ES2230852T3 - Canales ionicos de k+humanos y aplicaciones terapeuticas de los mismos. - Google Patents
Canales ionicos de k+humanos y aplicaciones terapeuticas de los mismos.Info
- Publication number
- ES2230852T3 ES2230852T3 ES99920731T ES99920731T ES2230852T3 ES 2230852 T3 ES2230852 T3 ES 2230852T3 ES 99920731 T ES99920731 T ES 99920731T ES 99920731 T ES99920731 T ES 99920731T ES 2230852 T3 ES2230852 T3 ES 2230852T3
- Authority
- ES
- Spain
- Prior art keywords
- nucleic acid
- acid molecule
- cells
- baselineskip
- poly
- 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.)
- Expired - Lifetime
Links
- 241000282414 Homo sapiens Species 0.000 title claims abstract description 64
- 230000001225 therapeutic effect Effects 0.000 title description 5
- 150000007523 nucleic acids Chemical class 0.000 claims abstract description 99
- 102000039446 nucleic acids Human genes 0.000 claims abstract description 95
- 108020004707 nucleic acids Proteins 0.000 claims abstract description 95
- 108090000765 processed proteins & peptides Proteins 0.000 claims abstract description 85
- 206010028980 Neoplasm Diseases 0.000 claims abstract description 71
- 238000000034 method Methods 0.000 claims abstract description 64
- 230000014509 gene expression Effects 0.000 claims abstract description 61
- 239000013598 vector Substances 0.000 claims abstract description 50
- 239000003814 drug Substances 0.000 claims abstract description 44
- 229940079593 drug Drugs 0.000 claims abstract description 43
- 102000004196 processed proteins & peptides Human genes 0.000 claims abstract description 43
- 229920001184 polypeptide Polymers 0.000 claims abstract description 40
- 239000003112 inhibitor Substances 0.000 claims abstract description 38
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 33
- 201000010099 disease Diseases 0.000 claims abstract description 32
- 201000011510 cancer Diseases 0.000 claims abstract description 28
- 230000000692 anti-sense effect Effects 0.000 claims abstract description 21
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 15
- 238000001415 gene therapy Methods 0.000 claims abstract description 14
- 230000007257 malfunction Effects 0.000 claims abstract description 11
- 208000015122 neurodegenerative disease Diseases 0.000 claims abstract description 10
- 230000004770 neurodegeneration Effects 0.000 claims abstract description 9
- 210000004027 cell Anatomy 0.000 claims description 206
- 108090000623 proteins and genes Proteins 0.000 claims description 50
- 108091032973 (ribonucleotides)n+m Proteins 0.000 claims description 35
- 229940046166 oligodeoxynucleotide Drugs 0.000 claims description 28
- 108020004414 DNA Proteins 0.000 claims description 27
- 230000000694 effects Effects 0.000 claims description 25
- 108091034117 Oligonucleotide Proteins 0.000 claims description 21
- 239000002253 acid Substances 0.000 claims description 19
- GXDALQBWZGODGZ-UHFFFAOYSA-N astemizole Chemical compound C1=CC(OC)=CC=C1CCN1CCC(NC=2N(C3=CC=CC=C3N=2)CC=2C=CC(F)=CC=2)CC1 GXDALQBWZGODGZ-UHFFFAOYSA-N 0.000 claims description 18
- 102000004169 proteins and genes Human genes 0.000 claims description 18
- 229960004754 astemizole Drugs 0.000 claims description 16
- 239000000203 mixture Substances 0.000 claims description 16
- 238000011282 treatment Methods 0.000 claims description 15
- 206010006187 Breast cancer Diseases 0.000 claims description 13
- 150000001875 compounds Chemical class 0.000 claims description 13
- 201000004681 Psoriasis Diseases 0.000 claims description 12
- 230000005764 inhibitory process Effects 0.000 claims description 12
- 238000012360 testing method Methods 0.000 claims description 11
- GUGOEEXESWIERI-UHFFFAOYSA-N Terfenadine Chemical compound C1=CC(C(C)(C)C)=CC=C1C(O)CCCN1CCC(C(O)(C=2C=CC=CC=2)C=2C=CC=CC=2)CC1 GUGOEEXESWIERI-UHFFFAOYSA-N 0.000 claims description 10
- 238000002360 preparation method Methods 0.000 claims description 10
- 229960000351 terfenadine Drugs 0.000 claims description 10
- 238000013518 transcription Methods 0.000 claims description 10
- 230000035897 transcription Effects 0.000 claims description 10
- 108091028043 Nucleic acid sequence Proteins 0.000 claims description 9
- 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 description 9
- 208000026310 Breast neoplasm Diseases 0.000 claims description 8
- 206010029260 Neuroblastoma Diseases 0.000 claims description 8
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 claims description 8
- 238000013461 design Methods 0.000 claims description 8
- 239000013604 expression vector Substances 0.000 claims description 8
- 230000004048 modification Effects 0.000 claims description 8
- 238000012986 modification Methods 0.000 claims description 8
- 230000002018 overexpression Effects 0.000 claims description 8
- 239000011591 potassium Substances 0.000 claims description 8
- 229910052700 potassium Inorganic materials 0.000 claims description 8
- 238000000338 in vitro Methods 0.000 claims description 7
- 201000008275 breast carcinoma Diseases 0.000 claims description 6
- 239000000816 peptidomimetic Substances 0.000 claims description 6
- 238000012546 transfer Methods 0.000 claims description 6
- 102000003834 Histamine H1 Receptors Human genes 0.000 claims description 5
- 108090000110 Histamine H1 Receptors Proteins 0.000 claims description 5
- 201000008274 breast adenocarcinoma Diseases 0.000 claims description 5
- 239000003937 drug carrier Substances 0.000 claims description 5
- 210000004962 mammalian cell Anatomy 0.000 claims description 5
- 201000006417 multiple sclerosis Diseases 0.000 claims description 5
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 5
- 239000000074 antisense oligonucleotide Substances 0.000 claims description 4
- 238000012230 antisense oligonucleotides Methods 0.000 claims description 4
- 230000001580 bacterial effect Effects 0.000 claims description 4
- 239000003795 chemical substances by application Substances 0.000 claims description 4
- 230000000295 complement effect Effects 0.000 claims description 4
- 238000011161 development Methods 0.000 claims description 4
- 230000003389 potentiating effect Effects 0.000 claims description 4
- 230000002265 prevention Effects 0.000 claims description 4
- 238000013519 translation Methods 0.000 claims description 4
- 201000009030 Carcinoma Diseases 0.000 claims description 3
- 241000238631 Hexapoda Species 0.000 claims description 3
- 241000124008 Mammalia Species 0.000 claims description 3
- 208000018737 Parkinson disease Diseases 0.000 claims description 3
- 206010002026 amyotrophic lateral sclerosis Diseases 0.000 claims description 3
- 230000000903 blocking effect Effects 0.000 claims description 3
- 208000019065 cervical carcinoma Diseases 0.000 claims description 3
- 210000000038 chest Anatomy 0.000 claims description 3
- 230000002538 fungal effect Effects 0.000 claims description 3
- 108020001507 fusion proteins Proteins 0.000 claims description 3
- 102000037865 fusion proteins Human genes 0.000 claims description 3
- 230000000626 neurodegenerative effect Effects 0.000 claims description 3
