JP2019527736A5 - - Google Patents

Info

Publication number

JP2019527736A5

JP2019527736A5 JP2019529143A JP2019529143A JP2019527736A5 JP 2019527736 A5 JP2019527736 A5 JP 2019527736A5 JP 2019529143 A JP2019529143 A JP 2019529143A JP 2019529143 A JP2019529143 A JP 2019529143A JP 2019527736 A5 JP2019527736 A5 JP 2019527736A5

Authority

JP

Japan

Prior art keywords

bag3

pharmaceutical composition

ischemia

vector

composition according

Prior art date

2017-08-10

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.)

Granted

Links

• Espacenet
• Global Dossier
• Discuss

• 239000000203 mixture Substances 0.000 claims description 65
• 150000007523 nucleic acids Chemical group 0.000 claims description 65
• 208000028867 ischemia Diseases 0.000 claims description 59
• 239000013598 vector Substances 0.000 claims description 57
• 206010063837 Reperfusion injury Diseases 0.000 claims description 53
• 108090000765 processed proteins & peptides Proteins 0.000 claims description 52
• 102000004196 processed proteins & peptides Human genes 0.000 claims description 49
• 229920001184 polypeptide Polymers 0.000 claims description 46
• 210000001519 tissue Anatomy 0.000 claims description 33
• 239000012634 fragment Substances 0.000 claims description 26
• 102100021569 Apoptosis regulator Bcl-2 Human genes 0.000 claims description 25
• 230000000302 ischemic effect Effects 0.000 claims description 23
• 238000001356 surgical procedure Methods 0.000 claims description 22
• 238000011282 treatment Methods 0.000 claims description 22
• 101150017888 Bcl2 gene Proteins 0.000 claims description 20
• 239000003814 drug Substances 0.000 claims description 20
• 239000008194 pharmaceutical composition Substances 0.000 claims description 19
• 239000013603 viral vector Substances 0.000 claims description 16
• 208000010125 myocardial infarction Diseases 0.000 claims description 12
• 108091028043 Nucleic acid sequence Proteins 0.000 claims description 11
• 241000701161 unidentified adenovirus Species 0.000 claims description 11
• 208000006011 Stroke Diseases 0.000 claims description 9
• 238000002399 angioplasty Methods 0.000 claims description 9
• 230000000747 cardiac effect Effects 0.000 claims description 8
• 208000014674 injury Diseases 0.000 claims description 7
• 229940124597 therapeutic agent Drugs 0.000 claims description 7
• 241000702421 Dependoparvovirus Species 0.000 claims description 6
• 230000002792 vascular Effects 0.000 claims description 5
• 208000018262 Peripheral vascular disease Diseases 0.000 claims description 4
• 210000004556 brain Anatomy 0.000 claims description 4
• 230000002265 prevention Effects 0.000 claims description 4
• 210000002027 skeletal muscle Anatomy 0.000 claims description 4
• 230000008733 trauma Effects 0.000 claims description 4
• 239000003146 anticoagulant agent Substances 0.000 claims description 3
• 210000004369 blood Anatomy 0.000 claims description 3
• 239000008280 blood Substances 0.000 claims description 3
• 201000006370 kidney failure Diseases 0.000 claims description 3
• 208000033808 peripheral neuropathy Diseases 0.000 claims description 3
• 238000002054 transplantation Methods 0.000 claims description 3
• 206010002388 Angina unstable Diseases 0.000 claims description 2
• 201000001320 Atherosclerosis Diseases 0.000 claims description 2
• 201000006474 Brain Ischemia Diseases 0.000 claims description 2
• 229940127291 Calcium channel antagonist Drugs 0.000 claims description 2
• 208000007814 Unstable Angina Diseases 0.000 claims description 2
• 206010047249 Venous thrombosis Diseases 0.000 claims description 2
• 229940121363 anti-inflammatory agent Drugs 0.000 claims description 2
• 239000002260 anti-inflammatory agent Substances 0.000 claims description 2
• 239000003529 anticholesteremic agent Substances 0.000 claims description 2
• 229940127226 anticholesterol agent Drugs 0.000 claims description 2
• 229940127219 anticoagulant drug Drugs 0.000 claims description 2
• 239000002876 beta blocker Substances 0.000 claims description 2
• 229940097320 beta blocking agent Drugs 0.000 claims description 2
• 230000005250 beta ray Effects 0.000 claims description 2
• 239000000480 calcium channel blocker Substances 0.000 claims description 2
• 230000005251 gamma ray Effects 0.000 claims description 2
• 208000027866 inflammatory disease Diseases 0.000 claims description 2
• 201000004332 intermediate coronary syndrome Diseases 0.000 claims description 2
• 238000002608 intravascular ultrasound Methods 0.000 claims description 2
• 230000002285 radioactive effect Effects 0.000 claims description 2
• 230000001177 retroviral effect Effects 0.000 claims description 2
• 230000010415 tropism Effects 0.000 claims description 2
• 229940124549 vasodilator Drugs 0.000 claims description 2
• 239000003071 vasodilator agent Substances 0.000 claims description 2
• 239000013607 AAV vector Substances 0.000 claims 2
• 239000005541 ACE inhibitor Substances 0.000 claims 1
• 206010002329 Aneurysm Diseases 0.000 claims 1
• 101710129690 Angiotensin-converting enzyme inhibitor Proteins 0.000 claims 1
• 101710086378 Bradykinin-potentiating and C-type natriuretic peptides Proteins 0.000 claims 1
• 208000010378 Pulmonary Embolism Diseases 0.000 claims 1
• 208000032109 Transient ischaemic attack Diseases 0.000 claims 1
• 229940044094 angiotensin-converting-enzyme inhibitor Drugs 0.000 claims 1
• 210000004204 blood vessel Anatomy 0.000 claims 1
• 210000000234 capsid Anatomy 0.000 claims 1
• 238000001990 intravenous administration Methods 0.000 claims 1
• 208000017169 kidney disease Diseases 0.000 claims 1
• 210000005228 liver tissue Anatomy 0.000 claims 1
• 201000001119 neuropathy Diseases 0.000 claims 1
• 230000007823 neuropathy Effects 0.000 claims 1
• 210000005084 renal tissue Anatomy 0.000 claims 1
• 238000002271 resection Methods 0.000 claims 1
• 201000010875 transient cerebral ischemia Diseases 0.000 claims 1
• 102000039446 nucleic acids Human genes 0.000 description 53
• 108020004707 nucleic acids Proteins 0.000 description 53
• 210000004027 cell Anatomy 0.000 description 43
• 230000004900 autophagic degradation Effects 0.000 description 40
• 238000000034 method Methods 0.000 description 40
• 241000699670 Mus sp. Species 0.000 description 39
• 108090000623 proteins and genes Proteins 0.000 description 37
• 239000005090 green fluorescent protein Substances 0.000 description 33
• 102000004169 proteins and genes Human genes 0.000 description 28
• 235000018102 proteins Nutrition 0.000 description 27
• 230000001965 increasing effect Effects 0.000 description 26
• 108020004414 DNA Proteins 0.000 description 25
• 230000001105 regulatory effect Effects 0.000 description 23
• 230000014509 gene expression Effects 0.000 description 22
• 230000002829 reductive effect Effects 0.000 description 22
• 239000003795 chemical substances by application Substances 0.000 description 21
• 210000002216 heart Anatomy 0.000 description 21
• 230000010410 reperfusion Effects 0.000 description 20
• 238000001262 western blot Methods 0.000 description 20
• 206010021143 Hypoxia Diseases 0.000 description 19
• 230000002018 overexpression Effects 0.000 description 17
• 108010043121 Green Fluorescent Proteins Proteins 0.000 description 16
• 102000004144 Green Fluorescent Proteins Human genes 0.000 description 16
• 238000002474 experimental method Methods 0.000 description 16
• 238000001802 infusion Methods 0.000 description 16
• 230000002269 spontaneous effect Effects 0.000 description 15
• 108090000397 Caspase 3 Proteins 0.000 description 14
• 102100029855 Caspase-3 Human genes 0.000 description 14
• 206010061216 Infarction Diseases 0.000 description 14
• 230000006907 apoptotic process Effects 0.000 description 14
• QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 14
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 14
• 230000007574 infarction Effects 0.000 description 14
• 239000001301 oxygen Substances 0.000 description 14
• 229910052760 oxygen Inorganic materials 0.000 description 14
• 230000002861 ventricular Effects 0.000 description 13
• IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 12
• 235000001014 amino acid Nutrition 0.000 description 12
• 229940079593 drug Drugs 0.000 description 12
• 230000006870 function Effects 0.000 description 12
• 239000013612 plasmid Substances 0.000 description 12
• 108091033319 polynucleotide Proteins 0.000 description 12
• 102000040430 polynucleotide Human genes 0.000 description 12
• 239000002157 polynucleotide Substances 0.000 description 12
• 239000000047 product Substances 0.000 description 12
• 238000011002 quantification Methods 0.000 description 12
• 125000000539 amino acid group Chemical group 0.000 description 11
• 210000004413 cardiac myocyte Anatomy 0.000 description 11
• 230000007423 decrease Effects 0.000 description 11
• 230000003247 decreasing effect Effects 0.000 description 11
• 208000037906 ischaemic injury Diseases 0.000 description 11
