AU2006321610A1 - Method of using IL6 antagonists with proteasome inhibitors - Google Patents
Method of using IL6 antagonists with proteasome inhibitors Download PDFInfo
- Publication number
- AU2006321610A1 AU2006321610A1 AU2006321610A AU2006321610A AU2006321610A1 AU 2006321610 A1 AU2006321610 A1 AU 2006321610A1 AU 2006321610 A AU2006321610 A AU 2006321610A AU 2006321610 A AU2006321610 A AU 2006321610A AU 2006321610 A1 AU2006321610 A1 AU 2006321610A1
- Authority
- AU
- Australia
- Prior art keywords
- antibody
- bortezomib
- proteasome inhibitor
- mammal
- cell
- 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.)
- Abandoned
Links
- 238000000034 method Methods 0.000 title claims description 57
- 229940079156 Proteasome inhibitor Drugs 0.000 title claims description 47
- 239000003207 proteasome inhibitor Substances 0.000 title claims description 47
- 239000005557 antagonist Substances 0.000 title claims description 17
- 102000004889 Interleukin-6 Human genes 0.000 claims description 122
- 108090001005 Interleukin-6 Proteins 0.000 claims description 122
- 210000004027 cell Anatomy 0.000 claims description 76
- GXJABQQUPOEUTA-RDJZCZTQSA-N bortezomib Chemical compound C([C@@H](C(=O)N[C@@H](CC(C)C)B(O)O)NC(=O)C=1N=CC=NC=1)C1=CC=CC=C1 GXJABQQUPOEUTA-RDJZCZTQSA-N 0.000 claims description 73
- 229960001467 bortezomib Drugs 0.000 claims description 72
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 35
- 206010035226 Plasma cell myeloma Diseases 0.000 claims description 29
- 206010028980 Neoplasm Diseases 0.000 claims description 25
- 238000011282 treatment Methods 0.000 claims description 23
- 208000034578 Multiple myelomas Diseases 0.000 claims description 16
- 230000027455 binding Effects 0.000 claims description 16
- 239000003112 inhibitor Substances 0.000 claims description 16
- 241000124008 Mammalia Species 0.000 claims description 14
- 230000011664 signaling Effects 0.000 claims description 14
- 208000035475 disorder Diseases 0.000 claims description 12
- 239000012634 fragment Substances 0.000 claims description 12
- 208000011580 syndromic disease Diseases 0.000 claims description 10
- -1 1 - hydroxy - 2 -methylpropyl Chemical group 0.000 claims description 7
- 101001076408 Homo sapiens Interleukin-6 Proteins 0.000 claims description 7
- 230000004913 activation Effects 0.000 claims description 7
- 102000052611 human IL6 Human genes 0.000 claims description 6
- 230000002401 inhibitory effect Effects 0.000 claims description 6
- 210000003719 b-lymphocyte Anatomy 0.000 claims description 5
- 230000012010 growth Effects 0.000 claims description 5
- 108020003175 receptors Proteins 0.000 claims description 5
- 102000005962 receptors Human genes 0.000 claims description 5
- 208000024893 Acute lymphoblastic leukemia Diseases 0.000 claims description 4
- 108010004877 CEP 1612 Proteins 0.000 claims description 4
- 108010016626 Dipeptides Proteins 0.000 claims description 4
- 102000008394 Immunoglobulin Fragments Human genes 0.000 claims description 4
- 108010021625 Immunoglobulin Fragments Proteins 0.000 claims description 4
- 108010038501 Interleukin-6 Receptors Proteins 0.000 claims description 4
- 206010025323 Lymphomas Diseases 0.000 claims description 4
- 210000001744 T-lymphocyte Anatomy 0.000 claims description 4
- 108010002974 benzyloxycarbonylleucyl-leucyl-leucine aldehyde Proteins 0.000 claims description 4
- ZADPBFCGQRWHPN-UHFFFAOYSA-N boronic acid Chemical compound OBO ZADPBFCGQRWHPN-UHFFFAOYSA-N 0.000 claims description 4
- FWPWHHUJACGNMZ-LIPLLEKLSA-N (1r,2s)-5-(1-hydroxy-2-methylpropyl)-2-methyl-7-oxa-4-azabicyclo[3.2.0]heptane-3,6-dione Chemical compound N1C(=O)[C@@H](C)[C@H]2OC(=O)C21C(O)C(C)C FWPWHHUJACGNMZ-LIPLLEKLSA-N 0.000 claims description 3
- 108010057834 5-methoxy-1-indanone-3-acetyl-leu-D-leu-1-indanylamide Proteins 0.000 claims description 3
- 208000031261 Acute myeloid leukaemia Diseases 0.000 claims description 3
- 206010009944 Colon cancer Diseases 0.000 claims description 3
- 208000001333 Colorectal Neoplasms Diseases 0.000 claims description 3
- 208000017604 Hodgkin disease Diseases 0.000 claims description 3
- 208000010747 Hodgkins lymphoma Diseases 0.000 claims description 3
- DAQAKHDKYAWHCG-UHFFFAOYSA-N Lactacystin Natural products CC(=O)NC(C(O)=O)CSC(=O)C1(C(O)C(C)C)NC(=O)C(C)C1O DAQAKHDKYAWHCG-UHFFFAOYSA-N 0.000 claims description 3
- 108010017230 TMC 96 Proteins 0.000 claims description 3
- CEWYDURMTVVVNH-UHFFFAOYSA-N TMC-96 Natural products CC(C)CC(=O)NC(C(C)O)C(=O)NC(CC(C)C)C(=O)C1(CO)CO1 CEWYDURMTVVVNH-UHFFFAOYSA-N 0.000 claims description 3
- 239000004473 Threonine Substances 0.000 claims description 3
- DOGIDQKFVLKMLQ-JTHVHQAWSA-N epoxomicin Chemical compound CC[C@H](C)[C@H](N(C)C(C)=O)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC(C)C)C(=O)[C@@]1(C)CO1 DOGIDQKFVLKMLQ-JTHVHQAWSA-N 0.000 claims description 3
- 108700002672 epoxomicin Proteins 0.000 claims description 3
- DAQAKHDKYAWHCG-RWTHQLGUSA-N lactacystin Chemical compound CC(=O)N[C@H](C(O)=O)CSC(=O)[C@]1([C@@H](O)C(C)C)NC(=O)[C@H](C)[C@@H]1O DAQAKHDKYAWHCG-RWTHQLGUSA-N 0.000 claims description 3
- 239000012528 membrane Substances 0.000 claims description 3
- 208000008443 pancreatic carcinoma Diseases 0.000 claims description 3
- 229960002898 threonine Drugs 0.000 claims description 3
- WRQRFXKEXAQFFX-UHFFFAOYSA-N 2-amino-1-[2-(hydroxymethyl)oxiran-2-yl]-4-methylpent-4-en-1-one Chemical compound CC(=C)CC(N)C(=O)C1(CO)CO1 WRQRFXKEXAQFFX-UHFFFAOYSA-N 0.000 claims description 2
- DGCBTMCXHXNPHH-UHFFFAOYSA-N 5-oxoheptanal Chemical compound CCC(=O)CCCC=O DGCBTMCXHXNPHH-UHFFFAOYSA-N 0.000 claims description 2
- 206010000830 Acute leukaemia Diseases 0.000 claims description 2
- 208000014697 Acute lymphocytic leukaemia Diseases 0.000 claims description 2
- 208000010839 B-cell chronic lymphocytic leukemia Diseases 0.000 claims description 2
- 208000011691 Burkitt lymphomas Diseases 0.000 claims description 2
- 208000002291 Histiocytic Sarcoma Diseases 0.000 claims description 2
- 206010020584 Hypercalcaemia of malignancy Diseases 0.000 claims description 2
- 102000010781 Interleukin-6 Receptors Human genes 0.000 claims description 2
- 208000007766 Kaposi sarcoma Diseases 0.000 claims description 2
- 208000002454 Nasopharyngeal Carcinoma Diseases 0.000 claims description 2
- 206010061306 Nasopharyngeal cancer Diseases 0.000 claims description 2
- 208000015914 Non-Hodgkin lymphomas Diseases 0.000 claims description 2
- 208000006664 Precursor Cell Lymphoblastic Leukemia-Lymphoma Diseases 0.000 claims description 2
- 208000006265 Renal cell carcinoma Diseases 0.000 claims description 2
- 206010039491 Sarcoma Diseases 0.000 claims description 2
- 208000009956 adenocarcinoma Diseases 0.000 claims description 2
- 201000010989 colorectal carcinoma Diseases 0.000 claims description 2
- 208000035250 cutaneous malignant susceptibility to 1 melanoma Diseases 0.000 claims description 2
- 208000021045 exocrine pancreatic carcinoma Diseases 0.000 claims description 2
- 201000008825 fibrosarcoma of bone Diseases 0.000 claims description 2
- 201000009277 hairy cell leukemia Diseases 0.000 claims description 2
- 208000008750 humoral hypercalcemia of malignancy Diseases 0.000 claims description 2
- 208000032839 leukemia Diseases 0.000 claims description 2
- 201000006812 malignant histiocytosis Diseases 0.000 claims description 2
- 201000001441 melanoma Diseases 0.000 claims description 2
- 201000011216 nasopharynx carcinoma Diseases 0.000 claims description 2
- 208000012111 paraneoplastic syndrome Diseases 0.000 claims description 2
- 208000032791 BCR-ABL1 positive chronic myelogenous leukemia Diseases 0.000 claims 2
- 208000010833 Chronic myeloid leukaemia Diseases 0.000 claims 2
- 206010027476 Metastases Diseases 0.000 claims 2
- 208000033761 Myelogenous Chronic BCR-ABL Positive Leukemia Diseases 0.000 claims 2
- XJEVHMGJSYVQBQ-UHFFFAOYSA-N 2,3-dihydro-1h-inden-1-amine Chemical compound C1=CC=C2C(N)CCC2=C1 XJEVHMGJSYVQBQ-UHFFFAOYSA-N 0.000 claims 1
- 201000009030 Carcinoma Diseases 0.000 claims 1
- 230000037396 body weight Effects 0.000 claims 1
- 238000001802 infusion Methods 0.000 claims 1
- 230000004614 tumor growth Effects 0.000 claims 1
- 229940100601 interleukin-6 Drugs 0.000 description 75
- 229960003323 siltuximab Drugs 0.000 description 39
- 230000000694 effects Effects 0.000 description 36
- 201000010099 disease Diseases 0.000 description 23
- 108090000623 proteins and genes Proteins 0.000 description 23
- 102000004245 Proteasome Endopeptidase Complex Human genes 0.000 description 22
- 108090000708 Proteasome Endopeptidase Complex Proteins 0.000 description 22
- 235000018102 proteins Nutrition 0.000 description 22
- 102000004169 proteins and genes Human genes 0.000 description 22
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 18
- 201000011510 cancer Diseases 0.000 description 17
- 102100037792 Interleukin-6 receptor subunit alpha Human genes 0.000 description 16
- 239000003814 drug Substances 0.000 description 16
- 108090000765 processed proteins & peptides Proteins 0.000 description 16
- 230000006907 apoptotic process Effects 0.000 description 15
- 210000000056 organ Anatomy 0.000 description 14
- 210000001519 tissue Anatomy 0.000 description 14
- 101000839464 Leishmania braziliensis Heat shock 70 kDa protein Proteins 0.000 description 13
- 230000001965 increasing effect Effects 0.000 description 13
- 230000001404 mediated effect Effects 0.000 description 13
- 201000000050 myeloid neoplasm Diseases 0.000 description 13
- 241001465754 Metazoa Species 0.000 description 12
