JP2013514795A - 治療における使用のための四価cd47抗体定常領域融合タンパク質 - Google Patents
治療における使用のための四価cd47抗体定常領域融合タンパク質 Download PDFInfo
- Publication number
- JP2013514795A JP2013514795A JP2012545290A JP2012545290A JP2013514795A JP 2013514795 A JP2013514795 A JP 2013514795A JP 2012545290 A JP2012545290 A JP 2012545290A JP 2012545290 A JP2012545290 A JP 2012545290A JP 2013514795 A JP2013514795 A JP 2013514795A
- Authority
- JP
- Japan
- Prior art keywords
- seq
- sirpα
- soluble protein
- nucleotide sequence
- binding
- 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.)
- Pending
Links
- 101000868279 Homo sapiens Leukocyte surface antigen CD47 Proteins 0.000 title claims description 52
- 102100032913 Leukocyte surface antigen CD47 Human genes 0.000 title claims description 46
- 108020001507 fusion proteins Proteins 0.000 title description 9
- 102000037865 fusion proteins Human genes 0.000 title description 9
- 238000002560 therapeutic procedure Methods 0.000 title description 3
- 101000863873 Homo sapiens Tyrosine-protein phosphatase non-receptor type substrate 1 Proteins 0.000 claims abstract description 428
- 102100029948 Tyrosine-protein phosphatase non-receptor type substrate 1 Human genes 0.000 claims abstract description 324
- 230000027455 binding Effects 0.000 claims abstract description 293
- 238000009739 binding Methods 0.000 claims abstract description 289
- 108090000623 proteins and genes Proteins 0.000 claims abstract description 216
- 102000004169 proteins and genes Human genes 0.000 claims abstract description 197
- 108090000765 processed proteins & peptides Proteins 0.000 claims abstract description 154
- 102000004196 processed proteins & peptides Human genes 0.000 claims abstract description 145
- 229920001184 polypeptide Polymers 0.000 claims abstract description 144
- 239000003814 drug Substances 0.000 claims abstract description 43
- 238000011282 treatment Methods 0.000 claims abstract description 41
- 239000000833 heterodimer Substances 0.000 claims abstract description 36
- 208000022559 Inflammatory bowel disease Diseases 0.000 claims abstract description 15
- 208000006673 asthma Diseases 0.000 claims abstract description 14
- 239000002773 nucleotide Substances 0.000 claims description 121
- 125000003729 nucleotide group Chemical group 0.000 claims description 121
- 210000004027 cell Anatomy 0.000 claims description 116
- 102000004127 Cytokines Human genes 0.000 claims description 47
- 108090000695 Cytokines Proteins 0.000 claims description 47
- 210000004443 dendritic cell Anatomy 0.000 claims description 40
- 230000002757 inflammatory effect Effects 0.000 claims description 39
- 210000001616 monocyte Anatomy 0.000 claims description 36
- -1 serine amino acids Chemical class 0.000 claims description 33
- 239000002245 particle Substances 0.000 claims description 32
- 238000000338 in vitro Methods 0.000 claims description 31
- 150000001413 amino acids Chemical class 0.000 claims description 29
- 229940079593 drug Drugs 0.000 claims description 29
- 239000012634 fragment Substances 0.000 claims description 24
- 230000023404 leukocyte cell-cell adhesion Effects 0.000 claims description 19
- 102000039446 nucleic acids Human genes 0.000 claims description 19
- 108020004707 nucleic acids Proteins 0.000 claims description 19
- 150000007523 nucleic acids Chemical class 0.000 claims description 19
- 206010028980 Neoplasm Diseases 0.000 claims description 15
- 238000003556 assay Methods 0.000 claims description 14
- 230000001404 mediated effect Effects 0.000 claims description 14
- 108060003951 Immunoglobulin Proteins 0.000 claims description 13
- 239000004480 active ingredient Substances 0.000 claims description 13
- 102000018358 immunoglobulin Human genes 0.000 claims description 13
- 238000004519 manufacturing process Methods 0.000 claims description 13
- 239000008194 pharmaceutical composition Substances 0.000 claims description 12
- 230000002829 reductive effect Effects 0.000 claims description 11
- 239000013604 expression vector Substances 0.000 claims description 10
- 108010001857 Cell Surface Receptors Proteins 0.000 claims description 9
- 201000011510 cancer Diseases 0.000 claims description 9
- 239000003446 ligand Substances 0.000 claims description 9
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 claims description 8
- 229920001519 homopolymer Polymers 0.000 claims description 8
- 229940088597 hormone Drugs 0.000 claims description 8
- 239000005556 hormone Substances 0.000 claims description 8
- 208000026935 allergic disease Diseases 0.000 claims description 7
- 239000012636 effector Substances 0.000 claims description 7
- 241000124008 Mammalia Species 0.000 claims description 6
- 230000010056 antibody-dependent cellular cytotoxicity Effects 0.000 claims description 6
- 206010003246 arthritis Diseases 0.000 claims description 6
- 238000003352 cell adhesion assay Methods 0.000 claims description 6
- 102000044459 human CD47 Human genes 0.000 claims description 6
- 230000028327 secretion Effects 0.000 claims description 6
- 210000004962 mammalian cell Anatomy 0.000 claims description 5
- 150000003384 small molecules Chemical class 0.000 claims description 5
- 239000004471 Glycine Substances 0.000 claims description 4
- 230000001154 acute effect Effects 0.000 claims description 4
- 208000030090 Acute Disease Diseases 0.000 claims description 3
- 241000191967 Staphylococcus aureus Species 0.000 claims description 3
- 230000005784 autoimmunity Effects 0.000 claims description 3
- 208000037976 chronic inflammation Diseases 0.000 claims description 3
- 238000003745 diagnosis Methods 0.000 claims description 3
- 239000003102 growth factor Substances 0.000 claims description 3
- 208000023589 ischemic disease Diseases 0.000 claims description 3
- 208000032839 leukemia Diseases 0.000 claims description 3
- 229920000642 polymer Polymers 0.000 claims description 3
- 102000034285 signal transducing proteins Human genes 0.000 claims description 3
- 108091006024 signal transducing proteins Proteins 0.000 claims description 3
- MTCFGRXMJLQNBG-UHFFFAOYSA-N Serine Natural products OCC(N)C(O)=O MTCFGRXMJLQNBG-UHFFFAOYSA-N 0.000 claims description 2
- 208000037883 airway inflammation Diseases 0.000 claims description 2
- 208000037893 chronic inflammatory disorder Diseases 0.000 claims description 2
- 238000010367 cloning Methods 0.000 claims description 2
- 238000012258 culturing Methods 0.000 claims description 2
- 230000003394 haemopoietic effect Effects 0.000 claims description 2
- 102000006240 membrane receptors Human genes 0.000 claims 4
- 239000013599 cloning vector Substances 0.000 claims 1
- 230000002265 prevention Effects 0.000 abstract description 11
- 208000023275 Autoimmune disease Diseases 0.000 abstract description 8
- 201000009961 allergic asthma Diseases 0.000 abstract description 8
- 208000027866 inflammatory disease Diseases 0.000 abstract description 6
- 230000001363 autoimmune Effects 0.000 abstract description 5
- 235000018102 proteins Nutrition 0.000 description 144
- 239000003795 chemical substances by application Substances 0.000 description 41
- 235000001014 amino acid Nutrition 0.000 description 37
- 125000003275 alpha amino acid group Chemical group 0.000 description 35
- 238000000034 method Methods 0.000 description 32
- 239000013612 plasmid Substances 0.000 description 32
- 229940024606 amino acid Drugs 0.000 description 26
- 239000000203 mixture Substances 0.000 description 26
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 25
- 230000001225 therapeutic effect Effects 0.000 description 23
- 230000014509 gene expression Effects 0.000 description 19
- 201000010099 disease Diseases 0.000 description 18
- 230000001580 bacterial effect Effects 0.000 description 17
- 238000006467 substitution reaction Methods 0.000 description 17
- 241000699670 Mus sp. Species 0.000 description 16
- 230000006870 function Effects 0.000 description 15
- 230000013595 glycosylation Effects 0.000 description 14
- 238000006206 glycosylation reaction Methods 0.000 description 14
- 125000000539 amino acid group Chemical group 0.000 description 13
- 150000001875 compounds Chemical class 0.000 description 13
- NHJVRSWLHSJWIN-UHFFFAOYSA-N 2,4,6-trinitrobenzenesulfonic acid Chemical compound OS(=O)(=O)C1=C([N+]([O-])=O)C=C([N+]([O-])=O)C=C1[N+]([O-])=O NHJVRSWLHSJWIN-UHFFFAOYSA-N 0.000 description 12
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 12
- 241001465754 Metazoa Species 0.000 description 12
- 239000002202 Polyethylene glycol Substances 0.000 description 12
- 230000037396 body weight Effects 0.000 description 12
- 206010009887 colitis Diseases 0.000 description 12
- 239000002953 phosphate buffered saline Substances 0.000 description 12
- 229920001223 polyethylene glycol Polymers 0.000 description 12
- 102220259502 rs1357038342 Human genes 0.000 description 12
- 108020004414 DNA Proteins 0.000 description 11
- 210000004369 blood Anatomy 0.000 description 11
- 239000008280 blood Substances 0.000 description 11
- 238000002347 injection Methods 0.000 description 11
- 239000007924 injection Substances 0.000 description 11
- 230000001684 chronic effect Effects 0.000 description 10
- 231100000599 cytotoxic agent Toxicity 0.000 description 10
- 238000012217 deletion Methods 0.000 description 10
- 230000037430 deletion Effects 0.000 description 10
- 238000001727 in vivo Methods 0.000 description 10
- 210000000265 leukocyte Anatomy 0.000 description 10
- 102000005962 receptors Human genes 0.000 description 10
- 108020003175 receptors Proteins 0.000 description 10
- 150000003839 salts Chemical class 0.000 description 10
- 101100477532 Mus musculus Sirpa gene Proteins 0.000 description 9
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 9
- 108010076504 Protein Sorting Signals Proteins 0.000 description 9
- 230000001413 cellular effect Effects 0.000 description 9
- 101000946889 Homo sapiens Monocyte differentiation antigen CD14 Proteins 0.000 description 8
- 101000835928 Homo sapiens Signal-regulatory protein gamma Proteins 0.000 description 8
- 102100035877 Monocyte differentiation antigen CD14 Human genes 0.000 description 8
- 238000013459 approach Methods 0.000 description 8
- 230000003993 interaction Effects 0.000 description 8
- 206010064147 Gastrointestinal inflammation Diseases 0.000 description 7
- 206010020751 Hypersensitivity Diseases 0.000 description 7
- 241000699666 Mus <mouse, genus> Species 0.000 description 7
- 108091028043 Nucleic acid sequence Proteins 0.000 description 7
- 239000002253 acid Substances 0.000 description 7
- 125000000151 cysteine group Chemical group N[C@@H](CS)C(=O)* 0.000 description 7
- 208000035475 disorder Diseases 0.000 description 7
- 239000003937 drug carrier Substances 0.000 description 7
- 238000003780 insertion Methods 0.000 description 7
- 230000037431 insertion Effects 0.000 description 7
- 230000003834 intracellular effect Effects 0.000 description 7
- 238000007912 intraperitoneal administration Methods 0.000 description 7
- 239000003550 marker Substances 0.000 description 7
- 230000001105 regulatory effect Effects 0.000 description 7
- 239000013598 vector Substances 0.000 description 7
- 102000017420 CD3 protein, epsilon/gamma/delta subunit Human genes 0.000 description 6
- 108050005493 CD3 protein, epsilon/gamma/delta subunit Proteins 0.000 description 6
- 108010047041 Complementarity Determining Regions Proteins 0.000 description 6
- AOJJSUZBOXZQNB-TZSSRYMLSA-N Doxorubicin Chemical compound O([C@H]1C[C@@](O)(CC=2C(O)=C3C(=O)C=4C=CC=C(C=4C(=O)C3=C(O)C=21)OC)C(=O)CO)[C@H]1C[C@H](N)[C@H](O)[C@H](C)O1 AOJJSUZBOXZQNB-TZSSRYMLSA-N 0.000 description 6
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 6
- 102000003886 Glycoproteins Human genes 0.000 description 6
- 108090000288 Glycoproteins Proteins 0.000 description 6
- 102100029185 Low affinity immunoglobulin gamma Fc region receptor III-B Human genes 0.000 description 6
- 102100025795 Signal-regulatory protein gamma Human genes 0.000 description 6
- 238000007792 addition Methods 0.000 description 6
- 239000000427 antigen Substances 0.000 description 6
- 108091007433 antigens Proteins 0.000 description 6
- 102000036639 antigens Human genes 0.000 description 6
- 150000001720 carbohydrates Chemical class 0.000 description 6
- 235000014633 carbohydrates Nutrition 0.000 description 6
- 210000004978 chinese hamster ovary cell Anatomy 0.000 description 6
- 229940127089 cytotoxic agent Drugs 0.000 description 6
- 239000002619 cytotoxin Substances 0.000 description 6
- 230000004927 fusion Effects 0.000 description 6
- 238000001802 infusion Methods 0.000 description 6
- 239000000243 solution Substances 0.000 description 6
- 238000012360 testing method Methods 0.000 description 6
- 229940124597 therapeutic agent Drugs 0.000 description 6
- 102000000844 Cell Surface Receptors Human genes 0.000 description 5
- 108091006020 Fc-tagged proteins Proteins 0.000 description 5
- 241000282412 Homo Species 0.000 description 5
- 101000917858 Homo sapiens Low affinity immunoglobulin gamma Fc region receptor III-A Proteins 0.000 description 5
- 101000917839 Homo sapiens Low affinity immunoglobulin gamma Fc region receptor III-B Proteins 0.000 description 5
- 101000716102 Homo sapiens T-cell surface glycoprotein CD4 Proteins 0.000 description 5
- 101000946843 Homo sapiens T-cell surface glycoprotein CD8 alpha chain Proteins 0.000 description 5
- 101000914514 Homo sapiens T-cell-specific surface glycoprotein CD28 Proteins 0.000 description 5
- 102100037877 Intercellular adhesion molecule 1 Human genes 0.000 description 5
- 102000004889 Interleukin-6 Human genes 0.000 description 5
- 108090001005 Interleukin-6 Proteins 0.000 description 5
- FBOZXECLQNJBKD-ZDUSSCGKSA-N L-methotrexate Chemical compound C=1N=C2N=C(N)N=C(N)C2=NC=1CN(C)C1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 FBOZXECLQNJBKD-ZDUSSCGKSA-N 0.000 description 5
- 206010035226 Plasma cell myeloma Diseases 0.000 description 5
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 5
- 102100036011 T-cell surface glycoprotein CD4 Human genes 0.000 description 5
- 102100034922 T-cell surface glycoprotein CD8 alpha chain Human genes 0.000 description 5
- 102100027213 T-cell-specific surface glycoprotein CD28 Human genes 0.000 description 5
- 102100040247 Tumor necrosis factor Human genes 0.000 description 5
- 235000018417 cysteine Nutrition 0.000 description 5
- 239000002612 dispersion medium Substances 0.000 description 5
- 238000012377 drug delivery Methods 0.000 description 5
- 230000000694 effects Effects 0.000 description 5
- 238000009472 formulation Methods 0.000 description 5
- 210000003958 hematopoietic stem cell Anatomy 0.000 description 5
- 230000001506 immunosuppresive effect Effects 0.000 description 5
- 239000000543 intermediate Substances 0.000 description 5
- 229960000485 methotrexate Drugs 0.000 description 5
- 230000006320 pegylation Effects 0.000 description 5
- 238000000159 protein binding assay Methods 0.000 description 5
- 210000001519 tissue Anatomy 0.000 description 5
- 238000005406 washing Methods 0.000 description 5
- 102100032937 CD40 ligand Human genes 0.000 description 4
- 102000014914 Carrier Proteins Human genes 0.000 description 4
- 101000934346 Homo sapiens T-cell surface antigen CD2 Proteins 0.000 description 4
- 101000980827 Homo sapiens T-cell surface glycoprotein CD1a Proteins 0.000 description 4
- 206010061218 Inflammation Diseases 0.000 description 4
- 108010064593 Intercellular Adhesion Molecule-1 Proteins 0.000 description 4
- 102000000589 Interleukin-1 Human genes 0.000 description 4
- 108010002352 Interleukin-1 Proteins 0.000 description 4
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 4
- 102100025237 T-cell surface antigen CD2 Human genes 0.000 description 4
- 102100024219 T-cell surface glycoprotein CD1a Human genes 0.000 description 4
- 108060008682 Tumor Necrosis Factor Proteins 0.000 description 4
- 238000010521 absorption reaction Methods 0.000 description 4
- RJURFGZVJUQBHK-UHFFFAOYSA-N actinomycin D Natural products CC1OC(=O)C(C(C)C)N(C)C(=O)CN(C)C(=O)C2CCCN2C(=O)C(C(C)C)NC(=O)C1NC(=O)C1=C(N)C(=O)C(C)=C2OC(C(C)=CC=C3C(=O)NC4C(=O)NC(C(N5CCCC5C(=O)N(C)CC(=O)N(C)C(C(C)C)C(=O)OC4C)=O)C(C)C)=C3N=C21 RJURFGZVJUQBHK-UHFFFAOYSA-N 0.000 description 4
- 239000005557 antagonist Substances 0.000 description 4
- 239000003242 anti bacterial agent Substances 0.000 description 4
- 239000002260 anti-inflammatory agent Substances 0.000 description 4
- 229940124599 anti-inflammatory drug Drugs 0.000 description 4
- 239000003963 antioxidant agent Substances 0.000 description 4
- 235000006708 antioxidants Nutrition 0.000 description 4
- 108091008324 binding proteins Proteins 0.000 description 4
- 210000001185 bone marrow Anatomy 0.000 description 4
- 229940124630 bronchodilator Drugs 0.000 description 4
- 238000002512 chemotherapy Methods 0.000 description 4
- 230000000295 complement effect Effects 0.000 description 4
- 239000002254 cytotoxic agent Substances 0.000 description 4
- 238000011161 development Methods 0.000 description 4
- 230000018109 developmental process Effects 0.000 description 4
- 238000010494 dissociation reaction Methods 0.000 description 4
- 230000005593 dissociations Effects 0.000 description 4
- 210000003527 eukaryotic cell Anatomy 0.000 description 4
- 239000012530 fluid Substances 0.000 description 4
- 238000002825 functional assay Methods 0.000 description 4
- 208000018706 hematopoietic system disease Diseases 0.000 description 4
- 230000009610 hypersensitivity Effects 0.000 description 4
- 230000002519 immonomodulatory effect Effects 0.000 description 4
- 210000000987 immune system Anatomy 0.000 description 4
- 239000007943 implant Substances 0.000 description 4
- 230000004054 inflammatory process Effects 0.000 description 4
- 238000001990 intravenous administration Methods 0.000 description 4
- 239000002502 liposome Substances 0.000 description 4
- 210000004698 lymphocyte Anatomy 0.000 description 4
- 230000004048 modification Effects 0.000 description 4
- 238000012986 modification Methods 0.000 description 4
- 230000035772 mutation Effects 0.000 description 4
- 230000000414 obstructive effect Effects 0.000 description 4
- 238000002360 preparation method Methods 0.000 description 4
- 210000001236 prokaryotic cell Anatomy 0.000 description 4
- 238000003259 recombinant expression Methods 0.000 description 4
- MZOFCQQQCNRIBI-VMXHOPILSA-N (3s)-4-[[(2s)-1-[[(2s)-1-[[(1s)-1-carboxy-2-hydroxyethyl]amino]-4-methyl-1-oxopentan-2-yl]amino]-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-3-[[2-[[(2s)-2,6-diaminohexanoyl]amino]acetyl]amino]-4-oxobutanoic acid Chemical compound OC[C@@H](C(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCN=C(N)N)NC(=O)[C@H](CC(O)=O)NC(=O)CNC(=O)[C@@H](N)CCCCN MZOFCQQQCNRIBI-VMXHOPILSA-N 0.000 description 3
- IIZPXYDJLKNOIY-JXPKJXOSSA-N 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCC\C=C/C\C=C/C\C=C/C\C=C/CCCCC IIZPXYDJLKNOIY-JXPKJXOSSA-N 0.000 description 3
- STQGQHZAVUOBTE-UHFFFAOYSA-N 7-Cyan-hept-2t-en-4,6-diinsaeure Natural products C1=2C(O)=C3C(=O)C=4C(OC)=CC=CC=4C(=O)C3=C(O)C=2CC(O)(C(C)=O)CC1OC1CC(N)C(O)C(C)O1 STQGQHZAVUOBTE-UHFFFAOYSA-N 0.000 description 3
- 208000024893 Acute lymphoblastic leukemia Diseases 0.000 description 3
- 208000014697 Acute lymphocytic leukaemia Diseases 0.000 description 3
- 208000031261 Acute myeloid leukaemia Diseases 0.000 description 3
- 239000012114 Alexa Fluor 647 Substances 0.000 description 3
- 102100035248 Alpha-(1,3)-fucosyltransferase 4 Human genes 0.000 description 3
- 208000032467 Aplastic anaemia Diseases 0.000 description 3
- 208000010839 B-cell chronic lymphocytic leukemia Diseases 0.000 description 3
- 102100024222 B-lymphocyte antigen CD19 Human genes 0.000 description 3
- 208000032791 BCR-ABL1 positive chronic myelogenous leukemia Diseases 0.000 description 3
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 3
- 101150013553 CD40 gene Proteins 0.000 description 3
- 208000010833 Chronic myeloid leukaemia Diseases 0.000 description 3
- 208000015943 Coeliac disease Diseases 0.000 description 3
- 206010009900 Colitis ulcerative Diseases 0.000 description 3
- 108010092160 Dactinomycin Proteins 0.000 description 3
- 229920002307 Dextran Polymers 0.000 description 3
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 3
- 208000007882 Gastritis Diseases 0.000 description 3
- 108010051696 Growth Hormone Proteins 0.000 description 3
- 101001022185 Homo sapiens Alpha-(1,3)-fucosyltransferase 4 Proteins 0.000 description 3
- 101000980825 Homo sapiens B-lymphocyte antigen CD19 Proteins 0.000 description 3
- 101001046677 Homo sapiens Integrin alpha-V Proteins 0.000 description 3
- 101001057504 Homo sapiens Interferon-stimulated gene 20 kDa protein Proteins 0.000 description 3
- 101001055144 Homo sapiens Interleukin-2 receptor subunit alpha Proteins 0.000 description 3
- 101000917826 Homo sapiens Low affinity immunoglobulin gamma Fc region receptor II-a Proteins 0.000 description 3
- 101000917824 Homo sapiens Low affinity immunoglobulin gamma Fc region receptor II-b Proteins 0.000 description 3
- 101000589307 Homo sapiens Natural cytotoxicity triggering receptor 3 Proteins 0.000 description 3
- 101000914496 Homo sapiens T-cell antigen CD7 Proteins 0.000 description 3
- 101000716124 Homo sapiens T-cell surface glycoprotein CD1c Proteins 0.000 description 3
- 101000934341 Homo sapiens T-cell surface glycoprotein CD5 Proteins 0.000 description 3
- 101000795167 Homo sapiens Tumor necrosis factor receptor superfamily member 13B Proteins 0.000 description 3
- 108010073807 IgG Receptors Proteins 0.000 description 3
- 108010091135 Immunoglobulin Fc Fragments Proteins 0.000 description 3
- 102000018071 Immunoglobulin Fc Fragments Human genes 0.000 description 3
- 102100022337 Integrin alpha-V Human genes 0.000 description 3
- 102100037871 Intercellular adhesion molecule 3 Human genes 0.000 description 3
- 102100027268 Interferon-stimulated gene 20 kDa protein Human genes 0.000 description 3
- 102000003814 Interleukin-10 Human genes 0.000 description 3
- 108090000174 Interleukin-10 Proteins 0.000 description 3
- 108010065637 Interleukin-23 Proteins 0.000 description 3
- 102000013264 Interleukin-23 Human genes 0.000 description 3
- 102100037792 Interleukin-6 receptor subunit alpha Human genes 0.000 description 3
- 102000004890 Interleukin-8 Human genes 0.000 description 3
- 108090001007 Interleukin-8 Proteins 0.000 description 3
- DCXYFEDJOCDNAF-REOHCLBHSA-N L-asparagine Chemical compound OC(=O)[C@@H](N)CC(N)=O DCXYFEDJOCDNAF-REOHCLBHSA-N 0.000 description 3
- 102100029204 Low affinity immunoglobulin gamma Fc region receptor II-a Human genes 0.000 description 3
- 208000019693 Lung disease Diseases 0.000 description 3
- 208000031422 Lymphocytic Chronic B-Cell Leukemia Diseases 0.000 description 3
- 241000829100 Macaca mulatta polyomavirus 1 Species 0.000 description 3
- 208000034578 Multiple myelomas Diseases 0.000 description 3
- 201000003793 Myelodysplastic syndrome Diseases 0.000 description 3
- 208000033761 Myelogenous Chronic BCR-ABL Positive Leukemia Diseases 0.000 description 3
- 208000033776 Myeloid Acute Leukemia Diseases 0.000 description 3
- 208000014767 Myeloproliferative disease Diseases 0.000 description 3
- 201000002481 Myositis Diseases 0.000 description 3
- NWIBSHFKIJFRCO-WUDYKRTCSA-N Mytomycin Chemical compound C1N2C(C(C(C)=C(N)C3=O)=O)=C3[C@@H](COC(N)=O)[C@@]2(OC)[C@@H]2[C@H]1N2 NWIBSHFKIJFRCO-WUDYKRTCSA-N 0.000 description 3
- 102100032852 Natural cytotoxicity triggering receptor 3 Human genes 0.000 description 3
- 208000015914 Non-Hodgkin lymphomas Diseases 0.000 description 3
- 208000006664 Precursor Cell Lymphoblastic Leukemia-Lymphoma Diseases 0.000 description 3
- 239000012980 RPMI-1640 medium Substances 0.000 description 3
- 102100038803 Somatotropin Human genes 0.000 description 3
- 102100027208 T-cell antigen CD7 Human genes 0.000 description 3
- 102100025244 T-cell surface glycoprotein CD5 Human genes 0.000 description 3
- 102100024586 Tumor necrosis factor ligand superfamily member 14 Human genes 0.000 description 3
- 102100031988 Tumor necrosis factor ligand superfamily member 6 Human genes 0.000 description 3
- 102100029675 Tumor necrosis factor receptor superfamily member 13B Human genes 0.000 description 3
- 102100040245 Tumor necrosis factor receptor superfamily member 5 Human genes 0.000 description 3
- 201000006704 Ulcerative Colitis Diseases 0.000 description 3
- 150000007513 acids Chemical class 0.000 description 3
- 239000000443 aerosol Substances 0.000 description 3
- 230000007815 allergy Effects 0.000 description 3
- 230000002924 anti-infective effect Effects 0.000 description 3
- 230000003110 anti-inflammatory effect Effects 0.000 description 3
- 230000008901 benefit Effects 0.000 description 3
- 230000004071 biological effect Effects 0.000 description 3
- 230000008499 blood brain barrier function Effects 0.000 description 3
- 210000001218 blood-brain barrier Anatomy 0.000 description 3
- 239000000969 carrier Substances 0.000 description 3
- 230000021164 cell adhesion Effects 0.000 description 3
- 208000032852 chronic lymphocytic leukemia Diseases 0.000 description 3
- DQLATGHUWYMOKM-UHFFFAOYSA-L cisplatin Chemical compound N[Pt](N)(Cl)Cl DQLATGHUWYMOKM-UHFFFAOYSA-L 0.000 description 3
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
- 238000000576 coating method Methods 0.000 description 3
- 238000002648 combination therapy Methods 0.000 description 3
- 230000004540 complement-dependent cytotoxicity Effects 0.000 description 3
- STQGQHZAVUOBTE-VGBVRHCVSA-N daunorubicin Chemical compound O([C@H]1C[C@@](O)(CC=2C(O)=C3C(=O)C=4C=CC=C(C=4C(=O)C3=C(O)C=21)OC)C(C)=O)[C@H]1C[C@H](N)[C@H](O)[C@H](C)O1 STQGQHZAVUOBTE-VGBVRHCVSA-N 0.000 description 3
- 230000001419 dependent effect Effects 0.000 description 3
- 229960002086 dextran Drugs 0.000 description 3
- 239000006185 dispersion Substances 0.000 description 3
- 229960004679 doxorubicin Drugs 0.000 description 3
- 239000003623 enhancer Substances 0.000 description 3
- 150000002148 esters Chemical class 0.000 description 3
- 239000003862 glucocorticoid Substances 0.000 description 3
- 239000000122 growth hormone Substances 0.000 description 3
- 210000005260 human cell Anatomy 0.000 description 3
- 230000008595 infiltration Effects 0.000 description 3
- 238000001764 infiltration Methods 0.000 description 3
- 239000004615 ingredient Substances 0.000 description 3
- 239000003112 inhibitor Substances 0.000 description 3
- 230000005764 inhibitory process Effects 0.000 description 3
- 238000007918 intramuscular administration Methods 0.000 description 3
- 239000007951 isotonicity adjuster Substances 0.000 description 3
- 210000002429 large intestine Anatomy 0.000 description 3
- 239000000787 lecithin Substances 0.000 description 3
- 229940067606 lecithin Drugs 0.000 description 3
- 235000010445 lecithin Nutrition 0.000 description 3
- 230000000670 limiting effect Effects 0.000 description 3
- 230000003211 malignant effect Effects 0.000 description 3
- 239000000463 material Substances 0.000 description 3
- 238000002703 mutagenesis Methods 0.000 description 3
- 231100000350 mutagenesis Toxicity 0.000 description 3
- 210000000653 nervous system Anatomy 0.000 description 3
- 231100000252 nontoxic Toxicity 0.000 description 3
- 230000003000 nontoxic effect Effects 0.000 description 3
- 229920005862 polyol Polymers 0.000 description 3
- 150000003077 polyols Chemical class 0.000 description 3
- 239000000843 powder Substances 0.000 description 3
- 230000000069 prophylactic effect Effects 0.000 description 3
- 238000000746 purification Methods 0.000 description 3
- 208000023504 respiratory system disease Diseases 0.000 description 3
- 230000004044 response Effects 0.000 description 3
- 230000000717 retained effect Effects 0.000 description 3
- 239000000523 sample Substances 0.000 description 3
- 239000011780 sodium chloride Substances 0.000 description 3
- 239000002904 solvent Substances 0.000 description 3
- 238000010561 standard procedure Methods 0.000 description 3
- 238000007920 subcutaneous administration Methods 0.000 description 3
- 235000000346 sugar Nutrition 0.000 description 3
- 238000002198 surface plasmon resonance spectroscopy Methods 0.000 description 3
- 208000024891 symptom Diseases 0.000 description 3
- 208000011580 syndromic disease Diseases 0.000 description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 3