• 241000701022 Cytomegalovirus Species 0.000 description 10
• 102000019145 JUN kinase activity proteins Human genes 0.000 description 10
• 241001465754 Metazoa Species 0.000 description 10
• 241000700605 Viruses Species 0.000 description 10
• 229940024606 amino acid Drugs 0.000 description 10
• 150000001413 amino acids Chemical class 0.000 description 10
• 210000004961 autolysosome Anatomy 0.000 description 10
• 230000027455 binding Effects 0.000 description 10
• 239000002609 medium Substances 0.000 description 10
• 239000002773 nucleotide Substances 0.000 description 10
• 125000003729 nucleotide group Chemical group 0.000 description 10
• -1 unique sequences Chemical class 0.000 description 10
• 241000699666 Mus <mouse, genus> Species 0.000 description 9
• 241000212749 Zesius chrysomallus Species 0.000 description 9
• 125000003275 alpha amino acid group Chemical group 0.000 description 9
• 230000017531 blood circulation Effects 0.000 description 9
• 201000010099 disease Diseases 0.000 description 9
• 230000004048 modification Effects 0.000 description 9
• 238000012986 modification Methods 0.000 description 9
• 210000000056 organ Anatomy 0.000 description 9
• 230000001086 cytosolic effect Effects 0.000 description 8
• 238000005516 engineering process Methods 0.000 description 8
• 210000004165 myocardium Anatomy 0.000 description 8
• 238000003752 polymerase chain reaction Methods 0.000 description 8
• 230000001225 therapeutic effect Effects 0.000 description 8
• 108020004459 Small interfering RNA Proteins 0.000 description 7
• 238000007792 addition Methods 0.000 description 7
• 230000036770 blood supply Effects 0.000 description 7
• 230000006378 damage Effects 0.000 description 7
• 239000013604 expression vector Substances 0.000 description 7
• 208000015181 infectious disease Diseases 0.000 description 7
• 210000000107 myocyte Anatomy 0.000 description 7
• 229910052757 nitrogen Inorganic materials 0.000 description 7
• 238000006467 substitution reaction Methods 0.000 description 7
• 238000012360 testing method Methods 0.000 description 7
• 231100000419 toxicity Toxicity 0.000 description 7
• 230000001988 toxicity Effects 0.000 description 7
• 102000053602 DNA Human genes 0.000 description 6
• 231100000517 death Toxicity 0.000 description 6
• 230000000694 effects Effects 0.000 description 6
• 230000010076 replication Effects 0.000 description 6
• 208000024891 symptom Diseases 0.000 description 6
• 108091032973 (ribonucleotides)n+m Proteins 0.000 description 5
• 238000011771 FVB mouse Methods 0.000 description 5
• WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 5
• 108091034117 Oligonucleotide Proteins 0.000 description 5
• 230000004913 activation Effects 0.000 description 5
• 239000000090 biomarker Substances 0.000 description 5
• 230000005754 cellular signaling Effects 0.000 description 5
• 230000034994 death Effects 0.000 description 5
• 208000035475 disorder Diseases 0.000 description 5
• 239000008103 glucose Substances 0.000 description 5
• 230000007954 hypoxia Effects 0.000 description 5
• 238000003119 immunoblot Methods 0.000 description 5
• 238000001727 in vivo Methods 0.000 description 5
• 210000004185 liver Anatomy 0.000 description 5
• 239000003550 marker Substances 0.000 description 5
• 239000012528 membrane Substances 0.000 description 5
• 239000002953 phosphate buffered saline Substances 0.000 description 5
• 230000009467 reduction Effects 0.000 description 5
• 230000035882 stress Effects 0.000 description 5
• 238000002560 therapeutic procedure Methods 0.000 description 5
• 238000013519 translation Methods 0.000 description 5
• MTCFGRXMJLQNBG-REOHCLBHSA-N (2S)-2-Amino-3-hydroxypropansäure Chemical compound OC[C@H](N)C(O)=O MTCFGRXMJLQNBG-REOHCLBHSA-N 0.000 description 4
• COXVTLYNGOIATD-HVMBLDELSA-N CC1=C(C=CC(=C1)C1=CC(C)=C(C=C1)\N=N\C1=C(O)C2=C(N)C(=CC(=C2C=C1)S(O)(=O)=O)S(O)(=O)=O)\N=N\C1=CC=C2C(=CC(=C(N)C2=C1O)S(O)(=O)=O)S(O)(=O)=O Chemical compound CC1=C(C=CC(=C1)C1=CC(C)=C(C=C1)\N=N\C1=C(O)C2=C(N)C(=CC(=C2C=C1)S(O)(=O)=O)S(O)(=O)=O)\N=N\C1=CC=C2C(=CC(=C(N)C2=C1O)S(O)(=O)=O)S(O)(=O)=O COXVTLYNGOIATD-HVMBLDELSA-N 0.000 description 4
• 241000283707 Capra Species 0.000 description 4
• 108091026890 Coding region Proteins 0.000 description 4
• 101000971171 Homo sapiens Apoptosis regulator Bcl-2 Proteins 0.000 description 4
• KDXKERNSBIXSRK-YFKPBYRVSA-N L-lysine Chemical compound NCCCC[C@H](N)C(O)=O KDXKERNSBIXSRK-YFKPBYRVSA-N 0.000 description 4
• KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 4
• JLCPHMBAVCMARE-UHFFFAOYSA-N [3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-[[3-[[3-[[3-[[3-[[3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-hydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methyl [5-(6-aminopurin-9-yl)-2-(hydroxymethyl)oxolan-3-yl] hydrogen phosphate Polymers Cc1cn(C2CC(OP(O)(=O)OCC3OC(CC3OP(O)(=O)OCC3OC(CC3O)n3cnc4c3nc(N)[nH]c4=O)n3cnc4c3nc(N)[nH]c4=O)C(COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3CO)n3cnc4c(N)ncnc34)n3ccc(N)nc3=O)n3cnc4c(N)ncnc34)n3ccc(N)nc3=O)n3ccc(N)nc3=O)n3ccc(N)nc3=O)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cc(C)c(=O)[nH]c3=O)n3cc(C)c(=O)[nH]c3=O)n3ccc(N)nc3=O)n3cc(C)c(=O)[nH]c3=O)n3cnc4c3nc(N)[nH]c4=O)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)O2)c(=O)[nH]c1=O JLCPHMBAVCMARE-UHFFFAOYSA-N 0.000 description 4
• 230000001154 acute effect Effects 0.000 description 4
• 238000010171 animal model Methods 0.000 description 4
• 230000008901 benefit Effects 0.000 description 4
• 239000000872 buffer Substances 0.000 description 4
• 238000004113 cell culture Methods 0.000 description 4
• 210000003855 cell nucleus Anatomy 0.000 description 4
• 230000008859 change Effects 0.000 description 4
• 239000002299 complementary DNA Substances 0.000 description 4
• 210000004351 coronary vessel Anatomy 0.000 description 4
• 230000002526 effect on cardiovascular system Effects 0.000 description 4
• 229960003699 evans blue Drugs 0.000 description 4
• 238000009472 formulation Methods 0.000 description 4
• 230000004927 fusion Effects 0.000 description 4
• 239000003112 inhibitor Substances 0.000 description 4
• 238000002347 injection Methods 0.000 description 4
• 239000007924 injection Substances 0.000 description 4
• 238000002955 isolation Methods 0.000 description 4
• 230000000670 limiting effect Effects 0.000 description 4
• 210000004379 membrane Anatomy 0.000 description 4
• 210000000663 muscle cell Anatomy 0.000 description 4
• 230000002107 myocardial effect Effects 0.000 description 4
• 208000031225 myocardial ischemia Diseases 0.000 description 4
• 230000004044 response Effects 0.000 description 4
• 238000013518 transcription Methods 0.000 description 4
• 230000035897 transcription Effects 0.000 description 4
• 238000011144 upstream manufacturing Methods 0.000 description 4
• 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 3
• 102000010825 Actinin Human genes 0.000 description 3
• 108010063503 Actinin Proteins 0.000 description 3
• 102000007469 Actins Human genes 0.000 description 3
• 108010085238 Actins Proteins 0.000 description 3
• 102100027954 BAG family molecular chaperone regulator 3 Human genes 0.000 description 3
• DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 3
• 241000282412 Homo Species 0.000 description 3
• CKLJMWTZIZZHCS-REOHCLBHSA-N L-aspartic acid Chemical compound OC(=O)[C@@H](N)CC(O)=O CKLJMWTZIZZHCS-REOHCLBHSA-N 0.000 description 3
• 239000004472 Lysine Substances 0.000 description 3
• 108010009491 Lysosomal-Associated Membrane Protein 2 Proteins 0.000 description 3
• 102100038225 Lysosome-associated membrane glycoprotein 2 Human genes 0.000 description 3
• 108091000080 Phosphotransferase Proteins 0.000 description 3
• 229940079156 Proteasome inhibitor Drugs 0.000 description 3
• MTCFGRXMJLQNBG-UHFFFAOYSA-N Serine Natural products OCC(N)C(O)=O MTCFGRXMJLQNBG-UHFFFAOYSA-N 0.000 description 3
• 102000004243 Tubulin Human genes 0.000 description 3
• 108090000704 Tubulin Proteins 0.000 description 3
• 208000027418 Wounds and injury Diseases 0.000 description 3
• 238000004458 analytical method Methods 0.000 description 3
• 210000001367 artery Anatomy 0.000 description 3
• 238000003556 assay Methods 0.000 description 3
• 208000036815 beta tubulin Diseases 0.000 description 3
• 230000004071 biological effect Effects 0.000 description 3
• 229960001467 bortezomib Drugs 0.000 description 3
• GXJABQQUPOEUTA-RDJZCZTQSA-N bortezomib Chemical compound C([C@@H](C(=O)N[C@@H](CC(C)C)B(O)O)NC(=O)C=1N=CC=NC=1)C1=CC=CC=C1 GXJABQQUPOEUTA-RDJZCZTQSA-N 0.000 description 3
• 238000005119 centrifugation Methods 0.000 description 3
• 150000001875 compounds Chemical class 0.000 description 3
• 238000004624 confocal microscopy Methods 0.000 description 3
• 210000000805 cytoplasm Anatomy 0.000 description 3
• 238000012217 deletion Methods 0.000 description 3
• 230000037430 deletion Effects 0.000 description 3
