JP2022512132A - 抗クローディン抗体及びそれらの使用 - Google Patents
抗クローディン抗体及びそれらの使用 Download PDFInfo
- Publication number
- JP2022512132A JP2022512132A JP2021532180A JP2021532180A JP2022512132A JP 2022512132 A JP2022512132 A JP 2022512132A JP 2021532180 A JP2021532180 A JP 2021532180A JP 2021532180 A JP2021532180 A JP 2021532180A JP 2022512132 A JP2022512132 A JP 2022512132A
- Authority
- JP
- Japan
- Prior art keywords
- antibody
- seq
- region
- cldn
- sequence
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
Links
- 238000000034 method Methods 0.000 claims abstract description 108
- 230000000694 effects Effects 0.000 claims abstract description 89
- 206010028980 Neoplasm Diseases 0.000 claims abstract description 59
- 201000011510 cancer Diseases 0.000 claims abstract description 37
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 35
- 230000022534 cell killing Effects 0.000 claims abstract description 15
- 230000001939 inductive effect Effects 0.000 claims abstract description 11
- 210000004027 cell Anatomy 0.000 claims description 354
- 230000027455 binding Effects 0.000 claims description 231
- 230000035772 mutation Effects 0.000 claims description 100
- 230000010056 antibody-dependent cellular cytotoxicity Effects 0.000 claims description 85
- 235000001014 amino acid Nutrition 0.000 claims description 84
- 241000282414 Homo sapiens Species 0.000 claims description 81
- 239000003814 drug Substances 0.000 claims description 69
- 239000012634 fragment Substances 0.000 claims description 65
- 102100035361 Cerebellar degeneration-related protein 2 Human genes 0.000 claims description 62
- 101000737796 Homo sapiens Cerebellar degeneration-related protein 2 Proteins 0.000 claims description 62
- 101100112922 Candida albicans CDR3 gene Proteins 0.000 claims description 61
- 208000005718 Stomach Neoplasms Diseases 0.000 claims description 45
- 206010017758 gastric cancer Diseases 0.000 claims description 45
- 201000011549 stomach cancer Diseases 0.000 claims description 45
- 229940124597 therapeutic agent Drugs 0.000 claims description 41
- 108090000623 proteins and genes Proteins 0.000 claims description 39
- 150000001413 amino acids Chemical group 0.000 claims description 37
- 150000007523 nucleic acids Chemical class 0.000 claims description 35
- 125000000539 amino acid group Chemical group 0.000 claims description 34
- 102000039446 nucleic acids Human genes 0.000 claims description 33
- 108020004707 nucleic acids Proteins 0.000 claims description 33
- 102000004169 proteins and genes Human genes 0.000 claims description 33
- 235000018102 proteins Nutrition 0.000 claims description 32
- 230000004481 post-translational protein modification Effects 0.000 claims description 27
- 206010017993 Gastrointestinal neoplasms Diseases 0.000 claims description 26
- 239000013598 vector Substances 0.000 claims description 25
- 108010044540 auristatin Proteins 0.000 claims description 23
- 229920000642 polymer Polymers 0.000 claims description 21
- 230000004540 complement-dependent cytotoxicity Effects 0.000 claims description 20
- 206010061902 Pancreatic neoplasm Diseases 0.000 claims description 18
- 208000015486 malignant pancreatic neoplasm Diseases 0.000 claims description 18
- 201000002528 pancreatic cancer Diseases 0.000 claims description 18
- 208000008443 pancreatic carcinoma Diseases 0.000 claims description 18
- IEDXPSOJFSVCKU-HOKPPMCLSA-N [4-[[(2S)-5-(carbamoylamino)-2-[[(2S)-2-[6-(2,5-dioxopyrrolidin-1-yl)hexanoylamino]-3-methylbutanoyl]amino]pentanoyl]amino]phenyl]methyl N-[(2S)-1-[[(2S)-1-[[(3R,4S,5S)-1-[(2S)-2-[(1R,2R)-3-[[(1S,2R)-1-hydroxy-1-phenylpropan-2-yl]amino]-1-methoxy-2-methyl-3-oxopropyl]pyrrolidin-1-yl]-3-methoxy-5-methyl-1-oxoheptan-4-yl]-methylamino]-3-methyl-1-oxobutan-2-yl]amino]-3-methyl-1-oxobutan-2-yl]-N-methylcarbamate Chemical group CC[C@H](C)[C@@H]([C@@H](CC(=O)N1CCC[C@H]1[C@H](OC)[C@@H](C)C(=O)N[C@H](C)[C@@H](O)c1ccccc1)OC)N(C)C(=O)[C@@H](NC(=O)[C@H](C(C)C)N(C)C(=O)OCc1ccc(NC(=O)[C@H](CCCNC(N)=O)NC(=O)[C@@H](NC(=O)CCCCCN2C(=O)CCC2=O)C(C)C)cc1)C(C)C IEDXPSOJFSVCKU-HOKPPMCLSA-N 0.000 claims description 15
- 229910052717 sulfur Inorganic materials 0.000 claims description 15
- MFRNYXJJRJQHNW-DEMKXPNLSA-N (2s)-2-[[(2r,3r)-3-methoxy-3-[(2s)-1-[(3r,4s,5s)-3-methoxy-5-methyl-4-[methyl-[(2s)-3-methyl-2-[[(2s)-3-methyl-2-(methylamino)butanoyl]amino]butanoyl]amino]heptanoyl]pyrrolidin-2-yl]-2-methylpropanoyl]amino]-3-phenylpropanoic acid Chemical group CN[C@@H](C(C)C)C(=O)N[C@@H](C(C)C)C(=O)N(C)[C@@H]([C@@H](C)CC)[C@H](OC)CC(=O)N1CCC[C@H]1[C@H](OC)[C@@H](C)C(=O)N[C@H](C(O)=O)CC1=CC=CC=C1 MFRNYXJJRJQHNW-DEMKXPNLSA-N 0.000 claims description 14
- 108010093470 monomethyl auristatin E Proteins 0.000 claims description 14
- 108010059074 monomethylauristatin F Proteins 0.000 claims description 14
- 229910052698 phosphorus Inorganic materials 0.000 claims description 14
- 229910052727 yttrium Inorganic materials 0.000 claims description 14
- 241000282567 Macaca fascicularis Species 0.000 claims description 12
- 108010029485 Protein Isoforms Proteins 0.000 claims description 12
- 102000001708 Protein Isoforms Human genes 0.000 claims description 12
- AGPKZVBTJJNPAG-WHFBIAKZSA-N L-isoleucine Chemical compound CC[C@H](C)[C@H](N)C(O)=O AGPKZVBTJJNPAG-WHFBIAKZSA-N 0.000 claims description 11