- 230000004044 response Effects 0.000 description 12
- 230000005764 inhibitory process Effects 0.000 description 11
- 108040006858 interleukin-6 receptor activity proteins Proteins 0.000 description 11
- 239000012472 biological sample Substances 0.000 description 10
- 230000003247 decreasing effect Effects 0.000 description 10
- 229940079593 drug Drugs 0.000 description 10
- 102000002812 Heat-Shock Proteins Human genes 0.000 description 9
- 108010004889 Heat-Shock Proteins Proteins 0.000 description 9
- 230000001419 dependent effect Effects 0.000 description 9
- 230000006698 induction Effects 0.000 description 9
- 102000004196 processed proteins & peptides Human genes 0.000 description 9
- LZGGUFLRKIMBDQ-BJMVGYQFSA-N (3e)-3-(1,3-benzodioxol-5-ylmethylidene)-2-oxopyrrolidine-1-carbaldehyde Chemical compound O=C1N(C=O)CC\C1=C/C1=CC=C(OCO2)C2=C1 LZGGUFLRKIMBDQ-BJMVGYQFSA-N 0.000 description 8
- 101710132784 Dual specificity protein phosphatase 1 Proteins 0.000 description 8
- 102100034428 Dual specificity protein phosphatase 1 Human genes 0.000 description 8
- 102000004190 Enzymes Human genes 0.000 description 8
- 108090000790 Enzymes Proteins 0.000 description 8
- 229940088598 enzyme Drugs 0.000 description 8
- 239000000203 mixture Substances 0.000 description 8
- 108091054455 MAP kinase family Proteins 0.000 description 7
- 102000043136 MAP kinase family Human genes 0.000 description 7
- 230000001446 anti-myeloma Effects 0.000 description 7
- 238000002560 therapeutic procedure Methods 0.000 description 7
- 239000006146 Roswell Park Memorial Institute medium Substances 0.000 description 6
- 206010052779 Transplant rejections Diseases 0.000 description 6
- 230000003833 cell viability Effects 0.000 description 6
- 239000003795 chemical substances by application Substances 0.000 description 6
- 230000003828 downregulation Effects 0.000 description 6
- 230000036961 partial effect Effects 0.000 description 6
- 230000003389 potentiating effect Effects 0.000 description 6
- 230000009467 reduction Effects 0.000 description 6
- 230000035939 shock Effects 0.000 description 6
- 102100032606 Heat shock factor protein 1 Human genes 0.000 description 5
- 101710190344 Heat shock factor protein 1 Proteins 0.000 description 5
- 102000015696 Interleukins Human genes 0.000 description 5
- 108010063738 Interleukins Proteins 0.000 description 5
- 102000044159 Ubiquitin Human genes 0.000 description 5
- 108090000848 Ubiquitin Proteins 0.000 description 5
- 230000002424 anti-apoptotic effect Effects 0.000 description 5
- 208000006673 asthma Diseases 0.000 description 5
- 230000001684 chronic effect Effects 0.000 description 5
- 230000003211 malignant effect Effects 0.000 description 5
- 229940124597 therapeutic agent Drugs 0.000 description 5
- 230000001225 therapeutic effect Effects 0.000 description 5
- 230000035899 viability Effects 0.000 description 5
- 206010006895 Cachexia Diseases 0.000 description 4
- 102000004127 Cytokines Human genes 0.000 description 4
- 108090000695 Cytokines Proteins 0.000 description 4
- 108050008339 Heat Shock Transcription Factor Proteins 0.000 description 4
- 102000000039 Heat Shock Transcription Factor Human genes 0.000 description 4
- 208000012902 Nervous system disease Diseases 0.000 description 4
- 102000035195 Peptidases Human genes 0.000 description 4
- 108091005804 Peptidases Proteins 0.000 description 4
- 230000001154 acute effect Effects 0.000 description 4
- 239000000427 antigen Substances 0.000 description 4
- 102000036639 antigens Human genes 0.000 description 4
- 108091007433 antigens Proteins 0.000 description 4
- 230000001413 cellular effect Effects 0.000 description 4
- 230000007423 decrease Effects 0.000 description 4
- 230000007850 degeneration Effects 0.000 description 4
- 206010012601 diabetes mellitus Diseases 0.000 description 4
- 230000002757 inflammatory effect Effects 0.000 description 4
- 230000007246 mechanism Effects 0.000 description 4
- 230000003472 neutralizing effect Effects 0.000 description 4
- 230000008506 pathogenesis Effects 0.000 description 4
- 230000001105 regulatory effect Effects 0.000 description 4
- 230000004083 survival effect Effects 0.000 description 4
- 238000012360 testing method Methods 0.000 description 4
- 102000011767 Acute-Phase Proteins Human genes 0.000 description 3
- 108010062271 Acute-Phase Proteins Proteins 0.000 description 3
- 208000006386 Bone Resorption Diseases 0.000 description 3
- 102000010778 Dual Specificity Phosphatase 1 Human genes 0.000 description 3
- 108010038537 Dual Specificity Phosphatase 1 Proteins 0.000 description 3
- 101000599048 Homo sapiens Interleukin-6 receptor subunit alpha Proteins 0.000 description 3
- 108060003951 Immunoglobulin Proteins 0.000 description 3
- 229940124103 Interleukin 6 antagonist Drugs 0.000 description 3
- 102000004058 Leukemia inhibitory factor Human genes 0.000 description 3
- 108090000581 Leukemia inhibitory factor Proteins 0.000 description 3
- 241001529936 Murinae Species 0.000 description 3
- 108091034117 Oligonucleotide Proteins 0.000 description 3
- 108700020796 Oncogene Proteins 0.000 description 3
- 102000004140 Oncostatin M Human genes 0.000 description 3
- 108090000630 Oncostatin M Proteins 0.000 description 3
- 239000012980 RPMI-1640 medium Substances 0.000 description 3
- 206010040047 Sepsis Diseases 0.000 description 3
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 3
- 150000001299 aldehydes Chemical class 0.000 description 3
- 206010003119 arrhythmia Diseases 0.000 description 3
- 210000001185 bone marrow Anatomy 0.000 description 3
- 230000024279 bone resorption Effects 0.000 description 3
- 230000015556 catabolic process Effects 0.000 description 3
- 230000024245 cell differentiation Effects 0.000 description 3
- 230000002490 cerebral effect Effects 0.000 description 3
- 231100000135 cytotoxicity Toxicity 0.000 description 3
- 230000003013 cytotoxicity Effects 0.000 description 3
- 230000006378 damage Effects 0.000 description 3
- 210000004602 germ cell Anatomy 0.000 description 3
- 102000018358 immunoglobulin Human genes 0.000 description 3
- 238000001727 in vivo Methods 0.000 description 3
- 230000006882 induction of apoptosis Effects 0.000 description 3
- 208000015181 infectious disease Diseases 0.000 description 3
- 208000027866 inflammatory disease Diseases 0.000 description 3
- 230000003834 intracellular effect Effects 0.000 description 3
- 238000012544 monitoring process Methods 0.000 description 3
- 201000006417 multiple sclerosis Diseases 0.000 description 3
- 208000010125 myocardial infarction Diseases 0.000 description 3
- 230000007170 pathology Effects 0.000 description 3
- 230000037361 pathway Effects 0.000 description 3
- 239000008194 pharmaceutical composition Substances 0.000 description 3
- 210000004180 plasmocyte Anatomy 0.000 description 3
- 229920001184 polypeptide Polymers 0.000 description 3
- 230000008569 process Effects 0.000 description 3
- 230000035755 proliferation Effects 0.000 description 3
- 206010039073 rheumatoid arthritis Diseases 0.000 description 3
- 230000019491 signal transduction Effects 0.000 description 3
- 210000003491 skin Anatomy 0.000 description 3
- 230000009885 systemic effect Effects 0.000 description 3
- 238000013518 transcription Methods 0.000 description 3
- 230000035897 transcription Effects 0.000 description 3
- 230000006663 ubiquitin-proteasome pathway Effects 0.000 description 3
- 238000010798 ubiquitination Methods 0.000 description 3
- 230000003827 upregulation Effects 0.000 description 3
- 239000003981 vehicle Substances 0.000 description 3
- 208000024827 Alzheimer disease Diseases 0.000 description 2
- 208000003343 Antiphospholipid Syndrome Diseases 0.000 description 2
- 206010003591 Ataxia Diseases 0.000 description 2
- 208000012657 Atopic disease Diseases 0.000 description 2
- 208000023275 Autoimmune disease Diseases 0.000 description 2
- 208000035143 Bacterial infection Diseases 0.000 description 2
- 208000024172 Cardiovascular disease Diseases 0.000 description 2
- 108090000227 Chymases Proteins 0.000 description 2
- 208000035473 Communicable disease Diseases 0.000 description 2
- 206010010254 Concussion Diseases 0.000 description 2
- 201000004624 Dermatitis Diseases 0.000 description 2
- 206010012442 Dermatitis contact Diseases 0.000 description 2
- 238000002965 ELISA Methods 0.000 description 2
- 108010017080 Granulocyte Colony-Stimulating Factor Proteins 0.000 description 2
- 102100039619 Granulocyte colony-stimulating factor Human genes 0.000 description 2
- 206010019280 Heart failures Diseases 0.000 description 2
- 208000032843 Hemorrhage Diseases 0.000 description 2
- 206010061218 Inflammation Diseases 0.000 description 2
- 108010002352 Interleukin-1 Proteins 0.000 description 2
- 208000003456 Juvenile Arthritis Diseases 0.000 description 2
- 206010059176 Juvenile idiopathic arthritis Diseases 0.000 description 2
- 206010060880 Monoclonal gammopathy Diseases 0.000 description 2
- 208000016285 Movement disease Diseases 0.000 description 2
- 241000699666 Mus <mouse, genus> Species 0.000 description 2
- 101710187863 Myelomonocytic growth factor Proteins 0.000 description 2
- 206010029164 Nephrotic syndrome Diseases 0.000 description 2
- 208000002774 Paraproteinemias Diseases 0.000 description 2
- 206010036105 Polyneuropathy Diseases 0.000 description 2
- 239000004365 Protease Substances 0.000 description 2
- 208000012322 Raynaud phenomenon Diseases 0.000 description 2
- 206010063837 Reperfusion injury Diseases 0.000 description 2
- 206010039085 Rhinitis allergic Diseases 0.000 description 2
