MX2011005257A - Moleculas biespecificas de union a receptor de factor de crecimiento epidermial/receptor i de factor de crecimiento tipo insulina (egfr/igfir). - Google Patents

Info

Publication number

MX2011005257A

MX2011005257A MX2011005257A MX2011005257A MX2011005257A MX 2011005257 A MX2011005257 A MX 2011005257A MX 2011005257 A MX2011005257 A MX 2011005257A MX 2011005257 A MX2011005257 A MX 2011005257A MX 2011005257 A MX2011005257 A MX 2011005257A

Authority

MX

Mexico

Prior art keywords

seq

amino acid

loop

acid sequence

binding

Prior art date

2008-11-24

Links

• Espacenet
• Global Dossier
• Discuss

• 238000009739 binding Methods 0.000 title claims abstract description 356
• 230000027455 binding Effects 0.000 title claims abstract description 355
• 108060006698 EGF receptor Proteins 0.000 title description 396
• 108090000623 proteins and genes Proteins 0.000 claims abstract description 192
• 102000004169 proteins and genes Human genes 0.000 claims abstract description 187
• 101001034652 Homo sapiens Insulin-like growth factor 1 receptor Proteins 0.000 claims abstract description 152
• 102100039688 Insulin-like growth factor 1 receptor Human genes 0.000 claims abstract description 152
• 239000013636 protein dimer Substances 0.000 claims abstract description 59
• 102000002090 Fibronectin type III Human genes 0.000 claims abstract description 3
• 108050009401 Fibronectin type III Proteins 0.000 claims abstract description 3
• 102000052116 epidermal growth factor receptor activity proteins Human genes 0.000 claims abstract 23
• 108700015053 epidermal growth factor receptor activity proteins Proteins 0.000 claims abstract 23
• 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 claims abstract 23
• 125000003275 alpha amino acid group Chemical group 0.000 claims description 512
• 150000001413 amino acids Chemical class 0.000 claims description 397
• 108090000765 processed proteins & peptides Proteins 0.000 claims description 96
• 102000004196 processed proteins & peptides Human genes 0.000 claims description 90
• 229920001184 polypeptide Polymers 0.000 claims description 85
• 229920001223 polyethylene glycol Polymers 0.000 claims description 81
• 239000002202 Polyethylene glycol Substances 0.000 claims description 48
• 102100037362 Fibronectin Human genes 0.000 claims description 28
• 108010067306 Fibronectins Proteins 0.000 claims description 28
• 239000000203 mixture Substances 0.000 claims description 27
• 239000003814 drug Substances 0.000 claims description 23
• 238000004519 manufacturing process Methods 0.000 claims description 8
• 239000002510 pyrogen Substances 0.000 claims description 5
• 125000003827 glycol group Chemical group 0.000 claims description 4
• 230000003463 hyperproliferative effect Effects 0.000 claims description 3
• 230000001225 therapeutic effect Effects 0.000 abstract description 19
• 239000012634 fragment Substances 0.000 abstract description 13
• 239000013598 vector Substances 0.000 abstract description 13
• 108091033319 polynucleotide Proteins 0.000 abstract description 5
• 239000002157 polynucleotide Substances 0.000 abstract description 5
• 102000040430 polynucleotide Human genes 0.000 abstract description 5
• 238000011160 research Methods 0.000 abstract description 4
• 102000001301 EGF receptor Human genes 0.000 description 392
• 235000001014 amino acid Nutrition 0.000 description 384
• 229940024606 amino acid Drugs 0.000 description 378
• 239000011230 binding agent Substances 0.000 description 303
• 210000004027 cell Anatomy 0.000 description 193
• 235000018102 proteins Nutrition 0.000 description 175
• 238000001542 size-exclusion chromatography Methods 0.000 description 113
• 206010028980 Neoplasm Diseases 0.000 description 106
• 239000003795 chemical substances by application Substances 0.000 description 86
• 238000000034 method Methods 0.000 description 73
• XUJNEKJLAYXESH-REOHCLBHSA-N L-Cysteine Chemical compound SC[C@H](N)C(O)=O XUJNEKJLAYXESH-REOHCLBHSA-N 0.000 description 70
• 239000000178 monomer Substances 0.000 description 68
• FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 59
• 239000003550 marker Substances 0.000 description 56
• 238000006467 substitution reaction Methods 0.000 description 50
• MTCFGRXMJLQNBG-REOHCLBHSA-N (2S)-2-Amino-3-hydroxypropansäure Chemical compound OC[C@H](N)C(O)=O MTCFGRXMJLQNBG-REOHCLBHSA-N 0.000 description 44
• 230000026731 phosphorylation Effects 0.000 description 42
• 238000006366 phosphorylation reaction Methods 0.000 description 42
• 241000282414 Homo sapiens Species 0.000 description 41
• 210000004899 c-terminal region Anatomy 0.000 description 38
• 230000005764 inhibitory process Effects 0.000 description 38
• 230000000694 effects Effects 0.000 description 35
• 102100033237 Pro-epidermal growth factor Human genes 0.000 description 34
• 125000000539 amino acid group Chemical group 0.000 description 34
• 238000003556 assay Methods 0.000 description 34
• 241000699670 Mus sp. Species 0.000 description 30
• 239000003446 ligand Substances 0.000 description 30
• 239000011780 sodium chloride Substances 0.000 description 30
• 241000699666 Mus <mouse, genus> Species 0.000 description 25
• 239000002609 medium Substances 0.000 description 25
• RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 24
• 102000005962 receptors Human genes 0.000 description 24
• 108020003175 receptors Proteins 0.000 description 24
• 238000012217 deletion Methods 0.000 description 23
• 230000037430 deletion Effects 0.000 description 23
• LOKCTEFSRHRXRJ-UHFFFAOYSA-I dipotassium trisodium dihydrogen phosphate hydrogen phosphate dichloride Chemical compound P(=O)(O)(O)[O-].[K+].P(=O)(O)([O-])[O-].[Na+].[Na+].[Cl-].[K+].[Cl-].[Na+] LOKCTEFSRHRXRJ-UHFFFAOYSA-I 0.000 description 23
• 239000002953 phosphate buffered saline Substances 0.000 description 23
• 238000011282 treatment Methods 0.000 description 22
• DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 21
• 238000007792 addition Methods 0.000 description 21
• 150000007523 nucleic acids Chemical class 0.000 description 21
• 238000004458 analytical method Methods 0.000 description 20
• 229960005395 cetuximab Drugs 0.000 description 20
• 238000002965 ELISA Methods 0.000 description 18
• 239000004230 Fast Yellow AB Substances 0.000 description 18
• 210000002966 serum Anatomy 0.000 description 18
• 150000001875 compounds Chemical class 0.000 description 17
• XEEYBQQBJWHFJM-UHFFFAOYSA-N iron Substances [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 17
• 229960001972 panitumumab Drugs 0.000 description 17
• 201000011510 cancer Diseases 0.000 description 16
• 229940079593 drug Drugs 0.000 description 16
• 108020004707 nucleic acids Proteins 0.000 description 16
• 102000039446 nucleic acids Human genes 0.000 description 16
• 229920000642 polymer Polymers 0.000 description 16
• 230000014509 gene expression Effects 0.000 description 15
• 101000599951 Homo sapiens Insulin-like growth factor I Proteins 0.000 description 14
• 102100037852 Insulin-like growth factor I Human genes 0.000 description 14
• -1 VEGF3) Proteins 0.000 description 14
• 239000000872 buffer Substances 0.000 description 14
• 230000006320 pegylation Effects 0.000 description 14
• 230000004913 activation Effects 0.000 description 13
• 239000003153 chemical reaction reagent Substances 0.000 description 12
• 230000011664 signaling Effects 0.000 description 12
• 108090000723 Insulin-Like Growth Factor I Proteins 0.000 description 11
• 241001465754 Metazoa Species 0.000 description 11
• 102100033810 RAC-alpha serine/threonine-protein kinase Human genes 0.000 description 11
• 125000000151 cysteine group Chemical group N[C@@H](CS)C(=O)* 0.000 description 11
• 239000000539 dimer Substances 0.000 description 11
• 238000003780 insertion Methods 0.000 description 11
• 230000037431 insertion Effects 0.000 description 11
• 238000012360 testing method Methods 0.000 description 11
• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 11
• 102100031968 Ephrin type-B receptor 2 Human genes 0.000 description 10
• MTCFGRXMJLQNBG-UHFFFAOYSA-N Serine Natural products OCC(N)C(O)=O MTCFGRXMJLQNBG-UHFFFAOYSA-N 0.000 description 10
• 210000001744 T-lymphocyte Anatomy 0.000 description 10
• 230000004075 alteration Effects 0.000 description 10
• 230000021615 conjugation Effects 0.000 description 10
• 230000012010 growth Effects 0.000 description 10
• 238000001727 in vivo Methods 0.000 description 10
• 239000000463 material Substances 0.000 description 10
• 238000005259 measurement Methods 0.000 description 10
• 239000012071 phase Substances 0.000 description 10
• 230000036515 potency Effects 0.000 description 10
• 230000035755 proliferation Effects 0.000 description 10
• 229910000162 sodium phosphate Inorganic materials 0.000 description 10
• 230000014616 translation Effects 0.000 description 10
• 230000000259 anti-tumor effect Effects 0.000 description 9
• 235000018417 cysteine Nutrition 0.000 description 9
• XUJNEKJLAYXESH-UHFFFAOYSA-N cysteine Natural products SCC(N)C(O)=O XUJNEKJLAYXESH-UHFFFAOYSA-N 0.000 description 9
• 238000010494 dissociation reaction Methods 0.000 description 9
• 230000005593 dissociations Effects 0.000 description 9
• 238000009472 formulation Methods 0.000 description 9
• 230000005847 immunogenicity Effects 0.000 description 9
• 238000002513 implantation Methods 0.000 description 9
• 101100301828 Arabidopsis thaliana RH41 gene Proteins 0.000 description 8
• 108091035707 Consensus sequence Proteins 0.000 description 8
• 241000588724 Escherichia coli Species 0.000 description 8
• 102000004218 Insulin-Like Growth Factor I Human genes 0.000 description 8
• QXOHLNCNYLGICT-YFKPBYRVSA-N Met-Gly Chemical group CSCC[C@H](N)C(=O)NCC(O)=O QXOHLNCNYLGICT-YFKPBYRVSA-N 0.000 description 8
• 230000015556 catabolic process Effects 0.000 description 8
• 238000005119 centrifugation Methods 0.000 description 8
• 238000006731 degradation reaction Methods 0.000 description 8
• 238000000502 dialysis Methods 0.000 description 8
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 8
• 239000013604 expression vector Substances 0.000 description 8
• 230000001976 improved effect Effects 0.000 description 8
• 238000007912 intraperitoneal administration Methods 0.000 description 8
• 108010005942 methionylglycine Proteins 0.000 description 8
• 230000003389 potentiating effect Effects 0.000 description 8
• JKMHFZQWWAIEOD-UHFFFAOYSA-N 2-[4-(2-hydroxyethyl)piperazin-1-yl]ethanesulfonic acid Chemical compound OCC[NH+]1CCN(CCS([O-])(=O)=O)CC1 JKMHFZQWWAIEOD-UHFFFAOYSA-N 0.000 description 7
• LQVXSNNAFNGRAH-QHCPKHFHSA-N BMS-754807 Chemical compound C([C@@]1(C)C(=O)NC=2C=NC(F)=CC=2)CCN1C(=NN1C=CC=C11)N=C1NC(=NN1)C=C1C1CC1 LQVXSNNAFNGRAH-QHCPKHFHSA-N 0.000 description 7
• 108020004414 DNA Proteins 0.000 description 7
• OUYCCCASQSFEME-QMMMGPOBSA-N L-tyrosine Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-QMMMGPOBSA-N 0.000 description 7
• 241000699660 Mus musculus Species 0.000 description 7
• 108010076504 Protein Sorting Signals Proteins 0.000 description 7
• 239000012980 RPMI-1640 medium Substances 0.000 description 7
• 238000012300 Sequence Analysis Methods 0.000 description 7
• 239000000427 antigen Substances 0.000 description 7
• 108091007433 antigens Proteins 0.000 description 7
• 102000036639 antigens Human genes 0.000 description 7
• 230000001580 bacterial effect Effects 0.000 description 7
• 230000004071 biological effect Effects 0.000 description 7
• 230000005754 cellular signaling Effects 0.000 description 7
• 238000006243 chemical reaction Methods 0.000 description 7
• 238000011156 evaluation Methods 0.000 description 7
• 239000012091 fetal bovine serum Substances 0.000 description 7
• 238000000338 in vitro Methods 0.000 description 7
• 239000007924 injection Substances 0.000 description 7
• 238000002347 injection Methods 0.000 description 7
• 239000006166 lysate Substances 0.000 description 7
• 230000003472 neutralizing effect Effects 0.000 description 7
• 238000011580 nude mouse model Methods 0.000 description 7
• 239000008188 pellet Substances 0.000 description 7
• 239000000523 sample Substances 0.000 description 7
• 230000019491 signal transduction Effects 0.000 description 7
• 241000894007 species Species 0.000 description 7
