JP2005504829A - 構造的心疾患における心筋機能不全を処置するためのカルモジュリンキナーゼiiインヒビターの使用 - Google Patents
構造的心疾患における心筋機能不全を処置するためのカルモジュリンキナーゼiiインヒビターの使用 Download PDFInfo
- Publication number
- JP2005504829A JP2005504829A JP2003532646A JP2003532646A JP2005504829A JP 2005504829 A JP2005504829 A JP 2005504829A JP 2003532646 A JP2003532646 A JP 2003532646A JP 2003532646 A JP2003532646 A JP 2003532646A JP 2005504829 A JP2005504829 A JP 2005504829A
- Authority
- JP
- Japan
- Prior art keywords
- peptide
- inhibitor
- seq
- camkii
- animal
- 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
- 239000003112 inhibitor Substances 0.000 title claims abstract description 125
- 230000002107 myocardial effect Effects 0.000 title claims abstract description 47
- 208000019622 heart disease Diseases 0.000 title claims abstract description 45
- 230000004064 dysfunction Effects 0.000 title claims abstract description 24
- 108010026870 Calcium-Calmodulin-Dependent Protein Kinases Proteins 0.000 title claims description 8
- 102000019025 Calcium-Calmodulin-Dependent Protein Kinases Human genes 0.000 title claims description 8
- 238000000034 method Methods 0.000 claims abstract description 130
- 206010056370 Congestive cardiomyopathy Diseases 0.000 claims abstract description 50
- 201000010046 Dilated cardiomyopathy Diseases 0.000 claims abstract description 50
- 150000001875 compounds Chemical class 0.000 claims abstract description 32
- 108090000765 processed proteins & peptides Proteins 0.000 claims description 150
- 241001465754 Metazoa Species 0.000 claims description 86
- 230000009261 transgenic effect Effects 0.000 claims description 61
- 230000000747 cardiac effect Effects 0.000 claims description 50
- 102000004631 Calcineurin Human genes 0.000 claims description 49
- 108010042955 Calcineurin Proteins 0.000 claims description 49
- 208000010125 myocardial infarction Diseases 0.000 claims description 49
- 108020004707 nucleic acids Proteins 0.000 claims description 31
- 102000039446 nucleic acids Human genes 0.000 claims description 31
- 150000007523 nucleic acids Chemical class 0.000 claims description 31
- 230000001965 increasing effect Effects 0.000 claims description 26
- 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 25
- 210000002216 heart Anatomy 0.000 claims description 23
- 230000002829 reductive effect Effects 0.000 claims description 22
- 101800000407 Brain natriuretic peptide 32 Proteins 0.000 claims description 19
- 102400000667 Brain natriuretic peptide 32 Human genes 0.000 claims description 19
- 101800002247 Brain natriuretic peptide 45 Proteins 0.000 claims description 19
- HPNRHPKXQZSDFX-OAQDCNSJSA-N nesiritide Chemical compound C([C@H]1C(=O)NCC(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@H](C(N[C@@H](CO)C(=O)N[C@@H](CO)C(=O)N[C@@H](CO)C(=O)N[C@@H](CO)C(=O)NCC(=O)N[C@@H](CC(C)C)C(=O)NCC(=O)N[C@@H](CSSC[C@@H](C(=O)N1)NC(=O)CNC(=O)[C@H](CO)NC(=O)CNC(=O)[C@H](CCC(N)=O)NC(=O)[C@@H](NC(=O)[C@H](CCSC)NC(=O)[C@H](CCCCN)NC(=O)[C@H]1N(CCC1)C(=O)[C@@H](N)CO)C(C)C)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC=1N=CNC=1)C(O)=O)=O)[C@@H](C)CC)C1=CC=CC=C1 HPNRHPKXQZSDFX-OAQDCNSJSA-N 0.000 claims description 19
- 230000037396 body weight Effects 0.000 claims description 14
- 230000008602 contraction Effects 0.000 claims description 9
- 238000001514 detection method Methods 0.000 claims description 8
- 238000011282 treatment Methods 0.000 claims description 3
- 201000010099 disease Diseases 0.000 abstract description 7
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 abstract description 7
- 238000012216 screening Methods 0.000 abstract description 2
- 102000004657 Calcium-Calmodulin-Dependent Protein Kinase Type 2 Human genes 0.000 abstract 1
- 108010003721 Calcium-Calmodulin-Dependent Protein Kinase Type 2 Proteins 0.000 abstract 1
- 238000011820 transgenic animal model Methods 0.000 abstract 1
- 241000699670 Mus sp. Species 0.000 description 67
- 230000002861 ventricular Effects 0.000 description 49
- 230000000694 effects Effects 0.000 description 28
- 210000004027 cell Anatomy 0.000 description 27
- 230000005764 inhibitory process Effects 0.000 description 25
- 239000000203 mixture Substances 0.000 description 19
- 108090000623 proteins and genes Proteins 0.000 description 19
- 238000011830 transgenic mouse model Methods 0.000 description 19
- 230000008828 contractile function Effects 0.000 description 18
- 229940043709 CaM kinase II inhibitor Drugs 0.000 description 17
- 241000699660 Mus musculus Species 0.000 description 17
- 239000012657 CaMKII inhibitor Substances 0.000 description 15
- 238000005259 measurement Methods 0.000 description 14
- 108020004414 DNA Proteins 0.000 description 12
- 206010019280 Heart failures Diseases 0.000 description 12
- 230000003205 diastolic effect Effects 0.000 description 12
- 230000006870 function Effects 0.000 description 12
- 239000002502 liposome Substances 0.000 description 12
- 239000005090 green fluorescent protein Substances 0.000 description 11
- 102100022789 Calcium/calmodulin-dependent protein kinase type IV Human genes 0.000 description 10
- 101000974816 Homo sapiens Calcium/calmodulin-dependent protein kinase type IV Proteins 0.000 description 10
- 230000009467 reduction Effects 0.000 description 10
- 238000012546 transfer Methods 0.000 description 10
