CA2693001A1 - Compositions et methodes de traitement de l'angiogenese pathologique et de la permeabilite vasculaire - Google Patents

Info

Publication number

CA2693001A1

CA2693001A1 CA 2693001 CA2693001A CA2693001A1 CA 2693001 A1 CA2693001 A1 CA 2693001A1 CA 2693001 CA2693001 CA 2693001 CA 2693001 A CA2693001 A CA 2693001A CA 2693001 A1 CA2693001 A1 CA 2693001A1

Authority

CA

Canada

Prior art keywords

composition

robo4

activation

seq

slit2

Prior art date

2008-04-16

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.)

Abandoned

Links

• Espacenet
• Global Dossier
• CIPO
• Discuss

• 239000000203 mixture Substances 0.000 title claims abstract description 182
• 238000000034 method Methods 0.000 title claims abstract description 148
• 208000034038 Pathologic Neovascularization Diseases 0.000 title claims abstract description 77
• 230000009963 pathologic angiogenesis Effects 0.000 title claims abstract description 69
• 230000008728 vascular permeability Effects 0.000 title claims abstract description 36
• 150000001875 compounds Chemical class 0.000 claims abstract description 52
• 230000002401 inhibitory effect Effects 0.000 claims abstract description 42
• 101150050515 Robo4 gene Proteins 0.000 claims description 319
• 230000000694 effects Effects 0.000 claims description 169
• 108700011893 Slit homolog 2 Proteins 0.000 claims description 161
• 230000004913 activation Effects 0.000 claims description 151
• 102100027340 Slit homolog 2 protein Human genes 0.000 claims description 146
• 101150085024 Slit2 gene Proteins 0.000 claims description 146
• 230000005764 inhibitory process Effects 0.000 claims description 122
• 102000034257 ADP-Ribosylation Factor 6 Human genes 0.000 claims description 100
• 108090000067 ADP-Ribosylation Factor 6 Proteins 0.000 claims description 100
• 230000011664 signaling Effects 0.000 claims description 78
• 230000002792 vascular Effects 0.000 claims description 75
• 108010019530 Vascular Endothelial Growth Factors Proteins 0.000 claims description 74
• 230000035699 permeability Effects 0.000 claims description 71
• 239000003446 ligand Substances 0.000 claims description 61
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 49
• 230000033115 angiogenesis Effects 0.000 claims description 47
• 108090000765 processed proteins & peptides Proteins 0.000 claims description 45
• 201000010099 disease Diseases 0.000 claims description 42
• 102000004196 processed proteins & peptides Human genes 0.000 claims description 36
• 150000003384 small molecules Chemical class 0.000 claims description 34
• QPGYAMIHXLCFTJ-UHFFFAOYSA-N N-[4-[5-(1,3-benzodioxol-5-yl)-3-methoxy-1,2,4-triazol-1-yl]phenyl]-2-(phenylthio)acetamide Chemical compound N1=C(OC)N=C(C=2C=C3OCOC3=CC=2)N1C(C=C1)=CC=C1NC(=O)CSC1=CC=CC=C1 QPGYAMIHXLCFTJ-UHFFFAOYSA-N 0.000 claims description 33
• 125000000217 alkyl group Chemical group 0.000 claims description 31
• 230000002491 angiogenic effect Effects 0.000 claims description 30
• 238000011282 treatment Methods 0.000 claims description 29
• 150000001413 amino acids Chemical class 0.000 claims description 28
• 229910052760 oxygen Inorganic materials 0.000 claims description 28
• 206010012689 Diabetic retinopathy Diseases 0.000 claims description 27
• 102000005962 receptors Human genes 0.000 claims description 27
• 108020003175 receptors Proteins 0.000 claims description 27
• 206010038933 Retinopathy of prematurity Diseases 0.000 claims description 26
• 206010028980 Neoplasm Diseases 0.000 claims description 25
• 206010001052 Acute respiratory distress syndrome Diseases 0.000 claims description 23
• 208000013616 Respiratory Distress Syndrome Diseases 0.000 claims description 23
• 206010064930 age-related macular degeneration Diseases 0.000 claims description 22
• 208000002780 macular degeneration Diseases 0.000 claims description 22
• 229920001184 polypeptide Polymers 0.000 claims description 22
• 125000003545 alkoxy group Chemical group 0.000 claims description 21
• 201000000028 adult respiratory distress syndrome Diseases 0.000 claims description 20
• 108091008605 VEGF receptors Proteins 0.000 claims description 19
• 102000009484 Vascular Endothelial Growth Factor Receptors Human genes 0.000 claims description 19
• 208000011341 adult acute respiratory distress syndrome Diseases 0.000 claims description 19
• 125000000623 heterocyclic group Chemical group 0.000 claims description 19
• -1 methylene dioxy Chemical group 0.000 claims description 19
• 206010012688 Diabetic retinal oedema Diseases 0.000 claims description 18
• 230000000903 blocking effect Effects 0.000 claims description 18
• 206010052015 cytokine release syndrome Diseases 0.000 claims description 18
• 201000011190 diabetic macular edema Diseases 0.000 claims description 18
• 230000002757 inflammatory effect Effects 0.000 claims description 18
• 206010050685 Cytokine storm Diseases 0.000 claims description 17
• 206010038923 Retinopathy Diseases 0.000 claims description 17
• 125000003275 alpha amino acid group Chemical group 0.000 claims description 17
• 208000009329 Graft vs Host Disease Diseases 0.000 claims description 16
• 206010064097 avian influenza Diseases 0.000 claims description 16
• 230000008497 endothelial barrier function Effects 0.000 claims description 16
• 208000024908 graft versus host disease Diseases 0.000 claims description 16
• 238000004321 preservation Methods 0.000 claims description 16
• 125000001424 substituent group Chemical group 0.000 claims description 16
• 208000002979 Influenza in Birds Diseases 0.000 claims description 15
• 206010030113 Oedema Diseases 0.000 claims description 15
• 208000006011 Stroke Diseases 0.000 claims description 15
• 229910052736 halogen Inorganic materials 0.000 claims description 15
• 150000002367 halogens Chemical class 0.000 claims description 15
• 239000000126 substance Substances 0.000 claims description 15
• 230000004862 vasculogenesis Effects 0.000 claims description 15
• 208000028867 ischemia Diseases 0.000 claims description 14
• 230000000302 ischemic effect Effects 0.000 claims description 14
• 125000003118 aryl group Chemical group 0.000 claims description 13
• 125000000753 cycloalkyl group Chemical group 0.000 claims description 13
• 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 13
• 208000010125 myocardial infarction Diseases 0.000 claims description 13
• 150000003839 salts Chemical class 0.000 claims description 13
• 206010029113 Neovascularisation Diseases 0.000 claims description 11
• 206010061218 Inflammation Diseases 0.000 claims description 10
• 201000011510 cancer Diseases 0.000 claims description 10
• 230000004054 inflammatory process Effects 0.000 claims description 10
• 239000008194 pharmaceutical composition Substances 0.000 claims description 10
• 208000035473 Communicable disease Diseases 0.000 claims description 9
• 208000031662 Noncommunicable disease Diseases 0.000 claims description 9
• 206010063837 Reperfusion injury Diseases 0.000 claims description 9
• 206010051379 Systemic Inflammatory Response Syndrome Diseases 0.000 claims description 9
• 125000002947 alkylene group Chemical group 0.000 claims description 9
• 125000001072 heteroaryl group Chemical group 0.000 claims description 9
• 150000004677 hydrates Chemical class 0.000 claims description 9
• 229910052739 hydrogen Inorganic materials 0.000 claims description 9
• 239000001257 hydrogen Substances 0.000 claims description 9
• 230000002458 infectious effect Effects 0.000 claims description 9
• 230000002062 proliferating effect Effects 0.000 claims description 9
• 239000012453 solvate Substances 0.000 claims description 9
• 229910052717 sulfur Inorganic materials 0.000 claims description 9
• 208000004644 retinal vein occlusion Diseases 0.000 claims description 8
• 206010003445 Ascites Diseases 0.000 claims description 7
• 208000003174 Brain Neoplasms Diseases 0.000 claims description 7
• 206010019280 Heart failures Diseases 0.000 claims description 7
• 208000006395 Meigs Syndrome Diseases 0.000 claims description 7
• 206010027139 Meigs' syndrome Diseases 0.000 claims description 7
• 206010027476 Metastases Diseases 0.000 claims description 7
• 206010029164 Nephrotic syndrome Diseases 0.000 claims description 7
• 208000005228 Pericardial Effusion Diseases 0.000 claims description 7
• 208000002151 Pleural effusion Diseases 0.000 claims description 7
• 206010035664 Pneumonia Diseases 0.000 claims description 7
• 206010040047 Sepsis Diseases 0.000 claims description 7
• 241000700647 Variola virus Species 0.000 claims description 7
• 230000036210 malignancy Effects 0.000 claims description 7
• 230000009401 metastasis Effects 0.000 claims description 7
• 230000002107 myocardial effect Effects 0.000 claims description 7
• 230000002685 pulmonary effect Effects 0.000 claims description 7
• 230000029663 wound healing Effects 0.000 claims description 7
• 206010017076 Fracture Diseases 0.000 claims description 6
• 208000010412 Glaucoma Diseases 0.000 claims description 6
• 208000002260 Keloid Diseases 0.000 claims description 6
• 208000008469 Peptic Ulcer Diseases 0.000 claims description 6
• 201000004681 Psoriasis Diseases 0.000 claims description 6
• 206010037649 Pyogenic granuloma Diseases 0.000 claims description 6
• 208000001647 Renal Insufficiency Diseases 0.000 claims description 6
• 101150018985 SLIT3 gene Proteins 0.000 claims description 6
• 206010039710 Scleroderma Diseases 0.000 claims description 6
• 102100027339 Slit homolog 3 protein Human genes 0.000 claims description 6
• 206010043189 Telangiectasia Diseases 0.000 claims description 6
• 208000026935 allergic disease Diseases 0.000 claims description 6
• 206010003246 arthritis Diseases 0.000 claims description 6
• 208000021921 corneal disease Diseases 0.000 claims description 6
• 201000011066 hemangioma Diseases 0.000 claims description 6
• 230000011132 hemopoiesis Effects 0.000 claims description 6
• 125000005842 heteroatom Chemical group 0.000 claims description 6
• 210000001117 keloid Anatomy 0.000 claims description 6
