PT1368060E - Inibidores e/ou antagonistas da proteína hmgb1 para o tratamento de doenças vasculares - Google Patents
Inibidores e/ou antagonistas da proteína hmgb1 para o tratamento de doenças vasculares Download PDFInfo
- Publication number
- PT1368060E PT1368060E PT02717057T PT02717057T PT1368060E PT 1368060 E PT1368060 E PT 1368060E PT 02717057 T PT02717057 T PT 02717057T PT 02717057 T PT02717057 T PT 02717057T PT 1368060 E PT1368060 E PT 1368060E
- Authority
- PT
- Portugal
- Prior art keywords
- hmgb1
- cells
- hmg1
- cell
- migration
- Prior art date
Links
- 238000011282 treatment Methods 0.000 title claims abstract description 14
- 108700010013 HMGB1 Proteins 0.000 title claims description 187
- 102000055207 HMGB1 Human genes 0.000 title claims description 23
- 239000005557 antagonist Substances 0.000 title claims description 9
- 208000019553 vascular disease Diseases 0.000 title abstract description 5
- 229940076372 protein antagonist Drugs 0.000 title 1
- 229940121649 protein inhibitor Drugs 0.000 title 1
- 239000012268 protein inhibitor Substances 0.000 title 1
- 238000002360 preparation method Methods 0.000 claims abstract description 13
- 230000027455 binding Effects 0.000 claims abstract description 10
- 239000003814 drug Substances 0.000 claims abstract description 8
- 229940124597 therapeutic agent Drugs 0.000 claims abstract description 8
- 101150021904 HMGB1 gene Proteins 0.000 claims description 179
- 101100339431 Arabidopsis thaliana HMGB2 gene Proteins 0.000 claims description 170
- 210000004027 cell Anatomy 0.000 claims description 88
- 238000013508 migration Methods 0.000 claims description 28
- 230000005012 migration Effects 0.000 claims description 27
- 230000012292 cell migration Effects 0.000 claims description 22
- 102000005962 receptors Human genes 0.000 claims description 17
- 108020003175 receptors Proteins 0.000 claims description 17
- 239000003112 inhibitor Substances 0.000 claims description 13
- 101100178203 Arabidopsis thaliana HMGB3 gene Proteins 0.000 claims description 9
- 101150091750 HMG1 gene Proteins 0.000 claims description 9
- 210000002808 connective tissue Anatomy 0.000 claims description 9
- 230000001338 necrotic effect Effects 0.000 claims description 9
- 208000031481 Pathologic Constriction Diseases 0.000 claims description 8
- 244000309466 calf Species 0.000 claims description 8
- 239000012634 fragment Substances 0.000 claims description 8
- 230000036262 stenosis Effects 0.000 claims description 8
- 208000037804 stenosis Diseases 0.000 claims description 8
- 210000001541 thymus gland Anatomy 0.000 claims description 8
- 201000001320 Atherosclerosis Diseases 0.000 claims description 7
- 102100024785 Fibroblast growth factor 2 Human genes 0.000 claims description 7
- 108090000379 Fibroblast growth factor 2 Proteins 0.000 claims description 7
- 240000004808 Saccharomyces cerevisiae Species 0.000 claims description 7
- 230000000306 recurrent effect Effects 0.000 claims description 7
- 230000008929 regeneration Effects 0.000 claims description 7
- 238000011069 regeneration method Methods 0.000 claims description 7
- 238000002399 angioplasty Methods 0.000 claims description 6
- 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 claims description 5
- 108091064358 Holliday junction Proteins 0.000 claims description 5
- 102000039011 Holliday junction Human genes 0.000 claims description 5
- 102000008394 Immunoglobulin Fragments Human genes 0.000 claims description 5
- 108010021625 Immunoglobulin Fragments Proteins 0.000 claims description 5
- PRQROPMIIGLWRP-UHFFFAOYSA-N N-formyl-methionyl-leucyl-phenylalanin Chemical compound CSCCC(NC=O)C(=O)NC(CC(C)C)C(=O)NC(C(O)=O)CC1=CC=CC=C1 PRQROPMIIGLWRP-UHFFFAOYSA-N 0.000 claims description 5
- 230000004913 activation Effects 0.000 claims description 4
- 230000002401 inhibitory effect Effects 0.000 claims description 4
- 101710168537 High mobility group protein B1 Proteins 0.000 claims description 2
- AEICTKLHPYUJKJ-FUCZZUMBSA-N (3s,5s,9r,10s,13r,15r,17r)-17-[(2r,6r)-7-hydroxy-6-methylheptan-2-yl]-10,13-dimethyl-2,3,4,5,6,7,9,11,12,15,16,17-dodecahydro-1h-cyclopenta[a]phenanthrene-3,15-diol Chemical compound C([C@@H]1CC2)[C@@H](O)CC[C@]1(C)[C@@H]1C2=C2[C@H](O)C[C@H]([C@H](C)CCC[C@H](CO)C)[C@@]2(C)CC1 AEICTKLHPYUJKJ-FUCZZUMBSA-N 0.000 claims 1
- 210000003719 b-lymphocyte Anatomy 0.000 claims 1
- 238000003359 percent control normalization Methods 0.000 claims 1
- 230000029663 wound healing Effects 0.000 claims 1
- 102100037907 High mobility group protein B1 Human genes 0.000 description 166
- 102000004169 proteins and genes Human genes 0.000 description 20
- 108090000623 proteins and genes Proteins 0.000 description 20
- 230000000694 effects Effects 0.000 description 19
- 235000018102 proteins Nutrition 0.000 description 19
- 230000004044 response Effects 0.000 description 17
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 15
- 238000003556 assay Methods 0.000 description 15
- 210000000329 smooth muscle myocyte Anatomy 0.000 description 15
- 208000027418 Wounds and injury Diseases 0.000 description 14
- 230000003993 interaction Effects 0.000 description 13
- 108010081690 Pertussis Toxin Proteins 0.000 description 11
- 210000004292 cytoskeleton Anatomy 0.000 description 11
- 230000006378 damage Effects 0.000 description 11
- 210000002950 fibroblast Anatomy 0.000 description 11
- 208000014674 injury Diseases 0.000 description 11
- 210000004940 nucleus Anatomy 0.000 description 11
- 239000002975 chemoattractant Substances 0.000 description 10
