JP2007532135A - 高血糖症および関連障害の処置のための、ヒトｇタンパク質共役レセプターおよびそのモジュレーター - Google Patents
高血糖症および関連障害の処置のための、ヒトｇタンパク質共役レセプターおよびそのモジュレーター Download PDFInfo
- Publication number
- JP2007532135A JP2007532135A JP2007508478A JP2007508478A JP2007532135A JP 2007532135 A JP2007532135 A JP 2007532135A JP 2007508478 A JP2007508478 A JP 2007508478A JP 2007508478 A JP2007508478 A JP 2007508478A JP 2007532135 A JP2007532135 A JP 2007532135A
- Authority
- JP
- Japan
- Prior art keywords
- modulator
- amino acid
- acid sequence
- compound
- certain embodiments
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
- 102000005962 receptors Human genes 0.000 title claims description 242
- 108020003175 receptors Proteins 0.000 title claims description 242
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 title claims description 62
- 201000001421 hyperglycemia Diseases 0.000 title description 6
- 101000887490 Homo sapiens Guanine nucleotide-binding protein G(z) subunit alpha Proteins 0.000 title 1
- 102000052301 human GNAZ Human genes 0.000 title 1
- 238000000034 method Methods 0.000 claims abstract description 432
- 102000003688 G-Protein-Coupled Receptors Human genes 0.000 claims abstract description 367
- 108090000045 G-Protein-Coupled Receptors Proteins 0.000 claims abstract description 367
- 239000000556 agonist Substances 0.000 claims abstract description 288
- 150000001875 compounds Chemical class 0.000 claims abstract description 234
- 208000030159 metabolic disease Diseases 0.000 claims abstract description 185
- 241000282414 Homo sapiens Species 0.000 claims abstract description 167
- 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 claims abstract description 131
- 239000008103 glucose Substances 0.000 claims abstract description 131
- 210000004369 blood Anatomy 0.000 claims abstract description 124
- 239000008280 blood Substances 0.000 claims abstract description 124
- 208000001072 type 2 diabetes mellitus Diseases 0.000 claims abstract description 89
- 206010020772 Hypertension Diseases 0.000 claims abstract description 82
- 206010012601 diabetes mellitus Diseases 0.000 claims abstract description 80
- 208000019622 heart disease Diseases 0.000 claims abstract description 66
- 206010022489 Insulin Resistance Diseases 0.000 claims abstract description 57
- 208000018262 Peripheral vascular disease Diseases 0.000 claims abstract description 51
- 201000001320 Atherosclerosis Diseases 0.000 claims abstract description 50
- 208000002705 Glucose Intolerance Diseases 0.000 claims abstract description 50
- 201000009104 prediabetes syndrome Diseases 0.000 claims abstract description 50
- 239000003814 drug Substances 0.000 claims abstract description 29
- 238000003556 assay Methods 0.000 claims description 519
- 125000003275 alpha amino acid group Chemical group 0.000 claims description 361
- 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 190
- 241000124008 Mammalia Species 0.000 claims description 169
- 102100025353 G-protein coupled bile acid receptor 1 Human genes 0.000 claims description 138
- 101000857733 Homo sapiens G-protein coupled bile acid receptor 1 Proteins 0.000 claims description 138
- 210000004027 cell Anatomy 0.000 claims description 122
- 235000001014 amino acid Nutrition 0.000 claims description 92
- 239000008194 pharmaceutical composition Substances 0.000 claims description 76
- 239000000203 mixture Substances 0.000 claims description 71
- 230000008569 process Effects 0.000 claims description 69
- 201000001119 neuropathy Diseases 0.000 claims description 65
- 230000007823 neuropathy Effects 0.000 claims description 65
- 208000033808 peripheral neuropathy Diseases 0.000 claims description 65
- 230000004190 glucose uptake Effects 0.000 claims description 59
- 201000010099 disease Diseases 0.000 claims description 57
- 102000040430 polynucleotide Human genes 0.000 claims description 57
- 108091033319 polynucleotide Proteins 0.000 claims description 57
- 239000002157 polynucleotide Substances 0.000 claims description 57
- 150000007523 nucleic acids Chemical group 0.000 claims description 54
- 229940125782 compound 2 Drugs 0.000 claims description 53
- 229940126214 compound 3 Drugs 0.000 claims description 53
- 241001465754 Metazoa Species 0.000 claims description 52
- 150000001413 amino acids Chemical class 0.000 claims description 51
- 208000017442 Retinal disease Diseases 0.000 claims description 49
- 206010038923 Retinopathy Diseases 0.000 claims description 49
- 206010010904 Convulsion Diseases 0.000 claims description 48
- 206010060378 Hyperinsulinaemia Diseases 0.000 claims description 48
- 230000003143 atherosclerotic effect Effects 0.000 claims description 48
- 230000003451 hyperinsulinaemic effect Effects 0.000 claims description 48
- 201000008980 hyperinsulinism Diseases 0.000 claims description 48
- 208000011580 syndromic disease Diseases 0.000 claims description 48
- 230000002265 prevention Effects 0.000 claims description 47
- 239000003446 ligand Substances 0.000 claims description 46
- 108091006027 G proteins Proteins 0.000 claims description 44
- 102000030782 GTP binding Human genes 0.000 claims description 44
- 108091000058 GTP-Binding Proteins 0.000 claims description 44
- 230000027455 binding Effects 0.000 claims description 44
- 108091028043 Nucleic acid sequence Proteins 0.000 claims description 37
- 229940125904 compound 1 Drugs 0.000 claims description 34
- 208000017169 kidney disease Diseases 0.000 claims description 33
- 210000001789 adipocyte Anatomy 0.000 claims description 31
- 210000002363 skeletal muscle cell Anatomy 0.000 claims description 31
- 108020004414 DNA Proteins 0.000 claims description 29
- 239000005557 antagonist Substances 0.000 claims description 29
- 230000000694 effects Effects 0.000 claims description 29
- 239000004031 partial agonist Substances 0.000 claims description 28
- IVOMOUWHDPKRLL-KQYNXXCUSA-N Cyclic adenosine monophosphate Chemical compound C([C@H]1O2)OP(O)(=O)O[C@H]1[C@@H](O)[C@@H]2N1C(N=CN=C2N)=C2N=C1 IVOMOUWHDPKRLL-KQYNXXCUSA-N 0.000 claims description 24
- QNAYBMKLOCPYGJ-REOHCLBHSA-N L-alanine Chemical compound C[C@H](N)C(O)=O QNAYBMKLOCPYGJ-REOHCLBHSA-N 0.000 claims description 24
- 239000004472 Lysine Substances 0.000 claims description 24
- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 claims description 24
- IVOMOUWHDPKRLL-UHFFFAOYSA-N UNPD107823 Natural products O1C2COP(O)(=O)OC2C(O)C1N1C(N=CN=C2N)=C2N=C1 IVOMOUWHDPKRLL-UHFFFAOYSA-N 0.000 claims description 24
- 235000004279 alanine Nutrition 0.000 claims description 24
- 229940095074 cyclic amp Drugs 0.000 claims description 24
- 125000003588 lysine group Chemical group [H]N([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])(N([H])[H])C(*)=O 0.000 claims description 24