- AGPKZVBTJJNPAG-UHFFFAOYSA-N isoleucine Natural products CCC(C)C(N)C(O)=O AGPKZVBTJJNPAG-UHFFFAOYSA-N 0.000 claims description 11
- 229960000310 isoleucine Drugs 0.000 claims description 11
- 208000000461 Esophageal Neoplasms Diseases 0.000 claims description 9
- WHUUTDBJXJRKMK-UHFFFAOYSA-N Glutamic acid Natural products OC(=O)C(N)CCC(O)=O WHUUTDBJXJRKMK-UHFFFAOYSA-N 0.000 claims description 9
- CKLJMWTZIZZHCS-REOHCLBHSA-N L-aspartic acid Chemical compound OC(=O)[C@@H](N)CC(O)=O CKLJMWTZIZZHCS-REOHCLBHSA-N 0.000 claims description 9
- ROHFNLRQFUQHCH-YFKPBYRVSA-N L-leucine Chemical compound CC(C)C[C@H](N)C(O)=O ROHFNLRQFUQHCH-YFKPBYRVSA-N 0.000 claims description 9
- ROHFNLRQFUQHCH-UHFFFAOYSA-N Leucine Natural products CC(C)CC(N)C(O)=O ROHFNLRQFUQHCH-UHFFFAOYSA-N 0.000 claims description 9
- 206010061535 Ovarian neoplasm Diseases 0.000 claims description 9
- 235000013922 glutamic acid Nutrition 0.000 claims description 9
- 239000004220 glutamic acid Substances 0.000 claims description 9
- 229910052757 nitrogen Inorganic materials 0.000 claims description 9
- KZSNJWFQEVHDMF-BYPYZUCNSA-N L-valine Chemical compound CC(C)[C@H](N)C(O)=O KZSNJWFQEVHDMF-BYPYZUCNSA-N 0.000 claims description 8
- 206010030155 Oesophageal carcinoma Diseases 0.000 claims description 8
- KZSNJWFQEVHDMF-UHFFFAOYSA-N Valine Natural products CC(C)C(N)C(O)=O KZSNJWFQEVHDMF-UHFFFAOYSA-N 0.000 claims description 8
- 235000003704 aspartic acid Nutrition 0.000 claims description 8
- OQFSQFPPLPISGP-UHFFFAOYSA-N beta-carboxyaspartic acid Natural products OC(=O)C(N)C(C(O)=O)C(O)=O OQFSQFPPLPISGP-UHFFFAOYSA-N 0.000 claims description 8
- 201000004101 esophageal cancer Diseases 0.000 claims description 8
- 208000020816 lung neoplasm Diseases 0.000 claims description 8
- 239000004474 valine Substances 0.000 claims description 8
- QNAYBMKLOCPYGJ-REOHCLBHSA-N L-alanine Chemical compound C[C@H](N)C(O)=O QNAYBMKLOCPYGJ-REOHCLBHSA-N 0.000 claims description 7
- WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 claims description 7
- 206010058467 Lung neoplasm malignant Diseases 0.000 claims description 7
- 206010033128 Ovarian cancer Diseases 0.000 claims description 7
- 235000004279 alanine Nutrition 0.000 claims description 7
- VQNATVDKACXKTF-XELLLNAOSA-N duocarmycin Chemical compound COC1=C(OC)C(OC)=C2NC(C(=O)N3C4=CC(=O)C5=C([C@@]64C[C@@H]6C3)C=C(N5)C(=O)OC)=CC2=C1 VQNATVDKACXKTF-XELLLNAOSA-N 0.000 claims description 7
- 201000005202 lung cancer Diseases 0.000 claims description 7
- 229960005501 duocarmycin Drugs 0.000 claims description 6
- 229930184221 duocarmycin Natural products 0.000 claims description 6
- ZDXPYRJPNDTMRX-UHFFFAOYSA-N glutamine Natural products OC(=O)C(N)CCC(N)=O ZDXPYRJPNDTMRX-UHFFFAOYSA-N 0.000 claims description 6
- 230000003054 hormonal effect Effects 0.000 claims description 6
- 230000001976 improved effect Effects 0.000 claims description 6
- 229910052720 vanadium Inorganic materials 0.000 claims description 6
- 239000002246 antineoplastic agent Substances 0.000 claims description 5
- 229940127089 cytotoxic agent Drugs 0.000 claims description 5
- 239000002955 immunomodulating agent Substances 0.000 claims description 5
- 238000001727 in vivo Methods 0.000 claims description 5
- ZDXPYRJPNDTMRX-VKHMYHEASA-N L-glutamine Chemical compound OC(=O)[C@@H](N)CCC(N)=O ZDXPYRJPNDTMRX-VKHMYHEASA-N 0.000 claims description 4
- 229910052739 hydrogen Inorganic materials 0.000 claims description 4
- 238000000338 in vitro Methods 0.000 claims description 4
- WVHGJJRMKGDTEC-WCIJHFMNSA-N 2-[(1R,4S,8R,10S,13S,16S,27R,34S)-34-[(2S)-butan-2-yl]-8,22-dihydroxy-13-[(2R,3S)-3-hydroxybutan-2-yl]-2,5,11,14,27,30,33,36,39-nonaoxo-27lambda4-thia-3,6,12,15,25,29,32,35,38-nonazapentacyclo[14.12.11.06,10.018,26.019,24]nonatriaconta-18(26),19(24),20,22-tetraen-4-yl]acetamide Chemical compound CC[C@H](C)[C@@H]1NC(=O)CNC(=O)[C@@H]2Cc3c([nH]c4cc(O)ccc34)[S@](=O)C[C@H](NC(=O)CNC1=O)C(=O)N[C@@H](CC(N)=O)C(=O)N1C[C@H](O)C[C@H]1C(=O)N[C@@H]([C@@H](C)[C@H](C)O)C(=O)N2 WVHGJJRMKGDTEC-WCIJHFMNSA-N 0.000 claims description 3
- 231100000729 Amatoxin Toxicity 0.000 claims description 3
- 108010003723 Single-Domain Antibodies Proteins 0.000 claims description 3
- 108010014709 amatoxin Proteins 0.000 claims description 3
- 230000006872 improvement Effects 0.000 claims description 3
- 230000002018 overexpression Effects 0.000 claims description 3
- 210000000130 stem cell Anatomy 0.000 claims description 3
- 238000007911 parenteral administration Methods 0.000 claims description 2
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 2
- 230000005855 radiation Effects 0.000 claims description 2
- 238000007910 systemic administration Methods 0.000 claims description 2
- 102100035360 Cerebellar degeneration-related antigen 1 Human genes 0.000 claims 10
- 101000737793 Homo sapiens Cerebellar degeneration-related antigen 1 Proteins 0.000 claims 10
- 238000010586 diagram Methods 0.000 abstract 1
- -1 enediyne Chemical compound 0.000 description 63
- 125000005647 linker group Chemical group 0.000 description 63
- 239000000427 antigen Substances 0.000 description 57
- 108091007433 antigens Proteins 0.000 description 56
- 102000036639 antigens Human genes 0.000 description 56
- 125000003275 alpha amino acid group Chemical group 0.000 description 54
- 102000002029 Claudin Human genes 0.000 description 42
