CA2682390A1 - Pdgfr.beta.-specific inhibitors - Google Patents
Pdgfr.beta.-specific inhibitors Download PDFInfo
- Publication number
- CA2682390A1 CA2682390A1 CA002682390A CA2682390A CA2682390A1 CA 2682390 A1 CA2682390 A1 CA 2682390A1 CA 002682390 A CA002682390 A CA 002682390A CA 2682390 A CA2682390 A CA 2682390A CA 2682390 A1 CA2682390 A1 CA 2682390A1
- Authority
- CA
- Canada
- Prior art keywords
- antibody
- seq
- pdgfr
- beta
- antibodies
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Abandoned
Links
- 239000003112 inhibitor Substances 0.000 title description 12
- 101150093908 PDGFRB gene Proteins 0.000 title 1
- 102100026547 Platelet-derived growth factor receptor beta Human genes 0.000 claims abstract description 150
- 101000692455 Homo sapiens Platelet-derived growth factor receptor beta Proteins 0.000 claims abstract description 149
- 239000005557 antagonist Substances 0.000 claims abstract description 90
- 102100033177 Vascular endothelial growth factor receptor 2 Human genes 0.000 claims abstract description 49
- 108091008605 VEGF receptors Proteins 0.000 claims abstract description 47
- 239000002246 antineoplastic agent Substances 0.000 claims abstract description 40
- 230000004614 tumor growth Effects 0.000 claims abstract description 21
- 238000000034 method Methods 0.000 claims description 60
- 125000003275 alpha amino acid group Chemical group 0.000 claims description 38
- 239000003446 ligand Substances 0.000 claims description 29
- 230000014509 gene expression Effects 0.000 claims description 28
- 239000012634 fragment Substances 0.000 claims description 23
- 108010047041 Complementarity Determining Regions Proteins 0.000 claims description 22
- 241000124008 Mammalia Species 0.000 claims description 21
- 230000000694 effects Effects 0.000 claims description 21
- 230000033115 angiogenesis Effects 0.000 claims description 20
- 239000002773 nucleotide Substances 0.000 claims description 20
- 125000003729 nucleotide group Chemical group 0.000 claims description 20
- 229940034982 antineoplastic agent Drugs 0.000 claims description 16
- 230000012010 growth Effects 0.000 claims description 16
- 150000007523 nucleic acids Chemical class 0.000 claims description 16
- 102000039446 nucleic acids Human genes 0.000 claims description 15
- 108020004707 nucleic acids Proteins 0.000 claims description 15
- 239000013604 expression vector Substances 0.000 claims description 13
- 230000002401 inhibitory effect Effects 0.000 claims description 13
- 102000005789 Vascular Endothelial Growth Factors Human genes 0.000 claims description 12
- 108010019530 Vascular Endothelial Growth Factors Proteins 0.000 claims description 12
- 101000851007 Homo sapiens Vascular endothelial growth factor receptor 2 Proteins 0.000 claims description 11
- 230000000295 complement effect Effects 0.000 claims description 11
- 102000009484 Vascular Endothelial Growth Factor Receptors Human genes 0.000 claims description 8
- 102000040430 polynucleotide Human genes 0.000 claims description 8
- 108091033319 polynucleotide Proteins 0.000 claims description 8
- 239000002157 polynucleotide Substances 0.000 claims description 8
- 108010038512 Platelet-Derived Growth Factor Proteins 0.000 claims description 5
- 102000010780 Platelet-Derived Growth Factor Human genes 0.000 claims description 5
- 230000005855 radiation Effects 0.000 claims description 5
- 108010003723 Single-Domain Antibodies Proteins 0.000 claims description 4
- 230000001603 reducing effect Effects 0.000 claims description 4
- 101001001487 Homo sapiens Phosphatidylinositol-glycan biosynthesis class F protein Proteins 0.000 claims description 3
- 101000595923 Homo sapiens Placenta growth factor Proteins 0.000 claims description 3
- 101000851030 Homo sapiens Vascular endothelial growth factor receptor 3 Proteins 0.000 claims description 3
- 102100035194 Placenta growth factor Human genes 0.000 claims description 3
- 102100033178 Vascular endothelial growth factor receptor 1 Human genes 0.000 claims description 3
- 102100033179 Vascular endothelial growth factor receptor 3 Human genes 0.000 claims description 3
- 238000012258 culturing Methods 0.000 claims description 3
- 238000006471 dimerization reaction Methods 0.000 claims description 2
- 230000001105 regulatory effect Effects 0.000 claims description 2
- 101000851018 Homo sapiens Vascular endothelial growth factor receptor 1 Proteins 0.000 claims 2
- 238000011282 treatment Methods 0.000 abstract description 49
- 201000010099 disease Diseases 0.000 abstract description 20
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 abstract description 20
- 230000002491 angiogenic effect Effects 0.000 abstract description 8
- 230000001772 anti-angiogenic effect Effects 0.000 abstract description 6
- 239000004037 angiogenesis inhibitor Substances 0.000 abstract description 2
- 229940041181 antineoplastic drug Drugs 0.000 abstract 1
- 206010028980 Neoplasm Diseases 0.000 description 120
- 210000004027 cell Anatomy 0.000 description 87
- 230000027455 binding Effects 0.000 description 81
- 102000005962 receptors Human genes 0.000 description 71
- 108020003175 receptors Proteins 0.000 description 71
- 108090000623 proteins and genes Proteins 0.000 description 52
- 239000000427 antigen Substances 0.000 description 45
- 108091007433 antigens Proteins 0.000 description 45
- 102000036639 antigens Human genes 0.000 description 45
- 230000005764 inhibitory process Effects 0.000 description 34
- 102000004169 proteins and genes Human genes 0.000 description 28
- 235000018102 proteins Nutrition 0.000 description 25
- 241000699670 Mus sp. Species 0.000 description 24
- 235000001014 amino acid Nutrition 0.000 description 22
- 230000000259 anti-tumor effect Effects 0.000 description 21
- 230000026731 phosphorylation Effects 0.000 description 21
- 238000006366 phosphorylation reaction Methods 0.000 description 21
- 239000003795 chemical substances by application Substances 0.000 description 20
- 229940024606 amino acid Drugs 0.000 description 19
- 150000001413 amino acids Chemical class 0.000 description 19
- 108090000765 processed proteins & peptides Proteins 0.000 description 18
- 238000009396 hybridization Methods 0.000 description 16
- 108091008598 receptor tyrosine kinases Proteins 0.000 description 16
- 102000027426 receptor tyrosine kinases Human genes 0.000 description 16
- 230000019491 signal transduction Effects 0.000 description 16
- 241000699666 Mus <mouse, genus> Species 0.000 description 15
- 108091032973 (ribonucleotides)n+m Proteins 0.000 description 13
- 108020004414 DNA Proteins 0.000 description 13
- 240000004808 Saccharomyces cerevisiae Species 0.000 description 13
- 230000001404 mediated effect Effects 0.000 description 13
- 239000013598 vector Substances 0.000 description 13
- 102100024616 Platelet endothelial cell adhesion molecule Human genes 0.000 description 12
- 201000011510 cancer Diseases 0.000 description 12
- 229940127089 cytotoxic agent Drugs 0.000 description 12
- 239000000203 mixture Substances 0.000 description 12
- 102000004196 processed proteins & peptides Human genes 0.000 description 12
- 241000588724 Escherichia coli Species 0.000 description 11
- 101150038994 PDGFRA gene Proteins 0.000 description 11
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 11
- 238000003556 assay Methods 0.000 description 11
- 230000000903 blocking effect Effects 0.000 description 11
- 238000002512 chemotherapy Methods 0.000 description 11
- 238000000338 in vitro Methods 0.000 description 11
- 238000001727 in vivo Methods 0.000 description 11
- 210000003668 pericyte Anatomy 0.000 description 11
- 150000003384 small molecules Chemical class 0.000 description 11
- 238000006467 substitution reaction Methods 0.000 description 11
- 238000002560 therapeutic procedure Methods 0.000 description 11
- YBJHBAHKTGYVGT-ZKWXMUAHSA-N (+)-Biotin Chemical compound N1C(=O)N[C@@H]2[C@H](CCCCC(=O)O)SC[C@@H]21 YBJHBAHKTGYVGT-ZKWXMUAHSA-N 0.000 description 10
- 239000011780 sodium chloride Substances 0.000 description 10
- 241001529936 Murinae Species 0.000 description 9
- 102000025171 antigen binding proteins Human genes 0.000 description 9
- 108091000831 antigen binding proteins Proteins 0.000 description 9
- 108020004999 messenger RNA Proteins 0.000 description 9
- 230000035772 mutation Effects 0.000 description 9
- 238000002823 phage display Methods 0.000 description 9
- 239000013612 plasmid Substances 0.000 description 9
- 229920001184 polypeptide Polymers 0.000 description 9
- 102000043136 MAP kinase family Human genes 0.000 description 8
- 108091054455 MAP kinase family Proteins 0.000 description 8
- 229960005277 gemcitabine Drugs 0.000 description 8
- 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 8
- 238000006386 neutralization reaction Methods 0.000 description 8
- 239000000523 sample Substances 0.000 description 8
- 238000013414 tumor xenograft model Methods 0.000 description 8
- 102000040650 (ribonucleotides)n+m Human genes 0.000 description 7
- 102000004190 Enzymes Human genes 0.000 description 7
- 108090000790 Enzymes Proteins 0.000 description 7
- 108060003951 Immunoglobulin Proteins 0.000 description 7
- 125000000539 amino acid group Chemical group 0.000 description 7
- 102000018358 immunoglobulin Human genes 0.000 description 7
- 208000002154 non-small cell lung carcinoma Diseases 0.000 description 7
- 230000009467 reduction Effects 0.000 description 7
- 210000004881 tumor cell Anatomy 0.000 description 7
- 101100519721 Homo sapiens PDGFRB gene Proteins 0.000 description 6
- 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 6
- 241001465754 Metazoa Species 0.000 description 6
- 108091028043 Nucleic acid sequence Proteins 0.000 description 6
- 102000004022 Protein-Tyrosine Kinases Human genes 0.000 description 6
- 108090000412 Protein-Tyrosine Kinases Proteins 0.000 description 6
- 108010053099 Vascular Endothelial Growth Factor Receptor-2 Proteins 0.000 description 6
- 230000012292 cell migration Effects 0.000 description 6
- 229960000485 methotrexate Drugs 0.000 description 6
- 230000000638 stimulation Effects 0.000 description 6
- 238000007920 subcutaneous administration Methods 0.000 description 6
- 239000000758 substrate Substances 0.000 description 6
- 108090001008 Avidin Proteins 0.000 description 5
- 102000004127 Cytokines Human genes 0.000 description 5
- 108090000695 Cytokines Proteins 0.000 description 5
- 238000002965 ELISA Methods 0.000 description 5
- 108010021625 Immunoglobulin Fragments Proteins 0.000 description 5
- 102000008394 Immunoglobulin Fragments Human genes 0.000 description 5
- 206010027476 Metastases Diseases 0.000 description 5
- 229960002685 biotin Drugs 0.000 description 5
- 235000020958 biotin Nutrition 0.000 description 5