- 230000002062 proliferating effect Effects 0.000 claims description 3
- 230000009467 reduction Effects 0.000 claims description 3
- 208000024827 Alzheimer disease Diseases 0.000 claims description 2
- 108020000948 Antisense Oligonucleotides Proteins 0.000 claims description 2
- 108090000994 Catalytic RNA Proteins 0.000 claims description 2
- 102000053642 Catalytic RNA Human genes 0.000 claims description 2
- 108700039691 Genetic Promoter Regions Proteins 0.000 claims description 2
- 239000003085 diluting agent Substances 0.000 claims description 2
- 238000000302 molecular modelling Methods 0.000 claims description 2
- 108091092562 ribozyme Proteins 0.000 claims description 2
- NTYJJOPFIAHURM-UHFFFAOYSA-N Histamine Chemical compound NCCC1=CN=CN1 NTYJJOPFIAHURM-UHFFFAOYSA-N 0.000 claims 2
- 239000003607 modifier Substances 0.000 claims 2
- 206010008342 Cervix carcinoma Diseases 0.000 claims 1
- 208000018639 Parkinson disease 20 Diseases 0.000 claims 1
- 108091027981 Response element Proteins 0.000 claims 1
- 108091023040 Transcription factor Proteins 0.000 claims 1
- 102000040945 Transcription factor Human genes 0.000 claims 1
- 125000003275 alpha amino acid group Chemical group 0.000 claims 1
- 230000004927 fusion Effects 0.000 claims 1
- 229960001340 histamine Drugs 0.000 claims 1
- 108091006082 receptor inhibitors Proteins 0.000 claims 1
- 238000002741 site-directed mutagenesis Methods 0.000 claims 1
- 102000004310 Ion Channels Human genes 0.000 abstract description 19
- 230000004663 cell proliferation Effects 0.000 abstract description 13
- 229910001414 potassium ion Inorganic materials 0.000 abstract description 5
- 230000002401 inhibitory effect Effects 0.000 abstract description 3
- 238000009007 Diagnostic Kit Methods 0.000 abstract description 2
- 108091006146 Channels Proteins 0.000 description 62
- 239000012634 fragment Substances 0.000 description 33
- 102100022810 Potassium voltage-gated channel subfamily H member 1 Human genes 0.000 description 31
- 210000004556 brain Anatomy 0.000 description 24
- 239000002299 complementary DNA Substances 0.000 description 21
- 210000001519 tissue Anatomy 0.000 description 21
- 102000040430 polynucleotide Human genes 0.000 description 19
- 108091033319 polynucleotide Proteins 0.000 description 19
- 239000002157 polynucleotide Substances 0.000 description 19
- 235000018102 proteins Nutrition 0.000 description 17
- 108090000862 Ion Channels Proteins 0.000 description 16
- WOVKYSAHUYNSMH-RRKCRQDMSA-N 5-bromodeoxyuridine Chemical compound C1[C@H](O)[C@@H](CO)O[C@H]1N1C(=O)NC(=O)C(Br)=C1 WOVKYSAHUYNSMH-RRKCRQDMSA-N 0.000 description 15
- 230000035755 proliferation Effects 0.000 description 15
- 230000006820 DNA synthesis Effects 0.000 description 14
- 101001047090 Homo sapiens Potassium voltage-gated channel subfamily H member 2 Proteins 0.000 description 14
- 230000006870 function Effects 0.000 description 14
- 102100022807 Potassium voltage-gated channel subfamily H member 2 Human genes 0.000 description 13
- 241000700159 Rattus Species 0.000 description 13
- 210000004881 tumor cell Anatomy 0.000 description 13
- 150000001413 amino acids Chemical group 0.000 description 12
- 230000001105 regulatory effect Effects 0.000 description 12
- 102000004257 Potassium Channel Human genes 0.000 description 11
- 210000004978 chinese hamster ovary cell Anatomy 0.000 description 11
- 108020001213 potassium channel Proteins 0.000 description 11
- 238000010348 incorporation Methods 0.000 description 10
- 238000001890 transfection Methods 0.000 description 10
- 230000022131 cell cycle Effects 0.000 description 9
- 238000009826 distribution Methods 0.000 description 9
- 238000009396 hybridization Methods 0.000 description 9
- 210000005075 mammary gland Anatomy 0.000 description 9
- 239000000523 sample Substances 0.000 description 9
- 210000002966 serum Anatomy 0.000 description 9
- 102000040650 (ribonucleotides)n+m Human genes 0.000 description 8
- 241000699666 Mus <mouse, genus> Species 0.000 description 8
- 238000002105 Southern blotting Methods 0.000 description 8
- IQFYYKKMVGJFEH-XLPZGREQSA-N Thymidine Chemical compound O=C1NC(=O)C(C)=CN1[C@@H]1O[C@H](CO)[C@@H](O)C1 IQFYYKKMVGJFEH-XLPZGREQSA-N 0.000 description 8
- 230000004913 activation Effects 0.000 description 8
- 230000003321 amplification Effects 0.000 description 8
- 230000015572 biosynthetic process Effects 0.000 description 8
- 230000001419 dependent effect Effects 0.000 description 8
- 230000012010 growth Effects 0.000 description 8
- 238000001727 in vivo Methods 0.000 description 8
- 239000002609 medium Substances 0.000 description 8
- 238000003199 nucleic acid amplification method Methods 0.000 description 8
- 241000699670 Mus sp. Species 0.000 description 7
- 235000001014 amino acid Nutrition 0.000 description 7
- 210000002919 epithelial cell Anatomy 0.000 description 7
- 238000002474 experimental method Methods 0.000 description 7
- 239000012528 membrane Substances 0.000 description 7
- 108020004999 messenger RNA Proteins 0.000 description 7
- 238000003757 reverse transcription PCR Methods 0.000 description 7
- 241000283690 Bos taurus Species 0.000 description 6
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 6
- 230000018199 S phase Effects 0.000 description 6
- 230000010261 cell growth Effects 0.000 description 6
- 101150113410 eag gene Proteins 0.000 description 6
- 210000002216 heart Anatomy 0.000 description 6
- 210000005260 human cell Anatomy 0.000 description 6
- 238000002513 implantation Methods 0.000 description 6
- 230000002503 metabolic effect Effects 0.000 description 6
- 239000002773 nucleotide Substances 0.000 description 6
- 125000003729 nucleotide group Chemical group 0.000 description 6
- 230000002829 reductive effect Effects 0.000 description 6
- 238000012216 screening Methods 0.000 description 6
- 239000000243 solution Substances 0.000 description 6
- 238000003786 synthesis reaction Methods 0.000 description 6
- 229920001817 Agar Polymers 0.000 description 5
- 101100341862 Rattus norvegicus Kcnh1 gene Proteins 0.000 description 5
- 108020004511 Recombinant DNA Proteins 0.000 description 5
- 102000007238 Transferrin Receptors Human genes 0.000 description 5
- 108010033576 Transferrin Receptors Proteins 0.000 description 5
- 239000008272 agar Substances 0.000 description 5
- 239000003623 enhancer Substances 0.000 description 5
- 239000001963 growth medium Substances 0.000 description 5
- 238000005259 measurement Methods 0.000 description 5
- 230000017074 necrotic cell death Effects 0.000 description 5
- 239000013612 plasmid Substances 0.000 description 5
- 239000013603 viral vector Substances 0.000 description 5
- JKMHFZQWWAIEOD-UHFFFAOYSA-N 2-[4-(2-hydroxyethyl)piperazin-1-yl]ethanesulfonic acid Chemical compound OCC[NH+]1CCN(CCS([O-])(=O)=O)CC1 JKMHFZQWWAIEOD-UHFFFAOYSA-N 0.000 description 4
- DWRXFEITVBNRMK-UHFFFAOYSA-N Beta-D-1-Arabinofuranosylthymine Natural products O=C1NC(=O)C(C)=CN1C1C(O)C(O)C(CO)O1 DWRXFEITVBNRMK-UHFFFAOYSA-N 0.000 description 4
- 102000053602 DNA Human genes 0.000 description 4
- 241000196324 Embryophyta Species 0.000 description 4