- 230000008521 reorganization Effects 0.000 description 9
- 230000003399 chemotactic effect Effects 0.000 description 8
- 230000035605 chemotaxis Effects 0.000 description 8
- 210000002889 endothelial cell Anatomy 0.000 description 8
- 230000000638 stimulation Effects 0.000 description 8
- 108020004414 DNA Proteins 0.000 description 7
- 241000588724 Escherichia coli Species 0.000 description 7
- 102000043136 MAP kinase family Human genes 0.000 description 7
- 108091054455 MAP kinase family Proteins 0.000 description 7
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 6
- 102000010834 Extracellular Matrix Proteins Human genes 0.000 description 6
- 108010037362 Extracellular Matrix Proteins Proteins 0.000 description 6
- 108091006027 G proteins Proteins 0.000 description 6
- 102000030782 GTP binding Human genes 0.000 description 6
- 108091000058 GTP-Binding Proteins 0.000 description 6
- 230000003436 cytoskeletal effect Effects 0.000 description 6
- 230000001419 dependent effect Effects 0.000 description 6
- 210000002744 extracellular matrix Anatomy 0.000 description 6
- 210000003518 stress fiber Anatomy 0.000 description 6
- 239000006228 supernatant Substances 0.000 description 6
- 102000007469 Actins Human genes 0.000 description 5
- 108010085238 Actins Proteins 0.000 description 5
- 102000019149 MAP kinase activity proteins Human genes 0.000 description 5
- 108040008097 MAP kinase activity proteins Proteins 0.000 description 5
- 230000001413 cellular effect Effects 0.000 description 5
- 230000008859 change Effects 0.000 description 5
- 210000003632 microfilament Anatomy 0.000 description 5
- 230000001617 migratory effect Effects 0.000 description 5
- 230000017074 necrotic cell death Effects 0.000 description 5
- 230000008520 organization Effects 0.000 description 5
- 230000037361 pathway Effects 0.000 description 5
- 238000000746 purification Methods 0.000 description 5
- 230000008707 rearrangement Effects 0.000 description 5
- 238000002415 sodium dodecyl sulfate polyacrylamide gel electrophoresis Methods 0.000 description 5
- 108700004921 tetramethylrhodaminylphalloidine Proteins 0.000 description 5
- 238000001262 western blot Methods 0.000 description 5
- 239000006144 Dulbecco’s modified Eagle's medium Substances 0.000 description 4
- 102000034354 Gi proteins Human genes 0.000 description 4
- 108091006101 Gi proteins Proteins 0.000 description 4
- 241000235058 Komagataella pastoris Species 0.000 description 4
- KPKZJLCSROULON-QKGLWVMZSA-N Phalloidin Chemical compound N1C(=O)[C@@H]([C@@H](O)C)NC(=O)[C@H](C)NC(=O)[C@H](C[C@@](C)(O)CO)NC(=O)[C@H](C2)NC(=O)[C@H](C)NC(=O)[C@@H]3C[C@H](O)CN3C(=O)[C@@H]1CSC1=C2C2=CC=CC=C2N1 KPKZJLCSROULON-QKGLWVMZSA-N 0.000 description 4
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 4
- 230000000903 blocking effect Effects 0.000 description 4
- 238000002474 experimental method Methods 0.000 description 4
- 239000000499 gel Substances 0.000 description 4
- 238000000338 in vitro Methods 0.000 description 4
- 239000002609 medium Substances 0.000 description 4
- 239000012528 membrane Substances 0.000 description 4
- 230000000284 resting effect Effects 0.000 description 4
- 102000004127 Cytokines Human genes 0.000 description 3
- 108090000695 Cytokines Proteins 0.000 description 3
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 3
- 102100024193 Mitogen-activated protein kinase 1 Human genes 0.000 description 3
- 102000013566 Plasminogen Human genes 0.000 description 3
- 108010051456 Plasminogen Proteins 0.000 description 3
- 239000007983 Tris buffer Substances 0.000 description 3
- 235000001014 amino acid Nutrition 0.000 description 3
- 150000001413 amino acids Chemical class 0.000 description 3
- 238000000540 analysis of variance Methods 0.000 description 3
- 230000015572 biosynthetic process Effects 0.000 description 3
- 239000000872 buffer Substances 0.000 description 3
- 230000000875 corresponding effect Effects 0.000 description 3
- 210000000805 cytoplasm Anatomy 0.000 description 3
- 239000002158 endotoxin Substances 0.000 description 3
- 230000014511 neuron projection development Effects 0.000 description 3
- 230000003389 potentiating effect Effects 0.000 description 3
- 108090000765 processed proteins & peptides Proteins 0.000 description 3
- 230000035945 sensitivity Effects 0.000 description 3
- 230000019491 signal transduction Effects 0.000 description 3
- 230000011664 signaling Effects 0.000 description 3
- 239000000243 solution Substances 0.000 description 3
- 238000001356 surgical procedure Methods 0.000 description 3
- 238000012360 testing method Methods 0.000 description 3
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 3
- 210000005167 vascular cell Anatomy 0.000 description 3
- 241000588832 Bordetella pertussis Species 0.000 description 2
- 102000012422 Collagen Type I Human genes 0.000 description 2
- 108010022452 Collagen Type I Proteins 0.000 description 2
- 102000052510 DNA-Binding Proteins Human genes 0.000 description 2
- 108700020911 DNA-Binding Proteins Proteins 0.000 description 2
- 230000004568 DNA-binding Effects 0.000 description 2
- 101710089384 Extracellular protease Proteins 0.000 description 2
- 102000016359 Fibronectins Human genes 0.000 description 2
- 108010067306 Fibronectins Proteins 0.000 description 2
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 2
- WZUVPPKBWHMQCE-UHFFFAOYSA-N Haematoxylin Chemical compound C12=CC(O)=C(O)C=C2CC2(O)C1C1=CC=C(O)C(O)=C1OC2 WZUVPPKBWHMQCE-UHFFFAOYSA-N 0.000 description 2