- 208000031229 Cardiomyopathies Diseases 0.000 description 9
- 230000002401 inhibitory effect Effects 0.000 description 9
- 108020003175 receptors Proteins 0.000 description 9
- 102000005962 receptors Human genes 0.000 description 9
- 230000008685 targeting Effects 0.000 description 9
- 230000010339 dilation Effects 0.000 description 8
- 239000003814 drug Substances 0.000 description 8
- 238000002592 echocardiography Methods 0.000 description 8
- 108010043121 Green Fluorescent Proteins Proteins 0.000 description 7
- 102000004144 Green Fluorescent Proteins Human genes 0.000 description 7
- 241000699666 Mus <mouse, genus> Species 0.000 description 7
- 230000001976 improved effect Effects 0.000 description 7
- 239000003446 ligand Substances 0.000 description 7
- 102000004169 proteins and genes Human genes 0.000 description 7
- 238000001356 surgical procedure Methods 0.000 description 7
- 210000001519 tissue Anatomy 0.000 description 7
- 210000000596 ventricular septum Anatomy 0.000 description 7
- 206010007572 Cardiac hypertrophy Diseases 0.000 description 6
- 206010028980 Neoplasm Diseases 0.000 description 6
- 238000001727 in vivo Methods 0.000 description 6
- 230000013011 mating Effects 0.000 description 6
- 206010061216 Infarction Diseases 0.000 description 5
- 108700019146 Transgenes Proteins 0.000 description 5
- 150000001413 amino acids Chemical class 0.000 description 5
- 239000005557 antagonist Substances 0.000 description 5
- 206010003119 arrhythmia Diseases 0.000 description 5
- 230000007246 mechanism Effects 0.000 description 5
- 102000004196 processed proteins & peptides Human genes 0.000 description 5
- 239000013598 vector Substances 0.000 description 5
- 102100033086 Calcium/calmodulin-dependent protein kinase type 1 Human genes 0.000 description 4
- 208000006029 Cardiomegaly Diseases 0.000 description 4
- 101000944250 Homo sapiens Calcium/calmodulin-dependent protein kinase type 1 Proteins 0.000 description 4
- 102000002265 Human Growth Hormone Human genes 0.000 description 4
- 108010000521 Human Growth Hormone Proteins 0.000 description 4
- 239000000854 Human Growth Hormone Substances 0.000 description 4
- 206010020880 Hypertrophy Diseases 0.000 description 4
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 4
- 239000011575 calcium Substances 0.000 description 4
- 229940079593 drug Drugs 0.000 description 4
- 238000004520 electroporation Methods 0.000 description 4
- 230000010354 integration Effects 0.000 description 4
- 210000004165 myocardium Anatomy 0.000 description 4
- WEXRUCMBJFQVBZ-UHFFFAOYSA-N pentobarbital Chemical compound CCCC(C)C1(CC)C(=O)NC(=O)NC1=O WEXRUCMBJFQVBZ-UHFFFAOYSA-N 0.000 description 4
- 238000004904 shortening Methods 0.000 description 4
- 208000024891 symptom Diseases 0.000 description 4
- 206010013012 Dilatation ventricular Diseases 0.000 description 3
- 102000004190 Enzymes Human genes 0.000 description 3
- 108090000790 Enzymes Proteins 0.000 description 3
- 108091034117 Oligonucleotide Proteins 0.000 description 3
- 108010029485 Protein Isoforms Proteins 0.000 description 3
- 102000001708 Protein Isoforms Human genes 0.000 description 3
- 206010071436 Systolic dysfunction Diseases 0.000 description 3
- 241000700605 Viruses Species 0.000 description 3
- 238000002583 angiography Methods 0.000 description 3
- 238000010171 animal model Methods 0.000 description 3
- 238000013459 approach Methods 0.000 description 3
- 210000004369 blood Anatomy 0.000 description 3
- 239000008280 blood Substances 0.000 description 3
- 201000011510 cancer Diseases 0.000 description 3
- 210000004413 cardiac myocyte Anatomy 0.000 description 3
- 230000000295 complement effect Effects 0.000 description 3
- 230000006378 damage Effects 0.000 description 3
- 230000034994 death Effects 0.000 description 3
- 230000003247 decreasing effect Effects 0.000 description 3
- 239000003937 drug carrier Substances 0.000 description 3
- 239000003797 essential amino acid Substances 0.000 description 3
- 235000020776 essential amino acid Nutrition 0.000 description 3
- 239000012634 fragment Substances 0.000 description 3
- 230000036723 left ventricular dilatation Effects 0.000 description 3
- 230000001404 mediated effect Effects 0.000 description 3
- 239000012528 membrane Substances 0.000 description 3
- 210000000056 organ Anatomy 0.000 description 3
- 230000036961 partial effect Effects 0.000 description 3
- 230000037361 pathway Effects 0.000 description 3
- 238000011458 pharmacological treatment Methods 0.000 description 3
- 230000001105 regulatory effect Effects 0.000 description 3
- 239000000243 solution Substances 0.000 description 3
- 238000010561 standard procedure Methods 0.000 description 3
- 238000012360 testing method Methods 0.000 description 3
- 229940124597 therapeutic agent Drugs 0.000 description 3
- UUUHXMGGBIUAPW-UHFFFAOYSA-N 1-[1-[2-[[5-amino-2-[[1-[5-(diaminomethylideneamino)-2-[[1-[3-(1h-indol-3-yl)-2-[(5-oxopyrrolidine-2-carbonyl)amino]propanoyl]pyrrolidine-2-carbonyl]amino]pentanoyl]pyrrolidine-2-carbonyl]amino]-5-oxopentanoyl]amino]-3-methylpentanoyl]pyrrolidine-2-carbon Chemical compound C1CCC(C(=O)N2C(CCC2)C(O)=O)N1C(=O)C(C(C)CC)NC(=O)C(CCC(N)=O)NC(=O)C1CCCN1C(=O)C(CCCN=C(N)N)NC(=O)C1CCCN1C(=O)C(CC=1C2=CC=CC=C2NC=1)NC(=O)C1CCC(=O)N1 UUUHXMGGBIUAPW-UHFFFAOYSA-N 0.000 description 2