- 210000003574 melanophore Anatomy 0.000 claims description 23
- 239000012528 membrane Substances 0.000 claims description 23
- 238000002360 preparation method Methods 0.000 claims description 23
- 125000001360 methionine group Chemical group N[C@@H](CCSC)C(=O)* 0.000 claims description 22
- 239000013604 expression vector Substances 0.000 claims description 18
- 238000002560 therapeutic procedure Methods 0.000 claims description 16
- 230000033228 biological regulation Effects 0.000 claims description 12
- XOFLBQFBSOEHOG-UUOKFMHZSA-N γS-GTP Chemical compound C1=2NC(N)=NC(=O)C=2N=CN1[C@@H]1O[C@H](COP(O)(=O)OP(O)(=O)OP(O)(O)=S)[C@@H](O)[C@H]1O XOFLBQFBSOEHOG-UUOKFMHZSA-N 0.000 claims description 12
- 230000000295 complement effect Effects 0.000 claims description 11
- 238000005259 measurement Methods 0.000 claims description 11
- 230000009467 reduction Effects 0.000 claims description 11
- 238000012360 testing method Methods 0.000 claims description 10
- 125000000217 alkyl group Chemical group 0.000 claims description 9
- 150000001982 diacylglycerols Chemical class 0.000 claims description 8
- 230000007423 decrease Effects 0.000 claims description 7
- ZOOGRGPOEVQQDX-UUOKFMHZSA-N 3',5'-cyclic GMP Chemical compound C([C@H]1O2)OP(O)(=O)O[C@H]1[C@@H](O)[C@@H]2N1C(N=C(NC2=O)N)=C2N=C1 ZOOGRGPOEVQQDX-UUOKFMHZSA-N 0.000 claims description 6
- 230000008859 change Effects 0.000 claims description 6
- ZOOGRGPOEVQQDX-UHFFFAOYSA-N cyclic GMP Natural products O1C2COP(O)(=O)OC2C(O)C1N1C=NC2=C1NC(N)=NC2=O ZOOGRGPOEVQQDX-UHFFFAOYSA-N 0.000 claims description 6
- 230000005764 inhibitory process Effects 0.000 claims description 6
- 238000002156 mixing Methods 0.000 claims description 6
- -1 2-methyl-4,5,6,7-tetrahydro-2H-indazol-3-yl group Chemical group 0.000 claims description 4
- 229910052736 halogen Inorganic materials 0.000 claims description 3
- 150000002367 halogens Chemical class 0.000 claims description 3
- 150000003839 salts Chemical class 0.000 claims description 3
- 229910052799 carbon Inorganic materials 0.000 claims description 2
- 229910052739 hydrogen Inorganic materials 0.000 claims description 2
- 230000003993 interaction Effects 0.000 claims description 2
- 238000004519 manufacturing process Methods 0.000 claims description 2
- 229910052757 nitrogen Inorganic materials 0.000 claims description 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 2
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 2
- 239000003937 drug carrier Substances 0.000 claims 3
- 230000037041 intracellular level Effects 0.000 claims 2
- 230000002194 synthesizing effect Effects 0.000 claims 1
- 235000011178 triphosphate Nutrition 0.000 claims 1
- 239000001226 triphosphate Substances 0.000 claims 1
- UNXRWKVEANCORM-UHFFFAOYSA-N triphosphoric acid Chemical compound OP(O)(=O)OP(O)(=O)OP(O)(O)=O UNXRWKVEANCORM-UHFFFAOYSA-N 0.000 claims 1
- 229940124597 therapeutic agent Drugs 0.000 abstract description 6
- 208000006011 Stroke Diseases 0.000 abstract description 3
- 108090000765 processed proteins & peptides Proteins 0.000 description 113
- 102000004196 processed proteins & peptides Human genes 0.000 description 93
- 229920001184 polypeptide Polymers 0.000 description 91
- 238000007912 intraperitoneal administration Methods 0.000 description 58
- 241000699666 Mus <mouse, genus> Species 0.000 description 40
- 241000700159 Rattus Species 0.000 description 39
- 229940024606 amino acid Drugs 0.000 description 35
- 208000029078 coronary artery disease Diseases 0.000 description 34
- 206010019280 Heart failures Diseases 0.000 description 32
- 210000004351 coronary vessel Anatomy 0.000 description 32
- 206010067584 Type 1 diabetes mellitus Diseases 0.000 description 30
- 230000008499 blood brain barrier function Effects 0.000 description 29
- 210000001218 blood-brain barrier Anatomy 0.000 description 29
- 108090000623 proteins and genes Proteins 0.000 description 29
- 241000283690 Bos taurus Species 0.000 description 25
- 241000283973 Oryctolagus cuniculus Species 0.000 description 25
- 241000282326 Felis catus Species 0.000 description 23
- 241001494479 Pecora Species 0.000 description 23
- 239000000427 antigen Substances 0.000 description 23
- 108091007433 antigens Proteins 0.000 description 23
- 102000036639 antigens Human genes 0.000 description 23
- 241000282472 Canis lupus familiaris Species 0.000 description 22
- 241000283073 Equus caballus Species 0.000 description 22
- XUMBMVFBXHLACL-UHFFFAOYSA-N Melanin Chemical group O=C1C(=O)C(C2=CNC3=C(C(C(=O)C4=C32)=O)C)=C2C4=CNC2=C1C XUMBMVFBXHLACL-UHFFFAOYSA-N 0.000 description 22
- 241000282898 Sus scrofa Species 0.000 description 21
- 230000003834 intracellular effect Effects 0.000 description 21
- 102000039446 nucleic acids Human genes 0.000 description 19
- 108020004707 nucleic acids Proteins 0.000 description 19
- AICOOMRHRUFYCM-ZRRPKQBOSA-N oxazine, 1 Chemical group C([C@@H]1[C@H](C(C[C@]2(C)[C@@H]([C@H](C)N(C)C)[C@H](O)C[C@]21C)=O)CC1=CC2)C[C@H]1[C@@]1(C)[C@H]2N=C(C(C)C)OC1 AICOOMRHRUFYCM-ZRRPKQBOSA-N 0.000 description 19
- 230000004044 response Effects 0.000 description 19
- 239000000523 sample Substances 0.000 description 19
- 239000013598 vector Substances 0.000 description 17
- 208000031226 Hyperlipidaemia Diseases 0.000 description 16
- 201000010065 polycystic ovary syndrome Diseases 0.000 description 16
- 238000013262 cAMP assay Methods 0.000 description 15
- 230000014509 gene expression Effects 0.000 description 15
- 102000004169 proteins and genes Human genes 0.000 description 15
- 239000012634 fragment Substances 0.000 description 14
- 235000018102 proteins Nutrition 0.000 description 14
- 241000282412 Homo Species 0.000 description 13
- 238000003752 polymerase chain reaction Methods 0.000 description 13
- 229940125633 GPCR agonist Drugs 0.000 description 12
- 239000000126 substance Substances 0.000 description 11
- 108020001507 fusion proteins Proteins 0.000 description 10
- 102000037865 fusion proteins Human genes 0.000 description 10
- 239000002773 nucleotide Substances 0.000 description 10
- 125000003729 nucleotide group Chemical group 0.000 description 10
- 230000004913 activation Effects 0.000 description 9
- 229940125425 inverse agonist Drugs 0.000 description 9
- 238000012217 deletion Methods 0.000 description 7
- 230000037430 deletion Effects 0.000 description 7
- 238000006722 reduction reaction Methods 0.000 description 7
- 239000002299 complementary DNA Substances 0.000 description 6
