CA2694396A1

CA2694396A1 - Targeted binding agents directed to kdr and uses thereof - 035

Targeted binding agents directed to kdr and uses thereof - 035 Download PDF

Info

Publication number: CA2694396A1
Authority: CA; Canada
Prior art keywords: binding agent; targeted binding; antibody; kdr; antibodies
Prior art date: 2007-07-25
Legal status : Abandoned

Application number

CA2694396A

Other languages

English (en)

French (fr)

Inventor

Simon Thomas Barry

Vahe Bedian

Bradley Hedberg

Jaspal Singh Kang

Qing Zhou

Current Assignee

AstraZeneca AB

Original Assignee

Individual

Priority date

2007-07-25

Filing date

2008-07-23

Publication date

2009-01-29

2008-07-23 Application filed by Individual filed Critical Individual

2009-01-29 Publication of CA2694396A1 publication Critical patent/CA2694396A1/en

Status Abandoned legal-status Critical Current

Links

239000011230 binding agent Substances 0.000 title claims abstract description 299
241000282414 Homo sapiens Species 0.000 claims abstract description 135
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 90
201000010099 disease Diseases 0.000 claims abstract description 87
238000011282 treatment Methods 0.000 claims abstract description 67
108010053099 Vascular Endothelial Growth Factor Receptor-2 Proteins 0.000 claims description 377
102100033177 Vascular endothelial growth factor receptor 2 Human genes 0.000 claims description 377
210000004027 cell Anatomy 0.000 claims description 238
230000027455 binding Effects 0.000 claims description 169
238000000034 method Methods 0.000 claims description 124
241001465754 Metazoa Species 0.000 claims description 94
210000004602 germ cell Anatomy 0.000 claims description 73
150000001413 amino acids Chemical group 0.000 claims description 70
239000012634 fragment Substances 0.000 claims description 69
230000001404 mediated effect Effects 0.000 claims description 65
206010028980 Neoplasm Diseases 0.000 claims description 57
101000808011 Homo sapiens Vascular endothelial growth factor A Proteins 0.000 claims description 55
102000058223 human VEGFA Human genes 0.000 claims description 54
239000006228 supernatant Substances 0.000 claims description 39
210000004408 hybridoma Anatomy 0.000 claims description 37
101100112922 Candida albicans CDR3 gene Proteins 0.000 claims description 36
201000011510 cancer Diseases 0.000 claims description 36
102100040681 Platelet-derived growth factor C Human genes 0.000 claims description 34
108010017992 platelet-derived growth factor C Proteins 0.000 claims description 34
108020003175 receptors Proteins 0.000 claims description 32
238000010790 dilution Methods 0.000 claims description 29
239000012895 dilution Substances 0.000 claims description 29
150000007523 nucleic acids Chemical class 0.000 claims description 28
241000124008 Mammalia Species 0.000 claims description 26
102000039446 nucleic acids Human genes 0.000 claims description 25
108020004707 nucleic acids Proteins 0.000 claims description 25
OUYCCCASQSFEME-QMMMGPOBSA-N L-tyrosine Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-QMMMGPOBSA-N 0.000 claims description 24
230000026731 phosphorylation Effects 0.000 claims description 24
238000006366 phosphorylation reaction Methods 0.000 claims description 24
OUYCCCASQSFEME-UHFFFAOYSA-N tyrosine Natural products OC(=O)C(N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-UHFFFAOYSA-N 0.000 claims description 24
230000001613 neoplastic effect Effects 0.000 claims description 23
239000013598 vector Substances 0.000 claims description 21
210000002889 endothelial cell Anatomy 0.000 claims description 18
208000024891 symptom Diseases 0.000 claims description 16
230000008685 targeting Effects 0.000 claims description 11
210000003606 umbilical vein Anatomy 0.000 claims description 10
230000004614 tumor growth Effects 0.000 claims description 9
201000009030 Carcinoma Diseases 0.000 claims description 8
206010039491 Sarcoma Diseases 0.000 claims description 8
201000001441 melanoma Diseases 0.000 claims description 8
208000024172 Cardiovascular disease Diseases 0.000 claims description 6
206010009944 Colon cancer Diseases 0.000 claims description 6
208000032612 Glial tumor Diseases 0.000 claims description 6
206010018338 Glioma Diseases 0.000 claims description 6
208000008839 Kidney Neoplasms Diseases 0.000 claims description 6
206010058467 Lung neoplasm malignant Diseases 0.000 claims description 6
206010027476 Metastases Diseases 0.000 claims description 6
206010038389 Renal cancer Diseases 0.000 claims description 6
208000029742 colonic neoplasm Diseases 0.000 claims description 6
208000027866 inflammatory disease Diseases 0.000 claims description 6
201000010982 kidney cancer Diseases 0.000 claims description 6
201000005202 lung cancer Diseases 0.000 claims description 6
208000020816 lung neoplasm Diseases 0.000 claims description 6
230000009401 metastasis Effects 0.000 claims description 6
210000002784 stomach Anatomy 0.000 claims description 6
206010005003 Bladder cancer Diseases 0.000 claims description 5
206010014733 Endometrial cancer Diseases 0.000 claims description 5
206010014759 Endometrial neoplasm Diseases 0.000 claims description 5
208000022873 Ocular disease Diseases 0.000 claims description 5
206010033128 Ovarian cancer Diseases 0.000 claims description 5
206010061535 Ovarian neoplasm Diseases 0.000 claims description 5
206010061902 Pancreatic neoplasm Diseases 0.000 claims description 5
206010040047 Sepsis Diseases 0.000 claims description 5
208000024770 Thyroid neoplasm Diseases 0.000 claims description 5
208000007097 Urinary Bladder Neoplasms Diseases 0.000 claims description 5
230000002496 gastric effect Effects 0.000 claims description 5
208000005017 glioblastoma Diseases 0.000 claims description 5
210000004185 liver Anatomy 0.000 claims description 5
208000015486 malignant pancreatic neoplasm Diseases 0.000 claims description 5
208000002154 non-small cell lung carcinoma Diseases 0.000 claims description 5
201000002528 pancreatic cancer Diseases 0.000 claims description 5
208000008443 pancreatic carcinoma Diseases 0.000 claims description 5
206010041823 squamous cell carcinoma Diseases 0.000 claims description 5
208000029729 tumor suppressor gene on chromosome 11 Diseases 0.000 claims description 5
201000005112 urinary bladder cancer Diseases 0.000 claims description 5
206010006187 Breast cancer Diseases 0.000 claims description 4
208000026310 Breast neoplasm Diseases 0.000 claims description 4
206010030155 Oesophageal carcinoma Diseases 0.000 claims description 4
206010060862 Prostate cancer Diseases 0.000 claims description 4
208000000236 Prostatic Neoplasms Diseases 0.000 claims description 4
206010041067 Small cell lung cancer Diseases 0.000 claims description 4
201000010536 head and neck cancer Diseases 0.000 claims description 4
208000014829 head and neck neoplasm Diseases 0.000 claims description 4
208000000587 small cell lung carcinoma Diseases 0.000 claims description 4
208000017897 Carcinoma of esophagus Diseases 0.000 claims description 3
206010027406 Mesothelioma Diseases 0.000 claims description 3
208000006990 cholangiocarcinoma Diseases 0.000 claims description 3
201000005619 esophageal carcinoma Diseases 0.000 claims description 3
230000036210 malignancy Effects 0.000 claims description 3
206010073373 small intestine adenocarcinoma Diseases 0.000 claims description 3
230000000694 effects Effects 0.000 abstract description 60
239000003795 chemical substances by application Substances 0.000 abstract description 37
238000012261 overproduction Methods 0.000 abstract description 2
125000003275 alpha amino acid group Chemical group 0.000 description 82
239000000427 antigen Substances 0.000 description 81
235000001014 amino acid Nutrition 0.000 description 80
108091007433 antigens Proteins 0.000 description 80
102000036639 antigens Human genes 0.000 description 80
108090000623 proteins and genes Proteins 0.000 description 72
229940024606 amino acid Drugs 0.000 description 70
230000005764 inhibitory process Effects 0.000 description 69
125000003729 nucleotide group Chemical group 0.000 description 69
239000002773 nucleotide Substances 0.000 description 68
230000004071 biological effect Effects 0.000 description 63
108090000765 processed proteins & peptides Proteins 0.000 description 62
238000003556 assay Methods 0.000 description 60
102100039037 Vascular endothelial growth factor A Human genes 0.000 description 57
102000004169 proteins and genes Human genes 0.000 description 57
108010073929 Vascular Endothelial Growth Factor A Proteins 0.000 description 56
239000000203 mixture Substances 0.000 description 54
235000018102 proteins Nutrition 0.000 description 50
239000003814 drug Substances 0.000 description 47
102000004196 processed proteins & peptides Human genes 0.000 description 46
230000033115 angiogenesis Effects 0.000 description 45
108010019530 Vascular Endothelial Growth Factors Proteins 0.000 description 41
229920001184 polypeptide Polymers 0.000 description 40
239000005557 antagonist Substances 0.000 description 38
230000021164 cell adhesion Effects 0.000 description 38
108010047041 Complementarity Determining Regions Proteins 0.000 description 34
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 32
108060003951 Immunoglobulin Proteins 0.000 description 32
230000004709 cell invasion Effects 0.000 description 32
102000018358 immunoglobulin Human genes 0.000 description 32
230000035755 proliferation Effects 0.000 description 32
230000035772 mutation Effects 0.000 description 31
102000005962 receptors Human genes 0.000 description 31
230000004083 survival effect Effects 0.000 description 30
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 28
239000003112 inhibitor Substances 0.000 description 26
238000002965 ELISA Methods 0.000 description 24
238000009472 formulation Methods 0.000 description 22
230000014509 gene expression Effects 0.000 description 22
229910052760 oxygen Inorganic materials 0.000 description 22
241000699670 Mus sp. Species 0.000 description 21
230000006870 function Effects 0.000 description 21
238000013459 approach Methods 0.000 description 20
102000040430 polynucleotide Human genes 0.000 description 20
108091033319 polynucleotide Proteins 0.000 description 20
239000002157 polynucleotide Substances 0.000 description 20
101000851007 Homo sapiens Vascular endothelial growth factor receptor 2 Proteins 0.000 description 19
230000000295 complement effect Effects 0.000 description 19
239000012636 effector Substances 0.000 description 19
238000004519 manufacturing process Methods 0.000 description 19
230000011664 signaling Effects 0.000 description 19
230000001225 therapeutic effect Effects 0.000 description 19
150000001875 compounds Chemical class 0.000 description 18
230000036515 potency Effects 0.000 description 18
102100024952 Protein CBFA2T1 Human genes 0.000 description 17
238000001727 in vivo Methods 0.000 description 17
238000006467 substitution reaction Methods 0.000 description 17
241000283707 Capra Species 0.000 description 16
108091008605 VEGF receptors Proteins 0.000 description 16
239000002246 antineoplastic agent Substances 0.000 description 16
230000001965 increasing effect Effects 0.000 description 16
230000004913 activation Effects 0.000 description 15
238000007792 addition Methods 0.000 description 15
230000004540 complement-dependent cytotoxicity Effects 0.000 description 15
239000003446 ligand Substances 0.000 description 15
239000003053 toxin Substances 0.000 description 15
231100000765 toxin Toxicity 0.000 description 15
108700012359 toxins Proteins 0.000 description 15
101100381481 Caenorhabditis elegans baz-2 gene Proteins 0.000 description 14
102000004190 Enzymes Human genes 0.000 description 14
108090000790 Enzymes Proteins 0.000 description 14
108091034117 Oligonucleotide Proteins 0.000 description 14
101100372762 Rattus norvegicus Flt1 gene Proteins 0.000 description 14
238000004458 analytical method Methods 0.000 description 14
229940088598 enzyme Drugs 0.000 description 14
230000002401 inhibitory effect Effects 0.000 description 14
210000002966 serum Anatomy 0.000 description 14
-1 0-phosphoserine Chemical compound 0.000 description 13
108020004414 DNA Proteins 0.000 description 13
241001529936 Murinae Species 0.000 description 13
125000000539 amino acid group Chemical group 0.000 description 13
238000001943 fluorescence-activated cell sorting Methods 0.000 description 13
102000055590 human KDR Human genes 0.000 description 13
241000894007 species Species 0.000 description 13
CMSMOCZEIVJLDB-UHFFFAOYSA-N Cyclophosphamide Chemical compound ClCCN(CCCl)P1(=O)NCCCO1 CMSMOCZEIVJLDB-UHFFFAOYSA-N 0.000 description 12
241000699666 Mus <mouse, genus> Species 0.000 description 12
102000016549 Vascular Endothelial Growth Factor Receptor-2 Human genes 0.000 description 12
210000003719 b-lymphocyte Anatomy 0.000 description 12
230000015572 biosynthetic process Effects 0.000 description 12
230000009260 cross reactivity Effects 0.000 description 12
229960004397 cyclophosphamide Drugs 0.000 description 12
229920001223 polyethylene glycol Polymers 0.000 description 12
238000002360 preparation method Methods 0.000 description 12
239000013589 supplement Substances 0.000 description 12
210000001519 tissue Anatomy 0.000 description 12
108010021625 Immunoglobulin Fragments Proteins 0.000 description 11
102000008394 Immunoglobulin Fragments Human genes 0.000 description 11
229960004679 doxorubicin Drugs 0.000 description 11
238000005755 formation reaction Methods 0.000 description 11
238000002560 therapeutic procedure Methods 0.000 description 11
238000012413 Fluorescence activated cell sorting analysis Methods 0.000 description 10
238000012217 deletion Methods 0.000 description 10
230000037430 deletion Effects 0.000 description 10
239000000463 material Substances 0.000 description 10
230000007246 mechanism Effects 0.000 description 10
238000011533 pre-incubation Methods 0.000 description 10
YXHLJMWYDTXDHS-IRFLANFNSA-N 7-aminoactinomycin D Chemical compound C[C@H]1OC(=O)[C@H](C(C)C)N(C)C(=O)CN(C)C(=O)[C@@H]2CCCN2C(=O)[C@@H](C(C)C)NC(=O)[C@H]1NC(=O)C1=C(N)C(=O)C(C)=C2OC(C(C)=C(N)C=C3C(=O)N[C@@H]4C(=O)N[C@@H](C(N5CCC[C@H]5C(=O)N(C)CC(=O)N(C)[C@@H](C(C)C)C(=O)O[C@@H]4C)=O)C(C)C)=C3N=C21 YXHLJMWYDTXDHS-IRFLANFNSA-N 0.000 description 9
108010006654 Bleomycin Proteins 0.000 description 9
101100372766 Mus musculus Kdr gene Proteins 0.000 description 9
239000002202 Polyethylene glycol Substances 0.000 description 9
108010073923 Vascular Endothelial Growth Factor C Proteins 0.000 description 9
102100038232 Vascular endothelial growth factor C Human genes 0.000 description 9
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 9
229960001561 bleomycin Drugs 0.000 description 9
OYVAGSVQBOHSSS-UAPAGMARSA-O bleomycin A2 Chemical compound N([C@H](C(=O)N[C@H](C)[C@@H](O)[C@H](C)C(=O)N[C@@H]([C@H](O)C)C(=O)NCCC=1SC=C(N=1)C=1SC=C(N=1)C(=O)NCCC[S+](C)C)[C@@H](O[C@H]1[C@H]([C@@H](O)[C@H](O)[C@H](CO)O1)O[C@@H]1[C@H]([C@@H](OC(N)=O)[C@H](O)[C@@H](CO)O1)O)C=1N=CNC=1)C(=O)C1=NC([C@H](CC(N)=O)NC[C@H](N)C(N)=O)=NC(N)=C1C OYVAGSVQBOHSSS-UAPAGMARSA-O 0.000 description 9
230000000903 blocking effect Effects 0.000 description 9
238000006471 dimerization reaction Methods 0.000 description 9