- 108050009302 Claudin Proteins 0.000 description 42
- 108090000765 processed proteins & peptides Proteins 0.000 description 41
- 241000699666 Mus <mouse, genus> Species 0.000 description 36
- 239000012636 effector Substances 0.000 description 29
- 102000004196 processed proteins & peptides Human genes 0.000 description 29
- 229940049595 antibody-drug conjugate Drugs 0.000 description 28
- 239000000203 mixture Substances 0.000 description 28
- 241000699670 Mus sp. Species 0.000 description 25
- 108091022873 acetoacetate decarboxylase Proteins 0.000 description 25
- 229920001184 polypeptide Polymers 0.000 description 25
- 238000011282 treatment Methods 0.000 description 25
- 229920001223 polyethylene glycol Polymers 0.000 description 24
- 108091033319 polynucleotide Proteins 0.000 description 24
- 102000040430 polynucleotide Human genes 0.000 description 24
- 229940024606 amino acid Drugs 0.000 description 23
- 230000014509 gene expression Effects 0.000 description 21
- 210000003819 peripheral blood mononuclear cell Anatomy 0.000 description 21
- 239000002157 polynucleotide Substances 0.000 description 21
- 108020004414 DNA Proteins 0.000 description 20
- 230000004083 survival effect Effects 0.000 description 20
- 238000001943 fluorescence-activated cell sorting Methods 0.000 description 19
- 210000004408 hybridoma Anatomy 0.000 description 19
- 150000001875 compounds Chemical class 0.000 description 18
- 238000011534 incubation Methods 0.000 description 18
- 238000002474 experimental method Methods 0.000 description 17
- 108010047041 Complementarity Determining Regions Proteins 0.000 description 16
- 108060003951 Immunoglobulin Proteins 0.000 description 16
- 241001465754 Metazoa Species 0.000 description 16
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 16
- 239000000872 buffer Substances 0.000 description 16
- 102000018358 immunoglobulin Human genes 0.000 description 16
- 239000002953 phosphate buffered saline Substances 0.000 description 16
- 239000003795 chemical substances by application Substances 0.000 description 15
- 238000004458 analytical method Methods 0.000 description 14
- 125000003729 nucleotide group Chemical group 0.000 description 14
- 235000002639 sodium chloride Nutrition 0.000 description 14
- 241000700159 Rattus Species 0.000 description 13
- 239000003053 toxin Substances 0.000 description 13
- 231100000765 toxin Toxicity 0.000 description 13
- 108700012359 toxins Proteins 0.000 description 13
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 12
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 12
- 230000003053 immunization Effects 0.000 description 12
- 238000002649 immunization Methods 0.000 description 12
- 238000009472 formulation Methods 0.000 description 11
- 238000006467 substitution reaction Methods 0.000 description 11
- 230000021615 conjugation Effects 0.000 description 10
- 229940079593 drug Drugs 0.000 description 10
- 210000004602 germ cell Anatomy 0.000 description 10
- 239000002105 nanoparticle Substances 0.000 description 10
- 239000000126 substance Substances 0.000 description 10
- 238000005516 engineering process Methods 0.000 description 9
- 230000004927 fusion Effects 0.000 description 9
- 239000002609 medium Substances 0.000 description 9
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 9
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 9
- 239000011734 sodium Substances 0.000 description 9
- 230000009870 specific binding Effects 0.000 description 9
- YBJHBAHKTGYVGT-ZKWXMUAHSA-N (+)-Biotin Chemical compound N1C(=O)N[C@@H]2[C@H](CCCCC(=O)O)SC[C@@H]21 YBJHBAHKTGYVGT-ZKWXMUAHSA-N 0.000 description 8
- 239000002202 Polyethylene glycol Substances 0.000 description 8
- 238000003556 assay Methods 0.000 description 8
- 239000001913 cellulose Substances 0.000 description 8
- 239000003431 cross linking reagent Substances 0.000 description 8
- 230000001419 dependent effect Effects 0.000 description 8
- 231100000673 dose–response relationship Toxicity 0.000 description 8
- 239000000463 material Substances 0.000 description 8
- 230000001404 mediated effect Effects 0.000 description 8
- 238000012986 modification Methods 0.000 description 8
- 239000002773 nucleotide Substances 0.000 description 8
- 229920000233 poly(alkylene oxides) Polymers 0.000 description 8
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 8
- 239000000047 product Substances 0.000 description 8
- 229910052708 sodium Inorganic materials 0.000 description 8
- 235000015424 sodium Nutrition 0.000 description 8
- 239000011780 sodium chloride Substances 0.000 description 8
- 239000007787 solid Substances 0.000 description 8
- 238000002560 therapeutic procedure Methods 0.000 description 8
- URAYPUMNDPQOKB-UHFFFAOYSA-N triacetin Chemical compound CC(=O)OCC(OC(C)=O)COC(C)=O URAYPUMNDPQOKB-UHFFFAOYSA-N 0.000 description 8
- 230000004614 tumor growth Effects 0.000 description 8
- 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 7
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 7
- IAYPIBMASNFSPL-UHFFFAOYSA-N Ethylene oxide Chemical group C1CO1 IAYPIBMASNFSPL-UHFFFAOYSA-N 0.000 description 7
- 108091028043 Nucleic acid sequence Proteins 0.000 description 7
- 229920002472 Starch Polymers 0.000 description 7
- 239000002253 acid Substances 0.000 description 7
- 235000010980 cellulose Nutrition 0.000 description 7