- NOESYZHRGYRDHS-UHFFFAOYSA-N insulin Chemical compound N1C(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(NC(=O)CN)C(C)CC)CSSCC(C(NC(CO)C(=O)NC(CC(C)C)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CCC(N)=O)C(=O)NC(CC(C)C)C(=O)NC(CCC(O)=O)C(=O)NC(CC(N)=O)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CSSCC(NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2C=CC(O)=CC=2)NC(=O)C(CC(C)C)NC(=O)C(C)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2NC=NC=2)NC(=O)C(CO)NC(=O)CNC2=O)C(=O)NCC(=O)NC(CCC(O)=O)C(=O)NC(CCCNC(N)=N)C(=O)NCC(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC(O)=CC=3)C(=O)NC(C(C)O)C(=O)N3C(CCC3)C(=O)NC(CCCCN)C(=O)NC(C)C(O)=O)C(=O)NC(CC(N)=O)C(O)=O)=O)NC(=O)C(C(C)CC)NC(=O)C(CO)NC(=O)C(C(C)O)NC(=O)C1CSSCC2NC(=O)C(CC(C)C)NC(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CC(N)=O)NC(=O)C(NC(=O)C(N)CC=1C=CC=CC=1)C(C)C)CC1=CN=CN1 NOESYZHRGYRDHS-UHFFFAOYSA-N 0.000 description 6
- 210000003292 kidney cell Anatomy 0.000 description 6
- 239000003550 marker Substances 0.000 description 6
- 208000024891 symptom Diseases 0.000 description 6
- 229940079593 drug Drugs 0.000 description 5
- 230000004048 modification Effects 0.000 description 5
- 238000012986 modification Methods 0.000 description 5
- 230000019491 signal transduction Effects 0.000 description 5
- 238000013518 transcription Methods 0.000 description 5
- 230000035897 transcription Effects 0.000 description 5
- 108020004705 Codon Proteins 0.000 description 4
- 108060001084 Luciferase Proteins 0.000 description 4
- 102000043136 MAP kinase family Human genes 0.000 description 4
- 108091054455 MAP kinase family Proteins 0.000 description 4
- 102000030621 adenylate cyclase Human genes 0.000 description 4
- 108060000200 adenylate cyclase Proteins 0.000 description 4
- 108010005774 beta-Galactosidase Proteins 0.000 description 4
- 102000005936 beta-Galactosidase Human genes 0.000 description 4
- 239000003613 bile acid Substances 0.000 description 4
- 208000035475 disorder Diseases 0.000 description 4
- 238000000265 homogenisation Methods 0.000 description 4
- 229930182817 methionine Natural products 0.000 description 4
- 238000012216 screening Methods 0.000 description 4
- 238000003786 synthesis reaction Methods 0.000 description 4
- 241000282693 Cercopithecidae Species 0.000 description 3
- 241000699800 Cricetinae Species 0.000 description 3
- 102000004877 Insulin Human genes 0.000 description 3
- 108090001061 Insulin Proteins 0.000 description 3
- 239000005089 Luciferase Substances 0.000 description 3
- 102000014384 Type C Phospholipases Human genes 0.000 description 3
- 108010079194 Type C Phospholipases Proteins 0.000 description 3
- MMWCIQZXVOZEGG-HOZKJCLWSA-N [(1S,2R,3S,4S,5R,6S)-2,3,5-trihydroxy-4,6-diphosphonooxycyclohexyl] dihydrogen phosphate Chemical compound O[C@H]1[C@@H](O)[C@H](OP(O)(O)=O)[C@@H](OP(O)(O)=O)[C@H](O)[C@H]1OP(O)(O)=O MMWCIQZXVOZEGG-HOZKJCLWSA-N 0.000 description 3
- 125000000539 amino acid group Chemical group 0.000 description 3
- 150000001607 bioavailable molecules Chemical class 0.000 description 3
- 230000015572 biosynthetic process Effects 0.000 description 3
- 210000004899 c-terminal region Anatomy 0.000 description 3
- 239000011575 calcium Substances 0.000 description 3
- 210000000170 cell membrane Anatomy 0.000 description 3
- 230000008878 coupling Effects 0.000 description 3
- 238000010168 coupling process Methods 0.000 description 3
- 238000005859 coupling reaction Methods 0.000 description 3
- 238000005516 engineering process Methods 0.000 description 3
- 230000006870 function Effects 0.000 description 3
- 229940125396 insulin Drugs 0.000 description 3
- 150000002632 lipids Chemical class 0.000 description 3
- 239000000463 material Substances 0.000 description 3
- 238000010369 molecular cloning Methods 0.000 description 3
- 210000001616 monocyte Anatomy 0.000 description 3
- 238000003757 reverse transcription PCR Methods 0.000 description 3
- 241000894007 species Species 0.000 description 3
- 230000000638 stimulation Effects 0.000 description 3
- 210000001519 tissue Anatomy 0.000 description 3
- 230000003612 virological effect Effects 0.000 description 3
- 108091032973 (ribonucleotides)n+m Proteins 0.000 description 2
- 108700028369 Alleles Proteins 0.000 description 2
- 125000001433 C-terminal amino-acid group Chemical group 0.000 description 2
- 102000004190 Enzymes Human genes 0.000 description 2
- 108090000790 Enzymes Proteins 0.000 description 2
- ZHNUHDYFZUAESO-UHFFFAOYSA-N Formamide Chemical compound NC=O ZHNUHDYFZUAESO-UHFFFAOYSA-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
- 108091034117 Oligonucleotide Proteins 0.000 description 2
- 108700026244 Open Reading Frames Proteins 0.000 description 2
- 241000288906 Primates Species 0.000 description 2
- 108020004511 Recombinant DNA Proteins 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- 239000004098 Tetracycline Substances 0.000 description 2
- 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 2
- 108060008682 Tumor Necrosis Factor Proteins 0.000 description 2
- 102000000852 Tumor Necrosis Factor-alpha Human genes 0.000 description 2
- DRTQHJPVMGBUCF-XVFCMESISA-N Uridine Chemical compound O[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1N1C(=O)NC(=O)C=C1 DRTQHJPVMGBUCF-XVFCMESISA-N 0.000 description 2
- 238000009825 accumulation Methods 0.000 description 2
- 239000004480 active ingredient Substances 0.000 description 2
- 238000007792 addition Methods 0.000 description 2
- OIRDTQYFTABQOQ-KQYNXXCUSA-N adenosine Chemical compound C1=NC=2C(N)=NC=NC=2N1[C@@H]1O[C@H](CO)[C@@H](O)[C@H]1O OIRDTQYFTABQOQ-KQYNXXCUSA-N 0.000 description 2
- 238000013459 approach Methods 0.000 description 2
- 230000008901 benefit Effects 0.000 description 2
- 230000008512 biological response Effects 0.000 description 2
- 230000005540 biological transmission Effects 0.000 description 2
- 210000004556 brain Anatomy 0.000 description 2
- 150000001720 carbohydrates Chemical class 0.000 description 2
- 235000014633 carbohydrates Nutrition 0.000 description 2
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 2
- 230000001413 cellular effect Effects 0.000 description 2
- 230000036755 cellular response Effects 0.000 description 2
- 238000006243 chemical reaction Methods 0.000 description 2
- 210000004978 chinese hamster ovary cell Anatomy 0.000 description 2
- 230000001419 dependent effect Effects 0.000 description 2
- 238000003745 diagnosis Methods 0.000 description 2
- 238000000295 emission spectrum Methods 0.000 description 2
- 239000006274 endogenous ligand Substances 0.000 description 2
- 210000003527 eukaryotic cell Anatomy 0.000 description 2
- 238000002873 global sequence alignment Methods 0.000 description 2
- 230000006872 improvement Effects 0.000 description 2
- 210000005229 liver cell Anatomy 0.000 description 2
- 238000002703 mutagenesis Methods 0.000 description 2
- 231100000350 mutagenesis Toxicity 0.000 description 2
- 210000002569 neuron Anatomy 0.000 description 2
- 230000037361 pathway Effects 0.000 description 2