238000005516 engineering process Methods 0.000 description 9
238000002474 experimental method Methods 0.000 description 9
230000003053 immunization Effects 0.000 description 9
238000000338 in vitro Methods 0.000 description 9
230000009545 invasion Effects 0.000 description 9
230000002062 proliferating effect Effects 0.000 description 9
238000001959 radiotherapy Methods 0.000 description 9
239000000758 substrate Substances 0.000 description 9
229960004528 vincristine Drugs 0.000 description 9
OGWKCGZFUXNPDA-XQKSVPLYSA-N vincristine Chemical compound C([N@]1C[C@@H](C[C@]2(C(=O)OC)C=3C(=CC4=C([C@]56[C@H]([C@@]([C@H](OC(C)=O)[C@]7(CC)C=CCN([C@H]67)CC5)(O)C(=O)OC)N4C=O)C=3)OC)C[C@@](C1)(O)CC)CC1=C2NC2=CC=CC=C12 OGWKCGZFUXNPDA-XQKSVPLYSA-N 0.000 description 9
OGWKCGZFUXNPDA-UHFFFAOYSA-N vincristine Natural products C1C(CC)(O)CC(CC2(C(=O)OC)C=3C(=CC4=C(C56C(C(C(OC(C)=O)C7(CC)C=CCN(C67)CC5)(O)C(=O)OC)N4C=O)C=3)OC)CN1CCC1=C2NC2=CC=CC=C12 OGWKCGZFUXNPDA-UHFFFAOYSA-N 0.000 description 9
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 8
NWIBSHFKIJFRCO-WUDYKRTCSA-N Mytomycin Chemical compound C1N2C(C(C(C)=C(N)C3=O)=O)=C3[C@@H](COC(N)=O)[C@@]2(OC)[C@@H]2[C@H]1N2 NWIBSHFKIJFRCO-WUDYKRTCSA-N 0.000 description 8
230000002491 angiogenic effect Effects 0.000 description 8
229940044683 chemotherapy drug Drugs 0.000 description 8
231100000433 cytotoxic Toxicity 0.000 description 8
230000001472 cytotoxic effect Effects 0.000 description 8
230000001419 dependent effect Effects 0.000 description 8
229940079593 drug Drugs 0.000 description 8
230000004927 fusion Effects 0.000 description 8
238000009396 hybridization Methods 0.000 description 8
238000002649 immunization Methods 0.000 description 8
239000000523 sample Substances 0.000 description 8
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 7
206010035226 Plasma cell myeloma Diseases 0.000 description 7
239000008280 blood Substances 0.000 description 7
125000000151 cysteine group Chemical group N[C@@H](CS)C(=O)* 0.000 description 7
230000013595 glycosylation Effects 0.000 description 7
238000006206 glycosylation reaction Methods 0.000 description 7
238000011534 incubation Methods 0.000 description 7
229960000485 methotrexate Drugs 0.000 description 7
238000002703 mutagenesis Methods 0.000 description 7
231100000350 mutagenesis Toxicity 0.000 description 7
XOFYZVNMUHMLCC-ZPOLXVRWSA-N prednisone Chemical compound O=C1C=C[C@]2(C)[C@H]3C(=O)C[C@](C)([C@@](CC4)(O)C(=O)CO)[C@@H]4[C@@H]3CCC2=C1 XOFYZVNMUHMLCC-ZPOLXVRWSA-N 0.000 description 7
229960004618 prednisone Drugs 0.000 description 7
238000004448 titration Methods 0.000 description 7
230000003442 weekly effect Effects 0.000 description 7
MTCFGRXMJLQNBG-REOHCLBHSA-N (2S)-2-Amino-3-hydroxypropansäure Chemical compound OC[C@H](N)C(O)=O MTCFGRXMJLQNBG-REOHCLBHSA-N 0.000 description 6
108700012813 7-aminoactinomycin D Proteins 0.000 description 6
238000012286 ELISA Assay Methods 0.000 description 6
DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 6
238000012452 Xenomouse strains Methods 0.000 description 6
RJURFGZVJUQBHK-UHFFFAOYSA-N actinomycin D Natural products CC1OC(=O)C(C(C)C)N(C)C(=O)CN(C)C(=O)C2CCCN2C(=O)C(C(C)C)NC(=O)C1NC(=O)C1=C(N)C(=O)C(C)=C2OC(C(C)=CC=C3C(=O)NC4C(=O)NC(C(N5CCCC5C(=O)N(C)CC(=O)N(C)C(C(C)C)C(=O)OC4C)=O)C(C)C)=C3N=C21 RJURFGZVJUQBHK-UHFFFAOYSA-N 0.000 description 6
230000000259 anti-tumor effect Effects 0.000 description 6
210000004369 blood Anatomy 0.000 description 6
239000011575 calcium Substances 0.000 description 6
239000013592 cell lysate Substances 0.000 description 6
230000003013 cytotoxicity Effects 0.000 description 6
231100000135 cytotoxicity Toxicity 0.000 description 6
239000003937 drug carrier Substances 0.000 description 6
230000012010 growth Effects 0.000 description 6
230000001900 immune effect Effects 0.000 description 6
229940127121 immunoconjugate Drugs 0.000 description 6
230000001976 improved effect Effects 0.000 description 6
201000000050 myeloid neoplasm Diseases 0.000 description 6
239000008194 pharmaceutical composition Substances 0.000 description 6
210000004180 plasmocyte Anatomy 0.000 description 6
239000000126 substance Substances 0.000 description 6
108091032973 (ribonucleotides)n+m Proteins 0.000 description 5
239000006144 Dulbecco’s modiﬁed Eagle's medium Substances 0.000 description 5
108010087819 Fc receptors Proteins 0.000 description 5
102000009109 Fc receptors Human genes 0.000 description 5
WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 description 5
ZDXPYRJPNDTMRX-VKHMYHEASA-N L-glutamine Chemical compound OC(=O)[C@@H](N)CCC(N)=O ZDXPYRJPNDTMRX-VKHMYHEASA-N 0.000 description 5
AYFVYJQAPQTCCC-GBXIJSLDSA-N L-threonine Chemical compound C[C@@H](O)[C@H](N)C(O)=O AYFVYJQAPQTCCC-GBXIJSLDSA-N 0.000 description 5
206010025323 Lymphomas Diseases 0.000 description 5
208000015914 Non-Hodgkin lymphomas Diseases 0.000 description 5
229930012538 Paclitaxel Natural products 0.000 description 5
241001494479 Pecora Species 0.000 description 5
101000762949 Pseudomonas aeruginosa (strain ATCC 15692 / DSM 22644 / CIP 104116 / JCM 14847 / LMG 12228 / 1C / PRS 101 / PAO1) Exotoxin A Proteins 0.000 description 5
230000000692 anti-sense effect Effects 0.000 description 5
238000003149 assay kit Methods 0.000 description 5
230000008901 benefit Effects 0.000 description 5
150000001720 carbohydrates Chemical class 0.000 description 5
235000014633 carbohydrates Nutrition 0.000 description 5
230000008859 change Effects 0.000 description 5
210000004978 chinese hamster ovary cell Anatomy 0.000 description 5
229960004630 chlorambucil Drugs 0.000 description 5
JCKYGMPEJWAADB-UHFFFAOYSA-N chlorambucil Chemical compound OC(=O)CCCC1=CC=C(N(CCCl)CCCl)C=C1 JCKYGMPEJWAADB-UHFFFAOYSA-N 0.000 description 5
239000011248 coating agent Substances 0.000 description 5
238000000576 coating method Methods 0.000 description 5
229940127089 cytotoxic agent Drugs 0.000 description 5
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 5
229960005420 etoposide Drugs 0.000 description 5
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 5
229940072221 immunoglobulins Drugs 0.000 description 5
230000002637 immunotoxin Effects 0.000 description 5
239000002596 immunotoxin Substances 0.000 description 5
229940051026 immunotoxin Drugs 0.000 description 5
231100000608 immunotoxin Toxicity 0.000 description 5
238000002347 injection Methods 0.000 description 5
239000007924 injection Substances 0.000 description 5
229960000310 isoleucine Drugs 0.000 description 5
208000032839 leukemia Diseases 0.000 description 5
210000004698 lymphocyte Anatomy 0.000 description 5
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 5
229960001924 melphalan Drugs 0.000 description 5
230000004048 modification Effects 0.000 description 5
238000012986 modification Methods 0.000 description 5
239000013642 negative control Substances 0.000 description 5
230000003472 neutralizing effect Effects 0.000 description 5
239000000546 pharmaceutical excipient Substances 0.000 description 5
229920000642 polymer Polymers 0.000 description 5
150000003180 prostaglandins Chemical class 0.000 description 5
230000009467 reduction Effects 0.000 description 5
238000012552 review Methods 0.000 description 5
230000007781 signaling event Effects 0.000 description 5
239000000243 solution Substances 0.000 description 5
238000001890 transfection Methods 0.000 description 5
210000004881 tumor cell Anatomy 0.000 description 5
239000004474 valine Substances 0.000 description 5
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 4
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 4
239000004475 Arginine Substances 0.000 description 4
CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 4
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 4
BWGNESOTFCXPMA-UHFFFAOYSA-N Dihydrogen disulfide Chemical compound SS BWGNESOTFCXPMA-UHFFFAOYSA-N 0.000 description 4
201000008808 Fibrosarcoma Diseases 0.000 description 4
GHASVSINZRGABV-UHFFFAOYSA-N Fluorouracil Chemical compound FC1=CNC(=O)NC1=O GHASVSINZRGABV-UHFFFAOYSA-N 0.000 description 4
241000282412 Homo Species 0.000 description 4
101000851030 Homo sapiens Vascular endothelial growth factor receptor 3 Proteins 0.000 description 4
XDXDZDZNSLXDNA-TZNDIEGXSA-N Idarubicin Chemical compound C1[C@H](N)[C@H](O)[C@H](C)O[C@H]1O[C@@H]1C2=C(O)C(C(=O)C3=CC=CC=C3C3=O)=C3C(O)=C2C[C@@](O)(C(C)=O)C1 XDXDZDZNSLXDNA-TZNDIEGXSA-N 0.000 description 4
XDXDZDZNSLXDNA-UHFFFAOYSA-N Idarubicin Natural products C1C(N)C(O)C(C)OC1OC1C2=C(O)C(C(=O)C3=CC=CC=C3C3=O)=C3C(O)=C2CC(O)(C(C)=O)C1 XDXDZDZNSLXDNA-UHFFFAOYSA-N 0.000 description 4
108010054477 Immunoglobulin Fab Fragments Proteins 0.000 description 4
102000001706 Immunoglobulin Fab Fragments Human genes 0.000 description 4
DCXYFEDJOCDNAF-REOHCLBHSA-N L-asparagine Chemical compound OC(=O)[C@@H](N)CC(N)=O DCXYFEDJOCDNAF-REOHCLBHSA-N 0.000 description 4
HNDVDQJCIGZPNO-YFKPBYRVSA-N L-histidine Chemical compound OC(=O)[C@@H](N)CC1=CN=CN1 HNDVDQJCIGZPNO-YFKPBYRVSA-N 0.000 description 4
AGPKZVBTJJNPAG-WHFBIAKZSA-N L-isoleucine Chemical compound CC[C@H](C)[C@H](N)C(O)=O AGPKZVBTJJNPAG-WHFBIAKZSA-N 0.000 description 4
ROHFNLRQFUQHCH-YFKPBYRVSA-N L-leucine Chemical compound CC(C)C[C@H](N)C(O)=O ROHFNLRQFUQHCH-YFKPBYRVSA-N 0.000 description 4
KDXKERNSBIXSRK-YFKPBYRVSA-N L-lysine Chemical compound NCCCC[C@H](N)C(O)=O KDXKERNSBIXSRK-YFKPBYRVSA-N 0.000 description 4
KZSNJWFQEVHDMF-BYPYZUCNSA-N L-valine Chemical compound CC(C)[C@H](N)C(O)=O KZSNJWFQEVHDMF-BYPYZUCNSA-N 0.000 description 4
ROHFNLRQFUQHCH-UHFFFAOYSA-N Leucine Natural products CC(C)CC(N)C(O)=O ROHFNLRQFUQHCH-UHFFFAOYSA-N 0.000 description 4
ZDZOTLJHXYCWBA-VCVYQWHSSA-N N-debenzoyl-N-(tert-butoxycarbonyl)-10-deacetyltaxol Chemical compound O([C@H]1[C@H]2[C@@](C([C@H](O)C3=C(C)[C@@H](OC(=O)[C@H](O)[C@@H](NC(=O)OC(C)(C)C)C=4C=CC=CC=4)C[C@]1(O)C3(C)C)=O)(C)[C@@H](O)C[C@H]1OC[C@]12OC(=O)C)C(=O)C1=CC=CC=C1 ZDZOTLJHXYCWBA-VCVYQWHSSA-N 0.000 description 4
108091028043 Nucleic acid sequence Proteins 0.000 description 4
108010039491 Ricin Proteins 0.000 description 4
MTCFGRXMJLQNBG-UHFFFAOYSA-N Serine Natural products OCC(N)C(O)=O MTCFGRXMJLQNBG-UHFFFAOYSA-N 0.000 description 4
AYFVYJQAPQTCCC-UHFFFAOYSA-N Threonine Natural products CC(O)C(N)C(O)=O AYFVYJQAPQTCCC-UHFFFAOYSA-N 0.000 description 4
239000004473 Threonine Substances 0.000 description 4
KZSNJWFQEVHDMF-UHFFFAOYSA-N Valine Natural products CC(C)C(N)C(O)=O KZSNJWFQEVHDMF-UHFFFAOYSA-N 0.000 description 4
102100033179 Vascular endothelial growth factor receptor 3 Human genes 0.000 description 4
239000002253 acid Substances 0.000 description 4
230000009471 action Effects 0.000 description 4
230000003213 activating effect Effects 0.000 description 4
239000000556 agonist Substances 0.000 description 4
230000001668 ameliorated effect Effects 0.000 description 4
229940045799 anthracyclines and related substance Drugs 0.000 description 4
230000000340 anti-metabolite Effects 0.000 description 4
229940100197 antimetabolite Drugs 0.000 description 4
239000002256 antimetabolite Substances 0.000 description 4
230000003197 catalytic effect Effects 0.000 description 4
238000006243 chemical reaction Methods 0.000 description 4
238000002512 chemotherapy Methods 0.000 description 4
235000018417 cysteine Nutrition 0.000 description 4
238000001514 detection method Methods 0.000 description 4
238000011161 development Methods 0.000 description 4
230000018109 developmental process Effects 0.000 description 4
239000000539 dimer Substances 0.000 description 4
BFMYDTVEBKDAKJ-UHFFFAOYSA-L disodium;(2',7'-dibromo-3',6'-dioxido-3-oxospiro[2-benzofuran-1,9'-xanthene]-4'-yl)mercury;hydrate Chemical compound O.[Na+].[Na+].O1C(=O)C2=CC=CC=C2C21C1=CC(Br)=C([O-])C([Hg])=C1OC1=C2C=C(Br)C([O-])=C1 BFMYDTVEBKDAKJ-UHFFFAOYSA-L 0.000 description 4
229960002949 fluorouracil Drugs 0.000 description 4
ZDXPYRJPNDTMRX-UHFFFAOYSA-N glutamine Natural products OC(=O)C(N)CCC(N)=O ZDXPYRJPNDTMRX-UHFFFAOYSA-N 0.000 description 4
239000005090 green fluorescent protein Substances 0.000 description 4
238000003306 harvesting Methods 0.000 description 4
230000036541 health Effects 0.000 description 4
229960000908 idarubicin Drugs 0.000 description 4
AGPKZVBTJJNPAG-UHFFFAOYSA-N isoleucine Natural products CCC(C)C(N)C(O)=O AGPKZVBTJJNPAG-UHFFFAOYSA-N 0.000 description 4
210000003734 kidney Anatomy 0.000 description 4
150000002632 lipids Chemical class 0.000 description 4
239000002502 liposome Substances 0.000 description 4
210000004072 lung Anatomy 0.000 description 4
229960004857 mitomycin Drugs 0.000 description 4
230000009826 neoplastic cell growth Effects 0.000 description 4
229910052757 nitrogen Inorganic materials 0.000 description 4
229960001592 paclitaxel Drugs 0.000 description 4
239000013610 patient sample Substances 0.000 description 4
BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Chemical compound [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 description 4
239000000047 product Substances 0.000 description 4
238000012216 screening Methods 0.000 description 4
239000011734 sodium Substances 0.000 description 4
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 4
229940124597 therapeutic agent Drugs 0.000 description 4
238000012384 transportation and delivery Methods 0.000 description 4
229960004355 vindesine Drugs 0.000 description 4
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 4
AOJJSUZBOXZQNB-VTZDEGQISA-N 4'-epidoxorubicin 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-VTZDEGQISA-N 0.000 description 3
VVIAGPKUTFNRDU-UHFFFAOYSA-N 6S-folinic acid Natural products C1NC=2NC(N)=NC(=O)C=2N(C=O)C1CNC1=CC=C(C(=O)NC(CCC(O)=O)C(O)=O)C=C1 VVIAGPKUTFNRDU-UHFFFAOYSA-N 0.000 description 3
DCXYFEDJOCDNAF-UHFFFAOYSA-N Asparagine Natural products OC(=O)C(N)CC(N)=O DCXYFEDJOCDNAF-UHFFFAOYSA-N 0.000 description 3
201000001320 Atherosclerosis Diseases 0.000 description 3
COVZYZSDYWQREU-UHFFFAOYSA-N Busulfan Chemical compound CS(=O)(=O)OCCCCOS(C)(=O)=O COVZYZSDYWQREU-UHFFFAOYSA-N 0.000 description 3
108091035707 Consensus sequence Proteins 0.000 description 3
102000004127 Cytokines Human genes 0.000 description 3
108090000695 Cytokines Proteins 0.000 description 3
108010092160 Dactinomycin Proteins 0.000 description 3
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 3
HTIJFSOGRVMCQR-UHFFFAOYSA-N Epirubicin Natural products COc1cccc2C(=O)c3c(O)c4CC(O)(CC(OC5CC(N)C(=O)C(C)O5)c4c(O)c3C(=O)c12)C(=O)CO HTIJFSOGRVMCQR-UHFFFAOYSA-N 0.000 description 3
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 3
108700004714 Gelonium multiflorum GEL Proteins 0.000 description 3
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 3
239000004471 Glycine Substances 0.000 description 3
102000012745 Immunoglobulin Subunits Human genes 0.000 description 3
108010079585 Immunoglobulin Subunits Proteins 0.000 description 3
XUJNEKJLAYXESH-REOHCLBHSA-N L-Cysteine Chemical compound SC[C@H](N)C(O)=O XUJNEKJLAYXESH-REOHCLBHSA-N 0.000 description 3
QNAYBMKLOCPYGJ-REOHCLBHSA-N L-alanine Chemical compound C[C@H](N)C(O)=O QNAYBMKLOCPYGJ-REOHCLBHSA-N 0.000 description 3
ODKSFYDXXFIFQN-BYPYZUCNSA-P L-argininium(2+) Chemical compound NC(=[NH2+])NCCC[C@H]([NH3+])C(O)=O ODKSFYDXXFIFQN-BYPYZUCNSA-P 0.000 description 3