• 230000000638 stimulation Effects 0.000 description 7
• 238000013519 translation Methods 0.000 description 7
• 230000004614 tumor growth Effects 0.000 description 7
• OUYCCCASQSFEME-UHFFFAOYSA-N tyrosine Natural products OC(=O)C(N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-UHFFFAOYSA-N 0.000 description 7
• 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 6
• WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 6
• PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 6
• 229910019142 PO4 Inorganic materials 0.000 description 6
• 229920001213 Polysorbate 20 Polymers 0.000 description 6
• 102000004278 Receptor Protein-Tyrosine Kinases Human genes 0.000 description 6
• 108090000873 Receptor Protein-Tyrosine Kinases Proteins 0.000 description 6
• 240000004808 Saccharomyces cerevisiae Species 0.000 description 6
• VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 6
• 230000002776 aggregation Effects 0.000 description 6
• 238000004220 aggregation Methods 0.000 description 6
• 230000015572 biosynthetic process Effects 0.000 description 6
• 230000000903 blocking effect Effects 0.000 description 6
• 102220347773 c.185C>G Human genes 0.000 description 6
• 239000002254 cytotoxic agent Substances 0.000 description 6
• 238000010828 elution Methods 0.000 description 6
• 238000002474 experimental method Methods 0.000 description 6
• 108020001507 fusion proteins Proteins 0.000 description 6
• 102000037865 fusion proteins Human genes 0.000 description 6
• 238000002523 gelfiltration Methods 0.000 description 6
• 238000004128 high performance liquid chromatography Methods 0.000 description 6
• 230000001965 increasing effect Effects 0.000 description 6
• NOESYZHRGYRDHS-UHFFFAOYSA-N insulin Chemical compound N1C(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(NC(=O)CN)C(C)CC)CSSCC(C(NC(CO)C(=O)NC(CC(C)C)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CCC(N)=O)C(=O)NC(CC(C)C)C(=O)NC(CCC(O)=O)C(=O)NC(CC(N)=O)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CSSCC(NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2C=CC(O)=CC=2)NC(=O)C(CC(C)C)NC(=O)C(C)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2NC=NC=2)NC(=O)C(CO)NC(=O)CNC2=O)C(=O)NCC(=O)NC(CCC(O)=O)C(=O)NC(CCCNC(N)=N)C(=O)NCC(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC(O)=CC=3)C(=O)NC(C(C)O)C(=O)N3C(CCC3)C(=O)NC(CCCCN)C(=O)NC(C)C(O)=O)C(=O)NC(CC(N)=O)C(O)=O)=O)NC(=O)C(C(C)CC)NC(=O)C(CO)NC(=O)C(C(C)O)NC(=O)C1CSSCC2NC(=O)C(CC(C)C)NC(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CC(N)=O)NC(=O)C(NC(=O)C(N)CC=1C=CC=CC=1)C(C)C)CC1=CN=CN1 NOESYZHRGYRDHS-UHFFFAOYSA-N 0.000 description 6
• 239000012139 lysis buffer Substances 0.000 description 6
• 210000004962 mammalian cell Anatomy 0.000 description 6
• 108020004999 messenger RNA Proteins 0.000 description 6
• 239000002773 nucleotide Substances 0.000 description 6
• 125000003729 nucleotide group Chemical group 0.000 description 6
• 235000021317 phosphate Nutrition 0.000 description 6
• 239000000256 polyoxyethylene sorbitan monolaurate Substances 0.000 description 6
• 235000010486 polyoxyethylene sorbitan monolaurate Nutrition 0.000 description 6
• 239000000047 product Substances 0.000 description 6
• 230000004044 response Effects 0.000 description 6
• 239000000243 solution Substances 0.000 description 6
• 229940124597 therapeutic agent Drugs 0.000 description 6
• 229910052720 vanadium Inorganic materials 0.000 description 6
• 239000003981 vehicle Substances 0.000 description 6
• IYMAXBFPHPZYIK-BQBZGAKWSA-N Arg-Gly-Asp Chemical compound NC(N)=NCCC[C@H](N)C(=O)NCC(=O)N[C@@H](CC(O)=O)C(O)=O IYMAXBFPHPZYIK-BQBZGAKWSA-N 0.000 description 5
• 241000282693 Cercopithecidae Species 0.000 description 5
• 239000004471 Glycine Substances 0.000 description 5
• 108060003951 Immunoglobulin Proteins 0.000 description 5
• 241000124008 Mammalia Species 0.000 description 5
• 108091028043 Nucleic acid sequence Proteins 0.000 description 5
• 241000700159 Rattus Species 0.000 description 5
• 239000012505 Superdex™ Substances 0.000 description 5
• 239000013504 Triton X-100 Substances 0.000 description 5
• 229920004890 Triton X-100 Polymers 0.000 description 5
• 230000001413 cellular effect Effects 0.000 description 5
• 238000004587 chromatography analysis Methods 0.000 description 5
• 229940127089 cytotoxic agent Drugs 0.000 description 5
• 231100000599 cytotoxic agent Toxicity 0.000 description 5
• 230000003247 decreasing effect Effects 0.000 description 5
• 208000035475 disorder Diseases 0.000 description 5
• 230000006870 function Effects 0.000 description 5
• 239000001963 growth medium Substances 0.000 description 5
• 238000003119 immunoblot Methods 0.000 description 5
• 102000018358 immunoglobulin Human genes 0.000 description 5
• 238000003121 in-cell western assay Methods 0.000 description 5
• 238000011068 loading method Methods 0.000 description 5
• 208000002154 non-small cell lung carcinoma Diseases 0.000 description 5
• 239000010452 phosphate Substances 0.000 description 5
• NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 5
• 238000002360 preparation method Methods 0.000 description 5
• 238000000746 purification Methods 0.000 description 5
• 230000002829 reductive effect Effects 0.000 description 5
• 230000001105 regulatory effect Effects 0.000 description 5
• 238000002415 sodium dodecyl sulfate polyacrylamide gel electrophoresis Methods 0.000 description 5
• 238000002198 surface plasmon resonance spectroscopy Methods 0.000 description 5
• 238000003786 synthesis reaction Methods 0.000 description 5
• 210000001519 tissue Anatomy 0.000 description 5
• 238000013518 transcription Methods 0.000 description 5
• 230000035897 transcription Effects 0.000 description 5
• 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 4
• 102000007469 Actins Human genes 0.000 description 4
• 108010085238 Actins Proteins 0.000 description 4
• IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 4
• 206010006187 Breast cancer Diseases 0.000 description 4
• AOJJSUZBOXZQNB-TZSSRYMLSA-N Doxorubicin Chemical compound O([C@H]1C[C@@](O)(CC=2C(O)=C3C(=O)C=4C=CC=C(C=4C(=O)C3=C(O)C=21)OC)C(=O)CO)[C@H]1C[C@H](N)[C@H](O)[C@H](C)O1 AOJJSUZBOXZQNB-TZSSRYMLSA-N 0.000 description 4
• 101150086096 Eif2ak3 gene Proteins 0.000 description 4
• 102000004190 Enzymes Human genes 0.000 description 4
• 108090000790 Enzymes Proteins 0.000 description 4
• 241000238631 Hexapoda Species 0.000 description 4
• TWRXJAOTZQYOKJ-UHFFFAOYSA-L Magnesium chloride Chemical compound [Mg+2].[Cl-].[Cl-] TWRXJAOTZQYOKJ-UHFFFAOYSA-L 0.000 description 4
• 108091005804 Peptidases Proteins 0.000 description 4
• 239000002253 acid Substances 0.000 description 4
• 125000003277 amino group Chemical group 0.000 description 4
• 229920000249 biocompatible polymer Polymers 0.000 description 4
• 239000007767 bonding agent Substances 0.000 description 4
• 238000010367 cloning Methods 0.000 description 4
• 238000010276 construction Methods 0.000 description 4
• 230000007423 decrease Effects 0.000 description 4
• 238000000113 differential scanning calorimetry Methods 0.000 description 4
• 238000006471 dimerization reaction Methods 0.000 description 4
• 239000002158 endotoxin Substances 0.000 description 4
• 229940088598 enzyme Drugs 0.000 description 4
• 230000013595 glycosylation Effects 0.000 description 4
• 238000006206 glycosylation reaction Methods 0.000 description 4
• 239000012216 imaging agent Substances 0.000 description 4
• 230000002163 immunogen Effects 0.000 description 4
• 238000000099 in vitro assay Methods 0.000 description 4
• 102000006495 integrins Human genes 0.000 description 4
• 108010044426 integrins Proteins 0.000 description 4
• 229910052742 iron Inorganic materials 0.000 description 4
• BPHPUYQFMNQIOC-NXRLNHOXSA-N isopropyl beta-D-thiogalactopyranoside Chemical compound CC(C)S[C@@H]1O[C@H](CO)[C@H](O)[C@H](O)[C@H]1O BPHPUYQFMNQIOC-NXRLNHOXSA-N 0.000 description 4
• 229930027917 kanamycin Natural products 0.000 description 4
• SBUJHOSQTJFQJX-NOAMYHISSA-N kanamycin Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CN)O[C@@H]1O[C@H]1[C@H](O)[C@@H](O[C@@H]2[C@@H]([C@@H](N)[C@H](O)[C@@H](CO)O2)O)[C@H](N)C[C@@H]1N SBUJHOSQTJFQJX-NOAMYHISSA-N 0.000 description 4
• 229960000318 kanamycin Drugs 0.000 description 4
• 229930182823 kanamycin A Natural products 0.000 description 4
• 238000013507 mapping Methods 0.000 description 4
• BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 4
• 230000004048 modification Effects 0.000 description 4
• 238000012986 modification Methods 0.000 description 4
• 230000035772 mutation Effects 0.000 description 4
• 230000037361 pathway Effects 0.000 description 4
• 239000000137 peptide hydrolase inhibitor Substances 0.000 description 4
• 239000000546 pharmaceutical excipient Substances 0.000 description 4
• 230000003285 pharmacodynamic effect Effects 0.000 description 4
• 230000004481 post-translational protein modification Effects 0.000 description 4
• 230000002285 radioactive effect Effects 0.000 description 4
• 150000003839 salts Chemical class 0.000 description 4
• 238000013207 serial dilution Methods 0.000 description 4
• 238000007920 subcutaneous administration Methods 0.000 description 4
• 235000000346 sugar Nutrition 0.000 description 4
• 238000012546 transfer Methods 0.000 description 4
• 210000005253 yeast cell Anatomy 0.000 description 4
• OOIBFPKQHULHSQ-UHFFFAOYSA-N (3-hydroxy-1-adamantyl) 2-methylprop-2-enoate Chemical compound C1C(C2)CC3CC2(O)CC1(OC(=O)C(=C)C)C3 OOIBFPKQHULHSQ-UHFFFAOYSA-N 0.000 description 3
• UMCMPZBLKLEWAF-BCTGSCMUSA-N 3-[(3-cholamidopropyl)dimethylammonio]propane-1-sulfonate Chemical compound C([C@H]1C[C@H]2O)[C@H](O)CC[C@]1(C)[C@@H]1[C@@H]2[C@@H]2CC[C@H]([C@@H](CCC(=O)NCCC[N+](C)(C)CCCS([O-])(=O)=O)C)[C@@]2(C)[C@@H](O)C1 UMCMPZBLKLEWAF-BCTGSCMUSA-N 0.000 description 3
• QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 3
• WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
• 238000000035 BCA protein assay Methods 0.000 description 3
• 108091003079 Bovine Serum Albumin Proteins 0.000 description 3
• 208000026310 Breast neoplasm Diseases 0.000 description 3
• 201000009030 Carcinoma Diseases 0.000 description 3
• 206010009944 Colon cancer Diseases 0.000 description 3
• 239000006144 Dulbecco’s modified Eagle's medium Substances 0.000 description 3
• LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical group OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 3
• 108091008794 FGF receptors Proteins 0.000 description 3
• BCCRXDTUTZHDEU-VKHMYHEASA-N Gly-Ser Chemical compound NCC(=O)N[C@@H](CO)C(O)=O BCCRXDTUTZHDEU-VKHMYHEASA-N 0.000 description 3
• 102100031181 Glyceraldehyde-3-phosphate dehydrogenase Human genes 0.000 description 3
• 101000851007 Homo sapiens Vascular endothelial growth factor receptor 2 Proteins 0.000 description 3
• 102000004877 Insulin Human genes 0.000 description 3
• 108090001061 Insulin Proteins 0.000 description 3
• 102000003746 Insulin Receptor Human genes 0.000 description 3
• 108010001127 Insulin Receptor Proteins 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
• 101500021084 Locusta migratoria 5 kDa peptide Proteins 0.000 description 3
• 102000043131 MHC class II family Human genes 0.000 description 3
• 108091054438 MHC class II family Proteins 0.000 description 3
• 108091006006 PEGylated Proteins Proteins 0.000 description 3
• 239000004365 Protease Substances 0.000 description 3
• 229940124158 Protease/peptidase inhibitor Drugs 0.000 description 3
• 102000004022 Protein-Tyrosine Kinases Human genes 0.000 description 3
• 108090000412 Protein-Tyrosine Kinases Proteins 0.000 description 3
• 102100037486 Reverse transcriptase/ribonuclease H Human genes 0.000 description 3
• 108010071390 Serum Albumin Proteins 0.000 description 3
• 102000007562 Serum Albumin Human genes 0.000 description 3
• HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
• 102000013275 Somatomedins Human genes 0.000 description 3
• AYFVYJQAPQTCCC-UHFFFAOYSA-N Threonine Natural products CC(O)C(N)C(O)=O AYFVYJQAPQTCCC-UHFFFAOYSA-N 0.000 description 3
• 239000004473 Threonine Substances 0.000 description 3
• IQFYYKKMVGJFEH-XLPZGREQSA-N Thymidine Chemical compound O=C1NC(=O)C(C)=CN1[C@@H]1O[C@H](CO)[C@@H](O)C1 IQFYYKKMVGJFEH-XLPZGREQSA-N 0.000 description 3