- 239000005541 ACE inhibitor Substances 0.000 description 2
- 206010002091 Anaesthesia Diseases 0.000 description 2
- 102100026479 Calcium/calmodulin-dependent protein kinase II inhibitor 2 Human genes 0.000 description 2
- 101710193671 Calcium/calmodulin-dependent protein kinase II inhibitor 2 Proteins 0.000 description 2
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
- 108020004705 Codon Proteins 0.000 description 2
- ZHNUHDYFZUAESO-UHFFFAOYSA-N Formamide Chemical compound NC=O ZHNUHDYFZUAESO-UHFFFAOYSA-N 0.000 description 2
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 2
- 102000003979 Mineralocorticoid Receptors Human genes 0.000 description 2
- 108090000375 Mineralocorticoid Receptors Proteins 0.000 description 2
- 102000004270 Peptidyl-Dipeptidase A Human genes 0.000 description 2
- 108090000882 Peptidyl-Dipeptidase A Proteins 0.000 description 2
- 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 2
- 239000011543 agarose gel Substances 0.000 description 2
- 230000037005 anaesthesia Effects 0.000 description 2
- 229940044094 angiotensin-converting-enzyme inhibitor Drugs 0.000 description 2
- 230000000692 anti-sense effect Effects 0.000 description 2
- 230000006793 arrhythmia Effects 0.000 description 2
- 238000003556 assay Methods 0.000 description 2
- 229910000389 calcium phosphate Inorganic materials 0.000 description 2
- 239000001506 calcium phosphate Substances 0.000 description 2
- 235000011010 calcium phosphates Nutrition 0.000 description 2
- 210000005242 cardiac chamber Anatomy 0.000 description 2
- 230000003683 cardiac damage Effects 0.000 description 2
- 239000000496 cardiotonic agent Substances 0.000 description 2
- 230000015556 catabolic process Effects 0.000 description 2
- 125000002091 cationic group Chemical group 0.000 description 2
- 210000000170 cell membrane Anatomy 0.000 description 2
- 210000000038 chest Anatomy 0.000 description 2
- 238000006731 degradation reaction Methods 0.000 description 2
- 108010048367 enhanced green fluorescent protein Proteins 0.000 description 2
- 238000000605 extraction Methods 0.000 description 2
- 230000004927 fusion Effects 0.000 description 2
- 239000000499 gel Substances 0.000 description 2
- 230000002068 genetic effect Effects 0.000 description 2
- 230000036541 health Effects 0.000 description 2
- 210000002064 heart cell Anatomy 0.000 description 2
- 230000004217 heart function Effects 0.000 description 2
- 230000006801 homologous recombination Effects 0.000 description 2
- 238000002744 homologous recombination Methods 0.000 description 2
- 238000000338 in vitro Methods 0.000 description 2
- 230000001939 inductive effect Effects 0.000 description 2
- 239000007924 injection Substances 0.000 description 2
- 238000002347 injection Methods 0.000 description 2
- 230000000302 ischemic effect Effects 0.000 description 2
- PHTQWCKDNZKARW-UHFFFAOYSA-N isoamylol Chemical compound CC(C)CCO PHTQWCKDNZKARW-UHFFFAOYSA-N 0.000 description 2
- 150000002632 lipids Chemical class 0.000 description 2
- 210000004072 lung Anatomy 0.000 description 2
- 238000002595 magnetic resonance imaging Methods 0.000 description 2
- 239000003094 microcapsule Substances 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- 238000010172 mouse model Methods 0.000 description 2
- 238000007911 parenteral administration Methods 0.000 description 2
- 229960001412 pentobarbital Drugs 0.000 description 2
- 239000011780 sodium chloride Substances 0.000 description 2
- 241000894007 species Species 0.000 description 2
- 238000006467 substitution reaction Methods 0.000 description 2
- 239000000758 substrate Substances 0.000 description 2
- 239000000725 suspension Substances 0.000 description 2
- 230000000699 topical effect Effects 0.000 description 2
- QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 description 2
- 238000001262 western blot Methods 0.000 description 2
- OPCHFPHZPIURNA-MFERNQICSA-N (2s)-2,5-bis(3-aminopropylamino)-n-[2-(dioctadecylamino)acetyl]pentanamide Chemical compound CCCCCCCCCCCCCCCCCCN(CC(=O)NC(=O)[C@H](CCCNCCCN)NCCCN)CCCCCCCCCCCCCCCCCC OPCHFPHZPIURNA-MFERNQICSA-N 0.000 description 1
- NKBRRWBNPNUBDD-TYKVATLISA-N (2s)-6-amino-2-[[(2s)-6-amino-2-[[2-[[(2s)-1-[(2s)-2-[[2-[[(2s)-2-[[(2s)-2-[[(2s)-2-[[(2s)-2-[[(2s,3r)-2-[[(2s)-5-(diaminomethylideneamino)-2-[[(2s)-2-[[(2s)-4-methyl-2-[[(2s)-pyrrolidine-2-carbonyl]amino]pentanoyl]amino]propanoyl]amino]pentanoyl]amino]-3 Chemical compound N([C@@H](CC(C)C)C(=O)N[C@@H](C)C(=O)N[C@@H](CCCN=C(N)N)C(=O)N[C@H](C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CO)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](C)C(=O)NCC(=O)N[C@@H](CC(C)C)C(=O)N1[C@@H](CCC1)C(=O)NCC(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCCCN)C(O)=O)[C@@H](C)O)C(=O)[C@@H]1CCCN1 NKBRRWBNPNUBDD-TYKVATLISA-N 0.000 description 1
- 108091032973 (ribonucleotides)n+m Proteins 0.000 description 1
- LDGWQMRUWMSZIU-LQDDAWAPSA-M 2,3-bis[(z)-octadec-9-enoxy]propyl-trimethylazanium;chloride Chemical compound [Cl-].CCCCCCCC\C=C/CCCCCCCCOCC(C[N+](C)(C)C)OCCCCCCCC\C=C/CCCCCCCC LDGWQMRUWMSZIU-LQDDAWAPSA-M 0.000 description 1
- 108010008509 AC3-I peptide Proteins 0.000 description 1
- 206010003671 Atrioventricular Block Diseases 0.000 description 1
- 241000972773 Aulopiformes Species 0.000 description 1
- 241000283690 Bos taurus Species 0.000 description 1
