CA2381004A1 - Nucleic acid ligands to hepatocyte growth factor/scatter factor (hgf/sf) or its receptor c-met and to integrins - Google Patents
Nucleic acid ligands to hepatocyte growth factor/scatter factor (hgf/sf) or its receptor c-met and to integrins Download PDFInfo
- Publication number
- CA2381004A1 CA2381004A1 CA002381004A CA2381004A CA2381004A1 CA 2381004 A1 CA2381004 A1 CA 2381004A1 CA 002381004 A CA002381004 A CA 002381004A CA 2381004 A CA2381004 A CA 2381004A CA 2381004 A1 CA2381004 A1 CA 2381004A1
- Authority
- CA
- Canada
- Prior art keywords
- nucleic acid
- artificial sequence
- acid ligand
- rna
- hgf
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Abandoned
Links
- 150000007523 nucleic acids Chemical class 0.000 title claims abstract description 345
- 102000039446 nucleic acids Human genes 0.000 title claims abstract description 344
- 108020004707 nucleic acids Proteins 0.000 title claims abstract description 344
- 239000003446 ligand Substances 0.000 title claims abstract description 289
- 102000006495 integrins Human genes 0.000 title claims abstract description 139
- 108010044426 integrins Proteins 0.000 title claims abstract description 139
- 102000003745 Hepatocyte Growth Factor Human genes 0.000 title claims abstract description 29
- 108090000100 Hepatocyte Growth Factor Proteins 0.000 title claims abstract description 29
- 102000005962 receptors Human genes 0.000 title claims abstract description 21
- 108020003175 receptors Proteins 0.000 title claims abstract description 21
- 102100021866 Hepatocyte growth factor Human genes 0.000 claims abstract description 237
- 238000000034 method Methods 0.000 claims abstract description 170
- 238000009739 binding Methods 0.000 claims description 182
- 230000027455 binding Effects 0.000 claims description 179
- 239000000203 mixture Substances 0.000 claims description 102
- 108010073929 Vascular Endothelial Growth Factor A Proteins 0.000 claims description 41
- 102000005789 Vascular Endothelial Growth Factors Human genes 0.000 claims description 41
- 108010019530 Vascular Endothelial Growth Factors Proteins 0.000 claims description 41
- 108020004414 DNA Proteins 0.000 claims description 34
- 206010028980 Neoplasm Diseases 0.000 claims description 33
- 238000000638 solvent extraction Methods 0.000 claims description 22
- 201000010099 disease Diseases 0.000 claims description 20
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 20
- 230000002401 inhibitory effect Effects 0.000 claims description 20
- 125000003729 nucleotide group Chemical group 0.000 claims description 19
- 238000011282 treatment Methods 0.000 claims description 18
- 239000011324 bead Substances 0.000 claims description 16
- 239000007787 solid Substances 0.000 claims description 16
- 239000000020 Nitrocellulose Substances 0.000 claims description 15
- 229920001220 nitrocellulos Polymers 0.000 claims description 15
- 208000007536 Thrombosis Diseases 0.000 claims description 14
- 230000033115 angiogenesis Effects 0.000 claims description 14
- 102000003974 Fibroblast growth factor 2 Human genes 0.000 claims description 12
- 108090000379 Fibroblast growth factor 2 Proteins 0.000 claims description 12
- 239000003102 growth factor Substances 0.000 claims description 12
- 201000011510 cancer Diseases 0.000 claims description 10
- 102000003972 Fibroblast growth factor 7 Human genes 0.000 claims description 8
- 108090000385 Fibroblast growth factor 7 Proteins 0.000 claims description 8
- 108010038512 Platelet-Derived Growth Factor Proteins 0.000 claims description 8
- 102000010780 Platelet-Derived Growth Factor Human genes 0.000 claims description 8
- 206010047249 Venous thrombosis Diseases 0.000 claims description 7
- 238000002955 isolation Methods 0.000 claims description 7
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 7
- 206010039073 rheumatoid arthritis Diseases 0.000 claims description 7
- 208000001132 Osteoporosis Diseases 0.000 claims description 5
- 102000004887 Transforming Growth Factor beta Human genes 0.000 claims description 5
- 108090001012 Transforming Growth Factor beta Proteins 0.000 claims description 5
- 208000037803 restenosis Diseases 0.000 claims description 5
- ZRKFYGHZFMAOKI-QMGMOQQFSA-N tgfbeta Chemical compound C([C@H](NC(=O)[C@H](C(C)C)NC(=O)CNC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H]([C@@H](C)O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H]([C@@H](C)O)NC(=O)[C@H](CC(C)C)NC(=O)CNC(=O)[C@H](C)NC(=O)[C@H](CO)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@@H](NC(=O)[C@H](C)NC(=O)[C@H](C)NC(=O)[C@@H](NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](N)CCSC)C(C)C)[C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](C)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](C)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](C)C(=O)N[C@@H](CC(C)C)C(=O)N1[C@@H](CCC1)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(C)C)C(O)=O)C1=CC=C(O)C=C1 ZRKFYGHZFMAOKI-QMGMOQQFSA-N 0.000 claims description 5
- 102000053602 DNA Human genes 0.000 claims description 4
- 206010051055 Deep vein thrombosis Diseases 0.000 claims description 4
- 201000004681 Psoriasis Diseases 0.000 claims description 4
- 239000008194 pharmaceutical composition Substances 0.000 claims description 4
- 230000010118 platelet activation Effects 0.000 claims description 4
- 208000004476 Acute Coronary Syndrome Diseases 0.000 claims description 3
- 201000009273 Endometriosis Diseases 0.000 claims description 3
- 208000006011 Stroke Diseases 0.000 claims description 3
- 230000004913 activation Effects 0.000 claims description 3
- 238000013146 percutaneous coronary intervention Methods 0.000 claims description 3
- 206010012689 Diabetic retinopathy Diseases 0.000 claims description 2
- 206010038933 Retinopathy of prematurity Diseases 0.000 claims description 2
- 230000001455 anti-clotting effect Effects 0.000 claims description 2
- 208000002780 macular degeneration Diseases 0.000 claims description 2
- 229920002477 rna polymer Polymers 0.000 claims 9
- 230000005748 tumor development Effects 0.000 claims 6
- 108010009583 Transforming Growth Factors Proteins 0.000 claims 3
- 102000009618 Transforming Growth Factors Human genes 0.000 claims 3
- 241001197082 Knodus beta Species 0.000 claims 1
- 239000013060 biological fluid Substances 0.000 claims 1
- 230000004807 localization Effects 0.000 claims 1
- 230000001717 pathogenic effect Effects 0.000 claims 1
- 230000002285 radioactive effect Effects 0.000 claims 1
- 230000009897 systematic effect Effects 0.000 abstract description 16
- 239000003814 drug Substances 0.000 abstract description 11
- 229940124597 therapeutic agent Drugs 0.000 abstract description 7
- 239000000032 diagnostic agent Substances 0.000 abstract description 6
- 229940039227 diagnostic agent Drugs 0.000 abstract description 6
- 108091032973 (ribonucleotides)n+m Proteins 0.000 description 437
- 150000003230 pyrimidines Chemical group 0.000 description 301
- 108091023037 Aptamer Proteins 0.000 description 175
- 210000004027 cell Anatomy 0.000 description 62
- 102000004169 proteins and genes Human genes 0.000 description 62
- 108090000623 proteins and genes Proteins 0.000 description 62
- 230000008569 process Effects 0.000 description 38
- 230000004048 modification Effects 0.000 description 34
- 238000012986 modification Methods 0.000 description 34
- 230000005764 inhibitory process Effects 0.000 description 32
- 238000002474 experimental method Methods 0.000 description 26
- 108091034117 Oligonucleotide Proteins 0.000 description 25
- 239000003112 inhibitor Substances 0.000 description 24
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 24
- 230000000694 effects Effects 0.000 description 20
- 108010049003 Fibrinogen Proteins 0.000 description 19
- 102000008946 Fibrinogen Human genes 0.000 description 19
- JLCPHMBAVCMARE-UHFFFAOYSA-N [3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-[[3-[[3-[[3-[[3-[[3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-hydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methyl [5-(6-aminopurin-9-yl)-2-(hydroxymethyl)oxolan-3-yl] hydrogen phosphate Polymers Cc1cn(C2CC(OP(O)(=O)OCC3OC(CC3OP(O)(=O)OCC3OC(CC3O)n3cnc4c3nc(N)[nH]c4=O)n3cnc4c3nc(N)[nH]c4=O)C(COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3CO)n3cnc4c(N)ncnc34)n3ccc(N)nc3=O)n3cnc4c(N)ncnc34)n3ccc(N)nc3=O)n3ccc(N)nc3=O)n3ccc(N)nc3=O)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cc(C)c(=O)[nH]c3=O)n3cc(C)c(=O)[nH]c3=O)n3ccc(N)nc3=O)n3cc(C)c(=O)[nH]c3=O)n3cnc4c3nc(N)[nH]c4=O)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)O2)c(=O)[nH]c1=O JLCPHMBAVCMARE-UHFFFAOYSA-N 0.000 description 19
- 229940012952 fibrinogen Drugs 0.000 description 19
- 238000003752 polymerase chain reaction Methods 0.000 description 18
- 239000012148 binding buffer Substances 0.000 description 16
- 239000013615 primer Substances 0.000 description 16
- 150000003212 purines Chemical class 0.000 description 16
- 102000040650 (ribonucleotides)n+m Human genes 0.000 description 15
- 108010031318 Vitronectin Proteins 0.000 description 15
