JP2004537291A - 新規混合系統キナーゼ(7)(mlk7)ポリペプチド、それをコードするポリヌクレオチド、およびそれらの使用方法 - Google Patents
新規混合系統キナーゼ(7)(mlk7)ポリペプチド、それをコードするポリヌクレオチド、およびそれらの使用方法 Download PDFInfo
- Publication number
- JP2004537291A JP2004537291A JP2002592480A JP2002592480A JP2004537291A JP 2004537291 A JP2004537291 A JP 2004537291A JP 2002592480 A JP2002592480 A JP 2002592480A JP 2002592480 A JP2002592480 A JP 2002592480A JP 2004537291 A JP2004537291 A JP 2004537291A
- Authority
- JP
- Japan
- Prior art keywords
- polypeptide
- mlk7
- compound
- polynucleotide
- kinase
- 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.)
- Withdrawn
Links
- 102000040430 polynucleotide Human genes 0.000 title claims abstract description 94
- 108091033319 polynucleotide Proteins 0.000 title claims abstract description 94
- 239000002157 polynucleotide Substances 0.000 title claims abstract description 94
- 108090000765 processed proteins & peptides Proteins 0.000 title claims abstract description 93
- 102000004196 processed proteins & peptides Human genes 0.000 title claims abstract description 91
- 229920001184 polypeptide Polymers 0.000 title claims abstract description 87
- 238000000034 method Methods 0.000 title claims abstract description 61
- 101001018157 Homo sapiens Mitogen-activated protein kinase kinase kinase 20 Proteins 0.000 title description 189
- 102100033116 Mitogen-activated protein kinase kinase kinase 20 Human genes 0.000 title description 188
- 108091000080 Phosphotransferase Proteins 0.000 title description 62
- 102000020233 phosphotransferase Human genes 0.000 title description 62
- 150000001875 compounds Chemical class 0.000 claims abstract description 99
- 230000000694 effects Effects 0.000 claims abstract description 54
- 239000013604 expression vector Substances 0.000 claims abstract description 24
- 239000000203 mixture Substances 0.000 claims abstract description 22
- 210000004027 cell Anatomy 0.000 claims description 76
- 230000027455 binding Effects 0.000 claims description 44
- 230000014509 gene expression Effects 0.000 claims description 32
- 238000003556 assay Methods 0.000 claims description 27
- 239000013598 vector Substances 0.000 claims description 23
- 239000002773 nucleotide Substances 0.000 claims description 18
- 125000003729 nucleotide group Chemical group 0.000 claims description 18
- 239000000758 substrate Substances 0.000 claims description 15
- 230000026731 phosphorylation Effects 0.000 claims description 14
- 238000006366 phosphorylation reaction Methods 0.000 claims description 14
- 238000002965 ELISA Methods 0.000 claims description 13
- 239000003085 diluting agent Substances 0.000 claims description 12
- 230000004913 activation Effects 0.000 claims description 10
- 238000004458 analytical method Methods 0.000 claims description 10
- 239000013612 plasmid Substances 0.000 claims description 10
- 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 9
- 230000003993 interaction Effects 0.000 claims description 9
- 238000003259 recombinant expression Methods 0.000 claims description 8
- 241000238631 Hexapoda Species 0.000 claims description 6
- 230000000295 complement effect Effects 0.000 claims description 6
- 210000004962 mammalian cell Anatomy 0.000 claims description 6
- 238000001262 western blot Methods 0.000 claims description 4
- 241000700605 Viruses Species 0.000 claims description 3
- 239000002245 particle Substances 0.000 claims description 3
- 238000000159 protein binding assay Methods 0.000 claims description 3
- 230000001580 bacterial effect Effects 0.000 claims description 2
- 238000000975 co-precipitation Methods 0.000 claims description 2
- 238000004132 cross linking Methods 0.000 claims description 2
- 238000001400 expression cloning Methods 0.000 claims description 2
- 238000005194 fractionation Methods 0.000 claims description 2
- 210000005253 yeast cell Anatomy 0.000 claims description 2
- 238000004519 manufacturing process Methods 0.000 abstract description 5
- 108090000623 proteins and genes Proteins 0.000 description 60
- 102000004169 proteins and genes Human genes 0.000 description 48
- 229940024606 amino acid Drugs 0.000 description 30
- 241000282414 Homo sapiens Species 0.000 description 29
- 150000001413 amino acids Chemical class 0.000 description 28
- ROHFNLRQFUQHCH-YFKPBYRVSA-N L-leucine Chemical compound CC(C)C[C@H](N)C(O)=O ROHFNLRQFUQHCH-YFKPBYRVSA-N 0.000 description 25
- 239000012634 fragment Substances 0.000 description 25
- ROHFNLRQFUQHCH-UHFFFAOYSA-N Leucine Natural products CC(C)CC(N)C(O)=O ROHFNLRQFUQHCH-UHFFFAOYSA-N 0.000 description 23
- 102100023274 Dual specificity mitogen-activated protein kinase kinase 4 Human genes 0.000 description 22
- 108010068304 MAP Kinase Kinase 4 Proteins 0.000 description 22
- 101001005609 Homo sapiens Mitogen-activated protein kinase kinase kinase 13 Proteins 0.000 description 20
- 102100025184 Mitogen-activated protein kinase kinase kinase 13 Human genes 0.000 description 20
- 239000000047 product Substances 0.000 description 18
- 102100023332 Dual specificity mitogen-activated protein kinase kinase 7 Human genes 0.000 description 17
- 241000701447 unidentified baculovirus Species 0.000 description 16
- 230000002159 abnormal effect Effects 0.000 description 15
- 239000002299 complementary DNA Substances 0.000 description 15
- 108090001035 mitogen-activated protein kinase kinase kinase 12 Proteins 0.000 description 15
- 238000006467 substitution reaction Methods 0.000 description 15
- 108020004414 DNA Proteins 0.000 description 14
- 238000006243 chemical reaction Methods 0.000 description 14
- 239000000243 solution Substances 0.000 description 14
- 102000004190 Enzymes Human genes 0.000 description 13
- 108090000790 Enzymes Proteins 0.000 description 13
- 102100025180 Mitogen-activated protein kinase kinase kinase 12 Human genes 0.000 description 13
- 108091028043 Nucleic acid sequence Proteins 0.000 description 13
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 13
- 229940088598 enzyme Drugs 0.000 description 13
- 230000037361 pathway Effects 0.000 description 13
- DHCLVCXQIBBOPH-UHFFFAOYSA-N Glycerol 2-phosphate Chemical compound OCC(CO)OP(O)(O)=O DHCLVCXQIBBOPH-UHFFFAOYSA-N 0.000 description 12
- 125000003275 alpha amino acid group Chemical group 0.000 description 12
- 210000001519 tissue Anatomy 0.000 description 12
- 101001005602 Homo sapiens Mitogen-activated protein kinase kinase kinase 11 Proteins 0.000 description 11
- 102100025207 Mitogen-activated protein kinase kinase kinase 11 Human genes 0.000 description 11
- 239000000872 buffer Substances 0.000 description 11
- 201000010099 disease Diseases 0.000 description 11
- 238000012216 screening Methods 0.000 description 11
- 230000000903 blocking effect Effects 0.000 description 10
- MTCFGRXMJLQNBG-REOHCLBHSA-N (2S)-2-Amino-3-hydroxypropansäure Chemical compound OC[C@H](N)C(O)=O MTCFGRXMJLQNBG-REOHCLBHSA-N 0.000 description 9
- KISWVXRQTGLFGD-UHFFFAOYSA-N 2-[[2-[[6-amino-2-[[2-[[2-[[5-amino-2-[[2-[[1-[2-[[6-amino-2-[(2,5-diamino-5-oxopentanoyl)amino]hexanoyl]amino]-5-(diaminomethylideneamino)pentanoyl]pyrrolidine-2-carbonyl]amino]-3-hydroxypropanoyl]amino]-5-oxopentanoyl]amino]-5-(diaminomethylideneamino)p Chemical compound C1CCN(C(=O)C(CCCN=C(N)N)NC(=O)C(CCCCN)NC(=O)C(N)CCC(N)=O)C1C(=O)NC(CO)C(=O)NC(CCC(N)=O)C(=O)NC(CCCN=C(N)N)C(=O)NC(CO)C(=O)NC(CCCCN)C(=O)NC(C(=O)NC(CC(C)C)C(O)=O)CC1=CC=C(O)C=C1 KISWVXRQTGLFGD-UHFFFAOYSA-N 0.000 description 9
- 101000624594 Homo sapiens Dual specificity mitogen-activated protein kinase kinase 7 Proteins 0.000 description 9
- 125000000539 amino acid group Chemical group 0.000 description 9
- 230000004927 fusion Effects 0.000 description 9
- 238000000338 in vitro Methods 0.000 description 9