- MTCFGRXMJLQNBG-REOHCLBHSA-N (2S)-2-Amino-3-hydroxypropansäure Chemical compound OC[C@H](N)C(O)=O MTCFGRXMJLQNBG-REOHCLBHSA-N 0.000 description 2
- IAKHMKGGTNLKSZ-INIZCTEOSA-N (S)-colchicine Chemical compound C1([C@@H](NC(C)=O)CC2)=CC(=O)C(OC)=CC=C1C1=C2C=C(OC)C(OC)=C1OC IAKHMKGGTNLKSZ-INIZCTEOSA-N 0.000 description 2
- NHBKXEKEPDILRR-UHFFFAOYSA-N 2,3-bis(butanoylsulfanyl)propyl butanoate Chemical compound CCCC(=O)OCC(SC(=O)CCC)CSC(=O)CCC NHBKXEKEPDILRR-UHFFFAOYSA-N 0.000 description 2
- HZAXFHJVJLSVMW-UHFFFAOYSA-N 2-Aminoethan-1-ol Chemical compound NCCO HZAXFHJVJLSVMW-UHFFFAOYSA-N 0.000 description 2
- KIUMMUBSPKGMOY-UHFFFAOYSA-N 3,3'-Dithiobis(6-nitrobenzoic acid) Chemical compound C1=C([N+]([O-])=O)C(C(=O)O)=CC(SSC=2C=C(C(=CC=2)[N+]([O-])=O)C(O)=O)=C1 KIUMMUBSPKGMOY-UHFFFAOYSA-N 0.000 description 2
- VXPSQDAMFATNNG-UHFFFAOYSA-N 3-[2-(2,5-dioxopyrrol-3-yl)phenyl]pyrrole-2,5-dione Chemical compound O=C1NC(=O)C(C=2C(=CC=CC=2)C=2C(NC(=O)C=2)=O)=C1 VXPSQDAMFATNNG-UHFFFAOYSA-N 0.000 description 2
- CORXEUSRKLNMDW-UHFFFAOYSA-N 3-[[1-(2,5-dioxopyrrolidin-1-yl)-2h-pyridin-2-yl]disulfanyl]propanoic acid Chemical compound OC(=O)CCSSC1C=CC=CN1N1C(=O)CCC1=O CORXEUSRKLNMDW-UHFFFAOYSA-N 0.000 description 2
- 102100040842 3-galactosyl-N-acetylglucosaminide 4-alpha-L-fucosyltransferase FUT3 Human genes 0.000 description 2
- 102100033400 4F2 cell-surface antigen heavy chain Human genes 0.000 description 2
- 102100022464 5'-nucleotidase Human genes 0.000 description 2
- 102100031585 ADP-ribosyl cyclase/cyclic ADP-ribose hydrolase 1 Human genes 0.000 description 2
- 102100029824 ADP-ribosyl cyclase/cyclic ADP-ribose hydrolase 2 Human genes 0.000 description 2
- 102100033793 ALK tyrosine kinase receptor Human genes 0.000 description 2
- 102100033350 ATP-dependent translocase ABCB1 Human genes 0.000 description 2
- 102100026402 Adhesion G protein-coupled receptor E2 Human genes 0.000 description 2
- 102100034452 Alternative prion protein Human genes 0.000 description 2
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 2
- 208000012657 Atopic disease Diseases 0.000 description 2
- 102100029822 B- and T-lymphocyte attenuator Human genes 0.000 description 2
- 102100025218 B-cell differentiation antigen CD72 Human genes 0.000 description 2
- 102100022005 B-lymphocyte antigen CD20 Human genes 0.000 description 2
- 102100028239 Basal cell adhesion molecule Human genes 0.000 description 2
- 102100032412 Basigin Human genes 0.000 description 2
- 206010005003 Bladder cancer Diseases 0.000 description 2
- 102100038341 Blood group Rh(CE) polypeptide Human genes 0.000 description 2
- 102100025423 Bone morphogenetic protein receptor type-1A Human genes 0.000 description 2
- 102100027052 Bone morphogenetic protein receptor type-1B Human genes 0.000 description 2
- NLZUEZXRPGMBCV-UHFFFAOYSA-N Butylhydroxytoluene Chemical compound CC1=CC(C(C)(C)C)=C(O)C(C(C)(C)C)=C1 NLZUEZXRPGMBCV-UHFFFAOYSA-N 0.000 description 2
- 102100031172 C-C chemokine receptor type 1 Human genes 0.000 description 2
- 102100031151 C-C chemokine receptor type 2 Human genes 0.000 description 2
- 102100024167 C-C chemokine receptor type 3 Human genes 0.000 description 2
- 102100037853 C-C chemokine receptor type 4 Human genes 0.000 description 2
- 102100035875 C-C chemokine receptor type 5 Human genes 0.000 description 2
- 102100036301 C-C chemokine receptor type 7 Human genes 0.000 description 2
- 102100036305 C-C chemokine receptor type 8 Human genes 0.000 description 2
- 102100036303 C-C chemokine receptor type 9 Human genes 0.000 description 2
- 102100036166 C-X-C chemokine receptor type 1 Human genes 0.000 description 2
- 102100028989 C-X-C chemokine receptor type 2 Human genes 0.000 description 2
- 102100028990 C-X-C chemokine receptor type 3 Human genes 0.000 description 2
- 102100031658 C-X-C chemokine receptor type 5 Human genes 0.000 description 2
- 102100025618 C-X-C chemokine receptor type 6 Human genes 0.000 description 2
- 102100040843 C-type lectin domain family 4 member M Human genes 0.000 description 2
- 102100037917 CD109 antigen Human genes 0.000 description 2
- 102100035893 CD151 antigen Human genes 0.000 description 2
- 102100024263 CD160 antigen Human genes 0.000 description 2
- 108010009992 CD163 antigen Proteins 0.000 description 2
- 102100024210 CD166 antigen Human genes 0.000 description 2
- 102100024209 CD177 antigen Human genes 0.000 description 2
- 102100038077 CD226 antigen Human genes 0.000 description 2
- 102100038078 CD276 antigen Human genes 0.000 description 2
- 102100025240 CD320 antigen Human genes 0.000 description 2
- 108010045374 CD36 Antigens Proteins 0.000 description 2
- 102000053028 CD36 Antigens Human genes 0.000 description 2
- 101150112561 CD36 gene Proteins 0.000 description 2
- 108010029697 CD40 Ligand Proteins 0.000 description 2
- 102100032912 CD44 antigen Human genes 0.000 description 2
- 102100036008 CD48 antigen Human genes 0.000 description 2
- 102100022002 CD59 glycoprotein Human genes 0.000 description 2
- 102100025222 CD63 antigen Human genes 0.000 description 2
- 102100025221 CD70 antigen Human genes 0.000 description 2
- 102100027221 CD81 antigen Human genes 0.000 description 2
- 102100027217 CD82 antigen Human genes 0.000 description 2
- 102100035793 CD83 antigen Human genes 0.000 description 2
- 108060001253 CD99 Proteins 0.000 description 2
- 102000024905 CD99 Human genes 0.000 description 2
- 102100035350 CUB domain-containing protein 1 Human genes 0.000 description 2
- 102100025805 Cadherin-1 Human genes 0.000 description 2
- 102100036364 Cadherin-2 Human genes 0.000 description 2
- 241000282836 Camelus dromedarius Species 0.000 description 2
- 102100029391 Cardiotrophin-like cytokine factor 1 Human genes 0.000 description 2
- 101710107109 Cardiotrophin-like cytokine factor 1 Proteins 0.000 description 2
- 102000005600 Cathepsins Human genes 0.000 description 2
- 108010084457 Cathepsins Proteins 0.000 description 2
- 102100037182 Cation-independent mannose-6-phosphate receptor Human genes 0.000 description 2
- 102100031699 Choline transporter-like protein 1 Human genes 0.000 description 2
- 208000006545 Chronic Obstructive Pulmonary Disease Diseases 0.000 description 2
- 108020004705 Codon Proteins 0.000 description 2
- 102100025877 Complement component C1q receptor Human genes 0.000 description 2
- 206010053138 Congenital aplastic anaemia Diseases 0.000 description 2
- 102400000739 Corticotropin Human genes 0.000 description 2
- 101800000414 Corticotropin Proteins 0.000 description 2
- 208000011231 Crohn disease Diseases 0.000 description 2
- CMSMOCZEIVJLDB-UHFFFAOYSA-N Cyclophosphamide Chemical compound ClCCN(CCCl)P1(=O)NCCCO1 CMSMOCZEIVJLDB-UHFFFAOYSA-N 0.000 description 2
- 229930105110 Cyclosporin A Natural products 0.000 description 2
- PMATZTZNYRCHOR-CGLBZJNRSA-N Cyclosporin A Chemical compound CC[C@@H]1NC(=O)[C@H]([C@H](O)[C@H](C)C\C=C\C)N(C)C(=O)[C@H](C(C)C)N(C)C(=O)[C@H](CC(C)C)N(C)C(=O)[C@H](CC(C)C)N(C)C(=O)[C@@H](C)NC(=O)[C@H](C)NC(=O)[C@H](CC(C)C)N(C)C(=O)[C@H](C(C)C)NC(=O)[C@H](CC(C)C)N(C)C(=O)CN(C)C1=O PMATZTZNYRCHOR-CGLBZJNRSA-N 0.000 description 2
- 108010036949 Cyclosporine Proteins 0.000 description 2
- 241000701022 Cytomegalovirus Species 0.000 description 2
- 102100039498 Cytotoxic T-lymphocyte protein 4 Human genes 0.000 description 2
- 101710112752 Cytotoxin Proteins 0.000 description 2
- 239000009261 D 400 Substances 0.000 description 2
- FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 2
- FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 description 2
- 239000004375 Dextrin Substances 0.000 description 2
- 229920001353 Dextrin Polymers 0.000 description 2
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 2
- 102100024364 Disintegrin and metalloproteinase domain-containing protein 8 Human genes 0.000 description 2
- KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 2
- 102100025137 Early activation antigen CD69 Human genes 0.000 description 2
- 102100029722 Ectonucleoside triphosphate diphosphohydrolase 1 Human genes 0.000 description 2
- 102100040897 Embryonic growth/differentiation factor 1 Human genes 0.000 description 2
- 102100037241 Endoglin Human genes 0.000 description 2
- 108010066687 Epithelial Cell Adhesion Molecule Proteins 0.000 description 2
- 102000018651 Epithelial Cell Adhesion Molecule Human genes 0.000 description 2
- 102100036725 Epithelial discoidin domain-containing receptor 1 Human genes 0.000 description 2
- 201000004939 Fanconi anemia Diseases 0.000 description 2
- 102100023593 Fibroblast growth factor receptor 1 Human genes 0.000 description 2
- 102100023600 Fibroblast growth factor receptor 2 Human genes 0.000 description 2
- 102100027842 Fibroblast growth factor receptor 3 Human genes 0.000 description 2
- 102100027844 Fibroblast growth factor receptor 4 Human genes 0.000 description 2
- GHASVSINZRGABV-UHFFFAOYSA-N Fluorouracil Chemical compound FC1=CNC(=O)NC1=O GHASVSINZRGABV-UHFFFAOYSA-N 0.000 description 2
- 102000012673 Follicle Stimulating Hormone Human genes 0.000 description 2
- 108010079345 Follicle Stimulating Hormone Proteins 0.000 description 2
- 102100021261 Frizzled-10 Human genes 0.000 description 2
- 102100039820 Frizzled-4 Human genes 0.000 description 2
- 102100028461 Frizzled-9 Human genes 0.000 description 2
- 102100021260 Galactosylgalactosylxylosylprotein 3-beta-glucuronosyltransferase 1 Human genes 0.000 description 2
- 206010017969 Gastrointestinal inflammatory conditions Diseases 0.000 description 2
- 108010010803 Gelatin Proteins 0.000 description 2
- 102100025783 Glutamyl aminopeptidase Human genes 0.000 description 2
- 102100033366 Glutathione hydrolase 1 proenzyme Human genes 0.000 description 2
- 102100039622 Granulocyte colony-stimulating factor receptor Human genes 0.000 description 2
- 108010017213 Granulocyte-Macrophage Colony-Stimulating Factor Proteins 0.000 description 2
- 102100039620 Granulocyte-macrophage colony-stimulating factor Human genes 0.000 description 2
- 108010090296 Growth Differentiation Factor 1 Proteins 0.000 description 2
- 102100030595 HLA class II histocompatibility antigen gamma chain Human genes 0.000 description 2
- 102100031573 Hematopoietic progenitor cell antigen CD34 Human genes 0.000 description 2
- 208000036066 Hemophagocytic Lymphohistiocytosis Diseases 0.000 description 2
- 102100026122 High affinity immunoglobulin gamma Fc receptor I Human genes 0.000 description 2
- 208000032672 Histiocytosis haematophagic Diseases 0.000 description 2
- 208000017604 Hodgkin disease Diseases 0.000 description 2
- 208000010747 Hodgkins lymphoma Diseases 0.000 description 2
- 101000800023 Homo sapiens 4F2 cell-surface antigen heavy chain Proteins 0.000 description 2
- 101000678236 Homo sapiens 5'-nucleotidase Proteins 0.000 description 2
- 101000777636 Homo sapiens ADP-ribosyl cyclase/cyclic ADP-ribose hydrolase 1 Proteins 0.000 description 2
- 101000794082 Homo sapiens ADP-ribosyl cyclase/cyclic ADP-ribose hydrolase 2 Proteins 0.000 description 2
- 101000718211 Homo sapiens Adhesion G protein-coupled receptor E2 Proteins 0.000 description 2
- 101000924727 Homo sapiens Alternative prion protein Proteins 0.000 description 2
- 101000864344 Homo sapiens B- and T-lymphocyte attenuator Proteins 0.000 description 2
- 101000934359 Homo sapiens B-cell differentiation antigen CD72 Proteins 0.000 description 2
- 101000897405 Homo sapiens B-lymphocyte antigen CD20 Proteins 0.000 description 2
- 101000935638 Homo sapiens Basal cell adhesion molecule Proteins 0.000 description 2
- 101000666610 Homo sapiens Blood group Rh(CE) polypeptide Proteins 0.000 description 2
- 101000934638 Homo sapiens Bone morphogenetic protein receptor type-1A Proteins 0.000 description 2
- 101000984546 Homo sapiens Bone morphogenetic protein receptor type-1B Proteins 0.000 description 2
- 101000716063 Homo sapiens C-C chemokine receptor type 8 Proteins 0.000 description 2
- 101000716070 Homo sapiens C-C chemokine receptor type 9 Proteins 0.000 description 2
- 101000947174 Homo sapiens C-X-C chemokine receptor type 1 Proteins 0.000 description 2
- 101000916059 Homo sapiens C-X-C chemokine receptor type 2 Proteins 0.000 description 2
- 101000916050 Homo sapiens C-X-C chemokine receptor type 3 Proteins 0.000 description 2
- 101000922405 Homo sapiens C-X-C chemokine receptor type 5 Proteins 0.000 description 2
- 101000856683 Homo sapiens C-X-C chemokine receptor type 6 Proteins 0.000 description 2
- 101000749311 Homo sapiens C-type lectin domain family 4 member M Proteins 0.000 description 2
- 101000738399 Homo sapiens CD109 antigen Proteins 0.000 description 2
- 101000946874 Homo sapiens CD151 antigen Proteins 0.000 description 2
- 101000761938 Homo sapiens CD160 antigen Proteins 0.000 description 2
- 101000980845 Homo sapiens CD177 antigen Proteins 0.000 description 2
- 101000884298 Homo sapiens CD226 antigen Proteins 0.000 description 2
- 101000884279 Homo sapiens CD276 antigen Proteins 0.000 description 2
- 101000934335 Homo sapiens CD320 antigen Proteins 0.000 description 2
- 101000868215 Homo sapiens CD40 ligand Proteins 0.000 description 2
- 101000868273 Homo sapiens CD44 antigen Proteins 0.000 description 2
- 101000716130 Homo sapiens CD48 antigen Proteins 0.000 description 2
- 101000897400 Homo sapiens CD59 glycoprotein Proteins 0.000 description 2
- 101000934368 Homo sapiens CD63 antigen Proteins 0.000 description 2
- 101000934356 Homo sapiens CD70 antigen Proteins 0.000 description 2
- 101000914479 Homo sapiens CD81 antigen Proteins 0.000 description 2
- 101000914469 Homo sapiens CD82 antigen Proteins 0.000 description 2
- 101000946856 Homo sapiens CD83 antigen Proteins 0.000 description 2
- 101000737742 Homo sapiens CUB domain-containing protein 1 Proteins 0.000 description 2
- 101000714537 Homo sapiens Cadherin-2 Proteins 0.000 description 2
- 101000933665 Homo sapiens Complement component C1q receptor Proteins 0.000 description 2
- 101000832767 Homo sapiens Disintegrin and metalloproteinase domain-containing protein 8 Proteins 0.000 description 2
- 101000934374 Homo sapiens Early activation antigen CD69 Proteins 0.000 description 2
- 101001024566 Homo sapiens Ecto-ADP-ribosyltransferase 4 Proteins 0.000 description 2
- 101001012447 Homo sapiens Ectonucleoside triphosphate diphosphohydrolase 1 Proteins 0.000 description 2
- 101000819451 Homo sapiens Frizzled-10 Proteins 0.000 description 2
- 101000885581 Homo sapiens Frizzled-4 Proteins 0.000 description 2
- 101001061405 Homo sapiens Frizzled-9 Proteins 0.000 description 2
- 101000894906 Homo sapiens Galactosylgalactosylxylosylprotein 3-beta-glucuronosyltransferase 1 Proteins 0.000 description 2
- 101000997558 Homo sapiens Glutathione hydrolase 1 proenzyme Proteins 0.000 description 2
- 101001082627 Homo sapiens HLA class II histocompatibility antigen gamma chain Proteins 0.000 description 2
- 101000777663 Homo sapiens Hematopoietic progenitor cell antigen CD34 Proteins 0.000 description 2
- 101000913074 Homo sapiens High affinity immunoglobulin gamma Fc receptor I Proteins 0.000 description 2
- 101001019455 Homo sapiens ICOS ligand Proteins 0.000 description 2
- 101000878602 Homo sapiens Immunoglobulin alpha Fc receptor Proteins 0.000 description 2
- 101001042104 Homo sapiens Inducible T-cell costimulator Proteins 0.000 description 2
- 101001078143 Homo sapiens Integrin alpha-IIb Proteins 0.000 description 2
- 101000599858 Homo sapiens Intercellular adhesion molecule 2 Proteins 0.000 description 2
- 101001034844 Homo sapiens Interferon-induced transmembrane protein 1 Proteins 0.000 description 2
- 101001076418 Homo sapiens Interleukin-1 receptor type 1 Proteins 0.000 description 2
- 101001003142 Homo sapiens Interleukin-12 receptor subunit beta-1 Proteins 0.000 description 2
- 101001019598 Homo sapiens Interleukin-17 receptor A Proteins 0.000 description 2
- 101000998120 Homo sapiens Interleukin-3 receptor subunit alpha Proteins 0.000 description 2
- 101000599048 Homo sapiens Interleukin-6 receptor subunit alpha Proteins 0.000 description 2
- 101001050320 Homo sapiens Junctional adhesion molecule B Proteins 0.000 description 2
- 101001049181 Homo sapiens Killer cell lectin-like receptor subfamily B member 1 Proteins 0.000 description 2
- 101000605020 Homo sapiens Large neutral amino acids transporter small subunit 1 Proteins 0.000 description 2
- 101000777628 Homo sapiens Leukocyte antigen CD37 Proteins 0.000 description 2
- 101000980823 Homo sapiens Leukocyte surface antigen CD53 Proteins 0.000 description 2
- 101001138062 Homo sapiens Leukocyte-associated immunoglobulin-like receptor 1 Proteins 0.000 description 2
- 101000608935 Homo sapiens Leukosialin Proteins 0.000 description 2
- 101000878605 Homo sapiens Low affinity immunoglobulin epsilon Fc receptor Proteins 0.000 description 2
- 101001137987 Homo sapiens Lymphocyte activation gene 3 protein Proteins 0.000 description 2
- 101001018034 Homo sapiens Lymphocyte antigen 75 Proteins 0.000 description 2
- 101001063392 Homo sapiens Lymphocyte function-associated antigen 3 Proteins 0.000 description 2
- 101000604998 Homo sapiens Lysosome-associated membrane glycoprotein 3 Proteins 0.000 description 2
- 101000916644 Homo sapiens Macrophage colony-stimulating factor 1 receptor Proteins 0.000 description 2
- 101001134216 Homo sapiens Macrophage scavenger receptor types I and II Proteins 0.000 description 2
- 101000934372 Homo sapiens Macrosialin Proteins 0.000 description 2
- 101000573901 Homo sapiens Major prion protein Proteins 0.000 description 2
- 101000798109 Homo sapiens Melanotransferrin Proteins 0.000 description 2
- 101000961414 Homo sapiens Membrane cofactor protein Proteins 0.000 description 2
- 101001133056 Homo sapiens Mucin-1 Proteins 0.000 description 2
- 101001109501 Homo sapiens NKG2-D type II integral membrane protein Proteins 0.000 description 2
- 101000589301 Homo sapiens Natural cytotoxicity triggering receptor 1 Proteins 0.000 description 2
- 101000589305 Homo sapiens Natural cytotoxicity triggering receptor 2 Proteins 0.000 description 2
- 101000884270 Homo sapiens Natural killer cell receptor 2B4 Proteins 0.000 description 2
- 101000971513 Homo sapiens Natural killer cells antigen CD94 Proteins 0.000 description 2
- 101001023712 Homo sapiens Nectin-3 Proteins 0.000 description 2
- 101000581981 Homo sapiens Neural cell adhesion molecule 1 Proteins 0.000 description 2
- 101001098352 Homo sapiens OX-2 membrane glycoprotein Proteins 0.000 description 2
- 101001117312 Homo sapiens Programmed cell death 1 ligand 2 Proteins 0.000 description 2
- 101001043564 Homo sapiens Prolow-density lipoprotein receptor-related protein 1 Proteins 0.000 description 2
- 101001117314 Homo sapiens Prostaglandin D2 receptor 2 Proteins 0.000 description 2
- 101000931590 Homo sapiens Prostaglandin F2 receptor negative regulator Proteins 0.000 description 2
- 101000994437 Homo sapiens Protein jagged-1 Proteins 0.000 description 2
- 101001012157 Homo sapiens Receptor tyrosine-protein kinase erbB-2 Proteins 0.000 description 2
- 101000738771 Homo sapiens Receptor-type tyrosine-protein phosphatase C Proteins 0.000 description 2
- 101000633778 Homo sapiens SLAM family member 5 Proteins 0.000 description 2
- 101000739767 Homo sapiens Semaphorin-7A Proteins 0.000 description 2
- 101000863900 Homo sapiens Sialic acid-binding Ig-like lectin 5 Proteins 0.000 description 2
- 101000863882 Homo sapiens Sialic acid-binding Ig-like lectin 7 Proteins 0.000 description 2
- 101000974834 Homo sapiens Sodium/potassium-transporting ATPase subunit beta-3 Proteins 0.000 description 2
- 101000934376 Homo sapiens T-cell differentiation antigen CD6 Proteins 0.000 description 2
- 101000716149 Homo sapiens T-cell surface glycoprotein CD1b Proteins 0.000 description 2
- 101000596234 Homo sapiens T-cell surface protein tactile Proteins 0.000 description 2
- 101001018021 Homo sapiens T-lymphocyte surface antigen Ly-9 Proteins 0.000 description 2
- 101000799466 Homo sapiens Thrombopoietin receptor Proteins 0.000 description 2
- 101000800116 Homo sapiens Thy-1 membrane glycoprotein Proteins 0.000 description 2
- 101000763579 Homo sapiens Toll-like receptor 1 Proteins 0.000 description 2
- 101000669406 Homo sapiens Toll-like receptor 6 Proteins 0.000 description 2
- 101000800483 Homo sapiens Toll-like receptor 8 Proteins 0.000 description 2
- 101000830600 Homo sapiens Tumor necrosis factor ligand superfamily member 13 Proteins 0.000 description 2
- 101000610604 Homo sapiens Tumor necrosis factor receptor superfamily member 10B Proteins 0.000 description 2
- 101000610609 Homo sapiens Tumor necrosis factor receptor superfamily member 10D Proteins 0.000 description 2
- 101000648505 Homo sapiens Tumor necrosis factor receptor superfamily member 12A Proteins 0.000 description 2
- 101000801255 Homo sapiens Tumor necrosis factor receptor superfamily member 17 Proteins 0.000 description 2
- 101000679851 Homo sapiens Tumor necrosis factor receptor superfamily member 4 Proteins 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
- 229920001612 Hydroxyethyl starch Polymers 0.000 description 2
- 102100034980 ICOS ligand Human genes 0.000 description 2
- 102000009490 IgG Receptors Human genes 0.000 description 2
- 102100038005 Immunoglobulin alpha Fc receptor Human genes 0.000 description 2
- 102100022516 Immunoglobulin superfamily member 2 Human genes 0.000 description 2
- 102100036489 Immunoglobulin superfamily member 8 Human genes 0.000 description 2
- 102100021317 Inducible T-cell costimulator Human genes 0.000 description 2
- 102100036721 Insulin receptor Human genes 0.000 description 2
- 102100039688 Insulin-like growth factor 1 receptor Human genes 0.000 description 2
- 102100025306 Integrin alpha-IIb Human genes 0.000 description 2
- 102100022297 Integrin alpha-X Human genes 0.000 description 2
- 102100025390 Integrin beta-2 Human genes 0.000 description 2
- 108010064600 Intercellular Adhesion Molecule-3 Proteins 0.000 description 2
- 102100037872 Intercellular adhesion molecule 2 Human genes 0.000 description 2
- 102100037850 Interferon gamma Human genes 0.000 description 2
- 102100035678 Interferon gamma receptor 1 Human genes 0.000 description 2
- 108010074328 Interferon-gamma Proteins 0.000 description 2
- 102100040021 Interferon-induced transmembrane protein 1 Human genes 0.000 description 2
- 102100026016 Interleukin-1 receptor type 1 Human genes 0.000 description 2
- 102000013462 Interleukin-12 Human genes 0.000 description 2
- 108010065805 Interleukin-12 Proteins 0.000 description 2
- 102100020790 Interleukin-12 receptor subunit beta-1 Human genes 0.000 description 2
- 102100035018 Interleukin-17 receptor A Human genes 0.000 description 2
- 102100030703 Interleukin-22 Human genes 0.000 description 2
- 102100033493 Interleukin-3 receptor subunit alpha Human genes 0.000 description 2
- 102000004388 Interleukin-4 Human genes 0.000 description 2
- 108090000978 Interleukin-4 Proteins 0.000 description 2
- 102100039078 Interleukin-4 receptor subunit alpha Human genes 0.000 description 2
- 102100021593 Interleukin-7 receptor subunit alpha Human genes 0.000 description 2
- 102100026244 Interleukin-9 receptor Human genes 0.000 description 2
- 102100022304 Junctional adhesion molecule A Human genes 0.000 description 2
- 102100023430 Junctional adhesion molecule B Human genes 0.000 description 2
- 102100023678 Killer cell lectin-like receptor subfamily B member 1 Human genes 0.000 description 2
- XUJNEKJLAYXESH-REOHCLBHSA-N L-Cysteine Chemical compound SC[C@H](N)C(O)=O XUJNEKJLAYXESH-REOHCLBHSA-N 0.000 description 2
- QNAYBMKLOCPYGJ-REOHCLBHSA-N L-alanine Chemical compound C[C@H](N)C(O)=O QNAYBMKLOCPYGJ-REOHCLBHSA-N 0.000 description 2
- HNDVDQJCIGZPNO-YFKPBYRVSA-N L-histidine Chemical compound OC(=O)[C@@H](N)CC1=CN=CN1 HNDVDQJCIGZPNO-YFKPBYRVSA-N 0.000 description 2
- AGPKZVBTJJNPAG-WHFBIAKZSA-N L-isoleucine Chemical compound CC[C@H](C)[C@H](N)C(O)=O AGPKZVBTJJNPAG-WHFBIAKZSA-N 0.000 description 2
- COLNVLDHVKWLRT-QMMMGPOBSA-N L-phenylalanine Chemical compound OC(=O)[C@@H](N)CC1=CC=CC=C1 COLNVLDHVKWLRT-QMMMGPOBSA-N 0.000 description 2
- AYFVYJQAPQTCCC-GBXIJSLDSA-N L-threonine Chemical compound C[C@@H](O)[C@H](N)C(O)=O AYFVYJQAPQTCCC-GBXIJSLDSA-N 0.000 description 2
- QIVBCDIJIAJPQS-VIFPVBQESA-N L-tryptophane Chemical compound C1=CC=C2C(C[C@H](N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-VIFPVBQESA-N 0.000 description 2
- OUYCCCASQSFEME-QMMMGPOBSA-N L-tyrosine Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-QMMMGPOBSA-N 0.000 description 2
- KZSNJWFQEVHDMF-BYPYZUCNSA-N L-valine Chemical compound CC(C)[C@H](N)C(O)=O KZSNJWFQEVHDMF-BYPYZUCNSA-N 0.000 description 2
- 102000017578 LAG3 Human genes 0.000 description 2
- 201000005099 Langerhans cell histiocytosis Diseases 0.000 description 2
- 102100031775 Leptin receptor Human genes 0.000 description 2
- 102000004058 Leukemia inhibitory factor Human genes 0.000 description 2
- 108090000581 Leukemia inhibitory factor Proteins 0.000 description 2
- 102100021747 Leukemia inhibitory factor receptor Human genes 0.000 description 2
- 102100031586 Leukocyte antigen CD37 Human genes 0.000 description 2
- 102100025584 Leukocyte immunoglobulin-like receptor subfamily B member 1 Human genes 0.000 description 2
- 102100024221 Leukocyte surface antigen CD53 Human genes 0.000 description 2
- 102100020943 Leukocyte-associated immunoglobulin-like receptor 1 Human genes 0.000 description 2
- 102100039564 Leukosialin Human genes 0.000 description 2
- GQYIWUVLTXOXAJ-UHFFFAOYSA-N Lomustine Chemical compound ClCCN(N=O)C(=O)NC1CCCCC1 GQYIWUVLTXOXAJ-UHFFFAOYSA-N 0.000 description 2
- 102100038007 Low affinity immunoglobulin epsilon Fc receptor Human genes 0.000 description 2
- 102000009151 Luteinizing Hormone Human genes 0.000 description 2
- 108010073521 Luteinizing Hormone Proteins 0.000 description 2
- 102100033486 Lymphocyte antigen 75 Human genes 0.000 description 2
- 102100030984 Lymphocyte function-associated antigen 3 Human genes 0.000 description 2
- 102100038213 Lysosome-associated membrane glycoprotein 3 Human genes 0.000 description 2
- 102100028198 Macrophage colony-stimulating factor 1 receptor Human genes 0.000 description 2
- 102100034184 Macrophage scavenger receptor types I and II Human genes 0.000 description 2
- 102100025136 Macrosialin Human genes 0.000 description 2
- 102100032239 Melanotransferrin Human genes 0.000 description 2
- 102000018697 Membrane Proteins Human genes 0.000 description 2
- 108010052285 Membrane Proteins Proteins 0.000 description 2
- 102100039373 Membrane cofactor protein Human genes 0.000 description 2
- 102100034256 Mucin-1 Human genes 0.000 description 2
- 102100031789 Myeloid-derived growth factor Human genes 0.000 description 2
- 102100022680 NKG2-D type II integral membrane protein Human genes 0.000 description 2
- 102100032870 Natural cytotoxicity triggering receptor 1 Human genes 0.000 description 2
- 102100032851 Natural cytotoxicity triggering receptor 2 Human genes 0.000 description 2
- 102100038082 Natural killer cell receptor 2B4 Human genes 0.000 description 2
- 102100021462 Natural killer cells antigen CD94 Human genes 0.000 description 2
- 102100035488 Nectin-2 Human genes 0.000 description 2
- 102100035487 Nectin-3 Human genes 0.000 description 2
- 102100027347 Neural cell adhesion molecule 1 Human genes 0.000 description 2
- 102100037589 OX-2 membrane glycoprotein Human genes 0.000 description 2
- 102100034925 P-selectin glycoprotein ligand 1 Human genes 0.000 description 2
- 102000003982 Parathyroid hormone Human genes 0.000 description 2
- 108090000445 Parathyroid hormone Proteins 0.000 description 2
- 208000000733 Paroxysmal Hemoglobinuria Diseases 0.000 description 2
- 108091005804 Peptidases Proteins 0.000 description 2
- 102000035195 Peptidases Human genes 0.000 description 2
- 206010057249 Phagocytosis Diseases 0.000 description 2
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 2
- 102100036050 Phosphatidylinositol N-acetylglucosaminyltransferase subunit A Human genes 0.000 description 2
- 102100024616 Platelet endothelial cell adhesion molecule Human genes 0.000 description 2
- 102100026547 Platelet-derived growth factor receptor beta Human genes 0.000 description 2
- 206010035664 Pneumonia Diseases 0.000 description 2
- 102100029740 Poliovirus receptor Human genes 0.000 description 2
- 239000004698 Polyethylene Substances 0.000 description 2
- RJKFOVLPORLFTN-LEKSSAKUSA-N Progesterone Chemical compound C1CC2=CC(=O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H](C(=O)C)[C@@]1(C)CC2 RJKFOVLPORLFTN-LEKSSAKUSA-N 0.000 description 2