- ZHNUHDYFZUAESO-UHFFFAOYSA-N Formamide Chemical compound NC=O ZHNUHDYFZUAESO-UHFFFAOYSA-N 0.000 description 4
- 102100034343 Integrase Human genes 0.000 description 4
- TWRXJAOTZQYOKJ-UHFFFAOYSA-L Magnesium chloride Chemical compound [Mg+2].[Cl-].[Cl-] TWRXJAOTZQYOKJ-UHFFFAOYSA-L 0.000 description 4
- 238000012408 PCR amplification Methods 0.000 description 4
- 108010092799 RNA-directed DNA polymerase Proteins 0.000 description 4
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 4
- IQFYYKKMVGJFEH-UHFFFAOYSA-N beta-L-thymidine Natural products O=C1NC(=O)C(C)=CN1C1OC(CO)C(O)C1 IQFYYKKMVGJFEH-UHFFFAOYSA-N 0.000 description 4
- 230000033228 biological regulation Effects 0.000 description 4
- 238000003745 diagnosis Methods 0.000 description 4
- 230000002068 genetic effect Effects 0.000 description 4
- 229960004580 glibenclamide Drugs 0.000 description 4
- ZNNLBTZKUZBEKO-UHFFFAOYSA-N glyburide Chemical compound COC1=CC=C(Cl)C=C1C(=O)NCCC1=CC=C(S(=O)(=O)NC(=O)NC2CCCCC2)C=C1 ZNNLBTZKUZBEKO-UHFFFAOYSA-N 0.000 description 4
- 238000011534 incubation Methods 0.000 description 4
- 210000003734 kidney Anatomy 0.000 description 4
- 239000002502 liposome Substances 0.000 description 4
- 208000004731 long QT syndrome Diseases 0.000 description 4
- 239000003550 marker Substances 0.000 description 4
- 238000002703 mutagenesis Methods 0.000 description 4
- 231100000350 mutagenesis Toxicity 0.000 description 4
- 210000004940 nucleus Anatomy 0.000 description 4
- 239000003450 potassium channel blocker Substances 0.000 description 4
- LOUPRKONTZGTKE-LHHVKLHASA-N quinidine Chemical compound C([C@H]([C@H](C1)C=C)C2)C[N@@]1[C@H]2[C@@H](O)C1=CC=NC2=CC=C(OC)C=C21 LOUPRKONTZGTKE-LHHVKLHASA-N 0.000 description 4
- 230000002441 reversible effect Effects 0.000 description 4
- 241000894007 species Species 0.000 description 4
- 210000000278 spinal cord Anatomy 0.000 description 4
- 238000007920 subcutaneous administration Methods 0.000 description 4
- 229940104230 thymidine Drugs 0.000 description 4
- WOVKYSAHUYNSMH-UHFFFAOYSA-N BROMODEOXYURIDINE Natural products C1C(O)C(CO)OC1N1C(=O)NC(=O)C(Br)=C1 WOVKYSAHUYNSMH-UHFFFAOYSA-N 0.000 description 3
- 241000894006 Bacteria Species 0.000 description 3
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 3
- 241000699802 Cricetulus griseus Species 0.000 description 3
- 108091082532 Eag family Proteins 0.000 description 3
- 241000588724 Escherichia coli Species 0.000 description 3
- 206010064912 Malignant transformation Diseases 0.000 description 3
- 241001465754 Metazoa Species 0.000 description 3
- 101100341861 Mus musculus Kcnh1 gene Proteins 0.000 description 3
- 238000000636 Northern blotting Methods 0.000 description 3
- 102000010780 Platelet-Derived Growth Factor Human genes 0.000 description 3
- 108010038512 Platelet-Derived Growth Factor Proteins 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- 108091081024 Start codon Proteins 0.000 description 3
- 241000700605 Viruses Species 0.000 description 3
- 238000007792 addition Methods 0.000 description 3
- 238000004458 analytical method Methods 0.000 description 3
- 238000013459 approach Methods 0.000 description 3
- 210000005013 brain tissue Anatomy 0.000 description 3
- 210000004899 c-terminal region Anatomy 0.000 description 3
- 238000006243 chemical reaction Methods 0.000 description 3
- 238000011109 contamination Methods 0.000 description 3
- 238000007796 conventional method Methods 0.000 description 3
- 230000007423 decrease Effects 0.000 description 3
- 230000018109 developmental process Effects 0.000 description 3
- 229960002994 dofetilide Drugs 0.000 description 3
- IXTMWRCNAAVVAI-UHFFFAOYSA-N dofetilide Chemical compound C=1C=C(NS(C)(=O)=O)C=CC=1CCN(C)CCOC1=CC=C(NS(C)(=O)=O)C=C1 IXTMWRCNAAVVAI-UHFFFAOYSA-N 0.000 description 3
- 238000005516 engineering process Methods 0.000 description 3
- 210000003527 eukaryotic cell Anatomy 0.000 description 3
- 238000011156 evaluation Methods 0.000 description 3
- 239000012894 fetal calf serum Substances 0.000 description 3
- 239000003102 growth factor Substances 0.000 description 3
- 239000007943 implant Substances 0.000 description 3
- 230000003993 interaction Effects 0.000 description 3
- 230000003834 intracellular effect Effects 0.000 description 3
- 150000002500 ions Chemical class 0.000 description 3
- 238000002955 isolation Methods 0.000 description 3
- 238000002372 labelling Methods 0.000 description 3
- 210000004185 liver Anatomy 0.000 description 3
- 230000036212 malign transformation Effects 0.000 description 3
- 230000007246 mechanism Effects 0.000 description 3
- 230000028161 membrane depolarization Effects 0.000 description 3
- 238000010369 molecular cloning Methods 0.000 description 3
- 210000000287 oocyte Anatomy 0.000 description 3
- 230000003287 optical effect Effects 0.000 description 3
- 230000010076 replication Effects 0.000 description 3
- 210000002027 skeletal muscle Anatomy 0.000 description 3
- 238000010561 standard procedure Methods 0.000 description 3
- 239000000758 substrate Substances 0.000 description 3
- 238000002560 therapeutic procedure Methods 0.000 description 3
- FTEDXVNDVHYDQW-UHFFFAOYSA-N BAPTA Chemical compound OC(=O)CN(CC(O)=O)C1=CC=CC=C1OCCOC1=CC=CC=C1N(CC(O)=O)CC(O)=O FTEDXVNDVHYDQW-UHFFFAOYSA-N 0.000 description 2
- UXVMQQNJUSDDNG-UHFFFAOYSA-L Calcium chloride Chemical compound [Cl-].[Cl-].[Ca+2] UXVMQQNJUSDDNG-UHFFFAOYSA-L 0.000 description 2
- 108091026890 Coding region Proteins 0.000 description 2
- 102000036364 Cullin Ring E3 Ligases Human genes 0.000 description 2
- 241000192125 Firmicutes Species 0.000 description 2
- 239000007995 HEPES buffer Substances 0.000 description 2
- SIKJAQJRHWYJAI-UHFFFAOYSA-N Indole Chemical compound C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 description 2
- 102000052812 Ornithine decarboxylases Human genes 0.000 description 2
- 108700005126 Ornithine decarboxylases Proteins 0.000 description 2
- 108091034057 RNA (poly(A)) Proteins 0.000 description 2
- 102000004338 Transferrin Human genes 0.000 description 2
- 108090000901 Transferrin Proteins 0.000 description 2
- 241000269370 Xenopus <genus> Species 0.000 description 2
- 210000004100 adrenal gland Anatomy 0.000 description 2
- 210000004102 animal cell Anatomy 0.000 description 2
- 230000006907 apoptotic process Effects 0.000 description 2
- 206010003119 arrhythmia Diseases 0.000 description 2
- 230000006793 arrhythmia Effects 0.000 description 2
- 210000004369 blood Anatomy 0.000 description 2
- 239000008280 blood Substances 0.000 description 2
- 210000000481 breast Anatomy 0.000 description 2
- 208000014581 breast ductal adenocarcinoma Diseases 0.000 description 2
- 239000007853 buffer solution Substances 0.000 description 2
- 239000001110 calcium chloride Substances 0.000 description 2
- 235000011148 calcium chloride Nutrition 0.000 description 2
- 229910001628 calcium chloride Inorganic materials 0.000 description 2
- 230000006369 cell cycle progression Effects 0.000 description 2
- 230000001413 cellular effect Effects 0.000 description 2
- 230000008859 change Effects 0.000 description 2
- 238000012512 characterization method Methods 0.000 description 2