- TWRXJAOTZQYOKJ-UHFFFAOYSA-L Magnesium chloride Chemical compound [Mg+2].[Cl-].[Cl-] TWRXJAOTZQYOKJ-UHFFFAOYSA-L 0.000 description 2
- 241000283973 Oryctolagus cuniculus Species 0.000 description 2
- 108010009711 Phalloidine Proteins 0.000 description 2
- PXIPVTKHYLBLMZ-UHFFFAOYSA-N Sodium azide Chemical compound [Na+].[N-]=[N+]=[N-] PXIPVTKHYLBLMZ-UHFFFAOYSA-N 0.000 description 2
- 229930006000 Sucrose Natural products 0.000 description 2
- 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 2
- 239000006180 TBST buffer Substances 0.000 description 2
- QPMSXSBEVQLBIL-CZRHPSIPSA-N ac1mix0p Chemical compound C1=CC=C2N(C[C@H](C)CN(C)C)C3=CC(OC)=CC=C3SC2=C1.O([C@H]1[C@]2(OC)C=CC34C[C@@H]2[C@](C)(O)CCC)C2=C5[C@]41CCN(C)[C@@H]3CC5=CC=C2O QPMSXSBEVQLBIL-CZRHPSIPSA-N 0.000 description 2
- 230000003213 activating effect Effects 0.000 description 2
- 210000001367 artery Anatomy 0.000 description 2
- 230000004071 biological effect Effects 0.000 description 2
- 230000033228 biological regulation Effects 0.000 description 2
- 210000004369 blood Anatomy 0.000 description 2
- 239000008280 blood Substances 0.000 description 2
- 230000032823 cell division Effects 0.000 description 2
- 210000003855 cell nucleus Anatomy 0.000 description 2
- 239000003153 chemical reaction reagent Substances 0.000 description 2
- 239000013078 crystal Substances 0.000 description 2
- 238000011156 evaluation Methods 0.000 description 2
- 239000011521 glass Substances 0.000 description 2
- 239000003102 growth factor Substances 0.000 description 2
- 238000010166 immunofluorescence Methods 0.000 description 2
- 238000011534 incubation Methods 0.000 description 2
- 210000002540 macrophage Anatomy 0.000 description 2
- 238000012423 maintenance Methods 0.000 description 2
- 238000004519 manufacturing process Methods 0.000 description 2
- 238000000034 method Methods 0.000 description 2
- 230000004660 morphological change Effects 0.000 description 2
- 210000002569 neuron Anatomy 0.000 description 2
- 230000005937 nuclear translocation Effects 0.000 description 2
- 239000008188 pellet Substances 0.000 description 2
- 239000002831 pharmacologic agent Substances 0.000 description 2
- 230000000144 pharmacologic effect Effects 0.000 description 2
- 239000013612 plasmid Substances 0.000 description 2
- 239000011148 porous material Substances 0.000 description 2
- 230000008569 process Effects 0.000 description 2
- 239000012679 serum free medium Substances 0.000 description 2
- 239000011780 sodium chloride Substances 0.000 description 2
- 238000007619 statistical method Methods 0.000 description 2
- 239000005720 sucrose Substances 0.000 description 2
- 230000002792 vascular Effects 0.000 description 2
- DGVVWUTYPXICAM-UHFFFAOYSA-N β‐Mercaptoethanol Chemical compound OCCS DGVVWUTYPXICAM-UHFFFAOYSA-N 0.000 description 2
- VRYALKFFQXWPIH-PBXRRBTRSA-N (3r,4s,5r)-3,4,5,6-tetrahydroxyhexanal Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)CC=O VRYALKFFQXWPIH-PBXRRBTRSA-N 0.000 description 1
- PWVRXSQPCQPQHM-UHFFFAOYSA-N 2-(4-aminophenyl)-1h-indol-6-amine Chemical compound C1=CC(N)=CC=C1C1=CC2=CC=C(N)C=C2N1 PWVRXSQPCQPQHM-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
- HRPVXLWXLXDGHG-UHFFFAOYSA-N Acrylamide Chemical compound NC(=O)C=C HRPVXLWXLXDGHG-UHFFFAOYSA-N 0.000 description 1
- 206010002023 Amyloidoses Diseases 0.000 description 1
- OUFUEOCARHOWCD-DAXSKMNVSA-N BOX A Chemical compound CC1=C(C=C)\C(=C\C(N)=O)NC1=O OUFUEOCARHOWCD-DAXSKMNVSA-N 0.000 description 1
- UGTJLJZQQFGTJD-UHFFFAOYSA-N Carbonylcyanide-3-chlorophenylhydrazone Chemical compound ClC1=CC=CC(NN=C(C#N)C#N)=C1 UGTJLJZQQFGTJD-UHFFFAOYSA-N 0.000 description 1
- 102000003688 G-Protein-Coupled Receptors Human genes 0.000 description 1
- 108090000045 G-Protein-Coupled Receptors Proteins 0.000 description 1
- 208000032612 Glial tumor Diseases 0.000 description 1
- 206010018338 Glioma Diseases 0.000 description 1
- WHUUTDBJXJRKMK-UHFFFAOYSA-N Glutamic acid Natural products OC(=O)C(N)CCC(O)=O WHUUTDBJXJRKMK-UHFFFAOYSA-N 0.000 description 1
- 239000004471 Glycine Substances 0.000 description 1
- 239000004378 Glycyrrhizin Substances 0.000 description 1
- 102000000849 HMGB Proteins Human genes 0.000 description 1
- 108010001860 HMGB Proteins Proteins 0.000 description 1
- HTTJABKRGRZYRN-UHFFFAOYSA-N Heparin Chemical compound OC1C(NC(=O)C)C(O)OC(COS(O)(=O)=O)C1OC1C(OS(O)(=O)=O)C(O)C(OC2C(C(OS(O)(=O)=O)C(OC3C(C(O)C(O)C(O3)C(O)=O)OS(O)(=O)=O)C(CO)O2)NS(O)(=O)=O)C(C(O)=O)O1 HTTJABKRGRZYRN-UHFFFAOYSA-N 0.000 description 1
- 101000817629 Homo sapiens Dymeclin Proteins 0.000 description 1
- 101001013403 Homo sapiens Meiosis initiator protein Proteins 0.000 description 1
- 206010065042 Immune reconstitution inflammatory syndrome Diseases 0.000 description 1
- 108060003951 Immunoglobulin Proteins 0.000 description 1
- 206010061218 Inflammation Diseases 0.000 description 1
- CKLJMWTZIZZHCS-REOHCLBHSA-N L-aspartic acid Chemical compound OC(=O)[C@@H](N)CC(O)=O CKLJMWTZIZZHCS-REOHCLBHSA-N 0.000 description 1
- WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 description 1
- 229940124647 MEK inhibitor Drugs 0.000 description 1
- 241000124008 Mammalia Species 0.000 description 1
- 102000002274 Matrix Metalloproteinases Human genes 0.000 description 1
- 108010000684 Matrix Metalloproteinases Proteins 0.000 description 1
- 102100029699 Meiosis initiator protein Human genes 0.000 description 1
- 206010027476 Metastases Diseases 0.000 description 1
- 102000004232 Mitogen-Activated Protein Kinase Kinases Human genes 0.000 description 1