- 102100024216 Programmed cell death 1 ligand 1 Human genes 0.000 description 2
- 102100024213 Programmed cell death 1 ligand 2 Human genes 0.000 description 2
- 102100040678 Programmed cell death protein 1 Human genes 0.000 description 2
- 102000003946 Prolactin Human genes 0.000 description 2
- 108010057464 Prolactin Proteins 0.000 description 2
- 102100021923 Prolow-density lipoprotein receptor-related protein 1 Human genes 0.000 description 2
- ZTHYODDOHIVTJV-UHFFFAOYSA-N Propyl gallate Chemical compound CCCOC(=O)C1=CC(O)=C(O)C(O)=C1 ZTHYODDOHIVTJV-UHFFFAOYSA-N 0.000 description 2
- 102100024218 Prostaglandin D2 receptor 2 Human genes 0.000 description 2
- 102100020864 Prostaglandin F2 receptor negative regulator Human genes 0.000 description 2
- 239000004365 Protease Substances 0.000 description 2
- 102100032702 Protein jagged-1 Human genes 0.000 description 2
- 201000001263 Psoriatic Arthritis Diseases 0.000 description 2
- 208000036824 Psoriatic arthropathy Diseases 0.000 description 2
- 102100030086 Receptor tyrosine-protein kinase erbB-2 Human genes 0.000 description 2
- 102100037422 Receptor-type tyrosine-protein phosphatase C Human genes 0.000 description 2
- 108020004511 Recombinant DNA Proteins 0.000 description 2
- 208000025747 Rheumatic disease Diseases 0.000 description 2
- 102100029216 SLAM family member 5 Human genes 0.000 description 2
- 240000004808 Saccharomyces cerevisiae Species 0.000 description 2
- 102100025831 Scavenger receptor cysteine-rich type 1 protein M130 Human genes 0.000 description 2
- 102100027744 Semaphorin-4D Human genes 0.000 description 2
- 102100037545 Semaphorin-7A Human genes 0.000 description 2
- 108010071390 Serum Albumin Proteins 0.000 description 2
- 102000007562 Serum Albumin Human genes 0.000 description 2
- 102100029957 Sialic acid-binding Ig-like lectin 5 Human genes 0.000 description 2
- 102100029946 Sialic acid-binding Ig-like lectin 7 Human genes 0.000 description 2
- 102100032855 Sialoadhesin Human genes 0.000 description 2
- 102100029215 Signaling lymphocytic activation molecule Human genes 0.000 description 2
- PXIPVTKHYLBLMZ-UHFFFAOYSA-N Sodium azide Chemical compound [Na+].[N-]=[N+]=[N-] PXIPVTKHYLBLMZ-UHFFFAOYSA-N 0.000 description 2
- 102100022792 Sodium/potassium-transporting ATPase subunit beta-3 Human genes 0.000 description 2
- 229920002472 Starch Polymers 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- 102100025131 T-cell differentiation antigen CD6 Human genes 0.000 description 2
- 102100035268 T-cell surface protein tactile Human genes 0.000 description 2
- 210000001744 T-lymphocyte Anatomy 0.000 description 2
- 102100033447 T-lymphocyte surface antigen Ly-9 Human genes 0.000 description 2
- 108091007178 TNFRSF10A Proteins 0.000 description 2
- QJJXYPPXXYFBGM-LFZNUXCKSA-N Tacrolimus Chemical compound C1C[C@@H](O)[C@H](OC)C[C@@H]1\C=C(/C)[C@@H]1[C@H](C)[C@@H](O)CC(=O)[C@H](CC=C)/C=C(C)/C[C@H](C)C[C@H](OC)[C@H]([C@H](C[C@H]2C)OC)O[C@@]2(O)C(=O)C(=O)N2CCCC[C@H]2C(=O)O1 QJJXYPPXXYFBGM-LFZNUXCKSA-N 0.000 description 2
- MUMGGOZAMZWBJJ-DYKIIFRCSA-N Testostosterone Chemical compound O=C1CC[C@]2(C)[C@H]3CC[C@](C)([C@H](CC4)O)[C@@H]4[C@@H]3CCC2=C1 MUMGGOZAMZWBJJ-DYKIIFRCSA-N 0.000 description 2
- AYFVYJQAPQTCCC-UHFFFAOYSA-N Threonine Natural products CC(O)C(N)C(O)=O AYFVYJQAPQTCCC-UHFFFAOYSA-N 0.000 description 2
- 239000004473 Threonine Substances 0.000 description 2
- 108010022394 Threonine synthase Proteins 0.000 description 2
- 102100034196 Thrombopoietin receptor Human genes 0.000 description 2
- 102100033523 Thy-1 membrane glycoprotein Human genes 0.000 description 2
- 102000011923 Thyrotropin Human genes 0.000 description 2
- 108010061174 Thyrotropin Proteins 0.000 description 2
- 102100030859 Tissue factor Human genes 0.000 description 2
- 102100027010 Toll-like receptor 1 Human genes 0.000 description 2
- 102100039387 Toll-like receptor 6 Human genes 0.000 description 2
- 102100033110 Toll-like receptor 8 Human genes 0.000 description 2
- QIVBCDIJIAJPQS-UHFFFAOYSA-N Tryptophan Natural products C1=CC=C2C(CC(N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-UHFFFAOYSA-N 0.000 description 2
- 108010065158 Tumor Necrosis Factor Ligand Superfamily Member 14 Proteins 0.000 description 2
- 102100024568 Tumor necrosis factor ligand superfamily member 11 Human genes 0.000 description 2
- 102100024585 Tumor necrosis factor ligand superfamily member 13 Human genes 0.000 description 2
- 102100026890 Tumor necrosis factor ligand superfamily member 4 Human genes 0.000 description 2
- 108050002568 Tumor necrosis factor ligand superfamily member 6 Proteins 0.000 description 2
- 102100032100 Tumor necrosis factor ligand superfamily member 8 Human genes 0.000 description 2
- 102100040113 Tumor necrosis factor receptor superfamily member 10A Human genes 0.000 description 2
- 102100040112 Tumor necrosis factor receptor superfamily member 10B Human genes 0.000 description 2
- 102100040110 Tumor necrosis factor receptor superfamily member 10D Human genes 0.000 description 2
- 102100028786 Tumor necrosis factor receptor superfamily member 12A Human genes 0.000 description 2
- 102100033726 Tumor necrosis factor receptor superfamily member 17 Human genes 0.000 description 2
- 102100033732 Tumor necrosis factor receptor superfamily member 1A Human genes 0.000 description 2
- 102100022153 Tumor necrosis factor receptor superfamily member 4 Human genes 0.000 description 2
- 206010067584 Type 1 diabetes mellitus Diseases 0.000 description 2
- 208000025865 Ulcer Diseases 0.000 description 2
- 208000007097 Urinary Bladder Neoplasms Diseases 0.000 description 2
- KZSNJWFQEVHDMF-UHFFFAOYSA-N Valine Natural products CC(C)C(N)C(O)=O KZSNJWFQEVHDMF-UHFFFAOYSA-N 0.000 description 2
- 102100023543 Vascular cell adhesion protein 1 Human genes 0.000 description 2
- 102100033177 Vascular endothelial growth factor receptor 2 Human genes 0.000 description 2
- 108010004977 Vasopressins Proteins 0.000 description 2
- 102000002852 Vasopressins Human genes 0.000 description 2
- JXLYSJRDGCGARV-WWYNWVTFSA-N Vinblastine Natural products O=C(O[C@H]1[C@](O)(C(=O)OC)[C@@H]2N(C)c3c(cc(c(OC)c3)[C@]3(C(=O)OC)c4[nH]c5c(c4CCN4C[C@](O)(CC)C[C@H](C3)C4)cccc5)[C@@]32[C@H]2[C@@]1(CC)C=CCN2CC3)C JXLYSJRDGCGARV-WWYNWVTFSA-N 0.000 description 2
- 230000002159 abnormal effect Effects 0.000 description 2
- NTECHUXHORNEGZ-UHFFFAOYSA-N acetyloxymethyl 3',6'-bis(acetyloxymethoxy)-2',7'-bis[3-(acetyloxymethoxy)-3-oxopropyl]-3-oxospiro[2-benzofuran-1,9'-xanthene]-5-carboxylate Chemical compound O1C(=O)C2=CC(C(=O)OCOC(C)=O)=CC=C2C21C1=CC(CCC(=O)OCOC(C)=O)=C(OCOC(C)=O)C=C1OC1=C2C=C(CCC(=O)OCOC(=O)C)C(OCOC(C)=O)=C1 NTECHUXHORNEGZ-UHFFFAOYSA-N 0.000 description 2
- RJURFGZVJUQBHK-IIXSONLDSA-N actinomycin D Chemical compound C[C@H]1OC(=O)[C@H](C(C)C)N(C)C(=O)CN(C)C(=O)[C@@H]2CCCN2C(=O)[C@@H](C(C)C)NC(=O)[C@H]1NC(=O)C1=C(N)C(=O)C(C)=C2OC(C(C)=CC=C3C(=O)N[C@@H]4C(=O)N[C@@H](C(N5CCC[C@H]5C(=O)N(C)CC(=O)N(C)[C@@H](C(C)C)C(=O)O[C@@H]4C)=O)C(C)C)=C3N=C21 RJURFGZVJUQBHK-IIXSONLDSA-N 0.000 description 2
- 210000001642 activated microglia Anatomy 0.000 description 2
- 230000004913 activation Effects 0.000 description 2
- 230000001464 adherent effect Effects 0.000 description 2
- 239000002671 adjuvant Substances 0.000 description 2
- 235000004279 alanine Nutrition 0.000 description 2
- 125000001931 aliphatic group Chemical group 0.000 description 2
- 108010004469 allophycocyanin Proteins 0.000 description 2
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 2
- 150000001412 amines Chemical class 0.000 description 2
- 239000012491 analyte Substances 0.000 description 2
- 238000004458 analytical method Methods 0.000 description 2
- 238000010171 animal model Methods 0.000 description 2
- 230000000844 anti-bacterial effect Effects 0.000 description 2
- 230000001078 anti-cholinergic effect Effects 0.000 description 2
- 229940121363 anti-inflammatory agent Drugs 0.000 description 2
- 229940088710 antibiotic agent Drugs 0.000 description 2
- 229940121375 antifungal agent Drugs 0.000 description 2
- 239000003429 antifungal agent Substances 0.000 description 2
- 239000002246 antineoplastic agent Substances 0.000 description 2
- 239000007864 aqueous solution Substances 0.000 description 2
- KBZOIRJILGZLEJ-LGYYRGKSSA-N argipressin Chemical compound C([C@H]1C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CSSC[C@@H](C(N[C@@H](CC=2C=CC(O)=CC=2)C(=O)N1)=O)N)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCCN=C(N)N)C(=O)NCC(N)=O)C1=CC=CC=C1 KBZOIRJILGZLEJ-LGYYRGKSSA-N 0.000 description 2
- 208000010668 atopic eczema Diseases 0.000 description 2
- 229960002170 azathioprine Drugs 0.000 description 2
- LMEKQMALGUDUQG-UHFFFAOYSA-N azathioprine Chemical compound CN1C=NC([N+]([O-])=O)=C1SC1=NC=NC2=C1NC=N2 LMEKQMALGUDUQG-UHFFFAOYSA-N 0.000 description 2
- 239000002585 base Substances 0.000 description 2
- 239000011230 binding agent Substances 0.000 description 2
- 229940098773 bovine serum albumin Drugs 0.000 description 2
- CZBZUDVBLSSABA-UHFFFAOYSA-N butylated hydroxyanisole Chemical compound COC1=CC=C(O)C(C(C)(C)C)=C1.COC1=CC=C(O)C=C1C(C)(C)C CZBZUDVBLSSABA-UHFFFAOYSA-N 0.000 description 2
- 239000012876 carrier material Substances 0.000 description 2
- 230000012292 cell migration Effects 0.000 description 2
- 239000001913 cellulose Substances 0.000 description 2
- 229920002678 cellulose Polymers 0.000 description 2
- 230000008859 change Effects 0.000 description 2
- OSASVXMJTNOKOY-UHFFFAOYSA-N chlorobutanol Chemical compound CC(C)(O)C(Cl)(Cl)Cl OSASVXMJTNOKOY-UHFFFAOYSA-N 0.000 description 2
- 239000000812 cholinergic antagonist Substances 0.000 description 2
- 229960001265 ciclosporin Drugs 0.000 description 2
- 238000003776 cleavage reaction Methods 0.000 description 2
- 239000011248 coating agent Substances 0.000 description 2
- 239000002299 complementary DNA Substances 0.000 description 2
- 230000001268 conjugating effect Effects 0.000 description 2
- 238000013270 controlled release Methods 0.000 description 2
- IDLFZVILOHSSID-OVLDLUHVSA-N corticotropin Chemical compound C([C@@H](C(=O)N[C@@H](CO)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC=1NC=NC=1)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)NCC(=O)N[C@@H](CCCCN)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](C(C)C)C(=O)NCC(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CC(N)=O)C(=O)NCC(=O)N[C@@H](C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CO)C(=O)N[C@@H](C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](C)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC=1C=CC=CC=1)C(O)=O)NC(=O)[C@@H](N)CO)C1=CC=C(O)C=C1 IDLFZVILOHSSID-OVLDLUHVSA-N 0.000 description 2
- 229960000258 corticotropin Drugs 0.000 description 2
- 230000008878 coupling Effects 0.000 description 2
- 238000010168 coupling process Methods 0.000 description 2
- 238000005859 coupling reaction Methods 0.000 description 2
- 239000003431 cross linking reagent Substances 0.000 description 2
- 229960004397 cyclophosphamide Drugs 0.000 description 2
- 229960002433 cysteine Drugs 0.000 description 2
- XUJNEKJLAYXESH-UHFFFAOYSA-N cysteine Natural products SCC(N)C(O)=O XUJNEKJLAYXESH-UHFFFAOYSA-N 0.000 description 2
- 230000001472 cytotoxic effect Effects 0.000 description 2
- 229960000640 dactinomycin Drugs 0.000 description 2
- 229960000975 daunorubicin Drugs 0.000 description 2
- 230000003247 decreasing effect Effects 0.000 description 2
- 235000019425 dextrin Nutrition 0.000 description 2
- 238000010586 diagram Methods 0.000 description 2
- 102000004419 dihydrofolate reductase Human genes 0.000 description 2
- LOKCTEFSRHRXRJ-UHFFFAOYSA-I dipotassium trisodium dihydrogen phosphate hydrogen phosphate dichloride Chemical compound P(=O)(O)(O)[O-].[K+].P(=O)(O)([O-])[O-].[Na+].[Na+].[Cl-].[K+].[Cl-].[Na+] LOKCTEFSRHRXRJ-UHFFFAOYSA-I 0.000 description 2
- 239000003136 dopamine receptor stimulating agent Substances 0.000 description 2
- 239000002552 dosage form Substances 0.000 description 2
- 239000012893 effector ligand Substances 0.000 description 2
- 238000005516 engineering process Methods 0.000 description 2
- 210000003979 eosinophil Anatomy 0.000 description 2
- 210000003743 erythrocyte Anatomy 0.000 description 2
- 238000011156 evaluation Methods 0.000 description 2
- 238000002474 experimental method Methods 0.000 description 2
- KKGQTZUTZRNORY-UHFFFAOYSA-N fingolimod Chemical compound CCCCCCCCC1=CC=C(CCC(N)(CO)CO)C=C1 KKGQTZUTZRNORY-UHFFFAOYSA-N 0.000 description 2
- 238000000684 flow cytometry Methods 0.000 description 2
- MHMNJMPURVTYEJ-UHFFFAOYSA-N fluorescein-5-isothiocyanate Chemical compound O1C(=O)C2=CC(N=C=S)=CC=C2C21C1=CC=C(O)C=C1OC1=CC(O)=CC=C21 MHMNJMPURVTYEJ-UHFFFAOYSA-N 0.000 description 2
- 229960002949 fluorouracil Drugs 0.000 description 2
- 229940028334 follicle stimulating hormone Drugs 0.000 description 2
- 239000008273 gelatin Substances 0.000 description 2
- 229920000159 gelatin Polymers 0.000 description 2
- 235000019322 gelatine Nutrition 0.000 description 2
- 235000011852 gelatine desserts Nutrition 0.000 description 2
- 230000002068 genetic effect Effects 0.000 description 2
- 150000004676 glycans Chemical class 0.000 description 2
- 102000035122 glycosylated proteins Human genes 0.000 description 2
- 108091005608 glycosylated proteins Proteins 0.000 description 2
- 125000003630 glycyl group Chemical group [H]N([H])C([H])([H])C(*)=O 0.000 description 2
- 239000001963 growth medium Substances 0.000 description 2
- 208000014752 hemophagocytic syndrome Diseases 0.000 description 2
- 229960002897 heparin Drugs 0.000 description 2
- 229920000669 heparin Polymers 0.000 description 2
- HNDVDQJCIGZPNO-UHFFFAOYSA-N histidine Natural products OC(=O)C(N)CC1=CN=CN1 HNDVDQJCIGZPNO-UHFFFAOYSA-N 0.000 description 2
- 102000054510 human SIRPG Human genes 0.000 description 2
- 229910052739 hydrogen Inorganic materials 0.000 description 2
- 229940050526 hydroxyethylstarch Drugs 0.000 description 2
- 229940127121 immunoconjugate Drugs 0.000 description 2
- 229940072221 immunoglobulins Drugs 0.000 description 2
- 239000003018 immunosuppressive agent Substances 0.000 description 2
- 238000011534 incubation Methods 0.000 description 2
- 208000015181 infectious disease Diseases 0.000 description 2
- 230000004968 inflammatory condition Effects 0.000 description 2
- 230000004941 influx Effects 0.000 description 2
- NOESYZHRGYRDHS-UHFFFAOYSA-N insulin Chemical compound N1C(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(NC(=O)CN)C(C)CC)CSSCC(C(NC(CO)C(=O)NC(CC(C)C)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CCC(N)=O)C(=O)NC(CC(C)C)C(=O)NC(CCC(O)=O)C(=O)NC(CC(N)=O)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CSSCC(NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2C=CC(O)=CC=2)NC(=O)C(CC(C)C)NC(=O)C(C)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2NC=NC=2)NC(=O)C(CO)NC(=O)CNC2=O)C(=O)NCC(=O)NC(CCC(O)=O)C(=O)NC(CCCNC(N)=N)C(=O)NCC(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC(O)=CC=3)C(=O)NC(C(C)O)C(=O)N3C(CCC3)C(=O)NC(CCCCN)C(=O)NC(C)C(O)=O)C(=O)NC(CC(N)=O)C(O)=O)=O)NC(=O)C(C(C)CC)NC(=O)C(CO)NC(=O)C(C(C)O)NC(=O)C1CSSCC2NC(=O)C(CC(C)C)NC(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CC(N)=O)NC(=O)C(NC(=O)C(N)CC=1C=CC=CC=1)C(C)C)CC1=CN=CN1 NOESYZHRGYRDHS-UHFFFAOYSA-N 0.000 description 2
- 102000006495 integrins Human genes 0.000 description 2
- 108010044426 integrins Proteins 0.000 description 2
- 230000000968 intestinal effect Effects 0.000 description 2
- 238000007913 intrathecal administration Methods 0.000 description 2
- 229960000310 isoleucine Drugs 0.000 description 2
- AGPKZVBTJJNPAG-UHFFFAOYSA-N isoleucine Natural products CCC(C)C(N)C(O)=O AGPKZVBTJJNPAG-UHFFFAOYSA-N 0.000 description 2
- 229960000681 leflunomide Drugs 0.000 description 2
- VHOGYURTWQBHIL-UHFFFAOYSA-N leflunomide Chemical compound O1N=CC(C(=O)NC=2C=CC(=CC=2)C(F)(F)F)=C1C VHOGYURTWQBHIL-UHFFFAOYSA-N 0.000 description 2
- 230000007774 longterm Effects 0.000 description 2
- 229940040129 luteinizing hormone Drugs 0.000 description 2
- 210000002540 macrophage Anatomy 0.000 description 2
- 238000012423 maintenance Methods 0.000 description 2
- 230000007246 mechanism Effects 0.000 description 2
- GLVAUDGFNGKCSF-UHFFFAOYSA-N mercaptopurine Chemical compound S=C1NC=NC2=C1NC=N2 GLVAUDGFNGKCSF-UHFFFAOYSA-N 0.000 description 2
- HPNSFSBZBAHARI-UHFFFAOYSA-N micophenolic acid Natural products OC1=C(CC=C(C)CCC(O)=O)C(OC)=C(C)C2=C1C(=O)OC2 HPNSFSBZBAHARI-UHFFFAOYSA-N 0.000 description 2
- 230000003278 mimic effect Effects 0.000 description 2
- CFCUWKMKBJTWLW-BKHRDMLASA-N mithramycin Chemical compound O([C@@H]1C[C@@H](O[C@H](C)[C@H]1O)OC=1C=C2C=C3C[C@H]([C@@H](C(=O)C3=C(O)C2=C(O)C=1C)O[C@@H]1O[C@H](C)[C@@H](O)[C@H](O[C@@H]2O[C@H](C)[C@H](O)[C@H](O[C@@H]3O[C@H](C)[C@@H](O)[C@@](C)(O)C3)C2)C1)[C@H](OC)C(=O)[C@@H](O)[C@@H](C)O)[C@H]1C[C@@H](O)[C@H](O)[C@@H](C)O1 CFCUWKMKBJTWLW-BKHRDMLASA-N 0.000 description 2
- 229960004857 mitomycin Drugs 0.000 description 2
- 210000005087 mononuclear cell Anatomy 0.000 description 2
- 201000006417 multiple sclerosis Diseases 0.000 description 2
- 239000003149 muscarinic antagonist Substances 0.000 description 2
- 229960000951 mycophenolic acid Drugs 0.000 description 2
- HPNSFSBZBAHARI-RUDMXATFSA-N mycophenolic acid Chemical compound OC1=C(C\C=C(/C)CCC(O)=O)C(OC)=C(C)C2=C1C(=O)OC2 HPNSFSBZBAHARI-RUDMXATFSA-N 0.000 description 2
- 201000000050 myeloid neoplasm Diseases 0.000 description 2
- 210000000440 neutrophil Anatomy 0.000 description 2
- 238000011275 oncology therapy Methods 0.000 description 2
- 210000000056 organ Anatomy 0.000 description 2
- 230000003204 osmotic effect Effects 0.000 description 2
- 229960001319 parathyroid hormone Drugs 0.000 description 2
- 239000000199 parathyroid hormone Substances 0.000 description 2
- 201000003045 paroxysmal nocturnal hemoglobinuria Diseases 0.000 description 2
- 230000001575 pathological effect Effects 0.000 description 2
- 230000037361 pathway Effects 0.000 description 2
- 230000008782 phagocytosis Effects 0.000 description 2
- COLNVLDHVKWLRT-UHFFFAOYSA-N phenylalanine Natural products OC(=O)C(N)CC1=CC=CC=C1 COLNVLDHVKWLRT-UHFFFAOYSA-N 0.000 description 2
- 229960003171 plicamycin Drugs 0.000 description 2
- 108010048507 poliovirus receptor Proteins 0.000 description 2
- 108091033319 polynucleotide Chemical group 0.000 description 2
- 102000040430 polynucleotide Human genes 0.000 description 2
- 239000002157 polynucleotide Chemical group 0.000 description 2
- 229920001282 polysaccharide Polymers 0.000 description 2
- 239000005017 polysaccharide Substances 0.000 description 2
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 2
- MFDFERRIHVXMIY-UHFFFAOYSA-N procaine Chemical compound CCN(CC)CCOC(=O)C1=CC=C(N)C=C1 MFDFERRIHVXMIY-UHFFFAOYSA-N 0.000 description 2
- 229960004919 procaine Drugs 0.000 description 2
- 229940097325 prolactin Drugs 0.000 description 2
- 230000002035 prolonged effect Effects 0.000 description 2
- AQHHHDLHHXJYJD-UHFFFAOYSA-N propranolol Chemical compound C1=CC=C2C(OCC(O)CNC(C)C)=CC=CC2=C1 AQHHHDLHHXJYJD-UHFFFAOYSA-N 0.000 description 2
- 230000006916 protein interaction Effects 0.000 description 2
- 230000012743 protein tagging Effects 0.000 description 2
- 230000004850 protein–protein interaction Effects 0.000 description 2
- RXWNCPJZOCPEPQ-NVWDDTSBSA-N puromycin Chemical compound C1=CC(OC)=CC=C1C[C@H](N)C(=O)N[C@H]1[C@@H](O)[C@H](N2C3=NC=NC(=C3N=C2)N(C)C)O[C@@H]1CO RXWNCPJZOCPEPQ-NVWDDTSBSA-N 0.000 description 2
- 229940051022 radioimmunoconjugate Drugs 0.000 description 2
- 239000012217 radiopharmaceutical Substances 0.000 description 2
- 229940121896 radiopharmaceutical Drugs 0.000 description 2
- 230000002799 radiopharmaceutical effect Effects 0.000 description 2
- ZAHRKKWIAAJSAO-UHFFFAOYSA-N rapamycin Natural products COCC(O)C(=C/C(C)C(=O)CC(OC(=O)C1CCCCN1C(=O)C(=O)C2(O)OC(CC(OC)C(=CC=CC=CC(C)CC(C)C(=O)C)C)CCC2C)C(C)CC3CCC(O)C(C3)OC)C ZAHRKKWIAAJSAO-UHFFFAOYSA-N 0.000 description 2
- 208000002574 reactive arthritis Diseases 0.000 description 2
- 230000010076 replication Effects 0.000 description 2
- 108091008146 restriction endonucleases Proteins 0.000 description 2
- 108010038196 saccharide-binding proteins Proteins 0.000 description 2
- 230000007017 scission Effects 0.000 description 2
- 210000002966 serum Anatomy 0.000 description 2
- 208000002491 severe combined immunodeficiency Diseases 0.000 description 2
- 208000007056 sickle cell anemia Diseases 0.000 description 2
- 229960002930 sirolimus Drugs 0.000 description 2
- QFJCIRLUMZQUOT-HPLJOQBZSA-N sirolimus Chemical compound C1C[C@@H](O)[C@H](OC)C[C@@H]1C[C@@H](C)[C@H]1OC(=O)[C@@H]2CCCCN2C(=O)C(=O)[C@](O)(O2)[C@H](C)CC[C@H]2C[C@H](OC)/C(C)=C/C=C/C=C/[C@@H](C)C[C@@H](C)C(=O)[C@H](OC)[C@H](O)/C(C)=C/[C@@H](C)C(=O)C1 QFJCIRLUMZQUOT-HPLJOQBZSA-N 0.000 description 2
- 239000011734 sodium Substances 0.000 description 2
- 239000000600 sorbitol Substances 0.000 description 2
- 125000006850 spacer group Chemical group 0.000 description 2
- 235000019698 starch Nutrition 0.000 description 2
- 239000008107 starch Substances 0.000 description 2
- 210000000130 stem cell Anatomy 0.000 description 2
- 238000011476 stem cell transplantation Methods 0.000 description 2
- 150000003431 steroids Chemical class 0.000 description 2
- 238000003860 storage Methods 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- 150000008163 sugars Chemical class 0.000 description 2
- 239000004094 surface-active agent Substances 0.000 description 2
- 238000013268 sustained release Methods 0.000 description 2
- QJJXYPPXXYFBGM-SHYZHZOCSA-N tacrolimus Natural products CO[C@H]1C[C@H](CC[C@@H]1O)C=C(C)[C@H]2OC(=O)[C@H]3CCCCN3C(=O)C(=O)[C@@]4(O)O[C@@H]([C@H](C[C@H]4C)OC)[C@@H](C[C@H](C)CC(=C[C@@H](CC=C)C(=O)C[C@H](O)[C@H]2C)C)OC QJJXYPPXXYFBGM-SHYZHZOCSA-N 0.000 description 2
- 230000004797 therapeutic response Effects 0.000 description 2
- 230000008719 thickening Effects 0.000 description 2
- WYWHKKSPHMUBEB-UHFFFAOYSA-N tioguanine Chemical compound N1C(N)=NC(=S)C2=C1N=CN2 WYWHKKSPHMUBEB-UHFFFAOYSA-N 0.000 description 2
- 239000003053 toxin Substances 0.000 description 2
- 231100000765 toxin Toxicity 0.000 description 2
- 108700012359 toxins Proteins 0.000 description 2
- 238000001890 transfection Methods 0.000 description 2
- OUYCCCASQSFEME-UHFFFAOYSA-N tyrosine Natural products OC(=O)C(N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-UHFFFAOYSA-N 0.000 description 2
- 241000701161 unidentified adenovirus Species 0.000 description 2
- 201000005112 urinary bladder cancer Diseases 0.000 description 2
- 239000004474 valine Substances 0.000 description 2
- 229910052720 vanadium Inorganic materials 0.000 description 2
- 229960003726 vasopressin Drugs 0.000 description 2
- 229960003048 vinblastine Drugs 0.000 description 2
- JXLYSJRDGCGARV-XQKSVPLYSA-N vincaleukoblastine Chemical compound C([C@@H](C[C@]1(C(=O)OC)C=2C(=CC3=C([C@]45[C@H]([C@@]([C@H](OC(C)=O)[C@]6(CC)C=CCN([C@H]56)CC4)(O)C(=O)OC)N3C)C=2)OC)C[C@@](C2)(O)CC)N2CCC2=C1NC1=CC=CC=C21 JXLYSJRDGCGARV-XQKSVPLYSA-N 0.000 description 2
- OGWKCGZFUXNPDA-XQKSVPLYSA-N vincristine Chemical compound C([N@]1C[C@@H](C[C@]2(C(=O)OC)C=3C(=CC4=C([C@]56[C@H]([C@@]([C@H](OC(C)=O)[C@]7(CC)C=CCN([C@H]67)CC5)(O)C(=O)OC)N4C=O)C=3)OC)C[C@@](C1)(O)CC)CC1=C2NC2=CC=CC=C12 OGWKCGZFUXNPDA-XQKSVPLYSA-N 0.000 description 2
- 229960004528 vincristine Drugs 0.000 description 2
- OGWKCGZFUXNPDA-UHFFFAOYSA-N vincristine Natural products C1C(CC)(O)CC(CC2(C(=O)OC)C=3C(=CC4=C(C56C(C(C(OC(C)=O)C7(CC)C=CCN(C67)CC5)(O)C(=O)OC)N4C=O)C=3)OC)CN1CCC1=C2NC2=CC=CC=C12 OGWKCGZFUXNPDA-UHFFFAOYSA-N 0.000 description 2
- 230000003612 virological effect Effects 0.000 description 2
- 229920003169 water-soluble polymer Polymers 0.000 description 2
- 230000004580 weight loss Effects 0.000 description 2
- SFLSHLFXELFNJZ-QMMMGPOBSA-N (-)-norepinephrine Chemical compound NC[C@H](O)C1=CC=C(O)C(O)=C1 SFLSHLFXELFNJZ-QMMMGPOBSA-N 0.000 description 1
- QIJRTFXNRTXDIP-UHFFFAOYSA-N (1-carboxy-2-sulfanylethyl)azanium;chloride;hydrate Chemical compound O.Cl.SCC(N)C(O)=O QIJRTFXNRTXDIP-UHFFFAOYSA-N 0.000 description 1
- FLCQLSRLQIPNLM-UHFFFAOYSA-N (2,5-dioxopyrrolidin-1-yl) 2-acetylsulfanylacetate Chemical compound CC(=O)SCC(=O)ON1C(=O)CCC1=O FLCQLSRLQIPNLM-UHFFFAOYSA-N 0.000 description 1
- KIUKXJAPPMFGSW-DNGZLQJQSA-N (2S,3S,4S,5R,6R)-6-[(2S,3R,4R,5S,6R)-3-Acetamido-2-[(2S,3S,4R,5R,6R)-6-[(2R,3R,4R,5S,6R)-3-acetamido-2,5-dihydroxy-6-(hydroxymethyl)oxan-4-yl]oxy-2-carboxy-4,5-dihydroxyoxan-3-yl]oxy-5-hydroxy-6-(hydroxymethyl)oxan-4-yl]oxy-3,4,5-trihydroxyoxane-2-carboxylic acid Chemical compound CC(=O)N[C@H]1[C@H](O)O[C@H](CO)[C@@H](O)[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@H](O[C@H]2[C@@H]([C@@H](O[C@H]3[C@@H]([C@@H](O)[C@H](O)[C@H](O3)C(O)=O)O)[C@H](O)[C@@H](CO)O2)NC(C)=O)[C@@H](C(O)=O)O1 KIUKXJAPPMFGSW-DNGZLQJQSA-N 0.000 description 1
- OMJKFYKNWZZKTK-POHAHGRESA-N (5z)-5-(dimethylaminohydrazinylidene)imidazole-4-carboxamide Chemical compound CN(C)N\N=C1/N=CN=C1C(N)=O OMJKFYKNWZZKTK-POHAHGRESA-N 0.000 description 1
- HMLGSIZOMSVISS-ONJSNURVSA-N (7r)-7-[[(2z)-2-(2-amino-1,3-thiazol-4-yl)-2-(2,2-dimethylpropanoyloxymethoxyimino)acetyl]amino]-3-ethenyl-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid Chemical compound N([C@@H]1C(N2C(=C(C=C)CSC21)C(O)=O)=O)C(=O)\C(=N/OCOC(=O)C(C)(C)C)C1=CSC(N)=N1 HMLGSIZOMSVISS-ONJSNURVSA-N 0.000 description 1
- UCTWMZQNUQWSLP-VIFPVBQESA-N (R)-adrenaline Chemical compound CNC[C@H](O)C1=CC=C(O)C(O)=C1 UCTWMZQNUQWSLP-VIFPVBQESA-N 0.000 description 1
- 229930182837 (R)-adrenaline Natural products 0.000 description 1
- GVJHHUAWPYXKBD-IEOSBIPESA-N (R)-alpha-Tocopherol Natural products OC1=C(C)C(C)=C2O[C@@](CCC[C@H](C)CCC[C@H](C)CCCC(C)C)(C)CCC2=C1C GVJHHUAWPYXKBD-IEOSBIPESA-N 0.000 description 1
- 108091032973 (ribonucleotides)n+m Proteins 0.000 description 1
- RTQWWZBSTRGEAV-PKHIMPSTSA-N 2-[[(2s)-2-[bis(carboxymethyl)amino]-3-[4-(methylcarbamoylamino)phenyl]propyl]-[2-[bis(carboxymethyl)amino]propyl]amino]acetic acid Chemical compound CNC(=O)NC1=CC=C(C[C@@H](CN(CC(C)N(CC(O)=O)CC(O)=O)CC(O)=O)N(CC(O)=O)CC(O)=O)C=C1 RTQWWZBSTRGEAV-PKHIMPSTSA-N 0.000 description 1
- 125000000954 2-hydroxyethyl group Chemical group [H]C([*])([H])C([H])([H])O[H] 0.000 description 1
- BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 1
- 101710147124 3-galactosyl-N-acetylglucosaminide 4-alpha-L-fucosyltransferase FUT3 Proteins 0.000 description 1
- 108010082808 4-1BB Ligand Proteins 0.000 description 1
- 102000002627 4-1BB Ligand Human genes 0.000 description 1
- FWMNVWWHGCHHJJ-SKKKGAJSSA-N 4-amino-1-[(2r)-6-amino-2-[[(2r)-2-[[(2r)-2-[[(2r)-2-amino-3-phenylpropanoyl]amino]-3-phenylpropanoyl]amino]-4-methylpentanoyl]amino]hexanoyl]piperidine-4-carboxylic acid Chemical compound C([C@H](C(=O)N[C@H](CC(C)C)C(=O)N[C@H](CCCCN)C(=O)N1CCC(N)(CC1)C(O)=O)NC(=O)[C@H](N)CC=1C=CC=CC=1)C1=CC=CC=C1 FWMNVWWHGCHHJJ-SKKKGAJSSA-N 0.000 description 1
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
- 108091007505 ADAM17 Proteins 0.000 description 1
- 101710168331 ALK tyrosine kinase receptor Proteins 0.000 description 1
- BUROJSBIWGDYCN-GAUTUEMISA-N AP 23573 Chemical compound C1C[C@@H](OP(C)(C)=O)[C@H](OC)C[C@@H]1C[C@@H](C)[C@H]1OC(=O)[C@@H]2CCCCN2C(=O)C(=O)[C@](O)(O2)[C@H](C)CC[C@H]2C[C@H](OC)/C(C)=C/C=C/C=C/[C@@H](C)C[C@@H](C)C(=O)[C@H](OC)[C@H](O)/C(C)=C/[C@@H](C)C(=O)C1 BUROJSBIWGDYCN-GAUTUEMISA-N 0.000 description 1
- RZVAJINKPMORJF-UHFFFAOYSA-N Acetaminophen Chemical compound CC(=O)NC1=CC=C(O)C=C1 RZVAJINKPMORJF-UHFFFAOYSA-N 0.000 description 1
- 108010075348 Activated-Leukocyte Cell Adhesion Molecule Proteins 0.000 description 1
- 102100034540 Adenomatous polyposis coli protein Human genes 0.000 description 1
- 102100026423 Adhesion G protein-coupled receptor E5 Human genes 0.000 description 1
- 206010027654 Allergic conditions Diseases 0.000 description 1
- 102100022749 Aminopeptidase N Human genes 0.000 description 1
- 102100020895 Ammonium transporter Rh type A Human genes 0.000 description 1
- 102100022014 Angiopoietin-1 receptor Human genes 0.000 description 1
- 102100030988 Angiotensin-converting enzyme Human genes 0.000 description 1
- 206010002556 Ankylosing Spondylitis Diseases 0.000 description 1
- 108010083359 Antigen Receptors Proteins 0.000 description 1
- 102000006306 Antigen Receptors Human genes 0.000 description 1
- 239000004475 Arginine Substances 0.000 description 1
