JP2009500448A - 光学イメージング造影剤 - Google Patents
光学イメージング造影剤 Download PDFInfo
- Publication number
- JP2009500448A JP2009500448A JP2008521342A JP2008521342A JP2009500448A JP 2009500448 A JP2009500448 A JP 2009500448A JP 2008521342 A JP2008521342 A JP 2008521342A JP 2008521342 A JP2008521342 A JP 2008521342A JP 2009500448 A JP2009500448 A JP 2009500448A
- Authority
- JP
- Japan
- Prior art keywords
- contrast agent
- group
- enzyme
- receptor
- peptide
- 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.)
- Pending
Links
- 239000002872 contrast media Substances 0.000 title claims abstract description 102
- 238000012634 optical imaging Methods 0.000 title claims abstract description 20
- 230000027455 binding Effects 0.000 claims abstract description 51
- 239000003446 ligand Substances 0.000 claims abstract description 44
- 238000000034 method Methods 0.000 claims abstract description 30
- 230000008685 targeting Effects 0.000 claims abstract description 12
- 238000012544 monitoring process Methods 0.000 claims abstract description 7
- 230000001225 therapeutic effect Effects 0.000 claims abstract description 6
- 108090000765 processed proteins & peptides Proteins 0.000 claims description 66
- 102000005962 receptors Human genes 0.000 claims description 39
- 108020003175 receptors Proteins 0.000 claims description 39
- 102000004190 Enzymes Human genes 0.000 claims description 35
- 108090000790 Enzymes Proteins 0.000 claims description 35
- -1 dealkylase Proteins 0.000 claims description 30
- 125000005647 linker group Chemical group 0.000 claims description 19
- 150000001875 compounds Chemical class 0.000 claims description 17
- 239000000975 dye Substances 0.000 claims description 17
- 102000004169 proteins and genes Human genes 0.000 claims description 12
- 108090000623 proteins and genes Proteins 0.000 claims description 12
- 239000000758 substrate Substances 0.000 claims description 11
- 241001465754 Metazoa Species 0.000 claims description 9
- 102000035195 Peptidases Human genes 0.000 claims description 9
- 108091005804 Peptidases Proteins 0.000 claims description 9
- 102000001399 Kallikrein Human genes 0.000 claims description 7
- 108060005987 Kallikrein Proteins 0.000 claims description 7
- 102000012479 Serine Proteases Human genes 0.000 claims description 7
- 108010022999 Serine Proteases Proteins 0.000 claims description 7
- 238000002866 fluorescence resonance energy transfer Methods 0.000 claims description 7
- 230000003287 optical effect Effects 0.000 claims description 7
- 206010028980 Neoplasm Diseases 0.000 claims description 6
- 108091034117 Oligonucleotide Proteins 0.000 claims description 6
- 239000002253 acid Substances 0.000 claims description 6
- 238000001514 detection method Methods 0.000 claims description 6
- 239000003112 inhibitor Substances 0.000 claims description 6
- 150000002632 lipids Chemical class 0.000 claims description 6
- 239000000203 mixture Substances 0.000 claims description 6
- 102000005600 Cathepsins Human genes 0.000 claims description 5
- 108010084457 Cathepsins Proteins 0.000 claims description 5
- 102000002274 Matrix Metalloproteinases Human genes 0.000 claims description 5
- 108010000684 Matrix Metalloproteinases Proteins 0.000 claims description 5
- 239000003795 chemical substances by application Substances 0.000 claims description 5
- 239000012528 membrane Substances 0.000 claims description 5
- 235000019833 protease Nutrition 0.000 claims description 5
- 125000001917 2,4-dinitrophenyl group Chemical group [H]C1=C([H])C(=C([H])C(=C1*)[N+]([O-])=O)[N+]([O-])=O 0.000 claims description 4
- 239000004365 Protease Substances 0.000 claims description 4
- ZYGHJZDHTFUPRJ-UHFFFAOYSA-N coumarin Chemical compound C1=CC=C2OC(=O)C=CC2=C1 ZYGHJZDHTFUPRJ-UHFFFAOYSA-N 0.000 claims description 4
- 229920001542 oligosaccharide Polymers 0.000 claims description 4
- 150000002482 oligosaccharides Chemical class 0.000 claims description 4
- 239000001018 xanthene dye Substances 0.000 claims description 4
- 102000003886 Glycoproteins Human genes 0.000 claims description 3
- 108090000288 Glycoproteins Proteins 0.000 claims description 3
- 108010031186 Glycoside Hydrolases Proteins 0.000 claims description 3
- 102000005744 Glycoside Hydrolases Human genes 0.000 claims description 3
- 108090001030 Lipoproteins Proteins 0.000 claims description 3
- 102000004895 Lipoproteins Human genes 0.000 claims description 3
- 102000006437 Proprotein Convertases Human genes 0.000 claims description 3
- 108010044159 Proprotein Convertases Proteins 0.000 claims description 3
- 239000000427 antigen Substances 0.000 claims description 3
- 102000036639 antigens Human genes 0.000 claims description 3
- 108091007433 antigens Proteins 0.000 claims description 3
- 201000011510 cancer Diseases 0.000 claims description 3
- 102000006495 integrins Human genes 0.000 claims description 3
- 108010044426 integrins Proteins 0.000 claims description 3
- 108020004707 nucleic acids Proteins 0.000 claims description 3
- 102000039446 nucleic acids Human genes 0.000 claims description 3
- 150000007523 nucleic acids Chemical class 0.000 claims description 3
- TZMSYXZUNZXBOL-UHFFFAOYSA-N 10H-phenoxazine Chemical compound C1=CC=C2NC3=CC=CC=C3OC2=C1 TZMSYXZUNZXBOL-UHFFFAOYSA-N 0.000 claims description 2
- WCKQPPQRFNHPRJ-UHFFFAOYSA-N 4-[[4-(dimethylamino)phenyl]diazenyl]benzoic acid Chemical compound C1=CC(N(C)C)=CC=C1N=NC1=CC=C(C(O)=O)C=C1 WCKQPPQRFNHPRJ-UHFFFAOYSA-N 0.000 claims description 2
- JKOCGAMDKVAHCI-UHFFFAOYSA-N 6,7-Benzocoumarin Chemical compound C1=CC=C2C=C(OC(=O)C=C3)C3=CC2=C1 JKOCGAMDKVAHCI-UHFFFAOYSA-N 0.000 claims description 2
- GDALETGZDYOOGB-UHFFFAOYSA-N Acridone Natural products C1=C(O)C=C2N(C)C3=CC=CC=C3C(=O)C2=C1O GDALETGZDYOOGB-UHFFFAOYSA-N 0.000 claims description 2
- 108090000371 Esterases Proteins 0.000 claims description 2
- 108010021625 Immunoglobulin Fragments Proteins 0.000 claims description 2
- 102000008394 Immunoglobulin Fragments Human genes 0.000 claims description 2
- 108010043958 Peptoids Proteins 0.000 claims description 2
- 108700019535 Phosphoprotein Phosphatases Proteins 0.000 claims description 2
- 102000045595 Phosphoprotein Phosphatases Human genes 0.000 claims description 2
- 108090001050 Phosphoric Diester Hydrolases Proteins 0.000 claims description 2
- 102000004861 Phosphoric Diester Hydrolases Human genes 0.000 claims description 2
- FZEYVTFCMJSGMP-UHFFFAOYSA-N acridone Chemical compound C1=CC=C2C(=O)C3=CC=CC=C3NC2=C1 FZEYVTFCMJSGMP-UHFFFAOYSA-N 0.000 claims description 2
- 239000002671 adjuvant Substances 0.000 claims description 2
- 229960000956 coumarin Drugs 0.000 claims description 2
- 235000001671 coumarin Nutrition 0.000 claims description 2
- 238000002405 diagnostic procedure Methods 0.000 claims description 2
- OKZIUSOJQLYFSE-UHFFFAOYSA-N difluoroboron Chemical compound F[B]F OKZIUSOJQLYFSE-UHFFFAOYSA-N 0.000 claims description 2
- 239000003085 diluting agent Substances 0.000 claims description 2
- 229940079593 drug Drugs 0.000 claims description 2
- 239000003814 drug Substances 0.000 claims description 2
- 229940088597 hormone Drugs 0.000 claims description 2
- 239000005556 hormone Substances 0.000 claims description 2
- 238000004519 manufacturing process Methods 0.000 claims description 2
- DZVCFNFOPIZQKX-LTHRDKTGSA-M merocyanine Chemical compound [Na+].O=C1N(CCCC)C(=O)N(CCCC)C(=O)C1=C\C=C\C=C/1N(CCCS([O-])(=O)=O)C2=CC=CC=C2O\1 DZVCFNFOPIZQKX-LTHRDKTGSA-M 0.000 claims description 2
- 239000002858 neurotransmitter agent Substances 0.000 claims description 2
- 239000000816 peptidomimetic Substances 0.000 claims description 2
- 239000008194 pharmaceutical composition Substances 0.000 claims description 2
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 2
- 235000019419 proteases Nutrition 0.000 claims description 2
- 108091008598 receptor tyrosine kinases Proteins 0.000 claims description 2
- 102000027426 receptor tyrosine kinases Human genes 0.000 claims description 2
- 239000001022 rhodamine dye Substances 0.000 claims description 2
- 239000011782 vitamin Substances 0.000 claims description 2
- 229940088594 vitamin Drugs 0.000 claims description 2
- 229930003231 vitamin Natural products 0.000 claims description 2
- 235000013343 vitamin Nutrition 0.000 claims description 2
- ANRHNWWPFJCPAZ-UHFFFAOYSA-M thionine Chemical compound [Cl-].C1=CC(N)=CC2=[S+]C3=CC(N)=CC=C3N=C21 ANRHNWWPFJCPAZ-UHFFFAOYSA-M 0.000 claims 2
- 230000010485 coping Effects 0.000 claims 1
- 230000001575 pathological effect Effects 0.000 claims 1
- 150000003722 vitamin derivatives Chemical class 0.000 claims 1
- 230000004913 activation Effects 0.000 abstract description 7
- 150000001413 amino acids Chemical class 0.000 description 35
- 229940024606 amino acid Drugs 0.000 description 32
- 235000001014 amino acid Nutrition 0.000 description 32
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 30
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 30
- 229940088598 enzyme Drugs 0.000 description 29
- SJRJJKPEHAURKC-UHFFFAOYSA-N N-Methylmorpholine Chemical compound CN1CCOCC1 SJRJJKPEHAURKC-UHFFFAOYSA-N 0.000 description 18