- 210000000349 chromosome Anatomy 0.000 description 2
- LOUPRKONTZGTKE-UHFFFAOYSA-N cinchonine Natural products C1C(C(C2)C=C)CCN2C1C(O)C1=CC=NC2=CC=C(OC)C=C21 LOUPRKONTZGTKE-UHFFFAOYSA-N 0.000 description 2
- 238000010367 cloning Methods 0.000 description 2
- 238000005094 computer simulation Methods 0.000 description 2
- 230000001276 controlling effect Effects 0.000 description 2
- 239000013078 crystal Substances 0.000 description 2
- 230000007547 defect Effects 0.000 description 2
- 238000001514 detection method Methods 0.000 description 2
- 230000029087 digestion Effects 0.000 description 2
- 231100000673 dose–response relationship Toxicity 0.000 description 2
- VLCYCQAOQCDTCN-UHFFFAOYSA-N eflornithine Chemical compound NCCCC(N)(C(F)F)C(O)=O VLCYCQAOQCDTCN-UHFFFAOYSA-N 0.000 description 2
- 239000000839 emulsion 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
- 238000013467 fragmentation Methods 0.000 description 2
- 238000006062 fragmentation reaction Methods 0.000 description 2
- 238000010363 gene targeting Methods 0.000 description 2
- 210000004293 human mammary gland Anatomy 0.000 description 2
- 230000002209 hydrophobic effect Effects 0.000 description 2
- 230000001900 immune effect Effects 0.000 description 2
- 230000000415 inactivating effect Effects 0.000 description 2
- 230000000977 initiatory effect Effects 0.000 description 2
- 230000002601 intratumoral effect Effects 0.000 description 2
- 229910001629 magnesium chloride Inorganic materials 0.000 description 2
- 238000012423 maintenance Methods 0.000 description 2
- 230000001404 mediated effect Effects 0.000 description 2
- VMGAPWLDMVPYIA-HIDZBRGKSA-N n'-amino-n-iminomethanimidamide Chemical compound N\N=C\N=N VMGAPWLDMVPYIA-HIDZBRGKSA-N 0.000 description 2
- 210000002569 neuron Anatomy 0.000 description 2
- 230000002246 oncogenic effect Effects 0.000 description 2
- 239000012188 paraffin wax Substances 0.000 description 2
- 230000000144 pharmacologic effect Effects 0.000 description 2
- 238000007747 plating Methods 0.000 description 2
- 210000004910 pleural fluid Anatomy 0.000 description 2
- 238000004393 prognosis Methods 0.000 description 2
- 210000001236 prokaryotic cell Anatomy 0.000 description 2
- RXWNCPJZOCPEPQ-NVWDDTSBSA-N puromycin Chemical compound C1=CC(OC)=CC=C1C[C@H](N)C(=O)N[C@H]1[C@@H](O)[C@H](N2C3=NC=NC(=C3N=C2)N(C)C)O[C@@H]1CO RXWNCPJZOCPEPQ-NVWDDTSBSA-N 0.000 description 2
- 238000004451 qualitative analysis Methods 0.000 description 2
- 238000004445 quantitative analysis Methods 0.000 description 2
- 229960001404 quinidine Drugs 0.000 description 2
- 102000005962 receptors Human genes 0.000 description 2
- 108020003175 receptors Proteins 0.000 description 2
- BOLDJAUMGUJJKM-LSDHHAIUSA-N renifolin D Natural products CC(=C)[C@@H]1Cc2c(O)c(O)ccc2[C@H]1CC(=O)c3ccc(O)cc3O BOLDJAUMGUJJKM-LSDHHAIUSA-N 0.000 description 2
- 238000011160 research Methods 0.000 description 2
- 230000001177 retroviral effect Effects 0.000 description 2
- 238000010839 reverse transcription Methods 0.000 description 2
- 208000002491 severe combined immunodeficiency Diseases 0.000 description 2
- 239000002356 single layer Substances 0.000 description 2
- 239000011780 sodium chloride Substances 0.000 description 2
- 239000007787 solid Substances 0.000 description 2
- 238000010186 staining Methods 0.000 description 2
- 210000003437 trachea Anatomy 0.000 description 2
- 239000012581 transferrin Substances 0.000 description 2
- 230000001131 transforming effect Effects 0.000 description 2
- 241000701161 unidentified adenovirus Species 0.000 description 2
- 241001430294 unidentified retrovirus Species 0.000 description 2
- VBEQCZHXXJYVRD-GACYYNSASA-N uroanthelone Chemical compound C([C@@H](C(=O)N[C@H](C(=O)N[C@@H](CS)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CS)C(=O)N[C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)NCC(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N[C@@H](CO)C(=O)NCC(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CS)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O)C(C)C)[C@@H](C)O)NC(=O)[C@H](CO)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CO)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@@H](NC(=O)[C@H](CC=1NC=NC=1)NC(=O)[C@H](CCSC)NC(=O)[C@H](CS)NC(=O)[C@@H](NC(=O)CNC(=O)CNC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CS)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)CNC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CO)NC(=O)[C@H](CO)NC(=O)[C@H]1N(CCC1)C(=O)[C@H](CS)NC(=O)CNC(=O)[C@H]1N(CCC1)C(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CO)NC(=O)[C@@H](N)CC(N)=O)C(C)C)[C@@H](C)CC)C1=CC=C(O)C=C1 VBEQCZHXXJYVRD-GACYYNSASA-N 0.000 description 2
- 239000003981 vehicle Substances 0.000 description 2
- MTCFGRXMJLQNBG-REOHCLBHSA-N (2S)-2-Amino-3-hydroxypropansäure Chemical compound OC[C@H](N)C(O)=O MTCFGRXMJLQNBG-REOHCLBHSA-N 0.000 description 1
- PRDFBSVERLRRMY-UHFFFAOYSA-N 2'-(4-ethoxyphenyl)-5-(4-methylpiperazin-1-yl)-2,5'-bibenzimidazole Chemical compound C1=CC(OCC)=CC=C1C1=NC2=CC=C(C=3NC4=CC(=CC=C4N=3)N3CCN(C)CC3)C=C2N1 PRDFBSVERLRRMY-UHFFFAOYSA-N 0.000 description 1
- AZKSAVLVSZKNRD-UHFFFAOYSA-M 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide Chemical compound [Br-].S1C(C)=C(C)N=C1[N+]1=NC(C=2C=CC=CC=2)=NN1C1=CC=CC=C1 AZKSAVLVSZKNRD-UHFFFAOYSA-M 0.000 description 1
- 101150094949 APRT gene Proteins 0.000 description 1
- 102100029457 Adenine phosphoribosyltransferase Human genes 0.000 description 1
- 108010024223 Adenine phosphoribosyltransferase Proteins 0.000 description 1
- 102100036826 Aldehyde oxidase Human genes 0.000 description 1
- 244000105975 Antidesma platyphyllum Species 0.000 description 1
- 244000063299 Bacillus subtilis Species 0.000 description 1
- 235000014469 Bacillus subtilis Nutrition 0.000 description 1
- 108091007914 CDKs Proteins 0.000 description 1
- 102000034573 Channels Human genes 0.000 description 1
- 108010023798 Charybdotoxin Proteins 0.000 description 1
- 108091035707 Consensus sequence Proteins 0.000 description 1
- 241000699800 Cricetinae Species 0.000 description 1
- 108050006400 Cyclin Proteins 0.000 description 1
- 102000016736 Cyclin Human genes 0.000 description 1
- 108090000266 Cyclin-dependent kinases Proteins 0.000 description 1
- 102000003903 Cyclin-dependent kinases Human genes 0.000 description 1
- 241000701022 Cytomegalovirus Species 0.000 description 1
- 101150074155 DHFR gene Proteins 0.000 description 1
- 241000702421 Dependoparvovirus Species 0.000 description 1
- 241000255581 Drosophila <fruit fly, genus> Species 0.000 description 1
- 208000037162 Ductal Breast Carcinoma Diseases 0.000 description 1
- 208000006402 Ductal Carcinoma Diseases 0.000 description 1
- 238000002965 ELISA Methods 0.000 description 1
- 102400001368 Epidermal growth factor Human genes 0.000 description 1
- 101800003838 Epidermal growth factor Proteins 0.000 description 1
- YQYJSBFKSSDGFO-UHFFFAOYSA-N Epihygromycin Natural products OC1C(O)C(C(=O)C)OC1OC(C(=C1)O)=CC=C1C=C(C)C(=O)NC1C(O)C(O)C2OCOC2C1O YQYJSBFKSSDGFO-UHFFFAOYSA-N 0.000 description 1
