JP2005505545A - 高血圧及び心不全を減少させる方法 - Google Patents
高血圧及び心不全を減少させる方法 Download PDFInfo
- Publication number
- JP2005505545A JP2005505545A JP2003524516A JP2003524516A JP2005505545A JP 2005505545 A JP2005505545 A JP 2005505545A JP 2003524516 A JP2003524516 A JP 2003524516A JP 2003524516 A JP2003524516 A JP 2003524516A JP 2005505545 A JP2005505545 A JP 2005505545A
- Authority
- JP
- Japan
- Prior art keywords
- heart
- tyrphostin
- hypertension
- hypertrophy
- ischemia
- 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
- 206010020772 Hypertension Diseases 0.000 title claims abstract description 62
- 238000000034 method Methods 0.000 title claims abstract description 51
- 206010019280 Heart failures Diseases 0.000 title claims abstract description 48
- TUCIOBMMDDOEMM-RIYZIHGNSA-N tyrphostin B42 Chemical compound C1=C(O)C(O)=CC=C1\C=C(/C#N)C(=O)NCC1=CC=CC=C1 TUCIOBMMDDOEMM-RIYZIHGNSA-N 0.000 claims abstract description 43
- 229940121730 Janus kinase 2 inhibitor Drugs 0.000 claims abstract description 38
- 241000124008 Mammalia Species 0.000 claims abstract description 31
- 229940121358 tyrosine kinase inhibitor Drugs 0.000 claims abstract description 18
- 230000006378 damage Effects 0.000 claims description 12
- 239000000203 mixture Substances 0.000 claims description 12
- 210000002966 serum Anatomy 0.000 claims description 6
- 230000009885 systemic effect Effects 0.000 claims description 4
- 230000003683 cardiac damage Effects 0.000 abstract 1
- 210000002216 heart Anatomy 0.000 description 63
- 208000028867 ischemia Diseases 0.000 description 56
- 206010020880 Hypertrophy Diseases 0.000 description 43
- 101150009057 JAK2 gene Proteins 0.000 description 28
- 230000010410 reperfusion Effects 0.000 description 27
- 108090001067 Angiotensinogen Proteins 0.000 description 24
- 102000004881 Angiotensinogen Human genes 0.000 description 23
- 210000000056 organ Anatomy 0.000 description 23
- 108020004999 messenger RNA Proteins 0.000 description 20
- 230000002829 reductive effect Effects 0.000 description 19
- 241000700159 Rattus Species 0.000 description 17
- 230000000694 effects Effects 0.000 description 15
- 101000617830 Homo sapiens Sterol O-acyltransferase 1 Proteins 0.000 description 14
- 102100021993 Sterol O-acyltransferase 1 Human genes 0.000 description 14
- 101000697584 Streptomyces lavendulae Streptothricin acetyltransferase Proteins 0.000 description 14
- 150000001875 compounds Chemical class 0.000 description 14
- 239000008194 pharmaceutical composition Substances 0.000 description 13
- 238000011282 treatment Methods 0.000 description 13
- 206010061216 Infarction Diseases 0.000 description 12
- 210000004027 cell Anatomy 0.000 description 12
- 230000007574 infarction Effects 0.000 description 12
- 230000000302 ischemic effect Effects 0.000 description 12
- 208000007177 Left Ventricular Hypertrophy Diseases 0.000 description 10
- 210000004369 blood Anatomy 0.000 description 10
- 239000008280 blood Substances 0.000 description 10
- 230000036772 blood pressure Effects 0.000 description 10
- 206010007572 Cardiac hypertrophy Diseases 0.000 description 9
- 241001465754 Metazoa Species 0.000 description 9
- 230000027455 binding Effects 0.000 description 9
- 210000004165 myocardium Anatomy 0.000 description 9
- 108020004414 DNA Proteins 0.000 description 8
- 230000004913 activation Effects 0.000 description 8
- 230000007423 decrease Effects 0.000 description 8
- 230000014509 gene expression Effects 0.000 description 8
- 238000001356 surgical procedure Methods 0.000 description 8
- CZGUSIXMZVURDU-JZXHSEFVSA-N Ile(5)-angiotensin II Chemical compound C([C@@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CC=1NC=NC=1)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CC=1C=CC=CC=1)C([O-])=O)NC(=O)[C@@H](NC(=O)[C@H](CCCNC(N)=[NH2+])NC(=O)[C@@H]([NH3+])CC([O-])=O)C(C)C)C1=CC=C(O)C=C1 CZGUSIXMZVURDU-JZXHSEFVSA-N 0.000 description 7
- 241000699670 Mus sp. Species 0.000 description 7
- 108010011005 STAT6 Transcription Factor Proteins 0.000 description 7
- 102100024481 Signal transducer and activator of transcription 5A Human genes 0.000 description 7
- 238000003556 assay Methods 0.000 description 7
- 230000009467 reduction Effects 0.000 description 7
- 230000036454 renin-angiotensin system Effects 0.000 description 7
- 150000003839 salts Chemical class 0.000 description 7
- 102000005862 Angiotensin II Human genes 0.000 description 6
- 101800000733 Angiotensin-2 Proteins 0.000 description 6
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 6
- 102000013968 STAT6 Transcription Factor Human genes 0.000 description 6
- 229950006323 angiotensin ii Drugs 0.000 description 6
- 230000004217 heart function Effects 0.000 description 6
- 108090000623 proteins and genes Proteins 0.000 description 6
- 239000000523 sample Substances 0.000 description 6
- 208000024891 symptom Diseases 0.000 description 6
- 210000001519 tissue Anatomy 0.000 description 6
- 201000001320 Atherosclerosis Diseases 0.000 description 5
- 208000006029 Cardiomegaly Diseases 0.000 description 5
- 102000004022 Protein-Tyrosine Kinases Human genes 0.000 description 5
- 108090000412 Protein-Tyrosine Kinases Proteins 0.000 description 5
- 101150058731 STAT5A gene Proteins 0.000 description 5
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 5
- 230000006907 apoptotic process Effects 0.000 description 5
- 238000009739 binding Methods 0.000 description 5
- 230000017531 blood circulation Effects 0.000 description 5
- 210000004204 blood vessel Anatomy 0.000 description 5
- 239000003814 drug Substances 0.000 description 5
- 239000000284 extract Substances 0.000 description 5
- 230000002107 myocardial effect Effects 0.000 description 5
- 208000031225 myocardial ischemia Diseases 0.000 description 5
- 239000003381 stabilizer Substances 0.000 description 5
- 230000002861 ventricular Effects 0.000 description 5
- 239000002083 C09CA01 - Losartan Substances 0.000 description 4
- 206010056370 Congestive cardiomyopathy Diseases 0.000 description 4
- 125000000217 alkyl group Chemical group 0.000 description 4
- 239000000872 buffer Substances 0.000 description 4
- 210000004413 cardiac myocyte Anatomy 0.000 description 4
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 4
- 230000005764 inhibitory process Effects 0.000 description 4
- 210000003734 kidney Anatomy 0.000 description 4
- 230000007774 longterm Effects 0.000 description 4
- KJJZZJSZUJXYEA-UHFFFAOYSA-N losartan Chemical compound CCCCC1=NC(Cl)=C(CO)N1CC1=CC=C(C=2C(=CC=CC=2)C=2[N]N=NN=2)C=C1 KJJZZJSZUJXYEA-UHFFFAOYSA-N 0.000 description 4
