CA2838662C - Peptide compositions and methods for treating lung injury, asthma, anaphylaxis, angioedema, systemic vascular permeability syndromes, and nasal congestion - Google Patents
Peptide compositions and methods for treating lung injury, asthma, anaphylaxis, angioedema, systemic vascular permeability syndromes, and nasal congestion Download PDFInfo
- Publication number
- CA2838662C CA2838662C CA2838662A CA2838662A CA2838662C CA 2838662 C CA2838662 C CA 2838662C CA 2838662 A CA2838662 A CA 2838662A CA 2838662 A CA2838662 A CA 2838662A CA 2838662 C CA2838662 C CA 2838662C
- Authority
- CA
- Canada
- Prior art keywords
- peptide
- ip3r3
- angioedema
- induced
- mins
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Active
Links
- 108090000765 processed proteins & peptides Proteins 0.000 title claims abstract description 195
- 208000028185 Angioedema Diseases 0.000 title claims abstract description 26
- 208000004852 Lung Injury Diseases 0.000 title claims abstract description 24
- 206010069363 Traumatic lung injury Diseases 0.000 title claims abstract description 24
- 231100000515 lung injury Toxicity 0.000 title claims abstract description 23
- 208000006673 asthma Diseases 0.000 title claims abstract description 22
- 208000003455 anaphylaxis Diseases 0.000 title claims abstract description 21
- 206010002198 Anaphylactic reaction Diseases 0.000 title claims abstract description 15
- 208000011580 syndromic disease Diseases 0.000 title claims abstract description 15
- 230000009269 systemic vascular permeability Effects 0.000 title claims abstract description 15
- 230000036783 anaphylactic response Effects 0.000 title claims abstract description 12
- 206010028735 Nasal congestion Diseases 0.000 title claims abstract description 11
- 239000000203 mixture Substances 0.000 title claims description 22
- 238000000034 method Methods 0.000 title abstract description 27
- 230000003993 interaction Effects 0.000 claims abstract description 56
- 230000002792 vascular Effects 0.000 claims abstract description 22
- 206010030113 Oedema Diseases 0.000 claims abstract description 11
- 239000003112 inhibitor Substances 0.000 claims abstract description 4
- 101000975401 Homo sapiens Inositol 1,4,5-trisphosphate receptor type 3 Proteins 0.000 claims description 88
- 102100024035 Inositol 1,4,5-trisphosphate receptor type 3 Human genes 0.000 claims description 88
- 238000011282 treatment Methods 0.000 claims description 33
- 230000000694 effects Effects 0.000 claims description 29
- 230000001404 mediated effect Effects 0.000 claims description 21
- 206010061218 Inflammation Diseases 0.000 claims description 17
- 239000003814 drug Substances 0.000 claims description 17
- 230000004054 inflammatory process Effects 0.000 claims description 17
- MCYTYTUNNNZWOK-LCLOTLQISA-N penetratin Chemical group C([C@H](NC(=O)[C@H](CC=1C2=CC=CC=C2NC=1)NC(=O)[C@H]([C@@H](C)CC)NC(=O)[C@H](CCCCN)NC(=O)[C@@H](NC(=O)[C@H](CCC(N)=O)NC(=O)[C@@H](N)CCCNC(N)=N)[C@@H](C)CC)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCCCN)C(N)=O)C1=CC=CC=C1 MCYTYTUNNNZWOK-LCLOTLQISA-N 0.000 claims description 17
- 229940079593 drug Drugs 0.000 claims description 12
- 239000013566 allergen Substances 0.000 claims description 11
- 238000002360 preparation method Methods 0.000 claims description 10
- 230000000172 allergic effect Effects 0.000 claims description 9
- 230000001684 chronic effect Effects 0.000 claims description 8
- 239000008194 pharmaceutical composition Substances 0.000 claims description 7
- 206010028980 Neoplasm Diseases 0.000 claims description 6
- 230000001154 acute effect Effects 0.000 claims description 6
- 208000010668 atopic eczema Diseases 0.000 claims description 6
- 239000000994 contrast dye Substances 0.000 claims description 6
- 208000037487 Endotoxemia Diseases 0.000 claims description 5
- 201000009961 allergic asthma Diseases 0.000 claims description 5
- 238000003384 imaging method Methods 0.000 claims description 5
- 208000014674 injury Diseases 0.000 claims description 5
- 206010002216 Anaphylactoid reaction Diseases 0.000 claims description 4
- 230000000295 complement effect Effects 0.000 claims description 4
- 230000007812 deficiency Effects 0.000 claims description 4
- 239000002085 irritant Substances 0.000 claims description 4
- 231100000021 irritant Toxicity 0.000 claims description 4
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 4
- 230000009885 systemic effect Effects 0.000 claims description 4
- 208000004262 Food Hypersensitivity Diseases 0.000 claims description 3
- 206010016946 Food allergy Diseases 0.000 claims description 3
- 241000257303 Hymenoptera Species 0.000 claims description 3
- 108010002350 Interleukin-2 Proteins 0.000 claims description 3
- 206010039085 Rhinitis allergic Diseases 0.000 claims description 3
- 241000700605 Viruses Species 0.000 claims description 3
- 201000010105 allergic rhinitis Diseases 0.000 claims description 3
- 201000011510 cancer Diseases 0.000 claims description 3
- 231100000740 envenomation Toxicity 0.000 claims description 3
- 235000020932 food allergy Nutrition 0.000 claims description 3
- 208000037916 non-allergic rhinitis Diseases 0.000 claims description 3
- 230000000241 respiratory effect Effects 0.000 claims description 3
- 230000008733 trauma Effects 0.000 claims description 3
- 101710099430 Microtubule-associated protein RP/EB family member 3 Proteins 0.000 abstract description 119
- 102100038678 Microtubule-associated protein RP/EB family member 3 Human genes 0.000 abstract description 119
- 210000004072 lung Anatomy 0.000 abstract description 42
- 206010069351 acute lung injury Diseases 0.000 abstract description 8
- 238000011161 development Methods 0.000 abstract description 6
- 239000000463 material Substances 0.000 abstract description 4
- 102000007640 Inositol 1,4,5-Trisphosphate Receptors Human genes 0.000 abstract description 3
- 108010032354 Inositol 1,4,5-Trisphosphate Receptors Proteins 0.000 abstract 2
- 101000975407 Caenorhabditis elegans Inositol 1,4,5-trisphosphate receptor itr-1 Proteins 0.000 description 60
- 101000975393 Drosophila melanogaster Inositol 1,4,5-trisphosphate receptor Proteins 0.000 description 60
- 230000027455 binding Effects 0.000 description 49
- 241000699670 Mus sp. Species 0.000 description 45
- 210000004027 cell Anatomy 0.000 description 42
- 230000004913 activation Effects 0.000 description 40
- 239000002158 endotoxin Substances 0.000 description 40
- 229920006008 lipopolysaccharide Polymers 0.000 description 39
- 210000004688 microtubule Anatomy 0.000 description 34
- 230000004044 response Effects 0.000 description 31
- 210000002472 endoplasmic reticulum Anatomy 0.000 description 30
- 229960004072 thrombin Drugs 0.000 description 29
- 102000029749 Microtubule Human genes 0.000 description 28
- 108091022875 Microtubule Proteins 0.000 description 28
- 108090000190 Thrombin Proteins 0.000 description 28
- NTYJJOPFIAHURM-UHFFFAOYSA-N Histamine Chemical compound NCCC1=CN=CN1 NTYJJOPFIAHURM-UHFFFAOYSA-N 0.000 description 26
- 230000035699 permeability Effects 0.000 description 26
- 235000001014 amino acid Nutrition 0.000 description 25