- 102100035140 Vitronectin Human genes 0.000 description 15
- 239000000872 buffer Substances 0.000 description 15
- 230000000638 stimulation Effects 0.000 description 15
- 239000012634 fragment Substances 0.000 description 14
- HTTJABKRGRZYRN-UHFFFAOYSA-N Heparin Chemical compound OC1C(NC(=O)C)C(O)OC(COS(O)(=O)=O)C1OC1C(OS(O)(=O)=O)C(O)C(OC2C(C(OS(O)(=O)=O)C(OC3C(C(O)C(O)C(O3)C(O)=O)OS(O)(=O)=O)C(CO)O2)NS(O)(=O)=O)C(C(O)=O)O1 HTTJABKRGRZYRN-UHFFFAOYSA-N 0.000 description 13
- 230000006870 function Effects 0.000 description 13
- 229920000669 heparin Polymers 0.000 description 13
- 229960002897 heparin Drugs 0.000 description 13
- 230000001976 improved effect Effects 0.000 description 13
- 210000003462 vein Anatomy 0.000 description 13
- YBJHBAHKTGYVGT-ZKWXMUAHSA-N (+)-Biotin Chemical group N1C(=O)N[C@@H]2[C@H](CCCCC(=O)O)SC[C@@H]21 YBJHBAHKTGYVGT-ZKWXMUAHSA-N 0.000 description 12
- KDCGOANMDULRCW-UHFFFAOYSA-N 7H-purine Chemical compound N1=CNC2=NC=NC2=C1 KDCGOANMDULRCW-UHFFFAOYSA-N 0.000 description 12
- 150000001413 amino acids Chemical class 0.000 description 12
- 238000006243 chemical reaction Methods 0.000 description 12
- 238000000338 in vitro Methods 0.000 description 12
- 230000003993 interaction Effects 0.000 description 12
- 238000006467 substitution reaction Methods 0.000 description 12
- 102000004127 Cytokines Human genes 0.000 description 11
- 108090000695 Cytokines Proteins 0.000 description 11
- 229920001223 polyethylene glycol Polymers 0.000 description 11
- 210000001519 tissue Anatomy 0.000 description 11
- 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 10
- TWRXJAOTZQYOKJ-UHFFFAOYSA-L Magnesium chloride Chemical compound [Mg+2].[Cl-].[Cl-] TWRXJAOTZQYOKJ-UHFFFAOYSA-L 0.000 description 10
- 238000003556 assay Methods 0.000 description 10
- 150000001875 compounds Chemical class 0.000 description 10
- 108020001507 fusion proteins Proteins 0.000 description 10
- 102000037865 fusion proteins Human genes 0.000 description 10
- 230000000284 resting effect Effects 0.000 description 10
- 241000283973 Oryctolagus cuniculus Species 0.000 description 9
- 239000004793 Polystyrene Substances 0.000 description 9
- 102100033177 Vascular endothelial growth factor receptor 2 Human genes 0.000 description 9
- 238000004458 analytical method Methods 0.000 description 9
- 230000015572 biosynthetic process Effects 0.000 description 9
- 238000001727 in vivo Methods 0.000 description 9
- 238000011534 incubation Methods 0.000 description 9
- 239000000463 material Substances 0.000 description 9
- 230000001404 mediated effect Effects 0.000 description 9
- 238000013508 migration Methods 0.000 description 9
- 229920002223 polystyrene Polymers 0.000 description 9
- 108090000765 processed proteins & peptides Proteins 0.000 description 9
- 230000000717 retained effect Effects 0.000 description 9
- 239000000243 solution Substances 0.000 description 9
- 238000013518 transcription Methods 0.000 description 9
- 230000035897 transcription Effects 0.000 description 9
- 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 8
- 206010027476 Metastases Diseases 0.000 description 8
- 108090000190 Thrombin Proteins 0.000 description 8
- 238000002835 absorbance Methods 0.000 description 8
- 230000003321 amplification Effects 0.000 description 8
- 230000009401 metastasis Effects 0.000 description 8
- 230000005012 migration Effects 0.000 description 8
- 230000009871 nonspecific binding Effects 0.000 description 8
- 238000003199 nucleic acid amplification method Methods 0.000 description 8
- 230000035755 proliferation Effects 0.000 description 8
- 230000001225 therapeutic effect Effects 0.000 description 8
- 229960004072 thrombin Drugs 0.000 description 8
- 229960002685 biotin Drugs 0.000 description 7
- 239000011616 biotin Substances 0.000 description 7
- 210000002889 endothelial cell Anatomy 0.000 description 7
- 238000009396 hybridization Methods 0.000 description 7
- 208000010125 myocardial infarction Diseases 0.000 description 7
- 241000894007 species Species 0.000 description 7
- 102000008022 Proto-Oncogene Proteins c-met Human genes 0.000 description 6
- 108010089836 Proto-Oncogene Proteins c-met Proteins 0.000 description 6
- 235000020958 biotin Nutrition 0.000 description 6
- 239000002981 blocking agent Substances 0.000 description 6
- 238000003776 cleavage reaction Methods 0.000 description 6
- 230000000875 corresponding effect Effects 0.000 description 6
- 230000014509 gene expression Effects 0.000 description 6
- 230000006872 improvement Effects 0.000 description 6
- 239000002773 nucleotide Substances 0.000 description 6
- 230000007017 scission Effects 0.000 description 6
- NYHBQMYGNKIUIF-UUOKFMHZSA-N Guanosine Chemical compound C1=NC=2C(=O)NC(N)=NC=2N1[C@@H]1O[C@H](CO)[C@@H](O)[C@H]1O NYHBQMYGNKIUIF-UUOKFMHZSA-N 0.000 description 5
- 230000012292 cell migration Effects 0.000 description 5
- 230000004087 circulation Effects 0.000 description 5
- 238000010494 dissociation reaction Methods 0.000 description 5
- 230000005593 dissociations Effects 0.000 description 5
- 239000000833 heterodimer Substances 0.000 description 5
- 229910001629 magnesium chloride Inorganic materials 0.000 description 5
- 210000004623 platelet-rich plasma Anatomy 0.000 description 5
- 229940107685 reopro Drugs 0.000 description 5
- 210000000329 smooth muscle myocyte Anatomy 0.000 description 5
- 230000009870 specific binding Effects 0.000 description 5
- JKMHFZQWWAIEOD-UHFFFAOYSA-N 2-[4-(2-hydroxyethyl)piperazin-1-yl]ethanesulfonic acid Chemical compound OCC[NH+]1CCN(CCS([O-])(=O)=O)CC1 JKMHFZQWWAIEOD-UHFFFAOYSA-N 0.000 description 4
- UXVMQQNJUSDDNG-UHFFFAOYSA-L Calcium chloride Chemical compound [Cl-].[Cl-].[Ca+2] UXVMQQNJUSDDNG-UHFFFAOYSA-L 0.000 description 4
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 4
- 102000010834 Extracellular Matrix Proteins Human genes 0.000 description 4
- 108010037362 Extracellular Matrix Proteins Proteins 0.000 description 4
- 102100034343 Integrase Human genes 0.000 description 4
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 4
- 108010092799 RNA-directed DNA polymerase Proteins 0.000 description 4
- PXIPVTKHYLBLMZ-UHFFFAOYSA-N Sodium azide Chemical compound [Na+].[N-]=[N+]=[N-] PXIPVTKHYLBLMZ-UHFFFAOYSA-N 0.000 description 4
- 238000010171 animal model Methods 0.000 description 4
- 239000003146 anticoagulant agent Substances 0.000 description 4
- 108010072041 arginyl-glycyl-aspartic acid Proteins 0.000 description 4
- 210000004369 blood Anatomy 0.000 description 4
- 239000008280 blood Substances 0.000 description 4
- RYYVLZVUVIJVGH-UHFFFAOYSA-N caffeine Chemical compound CN1C(=O)N(C)C(=O)C2=C1N=CN2C RYYVLZVUVIJVGH-UHFFFAOYSA-N 0.000 description 4
- 239000001110 calcium chloride Substances 0.000 description 4
- 229910001628 calcium chloride Inorganic materials 0.000 description 4
- 235000011148 calcium chloride Nutrition 0.000 description 4
- 238000005119 centrifugation Methods 0.000 description 4
- 239000003795 chemical substances by application Substances 0.000 description 4
- 108010045325 cyclic arginine-glycine-aspartic acid peptide Proteins 0.000 description 4
- 238000001514 detection method Methods 0.000 description 4
- 238000011161 development Methods 0.000 description 4
- 230000018109 developmental process Effects 0.000 description 4
- 238000010790 dilution Methods 0.000 description 4
- 239000012895 dilution Substances 0.000 description 4
- 210000002744 extracellular matrix Anatomy 0.000 description 4
- 230000012010 growth Effects 0.000 description 4
- 238000011065 in-situ storage Methods 0.000 description 4
- 238000010348 incorporation Methods 0.000 description 4
- 230000003834 intracellular effect Effects 0.000 description 4
- 230000003447 ipsilateral effect Effects 0.000 description 4
- 238000002372 labelling Methods 0.000 description 4
- 108010082117 matrigel Proteins 0.000 description 4
- 210000002997 osteoclast Anatomy 0.000 description 4
- 239000000126 substance Substances 0.000 description 4
- 238000012360 testing method Methods 0.000 description 4
- ZFXYFBGIUFBOJW-UHFFFAOYSA-N theophylline Chemical compound O=C1N(C)C(=O)N(C)C2=C1NC=N2 ZFXYFBGIUFBOJW-UHFFFAOYSA-N 0.000 description 4
- 210000004881 tumor cell Anatomy 0.000 description 4
- WXPZDDCNKXMOMC-AVGNSLFASA-N (2s)-1-[(2s)-2-[[(2s)-1-(2-aminoacetyl)pyrrolidine-2-carbonyl]amino]-5-(diaminomethylideneamino)pentanoyl]pyrrolidine-2-carboxylic acid Chemical compound NCC(=O)N1CCC[C@H]1C(=O)N[C@@H](CCCNC(N)=N)C(=O)N1[C@H](C(O)=O)CCC1 WXPZDDCNKXMOMC-AVGNSLFASA-N 0.000 description 3
- XZKIHKMTEMTJQX-UHFFFAOYSA-N 4-Nitrophenyl Phosphate Chemical compound OP(O)(=O)OC1=CC=C([N+]([O-])=O)C=C1 XZKIHKMTEMTJQX-UHFFFAOYSA-N 0.000 description 3
- 206010003210 Arteriosclerosis Diseases 0.000 description 3
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 3
- LCGLNKUTAGEVQW-UHFFFAOYSA-N Dimethyl ether Chemical compound COC LCGLNKUTAGEVQW-UHFFFAOYSA-N 0.000 description 3
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 3
- 102000004190 Enzymes Human genes 0.000 description 3