- 229960004773 losartan Drugs 0.000 description 4
- 238000012423 maintenance Methods 0.000 description 4
- 208000010125 myocardial infarction Diseases 0.000 description 4
- 230000010412 perfusion Effects 0.000 description 4
- 239000013612 plasmid Substances 0.000 description 4
- 230000003389 potentiating effect Effects 0.000 description 4
- 102000004169 proteins and genes Human genes 0.000 description 4
- 230000004044 response Effects 0.000 description 4
- 230000019491 signal transduction Effects 0.000 description 4
- 230000035488 systolic blood pressure Effects 0.000 description 4
- 230000003827 upregulation Effects 0.000 description 4
- 108091032973 (ribonucleotides)n+m Proteins 0.000 description 3
- 206010007559 Cardiac failure congestive Diseases 0.000 description 3
- 208000024172 Cardiovascular disease Diseases 0.000 description 3
- 201000010046 Dilated cardiomyopathy Diseases 0.000 description 3
- 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 3
- 102000004190 Enzymes Human genes 0.000 description 3
- 108090000790 Enzymes Proteins 0.000 description 3
- 230000004163 JAK-STAT signaling pathway Effects 0.000 description 3
- 206010030124 Oedema peripheral Diseases 0.000 description 3
- 241000283973 Oryctolagus cuniculus Species 0.000 description 3
- 108010017324 STAT3 Transcription Factor Proteins 0.000 description 3
- 102100024040 Signal transducer and activator of transcription 3 Human genes 0.000 description 3
- 102000000887 Transcription factor STAT Human genes 0.000 description 3
- 108050007918 Transcription factor STAT Proteins 0.000 description 3
- 239000012190 activator Substances 0.000 description 3
- 239000000654 additive Substances 0.000 description 3
- 206010002906 aortic stenosis Diseases 0.000 description 3
- 230000037396 body weight Effects 0.000 description 3
- 239000006172 buffering agent Substances 0.000 description 3
- OSASVXMJTNOKOY-UHFFFAOYSA-N chlorobutanol Chemical compound CC(C)(O)C(Cl)(Cl)Cl OSASVXMJTNOKOY-UHFFFAOYSA-N 0.000 description 3
- 239000002299 complementary DNA Substances 0.000 description 3
- 230000034994 death Effects 0.000 description 3
- 230000035487 diastolic blood pressure Effects 0.000 description 3
- 230000010339 dilation Effects 0.000 description 3
- 201000010099 disease Diseases 0.000 description 3
- 229940079593 drug Drugs 0.000 description 3
- 238000001962 electrophoresis Methods 0.000 description 3
- 238000001727 in vivo Methods 0.000 description 3
- 239000003112 inhibitor Substances 0.000 description 3
- 208000037906 ischaemic injury Diseases 0.000 description 3
- 210000005240 left ventricle Anatomy 0.000 description 3
- 210000000663 muscle cell Anatomy 0.000 description 3
- 230000003680 myocardial damage Effects 0.000 description 3
- WEXRUCMBJFQVBZ-UHFFFAOYSA-N pentobarbital Chemical compound CCCC(C)C1(CC)C(=O)NC(=O)NC1=O WEXRUCMBJFQVBZ-UHFFFAOYSA-N 0.000 description 3
- 230000026731 phosphorylation Effects 0.000 description 3
- 238000006366 phosphorylation reaction Methods 0.000 description 3
- 239000013615 primer Substances 0.000 description 3
- 108020003175 receptors Proteins 0.000 description 3
- 102000005962 receptors Human genes 0.000 description 3
- 239000011780 sodium chloride Substances 0.000 description 3
- 239000000126 substance Substances 0.000 description 3
- 239000004094 surface-active agent Substances 0.000 description 3
- 230000004083 survival effect Effects 0.000 description 3
- GWCNJMUSWLTSCW-SFQUDFHCSA-N (e)-2-cyano-3-(3,4-dihydroxyphenyl)-n-(4-phenylbutyl)prop-2-enamide Chemical compound C1=C(O)C(O)=CC=C1\C=C(/C#N)C(=O)NCCCCC1=CC=CC=C1 GWCNJMUSWLTSCW-SFQUDFHCSA-N 0.000 description 2
- UUUHXMGGBIUAPW-UHFFFAOYSA-N 1-[1-[2-[[5-amino-2-[[1-[5-(diaminomethylideneamino)-2-[[1-[3-(1h-indol-3-yl)-2-[(5-oxopyrrolidine-2-carbonyl)amino]propanoyl]pyrrolidine-2-carbonyl]amino]pentanoyl]pyrrolidine-2-carbonyl]amino]-5-oxopentanoyl]amino]-3-methylpentanoyl]pyrrolidine-2-carbon Chemical compound C1CCC(C(=O)N2C(CCC2)C(O)=O)N1C(=O)C(C(C)CC)NC(=O)C(CCC(N)=O)NC(=O)C1CCCN1C(=O)C(CCCN=C(N)N)NC(=O)C1CCCN1C(=O)C(CC=1C2=CC=CC=C2NC=1)NC(=O)C1CCC(=O)N1 UUUHXMGGBIUAPW-UHFFFAOYSA-N 0.000 description 2
- 206010002383 Angina Pectoris Diseases 0.000 description 2
- 101800000734 Angiotensin-1 Proteins 0.000 description 2
- 102400000344 Angiotensin-1 Human genes 0.000 description 2
- 206010060965 Arterial stenosis Diseases 0.000 description 2
- 239000003298 DNA probe Substances 0.000 description 2
- 230000004568 DNA-binding Effects 0.000 description 2
- AHCYMLUZIRLXAA-SHYZEUOFSA-N Deoxyuridine 5'-triphosphate Chemical group O1[C@H](COP(O)(=O)OP(O)(=O)OP(O)(O)=O)[C@@H](O)C[C@@H]1N1C(=O)NC(=O)C=C1 AHCYMLUZIRLXAA-SHYZEUOFSA-N 0.000 description 2
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 2
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 2
- 101150069380 JAK3 gene Proteins 0.000 description 2
- 108060001084 Luciferase Proteins 0.000 description 2
- 239000005089 Luciferase Substances 0.000 description 2
- 241000699666 Mus <mouse, genus> Species 0.000 description 2
- 206010028594 Myocardial fibrosis Diseases 0.000 description 2
- 239000000020 Nitrocellulose Substances 0.000 description 2
- 108091034117 Oligonucleotide Proteins 0.000 description 2
- 241001494479 Pecora Species 0.000 description 2
- 102000004270 Peptidyl-Dipeptidase A Human genes 0.000 description 2
- 108090000882 Peptidyl-Dipeptidase A Proteins 0.000 description 2
- 101000796258 Rattus norvegicus Angiotensinogen Proteins 0.000 description 2
- 102100028255 Renin Human genes 0.000 description 2
- 108090000783 Renin Proteins 0.000 description 2
- 108010044012 STAT1 Transcription Factor Proteins 0.000 description 2
- 108010029477 STAT5 Transcription Factor Proteins 0.000 description 2
- 229940124639 Selective inhibitor Drugs 0.000 description 2
- 102100029904 Signal transducer and activator of transcription 1-alpha/beta Human genes 0.000 description 2
- 206010049418 Sudden Cardiac Death Diseases 0.000 description 2
- 102000040945 Transcription factor Human genes 0.000 description 2
- 108091023040 Transcription factor Proteins 0.000 description 2
- 239000002253 acid Substances 0.000 description 2
- 230000009471 action Effects 0.000 description 2
- 150000001413 amino acids Chemical class 0.000 description 2
- 230000003941 amyloidogenesis Effects 0.000 description 2
- ORWYRWWVDCYOMK-HBZPZAIKSA-N angiotensin I Chemical compound C([C@@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CC=1NC=NC=1)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CC=1NC=NC=1)C(=O)N[C@@H](CC(C)C)C(O)=O)NC(=O)[C@@H](NC(=O)[C@H](CCCN=C(N)N)NC(=O)[C@@H](N)CC(O)=O)C(C)C)C1=CC=C(O)C=C1 ORWYRWWVDCYOMK-HBZPZAIKSA-N 0.000 description 2