- 230000026731 phosphorylation Effects 0.000 description 24
- 238000006366 phosphorylation reaction Methods 0.000 description 24
- 102000004196 processed proteins & peptides Human genes 0.000 description 24
- 150000001413 amino acids Chemical class 0.000 description 23
- 238000002347 injection Methods 0.000 description 22
- 239000007924 injection Substances 0.000 description 22
- 101710121440 Proteinase-activated receptor 1 Proteins 0.000 description 19
- 102100028904 Serine/threonine-protein kinase MARK2 Human genes 0.000 description 19
- 230000003511 endothelial effect Effects 0.000 description 19
- 230000003834 intracellular effect Effects 0.000 description 19
- 230000007246 mechanism Effects 0.000 description 18
- 206010040047 Sepsis Diseases 0.000 description 16
- MMWCIQZXVOZEGG-HOZKJCLWSA-N [(1S,2R,3S,4S,5R,6S)-2,3,5-trihydroxy-4,6-diphosphonooxycyclohexyl] dihydrogen phosphate Chemical compound O[C@H]1[C@@H](O)[C@H](OP(O)(O)=O)[C@@H](OP(O)(O)=O)[C@H](O)[C@H]1OP(O)(O)=O MMWCIQZXVOZEGG-HOZKJCLWSA-N 0.000 description 15
- 102000004657 Calcium-Calmodulin-Dependent Protein Kinase Type 2 Human genes 0.000 description 14
- 108010003721 Calcium-Calmodulin-Dependent Protein Kinase Type 2 Proteins 0.000 description 14
- 102000003627 TRPC1 Human genes 0.000 description 13
- 101150017559 TRPC1 gene Proteins 0.000 description 13
- 239000000556 agonist Substances 0.000 description 13
- 229960001340 histamine Drugs 0.000 description 13
- 230000003185 calcium uptake Effects 0.000 description 12
- 238000002474 experimental method Methods 0.000 description 12
- 230000004083 survival effect Effects 0.000 description 12
- 239000003795 chemical substances by application Substances 0.000 description 11
- 230000008497 endothelial barrier function Effects 0.000 description 11
- 108091006146 Channels Proteins 0.000 description 10
- 102100039560 Microtubule-associated protein RP/EB family member 1 Human genes 0.000 description 10
- 101710099411 Microtubule-associated protein RP/EB family member 1 Proteins 0.000 description 10
- 101710107943 Trans-activator protein BZLF1 Proteins 0.000 description 10
- 238000007912 intraperitoneal administration Methods 0.000 description 10
- 230000001105 regulatory effect Effects 0.000 description 10
- 102000005962 receptors Human genes 0.000 description 9
- 108020003175 receptors Proteins 0.000 description 9
- 230000000638 stimulation Effects 0.000 description 9
- 230000015572 biosynthetic process Effects 0.000 description 8
- 230000008859 change Effects 0.000 description 8
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 8
- 230000005764 inhibitory process Effects 0.000 description 8
- 230000000770 proinflammatory effect Effects 0.000 description 8
- 230000002829 reductive effect Effects 0.000 description 8
- 238000006467 substitution reaction Methods 0.000 description 8
- 230000001052 transient effect Effects 0.000 description 8
- 102100028906 Catenin delta-1 Human genes 0.000 description 7
- 101150020891 PRKCA gene Proteins 0.000 description 7
- 102000008790 VE-cadherin Human genes 0.000 description 7
- 230000037396 body weight Effects 0.000 description 7
- 108010018828 cadherin 5 Proteins 0.000 description 7
- 108010031971 delta catenin Proteins 0.000 description 7
- 239000012634 fragment Substances 0.000 description 7
- 231100000225 lethality Toxicity 0.000 description 7
- 125000002842 L-seryl group Chemical group O=C([*])[C@](N([H])[H])([H])C([H])([H])O[H] 0.000 description 6
- 241001465754 Metazoa Species 0.000 description 6
- 229930012538 Paclitaxel Natural products 0.000 description 6
- 108020004459 Small interfering RNA Proteins 0.000 description 6
- 230000001419 dependent effect Effects 0.000 description 6
- 238000009826 distribution Methods 0.000 description 6
- 238000009472 formulation Methods 0.000 description 6
- 230000002401 inhibitory effect Effects 0.000 description 6
- 238000004519 manufacturing process Methods 0.000 description 6
- 210000000440 neutrophil Anatomy 0.000 description 6
- 229960001592 paclitaxel Drugs 0.000 description 6
- RCINICONZNJXQF-MZXODVADSA-N taxol Chemical compound O([C@@H]1[C@@]2(C[C@@H](C(C)=C(C2(C)C)[C@H](C([C@]2(C)[C@@H](O)C[C@H]3OC[C@]3([C@H]21)OC(C)=O)=O)OC(=O)C)OC(=O)[C@H](O)[C@@H](NC(=O)C=1C=CC=CC=1)C=1C=CC=CC=1)O)C(=O)C1=CC=CC=C1 RCINICONZNJXQF-MZXODVADSA-N 0.000 description 6
- HAGOWCONESKMDW-FRSCJGFNSA-N (2s)-4-amino-2-[[(2s)-2-[[(2s)-2-[[(2s)-2-[[(2s)-2-[[(2s)-2-amino-3-hydroxypropanoyl]amino]-3-phenylpropanoyl]amino]-4-methylpentanoyl]amino]-4-methylpentanoyl]amino]-5-(diaminomethylideneamino)pentanoyl]amino]-4-oxobutanoic acid Chemical compound NC(N)=NCCC[C@@H](C(=O)N[C@@H](CC(N)=O)C(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](NC(=O)[C@@H](N)CO)CC1=CC=CC=C1 HAGOWCONESKMDW-FRSCJGFNSA-N 0.000 description 5
- 101100356682 Caenorhabditis elegans rho-1 gene Proteins 0.000 description 5
- 102100028452 Nitric oxide synthase, endothelial Human genes 0.000 description 5
- 206010035664 Pneumonia Diseases 0.000 description 5
- 101150111584 RHOA gene Proteins 0.000 description 5
- 125000003275 alpha amino acid group Chemical group 0.000 description 5
- 230000002238 attenuated effect Effects 0.000 description 5
- 230000028956 calcium-mediated signaling Effects 0.000 description 5
- 210000004323 caveolae Anatomy 0.000 description 5
- 208000035475 disorder Diseases 0.000 description 5
- 210000002889 endothelial cell Anatomy 0.000 description 5
- 230000006872 improvement Effects 0.000 description 5
- 238000010253 intravenous injection Methods 0.000 description 5
- 238000002203 pretreatment Methods 0.000 description 5
- 235000018102 proteins Nutrition 0.000 description 5
- 102000004169 proteins and genes Human genes 0.000 description 5
- 108090000623 proteins and genes Proteins 0.000 description 5
- 230000002685 pulmonary effect Effects 0.000 description 5
- 230000011664 signaling Effects 0.000 description 5
- 230000000087 stabilizing effect Effects 0.000 description 5
- 238000007920 subcutaneous administration Methods 0.000 description 5
- 238000001356 surgical procedure Methods 0.000 description 5
- 230000008728 vascular permeability Effects 0.000 description 5
- 108010043137 Actomyosin Proteins 0.000 description 4
- 102000014914 Carrier Proteins Human genes 0.000 description 4
- 101000669447 Homo sapiens Toll-like receptor 4 Proteins 0.000 description 4
- 102000003896 Myeloperoxidases Human genes 0.000 description 4
- 108090000235 Myeloperoxidases Proteins 0.000 description 4
- 101710090055 Nitric oxide synthase, endothelial Proteins 0.000 description 4
- HATRDXDCPOXQJX-UHFFFAOYSA-N Thapsigargin Natural products CCCCCCCC(=O)OC1C(OC(O)C(=C/C)C)C(=C2C3OC(=O)C(C)(O)C3(O)C(CC(C)(OC(=O)C)C12)OC(=O)CCC)C HATRDXDCPOXQJX-UHFFFAOYSA-N 0.000 description 4
- 102100039360 Toll-like receptor 4 Human genes 0.000 description 4
- -1 accacia Substances 0.000 description 4
- 108091008324 binding proteins Proteins 0.000 description 4
- 230000004071 biological effect Effects 0.000 description 4
- 230000033228 biological regulation Effects 0.000 description 4
- 239000011575 calcium Substances 0.000 description 4
- 239000000839 emulsion Substances 0.000 description 4