- 108090000790 Enzymes Proteins 0.000 description 3
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 3
- 108060003393 Granulin Proteins 0.000 description 3
- 241000282412 Homo Species 0.000 description 3
- 206010020772 Hypertension Diseases 0.000 description 3
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 3
- BKAYIFDRRZZKNF-VIFPVBQESA-N N-acetylcarnosine Chemical compound CC(=O)NCCC(=O)N[C@H](C(O)=O)CC1=CN=CN1 BKAYIFDRRZZKNF-VIFPVBQESA-N 0.000 description 3
- 102000004264 Osteopontin Human genes 0.000 description 3
- 108010081689 Osteopontin Proteins 0.000 description 3
- 229910019142 PO4 Chemical group 0.000 description 3
- 102000004160 Phosphoric Monoester Hydrolases Human genes 0.000 description 3
- 108090000608 Phosphoric Monoester Hydrolases Proteins 0.000 description 3
- 102000003990 Urokinase-type plasminogen activator Human genes 0.000 description 3
- 108090000435 Urokinase-type plasminogen activator Proteins 0.000 description 3
- 238000009825 accumulation Methods 0.000 description 3
- 230000009471 action Effects 0.000 description 3
- 239000000654 additive Substances 0.000 description 3
- 230000000996 additive effect Effects 0.000 description 3
- 238000005904 alkaline hydrolysis reaction Methods 0.000 description 3
- -1 amino, carboxyl Chemical group 0.000 description 3
- 208000011775 arteriosclerosis disease Diseases 0.000 description 3
- 230000017531 blood circulation Effects 0.000 description 3
- 210000000988 bone and bone Anatomy 0.000 description 3
- 239000011575 calcium Substances 0.000 description 3
- 229910052791 calcium Inorganic materials 0.000 description 3
- 150000001768 cations Chemical class 0.000 description 3
- 238000010367 cloning Methods 0.000 description 3
- 230000035602 clotting Effects 0.000 description 3
- 239000011248 coating agent Substances 0.000 description 3
- 238000000576 coating method Methods 0.000 description 3
- 239000002299 complementary DNA Substances 0.000 description 3
- 238000009826 distribution Methods 0.000 description 3
- 229940088598 enzyme Drugs 0.000 description 3
- 238000001502 gel electrophoresis Methods 0.000 description 3
- 108010017446 glycyl-prolyl-arginyl-proline Proteins 0.000 description 3
- 239000012216 imaging agent Substances 0.000 description 3
- 238000003384 imaging method Methods 0.000 description 3
- 210000004731 jugular vein Anatomy 0.000 description 3
- 210000003734 kidney Anatomy 0.000 description 3
- 239000011159 matrix material Substances 0.000 description 3
- 210000004379 membrane Anatomy 0.000 description 3
- 239000012528 membrane Substances 0.000 description 3
- 239000010452 phosphate Chemical group 0.000 description 3
- 239000013641 positive control Substances 0.000 description 3
- 102000004196 processed proteins & peptides Human genes 0.000 description 3
- 230000002829 reductive effect Effects 0.000 description 3
- 230000010076 replication Effects 0.000 description 3
- 230000011664 signaling Effects 0.000 description 3
- 150000003384 small molecules Chemical class 0.000 description 3
- 230000004936 stimulating effect Effects 0.000 description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 3
- 0 *CC(*)C(*)C(*)*C(*)C(*)C(*)C(*)C(*)(C(C(*)C(C(C(*)C*)N=O)O)O)N=O Chemical compound *CC(*)C(*)C(*)*C(*)C(*)C(*)C(*)C(*)(C(C(*)C(C(C(*)C*)N=O)O)O)N=O 0.000 description 2
- RGNOTKMIMZMNRX-XVFCMESISA-N 2-amino-1-[(2r,3r,4s,5r)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]pyrimidin-4-one Chemical compound NC1=NC(=O)C=CN1[C@H]1[C@H](O)[C@H](O)[C@@H](CO)O1 RGNOTKMIMZMNRX-XVFCMESISA-N 0.000 description 2
- QKNYBSVHEMOAJP-UHFFFAOYSA-N 2-amino-2-(hydroxymethyl)propane-1,3-diol;hydron;chloride Chemical compound Cl.OCC(N)(CO)CO QKNYBSVHEMOAJP-UHFFFAOYSA-N 0.000 description 2
- ZLOIGESWDJYCTF-UHFFFAOYSA-N 4-Thiouridine Natural products OC1C(O)C(CO)OC1N1C(=O)NC(=S)C=C1 ZLOIGESWDJYCTF-UHFFFAOYSA-N 0.000 description 2
- ZLOIGESWDJYCTF-XVFCMESISA-N 4-thiouridine Chemical class O[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1N1C(=O)NC(=S)C=C1 ZLOIGESWDJYCTF-XVFCMESISA-N 0.000 description 2
- KSNXJLQDQOIRIP-UHFFFAOYSA-N 5-iodouracil Chemical compound IC1=CNC(=O)NC1=O KSNXJLQDQOIRIP-UHFFFAOYSA-N 0.000 description 2
- 102000002260 Alkaline Phosphatase Human genes 0.000 description 2
- 108020004774 Alkaline Phosphatase Proteins 0.000 description 2
- 206010002388 Angina unstable Diseases 0.000 description 2
- 241000713838 Avian myeloblastosis virus Species 0.000 description 2
- 102000004506 Blood Proteins Human genes 0.000 description 2
- 108010017384 Blood Proteins Proteins 0.000 description 2
- 208000006386 Bone Resorption Diseases 0.000 description 2
- 206010006187 Breast cancer Diseases 0.000 description 2
- 208000026310 Breast neoplasm Diseases 0.000 description 2
- 208000005623 Carcinogenesis Diseases 0.000 description 2
- 108010035532 Collagen Proteins 0.000 description 2
- 102000008186 Collagen Human genes 0.000 description 2
- MIKUYHXYGGJMLM-GIMIYPNGSA-N Crotonoside Natural products C1=NC2=C(N)NC(=O)N=C2N1[C@H]1O[C@@H](CO)[C@H](O)[C@@H]1O MIKUYHXYGGJMLM-GIMIYPNGSA-N 0.000 description 2
- NYHBQMYGNKIUIF-UHFFFAOYSA-N D-guanosine Natural products C1=2NC(N)=NC(=O)C=2N=CN1C1OC(CO)C(O)C1O NYHBQMYGNKIUIF-UHFFFAOYSA-N 0.000 description 2
- HMFHBZSHGGEWLO-SOOFDHNKSA-N D-ribofuranose Chemical group OC[C@H]1OC(O)[C@H](O)[C@@H]1O HMFHBZSHGGEWLO-SOOFDHNKSA-N 0.000 description 2
- 108010014303 DNA-directed DNA polymerase Proteins 0.000 description 2
- 102000016928 DNA-directed DNA polymerase Human genes 0.000 description 2
- 108010056764 Eptifibatide Proteins 0.000 description 2
- 206010063560 Excessive granulation tissue Diseases 0.000 description 2
- 108010067306 Fibronectins Proteins 0.000 description 2
- 102000016359 Fibronectins Human genes 0.000 description 2
- 239000007995 HEPES buffer Substances 0.000 description 2
- 208000032843 Hemorrhage Diseases 0.000 description 2
- 108010093488 His-His-His-His-His-His Proteins 0.000 description 2
- 101000898034 Homo sapiens Hepatocyte growth factor Proteins 0.000 description 2
- 108700020121 Human Immunodeficiency Virus-1 rev Proteins 0.000 description 2
- 102000001706 Immunoglobulin Fab Fragments Human genes 0.000 description 2
- 108010054477 Immunoglobulin Fab Fragments Proteins 0.000 description 2
- LPHGQDQBBGAPDZ-UHFFFAOYSA-N Isocaffeine Natural products CN1C(=O)N(C)C(=O)C2=C1N(C)C=N2 LPHGQDQBBGAPDZ-UHFFFAOYSA-N 0.000 description 2
- 206010058467 Lung neoplasm malignant Diseases 0.000 description 2
- 239000007987 MES buffer Substances 0.000 description 2
- 241001465754 Metazoa Species 0.000 description 2
- 241000699666 Mus <mouse, genus> Species 0.000 description 2
- 208000022873 Ocular disease Diseases 0.000 description 2
- 102100023472 P-selectin Human genes 0.000 description 2
- 108091005804 Peptidases Proteins 0.000 description 2
- 102000035195 Peptidases Human genes 0.000 description 2
- 206010035226 Plasma cell myeloma Diseases 0.000 description 2
- 239000004365 Protease Substances 0.000 description 2
- 108010076504 Protein Sorting Signals Proteins 0.000 description 2
- 108090000412 Protein-Tyrosine Kinases Proteins 0.000 description 2
- 102000004022 Protein-Tyrosine Kinases Human genes 0.000 description 2
- CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 description 2
- 238000002123 RNA extraction Methods 0.000 description 2
- PYMYPHUHKUWMLA-LMVFSUKVSA-N Ribose Natural products OC[C@@H](O)[C@@H](O)[C@@H](O)C=O PYMYPHUHKUWMLA-LMVFSUKVSA-N 0.000 description 2
- 101710137500 T7 RNA polymerase Proteins 0.000 description 2
- IQFYYKKMVGJFEH-XLPZGREQSA-N Thymidine Chemical compound O=C1NC(=O)C(C)=CN1[C@@H]1O[C@H](CO)[C@@H](O)C1 IQFYYKKMVGJFEH-XLPZGREQSA-N 0.000 description 2
- 208000007814 Unstable Angina Diseases 0.000 description 2
- 241000700605 Viruses Species 0.000 description 2
- 229960000446 abciximab Drugs 0.000 description 2
- 239000000853 adhesive Substances 0.000 description 2
- 230000001070 adhesive effect Effects 0.000 description 2
- 229940000279 aggrastat Drugs 0.000 description 2
- HMFHBZSHGGEWLO-UHFFFAOYSA-N alpha-D-Furanose-Ribose Natural products OCC1OC(O)C(O)C1O HMFHBZSHGGEWLO-UHFFFAOYSA-N 0.000 description 2
- 150000001412 amines Chemical class 0.000 description 2
- 239000002870 angiogenesis inducing agent Substances 0.000 description 2
- 239000005557 antagonist Substances 0.000 description 2
- 229940127219 anticoagulant drug Drugs 0.000 description 2
- 230000006907 apoptotic process Effects 0.000 description 2
- 238000013459 approach Methods 0.000 description 2
- 230000008901 benefit Effects 0.000 description 2
- 230000002051 biphasic effect Effects 0.000 description 2
- 208000034158 bleeding Diseases 0.000 description 2
- 230000000740 bleeding effect Effects 0.000 description 2
- 230000036770 blood supply Effects 0.000 description 2
- 210000004204 blood vessel Anatomy 0.000 description 2
- 210000001124 body fluid Anatomy 0.000 description 2
- 230000024279 bone resorption Effects 0.000 description 2
- 210000004556 brain Anatomy 0.000 description 2
- 210000000481 breast Anatomy 0.000 description 2
- 239000007975 buffered saline Substances 0.000 description 2
