 1
- 108010034892 glycyl-arginyl-glycyl-aspartyl-serine Proteins 0.000 description 1
- 238000005469 granulation Methods 0.000 description 1
- 230000003179 granulation Effects 0.000 description 1
- 238000000227 grinding Methods 0.000 description 1
- 230000009036 growth inhibition Effects 0.000 description 1
- 230000009931 harmful effect Effects 0.000 description 1
- 230000035876 healing Effects 0.000 description 1
- 230000002008 hemorrhagic effect Effects 0.000 description 1
- 230000003054 hormonal effect Effects 0.000 description 1
- 229940042795 hydrazides for tuberculosis treatment Drugs 0.000 description 1
- 230000007062 hydrolysis Effects 0.000 description 1
- 238000006460 hydrolysis reaction Methods 0.000 description 1
- 230000002209 hydrophobic effect Effects 0.000 description 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 1
- NPZTUJOABDZTLV-UHFFFAOYSA-N hydroxybenzotriazole Substances O=C1C=CC=C2NNN=C12 NPZTUJOABDZTLV-UHFFFAOYSA-N 0.000 description 1
- 229960002591 hydroxyproline Drugs 0.000 description 1
- 238000003384 imaging method Methods 0.000 description 1
- 230000001900 immune effect Effects 0.000 description 1
- 238000002649 immunization Methods 0.000 description 1
- 230000003053 immunization Effects 0.000 description 1
- 230000002163 immunogen Effects 0.000 description 1
- 238000002991 immunohistochemical analysis Methods 0.000 description 1
- 238000011532 immunohistochemical staining Methods 0.000 description 1
- 238000005462 in vivo assay Methods 0.000 description 1
- 238000011065 in-situ storage Methods 0.000 description 1
- 238000011081 inoculation Methods 0.000 description 1
- 238000003780 insertion Methods 0.000 description 1
- 230000037431 insertion Effects 0.000 description 1
- 210000000936 intestine Anatomy 0.000 description 1
- 230000009545 invasion Effects 0.000 description 1
- 238000011835 investigation Methods 0.000 description 1
- PGLTVOMIXTUURA-UHFFFAOYSA-N iodoacetamide Chemical compound NC(=O)CI PGLTVOMIXTUURA-UHFFFAOYSA-N 0.000 description 1
- 150000002500 ions Chemical class 0.000 description 1
- IEECXTSVVFWGSE-UHFFFAOYSA-M iron(3+);oxygen(2-);hydroxide Chemical compound [OH-].[O-2].[Fe+3] IEECXTSVVFWGSE-UHFFFAOYSA-M 0.000 description 1
- JJWLVOIRVHMVIS-UHFFFAOYSA-N isopropylamine Chemical compound CC(C)N JJWLVOIRVHMVIS-UHFFFAOYSA-N 0.000 description 1
- 210000001503 joint Anatomy 0.000 description 1
- 239000004310 lactic acid Substances 0.000 description 1
- 235000014655 lactic acid Nutrition 0.000 description 1
- 108010034897 lentil lectin Proteins 0.000 description 1
- 230000003902 lesion Effects 0.000 description 1
- 230000000670 limiting effect Effects 0.000 description 1
- 150000002632 lipids Chemical class 0.000 description 1
- 239000006193 liquid solution Substances 0.000 description 1
- 239000006194 liquid suspension Substances 0.000 description 1
- 230000004807 localization Effects 0.000 description 1
- 231100000053 low toxicity Toxicity 0.000 description 1
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
- 239000011976 maleic acid Substances 0.000 description 1
- 230000001394 metastastic effect Effects 0.000 description 1
- 208000037819 metastatic cancer Diseases 0.000 description 1
- 208000011575 metastatic malignant neoplasm Diseases 0.000 description 1
- 206010061289 metastatic neoplasm Diseases 0.000 description 1
- 150000004702 methyl esters Chemical class 0.000 description 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
- WBYWAXJHAXSJNI-UHFFFAOYSA-N methyl p-hydroxycinnamate Natural products OC(=O)C=CC1=CC=CC=C1 WBYWAXJHAXSJNI-UHFFFAOYSA-N 0.000 description 1
- 238000007431 microscopic evaluation Methods 0.000 description 1
- 238000000386 microscopy Methods 0.000 description 1
- 210000004925 microvascular endothelial cell Anatomy 0.000 description 1
- 230000003278 mimic effect Effects 0.000 description 1
- 239000002480 mineral oil Substances 0.000 description 1
- 235000010446 mineral oil Nutrition 0.000 description 1
- 239000007758 minimum essential medium Substances 0.000 description 1
- 108091005601 modified peptides Proteins 0.000 description 1
- 238000000302 molecular modelling Methods 0.000 description 1
- 230000021332 multicellular organism growth Effects 0.000 description 1
- 210000003205 muscle Anatomy 0.000 description 1
- PSZYNBSKGUBXEH-UHFFFAOYSA-N naphthalene-1-sulfonic acid Chemical compound C1=CC=C2C(S(=O)(=O)O)=CC=CC2=C1 PSZYNBSKGUBXEH-UHFFFAOYSA-N 0.000 description 1
- 210000001989 nasopharynx Anatomy 0.000 description 1
- 230000008693 nausea Effects 0.000 description 1
- 230000017074 necrotic cell death Effects 0.000 description 1
- 230000001338 necrotic effect Effects 0.000 description 1
- 239000013642 negative control Substances 0.000 description 1
- 230000006654 negative regulation of apoptotic process Effects 0.000 description 1
- 230000009826 neoplastic cell growth Effects 0.000 description 1
- 230000003472 neutralizing effect Effects 0.000 description 1
- 229910017604 nitric acid Inorganic materials 0.000 description 1
- 231100000957 no side effect Toxicity 0.000 description 1
- 231100000252 nontoxic Toxicity 0.000 description 1
- 230000003000 nontoxic effect Effects 0.000 description 1
- 238000012758 nuclear staining Methods 0.000 description 1
- 210000000056 organ Anatomy 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 235000005985 organic acids Nutrition 0.000 description 1
- 235000006408 oxalic acid Nutrition 0.000 description 1
- 239000006179 pH buffering agent Substances 0.000 description 1
- 229940055729 papain Drugs 0.000 description 1
- 235000019834 papain Nutrition 0.000 description 1
- 239000012188 paraffin wax Substances 0.000 description 1
- 229920002866 paraformaldehyde Polymers 0.000 description 1
- 230000008506 pathogenesis Effects 0.000 description 1
- 230000007170 pathology Effects 0.000 description 1
- 230000037361 pathway Effects 0.000 description 1
- 229940111202 pepsin Drugs 0.000 description 1
- 230000002093 peripheral effect Effects 0.000 description 1
- 230000002572 peristaltic effect Effects 0.000 description 1
- 239000008194 pharmaceutical composition Substances 0.000 description 1