- 125000002467 phosphate group Chemical group [H]OP(=O)(O[H])O[*] 0.000 description 2
- 229920000642 polymer Polymers 0.000 description 2
- 230000000291 postprandial effect Effects 0.000 description 2
- 239000000955 prescription drug Substances 0.000 description 2
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 2
- 208000037920 primary disease Diseases 0.000 description 2
- 230000006798 recombination Effects 0.000 description 2
- 238000005215 recombination Methods 0.000 description 2
- 230000010076 replication Effects 0.000 description 2
- 238000007423 screening assay Methods 0.000 description 2
- 238000002864 sequence alignment Methods 0.000 description 2
- 239000000243 solution Substances 0.000 description 2
- 125000006850 spacer group Chemical group 0.000 description 2
- 238000006467 substitution reaction Methods 0.000 description 2
- 229960002180 tetracycline Drugs 0.000 description 2
- 229930101283 tetracycline Natural products 0.000 description 2
- 235000019364 tetracycline Nutrition 0.000 description 2
- 150000003522 tetracyclines Chemical class 0.000 description 2
- 238000013519 translation Methods 0.000 description 2
- HSINOMROUCMIEA-FGVHQWLLSA-N (2s,4r)-4-[(3r,5s,6r,7r,8s,9s,10s,13r,14s,17r)-6-ethyl-3,7-dihydroxy-10,13-dimethyl-2,3,4,5,6,7,8,9,11,12,14,15,16,17-tetradecahydro-1h-cyclopenta[a]phenanthren-17-yl]-2-methylpentanoic acid Chemical compound C([C@@]12C)C[C@@H](O)C[C@H]1[C@@H](CC)[C@@H](O)[C@@H]1[C@@H]2CC[C@]2(C)[C@@H]([C@H](C)C[C@H](C)C(O)=O)CC[C@H]21 HSINOMROUCMIEA-FGVHQWLLSA-N 0.000 description 1
- UHDGCWIWMRVCDJ-UHFFFAOYSA-N 1-beta-D-Xylofuranosyl-NH-Cytosine Natural products O=C1N=C(N)C=CN1C1C(O)C(O)C(CO)O1 UHDGCWIWMRVCDJ-UHFFFAOYSA-N 0.000 description 1
- NEWKHUASLBMWRE-UHFFFAOYSA-N 2-methyl-6-(phenylethynyl)pyridine Chemical compound CC1=CC=CC(C#CC=2C=CC=CC=2)=N1 NEWKHUASLBMWRE-UHFFFAOYSA-N 0.000 description 1
- 101710169336 5'-deoxyadenosine deaminase Proteins 0.000 description 1
- 241000251468 Actinopterygii Species 0.000 description 1
- 241000242757 Anthozoa Species 0.000 description 1
- 241000219194 Arabidopsis Species 0.000 description 1
- 108010070255 Aspartate-ammonia ligase Proteins 0.000 description 1
- 241000972773 Aulopiformes Species 0.000 description 1
- 241000271566 Aves Species 0.000 description 1
- 241000894006 Bacteria Species 0.000 description 1
- 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 1
- 206010006187 Breast cancer Diseases 0.000 description 1
- 239000002126 C01EB10 - Adenosine Substances 0.000 description 1
- 241000282836 Camelus dromedarius Species 0.000 description 1
- 241000282465 Canis Species 0.000 description 1
- 241000283707 Capra Species 0.000 description 1
- 235000014653 Carica parviflora Nutrition 0.000 description 1
- 241000700199 Cavia porcellus Species 0.000 description 1
- 206010008342 Cervix carcinoma Diseases 0.000 description 1
- 108010035563 Chloramphenicol O-acetyltransferase Proteins 0.000 description 1
- 241000282552 Chlorocebus aethiops Species 0.000 description 1
- 101710082464 Cis-aconitate decarboxylase 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
- 102000005636 Cyclic AMP Response Element-Binding Protein Human genes 0.000 description 1
- 108010045171 Cyclic AMP Response Element-Binding Protein Proteins 0.000 description 1
- UHDGCWIWMRVCDJ-PSQAKQOGSA-N Cytidine Natural products O=C1N=C(N)C=CN1[C@@H]1[C@@H](O)[C@@H](O)[C@H](CO)O1 UHDGCWIWMRVCDJ-PSQAKQOGSA-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
- 101710147299 DNA fragmentation factor subunit beta Proteins 0.000 description 1
- 230000004568 DNA-binding Effects 0.000 description 1
- 102000016928 DNA-directed DNA polymerase Human genes 0.000 description 1
- 108010014303 DNA-directed DNA polymerase Proteins 0.000 description 1
- 102000004163 DNA-directed RNA polymerases Human genes 0.000 description 1
- 108090000626 DNA-directed RNA polymerases Proteins 0.000 description 1
- 241000702421 Dependoparvovirus Species 0.000 description 1
- 238000002965 ELISA Methods 0.000 description 1
- UPEZCKBFRMILAV-JNEQICEOSA-N Ecdysone Natural products O=C1[C@H]2[C@@](C)([C@@H]3C([C@@]4(O)[C@@](C)([C@H]([C@H]([C@@H](O)CCC(O)(C)C)C)CC4)CC3)=C1)C[C@H](O)[C@H](O)C2 UPEZCKBFRMILAV-JNEQICEOSA-N 0.000 description 1
- 241000196324 Embryophyta Species 0.000 description 1
- 241000283086 Equidae Species 0.000 description 1
- 241000283074 Equus asinus Species 0.000 description 1
- 241000588724 Escherichia coli Species 0.000 description 1
- 101001091269 Escherichia coli Hygromycin-B 4-O-kinase Proteins 0.000 description 1
- 102000009109 Fc receptors Human genes 0.000 description 1
- 108010087819 Fc receptors Proteins 0.000 description 1
- 102000013446 GTP Phosphohydrolases Human genes 0.000 description 1
- 108091006109 GTPases Proteins 0.000 description 1
- 241000287828 Gallus gallus Species 0.000 description 1
- 102000053187 Glucuronidase Human genes 0.000 description 1
- 108010060309 Glucuronidase Proteins 0.000 description 1
- 108091006065 Gs proteins Proteins 0.000 description 1
- HVLSXIKZNLPZJJ-TXZCQADKSA-N HA peptide Chemical compound C([C@@H](C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](C(C)C)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N[C@@H](C)C(O)=O)NC(=O)[C@H]1N(CCC1)C(=O)[C@@H](N)CC=1C=CC(O)=CC=1)C1=CC=C(O)C=C1 HVLSXIKZNLPZJJ-TXZCQADKSA-N 0.000 description 1
- 101710154606 Hemagglutinin Proteins 0.000 description 1
- 241000238631 Hexapoda Species 0.000 description 1
- 102100034343 Integrase Human genes 0.000 description 1
- 108010025815 Kanamycin Kinase Proteins 0.000 description 1
- 241000254158 Lampyridae Species 0.000 description 1
- 108091026898 Leader sequence (mRNA) Proteins 0.000 description 1
- 241000270322 Lepidosauria Species 0.000 description 1
- 241000699673 Mesocricetus auratus Species 0.000 description 1
- 241001529936 Murinae Species 0.000 description 1
- 101000574441 Mus musculus Alkaline phosphatase, germ cell type Proteins 0.000 description 1
- 101000969137 Mus musculus Metallothionein-1 Proteins 0.000 description 1
- 241000699670 Mus sp. Species 0.000 description 1
- 125000000729 N-terminal amino-acid group Chemical group 0.000 description 1
- 229930193140 Neomycin Natural products 0.000 description 1
- 108010038807 Oligopeptides Proteins 0.000 description 1
- 102000015636 Oligopeptides Human genes 0.000 description 1
- 101710093908 Outer capsid protein VP4 Proteins 0.000 description 1
- 101710135467 Outer capsid protein sigma-1 Proteins 0.000 description 1
- 241000282520 Papio Species 0.000 description 1
- 108010081690 Pertussis Toxin Proteins 0.000 description 1
- 101710145525 Probable cinnamyl alcohol dehydrogenase Proteins 0.000 description 1
- 101710176177 Protein A56 Proteins 0.000 description 1
- 108010076504 Protein Sorting Signals Proteins 0.000 description 1