- 102000000584 Calmodulin Human genes 0.000 description 1
- 241000282472 Canis lupus familiaris Species 0.000 description 1
- 241000283707 Capra Species 0.000 description 1
- 241000700198 Cavia Species 0.000 description 1
- 102000005853 Clathrin Human genes 0.000 description 1
- 108010019874 Clathrin Proteins 0.000 description 1
- 108091033380 Coding strand Proteins 0.000 description 1
- 206010009944 Colon cancer Diseases 0.000 description 1
- 206010010356 Congenital anomaly Diseases 0.000 description 1
- 108010068426 Contractile Proteins Proteins 0.000 description 1
- 102000002585 Contractile Proteins Human genes 0.000 description 1
- 206010011224 Cough Diseases 0.000 description 1
- 102000008130 Cyclic AMP-Dependent Protein Kinases Human genes 0.000 description 1
- 108010049894 Cyclic AMP-Dependent Protein Kinases Proteins 0.000 description 1
- -1 DOPE Chemical compound 0.000 description 1
- 206010052337 Diastolic dysfunction Diseases 0.000 description 1
- KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 1
- 101000944251 Emericella nidulans (strain FGSC A4 / ATCC 38163 / CBS 112.46 / NRRL 194 / M139) Calcium/calmodulin-dependent protein kinase cmkA Proteins 0.000 description 1
- 108010067770 Endopeptidase K Proteins 0.000 description 1
- 241000283086 Equidae Species 0.000 description 1
- 102100021808 Eukaryotic elongation factor 2 kinase Human genes 0.000 description 1
- 108091029865 Exogenous DNA Proteins 0.000 description 1
- 241000282326 Felis catus Species 0.000 description 1
- 208000032612 Glial tumor Diseases 0.000 description 1
- 206010018338 Glioma Diseases 0.000 description 1
- 208000010271 Heart Block Diseases 0.000 description 1
- 101000895759 Homo sapiens Eukaryotic elongation factor 2 kinase Proteins 0.000 description 1
- 208000002682 Hyperkalemia Diseases 0.000 description 1
- 206010020772 Hypertension Diseases 0.000 description 1
- 208000001953 Hypotension Diseases 0.000 description 1
- 206010048858 Ischaemic cardiomyopathy Diseases 0.000 description 1
- YQEZLKZALYSWHR-UHFFFAOYSA-N Ketamine Chemical compound C=1C=CC=C(Cl)C=1C1(NC)CCCCC1=O YQEZLKZALYSWHR-UHFFFAOYSA-N 0.000 description 1
- 241000124008 Mammalia Species 0.000 description 1
- 102000005604 Myosin Heavy Chains Human genes 0.000 description 1
- 108091061960 Naked DNA Proteins 0.000 description 1
- 206010028851 Necrosis Diseases 0.000 description 1
- SNIOPGDIGTZGOP-UHFFFAOYSA-N Nitroglycerin Chemical compound [O-][N+](=O)OCC(O[N+]([O-])=O)CO[N+]([O-])=O SNIOPGDIGTZGOP-UHFFFAOYSA-N 0.000 description 1
- 239000000006 Nitroglycerin Substances 0.000 description 1
- 239000004677 Nylon Substances 0.000 description 1
- 241000283973 Oryctolagus cuniculus Species 0.000 description 1
- 241001494479 Pecora Species 0.000 description 1
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 1
- 241000288906 Primates Species 0.000 description 1
- 102000003923 Protein Kinase C Human genes 0.000 description 1
- 108090000315 Protein Kinase C Proteins 0.000 description 1
- 241000700159 Rattus Species 0.000 description 1
- 101100438227 Rattus norvegicus Calm2 gene Proteins 0.000 description 1
- 208000001647 Renal Insufficiency Diseases 0.000 description 1
- 206010038378 Renal artery stenosis Diseases 0.000 description 1
- 241000283984 Rodentia Species 0.000 description 1
- 238000000692 Student's t-test Methods 0.000 description 1
- 208000037065 Subacute sclerosing leukoencephalitis Diseases 0.000 description 1
- 206010042297 Subacute sclerosing panencephalitis Diseases 0.000 description 1
- 241000282887 Suidae Species 0.000 description 1
- 239000007983 Tris buffer Substances 0.000 description 1
- 108010051583 Ventricular Myosins Proteins 0.000 description 1
- ISXSJGHXHUZXNF-LXZPIJOJSA-N [(3s,8s,9s,10r,13r,14s,17r)-10,13-dimethyl-17-[(2r)-6-methylheptan-2-yl]-2,3,4,7,8,9,11,12,14,15,16,17-dodecahydro-1h-cyclopenta[a]phenanthren-3-yl] n-[2-(dimethylamino)ethyl]carbamate;hydrochloride Chemical compound Cl.C1C=C2C[C@@H](OC(=O)NCCN(C)C)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CCCC(C)C)[C@@]1(C)CC2 ISXSJGHXHUZXNF-LXZPIJOJSA-N 0.000 description 1
- HMNZFMSWFCAGGW-XPWSMXQVSA-N [3-[hydroxy(2-hydroxyethoxy)phosphoryl]oxy-2-[(e)-octadec-9-enoyl]oxypropyl] (e)-octadec-9-enoate Chemical compound CCCCCCCC\C=C\CCCCCCCC(=O)OCC(COP(O)(=O)OCCO)OC(=O)CCCCCCC\C=C\CCCCCCCC HMNZFMSWFCAGGW-XPWSMXQVSA-N 0.000 description 1
- 230000002159 abnormal effect Effects 0.000 description 1
- 230000005856 abnormality Effects 0.000 description 1
- 239000004480 active ingredient Substances 0.000 description 1
- 230000002411 adverse Effects 0.000 description 1
- 238000012387 aerosolization Methods 0.000 description 1
- 239000002170 aldosterone antagonist Substances 0.000 description 1
- 229940083712 aldosterone antagonist Drugs 0.000 description 1
- 230000000735 allogeneic effect Effects 0.000 description 1
- 238000000540 analysis of variance Methods 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 125000000129 anionic group Chemical group 0.000 description 1
- 230000008485 antagonism Effects 0.000 description 1
- 238000003782 apoptosis assay Methods 0.000 description 1
- 230000006907 apoptotic process Effects 0.000 description 1
- 210000001367 artery Anatomy 0.000 description 1
- 208000006673 asthma Diseases 0.000 description 1
