JP2011507861A5 - - Google Patents

Info

Publication number

JP2011507861A5

JP2011507861A5 JP2010539518A JP2010539518A JP2011507861A5 JP 2011507861 A5 JP2011507861 A5 JP 2011507861A5 JP 2010539518 A JP2010539518 A JP 2010539518A JP 2010539518 A JP2010539518 A JP 2010539518A JP 2011507861 A5 JP2011507861 A5 JP 2011507861A5

Authority

JP

Japan

Prior art keywords

connexin

composition

polynucleotide

medicament

item

Prior art date

2008-12-22

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.)

Withdrawn

Links

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• 239000000203 mixture Substances 0.000 claims description 79
• 238000000034 method Methods 0.000 claims description 58
• 108091033319 polynucleotide Proteins 0.000 claims description 58
• 239000002157 polynucleotide Substances 0.000 claims description 58
• 102000040430 polynucleotide Human genes 0.000 claims description 58
• 230000000692 anti-sense effect Effects 0.000 claims description 44
• 108090000765 processed proteins & peptides Proteins 0.000 claims description 38
• 239000003795 chemical substances by application Substances 0.000 claims description 37
• 239000008194 pharmaceutical composition Substances 0.000 claims description 37
• 230000003176 fibrotic effect Effects 0.000 claims description 30
• 239000003814 drug Substances 0.000 claims description 29
• 206010016654 Fibrosis Diseases 0.000 claims description 24
• 230000004761 fibrosis Effects 0.000 claims description 24
• 239000000816 peptidomimetic Substances 0.000 claims description 22
• 241000124008 Mammalia Species 0.000 claims description 20
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 20
• 102000001045 Connexin 43 Human genes 0.000 claims description 16
• 108010069241 Connexin 43 Proteins 0.000 claims description 16
• 241001465754 Metazoa Species 0.000 claims description 16
• 102000010970 Connexin Human genes 0.000 claims description 15
• 108050001175 Connexin Proteins 0.000 claims description 15
• 108020004999 messenger RNA Proteins 0.000 claims description 12
• 239000002773 nucleotide Substances 0.000 claims description 12
• 125000003729 nucleotide group Chemical group 0.000 claims description 12
• 201000010099 disease Diseases 0.000 claims description 10
• 208000035475 disorder Diseases 0.000 claims description 10
• 238000011282 treatment Methods 0.000 claims description 8
• FWMNVWWHGCHHJJ-SKKKGAJSSA-N 4-amino-1-[(2r)-6-amino-2-[[(2r)-2-[[(2r)-2-[[(2r)-2-amino-3-phenylpropanoyl]amino]-3-phenylpropanoyl]amino]-4-methylpentanoyl]amino]hexanoyl]piperidine-4-carboxylic acid Chemical compound C([C@H](C(=O)N[C@H](CC(C)C)C(=O)N[C@H](CCCCN)C(=O)N1CCC(N)(CC1)C(O)=O)NC(=O)[C@H](N)CC=1C=CC=CC=1)C1=CC=CC=C1 FWMNVWWHGCHHJJ-SKKKGAJSSA-N 0.000 claims description 6
• 108091030071 RNAI Proteins 0.000 claims description 6
• 108020004459 Small interfering RNA Proteins 0.000 claims description 6
• 230000000295 complement effect Effects 0.000 claims description 6
• 238000002844 melting Methods 0.000 claims description 6
• 230000008018 melting Effects 0.000 claims description 6
• 230000004962 physiological condition Effects 0.000 claims description 6
• 101800005309 Carboxy-terminal peptide Proteins 0.000 claims description 4
• 229920002134 Carboxymethyl cellulose Polymers 0.000 claims description 4
• 108091034117 Oligonucleotide Proteins 0.000 claims description 4
• 235000010948 carboxy methyl cellulose Nutrition 0.000 claims description 4
• 239000001768 carboxy methyl cellulose Substances 0.000 claims description 4
• 239000008112 carboxymethyl-cellulose Substances 0.000 claims description 4
• 150000001875 compounds Chemical class 0.000 claims description 4
• 210000003976 gap junction Anatomy 0.000 claims description 4
• 244000144972 livestock Species 0.000 claims description 4
• 229920002503 polyoxyethylene-polyoxypropylene Polymers 0.000 claims description 4
• 230000002265 prevention Effects 0.000 claims description 4
• 230000006916 protein interaction Effects 0.000 claims description 4
• 238000011200 topical administration Methods 0.000 claims description 4
• 230000003510 anti-fibrotic effect Effects 0.000 claims description 2
• 239000005022 packaging material Substances 0.000 claims description 2
• 229920001983 poloxamer Polymers 0.000 claims description 2
• 238000011321 prophylaxis Methods 0.000 claims description 2
• 102000004196 processed proteins & peptides Human genes 0.000 claims 3
• 230000026731 phosphorylation Effects 0.000 claims 2
• 238000006366 phosphorylation reaction Methods 0.000 claims 2
• 238000002560 therapeutic procedure Methods 0.000 claims 2
• 102100033299 Glia-derived nexin Human genes 0.000 claims 1
• 101000997803 Homo sapiens Glia-derived nexin Proteins 0.000 claims 1
• 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 claims 1
• 238000011257 definitive treatment Methods 0.000 claims 1
• 230000002401 inhibitory effect Effects 0.000 claims 1
• 230000002222 downregulating effect Effects 0.000 description 1
• 229940079593 drug Drugs 0.000 description 1
• 239000003607 modifier Substances 0.000 description 1