- 206010028980 Neoplasm Diseases 0.000 description 1
- 206010029260 Neuroblastoma Diseases 0.000 description 1
- 102000007999 Nuclear Proteins Human genes 0.000 description 1
- 108010089610 Nuclear Proteins Proteins 0.000 description 1
- 102000011931 Nucleoproteins Human genes 0.000 description 1
- 108010061100 Nucleoproteins Proteins 0.000 description 1
- 229930040373 Paraformaldehyde Natural products 0.000 description 1
- 208000037273 Pathologic Processes Diseases 0.000 description 1
- 108091005804 Peptidases Proteins 0.000 description 1
- 102000035195 Peptidases Human genes 0.000 description 1
- 201000005702 Pertussis Diseases 0.000 description 1
- 229920001213 Polysorbate 20 Polymers 0.000 description 1
- 102000016611 Proteoglycans Human genes 0.000 description 1
- 108010067787 Proteoglycans Proteins 0.000 description 1
- 102000005622 Receptor for Advanced Glycation End Products Human genes 0.000 description 1
- 108010045108 Receptor for Advanced Glycation End Products Proteins 0.000 description 1
- 102000001332 SRC Human genes 0.000 description 1
- 108060006706 SRC Proteins 0.000 description 1
- 238000000692 Student's t-test Methods 0.000 description 1
- 239000013504 Triton X-100 Substances 0.000 description 1
- 229920004890 Triton X-100 Polymers 0.000 description 1
- 108090000435 Urokinase-type plasminogen activator Proteins 0.000 description 1
- 102000003990 Urokinase-type plasminogen activator Human genes 0.000 description 1
- 208000032594 Vascular Remodeling Diseases 0.000 description 1
- 208000024248 Vascular System injury Diseases 0.000 description 1
- 208000012339 Vascular injury Diseases 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 239000012190 activator Substances 0.000 description 1
- 208000038016 acute inflammation Diseases 0.000 description 1
- 230000006022 acute inflammation Effects 0.000 description 1
- 230000004075 alteration Effects 0.000 description 1
- 230000003321 amplification Effects 0.000 description 1
- 206010002022 amyloidosis Diseases 0.000 description 1
- 230000002491 angiogenic effect Effects 0.000 description 1
- 239000002260 anti-inflammatory agent Substances 0.000 description 1
- 229940121363 anti-inflammatory agent Drugs 0.000 description 1
- 235000003704 aspartic acid Nutrition 0.000 description 1
- 230000001580 bacterial effect Effects 0.000 description 1
- 230000008901 benefit Effects 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
- 210000001772 blood platelet Anatomy 0.000 description 1
- 210000004204 blood vessel Anatomy 0.000 description 1
- 210000004556 brain Anatomy 0.000 description 1
- UDSAIICHUKSCKT-UHFFFAOYSA-N bromophenol blue Chemical compound C1=C(Br)C(O)=C(Br)C=C1C1(C=2C=C(Br)C(O)=C(Br)C=2)C2=CC=CC=C2S(=O)(=O)O1 UDSAIICHUKSCKT-UHFFFAOYSA-N 0.000 description 1
- 230000005779 cell damage Effects 0.000 description 1
- 230000024245 cell differentiation Effects 0.000 description 1
- 208000037887 cell injury Diseases 0.000 description 1
- 210000000170 cell membrane Anatomy 0.000 description 1
- 230000010252 chemokine signaling pathway Effects 0.000 description 1
- 230000010002 chemokinesis Effects 0.000 description 1
- 238000002512 chemotherapy Methods 0.000 description 1
- 239000012141 concentrate Substances 0.000 description 1
- 239000000356 contaminant Substances 0.000 description 1
- 238000007887 coronary angioplasty Methods 0.000 description 1
- 230000002596 correlated effect Effects 0.000 description 1
- 230000007423 decrease Effects 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 230000018109 developmental process Effects 0.000 description 1
- 206010012601 diabetes mellitus Diseases 0.000 description 1
- 239000012153 distilled water Substances 0.000 description 1
- 230000013020 embryo development Effects 0.000 description 1
- 210000003038 endothelium Anatomy 0.000 description 1
- 210000000981 epithelium Anatomy 0.000 description 1
- 210000001723 extracellular space Anatomy 0.000 description 1
- 230000008713 feedback mechanism Effects 0.000 description 1
- 239000000835 fiber Substances 0.000 description 1
- 230000020764 fibrinolysis Effects 0.000 description 1
- 235000013922 glutamic acid Nutrition 0.000 description 1
- 239000004220 glutamic acid Substances 0.000 description 1
- LPLVUJXQOOQHMX-UHFFFAOYSA-N glycyrrhetinic acid glycoside Natural products C1CC(C2C(C3(CCC4(C)CCC(C)(CC4C3=CC2=O)C(O)=O)C)(C)CC2)(C)C2C(C)(C)C1OC1OC(C(O)=O)C(O)C(O)C1OC1OC(C(O)=O)C(O)C(O)C1O LPLVUJXQOOQHMX-UHFFFAOYSA-N 0.000 description 1
- 229960004949 glycyrrhizic acid Drugs 0.000 description 1
- UYRUBYNTXSDKQT-UHFFFAOYSA-N glycyrrhizic acid Natural products CC1(C)C(CCC2(C)C1CCC3(C)C2C(=O)C=C4C5CC(C)(CCC5(C)CCC34C)C(=O)O)OC6OC(C(O)C(O)C6OC7OC(O)C(O)C(O)C7C(=O)O)C(=O)O UYRUBYNTXSDKQT-UHFFFAOYSA-N 0.000 description 1
- 235000019410 glycyrrhizin Nutrition 0.000 description 1
- LPLVUJXQOOQHMX-QWBHMCJMSA-N glycyrrhizinic acid Chemical compound O([C@@H]1[C@@H](O)[C@H](O)[C@H](O[C@@H]1O[C@@H]1C([C@H]2[C@]([C@@H]3[C@@]([C@@]4(CC[C@@]5(C)CC[C@@](C)(C[C@H]5C4=CC3=O)C(O)=O)C)(C)CC2)(C)CC1)(C)C)C(O)=O)[C@@H]1O[C@H](C(O)=O)[C@@H](O)[C@H](O)[C@H]1O LPLVUJXQOOQHMX-QWBHMCJMSA-N 0.000 description 1
- 230000035876 healing Effects 0.000 description 1
- 229960002897 heparin Drugs 0.000 description 1
- 229920000669 heparin Polymers 0.000 description 1
- 238000010185 immunofluorescence analysis Methods 0.000 description 1
- 102000018358 immunoglobulin Human genes 0.000 description 1
- 230000002055 immunohistochemical effect Effects 0.000 description 1
- 230000006698 induction Effects 0.000 description 1