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
- 230000001746 atrial effect Effects 0.000 description 1
- 238000000376 autoradiography Methods 0.000 description 1
- 102000012740 beta Adrenergic Receptors Human genes 0.000 description 1
- 108010079452 beta Adrenergic Receptors Proteins 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
- 230000009141 biological interaction Effects 0.000 description 1
- 230000033228 biological regulation Effects 0.000 description 1
- 238000001574 biopsy Methods 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 230000017531 blood circulation Effects 0.000 description 1
- 230000036471 bradycardia Effects 0.000 description 1
- 208000006218 bradycardia Diseases 0.000 description 1
- 210000000621 bronchi Anatomy 0.000 description 1
- 230000007248 cellular mechanism Effects 0.000 description 1
- 230000001684 chronic effect Effects 0.000 description 1
- 229930193282 clathrin Natural products 0.000 description 1
- 210000002806 clathrin-coated vesicle Anatomy 0.000 description 1
- 208000035850 clinical syndrome Diseases 0.000 description 1
- 208000029742 colonic neoplasm Diseases 0.000 description 1
- 230000001447 compensatory effect Effects 0.000 description 1
- 239000000039 congener Substances 0.000 description 1
- 230000006837 decompression Effects 0.000 description 1
- 230000006735 deficit Effects 0.000 description 1
- 230000002939 deleterious effect Effects 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 238000010586 diagram Methods 0.000 description 1
- 238000009792 diffusion process Methods 0.000 description 1
- 230000003292 diminished effect Effects 0.000 description 1
- 238000010494 dissociation reaction Methods 0.000 description 1
- 230000005593 dissociations Effects 0.000 description 1
- 239000002934 diuretic Substances 0.000 description 1
- 229940030606 diuretics Drugs 0.000 description 1
- 238000001962 electrophoresis Methods 0.000 description 1
- 210000001671 embryonic stem cell Anatomy 0.000 description 1
- 239000000839 emulsion Substances 0.000 description 1
- 230000012202 endocytosis Effects 0.000 description 1
- 230000001159 endocytotic effect Effects 0.000 description 1
- 210000001163 endosome Anatomy 0.000 description 1
- ZMMJGEGLRURXTF-UHFFFAOYSA-N ethidium bromide Chemical compound [Br-].C12=CC(N)=CC=C2C2=CC=C(N)C=C2[N+](CC)=C1C1=CC=CC=C1 ZMMJGEGLRURXTF-UHFFFAOYSA-N 0.000 description 1
- 229960005542 ethidium bromide Drugs 0.000 description 1
- 238000001476 gene delivery Methods 0.000 description 1
- 238000003205 genotyping method Methods 0.000 description 1
- 229960003711 glyceryl trinitrate Drugs 0.000 description 1
- 201000000079 gynecomastia Diseases 0.000 description 1
- 230000005802 health problem Effects 0.000 description 1
- 238000009396 hybridization Methods 0.000 description 1
- 230000036543 hypotension Effects 0.000 description 1
- 238000003384 imaging method Methods 0.000 description 1
- 201000001881 impotence Diseases 0.000 description 1
- 238000010348 incorporation Methods 0.000 description 1
- 230000007574 infarction Effects 0.000 description 1
- 230000000977 initiatory effect Effects 0.000 description 1
- 239000004041 inotropic agent Substances 0.000 description 1
- 238000001361 intraarterial administration Methods 0.000 description 1
- 230000003834 intracellular effect Effects 0.000 description 1
- 230000006662 intracellular pathway Effects 0.000 description 1
- 238000007918 intramuscular administration Methods 0.000 description 1
- 239000007927 intramuscular injection Substances 0.000 description 1
- 238000010255 intramuscular injection Methods 0.000 description 1
- 239000007928 intraperitoneal injection Substances 0.000 description 1
- 238000007913 intrathecal administration Methods 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- 230000002427 irreversible effect Effects 0.000 description 1
- 208000037906 ischaemic injury Diseases 0.000 description 1
- 229960003299 ketamine Drugs 0.000 description 1
- 208000017169 kidney disease Diseases 0.000 description 1
- 201000006370 kidney failure Diseases 0.000 description 1
- 238000001638 lipofection Methods 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 239000006193 liquid solution Substances 0.000 description 1
- 239000006194 liquid suspension Substances 0.000 description 1
- 244000144972 livestock Species 0.000 description 1
- 210000004698 lymphocyte Anatomy 0.000 description 1
- 210000003712 lysosome Anatomy 0.000 description 1
- 230000001868 lysosomic effect Effects 0.000 description 1
- 229920002521 macromolecule Polymers 0.000 description 1
- 210000002540 macrophage Anatomy 0.000 description 1
- 239000003550 marker Substances 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 238000002483 medication Methods 0.000 description 1
- 238000000520 microinjection Methods 0.000 description 1
- 239000011859 microparticle Substances 0.000 description 1
- 230000009456 molecular mechanism Effects 0.000 description 1
- 108700026460 mouse core Proteins 0.000 description 1
- 230000035772 mutation Effects 0.000 description 1
- 230000007498 myristoylation Effects 0.000 description 1
- 230000017074 necrotic cell death Effects 0.000 description 1
- 239000002773 nucleotide Substances 0.000 description 1
- 125000003729 nucleotide group Chemical group 0.000 description 1