• 230000003292 diminished effect Effects 0.000 description 3
• 238000005538 encapsulation Methods 0.000 description 3
• 239000000284 extract Substances 0.000 description 3
• 239000000796 flavoring agent Substances 0.000 description 3
• 235000019634 flavors Nutrition 0.000 description 3
• 239000000499 gel Substances 0.000 description 3
• 230000013595 glycosylation Effects 0.000 description 3
• 238000006206 glycosylation reaction Methods 0.000 description 3
• 239000001963 growth medium Substances 0.000 description 3
• 230000036541 health Effects 0.000 description 3
• 208000038002 heart failure with reduced ejection fraction Diseases 0.000 description 3
• 230000013632 homeostatic process Effects 0.000 description 3
• 230000002631 hypothermal effect Effects 0.000 description 3
• 238000000338 in vitro Methods 0.000 description 3
• 230000003993 interaction Effects 0.000 description 3
• 230000004807 localization Effects 0.000 description 3
• 210000003712 lysosome Anatomy 0.000 description 3
• 230000001868 lysosomic effect Effects 0.000 description 3
• 230000007246 mechanism Effects 0.000 description 3
• 108020004999 messenger RNA Proteins 0.000 description 3
• 210000003470 mitochondria Anatomy 0.000 description 3
• 239000002245 particle Substances 0.000 description 3
• 230000002093 peripheral effect Effects 0.000 description 3
• 102000020233 phosphotransferase Human genes 0.000 description 3
• 239000013600 plasmid vector Substances 0.000 description 3
• 230000008569 process Effects 0.000 description 3
• 239000003207 proteasome inhibitor Substances 0.000 description 3
• 239000013074 reference sample Substances 0.000 description 3
• 238000011160 research Methods 0.000 description 3
• 239000000523 sample Substances 0.000 description 3
• 241000894007 species Species 0.000 description 3
• 239000003381 stabilizer Substances 0.000 description 3
• 210000001550 testis Anatomy 0.000 description 3
• 230000000451 tissue damage Effects 0.000 description 3
• 231100000827 tissue damage Toxicity 0.000 description 3
• 230000007704 transition Effects 0.000 description 3
• 230000005945 translocation Effects 0.000 description 3
• 238000007492 two-way ANOVA Methods 0.000 description 3
• 230000003612 virological effect Effects 0.000 description 3
• YBJHBAHKTGYVGT-ZKWXMUAHSA-N (+)-Biotin Chemical compound N1C(=O)N[C@@H]2[C@H](CCCCC(=O)O)SC[C@@H]21 YBJHBAHKTGYVGT-ZKWXMUAHSA-N 0.000 description 2
• XBPKRVHTESHFAA-LURJTMIESA-N (2s)-2-azaniumyl-2-cyclopentylacetate Chemical compound OC(=O)[C@@H](N)C1CCCC1 XBPKRVHTESHFAA-LURJTMIESA-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
• FWBHETKCLVMNFS-UHFFFAOYSA-N 4',6-Diamino-2-phenylindol Chemical compound C1=CC(C(=N)N)=CC=C1C1=CC2=CC=C(C(N)=N)C=C2N1 FWBHETKCLVMNFS-UHFFFAOYSA-N 0.000 description 2
• 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 description 2
• ZKHQWZAMYRWXGA-KQYNXXCUSA-J ATP(4-) Chemical compound C1=NC=2C(N)=NC=NC=2N1[C@@H]1O[C@H](COP([O-])(=O)OP([O-])(=O)OP([O-])([O-])=O)[C@@H](O)[C@H]1O ZKHQWZAMYRWXGA-KQYNXXCUSA-J 0.000 description 2
• ZKHQWZAMYRWXGA-UHFFFAOYSA-N Adenosine triphosphate Natural products C1=NC=2C(N)=NC=NC=2N1C1OC(COP(O)(=O)OP(O)(=O)OP(O)(O)=O)C(O)C1O ZKHQWZAMYRWXGA-UHFFFAOYSA-N 0.000 description 2
• 102000007698 Alcohol dehydrogenase Human genes 0.000 description 2
• 108010021809 Alcohol dehydrogenase Proteins 0.000 description 2
• 101710089791 BAG family molecular chaperone regulator 3 Proteins 0.000 description 2
• 102000004072 Beclin-1 Human genes 0.000 description 2
• 108090000524 Beclin-1 Proteins 0.000 description 2
• 208000031229 Cardiomyopathies Diseases 0.000 description 2
• 108091006146 Channels Proteins 0.000 description 2
• 108020004705 Codon Proteins 0.000 description 2
• 206010011086 Coronary artery occlusion Diseases 0.000 description 2
• 108090000204 Dipeptidase 1 Proteins 0.000 description 2
• 239000006144 Dulbecco’s modified Eagle's medium Substances 0.000 description 2
• 241000588724 Escherichia coli Species 0.000 description 2
• LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 2
• 108700028146 Genetic Enhancer Elements Proteins 0.000 description 2
• WHUUTDBJXJRKMK-UHFFFAOYSA-N Glutamic acid Natural products OC(=O)C(N)CCC(O)=O WHUUTDBJXJRKMK-UHFFFAOYSA-N 0.000 description 2
• 102000005720 Glutathione transferase Human genes 0.000 description 2
• 108010070675 Glutathione transferase Proteins 0.000 description 2
• 208000010496 Heart Arrest Diseases 0.000 description 2
• 108010033040 Histones Proteins 0.000 description 2
• 108090001061 Insulin Proteins 0.000 description 2
• 108091092195 Intron Proteins 0.000 description 2
• DCXYFEDJOCDNAF-REOHCLBHSA-N L-asparagine Chemical compound OC(=O)[C@@H](N)CC(N)=O DCXYFEDJOCDNAF-REOHCLBHSA-N 0.000 description 2
• WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 description 2
• ZDXPYRJPNDTMRX-VKHMYHEASA-N L-glutamine Chemical compound OC(=O)[C@@H](N)CCC(N)=O ZDXPYRJPNDTMRX-VKHMYHEASA-N 0.000 description 2
• AYFVYJQAPQTCCC-GBXIJSLDSA-N L-threonine Chemical compound C[C@@H](O)[C@H](N)C(O)=O AYFVYJQAPQTCCC-GBXIJSLDSA-N 0.000 description 2
• OUYCCCASQSFEME-QMMMGPOBSA-N L-tyrosine Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-QMMMGPOBSA-N 0.000 description 2
• 108091054455 MAP kinase family Proteins 0.000 description 2
• 102000043136 MAP kinase family Human genes 0.000 description 2
• 241000124008 Mammalia Species 0.000 description 2
• PVNIIMVLHYAWGP-UHFFFAOYSA-N Niacin Chemical compound OC(=O)C1=CC=CN=C1 PVNIIMVLHYAWGP-UHFFFAOYSA-N 0.000 description 2
• 102000035195 Peptidases Human genes 0.000 description 2
• 108091005804 Peptidases Proteins 0.000 description 2
• 102000004270 Peptidyl-Dipeptidase A Human genes 0.000 description 2
• 108090000882 Peptidyl-Dipeptidase A Proteins 0.000 description 2
• 239000004365 Protease Substances 0.000 description 2
• 208000001647 Renal Insufficiency Diseases 0.000 description 2
• 240000004808 Saccharomyces cerevisiae Species 0.000 description 2
• AYFVYJQAPQTCCC-UHFFFAOYSA-N Threonine Natural products CC(O)C(N)C(O)=O AYFVYJQAPQTCCC-UHFFFAOYSA-N 0.000 description 2
• 239000004473 Threonine Substances 0.000 description 2
• 108700009124 Transcription Initiation Site Proteins 0.000 description 2
• 102000044159 Ubiquitin Human genes 0.000 description 2
• 108090000848 Ubiquitin Proteins 0.000 description 2
• 241000711975 Vesicular stomatitis virus Species 0.000 description 2
• 230000002378 acidificating effect Effects 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
• 230000009435 amidation Effects 0.000 description 2
• 238000007112 amidation reaction Methods 0.000 description 2
• 125000003277 amino group Chemical group 0.000 description 2
• 235000003704 aspartic acid Nutrition 0.000 description 2
• 230000003143 atherosclerotic effect Effects 0.000 description 2
• 230000001580 bacterial effect Effects 0.000 description 2
• 238000002869 basic local alignment search tool Methods 0.000 description 2
• 230000009286 beneficial effect Effects 0.000 description 2
• OQFSQFPPLPISGP-UHFFFAOYSA-N beta-carboxyaspartic acid Natural products OC(=O)C(N)C(C(O)=O)C(O)=O OQFSQFPPLPISGP-UHFFFAOYSA-N 0.000 description 2
• AIYUHDOJVYHVIT-UHFFFAOYSA-M caesium chloride Chemical compound [Cl-].[Cs+] AIYUHDOJVYHVIT-UHFFFAOYSA-M 0.000 description 2
• 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 2
• 230000005779 cell damage Effects 0.000 description 2
• 230000030833 cell death Effects 0.000 description 2
• 208000037887 cell injury Diseases 0.000 description 2
• 239000013592 cell lysate Substances 0.000 description 2
• 238000006243 chemical reaction Methods 0.000 description 2
• 239000003153 chemical reaction reagent Substances 0.000 description 2
• 210000000038 chest Anatomy 0.000 description 2
• 230000002759 chromosomal effect Effects 0.000 description 2
• 238000010276 construction Methods 0.000 description 2
• 230000008602 contraction Effects 0.000 description 2
• 239000013068 control sample Substances 0.000 description 2
• 208000029078 coronary artery disease Diseases 0.000 description 2
• 210000003748 coronary sinus Anatomy 0.000 description 2
• 230000002950 deficient Effects 0.000 description 2
• 239000003085 diluting agent Substances 0.000 description 2
• 239000002552 dosage form Substances 0.000 description 2
• 230000004064 dysfunction Effects 0.000 description 2
• 238000002592 echocardiography Methods 0.000 description 2
• 150000002148 esters Chemical class 0.000 description 2
• 230000005284 excitation Effects 0.000 description 2
• 230000002068 genetic effect Effects 0.000 description 2
• 230000004217 heart function Effects 0.000 description 2
• 230000001146 hypoxic effect Effects 0.000 description 2
• 230000006872 improvement Effects 0.000 description 2
• CGIGDMFJXJATDK-UHFFFAOYSA-N indomethacin Chemical compound CC1=C(CC(O)=O)C2=CC(OC)=CC=C2N1C(=O)C1=CC=C(Cl)C=C1 CGIGDMFJXJATDK-UHFFFAOYSA-N 0.000 description 2
• 230000028709 inflammatory response Effects 0.000 description 2