- 239000011616 biotin Substances 0.000 description 5
- 210000004204 blood vessel Anatomy 0.000 description 5
- 230000001413 cellular effect Effects 0.000 description 5
- 150000001875 compounds Chemical class 0.000 description 5
- 230000001419 dependent effect Effects 0.000 description 5
- 238000011161 development Methods 0.000 description 5
- 230000007783 downstream signaling Effects 0.000 description 5
- 230000009977 dual effect Effects 0.000 description 5
- 230000006870 function Effects 0.000 description 5
- 239000002609 medium Substances 0.000 description 5
- 239000012528 membrane Substances 0.000 description 5
- 230000001613 neoplastic effect Effects 0.000 description 5
- 239000002953 phosphate buffered saline Substances 0.000 description 5
- 210000000329 smooth muscle myocyte Anatomy 0.000 description 5
- 238000010186 staining Methods 0.000 description 5
- 238000012360 testing method Methods 0.000 description 5
- 210000001519 tissue Anatomy 0.000 description 5
- 230000014616 translation Effects 0.000 description 5
- 241000283707 Capra Species 0.000 description 4
- 102100024746 Dihydrofolate reductase Human genes 0.000 description 4
- 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 4
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 4
- -1 PDGF-BB Proteins 0.000 description 4
- 108091000080 Phosphotransferase Proteins 0.000 description 4
- 206010035226 Plasma cell myeloma Diseases 0.000 description 4
- 108010076504 Protein Sorting Signals Proteins 0.000 description 4
- 102000000574 RNA-Induced Silencing Complex Human genes 0.000 description 4
- 108010016790 RNA-Induced Silencing Complex Proteins 0.000 description 4
- 108020004459 Small interfering RNA Proteins 0.000 description 4
- 108010090804 Streptavidin Proteins 0.000 description 4
- 230000004913 activation Effects 0.000 description 4
- 238000004458 analytical method Methods 0.000 description 4
- 230000000692 anti-sense effect Effects 0.000 description 4
- 230000035578 autophosphorylation Effects 0.000 description 4
- 210000001072 colon Anatomy 0.000 description 4
- 238000007796 conventional method Methods 0.000 description 4
- 230000006378 damage Effects 0.000 description 4
- 238000006731 degradation reaction Methods 0.000 description 4
- 238000001514 detection method Methods 0.000 description 4
- 108020001096 dihydrofolate reductase Proteins 0.000 description 4
- 239000003937 drug carrier Substances 0.000 description 4
- 210000002889 endothelial cell Anatomy 0.000 description 4
- 208000005017 glioblastoma Diseases 0.000 description 4
- 210000004408 hybridoma Anatomy 0.000 description 4
- 238000003364 immunohistochemistry Methods 0.000 description 4
- 239000007928 intraperitoneal injection Substances 0.000 description 4
- 210000004962 mammalian cell Anatomy 0.000 description 4
- 230000007246 mechanism Effects 0.000 description 4
- 230000001575 pathological effect Effects 0.000 description 4
- 102000020233 phosphotransferase Human genes 0.000 description 4
- 108010017843 platelet-derived growth factor A Proteins 0.000 description 4
- 230000002829 reductive effect Effects 0.000 description 4
- 230000004044 response Effects 0.000 description 4
- 238000012216 screening Methods 0.000 description 4
- 238000009097 single-agent therapy Methods 0.000 description 4
- 239000007787 solid Substances 0.000 description 4
- 208000024891 symptom Diseases 0.000 description 4
- 230000008685 targeting Effects 0.000 description 4
- 208000026310 Breast neoplasm Diseases 0.000 description 3
- 102000014914 Carrier Proteins Human genes 0.000 description 3
- 108020004705 Codon Proteins 0.000 description 3
- 102000053602 DNA Human genes 0.000 description 3
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 3
- 238000012413 Fluorescence activated cell sorting analysis Methods 0.000 description 3
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 3
- 108010054477 Immunoglobulin Fab Fragments Proteins 0.000 description 3
- 102000001706 Immunoglobulin Fab Fragments Human genes 0.000 description 3
- 108700005091 Immunoglobulin Genes Proteins 0.000 description 3
- 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 3
- 206010025323 Lymphomas Diseases 0.000 description 3
- 108091034117 Oligonucleotide Proteins 0.000 description 3
- 229930012538 Paclitaxel Natural products 0.000 description 3
- QIVBCDIJIAJPQS-UHFFFAOYSA-N Tryptophan Natural products C1=CC=C2C(CC(N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-UHFFFAOYSA-N 0.000 description 3
- 102000016549 Vascular Endothelial Growth Factor Receptor-2 Human genes 0.000 description 3
- 238000007792 addition Methods 0.000 description 3
- 230000003321 amplification Effects 0.000 description 3
- 230000000890 antigenic effect Effects 0.000 description 3
- 230000001580 bacterial effect Effects 0.000 description 3
- 108091008324 binding proteins Proteins 0.000 description 3
- 230000015572 biosynthetic process Effects 0.000 description 3
- 230000015556 catabolic process Effects 0.000 description 3
- 230000020411 cell activation Effects 0.000 description 3
- 238000000423 cell based assay Methods 0.000 description 3
- 238000002648 combination therapy Methods 0.000 description 3
- 231100000135 cytotoxicity Toxicity 0.000 description 3
- 239000007857 degradation product Substances 0.000 description 3
- 239000000539 dimer Substances 0.000 description 3
- 238000010494 dissociation reaction Methods 0.000 description 3
- 230000005593 dissociations Effects 0.000 description 3
- 239000012636 effector Substances 0.000 description 3
- 230000002255 enzymatic effect Effects 0.000 description 3
- 238000002474 experimental method Methods 0.000 description 3
- 239000003102 growth factor Substances 0.000 description 3
- 230000005847 immunogenicity Effects 0.000 description 3
- 230000003993 interaction Effects 0.000 description 3
- 208000032839 leukemia Diseases 0.000 description 3
- 230000000670 limiting effect Effects 0.000 description 3
- 239000006166 lysate Substances 0.000 description 3
- 239000003550 marker Substances 0.000 description 3
- 201000001441 melanoma Diseases 0.000 description 3
- 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 3
- 229960001924 melphalan Drugs 0.000 description 3
- 230000009401 metastasis Effects 0.000 description 3
- 201000000050 myeloid neoplasm Diseases 0.000 description 3
- 238000003199 nucleic acid amplification method Methods 0.000 description 3
- 229960001592 paclitaxel Drugs 0.000 description 3
- 230000003389 potentiating effect Effects 0.000 description 3
- 229940002612 prodrug Drugs 0.000 description 3
- 239000000651 prodrug Substances 0.000 description 3
- 238000001959 radiotherapy Methods 0.000 description 3
- 230000033300 receptor internalization Effects 0.000 description 3
- 230000007115 recruitment Effects 0.000 description 3
- 239000012679 serum free medium Substances 0.000 description 3
- 241000894007 species Species 0.000 description 3
- 239000000126 substance Substances 0.000 description 3
- 230000004083 survival effect Effects 0.000 description 3
- 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 3
- 230000009261 transgenic effect Effects 0.000 description 3
- 238000013519 translation Methods 0.000 description 3
- 229940121358 tyrosine kinase inhibitor Drugs 0.000 description 3
- 239000005483 tyrosine kinase inhibitor Substances 0.000 description 3
- 210000005166 vasculature Anatomy 0.000 description 3
- 238000005406 washing Methods 0.000 description 3
- 230000003442 weekly effect Effects 0.000 description 3
- 238000001262 western blot Methods 0.000 description 3
- BJHCYTJNPVGSBZ-YXSASFKJSA-N 1-[4-[6-amino-5-[(Z)-methoxyiminomethyl]pyrimidin-4-yl]oxy-2-chlorophenyl]-3-ethylurea Chemical compound CCNC(=O)Nc1ccc(Oc2ncnc(N)c2\C=N/OC)cc1Cl BJHCYTJNPVGSBZ-YXSASFKJSA-N 0.000 description 2
- NDMPLJNOPCLANR-UHFFFAOYSA-N 3,4-dihydroxy-15-(4-hydroxy-18-methoxycarbonyl-5,18-seco-ibogamin-18-yl)-16-methoxy-1-methyl-6,7-didehydro-aspidospermidine-3-carboxylic acid methyl ester Natural products C1C(CC)(O)CC(CC2(C(=O)OC)C=3C(=CC4=C(C56C(C(C(O)C7(CC)C=CCN(C67)CC5)(O)C(=O)OC)N4C)C=3)OC)CN1CCC1=C2NC2=CC=CC=C12 NDMPLJNOPCLANR-UHFFFAOYSA-N 0.000 description 2
- FHIDNBAQOFJWCA-UAKXSSHOSA-N 5-fluorouridine Chemical compound O[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1N1C(=O)NC(=O)C(F)=C1 FHIDNBAQOFJWCA-UAKXSSHOSA-N 0.000 description 2
- 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 2
- 208000024893 Acute lymphoblastic leukemia Diseases 0.000 description 2
- 208000014697 Acute lymphocytic leukaemia Diseases 0.000 description 2
- 208000031261 Acute myeloid leukaemia Diseases 0.000 description 2
- 108010032595 Antibody Binding Sites Proteins 0.000 description 2
- 108020000948 Antisense Oligonucleotides Proteins 0.000 description 2
- 108020005544 Antisense RNA Proteins 0.000 description 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- 206010006187 Breast cancer Diseases 0.000 description 2
- 101100381481 Caenorhabditis elegans baz-2 gene Proteins 0.000 description 2
- 241000699802 Cricetulus griseus Species 0.000 description 2
- 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 2
- 102000016359 Fibronectins Human genes 0.000 description 2
- 108010067306 Fibronectins Proteins 0.000 description 2
- 241000724791 Filamentous phage Species 0.000 description 2
- ZHNUHDYFZUAESO-UHFFFAOYSA-N Formamide Chemical compound NC=O ZHNUHDYFZUAESO-UHFFFAOYSA-N 0.000 description 2
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 2
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 2
- 241000282412 Homo Species 0.000 description 2
- 241000701024 Human betaherpesvirus 5 Species 0.000 description 2
- 206010061218 Inflammation Diseases 0.000 description 2
- 108010002350 Interleukin-2 Proteins 0.000 description 2
- 102000000588 Interleukin-2 Human genes 0.000 description 2
- 102000004388 Interleukin-4 Human genes 0.000 description 2
- 108090000978 Interleukin-4 Proteins 0.000 description 2
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-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
- 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
- 208000006552 Lewis Lung Carcinoma Diseases 0.000 description 2
- 241000829100 Macaca mulatta polyomavirus 1 Species 0.000 description 2
- 102000044589 Mitogen-Activated Protein Kinase 1 Human genes 0.000 description 2
- 102000046795 Mitogen-Activated Protein Kinase 3 Human genes 0.000 description 2
- 108700027649 Mitogen-Activated Protein Kinase 3 Proteins 0.000 description 2
- 108700015928 Mitogen-activated protein kinase 13 Proteins 0.000 description 2
- 241000699660 Mus musculus Species 0.000 description 2
- 101100519722 Mus musculus Pdgfrb gene Proteins 0.000 description 2
- 208000033776 Myeloid Acute Leukemia Diseases 0.000 description 2
- 101710204212 Neocarzinostatin Proteins 0.000 description 2