• 201000006370 kidney failure Diseases 0.000 claims description 6
• 208000032839 leukemia Diseases 0.000 claims description 6
• 230000005906 menstruation Effects 0.000 claims description 6
• 201000003142 neovascular glaucoma Diseases 0.000 claims description 6
• 230000016087 ovulation Effects 0.000 claims description 6
• 208000011906 peptic ulcer disease Diseases 0.000 claims description 6
• 230000028742 placenta development Effects 0.000 claims description 6
• 125000003107 substituted aryl group Chemical group 0.000 claims description 6
• 125000005346 substituted cycloalkyl group Chemical group 0.000 claims description 6
• 208000009056 telangiectasis Diseases 0.000 claims description 6
• FWMNVWWHGCHHJJ-SKKKGAJSSA-N 4-amino-1-[(2r)-6-amino-2-[[(2r)-2-[[(2r)-2-[[(2r)-2-amino-3-phenylpropanoyl]amino]-3-phenylpropanoyl]amino]-4-methylpentanoyl]amino]hexanoyl]piperidine-4-carboxylic acid Chemical compound C([C@H](C(=O)N[C@H](CC(C)C)C(=O)N[C@H](CCCCN)C(=O)N1CCC(N)(CC1)C(O)=O)NC(=O)[C@H](N)CC=1C=CC=CC=1)C1=CC=CC=C1 FWMNVWWHGCHHJJ-SKKKGAJSSA-N 0.000 claims description 4
• 125000004435 hydrogen atom Chemical class [H]* 0.000 claims 6
• 102100025490 Slit homolog 1 protein Human genes 0.000 claims 4
• 101150028561 Slit1 gene Proteins 0.000 claims 4
• 102000005789 Vascular Endothelial Growth Factors Human genes 0.000 claims 4
• 230000019491 signal transduction Effects 0.000 abstract description 20
• 238000012216 screening Methods 0.000 abstract description 6
• 210000004027 cell Anatomy 0.000 description 242
• 108090000623 proteins and genes Proteins 0.000 description 122
• 102000004169 proteins and genes Human genes 0.000 description 113
• 235000018102 proteins Nutrition 0.000 description 112
• 102000018546 Paxillin Human genes 0.000 description 100
• 108700031954 Tgfb1i1/Leupaxin/TGFB1I1 Proteins 0.000 description 100
• ACNHBCIZLNNLRS-UHFFFAOYSA-N Paxilline 1 Natural products N1C2=CC=CC=C2C2=C1C1(C)C3(C)CCC4OC(C(C)(O)C)C(=O)C=C4C3(O)CCC1C2 ACNHBCIZLNNLRS-UHFFFAOYSA-N 0.000 description 99
• 102000009524 Vascular Endothelial Growth Factor A Human genes 0.000 description 98
• 108010073929 Vascular Endothelial Growth Factor A Proteins 0.000 description 98
• ACNHBCIZLNNLRS-UBGQALKQSA-N paxilline Chemical compound N1C2=CC=CC=C2C2=C1[C@]1(C)[C@@]3(C)CC[C@@H]4O[C@H](C(C)(O)C)C(=O)C=C4[C@]3(O)CC[C@H]1C2 ACNHBCIZLNNLRS-UBGQALKQSA-N 0.000 description 98
• 102100037362 Fibronectin Human genes 0.000 description 85
• 108010067306 Fibronectins Proteins 0.000 description 85
• 210000002889 endothelial cell Anatomy 0.000 description 79
• 241000699670 Mus sp. Species 0.000 description 71
• 230000007480 spreading Effects 0.000 description 55
• 238000003892 spreading Methods 0.000 description 55
• IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 48
• 238000003556 assay Methods 0.000 description 47
• 230000003511 endothelial effect Effects 0.000 description 47
• 230000003993 interaction Effects 0.000 description 40
• 230000001419 dependent effect Effects 0.000 description 37
• 239000013543 active substance Substances 0.000 description 36
• 238000013508 migration Methods 0.000 description 31
• 238000001262 western blot Methods 0.000 description 31
• 230000005012 migration Effects 0.000 description 30
• 230000015572 biosynthetic process Effects 0.000 description 29
• 210000002257 embryonic structure Anatomy 0.000 description 28
• 150000007523 nucleic acids Chemical class 0.000 description 28
• 238000002360 preparation method Methods 0.000 description 27
• 208000005590 Choroidal Neovascularization Diseases 0.000 description 26
• 206010060823 Choroidal neovascularisation Diseases 0.000 description 26
• 102100034031 Cytohesin-2 Human genes 0.000 description 26
• 101000870120 Homo sapiens Cytohesin-2 Proteins 0.000 description 26
• 101000808011 Homo sapiens Vascular endothelial growth factor A Proteins 0.000 description 26
• 235000001014 amino acid Nutrition 0.000 description 26
• 102000058223 human VEGFA Human genes 0.000 description 26
• 102000039446 nucleic acids Human genes 0.000 description 26
• 108020004707 nucleic acids Proteins 0.000 description 26
• 230000001413 cellular effect Effects 0.000 description 25
• 210000005220 cytoplasmic tail Anatomy 0.000 description 25
• 230000014509 gene expression Effects 0.000 description 25
• 230000002207 retinal effect Effects 0.000 description 25
• 102100024458 Cyclin-dependent kinase inhibitor 2A Human genes 0.000 description 23
• 101710102803 Tumor suppressor ARF Proteins 0.000 description 23
• 239000012634 fragment Substances 0.000 description 23
• 108020004459 Small interfering RNA Proteins 0.000 description 22
• QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 22
• 239000001301 oxygen Substances 0.000 description 22
• 210000001519 tissue Anatomy 0.000 description 22
• 239000003795 chemical substances by application Substances 0.000 description 21
• 238000002474 experimental method Methods 0.000 description 20
• 230000002829 reductive effect Effects 0.000 description 20
• 239000004055 small Interfering RNA Substances 0.000 description 20
• 102100033459 Transforming growth factor beta-1-induced transcript 1 protein Human genes 0.000 description 19
• 101710188061 Transforming growth factor beta-1-induced transcript 1 protein Proteins 0.000 description 19
• 210000004204 blood vessel Anatomy 0.000 description 19
• 230000035926 haptotaxis Effects 0.000 description 19
• 125000004573 morpholin-4-yl group Chemical group N1(CCOCC1)* 0.000 description 19
• 108091032973 (ribonucleotides)n+m Proteins 0.000 description 18
• 238000000338 in vitro Methods 0.000 description 18
• 239000000463 material Substances 0.000 description 17
• 230000001404 mediated effect Effects 0.000 description 17
• 238000010232 migration assay Methods 0.000 description 17
• 102100039601 ARF GTPase-activating protein GIT1 Human genes 0.000 description 16
• 101000888659 Homo sapiens ARF GTPase-activating protein GIT1 Proteins 0.000 description 16
• 238000001727 in vivo Methods 0.000 description 16
• 238000002347 injection Methods 0.000 description 15
• 239000007924 injection Substances 0.000 description 15
• 230000004044 response Effects 0.000 description 15
• 238000006467 substitution reaction Methods 0.000 description 15
• 239000013598 vector Substances 0.000 description 15
• 101150018624 ARF6 gene Proteins 0.000 description 14
• 108091003079 Bovine Serum Albumin Proteins 0.000 description 14
• 101100379471 Drosophila melanogaster Arf51F gene Proteins 0.000 description 14
• 102000008946 Fibrinogen Human genes 0.000 description 14
• 108010049003 Fibrinogen Proteins 0.000 description 14
• 229940098773 bovine serum albumin Drugs 0.000 description 14
• 229940012952 fibrinogen Drugs 0.000 description 14
• 239000005090 green fluorescent protein Substances 0.000 description 14
• 102000036801 ADP-Ribosylation Factor 1 Human genes 0.000 description 13
• 108010016281 ADP-Ribosylation Factor 1 Proteins 0.000 description 13
• 241000252212 Danio rerio Species 0.000 description 13
• 239000013592 cell lysate Substances 0.000 description 13
• 230000012292 cell migration Effects 0.000 description 13
• 230000001086 cytosolic effect Effects 0.000 description 13
• 238000012217 deletion Methods 0.000 description 13
• 230000037430 deletion Effects 0.000 description 13
• 239000003112 inhibitor Substances 0.000 description 13
• 102000011068 Cdc42 Human genes 0.000 description 12
• 108050001278 Cdc42 Proteins 0.000 description 12
• 102100024193 Mitogen-activated protein kinase 1 Human genes 0.000 description 12
• 239000000284 extract Substances 0.000 description 12
• 239000012528 membrane Substances 0.000 description 12
• 108020004999 messenger RNA Proteins 0.000 description 12
• 108090000379 Fibroblast growth factor 2 Proteins 0.000 description 11
• 102000003974 Fibroblast growth factor 2 Human genes 0.000 description 11
• 208000017442 Retinal disease Diseases 0.000 description 11
• 239000002299 complementary DNA Substances 0.000 description 11
• 210000004379 membrane Anatomy 0.000 description 11
• 230000009467 reduction Effects 0.000 description 11
• 238000011144 upstream manufacturing Methods 0.000 description 11
• 108091023037 Aptamer Proteins 0.000 description 10
• 241001465754 Metazoa Species 0.000 description 10
• 241001529936 Murinae Species 0.000 description 10
• 239000012190 activator Substances 0.000 description 10
• 230000006378 damage Effects 0.000 description 10
• 230000010595 endothelial cell migration Effects 0.000 description 10
• 210000001650 focal adhesion Anatomy 0.000 description 10
• 108020001507 fusion proteins Proteins 0.000 description 10
• 102000037865 fusion proteins Human genes 0.000 description 10
• 230000037361 pathway Effects 0.000 description 10
• 238000011002 quantification Methods 0.000 description 10
• 102000002260 Alkaline Phosphatase Human genes 0.000 description 9
• 108020004774 Alkaline Phosphatase Proteins 0.000 description 9
• 210000003038 endothelium Anatomy 0.000 description 9
• 239000002504 physiological saline solution Substances 0.000 description 9
• 102000004127 Cytokines Human genes 0.000 description 8
• 108090000695 Cytokines Proteins 0.000 description 8
• 108020004414 DNA Proteins 0.000 description 8
• 241000699666 Mus <mouse, genus> Species 0.000 description 8
• 210000004899 c-terminal region Anatomy 0.000 description 8
• 230000006870 function Effects 0.000 description 8
• 230000002779 inactivation Effects 0.000 description 8
• 238000003780 insertion Methods 0.000 description 8
• 230000037431 insertion Effects 0.000 description 8
• SQEHCNOBYLQFTG-UHFFFAOYSA-M lithium;thiophene-2-carboxylate Chemical compound [Li+].[O-]C(=O)C1=CC=CS1 SQEHCNOBYLQFTG-UHFFFAOYSA-M 0.000 description 8
• 230000001575 pathological effect Effects 0.000 description 8
• 230000026731 phosphorylation Effects 0.000 description 8
• 238000006366 phosphorylation reaction Methods 0.000 description 8
• 239000013612 plasmid Substances 0.000 description 8
• 230000008569 process Effects 0.000 description 8