- 206010003267 Arthritis reactive Diseases 0.000 description 1
- DCXYFEDJOCDNAF-UHFFFAOYSA-N Asparagine Natural products OC(=O)C(N)CC(N)=O DCXYFEDJOCDNAF-UHFFFAOYSA-N 0.000 description 1
- BSYNRYMUTXBXSQ-UHFFFAOYSA-N Aspirin Chemical compound CC(=O)OC1=CC=CC=C1C(O)=O BSYNRYMUTXBXSQ-UHFFFAOYSA-N 0.000 description 1
- 206010003591 Ataxia Diseases 0.000 description 1
- 201000001320 Atherosclerosis Diseases 0.000 description 1
- 206010003645 Atopy Diseases 0.000 description 1
- 102100022717 Atypical chemokine receptor 1 Human genes 0.000 description 1
- 241000271566 Aves Species 0.000 description 1
- 102100027205 B-cell antigen receptor complex-associated protein alpha chain Human genes 0.000 description 1
- 102100027203 B-cell antigen receptor complex-associated protein beta chain Human genes 0.000 description 1
- 210000002237 B-cell of pancreatic islet Anatomy 0.000 description 1
- 102100038080 B-cell receptor CD22 Human genes 0.000 description 1
- 108010074708 B7-H1 Antigen Proteins 0.000 description 1
- 101001027057 Bacillus subtilis (strain 168) Flagellin Proteins 0.000 description 1
- 102100021264 Band 3 anion transport protein Human genes 0.000 description 1
- 208000023328 Basedow disease Diseases 0.000 description 1
- 108010064528 Basigin Proteins 0.000 description 1
- 208000008439 Biliary Liver Cirrhosis Diseases 0.000 description 1
- 208000033222 Biliary cirrhosis primary Diseases 0.000 description 1
- 108010006654 Bleomycin Proteins 0.000 description 1
- 108010049931 Bone Morphogenetic Protein 2 Proteins 0.000 description 1
- 108010049955 Bone Morphogenetic Protein 4 Proteins 0.000 description 1
- 108010049976 Bone Morphogenetic Protein 5 Proteins 0.000 description 1
- 108010049974 Bone Morphogenetic Protein 6 Proteins 0.000 description 1
- 108010049870 Bone Morphogenetic Protein 7 Proteins 0.000 description 1
- 206010065687 Bone loss Diseases 0.000 description 1
- 102100037086 Bone marrow stromal antigen 2 Human genes 0.000 description 1
- 102100028726 Bone morphogenetic protein 10 Human genes 0.000 description 1
- 101710118482 Bone morphogenetic protein 10 Proteins 0.000 description 1
- 102000003928 Bone morphogenetic protein 15 Human genes 0.000 description 1
- 108090000349 Bone morphogenetic protein 15 Proteins 0.000 description 1
- 102100024506 Bone morphogenetic protein 2 Human genes 0.000 description 1
- 102100024505 Bone morphogenetic protein 4 Human genes 0.000 description 1
- 102100022526 Bone morphogenetic protein 5 Human genes 0.000 description 1
- 102100022525 Bone morphogenetic protein 6 Human genes 0.000 description 1
- 102100022544 Bone morphogenetic protein 7 Human genes 0.000 description 1
- 241000283690 Bos taurus Species 0.000 description 1
- 102100022595 Broad substrate specificity ATP-binding cassette transporter ABCG2 Human genes 0.000 description 1
- 206010006474 Bronchopulmonary aspergillosis allergic Diseases 0.000 description 1
- VOVIALXJUBGFJZ-KWVAZRHASA-N Budesonide Chemical compound C1CC2=CC(=O)C=C[C@]2(C)[C@@H]2[C@@H]1[C@@H]1C[C@H]3OC(CCC)O[C@@]3(C(=O)CO)[C@@]1(C)C[C@@H]2O VOVIALXJUBGFJZ-KWVAZRHASA-N 0.000 description 1
- COVZYZSDYWQREU-UHFFFAOYSA-N Busulfan Chemical compound CS(=O)(=O)OCCCCOS(C)(=O)=O COVZYZSDYWQREU-UHFFFAOYSA-N 0.000 description 1
- 101710149814 C-C chemokine receptor type 1 Proteins 0.000 description 1
- 101710149815 C-C chemokine receptor type 2 Proteins 0.000 description 1
- 101710149862 C-C chemokine receptor type 3 Proteins 0.000 description 1
- 101710149863 C-C chemokine receptor type 4 Proteins 0.000 description 1
- 101710149870 C-C chemokine receptor type 5 Proteins 0.000 description 1
- 102100036302 C-C chemokine receptor type 6 Human genes 0.000 description 1
- 101710149858 C-C chemokine receptor type 7 Proteins 0.000 description 1
- 102100031650 C-X-C chemokine receptor type 4 Human genes 0.000 description 1
- 102100028668 C-type lectin domain family 4 member C Human genes 0.000 description 1
- 102100028681 C-type lectin domain family 4 member K Human genes 0.000 description 1
- 102100025351 C-type mannose receptor 2 Human genes 0.000 description 1
- LWFDUMPGOAKHKC-UHFFFAOYSA-N C1=CC=C2C=C(C(=O)C(C(O)=C3O)=O)C3=CC2=C1 Chemical compound C1=CC=C2C=C(C(=O)C(C(O)=C3O)=O)C3=CC2=C1 LWFDUMPGOAKHKC-UHFFFAOYSA-N 0.000 description 1
- 102100032957 C5a anaphylatoxin chemotactic receptor 1 Human genes 0.000 description 1
- 102100024217 CAMPATH-1 antigen Human genes 0.000 description 1
- 108010056102 CD100 antigen Proteins 0.000 description 1
- 101150033066 CD101 gene Proteins 0.000 description 1
- 102100021992 CD209 antigen Human genes 0.000 description 1
- 102000007499 CD27 Ligand Human genes 0.000 description 1
- 108010046080 CD27 Ligand Proteins 0.000 description 1
- 102100027207 CD27 antigen Human genes 0.000 description 1
- 108010017987 CD30 Ligand Proteins 0.000 description 1
- 102100025238 CD302 antigen Human genes 0.000 description 1
- 108010065524 CD52 Antigen Proteins 0.000 description 1
- 108010062802 CD66 antigens Proteins 0.000 description 1
- 102100022436 CMRF35-like molecule 8 Human genes 0.000 description 1
- 108010021064 CTLA-4 Antigen Proteins 0.000 description 1
- 229940045513 CTLA4 antagonist Drugs 0.000 description 1
- LERNTVKEWCAPOY-VOGVJGKGSA-N C[N+]1(C)[C@H]2C[C@H](C[C@@H]1[C@H]1O[C@@H]21)OC(=O)C(O)(c1cccs1)c1cccs1 Chemical compound C[N+]1(C)[C@H]2C[C@H](C[C@@H]1[C@H]1O[C@@H]21)OC(=O)C(O)(c1cccs1)c1cccs1 LERNTVKEWCAPOY-VOGVJGKGSA-N 0.000 description 1
- KORNTPPJEAJQIU-KJXAQDMKSA-N Cabaser Chemical compound C1=CC([C@H]2C[C@H](CN(CC=C)[C@@H]2C2)C(=O)N(CCCN(C)C)C(=O)NCC)=C3C2=CNC3=C1 KORNTPPJEAJQIU-KJXAQDMKSA-N 0.000 description 1
- 102000000905 Cadherin Human genes 0.000 description 1
- 108050007957 Cadherin Proteins 0.000 description 1
- 102100029761 Cadherin-5 Human genes 0.000 description 1
- 102400000113 Calcitonin Human genes 0.000 description 1
- 108060001064 Calcitonin Proteins 0.000 description 1
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
- 241000282472 Canis lupus familiaris Species 0.000 description 1
- 229920002134 Carboxymethyl cellulose Polymers 0.000 description 1
- 102100024533 Carcinoembryonic antigen-related cell adhesion molecule 1 Human genes 0.000 description 1
- 102100025466 Carcinoembryonic antigen-related cell adhesion molecule 3 Human genes 0.000 description 1
- 102100025475 Carcinoembryonic antigen-related cell adhesion molecule 5 Human genes 0.000 description 1
- 102100025473 Carcinoembryonic antigen-related cell adhesion molecule 6 Human genes 0.000 description 1
- 102100025470 Carcinoembryonic antigen-related cell adhesion molecule 8 Human genes 0.000 description 1
- 102100028892 Cardiotrophin-1 Human genes 0.000 description 1
- DLGOEMSEDOSKAD-UHFFFAOYSA-N Carmustine Chemical compound ClCCNC(=O)N(N=O)CCCl DLGOEMSEDOSKAD-UHFFFAOYSA-N 0.000 description 1
- 101710145225 Cation-independent mannose-6-phosphate receptor Proteins 0.000 description 1
- 108091007854 Cdh1/Fizzy-related Proteins 0.000 description 1
- 102100023126 Cell surface glycoprotein MUC18 Human genes 0.000 description 1
- 102000009410 Chemokine receptor Human genes 0.000 description 1
- 108050000299 Chemokine receptor Proteins 0.000 description 1
- 102000019034 Chemokines Human genes 0.000 description 1
- 108010012236 Chemokines Proteins 0.000 description 1
- 229920001661 Chitosan Polymers 0.000 description 1
- 241000251730 Chondrichthyes Species 0.000 description 1
- 206010008909 Chronic Hepatitis Diseases 0.000 description 1
- 108010005939 Ciliary Neurotrophic Factor Proteins 0.000 description 1
- 102100031614 Ciliary neurotrophic factor Human genes 0.000 description 1
- KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 description 1
- 108091026890 Coding region Proteins 0.000 description 1
- 108010035532 Collagen Proteins 0.000 description 1
- 102000008186 Collagen Human genes 0.000 description 1
- 102100025680 Complement decay-accelerating factor Human genes 0.000 description 1
- 102100030886 Complement receptor type 1 Human genes 0.000 description 1
- 102100032768 Complement receptor type 2 Human genes 0.000 description 1
- 206010010356 Congenital anomaly Diseases 0.000 description 1
- 241000759568 Corixa Species 0.000 description 1
- 239000000055 Corticotropin-Releasing Hormone Substances 0.000 description 1
- 241000699800 Cricetinae Species 0.000 description 1
- 241000938605 Crocodylia Species 0.000 description 1
- 102100021906 Cyclin-O Human genes 0.000 description 1
- UHDGCWIWMRVCDJ-CCXZUQQUSA-N Cytarabine Chemical compound O=C1N=C(N)C=CN1[C@H]1[C@@H](O)[C@H](O)[C@@H](CO)O1 UHDGCWIWMRVCDJ-CCXZUQQUSA-N 0.000 description 1
- 102100025621 Cytochrome b-245 heavy chain Human genes 0.000 description 1
- 102100039061 Cytokine receptor common subunit beta Human genes 0.000 description 1
- 102100026234 Cytokine receptor common subunit gamma Human genes 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
- SHZGCJCMOBCMKK-UHFFFAOYSA-N D-mannomethylose Natural products CC1OC(O)C(O)C(O)C1O SHZGCJCMOBCMKK-UHFFFAOYSA-N 0.000 description 1
- VVNCNSJFMMFHPL-VKHMYHEASA-N D-penicillamine Chemical compound CC(C)(S)[C@@H](N)C(O)=O VVNCNSJFMMFHPL-VKHMYHEASA-N 0.000 description 1
- 108010037897 DC-specific ICAM-3 grabbing nonintegrin Proteins 0.000 description 1
- 102000053602 DNA Human genes 0.000 description 1
- WEAHRLBPCANXCN-UHFFFAOYSA-N Daunomycin Natural products CCC1(O)CC(OC2CC(N)C(O)C(C)O2)c3cc4C(=O)c5c(OC)cccc5C(=O)c4c(O)c3C1 WEAHRLBPCANXCN-UHFFFAOYSA-N 0.000 description 1
- 201000004624 Dermatitis Diseases 0.000 description 1
- 206010012434 Dermatitis allergic Diseases 0.000 description 1
- 206010012438 Dermatitis atopic Diseases 0.000 description 1
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 1
- 206010012735 Diarrhoea Diseases 0.000 description 1
- 102220485848 Dihydropteridine reductase_D300A_mutation Human genes 0.000 description 1
- 102100025012 Dipeptidyl peptidase 4 Human genes 0.000 description 1
- 102100036723 Discoidin domain-containing receptor 2 Human genes 0.000 description 1
- 101710127786 Discoidin domain-containing receptor 2 Proteins 0.000 description 1
- 206010061818 Disease progression Diseases 0.000 description 1
- 102100031111 Disintegrin and metalloproteinase domain-containing protein 17 Human genes 0.000 description 1
- 229940098778 Dopamine receptor agonist Drugs 0.000 description 1
- 101100347633 Drosophila melanogaster Mhc gene Proteins 0.000 description 1
- 208000032928 Dyslipidaemia Diseases 0.000 description 1
- 108010024212 E-Selectin Proteins 0.000 description 1
- 102100023471 E-selectin Human genes 0.000 description 1
- 238000002965 ELISA Methods 0.000 description 1
- 102100036993 Ecto-ADP-ribosyltransferase 4 Human genes 0.000 description 1
- LVGKNOAMLMIIKO-UHFFFAOYSA-N Elaidinsaeure-aethylester Natural products CCCCCCCCC=CCCCCCCCC(=O)OCC LVGKNOAMLMIIKO-UHFFFAOYSA-N 0.000 description 1
- MBYXEBXZARTUSS-QLWBXOBMSA-N Emetamine Natural products O(C)c1c(OC)cc2c(c(C[C@@H]3[C@H](CC)CN4[C@H](c5c(cc(OC)c(OC)c5)CC4)C3)ncc2)c1 MBYXEBXZARTUSS-QLWBXOBMSA-N 0.000 description 1
- 206010014561 Emphysema Diseases 0.000 description 1
- 108010036395 Endoglin Proteins 0.000 description 1
- 102100038083 Endosialin Human genes 0.000 description 1
- 108010009900 Endothelial Protein C Receptor Proteins 0.000 description 1
- 102000009839 Endothelial Protein C Receptor Human genes 0.000 description 1
- 102100030024 Endothelial protein C receptor Human genes 0.000 description 1
- 208000004232 Enteritis Diseases 0.000 description 1
- YQYJSBFKSSDGFO-UHFFFAOYSA-N Epihygromycin Natural products OC1C(O)C(C(=O)C)OC1OC(C(=C1)O)=CC=C1C=C(C)C(=O)NC1C(O)C(O)C2OCOC2C1O YQYJSBFKSSDGFO-UHFFFAOYSA-N 0.000 description 1
- 101710131668 Epithelial discoidin domain-containing receptor 1 Proteins 0.000 description 1
- 241000283086 Equidae Species 0.000 description 1
- 206010049466 Erythroblastosis Diseases 0.000 description 1
- 102000003951 Erythropoietin Human genes 0.000 description 1
- 108090000394 Erythropoietin Proteins 0.000 description 1
- 241000588724 Escherichia coli Species 0.000 description 1
- 108010008165 Etanercept Proteins 0.000 description 1
- PIICEJLVQHRZGT-UHFFFAOYSA-N Ethylenediamine Chemical compound NCCN PIICEJLVQHRZGT-UHFFFAOYSA-N 0.000 description 1
- 229910052693 Europium Inorganic materials 0.000 description 1
- HKVAMNSJSFKALM-GKUWKFKPSA-N Everolimus Chemical compound C1C[C@@H](OCCO)[C@H](OC)C[C@@H]1C[C@@H](C)[C@H]1OC(=O)[C@@H]2CCCCN2C(=O)C(=O)[C@](O)(O2)[C@H](C)CC[C@H]2C[C@H](OC)/C(C)=C/C=C/C=C/[C@@H](C)C[C@@H](C)C(=O)[C@H](OC)[C@H](O)/C(C)=C/[C@@H](C)C(=O)C1 HKVAMNSJSFKALM-GKUWKFKPSA-N 0.000 description 1
- 108091029865 Exogenous DNA Proteins 0.000 description 1
- 102100031507 Fc receptor-like protein 5 Human genes 0.000 description 1
- 108010087819 Fc receptors Proteins 0.000 description 1
- 102000009109 Fc receptors Human genes 0.000 description 1
- 101150032879 Fcrl5 gene Proteins 0.000 description 1
- 241000282326 Felis catus Species 0.000 description 1
- 101710182386 Fibroblast growth factor receptor 1 Proteins 0.000 description 1
- 101710182389 Fibroblast growth factor receptor 2 Proteins 0.000 description 1
- 101710182396 Fibroblast growth factor receptor 3 Proteins 0.000 description 1
- 101710182387 Fibroblast growth factor receptor 4 Proteins 0.000 description 1
- 206010016717 Fistula Diseases 0.000 description 1
- PNNNRSAQSRJVSB-SLPGGIOYSA-N Fucose Natural products C[C@H](O)[C@@H](O)[C@H](O)[C@H](O)C=O PNNNRSAQSRJVSB-SLPGGIOYSA-N 0.000 description 1
- 101710186842 Fucosyltransferase 3 Proteins 0.000 description 1
- 108010019236 Fucosyltransferases Proteins 0.000 description 1
- 102000006471 Fucosyltransferases Human genes 0.000 description 1
- 241000233866 Fungi Species 0.000 description 1
- 208000018522 Gastrointestinal disease Diseases 0.000 description 1
- 208000017189 Gastrointestinal inflammatory disease Diseases 0.000 description 1
- 206010018364 Glomerulonephritis Diseases 0.000 description 1
- 102400000321 Glucagon Human genes 0.000 description 1
- 108060003199 Glucagon Proteins 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
- 108010058940 Glutamyl Aminopeptidase Proteins 0.000 description 1
- 108010068370 Glutens Proteins 0.000 description 1
- 102100035716 Glycophorin-A Human genes 0.000 description 1
- 102100036430 Glycophorin-B Human genes 0.000 description 1
- 102100023849 Glycophorin-C Human genes 0.000 description 1
- 108091005250 Glycophorins Proteins 0.000 description 1
- 102000028180 Glycophorins Human genes 0.000 description 1
- 201000005569 Gout Diseases 0.000 description 1
- 108010026389 Gramicidin Proteins 0.000 description 1
- 108010017080 Granulocyte Colony-Stimulating Factor Proteins 0.000 description 1
- 108010054017 Granulocyte Colony-Stimulating Factor Receptors Proteins 0.000 description 1
- 102100039619 Granulocyte colony-stimulating factor Human genes 0.000 description 1
- 102000016355 Granulocyte-Macrophage Colony-Stimulating Factor Receptors Human genes 0.000 description 1
- 108010092372 Granulocyte-Macrophage Colony-Stimulating Factor Receptors Proteins 0.000 description 1
- 102100028113 Granulocyte-macrophage colony-stimulating factor receptor subunit alpha Human genes 0.000 description 1
- 206010018691 Granuloma Diseases 0.000 description 1
- 208000015023 Graves' disease Diseases 0.000 description 1
- 108010041881 Growth Differentiation Factor 10 Proteins 0.000 description 1
- 108010090293 Growth Differentiation Factor 3 Proteins 0.000 description 1
- 108010090250 Growth Differentiation Factor 6 Proteins 0.000 description 1
- 102000004858 Growth differentiation factor-9 Human genes 0.000 description 1
- 108090001086 Growth differentiation factor-9 Proteins 0.000 description 1
- 102100040895 Growth/differentiation factor 10 Human genes 0.000 description 1
- 102100040898 Growth/differentiation factor 11 Human genes 0.000 description 1
- 101710194452 Growth/differentiation factor 11 Proteins 0.000 description 1
- 102100040892 Growth/differentiation factor 2 Human genes 0.000 description 1
- 101710204270 Growth/differentiation factor 2 Proteins 0.000 description 1
- 102100035364 Growth/differentiation factor 3 Human genes 0.000 description 1
- 102100035368 Growth/differentiation factor 6 Human genes 0.000 description 1
- 102100035363 Growth/differentiation factor 7 Human genes 0.000 description 1
- 101710204283 Growth/differentiation factor 7 Proteins 0.000 description 1
- 102100039939 Growth/differentiation factor 8 Human genes 0.000 description 1
- 241000590002 Helicobacter pylori Species 0.000 description 1
- 208000032843 Hemorrhage Diseases 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
- 206010019755 Hepatitis chronic active Diseases 0.000 description 1
- 101000779641 Homo sapiens ALK tyrosine kinase receptor Proteins 0.000 description 1
- 101001017818 Homo sapiens ATP-dependent translocase ABCB1 Proteins 0.000 description 1
- 101000924577 Homo sapiens Adenomatous polyposis coli protein Proteins 0.000 description 1
- 101000718243 Homo sapiens Adhesion G protein-coupled receptor E5 Proteins 0.000 description 1
- 101000757160 Homo sapiens Aminopeptidase N Proteins 0.000 description 1
- 101001075525 Homo sapiens Ammonium transporter Rh type A Proteins 0.000 description 1
- 101000753291 Homo sapiens Angiopoietin-1 receptor Proteins 0.000 description 1
- 101000678879 Homo sapiens Atypical chemokine receptor 1 Proteins 0.000 description 1
- 101000678892 Homo sapiens Atypical chemokine receptor 2 Proteins 0.000 description 1
- 101000914489 Homo sapiens B-cell antigen receptor complex-associated protein alpha chain Proteins 0.000 description 1
- 101000914491 Homo sapiens B-cell antigen receptor complex-associated protein beta chain Proteins 0.000 description 1
- 101000884305 Homo sapiens B-cell receptor CD22 Proteins 0.000 description 1
- 101000894913 Homo sapiens Band 3 anion transport protein Proteins 0.000 description 1
- 101000740785 Homo sapiens Bone marrow stromal antigen 2 Proteins 0.000 description 1
- 101000766294 Homo sapiens Branched-chain-amino-acid aminotransferase, mitochondrial Proteins 0.000 description 1
- 101000777564 Homo sapiens C-C chemokine receptor type 1 Proteins 0.000 description 1
- 101000777599 Homo sapiens C-C chemokine receptor type 2 Proteins 0.000 description 1
- 101000980744 Homo sapiens C-C chemokine receptor type 3 Proteins 0.000 description 1
- 101000738584 Homo sapiens C-C chemokine receptor type 4 Proteins 0.000 description 1
- 101000946926 Homo sapiens C-C chemokine receptor type 5 Proteins 0.000 description 1
- 101000716068 Homo sapiens C-C chemokine receptor type 6 Proteins 0.000 description 1
- 101000716065 Homo sapiens C-C chemokine receptor type 7 Proteins 0.000 description 1
- 101000922348 Homo sapiens C-X-C chemokine receptor type 4 Proteins 0.000 description 1
- 101000766907 Homo sapiens C-type lectin domain family 4 member C Proteins 0.000 description 1
- 101000766965 Homo sapiens C-type lectin domain family 4 member K Proteins 0.000 description 1
- 101000576898 Homo sapiens C-type mannose receptor 2 Proteins 0.000 description 1
- 101000867983 Homo sapiens C5a anaphylatoxin chemotactic receptor 1 Proteins 0.000 description 1
- 101000897416 Homo sapiens CD209 antigen Proteins 0.000 description 1
- 101000914511 Homo sapiens CD27 antigen Proteins 0.000 description 1
- 101000934351 Homo sapiens CD302 antigen Proteins 0.000 description 1
- 101000901669 Homo sapiens CMRF35-like molecule 8 Proteins 0.000 description 1
- 101000984015 Homo sapiens Cadherin-1 Proteins 0.000 description 1
- 101000914337 Homo sapiens Carcinoembryonic antigen-related cell adhesion molecule 3 Proteins 0.000 description 1
- 101000914324 Homo sapiens Carcinoembryonic antigen-related cell adhesion molecule 5 Proteins 0.000 description 1
- 101000914326 Homo sapiens Carcinoembryonic antigen-related cell adhesion molecule 6 Proteins 0.000 description 1
- 101000914320 Homo sapiens Carcinoembryonic antigen-related cell adhesion molecule 8 Proteins 0.000 description 1
- 101001028831 Homo sapiens Cation-independent mannose-6-phosphate receptor Proteins 0.000 description 1
- 101000940912 Homo sapiens Choline transporter-like protein 1 Proteins 0.000 description 1
- 101000856022 Homo sapiens Complement decay-accelerating factor Proteins 0.000 description 1
- 101000727061 Homo sapiens Complement receptor type 1 Proteins 0.000 description 1
- 101000941929 Homo sapiens Complement receptor type 2 Proteins 0.000 description 1
- 101000897441 Homo sapiens Cyclin-O Proteins 0.000 description 1
- 101000908391 Homo sapiens Dipeptidyl peptidase 4 Proteins 0.000 description 1
- 101000881679 Homo sapiens Endoglin Proteins 0.000 description 1
- 101000884275 Homo sapiens Endosialin Proteins 0.000 description 1
- 101001012038 Homo sapiens Endothelial protein C receptor Proteins 0.000 description 1
- 101000827746 Homo sapiens Fibroblast growth factor receptor 1 Proteins 0.000 description 1
- 101000827688 Homo sapiens Fibroblast growth factor receptor 2 Proteins 0.000 description 1
- 101000917148 Homo sapiens Fibroblast growth factor receptor 3 Proteins 0.000 description 1
- 101000917134 Homo sapiens Fibroblast growth factor receptor 4 Proteins 0.000 description 1
- 101001099051 Homo sapiens GPI inositol-deacylase Proteins 0.000 description 1
- 101000719019 Homo sapiens Glutamyl aminopeptidase Proteins 0.000 description 1
- 101001074244 Homo sapiens Glycophorin-A Proteins 0.000 description 1
- 101001071776 Homo sapiens Glycophorin-B Proteins 0.000 description 1
- 101000746364 Homo sapiens Granulocyte colony-stimulating factor receptor Proteins 0.000 description 1
- 101000916625 Homo sapiens Granulocyte-macrophage colony-stimulating factor receptor subunit alpha Proteins 0.000 description 1
- 101000854886 Homo sapiens Immunoglobulin iota chain Proteins 0.000 description 1
- 101000840267 Homo sapiens Immunoglobulin lambda-like polypeptide 1 Proteins 0.000 description 1
- 101000999311 Homo sapiens Immunoglobulin superfamily member 8 Proteins 0.000 description 1
- 101000852815 Homo sapiens Insulin receptor Proteins 0.000 description 1
- 101001034652 Homo sapiens Insulin-like growth factor 1 receptor Proteins 0.000 description 1
- 101000994369 Homo sapiens Integrin alpha-5 Proteins 0.000 description 1
- 101000994365 Homo sapiens Integrin alpha-6 Proteins 0.000 description 1
- 101001046687 Homo sapiens Integrin alpha-E Proteins 0.000 description 1
- 101000935043 Homo sapiens Integrin beta-1 Proteins 0.000 description 1
- 101000935040 Homo sapiens Integrin beta-2 Proteins 0.000 description 1
- 101001015004 Homo sapiens Integrin beta-3 Proteins 0.000 description 1
- 101001015006 Homo sapiens Integrin beta-4 Proteins 0.000 description 1
- 101000599852 Homo sapiens Intercellular adhesion molecule 1 Proteins 0.000 description 1
- 101000599862 Homo sapiens Intercellular adhesion molecule 3 Proteins 0.000 description 1
- 101001002470 Homo sapiens Interferon lambda-1 Proteins 0.000 description 1
- 101001076422 Homo sapiens Interleukin-1 receptor type 2 Proteins 0.000 description 1
- 101001083151 Homo sapiens Interleukin-10 receptor subunit alpha Proteins 0.000 description 1
- 101001003149 Homo sapiens Interleukin-10 receptor subunit beta Proteins 0.000 description 1
- 101001003135 Homo sapiens Interleukin-13 receptor subunit alpha-1 Proteins 0.000 description 1
- 101001003132 Homo sapiens Interleukin-13 receptor subunit alpha-2 Proteins 0.000 description 1
- 101000961065 Homo sapiens Interleukin-18 receptor 1 Proteins 0.000 description 1
- 101001019615 Homo sapiens Interleukin-18 receptor accessory protein Proteins 0.000 description 1
- 101000853002 Homo sapiens Interleukin-25 Proteins 0.000 description 1
- 101000853000 Homo sapiens Interleukin-26 Proteins 0.000 description 1
- 101000998139 Homo sapiens Interleukin-32 Proteins 0.000 description 1
- 101001046633 Homo sapiens Junctional adhesion molecule A Proteins 0.000 description 1
- 101001027081 Homo sapiens Killer cell immunoglobulin-like receptor 2DL1 Proteins 0.000 description 1
- 101000945331 Homo sapiens Killer cell immunoglobulin-like receptor 2DL4 Proteins 0.000 description 1
- 101000945342 Homo sapiens Killer cell immunoglobulin-like receptor 2DS4 Proteins 0.000 description 1
- 101000945351 Homo sapiens Killer cell immunoglobulin-like receptor 3DL1 Proteins 0.000 description 1
- 101000967918 Homo sapiens Left-right determination factor 2 Proteins 0.000 description 1
- 101001129927 Homo sapiens Leptin receptor Proteins 0.000 description 1
- 101000984197 Homo sapiens Leukocyte immunoglobulin-like receptor subfamily A member 2 Proteins 0.000 description 1
- 101000984200 Homo sapiens Leukocyte immunoglobulin-like receptor subfamily A member 3 Proteins 0.000 description 1
- 101000984196 Homo sapiens Leukocyte immunoglobulin-like receptor subfamily A member 5 Proteins 0.000 description 1
- 101000984190 Homo sapiens Leukocyte immunoglobulin-like receptor subfamily B member 1 Proteins 0.000 description 1
- 101000984189 Homo sapiens Leukocyte immunoglobulin-like receptor subfamily B member 2 Proteins 0.000 description 1
- 101000984192 Homo sapiens Leukocyte immunoglobulin-like receptor subfamily B member 3 Proteins 0.000 description 1
- 101000984186 Homo sapiens Leukocyte immunoglobulin-like receptor subfamily B member 4 Proteins 0.000 description 1
- 101001138059 Homo sapiens Leukocyte-associated immunoglobulin-like receptor 2 Proteins 0.000 description 1
- 101000576894 Homo sapiens Macrophage mannose receptor 1 Proteins 0.000 description 1
- 101001008874 Homo sapiens Mast/stem cell growth factor receptor Kit Proteins 0.000 description 1
- 101000934338 Homo sapiens Myeloid cell surface antigen CD33 Proteins 0.000 description 1
- 101001128431 Homo sapiens Myeloid-derived growth factor Proteins 0.000 description 1
- 101001109508 Homo sapiens NKG2-A/NKG2-B type II integral membrane protein Proteins 0.000 description 1
- 101001109503 Homo sapiens NKG2-C type II integral membrane protein Proteins 0.000 description 1
- 101000979306 Homo sapiens Nectin-1 Proteins 0.000 description 1
- 101000577540 Homo sapiens Neuropilin-1 Proteins 0.000 description 1
- 101000896414 Homo sapiens Nuclear nucleic acid-binding protein C1D Proteins 0.000 description 1
- 101000622137 Homo sapiens P-selectin Proteins 0.000 description 1
- 101001070790 Homo sapiens Platelet glycoprotein Ib alpha chain Proteins 0.000 description 1
- 101001070786 Homo sapiens Platelet glycoprotein Ib beta chain Proteins 0.000 description 1
- 101001033026 Homo sapiens Platelet glycoprotein V Proteins 0.000 description 1
- 101000692455 Homo sapiens Platelet-derived growth factor receptor beta Proteins 0.000 description 1
- 101000617708 Homo sapiens Pregnancy-specific beta-1-glycoprotein 1 Proteins 0.000 description 1
- 101000617725 Homo sapiens Pregnancy-specific beta-1-glycoprotein 2 Proteins 0.000 description 1
- 101001117317 Homo sapiens Programmed cell death 1 ligand 1 Proteins 0.000 description 1
- 101000611936 Homo sapiens Programmed cell death protein 1 Proteins 0.000 description 1
- 101000650817 Homo sapiens Semaphorin-4D Proteins 0.000 description 1
- 101000863884 Homo sapiens Sialic acid-binding Ig-like lectin 8 Proteins 0.000 description 1
- 101000863883 Homo sapiens Sialic acid-binding Ig-like lectin 9 Proteins 0.000 description 1
- 101000884271 Homo sapiens Signal transducer CD24 Proteins 0.000 description 1
- 101000709256 Homo sapiens Signal-regulatory protein beta-1 Proteins 0.000 description 1
- 101000709188 Homo sapiens Signal-regulatory protein beta-1 isoform 3 Proteins 0.000 description 1
- 101000897407 Homo sapiens T-cell surface glycoprotein CD1e, membrane-associated Proteins 0.000 description 1
- 101000946863 Homo sapiens T-cell surface glycoprotein CD3 delta chain Proteins 0.000 description 1
- 101000738413 Homo sapiens T-cell surface glycoprotein CD3 gamma chain Proteins 0.000 description 1
- 101000738335 Homo sapiens T-cell surface glycoprotein CD3 zeta chain Proteins 0.000 description 1
- 101000845170 Homo sapiens Thymic stromal lymphopoietin Proteins 0.000 description 1
- 101000763537 Homo sapiens Toll-like receptor 10 Proteins 0.000 description 1
- 101000831567 Homo sapiens Toll-like receptor 2 Proteins 0.000 description 1
- 101000831496 Homo sapiens Toll-like receptor 3 Proteins 0.000 description 1
- 101000669447 Homo sapiens Toll-like receptor 4 Proteins 0.000 description 1
- 101000800479 Homo sapiens Toll-like receptor 9 Proteins 0.000 description 1
- 101000835093 Homo sapiens Transferrin receptor protein 1 Proteins 0.000 description 1