- 239000003656 tris buffered saline Substances 0.000 description 9
- 101001055085 Homo sapiens Mitogen-activated protein kinase kinase kinase 9 Proteins 0.000 description 8
- 108010068339 MAP Kinase Kinase 7 Proteins 0.000 description 8
- 102100026909 Mitogen-activated protein kinase kinase kinase 9 Human genes 0.000 description 8
- 102000047918 Myelin Basic Human genes 0.000 description 8
- 101710107068 Myelin basic protein Proteins 0.000 description 8
- 238000010790 dilution Methods 0.000 description 8
- 239000012895 dilution Substances 0.000 description 8
- 238000011534 incubation Methods 0.000 description 8
- 239000000523 sample Substances 0.000 description 8
- 239000007787 solid Substances 0.000 description 8
- 238000011282 treatment Methods 0.000 description 8
- 108010070675 Glutathione transferase Proteins 0.000 description 7
- 102100029100 Hematopoietic prostaglandin D synthase Human genes 0.000 description 7
- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 7
- 108091034117 Oligonucleotide Proteins 0.000 description 7
- 240000004808 Saccharomyces cerevisiae Species 0.000 description 7
- 230000000692 anti-sense effect Effects 0.000 description 7
- 102000048600 human MAP3K20 Human genes 0.000 description 7
- 238000009396 hybridization Methods 0.000 description 7
- 239000003446 ligand Substances 0.000 description 7
- 230000004048 modification Effects 0.000 description 7
- 238000012986 modification Methods 0.000 description 7
- 102000039446 nucleic acids Human genes 0.000 description 7
- 108020004707 nucleic acids Proteins 0.000 description 7
- 150000007523 nucleic acids Chemical class 0.000 description 7
- 239000000126 substance Substances 0.000 description 7
- 238000012360 testing method Methods 0.000 description 7
- 230000001225 therapeutic effect Effects 0.000 description 7
- -1 10% dextran sulfate Chemical compound 0.000 description 6
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 6
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 6
- AYFVYJQAPQTCCC-GBXIJSLDSA-N L-threonine Chemical compound C[C@@H](O)[C@H](N)C(O)=O AYFVYJQAPQTCCC-GBXIJSLDSA-N 0.000 description 6
- 108010066373 MLK-like mitogen-activated protein triple kinase Proteins 0.000 description 6
- 102000004022 Protein-Tyrosine Kinases Human genes 0.000 description 6
- 108090000412 Protein-Tyrosine Kinases Proteins 0.000 description 6
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 6
- 230000037396 body weight Effects 0.000 description 6
- 210000004899 c-terminal region Anatomy 0.000 description 6
- 108020001507 fusion proteins Proteins 0.000 description 6
- 102000037865 fusion proteins Human genes 0.000 description 6
- RWSXRVCMGQZWBV-WDSKDSINSA-N glutathione Chemical compound OC(=O)[C@@H](N)CCC(=O)N[C@@H](CS)C(=O)NCC(O)=O RWSXRVCMGQZWBV-WDSKDSINSA-N 0.000 description 6
- 239000006166 lysate Substances 0.000 description 6
- 108020004999 messenger RNA Proteins 0.000 description 6
- 239000013615 primer Substances 0.000 description 6
- 230000001105 regulatory effect Effects 0.000 description 6
- 230000010076 replication Effects 0.000 description 6
- 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 5
- 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 5
- OUYCCCASQSFEME-QMMMGPOBSA-N L-tyrosine Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-QMMMGPOBSA-N 0.000 description 5
- 102100038243 Mitogen-activated protein kinase kinase kinase 10 Human genes 0.000 description 5
- 108700020796 Oncogene Proteins 0.000 description 5
- 229920001213 Polysorbate 20 Polymers 0.000 description 5
- 238000010171 animal model Methods 0.000 description 5
- 210000004978 chinese hamster ovary cell Anatomy 0.000 description 5
- 238000012217 deletion Methods 0.000 description 5
- 230000037430 deletion Effects 0.000 description 5
- 238000005516 engineering process Methods 0.000 description 5
- DEFVIWRASFVYLL-UHFFFAOYSA-N ethylene glycol bis(2-aminoethyl)tetraacetic acid Chemical compound OC(=O)CN(CC(O)=O)CCOCCOCCN(CC(O)=O)CC(O)=O DEFVIWRASFVYLL-UHFFFAOYSA-N 0.000 description 5
- 210000003527 eukaryotic cell Anatomy 0.000 description 5
- 239000003112 inhibitor Substances 0.000 description 5
- 239000000256 polyoxyethylene sorbitan monolaurate Substances 0.000 description 5
- 235000010486 polyoxyethylene sorbitan monolaurate Nutrition 0.000 description 5
- 230000004083 survival effect Effects 0.000 description 5
- 108091032973 (ribonucleotides)n+m Proteins 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
- 101000958409 Homo sapiens Mitogen-activated protein kinase kinase kinase 10 Proteins 0.000 description 4
- AGPKZVBTJJNPAG-WHFBIAKZSA-N L-isoleucine Chemical group CC[C@H](C)[C@H](N)C(O)=O AGPKZVBTJJNPAG-WHFBIAKZSA-N 0.000 description 4
- 108700026244 Open Reading Frames Proteins 0.000 description 4
- 102000001253 Protein Kinase Human genes 0.000 description 4
- JLCPHMBAVCMARE-UHFFFAOYSA-N [3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-[[3-[[3-[[3-[[3-[[3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-hydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methyl [5-(6-aminopurin-9-yl)-2-(hydroxymethyl)oxolan-3-yl] hydrogen phosphate Polymers Cc1cn(C2CC(OP(O)(=O)OCC3OC(CC3OP(O)(=O)OCC3OC(CC3O)n3cnc4c3nc(N)[nH]c4=O)n3cnc4c3nc(N)[nH]c4=O)C(COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3CO)n3cnc4c(N)ncnc34)n3ccc(N)nc3=O)n3cnc4c(N)ncnc34)n3ccc(N)nc3=O)n3ccc(N)nc3=O)n3ccc(N)nc3=O)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cc(C)c(=O)[nH]c3=O)n3cc(C)c(=O)[nH]c3=O)n3ccc(N)nc3=O)n3cc(C)c(=O)[nH]c3=O)n3cnc4c3nc(N)[nH]c4=O)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)O2)c(=O)[nH]c1=O JLCPHMBAVCMARE-UHFFFAOYSA-N 0.000 description 4
- 238000001261 affinity purification Methods 0.000 description 4
- 230000004071 biological effect Effects 0.000 description 4
- 230000015572 biosynthetic process Effects 0.000 description 4
- 238000004113 cell culture Methods 0.000 description 4
- 238000001514 detection method Methods 0.000 description 4
- 230000006870 function Effects 0.000 description 4
- 230000001900 immune effect Effects 0.000 description 4
- 230000001965 increasing effect Effects 0.000 description 4
- 230000005764 inhibitory process Effects 0.000 description 4
- 238000002955 isolation Methods 0.000 description 4
- 239000002609 medium Substances 0.000 description 4
- 229930014626 natural product Natural products 0.000 description 4
- 208000015122 neurodegenerative disease Diseases 0.000 description 4
- 108060006633 protein kinase Proteins 0.000 description 4
- 230000002285 radioactive effect Effects 0.000 description 4
- 150000003839 salts Chemical class 0.000 description 4
- 241000894007 species Species 0.000 description 4
- 239000003981 vehicle Substances 0.000 description 4
- 230000003612 virological effect Effects 0.000 description 4
- QAPSNMNOIOSXSQ-YNEHKIRRSA-N 1-[(2r,4s,5r)-4-[tert-butyl(dimethyl)silyl]oxy-5-(hydroxymethyl)oxolan-2-yl]-5-methylpyrimidine-2,4-dione Chemical compound O=C1NC(=O)C(C)=CN1[C@@H]1O[C@H](CO)[C@@H](O[Si](C)(C)C(C)(C)C)C1 QAPSNMNOIOSXSQ-YNEHKIRRSA-N 0.000 description 3
- 102000002260 Alkaline Phosphatase Human genes 0.000 description 3
- 108020004774 Alkaline Phosphatase Proteins 0.000 description 3
- 241000283707 Capra Species 0.000 description 3
- 102100030013 Endoribonuclease Human genes 0.000 description 3
- 101710199605 Endoribonuclease Proteins 0.000 description 3
- 241000588724 Escherichia coli Species 0.000 description 3
- 241000701959 Escherichia virus Lambda Species 0.000 description 3
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 3
- 108010024636 Glutathione Proteins 0.000 description 3
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 3
- 101000950695 Homo sapiens Mitogen-activated protein kinase 8 Proteins 0.000 description 3