- 229960001948 caffeine Drugs 0.000 description 2
- VJEONQKOZGKCAK-UHFFFAOYSA-N caffeine Natural products CN1C(=O)N(C)C(=O)C2=C1C=CN2C VJEONQKOZGKCAK-UHFFFAOYSA-N 0.000 description 2
- 230000036952 cancer formation Effects 0.000 description 2
- 150000001720 carbohydrates Chemical class 0.000 description 2
- 235000014633 carbohydrates Nutrition 0.000 description 2
- 231100000504 carcinogenesis Toxicity 0.000 description 2
- 230000004663 cell proliferation Effects 0.000 description 2
- 230000001413 cellular effect Effects 0.000 description 2
- 230000008859 change Effects 0.000 description 2
- 125000003636 chemical group Chemical group 0.000 description 2
- 238000007385 chemical modification Methods 0.000 description 2
- 229920001436 collagen Polymers 0.000 description 2
- 230000000295 complement effect Effects 0.000 description 2
- 230000021615 conjugation Effects 0.000 description 2
- 230000001276 controlling effect Effects 0.000 description 2
- 230000009260 cross reactivity Effects 0.000 description 2
- 239000013078 crystal Substances 0.000 description 2
- 125000004122 cyclic group Chemical group 0.000 description 2
- 230000001351 cycling effect Effects 0.000 description 2
- 230000034994 death Effects 0.000 description 2
- 239000003599 detergent Substances 0.000 description 2
- 238000006073 displacement reaction Methods 0.000 description 2
- 229940079593 drug Drugs 0.000 description 2
- 230000009881 electrostatic interaction Effects 0.000 description 2
- 230000003511 endothelial effect Effects 0.000 description 2
- CZKPOZZJODAYPZ-LROMGURASA-N eptifibatide Chemical compound N1C(=O)[C@H](CC(O)=O)NC(=O)CNC(=O)[C@H](CCCCNC(=N)N)NC(=O)CCSSC[C@@H](C(N)=O)NC(=O)[C@@H]2CCCN2C(=O)[C@@H]1CC1=CNC2=CC=CC=C12 CZKPOZZJODAYPZ-LROMGURASA-N 0.000 description 2
- 230000002349 favourable effect Effects 0.000 description 2
- 238000001914 filtration Methods 0.000 description 2
- GNBHRKFJIUUOQI-UHFFFAOYSA-N fluorescein Chemical compound O1C(=O)C2=CC=CC=C2C21C1=CC=C(O)C=C1OC1=CC(O)=CC=C21 GNBHRKFJIUUOQI-UHFFFAOYSA-N 0.000 description 2
- 238000001943 fluorescence-activated cell sorting Methods 0.000 description 2
- 210000000232 gallbladder Anatomy 0.000 description 2
- 150000004676 glycans Chemical class 0.000 description 2
- 210000001126 granulation tissue Anatomy 0.000 description 2
- 229940029575 guanosine Drugs 0.000 description 2
- RQFCJASXJCIDSX-UUOKFMHZSA-N guanosine 5'-monophosphate Chemical class C1=2NC(N)=NC(=O)C=2N=CN1[C@@H]1O[C@H](COP(O)(O)=O)[C@@H](O)[C@H]1O RQFCJASXJCIDSX-UUOKFMHZSA-N 0.000 description 2
- 238000010438 heat treatment Methods 0.000 description 2
- 102000057308 human HGF Human genes 0.000 description 2
- 229910052739 hydrogen Inorganic materials 0.000 description 2
- 239000001257 hydrogen Substances 0.000 description 2
- 238000002347 injection Methods 0.000 description 2
- 239000007924 injection Substances 0.000 description 2
- 229940056984 integrilin Drugs 0.000 description 2
- 201000004332 intermediate coronary syndrome Diseases 0.000 description 2
- PHTQWCKDNZKARW-UHFFFAOYSA-N isoamylol Chemical compound CC(C)CCO PHTQWCKDNZKARW-UHFFFAOYSA-N 0.000 description 2
- 230000003902 lesion Effects 0.000 description 2
- 230000000670 limiting effect Effects 0.000 description 2
- 210000004185 liver Anatomy 0.000 description 2
- 230000007774 longterm Effects 0.000 description 2
- 210000004072 lung Anatomy 0.000 description 2
- 201000005296 lung carcinoma Diseases 0.000 description 2
- 230000007246 mechanism Effects 0.000 description 2
- 230000001394 metastastic effect Effects 0.000 description 2
- 206010061289 metastatic neoplasm Diseases 0.000 description 2
- 230000011987 methylation Effects 0.000 description 2
- 238000007069 methylation reaction Methods 0.000 description 2
- 238000010232 migration assay Methods 0.000 description 2
- 239000000178 monomer Substances 0.000 description 2
- 201000000050 myeloid neoplasm Diseases 0.000 description 2
- 239000013642 negative control Substances 0.000 description 2
- 230000014399 negative regulation of angiogenesis Effects 0.000 description 2
- 230000000269 nucleophilic effect Effects 0.000 description 2
- 125000003835 nucleoside group Chemical group 0.000 description 2
- 235000015097 nutrients Nutrition 0.000 description 2
- 210000001672 ovary Anatomy 0.000 description 2
- 210000000496 pancreas Anatomy 0.000 description 2
- 239000002245 particle Substances 0.000 description 2
- 230000007170 pathology Effects 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical group [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 2
- 239000002953 phosphate buffered saline Substances 0.000 description 2
- 230000035479 physiological effects, processes and functions Effects 0.000 description 2
- 210000002826 placenta Anatomy 0.000 description 2
- 210000002381 plasma Anatomy 0.000 description 2
- 229920001282 polysaccharide Polymers 0.000 description 2
- 239000005017 polysaccharide Substances 0.000 description 2
- 230000003389 potentiating effect Effects 0.000 description 2
- 238000002360 preparation method Methods 0.000 description 2
- 239000002987 primer (paints) Substances 0.000 description 2
- 230000002062 proliferating effect Effects 0.000 description 2
- 239000011541 reaction mixture Substances 0.000 description 2
- 230000009467 reduction Effects 0.000 description 2
- 238000011160 research Methods 0.000 description 2
- 238000010839 reverse transcription Methods 0.000 description 2
- 230000002441 reversible effect Effects 0.000 description 2
- 238000012163 sequencing technique Methods 0.000 description 2
- ATHGHQPFGPMSJY-UHFFFAOYSA-N spermidine Chemical compound NCCCCNCCCN ATHGHQPFGPMSJY-UHFFFAOYSA-N 0.000 description 2
- 239000000758 substrate Substances 0.000 description 2
- 230000002195 synergetic effect Effects 0.000 description 2
- 238000003786 synthesis reaction Methods 0.000 description 2
- 230000002194 synthesizing effect Effects 0.000 description 2
- 229960000278 theophylline Drugs 0.000 description 2
- 238000002560 therapeutic procedure Methods 0.000 description 2
- 230000008719 thickening Effects 0.000 description 2
- 230000002537 thrombolytic effect Effects 0.000 description 2
- COKMIXFXJJXBQG-NRFANRHFSA-N tirofiban Chemical compound C1=CC(C[C@H](NS(=O)(=O)CCCC)C(O)=O)=CC=C1OCCCCC1CCNCC1 COKMIXFXJJXBQG-NRFANRHFSA-N 0.000 description 2
- 238000000954 titration curve Methods 0.000 description 2
- 230000005760 tumorsuppression Effects 0.000 description 2
- 210000003606 umbilical vein Anatomy 0.000 description 2
- 210000003932 urinary bladder Anatomy 0.000 description 2
- 230000002792 vascular Effects 0.000 description 2
- 210000005166 vasculature Anatomy 0.000 description 2
- 230000007998 vessel formation Effects 0.000 description 2
- 108010047303 von Willebrand Factor Proteins 0.000 description 2
- 102100036537 von Willebrand factor Human genes 0.000 description 2
- 229960001134 von willebrand factor Drugs 0.000 description 2
- 238000005406 washing Methods 0.000 description 2
- 230000029663 wound healing Effects 0.000 description 2
- UCTWMZQNUQWSLP-VIFPVBQESA-N (R)-adrenaline Chemical compound CNC[C@H](O)C1=CC=C(O)C(O)=C1 UCTWMZQNUQWSLP-VIFPVBQESA-N 0.000 description 1
- 229930182837 (R)-adrenaline Natural products 0.000 description 1
- BMVXCPBXGZKUPN-UHFFFAOYSA-N 1-hexanamine Chemical compound CCCCCCN BMVXCPBXGZKUPN-UHFFFAOYSA-N 0.000 description 1
- XLBBKEHLEPNMMF-SSUNCQRMSA-N 129038-42-2 Chemical compound C([C@@H](C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCC(O)=O)C(=O)NCC(=O)N[C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CS)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)NCC(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N[C@@H](CS)C(=O)N[C@@H](CC(N)=O)C(=O)NCC(=O)N[C@@H](CCCCN)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CS)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CS)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(N)=O)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CC=1NC=NC=1)C(=O)N[C@@H](CCCCN)C(=O)NCC(=O)N1[C@@H](CCC1)C(=O)N[C@@H](C)C(=O)N[C@@H]([C@@H](C)O)C(O)=O)[C@@H](C)O)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CS)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CS)NC(=O)[C@H](CS)NC(=O)[C@H]1N(CCC1)C(=O)CNC(=O)[C@H](CO)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CS)NC(=O)[C@@H](N)CCC(O)=O)C1=CC=CC=C1 XLBBKEHLEPNMMF-SSUNCQRMSA-N 0.000 description 1
- SXGZJKUKBWWHRA-UHFFFAOYSA-N 2-(N-morpholiniumyl)ethanesulfonate Chemical compound [O-]S(=O)(=O)CC[NH+]1CCOCC1 SXGZJKUKBWWHRA-UHFFFAOYSA-N 0.000 description 1
- 125000001731 2-cyanoethyl group Chemical group [H]C([H])(*)C([H])([H])C#N 0.000 description 1
- LQLQRFGHAALLLE-UHFFFAOYSA-N 5-bromouracil Chemical class BrC1=CNC(=O)NC1=O LQLQRFGHAALLLE-UHFFFAOYSA-N 0.000 description 1
- HWRFTOWHSBECMR-UHFFFAOYSA-N 6-n-[(4-aminophenyl)methyl]-2-n-[[3-(trifluoromethyl)phenyl]methyl]-7h-purine-2,6-diamine Chemical compound C1=CC(N)=CC=C1CNC1=NC(NCC=2C=C(C=CC=2)C(F)(F)F)=NC2=C1NC=N2 HWRFTOWHSBECMR-UHFFFAOYSA-N 0.000 description 1
- 102000007469 Actins Human genes 0.000 description 1