CKLJMWTZIZZHCS-REOHCLBHSA-N L-aspartic acid Chemical compound OC(=O)[C@@H](N)CC(O)=O CKLJMWTZIZZHCS-REOHCLBHSA-N 0.000 description 3
COLNVLDHVKWLRT-QMMMGPOBSA-N L-phenylalanine Chemical compound OC(=O)[C@@H](N)CC1=CC=CC=C1 COLNVLDHVKWLRT-QMMMGPOBSA-N 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
108010000817 Leuprolide Proteins 0.000 description 3
239000004472 Lysine Substances 0.000 description 3
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
PXHVJJICTQNCMI-UHFFFAOYSA-N Nickel Chemical compound [Ni] PXHVJJICTQNCMI-UHFFFAOYSA-N 0.000 description 3
241000283973 Oryctolagus cuniculus Species 0.000 description 3
238000012228 RNA interference-mediated gene silencing Methods 0.000 description 3
108020004511 Recombinant DNA Proteins 0.000 description 3
201000000582 Retinoblastoma Diseases 0.000 description 3
241000283984 Rodentia Species 0.000 description 3
108010084592 Saporins Proteins 0.000 description 3
108010003723 Single-Domain Antibodies Proteins 0.000 description 3
BPEGJWRSRHCHSN-UHFFFAOYSA-N Temozolomide Chemical compound O=C1N(C)N=NC2=C(C(N)=O)N=CN21 BPEGJWRSRHCHSN-UHFFFAOYSA-N 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
102000009484 Vascular Endothelial Growth Factor Receptors Human genes 0.000 description 3
JXLYSJRDGCGARV-WWYNWVTFSA-N Vinblastine Natural products O=C(O[C@H]1[C@](O)(C(=O)OC)[C@@H]2N(C)c3c(cc(c(OC)c3)[C@]3(C(=O)OC)c4[nH]c5c(c4CCN4C[C@](O)(CC)C[C@H](C3)C4)cccc5)[C@@]32[C@H]2[C@@]1(CC)C=CCN2CC3)C JXLYSJRDGCGARV-WWYNWVTFSA-N 0.000 description 3
229940122803 Vinca alkaloid Drugs 0.000 description 3
241000700605 Viruses Species 0.000 description 3
230000001594 aberrant effect Effects 0.000 description 3
150000007513 acids Chemical class 0.000 description 3
RJURFGZVJUQBHK-IIXSONLDSA-N actinomycin D Chemical compound C[C@H]1OC(=O)[C@H](C(C)C)N(C)C(=O)CN(C)C(=O)[C@@H]2CCCN2C(=O)[C@@H](C(C)C)NC(=O)[C@H]1NC(=O)C1=C(N)C(=O)C(C)=C2OC(C(C)=CC=C3C(=O)N[C@@H]4C(=O)N[C@@H](C(N5CCC[C@H]5C(=O)N(C)CC(=O)N(C)[C@@H](C(C)C)C(=O)O[C@@H]4C)=O)C(C)C)=C3N=C21 RJURFGZVJUQBHK-IIXSONLDSA-N 0.000 description 3
229940009456 adriamycin Drugs 0.000 description 3
206010064930 age-related macular degeneration Diseases 0.000 description 3
235000004279 alanine Nutrition 0.000 description 3
239000003242 anti bacterial agent Substances 0.000 description 3
229940088710 antibiotic agent Drugs 0.000 description 3
229940045719 antineoplastic alkylating agent nitrosoureas Drugs 0.000 description 3
229940041181 antineoplastic drug Drugs 0.000 description 3
ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 3
235000009697 arginine Nutrition 0.000 description 3
235000009582 asparagine Nutrition 0.000 description 3
229960001230 asparagine Drugs 0.000 description 3
VSRXQHXAPYXROS-UHFFFAOYSA-N azanide;cyclobutane-1,1-dicarboxylic acid;platinum(2+) Chemical compound [NH2-].[NH2-].[Pt+2].OC(=O)C1(C(O)=O)CCC1 VSRXQHXAPYXROS-UHFFFAOYSA-N 0.000 description 3
230000001588 bifunctional effect Effects 0.000 description 3
239000012472 biological sample Substances 0.000 description 3
210000001124 body fluid Anatomy 0.000 description 3
239000010839 body fluid Substances 0.000 description 3
230000037396 body weight Effects 0.000 description 3
238000006664 bond formation reaction Methods 0.000 description 3
239000000872 buffer Substances 0.000 description 3
229960002092 busulfan Drugs 0.000 description 3
229930195731 calicheamicin Natural products 0.000 description 3
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 3
229960004562 carboplatin Drugs 0.000 description 3
230000004663 cell proliferation Effects 0.000 description 3
DQLATGHUWYMOKM-UHFFFAOYSA-L cisplatin Chemical compound N[Pt](N)(Cl)Cl DQLATGHUWYMOKM-UHFFFAOYSA-L 0.000 description 3
229960004316 cisplatin Drugs 0.000 description 3
239000002299 complementary DNA Substances 0.000 description 3
230000021615 conjugation Effects 0.000 description 3
229920001577 copolymer Polymers 0.000 description 3
239000013078 crystal Substances 0.000 description 3
238000012258 culturing Methods 0.000 description 3
230000009089 cytolysis Effects 0.000 description 3
229960000640 dactinomycin Drugs 0.000 description 3
208000035475 disorder Diseases 0.000 description 3
238000004520 electroporation Methods 0.000 description 3
230000002255 enzymatic effect Effects 0.000 description 3
229960001904 epirubicin Drugs 0.000 description 3
AAKJLRGGTJKAMG-UHFFFAOYSA-N erlotinib Chemical compound C=12C=C(OCCOC)C(OCCOC)=CC2=NC=NC=1NC1=CC=CC(C#C)=C1 AAKJLRGGTJKAMG-UHFFFAOYSA-N 0.000 description 3
229960000390 fludarabine Drugs 0.000 description 3
GIUYCYHIANZCFB-FJFJXFQQSA-N fludarabine phosphate Chemical compound C1=NC=2C(N)=NC(F)=NC=2N1[C@@H]1O[C@H](COP(O)(O)=O)[C@@H](O)[C@@H]1O GIUYCYHIANZCFB-FJFJXFQQSA-N 0.000 description 3
VVIAGPKUTFNRDU-ABLWVSNPSA-N folinic acid Chemical compound C1NC=2NC(N)=NC(=O)C=2N(C=O)C1CNC1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 VVIAGPKUTFNRDU-ABLWVSNPSA-N 0.000 description 3
235000008191 folinic acid Nutrition 0.000 description 3
239000011672 folinic acid Substances 0.000 description 3
XGALLCVXEZPNRQ-UHFFFAOYSA-N gefitinib Chemical compound C=12C=C(OCCCN3CCOCC3)C(OC)=CC2=NC=NC=1NC1=CC=C(F)C(Cl)=C1 XGALLCVXEZPNRQ-UHFFFAOYSA-N 0.000 description 3
229960005277 gemcitabine Drugs 0.000 description 3
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 3
230000009368 gene silencing by RNA Effects 0.000 description 3
239000008103 glucose Substances 0.000 description 3
239000003102 growth factor Substances 0.000 description 3
239000000833 heterodimer Substances 0.000 description 3
230000001939 inductive effect Effects 0.000 description 3
238000003780 insertion Methods 0.000 description 3
230000037431 insertion Effects 0.000 description 3
238000007912 intraperitoneal administration Methods 0.000 description 3
229960001691 leucovorin Drugs 0.000 description 3
RGLRXNKKBLIBQS-XNHQSDQCSA-N leuprolide acetate Chemical compound CC(O)=O.CCNC(=O)[C@@H]1CCCN1C(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](CC(C)C)NC(=O)[C@@H](NC(=O)[C@H](CO)NC(=O)[C@H](CC=1C2=CC=CC=C2NC=1)NC(=O)[C@H](CC=1N=CNC=1)NC(=O)[C@H]1NC(=O)CC1)CC1=CC=C(O)C=C1 RGLRXNKKBLIBQS-XNHQSDQCSA-N 0.000 description 3
208000025036 lymphosarcoma Diseases 0.000 description 3
239000003550 marker Substances 0.000 description 3
239000011159 matrix material Substances 0.000 description 3
238000005259 measurement Methods 0.000 description 3
230000010534 mechanism of action Effects 0.000 description 3
239000002609 medium Substances 0.000 description 3
238000002156 mixing Methods 0.000 description 3
210000001616 monocyte Anatomy 0.000 description 3
238000000491 multivariate analysis Methods 0.000 description 3
210000001672 ovary Anatomy 0.000 description 3
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 3
229960001756 oxaliplatin Drugs 0.000 description 3
208000003154 papilloma Diseases 0.000 description 3
230000001575 pathological effect Effects 0.000 description 3
COLNVLDHVKWLRT-UHFFFAOYSA-N phenylalanine Natural products OC(=O)C(N)CC1=CC=CC=C1 COLNVLDHVKWLRT-UHFFFAOYSA-N 0.000 description 3
DCWXELXMIBXGTH-QMMMGPOBSA-N phosphonotyrosine Chemical compound OC(=O)[C@@H](N)CC1=CC=C(OP(O)(O)=O)C=C1 DCWXELXMIBXGTH-QMMMGPOBSA-N 0.000 description 3
210000002381 plasma Anatomy 0.000 description 3
229910052697 platinum Inorganic materials 0.000 description 3
239000013641 positive control Substances 0.000 description 3
125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 3
230000008569 process Effects 0.000 description 3
108091008598 receptor tyrosine kinases Proteins 0.000 description 3
102000027426 receptor tyrosine kinases Human genes 0.000 description 3
238000011084 recovery Methods 0.000 description 3
230000002829 reductive effect Effects 0.000 description 3
206010039073 rheumatoid arthritis Diseases 0.000 description 3
230000003248 secreting effect Effects 0.000 description 3
239000007787 solid Substances 0.000 description 3
230000009870 specific binding Effects 0.000 description 3
239000000725 suspension Substances 0.000 description 3
238000013268 sustained release Methods 0.000 description 3
239000012730 sustained-release form Substances 0.000 description 3
229940063683 taxotere Drugs 0.000 description 3
229960004964 temozolomide Drugs 0.000 description 3
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 3
229960001278 teniposide Drugs 0.000 description 3
230000009466 transformation Effects 0.000 description 3
229940121358 tyrosine kinase inhibitor Drugs 0.000 description 3
239000005483 tyrosine kinase inhibitor Substances 0.000 description 3
230000002792 vascular Effects 0.000 description 3
230000008728 vascular permeability Effects 0.000 description 3
229960003048 vinblastine Drugs 0.000 description 3
JXLYSJRDGCGARV-XQKSVPLYSA-N vincaleukoblastine Chemical compound C([C@@H](C[C@]1(C(=O)OC)C=2C(=CC3=C([C@]45[C@H]([C@@]([C@H](OC(C)=O)[C@]6(CC)C=CCN([C@H]56)CC4)(O)C(=O)OC)N3C)C=2)OC)C[C@@](C2)(O)CC)N2CCC2=C1NC1=CC=CC=C21 JXLYSJRDGCGARV-XQKSVPLYSA-N 0.000 description 3
GBABOYUKABKIAF-GHYRFKGUSA-N vinorelbine Chemical compound C1N(CC=2C3=CC=CC=C3NC=22)CC(CC)=C[C@H]1C[C@]2(C(=O)OC)C1=CC([C@]23[C@H]([C@]([C@H](OC(C)=O)[C@]4(CC)C=CCN([C@H]34)CC2)(O)C(=O)OC)N2C)=C2C=C1OC GBABOYUKABKIAF-GHYRFKGUSA-N 0.000 description 3
229960002066 vinorelbine Drugs 0.000 description 3
238000005406 washing Methods 0.000 description 3
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 3
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 2
XXJWYDDUDKYVKI-UHFFFAOYSA-N 4-[(4-fluoro-2-methyl-1H-indol-5-yl)oxy]-6-methoxy-7-[3-(1-pyrrolidinyl)propoxy]quinazoline Chemical compound COC1=CC2=C(OC=3C(=C4C=C(C)NC4=CC=3)F)N=CN=C2C=C1OCCCN1CCCC1 XXJWYDDUDKYVKI-UHFFFAOYSA-N 0.000 description 2
108010066676 Abrin Proteins 0.000 description 2
108010032595 Antibody Binding Sites Proteins 0.000 description 2
102100021569 Apoptosis regulator Bcl-2 Human genes 0.000 description 2
241000283690 Bos taurus Species 0.000 description 2
208000003174 Brain Neoplasms Diseases 0.000 description 2
KLWPJMFMVPTNCC-UHFFFAOYSA-N Camptothecin Natural products CCC1(O)C(=O)OCC2=C1C=C3C4Nc5ccccc5C=C4CN3C2=O KLWPJMFMVPTNCC-UHFFFAOYSA-N 0.000 description 2
241000282472 Canis lupus familiaris Species 0.000 description 2
102000014914 Carrier Proteins Human genes 0.000 description 2
241000282693 Cercopithecidae Species 0.000 description 2
206010008583 Chloroma Diseases 0.000 description 2
208000010833 Chronic myeloid leukaemia Diseases 0.000 description 2
108091026890 Coding region Proteins 0.000 description 2
241000699802 Cricetulus griseus Species 0.000 description 2
150000008574 D-amino acids Chemical class 0.000 description 2
WQZGKKKJIJFFOK-QTVWNMPRSA-N D-mannopyranose Chemical compound OC[C@H]1OC(O)[C@@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-QTVWNMPRSA-N 0.000 description 2
102000053602 DNA Human genes 0.000 description 2
241000283086 Equidae Species 0.000 description 2
229930189413 Esperamicin Natural products 0.000 description 2
241000282326 Felis catus Species 0.000 description 2
102100037362 Fibronectin Human genes 0.000 description 2
102000002090 Fibronectin type III Human genes 0.000 description 2
108050009401 Fibronectin type III Proteins 0.000 description 2
108010067306 Fibronectins Proteins 0.000 description 2
102000003886 Glycoproteins Human genes 0.000 description 2
108090000288 Glycoproteins Proteins 0.000 description 2
108010043121 Green Fluorescent Proteins Proteins 0.000 description 2
102000004144 Green Fluorescent Proteins Human genes 0.000 description 2
102000009465 Growth Factor Receptors Human genes 0.000 description 2
108010009202 Growth Factor Receptors Proteins 0.000 description 2
208000006050 Hemangiopericytoma Diseases 0.000 description 2
101000971171 Homo sapiens Apoptosis regulator Bcl-2 Proteins 0.000 description 2
101100372760 Homo sapiens FLT1 gene Proteins 0.000 description 2
PMMYEEVYMWASQN-DMTCNVIQSA-N Hydroxyproline Chemical compound O[C@H]1CN[C@H](C(O)=O)C1 PMMYEEVYMWASQN-DMTCNVIQSA-N 0.000 description 2
VSNHCAURESNICA-UHFFFAOYSA-N Hydroxyurea Chemical compound NC(=O)NO VSNHCAURESNICA-UHFFFAOYSA-N 0.000 description 2
102100026120 IgG receptor FcRn large subunit p51 Human genes 0.000 description 2
101710177940 IgG receptor FcRn large subunit p51 Proteins 0.000 description 2
108010067060 Immunoglobulin Variable Region Proteins 0.000 description 2
102000017727 Immunoglobulin Variable Region Human genes 0.000 description 2
FFEARJCKVFRZRR-BYPYZUCNSA-N L-methionine Chemical compound CSCC[C@H](N)C(O)=O FFEARJCKVFRZRR-BYPYZUCNSA-N 0.000 description 2
KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 2
241000282567 Macaca fascicularis Species 0.000 description 2
206010029260 Neuroblastoma Diseases 0.000 description 2
229910019142 PO4 Inorganic materials 0.000 description 2
NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
108091000080 Phosphotransferase Proteins 0.000 description 2
108030005449 Polo kinases Proteins 0.000 description 2
201000004681 Psoriasis Diseases 0.000 description 2
208000015634 Rectal Neoplasms Diseases 0.000 description 2
208000017442 Retinal disease Diseases 0.000 description 2
206010038923 Retinopathy Diseases 0.000 description 2
102000006382 Ribonucleases Human genes 0.000 description 2
108010083644 Ribonucleases Proteins 0.000 description 2
108091028664 Ribonucleotide Proteins 0.000 description 2
108010022999 Serine Proteases Proteins 0.000 description 2
102000012479 Serine Proteases Human genes 0.000 description 2
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
208000005718 Stomach Neoplasms Diseases 0.000 description 2
NKANXQFJJICGDU-QPLCGJKRSA-N Tamoxifen Chemical compound C=1C=CC=CC=1C(/CC)=C(C=1C=CC(OCCN(C)C)=CC=1)/C1=CC=CC=C1 NKANXQFJJICGDU-QPLCGJKRSA-N 0.000 description 2
IVTVGDXNLFLDRM-HNNXBMFYSA-N Tomudex Chemical compound C=1C=C2NC(C)=NC(=O)C2=CC=1CN(C)C1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)S1 IVTVGDXNLFLDRM-HNNXBMFYSA-N 0.000 description 2
108010073925 Vascular Endothelial Growth Factor B Proteins 0.000 description 2
108010073919 Vascular Endothelial Growth Factor D Proteins 0.000 description 2
102100038217 Vascular endothelial growth factor B Human genes 0.000 description 2
102100038234 Vascular endothelial growth factor D Human genes 0.000 description 2
238000013019 agitation Methods 0.000 description 2
125000001931 aliphatic group Chemical group 0.000 description 2
229940100198 alkylating agent Drugs 0.000 description 2
239000002168 alkylating agent Substances 0.000 description 2
150000001408 amides Chemical class 0.000 description 2
230000006229 amino acid addition Effects 0.000 description 2
XCPGHVQEEXUHNC-UHFFFAOYSA-N amsacrine Chemical compound COC1=CC(NS(C)(=O)=O)=CC=C1NC1=C(C=CC=C2)C2=NC2=CC=CC=C12 XCPGHVQEEXUHNC-UHFFFAOYSA-N 0.000 description 2
229960001220 amsacrine Drugs 0.000 description 2
230000001093 anti-cancer Effects 0.000 description 2
230000003432 anti-folate effect Effects 0.000 description 2
230000001028 anti-proliverative effect Effects 0.000 description 2
229940124691 antibody therapeutics Drugs 0.000 description 2
229940127074 antifolate Drugs 0.000 description 2
239000003080 antimitotic agent Substances 0.000 description 2
239000003963 antioxidant agent Substances 0.000 description 2
235000006708 antioxidants Nutrition 0.000 description 2