- 208000006011 Stroke Diseases 0.000 description 2
- 206010051379 Systemic Inflammatory Response Syndrome Diseases 0.000 description 2
- 101710097834 Thiol protease Proteins 0.000 description 2
- 102000040945 Transcription factor Human genes 0.000 description 2
- 108091023040 Transcription factor Proteins 0.000 description 2
- 102000006275 Ubiquitin-Protein Ligases Human genes 0.000 description 2
- 108010083111 Ubiquitin-Protein Ligases Proteins 0.000 description 2
- 206010047115 Vasculitis Diseases 0.000 description 2
- 208000036142 Viral infection Diseases 0.000 description 2
- 230000002159 abnormal effect Effects 0.000 description 2
- 238000009825 accumulation Methods 0.000 description 2
- 230000009471 action Effects 0.000 description 2
- 201000010105 allergic rhinitis Diseases 0.000 description 2
- 125000003275 alpha amino acid group Chemical group 0.000 description 2
- 208000007502 anemia Diseases 0.000 description 2
- 230000000692 anti-sense effect Effects 0.000 description 2
- 230000000259 anti-tumor effect Effects 0.000 description 2
- 239000000074 antisense oligonucleotide Substances 0.000 description 2
- 238000012230 antisense oligonucleotides Methods 0.000 description 2
- 230000001640 apoptogenic effect Effects 0.000 description 2
- 238000003556 assay Methods 0.000 description 2
- 206010003549 asthenia Diseases 0.000 description 2
- 208000022362 bacterial infectious disease Diseases 0.000 description 2
- 230000004071 biological effect Effects 0.000 description 2
- 230000008827 biological function Effects 0.000 description 2
- 210000004369 blood Anatomy 0.000 description 2
- 239000008280 blood Substances 0.000 description 2
- 210000004271 bone marrow stromal cell Anatomy 0.000 description 2
- 230000010261 cell growth Effects 0.000 description 2
- 238000002512 chemotherapy Methods 0.000 description 2
- 208000019069 chronic childhood arthritis Diseases 0.000 description 2
- 208000019425 cirrhosis of liver Diseases 0.000 description 2
- 230000009514 concussion Effects 0.000 description 2
- 230000002596 correlated effect Effects 0.000 description 2
- 238000006731 degradation reaction Methods 0.000 description 2
- 238000001514 detection method Methods 0.000 description 2
- 230000004069 differentiation Effects 0.000 description 2
- 230000003292 diminished effect Effects 0.000 description 2
- 238000010494 dissociation reaction Methods 0.000 description 2
- 230000005593 dissociations Effects 0.000 description 2
- 239000000839 emulsion Substances 0.000 description 2
- 201000002491 encephalomyelitis Diseases 0.000 description 2
- 208000030172 endocrine system disease Diseases 0.000 description 2
- 201000001155 extrinsic allergic alveolitis Diseases 0.000 description 2
- 210000002950 fibroblast Anatomy 0.000 description 2
- 230000009368 gene silencing by RNA Effects 0.000 description 2
- 208000014829 head and neck neoplasm Diseases 0.000 description 2
- 208000006454 hepatitis Diseases 0.000 description 2
- 231100000283 hepatitis Toxicity 0.000 description 2
- 208000022098 hypersensitivity pneumonitis Diseases 0.000 description 2
- 238000003018 immunoassay Methods 0.000 description 2
- 238000003119 immunoblot Methods 0.000 description 2
- 239000007943 implant Substances 0.000 description 2
- 238000000338 in vitro Methods 0.000 description 2
- 230000001939 inductive effect Effects 0.000 description 2
- 230000004054 inflammatory process Effects 0.000 description 2
- 230000028709 inflammatory response Effects 0.000 description 2
- 208000014674 injury Diseases 0.000 description 2
- 238000005304 joining Methods 0.000 description 2
- 201000002215 juvenile rheumatoid arthritis Diseases 0.000 description 2
- 238000011813 knockout mouse model Methods 0.000 description 2
- 230000003902 lesion Effects 0.000 description 2
- 229960003136 leucine Drugs 0.000 description 2
- 239000008176 lyophilized powder Substances 0.000 description 2
- 230000036210 malignancy Effects 0.000 description 2
- 208000017972 multifocal atrial tachycardia Diseases 0.000 description 2
- 230000003387 muscular Effects 0.000 description 2
- 201000000585 muscular atrophy Diseases 0.000 description 2
- 230000035772 mutation Effects 0.000 description 2
- 230000001537 neural effect Effects 0.000 description 2
- 230000004770 neurodegeneration Effects 0.000 description 2
- 201000005737 orchitis Diseases 0.000 description 2
- 238000007911 parenteral administration Methods 0.000 description 2
- 230000001575 pathological effect Effects 0.000 description 2
- 230000002093 peripheral effect Effects 0.000 description 2
- 230000003285 pharmacodynamic effect Effects 0.000 description 2
- 230000007824 polyneuropathy Effects 0.000 description 2
- 239000000843 powder Substances 0.000 description 2
- 230000000861 pro-apoptotic effect Effects 0.000 description 2
- 235000019833 protease Nutrition 0.000 description 2
- 230000017854 proteolysis Effects 0.000 description 2
- 201000000306 sarcoidosis Diseases 0.000 description 2
- 230000035945 sensitivity Effects 0.000 description 2
- 210000002966 serum Anatomy 0.000 description 2
- 230000008054 signal transmission Effects 0.000 description 2
- 239000011780 sodium chloride Substances 0.000 description 2
- JUJBNYBVVQSIOU-UHFFFAOYSA-M sodium;4-[2-(4-iodophenyl)-3-(4-nitrophenyl)tetrazol-2-ium-5-yl]benzene-1,3-disulfonate Chemical compound [Na+].C1=CC([N+](=O)[O-])=CC=C1N1[N+](C=2C=CC(I)=CC=2)=NC(C=2C(=CC(=CC=2)S([O-])(=O)=O)S([O-])(=O)=O)=N1 JUJBNYBVVQSIOU-UHFFFAOYSA-M 0.000 description 2
- 241000894007 species Species 0.000 description 2
- 239000000725 suspension Substances 0.000 description 2
- 230000002195 synergetic effect Effects 0.000 description 2
- 230000036962 time dependent Effects 0.000 description 2
- 210000004881 tumor cell Anatomy 0.000 description 2
- 210000002700 urine Anatomy 0.000 description 2
- 229940099039 velcade Drugs 0.000 description 2
- 230000003612 virological effect Effects 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- IYKLZBIWFXPUCS-VIFPVBQESA-N (2s)-2-(naphthalen-1-ylamino)propanoic acid Chemical compound C1=CC=C2C(N[C@@H](C)C(O)=O)=CC=CC2=C1 IYKLZBIWFXPUCS-VIFPVBQESA-N 0.000 description 1
- OKGLROPOZIVCCZ-HQPKTYMTSA-N (e)-11-[5-[[(3s)-3-carboxybutanoyl]carbamoyl]-4-oxopyran-2-yl]undec-10-enoic acid Chemical compound OC(=O)[C@@H](C)CC(=O)NC(=O)C1=COC(\C=C\CCCCCCCCC(O)=O)=CC1=O OKGLROPOZIVCCZ-HQPKTYMTSA-N 0.000 description 1
- LKDMKWNDBAVNQZ-UHFFFAOYSA-N 4-[[1-[[1-[2-[[1-(4-nitroanilino)-1-oxo-3-phenylpropan-2-yl]carbamoyl]pyrrolidin-1-yl]-1-oxopropan-2-yl]amino]-1-oxopropan-2-yl]amino]-4-oxobutanoic acid Chemical compound OC(=O)CCC(=O)NC(C)C(=O)NC(C)C(=O)N1CCCC1C(=O)NC(C(=O)NC=1C=CC(=CC=1)[N+]([O-])=O)CC1=CC=CC=C1 LKDMKWNDBAVNQZ-UHFFFAOYSA-N 0.000 description 1
- 206010065040 AIDS dementia complex Diseases 0.000 description 1
- 206010069754 Acquired gene mutation Diseases 0.000 description 1
- 241000186361 Actinobacteria <class> Species 0.000 description 1
- 208000009304 Acute Kidney Injury Diseases 0.000 description 1
- 206010001052 Acute respiratory distress syndrome Diseases 0.000 description 1
- 208000026872 Addison Disease Diseases 0.000 description 1
- 208000007848 Alcoholism Diseases 0.000 description 1
- 208000035285 Allergic Seasonal Rhinitis Diseases 0.000 description 1
- 201000004384 Alopecia Diseases 0.000 description 1
- 206010002383 Angina Pectoris Diseases 0.000 description 1
- 206010002388 Angina unstable Diseases 0.000 description 1
- 101710081722 Antitrypsin Proteins 0.000 description 1
- 229940088872 Apoptosis inhibitor Drugs 0.000 description 1
- 200000000007 Arterial disease Diseases 0.000 description 1
- 206010003210 Arteriosclerosis Diseases 0.000 description 1
- 206010003226 Arteriovenous fistula Diseases 0.000 description 1
- 206010053555 Arthritis bacterial Diseases 0.000 description 1
- 208000006740 Aseptic Meningitis Diseases 0.000 description 1
- 201000001320 Atherosclerosis Diseases 0.000 description 1
- 206010003658 Atrial Fibrillation Diseases 0.000 description 1
- 208000002102 Atrial Premature Complexes Diseases 0.000 description 1
- 206010003662 Atrial flutter Diseases 0.000 description 1
- 206010003671 Atrioventricular Block Diseases 0.000 description 1
- 206010003694 Atrophy Diseases 0.000 description 1
- 206010003805 Autism Diseases 0.000 description 1
- 208000020706 Autistic disease Diseases 0.000 description 1
- 208000037157 Azotemia Diseases 0.000 description 1
- 230000003844 B-cell-activation Effects 0.000 description 1
- 108091007065 BIRCs Proteins 0.000 description 1
- 208000008439 Biliary Liver Cirrhosis Diseases 0.000 description 1
- 208000033222 Biliary cirrhosis primary Diseases 0.000 description 1
- 206010005003 Bladder cancer Diseases 0.000 description 1
- 206010006002 Bone pain Diseases 0.000 description 1
- 208000003174 Brain Neoplasms Diseases 0.000 description 1
- 206010048962 Brain oedema Diseases 0.000 description 1
- 206010006187 Breast cancer Diseases 0.000 description 1
- 208000026310 Breast neoplasm Diseases 0.000 description 1
- 206010006578 Bundle-Branch Block Diseases 0.000 description 1
- 101100124874 Caenorhabditis elegans hsf-1 gene Proteins 0.000 description 1
- 101100402341 Caenorhabditis elegans mpk-1 gene Proteins 0.000 description 1
- 208000005623 Carcinogenesis Diseases 0.000 description 1
- 206010007559 Cardiac failure congestive Diseases 0.000 description 1
- 206010061005 Cardiac myxoma Diseases 0.000 description 1
- 208000031229 Cardiomyopathies Diseases 0.000 description 1
- 102000011727 Caspases Human genes 0.000 description 1
- 108010076667 Caspases Proteins 0.000 description 1
- 208000005024 Castleman disease Diseases 0.000 description 1