- 125000006239 protecting group Chemical group 0.000 description 16
- QGKMIGUHVLGJBR-UHFFFAOYSA-M (4z)-1-(3-methylbutyl)-4-[[1-(3-methylbutyl)quinolin-1-ium-4-yl]methylidene]quinoline;iodide Chemical compound [I-].C12=CC=CC=C2N(CCC(C)C)C=CC1=CC1=CC=[N+](CCC(C)C)C2=CC=CC=C12 QGKMIGUHVLGJBR-UHFFFAOYSA-M 0.000 description 13
- 102000004196 processed proteins & peptides Human genes 0.000 description 13
- SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 description 12
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 12
- 150000002148 esters Chemical class 0.000 description 12
- 210000001519 tissue Anatomy 0.000 description 12
- 238000006243 chemical reaction Methods 0.000 description 11
- 201000010099 disease Diseases 0.000 description 11
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 11
- 229910052739 hydrogen Inorganic materials 0.000 description 11
- 238000003384 imaging method Methods 0.000 description 11
- 235000018102 proteins Nutrition 0.000 description 11
- 239000011347 resin Substances 0.000 description 11
- 229920005989 resin Polymers 0.000 description 11
- 238000003786 synthesis reaction Methods 0.000 description 11
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 10
- 230000015572 biosynthetic process Effects 0.000 description 10
- 238000010168 coupling process Methods 0.000 description 10
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 9
- 238000003776 cleavage reaction Methods 0.000 description 9
- 230000008878 coupling Effects 0.000 description 9
- 238000005859 coupling reaction Methods 0.000 description 9
- 125000000524 functional group Chemical group 0.000 description 9
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 9
- 230000007017 scission Effects 0.000 description 9
- 102100030412 Matrix metalloproteinase-9 Human genes 0.000 description 8
- 108010015302 Matrix metalloproteinase-9 Proteins 0.000 description 8
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 8
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 8
- 239000000047 product Substances 0.000 description 8
- 238000004007 reversed phase HPLC Methods 0.000 description 8
- 238000012546 transfer Methods 0.000 description 8
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 7
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 6
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 6
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 6
- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 6
- 210000004027 cell Anatomy 0.000 description 6
- 239000012043 crude product Substances 0.000 description 6
- 239000011541 reaction mixture Substances 0.000 description 6
- 239000000243 solution Substances 0.000 description 6
- ZGYICYBLPGRURT-UHFFFAOYSA-N tri(propan-2-yl)silicon Chemical compound CC(C)[Si](C(C)C)C(C)C ZGYICYBLPGRURT-UHFFFAOYSA-N 0.000 description 6
- 125000003088 (fluoren-9-ylmethoxy)carbonyl group Chemical group 0.000 description 5
- 102000003908 Cathepsin D Human genes 0.000 description 5
- 108090000258 Cathepsin D Proteins 0.000 description 5
- RJKFOVLPORLFTN-LEKSSAKUSA-N Progesterone Chemical compound C1CC2=CC(=O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H](C(=O)C)[C@@]1(C)CC2 RJKFOVLPORLFTN-LEKSSAKUSA-N 0.000 description 5
- 125000003118 aryl group Chemical group 0.000 description 5
- 229910052799 carbon Inorganic materials 0.000 description 5
- 239000012634 fragment Substances 0.000 description 5
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 5
- 229910052760 oxygen Inorganic materials 0.000 description 5
- 239000001301 oxygen Substances 0.000 description 5
- 235000000346 sugar Nutrition 0.000 description 5
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 5
- 102000004989 Hepsin Human genes 0.000 description 4
- 108090001101 Hepsin Proteins 0.000 description 4
- KDXKERNSBIXSRK-YFKPBYRVSA-N L-lysine Chemical compound NCCCC[C@H](N)C(O)=O KDXKERNSBIXSRK-YFKPBYRVSA-N 0.000 description 4
- JLCPHMBAVCMARE-UHFFFAOYSA-N [3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-[[3-[[3-[[3-[[3-[[3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-hydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methyl [5-(6-aminopurin-9-yl)-2-(hydroxymethyl)oxolan-3-yl] hydrogen phosphate Polymers Cc1cn(C2CC(OP(O)(=O)OCC3OC(CC3OP(O)(=O)OCC3OC(CC3O)n3cnc4c3nc(N)[nH]c4=O)n3cnc4c3nc(N)[nH]c4=O)C(COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3CO)n3cnc4c(N)ncnc34)n3ccc(N)nc3=O)n3cnc4c(N)ncnc34)n3ccc(N)nc3=O)n3ccc(N)nc3=O)n3ccc(N)nc3=O)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cc(C)c(=O)[nH]c3=O)n3cc(C)c(=O)[nH]c3=O)n3ccc(N)nc3=O)n3cc(C)c(=O)[nH]c3=O)n3cnc4c3nc(N)[nH]c4=O)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)O2)c(=O)[nH]c1=O JLCPHMBAVCMARE-UHFFFAOYSA-N 0.000 description 4
- 230000009471 action Effects 0.000 description 4
- 150000001408 amides Chemical class 0.000 description 4
- 125000004429 atom Chemical group 0.000 description 4
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 4
- 238000005119 centrifugation Methods 0.000 description 4
- HVYWMOMLDIMFJA-DPAQBDIFSA-N cholesterol Chemical compound C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CCCC(C)C)[C@@]1(C)CC2 HVYWMOMLDIMFJA-DPAQBDIFSA-N 0.000 description 4
- VYFYYTLLBUKUHU-UHFFFAOYSA-N dopamine Chemical compound NCCC1=CC=C(O)C(O)=C1 VYFYYTLLBUKUHU-UHFFFAOYSA-N 0.000 description 4
- 239000003480 eluent Substances 0.000 description 4
- 102000052116 epidermal growth factor receptor activity proteins Human genes 0.000 description 4
- 108700015053 epidermal growth factor receptor activity proteins Proteins 0.000 description 4
- 239000007850 fluorescent dye Substances 0.000 description 4
- 238000004128 high performance liquid chromatography Methods 0.000 description 4
- IKDUDTNKRLTJSI-UHFFFAOYSA-N hydrazine hydrate Chemical compound O.NN IKDUDTNKRLTJSI-UHFFFAOYSA-N 0.000 description 4
- 238000001727 in vivo Methods 0.000 description 4
- 230000003993 interaction Effects 0.000 description 4
- YOHYSYJDKVYCJI-UHFFFAOYSA-N n-[3-[[6-[3-(trifluoromethyl)anilino]pyrimidin-4-yl]amino]phenyl]cyclopropanecarboxamide Chemical compound FC(F)(F)C1=CC=CC(NC=2N=CN=C(NC=3C=C(NC(=O)C4CC4)C=CC=3)C=2)=C1 YOHYSYJDKVYCJI-UHFFFAOYSA-N 0.000 description 4
- 239000002777 nucleoside Substances 0.000 description 4
- 238000010647 peptide synthesis reaction Methods 0.000 description 4
- 230000035945 sensitivity Effects 0.000 description 4
- 239000007790 solid phase Substances 0.000 description 4
- VKUYLANQOAKALN-UHFFFAOYSA-N 2-[benzyl-(4-methoxyphenyl)sulfonylamino]-n-hydroxy-4-methylpentanamide Chemical compound C1=CC(OC)=CC=C1S(=O)(=O)N(C(CC(C)C)C(=O)NO)CC1=CC=CC=C1 VKUYLANQOAKALN-UHFFFAOYSA-N 0.000 description 3
- 108010022366 Carcinoembryonic Antigen Proteins 0.000 description 3
- 102100025475 Carcinoembryonic antigen-related cell adhesion molecule 5 Human genes 0.000 description 3
- 102100024025 Heparanase Human genes 0.000 description 3
- 239000004472 Lysine Substances 0.000 description 3
- 229910019142 PO4 Inorganic materials 0.000 description 3
- 102100030416 Stromelysin-1 Human genes 0.000 description 3
- 101710108790 Stromelysin-1 Proteins 0.000 description 3
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 3
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 3
- 108091008605 VEGF receptors Proteins 0.000 description 3
- 125000000217 alkyl group Chemical group 0.000 description 3
- 239000002585 base Substances 0.000 description 3
- 239000003153 chemical reaction reagent Substances 0.000 description 3
- 238000009833 condensation Methods 0.000 description 3
- 230000005494 condensation Effects 0.000 description 3
- 239000000470 constituent Substances 0.000 description 3
- 230000007423 decrease Effects 0.000 description 3
- 238000003745 diagnosis Methods 0.000 description 3
- 150000002016 disaccharides Chemical class 0.000 description 3
- 230000000694 effects Effects 0.000 description 3
- 230000002255 enzymatic effect Effects 0.000 description 3
- 108010037536 heparanase Proteins 0.000 description 3
- 239000001257 hydrogen Substances 0.000 description 3
- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 3
- 238000006460 hydrolysis reaction Methods 0.000 description 3
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 3
- 229910052757 nitrogen Inorganic materials 0.000 description 3
- 150000003833 nucleoside derivatives Chemical class 0.000 description 3
- 239000010452 phosphate Substances 0.000 description 3
- 238000010791 quenching Methods 0.000 description 3
- 230000000171 quenching effect Effects 0.000 description 3
- 239000000523 sample Substances 0.000 description 3
- 239000007787 solid Substances 0.000 description 3
- 125000001424 substituent group Chemical group 0.000 description 3
- BDHFUVZGWQCTTF-UHFFFAOYSA-M sulfonate Chemical compound [O-]S(=O)=O BDHFUVZGWQCTTF-UHFFFAOYSA-M 0.000 description 3
- 229910052717 sulfur Inorganic materials 0.000 description 3
- 239000011593 sulfur Substances 0.000 description 3
- WROMPOXWARCANT-UHFFFAOYSA-N tfa trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.OC(=O)C(F)(F)F WROMPOXWARCANT-UHFFFAOYSA-N 0.000 description 3