- 101000830565 Homo sapiens Tumor necrosis factor ligand superfamily member 10 Proteins 0.000 description 1
- 101000830603 Homo sapiens Tumor necrosis factor ligand superfamily member 11 Proteins 0.000 description 1
- 101000851434 Homo sapiens Tumor necrosis factor ligand superfamily member 13B Proteins 0.000 description 1
- 101000830594 Homo sapiens Tumor necrosis factor ligand superfamily member 14 Proteins 0.000 description 1
- 101000764263 Homo sapiens Tumor necrosis factor ligand superfamily member 4 Proteins 0.000 description 1
- 101000610602 Homo sapiens Tumor necrosis factor receptor superfamily member 10C Proteins 0.000 description 1
- 101000648503 Homo sapiens Tumor necrosis factor receptor superfamily member 11A Proteins 0.000 description 1
- 101000795169 Homo sapiens Tumor necrosis factor receptor superfamily member 13C Proteins 0.000 description 1
- 101000801228 Homo sapiens Tumor necrosis factor receptor superfamily member 1A Proteins 0.000 description 1
- 101000611023 Homo sapiens Tumor necrosis factor receptor superfamily member 6 Proteins 0.000 description 1
- 101000851376 Homo sapiens Tumor necrosis factor receptor superfamily member 8 Proteins 0.000 description 1
- 101000760337 Homo sapiens Urokinase plasminogen activator surface receptor Proteins 0.000 description 1
- 101000622304 Homo sapiens Vascular cell adhesion protein 1 Proteins 0.000 description 1
- 101000851007 Homo sapiens Vascular endothelial growth factor receptor 2 Proteins 0.000 description 1
- 102000003839 Human Proteins Human genes 0.000 description 1
- 108090000144 Human Proteins Proteins 0.000 description 1
- 241000714260 Human T-lymphotropic virus 1 Species 0.000 description 1
- 102100027735 Hyaluronan mediated motility receptor Human genes 0.000 description 1
- 101150091468 IGSF8 gene Proteins 0.000 description 1
- HEFNNWSXXWATRW-UHFFFAOYSA-N Ibuprofen Chemical compound CC(C)CC1=CC=C(C(C)C(O)=O)C=C1 HEFNNWSXXWATRW-UHFFFAOYSA-N 0.000 description 1
- 206010021245 Idiopathic thrombocytopenic purpura Diseases 0.000 description 1
- 102100026120 IgG receptor FcRn large subunit p51 Human genes 0.000 description 1
- 101710177940 IgG receptor FcRn large subunit p51 Proteins 0.000 description 1
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
- 206010061598 Immunodeficiency Diseases 0.000 description 1
- 208000029462 Immunodeficiency disease Diseases 0.000 description 1
- 108010054477 Immunoglobulin Fab Fragments Proteins 0.000 description 1
- 102000001706 Immunoglobulin Fab Fragments Human genes 0.000 description 1
- 102100020744 Immunoglobulin iota chain Human genes 0.000 description 1
- 102100029616 Immunoglobulin lambda-like polypeptide 1 Human genes 0.000 description 1
- 206010062016 Immunosuppression Diseases 0.000 description 1
- 208000001019 Inborn Errors Metabolism Diseases 0.000 description 1
- 208000026350 Inborn Genetic disease Diseases 0.000 description 1
- 206010065390 Inflammatory pain Diseases 0.000 description 1
- 102000004877 Insulin Human genes 0.000 description 1
- 108090001061 Insulin Proteins 0.000 description 1
- 108010001127 Insulin Receptor Proteins 0.000 description 1
- 101710184277 Insulin-like growth factor 1 receptor Proteins 0.000 description 1
- 102100032817 Integrin alpha-5 Human genes 0.000 description 1
- 102100032816 Integrin alpha-6 Human genes 0.000 description 1
- 102100022341 Integrin alpha-E Human genes 0.000 description 1
- 108010008212 Integrin alpha4beta1 Proteins 0.000 description 1
- 102100025304 Integrin beta-1 Human genes 0.000 description 1
- 102100032999 Integrin beta-3 Human genes 0.000 description 1
- 102100033000 Integrin beta-4 Human genes 0.000 description 1
- 102100026720 Interferon beta Human genes 0.000 description 1
- 101710174028 Interferon gamma receptor 1 Proteins 0.000 description 1
- 102100020990 Interferon lambda-1 Human genes 0.000 description 1
- 108010047761 Interferon-alpha Proteins 0.000 description 1
- 102000006992 Interferon-alpha Human genes 0.000 description 1
- 108090000467 Interferon-beta Proteins 0.000 description 1
- 108010050904 Interferons Proteins 0.000 description 1
- 102000014150 Interferons Human genes 0.000 description 1
- 102000051628 Interleukin-1 receptor antagonist Human genes 0.000 description 1
- 108700021006 Interleukin-1 receptor antagonist Proteins 0.000 description 1
- 102100026017 Interleukin-1 receptor type 2 Human genes 0.000 description 1
- 102100030236 Interleukin-10 receptor subunit alpha Human genes 0.000 description 1
- 102100020788 Interleukin-10 receptor subunit beta Human genes 0.000 description 1
- 108090000177 Interleukin-11 Proteins 0.000 description 1
- 102000003815 Interleukin-11 Human genes 0.000 description 1
- 102000003816 Interleukin-13 Human genes 0.000 description 1
- 108090000176 Interleukin-13 Proteins 0.000 description 1
- 102100020791 Interleukin-13 receptor subunit alpha-1 Human genes 0.000 description 1
- 102100020793 Interleukin-13 receptor subunit alpha-2 Human genes 0.000 description 1
- 108090000172 Interleukin-15 Proteins 0.000 description 1
- 102000003812 Interleukin-15 Human genes 0.000 description 1
- 101800003050 Interleukin-16 Proteins 0.000 description 1
- 102000049772 Interleukin-16 Human genes 0.000 description 1
- 108050003558 Interleukin-17 Proteins 0.000 description 1
- 102000013691 Interleukin-17 Human genes 0.000 description 1
- 102000003810 Interleukin-18 Human genes 0.000 description 1
- 108090000171 Interleukin-18 Proteins 0.000 description 1
- 102000004557 Interleukin-18 Receptors Human genes 0.000 description 1
- 108010017537 Interleukin-18 Receptors Proteins 0.000 description 1
- 102100039340 Interleukin-18 receptor 1 Human genes 0.000 description 1
- 102100035010 Interleukin-18 receptor accessory protein Human genes 0.000 description 1
- 102100039879 Interleukin-19 Human genes 0.000 description 1
- 108050009288 Interleukin-19 Proteins 0.000 description 1
- 108010002350 Interleukin-2 Proteins 0.000 description 1
- 102000000588 Interleukin-2 Human genes 0.000 description 1
- 102100026879 Interleukin-2 receptor subunit beta Human genes 0.000 description 1
- 102100036679 Interleukin-26 Human genes 0.000 description 1
- 108010066979 Interleukin-27 Proteins 0.000 description 1
- 108010002386 Interleukin-3 Proteins 0.000 description 1
- 102000000646 Interleukin-3 Human genes 0.000 description 1
- 102100021596 Interleukin-31 Human genes 0.000 description 1
- 101710181613 Interleukin-31 Proteins 0.000 description 1
- 102100033501 Interleukin-32 Human genes 0.000 description 1
- 102000017761 Interleukin-33 Human genes 0.000 description 1
- 108010067003 Interleukin-33 Proteins 0.000 description 1
- 102100033499 Interleukin-34 Human genes 0.000 description 1
- 101710181549 Interleukin-34 Proteins 0.000 description 1
- 108010038486 Interleukin-4 Receptors Proteins 0.000 description 1
- 102000000743 Interleukin-5 Human genes 0.000 description 1
- 108010002616 Interleukin-5 Proteins 0.000 description 1
- 108010072089 Interleukin-5 Receptor alpha Subunit Proteins 0.000 description 1
- 102000006760 Interleukin-5 Receptor alpha Subunit Human genes 0.000 description 1
- 102100039881 Interleukin-5 receptor subunit alpha Human genes 0.000 description 1
- 108010038501 Interleukin-6 Receptors Proteins 0.000 description 1
- 102100037795 Interleukin-6 receptor subunit beta Human genes 0.000 description 1
- 102000000704 Interleukin-7 Human genes 0.000 description 1
- 108010002586 Interleukin-7 Proteins 0.000 description 1
- 108010038498 Interleukin-7 Receptors Proteins 0.000 description 1
- 102000000585 Interleukin-9 Human genes 0.000 description 1
- 108010002335 Interleukin-9 Proteins 0.000 description 1
- 108010038414 Interleukin-9 Receptors Proteins 0.000 description 1
- 208000029523 Interstitial Lung disease Diseases 0.000 description 1
- UETNIIAIRMUTSM-UHFFFAOYSA-N Jacareubin Natural products CC1(C)OC2=CC3Oc4c(O)c(O)ccc4C(=O)C3C(=C2C=C1)O UETNIIAIRMUTSM-UHFFFAOYSA-N 0.000 description 1
- 208000009388 Job Syndrome Diseases 0.000 description 1
- 108010040082 Junctional Adhesion Molecule A Proteins 0.000 description 1
- 102100037363 Killer cell immunoglobulin-like receptor 2DL1 Human genes 0.000 description 1
- 102100033633 Killer cell immunoglobulin-like receptor 2DL4 Human genes 0.000 description 1
- 102100033624 Killer cell immunoglobulin-like receptor 2DS4 Human genes 0.000 description 1
- 102100033627 Killer cell immunoglobulin-like receptor 3DL1 Human genes 0.000 description 1
- 102100020880 Kit ligand Human genes 0.000 description 1
- 101710177504 Kit ligand Proteins 0.000 description 1
- ONIBWKKTOPOVIA-BYPYZUCNSA-N L-Proline Chemical compound OC(=O)[C@@H]1CCCN1 ONIBWKKTOPOVIA-BYPYZUCNSA-N 0.000 description 1
- ODKSFYDXXFIFQN-BYPYZUCNSA-P L-argininium(2+) Chemical compound NC(=[NH2+])NCCC[C@H]([NH3+])C(O)=O ODKSFYDXXFIFQN-BYPYZUCNSA-P 0.000 description 1
- CKLJMWTZIZZHCS-REOHCLBHSA-N L-aspartic acid Chemical compound OC(=O)[C@@H](N)CC(O)=O CKLJMWTZIZZHCS-REOHCLBHSA-N 0.000 description 1
- SHZGCJCMOBCMKK-DHVFOXMCSA-N L-fucopyranose Chemical compound C[C@@H]1OC(O)[C@@H](O)[C@H](O)[C@@H]1O SHZGCJCMOBCMKK-DHVFOXMCSA-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
- ZDXPYRJPNDTMRX-VKHMYHEASA-N L-glutamine Chemical compound OC(=O)[C@@H](N)CCC(N)=O ZDXPYRJPNDTMRX-VKHMYHEASA-N 0.000 description 1
- ROHFNLRQFUQHCH-YFKPBYRVSA-N L-leucine Chemical compound CC(C)C[C@H](N)C(O)=O ROHFNLRQFUQHCH-YFKPBYRVSA-N 0.000 description 1
- KDXKERNSBIXSRK-YFKPBYRVSA-N L-lysine Chemical compound NCCCC[C@H](N)C(O)=O KDXKERNSBIXSRK-YFKPBYRVSA-N 0.000 description 1
- FFEARJCKVFRZRR-BYPYZUCNSA-N L-methionine Chemical compound CSCC[C@H](N)C(O)=O FFEARJCKVFRZRR-BYPYZUCNSA-N 0.000 description 1
- 101710163560 Lamina-associated polypeptide 2, isoform alpha Proteins 0.000 description 1
- 101710189385 Lamina-associated polypeptide 2, isoforms beta/gamma Proteins 0.000 description 1
- 102100040511 Left-right determination factor 2 Human genes 0.000 description 1
- 102000016267 Leptin Human genes 0.000 description 1
- 108010092277 Leptin Proteins 0.000 description 1
- ROHFNLRQFUQHCH-UHFFFAOYSA-N Leucine Natural products CC(C)CC(N)C(O)=O ROHFNLRQFUQHCH-UHFFFAOYSA-N 0.000 description 1
- 108010017736 Leukocyte Immunoglobulin-like Receptor B1 Proteins 0.000 description 1
- 102100025586 Leukocyte immunoglobulin-like receptor subfamily A member 2 Human genes 0.000 description 1
- 102100025556 Leukocyte immunoglobulin-like receptor subfamily A member 3 Human genes 0.000 description 1
- 102100025583 Leukocyte immunoglobulin-like receptor subfamily B member 2 Human genes 0.000 description 1
- 102100025582 Leukocyte immunoglobulin-like receptor subfamily B member 3 Human genes 0.000 description 1
- 102100025578 Leukocyte immunoglobulin-like receptor subfamily B member 4 Human genes 0.000 description 1
- 102100020858 Leukocyte-associated immunoglobulin-like receptor 2 Human genes 0.000 description 1
- NNJVILVZKWQKPM-UHFFFAOYSA-N Lidocaine Chemical compound CCN(CC)CC(=O)NC1=C(C)C=CC=C1C NNJVILVZKWQKPM-UHFFFAOYSA-N 0.000 description 1
- 208000017170 Lipid metabolism disease Diseases 0.000 description 1
- 208000004883 Lipoid Nephrosis Diseases 0.000 description 1
- 102100029205 Low affinity immunoglobulin gamma Fc region receptor II-b Human genes 0.000 description 1
- 102100029193 Low affinity immunoglobulin gamma Fc region receptor III-A Human genes 0.000 description 1
- 108010064548 Lymphocyte Function-Associated Antigen-1 Proteins 0.000 description 1
- 206010051929 Lymphoplasia Diseases 0.000 description 1
- 208000030289 Lymphoproliferative disease Diseases 0.000 description 1
- 102000004083 Lymphotoxin-alpha Human genes 0.000 description 1
- 108090000542 Lymphotoxin-alpha Proteins 0.000 description 1
- 102100026894 Lymphotoxin-beta Human genes 0.000 description 1
- 108090000362 Lymphotoxin-beta Proteins 0.000 description 1
- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 1
- 239000004472 Lysine Substances 0.000 description 1
- 108010009254 Lysosomal-Associated Membrane Protein 1 Proteins 0.000 description 1
- 108010009491 Lysosomal-Associated Membrane Protein 2 Proteins 0.000 description 1
- 102100035133 Lysosome-associated membrane glycoprotein 1 Human genes 0.000 description 1
- 102100038225 Lysosome-associated membrane glycoprotein 2 Human genes 0.000 description 1
- 241000282567 Macaca fascicularis Species 0.000 description 1
- 241000282560 Macaca mulatta Species 0.000 description 1
- 108010046938 Macrophage Colony-Stimulating Factor Proteins 0.000 description 1
- 102100028123 Macrophage colony-stimulating factor 1 Human genes 0.000 description 1
- 102100025354 Macrophage mannose receptor 1 Human genes 0.000 description 1
- 102100021435 Macrophage-stimulating protein receptor Human genes 0.000 description 1
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
- 229930195725 Mannitol Natural products 0.000 description 1
- 102100027754 Mast/stem cell growth factor receptor Kit Human genes 0.000 description 1
- 229930126263 Maytansine Natural products 0.000 description 1
- YJPIGAIKUZMOQA-UHFFFAOYSA-N Melatonin Natural products COC1=CC=C2N(C(C)=O)C=C(CCN)C2=C1 YJPIGAIKUZMOQA-UHFFFAOYSA-N 0.000 description 1
- 108010047230 Member 1 Subfamily B ATP Binding Cassette Transporter Proteins 0.000 description 1
- 108010090306 Member 2 Subfamily G ATP Binding Cassette Transporter Proteins 0.000 description 1
- 108010006035 Metalloproteases Proteins 0.000 description 1
- 102000005741 Metalloproteases Human genes 0.000 description 1
- VFKZTMPDYBFSTM-KVTDHHQDSA-N Mitobronitol Chemical compound BrC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CBr VFKZTMPDYBFSTM-KVTDHHQDSA-N 0.000 description 1
- 229930192392 Mitomycin Natural products 0.000 description 1
- 241001529936 Murinae Species 0.000 description 1
- 101100175316 Mus musculus Gdf5 gene Proteins 0.000 description 1
- 108010074084 Muscle Proteins Proteins 0.000 description 1
- 102000008934 Muscle Proteins Human genes 0.000 description 1
- 208000021642 Muscular disease Diseases 0.000 description 1
- 102000008300 Mutant Proteins Human genes 0.000 description 1
- 108010021466 Mutant Proteins Proteins 0.000 description 1
- 102100025243 Myeloid cell surface antigen CD33 Human genes 0.000 description 1
- 201000007224 Myeloproliferative neoplasm Diseases 0.000 description 1
- 201000009623 Myopathy Diseases 0.000 description 1
- 108010056852 Myostatin Proteins 0.000 description 1
- MBBZMMPHUWSWHV-BDVNFPICSA-N N-methylglucamine Chemical compound CNC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO MBBZMMPHUWSWHV-BDVNFPICSA-N 0.000 description 1
- HIEKJRVYXXINKH-ADVKXBNGSA-N N1([C@H]2CC[C@H](C[C@H]2OC)/C=C(\C)[C@H]2OC(=O)[C@@H]3CCCCN3C(=O)C(=O)[C@]3(O)O[C@@H]([C@H](C[C@H]3C)OC)[C@@H](OC)C[C@@H](C)C/C(C)=C/[C@H](C(C[C@H](O)[C@H]2C)=O)CC)C=NN=N1 Chemical compound N1([C@H]2CC[C@H](C[C@H]2OC)/C=C(\C)[C@H]2OC(=O)[C@@H]3CCCCN3C(=O)C(=O)[C@]3(O)O[C@@H]([C@H](C[C@H]3C)OC)[C@@H](OC)C[C@@H](C)C/C(C)=C/[C@H](C(C[C@H](O)[C@H]2C)=O)CC)C=NN=N1 HIEKJRVYXXINKH-ADVKXBNGSA-N 0.000 description 1
- 101150065403 NECTIN2 gene Proteins 0.000 description 1
- 102100022682 NKG2-A/NKG2-B type II integral membrane protein Human genes 0.000 description 1
- 102100022683 NKG2-C type II integral membrane protein Human genes 0.000 description 1
- CMWTZPSULFXXJA-UHFFFAOYSA-N Naproxen Natural products C1=C(C(C)C(O)=O)C=CC2=CC(OC)=CC=C21 CMWTZPSULFXXJA-UHFFFAOYSA-N 0.000 description 1
- 102000002356 Nectin Human genes 0.000 description 1
- 108060005251 Nectin Proteins 0.000 description 1
- 102100023064 Nectin-1 Human genes 0.000 description 1
- 241001045988 Neogene Species 0.000 description 1
- 206010029164 Nephrotic syndrome Diseases 0.000 description 1
- 108090000028 Neprilysin Proteins 0.000 description 1
- 102000003729 Neprilysin Human genes 0.000 description 1
- 108010032605 Nerve Growth Factor Receptors Proteins 0.000 description 1
- 108010069196 Neural Cell Adhesion Molecules Proteins 0.000 description 1
- 102100024964 Neural cell adhesion molecule L1 Human genes 0.000 description 1
- 102100023616 Neural cell adhesion molecule L1-like protein Human genes 0.000 description 1
- 102100028762 Neuropilin-1 Human genes 0.000 description 1
- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 1
- 108091005461 Nucleic proteins Proteins 0.000 description 1
- 108010064527 OSM-LIF Receptors Proteins 0.000 description 1
- 108010042215 OX40 Ligand Proteins 0.000 description 1
- 206010030113 Oedema Diseases 0.000 description 1
- 108090000630 Oncostatin M Proteins 0.000 description 1
- 102000004140 Oncostatin M Human genes 0.000 description 1
- 241000283973 Oryctolagus cuniculus Species 0.000 description 1
- 102400000050 Oxytocin Human genes 0.000 description 1
- 101800000989 Oxytocin Proteins 0.000 description 1
- XNOPRXBHLZRZKH-UHFFFAOYSA-N Oxytocin Natural products N1C(=O)C(N)CSSCC(C(=O)N2C(CCC2)C(=O)NC(CC(C)C)C(=O)NCC(N)=O)NC(=O)C(CC(N)=O)NC(=O)C(CCC(N)=O)NC(=O)C(C(C)CC)NC(=O)C1CC1=CC=C(O)C=C1 XNOPRXBHLZRZKH-UHFFFAOYSA-N 0.000 description 1
- 102100023472 P-selectin Human genes 0.000 description 1
- 108010054395 P-selectin ligand protein Proteins 0.000 description 1
- 238000012408 PCR amplification Methods 0.000 description 1
- 101150062589 PTGS1 gene Proteins 0.000 description 1
- 229930012538 Paclitaxel Natural products 0.000 description 1
- 208000030852 Parasitic disease Diseases 0.000 description 1
- 241001494479 Pecora Species 0.000 description 1
- 241000235648 Pichia Species 0.000 description 1
- 102100034173 Platelet glycoprotein Ib alpha chain Human genes 0.000 description 1
- 102100034168 Platelet glycoprotein Ib beta chain Human genes 0.000 description 1
- 102100038411 Platelet glycoprotein V Human genes 0.000 description 1
- 108010051742 Platelet-Derived Growth Factor beta Receptor Proteins 0.000 description 1
- 229920002732 Polyanhydride Polymers 0.000 description 1
- 229920000954 Polyglycolide Polymers 0.000 description 1
- 229920001710 Polyorthoester Polymers 0.000 description 1
- 239000004743 Polypropylene Substances 0.000 description 1
- 239000004372 Polyvinyl alcohol Substances 0.000 description 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
- 102100022019 Pregnancy-specific beta-1-glycoprotein 2 Human genes 0.000 description 1
- 208000012654 Primary biliary cholangitis Diseases 0.000 description 1
- 101710089372 Programmed cell death protein 1 Proteins 0.000 description 1
- ONIBWKKTOPOVIA-UHFFFAOYSA-N Proline Natural products OC(=O)C1CCCN1 ONIBWKKTOPOVIA-UHFFFAOYSA-N 0.000 description 1
- 102100040120 Prominin-1 Human genes 0.000 description 1
- 102000001708 Protein Isoforms Human genes 0.000 description 1
- 108010029485 Protein Isoforms Proteins 0.000 description 1
- 201000004681 Psoriasis Diseases 0.000 description 1
- 108010025832 RANK Ligand Proteins 0.000 description 1
- 102100022491 RNA-binding protein NOB1 Human genes 0.000 description 1
- 241000700159 Rattus Species 0.000 description 1
- 102100020718 Receptor-type tyrosine-protein kinase FLT3 Human genes 0.000 description 1
- 102100039808 Receptor-type tyrosine-protein phosphatase eta Human genes 0.000 description 1
- 208000033464 Reiter syndrome Diseases 0.000 description 1
- 108010093560 Rezafungin Proteins 0.000 description 1
- 206010039085 Rhinitis allergic Diseases 0.000 description 1
- 241000283984 Rodentia Species 0.000 description 1
- AUVVAXYIELKVAI-UHFFFAOYSA-N SJ000285215 Natural products N1CCC2=CC(OC)=C(OC)C=C2C1CC1CC2C3=CC(OC)=C(OC)C=C3CCN2CC1CC AUVVAXYIELKVAI-UHFFFAOYSA-N 0.000 description 1
- 108091006998 SLC44A1 Proteins 0.000 description 1
- 241000235070 Saccharomyces Species 0.000 description 1
- 206010039710 Scleroderma Diseases 0.000 description 1
- 201000004283 Shwachman-Diamond syndrome Diseases 0.000 description 1
- 108010029176 Sialic Acid Binding Ig-like Lectin 1 Proteins 0.000 description 1
- 102100029964 Sialic acid-binding Ig-like lectin 8 Human genes 0.000 description 1
- 102100029965 Sialic acid-binding Ig-like lectin 9 Human genes 0.000 description 1
- 102100034258 Sialomucin core protein 24 Human genes 0.000 description 1
- 102100038081 Signal transducer CD24 Human genes 0.000 description 1
- 102100032770 Signal-regulatory protein beta-1 isoform 3 Human genes 0.000 description 1
- 108010074687 Signaling Lymphocytic Activation Molecule Family Member 1 Proteins 0.000 description 1
- 108010003723 Single-Domain Antibodies Proteins 0.000 description 1
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 1
- 208000035286 Spontaneous Remission Diseases 0.000 description 1
- ZSJLQEPLLKMAKR-UHFFFAOYSA-N Streptozotocin Natural products O=NN(C)C(=O)NC1C(O)OC(CO)C(O)C1O ZSJLQEPLLKMAKR-UHFFFAOYSA-N 0.000 description 1
- 102100035721 Syndecan-1 Human genes 0.000 description 1
- 102100021989 T-cell surface glycoprotein CD1e, membrane-associated Human genes 0.000 description 1
- 102100035891 T-cell surface glycoprotein CD3 delta chain Human genes 0.000 description 1
- 102100035794 T-cell surface glycoprotein CD3 epsilon chain Human genes 0.000 description 1
- 101710146340 T-cell surface glycoprotein CD3 epsilon chain Proteins 0.000 description 1
- 102100037911 T-cell surface glycoprotein CD3 gamma chain Human genes 0.000 description 1
- 102100037906 T-cell surface glycoprotein CD3 zeta chain Human genes 0.000 description 1
- FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 1
- CBPNZQVSJQDFBE-FUXHJELOSA-N Temsirolimus Chemical compound C1C[C@@H](OC(=O)C(C)(CO)CO)[C@H](OC)C[C@@H]1C[C@@H](C)[C@H]1OC(=O)[C@@H]2CCCCN2C(=O)C(=O)[C@](O)(O2)[C@H](C)CC[C@H]2C[C@H](OC)/C(C)=C/C=C/C=C/[C@@H](C)C[C@@H](C)C(=O)[C@H](OC)[C@H](O)/C(C)=C/[C@@H](C)C(=O)C1 CBPNZQVSJQDFBE-FUXHJELOSA-N 0.000 description 1
- 206010043391 Thalassaemia beta Diseases 0.000 description 1
- 208000002903 Thalassemia Diseases 0.000 description 1
- 241000906446 Theraps Species 0.000 description 1
- 102100026966 Thrombomodulin Human genes 0.000 description 1
- 108010000499 Thromboplastin Proteins 0.000 description 1
- 102100031294 Thymic stromal lymphopoietin Human genes 0.000 description 1
- 102400000159 Thymopoietin Human genes 0.000 description 1
- 239000000898 Thymopoietin Substances 0.000 description 1
- 102000007501 Thymosin Human genes 0.000 description 1
- 108010046075 Thymosin Proteins 0.000 description 1
- 102100027009 Toll-like receptor 10 Human genes 0.000 description 1
- 102100024333 Toll-like receptor 2 Human genes 0.000 description 1
- 102100024324 Toll-like receptor 3 Human genes 0.000 description 1
- 102100039360 Toll-like receptor 4 Human genes 0.000 description 1
- 102100033117 Toll-like receptor 9 Human genes 0.000 description 1
- 102100026144 Transferrin receptor protein 1 Human genes 0.000 description 1
- 102000004887 Transforming Growth Factor beta Human genes 0.000 description 1
- 108090001012 Transforming Growth Factor beta Proteins 0.000 description 1
- 102000011117 Transforming Growth Factor beta2 Human genes 0.000 description 1
- 101800000304 Transforming growth factor beta-2 Proteins 0.000 description 1
- 102000056172 Transforming growth factor beta-3 Human genes 0.000 description 1
- 108090000097 Transforming growth factor beta-3 Proteins 0.000 description 1
- 206010052779 Transplant rejections Diseases 0.000 description 1
- 241000223259 Trichoderma Species 0.000 description 1
- 241000499912 Trichoderma reesei Species 0.000 description 1
- 102000000852 Tumor Necrosis Factor-alpha Human genes 0.000 description 1
- 102100024598 Tumor necrosis factor ligand superfamily member 10 Human genes 0.000 description 1
- 102100036922 Tumor necrosis factor ligand superfamily member 13B Human genes 0.000 description 1
- 102100040115 Tumor necrosis factor receptor superfamily member 10C Human genes 0.000 description 1
- 102100028787 Tumor necrosis factor receptor superfamily member 11A Human genes 0.000 description 1
- 102100029690 Tumor necrosis factor receptor superfamily member 13C Human genes 0.000 description 1
- 102100033725 Tumor necrosis factor receptor superfamily member 16 Human genes 0.000 description 1
- 101710187743 Tumor necrosis factor receptor superfamily member 1A Proteins 0.000 description 1
- 102100033733 Tumor necrosis factor receptor superfamily member 1B Human genes 0.000 description 1
- 101710187830 Tumor necrosis factor receptor superfamily member 1B Proteins 0.000 description 1
- 102100040403 Tumor necrosis factor receptor superfamily member 6 Human genes 0.000 description 1
- 102100036857 Tumor necrosis factor receptor superfamily member 8 Human genes 0.000 description 1
- 102100036856 Tumor necrosis factor receptor superfamily member 9 Human genes 0.000 description 1
- 101710183617 Tyrosine-protein phosphatase non-receptor type substrate 1 Proteins 0.000 description 1
- GBOGMAARMMDZGR-UHFFFAOYSA-N UNPD149280 Natural products N1C(=O)C23OC(=O)C=CC(O)CCCC(C)CC=CC3C(O)C(=C)C(C)C2C1CC1=CC=CC=C1 GBOGMAARMMDZGR-UHFFFAOYSA-N 0.000 description 1
- 102000044159 Ubiquitin Human genes 0.000 description 1
- 108090000848 Ubiquitin Proteins 0.000 description 1
- 102100024689 Urokinase plasminogen activator surface receptor Human genes 0.000 description 1
- 208000024780 Urticaria Diseases 0.000 description 1
- 206010046851 Uveitis Diseases 0.000 description 1
- 108010000134 Vascular Cell Adhesion Molecule-1 Proteins 0.000 description 1
- 108010053099 Vascular Endothelial Growth Factor Receptor-2 Proteins 0.000 description 1
- 241000251539 Vertebrata <Metazoa> Species 0.000 description 1
- 208000016807 X-linked intellectual disability-macrocephaly-macroorchidism syndrome Diseases 0.000 description 1
- VWQVUPCCIRVNHF-OUBTZVSYSA-N Yttrium-90 Chemical compound [90Y] VWQVUPCCIRVNHF-OUBTZVSYSA-N 0.000 description 1
- 239000003070 absorption delaying agent Substances 0.000 description 1
- 239000008351 acetate buffer Substances 0.000 description 1
- 229960001138 acetylsalicylic acid Drugs 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- 229930183665 actinomycin Natural products 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 239000012190 activator Substances 0.000 description 1
- 239000013543 active substance Substances 0.000 description 1
- 125000002252 acyl group Chemical group 0.000 description 1
- 238000005917 acylation reaction Methods 0.000 description 1
- 229960002964 adalimumab Drugs 0.000 description 1
- 238000000246 agarose gel electrophoresis Methods 0.000 description 1
- 125000003295 alanine group Chemical group N[C@@H](C)C(=O)* 0.000 description 1
- 150000001299 aldehydes Chemical class 0.000 description 1
- 239000003513 alkali Substances 0.000 description 1
- 229910052784 alkaline earth metal Inorganic materials 0.000 description 1
- 150000001342 alkaline earth metals Chemical class 0.000 description 1
- 238000005804 alkylation reaction Methods 0.000 description 1
- 208000006778 allergic bronchopulmonary aspergillosis Diseases 0.000 description 1
- 230000000172 allergic effect Effects 0.000 description 1
- 201000010105 allergic rhinitis Diseases 0.000 description 1
- 229940087168 alpha tocopherol Drugs 0.000 description 1
- 229950004549 alvircept sudotox Drugs 0.000 description 1
- 150000001408 amides Chemical class 0.000 description 1
- 125000003277 amino group Chemical group 0.000 description 1
- 230000003321 amplification Effects 0.000 description 1
- 229960004238 anakinra Drugs 0.000 description 1
- 230000002052 anaphylactic effect Effects 0.000 description 1
- 239000003098 androgen Substances 0.000 description 1
- 208000007502 anemia Diseases 0.000 description 1
- 230000008485 antagonism Effects 0.000 description 1
- 229940045799 anthracyclines and related substance Drugs 0.000 description 1
- 230000000340 anti-metabolite Effects 0.000 description 1
- 238000011230 antibody-based therapy Methods 0.000 description 1
- 230000030741 antigen processing and presentation Effects 0.000 description 1
- 210000000612 antigen-presenting cell Anatomy 0.000 description 1
- 229960005475 antiinfective agent Drugs 0.000 description 1
- 239000003430 antimalarial agent Substances 0.000 description 1
- 229940033495 antimalarials Drugs 0.000 description 1
- 229940100197 antimetabolite Drugs 0.000 description 1
- 239000002256 antimetabolite Substances 0.000 description 1
- 239000004599 antimicrobial Substances 0.000 description 1
- 239000003080 antimitotic agent Substances 0.000 description 1
- 230000003078 antioxidant effect Effects 0.000 description 1
- 239000008365 aqueous carrier Substances 0.000 description 1
- ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 1
- 238000000149 argon plasma sintering Methods 0.000 description 1