- 108010085238 Actins Proteins 0.000 description 1
- 102000006306 Antigen Receptors Human genes 0.000 description 1
- 108010083359 Antigen Receptors Proteins 0.000 description 1
- 206010003162 Arterial injury Diseases 0.000 description 1
- 208000037260 Atherosclerotic Plaque Diseases 0.000 description 1
- 206010065687 Bone loss Diseases 0.000 description 1
- 208000018084 Bone neoplasm Diseases 0.000 description 1
- 201000006474 Brain Ischemia Diseases 0.000 description 1
- 208000003174 Brain Neoplasms Diseases 0.000 description 1
- 102000005701 Calcium-Binding Proteins Human genes 0.000 description 1
- 108010045403 Calcium-Binding Proteins Proteins 0.000 description 1
- 208000024172 Cardiovascular disease Diseases 0.000 description 1
- 241000282693 Cercopithecidae Species 0.000 description 1
- 206010008120 Cerebral ischaemia Diseases 0.000 description 1
- KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 description 1
- 206010053567 Coagulopathies Diseases 0.000 description 1
- 102000012422 Collagen Type I Human genes 0.000 description 1
- 108010022452 Collagen Type I Proteins 0.000 description 1
- 206010010144 Completed suicide Diseases 0.000 description 1
- 108020001019 DNA Primers Proteins 0.000 description 1
- 239000003155 DNA primer Substances 0.000 description 1
- 238000001712 DNA sequencing Methods 0.000 description 1
- 102000004163 DNA-directed RNA polymerases Human genes 0.000 description 1
- 108090000626 DNA-directed RNA polymerases Proteins 0.000 description 1
- 102000004533 Endonucleases Human genes 0.000 description 1
- 108010042407 Endonucleases Proteins 0.000 description 1
- 108060002716 Exonuclease Proteins 0.000 description 1
- 108050001049 Extracellular proteins Proteins 0.000 description 1
- 206010015866 Extravasation Diseases 0.000 description 1
- 108010074860 Factor Xa Proteins 0.000 description 1
- 108010012088 Fibrinogen Receptors Proteins 0.000 description 1
- 229920001917 Ficoll Polymers 0.000 description 1
- QJXJXBXFIOTYHB-UUOKFMHZSA-N GDP-beta-S Chemical compound C1=NC=2C(=O)NC(N)=NC=2N1[C@@H]1O[C@H](COP(O)(=O)OP(O)(O)=S)[C@@H](O)[C@H]1O QJXJXBXFIOTYHB-UUOKFMHZSA-N 0.000 description 1
- GYHNNYVSQQEPJS-UHFFFAOYSA-N Gallium Chemical compound [Ga] GYHNNYVSQQEPJS-UHFFFAOYSA-N 0.000 description 1
- 229920002527 Glycogen Polymers 0.000 description 1
- 102000003886 Glycoproteins Human genes 0.000 description 1
- 108090000288 Glycoproteins Proteins 0.000 description 1
- 102000027430 HGF receptors Human genes 0.000 description 1
- 108091008603 HGF receptors Proteins 0.000 description 1
- 101001015004 Homo sapiens Integrin beta-3 Proteins 0.000 description 1
- 101000622137 Homo sapiens P-selectin Proteins 0.000 description 1
- 102000008100 Human Serum Albumin Human genes 0.000 description 1
- 108091006905 Human Serum Albumin Proteins 0.000 description 1
- 108010058683 Immobilized Proteins Proteins 0.000 description 1
- 238000012404 In vitro experiment Methods 0.000 description 1
- 206010061218 Inflammation Diseases 0.000 description 1
- 102100032999 Integrin beta-3 Human genes 0.000 description 1
- 208000007766 Kaposi sarcoma Diseases 0.000 description 1
- 241000989747 Maba Species 0.000 description 1
- 229910021380 Manganese Chloride Inorganic materials 0.000 description 1
- GLFNIEUTAYBVOC-UHFFFAOYSA-L Manganese chloride Chemical compound Cl[Mn]Cl GLFNIEUTAYBVOC-UHFFFAOYSA-L 0.000 description 1
- 108010052285 Membrane Proteins Proteins 0.000 description 1
- 102000018697 Membrane Proteins Human genes 0.000 description 1
- 206010027458 Metastases to lung Diseases 0.000 description 1
- 241000699660 Mus musculus Species 0.000 description 1
- 241000699670 Mus sp. Species 0.000 description 1
- 208000034827 Neointima Diseases 0.000 description 1
- 206010061309 Neoplasm progression Diseases 0.000 description 1
- 108091028043 Nucleic acid sequence Proteins 0.000 description 1
- 239000004677 Nylon Substances 0.000 description 1
- 108700020796 Oncogene Proteins 0.000 description 1
- 108010035766 P-Selectin Proteins 0.000 description 1
- 108091000080 Phosphotransferase Proteins 0.000 description 1
- 102000013566 Plasminogen Human genes 0.000 description 1
- 108010051456 Plasminogen Proteins 0.000 description 1
- 239000002202 Polyethylene glycol Substances 0.000 description 1
- 108010021757 Polynucleotide 5'-Hydroxyl-Kinase Proteins 0.000 description 1
- 102000008422 Polynucleotide 5'-hydroxyl-kinase Human genes 0.000 description 1
- 229920001213 Polysorbate 20 Polymers 0.000 description 1
- 241001415846 Procellariidae Species 0.000 description 1
- 108010001267 Protein Subunits Proteins 0.000 description 1
- 101000781681 Protobothrops flavoviridis Disintegrin triflavin Proteins 0.000 description 1
- 108091008103 RNA aptamers Proteins 0.000 description 1
- 230000004570 RNA-binding Effects 0.000 description 1
- 230000010799 Receptor Interactions Effects 0.000 description 1
- 206010038389 Renal cancer Diseases 0.000 description 1
- 208000006265 Renal cell carcinoma Diseases 0.000 description 1
- 206010038563 Reocclusion Diseases 0.000 description 1
- 206010063837 Reperfusion injury Diseases 0.000 description 1
- 241000219061 Rheum Species 0.000 description 1
- 238000012300 Sequence Analysis Methods 0.000 description 1
- MTCFGRXMJLQNBG-UHFFFAOYSA-N Serine Natural products OCC(N)C(O)=O MTCFGRXMJLQNBG-UHFFFAOYSA-N 0.000 description 1
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 1
- 108010090804 Streptavidin Proteins 0.000 description 1
- 241000973887 Takayama Species 0.000 description 1
- 244000269722 Thea sinensis Species 0.000 description 1
- 108060008245 Thrombospondin Proteins 0.000 description 1
- 102000002938 Thrombospondin Human genes 0.000 description 1
- 240000001085 Trapa natans Species 0.000 description 1
- 239000013504 Triton X-100 Substances 0.000 description 1
- 229920004890 Triton X-100 Polymers 0.000 description 1
- 208000024248 Vascular System injury Diseases 0.000 description 1
- 208000012339 Vascular injury Diseases 0.000 description 1
- 206010052428 Wound Diseases 0.000 description 1
- 208000027418 Wounds and injury Diseases 0.000 description 1
- 230000001594 aberrant effect Effects 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 230000003213 activating effect Effects 0.000 description 1
- 239000013543 active substance Substances 0.000 description 1
- 230000001154 acute effect Effects 0.000 description 1
- 210000000577 adipose tissue Anatomy 0.000 description 1
- 230000002411 adverse Effects 0.000 description 1
- 238000001042 affinity chromatography Methods 0.000 description 1
- 238000003314 affinity selection Methods 0.000 description 1
- 230000002776 aggregation Effects 0.000 description 1
- 238000004220 aggregation Methods 0.000 description 1
- 230000019552 anatomical structure morphogenesis Effects 0.000 description 1
- 229940121369 angiogenesis inhibitor Drugs 0.000 description 1
- 239000004037 angiogenesis inhibitor Substances 0.000 description 1
- 230000002491 angiogenic effect Effects 0.000 description 1
- 238000002399 angioplasty Methods 0.000 description 1
- 230000001640 apoptogenic effect Effects 0.000 description 1
- 210000001367 artery Anatomy 0.000 description 1
- 206010003246 arthritis Diseases 0.000 description 1
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
- 238000003705 background correction Methods 0.000 description 1
- 108091006004 biotinylated proteins Proteins 0.000 description 1
- 239000010839 body fluid Substances 0.000 description 1
- 201000008275 breast carcinoma Diseases 0.000 description 1
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 1
- 230000003197 catalytic effect Effects 0.000 description 1
- 230000001364 causal effect Effects 0.000 description 1
- 238000004113 cell culture Methods 0.000 description 1
- 230000009087 cell motility Effects 0.000 description 1
- 238000001516 cell proliferation assay Methods 0.000 description 1
- 230000033077 cellular process Effects 0.000 description 1
- 206010008118 cerebral infarction Diseases 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 210000000038 chest Anatomy 0.000 description 1
- 210000004978 chinese hamster ovary cell Anatomy 0.000 description 1
- 210000003711 chorioallantoic membrane Anatomy 0.000 description 1
- 238000004587 chromatography analysis Methods 0.000 description 1
- AMLYAMJWYAIXIA-VWNVYAMZSA-N cilengitide 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)N(C)C(=O)[C@H]1CC1=CC=CC=C1 AMLYAMJWYAIXIA-VWNVYAMZSA-N 0.000 description 1
- 229950009003 cilengitide Drugs 0.000 description 1
- 238000005352 clarification Methods 0.000 description 1
- 229960005188 collagen Drugs 0.000 description 1
- 229940096422 collagen type i Drugs 0.000 description 1
- 238000011284 combination treatment Methods 0.000 description 1
- 230000002301 combined effect Effects 0.000 description 1
- 238000004891 communication Methods 0.000 description 1
- 230000000052 comparative effect Effects 0.000 description 1
- 230000009850 completed effect Effects 0.000 description 1
- 108091036078 conserved sequence Proteins 0.000 description 1
- 210000004246 corpus luteum Anatomy 0.000 description 1