- COLNVLDHVKWLRT-UHFFFAOYSA-N phenylalanine Natural products OC(=O)C(N)CC1=CC=CC=C1 COLNVLDHVKWLRT-UHFFFAOYSA-N 0.000 description 1
- RGCLLPNLLBQHPF-HJWRWDBZSA-N phosphamidon Chemical compound CCN(CC)C(=O)C(\Cl)=C(/C)OP(=O)(OC)OC RGCLLPNLLBQHPF-HJWRWDBZSA-N 0.000 description 1
- 230000001766 physiological effect Effects 0.000 description 1
- 239000002504 physiological saline solution Substances 0.000 description 1
- 230000026341 positive regulation of angiogenesis Effects 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 239000001103 potassium chloride Substances 0.000 description 1
- 235000011164 potassium chloride Nutrition 0.000 description 1
- 244000144977 poultry Species 0.000 description 1
- 239000002243 precursor Substances 0.000 description 1
- MFDFERRIHVXMIY-UHFFFAOYSA-N procaine Chemical compound CCN(CC)CCOC(=O)C1=CC=C(N)C=C1 MFDFERRIHVXMIY-UHFFFAOYSA-N 0.000 description 1
- 229960004919 procaine Drugs 0.000 description 1
- 238000012545 processing Methods 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 230000005522 programmed cell death Effects 0.000 description 1
- 230000002035 prolonged effect Effects 0.000 description 1
- 238000011321 prophylaxis Methods 0.000 description 1
- 235000019260 propionic acid Nutrition 0.000 description 1
- 238000000159 protein binding assay Methods 0.000 description 1
- 230000002797 proteolythic effect Effects 0.000 description 1
- 230000001185 psoriatic effect Effects 0.000 description 1
- 208000005333 pulmonary edema Diseases 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 238000004445 quantitative analysis Methods 0.000 description 1
- IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical compound O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 0.000 description 1
- 230000005855 radiation Effects 0.000 description 1
- 230000009257 reactivity Effects 0.000 description 1
- 239000012925 reference material Substances 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 239000011347 resin Substances 0.000 description 1
- 229920005989 resin Polymers 0.000 description 1
- 238000007423 screening assay Methods 0.000 description 1
- 238000012163 sequencing technique Methods 0.000 description 1
- 210000002966 serum Anatomy 0.000 description 1
- 230000019491 signal transduction Effects 0.000 description 1
- 201000000849 skin cancer Diseases 0.000 description 1
- 150000003384 small molecules Chemical class 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000001488 sodium phosphate Substances 0.000 description 1
- 229910000162 sodium phosphate Inorganic materials 0.000 description 1
- 229910052938 sodium sulfate Inorganic materials 0.000 description 1
- 235000011152 sodium sulphate Nutrition 0.000 description 1
- 210000000952 spleen Anatomy 0.000 description 1
- 210000004988 splenocyte Anatomy 0.000 description 1
- 150000003431 steroids Chemical class 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 210000002536 stromal cell Anatomy 0.000 description 1
- 238000012916 structural analysis Methods 0.000 description 1
- 229950000244 sulfanilic acid Drugs 0.000 description 1
- 239000006228 supernatant Substances 0.000 description 1
- 230000008093 supporting effect Effects 0.000 description 1
- 238000004114 suspension culture Methods 0.000 description 1
- 238000010998 test method Methods 0.000 description 1
- 239000004753 textile Substances 0.000 description 1
- 229960003433 thalidomide Drugs 0.000 description 1
- 238000011285 therapeutic regimen Methods 0.000 description 1
- 229940104230 thymidine Drugs 0.000 description 1
- 238000011200 topical administration Methods 0.000 description 1
- 230000000472 traumatic effect Effects 0.000 description 1
- 125000005270 trialkylamine group Chemical group 0.000 description 1
- 239000003656 tris buffered saline Substances 0.000 description 1
- RYFMWSXOAZQYPI-UHFFFAOYSA-K trisodium phosphate Chemical compound [Na+].[Na+].[Na+].[O-]P([O-])([O-])=O RYFMWSXOAZQYPI-UHFFFAOYSA-K 0.000 description 1
- 230000005740 tumor formation Effects 0.000 description 1
- 230000005760 tumorsuppression Effects 0.000 description 1
- 210000003932 urinary bladder Anatomy 0.000 description 1
- IBIDRSSEHFLGSD-UHFFFAOYSA-N valinyl-arginine Natural products CC(C)C(N)C(=O)NC(C(O)=O)CCCN=C(N)N IBIDRSSEHFLGSD-UHFFFAOYSA-N 0.000 description 1
- 230000006459 vascular development Effects 0.000 description 1
- 230000009790 vascular invasion Effects 0.000 description 1
- 235000015112 vegetable and seed oil Nutrition 0.000 description 1
- 239000008158 vegetable oil Substances 0.000 description 1
- 239000003981 vehicle Substances 0.000 description 1
- 230000000007 visual effect Effects 0.000 description 1
- 238000012800 visualization Methods 0.000 description 1
- QYSXJUFSXHHAJI-YRZJJWOYSA-N vitamin D3 Chemical class C1(/[C@@H]2CC[C@@H]([C@]2(CCC1)C)[C@H](C)CCCC(C)C)=C\C=C1\C[C@@H](O)CCC1=C QYSXJUFSXHHAJI-YRZJJWOYSA-N 0.000 description 1
- 238000003260 vortexing Methods 0.000 description 1
- 239000002569 water oil cream Substances 0.000 description 1
- 230000003442 weekly effect Effects 0.000 description 1
- 238000005303 weighing Methods 0.000 description 1
- 238000009736 wetting Methods 0.000 description 1
- 239000000080 wetting agent Substances 0.000 description 1
- 238000002424 x-ray crystallography Methods 0.000 description 1
- DGVVWUTYPXICAM-UHFFFAOYSA-N β‐Mercaptoethanol Chemical compound OCCS DGVVWUTYPXICAM-UHFFFAOYSA-N 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- C07K14/78—Connective tissue peptides, e.g. collagen, elastin, laminin, fibronectin, vitronectin or cold insoluble globulin [CIG]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K39/395—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/02—Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P27/00—Drugs for disorders of the senses
- A61P27/02—Ophthalmic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
- A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
- A61P35/04—Antineoplastic agents specific for metastasis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- 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