- 230000008595 infiltration Effects 0.000 description 4
- 238000001764 infiltration Methods 0.000 description 4
- 238000001990 intravenous administration Methods 0.000 description 4
- 210000004379 membrane Anatomy 0.000 description 4
- 239000012528 membrane Substances 0.000 description 4
- DZNKOAWEHDKBEP-UHFFFAOYSA-N methyl 2-[6-[bis(2-methoxy-2-oxoethyl)amino]-5-[2-[2-[bis(2-methoxy-2-oxoethyl)amino]-5-methylphenoxy]ethoxy]-1-benzofuran-2-yl]-1,3-oxazole-5-carboxylate Chemical compound COC(=O)CN(CC(=O)OC)C1=CC=C(C)C=C1OCCOC(C(=C1)N(CC(=O)OC)CC(=O)OC)=CC2=C1OC(C=1OC(=CN=1)C(=O)OC)=C2 DZNKOAWEHDKBEP-UHFFFAOYSA-N 0.000 description 4
- 230000010412 perfusion Effects 0.000 description 4
- 229920001184 polypeptide Polymers 0.000 description 4
- 230000024883 vasodilation Effects 0.000 description 4
- 108091035707 Consensus sequence Proteins 0.000 description 3
- YQEZLKZALYSWHR-UHFFFAOYSA-N Ketamine Chemical compound C=1C=CC=C(Cl)C=1C1(NC)CCCCC1=O YQEZLKZALYSWHR-UHFFFAOYSA-N 0.000 description 3
- QNAYBMKLOCPYGJ-REOHCLBHSA-N L-alanine Chemical compound C[C@H](N)C(O)=O QNAYBMKLOCPYGJ-REOHCLBHSA-N 0.000 description 3
- 108060001084 Luciferase Proteins 0.000 description 3
- 239000005089 Luciferase Substances 0.000 description 3
- 241000124008 Mammalia Species 0.000 description 3
- 102000011131 Myosin-Light-Chain Phosphatase Human genes 0.000 description 3
- 108010037801 Myosin-Light-Chain Phosphatase Proteins 0.000 description 3
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
- 206010037423 Pulmonary oedema Diseases 0.000 description 3
- 101100100680 Schizosaccharomyces pombe (strain 972 / ATCC 24843) trp4 gene Proteins 0.000 description 3
- 108091027967 Small hairpin RNA Proteins 0.000 description 3
- 102000003622 TRPC4 Human genes 0.000 description 3
- 102000002689 Toll-like receptor Human genes 0.000 description 3
- 108020000411 Toll-like receptor Proteins 0.000 description 3
- 101150099990 Trpc4 gene Proteins 0.000 description 3
- 208000027418 Wounds and injury Diseases 0.000 description 3
- NOSIYYJFMPDDSA-UHFFFAOYSA-N acepromazine Chemical compound C1=C(C(C)=O)C=C2N(CCCN(C)C)C3=CC=CC=C3SC2=C1 NOSIYYJFMPDDSA-UHFFFAOYSA-N 0.000 description 3
- 229960005054 acepromazine Drugs 0.000 description 3
- 235000004279 alanine Nutrition 0.000 description 3
- 125000000539 amino acid group Chemical group 0.000 description 3
- 238000004458 analytical method Methods 0.000 description 3
- 230000036772 blood pressure Effects 0.000 description 3
- 210000004534 cecum Anatomy 0.000 description 3
- 239000003638 chemical reducing agent Substances 0.000 description 3
- 150000001875 compounds Chemical class 0.000 description 3
- 230000006378 damage Effects 0.000 description 3
- 230000007423 decrease Effects 0.000 description 3
- 238000012217 deletion Methods 0.000 description 3
- 230000037430 deletion Effects 0.000 description 3
- 230000000368 destabilizing effect Effects 0.000 description 3
- 239000000539 dimer Substances 0.000 description 3
- 201000010099 disease Diseases 0.000 description 3
- 231100000673 dose–response relationship Toxicity 0.000 description 3
- 238000001914 filtration Methods 0.000 description 3
- 230000012010 growth Effects 0.000 description 3
- 230000002209 hydrophobic effect Effects 0.000 description 3
- 238000001802 infusion Methods 0.000 description 3
- 229960003299 ketamine Drugs 0.000 description 3
- 210000004924 lung microvascular endothelial cell Anatomy 0.000 description 3
- 238000010172 mouse model Methods 0.000 description 3
- 239000002687 nonaqueous vehicle Substances 0.000 description 3
- 239000002773 nucleotide Substances 0.000 description 3
- 230000002085 persistent effect Effects 0.000 description 3
- 239000002244 precipitate Substances 0.000 description 3
- 230000000284 resting effect Effects 0.000 description 3
- 239000004055 small Interfering RNA Substances 0.000 description 3
- 239000000243 solution Substances 0.000 description 3
- 239000000600 sorbitol Substances 0.000 description 3
- 235000010356 sorbitol Nutrition 0.000 description 3
- 239000003381 stabilizer Substances 0.000 description 3
- 239000000375 suspending agent Substances 0.000 description 3
- 239000000725 suspension Substances 0.000 description 3
- 239000003826 tablet Substances 0.000 description 3
- IXFPJGBNCFXKPI-FSIHEZPISA-N thapsigargin Chemical compound CCCC(=O)O[C@H]1C[C@](C)(OC(C)=O)[C@H]2[C@H](OC(=O)CCCCCCC)[C@@H](OC(=O)C(\C)=C/C)C(C)=C2[C@@H]2OC(=O)[C@@](C)(O)[C@]21O IXFPJGBNCFXKPI-FSIHEZPISA-N 0.000 description 3
- 210000003462 vein Anatomy 0.000 description 3
- BPICBUSOMSTKRF-UHFFFAOYSA-N xylazine Chemical compound CC1=CC=CC(C)=C1NC1=NCCCS1 BPICBUSOMSTKRF-UHFFFAOYSA-N 0.000 description 3
- 229960001600 xylazine Drugs 0.000 description 3
- BLZVCIGGICSWIG-UHFFFAOYSA-N 2-aminoethoxydiphenylborane Chemical compound C=1C=CC=CC=1B(OCCN)C1=CC=CC=C1 BLZVCIGGICSWIG-UHFFFAOYSA-N 0.000 description 2
- 206010001052 Acute respiratory distress syndrome Diseases 0.000 description 2
- 206010002091 Anaesthesia Diseases 0.000 description 2
- OGSQONVYSTZIJB-WDSOQIARSA-N Arg-Leu-Trp Chemical compound CC(C)C[C@H](NC(=O)[C@@H](N)CCCN=C(N)N)C(=O)N[C@@H](Cc1c[nH]c2ccccc12)C(O)=O OGSQONVYSTZIJB-WDSOQIARSA-N 0.000 description 2
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 2
- 102000000584 Calmodulin Human genes 0.000 description 2
- 108010041952 Calmodulin Proteins 0.000 description 2
- 108090000695 Cytokines Proteins 0.000 description 2
- 102000004127 Cytokines Human genes 0.000 description 2
- FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 2
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 2
- 108010010803 Gelatin Proteins 0.000 description 2
- KTNGVMMGIQWIDV-OSUNSFLBSA-N Ile-Pro-Thr Chemical compound CC[C@H](C)[C@H](N)C(=O)N1CCC[C@H]1C(=O)N[C@@H]([C@@H](C)O)C(O)=O KTNGVMMGIQWIDV-OSUNSFLBSA-N 0.000 description 2
- 102000005482 Lipopolysaccharide Receptors Human genes 0.000 description 2
- 108010031801 Lipopolysaccharide Receptors Proteins 0.000 description 2
- ALEVUGKHINJNIF-QEJZJMRPSA-N Lys-Phe-Ala Chemical compound NCCCC[C@H](N)C(=O)N[C@H](C(=O)N[C@@H](C)C(O)=O)CC1=CC=CC=C1 ALEVUGKHINJNIF-QEJZJMRPSA-N 0.000 description 2
- 208000004221 Multiple Trauma Diseases 0.000 description 2
- 208000006079 Near drowning Diseases 0.000 description 2
- 108091028043 Nucleic acid sequence Proteins 0.000 description 2
- 102000032626 PAR-1 Receptor Human genes 0.000 description 2
- 108010070519 PAR-1 Receptor Proteins 0.000 description 2
- 208000037273 Pathologic Processes Diseases 0.000 description 2
- 206010035669 Pneumonia aspiration Diseases 0.000 description 2
- KIDXAAQVMNLJFQ-KZVJFYERSA-N Pro-Thr-Ala Chemical compound C[C@@H](O)[C@H](NC(=O)[C@@H]1CCCN1)C(=O)N[C@@H](C)C(O)=O KIDXAAQVMNLJFQ-KZVJFYERSA-N 0.000 description 2
- 102000002020 Protease-activated receptors Human genes 0.000 description 2
- 108050009310 Protease-activated receptors Proteins 0.000 description 2
- 208000013616 Respiratory Distress Syndrome Diseases 0.000 description 2
- 241000283984 Rodentia Species 0.000 description 2
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- 102000004094 Stromal Interaction Molecule 1 Human genes 0.000 description 2