- 150000003568 thioethers Chemical class 0.000 description 3
- 125000003396 thiol group Chemical group [H]S* 0.000 description 3
- YBJHBAHKTGYVGT-ZKWXMUAHSA-N (+)-Biotin Chemical compound N1C(=O)N[C@@H]2[C@H](CCCCC(=O)O)SC[C@@H]21 YBJHBAHKTGYVGT-ZKWXMUAHSA-N 0.000 description 2
- FVKRBXYHROENKF-UHFFFAOYSA-N 2,3,5,6-tetrafluoro-4-hydroxybenzenesulfonic acid Chemical compound OC1=C(F)C(F)=C(S(O)(=O)=O)C(F)=C1F FVKRBXYHROENKF-UHFFFAOYSA-N 0.000 description 2
- 102100026802 72 kDa type IV collagenase Human genes 0.000 description 2
- 101710151806 72 kDa type IV collagenase Proteins 0.000 description 2
- LRFVTYWOQMYALW-UHFFFAOYSA-N 9H-xanthine Chemical compound O=C1NC(=O)NC2=C1NC=N2 LRFVTYWOQMYALW-UHFFFAOYSA-N 0.000 description 2
- 102100022749 Aminopeptidase N Human genes 0.000 description 2
- DCXYFEDJOCDNAF-UHFFFAOYSA-N Asparagine Chemical compound OC(=O)C(N)CC(N)=O DCXYFEDJOCDNAF-UHFFFAOYSA-N 0.000 description 2
- 206010006187 Breast cancer Diseases 0.000 description 2
- 208000026310 Breast neoplasm Diseases 0.000 description 2
- 108010049990 CD13 Antigens Proteins 0.000 description 2
- 102000004225 Cathepsin B Human genes 0.000 description 2
- 108090000712 Cathepsin B Proteins 0.000 description 2
- 102000004172 Cathepsin L Human genes 0.000 description 2
- 108090000624 Cathepsin L Proteins 0.000 description 2
- 108090001085 Cholecystokinin Receptors Proteins 0.000 description 2
- 102000004859 Cholecystokinin Receptors Human genes 0.000 description 2
- 206010009944 Colon cancer Diseases 0.000 description 2
- 208000001333 Colorectal Neoplasms Diseases 0.000 description 2
- 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 2
- 206010058467 Lung neoplasm malignant Diseases 0.000 description 2
- 108010076557 Matrix Metalloproteinase 14 Proteins 0.000 description 2
- 102100030216 Matrix metalloproteinase-14 Human genes 0.000 description 2
- 102000005741 Metalloproteases Human genes 0.000 description 2
- 108010006035 Metalloproteases Proteins 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- 102000004211 Platelet factor 4 Human genes 0.000 description 2
- 108090000778 Platelet factor 4 Proteins 0.000 description 2
- 229920000388 Polyphosphate Polymers 0.000 description 2
- 206010060862 Prostate cancer Diseases 0.000 description 2
- 108010072866 Prostate-Specific Antigen Proteins 0.000 description 2
- 102100038358 Prostate-specific antigen Human genes 0.000 description 2
- 208000000236 Prostatic Neoplasms Diseases 0.000 description 2
- QIVBCDIJIAJPQS-UHFFFAOYSA-N Tryptophan Natural products C1=CC=C2C(CC(N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-UHFFFAOYSA-N 0.000 description 2
- ISAKRJDGNUQOIC-UHFFFAOYSA-N Uracil Chemical compound O=C1C=CNC(=O)N1 ISAKRJDGNUQOIC-UHFFFAOYSA-N 0.000 description 2
- 108090000435 Urokinase-type plasminogen activator Proteins 0.000 description 2
- 102000005789 Vascular Endothelial Growth Factors Human genes 0.000 description 2
- 108010019530 Vascular Endothelial Growth Factors Proteins 0.000 description 2
- 102100033177 Vascular endothelial growth factor receptor 2 Human genes 0.000 description 2
- 238000010521 absorption reaction Methods 0.000 description 2
- 238000000862 absorption spectrum Methods 0.000 description 2
- 150000001412 amines Chemical class 0.000 description 2
- YZXBAPSDXZZRGB-DOFZRALJSA-N arachidonic acid Chemical compound CCCCC\C=C/C\C=C/C\C=C/C\C=C/CCCC(O)=O YZXBAPSDXZZRGB-DOFZRALJSA-N 0.000 description 2
- 239000012298 atmosphere Substances 0.000 description 2
- 230000005540 biological transmission Effects 0.000 description 2
- 150000001721 carbon Chemical group 0.000 description 2
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 2
- 235000012000 cholesterol Nutrition 0.000 description 2
- 230000000295 complement effect Effects 0.000 description 2
- 230000021615 conjugation Effects 0.000 description 2
- OPTASPLRGRRNAP-UHFFFAOYSA-N cytosine Chemical compound NC=1C=CNC(=O)N=1 OPTASPLRGRRNAP-UHFFFAOYSA-N 0.000 description 2
- 238000010511 deprotection reaction Methods 0.000 description 2
- 229960003638 dopamine Drugs 0.000 description 2
- 230000009977 dual effect Effects 0.000 description 2
- 238000005516 engineering process Methods 0.000 description 2
- 230000002708 enhancing effect Effects 0.000 description 2
- 239000002532 enzyme inhibitor Substances 0.000 description 2
- 230000005284 excitation Effects 0.000 description 2
- 239000012467 final product Substances 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
- OVBPIULPVIDEAO-LBPRGKRZSA-N folic acid Chemical compound C=1N=C2NC(N)=NC(=O)C2=NC=1CNC1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 OVBPIULPVIDEAO-LBPRGKRZSA-N 0.000 description 2
- UYTPUPDQBNUYGX-UHFFFAOYSA-N guanine Chemical compound O=C1NC(N)=NC2=C1N=CN2 UYTPUPDQBNUYGX-UHFFFAOYSA-N 0.000 description 2
- 150000004820 halides Chemical class 0.000 description 2
- JYGXADMDTFJGBT-VWUMJDOOSA-N hydrocortisone Chemical compound O=C1CC[C@]2(C)[C@H]3[C@@H](O)C[C@](C)([C@@](CC4)(O)C(=O)CO)[C@@H]4[C@@H]3CCC2=C1 JYGXADMDTFJGBT-VWUMJDOOSA-N 0.000 description 2
- 230000007062 hydrolysis Effects 0.000 description 2
- NPZTUJOABDZTLV-UHFFFAOYSA-N hydroxybenzotriazole Substances O=C1C=CC=C2NNN=C12 NPZTUJOABDZTLV-UHFFFAOYSA-N 0.000 description 2
- FDGQSTZJBFJUBT-UHFFFAOYSA-N hypoxanthine Chemical compound O=C1NC=NC2=C1NC=N2 FDGQSTZJBFJUBT-UHFFFAOYSA-N 0.000 description 2
- AEMOLEFTQBMNLQ-CLQWQSTFSA-N l-iduronic acid Chemical compound O[C@H]1O[C@H](C(O)=O)[C@H](O)[C@@H](O)[C@@H]1O AEMOLEFTQBMNLQ-CLQWQSTFSA-N 0.000 description 2
- 238000002372 labelling Methods 0.000 description 2
- 201000005202 lung cancer Diseases 0.000 description 2
- 208000020816 lung neoplasm Diseases 0.000 description 2
- 239000011159 matrix material Substances 0.000 description 2
- 238000001840 matrix-assisted laser desorption--ionisation time-of-flight mass spectrometry Methods 0.000 description 2
- 238000005259 measurement Methods 0.000 description 2
- 229910052751 metal Inorganic materials 0.000 description 2
- 239000002184 metal Substances 0.000 description 2
- 239000002082 metal nanoparticle Substances 0.000 description 2
- 244000005700 microbiome Species 0.000 description 2
- 239000002105 nanoparticle Substances 0.000 description 2
- 238000007911 parenteral administration Methods 0.000 description 2
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 2
- 125000002467 phosphate group Chemical group [H]OP(=O)(O[H])O[*] 0.000 description 2
- 150000003904 phospholipids Chemical class 0.000 description 2
- 229920000642 polymer Polymers 0.000 description 2
- 239000001205 polyphosphate Substances 0.000 description 2
- 235000011176 polyphosphates Nutrition 0.000 description 2
- 239000002244 precipitate Substances 0.000 description 2
- 239000000186 progesterone Substances 0.000 description 2
- 229960003387 progesterone Drugs 0.000 description 2
- 238000006862 quantum yield reaction Methods 0.000 description 2
- 125000001453 quaternary ammonium group Chemical group 0.000 description 2
- 230000002829 reductive effect Effects 0.000 description 2
- 230000001105 regulatory effect Effects 0.000 description 2
- 238000002165 resonance energy transfer Methods 0.000 description 2
- 238000012216 screening Methods 0.000 description 2
- QZAYGJVTTNCVMB-UHFFFAOYSA-N serotonin Chemical compound C1=C(O)C=C2C(CCN)=CNC2=C1 QZAYGJVTTNCVMB-UHFFFAOYSA-N 0.000 description 2
- 238000010532 solid phase synthesis reaction Methods 0.000 description 2
- 238000004611 spectroscopical analysis Methods 0.000 description 2
- 150000008163 sugars Chemical class 0.000 description 2
- 229940124530 sulfonamide Drugs 0.000 description 2
- RWQNBRDOKXIBIV-UHFFFAOYSA-N thymine Chemical compound CC1=CNC(=O)NC1=O RWQNBRDOKXIBIV-UHFFFAOYSA-N 0.000 description 2
- 238000003325 tomography Methods 0.000 description 2
- NMDDZEVVQDPECF-LURJTMIESA-N (2s)-2,7-diaminoheptanoic acid Chemical compound NCCCCC[C@H](N)C(O)=O NMDDZEVVQDPECF-LURJTMIESA-N 0.000 description 1
- XQQUSYWGKLRJRA-RABCQHRBSA-N (2s)-2-[[(2s)-2-[[(2s)-2-[[(2s)-6-amino-2-[[(2s,3s)-2-amino-3-methylpentanoyl]amino]hexanoyl]amino]-3-methylbutanoyl]amino]propanoyl]amino]-3-methylbutanoic acid Chemical compound CC[C@H](C)[C@H](N)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](C)C(=O)N[C@@H](C(C)C)C(O)=O XQQUSYWGKLRJRA-RABCQHRBSA-N 0.000 description 1
- MWOGMBZGFFZBMK-LJZWMIMPSA-N (2s)-2-[[(2s)-2-[[2-[[(2s,3s)-2-[[(2s)-2-amino-3-(4-hydroxyphenyl)propanoyl]amino]-3-methylpentanoyl]amino]acetyl]amino]-3-hydroxypropanoyl]amino]-5-(diaminomethylideneamino)pentanoic acid Chemical compound NC(N)=NCCC[C@@H](C(O)=O)NC(=O)[C@H](CO)NC(=O)CNC(=O)[C@H]([C@@H](C)CC)NC(=O)[C@@H](N)CC1=CC=C(O)C=C1 MWOGMBZGFFZBMK-LJZWMIMPSA-N 0.000 description 1
- PDBIHKPGRQQIEC-LURJTMIESA-N (3s)-3,7-diamino-1-chloroheptan-2-one Chemical compound NCCCC[C@H](N)C(=O)CCl PDBIHKPGRQQIEC-LURJTMIESA-N 0.000 description 1
- CUKWUWBLQQDQAC-VEQWQPCFSA-N (3s)-3-amino-4-[[(2s)-1-[[(2s)-1-[[(2s)-1-[[(2s,3s)-1-[[(2s)-1-[(2s)-2-[[(1s)-1-carboxyethyl]carbamoyl]pyrrolidin-1-yl]-3-(1h-imidazol-5-yl)-1-oxopropan-2-yl]amino]-3-methyl-1-oxopentan-2-yl]amino]-3-(4-hydroxyphenyl)-1-oxopropan-2-yl]amino]-3-methyl-1-ox Chemical compound C([C@@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CC=1NC=NC=1)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](C)C(O)=O)NC(=O)[C@@H](NC(=O)[C@H](CCCN=C(N)N)NC(=O)[C@@H](N)CC(O)=O)C(C)C)C1=CC=C(O)C=C1 CUKWUWBLQQDQAC-VEQWQPCFSA-N 0.000 description 1