- A61P9/08—Vasodilators for multiple indications
-
- 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
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
-
- 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
- A61P9/14—Vasoprotectives; Antihaemorrhoidals; Drugs for varicose therapy; Capillary stabilisers
-
- 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
- C07K14/705—Receptors; Cell surface antigens; Cell surface determinants
- C07K14/70546—Integrin superfamily
- C07K14/70557—Integrin beta3-subunit-containing molecules, e.g. CD41, CD51, CD61
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
-
- 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
-
- 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
- C07K16/28—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
-
- 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
- C07K16/28—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
- C07K16/2839—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against the integrin superfamily
- C07K16/2848—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against the integrin superfamily against integrin beta3-subunit-containing molecules, e.g. CD41, CD51, CD61
-
- 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
- C07K16/28—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
- C07K16/30—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants from tumour cells
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K2039/505—Medicinal preparations containing antigens or antibodies comprising antibodies
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- Medicinal Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Immunology (AREA)
- Animal Behavior & Ethology (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Pharmacology & Pharmacy (AREA)
- Molecular Biology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Biochemistry (AREA)
- Biophysics (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Engineering & Computer Science (AREA)
- Genetics & Genomics (AREA)
- Heart & Thoracic Surgery (AREA)
- Toxicology (AREA)
- Gastroenterology & Hepatology (AREA)
- Zoology (AREA)
- Cell Biology (AREA)
- Cardiology (AREA)
- Diabetes (AREA)
- Vascular Medicine (AREA)
- Rheumatology (AREA)
- Obesity (AREA)
- Mycology (AREA)
- Ophthalmology & Optometry (AREA)
- Urology & Nephrology (AREA)
- Oncology (AREA)
- Hematology (AREA)
- Endocrinology (AREA)
- Emergency Medicine (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Physical Education & Sports Medicine (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US08/210,715 US5753230A (en) | 1994-03-18 | 1994-03-18 | Methods and compositions useful for inhibition of angiogenesis |
| US08/366,665 US5766591A (en) | 1994-03-18 | 1994-12-30 | Methods and compositions useful for inhibition of angiogenesis |
| PCT/US1995/003035 WO1995025543A1 (en) | 1994-03-18 | 1995-03-09 | Methods and compositions useful for inhibition of angiogenesis |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| SK119096A3 SK119096A3 (en) | 1997-07-09 |
| SK284586B6 true SK284586B6 (sk) | 2005-07-01 |
Family
ID=22783992
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| SK1190-96A SK284586B6 (sk) | 1994-03-18 | 1995-03-09 | Použitie alfa_v_beta3 antagonistu na prípravu liečiva |
Country Status (25)
| Country | Link |
|---|---|
| US (7) | US5753230A (uk) |
| EP (3) | EP1468695B1 (uk) |
| JP (2) | JP4268222B2 (uk) |
| KR (1) | KR100327081B1 (uk) |
| CN (1) | CN1161152C (uk) |
| AT (3) | ATE534403T1 (uk) |
| AU (1) | AU709645B2 (uk) |
| CA (1) | CA2184493C (uk) |
| CZ (1) | CZ294650B6 (uk) |
| DE (2) | DE69536128D1 (uk) |
| DK (3) | DK1410807T3 (uk) |
| ES (3) | ES2355074T3 (uk) |
| FI (1) | FI121916B (uk) |
| HK (1) | HK1013960A1 (uk) |
| HU (1) | HU221988B1 (uk) |
| MX (1) | MX9604145A (uk) |
| NO (1) | NO322441B1 (uk) |
| NZ (3) | NZ511293A (uk) |
| PT (2) | PT1468695E (uk) |
| RU (1) | RU2162712C2 (uk) |
| SI (1) | SI0754059T2 (uk) |
| SK (1) | SK284586B6 (uk) |
| UA (1) | UA44729C2 (uk) |
| WO (1) | WO1995025543A1 (uk) |
| ZA (1) | ZA952214B (uk) |
Families Citing this family (176)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE4310643A1 (de) * | 1993-04-01 | 1994-10-06 | Merck Patent Gmbh | Cyclische Adhäsionsinhibitoren |
| US5753230A (en) * | 1994-03-18 | 1998-05-19 | The Scripps Research Institute | Methods and compositions useful for inhibition of angiogenesis |
| US5945403A (en) * | 1997-05-30 | 1999-08-31 | The Children's Medical Center Corporation | Angiostatin fragments and method of use |
| US5837682A (en) | 1996-03-08 | 1998-11-17 | The Children's Medical Center Corporation | Angiostatin fragments and method of use |
| US6949511B1 (en) | 1994-04-26 | 2005-09-27 | The Children's Medical Center Corporation | Methods of inhibiting angiogenesis via increasing in vivo concentrations of kringle region fragments of plasminogen |
| US6660842B1 (en) | 1994-04-28 | 2003-12-09 | Tripep Ab | Ligand/receptor specificity exchangers that redirect antibodies to receptors on a pathogen |
| DK0719859T3 (da) * | 1994-12-20 | 2003-10-20 | Merck Patent Gmbh | Anti-alfa V-integrin monoklonalt antistof |
| US6358735B1 (en) | 1995-06-30 | 2002-03-19 | University Of Kansas Medical Center | Method for inhibiting angiogenesis and tumors with the isolated NC1 α3 chain monomer of type IV collagen |
| US6440729B1 (en) * | 1995-06-30 | 2002-08-27 | University Of Kansas Medical Center | Treating angiogenesis-mediated diseases with the α2 monomer of type IV collagen |
| CA2754102C (en) * | 1995-08-14 | 2012-12-18 | The Scripps Research Institute | Monoclonal antibodies and compositions comprising such useful for inhibition of .alpha.v.beta.5 mediated angiogenesis |
| US6100423A (en) * | 1995-08-30 | 2000-08-08 | G. D. Searle & Co. | Amino benzenepropanoic acid compounds and derivatives thereof |
| ES2161373T3 (es) | 1995-08-30 | 2001-12-01 | Searle & Co | Derivados de meta-guanidina, urea, tiourea o acido azaciclico-aminobenzoico como antagonistas de integrinas. |
| US6346510B1 (en) | 1995-10-23 | 2002-02-12 | The Children's Medical Center Corporation | Therapeutic antiangiogenic endostatin compositions |