- 210000003423 ankle Anatomy 0.000 description 2
- 210000002376 aorta thoracic Anatomy 0.000 description 2
- 206010003119 arrhythmia Diseases 0.000 description 2
- 210000004556 brain Anatomy 0.000 description 2
- 229960004926 chlorobutanol Drugs 0.000 description 2
- 230000001684 chronic effect Effects 0.000 description 2
- 230000004087 circulation Effects 0.000 description 2
- 230000000295 complement effect Effects 0.000 description 2
- 230000009918 complex formation Effects 0.000 description 2
- 238000009833 condensation Methods 0.000 description 2
- 230000005494 condensation Effects 0.000 description 2
- 230000008602 contraction Effects 0.000 description 2
- 238000011161 development Methods 0.000 description 2
- 230000003205 diastolic effect Effects 0.000 description 2
- 235000005911 diet Nutrition 0.000 description 2
- 230000037213 diet Effects 0.000 description 2
- 230000004064 dysfunction Effects 0.000 description 2
- 230000009931 harmful effect Effects 0.000 description 2
- 230000010247 heart contraction Effects 0.000 description 2
- 208000019622 heart disease Diseases 0.000 description 2
- 208000018578 heart valve disease Diseases 0.000 description 2
- 230000000004 hemodynamic effect Effects 0.000 description 2
- 230000001631 hypertensive effect Effects 0.000 description 2
- 230000002452 interceptive effect Effects 0.000 description 2
- 210000000936 intestine Anatomy 0.000 description 2
- 238000002372 labelling Methods 0.000 description 2
- 210000004072 lung Anatomy 0.000 description 2
- 239000012528 membrane Substances 0.000 description 2
- 230000004060 metabolic process Effects 0.000 description 2
- 239000002207 metabolite Substances 0.000 description 2
- 230000005012 migration Effects 0.000 description 2
- 238000013508 migration Methods 0.000 description 2
- BQJCRHHNABKAKU-KBQPJGBKSA-N morphine Chemical class O([C@H]1[C@H](C=C[C@H]23)O)C4=C5[C@@]12CCN(C)[C@@H]3CC5=CC=C4O BQJCRHHNABKAKU-KBQPJGBKSA-N 0.000 description 2
- 210000003205 muscle Anatomy 0.000 description 2
- 229920001220 nitrocellulos Polymers 0.000 description 2
- 239000002736 nonionic surfactant Substances 0.000 description 2
- 235000021232 nutrient availability Nutrition 0.000 description 2
- 229960001412 pentobarbital Drugs 0.000 description 2
- 208000008494 pericarditis Diseases 0.000 description 2
- YBYRMVIVWMBXKQ-UHFFFAOYSA-N phenylmethanesulfonyl fluoride Chemical compound FS(=O)(=O)CC1=CC=CC=C1 YBYRMVIVWMBXKQ-UHFFFAOYSA-N 0.000 description 2
- DCWXELXMIBXGTH-UHFFFAOYSA-N phosphotyrosine Chemical compound OC(=O)C(N)CC1=CC=C(OP(O)(O)=O)C=C1 DCWXELXMIBXGTH-UHFFFAOYSA-N 0.000 description 2
- 229920002401 polyacrylamide Polymers 0.000 description 2
- 210000002307 prostate Anatomy 0.000 description 2
- 239000003223 protective agent Substances 0.000 description 2
- 230000029058 respiratory gaseous exchange Effects 0.000 description 2
- 210000002235 sarcomere Anatomy 0.000 description 2
- 239000011734 sodium Substances 0.000 description 2
- 239000000243 solution Substances 0.000 description 2
- 230000000638 stimulation Effects 0.000 description 2
- 239000000725 suspension Substances 0.000 description 2
- 208000011580 syndromic disease Diseases 0.000 description 2
- 238000007910 systemic administration Methods 0.000 description 2
- 238000013518 transcription Methods 0.000 description 2
- 230000035897 transcription Effects 0.000 description 2
- 238000001890 transfection Methods 0.000 description 2
- LWIHDJKSTIGBAC-UHFFFAOYSA-K tripotassium phosphate Chemical compound [K+].[K+].[K+].[O-]P([O-])([O-])=O LWIHDJKSTIGBAC-UHFFFAOYSA-K 0.000 description 2
- 208000019553 vascular disease Diseases 0.000 description 2
- 230000000007 visual effect Effects 0.000 description 2
- LNOBZXNCABUBKK-UHFFFAOYSA-N 2,3,5-triphenyltetrazolium Chemical compound C1=CC=CC=C1C(N=[N+]1C=2C=CC=CC=2)=NN1C1=CC=CC=C1 LNOBZXNCABUBKK-UHFFFAOYSA-N 0.000 description 1
- 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 1
- QKNYBSVHEMOAJP-UHFFFAOYSA-N 2-amino-2-(hydroxymethyl)propane-1,3-diol;hydron;chloride Chemical compound Cl.OCC(N)(CO)CO QKNYBSVHEMOAJP-UHFFFAOYSA-N 0.000 description 1
- LCSKNASZPVZHEG-UHFFFAOYSA-N 3,6-dimethyl-1,4-dioxane-2,5-dione;1,4-dioxane-2,5-dione Chemical group O=C1COC(=O)CO1.CC1OC(=O)C(C)OC1=O LCSKNASZPVZHEG-UHFFFAOYSA-N 0.000 description 1
- 229920000936 Agarose Polymers 0.000 description 1
- 108010072661 Angiotensin Amide Proteins 0.000 description 1
- 102000015427 Angiotensins Human genes 0.000 description 1
- 108010064733 Angiotensins Proteins 0.000 description 1
- 208000025494 Aortic disease Diseases 0.000 description 1
- 108010039627 Aprotinin Proteins 0.000 description 1
- 208000031104 Arterial Occlusive disease Diseases 0.000 description 1
- 206010003210 Arteriosclerosis Diseases 0.000 description 1
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 1
- 241000283690 Bos taurus Species 0.000 description 1
- 229940127291 Calcium channel antagonist Drugs 0.000 description 1
- 241000282472 Canis lupus familiaris Species 0.000 description 1
- 102000013602 Cardiac Myosins Human genes 0.000 description 1
- 108010051609 Cardiac Myosins Proteins 0.000 description 1
- 206010008479 Chest Pain Diseases 0.000 description 1
- 102000008130 Cyclic AMP-Dependent Protein Kinases Human genes 0.000 description 1
- 108010049894 Cyclic AMP-Dependent Protein Kinases Proteins 0.000 description 1
- 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
- 108020001019 DNA Primers Proteins 0.000 description 1
- 108010008286 DNA nucleotidylexotransferase Proteins 0.000 description 1
- 102100033215 DNA nucleotidylexotransferase Human genes 0.000 description 1
- 239000003155 DNA primer Substances 0.000 description 1
- 229920002307 Dextran Polymers 0.000 description 1
- SHIBSTMRCDJXLN-UHFFFAOYSA-N Digoxigenin Natural products C1CC(C2C(C3(C)CCC(O)CC3CC2)CC2O)(O)C2(C)C1C1=CC(=O)OC1 SHIBSTMRCDJXLN-UHFFFAOYSA-N 0.000 description 1
- 241000283086 Equidae Species 0.000 description 1
- 241000282326 Felis catus Species 0.000 description 1
- 206010016803 Fluid overload Diseases 0.000 description 1
- 229940123457 Free radical scavenger Drugs 0.000 description 1
- 102000003688 G-Protein-Coupled Receptors Human genes 0.000 description 1
- 108090000045 G-Protein-Coupled Receptors Proteins 0.000 description 1
- 208000034826 Genetic Predisposition to Disease Diseases 0.000 description 1
- 102100031181 Glyceraldehyde-3-phosphate dehydrogenase Human genes 0.000 description 1
- 239000004471 Glycine Substances 0.000 description 1
- 108010004889 Heat-Shock Proteins Proteins 0.000 description 1