- 108010092799 RNA-directed DNA polymerase Proteins 0.000 description 1
- 241000700157 Rattus norvegicus Species 0.000 description 1
- 241000242739 Renilla Species 0.000 description 1
- 241001521365 Renilla muelleri Species 0.000 description 1
- 241000242743 Renilla reniformis Species 0.000 description 1
- 108700008625 Reporter Genes Proteins 0.000 description 1
- 241000283984 Rodentia Species 0.000 description 1
- 240000004808 Saccharomyces cerevisiae Species 0.000 description 1
- 241000242583 Scyphozoa Species 0.000 description 1
- 108091081024 Start codon Proteins 0.000 description 1
- 101001091268 Streptomyces hygroscopicus Hygromycin-B 7''-O-kinase Proteins 0.000 description 1
- 241000006838 Stylatula Species 0.000 description 1
- 108091036066 Three prime untranslated region Proteins 0.000 description 1
- 108010022394 Threonine synthase Proteins 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
- 108091023045 Untranslated Region Proteins 0.000 description 1
- 208000006105 Uterine Cervical Neoplasms Diseases 0.000 description 1
- 241000238584 Vargula Species 0.000 description 1
- 241000251539 Vertebrata <Metazoa> Species 0.000 description 1
- 108010027570 Xanthine phosphoribosyltransferase Proteins 0.000 description 1
- 240000008042 Zea mays Species 0.000 description 1
- 235000005824 Zea mays ssp. parviglumis Nutrition 0.000 description 1
- 235000002017 Zea mays subsp mays Nutrition 0.000 description 1
- JLCPHMBAVCMARE-UHFFFAOYSA-N [3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-[[3-[[3-[[3-[[3-[[3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-hydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methyl [5-(6-aminopurin-9-yl)-2-(hydroxymethyl)oxolan-3-yl] hydrogen phosphate Polymers Cc1cn(C2CC(OP(O)(=O)OCC3OC(CC3OP(O)(=O)OCC3OC(CC3O)n3cnc4c3nc(N)[nH]c4=O)n3cnc4c3nc(N)[nH]c4=O)C(COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3CO)n3cnc4c(N)ncnc34)n3ccc(N)nc3=O)n3cnc4c(N)ncnc34)n3ccc(N)nc3=O)n3ccc(N)nc3=O)n3ccc(N)nc3=O)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cc(C)c(=O)[nH]c3=O)n3cc(C)c(=O)[nH]c3=O)n3ccc(N)nc3=O)n3cc(C)c(=O)[nH]c3=O)n3cnc4c3nc(N)[nH]c4=O)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)O2)c(=O)[nH]c1=O JLCPHMBAVCMARE-UHFFFAOYSA-N 0.000 description 1
- 230000002159 abnormal effect Effects 0.000 description 1
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 1
- 229960005305 adenosine Drugs 0.000 description 1
- UPEZCKBFRMILAV-UHFFFAOYSA-N alpha-Ecdysone Natural products C1C(O)C(O)CC2(C)C(CCC3(C(C(C(O)CCC(C)(C)O)C)CCC33O)C)C3=CC(=O)C21 UPEZCKBFRMILAV-UHFFFAOYSA-N 0.000 description 1
- 230000003321 amplification Effects 0.000 description 1
- 210000004102 animal cell Anatomy 0.000 description 1
- 238000010171 animal model Methods 0.000 description 1
- 210000004436 artificial bacterial chromosome Anatomy 0.000 description 1
- 210000004507 artificial chromosome Anatomy 0.000 description 1
- 210000001106 artificial yeast chromosome Anatomy 0.000 description 1
- 230000001580 bacterial effect Effects 0.000 description 1
- 239000002585 base Substances 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- IQFYYKKMVGJFEH-UHFFFAOYSA-N beta-L-thymidine Natural products O=C1NC(=O)C(C)=CN1C1OC(CO)C(O)C1 IQFYYKKMVGJFEH-UHFFFAOYSA-N 0.000 description 1
- DRTQHJPVMGBUCF-PSQAKQOGSA-N beta-L-uridine Natural products O[C@H]1[C@@H](O)[C@H](CO)O[C@@H]1N1C(=O)NC(=O)C=C1 DRTQHJPVMGBUCF-PSQAKQOGSA-N 0.000 description 1
- 238000010256 biochemical assay Methods 0.000 description 1
- 230000003115 biocidal effect Effects 0.000 description 1
- 125000001246 bromo group Chemical group Br* 0.000 description 1
- 230000001593 cAMP accumulation Effects 0.000 description 1
- 229910052791 calcium Inorganic materials 0.000 description 1
- 150000001723 carbon free-radicals Chemical class 0.000 description 1
- 238000006555 catalytic reaction Methods 0.000 description 1
- 230000020411 cell activation Effects 0.000 description 1
- 201000010881 cervical cancer Diseases 0.000 description 1
- 125000003636 chemical group Chemical group 0.000 description 1
- 235000013330 chicken meat Nutrition 0.000 description 1
- 125000001309 chloro group Chemical group Cl* 0.000 description 1
- 239000013611 chromosomal DNA Substances 0.000 description 1
- 210000000349 chromosome Anatomy 0.000 description 1
- 230000001684 chronic effect Effects 0.000 description 1
- 238000010367 cloning Methods 0.000 description 1
- 230000001010 compromised effect Effects 0.000 description 1
- 238000004590 computer program Methods 0.000 description 1
- 238000010276 construction Methods 0.000 description 1
- 230000001276 controlling effect Effects 0.000 description 1
- 235000005822 corn Nutrition 0.000 description 1
- 238000012937 correction Methods 0.000 description 1
- UHDGCWIWMRVCDJ-ZAKLUEHWSA-N cytidine Chemical compound O=C1N=C(N)C=CN1[C@H]1[C@H](O)[C@@H](O)[C@H](CO)O1 UHDGCWIWMRVCDJ-ZAKLUEHWSA-N 0.000 description 1
- 238000013461 design Methods 0.000 description 1
- 238000001514 detection method Methods 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
- 230000003292 diminished effect Effects 0.000 description 1
- 230000006806 disease prevention Effects 0.000 description 1
- 230000009977 dual effect Effects 0.000 description 1
- 230000008482 dysregulation Effects 0.000 description 1
- UPEZCKBFRMILAV-JMZLNJERSA-N ecdysone Chemical compound C1[C@@H](O)[C@@H](O)C[C@]2(C)[C@@H](CC[C@@]3([C@@H]([C@@H]([C@H](O)CCC(C)(C)O)C)CC[C@]33O)C)C3=CC(=O)[C@@H]21 UPEZCKBFRMILAV-JMZLNJERSA-N 0.000 description 1
- 230000002526 effect on cardiovascular system Effects 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 230000001610 euglycemic effect Effects 0.000 description 1
- 230000005284 excitation Effects 0.000 description 1
- 238000000695 excitation spectrum Methods 0.000 description 1
- 210000001723 extracellular space Anatomy 0.000 description 1
- 235000019688 fish Nutrition 0.000 description 1
- 108091006047 fluorescent proteins Proteins 0.000 description 1
- 102000034287 fluorescent proteins Human genes 0.000 description 1
- 125000001153 fluoro group Chemical group F* 0.000 description 1
- 125000002485 formyl group Chemical group [H]C(*)=O 0.000 description 1
- 230000002538 fungal effect Effects 0.000 description 1
- 230000004927 fusion Effects 0.000 description 1
- 238000010441 gene drive Methods 0.000 description 1
- 230000002068 genetic effect Effects 0.000 description 1
- 230000014101 glucose homeostasis Effects 0.000 description 1
- 238000007446 glucose tolerance test Methods 0.000 description 1
- 125000003147 glycosyl group Chemical group 0.000 description 1
- 229940029575 guanosine Drugs 0.000 description 1
- 125000005843 halogen group Chemical group 0.000 description 1
- 230000036541 health Effects 0.000 description 1