• 108090001090 Lectins Proteins 0.000 description 7
• 102000004856 Lectins Human genes 0.000 description 7
• 238000012228 RNA interference-mediated gene silencing Methods 0.000 description 7
• 240000004808 Saccharomyces cerevisiae Species 0.000 description 7
• 108090000190 Thrombin Proteins 0.000 description 7
• 125000004432 carbon atom Chemical group C* 0.000 description 7
• 230000009087 cell motility Effects 0.000 description 7
• 230000007423 decrease Effects 0.000 description 7
• 230000007547 defect Effects 0.000 description 7
• 208000035475 disorder Diseases 0.000 description 7
• 230000009368 gene silencing by RNA Effects 0.000 description 7
• 102000006495 integrins Human genes 0.000 description 7
• 108010044426 integrins Proteins 0.000 description 7
• 238000000059 patterning Methods 0.000 description 7
• 230000001105 regulatory effect Effects 0.000 description 7
• 210000001525 retina Anatomy 0.000 description 7
• 108700002783 roundabout Proteins 0.000 description 7
• 239000000243 solution Substances 0.000 description 7
• 230000001225 therapeutic effect Effects 0.000 description 7
• 229960004072 thrombin Drugs 0.000 description 7
• 230000014616 translation Effects 0.000 description 7
• 230000006459 vascular development Effects 0.000 description 7
• 102000010834 Extracellular Matrix Proteins Human genes 0.000 description 6
• 108010037362 Extracellular Matrix Proteins Proteins 0.000 description 6
• WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 6
• OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 6
• 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 6
• 239000003636 conditioned culture medium Substances 0.000 description 6
• 238000009472 formulation Methods 0.000 description 6
• 230000012010 growth Effects 0.000 description 6
• 238000001114 immunoprecipitation Methods 0.000 description 6
• 230000001965 increasing effect Effects 0.000 description 6
• 210000004924 lung microvascular endothelial cell Anatomy 0.000 description 6
• 230000035772 mutation Effects 0.000 description 6
• 230000010412 perfusion Effects 0.000 description 6
• 238000000746 purification Methods 0.000 description 6
• 230000007115 recruitment Effects 0.000 description 6
• 238000012360 testing method Methods 0.000 description 6
• 238000013518 transcription Methods 0.000 description 6
• 230000035897 transcription Effects 0.000 description 6
• 238000013519 translation Methods 0.000 description 6
• 230000004614 tumor growth Effects 0.000 description 6
• 210000003462 vein Anatomy 0.000 description 6
• 102000004190 Enzymes Human genes 0.000 description 5
• 108090000790 Enzymes Proteins 0.000 description 5
• ROHFNLRQFUQHCH-YFKPBYRVSA-N L-leucine Chemical compound CC(C)C[C@H](N)C(O)=O ROHFNLRQFUQHCH-YFKPBYRVSA-N 0.000 description 5
• KDXKERNSBIXSRK-YFKPBYRVSA-N L-lysine Chemical compound NCCCC[C@H](N)C(O)=O KDXKERNSBIXSRK-YFKPBYRVSA-N 0.000 description 5
• 208000027418 Wounds and injury Diseases 0.000 description 5
• 238000004458 analytical method Methods 0.000 description 5
• 230000037396 body weight Effects 0.000 description 5
• 238000004113 cell culture Methods 0.000 description 5
• 230000004663 cell proliferation Effects 0.000 description 5
• 229940079593 drug Drugs 0.000 description 5
• 239000003814 drug Substances 0.000 description 5
• 229940088598 enzyme Drugs 0.000 description 5
• 239000003102 growth factor Substances 0.000 description 5
• 150000002430 hydrocarbons Chemical group 0.000 description 5
• 239000012133 immunoprecipitate Substances 0.000 description 5
• 208000014674 injury Diseases 0.000 description 5
• 238000011813 knockout mouse model Methods 0.000 description 5
• 210000004072 lung Anatomy 0.000 description 5
• 239000006166 lysate Substances 0.000 description 5
• 230000004048 modification Effects 0.000 description 5
• 238000012986 modification Methods 0.000 description 5
• 238000010172 mouse model Methods 0.000 description 5
• 229920002113 octoxynol Polymers 0.000 description 5
• 210000003668 pericyte Anatomy 0.000 description 5
• 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 5
• 230000000638 stimulation Effects 0.000 description 5
• 208000024891 symptom Diseases 0.000 description 5
• 210000004509 vascular smooth muscle cell Anatomy 0.000 description 5
• 210000005166 vasculature Anatomy 0.000 description 5
• 102000041188 ARF family Human genes 0.000 description 4
• 108091061173 ARF family Proteins 0.000 description 4
• 108700028369 Alleles Proteins 0.000 description 4
• 101800001318 Capsid protein VP4 Proteins 0.000 description 4
• 241000588724 Escherichia coli Species 0.000 description 4
• HVLSXIKZNLPZJJ-TXZCQADKSA-N HA peptide Chemical compound C([C@@H](C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](C(C)C)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N[C@@H](C)C(O)=O)NC(=O)[C@H]1N(CCC1)C(=O)[C@@H](N)CC=1C=CC(O)=CC=1)C1=CC=C(O)C=C1 HVLSXIKZNLPZJJ-TXZCQADKSA-N 0.000 description 4
• NTYJJOPFIAHURM-UHFFFAOYSA-N Histamine Chemical compound NCCC1=CN=CN1 NTYJJOPFIAHURM-UHFFFAOYSA-N 0.000 description 4
• 241000124008 Mammalia Species 0.000 description 4
• 102220506950 Ras-related C3 botulinum toxin substrate 1_G12V_mutation Human genes 0.000 description 4
• 102100027609 Rho-related GTP-binding protein RhoD Human genes 0.000 description 4
• 241000700605 Viruses Species 0.000 description 4
• 230000002159 abnormal effect Effects 0.000 description 4
• 206010069351 acute lung injury Diseases 0.000 description 4
• 238000000787 affinity precipitation Methods 0.000 description 4
• 125000000539 amino acid group Chemical group 0.000 description 4
• 239000002870 angiogenesis inducing agent Substances 0.000 description 4
• 238000010171 animal model Methods 0.000 description 4
• 238000013459 approach Methods 0.000 description 4
• 230000002238 attenuated effect Effects 0.000 description 4
• 210000002469 basement membrane Anatomy 0.000 description 4
• 125000002619 bicyclic group Chemical group 0.000 description 4
• 230000033228 biological regulation Effects 0.000 description 4
• 239000003153 chemical reaction reagent Substances 0.000 description 4
• 238000000749 co-immunoprecipitation Methods 0.000 description 4
• 238000004624 confocal microscopy Methods 0.000 description 4
• 230000034994 death Effects 0.000 description 4
• 231100000517 death Toxicity 0.000 description 4
• 238000006073 displacement reaction Methods 0.000 description 4
• 239000002158 endotoxin Substances 0.000 description 4
• 238000005516 engineering process Methods 0.000 description 4
• 210000002744 extracellular matrix Anatomy 0.000 description 4
• 238000000799 fluorescence microscopy Methods 0.000 description 4
• 238000002875 fluorescence polarization Methods 0.000 description 4
• 238000005194 fractionation Methods 0.000 description 4
• 238000003197 gene knockdown Methods 0.000 description 4
• 238000011068 loading method Methods 0.000 description 4
• 210000004962 mammalian cell Anatomy 0.000 description 4
• 210000001161 mammalian embryo Anatomy 0.000 description 4
• 238000004519 manufacturing process Methods 0.000 description 4
• 239000011159 matrix material Substances 0.000 description 4
• 239000002773 nucleotide Substances 0.000 description 4
• 125000003729 nucleotide group Chemical group 0.000 description 4
• 235000015097 nutrients Nutrition 0.000 description 4
• 239000002953 phosphate buffered saline Substances 0.000 description 4
• 238000000159 protein binding assay Methods 0.000 description 4
• 238000010379 pull-down assay Methods 0.000 description 4
• 230000002441 reversible effect Effects 0.000 description 4
• 238000002741 site-directed mutagenesis Methods 0.000 description 4
• 208000011580 syndromic disease Diseases 0.000 description 4
• YFDSDPIBEUFTMI-UHFFFAOYSA-N tribromoethanol Chemical compound OCC(Br)(Br)Br YFDSDPIBEUFTMI-UHFFFAOYSA-N 0.000 description 4
• 229950004616 tribromoethanol Drugs 0.000 description 4
• 230000005740 tumor formation Effects 0.000 description 4
• 239000003981 vehicle Substances 0.000 description 4
• 238000001086 yeast two-hybrid system Methods 0.000 description 4
• 102000007469 Actins Human genes 0.000 description 3
• 108010085238 Actins Proteins 0.000 description 3
• 229920000936 Agarose Polymers 0.000 description 3
• 101100511175 Caenorhabditis elegans lim-4 gene Proteins 0.000 description 3
• 241000283707 Capra Species 0.000 description 3
• 102000014914 Carrier Proteins Human genes 0.000 description 3
• 150000008574 D-amino acids Chemical class 0.000 description 3
• 239000006144 Dulbecco’s modified Eagle's medium Substances 0.000 description 3
• 102000002090 Fibronectin type III Human genes 0.000 description 3
• 108050009401 Fibronectin type III Proteins 0.000 description 3
• 101001098520 Gallus gallus Paxillin Proteins 0.000 description 3
• DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 3
• 208000032843 Hemorrhage Diseases 0.000 description 3
• 108010001336 Horseradish Peroxidase Proteins 0.000 description 3
• ROHFNLRQFUQHCH-UHFFFAOYSA-N Leucine Natural products CC(C)CC(N)C(O)=O ROHFNLRQFUQHCH-UHFFFAOYSA-N 0.000 description 3
• KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 3
• 239000004472 Lysine Substances 0.000 description 3
• 102000002274 Matrix Metalloproteinases Human genes 0.000 description 3
• 108010000684 Matrix Metalloproteinases Proteins 0.000 description 3
• 208000037273 Pathologic Processes Diseases 0.000 description 3
• 102100022122 Ras-related C3 botulinum toxin substrate 1 Human genes 0.000 description 3
• 241000251539 Vertebrata <Metazoa> Species 0.000 description 3
• 230000035508 accumulation Effects 0.000 description 3
• 238000009825 accumulation Methods 0.000 description 3
• 230000002411 adverse Effects 0.000 description 3
• 230000000692 anti-sense effect Effects 0.000 description 3
• 210000000709 aorta Anatomy 0.000 description 3
• 210000001367 artery Anatomy 0.000 description 3
• 230000004888 barrier function Effects 0.000 description 3
• 230000008901 benefit Effects 0.000 description 3
• 108091008324 binding proteins Proteins 0.000 description 3