- 238000000636 Northern blotting Methods 0.000 description 2
- 108020004711 Nucleic Acid Probes Proteins 0.000 description 2
- 108091008606 PDGF receptors Proteins 0.000 description 2
- 229910019142 PO4 Inorganic materials 0.000 description 2
- 102000011653 Platelet-Derived Growth Factor Receptors Human genes 0.000 description 2
- 208000006664 Precursor Cell Lymphoblastic Leukemia-Lymphoma Diseases 0.000 description 2
- 238000010240 RT-PCR analysis Methods 0.000 description 2
- 101100372762 Rattus norvegicus Flt1 gene Proteins 0.000 description 2
- 108010039491 Ricin Proteins 0.000 description 2
- 206010039491 Sarcoma Diseases 0.000 description 2
- 208000000453 Skin Neoplasms Diseases 0.000 description 2
- 108091027967 Small hairpin RNA Proteins 0.000 description 2
- 238000002105 Southern blotting Methods 0.000 description 2
- 210000001744 T-lymphocyte Anatomy 0.000 description 2
- 108060008682 Tumor Necrosis Factor Proteins 0.000 description 2
- 102000000852 Tumor Necrosis Factor-alpha Human genes 0.000 description 2
- 208000036142 Viral infection Diseases 0.000 description 2
- 241000700605 Viruses Species 0.000 description 2
- 230000009471 action Effects 0.000 description 2
- 239000002671 adjuvant Substances 0.000 description 2
- 238000001042 affinity chromatography Methods 0.000 description 2
- 235000004279 alanine Nutrition 0.000 description 2
- 239000000074 antisense oligonucleotide Substances 0.000 description 2
- 238000012230 antisense oligonucleotides Methods 0.000 description 2
- 238000011717 athymic nude mouse Methods 0.000 description 2
- 229940120638 avastin Drugs 0.000 description 2
- 230000008901 benefit Effects 0.000 description 2
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 2
- 239000011230 binding agent Substances 0.000 description 2
- OWMVSZAMULFTJU-UHFFFAOYSA-N bis-tris Chemical compound OCCN(CCO)C(CO)(CO)CO OWMVSZAMULFTJU-UHFFFAOYSA-N 0.000 description 2
- 230000037396 body weight Effects 0.000 description 2
- 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 2
- 229930195731 calicheamicin Natural products 0.000 description 2
- 150000001720 carbohydrates Chemical class 0.000 description 2
- 229910052799 carbon Inorganic materials 0.000 description 2
- 238000006555 catalytic reaction Methods 0.000 description 2
- 238000004113 cell culture Methods 0.000 description 2
- 239000013592 cell lysate Substances 0.000 description 2
- 238000006243 chemical reaction Methods 0.000 description 2
- JCKYGMPEJWAADB-UHFFFAOYSA-N chlorambucil Chemical compound OC(=O)CCCC1=CC=C(N(CCCl)CCCl)C=C1 JCKYGMPEJWAADB-UHFFFAOYSA-N 0.000 description 2
- 229960004630 chlorambucil Drugs 0.000 description 2
- 238000010367 cloning Methods 0.000 description 2
- 230000002860 competitive effect Effects 0.000 description 2
- 230000001276 controlling effect Effects 0.000 description 2
- 230000009260 cross reactivity Effects 0.000 description 2
- 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 2
- 230000002950 deficient Effects 0.000 description 2
- UQLDLKMNUJERMK-UHFFFAOYSA-L di(octadecanoyloxy)lead Chemical compound [Pb+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O UQLDLKMNUJERMK-UHFFFAOYSA-L 0.000 description 2
- 238000002405 diagnostic procedure Methods 0.000 description 2
- 238000012137 double-staining Methods 0.000 description 2
- 229960004679 doxorubicin Drugs 0.000 description 2
- 239000000975 dye Substances 0.000 description 2
- 230000005670 electromagnetic radiation Effects 0.000 description 2
- 210000003527 eukaryotic cell Anatomy 0.000 description 2
- 208000021045 exocrine pancreatic carcinoma Diseases 0.000 description 2
- 210000002950 fibroblast Anatomy 0.000 description 2
- 238000001943 fluorescence-activated cell sorting Methods 0.000 description 2
- 239000001963 growth medium Substances 0.000 description 2
- 102000055590 human KDR Human genes 0.000 description 2
- YLMAHDNUQAMNNX-UHFFFAOYSA-N imatinib methanesulfonate Chemical compound CS(O)(=O)=O.C1CN(C)CCN1CC1=CC=C(C(=O)NC=2C=C(NC=3N=C(C=CN=3)C=3C=NC=CC=3)C(C)=CC=2)C=C1 YLMAHDNUQAMNNX-UHFFFAOYSA-N 0.000 description 2
- 210000000987 immune system Anatomy 0.000 description 2
- 238000010166 immunofluorescence Methods 0.000 description 2
- 230000002163 immunogen Effects 0.000 description 2
- 230000002779 inactivation Effects 0.000 description 2
- 238000011534 incubation Methods 0.000 description 2
- 230000004054 inflammatory process Effects 0.000 description 2
- 229940028885 interleukin-4 Drugs 0.000 description 2
- 230000003834 intracellular effect Effects 0.000 description 2
- 238000007918 intramuscular administration Methods 0.000 description 2
- 238000007912 intraperitoneal administration Methods 0.000 description 2
- 238000001990 intravenous administration Methods 0.000 description 2
- UWKQSNNFCGGAFS-XIFFEERXSA-N irinotecan Chemical compound C1=C2C(CC)=C3CN(C(C4=C([C@@](C(=O)OC4)(O)CC)C=4)=O)C=4C3=NC2=CC=C1OC(=O)N(CC1)CCC1N1CCCCC1 UWKQSNNFCGGAFS-XIFFEERXSA-N 0.000 description 2
- 210000002510 keratinocyte Anatomy 0.000 description 2
- 208000037841 lung tumor Diseases 0.000 description 2
- 230000003211 malignant effect Effects 0.000 description 2
- 238000005259 measurement Methods 0.000 description 2
- 238000010232 migration assay Methods 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- 230000000877 morphologic effect Effects 0.000 description 2
- LBWFXVZLPYTWQI-IPOVEDGCSA-N n-[2-(diethylamino)ethyl]-5-[(z)-(5-fluoro-2-oxo-1h-indol-3-ylidene)methyl]-2,4-dimethyl-1h-pyrrole-3-carboxamide;(2s)-2-hydroxybutanedioic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O.CCN(CC)CCNC(=O)C1=C(C)NC(\C=C/2C3=CC(F)=CC=C3NC\2=O)=C1C LBWFXVZLPYTWQI-IPOVEDGCSA-N 0.000 description 2
- QZGIWPZCWHMVQL-UIYAJPBUSA-N neocarzinostatin chromophore Chemical compound O1[C@H](C)[C@H](O)[C@H](O)[C@@H](NC)[C@H]1O[C@@H]1C/2=C/C#C[C@H]3O[C@@]3([C@@H]3OC(=O)OC3)C#CC\2=C[C@H]1OC(=O)C1=C(O)C=CC2=C(C)C=C(OC)C=C12 QZGIWPZCWHMVQL-UIYAJPBUSA-N 0.000 description 2
- 230000003472 neutralizing effect Effects 0.000 description 2
- 239000002853 nucleic acid probe Substances 0.000 description 2
- 238000011580 nude mouse model Methods 0.000 description 2
- 229940046166 oligodeoxynucleotide Drugs 0.000 description 2
- 210000001672 ovary Anatomy 0.000 description 2
- DWAFYCQODLXJNR-BNTLRKBRSA-L oxaliplatin Chemical compound O1C(=O)C(=O)O[Pt]11N[C@@H]2CCCC[C@H]2N1 DWAFYCQODLXJNR-BNTLRKBRSA-L 0.000 description 2
- 229960001756 oxaliplatin Drugs 0.000 description 2
- 208000008443 pancreatic carcinoma Diseases 0.000 description 2
- 239000008194 pharmaceutical composition Substances 0.000 description 2
- YBYRMVIVWMBXKQ-UHFFFAOYSA-N phenylmethanesulfonyl fluoride Chemical compound FS(=O)(=O)CC1=CC=CC=C1 YBYRMVIVWMBXKQ-UHFFFAOYSA-N 0.000 description 2
- 235000021317 phosphate Nutrition 0.000 description 2
- 150000003013 phosphoric acid derivatives Chemical class 0.000 description 2
- 108010000685 platelet-derived growth factor AB Proteins 0.000 description 2
- 108010017992 platelet-derived growth factor C Proteins 0.000 description 2
- 230000008569 process Effects 0.000 description 2
- 239000000047 product Substances 0.000 description 2
- 230000035755 proliferation Effects 0.000 description 2
- 230000000644 propagated effect Effects 0.000 description 2
- 238000000159 protein binding assay Methods 0.000 description 2
- 238000011002 quantification Methods 0.000 description 2
- 206010039073 rheumatoid arthritis Diseases 0.000 description 2
- 230000011664 signaling Effects 0.000 description 2
- 238000002198 surface plasmon resonance spectroscopy Methods 0.000 description 2
- 238000003786 synthesis reaction Methods 0.000 description 2
- 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 2
- 230000001225 therapeutic effect Effects 0.000 description 2
- 231100000167 toxic agent Toxicity 0.000 description 2
- 239000003440 toxic substance Substances 0.000 description 2
- 230000001988 toxicity Effects 0.000 description 2
- 231100000419 toxicity Toxicity 0.000 description 2
- 101150108727 trpl gene Proteins 0.000 description 2
- 238000007492 two-way ANOVA 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
- 150000004917 tyrosine kinase inhibitor derivatives Chemical class 0.000 description 2
- 241000701161 unidentified adenovirus Species 0.000 description 2
- 241001430294 unidentified retrovirus Species 0.000 description 2
- 230000002792 vascular Effects 0.000 description 2
- 206010055031 vascular neoplasm Diseases 0.000 description 2
- 230000004862 vasculogenesis Effects 0.000 description 2
- UGGWPQSBPIFKDZ-KOTLKJBCSA-N vindesine Chemical compound C([C@@H](C[C@]1(C(=O)OC)C=2C(=CC3=C([C@]45[C@H]([C@@]([C@H](O)[C@]6(CC)C=CCN([C@H]56)CC4)(O)C(N)=O)N3C)C=2)OC)C[C@@](C2)(O)CC)N2CCC2=C1N=C1[C]2C=CC=C1 UGGWPQSBPIFKDZ-KOTLKJBCSA-N 0.000 description 2
- 229960004355 vindesine Drugs 0.000 description 2
- 230000009385 viral infection Effects 0.000 description 2
- 229950009268 zinostatin Drugs 0.000 description 2
- FDKXTQMXEQVLRF-ZHACJKMWSA-N (E)-dacarbazine Chemical compound CN(C)\N=N\c1[nH]cnc1C(N)=O FDKXTQMXEQVLRF-ZHACJKMWSA-N 0.000 description 1
- NFGXHKASABOEEW-UHFFFAOYSA-N 1-methylethyl 11-methoxy-3,7,11-trimethyl-2,4-dodecadienoate Chemical compound COC(C)(C)CCCC(C)CC=CC(C)=CC(=O)OC(C)C NFGXHKASABOEEW-UHFFFAOYSA-N 0.000 description 1
- GZCWLCBFPRFLKL-UHFFFAOYSA-N 1-prop-2-ynoxypropan-2-ol Chemical compound CC(O)COCC#C GZCWLCBFPRFLKL-UHFFFAOYSA-N 0.000 description 1
- FSPQCTGGIANIJZ-UHFFFAOYSA-N 2-[[(3,4-dimethoxyphenyl)-oxomethyl]amino]-4,5,6,7-tetrahydro-1-benzothiophene-3-carboxamide Chemical compound C1=C(OC)C(OC)=CC=C1C(=O)NC1=C(C(N)=O)C(CCCC2)=C2S1 FSPQCTGGIANIJZ-UHFFFAOYSA-N 0.000 description 1
- OSJPPGNTCRNQQC-UWTATZPHSA-N 3-phospho-D-glyceric acid Chemical compound OC(=O)[C@H](O)COP(O)(O)=O OSJPPGNTCRNQQC-UWTATZPHSA-N 0.000 description 1
- FUXVKZWTXQUGMW-FQEVSTJZSA-N 9-Aminocamptothecin Chemical compound C1=CC(N)=C2C=C(CN3C4=CC5=C(C3=O)COC(=O)[C@]5(O)CC)C4=NC2=C1 FUXVKZWTXQUGMW-FQEVSTJZSA-N 0.000 description 1
- 102000013563 Acid Phosphatase Human genes 0.000 description 1
- 108010051457 Acid Phosphatase Proteins 0.000 description 1
- 102000007469 Actins Human genes 0.000 description 1
- 108010085238 Actins Proteins 0.000 description 1
- 208000010507 Adenocarcinoma of Lung Diseases 0.000 description 1
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 1
- 208000003120 Angiofibroma Diseases 0.000 description 1
- 108010039627 Aprotinin Proteins 0.000 description 1
- 239000004475 Arginine Substances 0.000 description 1
- DCXYFEDJOCDNAF-UHFFFAOYSA-N Asparagine Natural products OC(=O)C(N)CC(N)=O DCXYFEDJOCDNAF-UHFFFAOYSA-N 0.000 description 1
- 201000001320 Atherosclerosis Diseases 0.000 description 1
- 208000010839 B-cell chronic lymphocytic leukemia Diseases 0.000 description 1