- DEQANNDTNATYII-OULOTJBUSA-N (4r,7s,10s,13r,16s,19r)-10-(4-aminobutyl)-19-[[(2r)-2-amino-3-phenylpropanoyl]amino]-16-benzyl-n-[(2r,3r)-1,3-dihydroxybutan-2-yl]-7-[(1r)-1-hydroxyethyl]-13-(1h-indol-3-ylmethyl)-6,9,12,15,18-pentaoxo-1,2-dithia-5,8,11,14,17-pentazacycloicosane-4-carboxa Chemical compound C([C@@H](N)C(=O)N[C@H]1CSSC[C@H](NC(=O)[C@H]([C@@H](C)O)NC(=O)[C@H](CCCCN)NC(=O)[C@@H](CC=2C3=CC=CC=C3NC=2)NC(=O)[C@H](CC=2C=CC=CC=2)NC1=O)C(=O)N[C@H](CO)[C@H](O)C)C1=CC=CC=C1 DEQANNDTNATYII-OULOTJBUSA-N 0.000 description 1
- 108091032973 (ribonucleotides)n+m Proteins 0.000 description 1
- ASOKPJOREAFHNY-UHFFFAOYSA-N 1-Hydroxybenzotriazole Chemical compound C1=CC=C2N(O)N=NC2=C1 ASOKPJOREAFHNY-UHFFFAOYSA-N 0.000 description 1
- RYCNUMLMNKHWPZ-SNVBAGLBSA-N 1-acetyl-sn-glycero-3-phosphocholine Chemical compound CC(=O)OC[C@@H](O)COP([O-])(=O)OCC[N+](C)(C)C RYCNUMLMNKHWPZ-SNVBAGLBSA-N 0.000 description 1
- GZCWLCBFPRFLKL-UHFFFAOYSA-N 1-prop-2-ynoxypropan-2-ol Chemical compound CC(O)COCC#C GZCWLCBFPRFLKL-UHFFFAOYSA-N 0.000 description 1
- VOXZDWNPVJITMN-ZBRFXRBCSA-N 17β-estradiol Chemical compound OC1=CC=C2[C@H]3CC[C@](C)([C@H](CC4)O)[C@@H]4[C@@H]3CCC2=C1 VOXZDWNPVJITMN-ZBRFXRBCSA-N 0.000 description 1
- SKWCZPYWFRTSDD-UHFFFAOYSA-N 2,3-bis(azaniumyl)propanoate;chloride Chemical compound Cl.NCC(N)C(O)=O SKWCZPYWFRTSDD-UHFFFAOYSA-N 0.000 description 1
- QZDDFQLIQRYMBV-UHFFFAOYSA-N 2-[3-nitro-2-(2-nitrophenyl)-4-oxochromen-8-yl]acetic acid Chemical compound OC(=O)CC1=CC=CC(C(C=2[N+]([O-])=O)=O)=C1OC=2C1=CC=CC=C1[N+]([O-])=O QZDDFQLIQRYMBV-UHFFFAOYSA-N 0.000 description 1
- FSRNHDLQBNOYJK-UHFFFAOYSA-N 2-[[bis[(2-methylpropan-2-yl)oxycarbonyl]amino]-[(2-methylpropan-2-yl)oxycarbonyl]amino]acetic acid Chemical compound CC(C)(C)OC(=O)N(CC(O)=O)N(C(=O)OC(C)(C)C)C(=O)OC(C)(C)C FSRNHDLQBNOYJK-UHFFFAOYSA-N 0.000 description 1
- YEDUAINPPJYDJZ-UHFFFAOYSA-N 2-hydroxybenzothiazole Chemical compound C1=CC=C2SC(O)=NC2=C1 YEDUAINPPJYDJZ-UHFFFAOYSA-N 0.000 description 1
- IHDBZCJYSHDCKF-UHFFFAOYSA-N 4,6-dichlorotriazine Chemical class ClC1=CC(Cl)=NN=N1 IHDBZCJYSHDCKF-UHFFFAOYSA-N 0.000 description 1
- NJYVEMPWNAYQQN-UHFFFAOYSA-N 5-carboxyfluorescein Chemical compound C12=CC=C(O)C=C2OC2=CC(O)=CC=C2C21OC(=O)C1=CC(C(=O)O)=CC=C21 NJYVEMPWNAYQQN-UHFFFAOYSA-N 0.000 description 1
- 102000040125 5-hydroxytryptamine receptor family Human genes 0.000 description 1
- 108091032151 5-hydroxytryptamine receptor family Proteins 0.000 description 1
- ZKRFOXLVOKTUTA-KQYNXXCUSA-N 9-(5-phosphoribofuranosyl)-6-mercaptopurine Chemical compound O[C@@H]1[C@H](O)[C@@H](COP(O)(O)=O)O[C@H]1N1C(NC=NC2=S)=C2N=C1 ZKRFOXLVOKTUTA-KQYNXXCUSA-N 0.000 description 1
- 108010051457 Acid Phosphatase Proteins 0.000 description 1
- 102000013563 Acid Phosphatase Human genes 0.000 description 1
- 229930024421 Adenine Natural products 0.000 description 1
- GFFGJBXGBJISGV-UHFFFAOYSA-N Adenine Chemical compound NC1=NC=NC2=C1N=CN2 GFFGJBXGBJISGV-UHFFFAOYSA-N 0.000 description 1
- 208000036764 Adenocarcinoma of the esophagus Diseases 0.000 description 1
- 108020004774 Alkaline Phosphatase Proteins 0.000 description 1
- 102000002260 Alkaline Phosphatase Human genes 0.000 description 1
- QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 description 1
- 102400000345 Angiotensin-2 Human genes 0.000 description 1
- 101800000733 Angiotensin-2 Proteins 0.000 description 1
- 201000001320 Atherosclerosis Diseases 0.000 description 1
- 208000037260 Atherosclerotic Plaque Diseases 0.000 description 1
- 206010005003 Bladder cancer Diseases 0.000 description 1
- WDPFQABQVGJEBZ-MAKOZQESSA-N Bothermon Chemical compound OC1=CC=C2[C@H]3CC[C@](C)([C@H](CC4)O)[C@@H]4[C@@H]3CCC2=C1.O=C1CC[C@]2(C)[C@H]3CC[C@](C)([C@H](CC4)O)[C@@H]4[C@@H]3CCC2=C1 WDPFQABQVGJEBZ-MAKOZQESSA-N 0.000 description 1
- 102100021943 C-C motif chemokine 2 Human genes 0.000 description 1
- 101710155857 C-C motif chemokine 2 Proteins 0.000 description 1
- 108010074051 C-Reactive Protein Proteins 0.000 description 1
- 102100032752 C-reactive protein Human genes 0.000 description 1
- 125000001433 C-terminal amino-acid group Chemical group 0.000 description 1
- 102000049320 CD36 Human genes 0.000 description 1
- 108010045374 CD36 Antigens Proteins 0.000 description 1
- 102100032912 CD44 antigen Human genes 0.000 description 1
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 1
- 201000009030 Carcinoma Diseases 0.000 description 1
- 102000011632 Caseins Human genes 0.000 description 1
- 108010076119 Caseins Proteins 0.000 description 1
- 102000019034 Chemokines Human genes 0.000 description 1
- 108010012236 Chemokines Proteins 0.000 description 1
- 108010069514 Cyclic Peptides Proteins 0.000 description 1
- 102000001189 Cyclic Peptides Human genes 0.000 description 1
- 102000015833 Cystatin Human genes 0.000 description 1
- 102000004127 Cytokines Human genes 0.000 description 1
- 108090000695 Cytokines Proteins 0.000 description 1
- 150000008574 D-amino acids Chemical class 0.000 description 1
- WQZGKKKJIJFFOK-QTVWNMPRSA-N D-mannopyranose Chemical compound OC[C@H]1OC(O)[C@@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-QTVWNMPRSA-N 0.000 description 1
- 101000874334 Dalbergia nigrescens Isoflavonoid 7-O-beta-apiosyl-glucoside beta-glycosidase Proteins 0.000 description 1
- 108010002156 Depsipeptides Proteins 0.000 description 1
- BWGNESOTFCXPMA-UHFFFAOYSA-N Dihydrogen disulfide Chemical compound SS BWGNESOTFCXPMA-UHFFFAOYSA-N 0.000 description 1
- 108010044266 Dopamine Plasma Membrane Transport Proteins Proteins 0.000 description 1
- 108050009340 Endothelin Proteins 0.000 description 1
- 102000002045 Endothelin Human genes 0.000 description 1
- 102000010180 Endothelin receptor Human genes 0.000 description 1
- 108050001739 Endothelin receptor Proteins 0.000 description 1
- 101000757733 Enterococcus faecalis (strain ATCC 700802 / V583) Autolysin Proteins 0.000 description 1
- 102100023688 Eotaxin Human genes 0.000 description 1
- 101710139422 Eotaxin Proteins 0.000 description 1
- 102000009024 Epidermal Growth Factor Human genes 0.000 description 1
- 241000588724 Escherichia coli Species 0.000 description 1
- 208000000461 Esophageal Neoplasms Diseases 0.000 description 1
- JOYRKODLDBILNP-UHFFFAOYSA-N Ethyl urethane Chemical compound CCOC(N)=O JOYRKODLDBILNP-UHFFFAOYSA-N 0.000 description 1
- 108010037362 Extracellular Matrix Proteins Proteins 0.000 description 1
- 102000010834 Extracellular Matrix Proteins Human genes 0.000 description 1
- 108010049003 Fibrinogen Proteins 0.000 description 1
- 102000008946 Fibrinogen Human genes 0.000 description 1
- 108010067306 Fibronectins Proteins 0.000 description 1
- 102000016359 Fibronectins Human genes 0.000 description 1
- 229930091371 Fructose Natural products 0.000 description 1
- RFSUNEUAIZKAJO-ARQDHWQXSA-N Fructose Chemical compound OC[C@H]1O[C@](O)(CO)[C@@H](O)[C@@H]1O RFSUNEUAIZKAJO-ARQDHWQXSA-N 0.000 description 1
- 239000005715 Fructose Substances 0.000 description 1
- 108090000839 GABA-A Receptors Proteins 0.000 description 1
- 102000004300 GABA-A Receptors Human genes 0.000 description 1
- 108010001517 Galectin 3 Proteins 0.000 description 1
- 102100039558 Galectin-3 Human genes 0.000 description 1
- 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 1
- WHUUTDBJXJRKMK-UHFFFAOYSA-N Glutamic acid Natural products OC(=O)C(N)CCC(O)=O WHUUTDBJXJRKMK-UHFFFAOYSA-N 0.000 description 1
- 229930186217 Glycolipid Natural products 0.000 description 1
- 108010078321 Guanylate Cyclase Proteins 0.000 description 1
- 102000014469 Guanylate cyclase Human genes 0.000 description 1
- 108090000100 Hepatocyte Growth Factor Proteins 0.000 description 1
- 102100021866 Hepatocyte growth factor Human genes 0.000 description 1
- 101000868273 Homo sapiens CD44 antigen Proteins 0.000 description 1
- 101001091379 Homo sapiens Kallikrein-5 Proteins 0.000 description 1
- 101000669513 Homo sapiens Metalloproteinase inhibitor 1 Proteins 0.000 description 1
- 101000972282 Homo sapiens Mucin-5AC Proteins 0.000 description 1
- 102000004157 Hydrolases Human genes 0.000 description 1
- 108090000604 Hydrolases Proteins 0.000 description 1
- UGQMRVRMYYASKQ-UHFFFAOYSA-N Hypoxanthine nucleoside Natural products OC1C(O)C(CO)OC1N1C(NC=NC2=O)=C2N=C1 UGQMRVRMYYASKQ-UHFFFAOYSA-N 0.000 description 1
- 206010061218 Inflammation Diseases 0.000 description 1
- 102000014150 Interferons Human genes 0.000 description 1
- 108010050904 Interferons Proteins 0.000 description 1
- 102000015696 Interleukins Human genes 0.000 description 1
- 108010063738 Interleukins Proteins 0.000 description 1
- 102100038298 Kallikrein-14 Human genes 0.000 description 1
- 101710115806 Kallikrein-14 Proteins 0.000 description 1
- 102100034872 Kallikrein-4 Human genes 0.000 description 1
- WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 description 1