• 230000004071 biological effect Effects 0.000 description 3
• 210000004369 blood Anatomy 0.000 description 3
• 239000008280 blood Substances 0.000 description 3
• 239000011203 carbon fibre reinforced carbon Substances 0.000 description 3
• 239000000969 carrier Substances 0.000 description 3
• 230000015556 catabolic process Effects 0.000 description 3
• 210000000170 cell membrane Anatomy 0.000 description 3
• 239000013553 cell monolayer Substances 0.000 description 3
• 230000008859 change Effects 0.000 description 3
• 230000002950 deficient Effects 0.000 description 3
• 230000006735 deficit Effects 0.000 description 3
• 230000018109 developmental process Effects 0.000 description 3
• 208000037765 diseases and disorders Diseases 0.000 description 3
• 239000003937 drug carrier Substances 0.000 description 3
• 230000002500 effect on skin Effects 0.000 description 3
• 230000008030 elimination Effects 0.000 description 3
• 238000003379 elimination reaction Methods 0.000 description 3
• 238000000605 extraction Methods 0.000 description 3
• 230000005714 functional activity Effects 0.000 description 3
• 230000004927 fusion Effects 0.000 description 3
• 230000002068 genetic effect Effects 0.000 description 3
• 210000005119 human aortic smooth muscle cell Anatomy 0.000 description 3
• 150000002431 hydrogen Chemical class 0.000 description 3
• 238000011534 incubation Methods 0.000 description 3
• 230000001939 inductive effect Effects 0.000 description 3
• 230000028709 inflammatory response Effects 0.000 description 3
• 230000000977 initiatory effect Effects 0.000 description 3
• 230000033001 locomotion Effects 0.000 description 3
• 238000010369 molecular cloning Methods 0.000 description 3
• NKAAEMMYHLFEFN-UHFFFAOYSA-M monosodium tartrate Chemical compound [Na+].OC(=O)C(O)C(O)C([O-])=O NKAAEMMYHLFEFN-UHFFFAOYSA-M 0.000 description 3
• 238000002703 mutagenesis Methods 0.000 description 3
• 231100000350 mutagenesis Toxicity 0.000 description 3
• 230000013152 negative regulation of cell migration Effects 0.000 description 3
• 230000002018 overexpression Effects 0.000 description 3
• 230000009054 pathological process Effects 0.000 description 3
• 239000000137 peptide hydrolase inhibitor Substances 0.000 description 3
• 230000002265 prevention Effects 0.000 description 3
• 239000000047 product Substances 0.000 description 3
• 230000035755 proliferation Effects 0.000 description 3
• 230000001737 promoting effect Effects 0.000 description 3
• 230000010410 reperfusion Effects 0.000 description 3
• 239000000523 sample Substances 0.000 description 3
• 210000002966 serum Anatomy 0.000 description 3
• 102000030938 small GTPase Human genes 0.000 description 3
• 108060007624 small GTPase Proteins 0.000 description 3
• 102000009076 src-Family Kinases Human genes 0.000 description 3
• 108010087686 src-Family Kinases Proteins 0.000 description 3
• 238000001356 surgical procedure Methods 0.000 description 3
• 230000004083 survival effect Effects 0.000 description 3
• 238000003786 synthesis reaction Methods 0.000 description 3
• 230000005747 tumor angiogenesis Effects 0.000 description 3
• 210000004881 tumor cell Anatomy 0.000 description 3
• 230000004393 visual impairment Effects 0.000 description 3
• 238000012800 visualization Methods 0.000 description 3
• 108020004491 Antisense DNA Proteins 0.000 description 2
• 108020005544 Antisense RNA Proteins 0.000 description 2
• IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
• 102100026189 Beta-galactosidase Human genes 0.000 description 2
• 201000004569 Blindness Diseases 0.000 description 2
• 108090000994 Catalytic RNA Proteins 0.000 description 2
• 102000053642 Catalytic RNA Human genes 0.000 description 2
• 108091026890 Coding region Proteins 0.000 description 2
• 108700024394 Exon Proteins 0.000 description 2
• ZHNUHDYFZUAESO-UHFFFAOYSA-N Formamide Chemical compound NC=O ZHNUHDYFZUAESO-UHFFFAOYSA-N 0.000 description 2
• 102000018898 GTPase-Activating Proteins Human genes 0.000 description 2
• 108091006094 GTPase-accelerating proteins Proteins 0.000 description 2
• 208000016988 Hemorrhagic Stroke Diseases 0.000 description 2
• 101001027128 Homo sapiens Fibronectin Proteins 0.000 description 2
• 101001110286 Homo sapiens Ras-related C3 botulinum toxin substrate 1 Proteins 0.000 description 2
• 101000611183 Homo sapiens Tumor necrosis factor Proteins 0.000 description 2
• 206010021143 Hypoxia Diseases 0.000 description 2
• 108060003951 Immunoglobulin Proteins 0.000 description 2
• 102000006496 Immunoglobulin Heavy Chains Human genes 0.000 description 2
• 108010019476 Immunoglobulin Heavy Chains Proteins 0.000 description 2
• ONIBWKKTOPOVIA-BYPYZUCNSA-N L-Proline Chemical compound OC(=O)[C@@H]1CCCN1 ONIBWKKTOPOVIA-BYPYZUCNSA-N 0.000 description 2
• COLNVLDHVKWLRT-QMMMGPOBSA-N L-phenylalanine Chemical compound OC(=O)[C@@H](N)CC1=CC=CC=C1 COLNVLDHVKWLRT-QMMMGPOBSA-N 0.000 description 2
• QIVBCDIJIAJPQS-VIFPVBQESA-N L-tryptophane Chemical compound C1=CC=C2C(C[C@H](N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-VIFPVBQESA-N 0.000 description 2
• 239000012097 Lipofectamine 2000 Substances 0.000 description 2
• FULZLIGZKMKICU-UHFFFAOYSA-N N-phenylthiourea Chemical compound NC(=S)NC1=CC=CC=C1 FULZLIGZKMKICU-UHFFFAOYSA-N 0.000 description 2
• 108091028043 Nucleic acid sequence Proteins 0.000 description 2
• 238000013355 OIR mouse model Methods 0.000 description 2
• 108091034117 Oligonucleotide Proteins 0.000 description 2
• 108091005804 Peptidases Proteins 0.000 description 2
• 102000035195 Peptidases Human genes 0.000 description 2
• 108010038512 Platelet-Derived Growth Factor Proteins 0.000 description 2
• 102000010780 Platelet-Derived Growth Factor Human genes 0.000 description 2
• 229920001213 Polysorbate 20 Polymers 0.000 description 2
• 102100033237 Pro-epidermal growth factor Human genes 0.000 description 2
• ONIBWKKTOPOVIA-UHFFFAOYSA-N Proline Natural products OC(=O)C1CCCN1 ONIBWKKTOPOVIA-UHFFFAOYSA-N 0.000 description 2
• 206010037423 Pulmonary oedema Diseases 0.000 description 2
• 230000006819 RNA synthesis Effects 0.000 description 2
• 108020004511 Recombinant DNA Proteins 0.000 description 2
• 102000042463 Rho family Human genes 0.000 description 2
• 108091078243 Rho family Proteins 0.000 description 2
• IWUCXVSUMQZMFG-AFCXAGJDSA-N Ribavirin Chemical compound N1=C(C(=O)N)N=CN1[C@H]1[C@H](O)[C@H](O)[C@@H](CO)O1 IWUCXVSUMQZMFG-AFCXAGJDSA-N 0.000 description 2
• FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
• 229940122618 Trypsin inhibitor Drugs 0.000 description 2
• 101710162629 Trypsin inhibitor Proteins 0.000 description 2
• QIVBCDIJIAJPQS-UHFFFAOYSA-N Tryptophan Natural products C1=CC=C2C(CC(N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-UHFFFAOYSA-N 0.000 description 2
• 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 2
• 238000002835 absorbance Methods 0.000 description 2
• 239000004480 active ingredient Substances 0.000 description 2
• 102000035181 adaptor proteins Human genes 0.000 description 2
• 108091005764 adaptor proteins Proteins 0.000 description 2
• 125000003295 alanine group Chemical group N[C@@H](C)C(=O)* 0.000 description 2
• 125000003342 alkenyl group Chemical group 0.000 description 2
• 230000004075 alteration Effects 0.000 description 2
• 210000000648 angioblast Anatomy 0.000 description 2
• 239000003816 antisense DNA Substances 0.000 description 2
• 230000001580 bacterial effect Effects 0.000 description 2
• 230000009286 beneficial effect Effects 0.000 description 2
• 108010005774 beta-Galactosidase Proteins 0.000 description 2
• 230000017531 blood circulation Effects 0.000 description 2
• 210000001775 bruch membrane Anatomy 0.000 description 2
• 239000000872 buffer Substances 0.000 description 2
• 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 2
• 150000001721 carbon Chemical group 0.000 description 2
• 229910052799 carbon Inorganic materials 0.000 description 2
• 230000021164 cell adhesion Effects 0.000 description 2
• PBAYDYUZOSNJGU-UHFFFAOYSA-N chelidonic acid Natural products OC(=O)C1=CC(=O)C=C(C(O)=O)O1 PBAYDYUZOSNJGU-UHFFFAOYSA-N 0.000 description 2
• 238000006243 chemical reaction Methods 0.000 description 2
• 210000004978 chinese hamster ovary cell Anatomy 0.000 description 2
• 230000000295 complement effect Effects 0.000 description 2
• 239000003184 complementary RNA Substances 0.000 description 2
• 238000007796 conventional method Methods 0.000 description 2
• 239000000287 crude extract Substances 0.000 description 2
• 125000004122 cyclic group Chemical group 0.000 description 2
• 235000018417 cysteine Nutrition 0.000 description 2
• XUJNEKJLAYXESH-UHFFFAOYSA-N cysteine Natural products SCC(N)C(O)=O XUJNEKJLAYXESH-UHFFFAOYSA-N 0.000 description 2
• 238000006731 degradation reaction Methods 0.000 description 2
• 238000000326 densiometry Methods 0.000 description 2
• 210000004207 dermis Anatomy 0.000 description 2
• 238000003745 diagnosis Methods 0.000 description 2
• 230000004069 differentiation Effects 0.000 description 2
• 229940042399 direct acting antivirals protease inhibitors Drugs 0.000 description 2
• 238000009826 distribution Methods 0.000 description 2
• 230000003828 downregulation Effects 0.000 description 2
• 238000009509 drug development Methods 0.000 description 2
• 238000007876 drug discovery Methods 0.000 description 2
• 230000013020 embryo development Effects 0.000 description 2
• 239000000839 emulsion Substances 0.000 description 2
• 238000005538 encapsulation Methods 0.000 description 2
• 210000003989 endothelium vascular Anatomy 0.000 description 2
• 210000000981 epithelium Anatomy 0.000 description 2
• 230000004761 fibrosis Effects 0.000 description 2
• 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 2
• 125000000291 glutamic acid group Chemical group N[C@@H](CCC(O)=O)C(=O)* 0.000 description 2
• 125000000404 glutamine group Chemical group N[C@@H](CCC(N)=O)C(=O)* 0.000 description 2
• RWSXRVCMGQZWBV-WDSKDSINSA-N glutathione Chemical compound OC(=O)[C@@H](N)CCC(=O)N[C@@H](CS)C(=O)NCC(O)=O RWSXRVCMGQZWBV-WDSKDSINSA-N 0.000 description 2