- 108090000617 Cathepsin G Proteins 0.000 description 1
- 102100025975 Cathepsin G Human genes 0.000 description 1
- 102000005600 Cathepsins Human genes 0.000 description 1
- 108010084457 Cathepsins Proteins 0.000 description 1
- 229940123587 Cell cycle inhibitor Drugs 0.000 description 1
- 208000015879 Cerebellar disease Diseases 0.000 description 1
- 101710163595 Chaperone protein DnaK Proteins 0.000 description 1
- 206010008748 Chorea Diseases 0.000 description 1
- 206010008909 Chronic Hepatitis Diseases 0.000 description 1
- 208000006545 Chronic Obstructive Pulmonary Disease Diseases 0.000 description 1
- 102000003858 Chymases Human genes 0.000 description 1
- 108090000317 Chymotrypsin Proteins 0.000 description 1
- 102100025566 Chymotrypsin-like protease CTRL-1 Human genes 0.000 description 1
- 206010009900 Colitis ulcerative Diseases 0.000 description 1
- 206010056370 Congestive cardiomyopathy Diseases 0.000 description 1
- 206010010741 Conjunctivitis Diseases 0.000 description 1
- 206010010744 Conjunctivitis allergic Diseases 0.000 description 1
- 201000006306 Cor pulmonale Diseases 0.000 description 1
- 208000020406 Creutzfeldt Jacob disease Diseases 0.000 description 1
- 208000003407 Creutzfeldt-Jakob Syndrome Diseases 0.000 description 1
- 208000010859 Creutzfeldt-Jakob disease Diseases 0.000 description 1
- 208000011231 Crohn disease Diseases 0.000 description 1
- 206010011703 Cyanosis Diseases 0.000 description 1
- 102000005927 Cysteine Proteases Human genes 0.000 description 1
- 108010005843 Cysteine Proteases Proteins 0.000 description 1
- 201000003883 Cystic fibrosis Diseases 0.000 description 1
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 1
- 230000033616 DNA repair Effects 0.000 description 1
- 208000006313 Delayed Hypersensitivity Diseases 0.000 description 1
- 206010067889 Dementia with Lewy bodies Diseases 0.000 description 1
- 208000016192 Demyelinating disease Diseases 0.000 description 1
- 206010012310 Dengue fever Diseases 0.000 description 1
- 206010012689 Diabetic retinopathy Diseases 0.000 description 1
- 208000002251 Dissecting Aneurysm Diseases 0.000 description 1
- 102000015554 Dopamine receptor Human genes 0.000 description 1
- 108050004812 Dopamine receptor Proteins 0.000 description 1
- 201000010374 Down Syndrome Diseases 0.000 description 1
- 238000012286 ELISA Assay Methods 0.000 description 1
- 206010014612 Encephalitis viral Diseases 0.000 description 1
- 201000009273 Endometriosis Diseases 0.000 description 1
- 241000588724 Escherichia coli Species 0.000 description 1
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 1
- 206010073306 Exposure to radiation Diseases 0.000 description 1
- 208000004248 Familial Primary Pulmonary Hypertension Diseases 0.000 description 1
- 208000002633 Febrile Neutropenia Diseases 0.000 description 1
- 206010016654 Fibrosis Diseases 0.000 description 1
- 208000024412 Friedreich ataxia Diseases 0.000 description 1
- 206010017533 Fungal infection Diseases 0.000 description 1
- 206010058872 Fungal sepsis Diseases 0.000 description 1
- 201000000628 Gas Gangrene Diseases 0.000 description 1
- 206010018341 Gliosis Diseases 0.000 description 1
- 206010018364 Glomerulonephritis Diseases 0.000 description 1
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Chemical compound OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 1
- 108090000288 Glycoproteins Proteins 0.000 description 1
- 102000003886 Glycoproteins Human genes 0.000 description 1
- 208000009329 Graft vs Host Disease Diseases 0.000 description 1
- 206010018691 Granuloma Diseases 0.000 description 1
- 206010072579 Granulomatosis with polyangiitis Diseases 0.000 description 1
- 208000003807 Graves Disease Diseases 0.000 description 1
- 208000015023 Graves' disease Diseases 0.000 description 1
- 208000031886 HIV Infections Diseases 0.000 description 1
- 208000037357 HIV infectious disease Diseases 0.000 description 1
- 208000030836 Hashimoto thyroiditis Diseases 0.000 description 1
- 206010019315 Heart transplant rejection Diseases 0.000 description 1
- 101710178376 Heat shock 70 kDa protein Proteins 0.000 description 1
- 101710152018 Heat shock cognate 70 kDa protein Proteins 0.000 description 1
- 208000032759 Hemolytic-Uremic Syndrome Diseases 0.000 description 1
- 206010019755 Hepatitis chronic active Diseases 0.000 description 1
- 208000002972 Hepatolenticular Degeneration Diseases 0.000 description 1
- 208000021519 Hodgkin lymphoma Diseases 0.000 description 1
- 101000851058 Homo sapiens Neutrophil elastase Proteins 0.000 description 1
- 102000008100 Human Serum Albumin Human genes 0.000 description 1
- 108091006905 Human Serum Albumin Proteins 0.000 description 1
- 241000701044 Human gammaherpesvirus 4 Species 0.000 description 1
- 208000023105 Huntington disease Diseases 0.000 description 1
- 208000037147 Hypercalcaemia Diseases 0.000 description 1
- 208000019758 Hypergammaglobulinemia Diseases 0.000 description 1
- 208000000269 Hyperkinesis Diseases 0.000 description 1
- 206010020751 Hypersensitivity Diseases 0.000 description 1
- 206010020772 Hypertension Diseases 0.000 description 1
- 229940124790 IL-6 inhibitor Drugs 0.000 description 1
- 201000009794 Idiopathic Pulmonary Fibrosis Diseases 0.000 description 1
- 102000017727 Immunoglobulin Variable Region Human genes 0.000 description 1
- 108010067060 Immunoglobulin Variable Region Proteins 0.000 description 1
- 238000012404 In vitro experiment Methods 0.000 description 1
- 208000004575 Infectious Arthritis Diseases 0.000 description 1
- 208000022559 Inflammatory bowel disease Diseases 0.000 description 1
- 206010065390 Inflammatory pain Diseases 0.000 description 1
- 102000055031 Inhibitor of Apoptosis Proteins Human genes 0.000 description 1
- 206010022491 Insulin resistant diabetes Diseases 0.000 description 1
- 102000014150 Interferons Human genes 0.000 description 1
- 108010050904 Interferons Proteins 0.000 description 1
- 108010002350 Interleukin-2 Proteins 0.000 description 1
- 108090000978 Interleukin-4 Proteins 0.000 description 1
- 102100026019 Interleukin-6 Human genes 0.000 description 1
- 206010022941 Iridocyclitis Diseases 0.000 description 1
- 208000032382 Ischaemic stroke Diseases 0.000 description 1
- 108010055717 JNK Mitogen-Activated Protein Kinases Proteins 0.000 description 1
- 102100027612 Kallikrein-11 Human genes 0.000 description 1
- 208000006264 Korsakoff syndrome Diseases 0.000 description 1
- ROHFNLRQFUQHCH-YFKPBYRVSA-N L-leucine Chemical compound CC(C)C[C@H](N)C(O)=O ROHFNLRQFUQHCH-YFKPBYRVSA-N 0.000 description 1
- 239000004395 L-leucine Substances 0.000 description 1
- 208000031671 Large B-Cell Diffuse Lymphoma Diseases 0.000 description 1
- 241000589248 Legionella Species 0.000 description 1
- 208000007764 Legionnaires' Disease Diseases 0.000 description 1
- 208000004554 Leishmaniasis Diseases 0.000 description 1
- 206010024229 Leprosy Diseases 0.000 description 1
- ROHFNLRQFUQHCH-UHFFFAOYSA-N Leucine Natural products CC(C)CC(N)C(O)=O ROHFNLRQFUQHCH-UHFFFAOYSA-N 0.000 description 1
- 102100021747 Leukemia inhibitory factor receptor Human genes 0.000 description 1
- 101710142062 Leukemia inhibitory factor receptor Proteins 0.000 description 1
- 208000009829 Lewy Body Disease Diseases 0.000 description 1
- 206010024558 Lip oedema Diseases 0.000 description 1
- 208000007021 Lipedema Diseases 0.000 description 1
- 206010024715 Liver transplant rejection Diseases 0.000 description 1
- 208000019693 Lung disease Diseases 0.000 description 1
- 206010058467 Lung neoplasm malignant Diseases 0.000 description 1
- 206010051604 Lung transplant rejection Diseases 0.000 description 1
- 208000016604 Lyme disease Diseases 0.000 description 1
- 208000008771 Lymphadenopathy Diseases 0.000 description 1
- 208000028018 Lymphocytic leukaemia Diseases 0.000 description 1
- 208000035809 Lymphohistiocytosis Diseases 0.000 description 1
- 229930195725 Mannitol Natural products 0.000 description 1
- 201000009906 Meningitis Diseases 0.000 description 1
- 206010027201 Meningitis aseptic Diseases 0.000 description 1
- 206010058858 Meningococcal bacteraemia Diseases 0.000 description 1
- 208000019695 Migraine disease Diseases 0.000 description 1
- 102100023483 Mitogen-activated protein kinase 15 Human genes 0.000 description 1
- 101710109276 Mitogen-activated protein kinase 15 Proteins 0.000 description 1
- 208000003250 Mixed connective tissue disease Diseases 0.000 description 1
- 241000699660 Mus musculus Species 0.000 description 1
- 241000699670 Mus sp. Species 0.000 description 1
- 206010028289 Muscle atrophy Diseases 0.000 description 1
- 241000545499 Mycobacterium avium-intracellulare Species 0.000 description 1
- 241000187479 Mycobacterium tuberculosis Species 0.000 description 1
- 208000031888 Mycoses Diseases 0.000 description 1
- 208000003926 Myelitis Diseases 0.000 description 1
- 208000033776 Myeloid Acute Leukemia Diseases 0.000 description 1
- 201000002481 Myositis Diseases 0.000 description 1
- 108010057466 NF-kappa B Proteins 0.000 description 1
- 102000003945 NF-kappa B Human genes 0.000 description 1
- 208000025966 Neurological disease Diseases 0.000 description 1
- 102100033174 Neutrophil elastase Human genes 0.000 description 1
- 208000008589 Obesity Diseases 0.000 description 1
- 208000003435 Optic Neuritis Diseases 0.000 description 1
- 208000003076 Osteolysis Diseases 0.000 description 1
- 208000001132 Osteoporosis Diseases 0.000 description 1
- 206010033128 Ovarian cancer Diseases 0.000 description 1
- 206010061535 Ovarian neoplasm Diseases 0.000 description 1