| US5854205A (en) * | 1995-10-23 | 1998-12-29 | The Children's Medical Center Corporation | Therapeutic antiangiogenic compositions and methods |
| JP3840262B2 (ja) | 1995-10-23 | 2006-11-01 | ザ チルドレンズ メディカル センター コーポレイション | 治療用の抗血管新生組成物および方法 |
| US5854221A (en) * | 1996-12-12 | 1998-12-29 | The Children's Medical Center Corporation | Endothelial cell proliferation inhibitor and method of use |
| DE69727582T2 (de) * | 1996-08-15 | 2004-12-23 | Novartis Ag | Test zur quantifizierung von arthritiszustanden |
| GB9708265D0 (en) * | 1997-04-24 | 1997-06-18 | Nycomed Imaging As | Contrast agents |
| DE69739295D1 (de) * | 1996-12-09 | 2009-04-23 | Merck Patent Gmbh | Löslicher, rekombinanter alphaV beta3 Adhäsionsrezeptor |
| US6590079B2 (en) | 1997-01-30 | 2003-07-08 | Ixsys, Incorporated | Anti-αvβ3 recombinant human antibodies, nucleic acids encoding same |
| US6596850B1 (en) | 1998-01-30 | 2003-07-22 | Ixsys, Incorporated | Anti-αv3β3 recombinant human antibodies, nucleic acids encoding same |
| EP0968290B1 (en) * | 1997-03-12 | 2004-12-15 | SmithKline Beecham Corporation | Anti-alphavbeta3 humanized monoclonal antibodies |
| US7112338B2 (en) | 1997-03-12 | 2006-09-26 | The Regents Of The University Of California | Cationic liposome delivery of taxanes to angiogenic blood vessels |
| US5837283A (en) | 1997-03-12 | 1998-11-17 | The Regents Of The University Of California | Cationic lipid compositions targeting angiogenic endothelial cells |
| US5994388A (en) * | 1997-03-18 | 1999-11-30 | The Children's Medical Center Corporation | Cytochalasin and isoindolinone derivatives as inhibitors of angiogenesis |
| WO1998041158A1 (en) * | 1997-03-19 | 1998-09-24 | Lucid Technologies, Inc. | Cellular surgery utilizing confocal microscopy |
| JP2001521520A (ja) * | 1997-04-11 | 2001-11-06 | ジー．ディー．サール アンド カンパニー | 抗α▲下ｖ▼β▲下３▼インテグリン抗体アンタゴニスト |
| AU6954498A (en) * | 1997-04-11 | 1998-11-11 | G.D. Searle & Co. | Methods for using antagonistic anti-avb3 integrin antibodies |
| US6596276B1 (en) * | 1997-09-30 | 2003-07-22 | Beth Israel Deaconess Medical Center | Method for inhibiting tumor angiogenesis in a living subject |
| US6172256B1 (en) * | 1998-03-04 | 2001-01-09 | G.D. Searle & Co. | Chiral-β-amino acid compounds and derivatives thereof |
| US6372719B1 (en) * | 1998-03-04 | 2002-04-16 | Jay Cunningham | ανβ3 integrin antagonists in combination with chemotherapeutic agents |
| US6537520B1 (en) | 1998-03-31 | 2003-03-25 | Bristol-Myers Squibb Pharma Company | Pharmaceuticals for the imaging of angiogenic disorders |
| IL138093A0 (en) | 1998-03-31 | 2001-10-31 | Du Pont Pharm Co | Pharmaceuticals for the imaging of angiogenic disorders |
| US6548663B1 (en) | 1998-03-31 | 2003-04-15 | Bristol-Myers Squibb Pharma Company | Benzodiazepine vitronectin receptor antagonist pharmaceuticals |
| US6524553B2 (en) | 1998-03-31 | 2003-02-25 | Bristol-Myers Squibb Pharma Company | Quinolone vitronectin receptor antagonist pharmaceuticals |
| US6852318B1 (en) * | 1998-05-08 | 2005-02-08 | The Regents Of The University Of California | Methods for detecting and inhibiting angiogenesis |
| US6759047B1 (en) * | 1998-06-17 | 2004-07-06 | Beth Israel Deaconess Hospital Corp. | Anti-angiogenic proteins and methods of use thereof |
| US6962974B1 (en) | 1998-06-17 | 2005-11-08 | Beth Israel Deaconess Medical Center | Anti-angiogenic proteins and fragments and methods of use thereof |
| US7387779B2 (en) | 1998-06-17 | 2008-06-17 | Beth Israel Deaconess Medical Center | Anti-angiogenic proteins and fragments and methods of use thereof |
| AU771224B2 (en) | 1998-07-13 | 2004-03-18 | Board Of Regents, The University Of Texas System | Cancer treatment methods using antibodies to aminophospholipids |
| RU2167425C2 (ru) * | 1998-07-17 | 2001-05-20 | Малышев Игорь Юрьевич | Способ определения белков |
| US6164281A (en) * | 1998-07-20 | 2000-12-26 | Zhao; Iris Ginron | Method of making and/or treating diseases characterized by neovascularization |
| WO2000009143A1 (en) * | 1998-08-13 | 2000-02-24 | G.D. Searle & Co. | Multivalent avb3 and metastasis-associated receptor ligands |
| US6979697B1 (en) * | 1998-08-21 | 2005-12-27 | Point Therapeutics, Inc. | Regulation of substrate activity |
| US6703050B1 (en) * | 1998-09-04 | 2004-03-09 | The Regents Of The University Of Michigan | Methods and compositions for the prevention or treatment of cancer |
| US6537554B1 (en) | 1998-09-10 | 2003-03-25 | Curagen Corporation | Nucleotide sequences and amino acid sequences of secreted proteins involved in angiogenesis |
| US7176289B1 (en) | 1998-09-11 | 2007-02-13 | Vanderbilt University | Modulation of endothelial cell surface receptor activity in the regulation of angiogenesis |
| US6248327B1 (en) | 1998-09-11 | 2001-06-19 | Vanderbilt University | Modulation of endothelial cell surface receptor activity in the regulation of angiogenesis |
| US6235877B1 (en) | 1999-08-04 | 2001-05-22 | Sigma-Tau Industrie Farmaceutiche Riunite S.P.A. | Peptido-mimetic compounds containing RGD sequence useful as integrin inhibitors |
| US20030202977A1 (en) * | 1998-11-16 | 2003-10-30 | New York University | Treatment of osteoarthritis |
| JP2002530350A (ja) * | 1998-11-20 | 2002-09-17 | ジェネンテック・インコーポレーテッド | 血管障害を処置するためのＥｐｈレセプターのアンタゴニストおよびアゴニストについての使用 |
| US6339062B1 (en) * | 1998-11-23 | 2002-01-15 | Inkine Pharmaceutical Company, Inc. | Retroinverso polypeptides that mimic or inhibit thrombospondin activity |
| US6160099A (en) * | 1998-11-24 | 2000-12-12 | Jonak; Zdenka Ludmila | Anti-human αv β3 and αv β5 antibodies |
| CA2727746A1 (en) | 1998-12-18 | 2000-06-22 | Bristol-Myers Squibb Pharma Company | Quinolone vitronectin receptor antagonist pharmaceuticals |
| EP1140864A2 (en) | 1998-12-18 | 2001-10-10 | Du Pont Pharmaceuticals Company | Vitronectin receptor antagonist pharmaceuticals |
| US6569402B1 (en) * | 1998-12-18 | 2003-05-27 | Bristol-Myers Squibb Pharma Company | Vitronectin receptor antagonist pharmaceuticals |
| US6794518B1 (en) | 1998-12-18 | 2004-09-21 | Bristol-Myers Squibb Pharma Company | Vitronectin receptor antagonist pharmaceuticals |