- 235000021231 nutrient uptake Nutrition 0.000 description 1
- 229920001778 nylon Polymers 0.000 description 1
- 229910052760 oxygen Inorganic materials 0.000 description 1
- 239000001301 oxygen Substances 0.000 description 1
- 230000036284 oxygen consumption Effects 0.000 description 1
- 230000035699 permeability Effects 0.000 description 1
- 239000008194 pharmaceutical composition Substances 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 229920001184 polypeptide Polymers 0.000 description 1
- 230000009090 positive inotropic effect Effects 0.000 description 1
- 238000001556 precipitation Methods 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- 230000037452 priming Effects 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- 230000005522 programmed cell death Effects 0.000 description 1
- 108010030416 proteoliposomes Proteins 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 239000002464 receptor antagonist Substances 0.000 description 1
- 229940044551 receptor antagonist Drugs 0.000 description 1
- 230000010837 receptor-mediated endocytosis Effects 0.000 description 1
- 230000006798 recombination Effects 0.000 description 1
- 238000005215 recombination Methods 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 230000036387 respiratory rate Effects 0.000 description 1
- 210000002345 respiratory system Anatomy 0.000 description 1
- 230000004044 response Effects 0.000 description 1
- 230000000717 retained effect Effects 0.000 description 1
- 230000002441 reversible effect Effects 0.000 description 1
- 238000012552 review Methods 0.000 description 1
- 235000019515 salmon Nutrition 0.000 description 1
- 239000000523 sample Substances 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 238000012163 sequencing technique Methods 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 239000007921 spray Substances 0.000 description 1
- 210000001562 sternum Anatomy 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 230000002459 sustained effect Effects 0.000 description 1
- 238000013268 sustained release Methods 0.000 description 1
- 239000012730 sustained-release form Substances 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 108010065665 syntide-2 Proteins 0.000 description 1
- 238000012353 t test Methods 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 230000000287 tissue oxygenation Effects 0.000 description 1
- 239000003053 toxin Substances 0.000 description 1
- 231100000765 toxin Toxicity 0.000 description 1
- 108700012359 toxins Proteins 0.000 description 1
- 210000003437 trachea Anatomy 0.000 description 1
- 238000002627 tracheal intubation Methods 0.000 description 1
- 238000012549 training Methods 0.000 description 1
- 238000010361 transduction Methods 0.000 description 1
- 230000026683 transduction Effects 0.000 description 1
- 238000001890 transfection Methods 0.000 description 1
- 230000014621 translational initiation Effects 0.000 description 1
- 238000002054 transplantation Methods 0.000 description 1
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 1
- 210000004881 tumor cell Anatomy 0.000 description 1
- 239000003981 vehicle Substances 0.000 description 1
- 230000003612 virological effect Effects 0.000 description 1
Images
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/16—Amides, e.g. hydroxamic acids
- A61K31/18—Sulfonamides
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/005—Enzyme inhibitors
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/04—Peptides having up to 20 amino acids in a fully defined sequence; Derivatives thereof
- A61K38/10—Peptides having 12 to 20 amino acids
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/04—Inotropic agents, i.e. stimulants of cardiac contraction; Drugs for heart failure
-
- 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
- C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
- C12Q1/00—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions
- C12Q1/48—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving transferase
- C12Q1/485—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving transferase involving kinase
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
- G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
- G01N33/5005—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving human or animal cells
- G01N33/5008—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving human or animal cells for testing or evaluating the effect of chemical or biological compounds, e.g. drugs, cosmetics
- G01N33/5082—Supracellular entities, e.g. tissue, organisms
- G01N33/5088—Supracellular entities, e.g. tissue, organisms of vertebrates
-
- 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
- G01N33/68—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving proteins, peptides or amino acids
- G01N33/6893—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving proteins, peptides or amino acids related to diseases not provided for elsewhere
-
- 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
- G01N2333/575—Hormones
- G01N2333/58—Atrial natriuretic factor complex; Atriopeptin; Atrial natriuretic peptide [ANP]; Brain natriuretic peptide [BNP, proBNP]; Cardionatrin; Cardiodilatin
-
- 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
- G01N2333/90—Enzymes; Proenzymes
- G01N2333/91—Transferases (2.)