• 230000002401 inhibitory effect Effects 0.000 description 2
• 230000005764 inhibitory process Effects 0.000 description 2
• 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 2
• 210000000936 intestine Anatomy 0.000 description 2
• 230000003834 intracellular effect Effects 0.000 description 2
• 238000007918 intramuscular administration Methods 0.000 description 2
• 210000005240 left ventricle Anatomy 0.000 description 2
• 239000002502 liposome Substances 0.000 description 2
• 239000007788 liquid Substances 0.000 description 2
• 210000004962 mammalian cell Anatomy 0.000 description 2
• 238000004519 manufacturing process Methods 0.000 description 2
• 239000000463 material Substances 0.000 description 2
• 238000002483 medication Methods 0.000 description 2
• 230000002438 mitochondrial effect Effects 0.000 description 2
• 210000003205 muscle Anatomy 0.000 description 2
• 210000004940 nucleus Anatomy 0.000 description 2
• 238000004806 packaging method and process Methods 0.000 description 2
• 108010079892 phosphoglycerol kinase Proteins 0.000 description 2
• 238000006366 phosphorylation reaction Methods 0.000 description 2
• 229960002508 pindolol Drugs 0.000 description 2
• PHUTUTUABXHXLW-UHFFFAOYSA-N pindolol Chemical compound CC(C)NCC(O)COC1=CC=CC2=NC=C[C]12 PHUTUTUABXHXLW-UHFFFAOYSA-N 0.000 description 2
• 229920000642 polymer Polymers 0.000 description 2
• 239000013615 primer Substances 0.000 description 2
• AQHHHDLHHXJYJD-UHFFFAOYSA-N propranolol Chemical compound C1=CC=C2C(OCC(O)CNC(C)C)=CC=CC2=C1 AQHHHDLHHXJYJD-UHFFFAOYSA-N 0.000 description 2
• 210000002307 prostate Anatomy 0.000 description 2
• 238000004445 quantitative analysis Methods 0.000 description 2
• 239000003642 reactive oxygen metabolite Substances 0.000 description 2
• 210000001567 regular cardiac muscle cell of ventricle Anatomy 0.000 description 2
• 238000013077 scoring method Methods 0.000 description 2
• 238000002864 sequence alignment Methods 0.000 description 2
• 238000012163 sequencing technique Methods 0.000 description 2
• VWDWKYIASSYTQR-UHFFFAOYSA-N sodium nitrate Chemical compound [Na+].[O-][N+]([O-])=O VWDWKYIASSYTQR-UHFFFAOYSA-N 0.000 description 2
• 238000010561 standard procedure Methods 0.000 description 2
• 239000000126 substance Substances 0.000 description 2
• 208000011580 syndromic disease Diseases 0.000 description 2
• 230000001732 thrombotic effect Effects 0.000 description 2
• 238000001890 transfection Methods 0.000 description 2
• 230000014621 translational initiation Effects 0.000 description 2
• OUYCCCASQSFEME-UHFFFAOYSA-N tyrosine Natural products OC(=O)C(N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-UHFFFAOYSA-N 0.000 description 2
• 241001430294 unidentified retrovirus Species 0.000 description 2
• TWUSDDMONZULSC-HZMBPMFUSA-N (1r,2s)-2-(tert-butylamino)-1-(2,5-dimethoxyphenyl)propan-1-ol Chemical compound COC1=CC=C(OC)C([C@@H](O)[C@H](C)NC(C)(C)C)=C1 TWUSDDMONZULSC-HZMBPMFUSA-N 0.000 description 1
• DQJCDTNMLBYVAY-ZXXIYAEKSA-N (2S,5R,10R,13R)-16-{[(2R,3S,4R,5R)-3-{[(2S,3R,4R,5S,6R)-3-acetamido-4,5-dihydroxy-6-(hydroxymethyl)oxan-2-yl]oxy}-5-(ethylamino)-6-hydroxy-2-(hydroxymethyl)oxan-4-yl]oxy}-5-(4-aminobutyl)-10-carbamoyl-2,13-dimethyl-4,7,12,15-tetraoxo-3,6,11,14-tetraazaheptadecan-1-oic acid Chemical compound NCCCC[C@H](C(=O)N[C@@H](C)C(O)=O)NC(=O)CC[C@H](C(N)=O)NC(=O)[C@@H](C)NC(=O)C(C)O[C@@H]1[C@@H](NCC)C(O)O[C@H](CO)[C@H]1O[C@H]1[C@H](NC(C)=O)[C@@H](O)[C@H](O)[C@@H](CO)O1 DQJCDTNMLBYVAY-ZXXIYAEKSA-N 0.000 description 1
• FDKWRPBBCBCIGA-REOHCLBHSA-N (2r)-2-azaniumyl-3-$l^{1}-selanylpropanoate Chemical compound [Se]C[C@H](N)C(O)=O FDKWRPBBCBCIGA-REOHCLBHSA-N 0.000 description 1
• XBAXJCUNAGGGLR-JEDNCBNOSA-N (2s)-2,6-diaminohexanoic acid;1h-pyrrole Chemical compound C=1C=CNC=1.NCCCC[C@H](N)C(O)=O XBAXJCUNAGGGLR-JEDNCBNOSA-N 0.000 description 1
• 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
• METKIMKYRPQLGS-GFCCVEGCSA-N (R)-atenolol Chemical compound CC(C)NC[C@@H](O)COC1=CC=C(CC(N)=O)C=C1 METKIMKYRPQLGS-GFCCVEGCSA-N 0.000 description 1
• BFSVOASYOCHEOV-UHFFFAOYSA-N 2-diethylaminoethanol Chemical compound CCN(CC)CCO BFSVOASYOCHEOV-UHFFFAOYSA-N 0.000 description 1
• 102000004365 Actin Capping Proteins Human genes 0.000 description 1
• 108010017189 Actin Capping Proteins Proteins 0.000 description 1
• 206010001052 Acute respiratory distress syndrome Diseases 0.000 description 1
• 108010088751 Albumins Proteins 0.000 description 1
• 102000002260 Alkaline Phosphatase Human genes 0.000 description 1
• 108020004774 Alkaline Phosphatase Proteins 0.000 description 1
• 206010002198 Anaphylactic reaction Diseases 0.000 description 1
• 239000004475 Arginine Substances 0.000 description 1
• DCXYFEDJOCDNAF-UHFFFAOYSA-N Asparagine Natural products OC(=O)C(N)CC(N)=O DCXYFEDJOCDNAF-UHFFFAOYSA-N 0.000 description 1
• BSYNRYMUTXBXSQ-UHFFFAOYSA-N Aspirin Chemical compound CC(=O)OC1=CC=CC=C1C(O)=O BSYNRYMUTXBXSQ-UHFFFAOYSA-N 0.000 description 1
• XUKUURHRXDUEBC-KAYWLYCHSA-N Atorvastatin Chemical compound C=1C=CC=CC=1C1=C(C=2C=CC(F)=CC=2)N(CC[C@@H](O)C[C@@H](O)CC(O)=O)C(C(C)C)=C1C(=O)NC1=CC=CC=C1 XUKUURHRXDUEBC-KAYWLYCHSA-N 0.000 description 1
• XUKUURHRXDUEBC-UHFFFAOYSA-N Atorvastatin Natural products C=1C=CC=CC=1C1=C(C=2C=CC(F)=CC=2)N(CCC(O)CC(O)CC(O)=O)C(C(C)C)=C1C(=O)NC1=CC=CC=C1 XUKUURHRXDUEBC-UHFFFAOYSA-N 0.000 description 1
• 101800001288 Atrial natriuretic factor Proteins 0.000 description 1
• 101800001890 Atrial natriuretic peptide Proteins 0.000 description 1
• 102400001282 Atrial natriuretic peptide Human genes 0.000 description 1
• 102000003954 Autophagy-Related Proteins Human genes 0.000 description 1
• 108010082399 Autophagy-Related Proteins Proteins 0.000 description 1
• 210000002237 B-cell of pancreatic islet Anatomy 0.000 description 1
• 108091012583 BCL2 Proteins 0.000 description 1
• 101150039216 Bag3 gene Proteins 0.000 description 1
• XPCFTKFZXHTYIP-PMACEKPBSA-N Benazepril Chemical compound C([C@@H](C(=O)OCC)N[C@@H]1C(N(CC(O)=O)C2=CC=CC=C2CC1)=O)CC1=CC=CC=C1 XPCFTKFZXHTYIP-PMACEKPBSA-N 0.000 description 1
• 108010087504 Beta-Globulins Proteins 0.000 description 1
• 108010006654 Bleomycin Proteins 0.000 description 1
• 108091003079 Bovine Serum Albumin Proteins 0.000 description 1
• 238000009010 Bradford assay Methods 0.000 description 1
• 206010006187 Breast cancer Diseases 0.000 description 1
• 208000026310 Breast neoplasm Diseases 0.000 description 1
• 239000002126 C01EB10 - Adenosine Substances 0.000 description 1
• 241000282472 Canis lupus familiaris Species 0.000 description 1
• 101710167800 Capsid assembly scaffolding protein Proteins 0.000 description 1
• 206010007617 Cardio-respiratory arrest Diseases 0.000 description 1
• 102000004046 Caspase-2 Human genes 0.000 description 1
• 108090000552 Caspase-2 Proteins 0.000 description 1
• 108090000994 Catalytic RNA Proteins 0.000 description 1
• 102000053642 Catalytic RNA Human genes 0.000 description 1
• 241000282693 Cercopithecidae Species 0.000 description 1
• 101710163595 Chaperone protein DnaK Proteins 0.000 description 1
• 108010077544 Chromatin Proteins 0.000 description 1
• 108700010070 Codon Usage Proteins 0.000 description 1
• 208000001778 Coronary Occlusion Diseases 0.000 description 1
• PMATZTZNYRCHOR-CGLBZJNRSA-N Cyclosporin A Chemical compound CC[C@@H]1NC(=O)[C@H]([C@H](O)[C@H](C)C\C=C\C)N(C)C(=O)[C@H](C(C)C)N(C)C(=O)[C@H](CC(C)C)N(C)C(=O)[C@H](CC(C)C)N(C)C(=O)[C@@H](C)NC(=O)[C@H](C)NC(=O)[C@H](CC(C)C)N(C)C(=O)[C@H](C(C)C)NC(=O)[C@H](CC(C)C)N(C)C(=O)CN(C)C1=O PMATZTZNYRCHOR-CGLBZJNRSA-N 0.000 description 1
• 229930105110 Cyclosporin A Natural products 0.000 description 1
• 108010036949 Cyclosporine Proteins 0.000 description 1
• FDKWRPBBCBCIGA-UWTATZPHSA-N D-Selenocysteine Natural products [Se]C[C@@H](N)C(O)=O FDKWRPBBCBCIGA-UWTATZPHSA-N 0.000 description 1
• AGPKZVBTJJNPAG-CRCLSJGQSA-N D-allo-isoleucine Chemical compound CC[C@H](C)[C@@H](N)C(O)=O AGPKZVBTJJNPAG-CRCLSJGQSA-N 0.000 description 1
• 239000003155 DNA primer Substances 0.000 description 1
• 230000007023 DNA restriction-modification system Effects 0.000 description 1
• 230000007018 DNA scission Effects 0.000 description 1
• 230000006820 DNA synthesis 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
• 206010012289 Dementia Diseases 0.000 description 1
• 229920002307 Dextran Polymers 0.000 description 1
• 206010013647 Drowning Diseases 0.000 description 1
• 206010014498 Embolic stroke Diseases 0.000 description 1
• 108010061435 Enalapril Proteins 0.000 description 1
• YQYJSBFKSSDGFO-UHFFFAOYSA-N Epihygromycin Natural products OC1C(O)C(C(=O)C)OC1OC(C(=C1)O)=CC=C1C=C(C)C(=O)NC1C(O)C(O)C2OCOC2C1O YQYJSBFKSSDGFO-UHFFFAOYSA-N 0.000 description 1
• 102000003951 Erythropoietin Human genes 0.000 description 1
• 108090000394 Erythropoietin Proteins 0.000 description 1