125000003118 aryl group Chemical group 0.000 description 2
235000010323 ascorbic acid Nutrition 0.000 description 2
229960005070 ascorbic acid Drugs 0.000 description 2
239000011668 ascorbic acid Substances 0.000 description 2
229940009098 aspartate Drugs 0.000 description 2
239000011324 bead Substances 0.000 description 2
108091008324 binding proteins Proteins 0.000 description 2
230000008827 biological function Effects 0.000 description 2
210000004556 brain Anatomy 0.000 description 2
210000000481 breast Anatomy 0.000 description 2
DQXBYHZEEUGOBF-UHFFFAOYSA-N but-3-enoic acid;ethene Chemical compound C=C.OC(=O)CC=C DQXBYHZEEUGOBF-UHFFFAOYSA-N 0.000 description 2
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 2
229940127093 camptothecin Drugs 0.000 description 2
OMZCMEYTWSXEPZ-UHFFFAOYSA-N canertinib Chemical compound C1=C(Cl)C(F)=CC=C1NC1=NC=NC2=CC(OCCCN3CCOCC3)=C(NC(=O)C=C)C=C12 OMZCMEYTWSXEPZ-UHFFFAOYSA-N 0.000 description 2
229930188550 carminomycin Natural products 0.000 description 2
XREUEWVEMYWFFA-CSKJXFQVSA-N carminomycin Chemical compound C1[C@H](N)[C@H](O)[C@H](C)O[C@H]1O[C@@H]1C2=C(O)C(C(=O)C3=C(O)C=CC=C3C3=O)=C3C(O)=C2C[C@@](O)(C(C)=O)C1 XREUEWVEMYWFFA-CSKJXFQVSA-N 0.000 description 2
XREUEWVEMYWFFA-UHFFFAOYSA-N carminomycin I Natural products C1C(N)C(O)C(C)OC1OC1C2=C(O)C(C(=O)C3=C(O)C=CC=C3C3=O)=C3C(O)=C2CC(O)(C(C)=O)C1 XREUEWVEMYWFFA-UHFFFAOYSA-N 0.000 description 2
239000000969 carrier Substances 0.000 description 2
229950001725 carubicin Drugs 0.000 description 2
230000007910 cell fusion Effects 0.000 description 2
230000022534 cell killing Effects 0.000 description 2
238000012512 characterization method Methods 0.000 description 2
210000000349 chromosome Anatomy 0.000 description 2
238000003776 cleavage reaction Methods 0.000 description 2
229940046044 combinations of antineoplastic agent Drugs 0.000 description 2
238000010276 construction Methods 0.000 description 2
238000007796 conventional method Methods 0.000 description 2
XUJNEKJLAYXESH-UHFFFAOYSA-N cysteine Natural products SCC(N)C(O)=O XUJNEKJLAYXESH-UHFFFAOYSA-N 0.000 description 2
229960000684 cytarabine Drugs 0.000 description 2
239000002254 cytotoxic agent Substances 0.000 description 2
231100000599 cytotoxic agent Toxicity 0.000 description 2
230000002950 deficient Effects 0.000 description 2
CFCUWKMKBJTWLW-UHFFFAOYSA-N deoliosyl-3C-alpha-L-digitoxosyl-MTM Natural products CC=1C(O)=C2C(O)=C3C(=O)C(OC4OC(C)C(O)C(OC5OC(C)C(O)C(OC6OC(C)C(O)C(C)(O)C6)C5)C4)C(C(OC)C(=O)C(O)C(C)O)CC3=CC2=CC=1OC(OC(C)C1O)CC1OC1CC(O)C(O)C(C)O1 CFCUWKMKBJTWLW-UHFFFAOYSA-N 0.000 description 2
238000013461 design Methods 0.000 description 2
230000029087 digestion Effects 0.000 description 2
238000010494 dissociation reaction Methods 0.000 description 2
230000005593 dissociations Effects 0.000 description 2
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 2
PMMYEEVYMWASQN-UHFFFAOYSA-N dl-hydroxyproline Natural products OC1C[NH2+]C(C([O-])=O)C1 PMMYEEVYMWASQN-UHFFFAOYSA-N 0.000 description 2
239000003534 dna topoisomerase inhibitor Substances 0.000 description 2
239000000975 dye Substances 0.000 description 2
239000000839 emulsion Substances 0.000 description 2
229960001433 erlotinib Drugs 0.000 description 2
210000003743 erythrocyte Anatomy 0.000 description 2
239000005038 ethylene vinyl acetate Substances 0.000 description 2
238000011156 evaluation Methods 0.000 description 2
150000005699 fluoropyrimidines Chemical class 0.000 description 2
239000004052 folic acid antagonist Substances 0.000 description 2
238000004108 freeze drying Methods 0.000 description 2
206010017758 gastric cancer Diseases 0.000 description 2
229960002584 gefitinib Drugs 0.000 description 2
238000001415 gene therapy Methods 0.000 description 2
230000002068 genetic effect Effects 0.000 description 2
229930195712 glutamate Natural products 0.000 description 2
229940049906 glutamate Drugs 0.000 description 2
229960002989 glutamic acid Drugs 0.000 description 2
210000003128 head Anatomy 0.000 description 2
206010073071 hepatocellular carcinoma Diseases 0.000 description 2
231100000844 hepatocellular carcinoma Toxicity 0.000 description 2
HNDVDQJCIGZPNO-UHFFFAOYSA-N histidine Natural products OC(=O)C(N)CC1=CN=CN1 HNDVDQJCIGZPNO-UHFFFAOYSA-N 0.000 description 2
239000000710 homodimer Substances 0.000 description 2
JYGXADMDTFJGBT-VWUMJDOOSA-N hydrocortisone Chemical compound O=C1CC[C@]2(C)[C@H]3[C@@H](O)C[C@](C)([C@@](CC4)(O)C(=O)CO)[C@@H]4[C@@H]3CCC2=C1 JYGXADMDTFJGBT-VWUMJDOOSA-N 0.000 description 2
239000000017 hydrogel Substances 0.000 description 2
229960001330 hydroxycarbamide Drugs 0.000 description 2
229960002591 hydroxyproline Drugs 0.000 description 2
FDGQSTZJBFJUBT-UHFFFAOYSA-N hypoxanthine Chemical compound O=C1NC=NC2=C1NC=N2 FDGQSTZJBFJUBT-UHFFFAOYSA-N 0.000 description 2
230000002163 immunogen Effects 0.000 description 2
230000005847 immunogenicity Effects 0.000 description 2
208000015181 infectious disease Diseases 0.000 description 2
238000001802 infusion Methods 0.000 description 2
230000003993 interaction Effects 0.000 description 2
238000001990 intravenous administration Methods 0.000 description 2
230000000302 ischemic effect Effects 0.000 description 2
229940043355 kinase inhibitor Drugs 0.000 description 2
JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 2
229910052747 lanthanoid Inorganic materials 0.000 description 2
150000002602 lanthanoids Chemical class 0.000 description 2
229960004338 leuprorelin Drugs 0.000 description 2
230000000670 limiting effect Effects 0.000 description 2
201000003866 lung sarcoma Diseases 0.000 description 2
208000037841 lung tumor Diseases 0.000 description 2
210000001165 lymph node Anatomy 0.000 description 2
230000001926 lymphatic effect Effects 0.000 description 2
235000018977 lysine Nutrition 0.000 description 2
208000002780 macular degeneration Diseases 0.000 description 2
210000004962 mammalian cell Anatomy 0.000 description 2
201000006512 mast cell neoplasm Diseases 0.000 description 2
208000006971 mastocytoma Diseases 0.000 description 2
229960004961 mechlorethamine Drugs 0.000 description 2
HAWPXGHAZFHHAD-UHFFFAOYSA-N mechlorethamine Chemical class ClCCN(C)CCCl HAWPXGHAZFHHAD-UHFFFAOYSA-N 0.000 description 2
239000012528 membrane Substances 0.000 description 2
229930182817 methionine Natural products 0.000 description 2
CFCUWKMKBJTWLW-BKHRDMLASA-N mithramycin Chemical compound O([C@@H]1C[C@@H](O[C@H](C)[C@H]1O)OC=1C=C2C=C3C[C@H]([C@@H](C(=O)C3=C(O)C2=C(O)C=1C)O[C@@H]1O[C@H](C)[C@@H](O)[C@H](O[C@@H]2O[C@H](C)[C@H](O)[C@H](O[C@@H]3O[C@H](C)[C@@H](O)[C@@](C)(O)C3)C2)C1)[C@H](OC)C(=O)[C@@H](O)[C@@H](C)O)[C@H]1C[C@@H](O)[C@H](O)[C@@H](C)O1 CFCUWKMKBJTWLW-BKHRDMLASA-N 0.000 description 2
KKZJGLLVHKMTCM-UHFFFAOYSA-N mitoxantrone Chemical compound O=C1C2=C(O)C=CC(O)=C2C(=O)C2=C1C(NCCNCCO)=CC=C2NCCNCCO KKZJGLLVHKMTCM-UHFFFAOYSA-N 0.000 description 2
229960001156 mitoxantrone Drugs 0.000 description 2
210000005087 mononuclear cell Anatomy 0.000 description 2
201000005987 myeloid sarcoma Diseases 0.000 description 2
230000010807 negative regulation of binding Effects 0.000 description 2
201000008026 nephroblastoma Diseases 0.000 description 2
238000007857 nested PCR Methods 0.000 description 2
229960005419 nitrogen Drugs 0.000 description 2
229960000435 oblimersen Drugs 0.000 description 2
MIMNFCVQODTQDP-NDLVEFNKSA-N oblimersen Chemical compound O=C1NC(=O)C(C)=CN1[C@@H]1O[C@H](COP(S)(=O)O[C@@H]2[C@H](O[C@H](C2)N2C3=NC=NC(N)=C3N=C2)COP(O)(=S)O[C@@H]2[C@H](O[C@H](C2)N2C(N=C(N)C=C2)=O)COP(O)(=S)O[C@@H]2[C@H](O[C@H](C2)N2C(N=C(N)C=C2)=O)COP(O)(=S)O[C@@H]2[C@H](O[C@H](C2)N2C3=C(C(NC(N)=N3)=O)N=C2)COP(O)(=S)O[C@@H]2[C@H](O[C@H](C2)N2C(N=C(N)C=C2)=O)COP(O)(=S)O[C@@H]2[C@H](O[C@H](C2)N2C3=C(C(NC(N)=N3)=O)N=C2)COP(O)(=S)O[C@@H]2[C@H](O[C@H](C2)N2C(NC(=O)C(C)=C2)=O)COP(O)(=S)O[C@@H]2[C@H](O[C@H](C2)N2C3=C(C(NC(N)=N3)=O)N=C2)COP(O)(=S)O[C@@H]2[C@H](O[C@H](C2)N2C(N=C(N)C=C2)=O)COP(O)(=S)O[C@@H]2[C@H](O[C@H](C2)N2C3=C(C(NC(N)=N3)=O)N=C2)COP(O)(=S)O[C@@H]2[C@H](O[C@H](C2)N2C3=NC=NC(N)=C3N=C2)COP(O)(=S)O[C@@H]2[C@H](O[C@H](C2)N2C(N=C(N)C=C2)=O)COP(O)(=S)O[C@@H]2[C@H](O[C@H](C2)N2C(N=C(N)C=C2)=O)COP(O)(=S)O[C@@H]2[C@H](O[C@H](C2)N2C(N=C(N)C=C2)=O)COP(O)(=S)O[C@@H]2[C@H](O[C@H](C2)N2C(NC(=O)C(C)=C2)=O)COP(O)(=S)O[C@@H]2[C@H](O[C@H](C2)N2C(N=C(N)C=C2)=O)COP(O)(=S)O[C@@H]2[C@H](O[C@H](C2)N2C(NC(=O)C(C)=C2)=O)CO)[C@@H](O)C1 MIMNFCVQODTQDP-NDLVEFNKSA-N 0.000 description 2
239000003921 oil Substances 0.000 description 2
201000008968 osteosarcoma Diseases 0.000 description 2
230000002018 overexpression Effects 0.000 description 2
239000002245 particle Substances 0.000 description 2
239000000816 peptidomimetic Substances 0.000 description 2
210000003819 peripheral blood mononuclear cell Anatomy 0.000 description 2
239000008177 pharmaceutical agent Substances 0.000 description 2
230000000144 pharmacologic effect Effects 0.000 description 2
235000021317 phosphate Nutrition 0.000 description 2
102000020233 phosphotransferase Human genes 0.000 description 2
239000003757 phosphotransferase inhibitor Substances 0.000 description 2
ZWLUXSQADUDCSB-UHFFFAOYSA-N phthalaldehyde Chemical compound O=CC1=CC=CC=C1C=O ZWLUXSQADUDCSB-UHFFFAOYSA-N 0.000 description 2
230000001766 physiological effect Effects 0.000 description 2
229960003171 plicamycin Drugs 0.000 description 2
108700028325 pokeweed antiviral Proteins 0.000 description 2
229920001200 poly(ethylene-vinyl acetate) Polymers 0.000 description 2
239000000843 powder Substances 0.000 description 2
230000002035 prolonged effect Effects 0.000 description 2
210000002307 prostate Anatomy 0.000 description 2
230000017854 proteolysis Effects 0.000 description 2
230000005180 public health Effects 0.000 description 2
229960004432 raltitrexed Drugs 0.000 description 2
206010038038 rectal cancer Diseases 0.000 description 2
201000001275 rectum cancer Diseases 0.000 description 2
230000004044 response Effects 0.000 description 2
201000009410 rhabdomyosarcoma Diseases 0.000 description 2
239000002336 ribonucleotide Substances 0.000 description 2
125000002652 ribonucleotide group Chemical group 0.000 description 2
OUKYUETWWIPKQR-UHFFFAOYSA-N saracatinib Chemical compound C1CN(C)CCN1CCOC1=CC(OC2CCOCC2)=C(C(NC=2C(=CC=C3OCOC3=2)Cl)=NC=N2)C2=C1 OUKYUETWWIPKQR-UHFFFAOYSA-N 0.000 description 2
230000007017 scission Effects 0.000 description 2
238000013207 serial dilution Methods 0.000 description 2
239000004017 serum-free culture medium Substances 0.000 description 2
238000002741 site-directed mutagenesis Methods 0.000 description 2
150000003384 small molecules Chemical class 0.000 description 2
DAEPDZWVDSPTHF-UHFFFAOYSA-M sodium pyruvate Chemical compound [Na+].CC(=O)C([O-])=O DAEPDZWVDSPTHF-UHFFFAOYSA-M 0.000 description 2
238000010561 standard procedure Methods 0.000 description 2
230000000638 stimulation Effects 0.000 description 2
201000011549 stomach cancer Diseases 0.000 description 2
UCSJYZPVAKXKNQ-HZYVHMACSA-N streptomycin Chemical compound CN[C@H]1[C@H](O)[C@@H](O)[C@H](CO)O[C@H]1O[C@@H]1[C@](C=O)(O)[C@H](C)O[C@H]1O[C@@H]1[C@@H](NC(N)=N)[C@H](O)[C@@H](NC(N)=N)[C@H](O)[C@H]1O UCSJYZPVAKXKNQ-HZYVHMACSA-N 0.000 description 2
235000000346 sugar Nutrition 0.000 description 2
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 2
239000013595 supernatant sample Substances 0.000 description 2
238000003786 synthesis reaction Methods 0.000 description 2
229960001674 tegafur Drugs 0.000 description 2
WFWLQNSHRPWKFK-ZCFIWIBFSA-N tegafur Chemical compound O=C1NC(=O)C(F)=CN1[C@@H]1OCCC1 WFWLQNSHRPWKFK-ZCFIWIBFSA-N 0.000 description 2
125000003396 thiol group Chemical group [H]S* 0.000 description 2
229940044693 topoisomerase inhibitor Drugs 0.000 description 2
229960000303 topotecan Drugs 0.000 description 2
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 2
238000013518 transcription Methods 0.000 description 2
230000035897 transcription Effects 0.000 description 2
229950000578 vatalanib Drugs 0.000 description 2
YCOYDOIWSSHVCK-UHFFFAOYSA-N vatalanib Chemical compound C1=CC(Cl)=CC=C1NC(C1=CC=CC=C11)=NN=C1CC1=CC=NC=C1 YCOYDOIWSSHVCK-UHFFFAOYSA-N 0.000 description 2
239000003981 vehicle Substances 0.000 description 2
238000013389 whole blood assay Methods 0.000 description 2
DGVVWUTYPXICAM-UHFFFAOYSA-N β‐Mercaptoethanol Chemical compound OCCS DGVVWUTYPXICAM-UHFFFAOYSA-N 0.000 description 2
BEJKOYIMCGMNRB-GRHHLOCNSA-N (2s)-2-amino-3-(4-hydroxyphenyl)propanoic acid;(2s)-2-amino-3-phenylpropanoic acid Chemical compound OC(=O)[C@@H](N)CC1=CC=CC=C1.OC(=O)[C@@H](N)CC1=CC=C(O)C=C1 BEJKOYIMCGMNRB-GRHHLOCNSA-N 0.000 description 1
XMQUEQJCYRFIQS-YFKPBYRVSA-N (2s)-2-amino-5-ethoxy-5-oxopentanoic acid Chemical compound CCOC(=O)CC[C@H](N)C(O)=O XMQUEQJCYRFIQS-YFKPBYRVSA-N 0.000 description 1
MWWSFMDVAYGXBV-MYPASOLCSA-N (7r,9s)-7-[(2r,4s,5s,6s)-4-amino-5-hydroxy-6-methyloxan-2-yl]oxy-6,9,11-trihydroxy-9-(2-hydroxyacetyl)-4-methoxy-8,10-dihydro-7h-tetracene-5,12-dione;hydrochloride Chemical compound Cl.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 MWWSFMDVAYGXBV-MYPASOLCSA-N 0.000 description 1
INAUWOVKEZHHDM-PEDBPRJASA-N (7s,9s)-6,9,11-trihydroxy-9-(2-hydroxyacetyl)-7-[(2r,4s,5s,6s)-5-hydroxy-6-methyl-4-morpholin-4-yloxan-2-yl]oxy-4-methoxy-8,10-dihydro-7h-tetracene-5,12-dione;hydrochloride Chemical compound Cl.N1([C@H]2C[C@@H](O[C@@H](C)[C@H]2O)O[C@H]2C[C@@](O)(CC=3C(O)=C4C(=O)C=5C=CC=C(C=5C(=O)C4=C(O)C=32)OC)C(=O)CO)CCOCC1 INAUWOVKEZHHDM-PEDBPRJASA-N 0.000 description 1
OYIWRKOSDGPKFD-XGGCRALDSA-N (7s,9s)-9-acetyl-6,9,11-trihydroxy-7-[(2r,4s,5s,6s)-5-hydroxy-6-methyl-4-morpholin-4-yloxan-2-yl]oxy-4-methoxy-8,10-dihydro-7h-tetracene-5,12-dione Chemical compound N1([C@H]2C[C@@H](O[C@@H](C)[C@H]2O)O[C@H]2C[C@@](O)(CC=3C(O)=C4C(=O)C=5C=CC=C(C=5C(=O)C4=C(O)C=32)OC)C(C)=O)CCOCC1 OYIWRKOSDGPKFD-XGGCRALDSA-N 0.000 description 1
LKJPYSCBVHEWIU-KRWDZBQOSA-N (R)-bicalutamide Chemical compound C([C@@](O)(C)C(=O)NC=1C=C(C(C#N)=CC=1)C(F)(F)F)S(=O)(=O)C1=CC=C(F)C=C1 LKJPYSCBVHEWIU-KRWDZBQOSA-N 0.000 description 1
WHTVZRBIWZFKQO-AWEZNQCLSA-N (S)-chloroquine Chemical compound ClC1=CC=C2C(N[C@@H](C)CCCN(CC)CC)=CC=NC2=C1 WHTVZRBIWZFKQO-AWEZNQCLSA-N 0.000 description 1
VSNHCAURESNICA-NJFSPNSNSA-N 1-oxidanylurea Chemical compound N[14C](=O)NO VSNHCAURESNICA-NJFSPNSNSA-N 0.000 description 1
UEJJHQNACJXSKW-UHFFFAOYSA-N 2-(2,6-dioxopiperidin-3-yl)-1H-isoindole-1,3(2H)-dione Chemical compound O=C1C2=CC=CC=C2C(=O)N1C1CCC(=O)NC1=O UEJJHQNACJXSKW-UHFFFAOYSA-N 0.000 description 1
GOJUJUVQIVIZAV-UHFFFAOYSA-N 2-amino-4,6-dichloropyrimidine-5-carbaldehyde Chemical group NC1=NC(Cl)=C(C=O)C(Cl)=N1 GOJUJUVQIVIZAV-UHFFFAOYSA-N 0.000 description 1
XBBVURRQGJPTHH-UHFFFAOYSA-N 2-hydroxyacetic acid;2-hydroxypropanoic acid Chemical compound OCC(O)=O.CC(O)C(O)=O XBBVURRQGJPTHH-UHFFFAOYSA-N 0.000 description 1
BRMWTNUJHUMWMS-UHFFFAOYSA-N 3-Methylhistidine Natural products CN1C=NC(CC(N)C(O)=O)=C1 BRMWTNUJHUMWMS-UHFFFAOYSA-N 0.000 description 1
HHFBDROWDBDFBR-UHFFFAOYSA-N 4-[[9-chloro-7-(2,6-difluorophenyl)-5H-pyrimido[5,4-d][2]benzazepin-2-yl]amino]benzoic acid Chemical compound C1=CC(C(=O)O)=CC=C1NC1=NC=C(CN=C(C=2C3=CC=C(Cl)C=2)C=2C(=CC=CC=2F)F)C3=N1 HHFBDROWDBDFBR-UHFFFAOYSA-N 0.000 description 1
TVZGACDUOSZQKY-LBPRGKRZSA-N 4-aminofolic acid Chemical compound C1=NC2=NC(N)=NC(N)=C2N=C1CNC1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 TVZGACDUOSZQKY-LBPRGKRZSA-N 0.000 description 1