- G01N2333/912—Transferases (2.) transferring phosphorus containing groups, e.g. kinases (2.7)
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N2500/00—Screening for compounds of potential therapeutic value
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N2500/00—Screening for compounds of potential therapeutic value
- G01N2500/10—Screening for compounds of potential therapeutic value involving cells
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Engineering & Computer Science (AREA)
- Chemical & Material Sciences (AREA)
- Immunology (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Veterinary Medicine (AREA)
- Pharmacology & Pharmacy (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Biomedical Technology (AREA)
- Molecular Biology (AREA)
- Organic Chemistry (AREA)
- Urology & Nephrology (AREA)
- Epidemiology (AREA)
- Hematology (AREA)
- Biochemistry (AREA)
- Analytical Chemistry (AREA)
- Physics & Mathematics (AREA)
- Biotechnology (AREA)
- Cell Biology (AREA)
- Microbiology (AREA)
- General Physics & Mathematics (AREA)
- Gastroenterology & Hepatology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Zoology (AREA)
- Food Science & Technology (AREA)
- Wood Science & Technology (AREA)
- General Chemical & Material Sciences (AREA)
- Cardiology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pathology (AREA)
- Heart & Thoracic Surgery (AREA)
- Biophysics (AREA)
- General Engineering & Computer Science (AREA)
- Genetics & Genomics (AREA)
- Tropical Medicine & Parasitology (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US32657601P | 2001-10-01 | 2001-10-01 | |
| US32801001P | 2001-10-08 | 2001-10-08 | |
| PCT/US2002/031496 WO2003029428A2 (en) | 2001-10-01 | 2002-10-01 | Use of calmodulin kinase ii inhibitors to treat myocardial dysfunction in structural heart disease |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JP2005504829A true JP2005504829A (ja) | 2005-02-17 |
| JP2005504829A5 JP2005504829A5 (enExample) | 2007-10-18 |
Family
ID=26985461
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2003532646A Pending JP2005504829A (ja) | 2001-10-01 | 2002-10-01 | 構造的心疾患における心筋機能不全を処置するためのカルモジュリンキナーゼiiインヒビターの使用 |
Country Status (14)
| Country | Link |
|---|---|
| US (2) | US7320959B2 (enExample) |
| EP (1) | EP1439849A4 (enExample) |
| JP (1) | JP2005504829A (enExample) |
| KR (1) | KR20040045041A (enExample) |
| CN (1) | CN1599622A (enExample) |
| AU (1) | AU2002341938B2 (enExample) |
| BR (1) | BR0213043A (enExample) |
| CA (1) | CA2462443A1 (enExample) |
| IL (1) | IL161231A0 (enExample) |
| MX (1) | MXPA04003040A (enExample) |
| NO (1) | NO20041331L (enExample) |
| NZ (1) | NZ532327A (enExample) |
| PL (1) | PL369104A1 (enExample) |
| WO (1) | WO2003029428A2 (enExample) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2011516874A (ja) * | 2008-04-09 | 2011-05-26 | ベー.エル.アー.ハー.エム.エス ゲゼルシャフト ミット ベシュレンクテル ハフツング | 最大酸素消費量低下の予測のためのプロ−エンドセリン−1 |
Families Citing this family (11)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP1815867A4 (en) * | 2004-11-02 | 2010-06-09 | Dainippon Sumitomo Pharma Co | COMBINED MEDICINE FOR THE TREATMENT OF AUTOIMMUNE DISEASE |
| US8841423B2 (en) | 2008-04-28 | 2014-09-23 | University Of Iowa Research Foundation | Monoclonal antibodies specific for oxidized calcium/calmodulin dependent protein kinase II |
| US20090275514A1 (en) * | 2008-05-01 | 2009-11-05 | Anderson Mark E | Use of calmodulin kinase ii inhibitors to treat or prevent heart muscle inflammation |
| WO2010135676A1 (en) * | 2009-05-22 | 2010-11-25 | The United States Of America, As Represented By The Secretary, Department Of Health & Human Services | Engineered biological pacemakers |
| US8440656B2 (en) * | 2009-06-22 | 2013-05-14 | University Of Iowa Research Foundation | Methods of treating pulmonary diseases and disorders by modulating calcium/calmodulin dependent protein kinase II activity |
| US20110082084A1 (en) | 2009-10-05 | 2011-04-07 | Szeto Hazel H | Methods for the prevention or treatment of heart failure |
| US9951061B2 (en) | 2013-03-06 | 2018-04-24 | Allosteros Therapeutics, Inc. | CaMKII inhibitors and uses thereof |
| DE102014201651A1 (de) * | 2014-01-30 | 2015-07-30 | Georg-August-Universität Göttingen Stiftung Öffentlichen Rechts, Universitätsmedizin | Isoxazolderivate zur Verwendung bei der Behandlung und/oder Prophylaxe von Herzerkrankungen |
| CA2960101C (en) | 2014-09-05 | 2024-05-21 | Allosteros Therapeutics, Inc. | Substituted carboline derivative and compositions thereof useful as camkii inhibitors |
| WO2018031771A1 (en) | 2016-08-11 | 2018-02-15 | University Of Iowa Research Foundation | CATIONIC CaMKII INHIBITING NANOPARTICLES FOR THE TREATMENT OF ALLERGIC ASTHMA |
| CN112972447B (zh) * | 2021-03-02 | 2022-09-23 | 扬州大学附属医院 | CaMK II抑制剂在制备预防和/或治疗急性胰腺炎的药物中的应用 |
Family Cites Families (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| FR1601438A (enExample) * | 1968-10-17 | 1970-08-24 | ||