• HTQBXNHDCUEHJF-XWLPCZSASA-N Exenatide Chemical compound C([C@@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(N)=O)C(=O)NCC(=O)NCC(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CO)C(=O)N[C@@H](CO)C(=O)NCC(=O)N[C@@H](C)C(=O)N1[C@@H](CCC1)C(=O)N1[C@@H](CCC1)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CO)C(N)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@@H](NC(=O)[C@H](C)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CCSC)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CO)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@@H](NC(=O)CNC(=O)[C@H](CCC(O)=O)NC(=O)CNC(=O)[C@@H](N)CC=1NC=NC=1)[C@@H](C)O)[C@@H](C)O)C(C)C)C1=CC=CC=C1 HTQBXNHDCUEHJF-XWLPCZSASA-N 0.000 description 1
• 108010011459 Exenatide Proteins 0.000 description 1
• 108700024394 Exon Proteins 0.000 description 1
• 241000282326 Felis catus Species 0.000 description 1
• 241000233866 Fungi Species 0.000 description 1
• 108010001515 Galectin 4 Proteins 0.000 description 1
• 102100039556 Galectin-4 Human genes 0.000 description 1
• 108700039691 Genetic Promoter Regions Proteins 0.000 description 1
• 239000004471 Glycine Substances 0.000 description 1
• 102000002068 Glycopeptides Human genes 0.000 description 1
• 108010015899 Glycopeptides Proteins 0.000 description 1
• 102000003886 Glycoproteins Human genes 0.000 description 1
• 108090000288 Glycoproteins Proteins 0.000 description 1
• 229940121710 HMGCoA reductase inhibitor Drugs 0.000 description 1
• 206010019196 Head injury Diseases 0.000 description 1
• 206010019280 Heart failures Diseases 0.000 description 1
• 101710178376 Heat shock 70 kDa protein Proteins 0.000 description 1
• 101710152018 Heat shock cognate 70 kDa protein Proteins 0.000 description 1
• 102000002812 Heat-Shock Proteins Human genes 0.000 description 1
• 108010004889 Heat-Shock Proteins Proteins 0.000 description 1
• 101710154606 Hemagglutinin Proteins 0.000 description 1
• HTTJABKRGRZYRN-UHFFFAOYSA-N Heparin Chemical compound OC1C(NC(=O)C)C(O)OC(COS(O)(=O)=O)C1OC1C(OS(O)(=O)=O)C(O)C(OC2C(C(OS(O)(=O)=O)C(OC3C(C(O)C(O)C(O3)C(O)=O)OS(O)(=O)=O)C(CO)O2)NS(O)(=O)=O)C(C(O)=O)O1 HTTJABKRGRZYRN-UHFFFAOYSA-N 0.000 description 1
• 208000009889 Herpes Simplex Diseases 0.000 description 1
• 241000238631 Hexapoda Species 0.000 description 1
• 101000697871 Homo sapiens BAG family molecular chaperone regulator 3 Proteins 0.000 description 1
• LCWXJXMHJVIJFK-UHFFFAOYSA-N Hydroxylysine Natural products NCC(O)CC(N)CC(O)=O LCWXJXMHJVIJFK-UHFFFAOYSA-N 0.000 description 1
• 206010058490 Hyperoxia Diseases 0.000 description 1
• 206010020772 Hypertension Diseases 0.000 description 1
• 108700005091 Immunoglobulin Genes Proteins 0.000 description 1
• 102000004877 Insulin Human genes 0.000 description 1
• 208000033463 Ischaemic neuropathy Diseases 0.000 description 1
• PIWKPBJCKXDKJR-UHFFFAOYSA-N Isoflurane Chemical compound FC(F)OC(Cl)C(F)(F)F PIWKPBJCKXDKJR-UHFFFAOYSA-N 0.000 description 1
• 239000012825 JNK inhibitor Substances 0.000 description 1
• 108010038142 KAI 9803 Proteins 0.000 description 1
• QNAYBMKLOCPYGJ-REOHCLBHSA-N L-alanine Chemical compound C[C@H](N)C(O)=O QNAYBMKLOCPYGJ-REOHCLBHSA-N 0.000 description 1
• ODKSFYDXXFIFQN-BYPYZUCNSA-P L-argininium(2+) Chemical compound NC(=[NH2+])NCCC[C@H]([NH3+])C(O)=O ODKSFYDXXFIFQN-BYPYZUCNSA-P 0.000 description 1
• HNDVDQJCIGZPNO-YFKPBYRVSA-N L-histidine Chemical compound OC(=O)[C@@H](N)CC1=CN=CN1 HNDVDQJCIGZPNO-YFKPBYRVSA-N 0.000 description 1
• AGPKZVBTJJNPAG-WHFBIAKZSA-N L-isoleucine Chemical compound CC[C@H](C)[C@H](N)C(O)=O AGPKZVBTJJNPAG-WHFBIAKZSA-N 0.000 description 1
• ROHFNLRQFUQHCH-YFKPBYRVSA-N L-leucine Chemical compound CC(C)C[C@H](N)C(O)=O ROHFNLRQFUQHCH-YFKPBYRVSA-N 0.000 description 1
• COLNVLDHVKWLRT-QMMMGPOBSA-N L-phenylalanine Chemical compound OC(=O)[C@@H](N)CC1=CC=CC=C1 COLNVLDHVKWLRT-QMMMGPOBSA-N 0.000 description 1
• KZSNJWFQEVHDMF-BYPYZUCNSA-N L-valine Chemical compound CC(C)[C@H](N)C(O)=O KZSNJWFQEVHDMF-BYPYZUCNSA-N 0.000 description 1
• 108091026898 Leader sequence (mRNA) Proteins 0.000 description 1
• 241000713666 Lentivirus Species 0.000 description 1
• ROHFNLRQFUQHCH-UHFFFAOYSA-N Leucine Natural products CC(C)CC(N)C(O)=O ROHFNLRQFUQHCH-UHFFFAOYSA-N 0.000 description 1
• 108010007859 Lisinopril Proteins 0.000 description 1
• 102000019149 MAP kinase activity proteins Human genes 0.000 description 1
• 108040008097 MAP kinase activity proteins Proteins 0.000 description 1
• 108010052285 Membrane Proteins Proteins 0.000 description 1
• 101710169959 Membrane protein 2 Proteins 0.000 description 1
• 108700011259 MicroRNAs Proteins 0.000 description 1
• UWWDHYUMIORJTA-HSQYWUDLSA-N Moexipril Chemical compound C([C@@H](C(=O)OCC)N[C@@H](C)C(=O)N1[C@@H](CC2=CC(OC)=C(OC)C=C2C1)C(O)=O)CC1=CC=CC=C1 UWWDHYUMIORJTA-HSQYWUDLSA-N 0.000 description 1
• 108010006519 Molecular Chaperones Proteins 0.000 description 1
• 102000005431 Molecular Chaperones Human genes 0.000 description 1
• 241000713869 Moloney murine leukemia virus Species 0.000 description 1
• 208000034486 Multi-organ failure Diseases 0.000 description 1
• 241000282339 Mustela Species 0.000 description 1
• 101710135898 Myc proto-oncogene protein Proteins 0.000 description 1
• 102100038895 Myc proto-oncogene protein Human genes 0.000 description 1
• 101710107068 Myelin basic protein Proteins 0.000 description 1
• 206010028980 Neoplasm Diseases 0.000 description 1
• 208000009869 Neu-Laxova syndrome Diseases 0.000 description 1
• 239000000020 Nitrocellulose Substances 0.000 description 1
• SNIOPGDIGTZGOP-UHFFFAOYSA-N Nitroglycerin Chemical compound [O-][N+](=O)OCC(O[N+]([O-])=O)CO[N+]([O-])=O SNIOPGDIGTZGOP-UHFFFAOYSA-N 0.000 description 1
• 239000000006 Nitroglycerin Substances 0.000 description 1
• 108010077850 Nuclear Localization Signals Proteins 0.000 description 1
• 108020004711 Nucleic Acid Probes Proteins 0.000 description 1
• 208000008589 Obesity Diseases 0.000 description 1
• 241000283973 Oryctolagus cuniculus Species 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
• 229910019142 PO4 Inorganic materials 0.000 description 1
• 108010067372 Pancreatic elastase Proteins 0.000 description 1
• 229930040373 Paraformaldehyde Natural products 0.000 description 1
• 206010033799 Paralysis Diseases 0.000 description 1
• 102000004160 Phosphoric Monoester Hydrolases Human genes 0.000 description 1
• 108090000608 Phosphoric Monoester Hydrolases Proteins 0.000 description 1
• 206010035148 Plague Diseases 0.000 description 1
• 229920001213 Polysorbate 20 Polymers 0.000 description 1
• ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
• 101710130420 Probable capsid assembly scaffolding protein Proteins 0.000 description 1
• 101710176177 Protein A56 Proteins 0.000 description 1
• 102000001253 Protein Kinase Human genes 0.000 description 1
• 102100027378 Prothrombin Human genes 0.000 description 1
• 108010094028 Prothrombin Proteins 0.000 description 1
• 108091030071 RNAI Proteins 0.000 description 1
• 241000700159 Rattus Species 0.000 description 1
• 208000013616 Respiratory Distress Syndrome Diseases 0.000 description 1
• 208000004756 Respiratory Insufficiency Diseases 0.000 description 1
• 108091027981 Response element Proteins 0.000 description 1
• 206010039491 Sarcoma Diseases 0.000 description 1
• 101710204410 Scaffold protein Proteins 0.000 description 1
• 108091081021 Sense strand Proteins 0.000 description 1
• 206010040047 Sepsis Diseases 0.000 description 1
• 241000700584 Simplexvirus Species 0.000 description 1
• 108020004682 Single-Stranded DNA Proteins 0.000 description 1
• 241000282887 Suidae Species 0.000 description 1
• 206010042602 Supraventricular extrasystoles Diseases 0.000 description 1
• 108091036066 Three prime untranslated region Proteins 0.000 description 1
• 108091023040 Transcription factor Proteins 0.000 description 1
• 102000040945 Transcription factor Human genes 0.000 description 1
• 101710150448 Transcriptional regulator Myc Proteins 0.000 description 1
• 108020004566 Transfer RNA Proteins 0.000 description 1
• 206010044565 Tremor Diseases 0.000 description 1
• 239000013504 Triton X-100 Substances 0.000 description 1
• 229920004890 Triton X-100 Polymers 0.000 description 1
• 108091023045 Untranslated Region Proteins 0.000 description 1
• KZSNJWFQEVHDMF-UHFFFAOYSA-N Valine Natural products CC(C)C(N)C(O)=O KZSNJWFQEVHDMF-UHFFFAOYSA-N 0.000 description 1
• 206010047139 Vasoconstriction Diseases 0.000 description 1
• 241000607479 Yersinia pestis Species 0.000 description 1
• 210000000683 abdominal cavity Anatomy 0.000 description 1
• 230000005856 abnormality Effects 0.000 description 1
• 230000035508 accumulation Effects 0.000 description 1
• 238000009825 accumulation Methods 0.000 description 1
• 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 1
• 230000021736 acetylation Effects 0.000 description 1
• 238000006640 acetylation reaction Methods 0.000 description 1
• 229960001138 acetylsalicylic acid Drugs 0.000 description 1
• 150000008043 acidic salts Chemical class 0.000 description 1
• 230000036982 action potential Effects 0.000 description 1