- 230000002596 correlated effect Effects 0.000 description 1
- 238000004132 cross linking Methods 0.000 description 1
- 230000003436 cytoskeletal effect Effects 0.000 description 1
- 210000004292 cytoskeleton Anatomy 0.000 description 1
- 230000006378 damage Effects 0.000 description 1
- 238000007405 data analysis Methods 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 239000005549 deoxyribonucleoside Substances 0.000 description 1
- 230000001419 dependent effect Effects 0.000 description 1
- 230000008021 deposition Effects 0.000 description 1
- 238000000502 dialysis Methods 0.000 description 1
- 239000000539 dimer Substances 0.000 description 1
- 238000006471 dimerization reaction Methods 0.000 description 1
- LOKCTEFSRHRXRJ-UHFFFAOYSA-I dipotassium trisodium dihydrogen phosphate hydrogen phosphate dichloride Chemical compound P(=O)(O)(O)[O-].[K+].P(=O)(O)([O-])[O-].[Na+].[Na+].[Cl-].[K+].[Cl-].[Na+] LOKCTEFSRHRXRJ-UHFFFAOYSA-I 0.000 description 1
- 230000007783 downstream signaling Effects 0.000 description 1
- 230000009977 dual effect Effects 0.000 description 1
- 239000000975 dye Substances 0.000 description 1
- 108010025752 echistatin Proteins 0.000 description 1
- 230000000431 effect on proliferation Effects 0.000 description 1
- 239000012149 elution buffer Substances 0.000 description 1
- 230000013020 embryo development Effects 0.000 description 1
- 210000004696 endometrium Anatomy 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 229960005139 epinephrine Drugs 0.000 description 1
- 238000011067 equilibration Methods 0.000 description 1
- 238000012869 ethanol precipitation Methods 0.000 description 1
- 102000013165 exonuclease Human genes 0.000 description 1
- 230000036251 extravasation Effects 0.000 description 1
- 230000001815 facial effect Effects 0.000 description 1
- 238000000684 flow cytometry Methods 0.000 description 1
- 210000001650 focal adhesion Anatomy 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 230000005714 functional activity Effects 0.000 description 1
- 125000000524 functional group Chemical group 0.000 description 1
- 229910052733 gallium Inorganic materials 0.000 description 1
- 210000004602 germ cell Anatomy 0.000 description 1
- 229910052732 germanium Inorganic materials 0.000 description 1
- GNPVGFCGXDBREM-UHFFFAOYSA-N germanium atom Chemical compound [Ge] GNPVGFCGXDBREM-UHFFFAOYSA-N 0.000 description 1
- 239000011521 glass Substances 0.000 description 1
- 229940096919 glycogen Drugs 0.000 description 1
- 230000013595 glycosylation Effects 0.000 description 1
- 238000006206 glycosylation reaction Methods 0.000 description 1
- PCHJSUWPFVWCPO-UHFFFAOYSA-N gold Chemical compound [Au] PCHJSUWPFVWCPO-UHFFFAOYSA-N 0.000 description 1
- 229910052737 gold Inorganic materials 0.000 description 1
- 239000010931 gold Substances 0.000 description 1
- 239000001963 growth medium Substances 0.000 description 1
- 235000013928 guanylic acid Nutrition 0.000 description 1
- 230000036541 health Effects 0.000 description 1
- 238000003505 heat denaturation Methods 0.000 description 1
- 210000003494 hepatocyte Anatomy 0.000 description 1
- 238000004128 high performance liquid chromatography Methods 0.000 description 1
- 239000005556 hormone Substances 0.000 description 1
- 229940088597 hormone Drugs 0.000 description 1
- 230000007062 hydrolysis Effects 0.000 description 1
- 238000006460 hydrolysis reaction Methods 0.000 description 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 1
- 206010020718 hyperplasia Diseases 0.000 description 1
- 230000002163 immunogen Effects 0.000 description 1
- 238000000099 in vitro assay Methods 0.000 description 1
- 230000004054 inflammatory process Effects 0.000 description 1
- 238000013383 initial experiment Methods 0.000 description 1
- 239000003999 initiator Substances 0.000 description 1
- 230000000977 initiatory effect Effects 0.000 description 1
- 208000014674 injury Diseases 0.000 description 1
- 238000007689 inspection Methods 0.000 description 1
- 230000004068 intracellular signaling Effects 0.000 description 1
- 230000009545 invasion Effects 0.000 description 1
- 208000028867 ischemia Diseases 0.000 description 1
- 150000002605 large molecules Chemical class 0.000 description 1
- 210000000265 leukocyte Anatomy 0.000 description 1
- 150000002634 lipophilic molecules Chemical class 0.000 description 1
- 239000011565 manganese chloride Substances 0.000 description 1
- 235000002867 manganese chloride Nutrition 0.000 description 1
- 239000003550 marker Substances 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 201000001441 melanoma Diseases 0.000 description 1
- 239000002207 metabolite Substances 0.000 description 1
- 208000037819 metastatic cancer Diseases 0.000 description 1
- 208000011575 metastatic malignant neoplasm Diseases 0.000 description 1
- 210000004925 microvascular endothelial cell Anatomy 0.000 description 1
- 230000001617 migratory effect Effects 0.000 description 1
- 230000003278 mimic effect Effects 0.000 description 1
- 239000003226 mitogen Substances 0.000 description 1
- 230000002297 mitogenic effect Effects 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 238000010369 molecular cloning Methods 0.000 description 1
- 230000035772 mutation Effects 0.000 description 1
- UATCLPJEZJKNHE-UHFFFAOYSA-N n-(3',6'-dihydroxy-3-oxospiro[2-benzofuran-1,9'-xanthene]-5-yl)-2-iodoacetamide Chemical compound O1C(=O)C2=CC(NC(=O)CI)=CC=C2C21C1=CC=C(O)C=C1OC1=CC(O)=CC=C21 UATCLPJEZJKNHE-UHFFFAOYSA-N 0.000 description 1
- 208000002154 non-small cell lung carcinoma Diseases 0.000 description 1
- 229920001778 nylon Polymers 0.000 description 1
- 230000000771 oncological effect Effects 0.000 description 1
- 229910052760 oxygen Inorganic materials 0.000 description 1
- 239000001301 oxygen Substances 0.000 description 1
- 239000006174 pH buffer Substances 0.000 description 1
- 230000000849 parathyroid Effects 0.000 description 1
- 230000036961 partial effect Effects 0.000 description 1
- 230000001575 pathological effect Effects 0.000 description 1
- 230000037361 pathway Effects 0.000 description 1
- 230000006320 pegylation Effects 0.000 description 1
- 239000008188 pellet Substances 0.000 description 1
- 150000004713 phosphodiesters Chemical group 0.000 description 1
- 102000020233 phosphotransferase Human genes 0.000 description 1
- 230000035790 physiological processes and functions Effects 0.000 description 1
- 239000013612 plasmid Substances 0.000 description 1
- 238000002264 polyacrylamide gel electrophoresis Methods 0.000 description 1
- 229920000642 polymer Polymers 0.000 description 1
- 102000040430 polynucleotide Human genes 0.000 description 1
- 108091033319 polynucleotide Proteins 0.000 description 1
- 239000002157 polynucleotide Substances 0.000 description 1
- 239000000256 polyoxyethylene sorbitan monolaurate Substances 0.000 description 1
- 235000010486 polyoxyethylene sorbitan monolaurate Nutrition 0.000 description 1
- 239000004810 polytetrafluoroethylene Substances 0.000 description 1
- 229920001343 polytetrafluoroethylene Polymers 0.000 description 1
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 1
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
- 239000011148 porous material Substances 0.000 description 1
- 230000035409 positive regulation of cell proliferation Effects 0.000 description 1
- 239000002243 precursor Substances 0.000 description 1
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 1
- 210000002307 prostate Anatomy 0.000 description 1
- 238000000159 protein binding assay Methods 0.000 description 1
- 108020001580 protein domains Proteins 0.000 description 1
- 230000009822 protein phosphorylation Effects 0.000 description 1
- 230000006337 proteolytic cleavage Effects 0.000 description 1
- 239000013014 purified material Substances 0.000 description 1
- 125000000561 purinyl group Chemical group N1=C(N=C2N=CNC2=C1)* 0.000 description 1
- 125000000714 pyrimidinyl group Chemical group 0.000 description 1
- 238000011555 rabbit model Methods 0.000 description 1
- 238000011084 recovery Methods 0.000 description 1
- 230000000306 recurrent effect Effects 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 201000010174 renal carcinoma Diseases 0.000 description 1
- 230000004044 response Effects 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 125000003607 serino group Chemical group [H]N([H])[C@]([H])(C(=O)[*])C(O[H])([H])[H] 0.000 description 1
- 210000002966 serum Anatomy 0.000 description 1
- 230000019491 signal transduction Effects 0.000 description 1
- 239000010703 silicon Substances 0.000 description 1
- 229910052710 silicon Inorganic materials 0.000 description 1
- 229910052709 silver Inorganic materials 0.000 description 1
- 239000004332 silver Substances 0.000 description 1
- 239000003998 snake venom Substances 0.000 description 1
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 238000002415 sodium dodecyl sulfate polyacrylamide gel electrophoresis Methods 0.000 description 1
- 239000012064 sodium phosphate buffer Substances 0.000 description 1