- 208000032791 BCR-ABL1 positive chronic myelogenous leukemia Diseases 0.000 description 1
- 241000193830 Bacillus <bacterium> Species 0.000 description 1
- 244000063299 Bacillus subtilis Species 0.000 description 1
- 235000014469 Bacillus subtilis Nutrition 0.000 description 1
- 241000894006 Bacteria Species 0.000 description 1
- 206010004146 Basal cell carcinoma Diseases 0.000 description 1
- 108010081589 Becaplermin Proteins 0.000 description 1
- 208000008439 Biliary Liver Cirrhosis Diseases 0.000 description 1
- 208000033222 Biliary cirrhosis primary Diseases 0.000 description 1
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
- KLWPJMFMVPTNCC-UHFFFAOYSA-N Camptothecin Natural products CCC1(O)C(=O)OCC2=C1C=C3C4Nc5ccccc5C=C4CN3C2=O KLWPJMFMVPTNCC-UHFFFAOYSA-N 0.000 description 1
- 101710132601 Capsid protein Proteins 0.000 description 1
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 1
- 208000005623 Carcinogenesis Diseases 0.000 description 1
- 201000009030 Carcinoma Diseases 0.000 description 1
- 102000000844 Cell Surface Receptors Human genes 0.000 description 1
- 108010001857 Cell Surface Receptors Proteins 0.000 description 1
- 102000019034 Chemokines Human genes 0.000 description 1
- 108010012236 Chemokines Proteins 0.000 description 1
- 108010077544 Chromatin Proteins 0.000 description 1
- 101710094648 Coat protein Proteins 0.000 description 1
- 102000008186 Collagen Human genes 0.000 description 1
- 108010035532 Collagen Proteins 0.000 description 1
- 208000001333 Colorectal Neoplasms Diseases 0.000 description 1
- 108020004635 Complementary DNA Proteins 0.000 description 1
- 108091035707 Consensus sequence Proteins 0.000 description 1
- 206010011017 Corneal graft rejection Diseases 0.000 description 1
- CMSMOCZEIVJLDB-UHFFFAOYSA-N Cyclophosphamide Chemical compound ClCCN(CCCl)P1(=O)NCCCO1 CMSMOCZEIVJLDB-UHFFFAOYSA-N 0.000 description 1
- 206010011827 Cytomegaloviral infections Diseases 0.000 description 1
- 101710112752 Cytotoxin Proteins 0.000 description 1
- QNAYBMKLOCPYGJ-UWTATZPHSA-N D-alanine Chemical compound C[C@@H](N)C(O)=O QNAYBMKLOCPYGJ-UWTATZPHSA-N 0.000 description 1
- QNAYBMKLOCPYGJ-UHFFFAOYSA-N D-alpha-Ala Natural products CC([NH3+])C([O-])=O QNAYBMKLOCPYGJ-UHFFFAOYSA-N 0.000 description 1
- 101150074155 DHFR gene Proteins 0.000 description 1
- 102000003915 DNA Topoisomerases Human genes 0.000 description 1
- 108090000323 DNA Topoisomerases Proteins 0.000 description 1
- 230000004544 DNA amplification Effects 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
- 206010012442 Dermatitis contact Diseases 0.000 description 1
- 206010012689 Diabetic retinopathy Diseases 0.000 description 1
- 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 1
- 238000012286 ELISA Assay Methods 0.000 description 1
- 241000283074 Equus asinus Species 0.000 description 1
- 241001131785 Escherichia coli HB101 Species 0.000 description 1
- 241000701959 Escherichia virus Lambda Species 0.000 description 1
- 108091008794 FGF receptors Proteins 0.000 description 1
- 102000009109 Fc receptors Human genes 0.000 description 1
- 108010087819 Fc receptors Proteins 0.000 description 1
- 206010017533 Fungal infection Diseases 0.000 description 1
- 241000233866 Fungi Species 0.000 description 1
- 201000003741 Gastrointestinal carcinoma Diseases 0.000 description 1
- 108700028146 Genetic Enhancer Elements Proteins 0.000 description 1
- 108700039691 Genetic Promoter Regions Proteins 0.000 description 1
- 208000010412 Glaucoma Diseases 0.000 description 1
- 201000010915 Glioblastoma multiforme Diseases 0.000 description 1
- WHUUTDBJXJRKMK-UHFFFAOYSA-N Glutamic acid Natural products OC(=O)C(N)CCC(O)=O WHUUTDBJXJRKMK-UHFFFAOYSA-N 0.000 description 1
- 239000004471 Glycine Substances 0.000 description 1
- 102100021181 Golgi phosphoprotein 3 Human genes 0.000 description 1
- 102000009465 Growth Factor Receptors Human genes 0.000 description 1
- 108010009202 Growth Factor Receptors Proteins 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
- 206010019695 Hepatic neoplasm Diseases 0.000 description 1
- 208000017604 Hodgkin disease Diseases 0.000 description 1
- 208000021519 Hodgkin lymphoma Diseases 0.000 description 1
- 208000010747 Hodgkins lymphoma Diseases 0.000 description 1
- 101000690301 Homo sapiens Aldo-keto reductase family 1 member C4 Proteins 0.000 description 1
- 101100372770 Homo sapiens FLT4 gene Proteins 0.000 description 1
- 101001034652 Homo sapiens Insulin-like growth factor 1 receptor Proteins 0.000 description 1
- 101000599940 Homo sapiens Interferon gamma Proteins 0.000 description 1
- 101001116548 Homo sapiens Protein CBFA2T1 Proteins 0.000 description 1
- 241000257303 Hymenoptera Species 0.000 description 1
- 229940126049 IMC-1 Drugs 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
- 208000022559 Inflammatory bowel disease Diseases 0.000 description 1
- 101710201824 Insulin receptor substrate 1 Proteins 0.000 description 1
- 102100025087 Insulin receptor substrate 1 Human genes 0.000 description 1
- 102100039688 Insulin-like growth factor 1 receptor Human genes 0.000 description 1
- 208000007766 Kaposi sarcoma Diseases 0.000 description 1
- DCXYFEDJOCDNAF-REOHCLBHSA-N L-asparagine Chemical compound OC(=O)[C@@H](N)CC(N)=O DCXYFEDJOCDNAF-REOHCLBHSA-N 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
- AGPKZVBTJJNPAG-WHFBIAKZSA-N L-isoleucine Chemical compound CC[C@H](C)[C@H](N)C(O)=O AGPKZVBTJJNPAG-WHFBIAKZSA-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
- COLNVLDHVKWLRT-QMMMGPOBSA-N L-phenylalanine Chemical compound OC(=O)[C@@H](N)CC1=CC=CC=C1 COLNVLDHVKWLRT-QMMMGPOBSA-N 0.000 description 1
- KZSNJWFQEVHDMF-BYPYZUCNSA-N L-valine Chemical compound CC(C)[C@H](N)C(O)=O KZSNJWFQEVHDMF-BYPYZUCNSA-N 0.000 description 1
- 239000005517 L01XE01 - Imatinib Substances 0.000 description 1
- 239000002147 L01XE04 - Sunitinib Substances 0.000 description 1
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 1
- 208000018142 Leiomyosarcoma Diseases 0.000 description 1
- ROHFNLRQFUQHCH-UHFFFAOYSA-N Leucine Natural products CC(C)CC(N)C(O)=O ROHFNLRQFUQHCH-UHFFFAOYSA-N 0.000 description 1
- 206010024305 Leukaemia monocytic Diseases 0.000 description 1
- GDBQQVLCIARPGH-UHFFFAOYSA-N Leupeptin Natural products CC(C)CC(NC(C)=O)C(=O)NC(CC(C)C)C(=O)NC(C=O)CCCN=C(N)N GDBQQVLCIARPGH-UHFFFAOYSA-N 0.000 description 1
- 206010058467 Lung neoplasm malignant Diseases 0.000 description 1
- 239000004472 Lysine Substances 0.000 description 1
- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 1
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
- 101710125418 Major capsid protein Proteins 0.000 description 1
- PWHULOQIROXLJO-UHFFFAOYSA-N Manganese Chemical compound [Mn] PWHULOQIROXLJO-UHFFFAOYSA-N 0.000 description 1
- 208000034578 Multiple myelomas Diseases 0.000 description 1
- 101000957678 Mus musculus Cytochrome P450 7B1 Proteins 0.000 description 1
- 101100372766 Mus musculus Kdr gene Proteins 0.000 description 1
- 101100243646 Mus musculus Pdgfra gene Proteins 0.000 description 1
- 208000031888 Mycoses Diseases 0.000 description 1
- 229910020700 Na3VO4 Inorganic materials 0.000 description 1
- 229930193140 Neomycin Natural products 0.000 description 1
- 102000007339 Nerve Growth Factor Receptors Human genes 0.000 description 1
- 108010032605 Nerve Growth Factor Receptors Proteins 0.000 description 1
- 206010029260 Neuroblastoma Diseases 0.000 description 1
- 208000015914 Non-Hodgkin lymphomas Diseases 0.000 description 1
- 101710141454 Nucleoprotein Proteins 0.000 description 1
- 208000001132 Osteoporosis Diseases 0.000 description 1
- 206010033128 Ovarian cancer Diseases 0.000 description 1
- 206010061535 Ovarian neoplasm Diseases 0.000 description 1
- 101150012394 PHO5 gene Proteins 0.000 description 1
- 206010061902 Pancreatic neoplasm Diseases 0.000 description 1
- 206010033645 Pancreatitis Diseases 0.000 description 1
- 206010033647 Pancreatitis acute Diseases 0.000 description 1
- 208000030852 Parasitic disease Diseases 0.000 description 1
- 241000588701 Pectobacterium carotovorum Species 0.000 description 1
- 239000001888 Peptone Substances 0.000 description 1
- 108010080698 Peptones Proteins 0.000 description 1
- 102000003992 Peroxidases Human genes 0.000 description 1
- 108010069381 Platelet Endothelial Cell Adhesion Molecule-1 Proteins 0.000 description 1
- 101710164680 Platelet-derived growth factor receptor beta Proteins 0.000 description 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
- 208000012654 Primary biliary cholangitis Diseases 0.000 description 1
- 101710083689 Probable capsid protein Proteins 0.000 description 1
- 108010029485 Protein Isoforms Proteins 0.000 description 1
- 102000001708 Protein Isoforms Human genes 0.000 description 1
- 102000001253 Protein Kinase Human genes 0.000 description 1
- 108091008611 Protein Kinase B Proteins 0.000 description 1
- 108010014608 Proto-Oncogene Proteins c-kit Proteins 0.000 description 1
- 102000016971 Proto-Oncogene Proteins c-kit Human genes 0.000 description 1
- 241000589516 Pseudomonas Species 0.000 description 1
- 201000004681 Psoriasis Diseases 0.000 description 1
- 102000004879 Racemases and epimerases Human genes 0.000 description 1
- 108090001066 Racemases and epimerases Proteins 0.000 description 1
- 244000088415 Raphanus sativus Species 0.000 description 1
- 235000006140 Raphanus sativus var sativus Nutrition 0.000 description 1
- 101000957679 Rattus norvegicus 25-hydroxycholesterol 7-alpha-hydroxylase Proteins 0.000 description 1
- 102000004278 Receptor Protein-Tyrosine Kinases Human genes 0.000 description 1
- 108090000873 Receptor Protein-Tyrosine Kinases Proteins 0.000 description 1
- 102100020718 Receptor-type tyrosine-protein kinase FLT3 Human genes 0.000 description 1
- 101710151245 Receptor-type tyrosine-protein kinase FLT3 Proteins 0.000 description 1
- 108020004511 Recombinant DNA Proteins 0.000 description 1
- 102000007056 Recombinant Fusion Proteins Human genes 0.000 description 1
- 108010008281 Recombinant Fusion Proteins Proteins 0.000 description 1
- 206010038389 Renal cancer Diseases 0.000 description 1
- 208000006265 Renal cell carcinoma Diseases 0.000 description 1
- 206010038933 Retinopathy of prematurity Diseases 0.000 description 1
- 206010038934 Retinopathy proliferative Diseases 0.000 description 1
- 102000006382 Ribonucleases Human genes 0.000 description 1
- 108010083644 Ribonucleases Proteins 0.000 description 1
- 108091006629 SLC13A2 Proteins 0.000 description 1
- 229920002684 Sepharose Polymers 0.000 description 1
- 206010040070 Septic Shock Diseases 0.000 description 1
- MTCFGRXMJLQNBG-UHFFFAOYSA-N Serine Natural products OCC(N)C(O)=O MTCFGRXMJLQNBG-UHFFFAOYSA-N 0.000 description 1
- BQCADISMDOOEFD-UHFFFAOYSA-N Silver Chemical compound [Ag] BQCADISMDOOEFD-UHFFFAOYSA-N 0.000 description 1