- 206010021143 Hypoxia Diseases 0.000 description 1
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
- 102000042838 JAK family Human genes 0.000 description 1
- 108091082332 JAK family Proteins 0.000 description 1
- 229940122245 Janus kinase inhibitor Drugs 0.000 description 1
- YQEZLKZALYSWHR-UHFFFAOYSA-N Ketamine Chemical compound C=1C=CC=C(Cl)C=1C1(NC)CCCCC1=O YQEZLKZALYSWHR-UHFFFAOYSA-N 0.000 description 1
- 239000012839 Krebs-Henseleit buffer Substances 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
- 239000012741 Laemmli sample buffer Substances 0.000 description 1
- 102000043136 MAP kinase family Human genes 0.000 description 1
- 108091054455 MAP kinase family Proteins 0.000 description 1
- 229930195725 Mannitol Natural products 0.000 description 1
- 208000029549 Muscle injury Diseases 0.000 description 1
- 206010028851 Necrosis Diseases 0.000 description 1
- 206010028980 Neoplasm Diseases 0.000 description 1
- 238000000636 Northern blotting Methods 0.000 description 1
- 239000004677 Nylon Substances 0.000 description 1
- 241000282520 Papio Species 0.000 description 1
- 208000031481 Pathologic Constriction Diseases 0.000 description 1
- 108091000080 Phosphotransferase Proteins 0.000 description 1
- RVGRUAULSDPKGF-UHFFFAOYSA-N Poloxamer Chemical compound C1CO1.CC1CO1 RVGRUAULSDPKGF-UHFFFAOYSA-N 0.000 description 1
- 239000002202 Polyethylene glycol Substances 0.000 description 1
- 108010021757 Polynucleotide 5'-Hydroxyl-Kinase Proteins 0.000 description 1
- 102000008422 Polynucleotide 5'-hydroxyl-kinase Human genes 0.000 description 1
- 229920001213 Polysorbate 20 Polymers 0.000 description 1
- 241000288906 Primates Species 0.000 description 1
- 102000003923 Protein Kinase C Human genes 0.000 description 1
- 108090000315 Protein Kinase C Proteins 0.000 description 1
- 102000052575 Proto-Oncogene Human genes 0.000 description 1
- 108700020978 Proto-Oncogene Proteins 0.000 description 1
- 101000885869 Rattus norvegicus Glyceraldehyde-3-phosphate dehydrogenase Proteins 0.000 description 1
- 208000001647 Renal Insufficiency Diseases 0.000 description 1
- 241000283984 Rodentia Species 0.000 description 1
- 101150001535 SRC gene Proteins 0.000 description 1
- 102000004265 STAT2 Transcription Factor Human genes 0.000 description 1
- 108010081691 STAT2 Transcription Factor Proteins 0.000 description 1
- 102000005886 STAT4 Transcription Factor Human genes 0.000 description 1
- 108010019992 STAT4 Transcription Factor Proteins 0.000 description 1
- 101150063267 STAT5B gene Proteins 0.000 description 1
- 206010039491 Sarcoma Diseases 0.000 description 1
- 102100024474 Signal transducer and activator of transcription 5B Human genes 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
- 239000004809 Teflon Substances 0.000 description 1
- 229920006362 Teflon® Polymers 0.000 description 1
- 239000013504 Triton X-100 Substances 0.000 description 1
- 229920004890 Triton X-100 Polymers 0.000 description 1
- 206010047115 Vasculitis Diseases 0.000 description 1
- 208000027418 Wounds and injury Diseases 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
- 210000000683 abdominal cavity Anatomy 0.000 description 1
- 210000003815 abdominal wall Anatomy 0.000 description 1
- 230000002159 abnormal effect Effects 0.000 description 1
- 150000001408 amides Chemical class 0.000 description 1
- 229940035674 anesthetics Drugs 0.000 description 1
- 108010072788 angiogenin Proteins 0.000 description 1
- 238000002399 angioplasty Methods 0.000 description 1
- 238000010171 animal model Methods 0.000 description 1
- 239000003963 antioxidant agent Substances 0.000 description 1
- 229940027983 antiseptic and disinfectant quaternary ammonium compound Drugs 0.000 description 1
- 210000000709 aorta Anatomy 0.000 description 1
- 230000001640 apoptogenic effect Effects 0.000 description 1
- 229960004405 aprotinin Drugs 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 230000006793 arrhythmia Effects 0.000 description 1
- 208000021328 arterial occlusion Diseases 0.000 description 1
- 210000002565 arteriole Anatomy 0.000 description 1
- 208000011775 arteriosclerosis disease Diseases 0.000 description 1
- 206010003230 arteritis Diseases 0.000 description 1
- 210000001367 artery Anatomy 0.000 description 1
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
- 230000003305 autocrine Effects 0.000 description 1
- 238000000376 autoradiography Methods 0.000 description 1
- 238000010009 beating Methods 0.000 description 1
- 230000008901 benefit Effects 0.000 description 1
- XCFDKXLSJRKPRJ-UHFFFAOYSA-N benzaldehyde propanedinitrile Chemical compound C(CC#N)#N.C(C1=CC=CC=C1)=O XCFDKXLSJRKPRJ-UHFFFAOYSA-N 0.000 description 1
- 229960000686 benzalkonium chloride Drugs 0.000 description 1
- CADWTSSKOVRVJC-UHFFFAOYSA-N benzyl(dimethyl)azanium;chloride Chemical compound [Cl-].C[NH+](C)CC1=CC=CC=C1 CADWTSSKOVRVJC-UHFFFAOYSA-N 0.000 description 1
- 239000002876 beta blocker Substances 0.000 description 1
- 229940097320 beta blocking agent Drugs 0.000 description 1
- 230000008436 biogenesis Effects 0.000 description 1
- 230000033228 biological regulation Effects 0.000 description 1
- 201000011510 cancer Diseases 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 230000000747 cardiac effect Effects 0.000 description 1
- 229940030602 cardiac therapy drug Drugs 0.000 description 1
- 230000005961 cardioprotection Effects 0.000 description 1
- 230000003293 cardioprotective effect Effects 0.000 description 1
- 230000009084 cardiovascular function Effects 0.000 description 1
- 210000001168 carotid artery common Anatomy 0.000 description 1
- 230000005779 cell damage Effects 0.000 description 1
- 230000003915 cell function Effects 0.000 description 1
- 208000037887 cell injury Diseases 0.000 description 1
- 230000001413 cellular effect Effects 0.000 description 1
- 230000033077 cellular process Effects 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 210000000038 chest Anatomy 0.000 description 1
- 235000015218 chewing gum Nutrition 0.000 description 1
- 238000012761 co-transfection Methods 0.000 description 1
- 230000001447 compensatory effect Effects 0.000 description 1
- 230000008828 contractile function Effects 0.000 description 1
- 239000013068 control sample Substances 0.000 description 1
- 238000013270 controlled release Methods 0.000 description 1
- 208000029078 coronary artery disease Diseases 0.000 description 1
- 230000002596 correlated effect Effects 0.000 description 1
- 230000000875 corresponding effect Effects 0.000 description 1