- 108090000532 Stromal Interaction Molecule 1 Proteins 0.000 description 2
- 208000011341 adult acute respiratory distress syndrome Diseases 0.000 description 2
- 201000000028 adult respiratory distress syndrome Diseases 0.000 description 2
- 238000012867 alanine scanning Methods 0.000 description 2
- 230000004075 alteration Effects 0.000 description 2
- 230000003321 amplification Effects 0.000 description 2
- 230000037005 anaesthesia Effects 0.000 description 2
- 238000000540 analysis of variance Methods 0.000 description 2
- 238000013459 approach Methods 0.000 description 2
- 239000008135 aqueous vehicle Substances 0.000 description 2
- 201000009807 aspiration pneumonia Diseases 0.000 description 2
- 238000003556 assay Methods 0.000 description 2
- 238000000376 autoradiography Methods 0.000 description 2
- 230000004888 barrier function Effects 0.000 description 2
- 239000011230 binding agent Substances 0.000 description 2
- 230000008827 biological function Effects 0.000 description 2
- 230000000903 blocking effect Effects 0.000 description 2
- 229910052791 calcium Inorganic materials 0.000 description 2
- 230000009460 calcium influx Effects 0.000 description 2
- 238000004364 calculation method Methods 0.000 description 2
- 238000004113 cell culture Methods 0.000 description 2
- 230000008045 co-localization Effects 0.000 description 2
- 208000027744 congestion Diseases 0.000 description 2
- 210000004292 cytoskeleton Anatomy 0.000 description 2
- 230000003247 decreasing effect Effects 0.000 description 2
- 150000001982 diacylglycerols Chemical class 0.000 description 2
- 239000007884 disintegrant Substances 0.000 description 2
- 239000003995 emulsifying agent Substances 0.000 description 2
- 238000011067 equilibration Methods 0.000 description 2
- 239000000945 filler Substances 0.000 description 2
- 238000002866 fluorescence resonance energy transfer Methods 0.000 description 2
- 230000004907 flux Effects 0.000 description 2
- 239000003517 fume Substances 0.000 description 2
- 230000006870 function Effects 0.000 description 2
- 230000002496 gastric effect Effects 0.000 description 2
- 239000008273 gelatin Substances 0.000 description 2
- 229920000159 gelatin Polymers 0.000 description 2
- 235000019322 gelatine Nutrition 0.000 description 2
- 235000011852 gelatine desserts Nutrition 0.000 description 2
- 230000036541 health Effects 0.000 description 2
- 230000028993 immune response Effects 0.000 description 2
- 238000000126 in silico method Methods 0.000 description 2
- 230000006698 induction Effects 0.000 description 2
- 230000002757 inflammatory effect Effects 0.000 description 2
- 230000028709 inflammatory response Effects 0.000 description 2
- 230000004941 influx Effects 0.000 description 2
- 239000007928 intraperitoneal injection Substances 0.000 description 2
- 230000000670 limiting effect Effects 0.000 description 2
- 230000004807 localization Effects 0.000 description 2
- 231100000053 low toxicity Toxicity 0.000 description 2
- 239000000314 lubricant Substances 0.000 description 2
- 230000004199 lung function Effects 0.000 description 2
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
- 238000005259 measurement Methods 0.000 description 2
- 238000002483 medication Methods 0.000 description 2
- 230000035772 mutation Effects 0.000 description 2
- 238000003199 nucleic acid amplification method Methods 0.000 description 2
- 125000003729 nucleotide group Chemical group 0.000 description 2
- 230000008520 organization Effects 0.000 description 2
- 238000007911 parenteral administration Methods 0.000 description 2
- 230000009054 pathological process Effects 0.000 description 2
- 230000000865 phosphorylative effect Effects 0.000 description 2
- 230000003389 potentiating effect Effects 0.000 description 2
- 239000000843 powder Substances 0.000 description 2
- 239000003755 preservative agent Substances 0.000 description 2
- 230000001681 protective effect Effects 0.000 description 2
- 230000004043 responsiveness Effects 0.000 description 2
- 210000003296 saliva Anatomy 0.000 description 2
- 230000035939 shock Effects 0.000 description 2
- 239000011780 sodium chloride Substances 0.000 description 2
- 239000006188 syrup Substances 0.000 description 2
- 235000020357 syrup Nutrition 0.000 description 2
- 238000012360 testing method Methods 0.000 description 2
- 238000002560 therapeutic procedure Methods 0.000 description 2
- 210000001519 tissue Anatomy 0.000 description 2
- 231100000331 toxic Toxicity 0.000 description 2
- 230000002588 toxic effect Effects 0.000 description 2
- 231100000419 toxicity Toxicity 0.000 description 2
- 230000001988 toxicity Effects 0.000 description 2
- 239000003981 vehicle Substances 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- 239000000080 wetting agent Substances 0.000 description 2
- FBKFDSUZBVDZIX-FFGDOFBPSA-N (4s)-4-[[(2s)-2-[[(2s)-2-[[2-[[(2s)-2-[[(2s)-2-acetamido-3-phenylpropanoyl]amino]-4-methylsulfanylbutanoyl]amino]-2-methylpropanoyl]amino]-3-[4-(phosphonomethyl)phenyl]propanoyl]amino]-3-(6-chloro-1h-indol-3-yl)propanoyl]amino]-5-[[1-[[(2s)-1-amino-4-meth Chemical compound C([C@@H](C(=O)N[C@@H](CCSC)C(=O)NC(C)(C)C(=O)N[C@@H](CC=1C=CC(CP(O)(O)=O)=CC=1)C(=O)N[C@@H](CC=1C2=CC=C(Cl)C=C2NC=1)C(=O)N[C@@H](CCC(O)=O)C(=O)NC1(CC1)C(=O)N[C@@H](CC(C)C)C(N)=O)NC(C)=O)C1=CC=CC=C1 FBKFDSUZBVDZIX-FFGDOFBPSA-N 0.000 description 1
- ZORQXIQZAOLNGE-UHFFFAOYSA-N 1,1-difluorocyclohexane Chemical compound FC1(F)CCCCC1 ZORQXIQZAOLNGE-UHFFFAOYSA-N 0.000 description 1
- IIZPXYDJLKNOIY-JXPKJXOSSA-N 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCC\C=C/C\C=C/C\C=C/C\C=C/CCCCC IIZPXYDJLKNOIY-JXPKJXOSSA-N 0.000 description 1
- GGNHBHYDMUDXQB-KBIXCLLPSA-N Ala-Glu-Ile Chemical compound CC[C@H](C)[C@@H](C(O)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C)N GGNHBHYDMUDXQB-KBIXCLLPSA-N 0.000 description 1
- 102000009027 Albumins Human genes 0.000 description 1
- 108010088751 Albumins Proteins 0.000 description 1
- 235000019489 Almond oil Nutrition 0.000 description 1
- 241000416162 Astragalus gummifer Species 0.000 description 1
- 241000271566 Aves Species 0.000 description 1
- 241000894006 Bacteria Species 0.000 description 1
- 229940043709 CaM kinase II inhibitor Drugs 0.000 description 1
- 102000004612 Calcium-Transporting ATPases Human genes 0.000 description 1
- 108010017954 Calcium-Transporting ATPases Proteins 0.000 description 1
- 229920002134 Carboxymethyl cellulose Polymers 0.000 description 1
- 229920002261 Corn starch Polymers 0.000 description 1
- 206010011224 Cough Diseases 0.000 description 1
- FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 description 1
- 101000802895 Dendroaspis angusticeps Fasciculin-1 Proteins 0.000 description 1
- 239000004338 Dichlorodifluoromethane Substances 0.000 description 1
- 108010061435 Enalapril Proteins 0.000 description 1
- 108010066671 Enalaprilat Proteins 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- 241000282326 Felis catus Species 0.000 description 1
- 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 1
- 101001124309 Homo sapiens Nitric oxide synthase, endothelial Proteins 0.000 description 1