• 102000006747 Transforming Growth Factor alpha Human genes 0.000 description 3
• 101800004564 Transforming growth factor alpha Proteins 0.000 description 3
• 102100033177 Vascular endothelial growth factor receptor 2 Human genes 0.000 description 3
• 239000004480 active ingredient Substances 0.000 description 3
• 239000012830 cancer therapeutic Substances 0.000 description 3
• 230000008859 change Effects 0.000 description 3
• 238000012512 characterization method Methods 0.000 description 3
• 238000003776 cleavage reaction Methods 0.000 description 3
• 230000004540 complement-dependent cytotoxicity Effects 0.000 description 3
• 230000034994 death Effects 0.000 description 3
• 231100000517 death Toxicity 0.000 description 3
• 238000001514 detection method Methods 0.000 description 3
• 239000003085 diluting agent Substances 0.000 description 3
• 201000010099 disease Diseases 0.000 description 3
• 238000005516 engineering process Methods 0.000 description 3
• 230000007717 exclusion Effects 0.000 description 3
• 238000001914 filtration Methods 0.000 description 3
• 230000004927 fusion Effects 0.000 description 3
• 108020004445 glyceraldehyde-3-phosphate dehydrogenase Proteins 0.000 description 3
• 239000003102 growth factor Substances 0.000 description 3
• 229960000789 guanidine hydrochloride Drugs 0.000 description 3
• PJJJBBJSCAKJQF-UHFFFAOYSA-N guanidinium chloride Chemical compound [Cl-].NC(N)=[NH2+] PJJJBBJSCAKJQF-UHFFFAOYSA-N 0.000 description 3
• 238000003384 imaging method Methods 0.000 description 3
• 238000011534 incubation Methods 0.000 description 3
• 239000003112 inhibitor Substances 0.000 description 3
• 229940125396 insulin Drugs 0.000 description 3
• 238000012417 linear regression Methods 0.000 description 3
• 125000005647 linker group Chemical group 0.000 description 3
• 239000007788 liquid Substances 0.000 description 3
• 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 3
• 229910052751 metal Inorganic materials 0.000 description 3
• 239000002184 metal Substances 0.000 description 3
• 230000035407 negative regulation of cell proliferation Effects 0.000 description 3
• 229950010203 nimotuzumab Drugs 0.000 description 3
• 239000013612 plasmid Substances 0.000 description 3
• 238000012545 processing Methods 0.000 description 3
• 210000001236 prokaryotic cell Anatomy 0.000 description 3
• 235000019419 proteases Nutrition 0.000 description 3
• 239000011347 resin Substances 0.000 description 3
• 229920005989 resin Polymers 0.000 description 3
• 201000009410 rhabdomyosarcoma Diseases 0.000 description 3
• 230000007017 scission Effects 0.000 description 3
• 239000007787 solid Substances 0.000 description 3
• 125000006850 spacer group Chemical group 0.000 description 3
• 230000009870 specific binding Effects 0.000 description 3
• 239000006228 supernatant Substances 0.000 description 3
• 239000003826 tablet Substances 0.000 description 3
• 238000011269 treatment regimen Methods 0.000 description 3
• 239000003643 water by type Substances 0.000 description 3
• KZNQNBZMBZJQJO-UHFFFAOYSA-N 1-(2-azaniumylacetyl)pyrrolidine-2-carboxylate Chemical compound NCC(=O)N1CCCC1C(O)=O KZNQNBZMBZJQJO-UHFFFAOYSA-N 0.000 description 2
• OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 2
• SJVJMFXCINSXFF-UHFFFAOYSA-N 5-(5-prop-1-ynylthiophen-2-yl)thiophene-2-carboxylic acid Chemical compound S1C(C#CC)=CC=C1C1=CC=C(C(O)=O)S1 SJVJMFXCINSXFF-UHFFFAOYSA-N 0.000 description 2
• 102000008102 Ankyrins Human genes 0.000 description 2
• 108010049777 Ankyrins Proteins 0.000 description 2
• 241000894006 Bacteria Species 0.000 description 2
• 108091026890 Coding region Proteins 0.000 description 2
• 108020004705 Codon Proteins 0.000 description 2
• 108700010070 Codon Usage Proteins 0.000 description 2
• 108010047041 Complementarity Determining Regions Proteins 0.000 description 2
• KDXKERNSBIXSRK-RXMQYKEDSA-N D-lysine Chemical compound NCCCC[C@@H](N)C(O)=O KDXKERNSBIXSRK-RXMQYKEDSA-N 0.000 description 2
• 208000030453 Drug-Related Side Effects and Adverse reaction Diseases 0.000 description 2
• 241000196324 Embryophyta Species 0.000 description 2
• 229910052693 Europium Inorganic materials 0.000 description 2
• 102000044168 Fibroblast Growth Factor Receptor Human genes 0.000 description 2
• WHUUTDBJXJRKMK-UHFFFAOYSA-N Glutamic acid Natural products OC(=O)C(N)CCC(O)=O WHUUTDBJXJRKMK-UHFFFAOYSA-N 0.000 description 2
• 101001027128 Homo sapiens Fibronectin Proteins 0.000 description 2
• 101000851018 Homo sapiens Vascular endothelial growth factor receptor 1 Proteins 0.000 description 2
• VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
• 102000048143 Insulin-Like Growth Factor II Human genes 0.000 description 2
• 108090001117 Insulin-Like Growth Factor II Proteins 0.000 description 2
• QNAYBMKLOCPYGJ-REOHCLBHSA-N L-alanine Chemical compound C[C@H](N)C(O)=O QNAYBMKLOCPYGJ-REOHCLBHSA-N 0.000 description 2
• DCXYFEDJOCDNAF-REOHCLBHSA-N L-asparagine Chemical compound OC(=O)[C@@H](N)CC(N)=O DCXYFEDJOCDNAF-REOHCLBHSA-N 0.000 description 2
• WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 description 2
• KDXKERNSBIXSRK-YFKPBYRVSA-N L-lysine Chemical compound NCCCC[C@H](N)C(O)=O KDXKERNSBIXSRK-YFKPBYRVSA-N 0.000 description 2
• AYFVYJQAPQTCCC-GBXIJSLDSA-N L-threonine Chemical compound C[C@@H](O)[C@H](N)C(O)=O AYFVYJQAPQTCCC-GBXIJSLDSA-N 0.000 description 2
• KZSNJWFQEVHDMF-BYPYZUCNSA-N L-valine Chemical compound CC(C)[C@H](N)C(O)=O KZSNJWFQEVHDMF-BYPYZUCNSA-N 0.000 description 2
• KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 2
• 102000043136 MAP kinase family Human genes 0.000 description 2
• 108091054455 MAP kinase family Proteins 0.000 description 2
• PEEHTFAAVSWFBL-UHFFFAOYSA-N Maleimide Chemical compound O=C1NC(=O)C=C1 PEEHTFAAVSWFBL-UHFFFAOYSA-N 0.000 description 2
• 206010027476 Metastases Diseases 0.000 description 2
• 101100335081 Mus musculus Flt3 gene Proteins 0.000 description 2
• 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 2
• 108091007960 PI3Ks Proteins 0.000 description 2
• 102000003993 Phosphatidylinositol 3-kinases Human genes 0.000 description 2
• 108090000430 Phosphatidylinositol 3-kinases Proteins 0.000 description 2
• NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
• 108010038512 Platelet-Derived Growth Factor Proteins 0.000 description 2
• 102000010780 Platelet-Derived Growth Factor Human genes 0.000 description 2
• 108010029485 Protein Isoforms Proteins 0.000 description 2
• 102000001708 Protein Isoforms Human genes 0.000 description 2
• 108010014608 Proto-Oncogene Proteins c-kit Proteins 0.000 description 2
• 102000016971 Proto-Oncogene Proteins c-kit Human genes 0.000 description 2
• 241000589516 Pseudomonas Species 0.000 description 2
• 108020004511 Recombinant DNA Proteins 0.000 description 2
• 241000235070 Saccharomyces Species 0.000 description 2
• PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 2
• QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 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
• 229940123237 Taxane Drugs 0.000 description 2
• 102100024554 Tetranectin Human genes 0.000 description 2
• 206010070863 Toxicity to various agents Diseases 0.000 description 2
• 102000004338 Transferrin Human genes 0.000 description 2
• 108090000901 Transferrin Proteins 0.000 description 2
• 239000007983 Tris buffer Substances 0.000 description 2
• KZSNJWFQEVHDMF-UHFFFAOYSA-N Valine Natural products CC(C)C(N)C(O)=O KZSNJWFQEVHDMF-UHFFFAOYSA-N 0.000 description 2
• 108010073929 Vascular Endothelial Growth Factor A Proteins 0.000 description 2
• 108010019530 Vascular Endothelial Growth Factors Proteins 0.000 description 2
• 102100039037 Vascular endothelial growth factor A Human genes 0.000 description 2
• 102100033178 Vascular endothelial growth factor receptor 1 Human genes 0.000 description 2
• 241000251539 Vertebrata <Metazoa> Species 0.000 description 2
• SIIZPVYVXNXXQG-UQTMIEBXSA-N [(2r,3r,4r,5r)-5-(6-aminopurin-9-yl)-4-[[(2r,3s,4r,5r)-5-(6-aminopurin-9-yl)-3,4-dihydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-3-hydroxyoxolan-2-yl]methyl [(2r,3r,4r,5r)-2-(6-aminopurin-9-yl)-4-hydroxy-5-(phosphonooxymethyl)oxolan-3-yl] hydrogen phos Chemical compound C1=NC2=C(N)N=CN=C2N1[C@@H]1O[C@H](COP(O)(=O)O[C@H]2[C@@H](O[C@H](COP(O)(O)=O)[C@H]2O)N2C3=NC=NC(N)=C3N=C2)[C@@H](O)[C@H]1OP(O)(=O)OC[C@H]([C@@H](O)[C@H]1O)O[C@H]1N1C(N=CN=C2N)=C2N=C1 SIIZPVYVXNXXQG-UQTMIEBXSA-N 0.000 description 2
• 239000006096 absorbing agent Substances 0.000 description 2
• 238000009825 accumulation Methods 0.000 description 2
• OIRDTQYFTABQOQ-KQYNXXCUSA-N adenosine Chemical compound C1=NC=2C(N)=NC=NC=2N1[C@@H]1O[C@H](CO)[C@@H](O)[C@H]1O OIRDTQYFTABQOQ-KQYNXXCUSA-N 0.000 description 2
• 235000004279 alanine Nutrition 0.000 description 2
• 125000003295 alanine group Chemical group N[C@@H](C)C(=O)* 0.000 description 2
• 230000001028 anti-proliverative effect Effects 0.000 description 2
• 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 2
• 230000008901 benefit Effects 0.000 description 2
• IQFYYKKMVGJFEH-UHFFFAOYSA-N beta-L-thymidine Natural products O=C1NC(=O)C(C)=CN1C1OC(CO)C(O)C1 IQFYYKKMVGJFEH-UHFFFAOYSA-N 0.000 description 2
• 239000012148 binding buffer Substances 0.000 description 2
• 238000013378 biophysical characterization Methods 0.000 description 2
• 238000001574 biopsy Methods 0.000 description 2
• 210000004369 blood Anatomy 0.000 description 2
• 239000008280 blood Substances 0.000 description 2
• 210000000481 breast Anatomy 0.000 description 2
• 229960004562 carboplatin Drugs 0.000 description 2
• 238000005277 cation exchange chromatography Methods 0.000 description 2
• 230000004663 cell proliferation Effects 0.000 description 2
• 238000001516 cell proliferation assay Methods 0.000 description 2
• 108091092356 cellular DNA Proteins 0.000 description 2
• JCKYGMPEJWAADB-UHFFFAOYSA-N chlorambucil Chemical compound OC(=O)CCCC1=CC=C(N(CCCl)CCCl)C=C1 JCKYGMPEJWAADB-UHFFFAOYSA-N 0.000 description 2
• 229960004630 chlorambucil Drugs 0.000 description 2
• DQLATGHUWYMOKM-UHFFFAOYSA-L cisplatin Chemical compound N[Pt](N)(Cl)Cl DQLATGHUWYMOKM-UHFFFAOYSA-L 0.000 description 2
• 229960004316 cisplatin Drugs 0.000 description 2
• 230000005757 colony formation Effects 0.000 description 2
• 230000001268 conjugating effect Effects 0.000 description 2
• 230000008878 coupling Effects 0.000 description 2
• 238000010168 coupling process Methods 0.000 description 2
• 238000005859 coupling reaction Methods 0.000 description 2
• 230000009089 cytolysis Effects 0.000 description 2
• 210000000172 cytosol Anatomy 0.000 description 2
• 239000000824 cytostatic agent Substances 0.000 description 2
• 231100000433 cytotoxic Toxicity 0.000 description 2
• 230000001472 cytotoxic effect Effects 0.000 description 2
• 238000004807 desolvation Methods 0.000 description 2
• 238000011161 development Methods 0.000 description 2
• 230000018109 developmental process Effects 0.000 description 2
• 239000006185 dispersion Substances 0.000 description 2
• 230000007783 downstream signaling Effects 0.000 description 2
• 229960004679 doxorubicin Drugs 0.000 description 2
• 239000012149 elution buffer Substances 0.000 description 2
• 231100000655 enterotoxin Toxicity 0.000 description 2
• 210000003527 eukaryotic cell Anatomy 0.000 description 2
• OGPBJKLSAFTDLK-UHFFFAOYSA-N europium atom Chemical compound [Eu] OGPBJKLSAFTDLK-UHFFFAOYSA-N 0.000 description 2
• 230000005284 excitation Effects 0.000 description 2
• 238000001917 fluorescence detection Methods 0.000 description 2
• 239000007850 fluorescent dye Substances 0.000 description 2
• 235000019253 formic acid Nutrition 0.000 description 2
• 239000000499 gel Substances 0.000 description 2
• 239000007903 gelatin capsule Substances 0.000 description 2
• 208000014829 head and neck neoplasm Diseases 0.000 description 2
• 230000002209 hydrophobic effect Effects 0.000 description 2
• 229940072221 immunoglobulins Drugs 0.000 description 2
• 230000006698 induction Effects 0.000 description 2
• 239000002054 inoculum Substances 0.000 description 2
• 102000028416 insulin-like growth factor binding Human genes 0.000 description 2
• 108091022911 insulin-like growth factor binding Proteins 0.000 description 2