- 229920002678 cellulose Polymers 0.000 description 7
- 210000004978 chinese hamster ovary cell Anatomy 0.000 description 7
- 239000003085 diluting agent Substances 0.000 description 7
- 230000002496 gastric effect Effects 0.000 description 7
- 230000004048 modification Effects 0.000 description 7
- 230000008569 process Effects 0.000 description 7
- 229940032147 starch Drugs 0.000 description 7
- 239000008107 starch Substances 0.000 description 7
- 235000019698 starch Nutrition 0.000 description 7
- 239000006228 supernatant Substances 0.000 description 7
- 238000003786 synthesis reaction Methods 0.000 description 7
- ALYNCZNDIQEVRV-UHFFFAOYSA-N 4-aminobenzoic acid Chemical compound NC1=CC=C(C(O)=O)C=C1 ALYNCZNDIQEVRV-UHFFFAOYSA-N 0.000 description 6
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 6
- AOJJSUZBOXZQNB-TZSSRYMLSA-N Doxorubicin Chemical compound O([C@H]1C[C@@](O)(CC=2C(O)=C3C(=O)C=4C=CC=C(C=4C(=O)C3=C(O)C=21)OC)C(=O)CO)[C@H]1C[C@H](N)[C@H](O)[C@H](C)O1 AOJJSUZBOXZQNB-TZSSRYMLSA-N 0.000 description 6
- 108010043121 Green Fluorescent Proteins Proteins 0.000 description 6
- 102000004144 Green Fluorescent Proteins Human genes 0.000 description 6
- KDXKERNSBIXSRK-YFKPBYRVSA-N L-lysine Chemical compound NCCCC[C@H](N)C(O)=O KDXKERNSBIXSRK-YFKPBYRVSA-N 0.000 description 6
- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 6
- HSHXDCVZWHOWCS-UHFFFAOYSA-N N'-hexadecylthiophene-2-carbohydrazide Chemical compound CCCCCCCCCCCCCCCCNNC(=O)c1cccs1 HSHXDCVZWHOWCS-UHFFFAOYSA-N 0.000 description 6
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 6
- 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 6
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid group Chemical group C(C1=CC=CC=C1)(=O)O WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 6
- 229910002091 carbon monoxide Inorganic materials 0.000 description 6
- 239000006285 cell suspension Substances 0.000 description 6
- HVYWMOMLDIMFJA-DPAQBDIFSA-N cholesterol Chemical compound C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CCCC(C)C)[C@@]1(C)CC2 HVYWMOMLDIMFJA-DPAQBDIFSA-N 0.000 description 6
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 6
- 239000006185 dispersion Substances 0.000 description 6
- 239000013604 expression vector Substances 0.000 description 6
- 239000012091 fetal bovine serum Substances 0.000 description 6
- 238000000684 flow cytometry Methods 0.000 description 6
- 239000005090 green fluorescent protein Substances 0.000 description 6
- 235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 description 6
- 239000001866 hydroxypropyl methyl cellulose Substances 0.000 description 6
- 229920003088 hydroxypropyl methyl cellulose Polymers 0.000 description 6
- 229920000053 polysorbate 80 Polymers 0.000 description 6
- 238000000159 protein binding assay Methods 0.000 description 6
- 230000002829 reductive effect Effects 0.000 description 6
- 210000002966 serum Anatomy 0.000 description 6
- 239000004094 surface-active agent Substances 0.000 description 6
- 230000001225 therapeutic effect Effects 0.000 description 6
- 239000011534 wash buffer Substances 0.000 description 6
- 238000012447 xenograft mouse model Methods 0.000 description 6
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 5
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 5
- 239000004471 Glycine Substances 0.000 description 5
- 108010017213 Granulocyte-Macrophage Colony-Stimulating Factor Proteins 0.000 description 5
- 102100039620 Granulocyte-macrophage colony-stimulating factor Human genes 0.000 description 5
- 241000282412 Homo Species 0.000 description 5
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 5
- XUJNEKJLAYXESH-REOHCLBHSA-N L-Cysteine Chemical compound SC[C@H](N)C(O)=O XUJNEKJLAYXESH-REOHCLBHSA-N 0.000 description 5
- DBMJMQXJHONAFJ-UHFFFAOYSA-M Sodium laurylsulphate Chemical compound [Na+].CCCCCCCCCCCCOS([O-])(=O)=O DBMJMQXJHONAFJ-UHFFFAOYSA-M 0.000 description 5
- 230000015572 biosynthetic process Effects 0.000 description 5
- 239000001506 calcium phosphate Substances 0.000 description 5
- 239000000562 conjugate Substances 0.000 description 5
- 230000003013 cytotoxicity Effects 0.000 description 5
- 231100000135 cytotoxicity Toxicity 0.000 description 5
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 5
- FUZZWVXGSFPDMH-UHFFFAOYSA-N hexanoic acid Chemical compound CCCCCC(O)=O FUZZWVXGSFPDMH-UHFFFAOYSA-N 0.000 description 5
- 238000001990 intravenous administration Methods 0.000 description 5
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 5
- 235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 description 5
- 230000001105 regulatory effect Effects 0.000 description 5
- 230000000717 retained effect Effects 0.000 description 5
- 150000003839 salts Chemical class 0.000 description 5
- 235000019333 sodium laurylsulphate Nutrition 0.000 description 5
- 239000000243 solution Substances 0.000 description 5
- 238000012360 testing method 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
- 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 5
- JWDFQMWEFLOOED-UHFFFAOYSA-N (2,5-dioxopyrrolidin-1-yl) 3-(pyridin-2-yldisulfanyl)propanoate Chemical compound O=C1CCC(=O)N1OC(=O)CCSSC1=CC=CC=N1 JWDFQMWEFLOOED-UHFFFAOYSA-N 0.000 description 4