| US6511649B1 (en) * | 1998-12-18 | 2003-01-28 | Thomas D. Harris | Vitronectin receptor antagonist pharmaceuticals |
| JP2002533416A (ja) * | 1998-12-23 | 2002-10-08 | ジー．ディー．サール ＆ カンパニー | 新形成の治療における組み合わせ治療としてのシクロオキシゲナーゼ−２インヒビターおよび一つまたはそれ以上の抗腫瘍薬の使用方法 |
| US20050281821A1 (en) * | 1999-01-06 | 2005-12-22 | Flavia Pernasetti | Method and composition for angiogenesis inhibition |
| US6521593B1 (en) * | 1999-02-01 | 2003-02-18 | Childrens Hospital Los Angeles | Methods for inhibiting brain tumor growth |
| DK1156823T3 (da) * | 1999-02-12 | 2009-01-19 | Scripps Research Inst | Fremgangsmåder til behandling af tumorer og metastaser ved anvendelse af en kombination af anti-angiogene terapier og immunoterapier |
| AU4187200A (en) * | 1999-04-01 | 2000-10-23 | Biostratum, Inc. | The use of domains of type iv collagen t inhibit angiogenesis an tumour growth |
| WO2000067771A1 (en) * | 1999-05-06 | 2000-11-16 | The Burnham Institute | Antiangiogenic endostatin peptides, endostatin variants and methods of use |
| US6890904B1 (en) | 1999-05-25 | 2005-05-10 | Point Therapeutics, Inc. | Anti-tumor agents |
| US6531580B1 (en) | 1999-06-24 | 2003-03-11 | Ixsys, Inc. | Anti-αvβ3 recombinant human antibodies and nucleic acids encoding same |
| US6685914B1 (en) | 1999-09-13 | 2004-02-03 | Bristol-Myers Squibb Pharma Company | Macrocyclic chelants for metallopharmaceuticals |
| US20080038274A1 (en) | 1999-09-23 | 2008-02-14 | Foster Keith A | Inhibition of secretion from non-neuronal cells |
| MXPA02003079A (es) * | 1999-09-23 | 2004-04-21 | Scripps Research Inst | Metodo y composiciones para inhibir la formacion de adhesion. |
| DE60035057T2 (de) * | 1999-10-04 | 2008-01-31 | Novartis Vaccines and Diagnostics, Inc., Emeryville | CD40 Antagonist zur Behandlung von Psoriasis |
| EP1250155B1 (en) | 1999-12-22 | 2008-04-16 | The Scripps Research Institute | Angiogenesis and vascular permeability modulators and inhibitors |
| US7740841B1 (en) * | 2000-01-28 | 2010-06-22 | Sunnybrook Health Science Center | Therapeutic method for reducing angiogenesis |
| DE60141889D1 (de) * | 2000-02-03 | 2010-06-02 | Eisai R&D Man Co Ltd | Inhibitoren der integrinexpression |
| US7361643B2 (en) | 2000-02-09 | 2008-04-22 | University Of Puerto Rico | Methods for inhibiting angiogenesis |
| AU2001236909A1 (en) * | 2000-02-11 | 2001-08-20 | Duke University | Method of treating disorders of the eye |
| US6573096B1 (en) * | 2000-04-01 | 2003-06-03 | The Research Foundation At State University Of New York | Compositions and methods for inhibition of cancer invasion and angiogenesis |
| US6835806B2 (en) | 2000-04-03 | 2004-12-28 | Phoenix Pharmaceuticals, Inc. | Cell growth regulation system |
| JP5043271B2 (ja) | 2000-04-12 | 2012-10-10 | ジーイー・ヘルスケア・アクスイェ・セルスカプ | ペプチドベースの化合物 |
| US10293056B1 (en) * | 2000-05-24 | 2019-05-21 | Board Of Regents, The University Of Texas System | Methods and compositions for non-viral gene therapy for treatment of hyperproliferative diseases |
| US7163681B2 (en) * | 2000-08-07 | 2007-01-16 | Centocor, Inc. | Anti-integrin antibodies, compositions, methods and uses |
| US7288390B2 (en) * | 2000-08-07 | 2007-10-30 | Centocor, Inc. | Anti-dual integrin antibodies, compositions, methods and uses |
| US20030104573A1 (en) * | 2000-09-11 | 2003-06-05 | Shimkets Richard A. | Nucleotide sequences and amino acid sequences of secreted proteins involved in angiogenesis |
| NO20004795D0 (no) | 2000-09-26 | 2000-09-26 | Nycomed Imaging As | Peptidbaserte forbindelser |
| JP2005508831A (ja) * | 2000-10-02 | 2005-04-07 | ザ スクリプス リサーチ インスティテュート | 血管新生促進のための方法および組成物 |
| US6632835B2 (en) | 2001-02-22 | 2003-10-14 | Nanodesign Inc. | Dibenzo[c]chromen-6-one derivatives as anti-cancer agents |
| DE10109136A1 (de) * | 2001-02-26 | 2002-09-12 | Cytotools Gmbh | Mittel, die die Apoptose bei an der Wundheilung beteiligten Zellen inhibieren |
| CN1507354A (zh) * | 2001-03-02 | 2004-06-23 | ͨ��ҽ�ƹ�˾ | 通过给予整合蛋白αvβ3拮抗剂并与其它预防或治疗药剂配合来预防或者治疗炎性疾病或自身免疫疾病的方法 |
| KR100861466B1 (ko) | 2001-04-24 | 2008-10-02 | 메르크 파텐트 게엠베하 | 항혈관형성제 및 ＴＮＦα를 이용한 병용 요법 |
| SE0101854L (sv) * | 2001-05-28 | 2002-11-29 | Bioneris Ab | Användning av en förening med en negativt laddad region av grupper för behandling av restenos. |
| US7829087B2 (en) * | 2001-07-09 | 2010-11-09 | Elan Pharmaceuticals, Inc. | Methods of treating cognitive impairment |
| CA2453403C (en) * | 2001-07-09 | 2013-10-08 | Elan Pharmaceuticals, Inc. | Methods of inhibiting amyloid toxicity |
| CA2452923C (en) | 2001-07-10 | 2012-02-07 | Amersham Health As | Peptide-based compounds for targeting integrin receptors |
| US7122517B2 (en) * | 2001-07-27 | 2006-10-17 | Kansas University Medical Center | Crystallized structure of type IV collagen NC1 domain hexamer |
| US20060014697A1 (en) * | 2001-08-22 | 2006-01-19 | Travis Mickle | Pharmaceutical compositions for prevention of overdose or abuse |
| WO2003020280A2 (en) * | 2001-09-05 | 2003-03-13 | Minerva Biotechnologies Corporation | Compositions and use thereof in the treatment of cancer |
| WO2003059251A2 (en) | 2001-10-22 | 2003-07-24 | The Scripps Research Institute | Antibody targeting compounds |
| US20050085415A1 (en) * | 2002-02-14 | 2005-04-21 | Matthias Wiesner | Methods and compositions for the treatment of eye diseases |
| WO2003068258A1 (en) * | 2002-02-15 | 2003-08-21 | Richard Brunner | 7s immunoglobulin for treatment of choroidal neovascularisation_ |
| WO2003075957A1 (en) * | 2002-03-04 | 2003-09-18 | Medimmune, Inc. | The prevention or treatment of cancer using integrin alphavbeta3 antagonists in combination with other agents |
| AU2003213682C1 (en) * | 2002-03-04 | 2008-06-12 | Medimmune, Inc. | Methods of preventing or treating disorders by administering an integrin alphavbeta3 antagonist in combination with an HMG-CoA reductase inhibitor or a bisphosphonate |
| US7371383B2 (en) * | 2002-04-12 | 2008-05-13 | Medimmune, Inc. | Recombinant anti-interleukin-9 antibodies |
| EP2269656B1 (en) | 2002-07-15 | 2014-08-20 | Board Of Regents, The University Of Texas | Selected antibodies binding to aminophospholipids and their use in treatment, such as cancer |