- 108020004682 Single-Stranded DNA Proteins 0.000 description 1
- 241000187747 Streptomyces Species 0.000 description 1
- 238000000692 Student's t-test Methods 0.000 description 1
- 239000004098 Tetracycline Substances 0.000 description 1
- 241000011102 Thera Species 0.000 description 1
- AYFVYJQAPQTCCC-UHFFFAOYSA-N Threonine Natural products CC(O)C(N)C(O)=O AYFVYJQAPQTCCC-UHFFFAOYSA-N 0.000 description 1
- 239000004473 Threonine Substances 0.000 description 1
- 108010022394 Threonine synthase Proteins 0.000 description 1
- 208000024770 Thyroid neoplasm Diseases 0.000 description 1
- 101710120037 Toxin CcdB Proteins 0.000 description 1
- 206010067584 Type 1 diabetes mellitus Diseases 0.000 description 1
- 102000007537 Type II DNA Topoisomerases Human genes 0.000 description 1
- 108010046308 Type II DNA Topoisomerases Proteins 0.000 description 1
- KZSNJWFQEVHDMF-UHFFFAOYSA-N Valine Natural products CC(C)C(N)C(O)=O KZSNJWFQEVHDMF-UHFFFAOYSA-N 0.000 description 1
- 108010053096 Vascular Endothelial Growth Factor Receptor-1 Proteins 0.000 description 1
- 108010053100 Vascular Endothelial Growth Factor Receptor-3 Proteins 0.000 description 1
- 102000016663 Vascular Endothelial Growth Factor Receptor-3 Human genes 0.000 description 1
- 208000013058 Weber syndrome Diseases 0.000 description 1
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 1
- JLCPHMBAVCMARE-UHFFFAOYSA-N [3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-[[3-[[3-[[3-[[3-[[3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-hydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methyl [5-(6-aminopurin-9-yl)-2-(hydroxymethyl)oxolan-3-yl] hydrogen phosphate Polymers Cc1cn(C2CC(OP(O)(=O)OCC3OC(CC3OP(O)(=O)OCC3OC(CC3O)n3cnc4c3nc(N)[nH]c4=O)n3cnc4c3nc(N)[nH]c4=O)C(COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3CO)n3cnc4c(N)ncnc34)n3ccc(N)nc3=O)n3cnc4c(N)ncnc34)n3ccc(N)nc3=O)n3ccc(N)nc3=O)n3ccc(N)nc3=O)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cc(C)c(=O)[nH]c3=O)n3cc(C)c(=O)[nH]c3=O)n3ccc(N)nc3=O)n3cc(C)c(=O)[nH]c3=O)n3cnc4c3nc(N)[nH]c4=O)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)O2)c(=O)[nH]c1=O JLCPHMBAVCMARE-UHFFFAOYSA-N 0.000 description 1
- 230000001594 aberrant effect Effects 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- 239000012190 activator Substances 0.000 description 1
- 239000004480 active ingredient Substances 0.000 description 1
- 201000003229 acute pancreatitis Diseases 0.000 description 1
- 230000002411 adverse Effects 0.000 description 1
- 230000009824 affinity maturation Effects 0.000 description 1
- 229940100198 alkylating agent Drugs 0.000 description 1
- 239000002168 alkylating agent Substances 0.000 description 1
- 230000009285 allergic inflammation Effects 0.000 description 1
- 230000004075 alteration Effects 0.000 description 1
- 150000003863 ammonium salts Chemical class 0.000 description 1
- 229960000723 ampicillin Drugs 0.000 description 1
- AVKUERGKIZMTKX-NJBDSQKTSA-N ampicillin Chemical compound C1([C@@H](N)C(=O)N[C@H]2[C@H]3SC([C@@H](N3C2=O)C(O)=O)(C)C)=CC=CC=C1 AVKUERGKIZMTKX-NJBDSQKTSA-N 0.000 description 1
- 238000010171 animal model Methods 0.000 description 1
- 229940045799 anthracyclines and related substance Drugs 0.000 description 1
- 239000003242 anti bacterial agent Substances 0.000 description 1
- 230000003527 anti-angiogenesis Effects 0.000 description 1
- 230000001093 anti-cancer Effects 0.000 description 1
- 230000000340 anti-metabolite Effects 0.000 description 1
- 230000000118 anti-neoplastic effect Effects 0.000 description 1
- 229940088710 antibiotic agent Drugs 0.000 description 1
- 230000010056 antibody-dependent cellular cytotoxicity Effects 0.000 description 1
- 229940100197 antimetabolite Drugs 0.000 description 1
- 239000002256 antimetabolite Substances 0.000 description 1
- 238000013459 approach Methods 0.000 description 1
- 229960004405 aprotinin Drugs 0.000 description 1
- ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 1
- 125000003118 aryl group Chemical group 0.000 description 1
- 235000009582 asparagine Nutrition 0.000 description 1
- 229960001230 asparagine Drugs 0.000 description 1
- 235000003704 aspartic acid Nutrition 0.000 description 1
- 230000001363 autoimmune Effects 0.000 description 1
- 244000052616 bacterial pathogen Species 0.000 description 1
- 239000011324 bead Substances 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
- 229960000397 bevacizumab Drugs 0.000 description 1
- 238000010256 biochemical assay Methods 0.000 description 1
- 201000000053 blastoma Diseases 0.000 description 1
- 210000000988 bone and bone Anatomy 0.000 description 1
- 238000002725 brachytherapy Methods 0.000 description 1
- 210000004556 brain Anatomy 0.000 description 1
- 201000007293 brain stem infarction Diseases 0.000 description 1
- 239000000872 buffer Substances 0.000 description 1
- 238000010804 cDNA synthesis Methods 0.000 description 1
- 239000011575 calcium Substances 0.000 description 1
- 229910052791 calcium Inorganic materials 0.000 description 1
- 229940127093 camptothecin Drugs 0.000 description 1
- VSJKWCGYPAHWDS-FQEVSTJZSA-N camptothecin Chemical compound C1=CC=C2C=C(CN3C4=CC5=C(C3=O)COC(=O)[C@]5(O)CC)C4=NC2=C1 VSJKWCGYPAHWDS-FQEVSTJZSA-N 0.000 description 1
- 230000036952 cancer formation Effects 0.000 description 1
- 235000014633 carbohydrates Nutrition 0.000 description 1
- 150000004649 carbonic acid derivatives Chemical class 0.000 description 1
- 231100000504 carcinogenesis Toxicity 0.000 description 1
- 230000021164 cell adhesion Effects 0.000 description 1
- 230000003915 cell function Effects 0.000 description 1
- 230000009087 cell motility Effects 0.000 description 1
- 230000004663 cell proliferation Effects 0.000 description 1
- 239000006285 cell suspension Substances 0.000 description 1
- 230000036755 cellular response Effects 0.000 description 1
- 201000007455 central nervous system cancer Diseases 0.000 description 1
- 208000025997 central nervous system neoplasm Diseases 0.000 description 1
- 238000005119 centrifugation Methods 0.000 description 1
- 230000002490 cerebral effect Effects 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 238000012512 characterization method Methods 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 230000000973 chemotherapeutic effect Effects 0.000 description 1
- 210000004978 chinese hamster ovary cell Anatomy 0.000 description 1
- 210000003483 chromatin Anatomy 0.000 description 1
- DQLATGHUWYMOKM-UHFFFAOYSA-L cisplatin Chemical compound N[Pt](N)(Cl)Cl DQLATGHUWYMOKM-UHFFFAOYSA-L 0.000 description 1
- 229960004316 cisplatin Drugs 0.000 description 1
- 238000003776 cleavage reaction Methods 0.000 description 1
- 230000019771 cognition Effects 0.000 description 1
- 229920001436 collagen Polymers 0.000 description 1
- 239000002299 complementary DNA Substances 0.000 description 1
- 230000009918 complex formation Effects 0.000 description 1
- 238000010276 construction Methods 0.000 description 1
- 208000010247 contact dermatitis Diseases 0.000 description 1
- 239000000356 contaminant Substances 0.000 description 1
- 238000011109 contamination Methods 0.000 description 1
- 238000004132 cross linking Methods 0.000 description 1
- 239000012228 culture supernatant Substances 0.000 description 1
- 210000004748 cultured cell Anatomy 0.000 description 1
- 229960004397 cyclophosphamide Drugs 0.000 description 1
- 235000018417 cysteine Nutrition 0.000 description 1
- 150000001945 cysteines Chemical class 0.000 description 1
- 230000016396 cytokine production Effects 0.000 description 1
- 210000000805 cytoplasm Anatomy 0.000 description 1
- 230000001086 cytosolic effect Effects 0.000 description 1
- 239000002254 cytotoxic agent Substances 0.000 description 1
- 231100000599 cytotoxic agent Toxicity 0.000 description 1
- 230000003013 cytotoxicity Effects 0.000 description 1
- 239000002619 cytotoxin Substances 0.000 description 1
- 229960003901 dacarbazine Drugs 0.000 description 1
- 229960000975 daunorubicin Drugs 0.000 description 1
- 230000034994 death Effects 0.000 description 1
- 231100000517 death Toxicity 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 230000007812 deficiency Effects 0.000 description 1
- 230000003111 delayed effect Effects 0.000 description 1
- 238000012217 deletion Methods 0.000 description 1
- 230000037430 deletion Effects 0.000 description 1
- 238000013461 design Methods 0.000 description 1
- 239000008121 dextrose Substances 0.000 description 1
- 239000000032 diagnostic agent Substances 0.000 description 1
- 229940039227 diagnostic agent Drugs 0.000 description 1
- 230000004069 differentiation Effects 0.000 description 1
- 208000018554 digestive system carcinoma Diseases 0.000 description 1
- 102000004419 dihydrofolate reductase Human genes 0.000 description 1
- AIUDWMLXCFRVDR-UHFFFAOYSA-N dimethyl 2-(3-ethyl-3-methylpentyl)propanedioate Chemical class CCC(C)(CC)CCC(C(=O)OC)C(=O)OC AIUDWMLXCFRVDR-UHFFFAOYSA-N 0.000 description 1
- 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 1
- VSJKWCGYPAHWDS-UHFFFAOYSA-N dl-camptothecin Natural products C1=CC=C2C=C(CN3C4=CC5=C(C3=O)COC(=O)C5(O)CC)C4=NC2=C1 VSJKWCGYPAHWDS-UHFFFAOYSA-N 0.000 description 1
- 239000003534 dna topoisomerase inhibitor Substances 0.000 description 1
- 231100000673 dose–response relationship Toxicity 0.000 description 1
- 230000008030 elimination Effects 0.000 description 1
- 238000003379 elimination reaction Methods 0.000 description 1
- 201000008184 embryoma Diseases 0.000 description 1
- 239000003995 emulsifying agent Substances 0.000 description 1
- 210000003989 endothelium vascular Anatomy 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 239000003623 enhancer Substances 0.000 description 1
- 230000002708 enhancing effect Effects 0.000 description 1
- 230000007613 environmental effect Effects 0.000 description 1
- 238000007824 enzymatic assay Methods 0.000 description 1
- 102000052116 epidermal growth factor receptor activity proteins Human genes 0.000 description 1
- 108700015053 epidermal growth factor receptor activity proteins Proteins 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
- 238000011156 evaluation Methods 0.000 description 1
- 238000010228 ex vivo assay Methods 0.000 description 1
- ZVYVPGLRVWUPMP-FYSMJZIKSA-N exatecan Chemical compound C1C[C@H](N)C2=C(CN3C4=CC5=C(C3=O)COC(=O)[C@]5(O)CC)C4=NC3=CC(F)=C(C)C1=C32 ZVYVPGLRVWUPMP-FYSMJZIKSA-N 0.000 description 1
- 238000002710 external beam radiation therapy Methods 0.000 description 1
- 239000000284 extract Substances 0.000 description 1
- 102000052178 fibroblast growth factor receptor activity proteins Human genes 0.000 description 1
- 230000002344 fibroplastic effect Effects 0.000 description 1