HUDPLKWXRLNSPC-UHFFFAOYSA-N 4-aminophthalhydrazide Chemical compound O=C1NNC(=O)C=2C1=CC(N)=CC=2 HUDPLKWXRLNSPC-UHFFFAOYSA-N 0.000 description 1
SGOOQMRIPALTEL-UHFFFAOYSA-N 4-hydroxy-N,1-dimethyl-2-oxo-N-phenyl-3-quinolinecarboxamide Chemical compound OC=1C2=CC=CC=C2N(C)C(=O)C=1C(=O)N(C)C1=CC=CC=C1 SGOOQMRIPALTEL-UHFFFAOYSA-N 0.000 description 1
WOVKYSAHUYNSMH-RRKCRQDMSA-N 5-bromodeoxyuridine Chemical group C1[C@H](O)[C@@H](CO)O[C@H]1N1C(=O)NC(=O)C(Br)=C1 WOVKYSAHUYNSMH-RRKCRQDMSA-N 0.000 description 1
229940117976 5-hydroxylysine Drugs 0.000 description 1
102100031126 6-phosphogluconolactonase Human genes 0.000 description 1
108010029731 6-phosphogluconolactonase Proteins 0.000 description 1
CJIJXIFQYOPWTF-UHFFFAOYSA-N 7-hydroxycoumarin Natural products O1C(=O)C=CC2=CC(O)=CC=C21 CJIJXIFQYOPWTF-UHFFFAOYSA-N 0.000 description 1
HPLNQCPCUACXLM-PGUFJCEWSA-N ABT-737 Chemical compound C([C@@H](CCN(C)C)NC=1C(=CC(=CC=1)S(=O)(=O)NC(=O)C=1C=CC(=CC=1)N1CCN(CC=2C(=CC=CC=2)C=2C=CC(Cl)=CC=2)CC1)[N+]([O-])=O)SC1=CC=CC=C1 HPLNQCPCUACXLM-PGUFJCEWSA-N 0.000 description 1
GBJVVSCPOBPEIT-UHFFFAOYSA-N AZT-1152 Chemical compound N=1C=NC2=CC(OCCCN(CC)CCOP(O)(O)=O)=CC=C2C=1NC(=NN1)C=C1CC(=O)NC1=CC=CC(F)=C1 GBJVVSCPOBPEIT-UHFFFAOYSA-N 0.000 description 1
QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
108010022752 Acetylcholinesterase Proteins 0.000 description 1
102000012440 Acetylcholinesterase Human genes 0.000 description 1
241000251468 Actinopterygii Species 0.000 description 1
108010088751 Albumins Proteins 0.000 description 1
102000009027 Albumins Human genes 0.000 description 1
101710092462 Alpha-hemolysin Proteins 0.000 description 1
101710197219 Alpha-toxin Proteins 0.000 description 1
239000004382 Amylase Substances 0.000 description 1
102000013142 Amylases Human genes 0.000 description 1
108010065511 Amylases Proteins 0.000 description 1
201000003076 Angiosarcoma Diseases 0.000 description 1
102000012936 Angiostatins Human genes 0.000 description 1
108010079709 Angiostatins Proteins 0.000 description 1
108020000948 Antisense Oligonucleotides Proteins 0.000 description 1
244000105624 Arachis hypogaea Species 0.000 description 1
BFYIZQONLCFLEV-DAELLWKTSA-N Aromasine Chemical compound O=C1C=C[C@]2(C)[C@H]3CC[C@](C)(C(CC4)=O)[C@@H]4[C@@H]3CC(=C)C2=C1 BFYIZQONLCFLEV-DAELLWKTSA-N 0.000 description 1
241000271566 Aves Species 0.000 description 1
NOWKCMXCCJGMRR-UHFFFAOYSA-N Aziridine Chemical class C1CN1 NOWKCMXCCJGMRR-UHFFFAOYSA-N 0.000 description 1
208000003950 B-cell lymphoma Diseases 0.000 description 1
102100038080 B-cell receptor CD22 Human genes 0.000 description 1
108700020462 BRCA2 Proteins 0.000 description 1
WOVKYSAHUYNSMH-UHFFFAOYSA-N BROMODEOXYURIDINE Natural products C1C(O)C(CO)OC1N1C(=O)NC(=O)C(Br)=C1 WOVKYSAHUYNSMH-UHFFFAOYSA-N 0.000 description 1
206010004146 Basal cell carcinoma Diseases 0.000 description 1
102100024775 Beta-1,4-mannosyl-glycoprotein 4-beta-N-acetylglucosaminyltransferase Human genes 0.000 description 1
206010005949 Bone cancer Diseases 0.000 description 1
208000018084 Bone neoplasm Diseases 0.000 description 1
101001011741 Bos taurus Insulin Proteins 0.000 description 1
101150008921 Brca2 gene Proteins 0.000 description 1
102100025399 Breast cancer type 2 susceptibility protein Human genes 0.000 description 1
206010058354 Bronchioloalveolar carcinoma Diseases 0.000 description 1
208000011691 Burkitt lymphomas Diseases 0.000 description 1
108010037003 Buserelin Proteins 0.000 description 1
102100024217 CAMPATH-1 antigen Human genes 0.000 description 1
108010065524 CD52 Antigen Proteins 0.000 description 1
108010021064 CTLA-4 Antigen Proteins 0.000 description 1
229940045513 CTLA4 antagonist Drugs 0.000 description 1
OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 1
102000003846 Carbonic anhydrases Human genes 0.000 description 1
108090000209 Carbonic anhydrases Proteins 0.000 description 1
208000009458 Carcinoma in Situ Diseases 0.000 description 1
102000005600 Cathepsins Human genes 0.000 description 1
108010084457 Cathepsins Proteins 0.000 description 1
206010007953 Central nervous system lymphoma Diseases 0.000 description 1
206010008342 Cervix carcinoma Diseases 0.000 description 1
208000006332 Choriocarcinoma Diseases 0.000 description 1
KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 description 1
PTOAARAWEBMLNO-KVQBGUIXSA-N Cladribine Chemical compound C1=NC=2C(N)=NC(Cl)=NC=2N1[C@H]1C[C@H](O)[C@@H](CO)O1 PTOAARAWEBMLNO-KVQBGUIXSA-N 0.000 description 1
HVXBOLULGPECHP-WAYWQWQTSA-N Combretastatin A4 Chemical compound C1=C(O)C(OC)=CC=C1\C=C/C1=CC(OC)=C(OC)C(OC)=C1 HVXBOLULGPECHP-WAYWQWQTSA-N 0.000 description 1
241000557626 Corvus corax Species 0.000 description 1
241000186225 Corynebacterium pseudotuberculosis Species 0.000 description 1
241000699800 Cricetinae Species 0.000 description 1
108010024986 Cyclin-Dependent Kinase 2 Proteins 0.000 description 1
108010025464 Cyclin-Dependent Kinase 4 Proteins 0.000 description 1
102100036239 Cyclin-dependent kinase 2 Human genes 0.000 description 1
102100036252 Cyclin-dependent kinase 4 Human genes 0.000 description 1
108060002063 Cyclotide Proteins 0.000 description 1
201000005171 Cystadenoma Diseases 0.000 description 1
102000018832 Cytochromes Human genes 0.000 description 1
108010052832 Cytochromes Proteins 0.000 description 1
102000000311 Cytosine Deaminase Human genes 0.000 description 1
108010080611 Cytosine Deaminase Proteins 0.000 description 1
102100039498 Cytotoxic T-lymphocyte protein 4 Human genes 0.000 description 1
102100037579 D-3-phosphoglycerate dehydrogenase Human genes 0.000 description 1
FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 1
FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 1
FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 description 1
KDXKERNSBIXSRK-RXMQYKEDSA-N D-lysine Chemical compound NCCCC[C@@H](N)C(O)=O KDXKERNSBIXSRK-RXMQYKEDSA-N 0.000 description 1
230000004544 DNA amplification Effects 0.000 description 1
ZBNZXTGUTAYRHI-UHFFFAOYSA-N Dasatinib Chemical compound C=1C(N2CCN(CCO)CC2)=NC(C)=NC=1NC(S1)=NC=C1C(=O)NC1=C(C)C=CC=C1Cl ZBNZXTGUTAYRHI-UHFFFAOYSA-N 0.000 description 1
102000007260 Deoxyribonuclease I Human genes 0.000 description 1
108010008532 Deoxyribonuclease I Proteins 0.000 description 1
108700022150 Designed Ankyrin Repeat Proteins Proteins 0.000 description 1
229920002307 Dextran Polymers 0.000 description 1
239000004375 Dextrin Substances 0.000 description 1
229920001353 Dextrin Polymers 0.000 description 1
208000002699 Digestive System Neoplasms Diseases 0.000 description 1
BVTJGGGYKAMDBN-UHFFFAOYSA-N Dioxetane Chemical class C1COO1 BVTJGGGYKAMDBN-UHFFFAOYSA-N 0.000 description 1
108010053187 Diphtheria Toxin Proteins 0.000 description 1
102000016607 Diphtheria Toxin Human genes 0.000 description 1
206010061818 Disease progression Diseases 0.000 description 1
ZQZFYGIXNQKOAV-OCEACIFDSA-N Droloxifene Chemical compound C=1C=CC=CC=1C(/CC)=C(C=1C=C(O)C=CC=1)\C1=CC=C(OCCN(C)C)C=C1 ZQZFYGIXNQKOAV-OCEACIFDSA-N 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
LVGKNOAMLMIIKO-UHFFFAOYSA-N Elaidinsaeure-aethylester Natural products CCCCCCCCC=CCCCCCCCC(=O)OCC LVGKNOAMLMIIKO-UHFFFAOYSA-N 0.000 description 1
102400001047 Endostatin Human genes 0.000 description 1
108010079505 Endostatins Proteins 0.000 description 1
241000588724 Escherichia coli Species 0.000 description 1
208000000461 Esophageal Neoplasms Diseases 0.000 description 1
229910052693 Europium Inorganic materials 0.000 description 1
208000006168 Ewing Sarcoma Diseases 0.000 description 1
101150009958 FLT4 gene Proteins 0.000 description 1
108091006020 Fc-tagged proteins Proteins 0.000 description 1
102000009123 Fibrin Human genes 0.000 description 1
108010073385 Fibrin Proteins 0.000 description 1
BWGVNKXGVNDBDI-UHFFFAOYSA-N Fibrin monomer Chemical compound CNC(=O)CNC(=O)CN BWGVNKXGVNDBDI-UHFFFAOYSA-N 0.000 description 1
108090000386 Fibroblast Growth Factor 1 Proteins 0.000 description 1
102100031706 Fibroblast growth factor 1 Human genes 0.000 description 1
206010053717 Fibrous histiocytoma Diseases 0.000 description 1
VWUXBMIQPBEWFH-WCCTWKNTSA-N Fulvestrant Chemical compound OC1=CC=C2[C@H]3CC[C@](C)([C@H](CC4)O)[C@@H]4[C@@H]3[C@H](CCCCCCCCCS(=O)CCCC(F)(F)C(F)(F)F)CC2=C1 VWUXBMIQPBEWFH-WCCTWKNTSA-N 0.000 description 1
208000022072 Gallbladder Neoplasms Diseases 0.000 description 1
108010010803 Gelatin Proteins 0.000 description 1
208000002966 Giant Cell Tumor of Bone Diseases 0.000 description 1
108010018962 Glucosephosphate Dehydrogenase Proteins 0.000 description 1
WHUUTDBJXJRKMK-UHFFFAOYSA-N Glutamic acid Natural products OC(=O)C(N)CCC(O)=O WHUUTDBJXJRKMK-UHFFFAOYSA-N 0.000 description 1
AEMRFAOFKBGASW-UHFFFAOYSA-N Glycolic acid Natural products OCC(O)=O AEMRFAOFKBGASW-UHFFFAOYSA-N 0.000 description 1
108010031186 Glycoside Hydrolases Proteins 0.000 description 1
102000005744 Glycoside Hydrolases Human genes 0.000 description 1
108010069236 Goserelin Proteins 0.000 description 1
BLCLNMBMMGCOAS-URPVMXJPSA-N Goserelin Chemical compound C([C@@H](C(=O)N[C@H](COC(C)(C)C)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCN=C(N)N)C(=O)N1[C@@H](CCC1)C(=O)NNC(N)=O)NC(=O)[C@H](CO)NC(=O)[C@H](CC=1C2=CC=CC=C2NC=1)NC(=O)[C@H](CC=1NC=NC=1)NC(=O)[C@H]1NC(=O)CC1)C1=CC=C(O)C=C1 BLCLNMBMMGCOAS-URPVMXJPSA-N 0.000 description 1
108010017213 Granulocyte-Macrophage Colony-Stimulating Factor Proteins 0.000 description 1
102100039620 Granulocyte-macrophage colony-stimulating factor Human genes 0.000 description 1
208000012766 Growth delay Diseases 0.000 description 1
208000002125 Hemangioendothelioma Diseases 0.000 description 1
208000001258 Hemangiosarcoma Diseases 0.000 description 1
102100024025 Heparanase Human genes 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
108090000100 Hepatocyte Growth Factor Proteins 0.000 description 1
102100021866 Hepatocyte growth factor Human genes 0.000 description 1
108090001101 Hepsin Proteins 0.000 description 1
102000004989 Hepsin Human genes 0.000 description 1
229920000209 Hexadimethrine bromide Polymers 0.000 description 1
102100026122 High affinity immunoglobulin gamma Fc receptor I Human genes 0.000 description 1
108091006054 His-tagged proteins Proteins 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
101000884305 Homo sapiens B-cell receptor CD22 Proteins 0.000 description 1
101000913074 Homo sapiens High affinity immunoglobulin gamma Fc receptor I Proteins 0.000 description 1
101000878602 Homo sapiens Immunoglobulin alpha Fc receptor Proteins 0.000 description 1
101000599951 Homo sapiens Insulin-like growth factor I Proteins 0.000 description 1
101000917858 Homo sapiens Low affinity immunoglobulin gamma Fc region receptor III-A Proteins 0.000 description 1
101000917839 Homo sapiens Low affinity immunoglobulin gamma Fc region receptor III-B Proteins 0.000 description 1
101000904173 Homo sapiens Progonadoliberin-1 Proteins 0.000 description 1
101001059454 Homo sapiens Serine/threonine-protein kinase MARK2 Proteins 0.000 description 1
101000800116 Homo sapiens Thy-1 membrane glycoprotein Proteins 0.000 description 1
101000727826 Homo sapiens Tyrosine-protein kinase RYK Proteins 0.000 description 1
108010001336 Horseradish Peroxidase Proteins 0.000 description 1
102000003839 Human Proteins Human genes 0.000 description 1
108090000144 Human Proteins Proteins 0.000 description 1
101000963974 Hydrophis stokesii Alpha-elapitoxin-Ast2b Proteins 0.000 description 1
UGQMRVRMYYASKQ-UHFFFAOYSA-N Hypoxanthine nucleoside Natural products OC1C(O)C(CO)OC1N1C(NC=NC2=O)=C2N=C1 UGQMRVRMYYASKQ-UHFFFAOYSA-N 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
108700005091 Immunoglobulin Genes Proteins 0.000 description 1
102100038005 Immunoglobulin alpha Fc receptor Human genes 0.000 description 1
206010061218 Inflammation Diseases 0.000 description 1
108090000723 Insulin-Like Growth Factor I Proteins 0.000 description 1
102000014429 Insulin-like growth factor Human genes 0.000 description 1
102100037852 Insulin-like growth factor I Human genes 0.000 description 1
102000006992 Interferon-alpha Human genes 0.000 description 1
108010047761 Interferon-alpha Proteins 0.000 description 1
108010002350 Interleukin-2 Proteins 0.000 description 1
102100020873 Interleukin-2 Human genes 0.000 description 1
102000004388 Interleukin-4 Human genes 0.000 description 1
108090000978 Interleukin-4 Proteins 0.000 description 1
108090001005 Interleukin-6 Proteins 0.000 description 1
235000019766 L-Lysine Nutrition 0.000 description 1
ONIBWKKTOPOVIA-BYPYZUCNSA-N L-Proline Chemical compound OC(=O)[C@@H]1CCCN1 ONIBWKKTOPOVIA-BYPYZUCNSA-N 0.000 description 1
229930182816 L-glutamine Natural products 0.000 description 1
239000005517 L01XE01 - Imatinib Substances 0.000 description 1
239000005411 L01XE02 - Gefitinib Substances 0.000 description 1
239000005551 L01XE03 - Erlotinib Substances 0.000 description 1
239000002147 L01XE04 - Sunitinib Substances 0.000 description 1
239000002136 L01XE07 - Lapatinib Substances 0.000 description 1
206010023825 Laryngeal cancer Diseases 0.000 description 1
102000019298 Lipocalin Human genes 0.000 description 1
108050006654 Lipocalin Proteins 0.000 description 1
102100029185 Low affinity immunoglobulin gamma Fc region receptor III-B Human genes 0.000 description 1
108060001084 Luciferase Proteins 0.000 description 1
239000005089 Luciferase Substances 0.000 description 1
229940124041 Luteinizing hormone releasing hormone (LHRH) antagonist Drugs 0.000 description 1
108700041567 MDR Genes Proteins 0.000 description 1
102000007651 Macrophage Colony-Stimulating Factor Human genes 0.000 description 1
108010046938 Macrophage Colony-Stimulating Factor Proteins 0.000 description 1
108010026217 Malate Dehydrogenase Proteins 0.000 description 1
229930195725 Mannitol Natural products 0.000 description 1
108010091175 Matriptase Proteins 0.000 description 1
229930126263 Maytansine Natural products 0.000 description 1
229930192392 Mitomycin Natural products 0.000 description 1
208000034578 Multiple myelomas Diseases 0.000 description 1
108010085220 Multiprotein Complexes Proteins 0.000 description 1
102000007474 Multiprotein Complexes Human genes 0.000 description 1
102000016943 Muramidase Human genes 0.000 description 1
108010014251 Muramidase Proteins 0.000 description 1
241000282341 Mustela putorius furo Species 0.000 description 1
DTERQYGMUDWYAZ-ZETCQYMHSA-N N(6)-acetyl-L-lysine Chemical compound CC(=O)NCCCC[C@H]([NH3+])C([O-])=O DTERQYGMUDWYAZ-ZETCQYMHSA-N 0.000 description 1
JDHILDINMRGULE-LURJTMIESA-N N(pros)-methyl-L-histidine Chemical compound CN1C=NC=C1C[C@H](N)C(O)=O JDHILDINMRGULE-LURJTMIESA-N 0.000 description 1
108010062010 N-Acetylmuramoyl-L-alanine Amidase Proteins 0.000 description 1
JJIHLJJYMXLCOY-BYPYZUCNSA-N N-acetyl-L-serine Chemical compound CC(=O)N[C@@H](CO)C(O)=O JJIHLJJYMXLCOY-BYPYZUCNSA-N 0.000 description 1
PYUSHNKNPOHWEZ-YFKPBYRVSA-N N-formyl-L-methionine Chemical compound CSCC[C@@H](C(O)=O)NC=O PYUSHNKNPOHWEZ-YFKPBYRVSA-N 0.000 description 1
108091007491 NSP3 Papain-like protease domains Proteins 0.000 description 1
101000964025 Naja naja Long neurotoxin 3 Proteins 0.000 description 1