- 210000000805 cytoplasm Anatomy 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 230000001419 dependent effect Effects 0.000 description 1
- 230000004069 differentiation Effects 0.000 description 1
- QONQRTHLHBTMGP-UHFFFAOYSA-N digitoxigenin Natural products CC12CCC(C3(CCC(O)CC3CC3)C)C3C11OC1CC2C1=CC(=O)OC1 QONQRTHLHBTMGP-UHFFFAOYSA-N 0.000 description 1
- SHIBSTMRCDJXLN-KCZCNTNESA-N digoxigenin Chemical compound C1([C@@H]2[C@@]3([C@@](CC2)(O)[C@H]2[C@@H]([C@@]4(C)CC[C@H](O)C[C@H]4CC2)C[C@H]3O)C)=CC(=O)OC1 SHIBSTMRCDJXLN-KCZCNTNESA-N 0.000 description 1
- 201000011304 dilated cardiomyopathy 1A Diseases 0.000 description 1
- 238000010790 dilution Methods 0.000 description 1
- 239000012895 dilution Substances 0.000 description 1
- 229910001873 dinitrogen Inorganic materials 0.000 description 1
- 208000035475 disorder Diseases 0.000 description 1
- 239000003937 drug carrier Substances 0.000 description 1
- 238000002592 echocardiography Methods 0.000 description 1
- 210000003989 endothelium vascular Anatomy 0.000 description 1
- 230000007613 environmental effect Effects 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 239000013613 expression plasmid Substances 0.000 description 1
- 210000001105 femoral artery Anatomy 0.000 description 1
- 239000012530 fluid Substances 0.000 description 1
- MHMNJMPURVTYEJ-UHFFFAOYSA-N fluorescein-5-isothiocyanate Chemical compound O1C(=O)C2=CC(N=C=S)=CC=C2C21C1=CC=C(O)C=C1OC1=CC(O)=CC=C21 MHMNJMPURVTYEJ-UHFFFAOYSA-N 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 230000006870 function Effects 0.000 description 1
- 239000003193 general anesthetic agent Substances 0.000 description 1
- 108020004445 glyceraldehyde-3-phosphate dehydrogenase Proteins 0.000 description 1
- 230000001435 haemodynamic effect Effects 0.000 description 1
- 230000005802 health problem Effects 0.000 description 1
- 210000002064 heart cell Anatomy 0.000 description 1
- 210000005003 heart tissue Anatomy 0.000 description 1
- 210000003709 heart valve Anatomy 0.000 description 1
- 206010073071 hepatocellular carcinoma Diseases 0.000 description 1
- 210000003494 hepatocyte Anatomy 0.000 description 1
- WGCNASOHLSPBMP-UHFFFAOYSA-N hydroxyacetaldehyde Natural products OCC=O WGCNASOHLSPBMP-UHFFFAOYSA-N 0.000 description 1
- 230000001969 hypertrophic effect Effects 0.000 description 1
- 238000013115 immunohistochemical detection Methods 0.000 description 1
- 230000006698 induction Effects 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- ZPNFWUPYTFPOJU-LPYSRVMUSA-N iniprol Chemical compound C([C@H]1C(=O)NCC(=O)NCC(=O)N[C@H]2CSSC[C@H]3C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@H](C(N[C@H](C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC=4C=CC(O)=CC=4)C(=O)N[C@@H](CC=4C=CC=CC=4)C(=O)N[C@@H](CC=4C=CC(O)=CC=4)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](C)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](C)C(=O)NCC(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CSSC[C@H](NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C)NC(=O)[C@H](CO)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CC=4C=CC=CC=4)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CCCCN)NC(=O)[C@H](C)NC(=O)[C@H](CCCNC(N)=N)NC2=O)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CSSC[C@H](NC(=O)[C@H](CC=2C=CC=CC=2)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H]2N(CCC2)C(=O)[C@@H](N)CCCNC(N)=N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(O)=O)C(=O)N2[C@@H](CCC2)C(=O)N2[C@@H](CCC2)C(=O)N[C@@H](CC=2C=CC(O)=CC=2)C(=O)N[C@@H]([C@@H](C)O)C(=O)NCC(=O)N2[C@@H](CCC2)C(=O)N3)C(=O)NCC(=O)NCC(=O)N[C@@H](C)C(O)=O)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@H](C(=O)N[C@@H](CC=2C=CC=CC=2)C(=O)N[C@H](C(=O)N1)C(C)C)[C@@H](C)O)[C@@H](C)CC)=O)[C@@H](C)CC)C1=CC=C(O)C=C1 ZPNFWUPYTFPOJU-LPYSRVMUSA-N 0.000 description 1
- 230000000977 initiatory effect Effects 0.000 description 1
- 208000014674 injury Diseases 0.000 description 1
- 230000003993 interaction Effects 0.000 description 1
- 230000031146 intracellular signal transduction Effects 0.000 description 1
- 239000007928 intraperitoneal injection Substances 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- 238000011835 investigation Methods 0.000 description 1
- 239000007951 isotonicity adjuster Substances 0.000 description 1
- 229960003299 ketamine Drugs 0.000 description 1
- 201000006370 kidney failure Diseases 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 231100000636 lethal dose Toxicity 0.000 description 1
- 210000004185 liver Anatomy 0.000 description 1
- 238000011068 loading method Methods 0.000 description 1
- 230000033001 locomotion Effects 0.000 description 1
- 238000011866 long-term treatment Methods 0.000 description 1
- 238000003670 luciferase enzyme activity assay Methods 0.000 description 1
- 239000012139 lysis buffer Substances 0.000 description 1
- TWRXJAOTZQYOKJ-UHFFFAOYSA-L magnesium chloride Substances [Mg+2].[Cl-].[Cl-] TWRXJAOTZQYOKJ-UHFFFAOYSA-L 0.000 description 1
- 229910001629 magnesium chloride Inorganic materials 0.000 description 1
- 210000004962 mammalian cell Anatomy 0.000 description 1
- 239000000594 mannitol Substances 0.000 description 1
- 235000010355 mannitol Nutrition 0.000 description 1
- 239000003550 marker Substances 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 230000001404 mediated effect Effects 0.000 description 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
- 238000000386 microscopy Methods 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 238000010369 molecular cloning Methods 0.000 description 1
- 239000003147 molecular marker Substances 0.000 description 1
- 229960005181 morphine Drugs 0.000 description 1
- 229940126619 mouse monoclonal antibody Drugs 0.000 description 1
- 230000035772 mutation Effects 0.000 description 1
- 230000010016 myocardial function Effects 0.000 description 1
- 230000017074 necrotic cell death Effects 0.000 description 1
- 239000002773 nucleotide Substances 0.000 description 1
- 125000003729 nucleotide group Chemical group 0.000 description 1
- 229920001778 nylon Polymers 0.000 description 1
- 229920001542 oligosaccharide Polymers 0.000 description 1
- 150000002482 oligosaccharides Chemical class 0.000 description 1
- 238000000399 optical microscopy Methods 0.000 description 1
- 230000003204 osmotic effect Effects 0.000 description 1
- 230000003647 oxidation Effects 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- 239000001301 oxygen Substances 0.000 description 1
- 229910052760 oxygen Inorganic materials 0.000 description 1
- 230000036961 partial effect Effects 0.000 description 1