• 238000006206 glycosylation reaction Methods 0.000 description 2
• 229960001340 histamine Drugs 0.000 description 2
• 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 2
• 125000001165 hydrophobic group Chemical group 0.000 description 2
• 230000007954 hypoxia Effects 0.000 description 2
• 102000018358 immunoglobulin Human genes 0.000 description 2
• 238000000099 in vitro assay Methods 0.000 description 2
• 238000011065 in-situ storage Methods 0.000 description 2
• 210000004969 inflammatory cell Anatomy 0.000 description 2
• 230000006662 intracellular pathway Effects 0.000 description 2
• 208000020658 intracerebral hemorrhage Diseases 0.000 description 2
• 238000010253 intravenous injection Methods 0.000 description 2
• 238000002955 isolation Methods 0.000 description 2
• 210000003292 kidney cell Anatomy 0.000 description 2
• 238000013532 laser treatment Methods 0.000 description 2
• 239000002502 liposome Substances 0.000 description 2
• 235000018977 lysine Nutrition 0.000 description 2
• 238000013507 mapping Methods 0.000 description 2
• 230000007246 mechanism Effects 0.000 description 2
• 239000011859 microparticle Substances 0.000 description 2
• 210000004088 microvessel Anatomy 0.000 description 2
• 125000002950 monocyclic group Chemical group 0.000 description 2
• 230000000877 morphologic effect Effects 0.000 description 2
• 229930014626 natural product Natural products 0.000 description 2
• 239000013642 negative control Substances 0.000 description 2
• 210000000653 nervous system Anatomy 0.000 description 2
• 102000037979 non-receptor tyrosine kinases Human genes 0.000 description 2
• 108091008046 non-receptor tyrosine kinases Proteins 0.000 description 2
• 210000000056 organ Anatomy 0.000 description 2
• 238000007911 parenteral administration Methods 0.000 description 2
• 244000052769 pathogen Species 0.000 description 2
• 230000002085 persistent effect Effects 0.000 description 2
• 239000000049 pigment Substances 0.000 description 2
• 239000000256 polyoxyethylene sorbitan monolaurate Substances 0.000 description 2
• 230000003389 potentiating effect Effects 0.000 description 2
• 239000002244 precipitate Substances 0.000 description 2
• 230000001023 pro-angiogenic effect Effects 0.000 description 2
• 229940121649 protein inhibitor Drugs 0.000 description 2
• 239000012268 protein inhibitor Substances 0.000 description 2
• 230000002797 proteolythic effect Effects 0.000 description 2
• 230000000979 retarding effect Effects 0.000 description 2
• 210000001210 retinal vessel Anatomy 0.000 description 2
• 238000010839 reverse transcription Methods 0.000 description 2
• 238000003757 reverse transcription PCR Methods 0.000 description 2
• 238000012552 review Methods 0.000 description 2
• HZCAHMRRMINHDJ-DBRKOABJSA-N ribavirin Natural products O[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1N1N=CN=C1 HZCAHMRRMINHDJ-DBRKOABJSA-N 0.000 description 2
• 229960000329 ribavirin Drugs 0.000 description 2
• 108091092562 ribozyme Proteins 0.000 description 2
• 229920006395 saturated elastomer Polymers 0.000 description 2
• 125000003607 serino group Chemical group [H]N([H])[C@]([H])(C(=O)[*])C(O[H])([H])[H] 0.000 description 2
• 239000002356 single layer Substances 0.000 description 2
• 210000002460 smooth muscle Anatomy 0.000 description 2
• 239000011780 sodium chloride Substances 0.000 description 2
• 239000007787 solid Substances 0.000 description 2
• 241000894007 species Species 0.000 description 2
• 230000006641 stabilisation Effects 0.000 description 2
• 238000011105 stabilization Methods 0.000 description 2
• 230000000087 stabilizing effect Effects 0.000 description 2
• 238000010186 staining Methods 0.000 description 2
• 210000004158 stalk cell Anatomy 0.000 description 2
• 238000010561 standard procedure Methods 0.000 description 2
• UCSJYZPVAKXKNQ-HZYVHMACSA-N streptomycin Chemical compound CN[C@H]1[C@H](O)[C@@H](O)[C@H](CO)O[C@H]1O[C@@H]1[C@](C=O)(O)[C@H](C)O[C@H]1O[C@@H]1[C@@H](NC(N)=N)[C@H](O)[C@@H](NC(N)=N)[C@H](O)[C@H]1O UCSJYZPVAKXKNQ-HZYVHMACSA-N 0.000 description 2
• 229960005322 streptomycin Drugs 0.000 description 2
• 239000006228 supernatant Substances 0.000 description 2
• 230000001629 suppression Effects 0.000 description 2
• 239000000725 suspension Substances 0.000 description 2
• 230000009885 systemic effect Effects 0.000 description 2
• 238000002560 therapeutic procedure Methods 0.000 description 2
• 125000000341 threoninyl group Chemical group [H]OC([H])(C([H])([H])[H])C([H])(N([H])[H])C(*)=O 0.000 description 2
• 210000002262 tip cell Anatomy 0.000 description 2
• 230000009261 transgenic effect Effects 0.000 description 2
• 239000002753 trypsin inhibitor Substances 0.000 description 2
• 210000003556 vascular endothelial cell Anatomy 0.000 description 2
• 102000040650 (ribonucleotides)n+m Human genes 0.000 description 1
• 125000003287 1H-imidazol-4-ylmethyl group Chemical group [H]N1C([H])=NC(C([H])([H])[*])=C1[H] 0.000 description 1
• JVJUWEFOGFCHKR-UHFFFAOYSA-N 2-(diethylamino)ethyl 1-(3,4-dimethylphenyl)cyclopentane-1-carboxylate;hydrochloride Chemical compound Cl.C=1C=C(C)C(C)=CC=1C1(C(=O)OCCN(CC)CC)CCCC1 JVJUWEFOGFCHKR-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
• 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 1
• QFVHZQCOUORWEI-UHFFFAOYSA-N 4-[(4-anilino-5-sulfonaphthalen-1-yl)diazenyl]-5-hydroxynaphthalene-2,7-disulfonic acid Chemical compound C=12C(O)=CC(S(O)(=O)=O)=CC2=CC(S(O)(=O)=O)=CC=1N=NC(C1=CC=CC(=C11)S(O)(=O)=O)=CC=C1NC1=CC=CC=C1 QFVHZQCOUORWEI-UHFFFAOYSA-N 0.000 description 1
• VJVQKGYHIZPSNS-FXQIFTODSA-N Ala-Ser-Arg Chemical compound C[C@H](N)C(=O)N[C@@H](CO)C(=O)N[C@H](C(O)=O)CCCN=C(N)N VJVQKGYHIZPSNS-FXQIFTODSA-N 0.000 description 1
• 239000012103 Alexa Fluor 488 Substances 0.000 description 1
• 241000272525 Anas platyrhynchos Species 0.000 description 1
• 102000009840 Angiopoietins Human genes 0.000 description 1
• 108010009906 Angiopoietins Proteins 0.000 description 1
• 102000053157 Arf GTPase activating proteins Human genes 0.000 description 1
• 108700039571 Arf GTPase activating proteins Proteins 0.000 description 1
• 239000004475 Arginine Substances 0.000 description 1
• 206010003827 Autoimmune hepatitis Diseases 0.000 description 1
• 238000012935 Averaging Methods 0.000 description 1
• 238000011725 BALB/c mouse Methods 0.000 description 1
• 102000015081 Blood Coagulation Factors Human genes 0.000 description 1
• 108010039209 Blood Coagulation Factors Proteins 0.000 description 1
• 241000283690 Bos taurus Species 0.000 description 1
• 101100227322 Caenorhabditis elegans fli-1 gene Proteins 0.000 description 1
• 206010007559 Cardiac failure congestive Diseases 0.000 description 1
• KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 description 1
• 108091035707 Consensus sequence Proteins 0.000 description 1
• 238000011537 Coomassie blue staining Methods 0.000 description 1
• 241000557626 Corvus corax Species 0.000 description 1
• 229920000742 Cotton Polymers 0.000 description 1
• 241000699802 Cricetulus griseus Species 0.000 description 1
• ZGERHCJBLPQPGV-ACZMJKKPSA-N Cys-Ser-Gln Chemical compound C(CC(=O)N)[C@@H](C(=O)O)NC(=O)[C@H](CO)NC(=O)[C@H](CS)N ZGERHCJBLPQPGV-ACZMJKKPSA-N 0.000 description 1
• KDXKERNSBIXSRK-RXMQYKEDSA-N D-lysine Chemical compound NCCCC[C@@H](N)C(O)=O KDXKERNSBIXSRK-RXMQYKEDSA-N 0.000 description 1
• 102000053602 DNA Human genes 0.000 description 1
• 229920002307 Dextran Polymers 0.000 description 1
• 208000010837 Diabetic eye disease Diseases 0.000 description 1
• 208000000059 Dyspnea Diseases 0.000 description 1
• 206010013975 Dyspnoeas Diseases 0.000 description 1
• 102000016942 Elastin Human genes 0.000 description 1
• 108010014258 Elastin Proteins 0.000 description 1
• 241000196324 Embryophyta Species 0.000 description 1
• 102100038566 Endomucin Human genes 0.000 description 1
• 101800003838 Epidermal growth factor Proteins 0.000 description 1
• 206010016654 Fibrosis Diseases 0.000 description 1
• 241000287828 Gallus gallus Species 0.000 description 1
• 208000034826 Genetic Predisposition to Disease Diseases 0.000 description 1
• TWHDOEYLXXQYOZ-FXQIFTODSA-N Gln-Asn-Gln Chemical compound C(CC(=O)N)[C@@H](C(=O)N[C@@H](CC(=O)N)C(=O)N[C@@H](CCC(=O)N)C(=O)O)N TWHDOEYLXXQYOZ-FXQIFTODSA-N 0.000 description 1
• FTIJVMLAGRAYMJ-MNXVOIDGSA-N Gln-Ile-Leu Chemical compound CC(C)C[C@@H](C(O)=O)NC(=O)[C@H]([C@@H](C)CC)NC(=O)[C@@H](N)CCC(N)=O FTIJVMLAGRAYMJ-MNXVOIDGSA-N 0.000 description 1
• FALJZCPMTGJOHX-SRVKXCTJSA-N Gln-Met-Leu Chemical compound [H]N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CC(C)C)C(O)=O FALJZCPMTGJOHX-SRVKXCTJSA-N 0.000 description 1
• WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Chemical compound OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 1
• 108010024636 Glutathione Proteins 0.000 description 1
• ZZJVYSAQQMDIRD-UWVGGRQHSA-N Gly-Pro-His Chemical compound NCC(=O)N1CCC[C@H]1C(=O)N[C@@H](Cc1cnc[nH]1)C(O)=O ZZJVYSAQQMDIRD-UWVGGRQHSA-N 0.000 description 1
• 239000004471 Glycine Substances 0.000 description 1
• 244000068988 Glycine max Species 0.000 description 1
• 235000010469 Glycine max Nutrition 0.000 description 1
• 108060003393 Granulin Proteins 0.000 description 1
• 108010043121 Green Fluorescent Proteins Proteins 0.000 description 1
• 102000004144 Green Fluorescent Proteins Human genes 0.000 description 1
• 108010067218 Guanine Nucleotide Exchange Factors Proteins 0.000 description 1
• 102000016285 Guanine Nucleotide Exchange Factors Human genes 0.000 description 1
• 239000007995 HEPES buffer Substances 0.000 description 1
• 101710154606 Hemagglutinin Proteins 0.000 description 1
• 206010019663 Hepatic failure Diseases 0.000 description 1
• RXVOMIADLXPJGW-GUBZILKMSA-N His-Asp-Glu Chemical compound [H]N[C@@H](CC1=CNC=N1)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CCC(O)=O)C(O)=O RXVOMIADLXPJGW-GUBZILKMSA-N 0.000 description 1
• 241000282412 Homo Species 0.000 description 1