- 230000001939 inductive effect Effects 0.000 description 1
- 230000002757 inflammatory effect Effects 0.000 description 1
- 230000004054 inflammatory process Effects 0.000 description 1
- 230000005764 inhibitory process Effects 0.000 description 1
- 102000006495 integrins Human genes 0.000 description 1
- 108010044426 integrins Proteins 0.000 description 1
- 230000003834 intracellular effect Effects 0.000 description 1
- 230000009545 invasion Effects 0.000 description 1
- PGHMRUGBZOYCAA-ADZNBVRBSA-N ionomycin Chemical compound O1[C@H](C[C@H](O)[C@H](C)[C@H](O)[C@H](C)/C=C/C[C@@H](C)C[C@@H](C)C(/O)=C/C(=O)[C@@H](C)C[C@@H](C)C[C@@H](CCC(O)=O)C)CC[C@@]1(C)[C@@H]1O[C@](C)([C@@H](C)O)CC1 PGHMRUGBZOYCAA-ADZNBVRBSA-N 0.000 description 1
- PGHMRUGBZOYCAA-UHFFFAOYSA-N ionomycin Natural products O1C(CC(O)C(C)C(O)C(C)C=CCC(C)CC(C)C(O)=CC(=O)C(C)CC(C)CC(CCC(O)=O)C)CCC1(C)C1OC(C)(C(C)O)CC1 PGHMRUGBZOYCAA-UHFFFAOYSA-N 0.000 description 1
- 230000001788 irregular Effects 0.000 description 1
- 231100000225 lethality Toxicity 0.000 description 1
- 239000003446 ligand Substances 0.000 description 1
- 229920006008 lipopolysaccharide Polymers 0.000 description 1
- 210000004072 lung Anatomy 0.000 description 1
- 229910001629 magnesium chloride Inorganic materials 0.000 description 1
- 239000003550 marker Substances 0.000 description 1
- 239000011159 matrix material Substances 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- 102000006240 membrane receptors Human genes 0.000 description 1
- 108020004084 membrane receptors Proteins 0.000 description 1
- 230000009401 metastasis Effects 0.000 description 1
- 238000010232 migration assay Methods 0.000 description 1
- 239000002829 mitogen activated protein kinase inhibitor Substances 0.000 description 1
- 125000000896 monocarboxylic acid group Chemical group 0.000 description 1
- 210000001616 monocyte Anatomy 0.000 description 1
- 210000002864 mononuclear phagocyte Anatomy 0.000 description 1
- 230000000877 morphologic effect Effects 0.000 description 1
- 238000003199 nucleic acid amplification method Methods 0.000 description 1
- 230000003076 paracrine Effects 0.000 description 1
- 229920002866 paraformaldehyde Polymers 0.000 description 1
- 230000009054 pathological process Effects 0.000 description 1
- 230000007310 pathophysiology Effects 0.000 description 1
- 230000008823 permeabilization Effects 0.000 description 1
- 239000000825 pharmaceutical preparation Substances 0.000 description 1
- 108091005981 phosphorylated proteins Proteins 0.000 description 1
- 230000026731 phosphorylation Effects 0.000 description 1
- 238000006366 phosphorylation reaction Methods 0.000 description 1
- 229940012957 plasmin Drugs 0.000 description 1
- 230000010287 polarization Effects 0.000 description 1
- 239000000256 polyoxyethylene sorbitan monolaurate Substances 0.000 description 1
- 235000010486 polyoxyethylene sorbitan monolaurate Nutrition 0.000 description 1
- 229920001184 polypeptide Polymers 0.000 description 1
- 229920002451 polyvinyl alcohol Polymers 0.000 description 1
- 239000013641 positive control Substances 0.000 description 1
- 102000004196 processed proteins & peptides Human genes 0.000 description 1
- 238000004393 prognosis Methods 0.000 description 1
- 230000035755 proliferation Effects 0.000 description 1
- 235000019833 protease Nutrition 0.000 description 1
- 230000017854 proteolysis Effects 0.000 description 1
- 238000011002 quantification Methods 0.000 description 1
- 238000007634 remodeling Methods 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- PYWVYCXTNDRMGF-UHFFFAOYSA-N rhodamine B Chemical compound [Cl-].C=12C=CC(=[N+](CC)CC)C=C2OC2=CC(N(CC)CC)=CC=C2C=1C1=CC=CC=C1C(O)=O PYWVYCXTNDRMGF-UHFFFAOYSA-N 0.000 description 1
- 108010073863 saruplase Proteins 0.000 description 1
- 210000002966 serum Anatomy 0.000 description 1
- 239000004017 serum-free culture medium Substances 0.000 description 1
- 235000020183 skimmed milk Nutrition 0.000 description 1
- 210000002460 smooth muscle Anatomy 0.000 description 1
- TXBNDGDMWKVRQW-UHFFFAOYSA-M sodium;2-[[1,3-dihydroxy-2-(hydroxymethyl)propan-2-yl]azaniumyl]acetate;dodecyl sulfate Chemical compound [Na+].OCC(CO)(CO)NCC(O)=O.CCCCCCCCCCCCOS([O-])(=O)=O TXBNDGDMWKVRQW-UHFFFAOYSA-M 0.000 description 1
- 238000010186 staining Methods 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- JGVWCANSWKRBCS-UHFFFAOYSA-N tetramethylrhodamine thiocyanate Chemical compound [Cl-].C=12C=CC(N(C)C)=CC2=[O+]C2=CC(N(C)C)=CC=C2C=1C1=CC=C(SC#N)C=C1C(O)=O JGVWCANSWKRBCS-UHFFFAOYSA-N 0.000 description 1
- 230000008719 thickening Effects 0.000 description 1
- 210000001519 tissue Anatomy 0.000 description 1
- 230000017423 tissue regeneration Effects 0.000 description 1
- 230000007838 tissue remodeling Effects 0.000 description 1
- 230000001052 transient effect Effects 0.000 description 1
- 230000007704 transition Effects 0.000 description 1
- 230000005945 translocation Effects 0.000 description 1
- 230000000472 traumatic effect Effects 0.000 description 1
- 230000001960 triggered effect Effects 0.000 description 1
- 230000004614 tumor growth Effects 0.000 description 1
- 210000004026 tunica intima Anatomy 0.000 description 1
- 210000004231 tunica media Anatomy 0.000 description 1
- 238000011144 upstream manufacturing Methods 0.000 description 1
- 229960005356 urokinase Drugs 0.000 description 1
- 231100000216 vascular lesion Toxicity 0.000 description 1
- 210000004509 vascular smooth muscle cell Anatomy 0.000 description 1