- 238000011770 Fox Chase SCID mouse Methods 0.000 description 1
- 101150094690 GAL1 gene Proteins 0.000 description 1
- 102100028501 Galanin peptides 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
- 101000928314 Homo sapiens Aldehyde oxidase Proteins 0.000 description 1
- 101100121078 Homo sapiens GAL gene Proteins 0.000 description 1
- 101001092185 Homo sapiens Regulator of cell cycle RGCC Proteins 0.000 description 1
- 108010091358 Hypoxanthine Phosphoribosyltransferase Proteins 0.000 description 1
- 102100029098 Hypoxanthine-guanine phosphoribosyltransferase Human genes 0.000 description 1
- XQFRJNBWHJMXHO-RRKCRQDMSA-N IDUR Chemical compound C1[C@H](O)[C@@H](CO)O[C@H]1N1C(=O)NC(=O)C(I)=C1 XQFRJNBWHJMXHO-RRKCRQDMSA-N 0.000 description 1
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
- 102000008394 Immunoglobulin Fragments Human genes 0.000 description 1
- 108010021625 Immunoglobulin Fragments Proteins 0.000 description 1
- 101150104566 Kcnh1 gene Proteins 0.000 description 1
- ONIBWKKTOPOVIA-BYPYZUCNSA-N L-Proline Chemical compound OC(=O)[C@@H]1CCCN1 ONIBWKKTOPOVIA-BYPYZUCNSA-N 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
- FBOZXECLQNJBKD-ZDUSSCGKSA-N L-methotrexate Chemical compound C=1N=C2N=C(N)N=C(N)C2=NC=1CN(C)C1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 FBOZXECLQNJBKD-ZDUSSCGKSA-N 0.000 description 1
- AYFVYJQAPQTCCC-GBXIJSLDSA-N L-threonine Chemical compound C[C@@H](O)[C@H](N)C(O)=O AYFVYJQAPQTCCC-GBXIJSLDSA-N 0.000 description 1
- QIVBCDIJIAJPQS-VIFPVBQESA-N L-tryptophane Chemical compound C1=CC=C2C(C[C@H](N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-VIFPVBQESA-N 0.000 description 1
- 206010027476 Metastases Diseases 0.000 description 1
- 101100261636 Methanothermobacter marburgensis (strain ATCC BAA-927 / DSM 2133 / JCM 14651 / NBRC 100331 / OCM 82 / Marburg) trpB2 gene Proteins 0.000 description 1
- 108010021466 Mutant Proteins Proteins 0.000 description 1
- 102000008300 Mutant Proteins Human genes 0.000 description 1
- 108091061960 Naked DNA Proteins 0.000 description 1
- 108091092724 Noncoding DNA Proteins 0.000 description 1
- 102000043276 Oncogene Human genes 0.000 description 1
- 108700020796 Oncogene Proteins 0.000 description 1
- 229940122060 Ornithine decarboxylase inhibitor Drugs 0.000 description 1
- 238000010222 PCR analysis Methods 0.000 description 1
- 229930040373 Paraformaldehyde Natural products 0.000 description 1
- 108091093037 Peptide nucleic acid Proteins 0.000 description 1
- 102000003992 Peroxidases Human genes 0.000 description 1
- 108091000080 Phosphotransferase Proteins 0.000 description 1
- 101100124346 Photorhabdus laumondii subsp. laumondii (strain DSM 15139 / CIP 105565 / TT01) hisCD gene Proteins 0.000 description 1
- 208000002151 Pleural effusion Diseases 0.000 description 1
- ONIBWKKTOPOVIA-UHFFFAOYSA-N Proline Natural products OC(=O)C1CCCN1 ONIBWKKTOPOVIA-UHFFFAOYSA-N 0.000 description 1
- 102100035542 Regulator of cell cycle RGCC Human genes 0.000 description 1
- 108700008625 Reporter Genes Proteins 0.000 description 1
- 241000220317 Rosa Species 0.000 description 1
- 241000714474 Rous sarcoma virus Species 0.000 description 1
- 241000235070 Saccharomyces Species 0.000 description 1
- 240000004808 Saccharomyces cerevisiae Species 0.000 description 1
- 241000293869 Salmonella enterica subsp. enterica serovar Typhimurium Species 0.000 description 1
- 208000034189 Sclerosis Diseases 0.000 description 1
- MTCFGRXMJLQNBG-UHFFFAOYSA-N Serine Natural products OCC(N)C(O)=O MTCFGRXMJLQNBG-UHFFFAOYSA-N 0.000 description 1
- 241000607715 Serratia marcescens Species 0.000 description 1
- 108010026533 Shaker Superfamily of Potassium Channels Proteins 0.000 description 1
- 102000013541 Shaker Superfamily of Potassium Channels Human genes 0.000 description 1
- 241000700584 Simplexvirus Species 0.000 description 1
- 241000256251 Spodoptera frugiperda Species 0.000 description 1
- 108091036066 Three prime untranslated region Proteins 0.000 description 1
- AYFVYJQAPQTCCC-UHFFFAOYSA-N Threonine Natural products CC(O)C(N)C(O)=O AYFVYJQAPQTCCC-UHFFFAOYSA-N 0.000 description 1
- 239000004473 Threonine Substances 0.000 description 1
- 102000006601 Thymidine Kinase Human genes 0.000 description 1
- 108020004440 Thymidine kinase Proteins 0.000 description 1
- QIVBCDIJIAJPQS-UHFFFAOYSA-N Tryptophan Natural products C1=CC=C2C(CC(N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-UHFFFAOYSA-N 0.000 description 1
- 108091023045 Untranslated Region Proteins 0.000 description 1
- 241000700618 Vaccinia virus Species 0.000 description 1
- 102000003734 Voltage-Gated Potassium Channels Human genes 0.000 description 1
- 108090000013 Voltage-Gated Potassium Channels Proteins 0.000 description 1
- 241000269368 Xenopus laevis Species 0.000 description 1
- 108010084455 Zeocin Proteins 0.000 description 1
- HIHOWBSBBDRPDW-PTHRTHQKSA-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 Chemical compound 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 HIHOWBSBBDRPDW-PTHRTHQKSA-N 0.000 description 1
- 230000002159 abnormal effect Effects 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 230000003213 activating effect Effects 0.000 description 1
- 239000002671 adjuvant Substances 0.000 description 1
- 239000011543 agarose gel Substances 0.000 description 1
- 239000000556 agonist Substances 0.000 description 1
- 230000004075 alteration Effects 0.000 description 1
- 229940126575 aminoglycoside Drugs 0.000 description 1
- 239000005557 antagonist Substances 0.000 description 1
- 230000000340 anti-metabolite Effects 0.000 description 1
- 239000003416 antiarrhythmic agent Substances 0.000 description 1
- 229940100197 antimetabolite Drugs 0.000 description 1
- 239000002256 antimetabolite Substances 0.000 description 1
- 210000001367 artery Anatomy 0.000 description 1
- 238000003556 assay Methods 0.000 description 1
- 235000019606 astringent taste Nutrition 0.000 description 1
- 239000012298 atmosphere Substances 0.000 description 1
- 230000008901 benefit Effects 0.000 description 1
- YTCZZXIRLARSET-VJRSQJMHSA-M beraprost sodium Chemical compound [Na+].O([C@H]1C[C@@H](O)[C@@H]([C@@H]21)/C=C/[C@@H](O)C(C)CC#CC)C1=C2C=CC=C1CCCC([O-])=O YTCZZXIRLARSET-VJRSQJMHSA-M 0.000 description 1
- 235000021028 berry Nutrition 0.000 description 1
- 238000004166 bioassay Methods 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
- 230000037396 body weight Effects 0.000 description 1
- 201000010983 breast ductal carcinoma Diseases 0.000 description 1
- 229950004398 broxuridine Drugs 0.000 description 1
- 239000001506 calcium phosphate Substances 0.000 description 1
- 229910000389 calcium phosphate Inorganic materials 0.000 description 1
- 235000011010 calcium phosphates Nutrition 0.000 description 1
- 230000000747 cardiac effect Effects 0.000 description 1
- 238000004113 cell culture Methods 0.000 description 1
- 230000030833 cell death Effects 0.000 description 1
- 230000011712 cell development Effects 0.000 description 1
- 239000013592 cell lysate Substances 0.000 description 1
- 210000000170 cell membrane Anatomy 0.000 description 1