- VBICKXHEKHSIBG-UHFFFAOYSA-N 1-monostearoylglycerol Chemical compound CCCCCCCCCCCCCCCCCC(=O)OCC(O)CO VBICKXHEKHSIBG-UHFFFAOYSA-N 0.000 description 4
- AOJJSUZBOXZQNB-VTZDEGQISA-N 4'-epidoxorubicin Chemical compound O([C@H]1C[C@@](O)(CC=2C(O)=C3C(=O)C=4C=CC=C(C=4C(=O)C3=C(O)C=21)OC)C(=O)CO)[C@H]1C[C@H](N)[C@@H](O)[C@H](C)O1 AOJJSUZBOXZQNB-VTZDEGQISA-N 0.000 description 4
- YXHLJMWYDTXDHS-IRFLANFNSA-N 7-aminoactinomycin D Chemical compound C[C@H]1OC(=O)[C@H](C(C)C)N(C)C(=O)CN(C)C(=O)[C@@H]2CCCN2C(=O)[C@@H](C(C)C)NC(=O)[C@H]1NC(=O)C1=C(N)C(=O)C(C)=C2OC(C(C)=C(N)C=C3C(=O)N[C@@H]4C(=O)N[C@@H](C(N5CCC[C@H]5C(=O)N(C)CC(=O)N(C)[C@@H](C(C)C)C(=O)O[C@@H]4C)=O)C(C)C)=C3N=C21 YXHLJMWYDTXDHS-IRFLANFNSA-N 0.000 description 4
- 108700012813 7-aminoactinomycin D Proteins 0.000 description 4
- 239000012114 Alexa Fluor 647 Substances 0.000 description 4
- VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 description 4
- 201000009030 Carcinoma Diseases 0.000 description 4
- 102100040835 Claudin-18 Human genes 0.000 description 4
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 4
- 238000001712 DNA sequencing Methods 0.000 description 4
- 102000004190 Enzymes Human genes 0.000 description 4
- 108090000790 Enzymes Proteins 0.000 description 4
- 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 4
- 238000012413 Fluorescence activated cell sorting analysis Methods 0.000 description 4
- 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 4
- 102000014150 Interferons Human genes 0.000 description 4
- 108010050904 Interferons Proteins 0.000 description 4
- HNDVDQJCIGZPNO-YFKPBYRVSA-N L-histidine Chemical compound OC(=O)[C@@H](N)CC1=CN=CN1 HNDVDQJCIGZPNO-YFKPBYRVSA-N 0.000 description 4
- COLNVLDHVKWLRT-QMMMGPOBSA-N L-phenylalanine Chemical compound OC(=O)[C@@H](N)CC1=CC=CC=C1 COLNVLDHVKWLRT-QMMMGPOBSA-N 0.000 description 4
- OUYCCCASQSFEME-QMMMGPOBSA-N L-tyrosine Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-QMMMGPOBSA-N 0.000 description 4
- 239000004472 Lysine Substances 0.000 description 4
- 229930195725 Mannitol Natural products 0.000 description 4
- 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 4
- ZDZOTLJHXYCWBA-VCVYQWHSSA-N N-debenzoyl-N-(tert-butoxycarbonyl)-10-deacetyltaxol Chemical compound O([C@H]1[C@H]2[C@@](C([C@H](O)C3=C(C)[C@@H](OC(=O)[C@H](O)[C@@H](NC(=O)OC(C)(C)C)C=4C=CC=CC=4)C[C@]1(O)C3(C)C)=O)(C)[C@@H](O)C[C@H]1OC[C@]12OC(=O)C)C(=O)C1=CC=CC=C1 ZDZOTLJHXYCWBA-VCVYQWHSSA-N 0.000 description 4
- UGJBHEZMOKVTIM-UHFFFAOYSA-N N-formylglycine Chemical compound OC(=O)CNC=O UGJBHEZMOKVTIM-UHFFFAOYSA-N 0.000 description 4
- 241000283973 Oryctolagus cuniculus Species 0.000 description 4
- 240000007594 Oryza sativa Species 0.000 description 4
- 235000007164 Oryza sativa Nutrition 0.000 description 4
- 102000012338 Poly(ADP-ribose) Polymerases Human genes 0.000 description 4
- 108010061844 Poly(ADP-ribose) Polymerases Proteins 0.000 description 4
- 229920000776 Poly(Adenosine diphosphate-ribose) polymerase Polymers 0.000 description 4
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 4
- 150000007513 acids Chemical class 0.000 description 4
- RJURFGZVJUQBHK-UHFFFAOYSA-N actinomycin D Natural products CC1OC(=O)C(C(C)C)N(C)C(=O)CN(C)C(=O)C2CCCN2C(=O)C(C(C)C)NC(=O)C1NC(=O)C1=C(N)C(=O)C(C)=C2OC(C(C)=CC=C3C(=O)NC4C(=O)NC(C(N5CCCC5C(=O)N(C)CC(=O)N(C)C(C(C)C)C(=O)OC4C)=O)C(C)C)=C3N=C21 RJURFGZVJUQBHK-UHFFFAOYSA-N 0.000 description 4
- 208000009956 adenocarcinoma Diseases 0.000 description 4
- 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 4
- 235000010443 alginic acid Nutrition 0.000 description 4
- 229920000615 alginic acid Polymers 0.000 description 4
- 239000002585 base Substances 0.000 description 4
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 4
- 229960002685 biotin Drugs 0.000 description 4
- 235000020958 biotin Nutrition 0.000 description 4
- 239000011616 biotin Substances 0.000 description 4
- 239000001768 carboxy methyl cellulose Substances 0.000 description 4
- 235000018417 cysteine Nutrition 0.000 description 4
- XUJNEKJLAYXESH-UHFFFAOYSA-N cysteine Natural products SCC(N)C(O)=O XUJNEKJLAYXESH-UHFFFAOYSA-N 0.000 description 4
- 230000009089 cytolysis Effects 0.000 description 4
- 231100000433 cytotoxic Toxicity 0.000 description 4
- 230000001472 cytotoxic effect Effects 0.000 description 4
- 230000002354 daily effect Effects 0.000 description 4
- 201000010099 disease Diseases 0.000 description 4
- 239000002552 dosage form Substances 0.000 description 4
- 229960001904 epirubicin Drugs 0.000 description 4
- BTCSSZJGUNDROE-UHFFFAOYSA-N gamma-aminobutyric acid Chemical compound NCCCC(O)=O BTCSSZJGUNDROE-UHFFFAOYSA-N 0.000 description 4
- 229960001031 glucose Drugs 0.000 description 4
- 239000001087 glyceryl triacetate Substances 0.000 description 4
- 235000013773 glyceryl triacetate Nutrition 0.000 description 4
- 238000009169 immunotherapy Methods 0.000 description 4
- 230000001965 increasing effect Effects 0.000 description 4
- 239000003112 inhibitor Substances 0.000 description 4
- 229940079322 interferon Drugs 0.000 description 4
- 239000000594 mannitol Substances 0.000 description 4
- 235000010355 mannitol Nutrition 0.000 description 4
- 238000004519 manufacturing process Methods 0.000 description 4
- 239000003550 marker Substances 0.000 description 4
- 239000011159 matrix material Substances 0.000 description 4