| GB0217018D0 (en) * | 2002-07-23 | 2002-08-28 | Bioacta Ltd | Peptide 1 |
| CN1688303A (zh) * | 2002-07-23 | 2005-10-26 | 密歇根大学董事会 | 用于抗血管发生疗法的四硫代钼酸四丙铵及相关化合物 |
| EP1578254B1 (en) * | 2002-11-19 | 2013-03-06 | DRG International, Inc. | Diagnostic method for diseases by screening for hepcidin in human or animal tissues, blood or body fluids and therapeutic uses therefor |
| US7411048B2 (en) | 2002-11-19 | 2008-08-12 | Drg International, Inc. | Diagnostic method for diseases by screening for hepcidin in human or animal tissues, blood or body fluids |
| US8017737B2 (en) * | 2002-11-19 | 2011-09-13 | Hasan Kulaksiz | Diagnostic methods for diseases by screening for hepcidin in human or animal tissues, blood or body fluids; monoclonal antibodies specific to human hepcidin and associated uses therefor |
| US20040208869A1 (en) * | 2003-01-30 | 2004-10-21 | Medimmune, Inc. | Uses of anti-integrin alphanubeta3 antibody formulations |
| CA2514653A1 (en) * | 2003-01-30 | 2004-08-12 | Medimmune, Inc. | Uses of integrin alphavbeta3 antagonists |
| KR20050099536A (ko) | 2003-02-06 | 2005-10-13 | 트리펩 아베 | 글리코실화된 특이성 교환체 |
| US7335359B2 (en) * | 2003-02-06 | 2008-02-26 | Tripep Ab | Glycosylated specificity exchangers |
| EP2316487B1 (en) * | 2003-04-11 | 2014-06-11 | MedImmune, LLC | Recombinant IL-9 antibodies & uses thereof |
| CA2520518A1 (en) * | 2003-04-18 | 2004-10-28 | The University Of British Columbia | Method for treatment of angiogenic disorders |
| AU2004265226A1 (en) * | 2003-05-16 | 2005-02-24 | Receptor Biologix, Inc. | Intron fusion proteins, and methods of identifying and using same |
| US7605235B2 (en) | 2003-05-30 | 2009-10-20 | Centocor, Inc. | Anti-tissue factor antibodies and compositions |
| JP2006526641A (ja) * | 2003-05-30 | 2006-11-24 | セントカー・インコーポレーテツド | 抗−組織因子抗体を用いる腫瘍成長を抑制する方法 |
| US9708410B2 (en) | 2003-05-30 | 2017-07-18 | Janssen Biotech, Inc. | Anti-tissue factor antibodies and compositions |
| WO2004113361A2 (en) * | 2003-06-20 | 2004-12-29 | The Regents Of The University Of California | Novel prokineticin receptor isoforms and methods of use |
| WO2005053683A1 (en) * | 2003-11-26 | 2005-06-16 | Duke University | A method of preventing or treating glaucoma |
| KR20170102377A (ko) | 2004-01-22 | 2017-09-08 | 유니버시티 오브 마이애미 | 국소용 코-엔자임 큐10 제형 및 그의 사용 방법 |
| US7271245B2 (en) * | 2004-02-13 | 2007-09-18 | The Scripps Research Institute | Methods and compositions for inhibition of metastasis |
| WO2005079508A2 (en) * | 2004-02-17 | 2005-09-01 | Cancervax Corporation | Method and composition for angiogenesis inhibition |
| US7351739B2 (en) * | 2004-04-30 | 2008-04-01 | Wellgen, Inc. | Bioactive compounds and methods of uses thereof |
| US8187595B2 (en) * | 2004-05-07 | 2012-05-29 | The University Of North Carolina At Chapel Hill | Monoclonal antibodies for enhancing or inhibiting insulin-like growth factor-I |
| WO2005117936A2 (en) * | 2004-05-07 | 2005-12-15 | The University Of North Carolina At Chapel Hill | Method for enhancing or inhibiting insulin-like growth factor-i |
| AU2005245896A1 (en) * | 2004-05-14 | 2005-12-01 | Receptor Biologix, Inc. | Cell surface receptor isoforms and methods of identifying and using the same |
| ES2439390T3 (es) | 2004-06-04 | 2014-01-22 | The Scripps Research Institute | Composiciones y procedimiento para el tratamiento de enfermedades neovasculares |
| WO2006012415A2 (en) * | 2004-07-20 | 2006-02-02 | Critical Therapeutics, Inc. | Rage protein derivatives |
| US20060029544A1 (en) * | 2004-08-06 | 2006-02-09 | The Regents Of The University Of California Office Of Technology Transfer | Receptor-binding cyclic peptides and methods of use |
| AU2005277641A1 (en) * | 2004-08-16 | 2006-03-02 | Medimmune, Llc | Eph receptor Fc variants with enhanced antibody dependent cell-mediated cytotoxicity activity |
| WO2006047639A2 (en) | 2004-10-27 | 2006-05-04 | Medimmune, Inc. | Modulation of antibody specificity by tailoring the affinity to cognate antigens |
| KR100679100B1 (ko) * | 2004-10-29 | 2007-02-06 | 엘지.필립스 엘시디 주식회사 | 수평 전계 인가형 액정 표시 패널 및 그 제조방법 |
| KR20070102684A (ko) * | 2004-12-23 | 2007-10-19 | 몰메드 에스피에이 | 접합 생성물 |
| WO2006111925A2 (en) * | 2005-04-18 | 2006-10-26 | Sloan-Kettering Institute For Cancer Research | Inhibition of tumorigenesis by inhibition of a6b4 integrin |
| US20090170769A1 (en) * | 2005-05-13 | 2009-07-02 | Pei Jin | Cell surface receptor isoforms and methods of identifying and using the same |
| US20060286148A1 (en) * | 2005-05-18 | 2006-12-21 | Ppd, Inc. | Method of forming implants |
| EP2364998A1 (en) | 2005-06-16 | 2011-09-14 | The Feinstein Institute for Medical Research | Antibodies against HMGB1 and fragments thereof |
| EP1893647A2 (en) | 2005-06-23 | 2008-03-05 | MedImmune, Inc. | Antibody formulations having optimized aggregation and fragmentation profiles |
| CA2619654A1 (en) * | 2005-08-24 | 2007-03-01 | Cell Matrix | Combination therapies for inhibiting integrin-extracellular matrix interactions |
| WO2007084670A2 (en) | 2006-01-18 | 2007-07-26 | Merck Patent Gmbh | Specific therapy using integrin ligands for treating cancer |
| EP1984391A4 (en) | 2006-01-19 | 2009-08-12 | Eyegene Inc | PEPTIDE-SUBSTANCED PHARMACEUTICAL COMPOSITION FOR THE TREATMENT OF DISEASES CONNECTED WITH THE VASCULAR SYSTEM |
| AU2007257683A1 (en) * | 2006-06-12 | 2007-12-21 | Symphogen A/S | Pan-cell surface receptor- specific therapeutics |
| AU2007272970C1 (en) | 2006-07-11 | 2013-01-10 | Roy C. Levitt | Rhinosinusitis prevention and therapy with proinflammatory cytokine inhibitors |
| CA2660519A1 (en) | 2006-08-10 | 2008-02-21 | Roy C. Levitt | Localized therapy of lower airways inflammatory disorders with proinflammatory cytokine inhibitors |
| WO2008045252A2 (en) | 2006-10-04 | 2008-04-17 | The Board Of Trustees Of The Leland Stanford Junior University | Engineered integrin binding peptides |
| EA017864B1 (ru) | 2007-01-18 | 2013-03-29 | Мерк Патент Гмбх | Специфическая терапия и лекарственное средство на основе интегриновых лигандов для лечения рака |