- 238000001516 cell proliferation assay Methods 0.000 description 1
- 210000003169 central nervous system Anatomy 0.000 description 1
- 238000003889 chemical engineering Methods 0.000 description 1
- 238000007385 chemical modification Methods 0.000 description 1
- 238000002512 chemotherapy Methods 0.000 description 1
- 238000013375 chromatographic separation Methods 0.000 description 1
- 230000002759 chromosomal effect Effects 0.000 description 1
- 229940082627 class iii antiarrhythmics Drugs 0.000 description 1
- 230000005757 colony formation Effects 0.000 description 1
- 238000004891 communication Methods 0.000 description 1
- 238000004590 computer program Methods 0.000 description 1
- 238000009833 condensation Methods 0.000 description 1
- 230000005494 condensation Effects 0.000 description 1
- 108091036078 conserved sequence Proteins 0.000 description 1
- 238000010276 construction Methods 0.000 description 1
- 239000000356 contaminant Substances 0.000 description 1
- 230000008094 contradictory effect Effects 0.000 description 1
- CNVQLPPZGABUCM-LIGYZCPXSA-N ctx toxin Chemical compound C([C@@H](C(=O)N[C@H](C(=O)N[C@@H](CC(N)=O)C(=O)N[C@H](C(=O)N[C@@H](CO)C(=O)N[C@H]1CSSC[C@H]2C(=O)N[C@H](C(N[C@@H](CC(N)=O)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCCCN)C(=O)N[C@H]3CSSC[C@@H](C(N[C@@H](CC=4C5=CC=CC=C5NC=4)C(=O)N[C@@H](CO)C(=O)N[C@H](C(=O)N[C@@H](CSSC[C@H](NC(=O)[C@H](CCCNC(N)=N)NC3=O)C(=O)N[C@@H](CC=3C=CC(O)=CC=3)C(=O)N[C@@H](CO)C(O)=O)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC=3NC=NC=3)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCCNC(N)=N)C(=O)NCC(=O)N[C@@H](CCCCN)C(=O)N2)C(C)C)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CO)NC(=O)[C@H]([C@@H](C)O)NC(=O)[C@H]([C@@H](C)O)NC1=O)=O)CCSC)C(C)C)[C@@H](C)O)NC(=O)[C@H]1NC(=O)CC1)C1=CC=CC=C1 CNVQLPPZGABUCM-LIGYZCPXSA-N 0.000 description 1
- 238000012258 culturing Methods 0.000 description 1
- 125000004122 cyclic group Chemical group 0.000 description 1
- 230000001086 cytosolic effect Effects 0.000 description 1
- 230000034994 death Effects 0.000 description 1
- 230000002950 deficient Effects 0.000 description 1
- 230000007850 degeneration Effects 0.000 description 1
- 238000012217 deletion Methods 0.000 description 1
- 230000037430 deletion Effects 0.000 description 1
- 230000002999 depolarising effect Effects 0.000 description 1
- 238000002405 diagnostic procedure Methods 0.000 description 1
- 230000004069 differentiation Effects 0.000 description 1
- 238000010790 dilution Methods 0.000 description 1
- 239000012895 dilution Substances 0.000 description 1
- 239000012636 effector Substances 0.000 description 1
- 230000009881 electrostatic interaction Effects 0.000 description 1
- 229940116977 epidermal growth factor Drugs 0.000 description 1
- 229940011871 estrogen Drugs 0.000 description 1
- 239000000262 estrogen Substances 0.000 description 1
- 102000015694 estrogen receptors Human genes 0.000 description 1
- 108010038795 estrogen receptors Proteins 0.000 description 1
- 230000001605 fetal effect Effects 0.000 description 1
- 210000002950 fibroblast Anatomy 0.000 description 1
- 238000005194 fractionation Methods 0.000 description 1
- 102000034356 gene-regulatory proteins Human genes 0.000 description 1
- 108091006104 gene-regulatory proteins Proteins 0.000 description 1
- 210000004602 germ cell Anatomy 0.000 description 1
- 210000004907 gland Anatomy 0.000 description 1
- 102000018146 globin Human genes 0.000 description 1
- 108060003196 globin Proteins 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- 235000013922 glutamic acid Nutrition 0.000 description 1
- 239000004220 glutamic acid Substances 0.000 description 1
- 230000013595 glycosylation Effects 0.000 description 1
- 238000006206 glycosylation reaction Methods 0.000 description 1
- 230000009036 growth inhibition Effects 0.000 description 1
- 235000009424 haa Nutrition 0.000 description 1
- 230000036541 health Effects 0.000 description 1
- 230000002008 hemorrhagic effect Effects 0.000 description 1
- 101150113423 hisD gene Proteins 0.000 description 1
- HNDVDQJCIGZPNO-UHFFFAOYSA-N histidine Natural products OC(=O)C(N)CC1=CN=CN1 HNDVDQJCIGZPNO-UHFFFAOYSA-N 0.000 description 1
- 238000002744 homologous recombination Methods 0.000 description 1
- 230000006801 homologous recombination Effects 0.000 description 1
- 230000007062 hydrolysis Effects 0.000 description 1
- 238000006460 hydrolysis reaction Methods 0.000 description 1
- 230000002102 hyperpolarization Effects 0.000 description 1
- 238000005286 illumination Methods 0.000 description 1
- 230000009474 immediate action Effects 0.000 description 1
- 230000006872 improvement Effects 0.000 description 1
- 238000011065 in-situ storage Methods 0.000 description 1
- PZOUSPYUWWUPPK-UHFFFAOYSA-N indole Natural products CC1=CC=CC2=C1C=CN2 PZOUSPYUWWUPPK-UHFFFAOYSA-N 0.000 description 1
- RKJUIXBNRJVNHR-UHFFFAOYSA-N indolenine Natural products C1=CC=C2CC=NC2=C1 RKJUIXBNRJVNHR-UHFFFAOYSA-N 0.000 description 1
- 238000001802 infusion Methods 0.000 description 1
- 239000004615 ingredient Substances 0.000 description 1
- 238000003780 insertion Methods 0.000 description 1
- 230000037431 insertion Effects 0.000 description 1
- 238000007689 inspection Methods 0.000 description 1
- 230000002452 interceptive effect Effects 0.000 description 1
- 238000007918 intramuscular administration Methods 0.000 description 1
- 238000007912 intraperitoneal administration Methods 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- 206010073095 invasive ductal breast carcinoma Diseases 0.000 description 1
- 238000011835 investigation Methods 0.000 description 1
- 201000010901 lateral sclerosis Diseases 0.000 description 1
- 239000010410 layer Substances 0.000 description 1
- 210000004072 lung Anatomy 0.000 description 1
- 210000001161 mammalian embryo Anatomy 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 229960000485 methotrexate Drugs 0.000 description 1
- HPNSFSBZBAHARI-UHFFFAOYSA-N micophenolic acid Natural products OC1=C(CC=C(C)CCC(O)=O)C(OC)=C(C)C2=C1C(=O)OC2 HPNSFSBZBAHARI-UHFFFAOYSA-N 0.000 description 1
- 238000001000 micrograph Methods 0.000 description 1
- 208000005264 motor neuron disease Diseases 0.000 description 1
- 230000000869 mutational effect Effects 0.000 description 1
- HPNSFSBZBAHARI-RUDMXATFSA-N mycophenolic acid Chemical compound OC1=C(C\C=C(/C)CCC(O)=O)C(OC)=C(C)C2=C1C(=O)OC2 HPNSFSBZBAHARI-RUDMXATFSA-N 0.000 description 1
- 229960000951 mycophenolic acid Drugs 0.000 description 1
- 230000001338 necrotic effect Effects 0.000 description 1
- 108091027963 non-coding RNA Proteins 0.000 description 1
- 102000042567 non-coding RNA Human genes 0.000 description 1
- 210000004882 non-tumor cell Anatomy 0.000 description 1
- 238000007899 nucleic acid hybridization Methods 0.000 description 1
- 230000030648 nucleus localization Effects 0.000 description 1
- 229960000988 nystatin Drugs 0.000 description 1
- VQOXZBDYSJBXMA-NQTDYLQESA-N nystatin A1 Chemical compound O[C@H]1[C@@H](N)[C@H](O)[C@@H](C)O[C@H]1O[C@H]1/C=C/C=C/C=C/C=C/CC/C=C/C=C/[C@H](C)[C@@H](O)[C@@H](C)[C@H](C)OC(=O)C[C@H](O)C[C@H](O)C[C@H](O)CC[C@@H](O)[C@H](O)C[C@](O)(C[C@H](O)[C@H]2C(O)=O)O[C@H]2C1 VQOXZBDYSJBXMA-NQTDYLQESA-N 0.000 description 1