• 101001076407 Homo sapiens Interleukin-1 receptor antagonist protein Proteins 0.000 description 1
• 101000650590 Homo sapiens Roundabout homolog 4 Proteins 0.000 description 1
• 101000852214 Homo sapiens THO complex subunit 4 Proteins 0.000 description 1
• 101000851007 Homo sapiens Vascular endothelial growth factor receptor 2 Proteins 0.000 description 1
• 208000001953 Hypotension Diseases 0.000 description 1
• RENBRDSDKPSRIH-HJWJTTGWSA-N Ile-Phe-Met Chemical compound N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H](CCSC)C(=O)O RENBRDSDKPSRIH-HJWJTTGWSA-N 0.000 description 1
• 208000022559 Inflammatory bowel disease Diseases 0.000 description 1
• 206010022489 Insulin Resistance Diseases 0.000 description 1
• 229940119178 Interleukin 1 receptor antagonist Drugs 0.000 description 1
• 229940124042 Interleukin 10 antagonist Drugs 0.000 description 1
• 102000000589 Interleukin-1 Human genes 0.000 description 1
• 108010002352 Interleukin-1 Proteins 0.000 description 1
• 102000051628 Interleukin-1 receptor antagonist Human genes 0.000 description 1
• 102000003814 Interleukin-10 Human genes 0.000 description 1
• 102000004889 Interleukin-6 Human genes 0.000 description 1
• 108090001005 Interleukin-6 Proteins 0.000 description 1
• 208000032382 Ischaemic stroke Diseases 0.000 description 1
• XUJNEKJLAYXESH-REOHCLBHSA-N L-Cysteine Chemical compound SC[C@H](N)C(O)=O XUJNEKJLAYXESH-REOHCLBHSA-N 0.000 description 1
• 235000019766 L-Lysine Nutrition 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
• TYYLDKGBCJGJGW-UHFFFAOYSA-N L-tryptophan-L-tyrosine Natural products C=1NC2=CC=CC=C2C=1CC(N)C(=O)NC(C(O)=O)CC1=CC=C(O)C=C1 TYYLDKGBCJGJGW-UHFFFAOYSA-N 0.000 description 1
• OUYCCCASQSFEME-QMMMGPOBSA-N L-tyrosine Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-QMMMGPOBSA-N 0.000 description 1
• BFVQTKQTUCQRPI-YYEZTRBPSA-N LPS with O-antigen Chemical compound O([C@@H]1[C@@H](O[C@H]2[C@@H]([C@@H](O[C@H]3[C@@H]([C@@H](O[C@@H]4[C@@H]([C@@H](O)[C@@H](O)[C@@H](CO[C@@H]5[C@@H]([C@@H](O)[C@@H](O)[C@@H](CO)O5)O)O4)O)[C@@H](O)[C@@H](CO)O3)NC(C)=O)[C@@H](O)[C@@H](CO[C@H]3[C@@H]([C@@H](O)[C@H](O)[C@@H](CO)O3)NC(C)=O)O2)NC(C)=O)[C@H](O)[C@@H](CO)OC1O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@@H]1O[C@H]1[C@H](O)[C@@H](CO[C@@H]2[C@@H]([C@@H](O)[C@@H](O)[C@@H](CO)O2)O)OC([C@@H]1O)O[C@H]1[C@H](O)[C@@H]([C@@H](O)COC2[C@H]([C@@H](O)[C@H](OP(O)(O)=O)[C@@H]([C@@H](O)CO)O2)O)OC([C@H]1O)O[C@H]1[C@H](OP(O)(=O)OP(O)(=O)OCCN)[C@@H]([C@@H](O)CO)OC([C@H]1O)O[C@H]1[C@H](O[C@]2(O[C@@H]([C@@H](O)[C@H](O[C@]3(O[C@@H]([C@@H](O)[C@H](OP(O)(=O)OCCN)C3)[C@@H](O)CO)C(O)=O)C2)[C@@H](O)CO)C(O)=O)C[C@](O[C@@H]1[C@@H](O)CO)(OC[C@H]1O[C@@H](OC[C@@H]2[C@H]([C@H](OC(=O)C[C@H](O)CCCCCCCCCCC)[C@@H](NC(=O)C[C@H](O)CCCCCCCCCCC)[C@@H](OP(O)(O)=O)O2)O)[C@H](NC(=O)C[C@@H](CCCCCCCCCCC)OC(=O)CCCCCCCCCCC)[C@H]([C@@H]1OP(O)(O)=O)OC(=O)C[C@@H](CCCCCCCCCCC)OC(=O)CCCCCCCCCCCCC)C(O)=O)[C@@H]1O[C@H](CO)[C@@H](O)[C@H](O)[C@H]1NC(C)=O BFVQTKQTUCQRPI-YYEZTRBPSA-N 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
• 101100225689 Mus musculus Enah gene Proteins 0.000 description 1
• 101100281205 Mus musculus Fli1 gene Proteins 0.000 description 1
• 101100074807 Mus musculus Lhx3 gene Proteins 0.000 description 1
• 230000004988 N-glycosylation Effects 0.000 description 1
• 125000001429 N-terminal alpha-amino-acid group Chemical group 0.000 description 1
• 102000010803 Netrins Human genes 0.000 description 1
• 108010063605 Netrins Proteins 0.000 description 1
• 206010029538 Non-cardiogenic pulmonary oedema Diseases 0.000 description 1
• 208000022873 Ocular disease Diseases 0.000 description 1
• 206010053159 Organ failure Diseases 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
• 101150044441 PECAM1 gene Proteins 0.000 description 1
• 201000010183 Papilledema Diseases 0.000 description 1
• 229930040373 Paraformaldehyde Natural products 0.000 description 1
• 241001494479 Pecora Species 0.000 description 1
• 229930182555 Penicillin Natural products 0.000 description 1
• JGSARLDLIJGVTE-MBNYWOFBSA-N Penicillin G Chemical compound N([C@H]1[C@H]2SC([C@@H](N2C1=O)C(O)=O)(C)C)C(=O)CC1=CC=CC=C1 JGSARLDLIJGVTE-MBNYWOFBSA-N 0.000 description 1
• BQMFWUKNOCJDNV-HJWJTTGWSA-N Phe-Val-Ile Chemical compound [H]N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H]([C@@H](C)CC)C(O)=O BQMFWUKNOCJDNV-HJWJTTGWSA-N 0.000 description 1
• 229940122907 Phosphatase inhibitor Drugs 0.000 description 1
• 102000004160 Phosphoric Monoester Hydrolases Human genes 0.000 description 1
• 108090000608 Phosphoric Monoester Hydrolases Proteins 0.000 description 1
• 239000004365 Protease Substances 0.000 description 1
• 229940124158 Protease/peptidase inhibitor Drugs 0.000 description 1
• 101710176177 Protein A56 Proteins 0.000 description 1
• 102000001253 Protein Kinase Human genes 0.000 description 1
• 206010037660 Pyrexia Diseases 0.000 description 1
• 101150058540 RAC1 gene Proteins 0.000 description 1
• 108700008625 Reporter Genes Proteins 0.000 description 1
• 208000007135 Retinal Neovascularization Diseases 0.000 description 1
• 206010038848 Retinal detachment Diseases 0.000 description 1
• 206010038886 Retinal oedema Diseases 0.000 description 1
• 208000014139 Retinal vascular disease Diseases 0.000 description 1
• 102100027701 Roundabout homolog 4 Human genes 0.000 description 1
• 102000001332 SRC Human genes 0.000 description 1
• 108060006706 SRC Proteins 0.000 description 1
• 108050003978 Semaphorin Proteins 0.000 description 1
• 102000014105 Semaphorin Human genes 0.000 description 1
• 229920002684 Sepharose Polymers 0.000 description 1
• 102100028904 Serine/threonine-protein kinase MARK2 Human genes 0.000 description 1
• 108010061228 Sialomucins Proteins 0.000 description 1
• 229930006000 Sucrose Natural products 0.000 description 1
• CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 1
• NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 1
• 210000001744 T-lymphocyte Anatomy 0.000 description 1
• 208000001871 Tachycardia Diseases 0.000 description 1
• 108020005038 Terminator Codon Proteins 0.000 description 1
• GQPQJNMVELPZNQ-GBALPHGKSA-N Thr-Ser-Trp Chemical compound C[C@H]([C@@H](C(=O)N[C@@H](CO)C(=O)N[C@@H](CC1=CNC2=CC=CC=C21)C(=O)O)N)O GQPQJNMVELPZNQ-GBALPHGKSA-N 0.000 description 1
• 208000007536 Thrombosis Diseases 0.000 description 1
• 108091023040 Transcription factor Proteins 0.000 description 1
• 102000040945 Transcription factor Human genes 0.000 description 1
• 239000007983 Tris buffer Substances 0.000 description 1
• BGDKAVGWHJFAGW-UHFFFAOYSA-N Tropicamide Chemical compound C=1C=CC=CC=1C(CO)C(=O)N(CC)CC1=CC=NC=C1 BGDKAVGWHJFAGW-UHFFFAOYSA-N 0.000 description 1
• 108060008682 Tumor Necrosis Factor Proteins 0.000 description 1
• 102000000852 Tumor Necrosis Factor-alpha Human genes 0.000 description 1
• LUMQYLVYUIRHHU-YJRXYDGGSA-N Tyr-Ser-Thr Chemical compound [H]N[C@@H](CC1=CC=C(O)C=C1)C(=O)N[C@@H](CO)C(=O)N[C@@H]([C@@H](C)O)C(O)=O LUMQYLVYUIRHHU-YJRXYDGGSA-N 0.000 description 1
• FZADUTOCSFDBRV-RNXOBYDBSA-N Tyr-Tyr-Trp Chemical compound C([C@H](N)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(O)=O)C1=CC=C(O)C=C1 FZADUTOCSFDBRV-RNXOBYDBSA-N 0.000 description 1
• 102000008790 VE-cadherin Human genes 0.000 description 1
• GVJUTBOZZBTBIG-AVGNSLFASA-N Val-Lys-Arg Chemical compound CC(C)[C@@H](C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCCN=C(N)N)C(=O)O)N GVJUTBOZZBTBIG-AVGNSLFASA-N 0.000 description 1
• 208000009443 Vascular Malformations Diseases 0.000 description 1
• 102100033177 Vascular endothelial growth factor receptor 2 Human genes 0.000 description 1
• 208000036142 Viral infection Diseases 0.000 description 1
• 208000000208 Wet Macular Degeneration Diseases 0.000 description 1
• 238000002679 ablation Methods 0.000 description 1
• 230000005856 abnormality Effects 0.000 description 1
• 230000021736 acetylation Effects 0.000 description 1
• 238000006640 acetylation reaction Methods 0.000 description 1
• 230000002378 acidificating effect Effects 0.000 description 1
• 230000009471 action Effects 0.000 description 1
• 230000003213 activating effect Effects 0.000 description 1
• 206010000891 acute myocardial infarction Diseases 0.000 description 1
• 239000000654 additive Substances 0.000 description 1
• 239000000853 adhesive Substances 0.000 description 1
• 230000001070 adhesive effect Effects 0.000 description 1
• 238000000246 agarose gel electrophoresis Methods 0.000 description 1
• 235000004279 alanine Nutrition 0.000 description 1
• IYABWNGZIDDRAK-UHFFFAOYSA-N allene Chemical group C=C=C IYABWNGZIDDRAK-UHFFFAOYSA-N 0.000 description 1
• 230000000172 allergic effect Effects 0.000 description 1
• 230000009435 amidation Effects 0.000 description 1
• 238000007112 amidation reaction Methods 0.000 description 1
• 150000001412 amines Chemical group 0.000 description 1
• 208000003455 anaphylaxis Diseases 0.000 description 1
• 229940035674 anesthetics Drugs 0.000 description 1
• 238000002399 angioplasty Methods 0.000 description 1
• 210000004102 animal cell Anatomy 0.000 description 1
• 125000002178 anthracenyl group Chemical group C1(=CC=CC2=CC3=CC=CC=C3C=C12)* 0.000 description 1
• 239000002260 anti-inflammatory agent Substances 0.000 description 1
• 229940121363 anti-inflammatory agent Drugs 0.000 description 1
• 230000003110 anti-inflammatory effect Effects 0.000 description 1
• 239000004599 antimicrobial Substances 0.000 description 1
• 210000002403 aortic endothelial cell Anatomy 0.000 description 1
• ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 1
• 125000000637 arginyl group Chemical group N[C@@H](CCCNC(N)=N)C(=O)* 0.000 description 1
• 108010062796 arginyllysine Proteins 0.000 description 1
• 238000013528 artificial neural network Methods 0.000 description 1
• 125000000613 asparagine group Chemical group N[C@@H](CC(N)=O)C(=O)* 0.000 description 1
• 235000003704 aspartic acid Nutrition 0.000 description 1
• 208000010668 atopic eczema Diseases 0.000 description 1
• 230000008267 autocrine signaling Effects 0.000 description 1
• 230000035578 autophosphorylation Effects 0.000 description 1