- 229940063673 spermidine Drugs 0.000 description 1
- 208000010110 spontaneous platelet aggregation Diseases 0.000 description 1
- 230000010473 stable expression Effects 0.000 description 1
- 238000010186 staining Methods 0.000 description 1
- 239000012536 storage buffer Substances 0.000 description 1
- 230000008093 supporting effect Effects 0.000 description 1
- 230000001629 suppression Effects 0.000 description 1
- 238000001356 surgical procedure Methods 0.000 description 1
- 230000004083 survival effect Effects 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 150000003573 thiols Chemical group 0.000 description 1
- RYYWUUFWQRZTIU-UHFFFAOYSA-K thiophosphate Chemical compound [O-]P([O-])([O-])=S RYYWUUFWQRZTIU-UHFFFAOYSA-K 0.000 description 1
- 238000004448 titration Methods 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 238000011830 transgenic mouse model Methods 0.000 description 1
- 230000007704 transition Effects 0.000 description 1
- 230000008733 trauma Effects 0.000 description 1
- 230000005747 tumor angiogenesis Effects 0.000 description 1
- 230000004614 tumor growth Effects 0.000 description 1
- 230000005751 tumor progression Effects 0.000 description 1
- 208000029729 tumor suppressor gene on chromosome 11 Diseases 0.000 description 1
- 231100000588 tumorigenic Toxicity 0.000 description 1
- 230000000381 tumorigenic effect Effects 0.000 description 1
- 239000011534 wash buffer Substances 0.000 description 1
- 230000037314 wound repair Effects 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
- C07H21/00—Compounds containing two or more mononucleotide units having separate phosphate or polyphosphate groups linked by saccharide radicals of nucleoside groups, e.g. nucleic acids
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P15/00—Drugs for genital or sexual disorders; Contraceptives
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
- A61P17/06—Antipsoriatics
-
- 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
- A61P19/08—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease
- A61P19/10—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease for osteoporosis
-
- 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
- A61P27/06—Antiglaucoma agents or miotics
-
- 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
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
- A61P7/02—Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors
-
- 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
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
- C12N15/09—Recombinant DNA-technology
- C12N15/11—DNA or RNA fragments; Modified forms thereof; Non-coding nucleic acids having a biological activity
- C12N15/115—Aptamers, i.e. nucleic acids binding a target molecule specifically and with high affinity without hybridising therewith ; Nucleic acids binding to non-nucleic acids, e.g. aptamers
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
- G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
- G01N33/53—Immunoassay; Biospecific binding assay; Materials therefor
- G01N33/5308—Immunoassay; Biospecific binding assay; Materials therefor for analytes not provided for elsewhere, e.g. nucleic acids, uric acid, worms, mites
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
- G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
- G01N33/74—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving hormones or other non-cytokine intercellular protein regulatory factors such as growth factors, including receptors to hormones and growth factors
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N2310/00—Structure or type of the nucleic acid
- C12N2310/10—Type of nucleic acid
- C12N2310/16—Aptamers
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N2310/00—Structure or type of the nucleic acid
- C12N2310/30—Chemical structure
- C12N2310/32—Chemical structure of the sugar
- C12N2310/322—2'-R Modification
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N2333/00—Assays involving biological materials from specific organisms or of a specific nature
- G01N2333/435—Assays involving biological materials from specific organisms or of a specific nature from animals; from humans
- G01N2333/475—Assays involving growth factors
- G01N2333/4753—Hepatocyte growth factor; Scatter factor; Tumor cytotoxic factor II
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Engineering & Computer Science (AREA)
- Chemical & Material Sciences (AREA)
- Molecular Biology (AREA)
- Organic Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Biomedical Technology (AREA)
- Medicinal Chemistry (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Biotechnology (AREA)
- Genetics & Genomics (AREA)
- Immunology (AREA)
- Biochemistry (AREA)
- Urology & Nephrology (AREA)
- Hematology (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Microbiology (AREA)
- Physics & Mathematics (AREA)
- Analytical Chemistry (AREA)
- General Engineering & Computer Science (AREA)
- Zoology (AREA)
- Pathology (AREA)
- Wood Science & Technology (AREA)
- General Physics & Mathematics (AREA)
- Cell Biology (AREA)
- Food Science & Technology (AREA)
- Endocrinology (AREA)
- Rheumatology (AREA)
- Physical Education & Sports Medicine (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Plant Pathology (AREA)
- Biophysics (AREA)
- Tropical Medicine & Parasitology (AREA)
Applications Claiming Priority (6)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US53642890A | 1990-06-11 | 1990-06-11 | |
| US09/364,539 US6344321B1 (en) | 1990-06-11 | 1999-07-29 | Nucleic acid ligands which bind to hepatocyte growth factor/scatter factor (HGF/SF) or its receptor c-met |
| US09/364,543 US6331394B1 (en) | 1991-06-10 | 1999-07-29 | Nucleic acid ligands to integrins |
| US09/364,539 | 1999-07-29 | ||
| US09/364,543 | 1999-07-29 | ||
| PCT/US2000/020139 WO2001009159A1 (en) | 1990-06-11 | 2000-07-24 | Nucleic acid ligands to hepatocyte growth factor/scatter factor (hgf/sf) or its receptor c-met and to integrins |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA2381004A1 true CA2381004A1 (en) | 2001-02-08 |
Family
ID=48986297
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA002381004A Abandoned CA2381004A1 (en) | 1990-06-11 | 2000-07-24 | Nucleic acid ligands to hepatocyte growth factor/scatter factor (hgf/sf) or its receptor c-met and to integrins |
Country Status (5)
| Country | Link |
|---|---|
| US (2) | US6344321B1 (https=) |
| EP (1) | EP1203007B1 (https=) |
| JP (1) | JP2003506024A (https=) |
| CA (1) | CA2381004A1 (https=) |
| WO (1) | WO2001009159A1 (https=) |
Families Citing this family (52)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20070166741A1 (en) * | 1998-12-14 | 2007-07-19 | Somalogic, Incorporated | Multiplexed analyses of test samples |
| CA2328356A1 (en) | 1999-12-22 | 2001-06-22 | Itty Atcravi | Recreational vehicles |
| US7645743B2 (en) * | 1999-12-22 | 2010-01-12 | Altermune, Llc | Chemically programmable immunity |
| US7312325B2 (en) * | 2000-09-26 | 2007-12-25 | Duke University | RNA aptamers and methods for identifying the same |
| US20030118585A1 (en) | 2001-10-17 | 2003-06-26 | Agy Therapeutics | Use of protein biomolecular targets in the treatment and visualization of brain tumors |
| US7300922B2 (en) | 2001-05-25 | 2007-11-27 | Duke University | Modulators of pharmacological agents |
| ES2386775T3 (es) | 2001-07-23 | 2012-08-30 | The Board Of Trustees Of The Leland Stanford Junior University | Procedimientos y composiciones para la inhibición mediada por ARNi de la expresión génica en mamíferos |
| US10590418B2 (en) | 2001-07-23 | 2020-03-17 | The Board Of Trustees Of The Leland Stanford Junior University | Methods and compositions for RNAi mediated inhibition of gene expression in mammals |
| US7435542B2 (en) * | 2002-06-24 | 2008-10-14 | Cornell Research Foundation, Inc. | Exhaustive selection of RNA aptamers against complex targets |
| US8853376B2 (en) | 2002-11-21 | 2014-10-07 | Archemix Llc | Stabilized aptamers to platelet derived growth factor and their use as oncology therapeutics |
| US7670631B2 (en) * | 2003-03-12 | 2010-03-02 | ALFAMA—Investigação e Desenvolvimento de Produtos Farmacêuticos, Lda. | Method for the prevention of malaria infection of humans by hepatocyte growth factor antagonists |
| EP2924119A1 (en) * | 2003-04-21 | 2015-09-30 | Archemix LLC | Stabilized aptamers to platelet derived growth factor and their use as oncology therapeutics |
| US7727969B2 (en) * | 2003-06-06 | 2010-06-01 | Massachusetts Institute Of Technology | Controlled release nanoparticle having bound oligonucleotide for targeted delivery |
| MXPA05013181A (es) * | 2003-06-06 | 2006-06-23 | Genentech Inc | Metodos y composiciones para modular hgf/met. |
| US20050123932A1 (en) * | 2003-12-09 | 2005-06-09 | Mekbib Astatke | Nucleic acid-chelating agent conjugates |
| US20060193821A1 (en) * | 2004-03-05 | 2006-08-31 | Diener John L | Aptamers to the human IL-12 cytokine family and their use as autoimmune disease therapeutics |