• 206010000891 acute myocardial infarction Diseases 0.000 description 1
• 229960005305 adenosine Drugs 0.000 description 1
• 239000002671 adjuvant Substances 0.000 description 1
• 230000002411 adverse Effects 0.000 description 1
• 239000000443 aerosol Substances 0.000 description 1
• 235000004279 alanine Nutrition 0.000 description 1
• 125000000217 alkyl group Chemical group 0.000 description 1
• 230000029936 alkylation Effects 0.000 description 1
• 238000005804 alkylation reaction Methods 0.000 description 1
• 108010050122 alpha 1-Antitrypsin Proteins 0.000 description 1
• 108010026331 alpha-Fetoproteins Proteins 0.000 description 1
• 230000001668 ameliorated effect Effects 0.000 description 1
• 150000001408 amides Chemical class 0.000 description 1
• 229960000723 ampicillin Drugs 0.000 description 1
• AVKUERGKIZMTKX-NJBDSQKTSA-N ampicillin Chemical compound C1([C@@H](N)C(=O)N[C@H]2[C@H]3SC([C@@H](N3C2=O)C(O)=O)(C)C)=CC=CC=C1 AVKUERGKIZMTKX-NJBDSQKTSA-N 0.000 description 1
• 230000036783 anaphylactic response Effects 0.000 description 1
• 208000003455 anaphylaxis Diseases 0.000 description 1
• 239000003242 anti bacterial agent Substances 0.000 description 1
• 230000000692 anti-sense effect Effects 0.000 description 1
• 229940088710 antibiotic agent Drugs 0.000 description 1
• 230000001640 apoptogenic effect Effects 0.000 description 1
• 230000036528 appetite Effects 0.000 description 1
• 235000019789 appetite Nutrition 0.000 description 1
• 238000013459 approach Methods 0.000 description 1
• ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 1
• 206010003119 arrhythmia Diseases 0.000 description 1
• 230000006793 arrhythmia Effects 0.000 description 1
• 230000008321 arterial blood flow Effects 0.000 description 1
• 210000004507 artificial chromosome Anatomy 0.000 description 1
• 235000009582 asparagine Nutrition 0.000 description 1
• 229960001230 asparagine Drugs 0.000 description 1
• 229960002274 atenolol Drugs 0.000 description 1
• 229960005370 atorvastatin Drugs 0.000 description 1
• 210000004957 autophagosome Anatomy 0.000 description 1
• 230000004929 autophagosome-lysosome fusion Effects 0.000 description 1
• 239000011324 bead Substances 0.000 description 1
• 229960004530 benazepril Drugs 0.000 description 1
• UIEATEWHFDRYRU-UHFFFAOYSA-N bepridil Chemical compound C1CCCN1C(COCC(C)C)CN(C=1C=CC=CC=1)CC1=CC=CC=C1 UIEATEWHFDRYRU-UHFFFAOYSA-N 0.000 description 1
• 229960003665 bepridil Drugs 0.000 description 1
• 102000016967 beta-1 Adrenergic Receptors Human genes 0.000 description 1
• 108010014494 beta-1 Adrenergic Receptors Proteins 0.000 description 1
• WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 1
• 102000006635 beta-lactamase Human genes 0.000 description 1
• 229960004324 betaxolol Drugs 0.000 description 1
• CHDPSNLJFOQTRK-UHFFFAOYSA-N betaxolol hydrochloride Chemical compound [Cl-].C1=CC(OCC(O)C[NH2+]C(C)C)=CC=C1CCOCC1CC1 CHDPSNLJFOQTRK-UHFFFAOYSA-N 0.000 description 1
• 239000003613 bile acid Substances 0.000 description 1
• 230000000975 bioactive effect Effects 0.000 description 1
• 239000003139 biocide Substances 0.000 description 1
• 230000015572 biosynthetic process Effects 0.000 description 1
• 229960002685 biotin Drugs 0.000 description 1
• 235000020958 biotin Nutrition 0.000 description 1
• 239000011616 biotin Substances 0.000 description 1
• 230000006287 biotinylation Effects 0.000 description 1
• 238000007413 biotinylation Methods 0.000 description 1
• OWMVSZAMULFTJU-UHFFFAOYSA-N bis-tris Chemical compound OCCN(CCO)C(CO)(CO)CO OWMVSZAMULFTJU-UHFFFAOYSA-N 0.000 description 1
• 230000000740 bleeding effect Effects 0.000 description 1
• 229960001561 bleomycin Drugs 0.000 description 1
• OYVAGSVQBOHSSS-UAPAGMARSA-O bleomycin A2 Chemical compound N([C@H](C(=O)N[C@H](C)[C@@H](O)[C@H](C)C(=O)N[C@@H]([C@H](O)C)C(=O)NCCC=1SC=C(N=1)C=1SC=C(N=1)C(=O)NCCC[S+](C)C)[C@@H](O[C@H]1[C@H]([C@@H](O)[C@H](O)[C@H](CO)O1)O[C@@H]1[C@H]([C@@H](OC(N)=O)[C@H](O)[C@@H](CO)O1)O)C=1N=CNC=1)C(=O)C1=NC([C@H](CC(N)=O)NC[C@H](N)C(N)=O)=NC(N)=C1C OYVAGSVQBOHSSS-UAPAGMARSA-O 0.000 description 1
• 238000009534 blood test Methods 0.000 description 1
• 239000001045 blue dye Substances 0.000 description 1
• XPXZTVWPRKJTAA-PJKOMPQUSA-N bms-875944 Chemical compound C([C@@H](C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)NCC(=O)N[C@@H](CO)C(=O)N[C@@H](CC(C)C)C(O)=O)NC(=O)[C@H](CO)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@H](CO)NC(=O)[C@@H](N)CSSC[C@H](N)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)NCC(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O)C1=CC=C(O)C=C1 XPXZTVWPRKJTAA-PJKOMPQUSA-N 0.000 description 1
• 229950009770 butaxamine Drugs 0.000 description 1
• 210000004899 c-terminal region Anatomy 0.000 description 1
• 239000011575 calcium Substances 0.000 description 1
• 230000001964 calcium overload Effects 0.000 description 1
• 239000001506 calcium phosphate Substances 0.000 description 1
• 229910000389 calcium phosphate Inorganic materials 0.000 description 1
• 235000011010 calcium phosphates Nutrition 0.000 description 1
• 229960000830 captopril Drugs 0.000 description 1
• FAKRSMQSSFJEIM-RQJHMYQMSA-N captopril Chemical compound SC[C@@H](C)C(=O)N1CCC[C@H]1C(O)=O FAKRSMQSSFJEIM-RQJHMYQMSA-N 0.000 description 1
• 238000007675 cardiac surgery Methods 0.000 description 1
• NSQLIUXCMFBZME-MPVJKSABSA-N carperitide Chemical compound C([C@H]1C(=O)NCC(=O)NCC(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@H](C(NCC(=O)N[C@@H](C)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CO)C(=O)NCC(=O)N[C@@H](CC(C)C)C(=O)NCC(=O)N[C@@H](CSSC[C@@H](C(=O)N1)NC(=O)[C@H](CO)NC(=O)[C@H](CO)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](N)CO)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CO)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(O)=O)=O)[C@@H](C)CC)C1=CC=CC=C1 NSQLIUXCMFBZME-MPVJKSABSA-N 0.000 description 1
• 239000000969 carrier Substances 0.000 description 1
• 230000015556 catabolic process Effects 0.000 description 1
• 125000002091 cationic group Chemical group 0.000 description 1
• 230000027902 cell growth involved in cardiac muscle cell development Effects 0.000 description 1
• 230000006037 cell lysis Effects 0.000 description 1
• 210000000170 cell membrane Anatomy 0.000 description 1
• 108091092328 cellular RNA Proteins 0.000 description 1
• 230000007248 cellular mechanism Effects 0.000 description 1
• 230000002490 cerebral effect Effects 0.000 description 1
• 210000001175 cerebrospinal fluid Anatomy 0.000 description 1
• 238000007385 chemical modification Methods 0.000 description 1
• 239000003638 chemical reducing agent Substances 0.000 description 1
• 238000002512 chemotherapy Methods 0.000 description 1
• 230000001906 cholesterol absorption Effects 0.000 description 1
• 210000003483 chromatin Anatomy 0.000 description 1
• 229960001265 ciclosporin Drugs 0.000 description 1
• 230000004087 circulation Effects 0.000 description 1
• 238000003776 cleavage reaction Methods 0.000 description 1
• 238000010367 cloning Methods 0.000 description 1
• 238000011260 co-administration Methods 0.000 description 1
• 238000002591 computed tomography Methods 0.000 description 1
• 238000004590 computer program Methods 0.000 description 1
• 230000003750 conditioning effect Effects 0.000 description 1
• 238000012937 correction Methods 0.000 description 1
• 230000008878 coupling Effects 0.000 description 1
• 238000010168 coupling process Methods 0.000 description 1
• 238000005859 coupling reaction Methods 0.000 description 1
• 235000018417 cysteine Nutrition 0.000 description 1
• XUJNEKJLAYXESH-UHFFFAOYSA-N cysteine Natural products SCC(N)C(O)=O XUJNEKJLAYXESH-UHFFFAOYSA-N 0.000 description 1
• 230000001120 cytoprotective effect Effects 0.000 description 1
• 230000007812 deficiency Effects 0.000 description 1
• 238000006731 degradation reaction Methods 0.000 description 1
• 230000003111 delayed effect Effects 0.000 description 1
• 229950006252 delcasertib Drugs 0.000 description 1
• 238000002716 delivery method Methods 0.000 description 1
• YSMODUONRAFBET-UHFFFAOYSA-N delta-DL-hydroxylysine Natural products NCC(O)CCC(N)C(O)=O YSMODUONRAFBET-UHFFFAOYSA-N 0.000 description 1
• 238000013461 design Methods 0.000 description 1
• 238000001514 detection method Methods 0.000 description 1
• 230000001627 detrimental effect Effects 0.000 description 1
• 238000011161 development Methods 0.000 description 1
• 230000018109 developmental process Effects 0.000 description 1
• 229960001259 diclofenac Drugs 0.000 description 1
• DCOPUUMXTXDBNB-UHFFFAOYSA-N diclofenac Chemical compound OC(=O)CC1=CC=CC=C1NC1=C(Cl)C=CC=C1Cl DCOPUUMXTXDBNB-UHFFFAOYSA-N 0.000 description 1
• 235000020805 dietary restrictions Nutrition 0.000 description 1
• 238000010790 dilution Methods 0.000 description 1
• 239000012895 dilution Substances 0.000 description 1