• 210000003050 axon Anatomy 0.000 description 1
• 230000003376 axonal effect Effects 0.000 description 1
• 238000010009 beating Methods 0.000 description 1
• 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 1
• 238000002306 biochemical method Methods 0.000 description 1
• 230000008499 blood brain barrier function Effects 0.000 description 1
• 239000003114 blood coagulation factor Substances 0.000 description 1
• 210000001218 blood-brain barrier Anatomy 0.000 description 1
• 239000001045 blue dye Substances 0.000 description 1
• 210000004556 brain Anatomy 0.000 description 1
• 235000010633 broth Nutrition 0.000 description 1
• 238000010804 cDNA synthesis Methods 0.000 description 1
• 108010018828 cadherin 5 Proteins 0.000 description 1
• 125000000837 carbohydrate group Chemical group 0.000 description 1
• CREMABGTGYGIQB-UHFFFAOYSA-N carbon carbon Chemical compound C.C CREMABGTGYGIQB-UHFFFAOYSA-N 0.000 description 1
• 230000024245 cell differentiation Effects 0.000 description 1
• 230000010261 cell growth Effects 0.000 description 1
• 230000004640 cellular pathway Effects 0.000 description 1
• 230000036755 cellular response Effects 0.000 description 1
• 238000012512 characterization method Methods 0.000 description 1
• 150000005829 chemical entities Chemical class 0.000 description 1
• 108700010039 chimeric receptor Proteins 0.000 description 1
• 230000004087 circulation Effects 0.000 description 1
• 208000019425 cirrhosis of liver Diseases 0.000 description 1
• 238000003776 cleavage reaction Methods 0.000 description 1
• 238000010367 cloning Methods 0.000 description 1
• 239000011248 coating agent Substances 0.000 description 1
• 238000000576 coating method Methods 0.000 description 1
• 239000000306 component Substances 0.000 description 1
• 239000000470 constituent Substances 0.000 description 1
• 239000000356 contaminant Substances 0.000 description 1
• 230000001276 controlling effect Effects 0.000 description 1
• 210000004246 corpus luteum Anatomy 0.000 description 1
• 238000004132 cross linking Methods 0.000 description 1
• 230000037029 cross reaction Effects 0.000 description 1
• 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
• 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
• 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
• 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 1
• 125000000151 cysteine group Chemical group N[C@@H](CS)C(=O)* 0.000 description 1
• 230000003413 degradative effect Effects 0.000 description 1
• 239000003405 delayed action preparation Substances 0.000 description 1
• 230000002939 deleterious effect Effects 0.000 description 1
• 230000000994 depressogenic effect Effects 0.000 description 1
• 238000001212 derivatisation Methods 0.000 description 1
• 230000001687 destabilization Effects 0.000 description 1
• 238000001514 detection method Methods 0.000 description 1
• 230000014155 detection of activity Effects 0.000 description 1
• 230000001627 detrimental effect Effects 0.000 description 1
• 238000011161 development Methods 0.000 description 1
• 229950006137 dexfosfoserine Drugs 0.000 description 1
• 206010012601 diabetes mellitus Diseases 0.000 description 1
• 238000010586 diagram Methods 0.000 description 1
• 239000003085 diluting agent Substances 0.000 description 1
• 238000010790 dilution Methods 0.000 description 1
• 239000012895 dilution Substances 0.000 description 1
• 239000000975 dye Substances 0.000 description 1
• 230000008482 dysregulation Effects 0.000 description 1
• 210000002969 egg yolk Anatomy 0.000 description 1
• 229920002549 elastin Polymers 0.000 description 1
• 210000004696 endometrium Anatomy 0.000 description 1
• 239000003623 enhancer Substances 0.000 description 1
• 229940116977 epidermal growth factor Drugs 0.000 description 1
• 230000003628 erosive effect Effects 0.000 description 1
• ZMMJGEGLRURXTF-UHFFFAOYSA-N ethidium bromide Chemical compound [Br-].C12=CC(N)=CC=C2C2=CC=C(N)C=C2[N+](CC)=C1C1=CC=CC=C1 ZMMJGEGLRURXTF-UHFFFAOYSA-N 0.000 description 1
• 229960005542 ethidium bromide Drugs 0.000 description 1
• 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
• DEFVIWRASFVYLL-UHFFFAOYSA-N ethylene glycol bis(2-aminoethyl)tetraacetic acid Chemical compound OC(=O)CN(CC(O)=O)CCOCCOCCN(CC(O)=O)CC(O)=O DEFVIWRASFVYLL-UHFFFAOYSA-N 0.000 description 1
• 238000011156 evaluation Methods 0.000 description 1
• 230000001747 exhibiting effect Effects 0.000 description 1
• 239000011536 extraction buffer Substances 0.000 description 1
• 208000030533 eye disease Diseases 0.000 description 1
• 238000000855 fermentation Methods 0.000 description 1
• 230000004151 fermentation Effects 0.000 description 1
• 230000008175 fetal development Effects 0.000 description 1
• 210000003754 fetus Anatomy 0.000 description 1
• 239000010408 film Substances 0.000 description 1
• 238000000684 flow cytometry Methods 0.000 description 1
• 239000012530 fluid Substances 0.000 description 1
• 125000000524 functional group Chemical group 0.000 description 1
• 230000002538 fungal effect Effects 0.000 description 1
• 125000002541 furyl group Chemical group 0.000 description 1
• 239000000499 gel Substances 0.000 description 1
• 230000037440 gene silencing effect Effects 0.000 description 1
• 239000003193 general anesthetic agent Substances 0.000 description 1
• 239000011521 glass Substances 0.000 description 1
• 229960003180 glutathione Drugs 0.000 description 1
• 150000004676 glycans Chemical class 0.000 description 1
• 230000013595 glycosylation Effects 0.000 description 1
• 102000009543 guanyl-nucleotide exchange factor activity proteins Human genes 0.000 description 1
• 230000035876 healing Effects 0.000 description 1
• 230000004217 heart function Effects 0.000 description 1
• 239000000185 hemagglutinin Substances 0.000 description 1
• 230000002440 hepatic effect Effects 0.000 description 1
• 125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
• 238000004128 high performance liquid chromatography Methods 0.000 description 1
• 238000012188 high-throughput screening assay Methods 0.000 description 1
• HNDVDQJCIGZPNO-UHFFFAOYSA-N histidine Natural products OC(=O)C(N)CC1=CN=CN1 HNDVDQJCIGZPNO-UHFFFAOYSA-N 0.000 description 1
• 230000013632 homeostatic process Effects 0.000 description 1
• 230000006801 homologous recombination Effects 0.000 description 1
• 238000002744 homologous recombination Methods 0.000 description 1
• 229940088597 hormone Drugs 0.000 description 1
• 239000005556 hormone Substances 0.000 description 1
• 210000003917 human chromosome Anatomy 0.000 description 1
• 229920001600 hydrophobic polymer Polymers 0.000 description 1
• 230000033444 hydroxylation Effects 0.000 description 1
• 238000005805 hydroxylation reaction Methods 0.000 description 1
• 230000000222 hyperoxic effect Effects 0.000 description 1
• 230000036543 hypotension Effects 0.000 description 1
• 238000003384 imaging method Methods 0.000 description 1
• 125000002883 imidazolyl group Chemical group 0.000 description 1
• 210000001822 immobilized cell Anatomy 0.000 description 1
• 230000001900 immune effect Effects 0.000 description 1
• 230000028993 immune response Effects 0.000 description 1
• 210000000987 immune system Anatomy 0.000 description 1
• 230000000984 immunochemical effect Effects 0.000 description 1
• 238000003365 immunocytochemistry Methods 0.000 description 1
• 230000002163 immunogen Effects 0.000 description 1
• 230000005847 immunogenicity Effects 0.000 description 1
• 230000001771 impaired effect Effects 0.000 description 1
• 230000001976 improved effect Effects 0.000 description 1
• 230000000415 inactivating effect Effects 0.000 description 1
• 208000015181 infectious disease Diseases 0.000 description 1
• 206010022000 influenza Diseases 0.000 description 1
• 238000011081 inoculation Methods 0.000 description 1
• 238000007689 inspection Methods 0.000 description 1
• 210000004692 intercellular junction Anatomy 0.000 description 1
• 239000003407 interleukin 1 receptor blocking agent Substances 0.000 description 1
• 229940100601 interleukin-6 Drugs 0.000 description 1
• 230000003834 intracellular effect Effects 0.000 description 1
• 238000001990 intravenous administration Methods 0.000 description 1
• 150000002500 ions Chemical class 0.000 description 1
• 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 1
• 125000000741 isoleucyl group Chemical group [H]N([H])C(C(C([H])([H])[H])C([H])([H])C([H])([H])[H])C(=O)O* 0.000 description 1
• 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
• 229950003188 isovaleryl diethylamide Drugs 0.000 description 1
• 150000002605 large molecules Chemical class 0.000 description 1
• 239000010410 layer Substances 0.000 description 1
• 231100000518 lethal Toxicity 0.000 description 1
• 230000001665 lethal effect Effects 0.000 description 1
• 125000001909 leucine group Chemical group [H]N(*)C(C(*)=O)C([H])([H])C(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
• 210000000265 leukocyte Anatomy 0.000 description 1
• 125000003473 lipid group Chemical group 0.000 description 1
• 239000007788 liquid Substances 0.000 description 1
• 239000006193 liquid solution Substances 0.000 description 1
• 239000006194 liquid suspension Substances 0.000 description 1
• 210000005229 liver cell Anatomy 0.000 description 1
• 231100000835 liver failure Toxicity 0.000 description 1
• 208000007903 liver failure Diseases 0.000 description 1
• 230000004807 localization Effects 0.000 description 1
• 231100000516 lung damage Toxicity 0.000 description 1
• 210000002751 lymph Anatomy 0.000 description 1
• 210000004698 lymphocyte Anatomy 0.000 description 1
• 125000003588 lysine group Chemical group [H]N([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])(N([H])[H])C(*)=O 0.000 description 1
• 239000012139 lysis buffer Substances 0.000 description 1
• 108010012988 lysyl-glutamyl-aspartyl-glycine Proteins 0.000 description 1
• 229920002521 macromolecule Polymers 0.000 description 1
• 230000036244 malformation Effects 0.000 description 1