- 238000012800 visualization Methods 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
- C07K16/18—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
- C07K16/24—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against cytokines, lymphokines or interferons
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
- A61P17/02—Drugs for dermatological disorders for treating wounds, ulcers, burns, scars, keloids, or the like
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/08—Vasodilators for multiple indications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
- C07K16/18—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
- C07K16/28—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
- C07K16/2803—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against the immunoglobulin superfamily
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K2039/505—Medicinal preparations containing antigens or antibodies comprising antibodies
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Medicinal Chemistry (AREA)
- Immunology (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- General Chemical & Material Sciences (AREA)
- Veterinary Medicine (AREA)
- Pharmacology & Pharmacy (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Animal Behavior & Ethology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Public Health (AREA)
- Biochemistry (AREA)
- Biophysics (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Molecular Biology (AREA)
- Genetics & Genomics (AREA)
- Heart & Thoracic Surgery (AREA)
- Cardiology (AREA)
- Urology & Nephrology (AREA)
- Vascular Medicine (AREA)
- Dermatology (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
- Peptides Or Proteins (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| IT2001MI000562A ITMI20010562A1 (it) | 2001-03-16 | 2001-03-16 | Inibitori o antagonisti della proteina hmg1 per il trattamento di disordini vascolari |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| PT1368060E true PT1368060E (pt) | 2010-08-24 |
Family
ID=11447291
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| PT02717057T PT1368060E (pt) | 2001-03-16 | 2002-03-12 | Inibidores e/ou antagonistas da proteína hmgb1 para o tratamento de doenças vasculares |
Country Status (14)
| Country | Link |
|---|---|
| US (4) | US7754217B2 (enExample) |
| EP (1) | EP1368060B1 (enExample) |
| JP (1) | JP4822654B2 (enExample) |
| CN (2) | CN1537014B (enExample) |
| AT (1) | ATE468137T1 (enExample) |
| AU (1) | AU2002247977C1 (enExample) |
| CA (1) | CA2439530C (enExample) |
| DE (1) | DE60236413D1 (enExample) |
| DK (1) | DK1368060T3 (enExample) |
| ES (1) | ES2346408T3 (enExample) |
| IT (1) | ITMI20010562A1 (enExample) |
| MX (1) | MXPA03008364A (enExample) |
| PT (1) | PT1368060E (enExample) |
| WO (1) | WO2002074337A1 (enExample) |
Families Citing this family (46)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US7151082B2 (en) | 1999-02-11 | 2006-12-19 | The Feinstein Institute For Medical Research | Antagonists of HMG1 for treating inflammatory conditions |
| US6303321B1 (en) | 1999-02-11 | 2001-10-16 | North Shore-Long Island Jewish Research Institute | Methods for diagnosing sepsis |
| ITMI20010562A1 (it) * | 2001-03-16 | 2002-09-16 | Marco E Bianchi | Inibitori o antagonisti della proteina hmg1 per il trattamento di disordini vascolari |
| US7304034B2 (en) | 2001-05-15 | 2007-12-04 | The Feinstein Institute For Medical Research | Use of HMGB fragments as anti-inflammatory agents |
| HUP0500042A3 (en) * | 2001-05-15 | 2010-01-28 | Long Island Jewish Res Inst | Use of hmg fragments as anti-inflammatory agents |
| US7220723B2 (en) | 2001-05-15 | 2007-05-22 | The Feinstein Institute For Medical Research | Inhibitors of the interaction between HMGB polypeptides and toll-like receptor 2 as anti-inflammatory agents |
| ATE424416T1 (de) | 2002-07-03 | 2009-03-15 | San Raffaele Centro Fond | Die verwendung von hmgb1 zur behandlung von gewebeverletzungen und/oder zur unterstützung der gewebewiederherstellung |
| WO2004061456A2 (de) * | 2003-01-03 | 2004-07-22 | Alcedo Biotech Gmbh | Verwendungen von hmgb, hmgn, hmga proteinen |
| US7696169B2 (en) | 2003-06-06 | 2010-04-13 | The Feinstein Institute For Medical Research | Inhibitors of the interaction between HMGB polypeptides and toll-like receptor 2 as anti-inflammatory agents |
| CA2882022A1 (en) | 2003-09-11 | 2005-03-24 | Walter Newman | Monoclonal antibodies against hmgb1 |
| ITRM20040058A1 (it) * | 2004-02-03 | 2004-05-03 | Marco E Bianchi | Inibitori ed antagonisti di hmgb1 in grado di regolare la proliferazione delle cellule muscolari lisce ed endoteliali. |
| PT1768677E (pt) * | 2004-07-02 | 2008-10-06 | Creabilis Therapeutics Spa | Ácidos nucleicos para o tratamento de patologias relacionadas com hmgb1 |
| US20090062187A1 (en) | 2004-07-20 | 2009-03-05 | Marco Bianchi | Use of Hmgb1 for Wound Healing |
| MX2007001155A (es) * | 2004-07-29 | 2007-08-14 | Creabilis Therapeutics Spa | Uso de inhibidores de k-252a y de quinasa para la prevencion o el tratamiento de patologias asociadas con hmgb1. |
| EP1797118A2 (en) * | 2004-09-03 | 2007-06-20 | Creabilis Therapeutics S.P.A. | Protease resistant human and non-human hmgb1 box-a mutants and their therapeutic/diagnostic use |
| WO2007001422A2 (en) | 2004-10-22 | 2007-01-04 | Medimmune, Inc. | High affinity antibodies against hmgb1 and methods of use thereof |
| US8129130B2 (en) | 2004-10-22 | 2012-03-06 | The Feinstein Institute For Medical Research | High affinity antibodies against HMGB1 and methods of use thereof |