- 206010053869 POEMS syndrome Diseases 0.000 description 1
- 208000002193 Pain Diseases 0.000 description 1
- 206010049169 Pancreas transplant rejection Diseases 0.000 description 1
- 206010061902 Pancreatic neoplasm Diseases 0.000 description 1
- 206010033645 Pancreatitis Diseases 0.000 description 1
- 206010033647 Pancreatitis acute Diseases 0.000 description 1
- 206010033799 Paralysis Diseases 0.000 description 1
- 208000018737 Parkinson disease Diseases 0.000 description 1
- 241000721454 Pemphigus Species 0.000 description 1
- 208000025584 Pericardial disease Diseases 0.000 description 1
- 208000005764 Peripheral Arterial Disease Diseases 0.000 description 1
- 208000018262 Peripheral vascular disease Diseases 0.000 description 1
- 208000031845 Pernicious anaemia Diseases 0.000 description 1
- 241000577979 Peromyscus spicilegus Species 0.000 description 1
- 102000004160 Phosphoric Monoester Hydrolases Human genes 0.000 description 1
- 108090000608 Phosphoric Monoester Hydrolases Proteins 0.000 description 1
- 208000005384 Pneumocystis Pneumonia Diseases 0.000 description 1
- 206010073755 Pneumocystis jirovecii pneumonia Diseases 0.000 description 1
- 206010035664 Pneumonia Diseases 0.000 description 1
- 206010036030 Polyarthritis Diseases 0.000 description 1
- 208000012654 Primary biliary cholangitis Diseases 0.000 description 1
- 206010060862 Prostate cancer Diseases 0.000 description 1
- 208000000236 Prostatic Neoplasms Diseases 0.000 description 1
- 208000033526 Proximal spinal muscular atrophy type 3 Diseases 0.000 description 1
- 201000004681 Psoriasis Diseases 0.000 description 1
- 201000001263 Psoriatic Arthritis Diseases 0.000 description 1
- 208000036824 Psoriatic arthropathy Diseases 0.000 description 1
- 208000004186 Pulmonary Heart Disease Diseases 0.000 description 1
- 206010064911 Pulmonary arterial hypertension Diseases 0.000 description 1
- 208000003782 Raynaud disease Diseases 0.000 description 1
- 208000005587 Refsum Disease Diseases 0.000 description 1
- 208000033626 Renal failure acute Diseases 0.000 description 1
- 201000003099 Renovascular Hypertension Diseases 0.000 description 1
- 208000013616 Respiratory Distress Syndrome Diseases 0.000 description 1
- 206010038748 Restrictive cardiomyopathy Diseases 0.000 description 1
- 206010039094 Rhinitis perennial Diseases 0.000 description 1
- 206010039710 Scleroderma Diseases 0.000 description 1
- 229940124639 Selective inhibitor Drugs 0.000 description 1
- 206010039966 Senile dementia Diseases 0.000 description 1
- 206010053879 Sepsis syndrome Diseases 0.000 description 1
- 206010040070 Septic Shock Diseases 0.000 description 1
- 108010022999 Serine Proteases Proteins 0.000 description 1
- 102000012479 Serine Proteases Human genes 0.000 description 1
- 206010062164 Seronegative arthritis Diseases 0.000 description 1
- 208000009714 Severe Dengue Diseases 0.000 description 1
- 108020004459 Small interfering RNA Proteins 0.000 description 1
- 208000003954 Spinal Muscular Atrophies of Childhood Diseases 0.000 description 1
- 208000010112 Spinocerebellar Degenerations Diseases 0.000 description 1
- 208000007107 Stomach Ulcer Diseases 0.000 description 1
- 101710127774 Stress response protein Proteins 0.000 description 1
- 208000037065 Subacute sclerosing leukoencephalitis Diseases 0.000 description 1
- 206010042297 Subacute sclerosing panencephalitis Diseases 0.000 description 1
- 208000004732 Systemic Vasculitis Diseases 0.000 description 1
- 230000006044 T cell activation Effects 0.000 description 1
- 108700012920 TNF Proteins 0.000 description 1
- 208000001871 Tachycardia Diseases 0.000 description 1
- 206010043189 Telangiectasia Diseases 0.000 description 1
- 208000024313 Testicular Neoplasms Diseases 0.000 description 1
- 206010057644 Testis cancer Diseases 0.000 description 1
- AYFVYJQAPQTCCC-UHFFFAOYSA-N Threonine Natural products CC(O)C(N)C(O)=O AYFVYJQAPQTCCC-UHFFFAOYSA-N 0.000 description 1
- 108090000190 Thrombin Proteins 0.000 description 1
- 206010043540 Thromboangiitis obliterans Diseases 0.000 description 1
- 206010043561 Thrombocytopenic purpura Diseases 0.000 description 1
- 206010044248 Toxic shock syndrome Diseases 0.000 description 1
- 231100000650 Toxic shock syndrome Toxicity 0.000 description 1
- 206010070863 Toxicity to various agents Diseases 0.000 description 1
- 206010044688 Trisomy 21 Diseases 0.000 description 1
- 101710152431 Trypsin-like protease Proteins 0.000 description 1
- 102100040247 Tumor necrosis factor Human genes 0.000 description 1
- 206010053614 Type III immune complex mediated reaction Diseases 0.000 description 1
- 102000018478 Ubiquitin-Activating Enzymes Human genes 0.000 description 1
- 108010091546 Ubiquitin-Activating Enzymes Proteins 0.000 description 1
- 102000003431 Ubiquitin-Conjugating Enzyme Human genes 0.000 description 1
- 108060008747 Ubiquitin-Conjugating Enzyme Proteins 0.000 description 1
- 201000006704 Ulcerative Colitis Diseases 0.000 description 1
- 208000007814 Unstable Angina Diseases 0.000 description 1
- 208000007097 Urinary Bladder Neoplasms Diseases 0.000 description 1
- 206010048709 Urosepsis Diseases 0.000 description 1
- 208000024780 Urticaria Diseases 0.000 description 1
- 206010046851 Uveitis Diseases 0.000 description 1
- 206010046996 Varicose vein Diseases 0.000 description 1
- 206010047249 Venous thrombosis Diseases 0.000 description 1
- 206010047642 Vitiligo Diseases 0.000 description 1
- 201000008485 Wernicke-Korsakoff syndrome Diseases 0.000 description 1
- 208000018839 Wilson disease Diseases 0.000 description 1
- 208000027418 Wounds and injury Diseases 0.000 description 1
- JLCPHMBAVCMARE-UHFFFAOYSA-N [3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-[[3-[[3-[[3-[[3-[[3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-hydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methyl [5-(6-aminopurin-9-yl)-2-(hydroxymethyl)oxolan-3-yl] hydrogen phosphate Polymers Cc1cn(C2CC(OP(O)(=O)OCC3OC(CC3OP(O)(=O)OCC3OC(CC3O)n3cnc4c3nc(N)[nH]c4=O)n3cnc4c3nc(N)[nH]c4=O)C(COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3CO)n3cnc4c(N)ncnc34)n3ccc(N)nc3=O)n3cnc4c(N)ncnc34)n3ccc(N)nc3=O)n3ccc(N)nc3=O)n3ccc(N)nc3=O)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cc(C)c(=O)[nH]c3=O)n3cc(C)c(=O)[nH]c3=O)n3ccc(N)nc3=O)n3cc(C)c(=O)[nH]c3=O)n3cnc4c3nc(N)[nH]c4=O)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)O2)c(=O)[nH]c1=O JLCPHMBAVCMARE-UHFFFAOYSA-N 0.000 description 1
- 238000002835 absorbance Methods 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 230000003213 activating effect Effects 0.000 description 1
- 239000012190 activator Substances 0.000 description 1
- 239000013543 active substance Substances 0.000 description 1
- 201000011040 acute kidney failure Diseases 0.000 description 1
- 201000003229 acute pancreatitis Diseases 0.000 description 1
- 208000012998 acute renal failure Diseases 0.000 description 1
- 208000018254 acute transverse myelitis Diseases 0.000 description 1
- 230000002730 additional effect Effects 0.000 description 1
- 239000000654 additive Substances 0.000 description 1
- 208000030597 adult Refsum disease Diseases 0.000 description 1
- 208000011341 adult acute respiratory distress syndrome Diseases 0.000 description 1
- 201000000028 adult respiratory distress syndrome Diseases 0.000 description 1
- 125000003172 aldehyde group Chemical group 0.000 description 1
- 208000002205 allergic conjunctivitis Diseases 0.000 description 1
- 208000002029 allergic contact dermatitis Diseases 0.000 description 1
- 208000026935 allergic disease Diseases 0.000 description 1
- 230000000172 allergic effect Effects 0.000 description 1
- 231100000360 alopecia Toxicity 0.000 description 1
- 125000000539 amino acid group Chemical group 0.000 description 1
- 206010002026 amyotrophic lateral sclerosis Diseases 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 230000033115 angiogenesis Effects 0.000 description 1
- 210000002226 anterior horn cell Anatomy 0.000 description 1
- 201000004612 anterior uveitis Diseases 0.000 description 1
- 230000009949 anti-apoptotic pathway Effects 0.000 description 1
- 230000001475 anti-trypsic effect Effects 0.000 description 1
- 230000009830 antibody antigen interaction Effects 0.000 description 1
- 239000003146 anticoagulant agent Substances 0.000 description 1
- 230000030741 antigen processing and presentation Effects 0.000 description 1
- 210000000612 antigen-presenting cell Anatomy 0.000 description 1
- 210000000709 aorta Anatomy 0.000 description 1
- 210000000702 aorta abdominal Anatomy 0.000 description 1
- 206010002895 aortic dissection Diseases 0.000 description 1
- 239000000158 apoptosis inhibitor Substances 0.000 description 1
- 208000037849 arterial hypertension Diseases 0.000 description 1
- 208000011775 arteriosclerosis disease Diseases 0.000 description 1
- 208000037875 astrocytosis Diseases 0.000 description 1
- 230000007341 astrogliosis Effects 0.000 description 1
- 208000024998 atopic conjunctivitis Diseases 0.000 description 1
- 208000010668 atopic eczema Diseases 0.000 description 1
- 206010003668 atrial tachycardia Diseases 0.000 description 1
- 230000037444 atrophy Effects 0.000 description 1
- 230000003305 autocrine Effects 0.000 description 1
- 230000001580 bacterial effect Effects 0.000 description 1
- 210000004227 basal ganglia Anatomy 0.000 description 1
- 208000018300 basal ganglia disease Diseases 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 238000004166 bioassay Methods 0.000 description 1
- 230000003115 biocidal effect Effects 0.000 description 1