| US4897355A (en) * | 1985-01-07 | 1990-01-30 | Syntex (U.S.A.) Inc. | N[ω,(ω-1)-dialkyloxy]- and N-[ω,(ω-1)-dialkenyloxy]-alk-1-yl-N,N,N-tetrasubstituted ammonium lipids and uses therefor |
| EP0966274B1 (en) * | 1997-01-31 | 2002-06-12 | The Board Of Trustees Of The Leland Stanford Junior University | Treatment of arrhythmias via inhibition of a multifunctional calcium/calmodulin-dependent protein kinase |
| JP2963986B2 (ja) * | 1997-11-19 | 1999-10-18 | 工業技術院長 | カルモジュリン依存性リン酸化酵素iiの特異的阻害剤 |
-
2002
- 2002-10-01 MX MXPA04003040A patent/MXPA04003040A/es not_active Application Discontinuation
- 2002-10-01 IL IL16123102A patent/IL161231A0/xx unknown
- 2002-10-01 PL PL02369104A patent/PL369104A1/xx not_active Application Discontinuation
- 2002-10-01 KR KR10-2004-7004775A patent/KR20040045041A/ko not_active Withdrawn
- 2002-10-01 US US10/491,323 patent/US7320959B2/en not_active Expired - Fee Related
- 2002-10-01 BR BR0213043-2A patent/BR0213043A/pt not_active IP Right Cessation
- 2002-10-01 WO PCT/US2002/031496 patent/WO2003029428A2/en not_active Ceased
- 2002-10-01 CN CNA028241010A patent/CN1599622A/zh active Pending
- 2002-10-01 NZ NZ532327A patent/NZ532327A/en unknown
- 2002-10-01 JP JP2003532646A patent/JP2005504829A/ja active Pending
- 2002-10-01 CA CA002462443A patent/CA2462443A1/en not_active Abandoned
- 2002-10-01 EP EP02776099A patent/EP1439849A4/en not_active Withdrawn
- 2002-10-01 AU AU2002341938A patent/AU2002341938B2/en not_active Ceased
-
2004
- 2004-03-31 NO NO20041331A patent/NO20041331L/no not_active Application Discontinuation
-
2007
- 2007-11-13 US US11/983,987 patent/US7632815B2/en not_active Expired - Fee Related
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2011516874A (ja) * | 2008-04-09 | 2011-05-26 | ベー.エル.アー.ハー.エム.エス ゲゼルシャフト ミット ベシュレンクテル ハフツング | 最大酸素消費量低下の予測のためのプロ−エンドセリン−1 |
Also Published As
| Publication number | Publication date |
|---|---|
| WO2003029428A2 (en) | 2003-04-10 |
| MXPA04003040A (es) | 2004-07-15 |
| IL161231A0 (en) | 2004-09-27 |
| AU2002341938B2 (en) | 2007-08-30 |
| PL369104A1 (en) | 2005-04-18 |
| BR0213043A (pt) | 2004-10-05 |
| NZ532327A (en) | 2005-10-28 |
| US7320959B2 (en) | 2008-01-22 |
| US7632815B2 (en) | 2009-12-15 |
| US20040266675A1 (en) | 2004-12-30 |
| NO20041331L (no) | 2004-05-28 |
| WO2003029428A8 (en) | 2004-04-22 |
| US20090011989A1 (en) | 2009-01-08 |
| EP1439849A2 (en) | 2004-07-28 |
| KR20040045041A (ko) | 2004-05-31 |
| CA2462443A1 (en) | 2003-04-10 |
| WO2003029428A3 (en) | 2003-10-30 |
| EP1439849A4 (en) | 2005-09-28 |
| NO20041331D0 (no) | 2004-03-31 |
| CN1599622A (zh) | 2005-03-23 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| US7632815B2 (en) | Use of calmodulin kinase II inhibitors to treat myocardial dysfunction in structural heart disease | |
| AU2002337811A1 (en) | Adjustable child support structure with accessories | |
| EP1450650A2 (en) | Adjustable child support structure with accessories | |
| ES2958662T3 (es) | Tratamiento de cardiopatía por inhibición de la acción de la proteína de anclaje a la cinasa A del músculo (mAKAP) | |
| Huang et al. | Mineralocorticoid and AT1 receptors in the paraventricular nucleus contribute to sympathetic hyperactivity and cardiac dysfunction in rats post myocardial infarct | |
| ES2818556T3 (es) | Péptido con eficacia antiobesidad y antidiabética y uso del mismo | |
| AU2002341938A1 (en) | Use of calmodulin kinase II inhibitors to treat myocardial dysfunction in structural heart disease | |
| CN119112860A (zh) | 绿原酸在制备预防或治疗主动脉夹层药物中的应用 | |
| CN118141925A (zh) | p55γ基因和/或蛋白作为靶点在维持心脏铁稳态及治疗相关病症中的应用 | |
| JP4904269B2 (ja) | カルニチン輸送体アゴニストまたはアンタゴニストをスクリーニングする方法、およびその使用 | |
| KR102785286B1 (ko) | 특발성 폐 섬유증의 약물 표적 | |
| AU2007237240A1 (en) | Use of calmodulin kinase II inhibitors to treat myocardial dysfunction in structural heart disease | |
| US9993516B2 (en) | Treatment of left ventricular non-compaction and dilated cardiomyopathy by inhibiting melanocortin receptor four | |
| EP1613769B1 (en) | Insulin-induced gene as therapeutic target in diabetes | |
| NZ541833A (en) | Use of calmodulin kinase II inhibitors, mainly SEQ ID NO:4, to treat myocardial dysfunction in structural heart disease | |
| CN101130069A (zh) | 用钙调蛋白激酶ii抑制剂治疗结构性心脏病中的心肌功能障碍 | |
| Yáñez Bisbe | Role of TRPV4 channels in adverse cardiac remodelling | |
| WO2025155922A1 (en) | Hdac3 inhibitors to treat arrhythmogenic cardiomyopathy | |
| CN117959442A (zh) | 预防或治疗肺纤维化的试剂及应用 | |
| CA3258422A1 (en) | POLYTHERAPIES INCLUDING MYC MODULATION |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20050901 |
|
| A621 | Written request for application examination |
Free format text: JAPANESE INTERMEDIATE CODE: A621 Effective date: 20050901 |
|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20070412 |
|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20070801 |
|
| A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20081023 |
|
| A02 | Decision of refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A02 Effective date: 20090318 |