- 239000000185 hemagglutinin Substances 0.000 description 1
- 125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 210000000688 human artificial chromosome Anatomy 0.000 description 1
- 210000005260 human cell Anatomy 0.000 description 1
- 238000009396 hybridization Methods 0.000 description 1
- 230000002209 hydrophobic effect Effects 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 230000002779 inactivation Effects 0.000 description 1
- 238000011534 incubation Methods 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 230000000977 initiatory effect Effects 0.000 description 1
- 230000003914 insulin secretion Effects 0.000 description 1
- 230000031146 intracellular signal transduction Effects 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- 125000002346 iodo group Chemical group I* 0.000 description 1
- 150000002500 ions Chemical class 0.000 description 1
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 1
- 125000004491 isohexyl group Chemical group C(CCC(C)C)* 0.000 description 1
- 125000001972 isopentyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 210000003734 kidney Anatomy 0.000 description 1
- 210000000265 leukocyte Anatomy 0.000 description 1
- 125000003473 lipid group Chemical group 0.000 description 1
- 244000144972 livestock Species 0.000 description 1
- 210000005265 lung cell Anatomy 0.000 description 1
- 210000002540 macrophage Anatomy 0.000 description 1
- 210000004962 mammalian cell Anatomy 0.000 description 1
- 239000011159 matrix material Substances 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- 108020004999 messenger RNA Proteins 0.000 description 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
- 244000005700 microbiome Species 0.000 description 1
- 238000012544 monitoring process Methods 0.000 description 1
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000000740 n-pentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 230000010807 negative regulation of binding Effects 0.000 description 1
- 125000005244 neohexyl group Chemical group [H]C([H])([H])C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])C([H])([H])* 0.000 description 1
- 229960004927 neomycin Drugs 0.000 description 1
- 125000001971 neopentyl group Chemical group [H]C([*])([H])C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 238000003199 nucleic acid amplification method Methods 0.000 description 1
- 239000002777 nucleoside Substances 0.000 description 1
- 150000003833 nucleoside derivatives Chemical class 0.000 description 1
- 244000052769 pathogen Species 0.000 description 1
- 230000008506 pathogenesis Effects 0.000 description 1
- 230000001717 pathogenic effect Effects 0.000 description 1
- 230000000149 penetrating effect Effects 0.000 description 1
- 230000035515 penetration Effects 0.000 description 1
- 239000008177 pharmaceutical agent Substances 0.000 description 1
- 239000000825 pharmaceutical preparation Substances 0.000 description 1
- 229940127557 pharmaceutical product Drugs 0.000 description 1
- 150000003904 phospholipids Chemical class 0.000 description 1
- 230000004962 physiological condition Effects 0.000 description 1
- 230000035479 physiological effects, processes and functions Effects 0.000 description 1
- 239000013612 plasmid Substances 0.000 description 1
- 238000006116 polymerization reaction Methods 0.000 description 1
- 230000004481 post-translational protein modification Effects 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 230000004850 protein–protein interaction Effects 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 150000003254 radicals Chemical class 0.000 description 1
- 229940075993 receptor modulator Drugs 0.000 description 1
- 238000010188 recombinant method Methods 0.000 description 1
- 230000002829 reductive effect Effects 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 108091008146 restriction endonucleases Proteins 0.000 description 1
- 238000012552 review Methods 0.000 description 1
- 235000019515 salmon Nutrition 0.000 description 1
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 125000003548 sec-pentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 230000011664 signaling Effects 0.000 description 1
- 210000004927 skin cell Anatomy 0.000 description 1
- 150000003384 small molecules Chemical class 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 239000001509 sodium citrate Substances 0.000 description 1
- 239000001488 sodium phosphate Substances 0.000 description 1
- 229910000162 sodium phosphate Inorganic materials 0.000 description 1
- 230000009870 specific binding Effects 0.000 description 1
- 230000006641 stabilisation Effects 0.000 description 1
- 238000011105 stabilization Methods 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- 230000004083 survival effect Effects 0.000 description 1
- 230000002459 sustained effect Effects 0.000 description 1
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 229940104230 thymidine Drugs 0.000 description 1
- HRXKRNGNAMMEHJ-UHFFFAOYSA-K trisodium citrate Chemical compound [Na+].[Na+].[Na+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O HRXKRNGNAMMEHJ-UHFFFAOYSA-K 0.000 description 1
- 229940038773 trisodium citrate Drugs 0.000 description 1
- RYFMWSXOAZQYPI-UHFFFAOYSA-K trisodium phosphate Chemical compound [Na+].[Na+].[Na+].[O-]P([O-])([O-])=O RYFMWSXOAZQYPI-UHFFFAOYSA-K 0.000 description 1
- 241000701161 unidentified adenovirus Species 0.000 description 1
- 241000712461 unidentified influenza virus Species 0.000 description 1
- 241001430294 unidentified retrovirus Species 0.000 description 1
- DRTQHJPVMGBUCF-UHFFFAOYSA-N uracil arabinoside Natural products OC1C(O)C(CO)OC1N1C(=O)NC(=O)C=C1 DRTQHJPVMGBUCF-UHFFFAOYSA-N 0.000 description 1
- 229940045145 uridine Drugs 0.000 description 1
- 239000013603 viral vector Substances 0.000 description 1
Images
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
- C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
- C07D417/04—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings directly linked by a ring-member-to-ring-member bond
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
- A61K31/425—Thiazoles
- A61K31/427—Thiazoles not condensed and containing further heterocyclic rings
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/4427—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems
- A61K31/4439—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems containing a five-membered ring with nitrogen as a ring hetero atom, e.g. omeprazole
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P13/00—Drugs for disorders of the urinary system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P13/00—Drugs for disorders of the urinary system
- A61P13/12—Drugs for disorders of the urinary system of the kidneys
-