• LOKCTEFSRHRXRJ-UHFFFAOYSA-I dipotassium trisodium dihydrogen phosphate hydrogen phosphate dichloride Chemical compound P(=O)(O)(O)[O-].[K+].P(=O)(O)([O-])[O-].[Na+].[Na+].[Cl-].[K+].[Cl-].[Na+] LOKCTEFSRHRXRJ-UHFFFAOYSA-I 0.000 description 1
• 239000013583 drug formulation Substances 0.000 description 1
• 238000002651 drug therapy Methods 0.000 description 1
• 238000001962 electrophoresis Methods 0.000 description 1
• 238000004520 electroporation Methods 0.000 description 1
• 230000010102 embolization Effects 0.000 description 1
• 210000002253 embryonic cardiomyocyte Anatomy 0.000 description 1
• 229960000873 enalapril Drugs 0.000 description 1
• GBXSMTUPTTWBMN-XIRDDKMYSA-N enalapril Chemical compound C([C@@H](C(=O)OCC)N[C@@H](C)C(=O)N1[C@@H](CCC1)C(O)=O)CC1=CC=CC=C1 GBXSMTUPTTWBMN-XIRDDKMYSA-N 0.000 description 1
• 239000008393 encapsulating agent Substances 0.000 description 1
• 230000008694 endothelial dysfunction Effects 0.000 description 1
• 239000003623 enhancer Substances 0.000 description 1
• 108700004025 env Genes Proteins 0.000 description 1
• 101150030339 env gene Proteins 0.000 description 1
• YSMODUONRAFBET-UHNVWZDZSA-N erythro-5-hydroxy-L-lysine Chemical compound NC[C@H](O)CC[C@H](N)C(O)=O YSMODUONRAFBET-UHNVWZDZSA-N 0.000 description 1
• 229940105423 erythropoietin Drugs 0.000 description 1
• 210000003527 eukaryotic cell Anatomy 0.000 description 1
• 238000011156 evaluation Methods 0.000 description 1
• 230000029142 excretion Effects 0.000 description 1
• 230000005373 execution phase of apoptosis Effects 0.000 description 1
• 229960001519 exenatide Drugs 0.000 description 1
• 230000001747 exhibiting effect Effects 0.000 description 1
• 238000000605 extraction Methods 0.000 description 1
• 238000004992 fast atom bombardment mass spectroscopy Methods 0.000 description 1
• 239000012091 fetal bovine serum Substances 0.000 description 1
• 239000003527 fibrinolytic agent Substances 0.000 description 1
• 230000037406 food intake Effects 0.000 description 1
• 238000005194 fractionation Methods 0.000 description 1
• 238000013467 fragmentation Methods 0.000 description 1
• 238000006062 fragmentation reaction Methods 0.000 description 1
• 238000004108 freeze drying Methods 0.000 description 1
• 239000012737 fresh medium Substances 0.000 description 1
• 238000002825 functional assay Methods 0.000 description 1
• 108700004026 gag Genes Proteins 0.000 description 1
• 238000001476 gene delivery Methods 0.000 description 1
• 230000009368 gene silencing by RNA Effects 0.000 description 1
• 229960001031 glucose Drugs 0.000 description 1
• 235000013922 glutamic acid Nutrition 0.000 description 1
• 239000004220 glutamic acid Substances 0.000 description 1
• ZDXPYRJPNDTMRX-UHFFFAOYSA-N glutamine Natural products OC(=O)C(N)CCC(N)=O ZDXPYRJPNDTMRX-UHFFFAOYSA-N 0.000 description 1
• 150000004676 glycans Chemical class 0.000 description 1
• 229960003711 glyceryl trinitrate Drugs 0.000 description 1
• 125000003147 glycosyl group Chemical group 0.000 description 1
• 238000003306 harvesting Methods 0.000 description 1
• 208000019622 heart disease Diseases 0.000 description 1
• 210000005003 heart tissue Anatomy 0.000 description 1
• 239000000185 hemagglutinin Substances 0.000 description 1
• 230000002008 hemorrhagic effect Effects 0.000 description 1
• 229960002897 heparin Drugs 0.000 description 1
• 229920000669 heparin Polymers 0.000 description 1
• 201000011200 hepatorenal syndrome Diseases 0.000 description 1
• 238000004128 high performance liquid chromatography Methods 0.000 description 1
• 210000003630 histaminocyte Anatomy 0.000 description 1
• HNDVDQJCIGZPNO-UHFFFAOYSA-N histidine Natural products OC(=O)C(N)CC1=CN=CN1 HNDVDQJCIGZPNO-UHFFFAOYSA-N 0.000 description 1
• 125000000487 histidyl group Chemical group [H]N([H])C(C(=O)O*)C([H])([H])C1=C([H])N([H])C([H])=N1 0.000 description 1
• 239000005556 hormone Substances 0.000 description 1
• 229940088597 hormone Drugs 0.000 description 1
• 235000003642 hunger Nutrition 0.000 description 1
• QJHBJHUKURJDLG-UHFFFAOYSA-N hydroxy-L-lysine Natural products NCCCCC(NO)C(O)=O QJHBJHUKURJDLG-UHFFFAOYSA-N 0.000 description 1
• 239000002471 hydroxymethylglutaryl coenzyme A reductase inhibitor Substances 0.000 description 1
• 230000000222 hyperoxic effect Effects 0.000 description 1
• 210000003016 hypothalamus Anatomy 0.000 description 1
• 238000003384 imaging method Methods 0.000 description 1
• 230000001771 impaired effect Effects 0.000 description 1
• 229960000905 indomethacin Drugs 0.000 description 1
• 230000001939 inductive effect Effects 0.000 description 1
• 239000004615 ingredient Substances 0.000 description 1
• 230000000977 initiatory effect Effects 0.000 description 1
• 229940125396 insulin Drugs 0.000 description 1
• 230000000968 intestinal effect Effects 0.000 description 1
• 238000007917 intracranial administration Methods 0.000 description 1
• 238000007912 intraperitoneal administration Methods 0.000 description 1
• 238000007913 intrathecal administration Methods 0.000 description 1
• 238000011835 investigation Methods 0.000 description 1
• 230000002530 ischemic preconditioning effect Effects 0.000 description 1
• 229960002725 isoflurane Drugs 0.000 description 1
• AGPKZVBTJJNPAG-UHFFFAOYSA-N isoleucine Natural products CCC(C)C(N)C(O)=O AGPKZVBTJJNPAG-UHFFFAOYSA-N 0.000 description 1
• 229960000310 isoleucine Drugs 0.000 description 1
• 230000006122 isoprenylation Effects 0.000 description 1
• 210000001503 joint Anatomy 0.000 description 1
• 229960000318 kanamycin Drugs 0.000 description 1
• 229930027917 kanamycin Natural products 0.000 description 1
• SBUJHOSQTJFQJX-NOAMYHISSA-N kanamycin Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CN)O[C@@H]1O[C@H]1[C@H](O)[C@@H](O[C@@H]2[C@@H]([C@@H](N)[C@H](O)[C@@H](CO)O2)O)[C@H](N)C[C@@H]1N SBUJHOSQTJFQJX-NOAMYHISSA-N 0.000 description 1
• 229930182823 kanamycin A Natural products 0.000 description 1
• DKYWVDODHFEZIM-UHFFFAOYSA-N ketoprofen Chemical compound OC(=O)C(C)C1=CC=CC(C(=O)C=2C=CC=CC=2)=C1 DKYWVDODHFEZIM-UHFFFAOYSA-N 0.000 description 1
• 229960000991 ketoprofen Drugs 0.000 description 1
• 208000030175 lameness Diseases 0.000 description 1
• 231100000518 lethal Toxicity 0.000 description 1
• 230000001665 lethal effect Effects 0.000 description 1
• 150000002632 lipids Chemical class 0.000 description 1
• AGBQKNBQESQNJD-UHFFFAOYSA-M lipoate Chemical compound [O-]C(=O)CCCCC1CCSS1 AGBQKNBQESQNJD-UHFFFAOYSA-M 0.000 description 1
• 230000000598 lipoate effect Effects 0.000 description 1
• 230000006144 lipoylation Effects 0.000 description 1
• 229960002394 lisinopril Drugs 0.000 description 1
• RLAWWYSOJDYHDC-BZSNNMDCSA-N lisinopril Chemical compound C([C@H](N[C@@H](CCCCN)C(=O)N1[C@@H](CCC1)C(O)=O)C(O)=O)CC1=CC=CC=C1 RLAWWYSOJDYHDC-BZSNNMDCSA-N 0.000 description 1
• 208000019423 liver disease Diseases 0.000 description 1
• 230000007774 longterm Effects 0.000 description 1
• 210000004072 lung Anatomy 0.000 description 1
• 210000002751 lymph Anatomy 0.000 description 1
• 238000002595 magnetic resonance imaging Methods 0.000 description 1
• 239000011159 matrix material Substances 0.000 description 1
• 230000035800 maturation Effects 0.000 description 1
• 230000001404 mediated effect Effects 0.000 description 1
• 230000004060 metabolic process Effects 0.000 description 1
• 239000002679 microRNA Substances 0.000 description 1
• 238000000520 microinjection Methods 0.000 description 1
• 239000011859 microparticle Substances 0.000 description 1
• 208000024191 minimally invasive lung adenocarcinoma Diseases 0.000 description 1
• 210000001700 mitochondrial membrane Anatomy 0.000 description 1
• 229960005170 moexipril Drugs 0.000 description 1
• 208000029744 multiple organ dysfunction syndrome Diseases 0.000 description 1
• 238000002703 mutagenesis Methods 0.000 description 1
• 231100000350 mutagenesis Toxicity 0.000 description 1
• 230000035772 mutation Effects 0.000 description 1
• 210000000066 myeloid cell Anatomy 0.000 description 1
• 230000003680 myocardial damage Effects 0.000 description 1
• 210000003365 myofibril Anatomy 0.000 description 1
• 208000002086 myofibrillar myopathy Diseases 0.000 description 1
• 108010065781 myosin light chain 2 Proteins 0.000 description 1
• 229960004255 nadolol Drugs 0.000 description 1
• VWPOSFSPZNDTMJ-UCWKZMIHSA-N nadolol Chemical compound C1[C@@H](O)[C@@H](O)CC2=C1C=CC=C2OCC(O)CNC(C)(C)C VWPOSFSPZNDTMJ-UCWKZMIHSA-N 0.000 description 1
• CMWTZPSULFXXJA-VIFPVBQESA-N naproxen Chemical compound C1=C([C@H](C)C(O)=O)C=CC2=CC(OC)=CC=C21 CMWTZPSULFXXJA-VIFPVBQESA-N 0.000 description 1
• 210000002850 nasal mucosa Anatomy 0.000 description 1
• 210000000653 nervous system Anatomy 0.000 description 1
• 210000004498 neuroglial cell Anatomy 0.000 description 1
• 230000000926 neurological effect Effects 0.000 description 1
• 229960003512 nicotinic acid Drugs 0.000 description 1
• 235000001968 nicotinic acid Nutrition 0.000 description 1
• 239000011664 nicotinic acid Substances 0.000 description 1