- 230000001575 pathological effect Effects 0.000 description 1
- 230000007170 pathology Effects 0.000 description 1
- 230000037361 pathway Effects 0.000 description 1
- 230000000737 periodic effect Effects 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 1
- WVDDGKGOMKODPV-ZQBYOMGUSA-N phenyl(114C)methanol Chemical compound O[14CH2]C1=CC=CC=C1 WVDDGKGOMKODPV-ZQBYOMGUSA-N 0.000 description 1
- 239000008363 phosphate buffer Substances 0.000 description 1
- 102000020233 phosphotransferase Human genes 0.000 description 1
- 239000006187 pill Substances 0.000 description 1
- 201000003144 pneumothorax Diseases 0.000 description 1
- 229920001993 poloxamer 188 Polymers 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- 239000000256 polyoxyethylene sorbitan monolaurate Substances 0.000 description 1
- 235000010486 polyoxyethylene sorbitan monolaurate Nutrition 0.000 description 1
- 235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 description 1
- 229920002503 polyoxyethylene-polyoxypropylene Polymers 0.000 description 1
- 229920000136 polysorbate Polymers 0.000 description 1
- 229950008882 polysorbate Drugs 0.000 description 1
- 229920000053 polysorbate 80 Polymers 0.000 description 1
- 229910000160 potassium phosphate Inorganic materials 0.000 description 1
- 235000011009 potassium phosphates Nutrition 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 238000012545 processing Methods 0.000 description 1
- 230000002035 prolonged effect Effects 0.000 description 1
- 230000000069 prophylactic effect Effects 0.000 description 1
- 238000011321 prophylaxis Methods 0.000 description 1
- 230000004224 protection Effects 0.000 description 1
- 238000001243 protein synthesis Methods 0.000 description 1
- 230000002685 pulmonary effect Effects 0.000 description 1
- 230000000541 pulsatile effect Effects 0.000 description 1
- 230000001698 pyrogenic effect Effects 0.000 description 1
- 150000003856 quaternary ammonium compounds Chemical class 0.000 description 1
- 239000002516 radical scavenger Substances 0.000 description 1
- 239000000376 reactant Substances 0.000 description 1
- 239000011541 reaction mixture Substances 0.000 description 1
- 230000021419 recognition of apoptotic cell Effects 0.000 description 1
- 238000011084 recovery Methods 0.000 description 1
- 230000002040 relaxant effect Effects 0.000 description 1
- 230000000241 respiratory effect Effects 0.000 description 1
- 230000036387 respiratory rate Effects 0.000 description 1
- 208000004124 rheumatic heart disease Diseases 0.000 description 1
- 231100000241 scar Toxicity 0.000 description 1
- 238000012216 screening Methods 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 238000004904 shortening Methods 0.000 description 1
- 239000001488 sodium phosphate Substances 0.000 description 1
- 229910000162 sodium phosphate Inorganic materials 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 238000010186 staining Methods 0.000 description 1
- 230000036262 stenosis Effects 0.000 description 1
- 208000037804 stenosis Diseases 0.000 description 1
- 230000002966 stenotic effect Effects 0.000 description 1
- 210000001562 sternum Anatomy 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- 125000001424 substituent group Chemical group 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- 150000005846 sugar alcohols Chemical class 0.000 description 1
- 230000001629 suppression Effects 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 230000001839 systemic circulation Effects 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- -1 tetrarose Chemical compound 0.000 description 1
- 229940124597 therapeutic agent Drugs 0.000 description 1
- 210000001541 thymus gland Anatomy 0.000 description 1
- 230000000451 tissue damage Effects 0.000 description 1
- 231100000827 tissue damage Toxicity 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 238000002627 tracheal intubation Methods 0.000 description 1
- 230000002463 transducing effect Effects 0.000 description 1
- 230000014616 translation Effects 0.000 description 1
- 239000005483 tyrosine kinase inhibitor Substances 0.000 description 1
- 150000004917 tyrosine kinase inhibitor derivatives Chemical class 0.000 description 1
- 238000011144 upstream manufacturing Methods 0.000 description 1
- 230000002792 vascular Effects 0.000 description 1
- 230000006442 vascular tone Effects 0.000 description 1
- 210000005166 vasculature Anatomy 0.000 description 1
- 229940124549 vasodilator Drugs 0.000 description 1
- 239000003071 vasodilator agent Substances 0.000 description 1
- 235000012431 wafers Nutrition 0.000 description 1
- 239000011534 wash buffer Substances 0.000 description 1
- BPICBUSOMSTKRF-UHFFFAOYSA-N xylazine Chemical compound CC1=CC=CC(C)=C1NC1=NCCCS1 BPICBUSOMSTKRF-UHFFFAOYSA-N 0.000 description 1
- 229960001600 xylazine Drugs 0.000 description 1
Images
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/16—Amides, e.g. hydroxamic acids
- A61K31/165—Amides, e.g. hydroxamic acids having aromatic rings, e.g. colchicine, atenolol, progabide
-
- 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
- A61K31/275—Nitriles; Isonitriles
- A61K31/277—Nitriles; Isonitriles having a ring, e.g. verapamil
-
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/04—Inotropic agents, i.e. stimulants of cardiac contraction; Drugs for heart failure
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
-
- 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
Landscapes
- Health & Medical Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Veterinary Medicine (AREA)
- Pharmacology & Pharmacy (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Life Sciences & Earth Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Cardiology (AREA)
- Epidemiology (AREA)
- Heart & Thoracic Surgery (AREA)
- Urology & Nephrology (AREA)
- Vascular Medicine (AREA)
- Hospice & Palliative Care (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US09/945,192 US6433018B1 (en) | 2001-08-31 | 2001-08-31 | Method for reducing hypertrophy and ischemia |
| PCT/US2002/023444 WO2003020202A2 (en) | 2001-08-31 | 2002-07-23 | Method for reducing hypertension and heart failure |
Related Child Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2010180146A Division JP2010285455A (ja) | 2001-08-31 | 2010-08-11 | 高血圧及び心不全を減少させる方法 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JP2005505545A true JP2005505545A (ja) | 2005-02-24 |
| JP2005505545A5 JP2005505545A5 (OSRAM) | 2006-01-05 |
Family
ID=25482762
Family Applications (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2003524516A Pending JP2005505545A (ja) | 2001-08-31 | 2002-07-23 | 高血圧及び心不全を減少させる方法 |