- DWPCPZJAHOETAG-IMJSIDKUSA-N L-lanthionine Chemical compound OC(=O)[C@@H](N)CSC[C@H](N)C(O)=O DWPCPZJAHOETAG-IMJSIDKUSA-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
- OUYCCCASQSFEME-QMMMGPOBSA-N L-tyrosine Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-QMMMGPOBSA-N 0.000 description 1
- 108010085895 Laminin Proteins 0.000 description 1
- GDBQQVLCIARPGH-UHFFFAOYSA-N Leupeptin Natural products CC(C)CC(NC(C)=O)C(=O)NC(CC(C)C)C(=O)NC(C=O)CCCN=C(N)N GDBQQVLCIARPGH-UHFFFAOYSA-N 0.000 description 1
- 102000007651 Macrophage Colony-Stimulating Factor Human genes 0.000 description 1
- 108010046938 Macrophage Colony-Stimulating Factor Proteins 0.000 description 1
- 102100027998 Macrophage metalloelastase Human genes 0.000 description 1
- 101710187853 Macrophage metalloelastase Proteins 0.000 description 1
- PEEHTFAAVSWFBL-UHFFFAOYSA-N Maleimide Chemical compound O=C1NC(=O)C=C1 PEEHTFAAVSWFBL-UHFFFAOYSA-N 0.000 description 1
- 102100030417 Matrilysin Human genes 0.000 description 1
- 108090000855 Matrilysin Proteins 0.000 description 1
- 102100039364 Metalloproteinase inhibitor 1 Human genes 0.000 description 1
- 206010027476 Metastases Diseases 0.000 description 1
- 102100022496 Mucin-5AC Human genes 0.000 description 1
- 101710135898 Myc proto-oncogene protein Proteins 0.000 description 1
- 102100038895 Myc proto-oncogene protein Human genes 0.000 description 1
- 101000757734 Mycolicibacterium phlei 38 kDa autolysin Proteins 0.000 description 1
- OVRNDRQMDRJTHS-CBQIKETKSA-N N-Acetyl-D-Galactosamine Chemical compound CC(=O)N[C@H]1[C@@H](O)O[C@H](CO)[C@H](O)[C@@H]1O OVRNDRQMDRJTHS-CBQIKETKSA-N 0.000 description 1
- OVBPIULPVIDEAO-UHFFFAOYSA-N N-Pteroyl-L-glutaminsaeure Natural products C=1N=C2NC(N)=NC(=O)C2=NC=1CNC1=CC=C(C(=O)NC(CCC(O)=O)C(O)=O)C=C1 OVBPIULPVIDEAO-UHFFFAOYSA-N 0.000 description 1
- OVRNDRQMDRJTHS-UHFFFAOYSA-N N-acelyl-D-glucosamine Natural products CC(=O)NC1C(O)OC(CO)C(O)C1O OVRNDRQMDRJTHS-UHFFFAOYSA-N 0.000 description 1
- MBLBDJOUHNCFQT-UHFFFAOYSA-N N-acetyl-D-galactosamine Natural products CC(=O)NC(C=O)C(O)C(O)C(O)CO MBLBDJOUHNCFQT-UHFFFAOYSA-N 0.000 description 1
- OVRNDRQMDRJTHS-FMDGEEDCSA-N N-acetyl-beta-D-glucosamine Chemical compound CC(=O)N[C@H]1[C@H](O)O[C@H](CO)[C@@H](O)[C@@H]1O OVRNDRQMDRJTHS-FMDGEEDCSA-N 0.000 description 1
- MBLBDJOUHNCFQT-LXGUWJNJSA-N N-acetylglucosamine Natural products CC(=O)N[C@@H](C=O)[C@@H](O)[C@H](O)[C@H](O)CO MBLBDJOUHNCFQT-LXGUWJNJSA-N 0.000 description 1
- 102000003729 Neprilysin Human genes 0.000 description 1
- 108090000028 Neprilysin Proteins 0.000 description 1
- 108010025020 Nerve Growth Factor Proteins 0.000 description 1
- 102000015336 Nerve Growth Factor Human genes 0.000 description 1
- 102000007339 Nerve Growth Factor Receptors Human genes 0.000 description 1
- 108010032605 Nerve Growth Factor Receptors Proteins 0.000 description 1
- 101710163270 Nuclease Proteins 0.000 description 1
- 108010016076 Octreotide Proteins 0.000 description 1
- 206010030155 Oesophageal carcinoma Diseases 0.000 description 1
- 206010033128 Ovarian cancer Diseases 0.000 description 1
- 206010061535 Ovarian neoplasm Diseases 0.000 description 1
- 206010061902 Pancreatic neoplasm Diseases 0.000 description 1
- 108010033276 Peptide Fragments Proteins 0.000 description 1
- 102000007079 Peptide Fragments Human genes 0.000 description 1
- 108090000608 Phosphoric Monoester Hydrolases Proteins 0.000 description 1
- 102000004160 Phosphoric Monoester Hydrolases Human genes 0.000 description 1
- 108010038512 Platelet-Derived Growth Factor Proteins 0.000 description 1
- 102000010780 Platelet-Derived Growth Factor Human genes 0.000 description 1
- 229920000954 Polyglycolide Polymers 0.000 description 1
- 101710098940 Pro-epidermal growth factor Proteins 0.000 description 1
- 102100036735 Prostate stem cell antigen Human genes 0.000 description 1
- 101710120463 Prostate stem cell antigen Proteins 0.000 description 1
- 108091028664 Ribonucleotide Proteins 0.000 description 1
- 239000002262 Schiff base Substances 0.000 description 1
- 150000004753 Schiff bases Chemical class 0.000 description 1
- BUGBHKTXTAQXES-UHFFFAOYSA-N Selenium Chemical class [Se] BUGBHKTXTAQXES-UHFFFAOYSA-N 0.000 description 1
- 102000008847 Serpin Human genes 0.000 description 1
- 108050000761 Serpin Proteins 0.000 description 1
- FOIXSVOLVBLSDH-UHFFFAOYSA-N Silver ion Chemical compound [Ag+] FOIXSVOLVBLSDH-UHFFFAOYSA-N 0.000 description 1
- 208000000453 Skin Neoplasms Diseases 0.000 description 1
- 102100033928 Sodium-dependent dopamine transporter Human genes 0.000 description 1
- 108010056088 Somatostatin Proteins 0.000 description 1
- 102000005157 Somatostatin Human genes 0.000 description 1
- 208000036765 Squamous cell carcinoma of the esophagus Diseases 0.000 description 1
- 208000005718 Stomach Neoplasms Diseases 0.000 description 1
- 108090000190 Thrombin Proteins 0.000 description 1
- 108060008245 Thrombospondin Proteins 0.000 description 1
- 102000002938 Thrombospondin Human genes 0.000 description 1
- 101710150448 Transcriptional regulator Myc Proteins 0.000 description 1
- 108060008682 Tumor Necrosis Factor Proteins 0.000 description 1
- 208000007097 Urinary Bladder Neoplasms Diseases 0.000 description 1
- 102000003990 Urokinase-type plasminogen activator Human genes 0.000 description 1
- 102000009484 Vascular Endothelial Growth Factor Receptors Human genes 0.000 description 1
- WJFVEEAIYIOATH-RTRLPJTCSA-N [(2r,3s,4r,5r)-5-acetamido-3,4,6-trihydroxyoxan-2-yl]methyl hydrogen sulfate Chemical group CC(=O)N[C@H]1C(O)O[C@H](COS(O)(=O)=O)[C@@H](O)[C@@H]1O WJFVEEAIYIOATH-RTRLPJTCSA-N 0.000 description 1
- LGDAGYXJBDILKZ-UHFFFAOYSA-N [2-methyl-1,1-dioxo-3-(pyridin-2-ylcarbamoyl)-1$l^{6},2-benzothiazin-4-yl] 2,2-dimethylpropanoate Chemical compound CC(C)(C)C(=O)OC=1C2=CC=CC=C2S(=O)(=O)N(C)C=1C(=O)NC1=CC=CC=N1 LGDAGYXJBDILKZ-UHFFFAOYSA-N 0.000 description 1
- 239000006096 absorbing agent Substances 0.000 description 1
- 230000035508 accumulation Effects 0.000 description 1
- 238000009825 accumulation Methods 0.000 description 1
- DHKHKXVYLBGOIT-UHFFFAOYSA-N acetaldehyde Diethyl Acetal Natural products CCOC(C)OCC DHKHKXVYLBGOIT-UHFFFAOYSA-N 0.000 description 1
- 125000002777 acetyl group Chemical class [H]C([H])([H])C(*)=O 0.000 description 1
- 239000012445 acidic reagent Substances 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 239000012190 activator Substances 0.000 description 1
- 125000004442 acylamino group Chemical group 0.000 description 1
- 229960000643 adenine Drugs 0.000 description 1
- 239000000556 agonist Substances 0.000 description 1
- 230000001270 agonistic effect Effects 0.000 description 1
- 125000003172 aldehyde group Chemical group 0.000 description 1
- 150000001299 aldehydes Chemical class 0.000 description 1
- 125000002723 alicyclic group Chemical group 0.000 description 1
- 125000004183 alkoxy alkyl group Chemical group 0.000 description 1
- 125000002877 alkyl aryl group Chemical group 0.000 description 1
- 125000002947 alkylene group Chemical group 0.000 description 1
- 102000004139 alpha-Amylases Human genes 0.000 description 1
- 108090000637 alpha-Amylases Proteins 0.000 description 1
- WQZGKKKJIJFFOK-PHYPRBDBSA-N alpha-D-galactose Chemical compound OC[C@H]1O[C@H](O)[C@H](O)[C@@H](O)[C@H]1O WQZGKKKJIJFFOK-PHYPRBDBSA-N 0.000 description 1
- 229940024171 alpha-amylase Drugs 0.000 description 1
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
- 125000000539 amino acid group Chemical group 0.000 description 1
- 125000003277 amino group Chemical group 0.000 description 1
- 229950006323 angiotensin ii Drugs 0.000 description 1
- 230000003042 antagnostic effect Effects 0.000 description 1
- 239000005557 antagonist Substances 0.000 description 1
- 239000003963 antioxidant agent Substances 0.000 description 1
- 238000013459 approach Methods 0.000 description 1
- 229940114079 arachidonic acid Drugs 0.000 description 1
- 235000021342 arachidonic acid Nutrition 0.000 description 1
- 125000000637 arginyl group Chemical group N[C@@H](CCCNC(N)=N)C(=O)* 0.000 description 1
- 238000000149 argon plasma sintering Methods 0.000 description 1
- 125000000732 arylene group Chemical group 0.000 description 1
- 235000009582 asparagine Nutrition 0.000 description 1
- 229960001230 asparagine Drugs 0.000 description 1
- 235000003704 aspartic acid Nutrition 0.000 description 1
- CKLJMWTZIZZHCS-REOHCLBHSA-N aspartic acid group Chemical group N[C@@H](CC(=O)O)C(=O)O CKLJMWTZIZZHCS-REOHCLBHSA-N 0.000 description 1
- 210000003719 b-lymphocyte Anatomy 0.000 description 1
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 1
- MSWZFWKMSRAUBD-UHFFFAOYSA-N beta-D-galactosamine Natural products NC1C(O)OC(CO)C(O)C1O MSWZFWKMSRAUBD-UHFFFAOYSA-N 0.000 description 1
- MSWZFWKMSRAUBD-QZABAPFNSA-N beta-D-glucosamine Chemical compound N[C@H]1[C@H](O)O[C@H](CO)[C@@H](O)[C@@H]1O MSWZFWKMSRAUBD-QZABAPFNSA-N 0.000 description 1
- 102000006995 beta-Glucosidase Human genes 0.000 description 1
- 108010047754 beta-Glucosidase Proteins 0.000 description 1
- SQVRNKJHWKZAKO-UHFFFAOYSA-N beta-N-Acetyl-D-neuraminic acid Natural products CC(=O)NC1C(O)CC(O)(C(O)=O)OC1C(O)C(O)CO SQVRNKJHWKZAKO-UHFFFAOYSA-N 0.000 description 1