- 241001465754 Metazoa Species 0.000 description 3
- 102100037808 Mitogen-activated protein kinase 8 Human genes 0.000 description 3
- 208000009869 Neu-Laxova syndrome Diseases 0.000 description 3
- 108010077850 Nuclear Localization Signals Proteins 0.000 description 3
- 102000000395 SH3 domains Human genes 0.000 description 3
- 108050008861 SH3 domains Proteins 0.000 description 3
- MTCFGRXMJLQNBG-UHFFFAOYSA-N Serine Natural products OCC(N)C(O)=O MTCFGRXMJLQNBG-UHFFFAOYSA-N 0.000 description 3
- 101710113029 Serine/threonine-protein kinase Proteins 0.000 description 3
- 230000003321 amplification Effects 0.000 description 3
- 239000000074 antisense oligonucleotide Substances 0.000 description 3
- 238000012230 antisense oligonucleotides Methods 0.000 description 3
- YBJHBAHKTGYVGT-ZKWXMUAHSA-N biotin Natural products N1C(=O)N[C@@H]2[C@H](CCCCC(=O)O)SC[C@@H]21 YBJHBAHKTGYVGT-ZKWXMUAHSA-N 0.000 description 3
- 239000000969 carrier Substances 0.000 description 3
- 239000003795 chemical substances by application Substances 0.000 description 3
- 238000004587 chromatography analysis Methods 0.000 description 3
- 238000003776 cleavage reaction Methods 0.000 description 3
- 239000011248 coating agent Substances 0.000 description 3
- 238000000576 coating method Methods 0.000 description 3
- 230000001419 dependent effect Effects 0.000 description 3
- 230000002255 enzymatic effect Effects 0.000 description 3
- 238000002474 experimental method Methods 0.000 description 3
- 229960003180 glutathione Drugs 0.000 description 3
- 238000004128 high performance liquid chromatography Methods 0.000 description 3
- 230000002209 hydrophobic effect Effects 0.000 description 3
- 239000002502 liposome Substances 0.000 description 3
- 239000007788 liquid Substances 0.000 description 3
- 239000003550 marker Substances 0.000 description 3
- 238000010369 molecular cloning Methods 0.000 description 3
- 239000013642 negative control Substances 0.000 description 3
- 238000003199 nucleic acid amplification method Methods 0.000 description 3
- 239000008194 pharmaceutical composition Substances 0.000 description 3
- 239000002987 primer (paints) Substances 0.000 description 3
- 210000001236 prokaryotic cell Anatomy 0.000 description 3
- 230000002829 reductive effect Effects 0.000 description 3
- 230000007017 scission Effects 0.000 description 3
- 150000003384 small molecules Chemical class 0.000 description 3
- 239000011780 sodium chloride Substances 0.000 description 3
- 239000011534 wash buffer Substances 0.000 description 3
- 238000005406 washing Methods 0.000 description 3
- BCHIXGBGRHLSBE-UHFFFAOYSA-N (4-methyl-2-oxochromen-7-yl) dihydrogen phosphate Chemical compound C1=C(OP(O)(O)=O)C=CC2=C1OC(=O)C=C2C BCHIXGBGRHLSBE-UHFFFAOYSA-N 0.000 description 2
- 108020000948 Antisense Oligonucleotides Proteins 0.000 description 2
- 241000894006 Bacteria Species 0.000 description 2
- 102000001451 CRIB domains Human genes 0.000 description 2
- 108050009667 CRIB domains Proteins 0.000 description 2
- 108010047041 Complementarity Determining Regions Proteins 0.000 description 2
- 108020004635 Complementary DNA Proteins 0.000 description 2
- 239000003155 DNA primer Substances 0.000 description 2
- 238000012286 ELISA Assay Methods 0.000 description 2
- 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 2
- NYHBQMYGNKIUIF-UUOKFMHZSA-N Guanosine Chemical compound C1=NC=2C(=O)NC(N)=NC=2N1[C@@H]1O[C@H](CO)[C@@H](O)[C@H]1O NYHBQMYGNKIUIF-UUOKFMHZSA-N 0.000 description 2
- 239000007995 HEPES buffer Substances 0.000 description 2
- 101000956807 Homo sapiens Leukocyte tyrosine kinase receptor Proteins 0.000 description 2
- 101000950669 Homo sapiens Mitogen-activated protein kinase 9 Proteins 0.000 description 2
- 101001050288 Homo sapiens Transcription factor Jun Proteins 0.000 description 2
- 206010061218 Inflammation Diseases 0.000 description 2
- ONIBWKKTOPOVIA-BYPYZUCNSA-N L-Proline Chemical compound OC(=O)[C@@H]1CCCN1 ONIBWKKTOPOVIA-BYPYZUCNSA-N 0.000 description 2
- 125000000998 L-alanino group Chemical group [H]N([*])[C@](C([H])([H])[H])([H])C(=O)O[H] 0.000 description 2
- 125000000174 L-prolyl group Chemical group [H]N1C([H])([H])C([H])([H])C([H])([H])[C@@]1([H])C(*)=O 0.000 description 2
- 102100038420 Leukocyte tyrosine kinase receptor Human genes 0.000 description 2
- 241000124008 Mammalia Species 0.000 description 2
- 102000004232 Mitogen-Activated Protein Kinase Kinases Human genes 0.000 description 2
- 108090000744 Mitogen-Activated Protein Kinase Kinases Proteins 0.000 description 2
- 102100037809 Mitogen-activated protein kinase 9 Human genes 0.000 description 2
- 241000699666 Mus <mouse, genus> Species 0.000 description 2
- 125000000729 N-terminal amino-acid group Chemical group 0.000 description 2
- PXHVJJICTQNCMI-UHFFFAOYSA-N Nickel Chemical compound [Ni] PXHVJJICTQNCMI-UHFFFAOYSA-N 0.000 description 2
- ONIBWKKTOPOVIA-UHFFFAOYSA-N Proline Natural products OC(=O)C1CCCN1 ONIBWKKTOPOVIA-UHFFFAOYSA-N 0.000 description 2
- 102000009516 Protein Serine-Threonine Kinases Human genes 0.000 description 2
- 108010009341 Protein Serine-Threonine Kinases Proteins 0.000 description 2
- FKNQFGJONOIPTF-UHFFFAOYSA-N Sodium cation Chemical compound [Na+] FKNQFGJONOIPTF-UHFFFAOYSA-N 0.000 description 2
- NKANXQFJJICGDU-QPLCGJKRSA-N Tamoxifen Chemical compound C=1C=CC=CC=1C(/CC)=C(C=1C=CC(OCCN(C)C)=CC=1)/C1=CC=CC=C1 NKANXQFJJICGDU-QPLCGJKRSA-N 0.000 description 2
- 102100023132 Transcription factor Jun Human genes 0.000 description 2
- 239000012190 activator Substances 0.000 description 2
- 238000001042 affinity chromatography Methods 0.000 description 2
- 230000004075 alteration Effects 0.000 description 2
- 230000006907 apoptotic process Effects 0.000 description 2
- 125000003118 aryl group Chemical group 0.000 description 2
- 239000012131 assay buffer Substances 0.000 description 2
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 2
- 229960002685 biotin Drugs 0.000 description 2
- 235000020958 biotin Nutrition 0.000 description 2
- 239000011616 biotin Substances 0.000 description 2
- 210000004556 brain Anatomy 0.000 description 2
- 230000003197 catalytic effect Effects 0.000 description 2
- 238000000423 cell based assay Methods 0.000 description 2
- 230000030833 cell death Effects 0.000 description 2
- 230000024245 cell differentiation Effects 0.000 description 2
- 239000013592 cell lysate Substances 0.000 description 2
- 239000003153 chemical reaction reagent Substances 0.000 description 2
- 230000002759 chromosomal effect Effects 0.000 description 2
- 210000000349 chromosome Anatomy 0.000 description 2
- 238000010367 cloning Methods 0.000 description 2
- 230000001276 controlling effect Effects 0.000 description 2
- CVSVTCORWBXHQV-UHFFFAOYSA-N creatine Chemical compound NC(=[NH2+])N(C)CC([O-])=O CVSVTCORWBXHQV-UHFFFAOYSA-N 0.000 description 2
- OPTASPLRGRRNAP-UHFFFAOYSA-N cytosine Chemical compound NC=1C=CNC(=O)N=1 OPTASPLRGRRNAP-UHFFFAOYSA-N 0.000 description 2
- 230000007423 decrease Effects 0.000 description 2
- 239000010432 diamond Substances 0.000 description 2
- 208000035475 disorder Diseases 0.000 description 2
- 230000002708 enhancing effect Effects 0.000 description 2
- 230000005284 excitation Effects 0.000 description 2
- 238000000605 extraction Methods 0.000 description 2
- 239000007850 fluorescent dye Substances 0.000 description 2
- 239000000499 gel Substances 0.000 description 2
- 229960001031 glucose Drugs 0.000 description 2
- 238000000099 in vitro assay Methods 0.000 description 2
- 208000027866 inflammatory disease Diseases 0.000 description 2
- 230000004054 inflammatory process Effects 0.000 description 2
- 230000002401 inhibitory effect Effects 0.000 description 2
- 238000003780 insertion Methods 0.000 description 2