| JP2010180146A Pending JP2010285455A (ja) | 2001-08-31 | 2010-08-11 | 高血圧及び心不全を減少させる方法 |
Family Applications After (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2010180146A Pending JP2010285455A (ja) | 2001-08-31 | 2010-08-11 | 高血圧及び心不全を減少させる方法 |
Country Status (11)
| Country | Link |
|---|---|
| US (2) | US6433018B1 (OSRAM) |
| EP (1) | EP1427401A4 (OSRAM) |
| JP (2) | JP2005505545A (OSRAM) |
| KR (1) | KR20040050894A (OSRAM) |
| AU (1) | AU2002313700B2 (OSRAM) |
| BR (1) | BR0212252A (OSRAM) |
| CA (1) | CA2458798C (OSRAM) |
| MX (1) | MXPA04001913A (OSRAM) |
| NZ (1) | NZ531693A (OSRAM) |
| WO (1) | WO2003020202A2 (OSRAM) |
| ZA (1) | ZA200402540B (OSRAM) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2011126258A (ja) * | 2009-12-21 | 2011-06-30 | Panasonic Electric Works Co Ltd | 繊維ボードの製造方法 |
Families Citing this family (33)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6433018B1 (en) * | 2001-08-31 | 2002-08-13 | The Research Foundation Of State University Of New York | Method for reducing hypertrophy and ischemia |
| TWI329105B (en) | 2002-02-01 | 2010-08-21 | Rigel Pharmaceuticals Inc | 2,4-pyrimidinediamine compounds and their uses |
| US20050038450A1 (en) * | 2003-06-03 | 2005-02-17 | Ping Hu | Methods and apparatus for minimally invasive transverse aortic banding |
| CN102358738A (zh) | 2003-07-30 | 2012-02-22 | 里格尔药品股份有限公司 | 2,4-嘧啶二胺化合物及其预防和治疗自体免疫疾病的用途 |
| US20050130893A1 (en) * | 2003-09-30 | 2005-06-16 | Joan Smith-Sonneborn | Use of opioids in prevention of and recovery from a stress-induced crash in blood pressure |
| PT1701941E (pt) | 2003-12-11 | 2012-08-03 | Univ Texas | Compostos para o tratamento de doenças proliferativas celulares |
| US7662389B2 (en) * | 2003-12-17 | 2010-02-16 | Alcon, Inc. | Use of serum amyloid A gene in diagnosis and treatment of glaucoma and identification of anti-glaucoma agents |
| TWI398261B (zh) * | 2003-12-17 | 2013-06-11 | Alcon Inc | 血清類澱粉ａ基因於診斷及治療青光眼及鑑定抗青光眼劑上之用途 |
| US20100113481A1 (en) * | 2003-12-17 | 2010-05-06 | Alcon Research, Ltd. | Use of serum amyloid a gene in diagnosis and treatment of glaucoma and identification of anti-glaucoma agents |
| US8691877B2 (en) * | 2004-10-15 | 2014-04-08 | Palo Alto Investors | Methods and compositions for treating a disease condition in a subject |
| EP1904457B1 (en) | 2005-06-08 | 2017-09-06 | Rigel Pharmaceuticals, Inc. | Compositions and methods for inhibition of the jak pathway |
| US20070203161A1 (en) * | 2006-02-24 | 2007-08-30 | Rigel Pharmaceuticals, Inc. | Compositions and methods for inhibition of the jak pathway |
| US10517876B2 (en) | 2005-11-16 | 2019-12-31 | Cti Biopharma Corp. | Oxygen linked pyrimidine derivatives |
| ES2506040T3 (es) | 2005-11-16 | 2014-10-13 | Cti Biopharma Corp. | Derivados de pirimidina ligados a oxígeno |
| CA2637044A1 (en) * | 2006-01-13 | 2007-07-26 | President And Fellows Of Harvard College | Xenohormesis based compositions and methods |
| JP2009528295A (ja) * | 2006-02-24 | 2009-08-06 | ライジェル ファーマシューティカルズ， インコーポレイテッド | Ｊａｋ経路の阻害のための組成物および方法 |
| US8410173B2 (en) * | 2006-02-28 | 2013-04-02 | Ym Biosciences Australia Pty Ltd | Inhibition of JAK2 as a treatment of pulmonary arterial hypertension |
| PL2514742T3 (pl) * | 2006-03-31 | 2015-07-31 | Univ Texas | Leki przeciwnowotworowe będące pochodnymi kwasu kawowego dostępnymi biologicznie po podaniu doustnym |
| US8486941B2 (en) | 2007-03-12 | 2013-07-16 | Ym Biosciences Australia Pty Ltd | Phenyl amino pyrimidine compounds and uses thereof |
| HUE030912T2 (en) | 2008-02-15 | 2017-06-28 | Rigel Pharmaceuticals Inc | Pyrimidine-2-amine compounds and their use as inhibitors of yak kinases |
| MX2010011463A (es) | 2008-04-16 | 2011-06-03 | Portola Pharm Inc | 2,6-diamino-pirimidin-5-il-carboxamidas como inhibidores de syk o jak quinasas. |
| US8138339B2 (en) * | 2008-04-16 | 2012-03-20 | Portola Pharmaceuticals, Inc. | Inhibitors of protein kinases |
| JP2011518219A (ja) | 2008-04-22 | 2011-06-23 | ポートラ ファーマシューティカルズ， インコーポレイテッド | タンパク質キナーゼの阻害剤 |
| US10517839B2 (en) * | 2008-06-09 | 2019-12-31 | Cornell University | Mast cell inhibition in diseases of the retina and vitreous |
| JP5675606B2 (ja) | 2008-07-08 | 2015-02-25 | ボード・オブ・リージエンツ，ザ・ユニバーシテイ・オブ・テキサス・システム | シグナル伝達性転写因子（ｓｔａｔ）の増殖及び活性化の新規の抑制剤 |
| SG171907A1 (en) | 2008-12-11 | 2011-07-28 | S Bio Pte Ltd | 11-(2-pyrrolidin-1-yl-ethoxy)-14,19-dioxa-5,7,26-triaza-tetracyclo[19.3.1.1(2,6)1(8,12)]heptacosa-1(25),2(26),3,5,8,10,12(27)j16,21,23-decaene citrate salt |
| CA2768543C (en) * | 2009-07-28 | 2017-06-20 | Rigel Pharmaceuticals, Inc. | Compositions and methods for inhibition of the jak pathway |
| EP2635557A2 (en) | 2010-11-01 | 2013-09-11 | Portola Pharmaceuticals, Inc. | Nicotinamides as jak kinase modulators |
| SG11201402570QA (en) | 2011-11-23 | 2014-06-27 | Portola Pharm Inc | Pyrazine kinase inhibitors |
| US8809359B2 (en) | 2012-06-29 | 2014-08-19 | Ym Biosciences Australia Pty Ltd | Phenyl amino pyrimidine bicyclic compounds and uses thereof |
| US9676756B2 (en) | 2012-10-08 | 2017-06-13 | Portola Pharmaceuticals, Inc. | Substituted pyrimidinyl kinase inhibitors |
| TWI729644B (zh) | 2014-06-12 | 2021-06-01 | 美商西爾拉癌症醫學公司 | N-(氰基甲基)-4-(2-(4-𠰌啉基苯基胺基)嘧啶-4-基)苯甲醯胺 |
| WO2018002673A1 (en) | 2016-07-01 | 2018-01-04 | N4 Pharma Uk Limited | Novel formulations of angiotensin ii receptor antagonists |
Family Cites Families (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5138069A (en) * | 1986-07-11 | 1992-08-11 | E. I. Du Pont De Nemours And Company | Angiotensin II receptor blocking imidazoles |
| CA2012634A1 (en) * | 1990-03-20 | 1991-09-20 | Hassan Salari | Tyrphostins for treatment of allergic, inflammatory and cardiovascular diseases |
| US5443836A (en) | 1993-03-15 | 1995-08-22 | Gensia, Inc. | Methods for protecting tissues and organs from ischemic damage |
| US6255296B1 (en) | 1994-01-11 | 2001-07-03 | Endomatrix, Inc. | Composition and method for treating a patient susceptible to or suffering from a cardiovascular disorder or disease |
| IL119069A0 (en) | 1996-08-14 | 1996-11-14 | Mor Research Applic Ltd | Pharmaceutical composition comprising tyrphostins |
| US6358954B1 (en) * | 1999-11-09 | 2002-03-19 | Yissum Research Development Company Of The Hebrew University Of Jerusalem | PDGF receptor kinase inhibitory compounds, their preparation, purification and pharmaceutical compositions including same |
| US6433018B1 (en) * | 2001-08-31 | 2002-08-13 | The Research Foundation Of State University Of New York | Method for reducing hypertrophy and ischemia |