| EP2025685B1 (en) * | 2007-08-15 | 2013-06-19 | Canadian Blood Services | Monoclonal antibodies against BETA3 integrins |
| WO2009052184A2 (en) * | 2007-10-16 | 2009-04-23 | Receptor Biologix, Inc. | Compositions comprising optimized her1 and her3 multimers and methods of use thereof |
| WO2009060198A1 (en) | 2007-11-09 | 2009-05-14 | Peregrine Pharmaceuticals, Inc. | Anti-vegf antibody compositions and methods |
| WO2009137807A2 (en) | 2008-05-08 | 2009-11-12 | Asuragen, Inc. | Compositions and methods related to mirna modulation of neovascularization or angiogenesis |
| EP2323679A4 (en) | 2008-07-25 | 2012-08-22 | Univ Colorado | CLIP HEMMER AND METHOD FOR MODULATING THE IMMUNE FUNCTION |
| DK2352817T3 (en) | 2008-10-31 | 2016-04-18 | Univ Louisville Res Found | OLFACTORY EPITAL DERIVATIVE STEM CELLS AND PROCEDURES FOR USE THEREOF |
| JP2012513589A (ja) | 2008-12-23 | 2012-06-14 | ジーイー・ヘルスケア・リミテッド | 骨髄イメージング剤としての９９ｍＴｃ−ペプチド系化合物の応用 |
| JP2012517447A (ja) | 2009-02-10 | 2012-08-02 | ザ スクリプス リサーチ インスティチュート | 化学的にプログラムされたワクチン接種法 |
| JP2012528079A (ja) | 2009-05-25 | 2012-11-12 | メルク パテント ゲゼルシャフト ミット ベシュレンクテル ハフツング | 癌を治療するためのインテグリンリガンドの連続投与 |
| FR2949782B1 (fr) * | 2009-09-04 | 2015-10-16 | Isp Investments Inc | Peptide activateur de la transglutaminase et composition cosmetique ou pharmaceutique le contenant. |
| US8778888B2 (en) * | 2009-11-06 | 2014-07-15 | The Board Of Trustees Of The Leland Stanford Junior University | Cystine knot peptides binding to alpha IIb beta 3 integrins and methods of use |
| AU2011278700A1 (en) | 2010-07-16 | 2013-02-28 | Merck Patent Gmbh | Peptide for use in the treatment of breast cancer and/or bone metastases |
| MX352025B (es) | 2011-02-11 | 2017-11-07 | Merck Patent Gmbh | Anticuerpo anti-integrina alfa v para el tratamiento de cancer de prostata. |
| US8722044B2 (en) | 2011-03-15 | 2014-05-13 | Janssen Biotech, Inc. | Human tissue factor antibody and uses thereof |
| RU2531502C2 (ru) * | 2011-08-09 | 2014-10-20 | Федеральное государственное бюджетное образовательное учреждение высшего профессионального образования "Московский государственный университет имени М.В. Ломоносова" (МГУ) | Способ повышения ангиогенной активности стромальных клеток жировой ткани |
| RU2481115C1 (ru) * | 2011-10-13 | 2013-05-10 | Общество с ограниченной ответственностью Научно-Производственное Объединение "Тюменькриобанк" | Средство для заживления ран "целльгель", способ его получения и способ лечения ран различной этиологии полученным средством |
| US9775803B2 (en) | 2011-10-19 | 2017-10-03 | Samsung Electronics Co., Ltd. | Liposome comprising elastin-like polypeptide and tumor cell targeting material and use thereof |
| US20140350087A9 (en) | 2012-03-22 | 2014-11-27 | Halozyme, Inc. | Oncovector Nucleic Acid Molecules and Methods of Use |
| TWI580692B (zh) * | 2012-06-07 | 2017-05-01 | 國立成功大學 | 經修飾纖維黏連蛋白片段或變體及其用途 |
| BR112015004119A2 (pt) | 2012-08-31 | 2017-08-08 | Univ North Carolina Chapel Hill | anticorpos monoclonais para melhorar ou inibir o fator de crescimento semelhante à insulina tipo 1 (igf-1) |
| US9587001B2 (en) | 2012-10-19 | 2017-03-07 | The Board Of Trustees Of The Leland Stanford Junior University | Conjugated knottin mini-proteins containing non-natural amino acids |
| WO2014087429A1 (en) | 2012-12-07 | 2014-06-12 | Council Of Scientific & Industrial Research | Histidinylated cationic amphiphiles, process for preparation thereof and their liposomal formulation |
| CN105358708A (zh) | 2013-03-14 | 2016-02-24 | 儿童医学中心公司 | Cd36鉴定癌症对象以用于治疗的用途 |
| US20190144547A1 (en) | 2015-11-23 | 2019-05-16 | Merck Patent Gmbh | Anti-alpha-v integrin antibody for the treatment of fibrosis and/or fibrotic disorders |
| US10786471B2 (en) | 2017-02-06 | 2020-09-29 | Massachusetts Institute Of Technology | Methods and products related to glutaminase inhibitors |
| MX2019011717A (es) | 2017-03-31 | 2019-12-16 | Univ California | Composiciones y metodos para focalizar y matar celulas madre positivas a cancer alfa-v beta-3 y tratar cancer resistentes a farmacos. |
| KR102171433B1 (ko) * | 2018-05-25 | 2020-11-02 | 고려대학교 산학협력단 | 조직 재생을 위한 Substance P 펩타이드가 고정된 피브린 젤 및 이의 제조방법 |
| US20220133913A1 (en) * | 2019-07-24 | 2022-05-05 | Korea Basic Science Institute | SINGLE DOMAIN ANTIBODY TARGETING aVB3 INTEGRIN |
| BR112022001273A2 (pt) * | 2019-08-02 | 2022-06-07 | Univ California | Composições e métodos para direcionar e matar células tronco cancerosas (cscs) positivas para alfa-v beta-3 (avss3) (cscs) e tratar cânceres metastáticos e resistentes a fármacos |
| KR20230078657A (ko) | 2020-08-27 | 2023-06-02 | 에노시 테라퓨틱스 코퍼레이션 | 자가면역 질환 및 암을 치료하기 위한 방법 및 조성물 |
Family Cites Families (26)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5092885A (en) * | 1987-02-12 | 1992-03-03 | The Government Of The United States Of America As Represented By The Secretary Of The Department Of Health And Human Services | Peptides with laminin activity |
| JPH02502156A (ja) * | 1987-11-19 | 1990-07-19 | スクリップス クリニック アンド リサーチ ファウンデーション | 内皮細胞のｒｇｄ指向粘着レセプターに対するモノクローナル抗体 |
| JPH01169343A (ja) | 1987-12-25 | 1989-07-04 | Nippon Sheet Glass Co Ltd | ガラス板の切口欠点検出装置 |
| US5135919A (en) | 1988-01-19 | 1992-08-04 | Children's Medical Center Corporation | Method and a pharmaceutical composition for the inhibition of angiogenesis |
| IE64346B1 (en) * | 1988-01-19 | 1995-07-26 | Moses Judah Folkman | Growth inhibiting agent and the use thereof |
| US5575815A (en) | 1988-08-24 | 1996-11-19 | Endoluminal Therapeutics, Inc. | Local polymeric gel therapy |
| IE901736L (en) * | 1989-05-17 | 1990-11-17 | Fuller H B Licensing Financ | Polypeptide-antibody conjugate for inhibiting cell adhesion |
| US5686568A (en) | 1989-06-16 | 1997-11-11 | Cor Therapeutics, Inc. | Platelet aggregration inhibitors |
| US5112946A (en) * | 1989-07-06 | 1992-05-12 | Repligen Corporation | Modified pf4 compositions and methods of use |
| US5262520A (en) * | 1989-12-01 | 1993-11-16 | The Scripps Research Institute | Peptides and antibodies that inhibit integrin-ligand binding |
| US5192744A (en) * | 1990-01-12 | 1993-03-09 | Northwestern University | Method of inhibiting angiogenesis of tumors |