- 230000037431 insertion Effects 0.000 description 2
- 238000007918 intramuscular administration Methods 0.000 description 2
- 238000007912 intraperitoneal administration Methods 0.000 description 2
- 238000001990 intravenous administration Methods 0.000 description 2
- 230000000670 limiting effect Effects 0.000 description 2
- 230000029226 lipidation Effects 0.000 description 2
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
- 238000013507 mapping Methods 0.000 description 2
- MYWUZJCMWCOHBA-VIFPVBQESA-N methamphetamine Chemical compound CN[C@@H](C)CC1=CC=CC=C1 MYWUZJCMWCOHBA-VIFPVBQESA-N 0.000 description 2
- 244000005700 microbiome Species 0.000 description 2
- 102000004898 mitogen-activated protein kinase kinase kinase 12 Human genes 0.000 description 2
- 230000035772 mutation Effects 0.000 description 2
- 230000036961 partial effect Effects 0.000 description 2
- 230000001575 pathological effect Effects 0.000 description 2
- 239000000546 pharmaceutical excipient Substances 0.000 description 2
- 238000003566 phosphorylation assay Methods 0.000 description 2
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 2
- 238000000746 purification Methods 0.000 description 2
- 108091008598 receptor tyrosine kinases Proteins 0.000 description 2
- 102000027426 receptor tyrosine kinases Human genes 0.000 description 2
- 230000004044 response Effects 0.000 description 2
- 238000007894 restriction fragment length polymorphism technique Methods 0.000 description 2
- 238000007423 screening assay Methods 0.000 description 2
- 238000012163 sequencing technique Methods 0.000 description 2
- 239000011734 sodium Substances 0.000 description 2
- 229910001415 sodium ion Inorganic materials 0.000 description 2
- 125000006850 spacer group Chemical group 0.000 description 2
- 230000009870 specific binding Effects 0.000 description 2
- 210000002784 stomach Anatomy 0.000 description 2
- 230000006354 stress signaling Effects 0.000 description 2
- 238000007920 subcutaneous administration Methods 0.000 description 2
- 208000024891 symptom Diseases 0.000 description 2
- 238000003786 synthesis reaction Methods 0.000 description 2
- 238000013518 transcription Methods 0.000 description 2
- 230000035897 transcription Effects 0.000 description 2
- 230000002103 transcriptional effect Effects 0.000 description 2
- 238000001890 transfection Methods 0.000 description 2
- 230000009466 transformation Effects 0.000 description 2
- IHIXIJGXTJIKRB-UHFFFAOYSA-N trisodium vanadate Chemical compound [Na+].[Na+].[Na+].[O-][V]([O-])([O-])=O IHIXIJGXTJIKRB-UHFFFAOYSA-N 0.000 description 2
- 239000013603 viral vector Substances 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- DIGQNXIGRZPYDK-WKSCXVIASA-N (2R)-6-amino-2-[[2-[[(2S)-2-[[2-[[(2R)-2-[[(2S)-2-[[(2R,3S)-2-[[2-[[(2S)-2-[[2-[[(2S)-2-[[(2S)-2-[[(2R)-2-[[(2S,3S)-2-[[(2R)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[2-[[(2S)-2-[[(2R)-2-[[2-[[2-[[2-[(2-amino-1-hydroxyethylidene)amino]-3-carboxy-1-hydroxypropylidene]amino]-1-hydroxy-3-sulfanylpropylidene]amino]-1-hydroxyethylidene]amino]-1-hydroxy-3-sulfanylpropylidene]amino]-1,3-dihydroxypropylidene]amino]-1-hydroxyethylidene]amino]-1-hydroxypropylidene]amino]-1,3-dihydroxypropylidene]amino]-1,3-dihydroxypropylidene]amino]-1-hydroxy-3-sulfanylpropylidene]amino]-1,3-dihydroxybutylidene]amino]-1-hydroxy-3-sulfanylpropylidene]amino]-1-hydroxypropylidene]amino]-1,3-dihydroxypropylidene]amino]-1-hydroxyethylidene]amino]-1,5-dihydroxy-5-iminopentylidene]amino]-1-hydroxy-3-sulfanylpropylidene]amino]-1,3-dihydroxybutylidene]amino]-1-hydroxy-3-sulfanylpropylidene]amino]-1,3-dihydroxypropylidene]amino]-1-hydroxyethylidene]amino]-1-hydroxy-3-sulfanylpropylidene]amino]-1-hydroxyethylidene]amino]hexanoic acid Chemical compound C[C@@H]([C@@H](C(=N[C@@H](CS)C(=N[C@@H](C)C(=N[C@@H](CO)C(=NCC(=N[C@@H](CCC(=N)O)C(=NC(CS)C(=N[C@H]([C@H](C)O)C(=N[C@H](CS)C(=N[C@H](CO)C(=NCC(=N[C@H](CS)C(=NCC(=N[C@H](CCCCN)C(=O)O)O)O)O)O)O)O)O)O)O)O)O)O)O)N=C([C@H](CS)N=C([C@H](CO)N=C([C@H](CO)N=C([C@H](C)N=C(CN=C([C@H](CO)N=C([C@H](CS)N=C(CN=C(C(CS)N=C(C(CC(=O)O)N=C(CN)O)O)O)O)O)O)O)O)O)O)O)O DIGQNXIGRZPYDK-WKSCXVIASA-N 0.000 description 1
- FHVDTGUDJYJELY-UHFFFAOYSA-N 6-{[2-carboxy-4,5-dihydroxy-6-(phosphanyloxy)oxan-3-yl]oxy}-4,5-dihydroxy-3-phosphanyloxane-2-carboxylic acid Chemical compound O1C(C(O)=O)C(P)C(O)C(O)C1OC1C(C(O)=O)OC(OP)C(O)C1O FHVDTGUDJYJELY-UHFFFAOYSA-N 0.000 description 1
- WRDABNWSWOHGMS-UHFFFAOYSA-N AEBSF hydrochloride Chemical compound Cl.NCCC1=CC=C(S(F)(=O)=O)C=C1 WRDABNWSWOHGMS-UHFFFAOYSA-N 0.000 description 1
- 102000007469 Actins Human genes 0.000 description 1
- 108010085238 Actins Proteins 0.000 description 1
- 108700028369 Alleles Proteins 0.000 description 1
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 1
- 208000024827 Alzheimer disease Diseases 0.000 description 1
- 241000193830 Bacillus <bacterium> Species 0.000 description 1
- 101000798396 Bacillus licheniformis Phenylalanine racemase [ATP hydrolyzing] Proteins 0.000 description 1
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 1
- 206010006187 Breast cancer Diseases 0.000 description 1
- 208000026310 Breast neoplasm Diseases 0.000 description 1
- 241000700199 Cavia porcellus Species 0.000 description 1
- 102000011068 Cdc42 Human genes 0.000 description 1
- 108050001278 Cdc42 Proteins 0.000 description 1
- 241000282693 Cercopithecidae Species 0.000 description 1
- 108091092236 Chimeric RNA Proteins 0.000 description 1
- 241000282552 Chlorocebus aethiops Species 0.000 description 1
- 108091026890 Coding region Proteins 0.000 description 1
- 108091033380 Coding strand Proteins 0.000 description 1
- 108020004705 Codon Proteins 0.000 description 1
- MIKUYHXYGGJMLM-GIMIYPNGSA-N Crotonoside Natural products C1=NC2=C(N)NC(=O)N=C2N1[C@H]1O[C@@H](CO)[C@H](O)[C@@H]1O MIKUYHXYGGJMLM-GIMIYPNGSA-N 0.000 description 1
- 102100023033 Cyclic AMP-dependent transcription factor ATF-2 Human genes 0.000 description 1
- 208000026292 Cystic Kidney disease Diseases 0.000 description 1
- 241000701022 Cytomegalovirus Species 0.000 description 1
- FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 1
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 1
- FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 description 1
- NYHBQMYGNKIUIF-UHFFFAOYSA-N D-guanosine Natural products C1=2NC(N)=NC(=O)C=2N=CN1C1OC(CO)C(O)C1O NYHBQMYGNKIUIF-UHFFFAOYSA-N 0.000 description 1
- 241000702421 Dependoparvovirus Species 0.000 description 1
- 239000006144 Dulbecco’s modified Eagle's medium Substances 0.000 description 1
- 241000588722 Escherichia Species 0.000 description 1
- 241000206602 Eukaryota Species 0.000 description 1
- 206010064571 Gene mutation Diseases 0.000 description 1
- 108700028146 Genetic Enhancer Elements Proteins 0.000 description 1
- 108700039691 Genetic Promoter Regions Proteins 0.000 description 1
- 239000004471 Glycine Substances 0.000 description 1
- 102000001554 Hemoglobins Human genes 0.000 description 1
- 108010054147 Hemoglobins Proteins 0.000 description 1
- 102100027768 Histone-lysine N-methyltransferase 2D Human genes 0.000 description 1
- 241000282412 Homo Species 0.000 description 1
- 101000828732 Homo sapiens Cornifin-A Proteins 0.000 description 1
- 101000974934 Homo sapiens Cyclic AMP-dependent transcription factor ATF-2 Proteins 0.000 description 1
- 101000997829 Homo sapiens Glial cell line-derived neurotrophic factor Proteins 0.000 description 1
- 101001045848 Homo sapiens Histone-lysine N-methyltransferase 2B Proteins 0.000 description 1
- 101001008894 Homo sapiens Histone-lysine N-methyltransferase 2D Proteins 0.000 description 1
- 101001059454 Homo sapiens Serine/threonine-protein kinase MARK2 Proteins 0.000 description 1