- 229920000609 methyl cellulose Polymers 0.000 description 4
- 235000010981 methylcellulose Nutrition 0.000 description 4
- 239000001923 methylcellulose Substances 0.000 description 4
- 239000003607 modifier Substances 0.000 description 4
- 239000000178 monomer Substances 0.000 description 4
- COLNVLDHVKWLRT-UHFFFAOYSA-N phenylalanine Natural products OC(=O)C(N)CC1=CC=CC=C1 COLNVLDHVKWLRT-UHFFFAOYSA-N 0.000 description 4
- BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Chemical compound [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 description 4
- 229920000139 polyethylene terephthalate Polymers 0.000 description 4
- 239000005020 polyethylene terephthalate Substances 0.000 description 4
- 239000000244 polyoxyethylene sorbitan monooleate Substances 0.000 description 4
- 235000009566 rice Nutrition 0.000 description 4
- 238000012216 screening Methods 0.000 description 4
- 239000004055 small Interfering RNA Substances 0.000 description 4
- 150000003384 small molecules Chemical class 0.000 description 4
- 239000001601 sodium adipate Substances 0.000 description 4
- 238000007920 subcutaneous administration Methods 0.000 description 4
- 239000000758 substrate Substances 0.000 description 4
- 235000000346 sugar Nutrition 0.000 description 4
- 230000002103 transcriptional effect Effects 0.000 description 4
- 229960002622 triacetin Drugs 0.000 description 4
- OUYCCCASQSFEME-UHFFFAOYSA-N tyrosine Natural products OC(=O)C(N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-UHFFFAOYSA-N 0.000 description 4
- WOWDZACBATWTAU-FEFUEGSOSA-N (2s)-2-[[(2s)-2-(dimethylamino)-3-methylbutanoyl]amino]-n-[(3r,4s,5s)-1-[(2s)-2-[(1r,2r)-3-[[(1s,2r)-1-hydroxy-1-phenylpropan-2-yl]amino]-1-methoxy-2-methyl-3-oxopropyl]pyrrolidin-1-yl]-3-methoxy-5-methyl-1-oxoheptan-4-yl]-n,3-dimethylbutanamide Chemical group CC(C)[C@H](N(C)C)C(=O)N[C@@H](C(C)C)C(=O)N(C)[C@@H]([C@@H](C)CC)[C@H](OC)CC(=O)N1CCC[C@H]1[C@H](OC)[C@@H](C)C(=O)N[C@H](C)[C@@H](O)C1=CC=CC=C1 WOWDZACBATWTAU-FEFUEGSOSA-N 0.000 description 3
- AGGWFDNPHKLBBV-YUMQZZPRSA-N (2s)-2-[[(2s)-2-amino-3-methylbutanoyl]amino]-5-(carbamoylamino)pentanoic acid Chemical group CC(C)[C@H](N)C(=O)N[C@H](C(O)=O)CCCNC(N)=O AGGWFDNPHKLBBV-YUMQZZPRSA-N 0.000 description 3
- ZXSBHXZKWRIEIA-JTQLQIEISA-N (2s)-3-(4-acetylphenyl)-2-azaniumylpropanoate Chemical compound CC(=O)C1=CC=C(C[C@H](N)C(O)=O)C=C1 ZXSBHXZKWRIEIA-JTQLQIEISA-N 0.000 description 3
- RWZVMMQNDHPRQD-SFTDATJTSA-N (6as)-3-[3-[[(6as)-2-methoxy-8-methylidene-11-oxo-7,9-dihydro-6ah-pyrrolo[2,1-c][1,4]benzodiazepin-3-yl]oxy]propoxy]-2-methoxy-8-methylidene-7,9-dihydro-6ah-pyrrolo[2,1-c][1,4]benzodiazepin-11-one Chemical compound N1=C[C@@H]2CC(=C)CN2C(=O)C(C=C2OC)=C1C=C2OCCCOC1=CC(N=C[C@H]2N(CC(=C)C2)C2=O)=C2C=C1OC RWZVMMQNDHPRQD-SFTDATJTSA-N 0.000 description 3
- 108091032973 (ribonucleotides)n+m Proteins 0.000 description 3
- VILFTWLXLYIEMV-UHFFFAOYSA-N 1,5-difluoro-2,4-dinitrobenzene Chemical compound [O-][N+](=O)C1=CC([N+]([O-])=O)=C(F)C=C1F VILFTWLXLYIEMV-UHFFFAOYSA-N 0.000 description 3
- IXPNQXFRVYWDDI-UHFFFAOYSA-N 1-methyl-2,4-dioxo-1,3-diazinane-5-carboximidamide Chemical compound CN1CC(C(N)=N)C(=O)NC1=O IXPNQXFRVYWDDI-UHFFFAOYSA-N 0.000 description 3
- DGHHQBMTXTWTJV-BQAIUKQQSA-N 119413-54-6 Chemical compound Cl.C1=C(O)C(CN(C)C)=C2C=C(CN3C4=CC5=C(C3=O)COC(=O)[C@]5(O)CC)C4=NC2=C1 DGHHQBMTXTWTJV-BQAIUKQQSA-N 0.000 description 3
- STQGQHZAVUOBTE-UHFFFAOYSA-N 7-Cyan-hept-2t-en-4,6-diinsaeure Natural products C1=2C(O)=C3C(=O)C=4C(OC)=CC=CC=4C(=O)C3=C(O)C=2CC(O)(C(C)=O)CC1OC1CC(N)C(O)C(C)O1 STQGQHZAVUOBTE-UHFFFAOYSA-N 0.000 description 3
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 3
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 3
- 108050009324 Claudin-18 Proteins 0.000 description 3
- 229920002785 Croscarmellose sodium Polymers 0.000 description 3
- CMSMOCZEIVJLDB-UHFFFAOYSA-N Cyclophosphamide Chemical class ClCCN(CCCl)P1(=O)NCCCO1 CMSMOCZEIVJLDB-UHFFFAOYSA-N 0.000 description 3
- 238000002965 ELISA Methods 0.000 description 3
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 3
- 108010017080 Granulocyte Colony-Stimulating Factor Proteins 0.000 description 3
- 102000004269 Granulocyte Colony-Stimulating Factor Human genes 0.000 description 3
- 108010002350 Interleukin-2 Proteins 0.000 description 3
- 108010063738 Interleukins Proteins 0.000 description 3
- 102000015696 Interleukins Human genes 0.000 description 3
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 3
- ONIBWKKTOPOVIA-BYPYZUCNSA-N L-Proline Chemical compound OC(=O)[C@@H]1CCCN1 ONIBWKKTOPOVIA-BYPYZUCNSA-N 0.000 description 3
- FFEARJCKVFRZRR-BYPYZUCNSA-N L-methionine Chemical compound CSCC[C@H](N)C(O)=O FFEARJCKVFRZRR-BYPYZUCNSA-N 0.000 description 3
- QIVBCDIJIAJPQS-VIFPVBQESA-N L-tryptophane Chemical compound C1=CC=C2C(C[C@H](N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-VIFPVBQESA-N 0.000 description 3
- 235000010643 Leucaena leucocephala Nutrition 0.000 description 3
- 240000007472 Leucaena leucocephala Species 0.000 description 3
- 241000124008 Mammalia Species 0.000 description 3
- 102000029749 Microtubule Human genes 0.000 description 3
- 108091022875 Microtubule Proteins 0.000 description 3
- 229920000881 Modified starch Polymers 0.000 description 3
- 108091034117 Oligonucleotide Proteins 0.000 description 3
- 229920003171 Poly (ethylene oxide) Polymers 0.000 description 3