| DE602006000402T8 (de) * | 2006-06-02 | 2009-04-09 | Teva Pharmaceutical Industries Ltd. | Stabile Zubereitung enthaltend eine feuchtigkeitsempfindliche aktive Substanz und Verfahren zur Herstellung der Zubereitung. |
-
2001
- 2001-08-31 US US09/945,192 patent/US6433018B1/en not_active Expired - Lifetime
-
2002
- 2002-07-23 NZ NZ531693A patent/NZ531693A/en not_active IP Right Cessation
- 2002-07-23 JP JP2003524516A patent/JP2005505545A/ja active Pending
- 2002-07-23 CA CA2458798A patent/CA2458798C/en not_active Expired - Fee Related
- 2002-07-23 MX MXPA04001913A patent/MXPA04001913A/es active IP Right Grant
- 2002-07-23 EP EP02753409A patent/EP1427401A4/en not_active Withdrawn
- 2002-07-23 AU AU2002313700A patent/AU2002313700B2/en not_active Ceased
- 2002-07-23 WO PCT/US2002/023444 patent/WO2003020202A2/en not_active Ceased
- 2002-07-23 US US10/488,279 patent/US7235588B2/en not_active Expired - Lifetime
- 2002-07-23 KR KR10-2004-7003111A patent/KR20040050894A/ko not_active Ceased
- 2002-07-23 BR BR0212252-9A patent/BR0212252A/pt not_active IP Right Cessation
-
2004
- 2004-03-31 ZA ZA2004/02540A patent/ZA200402540B/en unknown
-
2010
- 2010-08-11 JP JP2010180146A patent/JP2010285455A/ja active Pending
Non-Patent Citations (10)
| Title |
|---|
| JPN6008060998, ＭＡＬＬＯＹ，Ｌ．Ｇ． ｅｔ ａｌ, "Ｔｙｒｏｓｉｎｅ ｋｉｎａｓｅ ｉｎｈｉｂｉｔｉｏｎ ｓｕｐｐｒｅｓｓｅｓ ａｎｇｉｏｔｅｎｓｉｎ ｃｏｎｔｒａｃｔｉｏｎ ｉｎ ｈｙｐｅｒｔｅｎｓｉｖｅ ａｎｄ ｎｏｒｍｏｔｅｎｓｉｖｅ ｓｍａｌｌ", Ｌｉｆｅ Ｓｃｉ, 1996, Ｖｏｌ．５８， Ｎｏ．１９, ｐ．ＰＬ３１７−２４ * |
| JPN6008061014, ＳＡＵＲＯ，Ｍ．Ｄ． ｅｔ ａｌ, "Ｔｙｒｐｈｏｓｔｉｎ ａｔｔｅｎｕａｔｅｓ ｐｌａｔｅｌｅｔ−ｄｅｒｉｖｅｄ ｇｒｏｗｔｈ ｆａｃｔｏｒ−ｉｎｄｕｃｅｄ ｃｏｎｔｒａｃｔｉｏｎ ｉｎ ａｏｒｔｉｃ ｓｍｏｏｔｈ ｍｕｓｃｌｅ ｔｈｒ", Ｊ Ｐｈａｒｍａｃｏｌ Ｅｘｐ Ｔｈｅｒ, 1993, Ｖｏｌ．２６７， Ｎｏ．３, ｐ．１１１９−２５ * |
| JPN6008061016, メルクマニュアル 日本語版, 1999, 第１７版, 第１６７４−１６７６頁, 日経ＢＰ社 * |
| JPN6008061018, "ＪＡＫ／ＳＴＡＴ ｓｉｇｎａｌｉｎｇ ｉｓ ａｓｓｏｃｉａｔｅｄ ｗｉｔｈ ｃａｒｄｉａｃ ｄｙｓｆｕｎｃｔｉｏｎ ｄｕｒｉｎｇ ｉｓｃｈｅｍｉａ ａｎｄ ｒｅｐｅｒｆｕｓｉｏｎ", Ｃｉｒｃｕｌａｔｉｏｎ, 200107, Ｖｏｌ．１０４， Ｎｏ．３, ｐ．３２５−９ * |
| JPN6009043351, ＡＭＥＲＩＣＡＮ ＪＯＵＲＮＡＬ ＯＦ ＨＹＰＥＲＴＥＮＳＩＯＮ, 200104, Ｖｏｌ．１４， Ｎｏ．４， Ｐａｒｔ ２, １５１Ａ−１５２Ａ * |
| JPN6009043353, ＲＵＥＴＴＥＮ，Ｈ． ｅｔ ａｌ, "Ｅｆｆｅｃｔｓ ｏｆ ｔｙｒｐｈｏｓｔｉｎｓ ａｎｄ ｇｅｎｉｓｔｅｉｎ ｏｎ ｔｈｅ ｃｉｒｃｕｌａｔｏｒｙ ｆａｉｌｕｒｅ ａｎｄ ｏｒｇａｎ ｄｙｓｆｕｎｃｔｉｏｎ ｃａｕｓｅｄ ｂｙ ｅｎｄｏ", Ｂｒ Ｊ Ｐｈａｒｍａｃｏｌ, 1997, Ｖｏｌ．１２２， Ｎｏ．１, ｐ．５９−７０ * |
| JPN6009043355, ＪＯＵＲＮＡＬ ＯＦ ＭＯＬＥＣＵＬＡＲ ＡＮＤ ＣＥＬＬＵＬＡＲ ＣＡＲＤＩＯＬＯＧＹ, 200106, Ｖｏｌ．３３， Ｎｏ．６, Ａ１０ * |
| JPN6009043357, ＭＡＮＡＢＥ，Ｔ． ｅｔ ａｌ, "Ｈｙｐｅｒｔｒｏｐｈｉｃ ｓｔｉｍｕｌｉ ａｕｇｍｅｎｔ ｅｘｐｒｅｓｓｉｏｎ ｏｆ ｃＭＧ１／ＥＲＦ−１， ａ ｐｕｔａｔｉｖｅ ｚｉｎｃ−ｆｉｎｇｅｒ ｍｏｔｉｆ ｔｒａｎｓｃｒｉｐｔｉｏｎ ｆａ", ＦＥＢＳ Ｌｅｔｔ, 1999, Ｖｏｌ．４６３， Ｎｏ．１−２, ｐ．３９−４２ * |
| JPN6009043358, "Ｃａｒｄｉｏｔｒｏｐｈｉｎ−１ ｉｎｃｒｅａｓｅｓ ａｎｇｉｏｔｅｎｓｉｎｏｇｅｎ ｍＲＮＡ ｉｎ ｒａｔ ｃａｒｄｉａｃ ｍｙｏｃｙｔｅｓ ｔｈｒｏｕｇｈ ＳＴＡＴ３ ： ａｎ ａｕｔｏｃｒｉｎｅ", Ｈｙｐｅｒｔｅｎｓｉｏｎ, 2000, Ｖｏｌ．３５， Ｎｏ．６, ｐ．１１９１−６ * |
| JPN6010018321, "高血圧性肥大心左室心筋におけるＪＡＫ−ＳＴＡＴ系の機械的伸展負荷に対する活性化亢進と内因性アンジオテンシンＩＩ", Ｊａｐａｎｅｓｅ Ｃｉｒｃｕｌａｔｉｏｎ Ｊｏｕｒｎａｌ, 2000, Ｖｏｌ．６４， Ｓｕｐｐｌ．１, 第６３４頁 * |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2011126258A (ja) * | 2009-12-21 | 2011-06-30 | Panasonic Electric Works Co Ltd | 繊維ボードの製造方法 |
Also Published As
| Publication number | Publication date |
|---|---|
| CA2458798A1 (en) | 2003-03-13 |
| ZA200402540B (en) | 2005-06-29 |
| US6433018B1 (en) | 2002-08-13 |
| BR0212252A (pt) | 2004-09-14 |
| WO2003020202A3 (en) | 2003-08-28 |
| NZ531693A (en) | 2006-05-26 |
| EP1427401A2 (en) | 2004-06-16 |
| AU2002313700B2 (en) | 2007-04-26 |
| JP2010285455A (ja) | 2010-12-24 |
| MXPA04001913A (es) | 2004-06-18 |
| CA2458798C (en) | 2013-06-25 |
| WO2003020202A2 (en) | 2003-03-13 |
| US7235588B2 (en) | 2007-06-26 |
| EP1427401A4 (en) | 2009-04-29 |
| KR20040050894A (ko) | 2004-06-17 |
| US20040266661A1 (en) | 2004-12-30 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| JP2010285455A (ja) | 高血圧及び心不全を減少させる方法 | |
| AU2002313700A1 (en) | Method for reducing hypertension and heart failure | |
| BG107994A (bg) | 4-"л"оро-n-индан-2-илб...нзамид и използван...'о м" ка'о "арма-...в'и-но 'р...д''во | |
| CZ330896A3 (cs) | Použití látky, která brání nebo minimalizuje oxidaci polynenasycené mastné kyseliny a způsoby s tímto použitím spojené | |
| JP7193874B2 (ja) | 筋肉Ａキナーゼアンカータンパク質（ｍＡＫＡＰ）作用の阻害による心臓病の処置 | |
| JP2004537582A (ja) | 心疾患の処置または予防における使用のためのａｐｊ受容体の調節 | |
| TW201026684A (en) | Phosphodiesterase type III (PDE III) inhibitors or Ca2+ -sensitizing agents for the treatment of hypertrophic cardiomyopathy | |
| US8361966B2 (en) | Use of interleukin-11 as therapeutic agent for heart disease | |
| JPWO2005105793A1 (ja) | 筋弛緩促進剤及び筋弛緩不全等の筋組織に係る疾病の治療薬 | |
| CN103429242A (zh) | 用于预防和治疗心脏肥大的方法和组合物 | |
| JP6688503B2 (ja) | 医薬用組成物 | |
| Mertes et al. | Consequences of coronary occlusion on changes in regional interstitial myocardial neuropeptide Y and norepinephrine concentrations | |
| KR102564240B1 (ko) | 선택적 히스톤탈아세틸화 효소 8 억제제를 포함하는 심장 질환 예방 또는 치료용 조성물 | |
| CN109758459B (zh) | 取代的吡啶的新用途 | |
| Yoshiyama et al. | Effect of manidipine hydrochloride, a calcium antagonist, on isoproterenol-induced left ventricular hypertrophy | |
| JP4723115B2 (ja) | アデニル酸シクラーゼ５型阻害剤 | |
| JP2003531114A (ja) | プロテインキナーゼα阻害剤の使用 | |
| CN121337997A (zh) | α-半乳糖苷酶抑制剂在制备治疗心肌损伤相关疾病药物中的应用 | |
| JP2025040825A (ja) | 間質性肺炎を予防又は治療するための医薬及び医薬組成物 | |
| WO2002026031A1 (en) | Method of constructing heart failure model animal | |
| WO2025100427A1 (ja) | 肺高血圧症の予防および／または治療用医薬 | |
| Editors | Hypertension Editors’ Picks: Novel Drugs | |
| KR20240020754A (ko) | Pad 저해제를 포함하는 퇴행성 판막 질환의 예방 또는 치료용 조성물 | |
| EP1438972A1 (en) | Remedy for ischemic heart failure | |
| KR20200044380A (ko) | 심장 질환 치료용 조성물 |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20050721 |
|
| A621 | Written request for application examination |
Free format text: JAPANESE INTERMEDIATE CODE: A621 Effective date: 20050721 |
|
| A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20081201 |
|
| A601 | Written request for extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A601 Effective date: 20090302 |
|
| A602 | Written permission of extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A602 Effective date: 20090309 |
|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20090601 |
|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A821 Effective date: 20090601 |
|
| A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20090824 |
|
| A601 | Written request for extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A601 Effective date: 20091124 |
|
| A602 | Written permission of extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A602 Effective date: 20091201 |
|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20100224 |
|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A821 Effective date: 20100224 |
|
| A02 | Decision of refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A02 Effective date: 20100412 |