- 240000005979 Hordeum vulgare Species 0.000 description 1
- 235000007340 Hordeum vulgare Nutrition 0.000 description 1
- 108091006905 Human Serum Albumin Proteins 0.000 description 1
- 102000008100 Human Serum Albumin Human genes 0.000 description 1
- 241000701044 Human gammaherpesvirus 4 Species 0.000 description 1
- 241000725303 Human immunodeficiency virus Species 0.000 description 1
- 208000023105 Huntington disease Diseases 0.000 description 1
- 206010020772 Hypertension Diseases 0.000 description 1
- 108010021625 Immunoglobulin Fragments Proteins 0.000 description 1
- 102000008394 Immunoglobulin Fragments Human genes 0.000 description 1
- 108091092195 Intron Proteins 0.000 description 1
- 241000235058 Komagataella pastoris Species 0.000 description 1
- 125000000393 L-methionino group Chemical group [H]OC(=O)[C@@]([H])(N([H])[*])C([H])([H])C(SC([H])([H])[H])([H])[H] 0.000 description 1
- COLNVLDHVKWLRT-QMMMGPOBSA-N L-phenylalanine Chemical compound OC(=O)[C@@H](N)CC1=CC=CC=C1 COLNVLDHVKWLRT-QMMMGPOBSA-N 0.000 description 1
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 1
- 108090001090 Lectins Proteins 0.000 description 1
- 102000004856 Lectins Human genes 0.000 description 1
- GDBQQVLCIARPGH-UHFFFAOYSA-N Leupeptin Natural products CC(C)CC(NC(C)=O)C(=O)NC(CC(C)C)C(=O)NC(C=O)CCCN=C(N)N GDBQQVLCIARPGH-UHFFFAOYSA-N 0.000 description 1
- 239000004472 Lysine Substances 0.000 description 1
- JLVVSXFLKOJNIY-UHFFFAOYSA-N Magnesium ion Chemical compound [Mg+2] JLVVSXFLKOJNIY-UHFFFAOYSA-N 0.000 description 1
- 229930195725 Mannitol Natural products 0.000 description 1
- 102000003792 Metallothionein Human genes 0.000 description 1
- 108090000157 Metallothionein Proteins 0.000 description 1
- 241000713333 Mouse mammary tumor virus Species 0.000 description 1
- 108060008487 Myosin Proteins 0.000 description 1
- 102000003505 Myosin Human genes 0.000 description 1
- 206010028980 Neoplasm Diseases 0.000 description 1
- 101100426589 Neurospora crassa (strain ATCC 24698 / 74-OR23-1A / CBS 708.71 / DSM 1257 / FGSC 987) trp-3 gene Proteins 0.000 description 1
- 241000283973 Oryctolagus cuniculus Species 0.000 description 1
- 238000010222 PCR analysis Methods 0.000 description 1
- 206010033645 Pancreatitis Diseases 0.000 description 1
- 208000018737 Parkinson disease Diseases 0.000 description 1
- 229940122907 Phosphatase inhibitor Drugs 0.000 description 1
- 241000235648 Pichia Species 0.000 description 1
- 239000004743 Polypropylene Substances 0.000 description 1
- 101710163352 Potassium voltage-gated channel subfamily H member 4 Proteins 0.000 description 1
- 102100025067 Potassium voltage-gated channel subfamily H member 4 Human genes 0.000 description 1
- 241000288906 Primates Species 0.000 description 1
- 229940124158 Protease/peptidase inhibitor Drugs 0.000 description 1
- 108010029485 Protein Isoforms Proteins 0.000 description 1
- 102000001708 Protein Isoforms Human genes 0.000 description 1
- 108090000315 Protein Kinase C Proteins 0.000 description 1
- 102000003923 Protein Kinase C Human genes 0.000 description 1
- 108010076504 Protein Sorting Signals Proteins 0.000 description 1
- 241000125945 Protoparvovirus Species 0.000 description 1
- 108091008109 Pseudogenes Proteins 0.000 description 1
- 102000057361 Pseudogenes Human genes 0.000 description 1
- 241000589516 Pseudomonas Species 0.000 description 1
- 241000700159 Rattus Species 0.000 description 1
- 108020004511 Recombinant DNA Proteins 0.000 description 1
- 206010038423 Renal cyst Diseases 0.000 description 1
- 241000219061 Rheum Species 0.000 description 1
- 241000714474 Rous sarcoma virus Species 0.000 description 1
- 241000235070 Saccharomyces Species 0.000 description 1
- 241000607142 Salmonella Species 0.000 description 1
- 241000710961 Semliki Forest virus Species 0.000 description 1
- 238000012300 Sequence Analysis Methods 0.000 description 1
- 102100028904 Serine/threonine-protein kinase MARK2 Human genes 0.000 description 1
- 241001147693 Staphylococcus sp. Species 0.000 description 1
- 229920002472 Starch Polymers 0.000 description 1
- 108091081024 Start codon Proteins 0.000 description 1
- 108010090804 Streptavidin Proteins 0.000 description 1
- 241000187747 Streptomyces Species 0.000 description 1
- 229930006000 Sucrose Natural products 0.000 description 1
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 1
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 1
- 108700026226 TATA Box Proteins 0.000 description 1
- 239000006180 TBST buffer Substances 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
- 108091023040 Transcription factor Proteins 0.000 description 1
- 102000040945 Transcription factor Human genes 0.000 description 1
- 208000030886 Traumatic Brain injury Diseases 0.000 description 1
- 239000007983 Tris buffer Substances 0.000 description 1
- 229920004890 Triton X-100 Polymers 0.000 description 1
- 239000013504 Triton X-100 Substances 0.000 description 1
- 241000700618 Vaccinia virus Species 0.000 description 1
- KZSNJWFQEVHDMF-UHFFFAOYSA-N Valine Chemical compound CC(C)C(N)C(O)=O KZSNJWFQEVHDMF-UHFFFAOYSA-N 0.000 description 1
- 241000251539 Vertebrata <Metazoa> Species 0.000 description 1
- 108020005202 Viral DNA Proteins 0.000 description 1
- ZKHQWZAMYRWXGA-KNYAHOBESA-N [[(2r,3s,4r,5r)-5-(6-aminopurin-9-yl)-3,4-dihydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl] dihydroxyphosphoryl hydrogen phosphate Chemical compound C1=NC=2C(N)=NC=NC=2N1[C@@H]1O[C@H](COP(O)(=O)OP(O)(=O)O[32P](O)(O)=O)[C@@H](O)[C@H]1O ZKHQWZAMYRWXGA-KNYAHOBESA-N 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 238000003916 acid precipitation Methods 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- 230000003213 activating effect Effects 0.000 description 1
- 230000001919 adrenal effect Effects 0.000 description 1
- 239000011543 agarose gel Substances 0.000 description 1
- 229940072056 alginate Drugs 0.000 description 1
- 235000010443 alginic acid Nutrition 0.000 description 1
- 229920000615 alginic acid Polymers 0.000 description 1
- 125000001931 aliphatic group Chemical group 0.000 description 1
- 150000001408 amides Chemical class 0.000 description 1
- 238000005571 anion exchange chromatography Methods 0.000 description 1
- 239000000427 antigen Substances 0.000 description 1
- 230000000890 antigenic effect Effects 0.000 description 1
- 108091007433 antigens Proteins 0.000 description 1
- 102000036639 antigens Human genes 0.000 description 1
- 238000003782 apoptosis assay Methods 0.000 description 1
- 238000013459 approach Methods 0.000 description 1
- 206010003246 arthritis Diseases 0.000 description 1
- 238000000429 assembly Methods 0.000 description 1
- 230000000712 assembly Effects 0.000 description 1
- 239000011324 bead Substances 0.000 description 1
- 230000001588 bifunctional effect Effects 0.000 description 1
- 230000033228 biological regulation Effects 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
- 230000003185 calcium uptake Effects 0.000 description 1
- 201000011510 cancer Diseases 0.000 description 1
- 238000010523 cascade reaction Methods 0.000 description 1
- 238000005277 cation exchange chromatography Methods 0.000 description 1
- 150000001768 cations Chemical class 0.000 description 1
- 230000010261 cell growth Effects 0.000 description 1
- 230000004663 cell proliferation Effects 0.000 description 1
- 230000023549 cell-cell signaling Effects 0.000 description 1
- 230000009920 chelation Effects 0.000 description 1
- 239000003638 chemical reducing agent Substances 0.000 description 1
- 238000002512 chemotherapy Methods 0.000 description 1
- 239000012539 chromatography resin Substances 0.000 description 1
- 230000004186 co-expression Effects 0.000 description 1