| EP0470569B1 (en) * | 1990-08-08 | 1995-11-22 | Takeda Chemical Industries, Ltd. | Intravascular embolizing agent containing angiogenesis inhibiting substance |
| CA2048078A1 (en) * | 1990-11-15 | 1992-05-16 | Wolfgang A. Wrasidlo | Chemical modification of antibodies for creation of immunoconjugates |
| DK0590058T3 (da) * | 1991-06-14 | 2004-03-29 | Genentech Inc | Humaniseret heregulin-antistof |
| ATE175241T1 (de) * | 1992-04-03 | 1999-01-15 | Genentech Inc | Antikörper gegen alpha v beta 3 integrin |
| SK57693A3 (en) * | 1992-06-18 | 1994-07-06 | Merck Patent Gmbh | Linear peptides and pharmaceutical agents on their base |
| UA43823C2 (uk) * | 1992-07-06 | 2002-01-15 | Мерк Патент Геселлшафт Міт Бесшренктер Хафтунг | ФАРМАЦЕВТИЧНА КОМПОЗИЦІЯ ДЛЯ ІНГІБУВАННЯ ІНТЕГРИН <font face="Symbol">a</font><sub>V</sub><font face="Symbol">b</font><sub>3</sub>-ОПОСЕРЕДКОВАНОЇ КЛІТИННОЇ АДГЕЗІЇ КЛІТИН ССАВЦІВ, СПОСІБ ЛІКУВАННЯ ТА ПРОФІЛАКТИКИ ЗАХВОРЮВАННЯ, АСОЦІЙОВАНОГО З ПОРУШЕННЯМ АДГЕЗІЇ КЛІТИН, СПОСІБ БЛОКУВАННЯ ЗВ'ЯЗУВАННЯ ФІБРИНОГЕНОМ ІНТЕГРИНУ, КОМПОЗИЦІЯ ДЛЯ ЗАГОЄННЯ РАН |
| SG78239A1 (en) | 1992-10-29 | 2001-02-20 | Univ Australian | Angiogenesis inhibitory antibodies |
| AU6235294A (en) * | 1993-02-02 | 1994-08-29 | Scripps Research Institute, The | Methods for producing polypeptide binding sites |
| DE4310643A1 (de) | 1993-04-01 | 1994-10-06 | Merck Patent Gmbh | Cyclische Adhäsionsinhibitoren |
| AU1172495A (en) † | 1993-11-05 | 1995-05-23 | Centocor Inc. | Platelet-specific chimeric immunoglobulin and methods of use therefor |
| US5981478A (en) | 1993-11-24 | 1999-11-09 | La Jolla Cancer Research Foundation | Integrin-binding peptides |
| US5753230A (en) * | 1994-03-18 | 1998-05-19 | The Scripps Research Institute | Methods and compositions useful for inhibition of angiogenesis |
| US5770565A (en) | 1994-04-13 | 1998-06-23 | La Jolla Cancer Research Center | Peptides for reducing or inhibiting bone resorption |
| DE19534177A1 (de) | 1995-09-15 | 1997-03-20 | Merck Patent Gmbh | Cyclische Adhäsionsinhibitoren |
| DE19538741A1 (de) | 1995-10-18 | 1997-04-24 | Merck Patent Gmbh | Cyclopeptidderivate |
-
1994
- 1994-03-18 US US08/210,715 patent/US5753230A/en not_active Expired - Lifetime
- 1994-12-30 US US08/366,665 patent/US5766591A/en not_active Expired - Lifetime
-
1995
- 1995-03-09 CN CNB951931334A patent/CN1161152C/zh not_active Expired - Lifetime
- 1995-03-09 DK DK03077708.0T patent/DK1410807T3/da active
- 1995-03-09 ES ES03077708T patent/ES2355074T3/es not_active Expired - Lifetime
- 1995-03-09 EP EP03078802A patent/EP1468695B1/en not_active Expired - Lifetime
- 1995-03-09 AT AT03078802T patent/ATE534403T1/de active
- 1995-03-09 NZ NZ511293A patent/NZ511293A/en not_active IP Right Cessation
- 1995-03-09 AT AT95913644T patent/ATE255907T1/de active
- 1995-03-09 AU AU19952/95A patent/AU709645B2/en not_active Expired
- 1995-03-09 MX MX9604145A patent/MX9604145A/es active IP Right Grant
- 1995-03-09 DK DK95913644.1T patent/DK0754059T4/da active
- 1995-03-09 KR KR1019960705163A patent/KR100327081B1/ko not_active IP Right Cessation
- 1995-03-09 ES ES03078802T patent/ES2376850T3/es not_active Expired - Lifetime
- 1995-03-09 NZ NZ283022A patent/NZ283022A/en not_active IP Right Cessation
- 1995-03-09 RU RU96120204/14A patent/RU2162712C2/ru not_active IP Right Cessation
- 1995-03-09 SK SK1190-96A patent/SK284586B6/sk not_active IP Right Cessation
- 1995-03-09 WO PCT/US1995/003035 patent/WO1995025543A1/en active IP Right Grant
- 1995-03-09 AT AT03077708T patent/ATE490784T1/de active
- 1995-03-09 JP JP52467595A patent/JP4268222B2/ja not_active Expired - Lifetime
- 1995-03-09 PT PT03078802T patent/PT1468695E/pt unknown
- 1995-03-09 DE DE69536128T patent/DE69536128D1/de not_active Expired - Lifetime
- 1995-03-09 PT PT95913644T patent/PT754059E/pt unknown
- 1995-03-09 DK DK03078802.0T patent/DK1468695T3/da active
- 1995-03-09 DE DE69532279T patent/DE69532279T3/de not_active Expired - Lifetime
- 1995-03-09 EP EP03077708A patent/EP1410807B1/en not_active Expired - Lifetime
- 1995-03-09 SI SI9530699T patent/SI0754059T2/sl unknown
- 1995-03-09 NZ NZ548433A patent/NZ548433A/en not_active IP Right Cessation
- 1995-03-09 CA CA2184493A patent/CA2184493C/en not_active Expired - Fee Related
- 1995-03-09 UA UA96093689A patent/UA44729C2/uk unknown
- 1995-03-09 EP EP95913644A patent/EP0754059B2/en not_active Expired - Lifetime
- 1995-03-09 CZ CZ19962711A patent/CZ294650B6/cs not_active IP Right Cessation
- 1995-03-09 HU HU9602541A patent/HU221988B1/hu not_active IP Right Cessation
- 1995-03-09 ES ES95913644T patent/ES2211901T5/es not_active Expired - Lifetime
- 1995-03-17 ZA ZA952214A patent/ZA952214B/xx unknown
-
1996
- 1996-09-17 NO NO19963894A patent/NO322441B1/no not_active IP Right Cessation
- 1996-09-18 FI FI963692A patent/FI121916B/fi not_active IP Right Cessation
-
1998
- 1998-05-19 US US09/081,522 patent/US6887473B1/en not_active Expired - Fee Related
- 1998-12-24 HK HK98115348A patent/HK1013960A1/ not_active IP Right Cessation
-
2004
- 2004-07-15 US US10/892,653 patent/US7329406B2/en not_active Expired - Fee Related
- 2004-07-15 US US10/892,745 patent/US7482007B2/en not_active Expired - Fee Related
- 2004-07-15 US US10/892,789 patent/US7354586B2/en not_active Expired - Fee Related
-
2006
- 2006-05-22 JP JP2006142020A patent/JP4758281B2/ja not_active Expired - Lifetime
-
2007
- 2007-10-30 US US11/980,211 patent/US7595051B2/en not_active Expired - Fee Related
Also Published As
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| EP0754059B1 (en) | Methods and compositions useful for inhibition of angiogenesis | |
| US6500924B1 (en) | Methods and compositions useful for inhibition of angiogenesis | |
| CA2256543C (en) | Methods and compositions useful for inhibition of angiogenesis | |
| US7053041B1 (en) | Methods and compositions useful for inhibition of αvβ5mediated angiogenesis | |
| US20030176334A1 (en) | Methods and compositions useful for inhibition of angiogenesis |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| MM4A | Patent lapsed due to non-payment of maintenance fees |
Effective date: 20140309 |