• 230000003993 interaction Effects 0.000 description 2
• 230000003834 intracellular effect Effects 0.000 description 2
• 238000001990 intravenous administration Methods 0.000 description 2
• 238000004255 ion exchange chromatography Methods 0.000 description 2
• 210000003292 kidney cell Anatomy 0.000 description 2
• JJTUDXZGHPGLLC-UHFFFAOYSA-N lactide Chemical compound CC1OC(=O)C(C)OC1=O JJTUDXZGHPGLLC-UHFFFAOYSA-N 0.000 description 2
• 108020001756 ligand binding domains Proteins 0.000 description 2
• 239000002502 liposome Substances 0.000 description 2
• 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 2
• 229910001629 magnesium chloride Inorganic materials 0.000 description 2
• HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
• 231100000682 maximum tolerated dose Toxicity 0.000 description 2
• 238000002844 melting Methods 0.000 description 2
• 230000008018 melting Effects 0.000 description 2
• MYWUZJCMWCOHBA-VIFPVBQESA-N methamphetamine Chemical compound CN[C@@H](C)CC1=CC=CC=C1 MYWUZJCMWCOHBA-VIFPVBQESA-N 0.000 description 2
• 229930182817 methionine Natural products 0.000 description 2
• 125000001360 methionine group Chemical group N[C@@H](CCSC)C(=O)* 0.000 description 2
• 239000007758 minimum essential medium Substances 0.000 description 2
• 239000002105 nanoparticle Substances 0.000 description 2
• 230000007935 neutral effect Effects 0.000 description 2
• 229910052757 nitrogen Inorganic materials 0.000 description 2
• 231100000252 nontoxic Toxicity 0.000 description 2
• 230000003000 nontoxic effect Effects 0.000 description 2
• 238000007911 parenteral administration Methods 0.000 description 2
• 230000036470 plasma concentration Effects 0.000 description 2
• BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Chemical compound [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 description 2
• 229920001515 polyalkylene glycol Polymers 0.000 description 2
• 230000000644 propagated effect Effects 0.000 description 2
• 238000000159 protein binding assay Methods 0.000 description 2
• 230000009467 reduction Effects 0.000 description 2
• 238000006722 reduction reaction Methods 0.000 description 2
• 238000006268 reductive amination reaction Methods 0.000 description 2
• 230000008929 regeneration Effects 0.000 description 2
• 238000011069 regeneration method Methods 0.000 description 2
• 238000012552 review Methods 0.000 description 2
• FGDZQCVHDSGLHJ-UHFFFAOYSA-M rubidium chloride Chemical compound [Cl-].[Rb+] FGDZQCVHDSGLHJ-UHFFFAOYSA-M 0.000 description 2
• 238000012216 screening Methods 0.000 description 2
• 230000035939 shock Effects 0.000 description 2
• 125000005629 sialic acid group Chemical group 0.000 description 2
• 229910052938 sodium sulfate Inorganic materials 0.000 description 2
• 235000011152 sodium sulphate Nutrition 0.000 description 2
• 239000007790 solid phase Substances 0.000 description 2
• 239000002904 solvent Substances 0.000 description 2
• 206010041823 squamous cell carcinoma Diseases 0.000 description 2
• 238000010186 staining Methods 0.000 description 2
• 239000000126 substance Substances 0.000 description 2
• 230000001629 suppression Effects 0.000 description 2
• 108010037401 tendamistate Proteins 0.000 description 2
• 108010013645 tetranectin Proteins 0.000 description 2
• 238000002560 therapeutic procedure Methods 0.000 description 2
• 230000001988 toxicity Effects 0.000 description 2
• 231100000419 toxicity Toxicity 0.000 description 2
• 239000012581 transferrin Substances 0.000 description 2
• 238000003146 transient transfection Methods 0.000 description 2
• LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 2
• 238000013414 tumor xenograft model Methods 0.000 description 2
• 239000004474 valine Substances 0.000 description 2
• 238000005406 washing Methods 0.000 description 2
• 229920003169 water-soluble polymer Polymers 0.000 description 2
• 238000001262 western blot Methods 0.000 description 2
• FQWZLZJRZNURGX-BYPYZUCNSA-N (2s)-2-(2-diazohydrazinyl)-4-methylsulfanylbutanoic acid Chemical group CSCC[C@@H](C(O)=O)NN=[N+]=[N-] FQWZLZJRZNURGX-BYPYZUCNSA-N 0.000 description 1
• TUSDEZXZIZRFGC-UHFFFAOYSA-N 1-O-galloyl-3,6-(R)-HHDP-beta-D-glucose Natural products OC1C(O2)COC(=O)C3=CC(O)=C(O)C(O)=C3C3=C(O)C(O)=C(O)C=C3C(=O)OC1C(O)C2OC(=O)C1=CC(O)=C(O)C(O)=C1 TUSDEZXZIZRFGC-UHFFFAOYSA-N 0.000 description 1
• NFGXHKASABOEEW-UHFFFAOYSA-N 1-methylethyl 11-methoxy-3,7,11-trimethyl-2,4-dodecadienoate Chemical compound COC(C)(C)CCCC(C)CC=CC(C)=CC(=O)OC(C)C NFGXHKASABOEEW-UHFFFAOYSA-N 0.000 description 1
• GZCWLCBFPRFLKL-UHFFFAOYSA-N 1-prop-2-ynoxypropan-2-ol Chemical compound CC(O)COCC#C GZCWLCBFPRFLKL-UHFFFAOYSA-N 0.000 description 1
• VOXZDWNPVJITMN-UHFFFAOYSA-N 13-methyl-6,7,8,9,11,12,14,15,16,17-decahydrocyclopenta[a]phenanthrene-3,17-diol Chemical compound OC1=CC=C2C3CCC(C)(C(CC4)O)C4C3CCC2=C1 VOXZDWNPVJITMN-UHFFFAOYSA-N 0.000 description 1
• BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 1
• 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 1
• FWMNVWWHGCHHJJ-SKKKGAJSSA-N 4-amino-1-[(2r)-6-amino-2-[[(2r)-2-[[(2r)-2-[[(2r)-2-amino-3-phenylpropanoyl]amino]-3-phenylpropanoyl]amino]-4-methylpentanoyl]amino]hexanoyl]piperidine-4-carboxylic acid Chemical compound C([C@H](C(=O)N[C@H](CC(C)C)C(=O)N[C@H](CCCCN)C(=O)N1CCC(N)(CC1)C(O)=O)NC(=O)[C@H](N)CC=1C=CC=CC=1)C1=CC=CC=C1 FWMNVWWHGCHHJJ-SKKKGAJSSA-N 0.000 description 1
• LLBZPESJRQGYMB-UHFFFAOYSA-N 4-one Natural products O1C(C(=O)CC)CC(C)C11C2(C)CCC(C3(C)C(C(C)(CO)C(OC4C(C(O)C(O)C(COC5C(C(O)C(O)CO5)OC5C(C(OC6C(C(O)C(O)C(CO)O6)O)C(O)C(CO)O5)OC5C(C(O)C(O)C(C)O5)O)O4)O)CC3)CC3)=C3C2(C)CC1 LLBZPESJRQGYMB-UHFFFAOYSA-N 0.000 description 1
• 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 1
• 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 1
• 230000005730 ADP ribosylation Effects 0.000 description 1
• 108010066676 Abrin Proteins 0.000 description 1
• RZVAJINKPMORJF-UHFFFAOYSA-N Acetaminophen Chemical compound CC(=O)NC1=CC=C(O)C=C1 RZVAJINKPMORJF-UHFFFAOYSA-N 0.000 description 1
• 108010051457 Acid Phosphatase Proteins 0.000 description 1
• 102000013563 Acid Phosphatase Human genes 0.000 description 1
• 206010000830 Acute leukaemia Diseases 0.000 description 1
• 208000010507 Adenocarcinoma of Lung Diseases 0.000 description 1
• 108020004774 Alkaline Phosphatase Proteins 0.000 description 1
• 102000002260 Alkaline Phosphatase Human genes 0.000 description 1
• 241000534414 Anotopterus nikparini Species 0.000 description 1
• 108010039627 Aprotinin Proteins 0.000 description 1
• 239000004475 Arginine Substances 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
• 108010024976 Asparaginase Proteins 0.000 description 1
• 102000015790 Asparaginase Human genes 0.000 description 1
• DCXYFEDJOCDNAF-UHFFFAOYSA-N Asparagine Natural products OC(=O)C(N)CC(N)=O DCXYFEDJOCDNAF-UHFFFAOYSA-N 0.000 description 1
• 241000193830 Bacillus <bacterium> Species 0.000 description 1
• 231100000699 Bacterial toxin Toxicity 0.000 description 1
• VGGGPCQERPFHOB-MCIONIFRSA-N Bestatin Chemical compound CC(C)C[C@H](C(O)=O)NC(=O)[C@@H](O)[C@H](N)CC1=CC=CC=C1 VGGGPCQERPFHOB-MCIONIFRSA-N 0.000 description 1
• VGGGPCQERPFHOB-UHFFFAOYSA-N Bestatin Natural products CC(C)CC(C(O)=O)NC(=O)C(O)C(N)CC1=CC=CC=C1 VGGGPCQERPFHOB-UHFFFAOYSA-N 0.000 description 1
• DWRXFEITVBNRMK-UHFFFAOYSA-N Beta-D-1-Arabinofuranosylthymine Natural products O=C1NC(=O)C(C)=CN1C1C(O)C(O)C(CO)O1 DWRXFEITVBNRMK-UHFFFAOYSA-N 0.000 description 1
• 206010005003 Bladder cancer Diseases 0.000 description 1
• 102000004506 Blood Proteins Human genes 0.000 description 1
• 108010017384 Blood Proteins Proteins 0.000 description 1
• 208000003174 Brain Neoplasms Diseases 0.000 description 1
• COVZYZSDYWQREU-UHFFFAOYSA-N Busulfan Chemical compound CS(=O)(=O)OCCCCOS(C)(=O)=O COVZYZSDYWQREU-UHFFFAOYSA-N 0.000 description 1
• 239000002126 C01EB10 - Adenosine Substances 0.000 description 1
• OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
• UXVMQQNJUSDDNG-UHFFFAOYSA-L Calcium chloride Chemical compound [Cl-].[Cl-].[Ca+2] UXVMQQNJUSDDNG-UHFFFAOYSA-L 0.000 description 1
• KLWPJMFMVPTNCC-UHFFFAOYSA-N Camptothecin Natural products CCC1(O)C(=O)OCC2=C1C=C3C4Nc5ccccc5C=C4CN3C2=O KLWPJMFMVPTNCC-UHFFFAOYSA-N 0.000 description 1
• 241000222122 Candida albicans Species 0.000 description 1
• GAGWJHPBXLXJQN-UORFTKCHSA-N Capecitabine Chemical compound C1=C(F)C(NC(=O)OCCCCC)=NC(=O)N1[C@H]1[C@H](O)[C@H](O)[C@@H](C)O1 GAGWJHPBXLXJQN-UORFTKCHSA-N 0.000 description 1
• GAGWJHPBXLXJQN-UHFFFAOYSA-N Capecitabine Natural products C1=C(F)C(NC(=O)OCCCCC)=NC(=O)N1C1C(O)C(O)C(C)O1 GAGWJHPBXLXJQN-UHFFFAOYSA-N 0.000 description 1
• 241000283707 Capra Species 0.000 description 1
• 101710167800 Capsid assembly scaffolding protein Proteins 0.000 description 1
• OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 1
• 229920002134 Carboxymethyl cellulose Polymers 0.000 description 1
• 208000005623 Carcinogenesis Diseases 0.000 description 1
• 102000014914 Carrier Proteins Human genes 0.000 description 1
• 102000004225 Cathepsin B Human genes 0.000 description 1
• 108090000712 Cathepsin B Proteins 0.000 description 1
• ZEOWTGPWHLSLOG-UHFFFAOYSA-N Cc1ccc(cc1-c1ccc2c(n[nH]c2c1)-c1cnn(c1)C1CC1)C(=O)Nc1cccc(c1)C(F)(F)F Chemical compound Cc1ccc(cc1-c1ccc2c(n[nH]c2c1)-c1cnn(c1)C1CC1)C(=O)Nc1cccc(c1)C(F)(F)F ZEOWTGPWHLSLOG-UHFFFAOYSA-N 0.000 description 1
• 231100000023 Cell-mediated cytotoxicity Toxicity 0.000 description 1
• 206010057250 Cell-mediated cytotoxicity Diseases 0.000 description 1
• 102000004626 Colony-Stimulating Factor Receptors Human genes 0.000 description 1
• 108010003384 Colony-Stimulating Factor Receptors Proteins 0.000 description 1
• 208000001333 Colorectal Neoplasms Diseases 0.000 description 1
• 241000557626 Corvus corax Species 0.000 description 1
• 241000699802 Cricetulus griseus Species 0.000 description 1
• CMSMOCZEIVJLDB-UHFFFAOYSA-N Cyclophosphamide Chemical compound ClCCN(CCCl)P1(=O)NCCCO1 CMSMOCZEIVJLDB-UHFFFAOYSA-N 0.000 description 1
• UHDGCWIWMRVCDJ-CCXZUQQUSA-N Cytarabine Chemical compound O=C1N=C(N)C=CN1[C@H]1[C@@H](O)[C@H](O)[C@@H](CO)O1 UHDGCWIWMRVCDJ-CCXZUQQUSA-N 0.000 description 1
• 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-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
• DWJXYEABWRJFSP-XOBRGWDASA-N DAPT Chemical compound N([C@@H](C)C(=O)N[C@H](C(=O)OC(C)(C)C)C=1C=CC=CC=1)C(=O)CC1=CC(F)=CC(F)=C1 DWJXYEABWRJFSP-XOBRGWDASA-N 0.000 description 1
• 102000007260 Deoxyribonuclease I Human genes 0.000 description 1
• 108010008532 Deoxyribonuclease I Proteins 0.000 description 1
• 108010053770 Deoxyribonucleases Proteins 0.000 description 1
• 102000016911 Deoxyribonucleases Human genes 0.000 description 1
• 229920002307 Dextran Polymers 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
• 101001004391 Drosophila melanogaster Protein jim lovell Proteins 0.000 description 1
• 206010013710 Drug interaction Diseases 0.000 description 1
• LTLYEAJONXGNFG-DCAQKATOSA-N E64 Chemical compound NC(=N)NCCCCNC(=O)[C@H](CC(C)C)NC(=O)[C@H]1O[C@@H]1C(O)=O LTLYEAJONXGNFG-DCAQKATOSA-N 0.000 description 1
• 101710146739 Enterotoxin Proteins 0.000 description 1
• 101800003838 Epidermal growth factor Proteins 0.000 description 1
• 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 1
• 102000003951 Erythropoietin Human genes 0.000 description 1
• 108090000394 Erythropoietin Proteins 0.000 description 1
• 241000672609 Escherichia coli BL21 Species 0.000 description 1
• 208000000461 Esophageal Neoplasms Diseases 0.000 description 1
• 108090000371 Esterases Proteins 0.000 description 1
• 208000006168 Ewing Sarcoma Diseases 0.000 description 1
• 102000010834 Extracellular Matrix Proteins Human genes 0.000 description 1
• 108010037362 Extracellular Matrix Proteins Proteins 0.000 description 1
• 239000001263 FEMA 3042 Substances 0.000 description 1
• 101150017750 FGFRL1 gene Proteins 0.000 description 1
• 241000282326 Felis catus Species 0.000 description 1
• 101710182386 Fibroblast growth factor receptor 1 Proteins 0.000 description 1
• 102100023593 Fibroblast growth factor receptor 1 Human genes 0.000 description 1
• 101710182389 Fibroblast growth factor receptor 2 Proteins 0.000 description 1