- 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 1
- 230000000975 bioactive effect Effects 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
- 239000012620 biological material Substances 0.000 description 1
- 229920001222 biopolymer Polymers 0.000 description 1
- 238000001574 biopsy Methods 0.000 description 1
- 229960002685 biotin Drugs 0.000 description 1
- 235000020958 biotin Nutrition 0.000 description 1
- 239000011616 biotin Substances 0.000 description 1
- 229910052796 boron Inorganic materials 0.000 description 1
- 239000000872 buffer Substances 0.000 description 1
- 239000000298 carbocyanine Substances 0.000 description 1
- 150000007942 carboxylates Chemical class 0.000 description 1
- 150000001735 carboxylic acids Chemical class 0.000 description 1
- 210000000170 cell membrane Anatomy 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 238000012512 characterization method Methods 0.000 description 1
- 238000012412 chemical coupling Methods 0.000 description 1
- 230000007073 chemical hydrolysis Effects 0.000 description 1
- 238000012790 confirmation Methods 0.000 description 1
- 238000010226 confocal imaging Methods 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 125000004093 cyano group Chemical group *C#N 0.000 description 1
- 125000004122 cyclic group Chemical group 0.000 description 1
- 150000001924 cycloalkanes Chemical class 0.000 description 1
- 125000002993 cycloalkylene group Chemical group 0.000 description 1
- ILRYLPWNYFXEMH-UHFFFAOYSA-N cystathionine Chemical compound OC(=O)C(N)CCSCC(N)C(O)=O ILRYLPWNYFXEMH-UHFFFAOYSA-N 0.000 description 1
- 108050004038 cystatin Proteins 0.000 description 1
- 125000000151 cysteine group Chemical group N[C@@H](CS)C(=O)* 0.000 description 1
- 229940104302 cytosine Drugs 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 150000001982 diacylglycerols Chemical class 0.000 description 1
- 238000002059 diagnostic imaging Methods 0.000 description 1
- 238000010494 dissociation reaction Methods 0.000 description 1
- 230000005593 dissociations Effects 0.000 description 1
- AFOSIXZFDONLBT-UHFFFAOYSA-N divinyl sulfone Chemical class C=CS(=O)(=O)C=C AFOSIXZFDONLBT-UHFFFAOYSA-N 0.000 description 1
- 230000005684 electric field Effects 0.000 description 1
- 238000001941 electron spectroscopy Methods 0.000 description 1
- 238000002265 electronic spectrum Methods 0.000 description 1
- 238000000295 emission spectrum Methods 0.000 description 1
- 238000001839 endoscopy Methods 0.000 description 1
- ZUBDGKVDJUIMQQ-UBFCDGJISA-N endothelin-1 Chemical compound C([C@@H](C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(O)=O)NC(=O)[C@H]1NC(=O)[C@H](CC=2C=CC=CC=2)NC(=O)[C@@H](CC=2C=CC(O)=CC=2)NC(=O)[C@H](C(C)C)NC(=O)[C@H]2CSSC[C@@H](C(N[C@H](CO)C(=O)N[C@@H](CO)C(=O)N[C@H](CC(C)C)C(=O)N[C@@H](CCSC)C(=O)N[C@H](CC(O)=O)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCC(O)=O)C(=O)N2)=O)NC(=O)[C@@H](CO)NC(=O)[C@H](N)CSSC1)C1=CNC=N1 ZUBDGKVDJUIMQQ-UBFCDGJISA-N 0.000 description 1
- 229940125532 enzyme inhibitor Drugs 0.000 description 1
- 208000028653 esophageal adenocarcinoma Diseases 0.000 description 1
- 201000004101 esophageal cancer Diseases 0.000 description 1
- 208000007276 esophageal squamous cell carcinoma Diseases 0.000 description 1
- 125000004185 ester group Chemical group 0.000 description 1
- 229960005309 estradiol Drugs 0.000 description 1
- 229930182833 estradiol Natural products 0.000 description 1
- 229940011871 estrogen Drugs 0.000 description 1
- 239000000262 estrogen Substances 0.000 description 1
- 150000002170 ethers Chemical class 0.000 description 1
- 230000005281 excited state Effects 0.000 description 1
- 210000002744 extracellular matrix Anatomy 0.000 description 1
- 210000001723 extracellular space Anatomy 0.000 description 1
- 229940012952 fibrinogen Drugs 0.000 description 1
- 125000001153 fluoro group Chemical group F* 0.000 description 1
- 125000003709 fluoroalkyl group Chemical group 0.000 description 1
- 229960000304 folic acid Drugs 0.000 description 1
- 235000019152 folic acid Nutrition 0.000 description 1
- 239000011724 folic acid Substances 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 238000007306 functionalization reaction Methods 0.000 description 1
- 229930182830 galactose Natural products 0.000 description 1
- 206010017758 gastric cancer Diseases 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- 229930182478 glucoside Natural products 0.000 description 1
- 125000002791 glucosyl group Chemical group C1([C@H](O)[C@@H](O)[C@H](O)[C@H](O1)CO)* 0.000 description 1
- 235000013922 glutamic acid Nutrition 0.000 description 1
- 239000004220 glutamic acid Substances 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
- 125000002795 guanidino group Chemical group C(N)(=N)N* 0.000 description 1
- 125000005843 halogen group Chemical group 0.000 description 1
- 125000001072 heteroaryl group Chemical group 0.000 description 1
- 125000005549 heteroarylene group Chemical group 0.000 description 1
- 102000018483 human kallikrein 5 Human genes 0.000 description 1
- 229940042795 hydrazides for tuberculosis treatment Drugs 0.000 description 1
- 229960000890 hydrocortisone Drugs 0.000 description 1
- 230000002209 hydrophobic effect Effects 0.000 description 1
- 125000002768 hydroxyalkyl group Chemical group 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 238000011503 in vivo imaging Methods 0.000 description 1
- 230000004054 inflammatory process Effects 0.000 description 1
- 239000004615 ingredient Substances 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 229940079322 interferon Drugs 0.000 description 1
- 230000007154 intracellular accumulation Effects 0.000 description 1
- 150000002500 ions Chemical class 0.000 description 1
- 108010088381 isoleucyl-lysyl-valyl-alanyl-valine Proteins 0.000 description 1
- 150000002540 isothiocyanates Chemical class 0.000 description 1
- 108010024383 kallikrein 4 Proteins 0.000 description 1
- 210000000265 leukocyte Anatomy 0.000 description 1
- GDBQQVLCIARPGH-ULQDDVLXSA-N leupeptin Chemical compound CC(C)C[C@H](NC(C)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@H](C=O)CCCN=C(N)N GDBQQVLCIARPGH-ULQDDVLXSA-N 0.000 description 1
- 108010052968 leupeptin Proteins 0.000 description 1
- 230000000670 limiting effect Effects 0.000 description 1
- 230000007774 longterm Effects 0.000 description 1
- 229920002521 macromolecule Polymers 0.000 description 1
- 210000002540 macrophage Anatomy 0.000 description 1
- 208000015486 malignant pancreatic neoplasm Diseases 0.000 description 1
- 238000004949 mass spectrometry Methods 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 238000000691 measurement method Methods 0.000 description 1
- 230000001404 mediated effect Effects 0.000 description 1
- DWPCPZJAHOETAG-UHFFFAOYSA-N meso-lanthionine Natural products OC(=O)C(N)CSCC(N)C(O)=O DWPCPZJAHOETAG-UHFFFAOYSA-N 0.000 description 1
- 230000003278 mimic effect Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 125000002950 monocyclic group Chemical group 0.000 description 1
- 210000003205 muscle Anatomy 0.000 description 1
- 229950006780 n-acetylglucosamine Drugs 0.000 description 1
- 229930014626 natural product Natural products 0.000 description 1
- 230000010807 negative regulation of binding Effects 0.000 description 1
- 210000005036 nerve Anatomy 0.000 description 1
- 229940053128 nerve growth factor Drugs 0.000 description 1
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 description 1
- 230000009871 nonspecific binding Effects 0.000 description 1
- 230000000269 nucleophilic effect Effects 0.000 description 1
- 238000010534 nucleophilic substitution reaction Methods 0.000 description 1
- 229960002700 octreotide Drugs 0.000 description 1
- 210000000056 organ Anatomy 0.000 description 1
- 230000003204 osmotic effect Effects 0.000 description 1
- 229940094443 oxytocics prostaglandins Drugs 0.000 description 1
- 239000003002 pH adjusting agent Substances 0.000 description 1
- 201000002528 pancreatic cancer Diseases 0.000 description 1
- 208000008443 pancreatic carcinoma Diseases 0.000 description 1
- 230000007170 pathology Effects 0.000 description 1
- KHIWWQKSHDUIBK-UHFFFAOYSA-N periodic acid Chemical compound OI(=O)(=O)=O KHIWWQKSHDUIBK-UHFFFAOYSA-N 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
- 150000004713 phosphodiesters Chemical class 0.000 description 1
- 150000008298 phosphoramidates Chemical class 0.000 description 1
- 125000004437 phosphorous atom Chemical group 0.000 description 1
- LFGREXWGYUGZLY-UHFFFAOYSA-N phosphoryl Chemical group [P]=O LFGREXWGYUGZLY-UHFFFAOYSA-N 0.000 description 1
- QWYZFXLSWMXLDM-UHFFFAOYSA-M pinacyanol iodide Chemical compound [I-].C1=CC2=CC=CC=C2N(CC)C1=CC=CC1=CC=C(C=CC=C2)C2=[N+]1CC QWYZFXLSWMXLDM-UHFFFAOYSA-M 0.000 description 1
- 229940012957 plasmin Drugs 0.000 description 1
- 230000010287 polarization Effects 0.000 description 1
- 229920001515 polyalkylene glycol Polymers 0.000 description 1
- 239000004633 polyglycolic acid Substances 0.000 description 1