- 238000000799 fluorescence microscopy Methods 0.000 description 1
- 230000002538 fungal effect Effects 0.000 description 1
- 230000002496 gastric effect Effects 0.000 description 1
- 230000030279 gene silencing Effects 0.000 description 1
- 238000012226 gene silencing method Methods 0.000 description 1
- 230000002068 genetic effect Effects 0.000 description 1
- 229940080856 gleevec Drugs 0.000 description 1
- 239000008103 glucose Substances 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
- 230000002414 glycolytic effect Effects 0.000 description 1
- 208000014829 head and neck neoplasm Diseases 0.000 description 1
- 230000036541 health Effects 0.000 description 1
- 201000002222 hemangioblastoma Diseases 0.000 description 1
- 201000011066 hemangioma Diseases 0.000 description 1
- 229960002897 heparin Drugs 0.000 description 1
- 229920000669 heparin Polymers 0.000 description 1
- 125000000623 heterocyclic group Chemical group 0.000 description 1
- 239000000833 heterodimer Substances 0.000 description 1
- HNDVDQJCIGZPNO-UHFFFAOYSA-N histidine Natural products OC(=O)C(N)CC1=CN=CN1 HNDVDQJCIGZPNO-UHFFFAOYSA-N 0.000 description 1
- 239000005556 hormone Substances 0.000 description 1
- 229940088597 hormone Drugs 0.000 description 1
- 230000005745 host immune response Effects 0.000 description 1
- 102000054751 human RUNX1T1 Human genes 0.000 description 1
- 210000005260 human cell Anatomy 0.000 description 1
- 229950006359 icrucumab Drugs 0.000 description 1
- 229960003685 imatinib mesylate Drugs 0.000 description 1
- 230000001900 immune effect Effects 0.000 description 1
- 230000028993 immune response Effects 0.000 description 1
- 229940127121 immunoconjugate Drugs 0.000 description 1
- 238000002991 immunohistochemical analysis Methods 0.000 description 1
- 238000013388 immunohistochemistry analysis Methods 0.000 description 1
- 238000002513 implantation Methods 0.000 description 1
- 238000007901 in situ hybridization Methods 0.000 description 1
- 238000001802 infusion Methods 0.000 description 1
- ZPNFWUPYTFPOJU-LPYSRVMUSA-N iniprol Chemical compound C([C@H]1C(=O)NCC(=O)NCC(=O)N[C@H]2CSSC[C@H]3C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@H](C(N[C@H](C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC=4C=CC(O)=CC=4)C(=O)N[C@@H](CC=4C=CC=CC=4)C(=O)N[C@@H](CC=4C=CC(O)=CC=4)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](C)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](C)C(=O)NCC(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CSSC[C@H](NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C)NC(=O)[C@H](CO)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CC=4C=CC=CC=4)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CCCCN)NC(=O)[C@H](C)NC(=O)[C@H](CCCNC(N)=N)NC2=O)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CSSC[C@H](NC(=O)[C@H](CC=2C=CC=CC=2)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H]2N(CCC2)C(=O)[C@@H](N)CCCNC(N)=N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(O)=O)C(=O)N2[C@@H](CCC2)C(=O)N2[C@@H](CCC2)C(=O)N[C@@H](CC=2C=CC(O)=CC=2)C(=O)N[C@@H]([C@@H](C)O)C(=O)NCC(=O)N2[C@@H](CCC2)C(=O)N3)C(=O)NCC(=O)NCC(=O)N[C@@H](C)C(O)=O)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@H](C(=O)N[C@@H](CC=2C=CC=CC=2)C(=O)N[C@H](C(=O)N1)C(C)C)[C@@H](C)O)[C@@H](C)CC)=O)[C@@H](C)CC)C1=CC=C(O)C=C1 ZPNFWUPYTFPOJU-LPYSRVMUSA-N 0.000 description 1
- 230000000977 initiatory effect Effects 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 238000003780 insertion Methods 0.000 description 1
- 230000037431 insertion Effects 0.000 description 1
- 230000002452 interceptive effect Effects 0.000 description 1
- 102000027411 intracellular receptors Human genes 0.000 description 1
- 108091008582 intracellular receptors Proteins 0.000 description 1
- 230000004068 intracellular signaling Effects 0.000 description 1
- 230000009545 invasion Effects 0.000 description 1
- 229960004768 irinotecan Drugs 0.000 description 1
- 229910052742 iron Inorganic materials 0.000 description 1
- 238000002955 isolation Methods 0.000 description 1
- 229960000310 isoleucine Drugs 0.000 description 1
- AGPKZVBTJJNPAG-UHFFFAOYSA-N isoleucine Natural products CCC(C)C(N)C(O)=O AGPKZVBTJJNPAG-UHFFFAOYSA-N 0.000 description 1
- 238000005304 joining Methods 0.000 description 1
- 210000003734 kidney Anatomy 0.000 description 1
- 238000012933 kinetic analysis Methods 0.000 description 1
- 238000011813 knockout mouse model Methods 0.000 description 1
- 238000011005 laboratory method Methods 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 210000000867 larynx Anatomy 0.000 description 1
- 230000003902 lesion Effects 0.000 description 1
- GDBQQVLCIARPGH-ULQDDVLXSA-N leupeptin Chemical compound CC(C)C[C@H](NC(C)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@H](C=O)CCCN=C(N)N GDBQQVLCIARPGH-ULQDDVLXSA-N 0.000 description 1
- 108010052968 leupeptin Proteins 0.000 description 1
- 108020001756 ligand binding domains Proteins 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 208000014018 liver neoplasm Diseases 0.000 description 1
- 238000011068 loading method Methods 0.000 description 1
- 210000004072 lung Anatomy 0.000 description 1
- 201000005249 lung adenocarcinoma Diseases 0.000 description 1
- 201000005296 lung carcinoma Diseases 0.000 description 1
- 210000004324 lymphatic system Anatomy 0.000 description 1
- 210000004698 lymphocyte Anatomy 0.000 description 1
- 230000002934 lysing effect Effects 0.000 description 1
- 239000012139 lysis buffer Substances 0.000 description 1
- 208000002780 macular degeneration Diseases 0.000 description 1
- 239000011777 magnesium Substances 0.000 description 1
- 229910052749 magnesium Inorganic materials 0.000 description 1
- 230000036210 malignancy Effects 0.000 description 1
- 229910052748 manganese Inorganic materials 0.000 description 1
- 239000011572 manganese Substances 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 238000013507 mapping Methods 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 239000011159 matrix material Substances 0.000 description 1
- 238000002844 melting Methods 0.000 description 1
- 230000008018 melting Effects 0.000 description 1
- 206010027191 meningioma Diseases 0.000 description 1
- 206010061289 metastatic neoplasm Diseases 0.000 description 1
- 238000013508 migration Methods 0.000 description 1
- 239000003226 mitogen Substances 0.000 description 1
- 230000002297 mitogenic effect Effects 0.000 description 1
- 238000010369 molecular cloning Methods 0.000 description 1
- 239000003068 molecular probe Substances 0.000 description 1
- 201000006894 monocytic leukemia Diseases 0.000 description 1
- 201000006417 multiple sclerosis Diseases 0.000 description 1
- 238000004713 multireference configuration interaction Methods 0.000 description 1
- 210000003205 muscle Anatomy 0.000 description 1
- 238000002703 mutagenesis Methods 0.000 description 1
- 231100000350 mutagenesis Toxicity 0.000 description 1
- 239000003471 mutagenic agent Substances 0.000 description 1
- 206010028417 myasthenia gravis Diseases 0.000 description 1
- YOHYSYJDKVYCJI-UHFFFAOYSA-N n-[3-[[6-[3-(trifluoromethyl)anilino]pyrimidin-4-yl]amino]phenyl]cyclopropanecarboxamide Chemical compound FC(F)(F)C1=CC=CC(NC=2N=CN=C(NC=3C=C(NC(=O)C4CC4)C=CC=3)C=2)=C1 YOHYSYJDKVYCJI-UHFFFAOYSA-N 0.000 description 1
- 230000017066 negative regulation of growth Effects 0.000 description 1
- 230000027405 negative regulation of phosphorylation Effects 0.000 description 1
- 229960004927 neomycin Drugs 0.000 description 1
- 201000003142 neovascular glaucoma Diseases 0.000 description 1
- 201000008383 nephritis Diseases 0.000 description 1
- 230000001537 neural effect Effects 0.000 description 1
- 210000004498 neuroglial cell Anatomy 0.000 description 1
- 230000007935 neutral effect Effects 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- 238000007899 nucleic acid hybridization Methods 0.000 description 1
- 235000015097 nutrients Nutrition 0.000 description 1
- 238000011275 oncology therapy Methods 0.000 description 1
- 210000000056 organ Anatomy 0.000 description 1
- 150000002894 organic compounds Chemical class 0.000 description 1
- 230000008520 organization Effects 0.000 description 1
- 201000008482 osteoarthritis Diseases 0.000 description 1
- 238000012856 packing Methods 0.000 description 1
- 201000002528 pancreatic cancer Diseases 0.000 description 1
- 230000003076 paracrine Effects 0.000 description 1
- 239000012188 paraffin wax Substances 0.000 description 1
- 230000003071 parasitic effect Effects 0.000 description 1
- 230000036961 partial effect Effects 0.000 description 1
- 230000006320 pegylation Effects 0.000 description 1
- 101150050446 pelB gene Proteins 0.000 description 1
- 229950000964 pepstatin Drugs 0.000 description 1
- 108010091212 pepstatin Proteins 0.000 description 1
- FAXGPCHRFPCXOO-LXTPJMTPSA-N pepstatin A Chemical compound OC(=O)C[C@H](O)[C@H](CC(C)C)NC(=O)[C@H](C)NC(=O)C[C@H](O)[C@H](CC(C)C)NC(=O)[C@H](C(C)C)NC(=O)[C@H](C(C)C)NC(=O)CC(C)C FAXGPCHRFPCXOO-LXTPJMTPSA-N 0.000 description 1
- 235000019319 peptone Nutrition 0.000 description 1
- 229940066779 peptones Drugs 0.000 description 1
- 210000005105 peripheral blood lymphocyte Anatomy 0.000 description 1
- 108040007629 peroxidase activity proteins Proteins 0.000 description 1
- COLNVLDHVKWLRT-UHFFFAOYSA-N phenylalanine Natural products OC(=O)C(N)CC1=CC=CC=C1 COLNVLDHVKWLRT-UHFFFAOYSA-N 0.000 description 1
- 238000003566 phosphorylation assay Methods 0.000 description 1
- DCWXELXMIBXGTH-UHFFFAOYSA-N phosphotyrosine Chemical compound OC(=O)C(N)CC1=CC=C(OP(O)(O)=O)C=C1 DCWXELXMIBXGTH-UHFFFAOYSA-N 0.000 description 1
- 239000013600 plasmid vector Substances 0.000 description 1
- 229910052697 platinum Inorganic materials 0.000 description 1
- BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Substances [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 description 1
- 230000008488 polyadenylation Effects 0.000 description 1
- 229920002981 polyvinylidene fluoride Polymers 0.000 description 1
- 239000013641 positive control Substances 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 239000002243 precursor Substances 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 1
- 210000005238 principal cell Anatomy 0.000 description 1
- 238000012545 processing Methods 0.000 description 1
- 210000001236 prokaryotic cell Anatomy 0.000 description 1
- 201000007914 proliferative diabetic retinopathy Diseases 0.000 description 1
- 230000002035 prolonged effect Effects 0.000 description 1
- 230000000069 prophylactic effect Effects 0.000 description 1
- 238000011321 prophylaxis Methods 0.000 description 1
- 208000023958 prostate neoplasm Diseases 0.000 description 1
- 230000003947 protein internalization Effects 0.000 description 1