• 102100023600 Fibroblast growth factor receptor 2 Human genes 0.000 description 1
• 101710182396 Fibroblast growth factor receptor 3 Proteins 0.000 description 1
• 102100027842 Fibroblast growth factor receptor 3 Human genes 0.000 description 1
• 102100026149 Fibroblast growth factor receptor-like 1 Human genes 0.000 description 1
• GHASVSINZRGABV-UHFFFAOYSA-N Fluorouracil Chemical compound FC1=CNC(=O)NC1=O GHASVSINZRGABV-UHFFFAOYSA-N 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
• 241000233866 Fungi Species 0.000 description 1
• 229910052688 Gadolinium Inorganic materials 0.000 description 1
• GYHNNYVSQQEPJS-UHFFFAOYSA-N Gallium Chemical compound [Ga] GYHNNYVSQQEPJS-UHFFFAOYSA-N 0.000 description 1
• 206010061968 Gastric neoplasm Diseases 0.000 description 1
• 108700004714 Gelonium multiflorum GEL Proteins 0.000 description 1
• 229930182566 Gentamicin Natural products 0.000 description 1
• CEAZRRDELHUEMR-URQXQFDESA-N Gentamicin Chemical compound O1[C@H](C(C)NC)CC[C@@H](N)[C@H]1O[C@H]1[C@H](O)[C@@H](O[C@@H]2[C@@H]([C@@H](NC)[C@@](C)(O)CO2)O)[C@H](N)C[C@@H]1N CEAZRRDELHUEMR-URQXQFDESA-N 0.000 description 1
• 108010073178 Glucan 1,4-alpha-Glucosidase Proteins 0.000 description 1
• 102100022624 Glucoamylase Human genes 0.000 description 1
• 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 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
• 108010069236 Goserelin Proteins 0.000 description 1
• 102000009465 Growth Factor Receptors Human genes 0.000 description 1
• 108010009202 Growth Factor Receptors Proteins 0.000 description 1
• HVLSXIKZNLPZJJ-TXZCQADKSA-N HA peptide Chemical compound C([C@@H](C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](C(C)C)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N[C@@H](C)C(O)=O)NC(=O)[C@H]1N(CCC1)C(=O)[C@@H](N)CC=1C=CC(O)=CC=1)C1=CC=C(O)C=C1 HVLSXIKZNLPZJJ-TXZCQADKSA-N 0.000 description 1
• 239000007995 HEPES buffer Substances 0.000 description 1
• 102100029966 HLA class II histocompatibility antigen, DP alpha 1 chain Human genes 0.000 description 1
• 101100082540 Haemophilus influenzae (strain ATCC 51907 / DSM 11121 / KW20 / Rd) pcp gene Proteins 0.000 description 1
• 208000009889 Herpes Simplex Diseases 0.000 description 1
• 101100118545 Holotrichia diomphalia EGF-like gene Proteins 0.000 description 1
• 241000282412 Homo Species 0.000 description 1
• 101000851181 Homo sapiens Epidermal growth factor receptor Proteins 0.000 description 1
• 101000864089 Homo sapiens HLA class II histocompatibility antigen, DP alpha 1 chain Proteins 0.000 description 1
• 101000930802 Homo sapiens HLA class II histocompatibility antigen, DQ alpha 1 chain Proteins 0.000 description 1
• 101000968032 Homo sapiens HLA class II histocompatibility antigen, DR beta 3 chain Proteins 0.000 description 1
• 101000852815 Homo sapiens Insulin receptor Proteins 0.000 description 1
• 101000878605 Homo sapiens Low affinity immunoglobulin epsilon Fc receptor Proteins 0.000 description 1
• 101001012157 Homo sapiens Receptor tyrosine-protein kinase erbB-2 Proteins 0.000 description 1
• 108010031794 IGF Type 1 Receptor Proteins 0.000 description 1
• 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 1
• 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 1
• 108010021625 Immunoglobulin Fragments Proteins 0.000 description 1
• 102000008394 Immunoglobulin Fragments Human genes 0.000 description 1
• 108010067060 Immunoglobulin Variable Region Proteins 0.000 description 1
• 102000017727 Immunoglobulin Variable Region Human genes 0.000 description 1
• 102000016844 Immunoglobulin-like domains Human genes 0.000 description 1
• 108050006430 Immunoglobulin-like domains Proteins 0.000 description 1
• 108700001097 Insect Genes Proteins 0.000 description 1
• 108010078049 Interferon alpha-2 Proteins 0.000 description 1
• 208000008839 Kidney Neoplasms Diseases 0.000 description 1
• 241000235649 Kluyveromyces Species 0.000 description 1
• ONIBWKKTOPOVIA-BYPYZUCNSA-N L-Proline Chemical compound OC(=O)[C@@H]1CCCN1 ONIBWKKTOPOVIA-BYPYZUCNSA-N 0.000 description 1
• ODKSFYDXXFIFQN-BYPYZUCNSA-P L-argininium(2+) Chemical compound NC(=[NH2+])NCCC[C@H]([NH3+])C(O)=O ODKSFYDXXFIFQN-BYPYZUCNSA-P 0.000 description 1
• ZDXPYRJPNDTMRX-VKHMYHEASA-N L-glutamine Chemical compound OC(=O)[C@@H](N)CCC(N)=O ZDXPYRJPNDTMRX-VKHMYHEASA-N 0.000 description 1
• AGPKZVBTJJNPAG-WHFBIAKZSA-N L-isoleucine Chemical compound CC[C@H](C)[C@H](N)C(O)=O AGPKZVBTJJNPAG-WHFBIAKZSA-N 0.000 description 1
• ROHFNLRQFUQHCH-YFKPBYRVSA-N L-leucine Chemical compound CC(C)C[C@H](N)C(O)=O ROHFNLRQFUQHCH-YFKPBYRVSA-N 0.000 description 1
• FFEARJCKVFRZRR-BYPYZUCNSA-N L-methionine Chemical compound CSCC[C@H](N)C(O)=O FFEARJCKVFRZRR-BYPYZUCNSA-N 0.000 description 1
• 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 1
• COLNVLDHVKWLRT-QMMMGPOBSA-N L-phenylalanine Chemical compound OC(=O)[C@@H](N)CC1=CC=CC=C1 COLNVLDHVKWLRT-QMMMGPOBSA-N 0.000 description 1
• 102100023162 L-serine dehydratase/L-threonine deaminase Human genes 0.000 description 1
• 239000005517 L01XE01 - Imatinib Substances 0.000 description 1
• 239000005411 L01XE02 - Gefitinib Substances 0.000 description 1
• ROHFNLRQFUQHCH-UHFFFAOYSA-N Leucine Natural products CC(C)CC(N)C(O)=O ROHFNLRQFUQHCH-UHFFFAOYSA-N 0.000 description 1
• 206010024305 Leukaemia monocytic Diseases 0.000 description 1
• GDBQQVLCIARPGH-UHFFFAOYSA-N Leupeptin Natural products CC(C)CC(NC(C)=O)C(=O)NC(CC(C)C)C(=O)NC(C=O)CCCN=C(N)N GDBQQVLCIARPGH-UHFFFAOYSA-N 0.000 description 1
• HLFSDGLLUJUHTE-SNVBAGLBSA-N Levamisole Chemical compound C1([C@H]2CN3CCSC3=N2)=CC=CC=C1 HLFSDGLLUJUHTE-SNVBAGLBSA-N 0.000 description 1
• 102100038007 Low affinity immunoglobulin epsilon Fc receptor Human genes 0.000 description 1
• 206010058467 Lung neoplasm malignant Diseases 0.000 description 1
• 206010025323 Lymphomas Diseases 0.000 description 1
• 239000004472 Lysine Substances 0.000 description 1
• FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
• PWHULOQIROXLJO-UHFFFAOYSA-N Manganese Chemical compound [Mn] PWHULOQIROXLJO-UHFFFAOYSA-N 0.000 description 1
• 208000034578 Multiple myelomas Diseases 0.000 description 1
• 108010014251 Muramidase Proteins 0.000 description 1
• 102000016943 Muramidase Human genes 0.000 description 1
• 101100118551 Mus musculus Egfr gene Proteins 0.000 description 1
• 101001026869 Mus musculus F-box/LRR-repeat protein 3 Proteins 0.000 description 1
• 101000807562 Mus musculus Tyrosine-protein kinase receptor UFO Proteins 0.000 description 1
• 108010062010 N-Acetylmuramoyl-L-alanine Amidase Proteins 0.000 description 1
• 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 1
• 125000001429 N-terminal alpha-amino-acid group Chemical group 0.000 description 1
• 238000005481 NMR spectroscopy Methods 0.000 description 1
• 108091061960 Naked DNA Proteins 0.000 description 1
• 239000000020 Nitrocellulose Substances 0.000 description 1
• 206010030155 Oesophageal carcinoma Diseases 0.000 description 1
• 229930012538 Paclitaxel Natural products 0.000 description 1
• 206010061902 Pancreatic neoplasm Diseases 0.000 description 1
• 108010087702 Penicillinase Proteins 0.000 description 1
• LRBQNJMCXXYXIU-PPKXGCFTSA-N Penta-digallate-beta-D-glucose Natural products OC1=C(O)C(O)=CC(C(=O)OC=2C(=C(O)C=C(C=2)C(=O)OC[C@@H]2[C@H]([C@H](OC(=O)C=3C=C(OC(=O)C=4C=C(O)C(O)=C(O)C=4)C(O)=C(O)C=3)[C@@H](OC(=O)C=3C=C(OC(=O)C=4C=C(O)C(O)=C(O)C=4)C(O)=C(O)C=3)[C@H](OC(=O)C=3C=C(OC(=O)C=4C=C(O)C(O)=C(O)C=4)C(O)=C(O)C=3)O2)OC(=O)C=2C=C(OC(=O)C=3C=C(O)C(O)=C(O)C=3)C(O)=C(O)C=2)O)=C1 LRBQNJMCXXYXIU-PPKXGCFTSA-N 0.000 description 1
• 102000035195 Peptidases Human genes 0.000 description 1
• 108090000608 Phosphoric Monoester Hydrolases Proteins 0.000 description 1
• 102000004160 Phosphoric Monoester Hydrolases Human genes 0.000 description 1
• 108091000080 Phosphotransferase Proteins 0.000 description 1
• 241001315609 Pittosporum crassifolium Species 0.000 description 1
• 231100000742 Plant toxin Toxicity 0.000 description 1
• 206010035226 Plasma cell myeloma Diseases 0.000 description 1
• 239000004743 Polypropylene Substances 0.000 description 1
• ZLMJMSJWJFRBEC-RNFDNDRNSA-N Potassium-43 Chemical compound [43K] ZLMJMSJWJFRBEC-RNFDNDRNSA-N 0.000 description 1
• 101710130420 Probable capsid assembly scaffolding protein Proteins 0.000 description 1
• ONIBWKKTOPOVIA-UHFFFAOYSA-N Proline Natural products OC(=O)C1CCCN1 ONIBWKKTOPOVIA-UHFFFAOYSA-N 0.000 description 1
• 102000001253 Protein Kinase Human genes 0.000 description 1
• 239000012979 RPMI medium Substances 0.000 description 1
• 101100261999 Rattus norvegicus Tpsab1 gene Proteins 0.000 description 1
• 102100030086 Receptor tyrosine-protein kinase erbB-2 Human genes 0.000 description 1
• 101710100969 Receptor tyrosine-protein kinase erbB-3 Proteins 0.000 description 1
• 102100029986 Receptor tyrosine-protein kinase erbB-3 Human genes 0.000 description 1
• 102100029981 Receptor tyrosine-protein kinase erbB-4 Human genes 0.000 description 1
• 101710100963 Receptor tyrosine-protein kinase erbB-4 Proteins 0.000 description 1
• 102000007056 Recombinant Fusion Proteins Human genes 0.000 description 1
• 108010008281 Recombinant Fusion Proteins Proteins 0.000 description 1
• 206010038389 Renal cancer Diseases 0.000 description 1
• 108010083644 Ribonucleases Proteins 0.000 description 1
• 102000006382 Ribonucleases Human genes 0.000 description 1
• 108010039491 Ricin Proteins 0.000 description 1
• 101710204410 Scaffold protein Proteins 0.000 description 1
• 101100129592 Schizosaccharomyces pombe (strain 972 / ATCC 24843) mcp7 gene Proteins 0.000 description 1
• 229920005654 Sephadex Polymers 0.000 description 1
• 239000012507 Sephadex™ Substances 0.000 description 1
• 229920002684 Sepharose Polymers 0.000 description 1
• 108010017622 Somatomedin Receptors Proteins 0.000 description 1
• 102000004584 Somatomedin Receptors Human genes 0.000 description 1
• 238000003800 Staudinger reaction Methods 0.000 description 1
• 235000021355 Stearic acid Nutrition 0.000 description 1
• 208000005718 Stomach Neoplasms Diseases 0.000 description 1
• 229930006000 Sucrose Natural products 0.000 description 1
• CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 1
• 101150109894 TGFA gene Proteins 0.000 description 1
• 108700012920 TNF Proteins 0.000 description 1
• 102100026966 Thrombomodulin Human genes 0.000 description 1
• 108010079274 Thrombomodulin Proteins 0.000 description 1
• 208000024770 Thyroid neoplasm Diseases 0.000 description 1
• 241001414989 Thysanoptera Species 0.000 description 1
• 108091023040 Transcription factor Proteins 0.000 description 1
• 102000040945 Transcription factor Human genes 0.000 description 1
• DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical class OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 1
• GLNADSQYFUSGOU-GPTZEZBUSA-J Trypan blue Chemical compound [Na+].[Na+].[Na+].[Na+].C1=C(S([O-])(=O)=O)C=C2C=C(S([O-])(=O)=O)C(/N=N/C3=CC=C(C=C3C)C=3C=C(C(=CC=3)\N=N\C=3C(=CC4=CC(=CC(N)=C4C=3O)S([O-])(=O)=O)S([O-])(=O)=O)C)=C(O)C2=C1N GLNADSQYFUSGOU-GPTZEZBUSA-J 0.000 description 1
• 108091023045 Untranslated Region Proteins 0.000 description 1
• 208000007097 Urinary Bladder Neoplasms Diseases 0.000 description 1
• 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 1
• 108020005202 Viral DNA Proteins 0.000 description 1
• 241000700605 Viruses Species 0.000 description 1
• IXKSXJFAGXLQOQ-XISFHERQSA-N WHWLQLKPGQPMY Chemical compound C([C@@H](C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC(C)C)C(=O)N1CCC[C@H]1C(=O)NCC(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC(O)=O)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(O)=O)NC(=O)[C@@H](N)CC=1C2=CC=CC=C2NC=1)C1=CNC=N1 IXKSXJFAGXLQOQ-XISFHERQSA-N 0.000 description 1
• 238000001793 Wilcoxon signed-rank test Methods 0.000 description 1
• HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 1
• AIWRTTMUVOZGPW-HSPKUQOVSA-N abarelix Chemical compound C([C@@H](C(=O)N[C@H](CC(N)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCCNC(C)C)C(=O)N1[C@@H](CCC1)C(=O)N[C@H](C)C(N)=O)N(C)C(=O)[C@H](CO)NC(=O)[C@@H](CC=1C=NC=CC=1)NC(=O)[C@@H](CC=1C=CC(Cl)=CC=1)NC(=O)[C@@H](CC=1C=C2C=CC=CC2=CC=1)NC(C)=O)C1=CC=C(O)C=C1 AIWRTTMUVOZGPW-HSPKUQOVSA-N 0.000 description 1
• 229960002184 abarelix Drugs 0.000 description 1