- 238000002953 preparative HPLC Methods 0.000 description 1
- 150000003140 primary amides Chemical class 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- 239000000583 progesterone congener Substances 0.000 description 1
- 150000003180 prostaglandins Chemical class 0.000 description 1
- 238000000163 radioactive labelling Methods 0.000 description 1
- 230000033300 receptor internalization Effects 0.000 description 1
- 238000001055 reflectance spectroscopy Methods 0.000 description 1
- 238000012552 review Methods 0.000 description 1
- 239000002336 ribonucleotide Substances 0.000 description 1
- 125000002652 ribonucleotide group Chemical group 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- 229910052711 selenium Inorganic materials 0.000 description 1
- 239000011669 selenium Chemical class 0.000 description 1
- 210000005005 sentinel lymph node Anatomy 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 239000003001 serine protease inhibitor Substances 0.000 description 1
- 229940076279 serotonin Drugs 0.000 description 1
- SQVRNKJHWKZAKO-OQPLDHBCSA-N sialic acid Chemical compound CC(=O)N[C@@H]1[C@@H](O)C[C@@](O)(C(O)=O)OC1[C@H](O)[C@H](O)CO SQVRNKJHWKZAKO-OQPLDHBCSA-N 0.000 description 1
- 201000000849 skin cancer Diseases 0.000 description 1
- 150000003384 small molecules Chemical class 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- NHXLMOGPVYXJNR-ATOGVRKGSA-N somatostatin Chemical compound C([C@H]1C(=O)N[C@H](C(N[C@@H](CO)C(=O)N[C@@H](CSSC[C@@H](C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC=2C=CC=CC=2)C(=O)N[C@@H](CC=2C=CC=CC=2)C(=O)N[C@@H](CC=2C3=CC=CC=C3NC=2)C(=O)N[C@@H](CCCCN)C(=O)N[C@H](C(=O)N1)[C@@H](C)O)NC(=O)CNC(=O)[C@H](C)N)C(O)=O)=O)[C@H](O)C)C1=CC=CC=C1 NHXLMOGPVYXJNR-ATOGVRKGSA-N 0.000 description 1
- 229960000553 somatostatin Drugs 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 238000010561 standard procedure Methods 0.000 description 1
- 239000008174 sterile solution Substances 0.000 description 1
- 239000003270 steroid hormone Substances 0.000 description 1
- 150000003431 steroids Chemical class 0.000 description 1
- 201000011549 stomach cancer Diseases 0.000 description 1
- 150000003460 sulfonic acids Chemical class 0.000 description 1
- 125000004434 sulfur atom Chemical group 0.000 description 1
- 238000001308 synthesis method Methods 0.000 description 1
- 238000010189 synthetic method Methods 0.000 description 1
- 150000003555 thioacetals Chemical class 0.000 description 1
- 150000003556 thioamides Chemical class 0.000 description 1
- 150000003582 thiophosphoric acids Chemical class 0.000 description 1
- 229960004072 thrombin Drugs 0.000 description 1
- 150000003595 thromboxanes Chemical class 0.000 description 1
- 229940113082 thymine Drugs 0.000 description 1
- 230000000699 topical effect Effects 0.000 description 1
- 239000003053 toxin Substances 0.000 description 1
- 231100000765 toxin Toxicity 0.000 description 1
- 108091005703 transmembrane proteins Proteins 0.000 description 1
- 102000035160 transmembrane proteins Human genes 0.000 description 1
- 125000002221 trityl group Chemical group [H]C1=C([H])C([H])=C([H])C([H])=C1C([*])(C1=C(C(=C(C(=C1[H])[H])[H])[H])[H])C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 1
- XLRPYZSEQKXZAA-OCAPTIKFSA-N tropane Chemical compound C1CC[C@H]2CC[C@@H]1N2C XLRPYZSEQKXZAA-OCAPTIKFSA-N 0.000 description 1
- 229930004006 tropane Natural products 0.000 description 1
- 230000005747 tumor angiogenesis Effects 0.000 description 1
- 102000003390 tumor necrosis factor Human genes 0.000 description 1
- OUYCCCASQSFEME-UHFFFAOYSA-N tyrosine Natural products OC(=O)C(N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-UHFFFAOYSA-N 0.000 description 1
- 108010052768 tyrosyl-isoleucyl-glycyl-seryl-arginine Proteins 0.000 description 1
- 229940035893 uracil Drugs 0.000 description 1
- 201000005112 urinary bladder cancer Diseases 0.000 description 1
- 230000002485 urinary effect Effects 0.000 description 1
- 230000002792 vascular Effects 0.000 description 1
- 238000012800 visualization Methods 0.000 description 1
- 229940075420 xanthine Drugs 0.000 description 1
- 229910052727 yttrium Inorganic materials 0.000 description 1
- AFVLVVWMAFSXCK-UHFFFAOYSA-N α-cyano-4-hydroxycinnamic acid Chemical compound OC(=O)C(C#N)=CC1=CC=C(O)C=C1 AFVLVVWMAFSXCK-UHFFFAOYSA-N 0.000 description 1
- 235000021247 β-casein Nutrition 0.000 description 1
- ORQXBVXKBGUSBA-QMMMGPOBSA-N β-cyclohexyl-alanine Chemical compound OC(=O)[C@@H](N)CC1CCCCC1 ORQXBVXKBGUSBA-QMMMGPOBSA-N 0.000 description 1
Images
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K49/00—Preparations for testing in vivo
- A61K49/001—Preparation for luminescence or biological staining
- A61K49/0013—Luminescence
- A61K49/0017—Fluorescence in vivo
- A61K49/005—Fluorescence in vivo characterised by the carrier molecule carrying the fluorescent agent
- A61K49/0056—Peptides, proteins, polyamino acids
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K49/00—Preparations for testing in vivo
- A61K49/001—Preparation for luminescence or biological staining
- A61K49/0013—Luminescence
- A61K49/0017—Fluorescence in vivo
- A61K49/0019—Fluorescence in vivo characterised by the fluorescent group, e.g. oligomeric, polymeric or dendritic molecules
- A61K49/0021—Fluorescence in vivo characterised by the fluorescent group, e.g. oligomeric, polymeric or dendritic molecules the fluorescent group being a small organic molecule
- A61K49/0032—Methine dyes, e.g. cyanine dyes
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Engineering & Computer Science (AREA)
- Biomedical Technology (AREA)
- Epidemiology (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
Abstract
【選択図】 なし
Description
標的結合性リガンド(V)、
酵素開裂性基(E)、
フルオロフォア(D)、及び
消光剤(Q)
が一分子中で互いに結合した二元ターゲティング光学造影剤を提供する。
i)E−Q、及び
ii)V−D
式中、
Eは酵素開裂性基を表し、
Qは消光剤を表し、
Vは標的結合性リガンドを表し、
Dはフルオロフォアを表す。
式中、Q、D、E及びVは、上記で定義した通りであり、
L1、L2及びL3はいずれも同一又は異なるリンカー基である。
式中、Q、D、E、V並びにL1、L2及びL3は上記で定義した通りである。
・マトリックスメタロプロテイナーゼ(MMP)、例えばMMP−2、MMP−3、MMP−7、MMP−9、MMP−14、
・カテプシン、例えばカテプシンB、D、K又はL、
・カリクレイン、
・プロタンパク質転換酵素、
・膜結合型セリンプロテアーゼ。
・リジン又はアルギニン残基を含む短鎖ペプチド(アミノ酸残基数1〜5のものなど)。これのアミノ酸配列は、カテプシンB及びK、ヘプシン及び幾つかのヘプシン関連セリンプロテアーゼによって、塩基性アミノ酸のC−末端で開裂する。
・Arg−Gly−Phe−Phe−Leu−又はArg−Gly−Phe−Phe−Pro−。これらはカテプシンDで開裂する。
・Pro−Phe−Arg−B−又は−Val−Leu−Arg−B−。これらはカリクレインで開裂する。
・Ala−Ala−Phe−又はAla−Gly−Leu−Ala−。これらは中性エンドペプチダーゼで開裂する。
・Pro−Lys−Pro−Gln−Gln−Phe−Phe−Gly−Leu−Lys−Gly。これはMMP−2で開裂する。
・Arg−Pro−Lys−Pro−Val−Glu−Nva−Trp−Arg−Lys−NH2。これはMMP−3で開裂する。
・ProOH−Gly−Pro−Gln−Gly−Phe−Gln−Gly−AsN−ProOH−Gly。これはMMP−9で開裂する。
・Leu−Arg−Leu−Ser−Ser−Tyr−Tyr−Ser−Gly。これは前立腺特異抗原、カリクレインファミリーのセリンプロテアーゼで開裂する。
・Arg−Leu−Ser−Ile−B。これはプロスターゼ、カリクレインファミリーのセリンプロテアーゼで開裂する。
・Phe−Arg−Arg−B。これはカテプシンLで開裂する。
・Gly−Pro−Arg−B。これはヒトカリクレイン5、カリクレインファミリーのセリンプロテアーゼで開裂する。
ただし、Bは、Q、D、V並びにL1及びL2から選択されるアミノ酸その他の適切な基であり、下線を付したアミノ酸はD−アミノ酸を表す。
X′は−C(CH3)2、硫黄、酸素、C(CH2)aCH3(CH2)bMからなる群から独立に選択され(式中、aは0〜5の整数であり、bは1〜5の整数であり、MはG基又はSO3H及びHからなる群から選択される。)、
Y′は、H、CH2NH2、SO3H、CH2COOH、NCS及びFからなる群から独立に選択される1〜4個の基であって、Y′基は芳香族環の任意の位置にあり、
Q′は、H、SO3H、NH2、COOH、アンモニウム、エステル基、ベンジル及びG基の群から独立に選択され、
lは1〜3の整数であり、
mは1〜5の整数である。
X′は、−C(CH3)2及びC(CH3)(CH2)4Mからなる群から選択され(式中、MはG基(好ましくはスクシンイミジルエステル)であるか、MはSO3Hである。)、
Y′は、SO3H、H又は1〜4個のF原子を表し、
Q′はG基(最も好ましくはスクシンイミジルエステル)及びSO3Hから選択され、、
lは好ましくは2であり、mは好ましくは3、4又は5である。
Z1及びZ2は各々、炭素原子と適宜2個以下の酸素、窒素及び硫黄原子から選択される原子数5又は6の1又は2つの縮合芳香族環の完成に必要な結合又は原子を表し、
X及びYは、同一又は異なるもので、ビスC1〜C4アルキル及びC4〜C5スピロアルキル置換炭素、酸素、硫黄、セレン、−CH=CH−並びにN−Wから選択されものであり、Nは窒素であり、Wは水素、−(CH2)oR8基から選択され(oは1〜26の整数であり、R8は水素、アミノ、アルデヒド、アセタール、ケタール、ハロ、シアノ、アリール、ヘテロアリール、ヒドロキシル、スルホネート、サルフェート、カルボキシレート、置換アミノ、第四アンモニウム、ニトロ、第一アミド、置換アミド、並びにアミノ、ヒドロキシル、カルボニル、カルボキシル、ホスホリル及びスルフヒドリル基と反応性の基から選択される。)、
R1、R2、R3、R4、R5、R6及びR7基の少なくとも1つは結合基であり、
残りのR3、R4、R5、R6及びR7基は、水素、C1〜C4アルキル、OR9、COOR9、ニトロ、アミノ、アシルアミノ、第四アンモニウム、リン酸、スルホネート及びサルフェートから選択され(R9はH及びC1〜C4アルキルから選択される。)、
残りのR1及びR2は、C1〜C10アルキル(置換されていなくても、フェニルで置換されていてもよく、フェニルは適宜カルボキシル、スルホネート及びニトロ基から選択される2以下の置換基で置換されていてもよい。)から選択され、
R1、R2、R3、R4、R6及びR7基の少なくとも1つが、消光剤が本質的に非蛍光性となるように消光剤の蛍光発光を低減させる置換基を含んでいることを特徴とする。
・ソマトスタチン、オクトレオチド及び類似体、
・ST受容体に結合するペプチド(STとは大腸菌その他の微生物で産生される熱安定性トキシンを表す。)、
・ラミニンフラグメント、例えばYIGSR、PDSGR、IKVAV、LRE及びKCQAGTFALRGDPQG、
・白血球蓄積の標的部位用のN−ホルミルペプチド、
・血小板第4因子(PF4)及びそのフラグメント、
・RGD含有ペプチド、
・アンジオテンシンII、
・エンドセリン、
・VEGF、EGF、肝細胞増殖因子、神経成長因子、インターフェロン、インターロイキン、血小板由来増殖因子、腫瘍壊死因子、マクロファージコロニー刺激因子などのサイトカイン及びそれらのフラグメント、
・MCP−1及びエオタキシンなどのケモカイン、
・α2−抗プラスミン、フィブロネクチン又はβ−カゼイン、フィブリノーゲン又はトロンボスポンジンのペプチド断片。
・例えば腫瘍血管新生では:MMP−9などのMMPとVEGFR;MT−1メタロプロテイナーゼとαvβ3インテグリン、
・例えば乳癌では:MMP−9とEGFR;カリクレイン−14とCD44;カテプシンDと神経成長因子受容体、
・例えば食道の扁平上皮癌では:カテプシンDとEGFR;MMP−9とMUC5AC、
・例えば食道の腺癌その他の癌腫では:MMP−12とコレシストキニン受容体;カテプシンDとグアニリルシクラーゼ、
・例えば肺癌では:ガレクチン−3とMMP−9;ウロキナーゼプラスミノーゲン活性化因子とCA125;カテプシンLとコレシストキニン受容体、
・例えば前立腺癌では:ヘプシンと前立腺幹細胞抗原;ヘプシンとEGFR;カテプシンDと前立腺特異抗原、
・例えば大腸癌では:アミノペプチダーゼN/CD13とCEA;MMP−9とc−Myc;カテプシンBとクルステリン;uPAとベンゾジアゼピン受容体;MMP−14とc−Met、
・例えばアテローム硬化性プラークでは:MMP−3とエンドセリン受容体;MMP−9とCD36;カテプシンBとC−反応性タンパク質。
化合物の構造を、図2に示す。
Claims (17)
- 以下の構成成分が一分子中で互いに結合した二元ターゲティング光学造影剤。
標的結合性リガンド(V)、
酵素開裂性基(E)、
フルオロフォア(D)、及び
消光剤(Q)。 - 以下の構成ブロックi)及びii)が互いに結合している、請求項1記載の造影剤。
i)E−Q、及び
ii)V−D
式中、
Eは酵素開裂性基を表し、
Qは消光剤を表し、
Vは標的結合性リガンドを表し、