101000822778 Naja naja Long neurotoxin 4 Proteins 0.000 description 1
101000822797 Naja naja Long neurotoxin 5 Proteins 0.000 description 1
208000005890 Neuroma Diseases 0.000 description 1
102000004459 Nitroreductase Human genes 0.000 description 1
108010038807 Oligopeptides Proteins 0.000 description 1
102000015636 Oligopeptides Human genes 0.000 description 1
241000700635 Orf virus Species 0.000 description 1
101150030083 PE38 gene Proteins 0.000 description 1
101150062285 PGF gene Proteins 0.000 description 1
108700034306 PROMACE-CytaBOM protocol Proteins 0.000 description 1
108090000526 Papain Proteins 0.000 description 1
235000019483 Peanut oil Nutrition 0.000 description 1
102000057297 Pepsin A Human genes 0.000 description 1
108090000284 Pepsin A Proteins 0.000 description 1
101710124951 Phospholipase C Proteins 0.000 description 1
102000004160 Phosphoric Monoester Hydrolases Human genes 0.000 description 1
108090000608 Phosphoric Monoester Hydrolases Proteins 0.000 description 1
108010053210 Phycocyanin Proteins 0.000 description 1
108010004729 Phycoerythrin Proteins 0.000 description 1
102100035194 Placenta growth factor Human genes 0.000 description 1
108010038512 Platelet-Derived Growth Factor Proteins 0.000 description 1
102000010780 Platelet-Derived Growth Factor Human genes 0.000 description 1
206010035603 Pleural mesothelioma Diseases 0.000 description 1
208000006664 Precursor Cell Lymphoblastic Leukemia-Lymphoma Diseases 0.000 description 1
241000288906 Primates Species 0.000 description 1
102100024028 Progonadoliberin-1 Human genes 0.000 description 1
ONIBWKKTOPOVIA-UHFFFAOYSA-N Proline Natural products OC(=O)C1CCCN1 ONIBWKKTOPOVIA-UHFFFAOYSA-N 0.000 description 1
102100038280 Prostaglandin G/H synthase 2 Human genes 0.000 description 1
108050003267 Prostaglandin G/H synthase 2 Proteins 0.000 description 1
239000004365 Protease Substances 0.000 description 1
229940079156 Proteasome inhibitor Drugs 0.000 description 1
108091008611 Protein Kinase B Proteins 0.000 description 1
102000016971 Proto-Oncogene Proteins c-kit Human genes 0.000 description 1
108010014608 Proto-Oncogene Proteins c-kit Proteins 0.000 description 1
241000589516 Pseudomonas Species 0.000 description 1
208000001671 Pulmonary Adenomatosis Diseases 0.000 description 1
LCTONWCANYUPML-UHFFFAOYSA-M Pyruvate Chemical compound CC(=O)C([O-])=O LCTONWCANYUPML-UHFFFAOYSA-M 0.000 description 1
102100033810 RAC-alpha serine/threonine-protein kinase Human genes 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
229940127361 Receptor Tyrosine Kinase Inhibitors Drugs 0.000 description 1
108010008281 Recombinant Fusion Proteins Proteins 0.000 description 1
102000007056 Recombinant Fusion Proteins Human genes 0.000 description 1
206010038802 Reticuloendothelial system stimulated Diseases 0.000 description 1
102000001332 SRC Human genes 0.000 description 1
108060006706 SRC Proteins 0.000 description 1
201000010208 Seminoma Diseases 0.000 description 1
102100028904 Serine/threonine-protein kinase MARK2 Human genes 0.000 description 1
108010071390 Serum Albumin Proteins 0.000 description 1
102000007562 Serum Albumin Human genes 0.000 description 1
244000000231 Sesamum indicum Species 0.000 description 1
208000000453 Skin Neoplasms Diseases 0.000 description 1
101710105463 Snake venom vascular endothelial growth factor toxin Proteins 0.000 description 1
101000677856 Stenotrophomonas maltophilia (strain K279a) Actin-binding protein Smlt3054 Proteins 0.000 description 1
241000282887 Suidae Species 0.000 description 1
NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 1
102100037942 Suppressor of tumorigenicity 14 protein Human genes 0.000 description 1
241000282898 Sus scrofa Species 0.000 description 1
101000996723 Sus scrofa Gonadotropin-releasing hormone receptor Proteins 0.000 description 1
230000017274 T cell anergy Effects 0.000 description 1
108091008874 T cell receptors Proteins 0.000 description 1
102000016266 T-Cell Antigen Receptors Human genes 0.000 description 1
229940123237 Taxane Drugs 0.000 description 1
208000024313 Testicular Neoplasms Diseases 0.000 description 1
206010057644 Testis cancer Diseases 0.000 description 1
102100024554 Tetranectin Human genes 0.000 description 1
FOCVUCIESVLUNU-UHFFFAOYSA-N Thiotepa Chemical compound C1CN1P(N1CC1)(=S)N1CC1 FOCVUCIESVLUNU-UHFFFAOYSA-N 0.000 description 1
102100033523 Thy-1 membrane glycoprotein Human genes 0.000 description 1
102000006601 Thymidine Kinase Human genes 0.000 description 1
108020004440 Thymidine kinase Proteins 0.000 description 1
101710182223 Toxin B Proteins 0.000 description 1
102000004338 Transferrin Human genes 0.000 description 1
108090000901 Transferrin Proteins 0.000 description 1
108700019146 Transgenes Proteins 0.000 description 1
239000007983 Tris buffer Substances 0.000 description 1
239000013504 Triton X-100 Substances 0.000 description 1
229920004890 Triton X-100 Polymers 0.000 description 1
206010064390 Tumour invasion Diseases 0.000 description 1
108010057266 Type A Botulinum Toxins Proteins 0.000 description 1
206010053613 Type IV hypersensitivity reaction Diseases 0.000 description 1
102100029759 Tyrosine-protein kinase RYK Human genes 0.000 description 1
208000025865 Ulcer Diseases 0.000 description 1
229910052770 Uranium Inorganic materials 0.000 description 1
108010042352 Urokinase Plasminogen Activator Receptors Proteins 0.000 description 1
102000004504 Urokinase Plasminogen Activator Receptors Human genes 0.000 description 1
102000003990 Urokinase-type plasminogen activator Human genes 0.000 description 1
108090000435 Urokinase-type plasminogen activator Proteins 0.000 description 1
208000006105 Uterine Cervical Neoplasms Diseases 0.000 description 1
208000002495 Uterine Neoplasms Diseases 0.000 description 1
108010053096 Vascular Endothelial Growth Factor Receptor-1 Proteins 0.000 description 1
102000016663 Vascular Endothelial Growth Factor Receptor-3 Human genes 0.000 description 1
102000005789 Vascular Endothelial Growth Factors Human genes 0.000 description 1
102100033178 Vascular endothelial growth factor receptor 1 Human genes 0.000 description 1
208000008383 Wilms tumor Diseases 0.000 description 1
XZSRRNFBEIOBDA-CFNBKWCHSA-N [2-[(2s,4s)-4-[(2r,4s,5s,6s)-4-amino-5-hydroxy-6-methyloxan-2-yl]oxy-2,5,12-trihydroxy-7-methoxy-6,11-dioxo-3,4-dihydro-1h-tetracen-2-yl]-2-oxoethyl] 2,2-diethoxyacetate Chemical compound O([C@H]1C[C@](CC2=C(O)C=3C(=O)C4=CC=CC(OC)=C4C(=O)C=3C(O)=C21)(O)C(=O)COC(=O)C(OCC)OCC)[C@H]1C[C@H](N)[C@H](O)[C@H](C)O1 XZSRRNFBEIOBDA-CFNBKWCHSA-N 0.000 description 1
230000002159 abnormal effect Effects 0.000 description 1
238000010521 absorption reaction Methods 0.000 description 1
229940022698 acetylcholinesterase Drugs 0.000 description 1
239000003929 acidic solution Substances 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
239000013543 active substance Substances 0.000 description 1
239000000654 additive Substances 0.000 description 1
208000009956 adenocarcinoma Diseases 0.000 description 1
201000008395 adenosquamous carcinoma Diseases 0.000 description 1
201000005179 adrenal carcinoma Diseases 0.000 description 1
230000001780 adrenocortical effect Effects 0.000 description 1
239000000443 aerosol Substances 0.000 description 1
230000002776 aggregation Effects 0.000 description 1
238000004220 aggregation Methods 0.000 description 1
210000004712 air sac Anatomy 0.000 description 1
229960000548 alemtuzumab Drugs 0.000 description 1
229930013930 alkaloid Natural products 0.000 description 1
150000003797 alkaloid derivatives Chemical class 0.000 description 1
229940045714 alkyl sulfonate alkylating agent Drugs 0.000 description 1
150000008052 alkyl sulfonates Chemical class 0.000 description 1
230000002152 alkylating effect Effects 0.000 description 1
108010004469 allophycocyanin Proteins 0.000 description 1
239000002776 alpha toxin Substances 0.000 description 1
102000005840 alpha-Galactosidase Human genes 0.000 description 1
108010030291 alpha-Galactosidase Proteins 0.000 description 1
230000004075 alteration Effects 0.000 description 1
229910000147 aluminium phosphate Inorganic materials 0.000 description 1
150000001412 amines Chemical class 0.000 description 1
238000003277 amino acid sequence analysis Methods 0.000 description 1
229960003896 aminopterin Drugs 0.000 description 1
235000019418 amylase Nutrition 0.000 description 1
229960002932 anastrozole Drugs 0.000 description 1
YBBLVLTVTVSKRW-UHFFFAOYSA-N anastrozole Chemical compound N#CC(C)(C)C1=CC(C(C)(C#N)C)=CC(CN2N=CN=C2)=C1 YBBLVLTVTVSKRW-UHFFFAOYSA-N 0.000 description 1
239000004037 angiogenesis inhibitor Substances 0.000 description 1
238000010171 animal model Methods 0.000 description 1
125000000129 anionic group Chemical group 0.000 description 1
230000003042 antagnostic effect Effects 0.000 description 1
230000008485 antagonism Effects 0.000 description 1
230000002280 anti-androgenic effect Effects 0.000 description 1
230000001772 anti-angiogenic effect Effects 0.000 description 1
230000003466 anti-cipated effect Effects 0.000 description 1
230000001740 anti-invasion Effects 0.000 description 1
230000000719 anti-leukaemic effect Effects 0.000 description 1
230000002927 anti-mitotic effect Effects 0.000 description 1
230000002137 anti-vascular effect Effects 0.000 description 1
239000000051 antiandrogen Substances 0.000 description 1
229940030495 antiandrogen sex hormone and modulator of the genital system Drugs 0.000 description 1
230000005875 antibody response Effects 0.000 description 1
230000010056 antibody-dependent cellular cytotoxicity Effects 0.000 description 1
230000000890 antigenic effect Effects 0.000 description 1
239000000063 antileukemic agent Substances 0.000 description 1
229940045687 antimetabolites folic acid analogs Drugs 0.000 description 1
239000000074 antisense oligonucleotide Substances 0.000 description 1
238000012230 antisense oligonucleotides Methods 0.000 description 1
210000002403 aortic endothelial cell Anatomy 0.000 description 1
230000001640 apoptogenic effect Effects 0.000 description 1
230000006907 apoptotic process Effects 0.000 description 1
239000003886 aromatase inhibitor Substances 0.000 description 1
229940046844 aromatase inhibitors Drugs 0.000 description 1
206010003246 arthritis Diseases 0.000 description 1
125000000613 asparagine group Chemical group N[C@@H](CC(N)=O)C(=O)* 0.000 description 1
235000003704 aspartic acid Nutrition 0.000 description 1
FZCSTZYAHCUGEM-UHFFFAOYSA-N aspergillomarasmine B Natural products OC(=O)CNC(C(O)=O)CNC(C(O)=O)CC(O)=O FZCSTZYAHCUGEM-UHFFFAOYSA-N 0.000 description 1
108010044540 auristatin Proteins 0.000 description 1
239000003719 aurora kinase inhibitor Substances 0.000 description 1
229950011321 azaserine Drugs 0.000 description 1
230000001580 bacterial effect Effects 0.000 description 1
210000000270 basal cell Anatomy 0.000 description 1
238000013398 bayesian method Methods 0.000 description 1
108700000711 bcl-X Proteins 0.000 description 1
102000055104 bcl-X Human genes 0.000 description 1
230000009286 beneficial effect Effects 0.000 description 1
108010087667 beta-1,4-mannosyl-glycoprotein beta-1,4-N-acetylglucosaminyltransferase Proteins 0.000 description 1
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 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
229960000997 bicalutamide Drugs 0.000 description 1
230000002457 bidirectional effect Effects 0.000 description 1
210000000013 bile duct Anatomy 0.000 description 1
201000009036 biliary tract cancer Diseases 0.000 description 1
208000020790 biliary tract neoplasm Diseases 0.000 description 1
230000003115 biocidal effect Effects 0.000 description 1
239000012620 biological material Substances 0.000 description 1
229920001222 biopolymer Polymers 0.000 description 1
238000001815 biotherapy Methods 0.000 description 1
229960002685 biotin Drugs 0.000 description 1
235000020958 biotin Nutrition 0.000 description 1
239000011616 biotin Substances 0.000 description 1
125000004057 biotinyl group Chemical group [H]N1C(=O)N([H])[C@]2([H])[C@@]([H])(SC([H])([H])[C@]12[H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C(*)=O 0.000 description 1
210000004204 blood vessel Anatomy 0.000 description 1
210000000988 bone and bone Anatomy 0.000 description 1
GXJABQQUPOEUTA-RDJZCZTQSA-N bortezomib Chemical compound C([C@@H](C(=O)N[C@@H](CC(C)C)B(O)O)NC(=O)C=1N=CC=NC=1)C1=CC=CC=C1 GXJABQQUPOEUTA-RDJZCZTQSA-N 0.000 description 1
IXIBAKNTJSCKJM-BUBXBXGNSA-N bovine insulin Chemical compound C([C@@H](C(=O)N[C@@H](CC(C)C)C(=O)N[C@H]1CSSC[C@H]2C(=O)N[C@@H](C)C(=O)N[C@@H](CO)C(=O)N[C@H](C(=O)N[C@H](C(N[C@@H](CO)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC=3C=CC(O)=CC=3)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC=3C=CC(O)=CC=3)C(=O)N[C@@H](CSSC[C@H](NC(=O)[C@H](C(C)C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC=3C=CC(O)=CC=3)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](C)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C(C)C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC=3NC=NC=3)NC(=O)[C@H](CO)NC(=O)CNC1=O)C(=O)NCC(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)NCC(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N[C@@H]([C@@H](C)O)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](C)C(O)=O)C(=O)N[C@@H](CC(N)=O)C(O)=O)=O)CSSC[C@@H](C(N2)=O)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C(C)C)NC(=O)[C@@H](NC(=O)CN)[C@@H](C)CC)C(C)C)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CC(N)=O)NC(=O)[C@@H](NC(=O)[C@@H](N)CC=1C=CC=CC=1)C(C)C)C1=CN=CN1 IXIBAKNTJSCKJM-BUBXBXGNSA-N 0.000 description 1
229950004398 broxuridine Drugs 0.000 description 1
108010049223 bryodin Proteins 0.000 description 1
229960002719 buserelin Drugs 0.000 description 1
CUWODFFVMXJOKD-UVLQAERKSA-N buserelin Chemical compound CCNC(=O)[C@@H]1CCCN1C(=O)[C@H](CCCN=C(N)N)NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](COC(C)(C)C)NC(=O)[C@@H](NC(=O)[C@H](CO)NC(=O)[C@H](CC=1C2=CC=CC=C2NC=1)NC(=O)[C@H](CC=1NC=NC=1)NC(=O)[C@H]1NC(=O)CC1)CC1=CC=C(O)C=C1 CUWODFFVMXJOKD-UVLQAERKSA-N 0.000 description 1
210000004899 c-terminal region Anatomy 0.000 description 1
239000001506 calcium phosphate Substances 0.000 description 1
229910000389 calcium phosphate Inorganic materials 0.000 description 1
235000011010 calcium phosphates Nutrition 0.000 description 1
244000309466 calf Species 0.000 description 1
229950002826 canertinib Drugs 0.000 description 1
235000013877 carbamide Nutrition 0.000 description 1
229910052799 carbon Inorganic materials 0.000 description 1
125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 1
231100000504 carcinogenesis Toxicity 0.000 description 1
208000002458 carcinoid tumor Diseases 0.000 description 1
238000012219 cassette mutagenesis Methods 0.000 description 1
230000015556 catabolic process Effects 0.000 description 1
239000003054 catalyst Substances 0.000 description 1
125000002091 cationic group Chemical group 0.000 description 1
229960002412 cediranib Drugs 0.000 description 1
238000003352 cell adhesion assay Methods 0.000 description 1
238000004113 cell culture Methods 0.000 description 1
210000000170 cell membrane Anatomy 0.000 description 1
230000012292 cell migration Effects 0.000 description 1
239000006285 cell suspension Substances 0.000 description 1