- ONIBWKKTOPOVIA-UHFFFAOYSA-N Proline Natural products OC(=O)C1CCCN1 ONIBWKKTOPOVIA-UHFFFAOYSA-N 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- 235000021355 Stearic acid Nutrition 0.000 description 3
- PZBFGYYEXUXCOF-UHFFFAOYSA-N TCEP Chemical compound OC(=O)CCP(CCC(O)=O)CCC(O)=O PZBFGYYEXUXCOF-UHFFFAOYSA-N 0.000 description 3
- AOBORMOPSGHCAX-UHFFFAOYSA-N Tocophersolan Chemical compound OCCOC(=O)CCC(=O)OC1=C(C)C(C)=C2OC(CCCC(C)CCCC(C)CCCC(C)C)(C)CCC2=C1C AOBORMOPSGHCAX-UHFFFAOYSA-N 0.000 description 3
- QIVBCDIJIAJPQS-UHFFFAOYSA-N Tryptophan Natural products C1=CC=C2C(CC(N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-UHFFFAOYSA-N 0.000 description 3
- 108060008682 Tumor Necrosis Factor Proteins 0.000 description 3
- JLCPHMBAVCMARE-UHFFFAOYSA-N [3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-[[3-[[3-[[3-[[3-[[3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-hydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methyl [5-(6-aminopurin-9-yl)-2-(hydroxymethyl)oxolan-3-yl] hydrogen phosphate Polymers Cc1cn(C2CC(OP(O)(=O)OCC3OC(CC3OP(O)(=O)OCC3OC(CC3O)n3cnc4c3nc(N)[nH]c4=O)n3cnc4c3nc(N)[nH]c4=O)C(COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3CO)n3cnc4c(N)ncnc34)n3ccc(N)nc3=O)n3cnc4c(N)ncnc34)n3ccc(N)nc3=O)n3ccc(N)nc3=O)n3ccc(N)nc3=O)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cc(C)c(=O)[nH]c3=O)n3cc(C)c(=O)[nH]c3=O)n3ccc(N)nc3=O)n3cc(C)c(=O)[nH]c3=O)n3cnc4c3nc(N)[nH]c4=O)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)O2)c(=O)[nH]c1=O JLCPHMBAVCMARE-UHFFFAOYSA-N 0.000 description 3
- DPXJVFZANSGRMM-UHFFFAOYSA-N acetic acid;2,3,4,5,6-pentahydroxyhexanal;sodium Chemical compound [Na].CC(O)=O.OCC(O)C(O)C(O)C(O)C=O DPXJVFZANSGRMM-UHFFFAOYSA-N 0.000 description 3
- SPTSIOTYTJZTOG-UHFFFAOYSA-N acetic acid;octadecanoic acid Chemical compound CC(O)=O.CCCCCCCCCCCCCCCCCC(O)=O SPTSIOTYTJZTOG-UHFFFAOYSA-N 0.000 description 3
- 230000002378 acidificating effect Effects 0.000 description 3
- 239000002671 adjuvant Substances 0.000 description 3
- 230000003321 amplification Effects 0.000 description 3
- 210000004102 animal cell Anatomy 0.000 description 3
- 229940045799 anthracyclines and related substance Drugs 0.000 description 3
- LMEKQMALGUDUQG-UHFFFAOYSA-N azathioprine Chemical class CN1C=NC([N+]([O-])=O)=C1SC1=NC=NC2=C1NC=N2 LMEKQMALGUDUQG-UHFFFAOYSA-N 0.000 description 3
- 229940098773 bovine serum albumin Drugs 0.000 description 3
- 239000011575 calcium Substances 0.000 description 3
- 229960005069 calcium Drugs 0.000 description 3
- 229910052791 calcium Inorganic materials 0.000 description 3
- 229910000389 calcium phosphate Inorganic materials 0.000 description 3
- 235000011010 calcium phosphates Nutrition 0.000 description 3
- OSGAYBCDTDRGGQ-UHFFFAOYSA-L calcium sulfate Chemical compound [Ca+2].[O-]S([O-])(=O)=O OSGAYBCDTDRGGQ-UHFFFAOYSA-L 0.000 description 3
- 239000012876 carrier material Substances 0.000 description 3
- 238000004113 cell culture Methods 0.000 description 3
- 230000030833 cell death Effects 0.000 description 3
- 238000002659 cell therapy Methods 0.000 description 3
- 239000003153 chemical reaction reagent Substances 0.000 description 3
- 235000012000 cholesterol Nutrition 0.000 description 3
- 238000010367 cloning Methods 0.000 description 3
- 238000010168 coupling process Methods 0.000 description 3
- NZNMSOFKMUBTKW-UHFFFAOYSA-N cyclohexanecarboxylic acid Chemical compound OC(=O)C1CCCCC1 NZNMSOFKMUBTKW-UHFFFAOYSA-N 0.000 description 3
- 229960004397 cyclophosphamide Drugs 0.000 description 3
- 229960000975 daunorubicin Drugs 0.000 description 3
- STQGQHZAVUOBTE-VGBVRHCVSA-N daunorubicin Chemical compound O([C@H]1C[C@@](O)(CC=2C(O)=C3C(=O)C=4C=CC=C(C=4C(=O)C3=C(O)C=21)OC)C(C)=O)[C@H]1C[C@H](N)[C@H](O)[C@H](C)O1 STQGQHZAVUOBTE-VGBVRHCVSA-N 0.000 description 3
- 230000003247 decreasing effect Effects 0.000 description 3
- 238000001514 detection method Methods 0.000 description 3
- 238000011161 development Methods 0.000 description 3
- 230000018109 developmental process Effects 0.000 description 3
- 239000008121 dextrose Substances 0.000 description 3
- 239000000539 dimer Substances 0.000 description 3
- 239000007884 disintegrant Substances 0.000 description 3
- 229960003668 docetaxel Drugs 0.000 description 3
- 229960004679 doxorubicin Drugs 0.000 description 3
- 229920001971 elastomer Polymers 0.000 description 3
- 230000001747 exhibiting effect Effects 0.000 description 3
- 230000013595 glycosylation Effects 0.000 description 3
- 238000006206 glycosylation reaction Methods 0.000 description 3
- WGCNASOHLSPBMP-UHFFFAOYSA-N hydroxyacetaldehyde Natural products OCC=O WGCNASOHLSPBMP-UHFFFAOYSA-N 0.000 description 3
- 230000002519 immonomodulatory effect Effects 0.000 description 3
- 230000028993 immune response Effects 0.000 description 3
- 238000003018 immunoassay Methods 0.000 description 3
- 230000005847 immunogenicity Effects 0.000 description 3
- 231100000608 immunotoxin Toxicity 0.000 description 3
- 230000002637 immunotoxin Effects 0.000 description 3
- 239000002596 immunotoxin Substances 0.000 description 3
- 229940051026 immunotoxin Drugs 0.000 description 3
- 239000007928 intraperitoneal injection Substances 0.000 description 3
- 239000000314 lubricant Substances 0.000 description 3
- 210000004072 lung Anatomy 0.000 description 3