- 101000611023 Homo sapiens Tumor necrosis factor receptor superfamily member 6 Proteins 0.000 description 1
- 239000004354 Hydroxyethyl cellulose Substances 0.000 description 1
- 229920000663 Hydroxyethyl cellulose Polymers 0.000 description 1
- 108091008585 IP3 receptors Proteins 0.000 description 1
- 208000001718 Immediate Hypersensitivity 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
- ODKSFYDXXFIFQN-BYPYZUCNSA-N L-arginine Chemical compound OC(=O)[C@@H](N)CCCN=C(N)N ODKSFYDXXFIFQN-BYPYZUCNSA-N 0.000 description 1
- 229930064664 L-arginine Natural products 0.000 description 1
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 1
- 208000009481 Laryngeal Edema Diseases 0.000 description 1
- 206010023845 Laryngeal oedema Diseases 0.000 description 1
- 235000010643 Leucaena leucocephala Nutrition 0.000 description 1
- 240000007472 Leucaena leucocephala Species 0.000 description 1
- 235000019759 Maize starch Nutrition 0.000 description 1
- 229920000168 Microcrystalline cellulose Polymers 0.000 description 1
- 229920000715 Mucilage Polymers 0.000 description 1
- 241000699666 Mus <mouse, genus> Species 0.000 description 1
- 102100035044 Myosin light chain kinase, smooth muscle Human genes 0.000 description 1
- 101710198035 Myosin light chain kinase, smooth muscle Proteins 0.000 description 1
- 244000061176 Nicotiana tabacum Species 0.000 description 1
- 235000002637 Nicotiana tabacum Nutrition 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
- KYRVNWMVYQXFEU-UHFFFAOYSA-N Nocodazole Chemical compound C1=C2NC(NC(=O)OC)=NC2=CC=C1C(=O)C1=CC=CS1 KYRVNWMVYQXFEU-UHFFFAOYSA-N 0.000 description 1
- CYZBFPYMSJGBRL-DRZSPHRISA-N Phe-Ala-Glu Chemical compound [H]N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H](C)C(=O)N[C@@H](CCC(O)=O)C(O)=O CYZBFPYMSJGBRL-DRZSPHRISA-N 0.000 description 1
- XNQMZHLAYFWSGJ-HTUGSXCWSA-N Phe-Thr-Glu Chemical compound [H]N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CCC(O)=O)C(O)=O XNQMZHLAYFWSGJ-HTUGSXCWSA-N 0.000 description 1
- 108091000080 Phosphotransferase Proteins 0.000 description 1
- 239000002202 Polyethylene glycol Substances 0.000 description 1
- 102000001253 Protein Kinase Human genes 0.000 description 1
- 102100034335 Rab GDP dissociation inhibitor alpha Human genes 0.000 description 1
- 101710102264 Rab GDP dissociation inhibitor alpha Proteins 0.000 description 1
- 108010053823 Rho Guanine Nucleotide Exchange Factors Proteins 0.000 description 1
- 102100021708 Rho guanine nucleotide exchange factor 1 Human genes 0.000 description 1
- 230000021194 SRP-dependent cotranslational protein targeting to membrane Effects 0.000 description 1
- DBMJMQXJHONAFJ-UHFFFAOYSA-M Sodium laurylsulphate Chemical compound [Na+].CCCCCCCCCCCCOS([O-])(=O)=O DBMJMQXJHONAFJ-UHFFFAOYSA-M 0.000 description 1
- 229920002472 Starch Polymers 0.000 description 1
- 235000021355 Stearic acid Nutrition 0.000 description 1
- JMGJDTNUMAZNLX-RWRJDSDZSA-N Thr-Glu-Ile Chemical compound [H]N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H]([C@@H](C)CC)C(O)=O JMGJDTNUMAZNLX-RWRJDSDZSA-N 0.000 description 1
- AYFVYJQAPQTCCC-UHFFFAOYSA-N Threonine Natural products CC(O)C(N)C(O)=O AYFVYJQAPQTCCC-UHFFFAOYSA-N 0.000 description 1
- 239000004473 Threonine Substances 0.000 description 1
- 229920001615 Tragacanth Polymers 0.000 description 1
- 102100040403 Tumor necrosis factor receptor superfamily member 6 Human genes 0.000 description 1
- 102000014384 Type C Phospholipases Human genes 0.000 description 1
- 108010079194 Type C Phospholipases Proteins 0.000 description 1
- 102000005789 Vascular Endothelial Growth Factors Human genes 0.000 description 1
- 108010019530 Vascular Endothelial Growth Factors Proteins 0.000 description 1
- 206010052428 Wound Diseases 0.000 description 1
- 230000002159 abnormal effect Effects 0.000 description 1
- 238000009825 accumulation Methods 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- 230000003213 activating effect Effects 0.000 description 1
- 239000000654 additive Substances 0.000 description 1
- 239000000853 adhesive Substances 0.000 description 1
- 239000000443 aerosol Substances 0.000 description 1
- 230000008371 airway function Effects 0.000 description 1
- 235000013334 alcoholic beverage Nutrition 0.000 description 1
- 239000008168 almond oil Substances 0.000 description 1
- CEGOLXSVJUTHNZ-UHFFFAOYSA-K aluminium tristearate Chemical compound [Al+3].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O CEGOLXSVJUTHNZ-UHFFFAOYSA-K 0.000 description 1
- 229940063655 aluminum stearate Drugs 0.000 description 1
- 239000005557 antagonist Substances 0.000 description 1
- 210000000709 aorta Anatomy 0.000 description 1
- YEESUBCSWGVPCE-UHFFFAOYSA-N azanylidyneoxidanium iron(2+) pentacyanide Chemical compound [Fe++].[C-]#N.[C-]#N.[C-]#N.[C-]#N.[C-]#N.N#[O+] YEESUBCSWGVPCE-UHFFFAOYSA-N 0.000 description 1
- 239000011324 bead Substances 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 238000007413 biotinylation Methods 0.000 description 1
- 238000009530 blood pressure measurement Methods 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
- 239000002775 capsule Substances 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
- 239000001768 carboxy methyl cellulose Substances 0.000 description 1
- 235000010948 carboxy methyl cellulose Nutrition 0.000 description 1
- 239000008112 carboxymethyl-cellulose Substances 0.000 description 1
- 150000001768 cations Chemical class 0.000 description 1
- 230000001364 causal effect Effects 0.000 description 1
- 210000000170 cell membrane Anatomy 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 208000037976 chronic inflammation Diseases 0.000 description 1
- 230000006020 chronic inflammation Effects 0.000 description 1
- 229940110456 cocoa butter Drugs 0.000 description 1
- 235000019868 cocoa butter Nutrition 0.000 description 1
- 239000003240 coconut oil Substances 0.000 description 1
- 235000019864 coconut oil Nutrition 0.000 description 1
- 230000008602 contraction Effects 0.000 description 1
- 230000001276 controlling effect Effects 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
- 239000006071 cream Substances 0.000 description 1
- 230000003436 cytoskeletal effect Effects 0.000 description 1
- 230000001086 cytosolic effect Effects 0.000 description 1
- 230000034994 death Effects 0.000 description 1
- 230000002950 deficient Effects 0.000 description 1
- 239000003405 delayed action preparation Substances 0.000 description 1
- 238000013461 design Methods 0.000 description 1
- 238000003745 diagnosis Methods 0.000 description 1
- PXBRQCKWGAHEHS-UHFFFAOYSA-N dichlorodifluoromethane Chemical compound FC(F)(Cl)Cl PXBRQCKWGAHEHS-UHFFFAOYSA-N 0.000 description 1
- 235000019404 dichlorodifluoromethane Nutrition 0.000 description 1
- 235000005911 diet Nutrition 0.000 description 1
- 230000000378 dietary effect Effects 0.000 description 1
- 239000002270 dispersing agent Substances 0.000 description 1
- 238000010494 dissociation reaction Methods 0.000 description 1
- 230000005593 dissociations Effects 0.000 description 1
- 239000002934 diuretic Substances 0.000 description 1
- 229940030606 diuretics Drugs 0.000 description 1