- 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
- A61P27/00—Drugs for disorders of the senses
- A61P27/02—Ophthalmic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/06—Antihyperlipidemics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
- A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P5/00—Drugs for disorders of the endocrine system
- A61P5/48—Drugs for disorders of the endocrine system of the pancreatic hormones
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/02—Non-specific cardiovascular stimulants, e.g. drugs for syncope, antihypotensives
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/08—Vasodilators for multiple indications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/12—Antihypertensives
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
- G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
- G01N33/74—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving hormones or other non-cytokine intercellular protein regulatory factors such as growth factors, including receptors to hormones and growth factors
- G01N33/76—Human chorionic gonadotropin including luteinising hormone, follicle stimulating hormone, thyroid stimulating hormone or their receptors
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N2333/00—Assays involving biological materials from specific organisms or of a specific nature
- G01N2333/435—Assays involving biological materials from specific organisms or of a specific nature from animals; from humans
- G01N2333/705—Assays involving receptors, cell surface antigens or cell surface determinants
- G01N2333/72—Assays involving receptors, cell surface antigens or cell surface determinants for hormones
- G01N2333/726—G protein coupled receptor, e.g. TSHR-thyrotropin-receptor, LH/hCG receptor, FSH
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Engineering & Computer Science (AREA)
- General Health & Medical Sciences (AREA)
- Organic Chemistry (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Hematology (AREA)
- Diabetes (AREA)
- Urology & Nephrology (AREA)
- Endocrinology (AREA)
- Cardiology (AREA)
- Molecular Biology (AREA)
- Heart & Thoracic Surgery (AREA)
- Biomedical Technology (AREA)
- Immunology (AREA)
- Obesity (AREA)
- Epidemiology (AREA)
- Physics & Mathematics (AREA)
- General Physics & Mathematics (AREA)
- Reproductive Health (AREA)
- Cell Biology (AREA)
- Pathology (AREA)
- Emergency Medicine (AREA)
- Biochemistry (AREA)
- Microbiology (AREA)
- Food Science & Technology (AREA)
- Biotechnology (AREA)
- Analytical Chemistry (AREA)
- Vascular Medicine (AREA)
- Ophthalmology & Optometry (AREA)
- Neurosurgery (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US56195404P | 2004-04-13 | 2004-04-13 | |
| PCT/US2005/012447 WO2005116653A2 (en) | 2004-04-13 | 2005-04-12 | Modulators of human g protein-coupled receptors for the treatment of hyperglycemia and related disorders |
Related Child Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2008104153A Division JP5769361B2 (ja) | 2004-04-13 | 2008-04-11 | 高血糖症および関連障害の処置のための、ヒトｇタンパク質共役レセプターおよびそのモジュレーター |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JP2007532135A true JP2007532135A (ja) | 2007-11-15 |
| JP2007532135A5 JP2007532135A5 (https=) | 2008-05-29 |
Family
ID=35451510
Family Applications (4)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2007508478A Pending JP2007532135A (ja) | 2004-04-13 | 2005-04-12 | 高血糖症および関連障害の処置のための、ヒトｇタンパク質共役レセプターおよびそのモジュレーター |
| JP2008104153A Expired - Fee Related JP5769361B2 (ja) | 2004-04-13 | 2008-04-11 | 高血糖症および関連障害の処置のための、ヒトｇタンパク質共役レセプターおよびそのモジュレーター |
| JP2011226811A Pending JP2012050454A (ja) | 2004-04-13 | 2011-10-14 | 高血糖症および関連障害の処置のための、ヒトｇタンパク質共役レセプターおよびそのモジュレーター |
| JP2014209937A Pending JP2015064359A (ja) | 2004-04-13 | 2014-10-14 | 高血糖症および関連障害の処置のための、ヒトｇタンパク質共役レセプターおよびそのモジュレーター |
Family Applications After (3)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2008104153A Expired - Fee Related JP5769361B2 (ja) | 2004-04-13 | 2008-04-11 | 高血糖症および関連障害の処置のための、ヒトｇタンパク質共役レセプターおよびそのモジュレーター |
| JP2011226811A Pending JP2012050454A (ja) | 2004-04-13 | 2011-10-14 | 高血糖症および関連障害の処置のための、ヒトｇタンパク質共役レセプターおよびそのモジュレーター |
| JP2014209937A Pending JP2015064359A (ja) | 2004-04-13 | 2014-10-14 | 高血糖症および関連障害の処置のための、ヒトｇタンパク質共役レセプターおよびそのモジュレーター |
Country Status (8)
| Country | Link |
|---|---|
| US (1) | US20080306114A1 (https=) |
| EP (1) | EP1735622A2 (https=) |
| JP (4) | JP2007532135A (https=) |
| CN (1) | CN101027560A (https=) |
| AU (1) | AU2005248722A1 (https=) |
| CA (1) | CA2564139A1 (https=) |
| TW (1) | TW200539867A (https=) |
| WO (1) | WO2005116653A2 (https=) |
Families Citing this family (20)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2005023253A1 (en) | 2003-09-05 | 2005-03-17 | Altana Pharma Ag | Use of pde4 inhibitors for the treatment of diabetes mellitus |
| WO2006094942A1 (en) * | 2005-03-08 | 2006-09-14 | Nycomed Gmbh | Roflumilast for the treatment of diabetes mellitus |
| AU2006222060B2 (en) | 2005-03-08 | 2011-09-01 | Takeda Gmbh | Roflumilast for the treatment of diabetes mellitus |
| TW200738701A (en) | 2005-07-26 | 2007-10-16 | Du Pont | Fungicidal carboxamides |
| WO2007100618A2 (en) * | 2006-02-23 | 2007-09-07 | Atto Bioscience | Novel cell-based phosphodiesterase assays |
| WO2007115805A2 (en) * | 2006-04-05 | 2007-10-18 | European Molecular Biology Laboratory (Embl) | Aurora kinase inhibitors |
| WO2008013622A2 (en) | 2006-07-27 | 2008-01-31 | E. I. Du Pont De Nemours And Company | Fungicidal azocyclic amides |
| US9090604B2 (en) | 2006-07-27 | 2015-07-28 | E I Du Pont De Nemours And Company | Fungicidal azocyclic amides |
| US7638541B2 (en) | 2006-12-28 | 2009-12-29 | Metabolex Inc. | 5-ethyl-2-{4-[4-(4-tetrazol-1-yl-phenoxymethyl)-thiazol-2-yl]-piperidin-1-yl}-pyrimidine |
| JP5337711B2 (ja) | 2007-01-25 | 2013-11-06 | イー・アイ・デュポン・ドウ・ヌムール・アンド・カンパニー | 殺菌性アミド |
| AU2008279447A1 (en) | 2007-07-19 | 2009-01-29 | Metabolex, Inc. | N-azacyclic substituted pyrrole, pyrazole, imidazole, triazole and tetrazole derivatives as agonists of the RUP3 or GPR119 receptor for the treatment of diabetes and metabolic disorders |
| DE102007047735A1 (de) * | 2007-10-05 | 2009-04-09 | Merck Patent Gmbh | Thiazolderivate |
| TWI428091B (zh) | 2007-10-23 | 2014-03-01 | Du Pont | 殺真菌劑混合物 |
| WO2010117090A1 (en) * | 2009-04-10 | 2010-10-14 | Banyu Pharmaceutical Co.,Ltd. | Novel isoquinolinyloxymethyl heteroaryl derivatives |
| WO2010117084A1 (en) * | 2009-04-10 | 2010-10-14 | Banyu Pharmaceutical Co.,Ltd. | Novel isoquinoline derivatives |
| US8410127B2 (en) | 2009-10-01 | 2013-04-02 | Metabolex, Inc. | Substituted tetrazol-1-yl-phenoxymethyl-thiazol-2-yl-piperidinyl-pyrimidine salts |
| KR20120101019A (ko) | 2009-10-30 | 2012-09-12 | 바이엘 크롭사이언스 아게 | 헤테로아릴피페리딘 및 -피페라진 유도체 |