| ITRM20050032A1 (it) * | 2005-01-21 | 2006-07-22 | Marco E Bianchi | Inibitori ed antagonisti di hmgb1 in grado di inibire la patogenesi e la progressione della malattia aterosclerotica. |
| WO2006114805A2 (en) * | 2005-04-28 | 2006-11-02 | Fondazione Centro San Raffaele Del Monte Tabor | Use of hmgb2 and hmgb3 proteins for medical applications |
| US20100040608A1 (en) | 2005-07-18 | 2010-02-18 | Marie Wahren-Herlenius | Use of HMGB1 antagonists for the treatment of inflammatory skin conditions |
| AU2006284096B2 (en) | 2005-08-25 | 2012-03-29 | Avro Life Sciences, Inc. | Polymer conjugates of K-252a and derivatives thereof |
| WO2007031100A1 (en) * | 2005-09-14 | 2007-03-22 | Ostini, Marco | Active immunotherapy of life-threatening systemic inflammation |
| CA2631212A1 (en) | 2005-11-28 | 2007-07-05 | Medimmune, Llc | Antagonists of hmgb1 and/or rage and methods of use thereof |
| US7829097B2 (en) * | 2006-02-06 | 2010-11-09 | University Of Pittsburgh - Of The Commonwealth System Of Higher Education | Use of HMGB1 for protection against ischemia reperfusion injury |
| CA2663300C (en) | 2006-09-15 | 2014-10-07 | Creabilis Therapeutics S.P.A. | Polymer conjugates of box-a of hmgb1 and box-a variants of hmgb1 |
| US8470325B2 (en) | 2007-02-15 | 2013-06-25 | Kagoshima University | Method of treating amykloidosis comprising administering an anti-HMGB-1 antibody |
| RU2519714C2 (ru) | 2008-04-30 | 2014-06-20 | Дженомикс Ко., Лтд. | Средство для вовлечения происходящей из костного мозга плюрипотентной стволовой клетки в периферический кровоток |
| WO2009133943A1 (ja) | 2008-04-30 | 2009-11-05 | 株式会社ジェノミックス | 生体内機能的細胞の高効率採取法 |
| JP5582580B2 (ja) * | 2009-07-16 | 2014-09-03 | Ｎｅｃソリューションイノベータ株式会社 | Ｈｍｇｂ１結合核酸分子およびその用途 |
| JP5467313B2 (ja) * | 2009-09-28 | 2014-04-09 | 国立大学法人 岡山大学 | アテローム動脈硬化抑制剤 |
| CN102711777B (zh) | 2009-10-28 | 2015-04-15 | 吉诺米克斯股份有限公司 | 利用骨髓间充质干细胞和/或多能干细胞的血中动员的组织再生促进剂 |
| CA2847197C (en) | 2010-10-30 | 2020-11-03 | Isis Innovation Limited | Treatment for dupuytren's disease |
| DK2703487T3 (en) | 2011-04-26 | 2018-09-10 | Genomix Co Ltd | TIME TO INDUCTION Tissue Regeneration and its Use |
| US9244074B2 (en) * | 2011-06-07 | 2016-01-26 | University Of Hawaii | Biomarker of asbestos exposure and mesothelioma |
| WO2012170742A2 (en) | 2011-06-07 | 2012-12-13 | University Of Hawaii | Treatment and prevention of cancer with hmgb1 antagonists |
| RU2647467C2 (ru) | 2012-10-25 | 2018-03-15 | Дженомикс Ко., Лтд. | Новый способ лечения инфаркта миокарда с применением фрагмента hmgb1 |
| EP2913059B1 (en) | 2012-10-25 | 2018-04-11 | Genomix Co., Ltd. | Novel method for treating spinal cord injury using hmgb1 fragment |
| MX2015009547A (es) | 2013-01-28 | 2015-11-25 | Evec Inc | Anticuerpo anti-hmgb1 humanizado o fragmento de union al antigeno del mismo. |
| IL242807A0 (en) * | 2015-11-26 | 2016-04-21 | Novamed Ltd | Test facility |
| US11274132B2 (en) | 2015-12-11 | 2022-03-15 | Ruprecht-Karls-Universität Heidelberg | Combined preparations of PKM2 modulators and HMGB1 |
| BR112019014921A2 (pt) | 2017-01-27 | 2020-03-31 | StemRIM Inc. | Agente terapêutico para miocardiopatia, infarto antigo do miocárdio e insuficiência cardíaca crônica |
| EP3719117A4 (en) | 2017-12-01 | 2021-11-03 | Stemrim Inc. | EECTODERMAL MESENCHYMAL STEM CELLS AND METHOD FOR PRODUCING THEM |
| US11298403B2 (en) | 2017-12-01 | 2022-04-12 | StemRIM Inc. | Therapeutic agent for inflammatory bowel disease |
| US20210024594A1 (en) | 2018-02-08 | 2021-01-28 | StemRIM Inc. | Therapeutic Agent for Psoriasis |
| US12304933B2 (en) | 2018-10-05 | 2025-05-20 | StemRIM Inc. | Disease treatment drug based on mesenchymal-stem-cell mobilization |
| CN115361966B (zh) * | 2020-04-22 | 2025-09-16 | 朱拉隆功大学 | 使dna恢复活力和防止dna损伤的组合物以及方法 |
Family Cites Families (13)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6054122A (en) * | 1990-11-27 | 2000-04-25 | The American National Red Cross | Supplemented and unsupplemented tissue sealants, methods of their production and use |
| US5470307A (en) * | 1994-03-16 | 1995-11-28 | Lindall; Arnold W. | Catheter system for controllably releasing a therapeutic agent at a remote tissue site |
| WO1997026913A1 (en) | 1996-01-26 | 1997-07-31 | The Trustees Of Columbia University In The City Of New York | A POLYPEPTIDE FROM LUNG EXTRACT WHICH BINDS AMYLOID-β PEPTIDE |
| US5864018A (en) * | 1996-04-16 | 1999-01-26 | Schering Aktiengesellschaft | Antibodies to advanced glycosylation end-product receptor polypeptides and uses therefor |
| WO1997039121A1 (en) | 1996-04-16 | 1997-10-23 | Schering Aktiengesellschaft | Advanced glycosylation end-product receptor peptides and uses therefor |
| US6790443B2 (en) | 1996-11-22 | 2004-09-14 | The Trustees Of Columbia University In The City Of New York | Method for treating symptoms of diabetes |
| US6303321B1 (en) * | 1999-02-11 | 2001-10-16 | North Shore-Long Island Jewish Research Institute | Methods for diagnosing sepsis |
| US6398808B1 (en) | 1999-06-15 | 2002-06-04 | Scimed Life Systems, Inc. | Localized delivery of genetic information from biostable materials |
| ITMI20010562A1 (it) * | 2001-03-16 | 2002-09-16 | Marco E Bianchi | Inibitori o antagonisti della proteina hmg1 per il trattamento di disordini vascolari |
| HUP0500042A3 (en) * | 2001-05-15 | 2010-01-28 | Long Island Jewish Res Inst | Use of hmg fragments as anti-inflammatory agents |
| ITRM20040058A1 (it) * | 2004-02-03 | 2004-05-03 | Marco E Bianchi | Inibitori ed antagonisti di hmgb1 in grado di regolare la proliferazione delle cellule muscolari lisce ed endoteliali. |