• 108010023617 abarelix Proteins 0.000 description 1
• 238000002835 absorbance Methods 0.000 description 1
• 230000021736 acetylation Effects 0.000 description 1
• 238000006640 acetylation reaction Methods 0.000 description 1
• 150000007513 acids Chemical class 0.000 description 1
• 239000008186 active pharmaceutical agent Substances 0.000 description 1
• 238000011374 additional therapy Methods 0.000 description 1
• 229960005305 adenosine Drugs 0.000 description 1
• 238000009098 adjuvant therapy Methods 0.000 description 1
• 238000005377 adsorption chromatography Methods 0.000 description 1
• 230000002411 adverse Effects 0.000 description 1
• MGSKVZWGBWPBTF-UHFFFAOYSA-N aebsf Chemical compound NCCC1=CC=C(S(F)(=O)=O)C=C1 MGSKVZWGBWPBTF-UHFFFAOYSA-N 0.000 description 1
• 238000001042 affinity chromatography Methods 0.000 description 1
• 238000001261 affinity purification Methods 0.000 description 1
• 238000013019 agitation Methods 0.000 description 1
• 125000003545 alkoxy group Chemical group 0.000 description 1
• 125000000217 alkyl group Chemical group 0.000 description 1
• 229960000473 altretamine Drugs 0.000 description 1
• 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
• 150000001412 amines Chemical class 0.000 description 1
• BFNBIHQBYMNNAN-UHFFFAOYSA-N ammonium sulfate Chemical compound N.N.OS(O)(=O)=O BFNBIHQBYMNNAN-UHFFFAOYSA-N 0.000 description 1
• 229910052921 ammonium sulfate Inorganic materials 0.000 description 1
• 235000011130 ammonium sulphate Nutrition 0.000 description 1
• 230000003698 anagen phase Effects 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
• 239000005557 antagonist Substances 0.000 description 1
• 239000003242 anti bacterial agent Substances 0.000 description 1
• 230000000181 anti-adherent effect Effects 0.000 description 1
• 230000001093 anti-cancer Effects 0.000 description 1
• 230000000840 anti-viral effect Effects 0.000 description 1
• 229940088710 antibiotic agent Drugs 0.000 description 1
• 229960004405 aprotinin Drugs 0.000 description 1
• ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 1
• 229960003272 asparaginase Drugs 0.000 description 1
• DCXYFEDJOCDNAF-UHFFFAOYSA-M asparaginate Chemical compound [O-]C(=O)C(N)CC(N)=O DCXYFEDJOCDNAF-UHFFFAOYSA-M 0.000 description 1
• 235000009582 asparagine Nutrition 0.000 description 1
• 229960001230 asparagine Drugs 0.000 description 1
• QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
• 230000035578 autophosphorylation Effects 0.000 description 1
• 210000003719 b-lymphocyte Anatomy 0.000 description 1
• 239000000688 bacterial toxin Substances 0.000 description 1
• 230000009286 beneficial effect Effects 0.000 description 1
• WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid group Chemical group C(C1=CC=CC=C1)(=O)O WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 1
• 108010051210 beta-Fructofuranosidase Proteins 0.000 description 1
• SQVRNKJHWKZAKO-UHFFFAOYSA-N beta-N-Acetyl-D-neuraminic acid Natural products CC(=O)NC1C(O)CC(O)(C(O)=O)OC1C(O)C(O)CO SQVRNKJHWKZAKO-UHFFFAOYSA-N 0.000 description 1
• 229960000397 bevacizumab Drugs 0.000 description 1
• 230000001588 bifunctional effect Effects 0.000 description 1
• 108091008324 binding proteins Proteins 0.000 description 1
• 239000012472 biological sample Substances 0.000 description 1
• 238000007413 biotinylation Methods 0.000 description 1
• 230000006287 biotinylation Effects 0.000 description 1
• 210000001124 body fluid Anatomy 0.000 description 1
• 239000010839 body fluid Substances 0.000 description 1
• 230000037396 body weight Effects 0.000 description 1
• 229960001467 bortezomib Drugs 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
• 108010006025 bovine growth hormone Proteins 0.000 description 1
• 201000008274 breast adenocarcinoma Diseases 0.000 description 1
• 201000008275 breast carcinoma Diseases 0.000 description 1
• 239000007975 buffered saline Substances 0.000 description 1
• 229960002092 busulfan Drugs 0.000 description 1
• 239000011575 calcium Substances 0.000 description 1
• 229910052791 calcium Inorganic materials 0.000 description 1
• 239000001110 calcium chloride Substances 0.000 description 1
• 229910001628 calcium chloride Inorganic materials 0.000 description 1
• 239000001506 calcium phosphate Substances 0.000 description 1
• 229910000389 calcium phosphate Inorganic materials 0.000 description 1
• 235000011010 calcium phosphates Nutrition 0.000 description 1
• HXCHCVDVKSCDHU-LULTVBGHSA-N calicheamicin Chemical compound C1[C@H](OC)[C@@H](NCC)CO[C@H]1O[C@H]1[C@H](O[C@@H]2C\3=C(NC(=O)OC)C(=O)C[C@](C/3=C/CSSSC)(O)C#C\C=C/C#C2)O[C@H](C)[C@@H](NO[C@@H]2O[C@H](C)[C@@H](SC(=O)C=3C(=C(OC)C(O[C@H]4[C@@H]([C@H](OC)[C@@H](O)[C@H](C)O4)O)=C(I)C=3C)OC)[C@@H](O)C2)[C@@H]1O HXCHCVDVKSCDHU-LULTVBGHSA-N 0.000 description 1
• 229930195731 calicheamicin Natural products 0.000 description 1
• 238000007707 calorimetry Methods 0.000 description 1
• 229940127093 camptothecin Drugs 0.000 description 1
• VSJKWCGYPAHWDS-FQEVSTJZSA-N camptothecin Chemical compound C1=CC=C2C=C(CN3C4=CC5=C(C3=O)COC(=O)[C@]5(O)CC)C4=NC2=C1 VSJKWCGYPAHWDS-FQEVSTJZSA-N 0.000 description 1
• 230000036952 cancer formation Effects 0.000 description 1
• 230000005907 cancer growth Effects 0.000 description 1
• 229960004117 capecitabine Drugs 0.000 description 1
• 239000002775 capsule Substances 0.000 description 1
• 150000001720 carbohydrates Chemical class 0.000 description 1
• 235000014633 carbohydrates Nutrition 0.000 description 1
• 229910052799 carbon Inorganic materials 0.000 description 1
• 230000006315 carbonylation Effects 0.000 description 1
• 238000005810 carbonylation reaction Methods 0.000 description 1
• 239000001768 carboxy methyl cellulose Substances 0.000 description 1
• 235000010948 carboxy methyl cellulose Nutrition 0.000 description 1
• 239000008112 carboxymethyl-cellulose Substances 0.000 description 1
• 231100000504 carcinogenesis Toxicity 0.000 description 1
• 238000005341 cation exchange Methods 0.000 description 1
• 238000004113 cell culture Methods 0.000 description 1
• 230000006037 cell lysis Effects 0.000 description 1
• 239000008004 cell lysis buffer Substances 0.000 description 1
• 210000000170 cell membrane Anatomy 0.000 description 1
• 230000005890 cell-mediated cytotoxicity Effects 0.000 description 1
• 230000009920 chelation Effects 0.000 description 1
• 125000003636 chemical group Chemical group 0.000 description 1
• 238000002512 chemotherapy Methods 0.000 description 1
• 239000007910 chewable tablet Substances 0.000 description 1
• 210000004978 chinese hamster ovary cell Anatomy 0.000 description 1
• 208000024207 chronic leukemia Diseases 0.000 description 1
• 210000001072 colon Anatomy 0.000 description 1
• 238000010293 colony formation assay Methods 0.000 description 1
• 238000004440 column chromatography Methods 0.000 description 1
• 238000012875 competitive assay Methods 0.000 description 1
• 230000009137 competitive binding Effects 0.000 description 1
• 230000002860 competitive effect Effects 0.000 description 1
• 230000000295 complement effect Effects 0.000 description 1
• 239000002299 complementary DNA Substances 0.000 description 1
• 238000002591 computed tomography Methods 0.000 description 1
• 238000012790 confirmation Methods 0.000 description 1
• 238000011109 contamination Methods 0.000 description 1
• 239000000994 contrast dye Substances 0.000 description 1
• 239000013256 coordination polymer Substances 0.000 description 1
• 229920001577 copolymer Polymers 0.000 description 1
• 239000006071 cream Substances 0.000 description 1
• 230000009260 cross reactivity Effects 0.000 description 1
• 239000013078 crystal Substances 0.000 description 1
• 238000012258 culturing Methods 0.000 description 1
• 229960004397 cyclophosphamide Drugs 0.000 description 1
• 229960000684 cytarabine Drugs 0.000 description 1
• 230000001086 cytosolic effect Effects 0.000 description 1
• 230000001085 cytostatic effect Effects 0.000 description 1
• 229960000975 daunorubicin Drugs 0.000 description 1
• 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 1
• 230000001419 dependent effect Effects 0.000 description 1
• 238000010612 desalination reaction Methods 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
• 229960003957 dexamethasone Drugs 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
• 230000004069 differentiation Effects 0.000 description 1
• 239000012470 diluted sample Substances 0.000 description 1
• FPAFDBFIGPHWGO-UHFFFAOYSA-N dioxosilane;oxomagnesium;hydrate Chemical compound O.[Mg]=O.[Mg]=O.[Mg]=O.O=[Si]=O.O=[Si]=O.O=[Si]=O.O=[Si]=O FPAFDBFIGPHWGO-UHFFFAOYSA-N 0.000 description 1
• 229940042399 direct acting antivirals protease inhibitors Drugs 0.000 description 1
• 230000005750 disease progression Effects 0.000 description 1
• 238000006073 displacement reaction Methods 0.000 description 1
• 238000009826 distribution Methods 0.000 description 1
• 125000002228 disulfide group Chemical group 0.000 description 1
• VSJKWCGYPAHWDS-UHFFFAOYSA-N dl-camptothecin Natural products C1=CC=C2C=C(CN3C4=CC5=C(C3=O)COC(=O)C5(O)CC)C4=NC2=C1 VSJKWCGYPAHWDS-UHFFFAOYSA-N 0.000 description 1
• 229960003668 docetaxel Drugs 0.000 description 1
• 239000003937 drug carrier Substances 0.000 description 1
• 238000007876 drug discovery Methods 0.000 description 1
• 238000011977 dual antiplatelet therapy Methods 0.000 description 1
• 239000000975 dye Substances 0.000 description 1
• 230000000431 effect on proliferation Effects 0.000 description 1
• 238000001962 electrophoresis Methods 0.000 description 1
• 238000004520 electroporation Methods 0.000 description 1
• 239000003974 emollient agent Substances 0.000 description 1
• 210000002889 endothelial cell Anatomy 0.000 description 1
• 239000000147 enterotoxin Substances 0.000 description 1
• 230000002255 enzymatic effect Effects 0.000 description 1
• 102000027412 enzyme-linked receptors Human genes 0.000 description 1
• 108091008592 enzyme-linked receptors Proteins 0.000 description 1
• 229940116977 epidermal growth factor Drugs 0.000 description 1
• 229960001904 epirubicin Drugs 0.000 description 1
• 229930013356 epothilone Natural products 0.000 description 1
• HESCAJZNRMSMJG-KKQRBIROSA-N epothilone A Chemical class C/C([C@@H]1C[C@@H]2O[C@@H]2CCC[C@@H]([C@@H]([C@@H](C)C(=O)C(C)(C)[C@@H](O)CC(=O)O1)O)C)=C\C1=CSC(C)=N1 HESCAJZNRMSMJG-KKQRBIROSA-N 0.000 description 1
• 239000006167 equilibration buffer Substances 0.000 description 1
• 229940105423 erythropoietin Drugs 0.000 description 1
• 201000004101 esophageal cancer Diseases 0.000 description 1
• FRPJXPJMRWBBIH-RBRWEJTLSA-N estramustine Chemical compound ClCCN(CCCl)C(=O)OC1=CC=C2[C@H]3CC[C@](C)([C@H](CC4)O)[C@@H]4[C@@H]3CCC2=C1 FRPJXPJMRWBBIH-RBRWEJTLSA-N 0.000 description 1
• 229960001842 estramustine Drugs 0.000 description 1
• 239000005038 ethylene vinyl acetate Substances 0.000 description 1
• 229960005420 etoposide Drugs 0.000 description 1
• VJJPUSNTGOMMGY-MRVIYFEKSA-N etoposide Chemical compound COC1=C(O)C(OC)=CC([C@@H]2C3=CC=4OCOC=4C=C3[C@@H](O[C@H]3[C@@H]([C@@H](O)[C@@H]4O[C@H](C)OC[C@H]4O3)O)[C@@H]3[C@@H]2C(OC3)=O)=C1 VJJPUSNTGOMMGY-MRVIYFEKSA-N 0.000 description 1
• 229960000255 exemestane Drugs 0.000 description 1
• 239000002095 exotoxin Substances 0.000 description 1
• 231100000776 exotoxin Toxicity 0.000 description 1
• 210000002744 extracellular matrix Anatomy 0.000 description 1
• 238000000605 extraction Methods 0.000 description 1
• 102000052178 fibroblast growth factor receptor activity proteins Human genes 0.000 description 1
• 239000000945 filler Substances 0.000 description 1
• 229960000390 fludarabine Drugs 0.000 description 1
• 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 1
• 238000005558 fluorometry Methods 0.000 description 1
• 229960002949 fluorouracil Drugs 0.000 description 1
• 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 1
• 235000008191 folinic acid Nutrition 0.000 description 1
• 239000011672 folinic acid Substances 0.000 description 1
• 235000013305 food Nutrition 0.000 description 1
• 229960002258 fulvestrant Drugs 0.000 description 1
• 238000002825 functional assay Methods 0.000 description 1
• 125000000524 functional group Chemical group 0.000 description 1