| US8653047B2 (en) * | 2010-01-08 | 2014-02-18 | Isis Pharmaceuticals, Inc. | Modulation of angiopoietin-like 3 expression |
| AU2017305392A1 (en) | 2016-08-03 | 2019-02-21 | Cymabay Therapeutics, Inc. | Oxymethylene aryl compounds for treating inflammatory gastrointestinal diseases or gastrointestinal conditions |
| CN113082020A (zh) * | 2021-04-08 | 2021-07-09 | 徐州医科大学 | 一种腺苷受体激动剂的增强剂及其应用 |
Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1992001810A1 (en) * | 1990-07-19 | 1992-02-06 | Lerner Michael R | Methods of identifying compounds that act as agonists or antagonists for proteins involved in signal transduction |
| JP2003315332A (ja) * | 2001-04-12 | 2003-11-06 | Takeda Chem Ind Ltd | スクリーニング方法 |
| JP2004346059A (ja) * | 2003-01-28 | 2004-12-09 | Takeda Chem Ind Ltd | 受容体作動薬 |
| JP2006513202A (ja) * | 2002-12-24 | 2006-04-20 | メトリス セラピューティクス リミテッド | 血管形成インヒビターとしてのピペリジニル−チアゾールカルボン酸誘導体 |
Family Cites Families (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6060465A (en) * | 1997-02-06 | 2000-05-09 | Miljkovic; Dusan | Bile acids and their derivatives as glycoregulatory agents |
| JP2002000281A (ja) | 2000-04-12 | 2002-01-08 | Takeda Chem Ind Ltd | 新規ｇ蛋白質共役型レセプター蛋白質およびそのｄｎａ |
| US7198914B2 (en) * | 2000-11-17 | 2007-04-03 | Banyu Pharmaceutical Co., Ltd. | Guanosine triphosphate (GTP)-binding protein-coupled receptor protein, BG37 |
| US7354726B2 (en) * | 2001-04-12 | 2008-04-08 | Takeda Pharmaceutical Company Limited | Screening method |
| US7625887B2 (en) * | 2003-01-28 | 2009-12-01 | Takeda Pharmaceutical Company Limited | Receptor agonists |
-
2005
- 2005-04-12 WO PCT/US2005/012447 patent/WO2005116653A2/en not_active Ceased
- 2005-04-12 CN CNA2005800187303A patent/CN101027560A/zh not_active Withdrawn
- 2005-04-12 TW TW094111561A patent/TW200539867A/zh unknown
- 2005-04-12 CA CA002564139A patent/CA2564139A1/en not_active Abandoned
- 2005-04-12 EP EP05780020A patent/EP1735622A2/en not_active Withdrawn
- 2005-04-12 US US11/578,257 patent/US20080306114A1/en not_active Abandoned
- 2005-04-12 AU AU2005248722A patent/AU2005248722A1/en not_active Withdrawn
- 2005-04-12 JP JP2007508478A patent/JP2007532135A/ja active Pending
-
2008
- 2008-04-11 JP JP2008104153A patent/JP5769361B2/ja not_active Expired - Fee Related
-
2011
- 2011-10-14 JP JP2011226811A patent/JP2012050454A/ja active Pending
-
2014
- 2014-10-14 JP JP2014209937A patent/JP2015064359A/ja active Pending
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1992001810A1 (en) * | 1990-07-19 | 1992-02-06 | Lerner Michael R | Methods of identifying compounds that act as agonists or antagonists for proteins involved in signal transduction |
| JP2003315332A (ja) * | 2001-04-12 | 2003-11-06 | Takeda Chem Ind Ltd | スクリーニング方法 |
| JP2006513202A (ja) * | 2002-12-24 | 2006-04-20 | メトリス セラピューティクス リミテッド | 血管形成インヒビターとしてのピペリジニル−チアゾールカルボン酸誘導体 |
| JP2004346059A (ja) * | 2003-01-28 | 2004-12-09 | Takeda Chem Ind Ltd | 受容体作動薬 |
Also Published As
| Publication number | Publication date |
|---|---|
| CA2564139A1 (en) | 2005-12-08 |
| CN101027560A (zh) | 2007-08-29 |
| TW200539867A (en) | 2005-12-16 |
| JP5769361B2 (ja) | 2015-08-26 |
| US20080306114A1 (en) | 2008-12-11 |
| JP2015064359A (ja) | 2015-04-09 |
| JP2012050454A (ja) | 2012-03-15 |
| AU2005248722A1 (en) | 2005-12-08 |
| EP1735622A2 (en) | 2006-12-27 |
| JP2008263979A (ja) | 2008-11-06 |
| WO2005116653A3 (en) | 2006-05-18 |
| WO2005116653A2 (en) | 2005-12-08 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| JP5769361B2 (ja) | 高血糖症および関連障害の処置のための、ヒトｇタンパク質共役レセプターおよびそのモジュレーター | |
| US7829298B2 (en) | Human G protein-coupled receptors for metabolic-related disorders | |
| US20140255310A1 (en) | Human G Protein-Coupled Receptor and Modulators Thereof for the Treatment of Atherosclerosis and Atherosclerotic Disease and for the Treatment of Conditions Related to MCP-1 Expression | |
| NZ571110A (en) | Methods of using GPR119 receptor to identify Glucose-dependent Insulinotropic Peptide (GIP) secretagogue compounds useful for increasing bone mass in an individual | |
| US20110038850A1 (en) | G Protein-Coupled Receptor and Modulators Thereof For The Treatment of Gaba-Related Neurological Disorders Including Sleep-Related Disorders | |
| US20160077113A1 (en) | Methods of Identifying Candidate Compounds of the Human G Protein-Coupled Receptor, GPR50, as Modulators of Body Mass or Adiposity | |
| JP2009538623A (ja) | 視床下部プロオピオメラノコルチン（ｐｏｍｃ）由来生物活性ペプチドに関連する障害の処置において有用な、視床下部プロオピオメラノコルチン（ｐｏｍｃ）由来生物活性ペプチドの分泌の調節因子を同定するための方法における、ｇｐｒ１０１受容体の使用 | |
| WO2005119252A2 (en) | Modulators of gpr35 for the treatment of metabolic-related disorders | |
| JP2011162567A (ja) | 心血管障害の処置のためのヒトｇタンパク質共役型レセプターおよびそのモジュレーター | |
| JP5774264B2 (ja) | 肥満および糖尿病、ならびにそれらに関連する病態の処置のため、ならびに血中ｇｌｐ−１レベルを増大させることによって緩和される病態の処置のための、併用療法 | |
| US7611832B2 (en) | Human G protein-coupled receptor and modulators thereof for the treatment of ischemic heart disease and congestive heart failure | |
| US20070231263A1 (en) | Human G protein-coupled receptor and modulators thereof for the treatment of hyperglycemia and related disorders | |
| CA2519230A1 (en) | Modulators of the g protein-coupled formyl peptide receptor-like 2 and their therapeutic use against cell death-related disorders | |
| CN100514066C (zh) | 人类g蛋白偶联受体和用于治疗细胞死亡相关病症的其调节物 |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20080411 |
|
| A621 | Written request for application examination |
Free format text: JAPANESE INTERMEDIATE CODE: A621 Effective date: 20080411 |
|
| A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20110104 |
|
| A601 | Written request for extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A601 Effective date: 20110401 |
|
| A602 | Written permission of extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A602 Effective date: 20110408 |
|
| A601 | Written request for extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A601 Effective date: 20110502 |
|
| A602 | Written permission of extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A602 Effective date: 20110512 |
|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20110606 |
|
| A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20110728 Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20110728 |
|
| A601 | Written request for extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A601 Effective date: 20110927 |
|
| A602 | Written permission of extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A602 Effective date: 20111004 |
|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20120130 |
|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A821 Effective date: 20120130 |
|
| A02 | Decision of refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A02 Effective date: 20120406 |