- 229940110456 cocoa butter Drugs 0.000 description 1
- 235000019868 cocoa butter Nutrition 0.000 description 1
- 238000001246 colloidal dispersion Methods 0.000 description 1
- 230000009918 complex formation Effects 0.000 description 1
- 238000010276 construction Methods 0.000 description 1
- 230000008878 coupling Effects 0.000 description 1
- 238000010168 coupling process Methods 0.000 description 1
- 238000005859 coupling reaction Methods 0.000 description 1
- 229960003624 creatine Drugs 0.000 description 1
- 239000006046 creatine Substances 0.000 description 1
- 125000004122 cyclic group Chemical group 0.000 description 1
- 229940104302 cytosine Drugs 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 230000007850 degeneration Effects 0.000 description 1
- 230000000368 destabilizing effect Effects 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 230000018109 developmental process Effects 0.000 description 1
- 229960000633 dextran sulfate Drugs 0.000 description 1
- 206010012601 diabetes mellitus Diseases 0.000 description 1
- 238000003745 diagnosis Methods 0.000 description 1
- 238000002405 diagnostic procedure Methods 0.000 description 1
- ZBCBWPMODOFKDW-UHFFFAOYSA-N diethanolamine Chemical compound OCCNCCO ZBCBWPMODOFKDW-UHFFFAOYSA-N 0.000 description 1
- 230000004069 differentiation Effects 0.000 description 1
- 229940079919 digestives enzyme preparation Drugs 0.000 description 1
- LOKCTEFSRHRXRJ-UHFFFAOYSA-I dipotassium trisodium dihydrogen phosphate hydrogen phosphate dichloride Chemical compound P(=O)(O)(O)[O-].[K+].P(=O)(O)([O-])[O-].[Na+].[Na+].[Cl-].[K+].[Cl-].[Na+] LOKCTEFSRHRXRJ-UHFFFAOYSA-I 0.000 description 1
- BNIILDVGGAEEIG-UHFFFAOYSA-L disodium hydrogen phosphate Chemical compound [Na+].[Na+].OP([O-])([O-])=O BNIILDVGGAEEIG-UHFFFAOYSA-L 0.000 description 1
- 229910000397 disodium phosphate Inorganic materials 0.000 description 1
- 235000019800 disodium phosphate Nutrition 0.000 description 1
- KAKKHKRHCKCAGH-UHFFFAOYSA-L disodium;(4-nitrophenyl) phosphate;hexahydrate Chemical compound O.O.O.O.O.O.[Na+].[Na+].[O-][N+](=O)C1=CC=C(OP([O-])([O-])=O)C=C1 KAKKHKRHCKCAGH-UHFFFAOYSA-L 0.000 description 1
- 238000009826 distribution Methods 0.000 description 1
- 231100000673 dose–response relationship Toxicity 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 238000007876 drug discovery Methods 0.000 description 1
- 230000002526 effect on cardiovascular system Effects 0.000 description 1
- 238000004520 electroporation Methods 0.000 description 1
- 210000002889 endothelial cell Anatomy 0.000 description 1
- 230000003511 endothelial effect Effects 0.000 description 1
- 239000003623 enhancer Substances 0.000 description 1
- HKSZLNNOFSGOKW-UHFFFAOYSA-N ent-staurosporine Natural products C12=C3N4C5=CC=CC=C5C3=C3CNC(=O)C3=C2C2=CC=CC=C2N1C1CC(NC)C(OC)C4(C)O1 HKSZLNNOFSGOKW-UHFFFAOYSA-N 0.000 description 1
- 238000001952 enzyme assay Methods 0.000 description 1
- 238000011156 evaluation Methods 0.000 description 1
- 230000001747 exhibiting effect Effects 0.000 description 1
- 238000000855 fermentation Methods 0.000 description 1
- 230000004151 fermentation Effects 0.000 description 1
- 239000012894 fetal calf serum Substances 0.000 description 1
- 210000002950 fibroblast Anatomy 0.000 description 1
- 230000037406 food intake Effects 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 230000002538 fungal effect Effects 0.000 description 1
- 238000001415 gene therapy Methods 0.000 description 1
- 230000004077 genetic alteration Effects 0.000 description 1
- 231100000118 genetic alteration Toxicity 0.000 description 1
- 230000002068 genetic effect Effects 0.000 description 1
- 210000001102 germinal center b cell Anatomy 0.000 description 1
- 208000005017 glioblastoma Diseases 0.000 description 1
- 235000011187 glycerol Nutrition 0.000 description 1
- 230000013595 glycosylation Effects 0.000 description 1
- 238000006206 glycosylation reaction Methods 0.000 description 1
- 125000003630 glycyl group Chemical group [H]N([H])C([H])([H])C(*)=O 0.000 description 1
- 229940029575 guanosine Drugs 0.000 description 1
- 125000000487 histidyl group Chemical group [H]N([H])C(C(=O)O*)C([H])([H])C1=C([H])N([H])C([H])=N1 0.000 description 1
- 230000006801 homologous recombination Effects 0.000 description 1
- 238000002744 homologous recombination Methods 0.000 description 1
- 229910052739 hydrogen Inorganic materials 0.000 description 1
- 239000001257 hydrogen Substances 0.000 description 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 1
- 230000003345 hyperglycaemic effect Effects 0.000 description 1
- 230000002163 immunogen Effects 0.000 description 1
- 239000012133 immunoprecipitate Substances 0.000 description 1
- 238000011065 in-situ storage Methods 0.000 description 1
- 230000002757 inflammatory effect Effects 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 238000001361 intraarterial administration Methods 0.000 description 1
- 230000003834 intracellular effect Effects 0.000 description 1
- 238000007914 intraventricular administration Methods 0.000 description 1
- 238000001038 ionspray mass spectrometry Methods 0.000 description 1
- 208000028867 ischemia Diseases 0.000 description 1
- AGPKZVBTJJNPAG-UHFFFAOYSA-N isoleucine Chemical group CCC(C)C(N)C(O)=O AGPKZVBTJJNPAG-UHFFFAOYSA-N 0.000 description 1
- 229960000310 isoleucine Drugs 0.000 description 1
- 125000000741 isoleucyl group Chemical group [H]N([H])C(C(C([H])([H])[H])C([H])([H])C([H])([H])[H])C(=O)O* 0.000 description 1
- 210000003734 kidney Anatomy 0.000 description 1
- 210000003292 kidney cell Anatomy 0.000 description 1
- 229940043355 kinase inhibitor Drugs 0.000 description 1
- 101150066555 lacZ gene Proteins 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 229960001375 lactose Drugs 0.000 description 1
- 238000011031 large-scale manufacturing process Methods 0.000 description 1
- 239000002523 lectin Substances 0.000 description 1
- 125000001909 leucine group Chemical group [H]N(*)C(C(*)=O)C([H])([H])C(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- GDBQQVLCIARPGH-ULQDDVLXSA-N leupeptin Chemical compound CC(C)C[C@H](NC(C)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@H](C=O)CCCN=C(N)N GDBQQVLCIARPGH-ULQDDVLXSA-N 0.000 description 1
- 108010052968 leupeptin Proteins 0.000 description 1
- 150000002632 lipids Chemical class 0.000 description 1
- 210000004185 liver Anatomy 0.000 description 1
- 210000001165 lymph node Anatomy 0.000 description 1
- 210000003563 lymphoid tissue Anatomy 0.000 description 1
- 108010026228 mRNA guanylyltransferase Proteins 0.000 description 1
- 239000011777 magnesium Substances 0.000 description 1
- 229910001425 magnesium ion Inorganic materials 0.000 description 1
- 235000019359 magnesium stearate Nutrition 0.000 description 1
- 229940057948 magnesium stearate Drugs 0.000 description 1
- 239000000594 mannitol Substances 0.000 description 1
- 235000010355 mannitol Nutrition 0.000 description 1
- 229960001855 mannitol Drugs 0.000 description 1
- 238000002844 melting Methods 0.000 description 1
- 230000008018 melting Effects 0.000 description 1
- 229910021645 metal ion Inorganic materials 0.000 description 1
- 229940095102 methyl benzoate Drugs 0.000 description 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
- YACKEPLHDIMKIO-UHFFFAOYSA-N methylphosphonic acid Chemical compound CP(O)(O)=O YACKEPLHDIMKIO-UHFFFAOYSA-N 0.000 description 1
- 239000000693 micelle Substances 0.000 description 1
- 238000002493 microarray Methods 0.000 description 1
- 238000000520 microinjection Methods 0.000 description 1
- 239000002480 mineral oil Substances 0.000 description 1
- 235000010446 mineral oil Nutrition 0.000 description 1
- 201000006417 multiple sclerosis Diseases 0.000 description 1