• 230000002538 fungal effect Effects 0.000 description 1
• UIWYJDYFSGRHKR-UHFFFAOYSA-N gadolinium atom Chemical compound [Gd] UIWYJDYFSGRHKR-UHFFFAOYSA-N 0.000 description 1
• 229910052733 gallium Inorganic materials 0.000 description 1
• 239000007789 gas Substances 0.000 description 1
• 206010017758 gastric cancer Diseases 0.000 description 1
• 229960002584 gefitinib Drugs 0.000 description 1
• 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 1
• 238000005227 gel permeation chromatography Methods 0.000 description 1
• SDUQYLNIPVEERB-QPPQHZFASA-N gemcitabine Chemical compound O=C1N=C(N)C=CN1[C@H]1C(F)(F)[C@H](O)[C@@H](CO)O1 SDUQYLNIPVEERB-QPPQHZFASA-N 0.000 description 1
• 229960005277 gemcitabine Drugs 0.000 description 1
• 238000001415 gene therapy Methods 0.000 description 1
• 230000002068 genetic effect Effects 0.000 description 1
• 208000005017 glioblastoma Diseases 0.000 description 1
• 239000008103 glucose Substances 0.000 description 1
• 235000013922 glutamic acid Nutrition 0.000 description 1
• 239000004220 glutamic acid Substances 0.000 description 1
• ZDXPYRJPNDTMRX-UHFFFAOYSA-N glutamine Natural products OC(=O)C(N)CCC(N)=O ZDXPYRJPNDTMRX-UHFFFAOYSA-N 0.000 description 1
• 150000004676 glycans Polymers 0.000 description 1
• 229960002913 goserelin Drugs 0.000 description 1
• 239000008187 granular material Substances 0.000 description 1
• 201000003911 head and neck carcinoma Diseases 0.000 description 1
• UUVWYPNAQBNQJQ-UHFFFAOYSA-N hexamethylmelamine Chemical compound CN(C)C1=NC(N(C)C)=NC(N(C)C)=N1 UUVWYPNAQBNQJQ-UHFFFAOYSA-N 0.000 description 1
• HNDVDQJCIGZPNO-UHFFFAOYSA-N histidine Natural products OC(=O)C(N)CC1=CN=CN1 HNDVDQJCIGZPNO-UHFFFAOYSA-N 0.000 description 1
• 238000000265 homogenisation Methods 0.000 description 1
• 229940088597 hormone Drugs 0.000 description 1
• 239000005556 hormone Substances 0.000 description 1
• 102000045108 human EGFR Human genes 0.000 description 1
• 102000045648 human IGF1R Human genes 0.000 description 1
• 102000047882 human INSR Human genes 0.000 description 1
• 238000013415 human tumor xenograft model Methods 0.000 description 1
• 239000001257 hydrogen Substances 0.000 description 1
• 229910052739 hydrogen Inorganic materials 0.000 description 1
• 239000008172 hydrogenated vegetable oil Substances 0.000 description 1
• 125000001165 hydrophobic group Chemical group 0.000 description 1
• 125000002887 hydroxy group Chemical group [H]O* 0.000 description 1
• 229960000908 idarubicin Drugs 0.000 description 1
• 229960002411 imatinib 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
• 230000001900 immune effect Effects 0.000 description 1
• 230000028993 immune response Effects 0.000 description 1
• 102000028557 immunoglobulin binding proteins Human genes 0.000 description 1
• 108091009323 immunoglobulin binding proteins Proteins 0.000 description 1
• 238000010324 immunological assay Methods 0.000 description 1
• 238000001114 immunoprecipitation Methods 0.000 description 1
• 238000009169 immunotherapy Methods 0.000 description 1
• 239000007943 implant Substances 0.000 description 1
• 230000006872 improvement Effects 0.000 description 1
• 238000010348 incorporation Methods 0.000 description 1
• 230000001939 inductive effect Effects 0.000 description 1
• 239000012678 infectious agent Substances 0.000 description 1
• 208000015181 infectious disease Diseases 0.000 description 1
• 230000008595 infiltration Effects 0.000 description 1
• 238000001764 infiltration Methods 0.000 description 1
• 238000003331 infrared imaging Methods 0.000 description 1
• 238000001802 infusion Methods 0.000 description 1
• ZPNFWUPYTFPOJU-LPYSRVMUSA-N iniprol Chemical compound C([C@H]1C(=O)NCC(=O)NCC(=O)N[C@H]2CSSC[C@H]3C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@H](C(N[C@H](C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC=4C=CC(O)=CC=4)C(=O)N[C@@H](CC=4C=CC=CC=4)C(=O)N[C@@H](CC=4C=CC(O)=CC=4)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](C)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](C)C(=O)NCC(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CSSC[C@H](NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C)NC(=O)[C@H](CO)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CC=4C=CC=CC=4)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CCCCN)NC(=O)[C@H](C)NC(=O)[C@H](CCCNC(N)=N)NC2=O)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CSSC[C@H](NC(=O)[C@H](CC=2C=CC=CC=2)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H]2N(CCC2)C(=O)[C@@H](N)CCCNC(N)=N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(O)=O)C(=O)N2[C@@H](CCC2)C(=O)N2[C@@H](CCC2)C(=O)N[C@@H](CC=2C=CC(O)=CC=2)C(=O)N[C@@H]([C@@H](C)O)C(=O)NCC(=O)N2[C@@H](CCC2)C(=O)N3)C(=O)NCC(=O)NCC(=O)N[C@@H](C)C(O)=O)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@H](C(=O)N[C@@H](CC=2C=CC=CC=2)C(=O)N[C@H](C(=O)N1)C(C)C)[C@@H](C)O)[C@@H](C)CC)=O)[C@@H](C)CC)C1=CC=C(O)C=C1 ZPNFWUPYTFPOJU-LPYSRVMUSA-N 0.000 description 1
• 150000002484 inorganic compounds Chemical class 0.000 description 1
• 229910010272 inorganic material Inorganic materials 0.000 description 1
• 230000008611 intercellular interaction Effects 0.000 description 1
• 230000002452 interceptive effect Effects 0.000 description 1
• 229960003507 interferon alfa-2b Drugs 0.000 description 1
• 239000001573 invertase Substances 0.000 description 1
• 235000011073 invertase Nutrition 0.000 description 1
• 150000002500 ions Chemical class 0.000 description 1
• 229960004768 irinotecan Drugs 0.000 description 1
• UWKQSNNFCGGAFS-XIFFEERXSA-N irinotecan Chemical compound C1=C2C(CC)=C3CN(C(C4=C([C@@](C(=O)OC4)(O)CC)C=4)=O)C=4C3=NC2=CC=C1OC(=O)N(CC1)CCC1N1CCCCC1 UWKQSNNFCGGAFS-XIFFEERXSA-N 0.000 description 1
• 239000000797 iron chelating agent Substances 0.000 description 1
• XEEYBQQBJWHFJM-AHCXROLUSA-N iron-52 Chemical compound [52Fe] XEEYBQQBJWHFJM-AHCXROLUSA-N 0.000 description 1
• 238000002955 isolation Methods 0.000 description 1
• AGPKZVBTJJNPAG-UHFFFAOYSA-N isoleucine Natural products CCC(C)C(N)C(O)=O AGPKZVBTJJNPAG-UHFFFAOYSA-N 0.000 description 1
• 229960000310 isoleucine Drugs 0.000 description 1
• QRYFGTULTGLGHU-NBERXCRTSA-N iturelix Chemical compound C([C@H](C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCCNC(C)C)C(=O)N1[C@@H](CCC1)C(=O)N[C@H](C)C(N)=O)NC(=O)[C@H](CCCCNC(=O)C=1C=NC=CC=1)NC(=O)[C@H](CO)NC(=O)[C@@H](CC=1C=NC=CC=1)NC(=O)[C@@H](CC=1C=CC(Cl)=CC=1)NC(=O)[C@@H](CC=1C=C2C=CC=CC2=CC=1)NC(C)=O)CCCNC(=O)C1=CC=CN=C1 QRYFGTULTGLGHU-NBERXCRTSA-N 0.000 description 1
• 108010083551 iturelix Proteins 0.000 description 1
• FABUFPQFXZVHFB-CFWQTKTJSA-N ixabepilone Chemical compound C/C([C@@H]1C[C@@H]2O[C@]2(C)CCC[C@@H]([C@@H]([C@H](C)C(=O)C(C)(C)[C@H](O)CC(=O)N1)O)C)=C\C1=CSC(C)=N1 FABUFPQFXZVHFB-CFWQTKTJSA-N 0.000 description 1
• 229960002014 ixabepilone Drugs 0.000 description 1
• 238000005304 joining Methods 0.000 description 1
• 201000010982 kidney cancer Diseases 0.000 description 1
• 229940043355 kinase inhibitor Drugs 0.000 description 1
• 238000012933 kinetic analysis Methods 0.000 description 1
• 201000004959 laryngeal benign neoplasm Diseases 0.000 description 1
• 206010023841 laryngeal neoplasm Diseases 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
• 229960001691 leucovorin Drugs 0.000 description 1
• GDBQQVLCIARPGH-ULQDDVLXSA-N leupeptin Chemical compound CC(C)C[C@H](NC(C)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@H](C=O)CCCN=C(N)N GDBQQVLCIARPGH-ULQDDVLXSA-N 0.000 description 1
• 108010052968 leupeptin Proteins 0.000 description 1
• 229960001614 levamisole Drugs 0.000 description 1
• 238000000670 ligand binding assay Methods 0.000 description 1
• 230000000670 limiting effect Effects 0.000 description 1
• 150000002632 lipids Chemical class 0.000 description 1
• 238000001638 lipofection Methods 0.000 description 1
• 238000004811 liquid chromatography Methods 0.000 description 1
• 201000007270 liver cancer Diseases 0.000 description 1
• 208000014018 liver neoplasm Diseases 0.000 description 1
• 238000002714 localization assay Methods 0.000 description 1
• 238000012153 long-term therapy Methods 0.000 description 1
• 239000006210 lotion Substances 0.000 description 1
• 101150074251 lpp gene Proteins 0.000 description 1
• 239000000314 lubricant Substances 0.000 description 1
• 201000005249 lung adenocarcinoma Diseases 0.000 description 1
• 201000005202 lung cancer Diseases 0.000 description 1
• 208000020816 lung neoplasm Diseases 0.000 description 1
• 210000004324 lymphatic system Anatomy 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
• 210000002540 macrophage Anatomy 0.000 description 1
• 239000011777 magnesium Substances 0.000 description 1
• 229910052749 magnesium Inorganic materials 0.000 description 1
• 235000019359 magnesium stearate Nutrition 0.000 description 1
• 230000014759 maintenance of location Effects 0.000 description 1
• 208000015486 malignant pancreatic neoplasm Diseases 0.000 description 1
• 208000026037 malignant tumor of neck Diseases 0.000 description 1
• 238000007726 management method Methods 0.000 description 1
• 229910052748 manganese Inorganic materials 0.000 description 1
• 239000011572 manganese Substances 0.000 description 1
• 238000004949 mass spectrometry Methods 0.000 description 1
• 239000011159 matrix material Substances 0.000 description 1
• 229950008001 matuzumab Drugs 0.000 description 1
• 230000007246 mechanism Effects 0.000 description 1
• 229960001924 melphalan Drugs 0.000 description 1
• SGDBTWWWUNNDEQ-LBPRGKRZSA-N melphalan Chemical compound OC(=O)[C@@H](N)CC1=CC=C(N(CCCl)CCCl)C=C1 SGDBTWWWUNNDEQ-LBPRGKRZSA-N 0.000 description 1
• 239000012528 membrane Substances 0.000 description 1
• 230000004060 metabolic process Effects 0.000 description 1
• 150000002739 metals Chemical class 0.000 description 1
• 230000009401 metastasis Effects 0.000 description 1
• 229960000485 methotrexate Drugs 0.000 description 1
• 230000011987 methylation Effects 0.000 description 1
• 238000007069 methylation reaction Methods 0.000 description 1
• 238000013508 migration Methods 0.000 description 1
• 230000005012 migration Effects 0.000 description 1
• 150000007522 mineralic acids Chemical class 0.000 description 1
• 229960004857 mitomycin Drugs 0.000 description 1
• KKZJGLLVHKMTCM-UHFFFAOYSA-N mitoxantrone Chemical compound O=C1C2=C(O)C=CC(O)=C2C(=O)C2=C1C(NCCNCCO)=CC=C2NCCNCCO KKZJGLLVHKMTCM-UHFFFAOYSA-N 0.000 description 1
• 229960001156 mitoxantrone Drugs 0.000 description 1
• 238000010369 molecular cloning Methods 0.000 description 1
• 201000006894 monocytic leukemia Diseases 0.000 description 1
• 238000004264 monolayer culture Methods 0.000 description 1
• 150000002772 monosaccharides Chemical class 0.000 description 1
• 108700039855 mouse a Proteins 0.000 description 1
• 150000002790 naphthalenes Chemical class 0.000 description 1
• 239000004309 nisin Substances 0.000 description 1
• 229920001220 nitrocellulos Polymers 0.000 description 1
• 238000010606 normalization Methods 0.000 description 1
• 238000010899 nucleation Methods 0.000 description 1
• 230000000269 nucleophilic effect Effects 0.000 description 1
• 235000015097 nutrients Nutrition 0.000 description 1
• QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 1
• OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 1
• 239000003921 oil Substances 0.000 description 1
• 235000019198 oils Nutrition 0.000 description 1
• 239000002674 ointment Substances 0.000 description 1
• 230000000771 oncological effect Effects 0.000 description 1
• 238000011275 oncology therapy Methods 0.000 description 1
• 210000000056 organ Anatomy 0.000 description 1
• 150000007524 organic acids Chemical class 0.000 description 1
• 235000005985 organic acids Nutrition 0.000 description 1
• 230000003204 osmotic effect Effects 0.000 description 1
• 230000001151 other effect Effects 0.000 description 1
• 210000001672 ovary Anatomy 0.000 description 1
• 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 1
• 229960001756 oxaliplatin Drugs 0.000 description 1
• 229910052760 oxygen Inorganic materials 0.000 description 1
• 239000001301 oxygen Substances 0.000 description 1
• 229960001592 paclitaxel Drugs 0.000 description 1
• IPCSVZSSVZVIGE-UHFFFAOYSA-N palmitic acid group Chemical group C(CCCCCCCCCCCCCCC)(=O)O IPCSVZSSVZVIGE-UHFFFAOYSA-N 0.000 description 1