- 159000000032 aromatic acids Chemical class 0.000 description 1
- 230000002917 arthritic effect Effects 0.000 description 1
- 125000003118 aryl group Chemical group 0.000 description 1
- ZDQSOHOQTUFQEM-PKUCKEGBSA-N ascomycin Chemical compound C/C([C@H]1OC(=O)[C@@H]2CCCCN2C(=O)C(=O)[C@]2(O)O[C@@H]([C@H](C[C@H]2C)OC)[C@@H](OC)C[C@@H](C)C\C(C)=C/[C@H](C(C[C@H](O)[C@H]1C)=O)CC)=C\[C@@H]1CC[C@@H](O)[C@H](OC)C1 ZDQSOHOQTUFQEM-PKUCKEGBSA-N 0.000 description 1
- ZDQSOHOQTUFQEM-XCXYXIJFSA-N ascomycin Natural products CC[C@H]1C=C(C)C[C@@H](C)C[C@@H](OC)[C@H]2O[C@@](O)([C@@H](C)C[C@H]2OC)C(=O)C(=O)N3CCCC[C@@H]3C(=O)O[C@H]([C@H](C)[C@@H](O)CC1=O)C(=C[C@@H]4CC[C@@H](O)[C@H](C4)OC)C ZDQSOHOQTUFQEM-XCXYXIJFSA-N 0.000 description 1
- 235000010323 ascorbic acid Nutrition 0.000 description 1
- 229960005070 ascorbic acid Drugs 0.000 description 1
- 239000011668 ascorbic acid Substances 0.000 description 1
- 235000009582 asparagine Nutrition 0.000 description 1
- 229960001230 asparagine Drugs 0.000 description 1
- 125000000613 asparagine group Chemical group N[C@@H](CC(N)=O)C(=O)* 0.000 description 1
- 235000003704 aspartic acid Nutrition 0.000 description 1
- 201000008937 atopic dermatitis Diseases 0.000 description 1
- 108010044540 auristatin Proteins 0.000 description 1
- 230000006472 autoimmune response Effects 0.000 description 1
- 201000003710 autoimmune thrombocytopenic purpura Diseases 0.000 description 1
- 210000003719 b-lymphocyte Anatomy 0.000 description 1
- 229940092705 beclomethasone Drugs 0.000 description 1
- NBMKJKDGKREAPL-DVTGEIKXSA-N beclomethasone Chemical compound C1CC2=CC(=O)C=C[C@]2(C)[C@]2(Cl)[C@@H]1[C@@H]1C[C@H](C)[C@@](C(=O)CO)(O)[C@@]1(C)C[C@@H]2O NBMKJKDGKREAPL-DVTGEIKXSA-N 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- JUHORIMYRDESRB-UHFFFAOYSA-N benzathine Chemical compound C=1C=CC=CC=1CNCCNCC1=CC=CC=C1 JUHORIMYRDESRB-UHFFFAOYSA-N 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
- 229920000249 biocompatible polymer Polymers 0.000 description 1
- 230000033228 biological regulation Effects 0.000 description 1
- 239000012472 biological sample Substances 0.000 description 1
- 230000005540 biological transmission Effects 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 229960001561 bleomycin Drugs 0.000 description 1
- OYVAGSVQBOHSSS-UAPAGMARSA-O bleomycin A2 Chemical compound N([C@H](C(=O)N[C@H](C)[C@@H](O)[C@H](C)C(=O)N[C@@H]([C@H](O)C)C(=O)NCCC=1SC=C(N=1)C=1SC=C(N=1)C(=O)NCCC[S+](C)C)[C@@H](O[C@H]1[C@H]([C@@H](O)[C@H](O)[C@H](CO)O1)O[C@@H]1[C@H]([C@@H](OC(N)=O)[C@H](O)[C@@H](CO)O1)O)C=1N=CNC=1)C(=O)C1=NC([C@H](CC(N)=O)NC[C@H](N)C(N)=O)=NC(N)=C1C OYVAGSVQBOHSSS-UAPAGMARSA-O 0.000 description 1
- 230000036765 blood level Effects 0.000 description 1
- 210000001124 body fluid Anatomy 0.000 description 1
- 239000010839 body fluid Substances 0.000 description 1
- RSIHSRDYCUFFLA-DYKIIFRCSA-N boldenone Chemical compound O=C1C=C[C@]2(C)[C@H]3CC[C@](C)([C@H](CC4)O)[C@@H]4[C@@H]3CCC2=C1 RSIHSRDYCUFFLA-DYKIIFRCSA-N 0.000 description 1
- 210000000988 bone and bone Anatomy 0.000 description 1
- 210000002798 bone marrow cell Anatomy 0.000 description 1
- 229960002802 bromocriptine Drugs 0.000 description 1
- OZVBMTJYIDMWIL-AYFBDAFISA-N bromocriptine Chemical compound C1=CC(C=2[C@H](N(C)C[C@@H](C=2)C(=O)N[C@]2(C(=O)N3[C@H](C(N4CCC[C@H]4[C@]3(O)O2)=O)CC(C)C)C(C)C)C2)=C3C2=C(Br)NC3=C1 OZVBMTJYIDMWIL-AYFBDAFISA-N 0.000 description 1
- 206010006451 bronchitis Diseases 0.000 description 1
- 229960004436 budesonide Drugs 0.000 description 1
- 239000000872 buffer Substances 0.000 description 1
- 229960002092 busulfan Drugs 0.000 description 1
- DQXBYHZEEUGOBF-UHFFFAOYSA-N but-3-enoic acid;ethene Chemical compound C=C.OC(=O)CC=C DQXBYHZEEUGOBF-UHFFFAOYSA-N 0.000 description 1
- 210000004899 c-terminal region Anatomy 0.000 description 1
- 229960004596 cabergoline Drugs 0.000 description 1
- AIYUHDOJVYHVIT-UHFFFAOYSA-M caesium chloride Chemical compound [Cl-].[Cs+] AIYUHDOJVYHVIT-UHFFFAOYSA-M 0.000 description 1
- BQRGNLJZBFXNCZ-UHFFFAOYSA-N calcein am Chemical compound O1C(=O)C2=CC=CC=C2C21C1=CC(CN(CC(=O)OCOC(C)=O)CC(=O)OCOC(C)=O)=C(OC(C)=O)C=C1OC1=C2C=C(CN(CC(=O)OCOC(C)=O)CC(=O)OCOC(=O)C)C(OC(C)=O)=C1 BQRGNLJZBFXNCZ-UHFFFAOYSA-N 0.000 description 1
- BBBFJLBPOGFECG-VJVYQDLKSA-N calcitonin Chemical compound N([C@H](C(=O)N[C@@H](CC(C)C)C(=O)NCC(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC=1NC=NC=1)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(=O)NCC(=O)N[C@@H](CO)C(=O)NCC(=O)N[C@@H]([C@@H](C)O)C(=O)N1[C@@H](CCC1)C(N)=O)C(C)C)C(=O)[C@@H]1CSSC[C@H](N)C(=O)N[C@@H](CO)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CO)C(=O)N[C@@H]([C@@H](C)O)C(=O)N1 BBBFJLBPOGFECG-VJVYQDLKSA-N 0.000 description 1
- 229960004015 calcitonin Drugs 0.000 description 1
- 229910052791 calcium Inorganic materials 0.000 description 1
- 239000011575 calcium Substances 0.000 description 1
- 239000001506 calcium phosphate Substances 0.000 description 1
- 229910000389 calcium phosphate Inorganic materials 0.000 description 1
- 235000011010 calcium phosphates Nutrition 0.000 description 1
- HXCHCVDVKSCDHU-LULTVBGHSA-N calicheamicin Chemical compound C1[C@H](OC)[C@@H](NCC)CO[C@H]1O[C@H]1[C@H](O[C@@H]2C\3=C(NC(=O)OC)C(=O)C[C@](C/3=C/CSSSC)(O)C#C\C=C/C#C2)O[C@H](C)[C@@H](NO[C@@H]2O[C@H](C)[C@@H](SC(=O)C=3C(=C(OC)C(O[C@H]4[C@@H]([C@H](OC)[C@@H](O)[C@H](C)O4)O)=C(I)C=3C)OC)[C@@H](O)C2)[C@@H]1O HXCHCVDVKSCDHU-LULTVBGHSA-N 0.000 description 1
- 229930195731 calicheamicin Natural products 0.000 description 1
- 229960001838 canakinumab Drugs 0.000 description 1
- 150000001718 carbodiimides Chemical class 0.000 description 1
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 1
- 239000001768 carboxy methyl cellulose Substances 0.000 description 1
- 235000010948 carboxy methyl cellulose Nutrition 0.000 description 1
- 150000001735 carboxylic acids Chemical class 0.000 description 1
- 125000002057 carboxymethyl group Chemical group [H]OC(=O)C([H])([H])[*] 0.000 description 1
- 239000008112 carboxymethyl-cellulose Substances 0.000 description 1
- 108010041776 cardiotrophin 1 Proteins 0.000 description 1
- 229960005243 carmustine Drugs 0.000 description 1
- 210000000845 cartilage Anatomy 0.000 description 1
- 238000004113 cell culture Methods 0.000 description 1
- 230000003915 cell function Effects 0.000 description 1
- 230000022534 cell killing Effects 0.000 description 1
- 239000013592 cell lysate Substances 0.000 description 1
- 230000011748 cell maturation Effects 0.000 description 1
- 229960003115 certolizumab pegol Drugs 0.000 description 1
- 239000002738 chelating agent Substances 0.000 description 1
- NDAYQJDHGXTBJL-MWWSRJDJSA-N chembl557217 Chemical compound C1=CC=C2C(C[C@H](NC(=O)[C@@H](CC(C)C)NC(=O)[C@H](CC=3C4=CC=CC=C4NC=3)NC(=O)[C@@H](CC(C)C)NC(=O)[C@H](CC=3C4=CC=CC=C4NC=3)NC(=O)[C@@H](CC(C)C)NC(=O)[C@H](CC=3C4=CC=CC=C4NC=3)NC(=O)[C@@H](C(C)C)NC(=O)[C@H](C(C)C)NC(=O)[C@@H](C(C)C)NC(=O)[C@H](C)NC(=O)[C@H](NC(=O)CNC(=O)[C@@H](NC=O)C(C)C)CC(C)C)C(=O)NCCO)=CNC2=C1 NDAYQJDHGXTBJL-MWWSRJDJSA-N 0.000 description 1
- 238000007385 chemical modification Methods 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 229960004926 chlorobutanol Drugs 0.000 description 1
- VDANGULDQQJODZ-UHFFFAOYSA-N chloroprocaine Chemical compound CCN(CC)CCOC(=O)C1=CC=C(N)C=C1Cl VDANGULDQQJODZ-UHFFFAOYSA-N 0.000 description 1
- 229960002023 chloroprocaine Drugs 0.000 description 1
- OEYIOHPDSNJKLS-UHFFFAOYSA-N choline Chemical compound C[N+](C)(C)CCO OEYIOHPDSNJKLS-UHFFFAOYSA-N 0.000 description 1
- 229960001231 choline Drugs 0.000 description 1
- 208000016532 chronic granulomatous disease Diseases 0.000 description 1
- 230000006020 chronic inflammation Effects 0.000 description 1
- 229960004316 cisplatin Drugs 0.000 description 1
- 238000011260 co-administration Methods 0.000 description 1
- 229940126523 co-drug Drugs 0.000 description 1
- 229960001338 colchicine Drugs 0.000 description 1
- 229920001436 collagen Polymers 0.000 description 1
- 210000001072 colon Anatomy 0.000 description 1
- 238000004440 column chromatography Methods 0.000 description 1
- 230000002860 competitive effect Effects 0.000 description 1
- 108010047295 complement receptors Proteins 0.000 description 1
- 102000006834 complement receptors Human genes 0.000 description 1
- 230000004154 complement system Effects 0.000 description 1
- 230000009918 complex formation Effects 0.000 description 1
- 239000000356 contaminant Substances 0.000 description 1
- 229920001577 copolymer Polymers 0.000 description 1
- 210000004087 cornea Anatomy 0.000 description 1
- 230000000139 costimulatory effect Effects 0.000 description 1
- 239000007822 coupling agent Substances 0.000 description 1
- 229940111134 coxibs Drugs 0.000 description 1
- 230000009260 cross reactivity Effects 0.000 description 1
- 239000012228 culture supernatant Substances 0.000 description 1
- NZNMSOFKMUBTKW-UHFFFAOYSA-N cyclohexanecarboxylic acid Chemical compound OC(=O)C1CCCCC1 NZNMSOFKMUBTKW-UHFFFAOYSA-N 0.000 description 1
- 239000003255 cyclooxygenase 2 inhibitor Substances 0.000 description 1
- 229960001305 cysteine hydrochloride Drugs 0.000 description 1
- 229960000684 cytarabine Drugs 0.000 description 1
- GBOGMAARMMDZGR-TYHYBEHESA-N cytochalasin B Chemical compound C([C@H]1[C@@H]2[C@@H](C([C@@H](O)[C@@H]3/C=C/C[C@H](C)CCC[C@@H](O)/C=C/C(=O)O[C@@]23C(=O)N1)=C)C)C1=CC=CC=C1 GBOGMAARMMDZGR-TYHYBEHESA-N 0.000 description 1
- GBOGMAARMMDZGR-JREHFAHYSA-N cytochalasin B Natural products C[C@H]1CCC[C@@H](O)C=CC(=O)O[C@@]23[C@H](C=CC1)[C@H](O)C(=C)[C@@H](C)[C@@H]2[C@H](Cc4ccccc4)NC3=O GBOGMAARMMDZGR-JREHFAHYSA-N 0.000 description 1
- 231100000409 cytocidal Toxicity 0.000 description 1
- 230000000445 cytocidal effect Effects 0.000 description 1
- 230000016396 cytokine production Effects 0.000 description 1
- 230000009089 cytolysis Effects 0.000 description 1
- 231100000433 cytotoxic Toxicity 0.000 description 1
- 230000003013 cytotoxicity Effects 0.000 description 1
- 231100000135 cytotoxicity Toxicity 0.000 description 1
- 229960003901 dacarbazine Drugs 0.000 description 1
- RSIHSRDYCUFFLA-UHFFFAOYSA-N dehydrotestosterone Natural products O=C1C=CC2(C)C3CCC(C)(C(CC4)O)C4C3CCC2=C1 RSIHSRDYCUFFLA-UHFFFAOYSA-N 0.000 description 1
- 230000001934 delay Effects 0.000 description 1
- 239000000412 dendrimer Substances 0.000 description 1
- 229920000736 dendritic polymer Polymers 0.000 description 1
- 201000001981 dermatomyositis Diseases 0.000 description 1
- 238000013461 design Methods 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 230000001627 detrimental effect Effects 0.000 description 1
- 229960000633 dextran sulfate Drugs 0.000 description 1
- 206010012601 diabetes mellitus Diseases 0.000 description 1
- 229960001259 diclofenac Drugs 0.000 description 1
- DCOPUUMXTXDBNB-UHFFFAOYSA-N diclofenac Chemical compound OC(=O)CC1=CC=CC=C1NC1=C(Cl)C=CC=C1Cl DCOPUUMXTXDBNB-UHFFFAOYSA-N 0.000 description 1
- ZBCBWPMODOFKDW-UHFFFAOYSA-N diethanolamine Chemical compound OCCNCCO ZBCBWPMODOFKDW-UHFFFAOYSA-N 0.000 description 1
- 229940043237 diethanolamine Drugs 0.000 description 1
- 230000004069 differentiation Effects 0.000 description 1
- UGMCXQCYOVCMTB-UHFFFAOYSA-K dihydroxy(stearato)aluminium Chemical compound CCCCCCCCCCCCCCCCCC(=O)O[Al](O)O UGMCXQCYOVCMTB-UHFFFAOYSA-K 0.000 description 1
- 238000006471 dimerization reaction Methods 0.000 description 1
- 229940042399 direct acting antivirals protease inhibitors Drugs 0.000 description 1
- 230000005750 disease progression Effects 0.000 description 1
- BFMYDTVEBKDAKJ-UHFFFAOYSA-L disodium;(2',7'-dibromo-3',6'-dioxido-3-oxospiro[2-benzofuran-1,9'-xanthene]-4'-yl)mercury;hydrate Chemical compound O.[Na+].[Na+].O1C(=O)C2=CC=CC=C2C21C1=CC(Br)=C([O-])C([Hg])=C1OC1=C2C=C(Br)C([O-])=C1 BFMYDTVEBKDAKJ-UHFFFAOYSA-L 0.000 description 1
- 239000002270 dispersing agent Substances 0.000 description 1
- 230000009429 distress Effects 0.000 description 1
- 238000009826 distribution Methods 0.000 description 1
- 150000002019 disulfides Chemical class 0.000 description 1
- VQNATVDKACXKTF-XELLLNAOSA-N duocarmycin Chemical compound COC1=C(OC)C(OC)=C2NC(C(=O)N3C4=CC(=O)C5=C([C@@]64C[C@@H]6C3)C=C(N5)C(=O)OC)=CC2=C1 VQNATVDKACXKTF-XELLLNAOSA-N 0.000 description 1
- 229930184221 duocarmycin Natural products 0.000 description 1
- 229960005501 duocarmycin Drugs 0.000 description 1
- 239000000975 dye Substances 0.000 description 1
- 238000004520 electroporation Methods 0.000 description 1
- 230000008030 elimination Effects 0.000 description 1
- 238000003379 elimination reaction Methods 0.000 description 1
- 239000012149 elution buffer Substances 0.000 description 1
- AUVVAXYIELKVAI-CKBKHPSWSA-N emetine Chemical compound N1CCC2=CC(OC)=C(OC)C=C2[C@H]1C[C@H]1C[C@H]2C3=CC(OC)=C(OC)C=C3CCN2C[C@@H]1CC AUVVAXYIELKVAI-CKBKHPSWSA-N 0.000 description 1
- 229960002694 emetine Drugs 0.000 description 1
- AUVVAXYIELKVAI-UWBTVBNJSA-N emetine Natural products N1CCC2=CC(OC)=C(OC)C=C2[C@H]1C[C@H]1C[C@H]2C3=CC(OC)=C(OC)C=C3CCN2C[C@H]1CC AUVVAXYIELKVAI-UWBTVBNJSA-N 0.000 description 1
- 239000003995 emulsifying agent Substances 0.000 description 1
- 230000002124 endocrine Effects 0.000 description 1
- 230000002357 endometrial effect Effects 0.000 description 1
- 230000003511 endothelial effect Effects 0.000 description 1
- 230000007613 environmental effect Effects 0.000 description 1
- 229960005139 epinephrine Drugs 0.000 description 1
- 230000002449 erythroblastic effect Effects 0.000 description 1
- 229940105423 erythropoietin Drugs 0.000 description 1
- 229940011871 estrogen Drugs 0.000 description 1
- 239000000262 estrogen Substances 0.000 description 1
- 229960000403 etanercept Drugs 0.000 description 1
- BEFDCLMNVWHSGT-UHFFFAOYSA-N ethenylcyclopentane Chemical compound C=CC1CCCC1 BEFDCLMNVWHSGT-UHFFFAOYSA-N 0.000 description 1
- ZMMJGEGLRURXTF-UHFFFAOYSA-N ethidium bromide Chemical compound [Br-].C12=CC(N)=CC=C2C2=CC=C(N)C=C2[N+](CC)=C1C1=CC=CC=C1 ZMMJGEGLRURXTF-UHFFFAOYSA-N 0.000 description 1
- 229960005542 ethidium bromide Drugs 0.000 description 1
- LVGKNOAMLMIIKO-QXMHVHEDSA-N ethyl oleate Chemical compound CCCCCCCC\C=C/CCCCCCCC(=O)OCC LVGKNOAMLMIIKO-QXMHVHEDSA-N 0.000 description 1
- 229940093471 ethyl oleate Drugs 0.000 description 1
- 239000005038 ethylene vinyl acetate Substances 0.000 description 1
- VJJPUSNTGOMMGY-MRVIYFEKSA-N etoposide Chemical compound COC1=C(O)C(OC)=CC([C@@H]2C3=CC=4OCOC=4C=C3[C@@H](O[C@H]3[C@@H]([C@@H](O)[C@@H]4O[C@H](C)OC[C@H]4O3)O)[C@@H]3[C@@H]2C(OC3)=O)=C1 VJJPUSNTGOMMGY-MRVIYFEKSA-N 0.000 description 1
- 229960005420 etoposide Drugs 0.000 description 1
- 208000030533 eye disease Diseases 0.000 description 1
- 239000012091 fetal bovine serum Substances 0.000 description 1
- 229960000556 fingolimod Drugs 0.000 description 1
- 230000003890 fistula Effects 0.000 description 1
- 238000001943 fluorescence-activated cell sorting Methods 0.000 description 1
- 229960002714 fluticasone Drugs 0.000 description 1
- MGNNYOODZCAHBA-GQKYHHCASA-N fluticasone Chemical compound C1([C@@H](F)C2)=CC(=O)C=C[C@]1(C)[C@]1(F)[C@@H]2[C@@H]2C[C@@H](C)[C@@](C(=O)SCF)(O)[C@@]2(C)C[C@@H]1O MGNNYOODZCAHBA-GQKYHHCASA-N 0.000 description 1
- 235000013305 food Nutrition 0.000 description 1
- 238000004108 freeze drying Methods 0.000 description 1
- 101150023212 fut8 gene Proteins 0.000 description 1
- 210000001035 gastrointestinal tract Anatomy 0.000 description 1
- 229960005277 gemcitabine Drugs 0.000 description 1
- SDUQYLNIPVEERB-QPPQHZFASA-N gemcitabine Chemical compound O=C1N=C(N)C=CN1[C@H]1C(F)(F)[C@H](O)[C@@H](CO)O1 SDUQYLNIPVEERB-QPPQHZFASA-N 0.000 description 1
- 230000030279 gene silencing Effects 0.000 description 1
- 238000012637 gene transfection Methods 0.000 description 1
- 208000016361 genetic disease Diseases 0.000 description 1
- MASNOZXLGMXCHN-ZLPAWPGGSA-N glucagon Chemical compound C([C@@H](C(=O)N[C@H](C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(O)=O)C(C)C)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](C)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CO)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CO)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@@H](NC(=O)CNC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CO)NC(=O)[C@@H](N)CC=1NC=NC=1)[C@@H](C)O)[C@@H](C)O)C1=CC=CC=C1 MASNOZXLGMXCHN-ZLPAWPGGSA-N 0.000 description 1
- 229960004666 glucagon Drugs 0.000 description 1
- 235000013922 glutamic acid Nutrition 0.000 description 1
- 239000004220 glutamic acid Substances 0.000 description 1
- ZDXPYRJPNDTMRX-UHFFFAOYSA-N glutamine Natural products OC(=O)C(N)CCC(N)=O ZDXPYRJPNDTMRX-UHFFFAOYSA-N 0.000 description 1
- 235000021312 gluten Nutrition 0.000 description 1
- 208000024908 graft versus host disease Diseases 0.000 description 1
- 210000003714 granulocyte Anatomy 0.000 description 1
- 229940093915 gynecological organic acid Drugs 0.000 description 1
- 230000035876 healing Effects 0.000 description 1
- 230000003862 health status Effects 0.000 description 1
- 229940037467 helicobacter pylori Drugs 0.000 description 1
- 208000014951 hematologic disease Diseases 0.000 description 1
- 208000007475 hemolytic anemia Diseases 0.000 description 1
- 239000002634 heparin fragment Substances 0.000 description 1
- 102000049963 human SIRPA Human genes 0.000 description 1
- 229920002674 hyaluronan Polymers 0.000 description 1
- 229960003160 hyaluronic acid Drugs 0.000 description 1
- 210000004408 hybridoma Anatomy 0.000 description 1
- 150000007857 hydrazones Chemical class 0.000 description 1
- XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 1
- 229910000043 hydrogen iodide Inorganic materials 0.000 description 1
- 150000002433 hydrophilic molecules Chemical class 0.000 description 1
- 230000002209 hydrophobic effect Effects 0.000 description 1
- 125000002768 hydroxyalkyl group Chemical group 0.000 description 1
- 206010051040 hyper-IgE syndrome Diseases 0.000 description 1
- 229960001001 ibritumomab tiuxetan Drugs 0.000 description 1
- 208000016036 idiopathic nephrotic syndrome Diseases 0.000 description 1
- 208000026278 immune system disease Diseases 0.000 description 1
- 230000036039 immunity Effects 0.000 description 1
- 230000007813 immunodeficiency Effects 0.000 description 1
- 210000000428 immunological synapse Anatomy 0.000 description 1
- 239000002955 immunomodulating agent Substances 0.000 description 1
- 229940121354 immunomodulator Drugs 0.000 description 1
- 230000002584 immunomodulator Effects 0.000 description 1
- 229960003444 immunosuppressant agent Drugs 0.000 description 1
- 230000001861 immunosuppressant effect Effects 0.000 description 1
- 229940125721 immunosuppressive agent Drugs 0.000 description 1
- 239000002596 immunotoxin Substances 0.000 description 1
- 230000006872 improvement Effects 0.000 description 1
- 230000002779 inactivation Effects 0.000 description 1
- 208000016245 inborn errors of metabolism Diseases 0.000 description 1
- 238000010348 incorporation Methods 0.000 description 1
- 229940055742 indium-111 Drugs 0.000 description 1
- APFVFJFRJDLVQX-AHCXROLUSA-N indium-111 Chemical compound [111In] APFVFJFRJDLVQX-AHCXROLUSA-N 0.000 description 1
- 230000006698 induction Effects 0.000 description 1
- 239000012678 infectious agent Substances 0.000 description 1
- 230000002458 infectious effect Effects 0.000 description 1
- 230000028709 inflammatory response Effects 0.000 description 1
- 229960000598 infliximab Drugs 0.000 description 1
- 208000015978 inherited metabolic disease Diseases 0.000 description 1
- 238000011221 initial treatment Methods 0.000 description 1
- 239000007972 injectable composition Substances 0.000 description 1
- 229940102223 injectable solution Drugs 0.000 description 1
- 229940125396 insulin Drugs 0.000 description 1
- 229940079322 interferon Drugs 0.000 description 1
- 108090000681 interleukin 20 Proteins 0.000 description 1
- 102000004114 interleukin 20 Human genes 0.000 description 1
- 108010074108 interleukin-21 Proteins 0.000 description 1
- 108010074109 interleukin-22 Proteins 0.000 description 1
- 210000000936 intestine Anatomy 0.000 description 1
- 238000001361 intraarterial administration Methods 0.000 description 1
- 229910052740 iodine Inorganic materials 0.000 description 1
- 239000011630 iodine Substances 0.000 description 1
- 229960001361 ipratropium bromide Drugs 0.000 description 1
- KEWHKYJURDBRMN-ZEODDXGYSA-M ipratropium bromide hydrate Chemical compound O.[Br-].O([C@H]1C[C@H]2CC[C@@H](C1)[N@@+]2(C)C(C)C)C(=O)C(CO)C1=CC=CC=C1 KEWHKYJURDBRMN-ZEODDXGYSA-M 0.000 description 1
- 230000001788 irregular Effects 0.000 description 1
- 230000000302 ischemic effect Effects 0.000 description 1
- 206010023332 keratitis Diseases 0.000 description 1
- 201000010666 keratoconjunctivitis Diseases 0.000 description 1
- 238000002372 labelling Methods 0.000 description 1
- 210000001821 langerhans cell Anatomy 0.000 description 1
- 229940039781 leptin Drugs 0.000 description 1
- NRYBAZVQPHGZNS-ZSOCWYAHSA-N leptin Chemical compound O=C([C@H](CO)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CC=1C2=CC=CC=C2NC=1)NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CO)NC(=O)CNC(=O)[C@H](CCC(N)=O)NC(=O)[C@@H](N)CC(C)C)CCSC)N1CCC[C@H]1C(=O)NCC(=O)N[C@@H](CS)C(O)=O NRYBAZVQPHGZNS-ZSOCWYAHSA-N 0.000 description 1
- 108010019813 leptin receptors Proteins 0.000 description 1
- 125000001909 leucine group Chemical group [H]N(*)C(C(*)=O)C([H])([H])C(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 229960004194 lidocaine Drugs 0.000 description 1
- 150000002632 lipids Chemical class 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 239000012669 liquid formulation Substances 0.000 description 1
- 229960002247 lomustine Drugs 0.000 description 1
- OHSVLFRHMCKCQY-NJFSPNSNSA-N lutetium-177 Chemical compound [177Lu] OHSVLFRHMCKCQY-NJFSPNSNSA-N 0.000 description 1
- 210000001165 lymph node Anatomy 0.000 description 1
- 230000002132 lysosomal effect Effects 0.000 description 1
- 229920001427 mPEG Polymers 0.000 description 1
- 229940124302 mTOR inhibitor Drugs 0.000 description 1
- 229910052749 magnesium Inorganic materials 0.000 description 1
- 239000011777 magnesium Substances 0.000 description 1
- 239000003628 mammalian target of rapamycin inhibitor Substances 0.000 description 1
- 239000000594 mannitol Substances 0.000 description 1
- 235000010355 mannitol Nutrition 0.000 description 1
- 239000011159 matrix material Substances 0.000 description 1
- WKPWGQKGSOKKOO-RSFHAFMBSA-N maytansine Chemical compound CO[C@@H]([C@@]1(O)C[C@](OC(=O)N1)([C@H]([C@@H]1O[C@@]1(C)[C@@H](OC(=O)[C@H](C)N(C)C(C)=O)CC(=O)N1C)C)[H])\C=C\C=C(C)\CC2=CC(OC)=C(Cl)C1=C2 WKPWGQKGSOKKOO-RSFHAFMBSA-N 0.000 description 1
- 229960003987 melatonin Drugs 0.000 description 1
- DRLFMBDRBRZALE-UHFFFAOYSA-N melatonin Chemical compound COC1=CC=C2NC=C(CCNC(C)=O)C2=C1 DRLFMBDRBRZALE-UHFFFAOYSA-N 0.000 description 1
- SGDBTWWWUNNDEQ-LBPRGKRZSA-N melphalan Chemical compound OC(=O)[C@@H](N)CC1=CC=C(N(CCCl)CCCl)C=C1 SGDBTWWWUNNDEQ-LBPRGKRZSA-N 0.000 description 1
- 229960001924 melphalan Drugs 0.000 description 1
- 239000012528 membrane Substances 0.000 description 1
- 210000004379 membrane Anatomy 0.000 description 1
- 229960001428 mercaptopurine Drugs 0.000 description 1
- 208000030159 metabolic disease Diseases 0.000 description 1
- 230000004060 metabolic process Effects 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- 229930182817 methionine Natural products 0.000 description 1
- 229920000609 methyl cellulose Polymers 0.000 description 1
- 239000001923 methylcellulose Substances 0.000 description 1
- 239000004530 micro-emulsion Substances 0.000 description 1
- 244000005700 microbiome Species 0.000 description 1
- 150000007522 mineralic acids Chemical class 0.000 description 1
- 239000002395 mineralocorticoid Substances 0.000 description 1
- 229960004023 minocycline Drugs 0.000 description 1
- DYKFCLLONBREIL-KVUCHLLUSA-N minocycline Chemical compound C([C@H]1C2)C3=C(N(C)C)C=CC(O)=C3C(=O)C1=C(O)[C@@]1(O)[C@@H]2[C@H](N(C)C)C(O)=C(C(N)=O)C1=O DYKFCLLONBREIL-KVUCHLLUSA-N 0.000 description 1
- 229960005485 mitobronitol Drugs 0.000 description 1
- KKZJGLLVHKMTCM-UHFFFAOYSA-N mitoxantrone Chemical compound O=C1C2=C(O)C=CC(O)=C2C(=O)C2=C1C(NCCNCCO)=CC=C2NCCNCCO KKZJGLLVHKMTCM-UHFFFAOYSA-N 0.000 description 1
- 229960001156 mitoxantrone Drugs 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 238000001823 molecular biology technique Methods 0.000 description 1
- 229960001664 mometasone Drugs 0.000 description 1
- QLIIKPVHVRXHRI-CXSFZGCWSA-N mometasone Chemical compound C1CC2=CC(=O)C=C[C@]2(C)[C@]2(Cl)[C@@H]1[C@@H]1C[C@@H](C)[C@@](C(=O)CCl)(O)[C@@]1(C)C[C@@H]2O QLIIKPVHVRXHRI-CXSFZGCWSA-N 0.000 description 1
- 238000012544 monitoring process Methods 0.000 description 1
- 238000010172 mouse model Methods 0.000 description 1
- 210000004877 mucosa Anatomy 0.000 description 1
- 210000004400 mucous membrane Anatomy 0.000 description 1
- 210000003097 mucus Anatomy 0.000 description 1
- 206010028417 myasthenia gravis Diseases 0.000 description 1
- RTGDFNSFWBGLEC-SYZQJQIISA-N mycophenolate mofetil Chemical compound COC1=C(C)C=2COC(=O)C=2C(O)=C1C\C=C(/C)CCC(=O)OCCN1CCOCC1 RTGDFNSFWBGLEC-SYZQJQIISA-N 0.000 description 1
- 229960004866 mycophenolate mofetil Drugs 0.000 description 1
- 210000003914 myeloid leukocyte Anatomy 0.000 description 1
- DAZSWUUAFHBCGE-KRWDZBQOSA-N n-[(2s)-3-methyl-1-oxo-1-pyrrolidin-1-ylbutan-2-yl]-3-phenylpropanamide Chemical compound N([C@@H](C(C)C)C(=O)N1CCCC1)C(=O)CCC1=CC=CC=C1 DAZSWUUAFHBCGE-KRWDZBQOSA-N 0.000 description 1
- OHDXDNUPVVYWOV-UHFFFAOYSA-N n-methyl-1-(2-naphthalen-1-ylsulfanylphenyl)methanamine Chemical compound CNCC1=CC=CC=C1SC1=CC=CC2=CC=CC=C12 OHDXDNUPVVYWOV-UHFFFAOYSA-N 0.000 description 1
- CMWTZPSULFXXJA-VIFPVBQESA-N naproxen Chemical compound C1=C([C@H](C)C(O)=O)C=CC2=CC(OC)=CC=C21 CMWTZPSULFXXJA-VIFPVBQESA-N 0.000 description 1
- 229960002009 naproxen Drugs 0.000 description 1
- 239000013642 negative control Substances 0.000 description 1
- 101150091879 neo gene Proteins 0.000 description 1
- 210000002569 neuron Anatomy 0.000 description 1
- 229910017604 nitric acid Inorganic materials 0.000 description 1
- 239000000041 non-steroidal anti-inflammatory agent Substances 0.000 description 1
- 229940021182 non-steroidal anti-inflammatory drug Drugs 0.000 description 1
- 238000007474 nonparametric Mann- Whitney U test Methods 0.000 description 1
- 229960002748 norepinephrine Drugs 0.000 description 1
- SFLSHLFXELFNJZ-UHFFFAOYSA-N norepinephrine Natural products NCC(O)C1=CC=C(O)C(O)=C1 SFLSHLFXELFNJZ-UHFFFAOYSA-N 0.000 description 1
- 238000003199 nucleic acid amplification method Methods 0.000 description 1
- 239000003921 oil Substances 0.000 description 1
- 235000019198 oils Nutrition 0.000 description 1
- 235000008390 olive oil Nutrition 0.000 description 1
- 239000004006 olive oil Substances 0.000 description 1
- 238000005457 optimization Methods 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 235000005985 organic acids Nutrition 0.000 description 1
- 150000002894 organic compounds Chemical class 0.000 description 1
- 150000002895 organic esters Chemical class 0.000 description 1
- 201000008482 osteoarthritis Diseases 0.000 description 1
- 229960001609 oxitropium bromide Drugs 0.000 description 1
- LCELQERNWLBPSY-KHSTUMNDSA-M oxitropium bromide Chemical compound [Br-].C1([C@@H](CO)C(=O)O[C@H]2C[C@@H]3[N+]([C@H](C2)[C@@H]2[C@H]3O2)(C)CC)=CC=CC=C1 LCELQERNWLBPSY-KHSTUMNDSA-M 0.000 description 1
- XNOPRXBHLZRZKH-DSZYJQQASA-N oxytocin Chemical compound C([C@H]1C(=O)N[C@H](C(N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CSSC[C@H](N)C(=O)N1)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CC(C)C)C(=O)NCC(N)=O)=O)[C@@H](C)CC)C1=CC=C(O)C=C1 XNOPRXBHLZRZKH-DSZYJQQASA-N 0.000 description 1
- 229960001723 oxytocin Drugs 0.000 description 1
- 229960001592 paclitaxel Drugs 0.000 description 1
- 229960005489 paracetamol Drugs 0.000 description 1
- 238000007911 parenteral administration Methods 0.000 description 1
- 230000036961 partial effect Effects 0.000 description 1
- 230000008506 pathogenesis Effects 0.000 description 1
- 229960001639 penicillamine Drugs 0.000 description 1
- 239000000137 peptide hydrolase inhibitor Substances 0.000 description 1
- 210000005259 peripheral blood Anatomy 0.000 description 1
- 239000011886 peripheral blood Substances 0.000 description 1
- 230000002093 peripheral effect Effects 0.000 description 1