- 210000003205 muscle Anatomy 0.000 description 1
- UPSFMJHZUCSEHU-JYGUBCOQSA-N n-[(2s,3r,4r,5s,6r)-2-[(2r,3s,4r,5r,6s)-5-acetamido-4-hydroxy-2-(hydroxymethyl)-6-(4-methyl-2-oxochromen-7-yl)oxyoxan-3-yl]oxy-4,5-dihydroxy-6-(hydroxymethyl)oxan-3-yl]acetamide Chemical compound CC(=O)N[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@H]1O[C@H]1[C@H](O)[C@@H](NC(C)=O)[C@H](OC=2C=C3OC(=O)C=C(C)C3=CC=2)O[C@@H]1CO UPSFMJHZUCSEHU-JYGUBCOQSA-N 0.000 description 1
- 230000003988 neural development Effects 0.000 description 1
- 208000004296 neuralgia Diseases 0.000 description 1
- 230000004770 neurodegeneration Effects 0.000 description 1
- 230000000626 neurodegenerative effect Effects 0.000 description 1
- 210000002569 neuron Anatomy 0.000 description 1
- 208000021722 neuropathic pain Diseases 0.000 description 1
- 229910052759 nickel Inorganic materials 0.000 description 1
- 239000002687 nonaqueous vehicle Substances 0.000 description 1
- 231100000252 nontoxic Toxicity 0.000 description 1
- 230000003000 nontoxic effect Effects 0.000 description 1
- 239000000346 nonvolatile oil Substances 0.000 description 1
- 238000005457 optimization Methods 0.000 description 1
- 150000002894 organic compounds Chemical class 0.000 description 1
- 230000002018 overexpression Effects 0.000 description 1
- 230000007170 pathology Effects 0.000 description 1
- NRNCYVBFPDDJNE-UHFFFAOYSA-N pemoline Chemical compound O1C(N)=NC(=O)C1C1=CC=CC=C1 NRNCYVBFPDDJNE-UHFFFAOYSA-N 0.000 description 1
- 108010091212 pepstatin Proteins 0.000 description 1
- FAXGPCHRFPCXOO-LXTPJMTPSA-N pepstatin A Chemical compound OC(=O)C[C@H](O)[C@H](CC(C)C)NC(=O)[C@H](C)NC(=O)C[C@H](O)[C@H](CC(C)C)NC(=O)[C@H](C(C)C)NC(=O)[C@H](C(C)C)NC(=O)CC(C)C FAXGPCHRFPCXOO-LXTPJMTPSA-N 0.000 description 1
- 239000000137 peptide hydrolase inhibitor Substances 0.000 description 1
- 239000000816 peptidomimetic Substances 0.000 description 1
- 239000002953 phosphate buffered saline Substances 0.000 description 1
- 230000000865 phosphorylative effect Effects 0.000 description 1
- USRGIUJOYOXOQJ-GBXIJSLDSA-N phosphothreonine Chemical compound OP(=O)(O)O[C@H](C)[C@H](N)C(O)=O USRGIUJOYOXOQJ-GBXIJSLDSA-N 0.000 description 1
- 239000003757 phosphotransferase inhibitor Substances 0.000 description 1
- 230000000704 physical effect Effects 0.000 description 1
- 238000000053 physical method Methods 0.000 description 1
- 230000004962 physiological condition Effects 0.000 description 1
- 230000035790 physiological processes and functions Effects 0.000 description 1
- 230000008488 polyadenylation Effects 0.000 description 1
- 229920002704 polyhistidine Polymers 0.000 description 1
- 229930001119 polyketide Natural products 0.000 description 1
- 125000000830 polyketide group Chemical group 0.000 description 1
- 229930001118 polyketide hybrid Natural products 0.000 description 1
- 125000003308 polyketide hybrid group Chemical group 0.000 description 1
- 229920000642 polymer Polymers 0.000 description 1
- 229920001155 polypropylene Polymers 0.000 description 1
- 239000013641 positive control Substances 0.000 description 1
- 230000004481 post-translational protein modification Effects 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- 230000005522 programmed cell death Effects 0.000 description 1
- 230000009465 prokaryotic expression Effects 0.000 description 1
- 230000035755 proliferation Effects 0.000 description 1
- 230000001737 promoting effect Effects 0.000 description 1
- 230000000069 prophylactic effect Effects 0.000 description 1
- QELSKZZBTMNZEB-UHFFFAOYSA-N propylparaben Chemical compound CCCOC(=O)C1=CC=C(O)C=C1 QELSKZZBTMNZEB-UHFFFAOYSA-N 0.000 description 1
- 229960003415 propylparaben Drugs 0.000 description 1
- 210000002307 prostate Anatomy 0.000 description 1
- 210000001938 protoplast Anatomy 0.000 description 1
- 238000011002 quantification Methods 0.000 description 1
- 239000011541 reaction mixture Substances 0.000 description 1
- 101150079601 recA gene Proteins 0.000 description 1
- 108020003175 receptors Proteins 0.000 description 1
- 102000005962 receptors Human genes 0.000 description 1
- 230000006798 recombination Effects 0.000 description 1
- 238000005215 recombination Methods 0.000 description 1
- 230000003362 replicative effect Effects 0.000 description 1
- 238000004007 reversed phase HPLC Methods 0.000 description 1
- 206010039073 rheumatoid arthritis Diseases 0.000 description 1
- 238000005204 segregation Methods 0.000 description 1
- 230000035945 sensitivity Effects 0.000 description 1
- 210000002966 serum Anatomy 0.000 description 1
- 230000001568 sexual effect Effects 0.000 description 1
- 230000035939 shock Effects 0.000 description 1
- 239000013605 shuttle vector Substances 0.000 description 1
- 238000001542 size-exclusion chromatography Methods 0.000 description 1
- 239000002689 soil Substances 0.000 description 1
- 239000000600 sorbitol Substances 0.000 description 1
- 229960002920 sorbitol Drugs 0.000 description 1
- 238000010561 standard procedure Methods 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 229940032147 starch Drugs 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- HKSZLNNOFSGOKW-FYTWVXJKSA-N staurosporine Chemical compound C12=C3N4C5=CC=CC=C5C3=C3CNC(=O)C3=C2C2=CC=CC=C2N1[C@H]1C[C@@H](NC)[C@@H](OC)[C@]4(C)O1 HKSZLNNOFSGOKW-FYTWVXJKSA-N 0.000 description 1
- CGPUWJWCVCFERF-UHFFFAOYSA-N staurosporine Natural products C12=C3N4C5=CC=CC=C5C3=C3CNC(=O)C3=C2C2=CC=CC=C2N1C1CC(NC)C(OC)C4(OC)O1 CGPUWJWCVCFERF-UHFFFAOYSA-N 0.000 description 1
- 230000004936 stimulating effect Effects 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- 229960004793 sucrose Drugs 0.000 description 1
- 239000011593 sulfur Substances 0.000 description 1
- 229910052717 sulfur Inorganic materials 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 230000001629 suppression Effects 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 235000012222 talc Nutrition 0.000 description 1
- 229940033134 talc Drugs 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- 229960001603 tamoxifen Drugs 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 125000003396 thiol group Chemical group [H]S* 0.000 description 1
- RYYWUUFWQRZTIU-UHFFFAOYSA-K thiophosphate Chemical compound [O-]P([O-])([O-])=S RYYWUUFWQRZTIU-UHFFFAOYSA-K 0.000 description 1
- 230000005030 transcription termination Effects 0.000 description 1
- 238000013519 translation Methods 0.000 description 1
- 230000009529 traumatic brain injury Effects 0.000 description 1
- 238000011269 treatment regimen Methods 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
- YNJBWRMUSHSURL-UHFFFAOYSA-N trichloroacetic acid Chemical compound OC(=O)C(Cl)(Cl)Cl YNJBWRMUSHSURL-UHFFFAOYSA-N 0.000 description 1
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 1
- OUYCCCASQSFEME-UHFFFAOYSA-N tyrosine Natural products OC(=O)C(N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-UHFFFAOYSA-N 0.000 description 1
- 238000000108 ultra-filtration Methods 0.000 description 1
- 241000701161 unidentified adenovirus Species 0.000 description 1
- 241001529453 unidentified herpesvirus Species 0.000 description 1
- 241001430294 unidentified retrovirus Species 0.000 description 1
- 238000011144 upstream manufacturing Methods 0.000 description 1
- 238000012800 visualization Methods 0.000 description 1
- 238000001086 yeast two-hybrid system Methods 0.000 description 1
- 229910000166 zirconium phosphate Inorganic materials 0.000 description 1
Images
Classifications
-
- 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
- C12N9/00—Enzymes; Proenzymes; Compositions thereof; Processes for preparing, activating, inhibiting, separating or purifying enzymes
- C12N9/10—Transferases (2.)