238000012054 celltiter-glo Methods 0.000 description 1
230000001413 cellular effect Effects 0.000 description 1
230000005754 cellular signaling Effects 0.000 description 1
239000001913 cellulose Substances 0.000 description 1
229920002678 cellulose Polymers 0.000 description 1
210000003169 central nervous system Anatomy 0.000 description 1
201000007455 central nervous system cancer Diseases 0.000 description 1
238000005119 centrifugation Methods 0.000 description 1
201000010881 cervical cancer Diseases 0.000 description 1
210000003679 cervix uteri Anatomy 0.000 description 1
229960005395 cetuximab Drugs 0.000 description 1
239000002738 chelating agent Substances 0.000 description 1
DGLFSNZWRYADFC-UHFFFAOYSA-N chembl2334586 Chemical compound C1CCC2=CN=C(N)N=C2C2=C1NC1=CC=C(C#CC(C)(O)C)C=C12 DGLFSNZWRYADFC-UHFFFAOYSA-N 0.000 description 1
125000003636 chemical group Chemical group 0.000 description 1
229960003677 chloroquine Drugs 0.000 description 1
WHTVZRBIWZFKQO-UHFFFAOYSA-N chloroquine Natural products ClC1=CC=C2C(NC(C)CCCN(CC)CC)=CC=NC2=C1 WHTVZRBIWZFKQO-UHFFFAOYSA-N 0.000 description 1
230000001684 chronic effect Effects 0.000 description 1
238000010367 cloning Methods 0.000 description 1
238000010372 cloning stem cell Methods 0.000 description 1
238000007621 cluster analysis Methods 0.000 description 1
238000003501 co-culture Methods 0.000 description 1
230000004186 co-expression Effects 0.000 description 1
239000005515 coenzyme Substances 0.000 description 1
210000001072 colon Anatomy 0.000 description 1
238000004440 column chromatography Methods 0.000 description 1
229960005537 combretastatin A-4 Drugs 0.000 description 1
HVXBOLULGPECHP-UHFFFAOYSA-N combretastatin A4 Natural products C1=C(O)C(OC)=CC=C1C=CC1=CC(OC)=C(OC)C(OC)=C1 HVXBOLULGPECHP-UHFFFAOYSA-N 0.000 description 1
238000012875 competitive assay Methods 0.000 description 1
230000002860 competitive effect Effects 0.000 description 1
230000024203 complement activation Effects 0.000 description 1
201000010918 connective tissue cancer Diseases 0.000 description 1
239000000470 constituent Substances 0.000 description 1
239000000356 contaminant Substances 0.000 description 1
230000001276 controlling effect Effects 0.000 description 1
201000002951 cornea squamous cell carcinoma Diseases 0.000 description 1
235000012343 cottonseed oil Nutrition 0.000 description 1
239000002385 cottonseed oil Substances 0.000 description 1
230000008878 coupling Effects 0.000 description 1
238000010168 coupling process Methods 0.000 description 1
238000005859 coupling reaction Methods 0.000 description 1
229940111134 coxibs Drugs 0.000 description 1
238000009402 cross-breeding Methods 0.000 description 1
239000002875 cyclin dependent kinase inhibitor Substances 0.000 description 1
229940043378 cyclin-dependent kinase inhibitor Drugs 0.000 description 1
239000003255 cyclooxygenase 2 inhibitor Substances 0.000 description 1
229960000978 cyproterone acetate Drugs 0.000 description 1
UWFYSQMTEOIJJG-FDTZYFLXSA-N cyproterone acetate Chemical compound C1=C(Cl)C2=CC(=O)[C@@H]3C[C@@H]3[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@@](C(C)=O)(OC(=O)C)[C@@]1(C)CC2 UWFYSQMTEOIJJG-FDTZYFLXSA-N 0.000 description 1
239000000824 cytostatic agent Substances 0.000 description 1
125000001295 dansyl group Chemical group [H]C1=C([H])C(N(C([H])([H])[H])C([H])([H])[H])=C2C([H])=C([H])C([H])=C(C2=C1[H])S(*)(=O)=O 0.000 description 1
238000007418 data mining Methods 0.000 description 1
229960000975 daunorubicin Drugs 0.000 description 1
238000006731 degradation reaction Methods 0.000 description 1
239000003405 delayed action preparation Substances 0.000 description 1
YSMODUONRAFBET-UHFFFAOYSA-N delta-DL-hydroxylysine Natural products NCC(O)CCC(N)C(O)=O YSMODUONRAFBET-UHFFFAOYSA-N 0.000 description 1
210000004443 dendritic cell Anatomy 0.000 description 1
239000005547 deoxyribonucleotide Substances 0.000 description 1
125000002637 deoxyribonucleotide group Chemical group 0.000 description 1
238000001212 derivatisation Methods 0.000 description 1
229950003913 detorubicin Drugs 0.000 description 1
229960003957 dexamethasone Drugs 0.000 description 1
UREBDLICKHMUKA-CXSFZGCWSA-N dexamethasone Chemical compound C1CC2=CC(=O)C=C[C@]2(C)[C@]2(F)[C@@H]1[C@@H]1C[C@@H](C)[C@@](C(=O)CO)(O)[C@@]1(C)C[C@@H]2O UREBDLICKHMUKA-CXSFZGCWSA-N 0.000 description 1
229950006137 dexfosfoserine Drugs 0.000 description 1
235000019425 dextrin Nutrition 0.000 description 1
238000003745 diagnosis Methods 0.000 description 1
235000005911 diet Nutrition 0.000 description 1
230000037213 diet Effects 0.000 description 1
PGUYAANYCROBRT-UHFFFAOYSA-N dihydroxy-selanyl-selanylidene-lambda5-phosphane Chemical compound OP(O)([SeH])=[Se] PGUYAANYCROBRT-UHFFFAOYSA-N 0.000 description 1
239000003085 diluting agent Substances 0.000 description 1
NAGJZTKCGNOGPW-UHFFFAOYSA-K dioxido-sulfanylidene-sulfido-$l^{5}-phosphane Chemical compound [O-]P([O-])([S-])=S NAGJZTKCGNOGPW-UHFFFAOYSA-K 0.000 description 1
150000002016 disaccharides Chemical class 0.000 description 1
230000005750 disease progression Effects 0.000 description 1
238000004090 dissolution Methods 0.000 description 1
238000009826 distribution Methods 0.000 description 1
229960003668 docetaxel Drugs 0.000 description 1
239000012154 double-distilled water Substances 0.000 description 1
229950004203 droloxifene Drugs 0.000 description 1
238000009510 drug design Methods 0.000 description 1
238000007876 drug discovery Methods 0.000 description 1
229960005501 duocarmycin Drugs 0.000 description 1
VQNATVDKACXKTF-XELLLNAOSA-N duocarmycin Chemical compound COC1=C(OC)C(OC)=C2NC(C(=O)N3C4=CC(=O)C5=C([C@@]64C[C@@H]6C3)C=C(N5)C(=O)OC)=CC2=C1 VQNATVDKACXKTF-XELLLNAOSA-N 0.000 description 1
229930184221 duocarmycin Natural products 0.000 description 1
238000005538 encapsulation Methods 0.000 description 1
230000002124 endocrine Effects 0.000 description 1
210000004696 endometrium Anatomy 0.000 description 1
230000003511 endothelial effect Effects 0.000 description 1
239000002158 endotoxin Substances 0.000 description 1
230000002708 enhancing effect Effects 0.000 description 1
238000006911 enzymatic reaction 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
229940082789 erbitux Drugs 0.000 description 1
YSMODUONRAFBET-UHNVWZDZSA-N erythro-5-hydroxy-L-lysine Chemical compound NC[C@H](O)CC[C@H](N)C(O)=O YSMODUONRAFBET-UHNVWZDZSA-N 0.000 description 1
201000004101 esophageal cancer Diseases 0.000 description 1
229950002017 esorubicin Drugs 0.000 description 1
ITSGNOIFAJAQHJ-BMFNZSJVSA-N esorubicin 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[C@H](C)O1 ITSGNOIFAJAQHJ-BMFNZSJVSA-N 0.000 description 1
LJQQFQHBKUKHIS-WJHRIEJJSA-N esperamicin Chemical compound O1CC(NC(C)C)C(OC)CC1OC1C(O)C(NOC2OC(C)C(SC)C(O)C2)C(C)OC1OC1C(\C2=C/CSSSC)=C(NC(=O)OC)C(=O)C(OC3OC(C)C(O)C(OC(=O)C=4C(=CC(OC)=C(OC)C=4)NC(=O)C(=C)OC)C3)C2(O)C#C\C=C/C#C1 LJQQFQHBKUKHIS-WJHRIEJJSA-N 0.000 description 1
239000003797 essential amino acid Substances 0.000 description 1
LVGKNOAMLMIIKO-QXMHVHEDSA-N ethyl oleate Chemical compound CCCCCCCC\C=C/CCCCCCCC(=O)OCC LVGKNOAMLMIIKO-QXMHVHEDSA-N 0.000 description 1
229940093471 ethyl oleate Drugs 0.000 description 1
OGPBJKLSAFTDLK-UHFFFAOYSA-N europium atom Chemical compound [Eu] OGPBJKLSAFTDLK-UHFFFAOYSA-N 0.000 description 1
229960000255 exemestane Drugs 0.000 description 1
239000013604 expression vector Substances 0.000 description 1
208000024519 eye neoplasm Diseases 0.000 description 1
229950003499 fibrin Drugs 0.000 description 1
210000002950 fibroblast Anatomy 0.000 description 1
206010016629 fibroma Diseases 0.000 description 1
238000001914 filtration Methods 0.000 description 1
DBEPLOCGEIEOCV-WSBQPABSSA-N finasteride Chemical compound N([C@@H]1CC2)C(=O)C=C[C@]1(C)[C@@H]1[C@@H]2[C@@H]2CC[C@H](C(=O)NC(C)(C)C)[C@@]2(C)CC1 DBEPLOCGEIEOCV-WSBQPABSSA-N 0.000 description 1
229960004039 finasteride Drugs 0.000 description 1
ZFKJVJIDPQDDFY-UHFFFAOYSA-N fluorescamine Chemical compound C12=CC=CC=C2C(=O)OC1(C1=O)OC=C1C1=CC=CC=C1 ZFKJVJIDPQDDFY-UHFFFAOYSA-N 0.000 description 1
GNBHRKFJIUUOQI-UHFFFAOYSA-N fluorescein Chemical compound O1C(=O)C2=CC=CC=C2C21C1=CC=C(O)C=C1OC1=CC(O)=CC=C21 GNBHRKFJIUUOQI-UHFFFAOYSA-N 0.000 description 1
MHMNJMPURVTYEJ-UHFFFAOYSA-N fluorescein-5-isothiocyanate Chemical compound O1C(=O)C2=CC(N=C=S)=CC=C2C21C1=CC=C(O)C=C1OC1=CC(O)=CC=C21 MHMNJMPURVTYEJ-UHFFFAOYSA-N 0.000 description 1
239000007850 fluorescent dye Substances 0.000 description 1
229960002074 flutamide Drugs 0.000 description 1
MKXKFYHWDHIYRV-UHFFFAOYSA-N flutamide Chemical compound CC(C)C(=O)NC1=CC=C([N+]([O-])=O)C(C(F)(F)F)=C1 MKXKFYHWDHIYRV-UHFFFAOYSA-N 0.000 description 1
150000002224 folic acids Chemical class 0.000 description 1
201000003444 follicular lymphoma Diseases 0.000 description 1
230000033581 fucosylation Effects 0.000 description 1
229960002258 fulvestrant Drugs 0.000 description 1
108020001507 fusion proteins Proteins 0.000 description 1
102000037865 fusion proteins Human genes 0.000 description 1
201000010175 gallbladder cancer Diseases 0.000 description 1
201000006585 gastric adenocarcinoma Diseases 0.000 description 1
208000017215 gastric mucosa-associated lymphoid tissue lymphoma Diseases 0.000 description 1
239000000499 gel Substances 0.000 description 1
239000008273 gelatin Substances 0.000 description 1
229920000159 gelatin Polymers 0.000 description 1
235000019322 gelatine Nutrition 0.000 description 1
235000011852 gelatine desserts Nutrition 0.000 description 1
210000004392 genitalia Anatomy 0.000 description 1
210000004907 gland Anatomy 0.000 description 1
102000010705 glucose-6-phosphate dehydrogenase activity proteins Human genes 0.000 description 1
108040005050 glucose-6-phosphate dehydrogenase activity proteins Proteins 0.000 description 1
235000013922 glutamic acid Nutrition 0.000 description 1
239000004220 glutamic acid Substances 0.000 description 1
125000000291 glutamic acid group Chemical group N[C@@H](CCC(O)=O)C(=O)* 0.000 description 1
125000000404 glutamine group Chemical group N[C@@H](CCC(N)=O)C(=O)* 0.000 description 1
150000002337 glycosamines Chemical group 0.000 description 1
XLXSAKCOAKORKW-UHFFFAOYSA-N gonadorelin Chemical compound C1CCC(C(=O)NCC(N)=O)N1C(=O)C(CCCN=C(N)N)NC(=O)C(CC(C)C)NC(=O)CNC(=O)C(NC(=O)C(CO)NC(=O)C(CC=1C2=CC=CC=C2NC=1)NC(=O)C(CC=1NC=NC=1)NC(=O)C1NC(=O)CC1)CC1=CC=C(O)C=C1 XLXSAKCOAKORKW-UHFFFAOYSA-N 0.000 description 1
229960002913 goserelin Drugs 0.000 description 1
208000017750 granulocytic sarcoma Diseases 0.000 description 1
238000000227 grinding Methods 0.000 description 1
201000005787 hematologic cancer Diseases 0.000 description 1
208000024200 hematopoietic and lymphoid system neoplasm Diseases 0.000 description 1
210000003958 hematopoietic stem cell Anatomy 0.000 description 1
230000002949 hemolytic effect Effects 0.000 description 1
108010037536 heparanase Proteins 0.000 description 1
229960002897 heparin Drugs 0.000 description 1
229920000669 heparin Polymers 0.000 description 1
230000002440 hepatic effect Effects 0.000 description 1
210000003494 hepatocyte Anatomy 0.000 description 1
201000000284 histiocytoma Diseases 0.000 description 1
229960000890 hydrocortisone Drugs 0.000 description 1
229920001477 hydrophilic polymer Polymers 0.000 description 1
229920001600 hydrophobic polymer Polymers 0.000 description 1
230000000521 hyperimmunizing effect Effects 0.000 description 1
HOMGKSMUEGBAAB-UHFFFAOYSA-N ifosfamide Chemical compound ClCCNP1(=O)OCCCN1CCCl HOMGKSMUEGBAAB-UHFFFAOYSA-N 0.000 description 1
229960001101 ifosfamide Drugs 0.000 description 1
KTUFNOKKBVMGRW-UHFFFAOYSA-N imatinib Chemical compound 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 KTUFNOKKBVMGRW-UHFFFAOYSA-N 0.000 description 1
229960002411 imatinib Drugs 0.000 description 1
125000001841 imino group Chemical group [H]N=* 0.000 description 1
210000002865 immune cell Anatomy 0.000 description 1
230000028993 immune response Effects 0.000 description 1
230000016784 immunoglobulin production Effects 0.000 description 1
239000012133 immunoprecipitate Substances 0.000 description 1
238000009169 immunotherapy Methods 0.000 description 1
230000006872 improvement Effects 0.000 description 1
238000010348 incorporation Methods 0.000 description 1
230000002458 infectious effect Effects 0.000 description 1
230000004054 inflammatory process Effects 0.000 description 1
230000000977 initiatory effect Effects 0.000 description 1
206010022498 insulinoma Diseases 0.000 description 1
102000006495 integrins Human genes 0.000 description 1
108010044426 integrins Proteins 0.000 description 1
229940028885 interleukin-4 Drugs 0.000 description 1
230000000968 intestinal effect Effects 0.000 description 1
238000001361 intraarterial administration Methods 0.000 description 1
230000004068 intracellular signaling Effects 0.000 description 1
208000020082 intraepithelial neoplasia Diseases 0.000 description 1
238000007918 intramuscular administration Methods 0.000 description 1
238000010255 intramuscular injection Methods 0.000 description 1
239000007927 intramuscular injection Substances 0.000 description 1
238000007913 intrathecal administration Methods 0.000 description 1
238000004255 ion exchange chromatography Methods 0.000 description 1
201000002529 islet cell tumor Diseases 0.000 description 1
210000004153 islets of langerhan Anatomy 0.000 description 1
238000002955 isolation Methods 0.000 description 1
235000015110 jellies Nutrition 0.000 description 1
238000005304 joining Methods 0.000 description 1
208000022013 kidney Wilms tumor Diseases 0.000 description 1
210000003292 kidney cell Anatomy 0.000 description 1
230000002147 killing effect Effects 0.000 description 1
239000004310 lactic acid Substances 0.000 description 1
235000014655 lactic acid Nutrition 0.000 description 1
229960004891 lapatinib Drugs 0.000 description 1
BCFGMOOMADDAQU-UHFFFAOYSA-N lapatinib Chemical compound O1C(CNCCS(=O)(=O)C)=CC=C1C1=CC=C(N=CN=C2NC=3C=C(Cl)C(OCC=4C=C(F)C=CC=4)=CC=3)C2=C1 BCFGMOOMADDAQU-UHFFFAOYSA-N 0.000 description 1
206010023841 laryngeal neoplasm Diseases 0.000 description 1
201000004962 larynx cancer Diseases 0.000 description 1
239000004816 latex Substances 0.000 description 1
229920000126 latex Polymers 0.000 description 1
229960003881 letrozole Drugs 0.000 description 1
HPJKCIUCZWXJDR-UHFFFAOYSA-N letrozole Chemical compound C1=CC(C#N)=CC=C1C(N1N=CN=C1)C1=CC=C(C#N)C=C1 HPJKCIUCZWXJDR-UHFFFAOYSA-N 0.000 description 1
238000002898 library design Methods 0.000 description 1
210000000088 lip Anatomy 0.000 description 1
238000001638 lipofection Methods 0.000 description 1
239000007788 liquid Substances 0.000 description 1
201000007270 liver cancer Diseases 0.000 description 1
208000014018 liver neoplasm Diseases 0.000 description 1
244000144972 livestock Species 0.000 description 1
230000004807 localization Effects 0.000 description 1
HWYHZTIRURJOHG-UHFFFAOYSA-N luminol Chemical compound O=C1NNC(=O)C2=C1C(N)=CC=C2 HWYHZTIRURJOHG-UHFFFAOYSA-N 0.000 description 1
229940087857 lupron Drugs 0.000 description 1
210000001365 lymphatic vessel Anatomy 0.000 description 1
201000011649 lymphoblastic lymphoma Diseases 0.000 description 1