- 238000001574 biopsy Methods 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 230000000903 blocking effect Effects 0.000 description 1
- 230000008499 blood brain barrier function Effects 0.000 description 1
- 210000001218 blood-brain barrier Anatomy 0.000 description 1
- 210000000988 bone and bone Anatomy 0.000 description 1
- 125000005621 boronate group Chemical class 0.000 description 1
- 208000006752 brain edema Diseases 0.000 description 1
- 201000008247 brain infarction Diseases 0.000 description 1
- 208000029028 brain injury Diseases 0.000 description 1
- 239000000872 buffer Substances 0.000 description 1
- 210000004375 bundle of his Anatomy 0.000 description 1
- 230000036952 cancer formation Effects 0.000 description 1
- 231100000504 carcinogenesis Toxicity 0.000 description 1
- 230000000747 cardiac effect Effects 0.000 description 1
- 230000002612 cardiopulmonary effect Effects 0.000 description 1
- 210000000748 cardiovascular system Anatomy 0.000 description 1
- 210000000845 cartilage Anatomy 0.000 description 1
- 230000003915 cell function Effects 0.000 description 1
- 239000013592 cell lysate Substances 0.000 description 1
- 230000033077 cellular process Effects 0.000 description 1
- 210000003169 central nervous system Anatomy 0.000 description 1
- 210000001638 cerebellum Anatomy 0.000 description 1
- 210000001175 cerebrospinal fluid Anatomy 0.000 description 1
- 230000000739 chaotic effect Effects 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 208000025302 chronic primary adrenal insufficiency Diseases 0.000 description 1
- 229960002376 chymotrypsin Drugs 0.000 description 1
- 230000001886 ciliary effect Effects 0.000 description 1
- 230000007882 cirrhosis Effects 0.000 description 1
- 238000011260 co-administration Methods 0.000 description 1
- 208000010877 cognitive disease Diseases 0.000 description 1
- 239000000084 colloidal system Substances 0.000 description 1
- 238000004737 colorimetric analysis Methods 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 230000001268 conjugating effect Effects 0.000 description 1
- 208000010247 contact dermatitis Diseases 0.000 description 1
- 208000029078 coronary artery disease Diseases 0.000 description 1
- 230000001054 cortical effect Effects 0.000 description 1
- 230000002594 corticospinal effect Effects 0.000 description 1
- 210000000172 cytosol Anatomy 0.000 description 1
- 230000007812 deficiency Effects 0.000 description 1
- 230000002950 deficient Effects 0.000 description 1
- 230000003413 degradative effect Effects 0.000 description 1
- 230000000593 degrading effect Effects 0.000 description 1
- 238000012217 deletion Methods 0.000 description 1
- 230000037430 deletion Effects 0.000 description 1
- 208000017004 dementia pugilistica Diseases 0.000 description 1
- 230000003210 demyelinating effect Effects 0.000 description 1
- 201000002950 dengue hemorrhagic fever Diseases 0.000 description 1
- 238000000326 densiometry Methods 0.000 description 1
- 230000002074 deregulated effect Effects 0.000 description 1
- 201000011304 dilated cardiomyopathy 1A Diseases 0.000 description 1
- 229940042399 direct acting antivirals protease inhibitors Drugs 0.000 description 1
- AFOSIXZFDONLBT-UHFFFAOYSA-N divinyl sulfone Chemical class C=CS(=O)(=O)C=C AFOSIXZFDONLBT-UHFFFAOYSA-N 0.000 description 1
- 230000002222 downregulating effect Effects 0.000 description 1
- 230000007783 downstream signaling Effects 0.000 description 1
- 239000003937 drug carrier Substances 0.000 description 1
- 230000000235 effect on cancer Effects 0.000 description 1
- 206010014665 endocarditis Diseases 0.000 description 1
- 230000002708 enhancing effect Effects 0.000 description 1
- 230000007613 environmental effect Effects 0.000 description 1
- 230000002255 enzymatic effect Effects 0.000 description 1
- 208000001606 epiglottitis Diseases 0.000 description 1
- 206010015037 epilepsy Diseases 0.000 description 1
- CURLTUGMZLYLDI-UHFFFAOYSA-N epoxyketone group Chemical group O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 1
- 201000011384 erythromelalgia Diseases 0.000 description 1
- 238000011156 evaluation Methods 0.000 description 1
- 238000010228 ex vivo assay Methods 0.000 description 1
- 230000001747 exhibiting effect Effects 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 230000001605 fetal effect Effects 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 230000006870 function Effects 0.000 description 1
- 201000005917 gastric ulcer Diseases 0.000 description 1
- 102000034356 gene-regulatory proteins Human genes 0.000 description 1
- 108091006104 gene-regulatory proteins Proteins 0.000 description 1
- 208000005017 glioblastoma Diseases 0.000 description 1
- 208000024908 graft versus host disease Diseases 0.000 description 1
- 239000003102 growth factor Substances 0.000 description 1
- 238000001631 haemodialysis Methods 0.000 description 1
- 208000024348 heart neoplasm Diseases 0.000 description 1
- 208000018578 heart valve disease Diseases 0.000 description 1
- 201000011066 hemangioma Diseases 0.000 description 1
- 230000000322 hemodialysis Effects 0.000 description 1
- 230000002949 hemolytic effect Effects 0.000 description 1
- 230000011132 hemopoiesis Effects 0.000 description 1
- 210000003494 hepatocyte Anatomy 0.000 description 1
- OKGLROPOZIVCCZ-HNNXBMFYSA-N himeic acid A Natural products C[C@@H](CC(=O)NC(=O)C1=COC(=CC1=O)C=CCCCCCCCCC(=O)O)C(=O)O OKGLROPOZIVCCZ-HNNXBMFYSA-N 0.000 description 1
- 210000005260 human cell Anatomy 0.000 description 1
- 208000033519 human immunodeficiency virus infectious disease Diseases 0.000 description 1
- 125000001165 hydrophobic group Chemical group 0.000 description 1
- 230000000148 hypercalcaemia Effects 0.000 description 1
- 208000030915 hypercalcemia disease Diseases 0.000 description 1
- 230000006951 hyperphosphorylation Effects 0.000 description 1
- 230000003483 hypokinetic effect Effects 0.000 description 1
- 230000004179 hypothalamic–pituitary–adrenal axis Effects 0.000 description 1
- 230000028993 immune response Effects 0.000 description 1
- 229940027941 immunoglobulin g Drugs 0.000 description 1
- 230000002779 inactivation Effects 0.000 description 1
- 238000011534 incubation Methods 0.000 description 1
- 230000002458 infectious effect Effects 0.000 description 1
- 230000008595 infiltration Effects 0.000 description 1
- 238000001764 infiltration Methods 0.000 description 1
- 206010022000 influenza Diseases 0.000 description 1
- 238000003780 insertion Methods 0.000 description 1
- 230000037431 insertion Effects 0.000 description 1
- 230000002452 interceptive effect Effects 0.000 description 1
- 229940079322 interferon Drugs 0.000 description 1
- 201000004332 intermediate coronary syndrome Diseases 0.000 description 1
- 208000036971 interstitial lung disease 2 Diseases 0.000 description 1
- 208000028774 intestinal disease Diseases 0.000 description 1
- 238000000185 intracerebroventricular administration Methods 0.000 description 1
- 238000007918 intramuscular administration Methods 0.000 description 1
- 238000007912 intraperitoneal administration Methods 0.000 description 1
- 238000007919 intrasynovial administration Methods 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- 230000005865 ionizing radiation Effects 0.000 description 1
- 208000012947 ischemia reperfusion injury Diseases 0.000 description 1
- 230000000302 ischemic effect Effects 0.000 description 1
- 201000004815 juvenile spinal muscular atrophy Diseases 0.000 description 1
- 210000002510 keratinocyte Anatomy 0.000 description 1
- 210000003734 kidney Anatomy 0.000 description 1
- 231100001231 less toxic Toxicity 0.000 description 1
- 210000004558 lewy body Anatomy 0.000 description 1
- 239000003446 ligand Substances 0.000 description 1
- 239000002502 liposome Substances 0.000 description 1
- 201000007270 liver cancer Diseases 0.000 description 1
- 208000014018 liver neoplasm Diseases 0.000 description 1
- 201000005202 lung cancer Diseases 0.000 description 1
- 208000020816 lung neoplasm Diseases 0.000 description 1
- 208000018555 lymphatic system disease Diseases 0.000 description 1
- 208000003747 lymphoid leukemia Diseases 0.000 description 1
- 208000029791 lytic metastatic bone lesion Diseases 0.000 description 1
- 201000004792 malaria Diseases 0.000 description 1
- 208000015486 malignant pancreatic neoplasm Diseases 0.000 description 1
- 208000026037 malignant tumor of neck Diseases 0.000 description 1
- 210000001161 mammalian embryo Anatomy 0.000 description 1
- 235000010355 mannitol Nutrition 0.000 description 1
- 239000000594 mannitol Substances 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 208000022089 meningococcemia Diseases 0.000 description 1
- 201000008265 mesangial proliferative glomerulonephritis Diseases 0.000 description 1
- 230000002503 metabolic effect Effects 0.000 description 1
- 206010061289 metastatic neoplasm Diseases 0.000 description 1
- 206010027599 migraine Diseases 0.000 description 1
- 230000002438 mitochondrial effect Effects 0.000 description 1
- 210000001616 monocyte Anatomy 0.000 description 1
- 206010028417 myasthenia gravis Diseases 0.000 description 1
- 208000025113 myeloid leukemia Diseases 0.000 description 1
- 230000002107 myocardial effect Effects 0.000 description 1
- VMGAPWLDMVPYIA-HIDZBRGKSA-N n'-amino-n-iminomethanimidamide Chemical class N\N=C\N=N VMGAPWLDMVPYIA-HIDZBRGKSA-N 0.000 description 1