• 201000002528 pancreatic cancer Diseases 0.000 description 1
• 208000008443 pancreatic carcinoma Diseases 0.000 description 1
• 239000002245 particle Substances 0.000 description 1
• 229950009506 penicillinase Drugs 0.000 description 1
• 108010091212 pepstatin Proteins 0.000 description 1
• FAXGPCHRFPCXOO-LXTPJMTPSA-N pepstatin A Chemical compound OC(=O)C[C@H](O)[C@H](CC(C)C)NC(=O)[C@H](C)NC(=O)C[C@H](O)[C@H](CC(C)C)NC(=O)[C@H](C(C)C)NC(=O)[C@H](C(C)C)NC(=O)CC(C)C FAXGPCHRFPCXOO-LXTPJMTPSA-N 0.000 description 1
• 238000010647 peptide synthesis reaction Methods 0.000 description 1
• 230000000737 periodic effect Effects 0.000 description 1
• 230000002093 peripheral effect Effects 0.000 description 1
• 239000008194 pharmaceutical composition Substances 0.000 description 1
• 239000000825 pharmaceutical preparation Substances 0.000 description 1
• 229940127557 pharmaceutical product Drugs 0.000 description 1
• COLNVLDHVKWLRT-UHFFFAOYSA-N phenylalanine Natural products OC(=O)C(N)CC1=CC=CC=C1 COLNVLDHVKWLRT-UHFFFAOYSA-N 0.000 description 1
• 150000003013 phosphoric acid derivatives Chemical class 0.000 description 1
• 102000020233 phosphotransferase Human genes 0.000 description 1
• 239000003757 phosphotransferase inhibitor Substances 0.000 description 1
• 239000006187 pill Substances 0.000 description 1
• 239000003123 plant toxin Substances 0.000 description 1
• 229910052697 platinum Inorganic materials 0.000 description 1
• 229920001200 poly(ethylene-vinyl acetate) Polymers 0.000 description 1
• 230000008488 polyadenylation Effects 0.000 description 1
• 229940068918 polyethylene glycol 400 Drugs 0.000 description 1
• 229920005862 polyol Polymers 0.000 description 1
• 150000003077 polyols Chemical group 0.000 description 1
• 229920002503 polyoxyethylene-polyoxypropylene Polymers 0.000 description 1
• 229920001155 polypropylene Polymers 0.000 description 1
• 150000004804 polysaccharides Polymers 0.000 description 1
• OXCMYAYHXIHQOA-UHFFFAOYSA-N potassium;[2-butyl-5-chloro-3-[[4-[2-(1,2,4-triaza-3-azanidacyclopenta-1,4-dien-5-yl)phenyl]phenyl]methyl]imidazol-4-yl]methanol Chemical compound [K+].CCCCC1=NC(Cl)=C(CO)N1CC1=CC=C(C=2C(=CC=CC=2)C2=N[N-]N=N2)C=C1 OXCMYAYHXIHQOA-UHFFFAOYSA-N 0.000 description 1
• 238000011533 pre-incubation Methods 0.000 description 1
• 239000002244 precipitate Substances 0.000 description 1
• 238000001556 precipitation Methods 0.000 description 1
• 239000002243 precursor Substances 0.000 description 1
• 239000003755 preservative agent Substances 0.000 description 1
• 230000008569 process Effects 0.000 description 1
• 125000001500 prolyl group Chemical group [H]N1C([H])(C(=O)[*])C([H])([H])C([H])([H])C1([H])[H] 0.000 description 1
• 230000001737 promoting effect Effects 0.000 description 1
• 238000011321 prophylaxis Methods 0.000 description 1
• 235000019833 protease Nutrition 0.000 description 1
• 108020001580 protein domains Proteins 0.000 description 1
• 239000003531 protein hydrolysate Substances 0.000 description 1
• 108060006633 protein kinase Proteins 0.000 description 1
• 239000012474 protein marker Substances 0.000 description 1
• 239000012460 protein solution Substances 0.000 description 1
• 230000012743 protein tagging Effects 0.000 description 1
• 230000006337 proteolytic cleavage Effects 0.000 description 1
• 238000002601 radiography Methods 0.000 description 1
• 238000001959 radiotherapy Methods 0.000 description 1
• 108700016418 rat Egfr Proteins 0.000 description 1
• 230000009257 reactivity Effects 0.000 description 1
• 238000001953 recrystallisation Methods 0.000 description 1
• 230000010076 replication Effects 0.000 description 1
• 238000004366 reverse phase liquid chromatography Methods 0.000 description 1
• 238000007151 ring opening polymerisation reaction Methods 0.000 description 1
• 229960004641 rituximab Drugs 0.000 description 1
• 229940102127 rubidium chloride Drugs 0.000 description 1
• 239000013017 sartobind Substances 0.000 description 1
• 238000007423 screening assay Methods 0.000 description 1
• 230000003248 secreting effect Effects 0.000 description 1
• 230000028327 secretion Effects 0.000 description 1
• 239000013049 sediment Substances 0.000 description 1
• 238000010187 selection method Methods 0.000 description 1
• 238000000926 separation method Methods 0.000 description 1
• 230000009919 sequestration Effects 0.000 description 1
• SQVRNKJHWKZAKO-OQPLDHBCSA-N sialic acid Chemical compound CC(=O)N[C@@H]1[C@@H](O)C[C@@](O)(C(O)=O)OC1[C@H](O)[C@H](O)CO SQVRNKJHWKZAKO-OQPLDHBCSA-N 0.000 description 1
• 230000009450 sialylation Effects 0.000 description 1
• 230000007781 signaling event Effects 0.000 description 1
• 230000009131 signaling function Effects 0.000 description 1
• 238000009097 single-agent therapy Methods 0.000 description 1
• 238000003998 size exclusion chromatography high performance liquid chromatography Methods 0.000 description 1
• 208000000587 small cell lung carcinoma Diseases 0.000 description 1
• 150000003384 small molecules Chemical class 0.000 description 1
• 239000001632 sodium acetate Substances 0.000 description 1
• 235000017281 sodium acetate Nutrition 0.000 description 1
• 239000001488 sodium phosphate Substances 0.000 description 1
• MIXCUJKCXRNYFM-UHFFFAOYSA-M sodium;diiodomethanesulfonate;n-propyl-n-[2-(2,4,6-trichlorophenoxy)ethyl]imidazole-1-carboxamide Chemical compound [Na+].[O-]S(=O)(=O)C(I)I.C1=CN=CN1C(=O)N(CCC)CCOC1=C(Cl)C=C(Cl)C=C1Cl MIXCUJKCXRNYFM-UHFFFAOYSA-M 0.000 description 1
• 239000002047 solid lipid nanoparticle Substances 0.000 description 1
• 239000000600 sorbitol Substances 0.000 description 1
• 238000001228 spectrum Methods 0.000 description 1
• 230000002269 spontaneous effect Effects 0.000 description 1
• 230000000087 stabilizing effect Effects 0.000 description 1
• 239000012192 staining solution Substances 0.000 description 1
• 238000010972 statistical evaluation Methods 0.000 description 1
• 239000008117 stearic acid Substances 0.000 description 1
• 239000008223 sterile water Substances 0.000 description 1
• 201000011549 stomach cancer Diseases 0.000 description 1
• ZSJLQEPLLKMAKR-GKHCUFPYSA-N streptozocin Chemical compound O=NN(C)C(=O)N[C@H]1[C@@H](O)O[C@H](CO)[C@@H](O)[C@@H]1O ZSJLQEPLLKMAKR-GKHCUFPYSA-N 0.000 description 1
• 229960001052 streptozocin Drugs 0.000 description 1
• 239000005720 sucrose Substances 0.000 description 1
• 150000008163 sugars Chemical class 0.000 description 1
• 229910052717 sulfur Inorganic materials 0.000 description 1
• 230000010741 sumoylation Effects 0.000 description 1
• 239000013589 supplement Substances 0.000 description 1
• 239000004094 surface-active agent Substances 0.000 description 1
• 238000011477 surgical intervention Methods 0.000 description 1
• 230000002459 sustained effect Effects 0.000 description 1
• 238000013268 sustained release Methods 0.000 description 1
• 239000007939 sustained release tablet Substances 0.000 description 1
• 239000012730 sustained-release form Substances 0.000 description 1
• 208000024891 symptom Diseases 0.000 description 1
• 230000002195 synergetic effect Effects 0.000 description 1
• 229960001603 tamoxifen Drugs 0.000 description 1
• LRBQNJMCXXYXIU-NRMVVENXSA-N tannic acid Chemical compound OC1=C(O)C(O)=CC(C(=O)OC=2C(=C(O)C=C(C=2)C(=O)OC[C@@H]2[C@H]([C@H](OC(=O)C=3C=C(OC(=O)C=4C=C(O)C(O)=C(O)C=4)C(O)=C(O)C=3)[C@@H](OC(=O)C=3C=C(OC(=O)C=4C=C(O)C(O)=C(O)C=4)C(O)=C(O)C=3)[C@@H](OC(=O)C=3C=C(OC(=O)C=4C=C(O)C(O)=C(O)C=4)C(O)=C(O)C=3)O2)OC(=O)C=2C=C(OC(=O)C=3C=C(O)C(O)=C(O)C=3)C(O)=C(O)C=2)O)=C1 LRBQNJMCXXYXIU-NRMVVENXSA-N 0.000 description 1
• 235000015523 tannic acid Nutrition 0.000 description 1
• 229920002258 tannic acid Polymers 0.000 description 1
• 229940033123 tannic acid Drugs 0.000 description 1
• RCINICONZNJXQF-MZXODVADSA-N taxol Chemical compound O([C@@H]1[C@@]2(C[C@@H](C(C)=C(C2(C)C)[C@H](C([C@]2(C)[C@@H](O)C[C@H]3OC[C@]3([C@H]21)OC(C)=O)=O)OC(=O)C)OC(=O)[C@H](O)[C@@H](NC(=O)C=1C=CC=CC=1)C=1C=CC=CC=1)O)C(=O)C1=CC=CC=C1 RCINICONZNJXQF-MZXODVADSA-N 0.000 description 1
• 238000011191 terminal modification Methods 0.000 description 1
• 125000000101 thioether group Chemical group 0.000 description 1
• 229940104230 thymidine Drugs 0.000 description 1
• 201000002510 thyroid cancer Diseases 0.000 description 1
• 238000003325 tomography Methods 0.000 description 1
• 230000000699 topical effect Effects 0.000 description 1
• 229960000303 topotecan Drugs 0.000 description 1
• UCFGDBYHRUNTLO-QHCPKHFHSA-N topotecan Chemical compound C1=C(O)C(CN(C)C)=C2C=C(CN3C4=CC5=C(C3=O)COC(=O)[C@]5(O)CC)C4=NC2=C1 UCFGDBYHRUNTLO-QHCPKHFHSA-N 0.000 description 1
• 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
• 229960005267 tositumomab Drugs 0.000 description 1
• 231100000331 toxic Toxicity 0.000 description 1
• 230000002588 toxic effect Effects 0.000 description 1
• 239000011573 trace mineral Substances 0.000 description 1
• 235000013619 trace mineral Nutrition 0.000 description 1
• 230000005030 transcription termination Effects 0.000 description 1
• 230000002103 transcriptional effect Effects 0.000 description 1
• 238000001890 transfection Methods 0.000 description 1
• 102000035160 transmembrane proteins Human genes 0.000 description 1
• 108091005703 transmembrane proteins Proteins 0.000 description 1
• 229960000575 trastuzumab Drugs 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
• RYFMWSXOAZQYPI-UHFFFAOYSA-K trisodium phosphate Chemical compound [Na+].[Na+].[Na+].[O-]P([O-])([O-])=O RYFMWSXOAZQYPI-UHFFFAOYSA-K 0.000 description 1
• 108010087967 type I signal peptidase Proteins 0.000 description 1
• 229950009811 ubenimex Drugs 0.000 description 1
• 238000010798 ubiquitination Methods 0.000 description 1
• 230000034512 ubiquitination Effects 0.000 description 1
• 238000000108 ultra-filtration Methods 0.000 description 1
• 241000701447 unidentified baculovirus Species 0.000 description 1
• 230000003827 upregulation Effects 0.000 description 1
• 201000005112 urinary bladder cancer Diseases 0.000 description 1
• VBEQCZHXXJYVRD-GACYYNSASA-N uroanthelone Chemical compound C([C@@H](C(=O)N[C@H](C(=O)N[C@@H](CS)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CS)C(=O)N[C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)NCC(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N[C@@H](CO)C(=O)NCC(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CS)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O)C(C)C)[C@@H](C)O)NC(=O)[C@H](CO)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CO)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@@H](NC(=O)[C@H](CC=1NC=NC=1)NC(=O)[C@H](CCSC)NC(=O)[C@H](CS)NC(=O)[C@@H](NC(=O)CNC(=O)CNC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CS)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)CNC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CO)NC(=O)[C@H](CO)NC(=O)[C@H]1N(CCC1)C(=O)[C@H](CS)NC(=O)CNC(=O)[C@H]1N(CCC1)C(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CO)NC(=O)[C@@H](N)CC(N)=O)C(C)C)[C@@H](C)CC)C1=CC=C(O)C=C1 VBEQCZHXXJYVRD-GACYYNSASA-N 0.000 description 1
• 235000013311 vegetables Nutrition 0.000 description 1
• 229960003048 vinblastine Drugs 0.000 description 1
• 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 1
• 229960004528 vincristine Drugs 0.000 description 1
• 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 1
• 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 1
• 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 1
• 229960002066 vinorelbine Drugs 0.000 description 1
• 230000003612 virological effect Effects 0.000 description 1
• 239000011534 wash buffer Substances 0.000 description 1
• 230000004580 weight loss Effects 0.000 description 1
• 229950008250 zalutumumab Drugs 0.000 description 1
• 229910052725 zinc Inorganic materials 0.000 description 1
• 239000011701 zinc Substances 0.000 description 1
• XOOUIPVCVHRTMJ-UHFFFAOYSA-L zinc stearate Chemical compound [Zn+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O XOOUIPVCVHRTMJ-UHFFFAOYSA-L 0.000 description 1
• XRASPMIURGNCCH-UHFFFAOYSA-N zoledronic acid Chemical compound OP(=O)(O)C(P(O)(O)=O)(O)CN1C=CN=C1 XRASPMIURGNCCH-UHFFFAOYSA-N 0.000 description 1
• 229960004276 zoledronic acid Drugs 0.000 description 1