- 230000035622 drinking Effects 0.000 description 1
- 230000008846 dynamic interplay Effects 0.000 description 1
- 230000004064 dysfunction Effects 0.000 description 1
- 239000008157 edible vegetable oil Substances 0.000 description 1
- 230000002900 effect on cell Effects 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
- 229960000873 enalapril Drugs 0.000 description 1
- OYFJQPXVCSSHAI-QFPUQLAESA-N enalapril maleate Chemical compound OC(=O)\C=C/C(O)=O.C([C@@H](C(=O)OCC)N[C@@H](C)C(=O)N1[C@@H](CCC1)C(O)=O)CC1=CC=CC=C1 OYFJQPXVCSSHAI-QFPUQLAESA-N 0.000 description 1
- 210000003038 endothelium Anatomy 0.000 description 1
- 210000001842 enterocyte Anatomy 0.000 description 1
- 229940088598 enzyme Drugs 0.000 description 1
- 210000002919 epithelial cell Anatomy 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- 235000019441 ethanol Nutrition 0.000 description 1
- BEFDCLMNVWHSGT-UHFFFAOYSA-N ethenylcyclopentane Chemical compound C=CC1CCCC1 BEFDCLMNVWHSGT-UHFFFAOYSA-N 0.000 description 1
- 230000000763 evoking effect Effects 0.000 description 1
- 239000003925 fat Substances 0.000 description 1
- 235000019197 fats Nutrition 0.000 description 1
- 210000003608 fece Anatomy 0.000 description 1
- 239000012530 fluid Substances 0.000 description 1
- ZZUFCTLCJUWOSV-UHFFFAOYSA-N furosemide Chemical compound C1=C(Cl)C(S(=O)(=O)N)=CC(C(O)=O)=C1NCC1=CC=CO1 ZZUFCTLCJUWOSV-UHFFFAOYSA-N 0.000 description 1
- 239000000499 gel Substances 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- 235000001727 glucose Nutrition 0.000 description 1
- 125000005456 glyceride group Chemical group 0.000 description 1
- 229960003711 glyceryl trinitrate Drugs 0.000 description 1
- 230000013632 homeostatic process Effects 0.000 description 1
- 230000007062 hydrolysis Effects 0.000 description 1
- 238000006460 hydrolysis reaction Methods 0.000 description 1
- 235000019447 hydroxyethyl cellulose Nutrition 0.000 description 1
- 238000003125 immunofluorescent labeling Methods 0.000 description 1
- 230000005847 immunogenicity Effects 0.000 description 1
- 238000012744 immunostaining Methods 0.000 description 1
- 238000002513 implantation Methods 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 230000002779 inactivation Effects 0.000 description 1
- 208000027866 inflammatory disease Diseases 0.000 description 1
- 238000003780 insertion Methods 0.000 description 1
- 230000037431 insertion Effects 0.000 description 1
- 230000000968 intestinal effect Effects 0.000 description 1
- 238000001361 intraarterial administration Methods 0.000 description 1
- 238000007918 intramuscular administration Methods 0.000 description 1
- 238000010255 intramuscular injection Methods 0.000 description 1
- 239000007927 intramuscular injection Substances 0.000 description 1
- 238000007913 intrathecal administration Methods 0.000 description 1
- 230000002601 intratumoral effect Effects 0.000 description 1
- 239000003456 ion exchange resin Substances 0.000 description 1
- 229920003303 ion-exchange polymer Polymers 0.000 description 1
- 229960002725 isoflurane Drugs 0.000 description 1
- 210000004731 jugular vein Anatomy 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 238000002350 laparotomy Methods 0.000 description 1
- 235000010445 lecithin Nutrition 0.000 description 1
- 239000000787 lecithin Substances 0.000 description 1
- 229940067606 lecithin Drugs 0.000 description 1
- 210000005240 left ventricle Anatomy 0.000 description 1
- 231100000518 lethal Toxicity 0.000 description 1
- 230000001665 lethal effect Effects 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 239000012669 liquid formulation Substances 0.000 description 1
- 238000010859 live-cell imaging Methods 0.000 description 1
- 238000001325 log-rank test Methods 0.000 description 1
- 239000006210 lotion Substances 0.000 description 1
- 239000007937 lozenge Substances 0.000 description 1
- 235000019359 magnesium stearate Nutrition 0.000 description 1
- 238000012423 maintenance Methods 0.000 description 1
- 238000005399 mechanical ventilation Methods 0.000 description 1
- 238000010946 mechanistic model Methods 0.000 description 1
- CSHFHJNMIMPJST-HOTGVXAUSA-N methyl (2s)-2-[[(2s)-2-[[2-[(2-aminoacetyl)amino]acetyl]amino]-3-phenylpropanoyl]amino]-4-methylpentanoate Chemical compound NCC(=O)NCC(=O)N[C@H](C(=O)N[C@@H](CC(C)C)C(=O)OC)CC1=CC=CC=C1 CSHFHJNMIMPJST-HOTGVXAUSA-N 0.000 description 1
- 229920000609 methyl cellulose Polymers 0.000 description 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
- 235000010270 methyl p-hydroxybenzoate Nutrition 0.000 description 1
- 239000004292 methyl p-hydroxybenzoate Substances 0.000 description 1
- 239000001923 methylcellulose Substances 0.000 description 1
- 235000010981 methylcellulose Nutrition 0.000 description 1
- 235000019813 microcrystalline cellulose Nutrition 0.000 description 1
- 229940016286 microcrystalline cellulose Drugs 0.000 description 1
- 239000008108 microcrystalline cellulose Substances 0.000 description 1
- 238000000520 microinjection Methods 0.000 description 1
- 210000004088 microvessel Anatomy 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 238000003032 molecular docking Methods 0.000 description 1
- 210000003550 mucous cell Anatomy 0.000 description 1
- 230000007935 neutral effect Effects 0.000 description 1
- 229940099644 nitropress Drugs 0.000 description 1
- 229960002460 nitroprusside Drugs 0.000 description 1
- 229950006344 nocodazole Drugs 0.000 description 1
- 150000007523 nucleic acids Chemical group 0.000 description 1
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 1
- OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 1
- 239000003921 oil Substances 0.000 description 1
- 235000019198 oils Nutrition 0.000 description 1
- 239000002674 ointment Substances 0.000 description 1
- 210000000056 organ Anatomy 0.000 description 1
- 230000036961 partial effect Effects 0.000 description 1
- 239000006072 paste Substances 0.000 description 1
- 230000007170 pathology Effects 0.000 description 1
- 230000035515 penetration Effects 0.000 description 1
- 238000003359 percent control normalization Methods 0.000 description 1
- 230000002093 peripheral effect Effects 0.000 description 1
- 206010034674 peritonitis Diseases 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 102000020233 phosphotransferase Human genes 0.000 description 1
- 230000006461 physiological response Effects 0.000 description 1
- 239000011505 plaster Substances 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 1
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
- 229920001592 potato starch Polymers 0.000 description 1
- 230000036316 preload Effects 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 230000001737 promoting effect Effects 0.000 description 1
- 239000003380 propellant Substances 0.000 description 1
- 235000010232 propyl p-hydroxybenzoate Nutrition 0.000 description 1
- 239000004405 propyl p-hydroxybenzoate Substances 0.000 description 1
- QELSKZZBTMNZEB-UHFFFAOYSA-N propylparaben Chemical compound CCCOC(=O)C1=CC=C(O)C=C1 QELSKZZBTMNZEB-UHFFFAOYSA-N 0.000 description 1
- 230000004853 protein function Effects 0.000 description 1