- OOEXUWDNTCTJMI-ZJHKYUCMSA-N n-[(2s)-5-[[amino(nitramido)methylidene]amino]-1-[[(2s)-4-methyl-1-oxopentan-2-yl]amino]-1-oxopentan-2-yl]-2-cyclopentyl-10-(1,3-dioxoisoindol-2-yl)decanamide Chemical compound O=C1C2=CC=CC=C2C(=O)N1CCCCCCCCC(C(=O)N[C@@H](CCCN\C(N)=N\[N+]([O-])=O)C(=O)N[C@@H](CC(C)C)C=O)C1CCCC1 OOEXUWDNTCTJMI-ZJHKYUCMSA-N 0.000 description 1
- 230000006654 negative regulation of apoptotic process Effects 0.000 description 1
- 201000008383 nephritis Diseases 0.000 description 1
- 208000009928 nephrosis Diseases 0.000 description 1
- 231100001027 nephrosis Toxicity 0.000 description 1
- 208000015122 neurodegenerative disease Diseases 0.000 description 1
- 230000007514 neuronal growth Effects 0.000 description 1
- 201000001119 neuropathy Diseases 0.000 description 1
- 230000007823 neuropathy Effects 0.000 description 1
- 230000004112 neuroprotection Effects 0.000 description 1
- 239000003076 neurotropic agent Substances 0.000 description 1
- 208000002154 non-small cell lung carcinoma Diseases 0.000 description 1
- 239000002687 nonaqueous vehicle Substances 0.000 description 1
- 239000000346 nonvolatile oil Substances 0.000 description 1
- 235000020824 obesity Nutrition 0.000 description 1
- 238000005457 optimization Methods 0.000 description 1
- 230000000399 orthopedic effect Effects 0.000 description 1
- 201000008482 osteoarthritis Diseases 0.000 description 1
- 210000002997 osteoclast Anatomy 0.000 description 1
- 238000012261 overproduction Methods 0.000 description 1
- 208000021090 palsy Diseases 0.000 description 1
- 201000002528 pancreatic cancer Diseases 0.000 description 1
- 230000003076 paracrine Effects 0.000 description 1
- 230000003071 parasitic effect Effects 0.000 description 1
- 230000000849 parathyroid Effects 0.000 description 1
- 230000001314 paroxysmal effect Effects 0.000 description 1
- 239000002245 particle Substances 0.000 description 1
- 230000007310 pathophysiology Effects 0.000 description 1
- 239000000137 peptide hydrolase inhibitor Substances 0.000 description 1
- 230000010412 perfusion Effects 0.000 description 1
- 208000033808 peripheral neuropathy Diseases 0.000 description 1
- 206010034674 peritonitis Diseases 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 238000001050 pharmacotherapy Methods 0.000 description 1
- 238000009521 phase II clinical trial Methods 0.000 description 1
- 230000026731 phosphorylation Effects 0.000 description 1
- 238000006366 phosphorylation reaction Methods 0.000 description 1
- 230000036470 plasma concentration Effects 0.000 description 1
- 201000000317 pneumocystosis Diseases 0.000 description 1
- 201000011461 pre-eclampsia Diseases 0.000 description 1
- 238000011533 pre-incubation Methods 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 201000008312 primary pulmonary hypertension Diseases 0.000 description 1
- 230000000750 progressive effect Effects 0.000 description 1
- 230000000770 proinflammatory effect Effects 0.000 description 1
- 230000026938 proteasomal ubiquitin-dependent protein catabolic process Effects 0.000 description 1
- 238000001243 protein synthesis Methods 0.000 description 1
- 230000002797 proteolythic effect Effects 0.000 description 1
- 238000001959 radiotherapy Methods 0.000 description 1
- 238000002708 random mutagenesis Methods 0.000 description 1
- 230000006798 recombination Effects 0.000 description 1
- 238000005215 recombination Methods 0.000 description 1
- 230000002829 reductive effect Effects 0.000 description 1
- 230000022983 regulation of cell cycle Effects 0.000 description 1
- 230000003252 repetitive effect Effects 0.000 description 1
- 230000008261 resistance mechanism Effects 0.000 description 1
- 230000003938 response to stress Effects 0.000 description 1
- 208000037803 restenosis Diseases 0.000 description 1
- 201000006845 reticulosarcoma Diseases 0.000 description 1
- 208000029922 reticulum cell sarcoma Diseases 0.000 description 1
- 238000003757 reverse transcription PCR Methods 0.000 description 1
- 230000002441 reversible effect Effects 0.000 description 1
- 230000028706 ribosome biogenesis Effects 0.000 description 1
- 239000000523 sample Substances 0.000 description 1
- 230000028327 secretion Effects 0.000 description 1
- 201000001223 septic arthritis Diseases 0.000 description 1
- 238000012163 sequencing technique Methods 0.000 description 1
- 208000007056 sickle cell anemia Diseases 0.000 description 1
- 102000034285 signal transducing proteins Human genes 0.000 description 1
- 108091006024 signal transducing proteins Proteins 0.000 description 1
- 238000002741 site-directed mutagenesis Methods 0.000 description 1
- 239000000243 solution Substances 0.000 description 1
- 230000037439 somatic mutation Effects 0.000 description 1
- 208000020431 spinal cord injury Diseases 0.000 description 1
- 230000004936 stimulating effect Effects 0.000 description 1
- 230000009221 stress response pathway Effects 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 230000002459 sustained effect Effects 0.000 description 1
- 206010042772 syncope Diseases 0.000 description 1
- 230000009044 synergistic interaction Effects 0.000 description 1
- 210000001179 synovial fluid Anatomy 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 208000006379 syphilis Diseases 0.000 description 1
- 201000000596 systemic lupus erythematosus Diseases 0.000 description 1
- 230000006794 tachycardia Effects 0.000 description 1
- 208000009056 telangiectasis Diseases 0.000 description 1
- 201000003120 testicular cancer Diseases 0.000 description 1
- 150000003573 thiols Chemical class 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
- 229960004072 thrombin Drugs 0.000 description 1
- 206010043554 thrombocytopenia Diseases 0.000 description 1
- 230000002537 thrombolytic effect Effects 0.000 description 1
- 210000001541 thymus gland Anatomy 0.000 description 1
- 206010043778 thyroiditis Diseases 0.000 description 1
- 208000037816 tissue injury Diseases 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 230000002103 transcriptional effect Effects 0.000 description 1
- 238000011830 transgenic mouse model Methods 0.000 description 1
- 230000014616 translation Effects 0.000 description 1
- 208000009174 transverse myelitis Diseases 0.000 description 1
- 230000008733 trauma Effects 0.000 description 1
- 239000002753 trypsin inhibitor Substances 0.000 description 1
- 208000029729 tumor suppressor gene on chromosome 11 Diseases 0.000 description 1
- 208000025883 type III hypersensitivity disease Diseases 0.000 description 1
- 230000005951 type IV hypersensitivity Effects 0.000 description 1
- 208000027930 type IV hypersensitivity disease Diseases 0.000 description 1
- 208000009852 uremia Diseases 0.000 description 1
- 201000005112 urinary bladder cancer Diseases 0.000 description 1
- 208000027185 varicose disease Diseases 0.000 description 1
- 238000007879 vasectomy Methods 0.000 description 1
- 208000037997 venous disease Diseases 0.000 description 1
- 208000003663 ventricular fibrillation Diseases 0.000 description 1
- 201000002498 viral encephalitis Diseases 0.000 description 1
- 230000009385 viral infection Effects 0.000 description 1
- 238000001262 western blot Methods 0.000 description 1
Classifications
-
- 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
- A61K39/395—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum
-
- 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
- C07K16/244—Interleukins [IL]
- C07K16/248—IL-6
-
- 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
- A61K39/395—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum
- A61K39/39533—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum against materials from animals
- A61K39/3955—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum against materials from animals against proteinaceous materials, e.g. enzymes, hormones, lymphokines
-
- 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
- A61P35/00—Antineoplastic agents
- A61P35/02—Antineoplastic agents specific for leukemia
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Organic Chemistry (AREA)
- Public Health (AREA)
- Immunology (AREA)
- Veterinary Medicine (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Epidemiology (AREA)
- Mycology (AREA)
- Microbiology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Molecular Biology (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Biochemistry (AREA)
- Biophysics (AREA)
- Genetics & Genomics (AREA)
- Endocrinology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Oncology (AREA)
- Hematology (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US74915205P | 2005-12-09 | 2005-12-09 | |
| US60/749,152 | 2005-12-09 | ||
| PCT/US2006/061786 WO2007067976A2 (en) | 2005-12-09 | 2006-12-08 | Method of using il6 antagonists with proteasome inhibitors |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| AU2006321610A1 true AU2006321610A1 (en) | 2007-06-14 |
Family
ID=38123650
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| AU2006321610A Abandoned AU2006321610A1 (en) | 2005-12-09 | 2006-12-08 | Method of using IL6 antagonists with proteasome inhibitors |
Country Status (15)
| Country | Link |
|---|---|
| US (1) | US20090022726A1 (OSRAM) |
| EP (1) | EP1954310A4 (OSRAM) |
| JP (1) | JP2009518447A (OSRAM) |
| KR (1) | KR20080072761A (OSRAM) |
| CN (1) | CN101325969A (OSRAM) |
| AR (1) | AR057227A1 (OSRAM) |
| AU (1) | AU2006321610A1 (OSRAM) |
| BR (1) | BRPI0619498A2 (OSRAM) |
| CA (1) | CA2632732A1 (OSRAM) |
| EA (1) | EA014675B1 (OSRAM) |
| IL (1) | IL191694A0 (OSRAM) |
| NO (1) | NO20082907L (OSRAM) |
| TW (1) | TW200803895A (OSRAM) |
| WO (1) | WO2007067976A2 (OSRAM) |
| ZA (1) | ZA200805956B (OSRAM) |