- 210000000056 organ Anatomy 0.000 description 1
- 239000002818 ornithine decarboxylase inhibitor Substances 0.000 description 1
- 210000001672 ovary Anatomy 0.000 description 1
- 238000002559 palpation Methods 0.000 description 1
- 210000000496 pancreas Anatomy 0.000 description 1
- 208000003154 papilloma Diseases 0.000 description 1
- 229920002866 paraformaldehyde Polymers 0.000 description 1
- 238000012402 patch clamp technique Methods 0.000 description 1
- 230000000737 periodic effect Effects 0.000 description 1
- 108040007629 peroxidase activity proteins Proteins 0.000 description 1
- 239000008024 pharmaceutical diluent Substances 0.000 description 1
- CWCMIVBLVUHDHK-ZSNHEYEWSA-N phleomycin D1 Chemical compound N([C@H](C(=O)N[C@H](C)[C@@H](O)[C@H](C)C(=O)N[C@@H]([C@H](O)C)C(=O)NCCC=1SC[C@@H](N=1)C=1SC=C(N=1)C(=O)NCCCCNC(N)=N)[C@@H](O[C@H]1[C@H]([C@@H](O)[C@H](O)[C@H](CO)O1)O[C@@H]1[C@H]([C@@H](OC(N)=O)[C@H](O)[C@@H](CO)O1)O)C=1N=CNC=1)C(=O)C1=NC([C@H](CC(N)=O)NC[C@H](N)C(N)=O)=NC(N)=C1C CWCMIVBLVUHDHK-ZSNHEYEWSA-N 0.000 description 1
- 239000008363 phosphate buffer Substances 0.000 description 1
- 230000026731 phosphorylation Effects 0.000 description 1
- 238000006366 phosphorylation reaction Methods 0.000 description 1
- 102000020233 phosphotransferase Human genes 0.000 description 1
- 210000002826 placenta Anatomy 0.000 description 1
- 229940125422 potassium channel blocker Drugs 0.000 description 1
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 1
- 230000004952 protein activity Effects 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 229950010131 puromycin Drugs 0.000 description 1
- 108010045647 puromycin N-acetyltransferase Proteins 0.000 description 1
- 125000001453 quaternary ammonium group Chemical group 0.000 description 1
- 230000006798 recombination Effects 0.000 description 1
- 238000005215 recombination Methods 0.000 description 1
- 230000000306 recurrent effect Effects 0.000 description 1
- 230000022983 regulation of cell cycle Effects 0.000 description 1
- 230000002336 repolarization Effects 0.000 description 1
- 230000001850 reproductive effect Effects 0.000 description 1
- 230000004044 response Effects 0.000 description 1
- 239000007320 rich medium Substances 0.000 description 1
- 239000006152 selective media Substances 0.000 description 1
- 230000035945 sensitivity Effects 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 238000012163 sequencing technique Methods 0.000 description 1
- 239000012679 serum free medium Substances 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 230000006641 stabilisation Effects 0.000 description 1
- 238000011105 stabilization Methods 0.000 description 1
- 239000008174 sterile solution Substances 0.000 description 1
- 230000000638 stimulation Effects 0.000 description 1
- 210000004003 subcutaneous fat Anatomy 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 230000001360 synchronised effect Effects 0.000 description 1
- 125000003831 tetrazolyl group Chemical group 0.000 description 1
- RYYWUUFWQRZTIU-UHFFFAOYSA-K thiophosphate Chemical compound [O-]P([O-])([O-])=S RYYWUUFWQRZTIU-UHFFFAOYSA-K 0.000 description 1
- 230000000699 topical effect Effects 0.000 description 1
- 230000002103 transcriptional effect Effects 0.000 description 1
- 239000012096 transfection reagent Substances 0.000 description 1
- 230000009466 transformation Effects 0.000 description 1
- 230000009261 transgenic effect Effects 0.000 description 1
- 238000003146 transient transfection Methods 0.000 description 1
- 230000007704 transition Effects 0.000 description 1
- 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 1
- 101150081616 trpB gene Proteins 0.000 description 1
- 101150111232 trpB-1 gene Proteins 0.000 description 1
- 230000005748 tumor development Effects 0.000 description 1
- 230000004614 tumor growth Effects 0.000 description 1
- 241001529453 unidentified herpesvirus Species 0.000 description 1
- 241001515965 unidentified phage Species 0.000 description 1
- 238000002255 vaccination Methods 0.000 description 1
- 230000003612 virological effect Effects 0.000 description 1
- 238000011179 visual inspection Methods 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
- 239000000080 wetting agent Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- C07K14/705—Receptors; Cell surface antigens; Cell surface determinants
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
- C12N15/09—Recombinant DNA-technology
- C12N15/11—DNA or RNA fragments; Modified forms thereof; Non-coding nucleic acids having a biological activity
- C12N15/113—Non-coding nucleic acids modulating the expression of genes, e.g. antisense oligonucleotides; Antisense DNA or RNA; Triplex- forming oligonucleotides; Catalytic nucleic acids, e.g. ribozymes; Nucleic acids used in co-suppression or gene silencing
- C12N15/1138—Non-coding nucleic acids modulating the expression of genes, e.g. antisense oligonucleotides; Antisense DNA or RNA; Triplex- forming oligonucleotides; Catalytic nucleic acids, e.g. ribozymes; Nucleic acids used in co-suppression or gene silencing against receptors or cell surface proteins
-
- 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
- A61K48/00—Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N2310/00—Structure or type of the nucleic acid
- C12N2310/30—Chemical structure
- C12N2310/31—Chemical structure of the backbone
- C12N2310/315—Phosphorothioates
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Genetics & Genomics (AREA)
- Biomedical Technology (AREA)
- General Health & Medical Sciences (AREA)
- Molecular Biology (AREA)
- Zoology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Medicinal Chemistry (AREA)
- Biochemistry (AREA)
- Biophysics (AREA)
- Wood Science & Technology (AREA)
- General Engineering & Computer Science (AREA)
- Biotechnology (AREA)
- Pharmacology & Pharmacy (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Animal Behavior & Ethology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Microbiology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Physics & Mathematics (AREA)
- Immunology (AREA)
- Cell Biology (AREA)
- Plant Pathology (AREA)
- Toxicology (AREA)
- Gastroenterology & Hepatology (AREA)
- Neurosurgery (AREA)
- Neurology (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Micro-Organisms Or Cultivation Processes Thereof (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Measuring Or Testing Involving Enzymes Or Micro-Organisms (AREA)
- Steroid Compounds (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EP98107268 | 1998-04-21 | ||
| EP98107268 | 1998-04-21 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| ES2230852T3 true ES2230852T3 (es) | 2005-05-01 |
Family
ID=8231794
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| ES99920731T Expired - Lifetime ES2230852T3 (es) | 1998-04-21 | 1999-04-21 | Canales ionicos de k+humanos y aplicaciones terapeuticas de los mismos. |
Country Status (10)
| Country | Link |
|---|---|
| US (7) | US6638736B1 (enExample) |