| AU2005220910A1 (en) * | 2004-03-05 | 2005-09-22 | Archemix Corp. | Aptamers to the human IL-12 cytokine family and their use as autoimmune disease therapeutics |
| WO2005110489A2 (en) * | 2004-04-13 | 2005-11-24 | (Osi) Eyetech, Inc. | Nucleic acid aptamers conjugated to high molecular weight steric groups |
| US7989613B2 (en) * | 2004-10-19 | 2011-08-02 | Texas Tech University | Inhibition of metallo-β-lactamase by RNA |
| CN101258241A (zh) * | 2005-07-05 | 2008-09-03 | 力博美科股份有限公司 | 与免疫球蛋白g结合的核酸及其利用方法 |
| US8637656B2 (en) * | 2005-07-05 | 2014-01-28 | Ribomic Inc. | Nucleic acid capable of binding to immunoglobulin G and use thereof |
| WO2007084886A2 (en) * | 2006-01-17 | 2007-07-26 | Somalogic, Incorporated | Multiplexed analyses of test samples |
| JP4698559B2 (ja) * | 2006-11-24 | 2011-06-08 | Ｎｅｃソフト株式会社 | ウサギ由来のＩｇＧ抗体に結合性を有する核酸分子 |
| US8975026B2 (en) | 2007-01-16 | 2015-03-10 | Somalogic, Inc. | Method for generating aptamers with improved off-rates |
| US7947447B2 (en) | 2007-01-16 | 2011-05-24 | Somalogic, Inc. | Method for generating aptamers with improved off-rates |
| US20110136099A1 (en) | 2007-01-16 | 2011-06-09 | Somalogic, Inc. | Multiplexed Analyses of Test Samples |
| WO2009111644A2 (en) * | 2008-03-05 | 2009-09-11 | The Regents Of The University Of Michigan | Compositions and methods for diagnosing and treating pancreatic cancer |
| CN104402998A (zh) | 2008-07-08 | 2015-03-11 | 昂考梅德药品有限公司 | 分离的抗体 |
| BRPI1011269A2 (pt) * | 2009-05-05 | 2016-09-27 | Altermune Technologies Llc | imunidade quimicamente programável |
| US8236570B2 (en) | 2009-11-03 | 2012-08-07 | Infoscitex | Methods for identifying nucleic acid ligands |
| US8841429B2 (en) | 2009-11-03 | 2014-09-23 | Vivonics, Inc. | Nucleic acid ligands against infectious prions |
| TWI535445B (zh) | 2010-01-12 | 2016-06-01 | 安可美德藥物股份有限公司 | Ｗｎｔ拮抗劑及治療和篩選方法 |
| WO2011099576A1 (ja) | 2010-02-12 | 2011-08-18 | 国立大学法人 東京大学 | Ｆｇｆ２に対するアプタマー及びその使用 |
| CN103037900B (zh) | 2010-02-24 | 2016-04-06 | 伊缪诺金公司 | 叶酸受体1抗体与免疫缀合物以及其用途 |
| SG183542A1 (en) | 2010-03-12 | 2012-10-30 | Immunogen Inc | Cd37-binding molecules and immunoconjugates thereof |
| JPWO2011125458A1 (ja) | 2010-04-02 | 2013-07-08 | 富士レビオ株式会社 | 抗癌剤の効果の診断用マーカー |
| WO2012014890A1 (ja) * | 2010-07-26 | 2012-02-02 | Ｎｅｃソフト株式会社 | ｃ－Ｍｅｔ結合核酸分子およびその用途 |
| WO2012019024A2 (en) | 2010-08-04 | 2012-02-09 | Immunogen, Inc. | Her3-binding molecules and immunoconjugates thereof |
| AU2011341018A1 (en) * | 2010-12-10 | 2013-07-25 | Merck Patent Gmbh | Aptamer labeled with F-19 nucleus for targeted molecular imaging by MRI |
| US20140301989A1 (en) * | 2011-06-17 | 2014-10-09 | Brian Johnstone | Methods for increasing the potency and efficacy of stem cells |
| GB201114662D0 (en) | 2011-08-24 | 2011-10-12 | Altermune Technologies Llc | Chemically programmable immunity |
| TWI649095B (zh) * | 2012-02-10 | 2019-02-01 | 捷百克股份有限公司 | 以非人類幹細胞之培養上清液為起始材料之化妝品或皮膚再生促進劑、及蛋白質之離子導入法 |
| US9863958B2 (en) * | 2012-04-18 | 2018-01-09 | Lemin Wang | Use of integrin beta subunits in the diagnosis of venous thromboembolism |
| CN104388422B (zh) * | 2014-10-24 | 2017-08-25 | 集美大学 | 寡核苷酸序列及其制备方法与应用 |
| WO2019033051A1 (en) * | 2017-08-11 | 2019-02-14 | City Of Hope | RNA APTAMERS AGAINST THE TRANSFERRIN RECEPTOR (TFR) |
| EP3924467A1 (en) | 2019-02-15 | 2021-12-22 | Editas Medicine, Inc. | Modified natural killer (nk) cells for immunotherapy |
| CN114853869B (zh) * | 2019-12-10 | 2023-12-26 | 湖南赛奥维生物技术有限公司 | 一种碱性成纤维细胞生长因子替代物及其组合物和应用 |
| EP4232567A1 (en) | 2020-10-26 | 2023-08-30 | Shoreline Biosciences, Inc. | Methods of inducing antibody-dependent cellular cytotoxicity (adcc) using modified natural killer (nk) cells |
| WO2022216524A1 (en) | 2021-04-07 | 2022-10-13 | Century Therapeutics, Inc. | Combined artificial cell death/reporter system polypeptide for chimeric antigen receptor cell and uses thereof |
| MX2023011927A (es) | 2021-04-07 | 2023-10-23 | Century Therapeutics Inc | Composiciones y metodos para la generacion de linfocitos t gamma-delta a partir de celulas madre pluripotentes inducidas. |
| US20220333074A1 (en) | 2021-04-07 | 2022-10-20 | Century Therapeutics, Inc. | Compositions and Methods for Generating Alpha-Beta T Cells from Induced Pluripotent Stem Cells |
| AU2022299551A1 (en) | 2021-06-23 | 2024-01-18 | Editas Medicine, Inc. | Engineered cells for therapy |
Family Cites Families (14)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB2183661B (en) | 1985-03-30 | 1989-06-28 | Marc Ballivet | Method for obtaining dna, rna, peptides, polypeptides or proteins by means of a dna recombinant technique |
| WO1989006694A1 (en) | 1988-01-15 | 1989-07-27 | Trustees Of The University Of Pennsylvania | Process for selection of proteinaceous substances which mimic growth-inducing molecules |
| US5837834A (en) * | 1990-06-11 | 1998-11-17 | Nexstar Pharmaceuticals, Inc. | High affinity HKGF nucleic acid ligands and inhibitors |
| US5731424A (en) * | 1990-06-11 | 1998-03-24 | Nexstar Pharmaceuticals, Inc. | High affinity TGFβ nucleic acid ligands and inhibitors |
| EP0786469B1 (en) * | 1990-06-11 | 2006-03-01 | Gilead Sciences, Inc. | Methods of use of nucleic acid ligands |
| US5683867A (en) * | 1990-06-11 | 1997-11-04 | Nexstar Pharmaceuticals, Inc. | Systematic evolution of ligands by exponential enrichment: blended SELEX |
| US5874218A (en) * | 1990-06-11 | 1999-02-23 | Nexstar Pharmaceuticals, Inc. | Method for detecting a target compound in a substance using a nucleic acid ligand |
| US5472841A (en) * | 1990-06-11 | 1995-12-05 | Nexstar Pharmaceuticals, Inc. | Methods for identifying nucleic acid ligands of human neutrophil elastase |
| CA2104698A1 (en) | 1991-02-21 | 1992-08-22 | John J. Toole | Aptamers specific for biomolecules and methods of making |
| AU651452B2 (en) * | 1991-05-10 | 1994-07-21 | Pharmacia & Upjohn S.P.A. | Truncated forms of the hepatocyte growth factor receptor |
| AU732820B2 (en) * | 1995-06-02 | 2001-05-03 | Nexstar Pharmaceuticals, Inc. | High-affinity oligonucleotide ligands to growth factors |
| US5756291A (en) * | 1992-08-21 | 1998-05-26 | Gilead Sciences, Inc. | Aptamers specific for biomolecules and methods of making |
| DE69334159D1 (de) * | 1992-09-18 | 2007-09-13 | Us Gov Health & Human Serv | Medizinische Verwendung eines Antikörpers oder eines Antikörperfragments gegen die extrazelluläre Domäne von Met zur Prevention von Metastasen |
| CA2169536A1 (en) * | 1993-09-08 | 1995-03-16 | Gilead Sciences, Inc. | Nucleic acid ligands and improved methods for producing the same |
-
1999
- 1999-07-29 US US09/364,539 patent/US6344321B1/en not_active Expired - Fee Related
-
2000
- 2000-07-24 WO PCT/US2000/020139 patent/WO2001009159A1/en not_active Ceased
- 2000-07-24 EP EP00948923A patent/EP1203007B1/en not_active Expired - Lifetime
- 2000-07-24 CA CA002381004A patent/CA2381004A1/en not_active Abandoned
- 2000-07-24 JP JP2001513966A patent/JP2003506024A/ja active Pending
-
2006
- 2006-08-22 US US11/508,024 patent/US20070010473A1/en not_active Abandoned
Also Published As
| Publication number | Publication date |
|---|---|
| EP1203007A4 (en) | 2003-06-04 |
| JP2003506024A (ja) | 2003-02-18 |
| WO2001009159A1 (en) | 2001-02-08 |
| EP1203007A1 (en) | 2002-05-08 |
| US20070010473A1 (en) | 2007-01-11 |
| EP1203007B1 (en) | 2009-04-15 |
| US6344321B1 (en) | 2002-02-05 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| EP1203007B1 (en) | Nucleic acid ligands to hepatocyte growth factor/scatter factor (hgf/sf) and its receptor c-met | |
| US20090075922A1 (en) | Nucleic Acid Ligands Which Bind to Hepatocyte Growth Factor/Scatter Factor (HGF/SF) or its Receptor c-met | |
| US6713616B2 (en) | High affinity TGFβ nucleic acid ligands and inhibitors | |
| CA3009846C (en) | Complement binding aptamers and anti-c5 agents useful in the treatment of ocular disorders | |
| CA2380473A1 (en) | Tenascin-c nucleic acid ligands | |
| CN103555725A (zh) | Sdf-1结合性核酸 | |
| US7094535B2 (en) | Nucleic acid ligands to integrins | |
| WO2008066621A2 (en) | Reversible platelet inhibition | |
| US6762290B1 (en) | High affinity vascular endothelial growth factor (VEGF) receptor nucleic acid ligands and inhibitors | |
| AU783347B2 (en) | Nucleic acid ligands to hepatocyte growth factor/scatter factor (HGF/SF) or its receptor C-Met and to integrins | |
| AU2004242462B2 (en) | Nucleic acid ligands to hepatocyte growth factor/scatter factor (HGF/SF) or its receptor C-Met and to integrins | |
| AU2008201752A1 (en) | Nucleic acid ligands to hepatocyte growth factor/scatter factor (HGF/SF) or its receptor C-Met and to integrins | |
| US20060084797A1 (en) | High affinity TGFbeta nucleic acid ligands and inhibitors | |
| AU2013204622B2 (en) | Complement Binding Aptamers and Anti-C5 Agents Useful in the Treatment of Ocular Disorders | |
| AU782620B2 (en) | High affinity vascular endothelial growth factor (VEGF) receptor nucleic acid ligands and inhibitors | |
| AU2004242532A1 (en) | High affinity TGF beta nucleic acid ligands and inhibitors |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| EEER | Examination request | ||
| FZDE | Discontinued |