Families Citing this family (35)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US8198270B2 (en) | 2004-04-15 | 2012-06-12 | Onyx Therapeutics, Inc. | Compounds for proteasome enzyme inhibition |
| US8129346B2 (en) | 2004-04-15 | 2012-03-06 | Onyx Therapeutics, Inc. | Compounds for enzyme inhibition |
| CA2565407A1 (en) | 2004-05-10 | 2005-11-24 | Proteolix, Inc. | Compounds for enzyme inhibition |
| WO2007046489A1 (ja) | 2005-10-21 | 2007-04-26 | Chugai Seiyaku Kabushiki Kaisha | 心疾患治療剤 |
| KR101434522B1 (ko) | 2005-11-09 | 2014-08-26 | 오닉스 세라퓨틱스, 인크. | 효소 저해를 위한 화합물 |
| AR057582A1 (es) * | 2005-11-15 | 2007-12-05 | Nat Hospital Organization | Agentes para suprimir la induccion de linfocitos t citotoxicos |
| WO2007086490A1 (ja) | 2006-01-27 | 2007-08-02 | Keio University | 脈絡膜血管新生を伴う疾患の治療剤 |
| US9260516B2 (en) * | 2006-04-07 | 2016-02-16 | Osaka University | Method for promoting muscle regeneration by administering an antibody to the IL-6 receptor |
| US7691852B2 (en) | 2006-06-19 | 2010-04-06 | Onyx Therapeutics, Inc. | Compounds for enzyme inhibition |
| MX2009007830A (es) * | 2007-01-23 | 2009-10-07 | Univ Shinshu | Inhibidor de rechazo cronico. |
| JP5424330B2 (ja) * | 2007-07-26 | 2014-02-26 | 国立大学法人大阪大学 | インターロイキン６受容体阻害剤を有効成分とする眼炎症疾患治療剤 |
| RS54847B2 (sr) | 2007-10-04 | 2019-09-30 | Onyx Therapeutics Inc | Inhibitori kristalne peptid epoksi keton proteaze i sinteza aminokiselinskih keto-epoksida |
| CA2728243C (en) * | 2008-06-05 | 2020-03-10 | National Cancer Center | Il-6 inhibitor for suppressing neuroinvasion in pancreatic cancer |
| WO2010039762A2 (en) * | 2008-10-01 | 2010-04-08 | Dr. Reddy's Laboratories Ltd. | Pharmaceutical compositions comprising boronic acid compounds |
| JP5675629B2 (ja) | 2008-10-21 | 2015-02-25 | オニキス セラピューティクス， インク．Ｏｎｙｘ Ｔｈｅｒａｐｅｕｔｉｃｓ， Ｉｎｃ． | ペプチドエポキシケトンを用いた併用療法 |
| US9492449B2 (en) | 2008-11-13 | 2016-11-15 | Gilead Calistoga Llc | Therapies for hematologic malignancies |
| ES2674719T3 (es) * | 2008-11-13 | 2018-07-03 | Gilead Calistoga Llc | Terapias para neoplasias hematológicas |
| AR075899A1 (es) | 2009-03-20 | 2011-05-04 | Onyx Therapeutics Inc | Tripeptidos epoxicetonas cristalinos inhibidores de proteasa |
| EP2464666B1 (en) | 2009-07-15 | 2018-03-21 | Eva Kovacs-Benke | Combination of a human interleukin-6 antagonist and a human interleukin-6 receptor antagonist in therapy of tumour diseases |
| TWI523661B (zh) * | 2009-07-31 | 2016-03-01 | Shin Maeda | Anti-IL-6 receptor antibody in the manufacture of inhibitors of metastatic inhibition of lung cancer metastasis to the liver |
| US8323883B1 (en) | 2009-10-09 | 2012-12-04 | Cold Spring Harbor Laboratory | Methods of assessing therapeutic benefits of patients having cancers resistant to epidermal growth factor receptor kinase inhibitors |
| US7947653B1 (en) | 2009-10-09 | 2011-05-24 | Cold Spring Harbor Laboratory | Methods for treating epidermal growth factor receptor tyrosine kinase inhibitor-resistant cancers |
| JP5919196B2 (ja) * | 2009-11-13 | 2016-05-18 | オニキス セラピューティクス， インク．Ｏｎｙｘ Ｔｈｅｒａｐｅｕｔｉｃｓ， Ｉｎｃ． | 転移抑制のためのペプチドエポキシケトンの使用 |
| MA34133B1 (fr) | 2010-03-01 | 2013-04-03 | Onyx Therapeutics Inc | Composes pour inhibiteurs de l'immunoproteasome |
| SI2578231T1 (sl) | 2010-05-28 | 2023-01-31 | Chugai Seiyaku Kabushiki Kaisha | Okrepljen protitumorski T celični odzivnik |
| US20140294854A1 (en) * | 2011-03-10 | 2014-10-02 | Albert Einstein College Of Medicine Of Yeshiva University | Target directed to adipocytes, methods and assays for treatment of obesity |
| WO2013175276A1 (en) * | 2012-05-23 | 2013-11-28 | Argen-X B.V | Il-6 binding molecules |
| US20140105921A1 (en) | 2012-07-09 | 2014-04-17 | Onyx Therapeutics, Inc. | Prodrugs of Peptide Epoxy Ketone Protease Inhibitors |
| KR101643041B1 (ko) * | 2014-04-25 | 2016-07-28 | 아주대학교산학협력단 | 프로테아좀 저해제 및 디히드로피리딘계 화합물을 유효성분으로 함유하는 암의 예방 또는 치료용 조성물 |
| CN108030916A (zh) * | 2015-07-03 | 2018-05-15 | 刘永庆 | 防治肿瘤和/或慢性结核病的Th2免疫反应抑制剂及其应用 |
| WO2017138008A2 (en) * | 2016-02-14 | 2017-08-17 | Yeda Research And Development Co. Ltd. | Methods of modulating protein exocytosis and uses of same in therapy |
| JP7185884B2 (ja) | 2017-05-02 | 2022-12-08 | 国立研究開発法人国立精神・神経医療研究センター | Ｉｌ－６及び好中球の関連する疾患の治療効果の予測及び判定方法 |
| US20200246488A1 (en) * | 2017-07-17 | 2020-08-06 | The Broad Institute, Inc. | Compositions and methods for treating inflammatory bowel diseases |
| WO2019078344A1 (ja) | 2017-10-20 | 2019-04-25 | 学校法人兵庫医科大学 | 抗ｉｌ－６受容体抗体を含有する術後の癒着を抑制するための医薬組成物 |
| US20200165608A1 (en) * | 2018-11-23 | 2020-05-28 | Florida State University Research Foundation, Inc. | Inhibition of vascular endothelial cell-mediated phagocytic processes for treatment of demyelinating conditions |
Family Cites Families (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5210075A (en) * | 1990-02-16 | 1993-05-11 | Tanabe Seiyaku Co., Ltd. | Interleukin 6 antagonist peptides |
| US5340736A (en) * | 1991-05-13 | 1994-08-23 | The President & Fellows Of Harvard College | ATP-dependent protease and use of inhibitors for same in the treatment of cachexia and muscle wasting |
| US5856135A (en) * | 1993-05-31 | 1999-01-05 | Chugai Seiyaku Kabushiki Kaisha | Reshaped human antibody to human interleukin-6 |
| US5888510A (en) * | 1993-07-21 | 1999-03-30 | Chugai Seiyaku Kabushiki Kaisha | Chronic rheumatoid arthritis therapy containing IL-6 antagonist as effective component |
| US5693617A (en) * | 1994-03-15 | 1997-12-02 | Proscript, Inc. | Inhibitors of the 26s proteolytic complex and the 20s proteasome contained therein |
| KR20010080267A (ko) * | 1998-10-20 | 2001-08-22 | 밀레니엄 파머슈티컬스 인코퍼레이티드 | 프로테아솜 억제제 약물 작용을 모니터링하는 방법 |
| PT2308888T (pt) * | 2001-11-14 | 2017-05-03 | Janssen Biotech Inc | Anticorpos anti-il-6, composições, métodos e utilizações |
| WO2004071404A2 (en) * | 2003-02-04 | 2004-08-26 | Centocor Inc. | Use of il-6 antagonists in combination with steroids to enhance apoptosis |
| PA8672101A1 (es) * | 2005-04-29 | 2006-12-07 | Centocor Inc | Anticuerpos anti-il-6, composiciones, métodos y usos |
-
2006
- 2006-12-07 AR ARP060105416A patent/AR057227A1/es not_active Application Discontinuation
- 2006-12-08 KR KR1020087016043A patent/KR20080072761A/ko not_active Withdrawn
- 2006-12-08 BR BRPI0619498-2A patent/BRPI0619498A2/pt not_active IP Right Cessation
- 2006-12-08 EA EA200870029A patent/EA014675B1/ru not_active IP Right Cessation
- 2006-12-08 CN CNA2006800459213A patent/CN101325969A/zh active Pending
- 2006-12-08 EP EP06840161A patent/EP1954310A4/en not_active Withdrawn
- 2006-12-08 AU AU2006321610A patent/AU2006321610A1/en not_active Abandoned
- 2006-12-08 CA CA002632732A patent/CA2632732A1/en not_active Abandoned
- 2006-12-08 JP JP2008544662A patent/JP2009518447A/ja active Pending
- 2006-12-08 US US11/608,342 patent/US20090022726A1/en not_active Abandoned
- 2006-12-08 TW TW095145881A patent/TW200803895A/zh unknown
- 2006-12-08 WO PCT/US2006/061786 patent/WO2007067976A2/en not_active Ceased
-
2008
- 2008-05-25 IL IL191694A patent/IL191694A0/en unknown
- 2008-06-27 NO NO20082907A patent/NO20082907L/no not_active Application Discontinuation
- 2008-07-08 ZA ZA200805956A patent/ZA200805956B/xx unknown
Also Published As
| Publication number | Publication date |
|---|---|
| EA200870029A1 (ru) | 2008-10-30 |
| EP1954310A4 (en) | 2009-04-22 |
| EA014675B1 (ru) | 2010-12-30 |
| WO2007067976A2 (en) | 2007-06-14 |
| JP2009518447A (ja) | 2009-05-07 |
| NO20082907L (no) | 2008-08-26 |
| WO2007067976A3 (en) | 2008-02-14 |
| US20090022726A1 (en) | 2009-01-22 |
| CA2632732A1 (en) | 2007-06-14 |
| ZA200805956B (en) | 2009-10-28 |
| IL191694A0 (en) | 2008-12-29 |
| AR057227A1 (es) | 2007-11-21 |
| BRPI0619498A2 (pt) | 2011-10-04 |
| KR20080072761A (ko) | 2008-08-06 |
| TW200803895A (en) | 2008-01-16 |
| EP1954310A2 (en) | 2008-08-13 |
| CN101325969A (zh) | 2008-12-17 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| US20090022726A1 (en) | Method of using il6 antagonists with proteasome inhibitors | |
| US20080081041A1 (en) | Method of Using IL6 Antagonists with Mitoxantrone for Prostate Cancer | |
| US8383778B2 (en) | IL-1 binding proteins | |
| Burger | Impact of interleukin-6 in hematological malignancies | |
| AU2006265932B2 (en) | IL-12/p40 binding proteins | |
| CA2201781C (en) | Chronic rheumatoid arthritis therapy containing il-6 antagonist as effective component | |
| CN105617387B (zh) | 治疗白介素-6相关疾病的方法 | |
| US20120275996A1 (en) | IL-1 Binding Proteins | |
| CA2775402A1 (en) | Il-1 binding proteins | |
| Bui et al. | Cytokine targeting in rheumatoid arthritis | |
| EP2182943B1 (en) | Methods and compositions for treating fibrosis related disorders using il-17 antagonists | |
| EP3837283A1 (en) | Anti-il1rap antibody compositions | |
| JP7680078B2 (ja) | 抗ヒトインターフェロンα受容体１モノクローナル抗体及びその使用 | |
| CA3174680A1 (en) | Anti-interleukin-33 antibodies and uses thereof | |
| WO2001019373A2 (en) | Methods and compositions for modulating responsiveness to corticosteroids | |
| US10183971B2 (en) | SAA-domain-specific antibodies and peptide antagonists and use thereof to treat inflammatory diseases | |
| MX2008007329A (en) | Method of using il6 antagonists with proteasome inhibitors | |
| EP4578873A1 (en) | Anti-human interleukin 36 receptor monoclonal antibody and use thereof | |
| JP6845237B2 (ja) | 抗−ヒトｉｌ−３抗体、ｉｌ−３の高められた発現又はレベルに関連する疾患又は機能障害へのそれらの使用、及びヒトｉｌ−３の検出方法へのそれらの使用 | |
| HK1158078A (en) | Methods for treating interleukin-6 related diseases | |
| HK1071304A1 (zh) | 结合至c5和c5a但不阻止c5b形成的补体途径抑制剂 |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| MK4 | Application lapsed section 142(2)(d) - no continuation fee paid for the application |