- 108060006633 protein kinase Proteins 0.000 description 1
- 238000010379 pull-down assay Methods 0.000 description 1
- 208000005333 pulmonary edema Diseases 0.000 description 1
- 238000004445 quantitative analysis Methods 0.000 description 1
- 230000005855 radiation Effects 0.000 description 1
- 230000007115 recruitment Effects 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 238000007634 remodeling Methods 0.000 description 1
- 230000000754 repressing effect Effects 0.000 description 1
- 102000000568 rho-Associated Kinases Human genes 0.000 description 1
- 108010041788 rho-Associated Kinases Proteins 0.000 description 1
- 239000011435 rock Substances 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- 210000001908 sarcoplasmic reticulum Anatomy 0.000 description 1
- 230000035945 sensitivity Effects 0.000 description 1
- 239000000377 silicon dioxide Substances 0.000 description 1
- 235000020374 simple syrup Nutrition 0.000 description 1
- 238000009097 single-agent therapy Methods 0.000 description 1
- 230000000391 smoking effect Effects 0.000 description 1
- 235000019333 sodium laurylsulphate Nutrition 0.000 description 1
- 229940080313 sodium starch Drugs 0.000 description 1
- RWVGQQGBQSJDQV-UHFFFAOYSA-M sodium;3-[[4-[(e)-[4-(4-ethoxyanilino)phenyl]-[4-[ethyl-[(3-sulfonatophenyl)methyl]azaniumylidene]-2-methylcyclohexa-2,5-dien-1-ylidene]methyl]-n-ethyl-3-methylanilino]methyl]benzenesulfonate Chemical compound [Na+].C1=CC(OCC)=CC=C1NC1=CC=C(C(=C2C(=CC(C=C2)=[N+](CC)CC=2C=C(C=CC=2)S([O-])(=O)=O)C)C=2C(=CC(=CC=2)N(CC)CC=2C=C(C=CC=2)S([O-])(=O)=O)C)C=C1 RWVGQQGBQSJDQV-UHFFFAOYSA-M 0.000 description 1
- 235000010199 sorbic acid Nutrition 0.000 description 1
- 239000004334 sorbic acid Substances 0.000 description 1
- 229940075582 sorbic acid Drugs 0.000 description 1
- 239000001593 sorbitan monooleate Substances 0.000 description 1
- 235000011069 sorbitan monooleate Nutrition 0.000 description 1
- 229940035049 sorbitan monooleate Drugs 0.000 description 1
- 230000006641 stabilisation Effects 0.000 description 1
- 238000011105 stabilization Methods 0.000 description 1
- 229940032147 starch Drugs 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 239000008117 stearic acid Substances 0.000 description 1
- 235000000346 sugar Nutrition 0.000 description 1
- 230000003319 supportive effect Effects 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 239000002511 suppository base Substances 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 230000035488 systolic blood pressure Effects 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- 235000012222 talc Nutrition 0.000 description 1
- 230000002123 temporal effect Effects 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
- 239000000196 tragacanth Substances 0.000 description 1
- 235000010487 tragacanth Nutrition 0.000 description 1
- 229940116362 tragacanth Drugs 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
- 238000011144 upstream manufacturing Methods 0.000 description 1
- 229940099270 vasotec Drugs 0.000 description 1
- 238000009423 ventilation Methods 0.000 description 1
- 238000001262 western blot Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K7/00—Peptides having 5 to 20 amino acids in a fully defined sequence; Derivatives thereof
- C07K7/04—Linear peptides containing only normal peptide links
- C07K7/06—Linear peptides containing only normal peptide links having 5 to 11 amino acids
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- A61K38/1703—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates
- A61K38/1709—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates from mammals
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
- A61P11/02—Nasal agents, e.g. decongestants
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
- A61P11/06—Antiasthmatics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/08—Antiallergic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
- A61P7/10—Antioedematous agents; Diuretics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/14—Vasoprotectives; Antihaemorrhoidals; Drugs for varicose therapy; Capillary stabilisers
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- C07K14/705—Receptors; Cell surface antigens; Cell surface determinants
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K7/00—Peptides having 5 to 20 amino acids in a fully defined sequence; Derivatives thereof
- C07K7/04—Linear peptides containing only normal peptide links
- C07K7/08—Linear peptides containing only normal peptide links having 12 to 20 amino acids
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2319/00—Fusion polypeptide
- C07K2319/01—Fusion polypeptide containing a localisation/targetting motif
- C07K2319/033—Fusion polypeptide containing a localisation/targetting motif containing a motif for targeting to the internal surface of the plasma membrane, e.g. containing a myristoylation motif
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2319/00—Fusion polypeptide
- C07K2319/01—Fusion polypeptide containing a localisation/targetting motif
- C07K2319/10—Fusion polypeptide containing a localisation/targetting motif containing a tag for extracellular membrane crossing, e.g. TAT or VP22
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Organic Chemistry (AREA)
- Medicinal Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Public Health (AREA)
- Pharmacology & Pharmacy (AREA)
- Veterinary Medicine (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Biochemistry (AREA)
- Molecular Biology (AREA)
- Genetics & Genomics (AREA)
- Biophysics (AREA)
- Immunology (AREA)
- Pulmonology (AREA)
- Zoology (AREA)
- Gastroenterology & Hepatology (AREA)
- Marine Sciences & Fisheries (AREA)
- Toxicology (AREA)
- Cell Biology (AREA)
- Epidemiology (AREA)
- Otolaryngology (AREA)
- Heart & Thoracic Surgery (AREA)
- Cardiology (AREA)
- Vascular Medicine (AREA)
- Hematology (AREA)
- Diabetes (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Peptides Or Proteins (AREA)
- Medicinal Preparation (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201161496409P | 2011-06-13 | 2011-06-13 | |
| US61/496,409 | 2011-06-13 | ||
| PCT/US2012/042118 WO2012174028A2 (en) | 2011-06-13 | 2012-06-13 | Peptide compositions and methods for treating lung injury, asthma, anaphylaxis, angioedema, systemic vascular permeability syndromes, and nasal congestion |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CA2838662A1 CA2838662A1 (en) | 2012-12-20 |
| CA2838662C true CA2838662C (en) | 2018-07-24 |
Family
ID=47357694
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA2838662A Active CA2838662C (en) | 2011-06-13 | 2012-06-13 | Peptide compositions and methods for treating lung injury, asthma, anaphylaxis, angioedema, systemic vascular permeability syndromes, and nasal congestion |
Country Status (15)
| Country | Link |
|---|---|
| US (2) | US9248198B2 (enExample) |
| EP (1) | EP2717897B1 (enExample) |
| JP (1) | JP6042425B2 (enExample) |
| KR (1) | KR102042015B1 (enExample) |
| CN (2) | CN106188232B (enExample) |
| AU (1) | AU2012271781C1 (enExample) |
| BR (1) | BR112013032108B1 (enExample) |