| US20090062187A1 (en) * | 2004-07-20 | 2009-03-05 | Marco Bianchi | Use of Hmgb1 for Wound Healing |
| WO2008137552A2 (en) * | 2007-05-02 | 2008-11-13 | Medimmune, Llc | Anti-rage antibodies and methods of use thereof |
-
2001
- 2001-03-16 IT IT2001MI000562A patent/ITMI20010562A1/it unknown
- 2001-03-16 US US10/471,641 patent/US7754217B2/en not_active Expired - Fee Related
-
2002
- 2002-03-12 EP EP02717057A patent/EP1368060B1/en not_active Expired - Lifetime
- 2002-03-12 CN CN028065670A patent/CN1537014B/zh not_active Expired - Fee Related
- 2002-03-12 AU AU2002247977A patent/AU2002247977C1/en not_active Ceased
- 2002-03-12 DK DK02717057.0T patent/DK1368060T3/da active
- 2002-03-12 CN CN200910252323A patent/CN101773669A/zh active Pending
- 2002-03-12 ES ES02717057T patent/ES2346408T3/es not_active Expired - Lifetime
- 2002-03-12 CA CA2439530A patent/CA2439530C/en not_active Expired - Fee Related
- 2002-03-12 MX MXPA03008364A patent/MXPA03008364A/es active IP Right Grant
- 2002-03-12 AT AT02717057T patent/ATE468137T1/de active
- 2002-03-12 DE DE60236413T patent/DE60236413D1/de not_active Expired - Lifetime
- 2002-03-12 JP JP2002573044A patent/JP4822654B2/ja not_active Expired - Fee Related
- 2002-03-12 PT PT02717057T patent/PT1368060E/pt unknown
- 2002-03-12 WO PCT/IT2002/000153 patent/WO2002074337A1/en not_active Ceased
-
2008
- 2008-01-02 US US11/968,506 patent/US8058239B2/en not_active Expired - Fee Related
-
2010
- 2010-02-17 US US12/707,222 patent/US20100172896A1/en not_active Abandoned
- 2010-02-17 US US12/707,264 patent/US20100297107A1/en not_active Abandoned
Also Published As
| Publication number | Publication date |
|---|---|
| CN1537014B (zh) | 2012-04-25 |
| JP2004523579A (ja) | 2004-08-05 |
| AU2002247977B8 (en) | 2007-03-15 |
| AU2002247977C1 (en) | 2008-09-18 |
| WO2002074337A1 (en) | 2002-09-26 |
| AU2002247977B2 (en) | 2006-12-14 |
| US20100297107A1 (en) | 2010-11-25 |
| DK1368060T3 (da) | 2010-08-30 |
| ES2346408T3 (es) | 2010-10-15 |
| EP1368060A1 (en) | 2003-12-10 |
| EP1368060B1 (en) | 2010-05-19 |
| AU2002247977A2 (en) | 2004-02-26 |
| ITMI20010562A1 (it) | 2002-09-16 |
| DE60236413D1 (de) | 2010-07-01 |
| US8058239B2 (en) | 2011-11-15 |
| US7754217B2 (en) | 2010-07-13 |
| US20100172896A1 (en) | 2010-07-08 |
| HK1069316A1 (en) | 2005-05-20 |
| CA2439530C (en) | 2016-11-08 |
| AU2002247977A1 (en) | 2002-10-03 |
| MXPA03008364A (es) | 2004-11-12 |
| US20080171052A1 (en) | 2008-07-17 |
| US20040136979A1 (en) | 2004-07-15 |
| CN1537014A (zh) | 2004-10-13 |
| ATE468137T1 (de) | 2010-06-15 |
| CA2439530A1 (en) | 2002-09-26 |
| CN101773669A (zh) | 2010-07-14 |
| WO2002074337A8 (en) | 2003-08-28 |
| JP4822654B2 (ja) | 2011-11-24 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| PT1368060E (pt) | Inibidores e/ou antagonistas da proteína hmgb1 para o tratamento de doenças vasculares | |
| Kuo et al. | Tight junction proteins occludin and ZO‐1 as regulators of epithelial proliferation and survival | |
| Sato et al. | Secretion of the baby hamster kidney 30-kDa galactose-binding lectin from polarized and nonpolarized cells: a pathway independent of the endoplasmic reticulum-Golgi complex | |
| Calzada et al. | Identification of novel β1 integrin binding sites in the type 1 and type 2 repeats of thrombospondin-1 | |
| JP7486821B2 (ja) | 患者由来アミロイド異種移植非ヒト動物モデル | |
| Castillo et al. | Laminin inhibition of β‐amyloid protein (Aβ) fibrillogenesis and identification of an Aβ binding site localized to the globular domain repeats on the laminin a chain | |
| Shao et al. | CD44/ERM/F‐actin complex mediates targeted nuclear degranulation and excessive neutrophil extracellular trap formation during sepsis | |
| Lv et al. | Cartilage oligomeric matrix protein fine-tunes disturbed flow-induced endothelial activation and atherogenesis | |
| US7824868B2 (en) | Formation of superfibronectin by BBK32 and uses therefor | |
| Maurice et al. | Antithrombotic effect of the type III collagen-related octapeptide (KOGEOGPK) in the mouse | |
| Martins-Silva et al. | A rat homologue of CED-6 is expressed in neurons and interacts with clathrin | |
| CN101735307B (zh) | 一种血小板膜糖蛋白寡肽或其修饰物/衍生物以及它们的应用 | |
| Geiger | Roles of Transient Receptor Potential (TRP) cation channels in primary pulmonary fibroblasts | |
| HK1146703A (en) | Hmgb1 protein inhibitors and/or antagonists for the treatment of vascular diseases | |
| HK1069316B (en) | Hmgb1 protein inhibitors and/or antagonists for the treatment of vascular diseases | |
| Das et al. | Evidence for binding of the ectodomain of amyloid precursor protein 695 and activated high molecular weight kininogen | |
| US20080118502A1 (en) | Tissue Repair By Modulation Of Beta-1 Integrin Biological Function | |
| ES2362655T3 (es) | Métodos y composiciones para suprimir la diferenciación de fibrocitos. | |
| Visconti | Causal role for ectoderm-neural tube interaction in avian otocyst formation | |
| Zhou | The Cytoskeleton in the Syncytial Epithelium of Adult Schistosoma Mansoni | |
| WO2012086428A1 (ja) | カルモジュリン様皮膚タンパク質を有効成分として含む医薬組成物 | |
| Fujiwara et al. | The Joint Meeting of the 43rd Annual Meeting of Japanese Society for Connective Tissue Research and the 58th Annual Meeting of Japan Matrix Club June 10–11, 2011, Beppu, Japan | |
| Quan | Studies of the rat CNS plasma membrane-associated nonpermissive/inhibitory factor on cell adhesion and neurite outgrowth | |
| Ughrin | Multiple domains of the NG2 chondroitin sulfate proteoglycan inhibit axonal growth and regeneration |