- C12N9/12—Transferases (2.) transferring phosphorus containing groups, e.g. kinases (2.7)
- C12N9/1205—Phosphotransferases with an alcohol group as acceptor (2.7.1), e.g. protein kinases
-
- 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
- A61P25/18—Antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Zoology (AREA)
- Molecular Biology (AREA)
- Wood Science & Technology (AREA)
- Genetics & Genomics (AREA)
- Pharmacology & Pharmacy (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Biomedical Technology (AREA)
- General Chemical & Material Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Engineering & Computer Science (AREA)
- Biochemistry (AREA)
- Biotechnology (AREA)
- Microbiology (AREA)
- Psychiatry (AREA)
- Neurosurgery (AREA)
- Neurology (AREA)
- Pain & Pain Management (AREA)
- Rheumatology (AREA)
- Micro-Organisms Or Cultivation Processes Thereof (AREA)
- Peptides Or Proteins (AREA)
- Enzymes And Modification Thereof (AREA)
- Measuring Or Testing Involving Enzymes Or Micro-Organisms (AREA)
- Investigating Or Analysing Biological Materials (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US29338101P | 2001-05-24 | 2001-05-24 | |
| PCT/US2002/016387 WO2002095017A1 (en) | 2001-05-24 | 2002-05-23 | Novel mixed lineage kinase (7) (mlk7) polypeptide, polynucleotides encoding the same, and methods of use thereof |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JP2004537291A true JP2004537291A (ja) | 2004-12-16 |
| JP2004537291A5 JP2004537291A5 (enExample) | 2005-12-22 |
Family
ID=23128847
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2002592480A Withdrawn JP2004537291A (ja) | 2001-05-24 | 2002-05-23 | 新規混合系統キナーゼ(7)(mlk7)ポリペプチド、それをコードするポリヌクレオチド、およびそれらの使用方法 |
Country Status (6)
| Country | Link |
|---|---|
| US (1) | US20040185460A1 (enExample) |
| EP (1) | EP1402009A4 (enExample) |
| JP (1) | JP2004537291A (enExample) |
| CA (1) | CA2448102A1 (enExample) |
| MX (1) | MXPA03010706A (enExample) |
| WO (1) | WO2002095017A1 (enExample) |
Families Citing this family (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2005103240A1 (en) * | 2004-04-24 | 2005-11-03 | Bayer Healthcare Ag | Diagnostics and therapeutics for diseases associated with casein kinase 1, delta, isoform 1 (csnk1d iso 1) |
| US9061009B2 (en) * | 2007-06-08 | 2015-06-23 | University Of Massachusetts | Mixed lineage kinases and metabolic disorders |
| EP2602993A1 (en) * | 2011-12-08 | 2013-06-12 | Research In Motion Limited | Apparatus and associated method for face tracking in video conference and video chat communications |
Family Cites Families (11)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4399216A (en) * | 1980-02-25 | 1983-08-16 | The Trustees Of Columbia University | Processes for inserting DNA into eucaryotic cells and for producing proteinaceous materials |
| US4879236A (en) * | 1984-05-16 | 1989-11-07 | The Texas A&M University System | Method for producing a recombinant baculovirus expression vector |
| US4683202A (en) * | 1985-03-28 | 1987-07-28 | Cetus Corporation | Process for amplifying nucleic acid sequences |
| US4683195A (en) * | 1986-01-30 | 1987-07-28 | Cetus Corporation | Process for amplifying, detecting, and/or-cloning nucleic acid sequences |
| US6514745B1 (en) * | 1993-07-19 | 2003-02-04 | The Regents Of The University Of California | Oncoprotein protein kinase |
| US5534426A (en) * | 1993-07-19 | 1996-07-09 | The Regents Of The University Of California | Oncoprotein protein kinase |
| US5554523A (en) * | 1994-03-01 | 1996-09-10 | Children's Hospital Of Philadelphia | Nucleic acid sequences encoding human leucine-zipper protein-kinase |
| US5817479A (en) * | 1996-08-07 | 1998-10-06 | Incyte Pharmaceuticals, Inc. | Human kinase homologs |
| AU2001234544A1 (en) * | 2000-01-25 | 2001-08-07 | Sugen, Inc. | Novel human protein kinases and protein kinase-like enzymes |
| AU2002303258A1 (en) * | 2001-04-06 | 2002-10-28 | Incyte Genomics, Inc. | Kinases and phosphatases |
| AU2003225535A1 (en) * | 2002-01-31 | 2003-09-02 | Millennium Pharmaceuticals, Inc. | Methods and compositions for treating cancer |
-
2002
- 2002-05-23 CA CA002448102A patent/CA2448102A1/en not_active Abandoned
- 2002-05-23 WO PCT/US2002/016387 patent/WO2002095017A1/en not_active Ceased
- 2002-05-23 JP JP2002592480A patent/JP2004537291A/ja not_active Withdrawn
- 2002-05-23 MX MXPA03010706A patent/MXPA03010706A/es unknown
- 2002-05-23 US US10/478,068 patent/US20040185460A1/en not_active Abandoned
- 2002-05-23 EP EP02731920A patent/EP1402009A4/en not_active Withdrawn
Also Published As
| Publication number | Publication date |
|---|---|
| MXPA03010706A (es) | 2004-05-27 |
| WO2002095017A1 (en) | 2002-11-28 |
| EP1402009A4 (en) | 2005-02-02 |
| EP1402009A1 (en) | 2004-03-31 |
| CA2448102A1 (en) | 2002-11-28 |
| US20040185460A1 (en) | 2004-09-23 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CA2209426C (en) | Human pak65 | |
| De La Mota-Peynado et al. | Identification of the atypical MAPK Erk3 as a novel substrate for p21-activated kinase (Pak) activity | |
| EP2534258B1 (en) | Dual activity kinase domains and uses thereof | |
| US6969596B2 (en) | Polynucleotide encoding a human receptor tyrosine kinase | |
| US20030143656A1 (en) | Protein kinase regulation | |
| AU9223198A (en) | Mammalian chk1 effector cell-cycle checkpoint protein kinase materials and methods | |
| US6048706A (en) | Human PAK65 | |
| JP2004537291A (ja) | 新規混合系統キナーゼ(7)(mlk7)ポリペプチド、それをコードするポリヌクレオチド、およびそれらの使用方法 | |
| WO2003040409A1 (en) | Novel germinal center kinase proteins, compositions, and methods of use | |
| JP2003519472A (ja) | P21活性化キナーゼ(pak)タンパク質ファミリーの一つであるpak5、これに関する核酸および方法 | |
| JP2001157590A (ja) | 紫外線照射仲介皮膚損傷に関連する遺伝子およびポリヌクレオチド並びにそれらの使用 | |
| US20040241739A1 (en) | Genes and polynucleotides associated with ultraviolet radiation-mediated skin damage and uses thereof | |
| JPWO1999001559A1 (ja) | 新規なmapkキナーゼ | |
| AU2001262296B2 (en) | Neuronal serine-threonine protein kinase | |
| US20040019918A1 (en) | Human MEKK2 protein and nucleic acid molecules and uses therefor | |
| US20050120396A1 (en) | Human MEKK1 protein and nucleic acid molecules and uses therefor | |
| US20030064496A1 (en) | Human MEKK2 protein and nucleic acid molecules and uses therefor | |
| US20060110769A1 (en) | Regulation of novel human prolyl 4-hydroxylases | |
| Watkins | Regulation of PP2Ac stability–discovery of a novel α4 monoubiquitination-dependent mechanism that is altered in Alzheimer’s disease | |
| JP2003144168A (ja) | 核外移行機能又は核−細胞質間移行機能を有する細胞周期関連タンパク質 | |
| CA2286073A1 (en) | Screening for compounds that inhibit phosphorylation of i?b.alpha. | |
| De La Mota-Peynado et al. | Identification of the atypical extracellular regulated kinase 3 (Erk3) as a novel substrate for p21-activated kinase (Pak) activity | |
| JP2005245403A (ja) | アポトーシス調節活性を測定する方法、及びアポトーシス調節活性を有する化合物のスクリーニング方法 | |
| US20130040894A1 (en) | Inhibition or activation of serine/threonine ulk3 kinase activity | |
| WO2004087903A2 (en) | Novel proteins homologous to kinase suppressor of ras |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20050510 |
|
| A621 | Written request for application examination |
Free format text: JAPANESE INTERMEDIATE CODE: A621 Effective date: 20050510 |
|
| A761 | Written withdrawal of application |
Free format text: JAPANESE INTERMEDIATE CODE: A761 Effective date: 20060629 |
|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A821 Effective date: 20060629 |