• 229920001220 nitrocellulos Polymers 0.000 description 1
• 238000004305 normal phase HPLC Methods 0.000 description 1
• 239000002853 nucleic acid probe Substances 0.000 description 1
• 230000030648 nucleus localization Effects 0.000 description 1
• 235000020824 obesity Nutrition 0.000 description 1
• 230000000414 obstructive effect Effects 0.000 description 1
• 210000004248 oligodendroglia Anatomy 0.000 description 1
• 238000005457 optimization Methods 0.000 description 1
• 230000004768 organ dysfunction Effects 0.000 description 1
• 230000003204 osmotic effect Effects 0.000 description 1
• 239000005022 packaging material Substances 0.000 description 1
• 229920002866 paraformaldehyde Polymers 0.000 description 1
• 238000004810 partition chromatography Methods 0.000 description 1
• 230000037361 pathway Effects 0.000 description 1
• 238000013146 percutaneous coronary intervention Methods 0.000 description 1
• 230000010412 perfusion Effects 0.000 description 1
• 229960002582 perindopril Drugs 0.000 description 1
• IPVQLZZIHOAWMC-QXKUPLGCSA-N perindopril Chemical compound C1CCC[C@H]2C[C@@H](C(O)=O)N(C(=O)[C@H](C)N[C@@H](CCC)C(=O)OCC)[C@H]21 IPVQLZZIHOAWMC-QXKUPLGCSA-N 0.000 description 1
• 208000027351 peripheral muscle weakness Diseases 0.000 description 1
• 230000002688 persistence Effects 0.000 description 1
• 210000000680 phagosome Anatomy 0.000 description 1
• 239000008177 pharmaceutical agent Substances 0.000 description 1
• 230000000144 pharmacologic effect Effects 0.000 description 1
• COLNVLDHVKWLRT-UHFFFAOYSA-N phenylalanine Natural products OC(=O)C(N)CC1=CC=CC=C1 COLNVLDHVKWLRT-UHFFFAOYSA-N 0.000 description 1
• NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
• 239000010452 phosphate Substances 0.000 description 1
• 150000008300 phosphoramidites Chemical class 0.000 description 1
• 230000026731 phosphorylation Effects 0.000 description 1
• 230000000865 phosphorylative effect Effects 0.000 description 1
• 230000007406 plaque accumulation Effects 0.000 description 1
• 230000036470 plasma concentration Effects 0.000 description 1
• 108700004029 pol Genes Proteins 0.000 description 1
• 230000008488 polyadenylation Effects 0.000 description 1
• 229920002704 polyhistidine Polymers 0.000 description 1
• 102000054765 polymorphisms of proteins Human genes 0.000 description 1
• 239000000256 polyoxyethylene sorbitan monolaurate Substances 0.000 description 1
• 235000010486 polyoxyethylene sorbitan monolaurate Nutrition 0.000 description 1
• 229920001282 polysaccharide Polymers 0.000 description 1
• 239000005017 polysaccharide Substances 0.000 description 1
• 235000017924 poor diet Nutrition 0.000 description 1
• 239000011148 porous material Substances 0.000 description 1
• 239000011591 potassium Substances 0.000 description 1
• 229910052700 potassium Inorganic materials 0.000 description 1
• OXCMYAYHXIHQOA-UHFFFAOYSA-N potassium;[2-butyl-5-chloro-3-[[4-[2-(1,2,4-triaza-3-azanidacyclopenta-1,4-dien-5-yl)phenyl]phenyl]methyl]imidazol-4-yl]methanol Chemical compound [K+].CCCCC1=NC(Cl)=C(CO)N1CC1=CC=C(C=2C(=CC=CC=2)C2=N[N-]N=N2)C=C1 OXCMYAYHXIHQOA-UHFFFAOYSA-N 0.000 description 1
• 238000002360 preparation method Methods 0.000 description 1
• 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 1
• 239000002987 primer (paints) Substances 0.000 description 1
• 230000009465 prokaryotic expression Effects 0.000 description 1
• 229960003712 propranolol Drugs 0.000 description 1
• 230000013777 protein digestion Effects 0.000 description 1
• 108060006633 protein kinase Proteins 0.000 description 1
• 238000001273 protein sequence alignment Methods 0.000 description 1
• 229940039716 prothrombin Drugs 0.000 description 1
• 210000001147 pulmonary artery Anatomy 0.000 description 1
• 208000002815 pulmonary hypertension Diseases 0.000 description 1
• 238000000746 purification Methods 0.000 description 1
• 238000003908 quality control method Methods 0.000 description 1
• 238000011158 quantitative evaluation Methods 0.000 description 1
• 229960001455 quinapril Drugs 0.000 description 1
• JSDRRTOADPPCHY-HSQYWUDLSA-N quinapril Chemical compound C([C@@H](C(=O)OCC)N[C@@H](C)C(=O)N1[C@@H](CC2=CC=CC=C2C1)C(O)=O)CC1=CC=CC=C1 JSDRRTOADPPCHY-HSQYWUDLSA-N 0.000 description 1
• 230000005855 radiation Effects 0.000 description 1
• 238000001959 radiotherapy Methods 0.000 description 1
• 229960003401 ramipril Drugs 0.000 description 1
• HDACQVRGBOVJII-JBDAPHQKSA-N ramipril Chemical compound C([C@@H](C(=O)OCC)N[C@@H](C)C(=O)N1[C@@H](C[C@@H]2CCC[C@@H]21)C(O)=O)CC1=CC=CC=C1 HDACQVRGBOVJII-JBDAPHQKSA-N 0.000 description 1
• 238000010188 recombinant method Methods 0.000 description 1
• 238000011084 recovery Methods 0.000 description 1
• 239000003488 releasing hormone Substances 0.000 description 1
• 239000011347 resin Substances 0.000 description 1
• 229920005989 resin Polymers 0.000 description 1
• 201000004193 respiratory failure Diseases 0.000 description 1
• 108091008146 restriction endonucleases Proteins 0.000 description 1
• 230000000717 retained effect Effects 0.000 description 1
• 230000002441 reversible effect Effects 0.000 description 1
• 206010039073 rheumatoid arthritis Diseases 0.000 description 1
• 108091092562 ribozyme Proteins 0.000 description 1
• 150000003839 salts Chemical class 0.000 description 1
• 210000000518 sarcolemma Anatomy 0.000 description 1
• 210000002235 sarcomere Anatomy 0.000 description 1
• 230000007017 scission Effects 0.000 description 1
• 239000000932 sedative agent Substances 0.000 description 1
• 230000001624 sedative effect Effects 0.000 description 1
• ZKZBPNGNEQAJSX-UHFFFAOYSA-N selenocysteine Natural products [SeH]CC(N)C(O)=O ZKZBPNGNEQAJSX-UHFFFAOYSA-N 0.000 description 1
• 235000016491 selenocysteine Nutrition 0.000 description 1
• 229940055619 selenocysteine Drugs 0.000 description 1
• 238000001612 separation test Methods 0.000 description 1
• 210000002966 serum Anatomy 0.000 description 1
• 230000019491 signal transduction Effects 0.000 description 1
• 238000001542 size-exclusion chromatography Methods 0.000 description 1
• 210000003491 skin Anatomy 0.000 description 1
• 230000005586 smoking cessation Effects 0.000 description 1
• 210000002460 smooth muscle Anatomy 0.000 description 1
• 238000002415 sodium dodecyl sulfate polyacrylamide gel electrophoresis Methods 0.000 description 1
• 235000010344 sodium nitrate Nutrition 0.000 description 1
• 239000004317 sodium nitrate Substances 0.000 description 1
• 239000000243 solution Substances 0.000 description 1
• 230000009870 specific binding Effects 0.000 description 1
• 230000037351 starvation Effects 0.000 description 1
• 230000003068 static effect Effects 0.000 description 1
• 238000007619 statistical method Methods 0.000 description 1
• 238000003860 storage Methods 0.000 description 1
• 229960005322 streptomycin Drugs 0.000 description 1
• 238000007920 subcutaneous administration Methods 0.000 description 1
• 239000000758 substrate Substances 0.000 description 1
• 239000013589 supplement Substances 0.000 description 1
• 239000004094 surface-active agent Substances 0.000 description 1
• 239000000725 suspension Substances 0.000 description 1
• 230000008961 swelling Effects 0.000 description 1
• 238000003786 synthesis reaction Methods 0.000 description 1
• 230000009897 systematic effect Effects 0.000 description 1
• 230000009885 systemic effect Effects 0.000 description 1
• 230000008685 targeting Effects 0.000 description 1
• 108700004027 tat Genes Proteins 0.000 description 1
• 101150098170 tat gene Proteins 0.000 description 1
• 150000003505 terpenes Chemical group 0.000 description 1
• 231100001274 therapeutic index Toxicity 0.000 description 1
• 125000000341 threoninyl group Chemical group [H]OC([H])(C([H])([H])[H])C([H])(N([H])[H])C(*)=O 0.000 description 1
• 230000002537 thrombolytic effect Effects 0.000 description 1
• 230000036962 time dependent Effects 0.000 description 1
• 230000019432 tissue death Effects 0.000 description 1
• 230000002103 transcriptional effect Effects 0.000 description 1
• 230000009261 transgenic effect Effects 0.000 description 1
• 230000001052 transient effect Effects 0.000 description 1
• QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 description 1
• 241000701447 unidentified baculovirus Species 0.000 description 1
• 241001529453 unidentified herpesvirus Species 0.000 description 1
• 241001515965 unidentified phage Species 0.000 description 1
• 239000004474 valine Substances 0.000 description 1
• 230000025033 vasoconstriction Effects 0.000 description 1
• 230000024883 vasodilation Effects 0.000 description 1
• 239000003981 vehicle Substances 0.000 description 1
• 210000003462 vein Anatomy 0.000 description 1
• 230000029812 viral genome replication Effects 0.000 description 1
• 230000004580 weight loss Effects 0.000 description 1
• 239000002676 xenobiotic agent Substances 0.000 description 1
• 230000002034 xenobiotic effect Effects 0.000 description 1