- 238000002823 phage display Methods 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- 230000003285 pharmacodynamic effect Effects 0.000 description 1
- 239000008055 phosphate buffer solution Substances 0.000 description 1
- 230000000704 physical effect Effects 0.000 description 1
- 230000010399 physical interaction Effects 0.000 description 1
- 239000013600 plasmid vector Substances 0.000 description 1
- 206010035653 pneumoconiosis Diseases 0.000 description 1
- 229920001200 poly(ethylene-vinyl acetate) Polymers 0.000 description 1
- 229920000747 poly(lactic acid) Polymers 0.000 description 1
- 230000008488 polyadenylation Effects 0.000 description 1
- 229920001515 polyalkylene glycol Polymers 0.000 description 1
- 229920000573 polyethylene Polymers 0.000 description 1
- 239000004633 polyglycolic acid Substances 0.000 description 1
- 239000004626 polylactic acid Substances 0.000 description 1
- 102000054765 polymorphisms of proteins Human genes 0.000 description 1
- 229920001155 polypropylene Polymers 0.000 description 1
- 229920005606 polypropylene copolymer Polymers 0.000 description 1
- 229920001451 polypropylene glycol Polymers 0.000 description 1
- 229920002451 polyvinyl alcohol Polymers 0.000 description 1
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 1
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
- 230000004481 post-translational protein modification Effects 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- OXCMYAYHXIHQOA-UHFFFAOYSA-N potassium;[2-butyl-5-chloro-3-[[4-[2-(1,2,4-triaza-3-azanidacyclopenta-1,4-dien-5-yl)phenyl]phenyl]methyl]imidazol-4-yl]methanol Chemical compound [K+].CCCCC1=NC(Cl)=C(CO)N1CC1=CC=C(C=2C(=CC=CC=2)C2=N[N-]N=N2)C=C1 OXCMYAYHXIHQOA-UHFFFAOYSA-N 0.000 description 1
- 230000003389 potentiating effect Effects 0.000 description 1
- 238000001556 precipitation Methods 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- 229960003387 progesterone Drugs 0.000 description 1
- 239000000186 progesterone Substances 0.000 description 1
- 230000000750 progressive effect Effects 0.000 description 1
- 229960003712 propranolol Drugs 0.000 description 1
- 239000000473 propyl gallate Substances 0.000 description 1
- 229940075579 propyl gallate Drugs 0.000 description 1
- 235000010388 propyl gallate Nutrition 0.000 description 1
- 108020001580 protein domains Proteins 0.000 description 1
- 238000001742 protein purification Methods 0.000 description 1
- 229950010131 puromycin Drugs 0.000 description 1
- 238000011002 quantification Methods 0.000 description 1
- 238000001959 radiotherapy Methods 0.000 description 1
- 231100001258 radiotoxin Toxicity 0.000 description 1
- 238000010188 recombinant method Methods 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 238000012552 review Methods 0.000 description 1
- 206010039073 rheumatoid arthritis Diseases 0.000 description 1
- 229960001302 ridaforolimus Drugs 0.000 description 1
- UHSKFQJFRQCDBE-UHFFFAOYSA-N ropinirole Chemical compound CCCN(CCC)CCC1=CC=CC2=C1CC(=O)N2 UHSKFQJFRQCDBE-UHFFFAOYSA-N 0.000 description 1
- 229960001879 ropinirole Drugs 0.000 description 1
- 201000000306 sarcoidosis Diseases 0.000 description 1
- 125000003607 serino group Chemical group [H]N([H])[C@]([H])(C(=O)[*])C(O[H])([H])[H] 0.000 description 1
- 239000012679 serum free medium Substances 0.000 description 1
- 230000001568 sexual effect Effects 0.000 description 1
- 230000019491 signal transduction Effects 0.000 description 1
- 230000011664 signaling Effects 0.000 description 1
- 210000003491 skin Anatomy 0.000 description 1
- 229940126586 small molecule drug Drugs 0.000 description 1
- 210000002460 smooth muscle Anatomy 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- WBHQBSYUUJJSRZ-UHFFFAOYSA-M sodium bisulfate Chemical compound [Na+].OS([O-])(=O)=O WBHQBSYUUJJSRZ-UHFFFAOYSA-M 0.000 description 1
- 229910000342 sodium bisulfate Inorganic materials 0.000 description 1
- 229940100996 sodium bisulfate Drugs 0.000 description 1
- HRZFUMHJMZEROT-UHFFFAOYSA-L sodium disulfite Chemical compound [Na+].[Na+].[O-]S(=O)S([O-])(=O)=O HRZFUMHJMZEROT-UHFFFAOYSA-L 0.000 description 1
- 229940001584 sodium metabisulfite Drugs 0.000 description 1
- 235000010262 sodium metabisulphite Nutrition 0.000 description 1
- 229910052938 sodium sulfate Inorganic materials 0.000 description 1
- 229960003010 sodium sulfate Drugs 0.000 description 1
- 235000011152 sodium sulphate Nutrition 0.000 description 1
- 235000010199 sorbic acid Nutrition 0.000 description 1
- 239000004334 sorbic acid Substances 0.000 description 1
- 229940075582 sorbic acid Drugs 0.000 description 1
- 230000009870 specific binding Effects 0.000 description 1
- 208000020431 spinal cord injury Diseases 0.000 description 1
- 230000002269 spontaneous effect Effects 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 230000003068 static effect Effects 0.000 description 1
- 238000007619 statistical method Methods 0.000 description 1
- 230000001954 sterilising effect Effects 0.000 description 1
- 238000004659 sterilization and disinfection Methods 0.000 description 1
- 238000013517 stratification Methods 0.000 description 1
- ZSJLQEPLLKMAKR-GKHCUFPYSA-N streptozocin Chemical compound O=NN(C)C(=O)N[C@H]1[C@@H](O)O[C@H](CO)[C@@H](O)[C@@H]1O ZSJLQEPLLKMAKR-GKHCUFPYSA-N 0.000 description 1
- 229960001052 streptozocin Drugs 0.000 description 1
- 230000035882 stress Effects 0.000 description 1
- 150000005846 sugar alcohols Polymers 0.000 description 1
- 229960001940 sulfasalazine Drugs 0.000 description 1
- NCEXYHBECQHGNR-QZQOTICOSA-N sulfasalazine Chemical compound C1=C(O)C(C(=O)O)=CC(\N=N\C=2C=CC(=CC=2)S(=O)(=O)NC=2N=CC=CC=2)=C1 NCEXYHBECQHGNR-QZQOTICOSA-N 0.000 description 1
- NCEXYHBECQHGNR-UHFFFAOYSA-N sulfasalazine Natural products C1=C(O)C(C(=O)O)=CC(N=NC=2C=CC(=CC=2)S(=O)(=O)NC=2N=CC=CC=2)=C1 NCEXYHBECQHGNR-UHFFFAOYSA-N 0.000 description 1
- 239000006228 supernatant Substances 0.000 description 1
- 230000001629 suppression Effects 0.000 description 1
- 230000002459 sustained effect Effects 0.000 description 1
- 239000012730 sustained-release form Substances 0.000 description 1
- 201000000596 systemic lupus erythematosus Diseases 0.000 description 1
- 229960001967 tacrolimus Drugs 0.000 description 1
- 230000008685 targeting Effects 0.000 description 1
- 239000011975 tartaric acid Substances 0.000 description 1
- 235000002906 tartaric acid Nutrition 0.000 description 1
- RCINICONZNJXQF-MZXODVADSA-N taxol Chemical compound O([C@@H]1[C@@]2(C[C@@H](C(C)=C(C2(C)C)[C@H](C([C@]2(C)[C@@H](O)C[C@H]3OC[C@]3([C@H]21)OC(C)=O)=O)OC(=O)C)OC(=O)[C@H](O)[C@@H](NC(=O)C=1C=CC=CC=1)C=1C=CC=CC=1)O)C(=O)C1=CC=CC=C1 RCINICONZNJXQF-MZXODVADSA-N 0.000 description 1
- 229960000235 temsirolimus Drugs 0.000 description 1
- NRUKOCRGYNPUPR-QBPJDGROSA-N teniposide Chemical compound COC1=C(O)C(OC)=CC([C@@H]2C3=CC=4OCOC=4C=C3[C@@H](O[C@H]3[C@@H]([C@@H](O)[C@@H]4O[C@@H](OC[C@H]4O3)C=3SC=CC=3)O)[C@@H]3[C@@H]2C(OC3)=O)=C1 NRUKOCRGYNPUPR-QBPJDGROSA-N 0.000 description 1
- 229960001278 teniposide Drugs 0.000 description 1
- ISIJQEHRDSCQIU-UHFFFAOYSA-N tert-butyl 2,7-diazaspiro[4.5]decane-7-carboxylate Chemical compound C1N(C(=O)OC(C)(C)C)CCCC11CNCC1 ISIJQEHRDSCQIU-UHFFFAOYSA-N 0.000 description 1
- 229960003604 testosterone Drugs 0.000 description 1
- 229960002372 tetracaine Drugs 0.000 description 1
- GKCBAIGFKIBETG-UHFFFAOYSA-N tetracaine Chemical compound CCCCNC1=CC=C(C(=O)OCCN(C)C)C=C1 GKCBAIGFKIBETG-UHFFFAOYSA-N 0.000 description 1
- ZRKFYGHZFMAOKI-QMGMOQQFSA-N tgfbeta Chemical compound C([C@H](NC(=O)[C@H](C(C)C)NC(=O)CNC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H]([C@@H](C)O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H]([C@@H](C)O)NC(=O)[C@H](CC(C)C)NC(=O)CNC(=O)[C@H](C)NC(=O)[C@H](CO)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@@H](NC(=O)[C@H](C)NC(=O)[C@H](C)NC(=O)[C@@H](NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](N)CCSC)C(C)C)[C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](C)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](C)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](C)C(=O)N[C@@H](CC(C)C)C(=O)N1[C@@H](CCC1)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(C)C)C(O)=O)C1=CC=C(O)C=C1 ZRKFYGHZFMAOKI-QMGMOQQFSA-N 0.000 description 1
- 150000003568 thioethers Chemical class 0.000 description 1
- 230000002992 thymic effect Effects 0.000 description 1
- LCJVIYPJPCBWKS-NXPQJCNCSA-N thymosin Chemical compound SC[C@@H](N)C(=O)N[C@H](CO)C(=O)N[C@H](CC(O)=O)C(=O)N[C@@H](C)C(=O)N[C@@H](C)C(=O)N[C@H](C(C)C)C(=O)N[C@H](CC(O)=O)C(=O)N[C@H](C(C)C)C(=O)N[C@H](CO)C(=O)N[C@H](CO)C(=O)N[C@H](CCC(O)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@H]([C@H](C)O)C(=O)N[C@H](C(C)C)C(=O)N[C@H](CCCCN)C(=O)N[C@H](CC(O)=O)C(=O)N[C@H](CC(C)C)C(=O)N[C@H](CCCCN)C(=O)N[C@H](CCC(O)=O)C(=O)N[C@H](CCCCN)C(=O)N[C@H](CCCCN)C(=O)N[C@H](CCC(O)=O)C(=O)N[C@H](C(C)C)C(=O)N[C@H](C(C)C)C(=O)N[C@H](CCC(O)=O)C(=O)N[C@H](CCC(O)=O)C(=O)N[C@@H](C)C(=O)N[C@H](CCC(O)=O)C(O)=O LCJVIYPJPCBWKS-NXPQJCNCSA-N 0.000 description 1
- 229960003087 tioguanine Drugs 0.000 description 1
- 229960000257 tiotropium bromide Drugs 0.000 description 1
- AOBORMOPSGHCAX-DGHZZKTQSA-N tocofersolan Chemical compound OCCOC(=O)CCC(=O)OC1=C(C)C(C)=C2O[C@](CCC[C@H](C)CCC[C@H](C)CCCC(C)C)(C)CCC2=C1C AOBORMOPSGHCAX-DGHZZKTQSA-N 0.000 description 1
- 229960000984 tocofersolan Drugs 0.000 description 1
- 238000011200 topical administration Methods 0.000 description 1
- 230000000699 topical effect Effects 0.000 description 1
- 229960005267 tositumomab Drugs 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- 230000002110 toxicologic effect Effects 0.000 description 1
- 231100000759 toxicological effect Toxicity 0.000 description 1
- 238000013518 transcription Methods 0.000 description 1
- 230000035897 transcription Effects 0.000 description 1
- 230000002103 transcriptional effect Effects 0.000 description 1
- 230000010474 transient expression Effects 0.000 description 1
- 238000013519 translation Methods 0.000 description 1
- 238000011269 treatment regimen Methods 0.000 description 1
- QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 description 1
- 239000002451 tumor necrosis factor inhibitor Substances 0.000 description 1
- 231100000397 ulcer Toxicity 0.000 description 1
- 238000012762 unpaired Student’s t-test Methods 0.000 description 1
- 238000001291 vacuum drying Methods 0.000 description 1
- 238000009777 vacuum freeze-drying Methods 0.000 description 1
- 230000000304 vasodilatating effect Effects 0.000 description 1
- 235000015112 vegetable and seed oil Nutrition 0.000 description 1
- 239000008158 vegetable oil Substances 0.000 description 1
- 239000003981 vehicle Substances 0.000 description 1
- 208000018464 vernal keratoconjunctivitis Diseases 0.000 description 1
- 229920002554 vinyl polymer Polymers 0.000 description 1
- 230000003442 weekly effect Effects 0.000 description 1
- 239000000080 wetting agent Substances 0.000 description 1
- CGTADGCBEXYWNE-JUKNQOCSSA-N zotarolimus Chemical compound N1([C@H]2CC[C@@H](C[C@@H](C)[C@H]3OC(=O)[C@@H]4CCCCN4C(=O)C(=O)[C@@]4(O)[C@H](C)CC[C@H](O4)C[C@@H](/C(C)=C/C=C/C=C/[C@@H](C)C[C@@H](C)C(=O)[C@H](OC)[C@H](O)/C(C)=C/[C@@H](C)C(=O)C3)OC)C[C@H]2OC)C=NN=N1 CGTADGCBEXYWNE-JUKNQOCSSA-N 0.000 description 1
- 229950009819 zotarolimus Drugs 0.000 description 1
- 239000002076 α-tocopherol Substances 0.000 description 1
- 235000004835 α-tocopherol Nutrition 0.000 description 1
Images
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- C07K14/705—Receptors; Cell surface antigens; Cell surface determinants
- C07K14/70503—Immunoglobulin superfamily
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K19/00—Hybrid peptides, i.e. peptides covalently bound to nucleic acids, or non-covalently bound protein-protein complexes
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/04—Drugs for disorders of the alimentary tract or the digestive system for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
- A61P11/06—Antiasthmatics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/02—Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
-
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/08—Antiallergic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- 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
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- C07K14/705—Receptors; Cell surface antigens; Cell surface determinants
- C07K14/70596—Molecules with a "CD"-designation not provided for elsewhere
-
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2319/00—Fusion polypeptide
- C07K2319/30—Non-immunoglobulin-derived peptide or protein having an immunoglobulin constant or Fc region, or a fragment thereof, attached thereto
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Organic Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Immunology (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Pharmacology & Pharmacy (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Biochemistry (AREA)
- Biophysics (AREA)
- Molecular Biology (AREA)
- Genetics & Genomics (AREA)
- Gastroenterology & Hepatology (AREA)
- Zoology (AREA)
- Cell Biology (AREA)
- Pulmonology (AREA)
- Toxicology (AREA)
- Rheumatology (AREA)
- Heart & Thoracic Surgery (AREA)
- Vascular Medicine (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Oncology (AREA)
- Hematology (AREA)
- Pain & Pain Management (AREA)
- Cardiology (AREA)
- Physical Education & Sports Medicine (AREA)
- Urology & Nephrology (AREA)
- Epidemiology (AREA)
- Peptides Or Proteins (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
Abstract
(i)抗体の重鎖定常領域のN−末端部分で融合した第1のSIRPα結合ドメインを含む第1の一価の一本鎖ポリペプチド;および、
(ii)抗体のCL軽鎖定常領域のN−末端部分で融合した第2のSIRPα結合ドメインを含む第2の一価の一本鎖ポリペプチド
からなる可溶性SIRPα結合タンパク質に関する。本発明は、さらに、図1に示されている可溶性SIRPα結合抗体様タンパク質に関する。
Description
(i)抗体の重鎖定常領域のN−末端部分に融合した第1のSIRPα結合ドメインを含む第1の一価の一本鎖ポリペプチド;および
(ii)抗体の軽鎖定常領域のN−末端部分に融合した第2のSIRPα結合ドメインを含む第2の一価の一本鎖ポリペプチドからなる少なくとも2つの二価ヘテロダイマーの複合体を含む可溶性SIRPα結合タンパク質に関する。本発明の1つの特定の態様は、図1によりさらに説明される。
(i)抗体の重鎖定常領域に融合した哺乳動物結合分子の領域を含む第1の一価の一本鎖ポリペプチド;および
(ii)抗体の軽鎖定常領域に融合した同じ結合分子の領域を含む第2の一価の一本鎖ポリペプチド
からなる可溶性タンパク質を提供する。
(i)抗体のCH1定常重鎖領域に融合した哺乳動物結合分子の領域を含む第1の一価の一本鎖ポリペプチド;および
(ii)抗体のCL定常軽鎖領域に融合した同じ結合分子の領域を含む第2の一価の一本鎖ポリペプチド
からなる可溶性タンパク質を提供する。
(i)抗体の定常領域重鎖に融合した哺乳動物結合分子の領域を含む第1の一価の一本鎖ポリペプチド;および
(ii)抗体の定常領域軽鎖に融合した同じ哺乳動物結合分子の領域を含む第2の一価の一本鎖ポリペプチドからなる可溶性タンパク質を提供する。
(i)抗体のCH1定常重鎖領域に融合した哺乳動物結合分子の領域を含む第1の一価の一本鎖ポリペプチド;および
(ii)抗体のCL定常軽鎖領域に融合した同じ結合分子の領域を含む第2の一価の一本鎖ポリペプチドからなる可溶性タンパク質を提供する。
(i)抗体の定常領域重鎖に融合した哺乳動物結合分子の領域を含む第1の一価の一本鎖ポリペプチド;および
(ii)抗体の定常領域軽鎖に融合した同じ哺乳動物結合分子の同じ領域を含む第2の一価の一本鎖ポリペプチドからなる可溶性タンパク質を提供する。
(i)抗体のCH1定常重鎖領域に融合した哺乳動物結合分子の領域を含む第1の一価の一本鎖ポリペプチド;および
(ii)抗体のCL定常軽鎖領域に融合した同じ結合分子の同じ領域を含む第2の一価の一本鎖ポリペプチドからなる可溶性タンパク質を提供する。
(i)抗体の定常CH1重鎖領域のN−末端部分で融合した第1のSIRPα結合ドメインを含む第1の一本鎖ポリペプチド;および
(ii)抗体の定常CL軽鎖領域のN−末端部分で融合した第2のSIRPα結合ドメインを含む第2の一本鎖ポリペプチドからなるものに関する。
(i)ヒトCD47の細胞外ドメイン;
(ii)配列番号:4のポリペプチドまたはSIRPα結合特性を保持する配列番号:4のフラグメント;および
(iii)配列番号:4と少なくとも60、70、80、90、95、96、97、98または99パーセントの配列同一性を有し、SIRPα結合特性を保持する配列番号:4の変異体ポリペプチド
からなる群から選択される少なくとも1つのSIRPα結合ドメインを含む。
本発明をより容易に理解することができるようにするため、特定の用語を最初に定義する。さらなる定義は、詳細な説明を通して記載される。
表1:SIRPαタンパク質の変異体
表2:CD47タンパク質の変異体
−B7.1(CD80)およびB7.2(B70)からなる群から選択されるサイトカインの免疫グロブリンスーパーファミリーのメンバー;
−TNF−アルファ、TNF−ベータ、LT−ベータ、CD40リガンド、Fasリガンド、CD27リガンド、CD30リガンドおよび4−1BBLからなる群から選択されるサイトカインのTNFファミリーのメンバー;
表3:SIRPγタンパク質の変異体
本明細書において使用される「SIRPα結合ドメイン」は、適当な条件下でSIRPαへの結合のために必要であるあらゆる一本鎖ポリペプチドドメインを示す。SIRPα結合ドメインは、SIRPαとの物理的相互作用に直接関与する全てのアミノ酸残基を含む。SIRPαと直接相互作用しないが、SIRPαと相互作用するためにSIRPα結合ドメインの適当な構造に必要である他のアミノ酸をさらに含み得る。SIRPα結合ドメインは、SIRPαに対する結合特性の有意な変化なしに、異種ドメインに融合させてもよい。SIRPα結合ドメインは、SIRPαへ結合することが知られているタンパク質、例えば、CD47タンパク質の結合ドメインの中から選択され得る。SIRPα結合ドメインは、さらに、SIRPαに対する人工バインダーからなり得る。特に、バインダーは、一本鎖免疫グロブリンスカフォールド、例えば、単一ドメイン抗体、一本鎖抗体(scFv)またはラクダ抗体由来であった。1つの態様において、「SIRPα結合ドメイン」なる用語は、SIRPαに結合する抗体の可変領域、例えば、VHおよびVL領域由来のSIRPα抗原結合領域を含まない。
(i)ヒトCD47の細胞外ドメイン;
(ii)配列番号:4のポリペプチドまたはSIRPα結合特性を保持する配列番号:4のフラグメント;および、
(iii)配列番号:4と少なくとも60、70、80、90、95、96、97、98または99パーセントの配列同一性を有し、SIRPα結合特性を保持する配列番号:4の変異体ポリペプチド
からなる群から選択される。
1つの態様において、本発明のSIRPα結合タンパク質は、SIRPαに結合する(Fab)様または(Fab’)2様タンパク質である。
さらなる局面において、本発明は、上記パラグラフに記載されている少なくとも1つのSIRPα結合ドメインまたは(Fab)様タンパク質を含むFusobodyに関する。
本発明のFusobodiesは、実施例における表4に記載されているとおりに構造的に特徴付けられるFusobodiesを含むが、これらに限定されない。これらの例において使用されるSIRPα結合ドメインは、配列番号:4、配列番号:21、配列番号:23または配列番号:27において示される。本発明のSIRPα結合Fusobodiesの重鎖アミノ酸配列の特異的な例は、配列番号:5、配列番号:12、配列番号:18、配列番号:19、配列番号:24、配列番号:29、配列番号:36、配列番号:38、配列番号:40、配列番号:42、配列番号:44、配列番号:46、配列番号:48、配列番号:50、配列番号:52、配列番号:54、配列番号:56および配列番号:58からなる群から選択されるポリペプチド配列である。本発明のSIRPα結合Fusobodiesの軽鎖アミノ酸配列の特定の例は、配列番号:6、配列番号:13、配列番号:20、配列番号:25、配列番号:37、配列番号:39、配列番号:41、配列番号:43、配列番号:45、配列番号:47、配列番号:49、配列番号:51、配列番号:53、配列番号:55および配列番号:57からなる群から選択されるポリペプチド配列である。
1つの態様において、実施例#2として記載されている本発明のSIRPα結合Fusobodyは、配列番号:18の重鎖および配列番号:6の軽鎖を含む。
1つの態様において、実施例#3として記載されている本発明のSIRPα結合Fusobodyは、配列番号:19の重鎖および配列番号:20の軽鎖を含む。
1つの態様において、実施例#4として記載されている本発明のSIRPα結合Fusobodyは、配列番号:12の重鎖および配列番号:13の軽鎖を含む。
1つの態様において、実施例#5として記載されている本発明のSIRPα結合Fusobodyは、配列番号:24の重鎖および配列番号:25の軽鎖を含む。
1つの態様において、実施例#6として記載されている本発明のSIRPα結合Fusobodyは、配列番号:36の重鎖および配列番号:37の軽鎖を含む。
1つの態様において、実施例#7として記載されている本発明のSIRPα結合Fusobodyは、配列番号:38の重鎖および配列番号:39の軽鎖を含む。
1つの態様において、実施例#8として記載されている本発明のSIRPα結合Fusobodyは、配列番号:40の重鎖および配列番号:41の軽鎖を含む。
1つの態様において、実施例#9として記載されている本発明のSIRPα結合Fusobodyは、配列番号:42の重鎖および配列番号:43の軽鎖を含む。
1つの態様において、実施例#10として記載されている本発明のSIRPα結合Fusobodyは、配列番号:44の重鎖および配列番号:45の軽鎖を含む。
1つの態様において、実施例#11として記載されている本発明のSIRPα結合Fusobodyは、配列番号:46の重鎖および配列番号:47の軽鎖を含む。
1つの態様において、実施例#12として記載されている本発明のSIRPα結合Fusobodyは、配列番号:48の重鎖および配列番号:49の軽鎖を含む。
1つの態様において、実施例#13として記載されている本発明のSIRPα結合Fusobodyは、配列番号:50の重鎖および配列番号:51の軽鎖を含む。
1つの態様において、実施例#14として記載されている本発明のSIRPα結合Fusobodyは、配列番号:52の重鎖および配列番号:53の軽鎖を含む。
1つの態様において、実施例#15として記載されている本発明のSIRPα結合Fusobodyは、配列番号:54の重鎖および配列番号:55の軽鎖を含む。
1つの態様において、実施例#16として記載されている本発明のSIRPα結合Fusobodyは、配列番号:56の重鎖および配列番号:57の軽鎖を含む。
1つの態様において、実施例#17として記載されている本発明のSIRPα結合Fusobodyは、配列番号:58の重鎖および配列番号:20の軽鎖を含む。
1つの態様において、実施例#18として記載されている本発明のSIRPα結合Fusobodyは、配列番号:29の重鎖および配列番号:20の軽鎖を含む。
別の局面において、本発明は、配列番号:59のヌクレオチド配列によってコードされる重鎖および配列番号:60のヌクレオチド配列によってコードされる軽鎖を有する実施例#3として記載されている本発明の単離されたFusobodyを提供する。
別の局面において、本発明は、配列番号:61のヌクレオチド配列によってコードされる重鎖および配列番号:62のヌクレオチド配列によってコードされる軽鎖を有する実施例#4として記載されている本発明の単離されたFusobodyを提供する。
別の局面において、本発明は、配列番号:63のヌクレオチド配列によってコードされる重鎖および配列番号:64のヌクレオチド配列によってコードされる軽鎖を有する実施例#5として記載されている本発明の単離されたFusobodyを提供する。
別の局面において、本発明は、配列番号:65のヌクレオチド配列によってコードされる重鎖および配列番号:66のヌクレオチド配列によってコードされる軽鎖を有する実施例#6として記載されている本発明の単離されたFusobodyを提供する。
別の局面において、本発明は、配列番号:67のヌクレオチド配列によってコードされる重鎖および配列番号:68のヌクレオチド配列によってコードされる軽鎖を有する実施例#7として記載されている本発明の単離されたFusobodyを提供する。
別の局面において、本発明は、配列番号:69のヌクレオチド配列によってコードされる重鎖および配列番号:70のヌクレオチド配列によってコードされる軽鎖を有する実施例#8として記載されている本発明の単離されたFusobodyを提供する。
別の局面において、本発明は、配列番号:71のヌクレオチド配列によってコードされる重鎖および配列番号:72のヌクレオチド配列によってコードされる軽鎖を有する実施例#9として記載されている本発明の単離されたFusobodyを提供する。
別の局面において、本発明は、配列番号:73のヌクレオチド配列によってコードされる重鎖および配列番号:74のヌクレオチド配列によってコードされる軽鎖を有する実施例#10として記載されている本発明の単離されたFusobodyを提供する。
別の局面において、本発明は、配列番号:75のヌクレオチド配列によってコードされる重鎖および配列番号:76のヌクレオチド配列によってコードされる軽鎖を有する実施例#11として記載されている本発明の単離されたFusobodyを提供する。
別の局面において、本発明は、配列番号:77のヌクレオチド配列によってコードされる重鎖および配列番号:78のヌクレオチド配列によってコードされる軽鎖を有する実施例#12として記載されている本発明の単離されたFusobodyを提供する。
別の局面において、本発明は、配列番号:79のヌクレオチド配列によってコードされる重鎖および配列番号:80のヌクレオチド配列によってコードされる軽鎖を有する実施例#13として記載されている本発明の単離されたFusobodyを提供する。
別の局面において、本発明は、配列番号:81のヌクレオチド配列によってコードされる重鎖および配列番号:82のヌクレオチド配列によってコードされる軽鎖を有する実施例#14として記載されている本発明の単離されたFusobodyを提供する。
別の局面において、本発明は、配列番号:83のヌクレオチド配列によってコードされる重鎖および配列番号:84のヌクレオチド配列によってコードされる軽鎖を有する実施例#15として記載されている本発明の単離されたFusobodyを提供する。
別の局面において、本発明は、配列番号:85のヌクレオチド配列によってコードされる重鎖および配列番号:86のヌクレオチド配列によってコードされる軽鎖を有する実施例#16として記載されている本発明の単離されたFusobodyを提供する。
別の局面において、本発明は、配列番号:87のヌクレオチド配列によってコードされる重鎖および配列番号:60のヌクレオチド配列によってコードされる軽鎖を有する実施例#17として記載されている本発明の単離されたFusobodyを提供する。
別の局面において、本発明は、配列番号:88のヌクレオチド配列によってコードされる重鎖および配列番号:60のヌクレオチド配列によってコードされる軽鎖を有する実施例#18として記載されている本発明の単離されたFusobodyを提供する。
さらに別の態様において、本発明のSIRPα結合Fusobodyは、上記パラグラフに記載されている特定のSIRPα結合Fusobodies、特に、表4に記載されている実施例#1−18の対応するアミノ酸およびヌクレオチド配列と同種である、重鎖および軽鎖アミノ酸配列;重鎖および軽鎖ヌクレオチド配列または重鎖および軽鎖定常領域に融合したSIRPα結合ドメインを有し、該Fusobodiesは、上記パラグラフに記載されている特定のSIRPα結合Fusobodies、特に、表4に記載されている実施例#1−18の少なくとも1つの実質的に同じ機能特性を保持する。
Fcドメインは、少なくとCH2およびCH3ドメインを含む。本明細書において使用されるFcドメインなる用語は、1、2、3、4または5個のアミノ酸位置でアミノ酸置換、欠失または挿入が抗体の天然Fcフラグメント、例えば、ヒトFcフラグメントと比較して導入されたFc変異体をさらに含むが、これらに限定されない。
さらに別の態様において、本発明の可溶性タンパク質、特にSIRPα結合タンパク質またはFusobodiesのグリコシル化パターンは、典型的な哺乳動物グリコシル化パターン、例えば、CHOまたはヒト細胞系において得られるものと比較して改変することができる。例えば、非グリコシル化タンパク質は、グリコシル化を欠くように操作されている宿主細胞または哺乳動物細胞として、原核細胞系を使用することにより行うことができる。炭水化物修飾はまた、例えば、SIRPα結合Fusobody内の1つ以上のグリコシル化部位を改変することにより達成することができる。
本発明により考えられる本明細書の可溶性タンパク質の別の態様は、ペグ化である。本発明の可溶性タンパク質、例えば、SIRPα結合タンパク質またはFusobodiesは、ペグ化することができる。ペグ化は、ペグ化なしの同じ生物学的製剤と比較して、得られる生物学的製剤の生物学的(例えば、血清)半減期を増大させることがよく知られている技術である。ポリペプチドをペグ化するために、ポリペプチドは、一般的に、1つ以上のPEG基がポリペプチドに結合する条件下で、ポリエチレングリコール(PEG)、例えば、PEGの反応性エステルまたはアルデヒド誘導体と反応させる。ペグ化は、反応性PEG分子(または類似の反応性水溶性ポリマー)とのアシル化反応またはアルキル化反応により実施することができる。本明細書において使用される「ポリエチレングリコール」なる用語は、他のタンパク質を誘導体化するために使用されているPEGのあらゆる形式、例えば、モノ(C1−C10)アルコキシ−もしくはアリールオキシ−ポリエチレングリコールまたはポリエチレングリコール−マレイミドを包含することを意図する。タンパク質をペグ化するための方法は、当分野で知られており、本発明の可溶性タンパク質に適用することができる。例えば、NishimuraらによるEP 0 154 316およびIshikawaらによるEP 0 401 384参照。
SIRPα結合タンパク質、特にSIRPα結合Fusobodiesは、特に炎症性および/または自己免疫性応答、特に、対象におけるSIRPα+細胞が介在する応答を(統計的に、または生物学的に有意な様式において)減少または抑制するための医薬として使用され得る。細胞毒性剤と接合しているとき、またはFc部分により提供される殺細胞エフェクター機能を有するとき、SIRPα結合タンパク質および特にSIRPα結合Fusobodiesもまた、癌または腫瘍、例えば、特に骨髄リンパ増殖性疾患、例えば、急性骨髄リンパ増殖性(AML)障害または膀胱癌の処置、減少または抑制において有利に使用することができる。
本発明の別の局面は、本発明の可溶性タンパク質をコードする核酸分子に関し、例えば実施例の表4に記載されているFusobodyに関連した態様を含むが、これらに限定されない。SIRPα結合Fusobodiesをコードするヌクレオチド配列の非限定的な例は、SIRPα結合Fusobodyの重鎖および軽鎖をそれぞれコードする配列番号:10および11を含む。
本発明の可溶性タンパク質、例えば、FusobodiesのSIRPα結合タンパク質は、例えば、当分野でよく知られている組換えDNA技術および遺伝子トランスフェクション方法の組合せを使用して、宿主細胞トランスフェクトーマにおいて生産することができる。宿主細胞トランスフェクトーマにおいて組換えFusobodiesを発現および生産させるために、当業者は、抗体分子または抗体様分子の発現および組換え生産に関連した一般知識を有利に使用することができる。
別の局面において、本発明は、少なくとも2つの同一のまたは異なる本発明の可溶性SIRPα結合タンパク質を含む多価タンパク質を提供する。1つの態様において、多価タンパク質は、少なくとも2つ、3つまたは4つの本発明の可溶性SIRPα結合タンパク質を含む。可溶性SIRPα結合タンパク質は、タンパク質融合または共有もしくは非共有結合を介して互いに連結することができる。本発明の多価タンパク質は、当分野で知られている方法を使用して、構成結合特異性を結合することにより製造することができる。例えば、多価タンパク質のそれぞれの結合特異性は、別々に生成され、互いに結合することができる。
別の局面において、本発明は、治療薬部分、例えば、細胞毒素、薬物(例えば、免疫抑制剤)または放射性毒素に接合されたSIRPα結合タンパク質、特に、SIRPα結合Fusobodyを特徴とする。このような抱合体は、本明細書において「接合SIRPα結合タンパク質」と称される。細胞毒素または細胞毒性剤は、細胞に対して有害である(例えば、殺す)あらゆる薬剤を含む。このような薬剤は、抗体の抱合体または免疫抱合体を製造するために使用されている。このような技術は、SIRPα結合タンパク質、特に、SIRPα結合Fusobodyで有利に適用することができる。細胞毒素または細胞毒性剤の例は、タクソン、サイトカラシンB、グラミシジンD、臭化エチジウム、エメチン、マイトマイシン、エトポシド、テノポシド(tenoposide)、ビンクリスチン、ビンブラスチン、t.コルヒチン、ドキソルビシン、ダウノルビシン、ジヒドロキシアントラセンジオン、ミトキサントロン、ミトラマイシン、アクチノマイシンD、1−デヒドロテストステロン、グルココルチコイド、プロカイン、テトラカイン、リドカイン、プロプラノロールおよびピューロマイシンならびにそれらのアナログまたはホモログを含む。治療剤はまた、例えば、代謝拮抗剤(例えば、メトトレキサート、6−メルカプトプリン、6−チオグアニン、シタラビン、5−フルオロウラシルダカルバジン)、アルキル化剤(ablating agents)(例えば、メクロレタミン、チオテパクロラムブシル、メルファラン、カルムスチン(BSNU)およびロムスチン(CCNU)、シクロホスファミド、ブスルファン、ジブロモマンニトール、ストレプトゾトシン、マイトマイシンCおよびシス−ジクロロジアミン白金(II)(DDP)シスプラチン、アントラサイクリン(例えば、ダウノルビシン(以前はダウノマイシン)およびドキソルビシン)、抗生物質(例えば、ダクチノマイシン(以前はアクチノマイシン)、ブレオマイシン、ミトラマイシンおよびアントラマイシン(AMC))、および抗有糸分裂剤(例えば、ビンクリスチンおよびビンブラスチン)を含む。
別の局面において、本発明は、薬学的に許容される担体と共に製剤化された、本発明の可溶性SIRPα結合タンパク質またはFusobodiesの1つまたは組合せを含む組成物、例えば、医薬組成物を提供する。
可溶性SIRPα結合タンパク質またはFusobodiesは、インビトロおよびインビボでの診断および治療の有用性を有する。例えば、これらの分子は、種々の障害を処置、予防、または診断するために、培養下の細胞に、例えば、インビトロまたはインビボで、または対象に、例えば、インビボで投与することができる。1つの態様において、可溶性SIRPα結合Fusobodiesは、別の方法で拡張を妨げる他の細胞型の存在下で、幹細胞または膵臓ベータ細胞のような他の細胞型のインビトロ拡張において使用することができる。加えて、特に、可溶性SIRPα結合タンパク質またはFusobodiesは、生物体、例えば、ヒトの生物学的サンプル由来の細胞の細胞表面で機能性SIRPαの発現をインビトロで弱める、および定量するために使用される。市販のSIRPα抗体がSIRPβの種々のアイソフォームと交差反応し、細胞表面上のSIRPαタンパク質発現を明確に定量することを困難にさせるため、本願は有用である。したがって、可溶性SIRPα結合タンパク質またはFusobodiesの定量化は、診断目的のために使用し、例えば、SIRPαタンパク質発現量と免疫疾患または癌との相関関係を評価することができ、したがって、例えば、接合SIRPα結合タンパク質またはSIRPαに対して標的化される抗体ベースの治療での処置について患者の選択(患者層化)を可能にする。
1.本発明のSIRPα結合Fusobodiesの実施例
以下の表4は、記載されている重鎖および軽鎖アミノ酸配列をコードするDNAを使用する組換え方法により生産され得る本発明のSIRPα結合Fusobodiesの例を提供する。
表4:
2.1.一価のSIRPαに対する結合アッセイ(BiaCOREアッセイ)
一価のヒトモノマー状SIRPα−APP CD47の親和性を、例えば、BiaCORE T100装置を使用するBiaCOREにより測定することができる。CM5チップは、標準アミン結合手段を使用してタンパク質Aと固定される。フローセル1を、参照として役立てるためにブランク固定化する。SIRPα結合タンパク質は、タンパク質AのFc結合特性を介して固定される。一価の、例えば、APPタグSIRPα Vドメインタンパク質を、HEK293細胞において発現させる。APP−SIRPαを、1:2の係数により12回連続希釈する。開始濃度は、25μM−0.5μMである。親和性データは、参照のAPP−SIRPα濃度系列の注入後、フローセルを測定することにより得られる。チップ表面は、50mMのクエン酸塩溶液によるそれぞれのアナライトの注入後に再生される。
試験を、384−ウェルマイクロタイタープレート(Nunc)にて行う。固定化されたヒトSIRPα−Fc融合タンパク質(0.5μg/mL、R&D systems, UK)を、CD47−ECD IgG1 Fc融合タンパク質(CD47−Fc、5nM)またはビオチン化CD47 Fusobody(実施例#4、1nM)のいずれか、および種々の濃度(30nM−0.003nM)の非標識SIRPα結合タンパク質または非標識SIRPα結合Fusobodiesからなるビオチン化SIRPα結合タンパク質の混合物とインキュベートする。RTで18時間複合体形成後、非結合タンパク質を、大規模洗浄により除去する。結合ビオチン化CD47−融合タンパク質を、ストレプトアビジン−ユーロピウム(PerkinElmer reagents)を介して検出する。標識Eu3+を、VICTOR2リーダー(PerkinElmer)を使用する解離増強時間分解蛍光(TRF)を使用して測定する。
SIRPα(ATCC)を発現する組織球性細胞系であるU937細胞を、標準細胞培養条件下で10%のウシ胎児血清および抗生物質を補ったRPMI1640中で増殖させる(全てInvitrogenから)。試験の前日に、細胞を1:1に分ける。細胞を回収し、ウシ血清アルブミン(BSA, SIGMA)を含むリン酸緩衝生理食塩水(PBS, SIGMA)(PBS/BSA)に再懸濁する。細胞は、5μg/mLのBCECF−AM(Invitrogen)または等量のCalcein AM(Invitrogen)のような色素で20分37℃で標識することができる。非結合BCECF−AMを洗浄工程により除去する。細胞を数え、数を0.5%のBSAを補ったRPMI 1640中で1×106細胞/mLに調節する。96ウェルプレートを、0.1MのNaHCθ3/Na2Cθ3バッファー中、3μg/mlの抗ヒトFcヤギIgG(Jackson ImmunoResearch Laboratories)をウェル当たり60μlで一晩でコーティングする。プレートをPBSで2回洗浄し、30分間PBS中の1.5%のBSAで(250μL/ウェル)でブロックし、次に、種々の濃度の可溶性SIRPα結合FusobodiesのようなSIRPα結合タンパク質またはCD47−ECD IgG1 Fc融合タンパク質(CD47−Fc、CD47 ECDのSeq1)(CD47−Fc)(0.01および30nM)とインキュベートする。RTで2時間後、プレートをPBS/BSAで2回洗浄し、BCECF標識U937細胞(ウェルあたり100000細胞)を加える。37℃で30分インキュベーション後、U937細胞を、0.5%のBSAを補ったRPMI 1640を使用する繰返し手動または自動洗浄工程による流体せん断応力に付す。一般的に、4−5回の洗浄工程が、ゆるい接着または非結合細胞を除去するために必要である。残りのU937接着細胞の蛍光は、VICTOR2 プレートリーダー(PerkinElmer)を使用することにより定量する。
健常者由来のヒト血液を、倫理ガイドラインを適用してNa−ヘパリンコートバキュテナー(BectonDickinison, BD)に回収する。血液を、96−ウェルディープウェルポリプロピレンプレート(Costar)にアリコートし、氷上で最終0.1%w/vのアジ化ナトリウムの存在下で種々の濃度の可溶性SIRPα結合FusobodiesのようなSIRPα結合タンパク質またはCD47−ECD IgG1 Fc融合タンパク質(CD47−Fc、CD47 ECDのSeq1)(CD47−Fc)とインキュベートする。フルオロクロム Alexa Fluor 647(AX647)を、標識キット(Invitrogen)を使用してSIRPα結合タンパク質に接合させることができる。AX647接合SIRPα結合タンパク質、例えば、実施例#4に記載されているFusobodyを、氷上で30分1−10nMの濃度で全血サンプルに加えることができる。最後の15分間に、表現型細胞表面マーカーに対する濃度最適化抗体を加える:CD14−PE(クローンMEM18、Immunotools, Germany)、CD3 Percp−Cy5.5(クローンSK7、BD)、CD16 FITC(クローン3G8、BD)。全血を、10×容量のFACSLYSING溶液(BD)の添加およびRTで10分間インキュベーションにより溶解する。サンプルを、0.5%のウシ血清アルブミン(SIGMA−ALDRICH)を含むリン酸バッファー溶液で2回洗浄する。サンプルを、溶解後24時間以内にFacs Canto II(BD)上で回収する。細胞サブセットを、単球光散乱プロフィールにしたがって、およびCD14+およびCD3− 発現によりゲートする。これらの細胞サブセットの蛍光ヒストグラムを作成し、読出した情報として中央蛍光強度を持つと統計的に評価することができる。
末梢血単球(CD14+)ならびに単球由来樹状細胞(DC)は、(Latourら J of Immunol, 2001: 167:2547)に記載されているとおりに製造される。慣用の(DC)は、アロフィコシアニン(APC)標識抗−CD11c(B−ly6)、リネッジマーカー、CD3、CD14、CD15、CD16、CD19およびCD56に対するFITC標識mAbおよびAPC−Cy7標識CD4(RPA−T4)の混合物を使用することにより、FACS Aria(BD Biosciences)により、CD11c+、リネッジ(lineage)−として単離され、>99%の純度を達成する。APCを、HB101またはX−VIVO15無血清培地中で種々の濃度のヒトSIRPα結合Fusobodies(1から10000pM)の存在下で、1/40.000(Pansorbin)での黄色ブドウ球菌コワン1粒子で刺激する。サイトカイン(IL−1、IL−6、IL−10、IL−12p70、IL−23、IL−8およびTNF−α)放出は、24時間または48時間培養上清中のELISAにより測定される。
メスBALB/c(6から8週齢)を、特定の病原体未感染条件下で維持されたCharles Riverから購入する。BALB/cマウスを、0および5日目に、ヒトIgG1骨格(mCD47 Fusobody:重鎖配列番号:34、軽鎖配列番号:35、またはmCD47 C15G Fusobody:重鎖配列番号:31、軽鎖配列番号:32)に融合した、C15G変異有り(mCD47 C15G Fusobody)または該変異無し(mCD47 Fusobody)のマウスCD47細胞外IgSFドメインを含む100μgのマウスSIRPα結合Fusobodies、またはコントロールヒトIgG1の非存在(PBSコントロール)または存在下で、1mgのImject Alum(Pierce)に吸着した10μgのOVAの腹腔内(IP)注射により感作した。12、16および20日目に、マウスを、0.5%のOVA エアロゾル(Sigma, Grade V)で30分間抗原投与する。最後の抗原投与から24時間後に、マウスを殺す。気管支肺胞洗浄液(BALF)を、0.5mLの生理食塩水で4回回収する。モデルの略図は、図6に記載されている。
トリニトロベンゼンスルホン酸(TNBS)(2または3mg)を50%のエタノールに溶解し、3.5Fカテーテルを介してオスBalb/cマウス(WTおよびCD47 KO)の大腸に染みこませる。コントロールマウスは、エタノール単独を与える。1.5mgのTNBSマウスの滴下により、TNBS大腸炎を数匹の動物(図7に示されているとおり)において7日目に再誘発する。マウスを24時間毎に計量する。マウスを14日目に殺す。血清、腸間膜リンパ節節および大腸を、さらなる分析のために回収する。大腸を、下痢、接着、腸壁の肥厚および潰瘍の存在を考慮に入れるWallace基準を使用して肉眼的にスコアリングすることができる。それらは、粘膜下層の肥厚、単核細胞での粘膜下層および固有層の浸潤、粘液枯渇、陰窩構造の喪失および浮腫に基づく採点システムであるAmeho基準を使用して炎症の顕微鏡的マーカーについて評価することができる(データは示されていない)。組換えマウスSIRPα結合タンパク質(mCD47 C15G Fusobody)を、TNBS大腸炎誘導の直前およびその後24時間目および48時間目および数匹の動物において72時間目に、腹腔内に(100μg/マウス)投与する。コントロールマウスに、リン酸緩衝生理食塩水単独(PBS)またはコントロールIgG1を与える。
ヒトおよび齧歯動物CD47/SIRPαタンパク質間の種間交差反応性が挙げられないため(示されていない)、マウスSIRPα結合Fusobodiesを、ヒトSIRPα結合タンパク質と同様に産生した。野生型(配列番号:33)またはC15G変異(配列番号:30)のいずれかのCD47部分(mCD47 Fusobody:重鎖配列番号:34、軽鎖配列番号:35、またはmCD47 C15G Fusobody:重鎖配列番号:31、軽鎖配列番号:32)を含むSIRPα結合Fusobodiesを、哺乳動物一時的発現系においてヒトIgG融合タンパク質として産生し、標準手段により会合体非含有およびエンドトキシン非含有材料を生産するために精製した。
100μg/動物のマウスSIRPα結合Fusobody(mCD47 C15G Fusobody、重鎖配列番号:31、軽鎖配列番号:32)の3−4回の腹腔内投与でのマウスの処置は、統計的に有意に減少した体重減少により示されるTNBSにより誘発される炎症性大腸炎の重症度を減少させた。TNBSでの疾患再誘導から7日後、mCD47 C15G Fusobody処置動物は、PBSまたはコントロール IgGコントロールを越える体重を維持した。したがって、マウスSIRPα結合タンパク質(mCD47−C15G Fusobody)の注射は、TNBS大腸炎における疾患発症の重症度を能動的に妨害する。データは、試験化合物の3または4のいずれかの連続投与での2つの異なる実験の要約である。n=グループあたりの使用された動物の数.