• 239000003550 marker Substances 0.000 description 1
• 108010082117 matrigel Proteins 0.000 description 1
• 239000002609 medium Substances 0.000 description 1
• 230000004060 metabolic process Effects 0.000 description 1
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
• 230000011987 methylation Effects 0.000 description 1
• 238000007069 methylation reaction Methods 0.000 description 1
• 238000000386 microscopy Methods 0.000 description 1
• 230000011278 mitosis Effects 0.000 description 1
• 230000009456 molecular mechanism Effects 0.000 description 1
• 239000003068 molecular probe Substances 0.000 description 1
• 238000012544 monitoring process Methods 0.000 description 1
• 238000004264 monolayer culture Methods 0.000 description 1
• 230000004899 motility Effects 0.000 description 1
• 210000004898 n-terminal fragment Anatomy 0.000 description 1
• 210000004897 n-terminal region Anatomy 0.000 description 1
• 125000001624 naphthyl group Chemical group 0.000 description 1
• 230000014399 negative regulation of angiogenesis Effects 0.000 description 1
• 230000010046 negative regulation of endothelial cell proliferation Effects 0.000 description 1
• 230000018103 negative regulation of vascular permeability Effects 0.000 description 1
• 238000007857 nested PCR Methods 0.000 description 1
• 230000001537 neural effect Effects 0.000 description 1
• 229910052757 nitrogen Inorganic materials 0.000 description 1
• 238000007899 nucleic acid hybridization Methods 0.000 description 1
• 210000004940 nucleus Anatomy 0.000 description 1
• 230000000474 nursing effect Effects 0.000 description 1
• 229940124276 oligodeoxyribonucleotide Drugs 0.000 description 1
• 210000004789 organ system Anatomy 0.000 description 1
• 210000001672 ovary Anatomy 0.000 description 1
• 230000014306 paracrine signaling Effects 0.000 description 1
• 229920002866 paraformaldehyde Polymers 0.000 description 1
• 230000008506 pathogenesis Effects 0.000 description 1
• 230000001717 pathogenic effect Effects 0.000 description 1
• 230000007170 pathology Effects 0.000 description 1
• 239000008188 pellet Substances 0.000 description 1
• 229940049954 penicillin Drugs 0.000 description 1
• 125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 1
• 239000000825 pharmaceutical preparation Substances 0.000 description 1
• 229940127557 pharmaceutical product Drugs 0.000 description 1
• 125000001792 phenanthrenyl group Chemical group C1(=CC=CC=2C3=CC=CC=C3C=CC12)* 0.000 description 1
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 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
• 125000000405 phenylalanyl group Chemical group 0.000 description 1
• 238000000053 physical method Methods 0.000 description 1
• 230000004962 physiological condition Effects 0.000 description 1
• 230000035790 physiological processes and functions Effects 0.000 description 1
• 210000002826 placenta Anatomy 0.000 description 1
• 230000010287 polarization Effects 0.000 description 1
• 238000002264 polyacrylamide gel electrophoresis Methods 0.000 description 1
• 229920000515 polycarbonate Polymers 0.000 description 1
• 239000004417 polycarbonate Substances 0.000 description 1
• 238000006116 polymerization reaction Methods 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
• 239000011148 porous material Substances 0.000 description 1
• 239000013641 positive control Substances 0.000 description 1
• 230000004481 post-translational protein modification Effects 0.000 description 1
• 230000001323 posttranslational effect Effects 0.000 description 1
• 239000000843 powder Substances 0.000 description 1
• 230000001376 precipitating effect Effects 0.000 description 1
• 239000003755 preservative agent Substances 0.000 description 1
• 230000002335 preservative effect Effects 0.000 description 1
• 238000002203 pretreatment Methods 0.000 description 1
• 230000000770 proinflammatory effect Effects 0.000 description 1
• 201000007914 proliferative diabetic retinopathy Diseases 0.000 description 1
• 230000000644 propagated effect Effects 0.000 description 1
• 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
• 235000019833 protease Nutrition 0.000 description 1
• 108060006633 protein kinase Proteins 0.000 description 1
• 108010008359 protein kinase C lambda Proteins 0.000 description 1
• 230000017854 proteolysis Effects 0.000 description 1
• 208000005333 pulmonary edema Diseases 0.000 description 1
• 210000001747 pupil Anatomy 0.000 description 1
• 125000004076 pyridyl group Chemical group 0.000 description 1
• 125000000168 pyrrolyl group Chemical group 0.000 description 1
• 150000003254 radicals Chemical class 0.000 description 1
• 108091008597 receptor serine/threonine kinases Proteins 0.000 description 1
• 238000007634 remodeling Methods 0.000 description 1
• 230000008439 repair process Effects 0.000 description 1
• 238000011160 research Methods 0.000 description 1
• 230000008458 response to injury Effects 0.000 description 1
• 230000004043 responsiveness Effects 0.000 description 1
• 230000000717 retained effect Effects 0.000 description 1
• 230000004264 retinal detachment Effects 0.000 description 1
• 201000011195 retinal edema Diseases 0.000 description 1
• 239000002342 ribonucleoside Substances 0.000 description 1
• 239000012723 sample buffer Substances 0.000 description 1
• 230000007017 scission Effects 0.000 description 1
• 238000007423 screening assay Methods 0.000 description 1
• 230000028327 secretion Effects 0.000 description 1
• 238000012163 sequencing technique Methods 0.000 description 1
• 108091006024 signal transducing proteins Proteins 0.000 description 1
• 102000034285 signal transducing proteins Human genes 0.000 description 1
• 210000003491 skin Anatomy 0.000 description 1
• 210000002023 somite Anatomy 0.000 description 1
• 230000003839 sprouting angiogenesis Effects 0.000 description 1
• 239000010421 standard material Substances 0.000 description 1
• 238000007619 statistical method Methods 0.000 description 1
• 210000000130 stem cell Anatomy 0.000 description 1
• 239000000021 stimulant Substances 0.000 description 1
• 238000003860 storage Methods 0.000 description 1
• 239000005720 sucrose Substances 0.000 description 1
• 230000019635 sulfation Effects 0.000 description 1
• 238000005670 sulfation reaction Methods 0.000 description 1
• 239000011593 sulfur Substances 0.000 description 1
• 239000004094 surface-active agent Substances 0.000 description 1
• 238000007892 surgical revascularization Methods 0.000 description 1
• 238000013268 sustained release Methods 0.000 description 1
• 239000012730 sustained-release form Substances 0.000 description 1
• 238000001308 synthesis method Methods 0.000 description 1
• 230000009897 systematic effect Effects 0.000 description 1
• 230000006794 tachycardia Effects 0.000 description 1
• 230000008685 targeting Effects 0.000 description 1
• 239000002562 thickening agent Substances 0.000 description 1
• 125000001544 thienyl group Chemical group 0.000 description 1
• 230000000451 tissue damage Effects 0.000 description 1
• 231100000827 tissue damage Toxicity 0.000 description 1
• 230000000699 topical effect Effects 0.000 description 1
• 238000006257 total synthesis reaction Methods 0.000 description 1
• 238000001890 transfection Methods 0.000 description 1
• 238000012546 transfer Methods 0.000 description 1
• 230000009466 transformation Effects 0.000 description 1
• 230000001052 transient effect Effects 0.000 description 1
• 230000014621 translational initiation Effects 0.000 description 1
• 230000005945 translocation Effects 0.000 description 1
• 102000035160 transmembrane proteins Human genes 0.000 description 1
• 108091005703 transmembrane proteins Proteins 0.000 description 1
• 238000002054 transplantation Methods 0.000 description 1
• 230000032258 transport Effects 0.000 description 1
• 230000001960 triggered effect Effects 0.000 description 1
• LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 1
• 229960004791 tropicamide Drugs 0.000 description 1
• 108010044292 tryptophyltyrosine Proteins 0.000 description 1
• 208000001072 type 2 diabetes mellitus Diseases 0.000 description 1
• 238000010798 ubiquitination Methods 0.000 description 1
• 230000034512 ubiquitination Effects 0.000 description 1
• 210000003606 umbilical vein Anatomy 0.000 description 1
• VBEQCZHXXJYVRD-GACYYNSASA-N uroanthelone Chemical compound C([C@@H](C(=O)N[C@H](C(=O)N[C@@H](CS)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CS)C(=O)N[C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)NCC(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N[C@@H](CO)C(=O)NCC(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CS)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O)C(C)C)[C@@H](C)O)NC(=O)[C@H](CO)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CO)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@@H](NC(=O)[C@H](CC=1NC=NC=1)NC(=O)[C@H](CCSC)NC(=O)[C@H](CS)NC(=O)[C@@H](NC(=O)CNC(=O)CNC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CS)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)CNC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CO)NC(=O)[C@H](CO)NC(=O)[C@H]1N(CCC1)C(=O)[C@H](CS)NC(=O)CNC(=O)[C@H]1N(CCC1)C(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CO)NC(=O)[C@@H](N)CC(N)=O)C(C)C)[C@@H](C)CC)C1=CC=C(O)C=C1 VBEQCZHXXJYVRD-GACYYNSASA-N 0.000 description 1
• 125000002987 valine group Chemical group [H]N([H])C([H])(C(*)=O)C([H])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
• 230000007556 vascular defect Effects 0.000 description 1
• 230000006426 vascular sprouting Effects 0.000 description 1
• 230000000982 vasogenic effect Effects 0.000 description 1
• 230000002861 ventricular Effects 0.000 description 1
• 230000009385 viral infection Effects 0.000 description 1
• 239000002699 waste material Substances 0.000 description 1
• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
• 210000005253 yeast cell Anatomy 0.000 description 1
• 238000003158 yeast two-hybrid assay Methods 0.000 description 1