| CA (1) | CA2838662C (enExample) |
| DK (1) | DK2717897T3 (enExample) |
| ES (1) | ES2633343T3 (enExample) |
| IL (1) | IL229771B (enExample) |
| MX (1) | MX349146B (enExample) |
| PL (1) | PL2717897T3 (enExample) |
| WO (1) | WO2012174028A2 (enExample) |
| ZA (1) | ZA201309161B (enExample) |
Families Citing this family (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| KR102042015B1 (ko) * | 2011-06-13 | 2019-11-07 | 더 보오드 오브 트러스티스 오브 더 유니버시티 오브 일리노이즈 | 폐 손상, 천식, 과민증, 혈관 부종, 전신 혈관 투과성 증후군 및 비충혈을 치료하는 펩티드 조성물과 이들로 이러한 질환을 치료하는 방법 |
| DK3265110T3 (da) * | 2015-03-02 | 2020-10-19 | The Board Of Trustees Of The Univ Of Illionis | Peptider til inhibering af angiogenese |
| CN110128506B (zh) * | 2019-05-22 | 2021-03-30 | 中国药科大学 | 一种寡肽及其应用 |
| CN110664990B (zh) * | 2019-11-07 | 2021-03-16 | 江南大学 | 一种trpc1肽类分子在制备治疗病毒感染引起的炎症的药物中的应用 |
| US20230218710A1 (en) * | 2020-04-15 | 2023-07-13 | Cohbar, Inc. | Method of treating coronavirus infections |
Family Cites Families (13)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4554101A (en) | 1981-01-09 | 1985-11-19 | New York Blood Center, Inc. | Identification and preparation of epitopes on antigens and allergens on the basis of hydrophilicity |
| US6093740A (en) * | 1997-04-30 | 2000-07-25 | Eli Lilly And Company | Therapeutic treatment for skin disorders |
| GB9718609D0 (en) * | 1997-09-02 | 1997-11-05 | Imp College Innovations Ltd | Fusion protein |
| CA2545062A1 (en) * | 2003-11-06 | 2005-05-26 | Research Development Foundation | Selective inhibitors of nuclear factor-kb activation and uses thereof |
| KR101260717B1 (ko) * | 2003-12-03 | 2013-05-09 | 와이엠 바이오사이언시즈 오스트레일리아 피티와이 엘티디 | 튜불린 저해제 |
| KR20080075494A (ko) * | 2005-09-21 | 2008-08-18 | 다스크 테크날러지, 엘엘씨 | 장기 및 조직 기능성을 위한 방법 및 조성물 |
| US7585865B2 (en) * | 2006-07-21 | 2009-09-08 | The Penn State Research Foundation | Protein kinase C zeta inhibition to treat vascular permeability |
| CA2657338C (en) * | 2006-07-21 | 2013-10-22 | Cristalia Produtos Quimicos Farmaceuticos Ltda. | Anti-inflammatory and antiallergic cyclic peptides |
| WO2009094172A2 (en) * | 2008-01-22 | 2009-07-30 | Araim Pharmaceuticals, Inc. | Tissue protective peptides and peptide analogs for preventing and treating diseases and disorders associated with tissue damage |
| FR2940032B1 (fr) | 2008-12-23 | 2013-08-09 | Seb Sa | Panier de cuisson d'aliments et systeme de cuisson correspondant |
| IT1392567B1 (it) * | 2008-12-24 | 2012-03-09 | Bioindustry Park Del Canavese S P A | Uso di un peptide derivato da er-alfa per il ripristino della sensibilita' a composti antiestrogenici in cellule di tumore mammario |
| US20100190691A1 (en) | 2009-01-27 | 2010-07-29 | Trojan Technologies, Ltd | Delivery of nucleic acids using cell-penetrating peptides |
| KR102042015B1 (ko) * | 2011-06-13 | 2019-11-07 | 더 보오드 오브 트러스티스 오브 더 유니버시티 오브 일리노이즈 | 폐 손상, 천식, 과민증, 혈관 부종, 전신 혈관 투과성 증후군 및 비충혈을 치료하는 펩티드 조성물과 이들로 이러한 질환을 치료하는 방법 |
-
2012
- 2012-06-13 KR KR1020137033193A patent/KR102042015B1/ko not_active Expired - Fee Related
- 2012-06-13 CA CA2838662A patent/CA2838662C/en active Active
- 2012-06-13 PL PL12800251T patent/PL2717897T3/pl unknown
- 2012-06-13 BR BR112013032108-3A patent/BR112013032108B1/pt not_active IP Right Cessation
- 2012-06-13 CN CN201610552695.3A patent/CN106188232B/zh active Active
- 2012-06-13 EP EP12800251.6A patent/EP2717897B1/en active Active
- 2012-06-13 JP JP2014515930A patent/JP6042425B2/ja not_active Expired - Fee Related
- 2012-06-13 US US14/105,385 patent/US9248198B2/en active Active
- 2012-06-13 DK DK12800251.6T patent/DK2717897T3/en active
- 2012-06-13 MX MX2013014650A patent/MX349146B/es active IP Right Grant
- 2012-06-13 WO PCT/US2012/042118 patent/WO2012174028A2/en not_active Ceased
- 2012-06-13 ES ES12800251.6T patent/ES2633343T3/es active Active
- 2012-06-13 CN CN201280029277.6A patent/CN103608026B/zh active Active
- 2012-06-13 AU AU2012271781A patent/AU2012271781C1/en active Active
-
2013
- 2013-12-03 IL IL229771A patent/IL229771B/en active IP Right Grant
- 2013-12-05 ZA ZA2013/09161A patent/ZA201309161B/en unknown
-
2014
- 2014-03-31 US US14/230,642 patent/US8912139B2/en active Active
Also Published As
| Publication number | Publication date |
|---|---|
| ZA201309161B (en) | 2015-03-25 |
| EP2717897A2 (en) | 2014-04-16 |
| AU2012271781C1 (en) | 2017-09-21 |
| EP2717897B1 (en) | 2017-04-19 |
| WO2012174028A3 (en) | 2013-02-21 |
| CA2838662A1 (en) | 2012-12-20 |
| DK2717897T3 (en) | 2017-07-17 |
| MX349146B (es) | 2017-07-14 |
| CN103608026A (zh) | 2014-02-26 |
| KR102042015B1 (ko) | 2019-11-07 |
| MX2013014650A (es) | 2014-01-24 |
| CN103608026B (zh) | 2016-08-24 |
| PL2717897T3 (pl) | 2017-09-29 |
| US9248198B2 (en) | 2016-02-02 |
| AU2012271781A1 (en) | 2014-01-09 |
| US20140155314A1 (en) | 2014-06-05 |
| AU2012271781B2 (en) | 2017-02-16 |
| US20140213505A1 (en) | 2014-07-31 |
| IL229771B (en) | 2019-07-31 |
| US8912139B2 (en) | 2014-12-16 |
| ES2633343T3 (es) | 2017-09-20 |
| EP2717897A4 (en) | 2015-01-07 |
| BR112013032108B1 (pt) | 2021-10-26 |
| JP2014518211A (ja) | 2014-07-28 |
| BR112013032108A2 (pt) | 2016-11-22 |
| WO2012174028A2 (en) | 2012-12-20 |
| JP6042425B2 (ja) | 2016-12-14 |
| CN106188232A (zh) | 2016-12-07 |
| KR20140056185A (ko) | 2014-05-09 |
| CN106188232B (zh) | 2020-01-07 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| Liu et al. | Cell and molecular mechanisms of insulin‐induced angiogenesis | |
| US8912139B2 (en) | Peptide compositions and methods for treating lung injury, asthma, anaphylaxis, angioedema, systemic vascular permeability syndromes, and nasal congestion | |
| KR102268883B1 (ko) | 누트린-3a 및 펩티드에 의한 폐 섬유증의 저해 | |
| Zhang et al. | NRG1-Fc improves metabolic health via dual hepatic and central action | |
| Xie et al. | Intranasal administration of recombinant Netrin-1 attenuates neuronal apoptosis by activating DCC/APPL-1/AKT signaling pathway after subarachnoid hemorrhage in rats | |
| US20250154199A1 (en) | Peptides for treating pain or reducing pain sensitivity | |
| US10064911B2 (en) | Peptides for treating cancer | |
| Chen et al. | Asiatic acid alleviates cisplatin-induced renal fibrosis in tumor-bearing mice by improving the TFEB-mediated autophagy-lysosome pathway | |
| Zhou et al. | Mitophagy deficiency activates stimulator of interferon genes activation and aggravates pathogenetic cardiac remodeling | |
| Lv et al. | Cytoglobin: a novel potential gene medicine for fibrosis and cancer therapy | |
| Liu et al. | Opticin Ameliorates Hypoxia-Induced Retinal Angiogenesis by Suppression of Integrin α2-I Domain–Collagen Complex Formation and RhoA/ROCK1 Signaling | |
| US20130345143A1 (en) | MODULATION OF p62 FUNCTION THROUGH THE PB1 DOMAIN | |
| US11103551B2 (en) | Method for treatment or prevention of a cancer | |
| HK40037093B (en) | Peptides and other agents for treating pain and increasing pain sensitivity | |
| HK40037093A (en) | Peptides and other agents for treating pain and increasing pain sensitivity | |
| HK1248101B (en) | Peptides for inhibiting angiogenesis |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| EEER | Examination request |
Effective date: 20150611 |