Claims (42)
- 少なくとも2つのヘテロダイマーの複合体を含む可溶性タンパク質であって、それぞれのヘテロダイマーは、本質的に、
(i)抗体の重鎖定常領域に融合した哺乳動物結合分子の領域を含む第1の一価の一本鎖ポリペプチド;および
(ii)抗体の軽鎖定常領域に融合した同じ結合分子の領域を含む第2の一価の一本鎖ポリペプチド
からなる可溶性タンパク質。 - 少なくとも2つのヘテロダイマーの複合体を含む可溶性タンパク質であって、それぞれのヘテロダイマーは、本質的に、
(i)抗体のCH1定常重鎖領域に融合した哺乳動物結合分子の領域を含む第1の一価の一本鎖ポリペプチド;および
(ii)抗体のCL定常軽鎖領域に融合した同じ結合分子の領域を含む第2の一価の一本鎖ポリペプチド
からなる可溶性タンパク質。 - 該哺乳動物結合分子の領域が同じである、請求項1または請求項2に記載の可溶性タンパク質。
- 該哺乳動物結合分子が、タンパク質、サイトカイン、成長因子、ホルモン、シグナル伝達タンパク質、炎症性メディエーター、低分子量化合物、リガンド、細胞表面受容体、またはそれらのフラグメントである、請求項1から3のいずれかに記載の可溶性タンパク質。
- 該哺乳動物結合分子が、モノマー状またはホモポリマー状細胞表面受容体の細胞外ドメインである、請求項4に記載の可溶性タンパク質。
- 該哺乳動物モノマー状またはホモポリマー状細胞表面受容体がIgSFドメインを含む、請求項5に記載の可溶性タンパク質。
- 該哺乳動物モノマー状細胞表面受容体の細胞外ドメインがCD47の細胞外ドメインである、請求項5または請求項6に記載の可溶性タンパク質。
- 2つのヘテロダイマーの複合体を含む可溶性タンパク質であって、それぞれのヘテロダイマーは、本質的に、
(i)抗体のCH1定常重鎖領域のN−末端部分で融合した第1のSIRPα結合ドメインを含む第1の一価の一本鎖ポリペプチド、および
(ii)抗体のCL定常軽鎖領域のN−末端部分で融合した第2のSIRPα結合ドメインを含む第2の一価の一本鎖ポリペプチド
からなる可溶性タンパク質。 - 2つのヘテロダイマーの複合体を含む可溶性タンパク質であって、それぞれのヘテロダイマーは、本質的に、
(i)抗体の重鎖定常領域に融合した第1のSIRPα結合ドメインを含む第1の一価の一本鎖ポリペプチド;および
(ii)抗体の軽鎖定常領域に融合した第2のSIRPα結合ドメインを含む第2の一価の一本鎖ポリペプチド
からなる可溶性タンパク質。 - 該第1および第2の一価の一本鎖ポリペプチドが、それぞれCH1定常重鎖およびCL定常軽鎖のN−末端部分に融合している、請求項1から9のいずれかに記載の可溶性タンパク質。
- 該第1および第2のSIRPα結合ドメインが、互いに少なくとも60、70、80、90、95、96、97、98または99パーセントの配列同一性を共有する、請求項8から10のいずれかに記載の可溶性タンパク質。
- BiaCOREアッセイにおいて測定されるとき、4μM以下のKDでヒトSIRPαに結合する、請求項7から11のいずれかに記載の可溶性タンパク質。
- プレートベースの細胞接着アッセイにおいて測定されるとき、2nM以下のEC50でSIRPα+白血球の接着を促進する、請求項8から12のいずれかに記載の可溶性タンパク質。
- インビトロで産生された単球由来樹状細胞における炎症性サイトカインの黄色ブドウ球菌コワン(Cowan)株粒子刺激放出を阻害する、請求項8から13のいずれかに記載の可溶性タンパク質。
- 樹状細胞サイトカイン放出アッセイにおいて測定されるとき、0.2nM以下のIC50でインビトロで産生された単球由来樹状細胞における炎症性サイトカインの黄色ブドウ球菌コワン株粒子刺激放出を阻害する、請求項14に記載の可溶性タンパク質。
- 該それぞれのヘテロダイマーの第1および第2の一本鎖ポリペプチドが、ジスルフィド架橋により共有結合している、請求項1から15のいずれかに記載の可溶性タンパク質。
- それぞれのヘテロダイマーが、ペプチドリンカーの非存在下で、それぞれの定常領域に融合したその第1および第2のSIRPα結合ドメインを有する、請求項8から16のいずれかに記載の可溶性タンパク質。
- それぞれのヘテロダイマーが、ペプチドリンカーを介してそれぞれの定常領域に融合したその第1および第2のSIRPα結合ドメインを有する、請求項8から16のいずれかに記載の可溶性タンパク質。
- 該ペプチドリンカーが5−20個のアミノ酸からなる、請求項18に記載の可溶性タンパク質。
- 該ペプチドリンカーが、グリシンおよびセリンアミノ酸のポリマー、好ましくは(GGGGS)nであり、nは1から4のいずれかの整数、好ましくは2である、請求項18または請求項19に記載の可溶性タンパク質。
- 本質的に2つのヘテロダイマーからなる請求項1から20のいずれかに記載の可溶性タンパク質であって、該それぞれのヘテロダイマーの第1の一本鎖ポリペプチドが免疫グロブリン定常部分のヒンジ領域を含み、該少なくとも2つのヘテロダイマーが該ヒンジ領域でジスルフィド架橋により互いに安定に結合している可溶性タンパク質。
- 抗体のCH1、CH2およびCH3領域が、減少したADCCエフェクター機能を有するヒトIgG1、IgG2またはIgG4の対応する領域のサイレント変異体由来である、請求項9から21のいずれかに記載の可溶性タンパク質。
- 、少なくとも1つのSIRPα結合ドメインが、
(i)ヒトCD47の細胞外ドメイン;
(ii)配列番号:4のポリペプチドまたはSIRPα結合特性を保持する配列番号:4のフラグメント;および、
(iii)配列番号:4と少なくとも60、70、80、90、95、96、97、98または99パーセントの配列同一性を有し、SIRPα結合特性を保持する配列番号:4の変異体ポリペプチド
からなる群から選択される、請求項8から22のいずれかに記載の可溶性タンパク質。 - 全てのSIRPα結合ドメインが同一のアミノ酸配列を有する、請求項8から23のいずれかに記載の可溶性タンパク質。
- 該SIRPα結合ドメインの同一のアミノ酸配列が、配列番号:3、配列番号:4、配列番号:21および配列番号:23からなる群から選択される、請求項24に記載の可溶性タンパク質。
- 2つのヘテロダイマーを含む可溶性タンパク質であって、該ヘテロダイマーが、
(i)配列番号:5の第1の一本鎖ポリペプチドおよび配列番号:6の第2の一本鎖ポリペプチド;
(ii)配列番号:18の第1の一本鎖ポリペプチドおよび配列番号:6の第2の一本鎖ポリペプチド;
(iii)配列番号:19の第1の一本鎖ポリペプチドおよび配列番号:20の第2の一本鎖ポリペプチド;
(iv)配列番号:12の第1の一本鎖ポリペプチドおよび配列番号:13の第2の一本鎖ポリペプチド;
(v)配列番号:24の第1の一本鎖ポリペプチドおよび配列番号:25の第2の一本鎖ポリペプチド;
(vi)配列番号:36の第1の一本鎖ポリペプチドおよび配列番号:37の第2の一本鎖ポリペプチド;
(vii)配列番号:38の第1の一本鎖ポリペプチドおよび配列番号:39の第2の一本鎖ポリペプチド;
(viii)配列番号:40の第1の一本鎖ポリペプチドおよび配列番号:41の第2の一本鎖ポリペプチド;
(ix)配列番号:42の第1の一本鎖ポリペプチドおよび配列番号:43の第2の一本鎖ポリペプチド;
(x)配列番号:44の第1の一本鎖ポリペプチドおよび配列番号:45の第2の一本鎖ポリペプチド;
(xi)配列番号:46の第1の一本鎖ポリペプチドおよび配列番号:47の第2の一本鎖ポリペプチド;
(xii)配列番号:48の第1の一本鎖ポリペプチドおよび配列番号:49の第2の一本鎖ポリペプチド;
(xiii)配列番号:50の第1の一本鎖ポリペプチドおよび配列番号:51の第2の一本鎖ポリペプチド;
(xiv)配列番号:52の第1の一本鎖ポリペプチドおよび配列番号:53の第2の一本鎖ポリペプチド;
(xv)配列番号:54の第1の一本鎖ポリペプチドおよび配列番号:55の第2の一本鎖ポリペプチド;
(xvi)配列番号:56の第1の一本鎖ポリペプチドおよび配列番号:57の第2の一本鎖ポリペプチド;
(xvii)配列番号:58の第1の一本鎖ポリペプチドおよび配列番号:20の第2の一本鎖ポリペプチド;または
(xviii)配列番号:29の第1の一本鎖ポリペプチドおよび配列番号:20の第2の一本鎖ポリペプチド
のいずれかを含む可溶性タンパク質。 - 請求項26に記載の可溶性タンパク質の対応する第1および第2の一本鎖ポリペプチドと、少なくとも60、70、80、90、95、96、97、98または99パーセントの配列同一性を有する該第1の一本鎖および第2の一本鎖ポリペプチド配列を含む、請求項9から25のいずれかに記載の可溶性タンパク質。
- 請求項26に記載の可溶性タンパク質の対応する第1および第2の一本鎖ポリペプチドと、少なくとも60、70、80、90、95、96、97、98または99パーセントの配列同一性を有するSIRPα結合ドメイン配列を含む、請求項9から25のいずれかに記載の可溶性タンパク質。
- (i)配列番号:10のヌクレオチド配列によってコードされる重鎖;および配列番号:11のヌクレオチド配列によってコードされる軽鎖、
(ii)配列番号:59のヌクレオチド配列によってコードされる重鎖;および配列番号:60のヌクレオチド配列によってコードされる軽鎖、
(iii)配列番号:61のヌクレオチド配列によってコードされる重鎖;および配列番号:62のヌクレオチド配列によってコードされる軽鎖、
(iv)配列番号:63のヌクレオチド配列によってコードされる重鎖;および配列番号:64のヌクレオチド配列によってコードされる軽鎖、
(v)配列番号:65のヌクレオチド配列によってコードされる重鎖;および配列番号:66のヌクレオチド配列によってコードされる軽鎖、
(vi)配列番号:67のヌクレオチド配列によってコードされる重鎖;および配列番号:68のヌクレオチド配列によってコードされる軽鎖、
(vii)配列番号:69のヌクレオチド配列によってコードされる重鎖;および配列番号:70のヌクレオチド配列によってコードされる軽鎖、
(viii)配列番号:71のヌクレオチド配列によってコードされる重鎖;および配列番号:72のヌクレオチド配列によってコードされる軽鎖、
(ix)配列番号:73のヌクレオチド配列によってコードされる重鎖;および配列番号:74のヌクレオチド配列によってコードされる軽鎖、
(x)配列番号:75のヌクレオチド配列によってコードされる重鎖;および配列番号:76のヌクレオチド配列によってコードされる軽鎖、
(xi)配列番号:77のヌクレオチド配列によってコードされる重鎖;および配列番号:78のヌクレオチド配列によってコードされる軽鎖、
(xii)配列番号:79のヌクレオチド配列によってコードされる重鎖;および配列番号:80のヌクレオチド配列によってコードされる軽鎖、
(xiii)配列番号:81のヌクレオチド配列によってコードされる重鎖;および配列番号:82のヌクレオチド配列によってコードされる軽鎖、
(xiv)配列番号:83のヌクレオチド配列によってコードされる重鎖;および配列番号:84のヌクレオチド配列によってコードされる軽鎖、
(xv)配列番号:85のヌクレオチド配列によってコードされる重鎖;および配列番号:86のヌクレオチド配列によってコードされる軽鎖、
(xvi)配列番号:87のヌクレオチド配列によってコードされる重鎖;および配列番号:60のヌクレオチド配列によってコードされる軽鎖、または
(xvii)配列番号:88のヌクレオチド配列によってコードされる重鎖;および配列番号:60のヌクレオチド配列によってコードされる軽鎖
を含む、請求項1から28のいずれかに記載の可溶性タンパク質。 - 薬物または診断ツールとしての使用のための、請求項1から29のいずれかに記載の可溶性タンパク質。
- 自己免疫性ならびに急性および慢性炎症性疾患の処置または診断における使用のための、請求項30に記載の可溶性タンパク質。
- Th2介在気道炎症、アレルギー性疾患、喘息、炎症性腸疾患および関節炎からなる群から選択される処置における使用のための、請求項31に記載の可溶性タンパク質。
- 虚血性疾患、白血病または他の癌の処置における使用のための、請求項30に記載の可溶性タンパク質。
- 必要とする対象における造血幹生着の増加における使用のための、請求項30に記載の可溶性タンパク質。
- 1つ以上の薬学的に許容されるビヒクルと共に、請求項1−29のいずれかに記載の可溶性タンパク質を含む医薬組成物。
- 少なくとも1つの他の活性成分をさらに含む、請求項35に記載の医薬組成物。
- 請求項1−29のいずれかに記載の可溶性タンパク質の1つのヘテロダイマーの少なくとも1つの一本鎖ポリペプチドをコードする単離された核酸。
- 配列番号:10、配列番号:11、配列番号:59、配列番号:60、配列番号:61、配列番号:62、配列番号:63、配列番号:64、配列番号:65、配列番号:66、配列番号:67、配列番号:68、配列番号:69、配列番号:70、配列番号:71、配列番号:72、配列番号:73、配列番号:74、配列番号:75、配列番号:76、配列番号:77、配列番号:78、配列番号:79、配列番号:80、配列番号:81、配列番号:82、配列番号:83、配列番号:84、配列番号:85、配列番号:86、配列番号:87および配列番号:88からなる群から選択される少なくとも1つの核酸を含むクローニングまたは発現ベクター。
- 該タンパク質の該ヘテロダイマーの該第1および第2の一本鎖ポリペプチドをコードする核酸、および所望により、分泌シグナルを含む、請求項1−29のいずれかに記載の可溶性タンパク質の生産のために適当な組換え宿主細胞。
- ゲノム中に安定に組み込まれている、配列番号:10、配列番号:11、配列番号:59、配列番号:60、配列番号:61、配列番号:62、配列番号:63、配列番号:64、配列番号:65、配列番号:66、配列番号:67、配列番号:68、配列番号:69、配列番号:70、配列番号:71、配列番号:72、配列番号:73、配列番号:74、配列番号:75、配列番号:76、配列番号:77、配列番号:78、配列番号:79、配列番号:80、配列番号:81、配列番号:82、配列番号:83、配列番号:84、配列番号:85、配列番号:86、配列番号:87および配列番号:88の核酸を含む、請求項39に記載の組換え宿主細胞。
- 該宿主が哺乳動物細胞系である、請求項39または請求項40に記載の組換え宿主細胞。
- 該可溶性タンパク質の生産のための適当な条件下で請求項39から41のいずれかに記載の宿主細胞を培養すること、および該タンパク質を単離することを含む、請求項1から29のいずれかに記載の可溶性タンパク質の生産方法。
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US28900709P | 2009-12-22 | 2009-12-22 | |
US61/289,007 | 2009-12-22 | ||
PCT/EP2010/070355 WO2011076781A1 (en) | 2009-12-22 | 2010-12-21 | Tetravalent cd47-antibody constant region fusion protein for use in therapy |
Publications (1)
Publication Number | Publication Date |
---|---|
JP2013514795A true JP2013514795A (ja) | 2013-05-02 |
Family
ID=43706449
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2012545290A Pending JP2013514795A (ja) | 2009-12-22 | 2010-12-21 | 治療における使用のための四価cd47抗体定常領域融合タンパク質 |
Country Status (13)
Country | Link |
---|---|
US (1) | US20130011401A1 (ja) |
EP (1) | EP2516458A1 (ja) |
JP (1) | JP2013514795A (ja) |
KR (1) | KR20120107122A (ja) |
CN (1) | CN102939303A (ja) |
AR (1) | AR079701A1 (ja) |
AU (1) | AU2010334974A1 (ja) |
BR (1) | BR112012017164A2 (ja) |
CA (1) | CA2785139A1 (ja) |
MX (1) | MX2012007318A (ja) |
TW (1) | TW201130511A (ja) |
UY (1) | UY33132A (ja) |
WO (1) | WO2011076781A1 (ja) |
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2020510643A (ja) * | 2017-02-17 | 2020-04-09 | オーエスイー・イミュノセラピューティクス | 抗SIRPg抗体の新規の使用 |
Families Citing this family (68)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
AU2012269929A1 (en) * | 2011-06-16 | 2013-12-12 | Novartis Ag | Soluble proteins for use as therapeutics |
US9458214B2 (en) | 2011-09-26 | 2016-10-04 | Novartis Ag | Dual function fibroblast growth factor 21 proteins |
US9006400B2 (en) | 2011-09-26 | 2015-04-14 | Novartis Ag | Fibroblast growth factor-21-Fc fusion proteins |
ES2784631T3 (es) * | 2012-12-03 | 2020-09-29 | Novimmune Sa | Anticuerpos anti-CD47 y métodos de uso de los mismos |
PT2931752T (pt) | 2012-12-17 | 2019-11-20 | Trillium Therapeutics Inc | Tratamento de células de doença cd47+ com fusões sirp alfa-fc |
WO2014121093A1 (en) * | 2013-01-31 | 2014-08-07 | Thomas Jefferson University | Fusion proteins that facilitate cancer cell destruction |
CA2905418C (en) * | 2013-03-13 | 2023-03-28 | The United States Of America, As Represented By The Secretary, Department Of Health And Human Services | Methods for modulating chemotherapeutic cytotoxicity |
US9580486B2 (en) * | 2013-03-14 | 2017-02-28 | Amgen Inc. | Interleukin-2 muteins for the expansion of T-regulatory cells |
WO2014144632A2 (en) | 2013-03-15 | 2014-09-18 | Amgen Inc. | Human pac1 antibodies |
US20140302037A1 (en) * | 2013-03-15 | 2014-10-09 | Amgen Inc. | BISPECIFIC-Fc MOLECULES |
CN103204944B (zh) * | 2013-03-26 | 2014-05-28 | 江苏健德生物药业有限公司 | 用于治疗糖尿病的长效免疫融合蛋白 |
CN103898189B (zh) * | 2014-04-10 | 2015-10-28 | 武汉大学 | 信号调节蛋白α(SHSP-1)基因在心肌梗死中的应用 |
CN103893743B (zh) * | 2014-04-10 | 2016-01-20 | 武汉大学 | 生长分化因子1(gdf1)基因在冠状动脉粥样硬化性心脏病中的功能和应用 |
NO2776305T3 (ja) | 2014-04-23 | 2018-01-27 | ||
EP3164417A1 (en) | 2014-07-01 | 2017-05-10 | Pfizer Inc. | Bispecific heterodimeric diabodies and uses thereof |
TWI702228B (zh) * | 2014-08-08 | 2020-08-21 | 美商Alx腫瘤技術股份有限公司 | 信號調節蛋白α(signal-regulatory protein α, SIRP-α)變體構築物及其用途 |
ES2962260T3 (es) | 2014-08-08 | 2024-03-18 | Univ Leland Stanford Junior | Proteínas de fusión SIRPa alfa-anticuerpo |
MX2017003247A (es) | 2014-09-15 | 2017-11-30 | Amgen Inc | Proteina de union a antigenos, bi-especificos del receptor anti-cgrp/receptor pac1 y usos de las mismas. |
KR102683584B1 (ko) * | 2014-09-19 | 2024-07-10 | 시티 오브 호프 | IL13Rα2를 표적화하는 공자극 키메라 항원 수용체 T 세포 |
EP3233920B1 (en) | 2014-12-19 | 2020-08-26 | Alkermes, Inc. | Single chain fc fusion proteins |
US10851144B2 (en) | 2015-04-10 | 2020-12-01 | Amgen Inc. | Interleukin-2 muteins for the expansion of T-regulatory cells |
GB201506402D0 (en) * | 2015-04-15 | 2015-05-27 | Berkel Patricius H C Van And Howard Philip W | Site-specific antibody-drug conjugates |
TWI737614B (zh) | 2015-06-11 | 2021-09-01 | 博錸生技股份有限公司 | 已編碼微載體及其製造方法以及用以進行多工分析之包含該等已編碼微載體之套件 |
EA034582B1 (ru) * | 2015-08-07 | 2020-02-21 | АЭлЭкс ОНКОЛОДЖИ ИНК. | Конструкции варианта sirp-альфа и их применение |
SI3331902T1 (sl) | 2015-08-07 | 2021-09-30 | ALX Oncology Inc. | Konstrukti z domeno SIRP-alfa ali njegove različice |
WO2017035480A1 (en) | 2015-08-26 | 2017-03-02 | The Board Of Trustees Of The Leland Stanford Junior University | Enhanced depletion of targeted cells with cd47 blockade and an immune costimulatory agonist |
WO2017106578A1 (en) | 2015-12-15 | 2017-06-22 | Amgen Inc. | Pacap antibodies and uses thereof |
KR102531889B1 (ko) | 2016-06-20 | 2023-05-17 | 키맵 리미티드 | 항-pd-l1 및 il-2 사이토카인 |
US10335459B2 (en) | 2016-06-22 | 2019-07-02 | Alkermes, Inc. | Compositions for modulating IL-10 immunostimulatory and anti-inflammatory properties |
WO2018081897A1 (en) | 2016-11-03 | 2018-05-11 | Trillium Therapeutics Inc. | Enhancement of cd47 blockade therapy by proteasome inhibitors |
PL3658589T3 (pl) | 2017-07-26 | 2024-03-18 | Forty Seven, Inc. | Przeciwciała anty-sirp-alfa i powiązane sposoby |
KR102646468B1 (ko) | 2017-08-02 | 2024-03-11 | 페인스 테라퓨틱스 인코포레이티드 | 항-cd47 항체 및 이의 용도 |
WO2019047885A1 (en) * | 2017-09-07 | 2019-03-14 | Dingfu Biotarget Co., Ltd. | IMMUNOCONJUGATES COMPRISING ALPHA REGULATORY SIGNAL PROTEIN |
CA3087951A1 (en) | 2018-01-12 | 2019-07-18 | Amgen Inc. | Pac1 antibodies and uses thereof |
WO2020113403A1 (en) * | 2018-12-04 | 2020-06-11 | Beijing Percans Oncology Co. Ltd. | Cytokine fusion proteins |
CN112912103A (zh) * | 2018-05-21 | 2021-06-04 | 拜奥普罗塞亚科技有限责任公司 | 多价蛋白质复合物 |
CN112566662A (zh) | 2018-06-15 | 2021-03-26 | 阿库鲁斯生物科学公司 | 针对cd47的阻断抗体及其使用方法 |
MX2020013068A (es) | 2018-07-10 | 2021-03-02 | Univ Kobe Nat Univ Corp | Anticuerpo anti proteína reguladora de señales alfa sirpalfana. |
CN110540589B (zh) * | 2019-01-08 | 2021-07-20 | 西南大学 | 一种多肽、多肽修饰的脂质载体及应用 |
BR112021024003A2 (pt) | 2019-05-31 | 2022-04-19 | Alx Oncology Inc | Métodos de tratamento de câncer com fusão sirp alfa-fc em combinação com um inibidor de checkpoint imunológico |
WO2020247820A1 (en) | 2019-06-07 | 2020-12-10 | ALX Oncology Inc. | Methods and reagents for reducing the interference of drugs that bind cd47 in serological assays |
KR20220032568A (ko) | 2019-06-25 | 2022-03-15 | 길리애드 사이언시즈, 인코포레이티드 | Flt3l-fc 융합 단백질 및 사용 방법 |
KR20220085796A (ko) | 2019-10-18 | 2022-06-22 | 포티 세븐, 인코포레이티드 | 골수이형성 증후군 및 급성 골수성 백혈병을 치료하기 위한 조합 치료 |
US20210147568A1 (en) | 2019-10-31 | 2021-05-20 | Forty Seven, Inc. | Anti-cd47 based treatment of blood cancer |
JP2023502441A (ja) | 2019-11-25 | 2023-01-24 | アルカームス インコーポレーテッド | 置換大環状化合物および関連する治療方法 |
EP4081305B1 (en) | 2019-12-24 | 2024-09-18 | Carna Biosciences, Inc. | Diacylglycerol kinase modulating compounds |
CN115087488A (zh) | 2020-02-14 | 2022-09-20 | 震动疗法股份有限公司 | 与ccr8结合的抗体和融合蛋白及其用途 |
JP2023552375A (ja) | 2020-12-06 | 2023-12-15 | エーエルエックス オンコロジー インコーポレイテッド | 血清学的アッセイにおいてcd47に結合する薬物の干渉を低減するための多量体 |
TW202302145A (zh) | 2021-04-14 | 2023-01-16 | 美商基利科學股份有限公司 | CD47/SIRPα結合及NEDD8活化酶E1調節次單元之共抑制以用於治療癌症 |
WO2022245671A1 (en) | 2021-05-18 | 2022-11-24 | Gilead Sciences, Inc. | Methods of using flt3l-fc fusion proteins |
KR20240025616A (ko) | 2021-06-23 | 2024-02-27 | 길리애드 사이언시즈, 인코포레이티드 | 다이아실글리세롤 키나제 조절 화합물 |
EP4359415A1 (en) | 2021-06-23 | 2024-05-01 | Gilead Sciences, Inc. | Diacylglyercol kinase modulating compounds |
EP4359411A1 (en) | 2021-06-23 | 2024-05-01 | Gilead Sciences, Inc. | Diacylglyercol kinase modulating compounds |
AU2022297367A1 (en) | 2021-06-23 | 2023-12-07 | Gilead Sciences, Inc. | Diacylglyercol kinase modulating compounds |
KR20240025597A (ko) | 2021-06-29 | 2024-02-27 | 씨젠 인크. | 비푸코실화 항-cd70 항체 및 cd47 길항제의 조합으로 암을 치료하는 방법 |
KR20240091056A (ko) | 2021-10-28 | 2024-06-21 | 길리애드 사이언시즈, 인코포레이티드 | 피리디진-3(2h)-온 유도체 |
CN118201941A (zh) | 2021-10-29 | 2024-06-14 | 吉利德科学公司 | Cd73化合物 |
CA3239528A1 (en) | 2021-12-22 | 2023-06-29 | Gilead Sciences, Inc. | Ikaros zinc finger family degraders and uses thereof |
AU2022417491A1 (en) | 2021-12-22 | 2024-05-23 | Gilead Sciences, Inc. | Ikaros zinc finger family degraders and uses thereof |
TW202340168A (zh) | 2022-01-28 | 2023-10-16 | 美商基利科學股份有限公司 | Parp7抑制劑 |
EP4245756A1 (en) | 2022-03-17 | 2023-09-20 | Gilead Sciences, Inc. | Ikaros zinc finger family degraders and uses thereof |
WO2023183890A1 (en) * | 2022-03-24 | 2023-09-28 | Bitterroot Bio, Inc. | Multivalent sirp-alpha fusion polypeptides |
US20230355796A1 (en) | 2022-03-24 | 2023-11-09 | Gilead Sciences, Inc. | Combination therapy for treating trop-2 expressing cancers |
TW202345901A (zh) | 2022-04-05 | 2023-12-01 | 美商基利科學股份有限公司 | 用於治療結腸直腸癌之組合療法 |
WO2023205719A1 (en) | 2022-04-21 | 2023-10-26 | Gilead Sciences, Inc. | Kras g12d modulating compounds |
US20240116928A1 (en) | 2022-07-01 | 2024-04-11 | Gilead Sciences, Inc. | Cd73 compounds |
US20240091351A1 (en) | 2022-09-21 | 2024-03-21 | Gilead Sciences, Inc. | FOCAL IONIZING RADIATION AND CD47/SIRPa DISRUPTION ANTICANCER COMBINATION THERAPY |
WO2024137852A1 (en) | 2022-12-22 | 2024-06-27 | Gilead Sciences, Inc. | Prmt5 inhibitors and uses thereof |
Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JPH05507854A (ja) * | 1991-02-08 | 1993-11-11 | プロゲニクス・ファーマスーティカルズ、インコーポレイテッド | CD4― ガンマ・2キメラ及びCD4 ― IgG2・キメラ |
WO2004084816A2 (en) * | 2003-03-21 | 2004-10-07 | Progenics Pharmaceuticals, Inc. | IMPROVED CD4-IgG2 FORMULATIONS |
JP2009537145A (ja) * | 2006-05-15 | 2009-10-29 | バイラル ロジック システムズ テクノロジー コーポレーション | 免疫学的疾患および障害を治療するためのcd47と関連した組成物および方法 |
Family Cites Families (37)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US4399216A (en) | 1980-02-25 | 1983-08-16 | The Trustees Of Columbia University | Processes for inserting DNA into eucaryotic cells and for producing proteinaceous materials |
US4634665A (en) | 1980-02-25 | 1987-01-06 | The Trustees Of Columbia University In The City Of New York | Processes for inserting DNA into eucaryotic cells and for producing proteinaceous materials |
US5179017A (en) | 1980-02-25 | 1993-01-12 | The Trustees Of Columbia University In The City Of New York | Processes for inserting DNA into eucaryotic cells and for producing proteinaceous materials |
US4475196A (en) | 1981-03-06 | 1984-10-02 | Zor Clair G | Instrument for locating faults in aircraft passenger reading light and attendant call control system |
US4447233A (en) | 1981-04-10 | 1984-05-08 | Parker-Hannifin Corporation | Medication infusion pump |
US4439196A (en) | 1982-03-18 | 1984-03-27 | Merck & Co., Inc. | Osmotic drug delivery system |
US4522811A (en) | 1982-07-08 | 1985-06-11 | Syntex (U.S.A.) Inc. | Serial injection of muramyldipeptides and liposomes enhances the anti-infective activity of muramyldipeptides |
US4447224A (en) | 1982-09-20 | 1984-05-08 | Infusaid Corporation | Variable flow implantable infusion apparatus |
US4487603A (en) | 1982-11-26 | 1984-12-11 | Cordis Corporation | Implantable microinfusion pump system |
US4486194A (en) | 1983-06-08 | 1984-12-04 | James Ferrara | Therapeutic device for administering medicaments through the skin |
EP0154316B1 (en) | 1984-03-06 | 1989-09-13 | Takeda Chemical Industries, Ltd. | Chemically modified lymphokine and production thereof |
US4596556A (en) | 1985-03-25 | 1986-06-24 | Bioject, Inc. | Hypodermic injection apparatus |
US5374548A (en) | 1986-05-02 | 1994-12-20 | Genentech, Inc. | Methods and compositions for the attachment of proteins to liposomes using a glycophospholipid anchor |
MX9203291A (es) | 1985-06-26 | 1992-08-01 | Liposome Co Inc | Metodo para acoplamiento de liposomas. |
DE3883899T3 (de) | 1987-03-18 | 1999-04-22 | Sb2, Inc., Danville, Calif. | Geänderte antikörper. |
US4941880A (en) | 1987-06-19 | 1990-07-17 | Bioject, Inc. | Pre-filled ampule and non-invasive hypodermic injection device assembly |
US4790824A (en) | 1987-06-19 | 1988-12-13 | Bioject, Inc. | Non-invasive hypodermic injection device |
US5677425A (en) | 1987-09-04 | 1997-10-14 | Celltech Therapeutics Limited | Recombinant antibody |
ATE135370T1 (de) | 1988-12-22 | 1996-03-15 | Kirin Amgen Inc | Chemisch modifizierte granulocytenkolonie erregender faktor |
US5225538A (en) | 1989-02-23 | 1993-07-06 | Genentech, Inc. | Lymphocyte homing receptor/immunoglobulin fusion proteins |
SE509359C2 (sv) | 1989-08-01 | 1999-01-18 | Cemu Bioteknik Ab | Användning av stabiliserade protein- eller peptidkonjugat för framställning av ett läkemedel |
US5312335A (en) | 1989-11-09 | 1994-05-17 | Bioject Inc. | Needleless hypodermic injection device |
US5064413A (en) | 1989-11-09 | 1991-11-12 | Bioject, Inc. | Needleless hypodermic injection device |
US7070991B2 (en) * | 1991-02-08 | 2006-07-04 | Progenics Pharmaceuticals, Inc. | Cells expressing a CD4-IgG2 chimeric heterotetramer |
US5383851A (en) | 1992-07-24 | 1995-01-24 | Bioject Inc. | Needleless hypodermic injection device |
WO1994029351A2 (en) | 1993-06-16 | 1994-12-22 | Celltech Limited | Antibodies |
US6277375B1 (en) | 1997-03-03 | 2001-08-21 | Board Of Regents, The University Of Texas System | Immunoglobulin-like domains with increased half-lives |
DE19709861C2 (de) | 1997-03-11 | 1999-04-01 | Vitcon Projektconsult Gmbh | Einrichtung zur Ablation von Material mit Hilfe von Laserstrahlung |
US6194551B1 (en) | 1998-04-02 | 2001-02-27 | Genentech, Inc. | Polypeptide variants |
PL209786B1 (pl) | 1999-01-15 | 2011-10-31 | Genentech Inc | Przeciwciało zawierające wariant regionu Fc ludzkiej IgG1, przeciwciało wiążące czynnik wzrostu śródbłonka naczyń oraz immunoadhezyna |
CA2704600C (en) | 1999-04-09 | 2016-10-25 | Kyowa Hakko Kirin Co., Ltd. | A method for producing antibodies with increased adcc activity |
ATE339450T1 (de) | 1999-12-23 | 2006-10-15 | Zymogenetics Inc | Verfahren zur behandlung von entzündungen |
EP1297172B1 (en) | 2000-06-28 | 2005-11-09 | Glycofi, Inc. | Methods for producing modified glycoproteins |
MXPA04003798A (es) | 2001-10-25 | 2004-07-30 | Genentech Inc | Composiciones de glicoproteina. |
JP3936673B2 (ja) | 2003-06-02 | 2007-06-27 | 国立大学法人群馬大学 | Cd47部分ペプチドと抗shps−1モノクロナール抗体 |
US8377448B2 (en) * | 2006-05-15 | 2013-02-19 | The Board Of Trustees Of The Leland Standford Junior University | CD47 related compositions and methods for treating immunological diseases and disorders |
WO2009046541A1 (en) | 2007-10-11 | 2009-04-16 | University Health Network | MODULATION OF SIRPα - CD47 INTERACTION FOR INCREASING HUMAN HEMATOPOIETIC STEM CELL ENGRAFTMENT AND COMPOUNDS THEREFOR |
-
2010
- 2010-12-21 MX MX2012007318A patent/MX2012007318A/es not_active Application Discontinuation
- 2010-12-21 US US13/517,989 patent/US20130011401A1/en not_active Abandoned
- 2010-12-21 TW TW099145049A patent/TW201130511A/zh unknown
- 2010-12-21 WO PCT/EP2010/070355 patent/WO2011076781A1/en active Application Filing
- 2010-12-21 CN CN2010800644263A patent/CN102939303A/zh active Pending
- 2010-12-21 BR BR112012017164A patent/BR112012017164A2/pt not_active IP Right Cessation
- 2010-12-21 JP JP2012545290A patent/JP2013514795A/ja active Pending
- 2010-12-21 EP EP10795387A patent/EP2516458A1/en not_active Withdrawn
- 2010-12-21 CA CA2785139A patent/CA2785139A1/en not_active Abandoned
- 2010-12-21 AU AU2010334974A patent/AU2010334974A1/en not_active Abandoned
- 2010-12-21 KR KR1020127019187A patent/KR20120107122A/ko not_active Application Discontinuation
- 2010-12-22 AR ARP100104886A patent/AR079701A1/es unknown
- 2010-12-22 UY UY33132A patent/UY33132A/xx not_active Application Discontinuation
Patent Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JPH05507854A (ja) * | 1991-02-08 | 1993-11-11 | プロゲニクス・ファーマスーティカルズ、インコーポレイテッド | CD4― ガンマ・2キメラ及びCD4 ― IgG2・キメラ |
WO2004084816A2 (en) * | 2003-03-21 | 2004-10-07 | Progenics Pharmaceuticals, Inc. | IMPROVED CD4-IgG2 FORMULATIONS |
JP2009537145A (ja) * | 2006-05-15 | 2009-10-29 | バイラル ロジック システムズ テクノロジー コーポレーション | 免疫学的疾患および障害を治療するためのcd47と関連した組成物および方法 |
Cited By (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2020510643A (ja) * | 2017-02-17 | 2020-04-09 | オーエスイー・イミュノセラピューティクス | 抗SIRPg抗体の新規の使用 |
JP7179743B2 (ja) | 2017-02-17 | 2022-11-29 | オーエスイー・イミュノセラピューティクス | 抗SIRPg抗体の新規の使用 |
Also Published As
Publication number | Publication date |
---|---|
EP2516458A1 (en) | 2012-10-31 |
US20130011401A1 (en) | 2013-01-10 |
BR112012017164A2 (pt) | 2019-09-24 |
AR079701A1 (es) | 2012-02-15 |
MX2012007318A (es) | 2012-07-20 |
TW201130511A (en) | 2011-09-16 |
KR20120107122A (ko) | 2012-09-28 |
CA2785139A1 (en) | 2011-06-30 |
CN102939303A (zh) | 2013-02-20 |
WO2011076781A1 (en) | 2011-06-30 |
AU2010334974A1 (en) | 2012-07-12 |
UY33132A (es) | 2011-07-29 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
JP2013514795A (ja) | 治療における使用のための四価cd47抗体定常領域融合タンパク質 | |
US20220242930A1 (en) | Immunomodulatory proteins with tunable affinities | |
JP6306201B2 (ja) | インターロイキン−2融合タンパク質及びその使用 | |
KR20190014525A (ko) | 면역 조절 단백질과 종양 항원을 결합하는 이중특이적 결합 단백질 | |
US20140193408A1 (en) | Soluble proteins for use as therapeutics | |
US20110237498A1 (en) | Soluble polypeptides for use in treating autoimmune and inflammatory disorders | |
TW201713694A (zh) | 抗ox40抗體及其使用方法 | |
KR102649757B1 (ko) | 5t4 및 4-1bb에 결합하는 항원 결합 단백질 및 관련 조성물 및 방법 | |
US20220002423A1 (en) | Agonistic tumor necrosis factor receptor superfamily polypeptides | |
JP2015523328A (ja) | Ctla−4バリアント | |
JP2020536552A (ja) | Ctla−4変異型免疫調節タンパク質およびそれらの使用 | |
JP2020536552A5 (ja) | ||
US20230110958A1 (en) | Il27 receptor agonists and methods of use thereof | |
US20230174659A1 (en) | Agonistic tumor necrosis factor receptor superfamily polypeptides | |
WO2024038198A1 (en) | Multi-domain binding molecules |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
A621 | Written request for application examination |
Free format text: JAPANESE INTERMEDIATE CODE: A621 Effective date: 20131107 |
|
RD04 | Notification of resignation of power of attorney |
Free format text: JAPANESE INTERMEDIATE CODE: A7424 Effective date: 20140120 |
|
RD03 | Notification of appointment of power of attorney |
Free format text: JAPANESE INTERMEDIATE CODE: A7423 Effective date: 20140820 |
|
RD04 | Notification of resignation of power of attorney |
Free format text: JAPANESE INTERMEDIATE CODE: A7424 Effective date: 20140902 |
|
A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20150203 |
|
A02 | Decision of refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A02 Effective date: 20150630 |