| EP (1) | EP1073738B1 (enExample) |
| JP (2) | JP2002512029A (enExample) |
| AT (1) | ATE278017T1 (enExample) |
| CA (1) | CA2323571A1 (enExample) |
| DE (1) | DE69920681T2 (enExample) |
| DK (1) | DK1073738T3 (enExample) |
| ES (1) | ES2230852T3 (enExample) |
| PT (1) | PT1073738E (enExample) |
| WO (1) | WO1999054463A2 (enExample) |
Families Citing this family (10)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| ES2230852T3 (es) * | 1998-04-21 | 2005-05-01 | Max-Planck-Gesellschaft Zur Forderung Der Wissenschaften E.V. | Canales ionicos de k+humanos y aplicaciones terapeuticas de los mismos. |
| DE10025620A1 (de) * | 2000-05-24 | 2001-12-06 | Forschungsgesellschaft Genion | Verfahren zur Herstellung von Chimären zwischen bakteriellen und eukaryotischen Kaliumkanälen auf festen Trägern und deren Verwendung zur Identifizierung von Kaliumkanalagonisten und -antagonisten |
| DE10224534A1 (de) | 2002-05-31 | 2003-12-11 | Juergen Dolderer | Verfahren zum Diagnostizieren des colorektaien Karzinoms in einer Gewebeprobe und Mittel zur Behandlung |
| MX2007003865A (es) * | 2004-10-01 | 2009-06-17 | Ct Investig Y Estudios Del Ipn | Métodos para el diagnóstico temprano de infecciones virales y enfermedades inflamatorias o de la predisposición de un individuo a desórdenes proliferativos o hiperplasia. |
| ATE497508T1 (de) | 2004-10-01 | 2011-02-15 | Max Planck Gesellschaft | Gegen das säugetier-eag1-ionenkanalprotein gerichtete antikörper |
| AU2013201604B2 (en) * | 2007-04-13 | 2014-08-14 | Southern Research Institute | Anti-angiogenic agents and methods of use |
| ES2334084B1 (es) * | 2007-12-21 | 2011-01-24 | Inst Cientifico Tecnol Navarra | Marcadores geneticos para el pronostico de la esclerosis multiple. |
| US8892184B2 (en) | 2010-10-18 | 2014-11-18 | Siemens Medical Solutions Usa, Inc. | Systems and methods for reducing interference in a dual modality imaging system |
| TWI570415B (zh) * | 2015-10-02 | 2017-02-11 | A spring probe having an outer sleeve and a probe device having the spring probe | |
| EP3195727A1 (en) | 2016-01-22 | 2017-07-26 | Forschungsinstitut Fur Biologischen Landbau (FiBL) | Duddingtonia flagrans strain and feed additive formulation for biological pest control |
Family Cites Families (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4394448A (en) * | 1978-02-24 | 1983-07-19 | Szoka Jr Francis C | Method of inserting DNA into living cells |
| US5703055A (en) * | 1989-03-21 | 1997-12-30 | Wisconsin Alumni Research Foundation | Generation of antibodies through lipid mediated DNA delivery |
| GB9303210D0 (en) | 1993-02-17 | 1993-03-31 | Univ Manitoba | Cancer treatment |
| WO1992011034A1 (en) | 1990-12-18 | 1992-07-09 | The Wellcome Foundation Limited | Agents for potentiating the effects of antitumor agents and combating multiple drug resistance |
| WO1998000168A1 (en) * | 1996-07-02 | 1998-01-08 | Novartis Consumer Health S.A. | Topical composition comprising a combination of antihistaminic compounds with terpenoid compounds |
| US6610827B1 (en) * | 1997-10-29 | 2003-08-26 | Elan Pharmaceuticals, Inc. | Potassium channel subunit polypeptide and polynucleotide compositions and uses therefor |
| ES2230852T3 (es) * | 1998-04-21 | 2005-05-01 | Max-Planck-Gesellschaft Zur Forderung Der Wissenschaften E.V. | Canales ionicos de k+humanos y aplicaciones terapeuticas de los mismos. |
-
1999
- 1999-04-21 ES ES99920731T patent/ES2230852T3/es not_active Expired - Lifetime
- 1999-04-21 EP EP99920731A patent/EP1073738B1/en not_active Expired - Lifetime
- 1999-04-21 AT AT99920731T patent/ATE278017T1/de not_active IP Right Cessation
- 1999-04-21 PT PT99920731T patent/PT1073738E/pt unknown
- 1999-04-21 DK DK99920731T patent/DK1073738T3/da active
- 1999-04-21 JP JP2000544795A patent/JP2002512029A/ja not_active Withdrawn
- 1999-04-21 WO PCT/EP1999/002695 patent/WO1999054463A2/en not_active Ceased
- 1999-04-21 CA CA002323571A patent/CA2323571A1/en not_active Abandoned
- 1999-04-21 DE DE69920681T patent/DE69920681T2/de not_active Expired - Lifetime
-
2000
- 2000-10-23 US US09/694,777 patent/US6638736B1/en not_active Expired - Fee Related
-
2002
- 2002-07-01 US US10/188,296 patent/US7364845B2/en not_active Expired - Fee Related
- 2002-07-01 US US10/188,341 patent/US7129207B2/en not_active Expired - Fee Related
- 2002-07-01 US US10/188,308 patent/US7364730B2/en not_active Expired - Fee Related
- 2002-07-01 US US10/188,297 patent/US7314914B2/en not_active Expired - Fee Related
-
2006
- 2006-11-30 US US11/633,085 patent/US20080020406A1/en not_active Abandoned
-
2009
- 2009-06-09 US US12/480,913 patent/US20100021467A1/en not_active Abandoned
- 2009-07-06 JP JP2009160236A patent/JP2009235091A/ja active Pending
Also Published As
| Publication number | Publication date |
|---|---|
| EP1073738B1 (en) | 2004-09-29 |
| US20030087377A1 (en) | 2003-05-08 |
| DK1073738T3 (da) | 2005-01-24 |
| US20030092120A1 (en) | 2003-05-15 |
| US20080020406A1 (en) | 2008-01-24 |
| US7364730B2 (en) | 2008-04-29 |
| EP1073738A2 (en) | 2001-02-07 |
| US6638736B1 (en) | 2003-10-28 |
| US7364845B2 (en) | 2008-04-29 |
| US7129207B2 (en) | 2006-10-31 |
| US20100021467A1 (en) | 2010-01-28 |
| JP2009235091A (ja) | 2009-10-15 |
| JP2002512029A (ja) | 2002-04-23 |
| CA2323571A1 (en) | 1999-10-28 |
| ATE278017T1 (de) | 2004-10-15 |
| US7314914B2 (en) | 2008-01-01 |
| WO1999054463A2 (en) | 1999-10-28 |
| WO1999054463A3 (en) | 2000-04-20 |
| DE69920681T2 (de) | 2005-09-08 |
| US20030077735A1 (en) | 2003-04-24 |
| DE69920681D1 (de) | 2004-11-04 |
| US20030087378A1 (en) | 2003-05-08 |
| PT1073738E (pt) | 2005-01-31 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| US20100021467A1 (en) | Method of detecting a cancer cell by aberrant expression of a human k+ ion channel | |
| KR102873006B1 (ko) | 17β-하이드록시스테로이드 데하이드로게나제 유형 13 (HSD17B13) iRNA 조성물 및 그것의 사용 방법 | |
| Jackson et al. | The mas oncogene encodes an angiotensin receptor | |
| US8586553B2 (en) | Therapies for cancer using RLIP76 | |
| JP2021191279A (ja) | 肝線維症治療用組成物および肝線維症の治療法 | |
| ES2428791T3 (es) | Anticuerpo dirigido contra una proteína asociada a los osteoclastos | |
| KR20240033237A (ko) | 류신이 풍부한 반복 키나아제 2(LRRK2) iRNA 제제 조성물 및 이의 사용 방법 | |
| WO2004087207A2 (en) | Method for inducing apoptosis and aneuploidy regression in cancer cells | |
| ES2429131T3 (es) | Uso de la proteína estimulante del crecimiento KIAA1524 | |
| KR20220133246A (ko) | 류신 풍부 반복 키나아제 2 (LRRK2) iRNA 작용제 조성물 및 이의 사용 방법 | |
| WO2004022075A1 (en) | Treatment of neurological disorders by dsrna adminitration | |
| ES2276466T3 (es) | Polipeptido humano leucocitico del canal de potasio activado por calcio. | |
| CA2388386A1 (en) | A new eag gene | |
| KR101121987B1 (ko) | 파골세포 골흡수 억제 ｓｉＲＮＡ 발현 벡터 및 이를 이용한 유전자 치료제 | |
| WO2002031117A2 (en) | Clasp-2 transmembrane proteins | |
| US20030143738A1 (en) | Compositions and methods for treating ischemic stroke | |
| KR100710549B1 (ko) | 라민 에이 유전자 또는 라민 에이 단백질을 포함하는암세포 증식 억제제, 이의 제조방법 및 이를 이용한암세포 증식 억제방법 | |
| WO2001042296A2 (en) | Clasp-5 transmembrane protein | |
| Smetsers | Antisense BCR-ABL oligonucleotides in chronic myeloid leukemia |