- 108060006633 protein kinase Proteins 0.000 description 1
- 230000017854 proteolysis Effects 0.000 description 1
- 238000003653 radioligand binding assay Methods 0.000 description 1
- 239000002464 receptor antagonist Substances 0.000 description 1
- 229940044551 receptor antagonist Drugs 0.000 description 1
- 201000010174 renal carcinoma Diseases 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 230000000979 retarding effect Effects 0.000 description 1
- 230000002441 reversible effect Effects 0.000 description 1
- 201000009410 rhabdomyosarcoma Diseases 0.000 description 1
- 238000002702 ribosome display Methods 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- 230000007017 scission Effects 0.000 description 1
- 238000013077 scoring method Methods 0.000 description 1
- 230000028327 secretion Effects 0.000 description 1
- 230000008684 selective degradation Effects 0.000 description 1
- 230000036303 septic shock Effects 0.000 description 1
- 210000002966 serum Anatomy 0.000 description 1
- 239000004017 serum-free culture medium Substances 0.000 description 1
- 239000013605 shuttle vector Substances 0.000 description 1
- 229910052709 silver Inorganic materials 0.000 description 1
- 239000004332 silver Substances 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000000243 solution Substances 0.000 description 1
- 230000009870 specific binding Effects 0.000 description 1
- 206010041823 squamous cell carcinoma Diseases 0.000 description 1
- 230000006641 stabilisation Effects 0.000 description 1
- 238000011105 stabilization Methods 0.000 description 1
- 238000007619 statistical method Methods 0.000 description 1
- 150000003431 steroids Chemical class 0.000 description 1
- 210000002784 stomach Anatomy 0.000 description 1
- 150000003467 sulfuric acid derivatives Chemical class 0.000 description 1
- WINHZLLDWRZWRT-ATVHPVEESA-N sunitinib Chemical compound CCN(CC)CCNC(=O)C1=C(C)NC(\C=C/2C3=CC(F)=CC=C3NC\2=O)=C1C WINHZLLDWRZWRT-ATVHPVEESA-N 0.000 description 1
- 229960002812 sunitinib malate Drugs 0.000 description 1
- 239000006228 supernatant Substances 0.000 description 1
- 230000002459 sustained effect Effects 0.000 description 1
- 229940034785 sutent Drugs 0.000 description 1
- 229960001278 teniposide Drugs 0.000 description 1
- 229960002180 tetracycline Drugs 0.000 description 1
- 229930101283 tetracycline Natural products 0.000 description 1
- 235000019364 tetracycline Nutrition 0.000 description 1
- 150000003522 tetracyclines Chemical class 0.000 description 1
- 208000013076 thyroid tumor Diseases 0.000 description 1
- 229940044693 topoisomerase inhibitor Drugs 0.000 description 1
- 229960000303 topotecan Drugs 0.000 description 1
- UCFGDBYHRUNTLO-QHCPKHFHSA-N topotecan Chemical compound C1=C(O)C(CN(C)C)=C2C=C(CN3C4=CC5=C(C3=O)COC(=O)[C@]5(O)CC)C4=NC2=C1 UCFGDBYHRUNTLO-QHCPKHFHSA-N 0.000 description 1
- 230000008791 toxic response Effects 0.000 description 1
- 239000003053 toxin Substances 0.000 description 1
- 231100000765 toxin Toxicity 0.000 description 1
- 108700012359 toxins Proteins 0.000 description 1
- 239000011573 trace mineral Substances 0.000 description 1
- 235000013619 trace mineral Nutrition 0.000 description 1
- 230000009466 transformation Effects 0.000 description 1
- 238000011830 transgenic mouse model Methods 0.000 description 1
- IHIXIJGXTJIKRB-UHFFFAOYSA-N trisodium vanadate Chemical compound [Na+].[Na+].[Na+].[O-][V]([O-])([O-])=O IHIXIJGXTJIKRB-UHFFFAOYSA-N 0.000 description 1
- 230000005747 tumor angiogenesis Effects 0.000 description 1
- 230000001875 tumorinhibitory effect Effects 0.000 description 1
- 208000035408 type 1 diabetes mellitus 1 Diseases 0.000 description 1
- 208000027930 type IV hypersensitivity disease Diseases 0.000 description 1
- 238000011144 upstream manufacturing Methods 0.000 description 1
- 239000004474 valine Substances 0.000 description 1
- 201000011531 vascular cancer Diseases 0.000 description 1
- 210000003556 vascular endothelial cell Anatomy 0.000 description 1
- 210000004509 vascular smooth muscle cell Anatomy 0.000 description 1
- 239000013603 viral vector Substances 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
- 238000009736 wetting Methods 0.000 description 1
- 239000000080 wetting agent Substances 0.000 description 1
- 210000005253 yeast cell Anatomy 0.000 description 1
- 239000011701 zinc Substances 0.000 description 1
- 229910052725 zinc Inorganic materials 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
- C07K16/18—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
- C07K16/28—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
- C07K16/18—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
- C07K16/28—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
- C07K16/2863—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against receptors for growth factors, growth regulators
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K39/395—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K39/395—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum
- A61K39/39533—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum against materials from animals
- A61K39/3955—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum against materials from animals against proteinaceous materials, e.g. enzymes, hormones, lymphokines
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K41/00—Medicinal preparations obtained by treating materials with wave energy or particle radiation ; Therapies using these preparations
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
- A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
-
- 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
- A61P35/04—Antineoplastic agents specific for metastasis
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
- C12N15/09—Recombinant DNA-technology
- C12N15/63—Introduction of foreign genetic material using vectors; Vectors; Use of hosts therefor; Regulation of expression
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K2039/505—Medicinal preparations containing antigens or antibodies comprising antibodies
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K2039/505—Medicinal preparations containing antigens or antibodies comprising antibodies
- A61K2039/507—Comprising a combination of two or more separate antibodies
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/20—Immunoglobulins specific features characterized by taxonomic origin
- C07K2317/21—Immunoglobulins specific features characterized by taxonomic origin from primates, e.g. man
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/50—Immunoglobulins specific features characterized by immunoglobulin fragments
- C07K2317/55—Fab or Fab'
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/50—Immunoglobulins specific features characterized by immunoglobulin fragments
- C07K2317/56—Immunoglobulins specific features characterized by immunoglobulin fragments variable (Fv) region, i.e. VH and/or VL
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/50—Immunoglobulins specific features characterized by immunoglobulin fragments
- C07K2317/56—Immunoglobulins specific features characterized by immunoglobulin fragments variable (Fv) region, i.e. VH and/or VL
- C07K2317/565—Complementarity determining region [CDR]
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/70—Immunoglobulins specific features characterized by effect upon binding to a cell or to an antigen
- C07K2317/73—Inducing cell death, e.g. apoptosis, necrosis or inhibition of cell proliferation
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/70—Immunoglobulins specific features characterized by effect upon binding to a cell or to an antigen
- C07K2317/76—Antagonist effect on antigen, e.g. neutralization or inhibition of binding
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/90—Immunoglobulins specific features characterized by (pharmaco)kinetic aspects or by stability of the immunoglobulin
- C07K2317/92—Affinity (KD), association rate (Ka), dissociation rate (Kd) or EC50 value
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Medicinal Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Organic Chemistry (AREA)
- Immunology (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Pharmacology & Pharmacy (AREA)
- Genetics & Genomics (AREA)
- Epidemiology (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Biophysics (AREA)
- Biochemistry (AREA)
- Molecular Biology (AREA)
- Microbiology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Mycology (AREA)
- Endocrinology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Zoology (AREA)
- Wood Science & Technology (AREA)
- Biomedical Technology (AREA)
- Biotechnology (AREA)
- General Engineering & Computer Science (AREA)
- Plant Pathology (AREA)
- Physics & Mathematics (AREA)
- Oncology (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
- Peptides Or Proteins (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Preparation Of Compounds By Using Micro-Organisms (AREA)
- Micro-Organisms Or Cultivation Processes Thereof (AREA)
- Fuel Cell (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US92397907P | 2007-04-17 | 2007-04-17 | |
| US60/923,979 | 2007-04-17 | ||
| PCT/US2008/005137 WO2008130704A2 (en) | 2007-04-17 | 2008-04-17 | PDGFRβ-SPECIFIC INHIBITORS |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA2682390A1 true CA2682390A1 (en) | 2008-10-30 |
Family
ID=39837443
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA002682390A Abandoned CA2682390A1 (en) | 2007-04-17 | 2008-04-17 | Pdgfr.beta.-specific inhibitors |
Country Status (14)
| Country | Link |
|---|---|
| US (3) | US7740850B2 (enExample) |
| EP (1) | EP2139921A2 (enExample) |
| JP (1) | JP5209702B2 (enExample) |
| KR (1) | KR101136262B1 (enExample) |
| CN (1) | CN101707882A (enExample) |
| AU (1) | AU2008242444B2 (enExample) |
| BR (1) | BRPI0810374A2 (enExample) |
| CA (1) | CA2682390A1 (enExample) |
| EA (1) | EA019595B1 (enExample) |
| IL (1) | IL200779A0 (enExample) |
| MX (1) | MX2009011226A (enExample) |
| NZ (1) | NZ579734A (enExample) |
| UA (1) | UA99608C2 (enExample) |
| WO (1) | WO2008130704A2 (enExample) |
Families Citing this family (40)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP2604280A3 (en) * | 2008-03-27 | 2013-10-16 | ZymoGenetics, Inc. | Compositions and methods for inhibiting PDGFRBETA and VEGF-A |
| AU2009242587B2 (en) * | 2008-04-30 | 2015-05-28 | Strike Bio, Inc. | Highly pure plasmid DNA preparations and processes for preparing the same |
| US20120231537A1 (en) * | 2008-04-30 | 2012-09-13 | Gradalis, Inc. | Highly Pure Plasmid DNA Preparations |
| US20110305672A1 (en) | 2008-07-25 | 2011-12-15 | University Of Georgia Research Foundation, Inc. | COMPOSITIONS FOR MESODERM DERIVED ISL1+ MULTIPOTENT CELLS (IMPs), EPICARDIAL PROGENITOR CELLS (EPCs) AND MULTIPOTENT CD56C CELLS (C56Cs) AND METHODS OF PRODUCING AND USING SAME |