Dはフルオロフォアを表す。 - 式(I)又は(II)の造影剤。
Q−L1−E−L2−V−L3−D (I)
Q−L1−E−L2−D−L3−V (II)
式中、Q、D、E及びVは上記で定義した通りであり、L1、L2及びL3はいずれも同一又は異なるリンカー基である。 - Vが生物学的受容体に対して親和性を有し、Eが酵素で活性化され、上記受容体及び酵素が同じ組織中で一緒に上方制御される、請求項1乃至請求項3のいずれか1項記載の造影剤。
- Vが受容体に結合する前に、Eが酵素によって開裂する、請求項1乃至請求項4のいずれか1項記載の造影剤。
- Vが、核酸、タンパク質、脂質、リポタンパク質及び糖タンパク質からなる群から選択される受容体に親和性を有する、請求項1乃至請求項5のいずれか1項記載の造影剤。
- Vが、ペプチド、ペプトイド/ペプチド模倣体、オリゴヌクレオチド、オリゴ糖、脂質関連化合物、合成低分子薬物様分子、阻害剤、抗体及び抗体フラグメント、ホルモン、ビタミン、神経伝達物質、並びにこれらの誘導体及び模倣体からなる群から選択される、請求項1乃至請求項6のいずれか1項記載の造影剤。
- Eが、プロテアーゼ、ペプチダーゼ、エステラーゼ、ホスファターゼ、ホスホジエステラーゼ、デアルキラーゼ及びグリコシダーゼ又はエンドグリカナーゼからなる群から選択される酵素の基質を含む、請求項1乃至請求項7のいずれか1項記載の造影剤。
- 受容体チロシンキナーゼ、インテグリン受容体のファミリー及び癌関連抗原からなる群から選択される受容体に親和性を有する標的結合性リガンドと、マトリックスメタロプロテイナーゼ、カテプシン、カリクレイン、プロタンパク質転換酵素及び膜結合型セリンプロテアーゼからなる群から選択される酵素に親和性を有する酵素開裂性基とを含む、請求項1乃至請求項8のいずれか1項記載の造影剤。
- FRETにおいてQが供与体発色団であってDが受容体発色団であり、Qが本質的に非蛍光性である、請求項1乃至請求項9のいずれか1項記載の造影剤。
- Dが、クマリン色素、ベンゾクマリン色素、キサンテン色素、フェノキサジン色素、ローダミン色素、アクリドン色素、メロシアニン色素、シアニン色素及びビスピロメテン二フッ化ホウ素発色団の誘導体からなる群から選択される、請求項1乃至請求項10のいずれか1項記載の造影剤。
- Qが、2,4−ジニトロフェニル(DNP)、4−(4−ジメチルアミノフェニル)アゾ安息香酸(DABCYL)、7−メトキシクマリン−4−イル)−アセチル(Mca)及び非蛍光性シアニン発色団からなる群から選択される、請求項1乃至請求項11のいずれか1項記載の造影剤。
- 請求項1乃至請求項12のいずれか1項記載の化合物の有効量を、薬学的に許容される1種以上の補助剤、賦形剤又は希釈剤と共に含んでなる医薬組成物。
- 光学イメージング造影剤として使用するための、請求項1乃至請求項13のいずれか1項記載の造影剤又は組成物。
- 造影剤をヒト又は動物の身体に投与して身体の少なくとも一部分の画像を生成させることを含む診断方法に用いられる光学イメージングコントラスト強調剤の製造における、請求項1乃至請求項12のいずれか1項記載の造影剤の使用。
- 請求項1乃至請求項12のいずれか1項記載の造影剤をヒト又は動物の身体に投与して造影剤が分布した身体の少なくとも一部分の画像を生成させることを含む、光学イメージングによってヒト又は動物の身体の画像を生成させる方法。
- 病態に対処するための薬剤によるヒト又は動物の身体の治療効果をモニタリングする方法であって、請求項1乃至請求項13のいずれか1項記載の造影剤又は組成物を身体に投与し、細胞受容体による上記化合物又は組成物の取込みを検出し、任意ではあるが好ましくは、投与と検出を、例えば上記化合物又は組成物による治療の前後途中のいずれかに繰り返すことを含んでなる方法。
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
NO20053354A NO20053354D0 (no) | 2005-07-11 | 2005-07-11 | Optical imaging contrast agent. |
PCT/NO2006/000264 WO2007008080A2 (en) | 2005-07-11 | 2006-07-10 | Optical imaging contrast agents |
Publications (2)
Publication Number | Publication Date |
---|---|
JP2009500448A true JP2009500448A (ja) | 2009-01-08 |
JP2009500448A5 JP2009500448A5 (ja) | 2009-07-30 |
Family
ID=35295161
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2008521342A Pending JP2009500448A (ja) | 2005-07-11 | 2006-07-10 | 光学イメージング造影剤 |
Country Status (6)
Country | Link |
---|---|
US (1) | US20080206141A1 (ja) |
EP (1) | EP1901780A2 (ja) |
JP (1) | JP2009500448A (ja) |
CN (1) | CN101257928A (ja) |
NO (1) | NO20053354D0 (ja) |
WO (1) | WO2007008080A2 (ja) |
Families Citing this family (18)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
PL2146749T3 (pl) | 2007-05-16 | 2012-09-28 | Ge Healthcare As | Znaczone peptydy wiążące HGF przydatne do obrazowania |
WO2009092062A2 (en) | 2008-01-18 | 2009-07-23 | Visen Medical, Inc. | Fluorescent imaging agents |
GB0823315D0 (en) | 2008-12-22 | 2009-01-28 | Ge Healthcare As | Fluorescent Probes |
EP2618849B1 (en) * | 2010-09-20 | 2020-10-21 | Caliper Life Sciences, Inc. | Multivalent fluorescent probes |
DE112012002570B4 (de) | 2011-06-23 | 2023-11-23 | Board Of Regents, The University Of Texas System | Identifizieren von Peptiden auf der Einzelmolekülebene |
US11435358B2 (en) | 2011-06-23 | 2022-09-06 | Board Of Regents, The University Of Texas System | Single molecule peptide sequencing |
EP3004375A4 (en) * | 2013-06-06 | 2017-05-10 | Agency For Science, Technology And Research | Protease-responsive peptide biosensors and methods for analyte detection |
PL405046A1 (pl) * | 2013-08-12 | 2015-02-16 | Instytut Biologii Doświadczalnej Im. Marcelego Nenckiego Pan | Genetycznie kodowany oparty na FRET biosensor aktywności MMP-9 i jego zastosowanie |
CN104792979B (zh) * | 2014-09-05 | 2017-02-01 | 昆明医科大学第一附属医院 | 一种检测人基质金属蛋白酶‑12活性的荧光多肽底物 |
EP3543703A1 (en) * | 2014-09-15 | 2019-09-25 | Board of Regents, The University of Texas System | Improved single molecule peptide sequencing |
GB201420222D0 (en) | 2014-11-13 | 2014-12-31 | Univ Edinburgh | Molecular probes and methods using the same |
GB201420223D0 (en) * | 2014-11-13 | 2014-12-31 | Univ Edinburgh | Molecular probes and methods using the same |
GB201420221D0 (en) | 2014-11-13 | 2014-12-31 | Univ Edinburgh | Molecular probes and methods using the same |
CN104672300A (zh) * | 2015-03-17 | 2015-06-03 | 武汉大学 | 一种双酶敏感型荧光探针及其制备方法和应用 |
GB201504778D0 (en) * | 2015-03-20 | 2015-05-06 | Univ Edinburgh | Optical probes for matrix metalloproteinases |
AU2019338403A1 (en) | 2018-09-11 | 2021-04-15 | Oregon Health & Science University | Near-infrared nerve-sparing benzo[C]phenoxazine fluorophores |
CN112494664A (zh) * | 2020-12-14 | 2021-03-16 | 武汉工程大学 | 一种多糖类磁共振及荧光双模式成像诊断剂及其制备方法和诊断试剂 |
CN113521313A (zh) * | 2021-07-22 | 2021-10-22 | 戴格普瑞生物科技(苏州)有限公司 | 靶向造影剂、产品、制备方法及应用 |
Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2003532745A (ja) * | 1998-06-11 | 2003-11-05 | アマシャム バイオサイエンス ユーケイ リミテッド | エネルギー伝達アッセイ法および試薬 |
WO2004028449A2 (en) * | 2002-09-24 | 2004-04-08 | The General Hospital Corporation | Azulene dimer-quenched, near-infrared fluorescent probes |
Family Cites Families (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US6592847B1 (en) * | 1998-05-14 | 2003-07-15 | The General Hospital Corporation | Intramolecularly-quenched near infrared flourescent probes |
US20050249668A1 (en) * | 2002-03-29 | 2005-11-10 | Ralph Weissleder | Nir-fluorescent cyanine dyes, their synthesis and biological use |
-
2005
- 2005-07-11 NO NO20053354A patent/NO20053354D0/no unknown
-
2006
- 2006-07-10 EP EP06769435A patent/EP1901780A2/en not_active Ceased
- 2006-07-10 WO PCT/NO2006/000264 patent/WO2007008080A2/en active Application Filing
- 2006-07-10 JP JP2008521342A patent/JP2009500448A/ja active Pending
- 2006-07-10 US US11/995,220 patent/US20080206141A1/en not_active Abandoned
- 2006-07-10 CN CNA2006800328876A patent/CN101257928A/zh active Pending
Patent Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2003532745A (ja) * | 1998-06-11 | 2003-11-05 | アマシャム バイオサイエンス ユーケイ リミテッド | エネルギー伝達アッセイ法および試薬 |
WO2004028449A2 (en) * | 2002-09-24 | 2004-04-08 | The General Hospital Corporation | Azulene dimer-quenched, near-infrared fluorescent probes |
Also Published As
Publication number | Publication date |
---|---|
WO2007008080A3 (en) | 2007-10-04 |
US20080206141A1 (en) | 2008-08-28 |
EP1901780A2 (en) | 2008-03-26 |
WO2007008080A2 (en) | 2007-01-18 |
NO20053354D0 (no) | 2005-07-11 |
CN101257928A (zh) | 2008-09-03 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
JP2009500448A (ja) | 光学イメージング造影剤 | |
Staderini et al. | Peptides for optical medical imaging and steps towards therapy | |
US8841085B2 (en) | Nanoparticle sensor for measuring protease activity and method for manufacturing the same | |
US10829477B2 (en) | Activity-based probe compounds, compositions, and methods of use | |
US10507247B2 (en) | Optical probes for matrix metalloproteinases | |
CN103597039A (zh) | 可活化的发荧光的化合物及其作为近红外探针的用途 | |
AU2022202947B2 (en) | Activity-based probe compounds, compositions, and methods of use | |
US20140140930A1 (en) | Non-peptidic quenched fluorescent imaging probes | |
US20240025945A1 (en) | Protease-activated contrast agents for in vivo imaging | |
US11851421B2 (en) | Near-infrared cyanine dyes and conjugates thereof | |
WO2003082988A1 (en) | Nir-fluorescent cyanine dyes, their synthesis and biological use | |
US20070212305A1 (en) | Optical Imaging Contrast Agents For Imaging Lung Cancer | |
WO2010002976A2 (en) | Enzyme-cleavable dye-containing fluor-quencher constructs | |
Schleyer et al. | Molecular probes for selective detection of cysteine cathepsins | |
US20080044350A1 (en) | Optical Imaging Contrast Agents for Imaging Lung Cancer | |
JP7149614B2 (ja) | in vivo画像化のためのプロテアーゼ活性化コントラスト剤 | |
US20070258904A1 (en) | Optical Imaging Contrast Agents | |
Mier et al. | Fluorescent somatostatin receptor probes for the intraoperative detection of tumor tissue with long-wavelength visible light | |
WO2005058153A2 (en) | Optical imaging contrast agents comprising a targeting vector linked to a fluorophore |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20090609 |
|
A621 | Written request for application examination |
Free format text: JAPANESE INTERMEDIATE CODE: A621 Effective date: 20090609 |
|
RD02 | Notification of acceptance of power of attorney |
Free format text: JAPANESE INTERMEDIATE CODE: A7422 Effective date: 20090609 |
|
RD04 | Notification of resignation of power of attorney |
Free format text: JAPANESE INTERMEDIATE CODE: A7424 Effective date: 20090609 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20100531 |
|
A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20111025 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20120124 |
|
A02 | Decision of refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A02 Effective date: 20120918 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20130118 |
|
A911 | Transfer to examiner for re-examination before appeal (zenchi) |
Free format text: JAPANESE INTERMEDIATE CODE: A911 Effective date: 20130322 |
|
A912 | Re-examination (zenchi) completed and case transferred to appeal board |
Free format text: JAPANESE INTERMEDIATE CODE: A912 Effective date: 20130524 |