125000003588 lysine group Chemical group [H]N([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])(N([H])[H])C(*)=O 0.000 description 1
239000004325 lysozyme Substances 0.000 description 1
229960000274 lysozyme Drugs 0.000 description 1
235000010335 lysozyme Nutrition 0.000 description 1
238000010801 machine learning Methods 0.000 description 1
229920002521 macromolecule Polymers 0.000 description 1
210000002540 macrophage Anatomy 0.000 description 1
230000003211 malignant effect Effects 0.000 description 1
239000000594 mannitol Substances 0.000 description 1
235000010355 mannitol Nutrition 0.000 description 1
OCSMOTCMPXTDND-OUAUKWLOSA-N marimastat Chemical compound CNC(=O)[C@H](C(C)(C)C)NC(=O)[C@H](CC(C)C)[C@H](O)C(=O)NO OCSMOTCMPXTDND-OUAUKWLOSA-N 0.000 description 1
229950008959 marimastat Drugs 0.000 description 1
238000004949 mass spectrometry Methods 0.000 description 1
108010082117 matrigel Proteins 0.000 description 1
WKPWGQKGSOKKOO-RSFHAFMBSA-N maytansine Chemical compound CO[C@@H]([C@@]1(O)C[C@](OC(=O)N1)([C@H]([C@@H]1O[C@@]1(C)[C@@H](OC(=O)[C@H](C)N(C)C(C)=O)CC(=O)N1C)C)[H])\C=C\C=C(C)\CC2=CC(OC)=C(Cl)C1=C2 WKPWGQKGSOKKOO-RSFHAFMBSA-N 0.000 description 1
238000002483 medication Methods 0.000 description 1
229960004296 megestrol acetate Drugs 0.000 description 1
RQZAXGRLVPAYTJ-GQFGMJRRSA-N megestrol acetate Chemical compound C1=C(C)C2=CC(=O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@@](C(C)=O)(OC(=O)C)[C@@]1(C)CC2 RQZAXGRLVPAYTJ-GQFGMJRRSA-N 0.000 description 1
229910052751 metal Inorganic materials 0.000 description 1
239000002184 metal Substances 0.000 description 1
239000003475 metalloproteinase inhibitor Substances 0.000 description 1
208000037819 metastatic cancer Diseases 0.000 description 1
208000011575 metastatic malignant neoplasm Diseases 0.000 description 1
210000002500 microbody Anatomy 0.000 description 1
239000003094 microcapsule Substances 0.000 description 1
238000000520 microinjection Methods 0.000 description 1
239000004005 microsphere Substances 0.000 description 1
230000005012 migration Effects 0.000 description 1
238000013508 migration Methods 0.000 description 1
235000013336 milk Nutrition 0.000 description 1
239000008267 milk Substances 0.000 description 1
210000004080 milk Anatomy 0.000 description 1
230000000116 mitigating effect Effects 0.000 description 1
238000010369 molecular cloning Methods 0.000 description 1
238000000302 molecular modelling Methods 0.000 description 1
HDZGCSFEDULWCS-UHFFFAOYSA-N monomethylhydrazine Chemical class CNN HDZGCSFEDULWCS-UHFFFAOYSA-N 0.000 description 1
150000002772 monosaccharides Chemical class 0.000 description 1
125000004573 morpholin-4-yl group Chemical group N1(CCOCC1)* 0.000 description 1
210000000214 mouth Anatomy 0.000 description 1
210000003205 muscle Anatomy 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
210000000822 natural killer cell Anatomy 0.000 description 1
210000003739 neck Anatomy 0.000 description 1
208000029974 neurofibrosarcoma Diseases 0.000 description 1
210000002569 neuron Anatomy 0.000 description 1
230000007935 neutral effect Effects 0.000 description 1
238000006386 neutralization reaction Methods 0.000 description 1
210000000440 neutrophil Anatomy 0.000 description 1
229910052759 nickel Inorganic materials 0.000 description 1
XWXYUMMDTVBTOU-UHFFFAOYSA-N nilutamide Chemical compound O=C1C(C)(C)NC(=O)N1C1=CC=C([N+]([O-])=O)C(C(F)(F)F)=C1 XWXYUMMDTVBTOU-UHFFFAOYSA-N 0.000 description 1
229960002653 nilutamide Drugs 0.000 description 1
108020001162 nitroreductase Proteins 0.000 description 1
239000002736 nonionic surfactant Substances 0.000 description 1
230000001254 nonsecretory effect Effects 0.000 description 1
231100000252 nontoxic Toxicity 0.000 description 1
230000003000 nontoxic effect Effects 0.000 description 1
210000004940 nucleus Anatomy 0.000 description 1
235000015097 nutrients Nutrition 0.000 description 1
201000008106 ocular cancer Diseases 0.000 description 1
235000019198 oils Nutrition 0.000 description 1
239000002674 ointment Substances 0.000 description 1
238000002515 oligonucleotide synthesis Methods 0.000 description 1
230000005868 ontogenesis Effects 0.000 description 1
201000005443 oral cavity cancer Diseases 0.000 description 1
229940126701 oral medication Drugs 0.000 description 1
208000008798 osteoma Diseases 0.000 description 1
KHPXUQMNIQBQEV-UHFFFAOYSA-N oxaloacetic acid Chemical compound OC(=O)CC(=O)C(O)=O KHPXUQMNIQBQEV-UHFFFAOYSA-N 0.000 description 1
230000003647 oxidation Effects 0.000 description 1
238000007254 oxidation reaction Methods 0.000 description 1
238000004806 packaging method and process Methods 0.000 description 1
210000000496 pancreas Anatomy 0.000 description 1
208000021255 pancreatic insulinoma Diseases 0.000 description 1
208000022102 pancreatic neuroendocrine neoplasm Diseases 0.000 description 1
229960001972 panitumumab Drugs 0.000 description 1
229940055729 papain Drugs 0.000 description 1
235000019834 papain Nutrition 0.000 description 1
208000029211 papillomatosis Diseases 0.000 description 1
230000036961 partial effect Effects 0.000 description 1
239000006072 paste Substances 0.000 description 1
238000003909 pattern recognition Methods 0.000 description 1
239000000312 peanut oil Substances 0.000 description 1
239000008188 pellet Substances 0.000 description 1
229940111202 pepsin Drugs 0.000 description 1
102000013415 peroxidase activity proteins Human genes 0.000 description 1
108040007629 peroxidase activity proteins Proteins 0.000 description 1
238000002823 phage display Methods 0.000 description 1
229940124531 pharmaceutical excipient Drugs 0.000 description 1
239000000825 pharmaceutical preparation Substances 0.000 description 1
210000003800 pharynx Anatomy 0.000 description 1
NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
239000010452 phosphate Substances 0.000 description 1
PTMHPRAIXMAOOB-UHFFFAOYSA-N phosphoramidic acid Chemical compound NP(O)(O)=O PTMHPRAIXMAOOB-UHFFFAOYSA-N 0.000 description 1
150000003013 phosphoric acid derivatives Chemical class 0.000 description 1
125000004194 piperazin-1-yl group Chemical group [H]N1C([H])([H])C([H])([H])N(*)C([H])([H])C1([H])[H] 0.000 description 1
238000007747 plating Methods 0.000 description 1
229920001983 poloxamer Polymers 0.000 description 1
229920000724 poly(L-arginine) polymer Polymers 0.000 description 1
229920000747 poly(lactic acid) Polymers 0.000 description 1
108010011110 polyarginine Proteins 0.000 description 1
229920000728 polyester Polymers 0.000 description 1
229920002338 polyhydroxyethylmethacrylate Polymers 0.000 description 1
229920000136 polysorbate Polymers 0.000 description 1
229920002451 polyvinyl alcohol Polymers 0.000 description 1
238000001556 precipitation Methods 0.000 description 1
239000003755 preservative agent Substances 0.000 description 1
208000016800 primary central nervous system lymphoma Diseases 0.000 description 1
229940002612 prodrug Drugs 0.000 description 1
239000000651 prodrug Substances 0.000 description 1
239000000583 progesterone congener Substances 0.000 description 1
229940095055 progestogen systemic hormonal contraceptives Drugs 0.000 description 1
230000000069 prophylactic effect Effects 0.000 description 1
239000003207 proteasome inhibitor Substances 0.000 description 1
238000000159 protein binding assay Methods 0.000 description 1
238000002818 protein evolution Methods 0.000 description 1
239000003528 protein farnesyltransferase inhibitor Substances 0.000 description 1
230000029983 protein stabilization Effects 0.000 description 1
210000001938 protoplast Anatomy 0.000 description 1
230000002685 pulmonary effect Effects 0.000 description 1
238000000746 purification Methods 0.000 description 1
150000003212 purines Chemical class 0.000 description 1
150000003230 pyrimidines Chemical class 0.000 description 1
229940076788 pyruvate Drugs 0.000 description 1
JWVCLYRUEFBMGU-UHFFFAOYSA-N quinazoline Chemical compound N1=CN=CC2=CC=CC=C21 JWVCLYRUEFBMGU-UHFFFAOYSA-N 0.000 description 1
230000005855 radiation Effects 0.000 description 1
229960004622 raloxifene Drugs 0.000 description 1
GZUITABIAKMVPG-UHFFFAOYSA-N raloxifene Chemical compound C1=CC(O)=CC=C1C1=C(C(=O)C=2C=CC(OCCN3CCCCC3)=CC=2)C2=CC=C(O)C=C2S1 GZUITABIAKMVPG-UHFFFAOYSA-N 0.000 description 1
230000009257 reactivity Effects 0.000 description 1
238000010188 recombinant method Methods 0.000 description 1
230000001105 regulatory effect Effects 0.000 description 1
238000007634 remodeling Methods 0.000 description 1
238000011160 research Methods 0.000 description 1
210000002345 respiratory system Anatomy 0.000 description 1
108091008146 restriction endonucleases Proteins 0.000 description 1
238000010839 reverse transcription Methods 0.000 description 1
230000002441 reversible effect Effects 0.000 description 1
PYWVYCXTNDRMGF-UHFFFAOYSA-N rhodamine B Chemical compound [Cl-].C=12C=CC(=[N+](CC)CC)C=C2OC2=CC(N(CC)CC)=CC=C2C=1C1=CC=CC=C1C(O)=O PYWVYCXTNDRMGF-UHFFFAOYSA-N 0.000 description 1
238000002702 ribosome display Methods 0.000 description 1
229960003522 roquinimex Drugs 0.000 description 1
239000012146 running buffer Substances 0.000 description 1
210000003079 salivary gland Anatomy 0.000 description 1
150000003839 salts Chemical class 0.000 description 1
229950009919 saracatinib Drugs 0.000 description 1
238000007423 screening assay Methods 0.000 description 1
239000006152 selective media Substances 0.000 description 1
JRPHGDYSKGJTKZ-UHFFFAOYSA-K selenophosphate Chemical compound [O-]P([O-])([O-])=[Se] JRPHGDYSKGJTKZ-UHFFFAOYSA-K 0.000 description 1
231100000489 sensitizer Toxicity 0.000 description 1
238000002864 sequence alignment Methods 0.000 description 1
210000000717 sertoli cell Anatomy 0.000 description 1
239000008159 sesame oil Substances 0.000 description 1
235000011803 sesame oil Nutrition 0.000 description 1
108091006024 signal transducing proteins Proteins 0.000 description 1
102000034285 signal transducing proteins Human genes 0.000 description 1
230000019491 signal transduction Effects 0.000 description 1
238000001542 size-exclusion chromatography Methods 0.000 description 1
210000003491 skin Anatomy 0.000 description 1
201000000849 skin cancer Diseases 0.000 description 1
108010010958 snake venom neurotoxin F Proteins 0.000 description 1
229910052708 sodium Inorganic materials 0.000 description 1
239000011780 sodium chloride Substances 0.000 description 1
239000001509 sodium citrate Substances 0.000 description 1
NLJMYIDDQXHKNR-UHFFFAOYSA-K sodium citrate Chemical compound O.O.[Na+].[Na+].[Na+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O NLJMYIDDQXHKNR-UHFFFAOYSA-K 0.000 description 1
238000002415 sodium dodecyl sulfate polyacrylamide gel electrophoresis Methods 0.000 description 1
229940054269 sodium pyruvate Drugs 0.000 description 1
239000008279 sol Substances 0.000 description 1
239000008247 solid mixture Substances 0.000 description 1
230000000392 somatic effect Effects 0.000 description 1
IVDHYUQIDRJSTI-UHFFFAOYSA-N sorafenib tosylate Chemical compound [H+].CC1=CC=C(S([O-])(=O)=O)C=C1.C1=NC(C(=O)NC)=CC(OC=2C=CC(NC(=O)NC=3C=C(C(Cl)=CC=3)C(F)(F)F)=CC=2)=C1 IVDHYUQIDRJSTI-UHFFFAOYSA-N 0.000 description 1
239000000600 sorbitol Substances 0.000 description 1
210000000952 spleen Anatomy 0.000 description 1
230000006641 stabilisation Effects 0.000 description 1
238000011105 stabilization Methods 0.000 description 1
239000003381 stabilizer Substances 0.000 description 1
238000010186 staining Methods 0.000 description 1
238000011146 sterile filtration Methods 0.000 description 1
238000003860 storage Methods 0.000 description 1
229960005322 streptomycin Drugs 0.000 description 1
238000012916 structural analysis Methods 0.000 description 1
238000010254 subcutaneous injection Methods 0.000 description 1
239000007929 subcutaneous injection Substances 0.000 description 1
150000005846 sugar alcohols Chemical class 0.000 description 1
150000008163 sugars Chemical class 0.000 description 1
229910052717 sulfur Inorganic materials 0.000 description 1
239000011593 sulfur Substances 0.000 description 1
229960001796 sunitinib Drugs 0.000 description 1
238000001356 surgical procedure Methods 0.000 description 1
230000007755 survival signaling Effects 0.000 description 1
201000004595 synovitis Diseases 0.000 description 1
230000009897 systematic effect Effects 0.000 description 1
229960001603 tamoxifen Drugs 0.000 description 1
150000004579 taxol derivatives Chemical class 0.000 description 1
230000002381 testicular Effects 0.000 description 1
201000003120 testicular cancer Diseases 0.000 description 1
238000012360 testing method Methods 0.000 description 1
210000001550 testis Anatomy 0.000 description 1
108010013645 tetranectin Proteins 0.000 description 1
229960003433 thalidomide Drugs 0.000 description 1
RYYWUUFWQRZTIU-UHFFFAOYSA-K thiophosphate Chemical compound [O-]P([O-])([O-])=S RYYWUUFWQRZTIU-UHFFFAOYSA-K 0.000 description 1
229960001196 thiotepa Drugs 0.000 description 1
208000008732 thymoma Diseases 0.000 description 1
201000002510 thyroid cancer Diseases 0.000 description 1
208000013077 thyroid gland carcinoma Diseases 0.000 description 1
210000002105 tongue Anatomy 0.000 description 1
229960005026 toremifene Drugs 0.000 description 1
XFCLJVABOIYOMF-QPLCGJKRSA-N toremifene Chemical compound C1=CC(OCCN(C)C)=CC=C1C(\C=1C=CC=CC=1)=C(\CCCl)C1=CC=CC=C1 XFCLJVABOIYOMF-QPLCGJKRSA-N 0.000 description 1
230000001988 toxicity Effects 0.000 description 1
231100000419 toxicity Toxicity 0.000 description 1
230000002463 transducing effect Effects 0.000 description 1
238000012546 transfer Methods 0.000 description 1
239000012581 transferrin Substances 0.000 description 1
230000009261 transgenic effect Effects 0.000 description 1
229960000575 trastuzumab Drugs 0.000 description 1
150000004654 triazenes Chemical class 0.000 description 1
QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 description 1
238000000870 ultraviolet spectroscopy Methods 0.000 description 1
ORHBXUUXSCNDEV-UHFFFAOYSA-N umbelliferone Chemical compound C1=CC(=O)OC2=CC(O)=CC=C21 ORHBXUUXSCNDEV-UHFFFAOYSA-N 0.000 description 1
HFTAFOQKODTIJY-UHFFFAOYSA-N umbelliferone Natural products Cc1cc2C=CC(=O)Oc2cc1OCC=CC(C)(C)O HFTAFOQKODTIJY-UHFFFAOYSA-N 0.000 description 1
238000011144 upstream manufacturing Methods 0.000 description 1
150000003672 ureas Chemical class 0.000 description 1
210000003932 urinary bladder Anatomy 0.000 description 1
230000002485 urinary effect Effects 0.000 description 1
210000002700 urine Anatomy 0.000 description 1
229960005356 urokinase Drugs 0.000 description 1
206010046766 uterine cancer Diseases 0.000 description 1
210000004291 uterus Anatomy 0.000 description 1
229960000241 vandetanib Drugs 0.000 description 1
230000006444 vascular growth Effects 0.000 description 1
235000015112 vegetable and seed oil Nutrition 0.000 description 1
239000008158 vegetable oil Substances 0.000 description 1
229940099039 velcade Drugs 0.000 description 1
108700026220 vif Genes Proteins 0.000 description 1
239000013603 viral vector Substances 0.000 description 1
238000012800 visualization Methods 0.000 description 1
210000003905 vulva Anatomy 0.000 description 1
229920003169 water-soluble polymer Polymers 0.000 description 1
239000001993 wax Substances 0.000 description 1