| WO2010069913A1 (en) | 2008-12-16 | 2010-06-24 | Novartis Ag | Yeast display systems |
| TW201102068A (en) * | 2009-06-02 | 2011-01-16 | Novartis Ag | Treatment of ophthalmologic disorders mediated by alpha-carbonic anhydrase isoforms |
| WO2011036305A2 (en) * | 2009-09-28 | 2011-03-31 | Medizinische Universität Wien | New use of pdgfrbeta inhibitors |
| US8765432B2 (en) | 2009-12-18 | 2014-07-01 | Oligasis, Llc | Targeted drug phosphorylcholine polymer conjugates |
| ES2926988T3 (es) | 2011-03-15 | 2022-10-31 | X Body Inc | Métodos de cribado de anticuerpos |
| CN102250249A (zh) * | 2011-06-18 | 2011-11-23 | 常州亚当生物技术有限公司 | 一种抗VEGF/PDGFRbeta双特异性抗体及其应用 |
| WO2013033008A2 (en) | 2011-08-26 | 2013-03-07 | Merrimack Pharmaceuticals, Inc. | Tandem fc bispecific antibodies |
| CA2857721C (en) | 2011-12-05 | 2022-05-31 | X-Body, Inc. | Pdgf receptor beta binding polypeptides |
| TWI613215B (zh) | 2012-02-22 | 2018-02-01 | 再生元醫藥公司 | 抗－大－內皮素－１（ｂｉｇ－ｅｔ－１）抗體及其用途 |
| JO3405B1 (ar) | 2013-01-09 | 2019-10-20 | Regeneron Pharma | الأجسام المضادة لمضاد مستقبل عامل النمو المشتق من الصفائح الدموية - بيتا واستخداماتها |
| MX2015011712A (es) | 2013-03-06 | 2016-04-04 | Merrimack Pharmaceuticals Inc | Anticerpos biespecificos fc en fila anti-c-met. |
| JP6463361B2 (ja) | 2013-09-08 | 2019-01-30 | コディアック サイエンシーズ インコーポレイテッドＫｏｄｉａｋ Ｓｃｉｅｎｃｅｓ Ｉｎｃ． | 第ｖｉｉｉ因子両性イオンポリマーコンジュゲート |
| DE202014010499U1 (de) | 2013-12-17 | 2015-10-20 | Kymab Limited | Targeting von humaner PCSK9 zur Cholesterinbehandlung |
| US9914769B2 (en) | 2014-07-15 | 2018-03-13 | Kymab Limited | Precision medicine for cholesterol treatment |
| KR102127408B1 (ko) * | 2014-01-29 | 2020-06-29 | 삼성전자주식회사 | 항 Her3 scFv 단편 및 이를 포함하는 항 c-Met/항 Her3 이중 특이 항체 |
| GB201403775D0 (en) | 2014-03-04 | 2014-04-16 | Kymab Ltd | Antibodies, uses & methods |
| US9840553B2 (en) | 2014-06-28 | 2017-12-12 | Kodiak Sciences Inc. | Dual PDGF/VEGF antagonists |
| JP6849590B2 (ja) | 2014-10-17 | 2021-03-24 | コディアック サイエンシーズ インコーポレイテッドＫｏｄｉａｋ Ｓｃｉｅｎｃｅｓ Ｉｎｃ． | ブチリルコリンエステラーゼ両性イオン性ポリマーコンジュゲート |
| CA2980385A1 (en) | 2015-03-20 | 2016-09-29 | Johann Wolfgang Goethe-Universitat Frankfurt Am Main | Pericyte long non-coding rnas |
| PL3389636T3 (pl) | 2015-12-16 | 2022-11-28 | Regeneron Pharmaceuticals, Inc. | Kompozycje i metody wytwarzania mikrocząstek białkowych |
| WO2017106609A2 (en) * | 2015-12-16 | 2017-06-22 | Kadmon Corporation, Llc. | Pdgfr beta antibody |
| WO2017117464A1 (en) | 2015-12-30 | 2017-07-06 | Kodiak Sciences Inc. | Antibodies and conjugates thereof |
| BR112018076260A2 (pt) | 2016-06-20 | 2019-03-26 | Kymab Limited | anticorpo ou fragmento do mesmo que se liga especificamente a hpd-l1, anticorpo biespecífico ou proteína de fusão, uso de um anticorpo ou fragmento, método, composição farmacêutica, método de modulação, método de inibição, método de tratamento, ácido nucleico, vetor, hospedeiro e imunocitocina |
| RU2770590C2 (ru) * | 2016-10-30 | 2022-04-18 | Шанхай Хенлиус Байотек, Инк. | Антитела против pd-l1 и их варианты |
| US11779604B2 (en) | 2016-11-03 | 2023-10-10 | Kymab Limited | Antibodies, combinations comprising antibodies, biomarkers, uses and methods |
| US11440951B2 (en) | 2017-03-13 | 2022-09-13 | The Government Of The United States, As Represented By The Secretary Of The Army | Therapeutic antibodies to Marburg virus |
| CN109021104B (zh) * | 2017-06-12 | 2022-08-12 | 上海睿智化学研究有限公司 | 一种抗人血小板衍生生长因子β受体的抗体及其应用 |
| WO2019165982A1 (en) | 2018-02-28 | 2019-09-06 | WuXi Biologics Ireland Limited | Monoclonal antibody against human lag-3, method for preparing same, and use thereof |
| BR112020017872A2 (pt) | 2018-03-02 | 2020-12-22 | Kodiak Sciences Inc. | Anticorpos de il-6 e construtos de fusão e conjugados dos mesmos |
| DE102018204828A1 (de) | 2018-03-29 | 2019-10-02 | Ford Global Technologies, Llc | Verhinderung von Glatteis durch Abwasser von Kraftfahrzeugen |
| US11773155B2 (en) | 2018-08-09 | 2023-10-03 | Beijing Wisdomab Biotechnology Co., Ltd | Bispecific antibody against rabies virus, and application thereof |
| BR112021006352A2 (pt) | 2018-10-05 | 2021-07-06 | Univ Ewha Ind Collaboration | anticorpo receptor de pdgf e uso do mesmo |
| WO2021072265A1 (en) | 2019-10-10 | 2021-04-15 | Kodiak Sciences Inc. | Methods of treating an eye disorder |
| WO2021158110A1 (en) * | 2020-02-07 | 2021-08-12 | Biorion Technologies B.V. | Platelet derived growth factor receptor (pdgfr) antibodies, conjugates, compositions, and uses thereof |
| WO2024258870A2 (en) | 2023-06-12 | 2024-12-19 | Amgen Inc. | Lymphotoxin beta receptor agonist binding proteins |
| CN118440214B (zh) * | 2024-04-02 | 2025-01-28 | 山东大学 | 一种靶向PDGFRβ的嵌合抗原受体、CAR-T细胞及应用 |
Family Cites Families (18)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5530101A (en) * | 1988-12-28 | 1996-06-25 | Protein Design Labs, Inc. | Humanized immunoglobulins |
| EP0584082B1 (en) | 1991-01-31 | 2000-05-31 | Cor Therapeutics, Inc. | Domains of extracellular region of human platelet derived growth factor receptor polypeptides |
| ATE408012T1 (de) | 1991-12-02 | 2008-09-15 | Medical Res Council | Herstellung von autoantikörpern auf phagenoberflächen ausgehend von antikörpersegmentbibliotheken |
| US20020009443A1 (en) * | 1991-12-02 | 2002-01-24 | Vanitha Ramakrishman | Inhibitory immunoglobulin polypeptides to human pdgf beta receptor |
| US5817310A (en) * | 1991-12-02 | 1998-10-06 | Cor Therapeutics, Inc. | Inhibitory immunoglobulin polypeptides to human PDGF beta receptor |
| US5976534A (en) | 1993-02-25 | 1999-11-02 | Zymogenetics, Inc. | Inhibition of intimal hyperplasia using antibodies to PDGF receptors and heparin |
| US5620687A (en) | 1993-02-25 | 1997-04-15 | Zymogenetics, Inc. | Inhibition of intimal hyperplasia using antibodies to PDGF beta receptors |
| US5840299A (en) * | 1994-01-25 | 1998-11-24 | Athena Neurosciences, Inc. | Humanized antibodies against leukocyte adhesion molecule VLA-4 |
| US6811779B2 (en) | 1994-02-10 | 2004-11-02 | Imclone Systems Incorporated | Methods for reducing tumor growth with VEGF receptor antibody combined with radiation and chemotherapy |
| US5882644A (en) | 1996-03-22 | 1999-03-16 | Protein Design Labs, Inc. | Monoclonal antibodies specific for the platelet derived growth factor β receptor and methods of use thereof |
| US6259971B1 (en) * | 1997-06-30 | 2001-07-10 | Compaq Computer Corporation | Portable fuel-cell-powered system with ultrasonic atomization of H2O by-product |
| US7740841B1 (en) * | 2000-01-28 | 2010-06-22 | Sunnybrook Health Science Center | Therapeutic method for reducing angiogenesis |
| WO2001090192A2 (en) | 2000-05-24 | 2001-11-29 | Imclone Systems Incorporated | Bispecific immunoglobulin-like antigen binding proteins and method of production |
| EP1325531B1 (de) * | 2000-09-22 | 2004-06-09 | Siemens Aktiengesellschaft | Verfahren zum überwachen des medienaustritts aus einer brennstoffzelle und brennstoffzellenanlage |
| EP1313161A1 (en) * | 2001-11-15 | 2003-05-21 | Ballard Power Systems AG | Fuel cell system and method for operating the same |
| US7582726B2 (en) * | 2003-11-10 | 2009-09-01 | Ghc Research Development Corporation | VEGF receptor antagonists |
| JP2008512352A (ja) | 2004-07-17 | 2008-04-24 | イムクローン システムズ インコーポレイティド | 新規な四価の二重特異性抗体 |
| WO2008011216A2 (en) | 2006-05-16 | 2008-01-24 | Pro-Pharmaceuticals, Inc. | Galactose-pronged polysaccharides in a formulation for antifibrotic therapies |
-
2008
- 2008-04-17 BR BRPI0810374-7A2A patent/BRPI0810374A2/pt not_active IP Right Cessation
- 2008-04-17 KR KR1020097021652A patent/KR101136262B1/ko not_active Expired - Fee Related
- 2008-04-17 CA CA002682390A patent/CA2682390A1/en not_active Abandoned
- 2008-04-17 NZ NZ579734A patent/NZ579734A/en not_active IP Right Cessation
- 2008-04-17 MX MX2009011226A patent/MX2009011226A/es active IP Right Grant
- 2008-04-17 US US12/148,482 patent/US7740850B2/en not_active Expired - Fee Related
- 2008-04-17 JP JP2010504124A patent/JP5209702B2/ja not_active Expired - Fee Related
- 2008-04-17 UA UAA200910244A patent/UA99608C2/ru unknown
- 2008-04-17 CN CN200880012257A patent/CN101707882A/zh active Pending
- 2008-04-17 EP EP08743156A patent/EP2139921A2/en not_active Withdrawn
- 2008-04-17 AU AU2008242444A patent/AU2008242444B2/en not_active Ceased
- 2008-04-17 EA EA200970953A patent/EA019595B1/ru not_active IP Right Cessation
- 2008-04-17 WO PCT/US2008/005137 patent/WO2008130704A2/en not_active Ceased
- 2008-06-25 US US12/674,350 patent/US20110207005A1/en not_active Abandoned
-
2009
- 2009-09-07 IL IL200779A patent/IL200779A0/en unknown
-
2010
- 2010-04-21 US US12/764,121 patent/US20100221267A1/en not_active Abandoned
Also Published As
| Publication number | Publication date |
|---|---|
| CN101707882A (zh) | 2010-05-12 |
| AU2008242444B2 (en) | 2013-05-02 |
| KR101136262B1 (ko) | 2012-07-05 |
| US20110207005A1 (en) | 2011-08-25 |
| EA019595B1 (ru) | 2014-04-30 |
| NZ579734A (en) | 2012-01-12 |
| WO2008130704A3 (en) | 2008-12-24 |
| AU2008242444A1 (en) | 2008-10-30 |
| KR20090130382A (ko) | 2009-12-23 |
| IL200779A0 (en) | 2010-05-17 |
| UA99608C2 (en) | 2012-09-10 |
| US7740850B2 (en) | 2010-06-22 |
| WO2008130704A2 (en) | 2008-10-30 |
| MX2009011226A (es) | 2010-04-01 |
| JP5209702B2 (ja) | 2013-06-12 |
| EA200970953A1 (ru) | 2010-10-29 |
| JP2010524466A (ja) | 2010-07-22 |
| US20090053241A1 (en) | 2009-02-26 |
| BRPI0810374A2 (pt) | 2014-10-29 |
| US20100221267A1 (en) | 2010-09-02 |
| EP2139921A2 (en) | 2010-01-06 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| AU2008242444B2 (en) | PDGFRBeta-specific inhibitors | |
| AU2009228158B2 (en) | Compositions and methods for inhibiting PDGFRbeta and VEGF-A | |
| CN101102791B (zh) | 抗血管内皮生长因子受体-1的抗体 | |
| EP2411407A1 (en) | Compositions and methods for using multispecific-binding proteins comprising an antibody-receptor combination | |
| JP2014501725A (ja) | Ｈｇｆを標的とする多特異的抗原結合タンパク質 | |
| TW201906858A (zh) | 拮抗腫瘤細胞中wnt訊息傳導之多肽 | |
| CN109160950B (zh) | 人抗vegfr-2/kdr抗体 | |
| JP2008508858A (ja) | マクロファージ−刺激タンパク質受容体（ｒｏｎ）の阻害 | |
| CA2995344C (en) | Human anti-vegfr-2/kdr antibodies | |
| EP3440111A1 (en) | Anti-vegfr-1 antibodies and uses thereof | |
| HK40032016B (en) | Human anti-vegfr-2/kdr antibodies | |
| HK40032016A (en) | Human anti-vegfr-2/kdr antibodies | |
| EA046752B1 (ru) | Полипептиды, препятствующие передаче wnt сигналов в опухолевых клетках | |
| HK1115302B (en) | Antibodies against vascular endothelial growth factor receptor-1 | |
| HK1167325B (en) | Antibodies against vascular endothelial growth factor receptor-1 |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| EEER | Examination request | ||
| FZDE | Discontinued |
Effective date: 20160208 |