- 125000005439 maleimidyl group Chemical group C1(C=CC(N1*)=O)=O 0.000 description 3
- 229910052751 metal Inorganic materials 0.000 description 3
- 239000002184 metal Substances 0.000 description 3
- 229930182817 methionine Natural products 0.000 description 3
- 210000004688 microtubule Anatomy 0.000 description 3
- 208000002154 non-small cell lung carcinoma Diseases 0.000 description 3
- 238000003199 nucleic acid amplification method Methods 0.000 description 3
- 125000003835 nucleoside group Chemical group 0.000 description 3
- 238000011580 nude mouse model Methods 0.000 description 3
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 3
- OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 3
- 230000003647 oxidation Effects 0.000 description 3
- 238000007254 oxidation reaction Methods 0.000 description 3
- 239000013612 plasmid Substances 0.000 description 3
- 229920003023 plastic Polymers 0.000 description 3
- 239000004033 plastic Substances 0.000 description 3
- 239000004014 plasticizer Substances 0.000 description 3
- 229910052700 potassium Inorganic materials 0.000 description 3
- 230000003389 potentiating effect Effects 0.000 description 3
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 3
- 239000003197 protein kinase B inhibitor Substances 0.000 description 3
- 238000000746 purification Methods 0.000 description 3
- ZAHRKKWIAAJSAO-UHFFFAOYSA-N rapamycin Natural products COCC(O)C(=C/C(C)C(=O)CC(OC(=O)C1CCCCN1C(=O)C(=O)C2(O)OC(CC(OC)C(=CC=CC=CC(C)CC(C)C(=O)C)C)CCC2C)C(C)CC3CCC(O)C(C3)OC)C ZAHRKKWIAAJSAO-UHFFFAOYSA-N 0.000 description 3
- 238000003757 reverse transcription PCR Methods 0.000 description 3
- QFJCIRLUMZQUOT-HPLJOQBZSA-N sirolimus Chemical compound C1C[C@@H](O)[C@H](OC)C[C@@H]1C[C@@H](C)[C@H]1OC(=O)[C@@H]2CCCCN2C(=O)C(=O)[C@](O)(O2)[C@H](C)CC[C@H]2C[C@H](OC)/C(C)=C/C=C/C=C/[C@@H](C)C[C@@H](C)C(=O)[C@H](OC)[C@H](O)/C(C)=C/[C@@H](C)C(=O)C1 QFJCIRLUMZQUOT-HPLJOQBZSA-N 0.000 description 3
- 229960002930 sirolimus Drugs 0.000 description 3
- 235000010413 sodium alginate Nutrition 0.000 description 3
- 239000000661 sodium alginate Substances 0.000 description 3
- 229940005550 sodium alginate Drugs 0.000 description 3
- 235000019812 sodium carboxymethyl cellulose Nutrition 0.000 description 3
- 229920001027 sodium carboxymethylcellulose Polymers 0.000 description 3
- 239000008109 sodium starch glycolate Substances 0.000 description 3
- 229920003109 sodium starch glycolate Polymers 0.000 description 3
- 229940079832 sodium starch glycolate Drugs 0.000 description 3
- 239000002904 solvent Substances 0.000 description 3
- 239000008117 stearic acid Substances 0.000 description 3
- 210000002784 stomach Anatomy 0.000 description 3
- 238000001356 surgical procedure Methods 0.000 description 3
- RCINICONZNJXQF-MZXODVADSA-N taxol Chemical compound O([C@@H]1[C@@]2(C[C@@H](C(C)=C(C2(C)C)[C@H](C([C@]2(C)[C@@H](O)C[C@H]3OC[C@]3([C@H]21)OC(C)=O)=O)OC(=O)C)OC(=O)[C@H](O)[C@@H](NC(=O)C=1C=CC=CC=1)C=1C=CC=CC=1)O)C(=O)C1=CC=CC=C1 RCINICONZNJXQF-MZXODVADSA-N 0.000 description 3
- 229960000303 topotecan Drugs 0.000 description 3
- 208000029729 tumor suppressor gene on chromosome 11 Diseases 0.000 description 3
- 239000000080 wetting agent Substances 0.000 description 3
- 229920001285 xanthan gum Polymers 0.000 description 3
- OGNSCSPNOLGXSM-UHFFFAOYSA-N (+/-)-DABA Natural products NCCC(N)C(O)=O OGNSCSPNOLGXSM-UHFFFAOYSA-N 0.000 description 2
- OZFAFGSSMRRTDW-UHFFFAOYSA-N (2,4-dichlorophenyl) benzenesulfonate Chemical compound ClC1=CC(Cl)=CC=C1OS(=O)(=O)C1=CC=CC=C1 OZFAFGSSMRRTDW-UHFFFAOYSA-N 0.000 description 2
- BQWBEDSJTMWJAE-UHFFFAOYSA-N (2,5-dioxopyrrolidin-1-yl) 4-[(2-iodoacetyl)amino]benzoate Chemical compound C1=CC(NC(=O)CI)=CC=C1C(=O)ON1C(=O)CCC1=O BQWBEDSJTMWJAE-UHFFFAOYSA-N 0.000 description 2
- LWAVGNJLLQSNNN-UHFFFAOYSA-N (2,5-dioxopyrrolidin-1-yl) 4-azidobenzoate Chemical compound C1=CC(N=[N+]=[N-])=CC=C1C(=O)ON1C(=O)CCC1=O LWAVGNJLLQSNNN-UHFFFAOYSA-N 0.000 description 2
- FUOJEDZPVVDXHI-UHFFFAOYSA-N (2,5-dioxopyrrolidin-1-yl) 5-azido-2-nitrobenzoate Chemical compound [O-][N+](=O)C1=CC=C(N=[N+]=[N-])C=C1C(=O)ON1C(=O)CCC1=O FUOJEDZPVVDXHI-UHFFFAOYSA-N 0.000 description 2
- NGXDNMNOQDVTRL-UHFFFAOYSA-N (2,5-dioxopyrrolidin-1-yl) 6-(4-azido-2-nitroanilino)hexanoate Chemical compound [O-][N+](=O)C1=CC(N=[N+]=[N-])=CC=C1NCCCCCC(=O)ON1C(=O)CCC1=O NGXDNMNOQDVTRL-UHFFFAOYSA-N 0.000 description 2
- MTCFGRXMJLQNBG-REOHCLBHSA-N (2S)-2-Amino-3-hydroxypropansäure Chemical compound OC[C@H](N)C(O)=O MTCFGRXMJLQNBG-REOHCLBHSA-N 0.000 description 2
- LNAZSHAWQACDHT-XIYTZBAFSA-N (2r,3r,4s,5r,6s)-4,5-dimethoxy-2-(methoxymethyl)-3-[(2s,3r,4s,5r,6r)-3,4,5-trimethoxy-6-(methoxymethyl)oxan-2-yl]oxy-6-[(2r,3r,4s,5r,6r)-4,5,6-trimethoxy-2-(methoxymethyl)oxan-3-yl]oxyoxane Chemical compound CO[C@@H]1[C@@H](OC)[C@H](OC)[C@@H](COC)O[C@H]1O[C@H]1[C@H](OC)[C@@H](OC)[C@H](O[C@H]2[C@@H]([C@@H](OC)[C@H](OC)O[C@@H]2COC)OC)O[C@@H]1COC LNAZSHAWQACDHT-XIYTZBAFSA-N 0.000 description 2
- LGNCNVVZCUVPOT-FUVGGWJZSA-N (2s)-2-[[(2r,3r)-3-[(2s)-1-[(3r,4s,5s)-4-[[(2s)-2-[[(2s)-2-(dimethylamino)-3-methylbutanoyl]amino]-3-methylbutanoyl]-methylamino]-3-methoxy-5-methylheptanoyl]pyrrolidin-2-yl]-3-methoxy-2-methylpropanoyl]amino]-3-phenylpropanoic acid Chemical compound CC(C)[C@H](N(C)C)C(=O)N[C@@H](C(C)C)C(=O)N(C)[C@@H]([C@@H](C)CC)[C@H](OC)CC(=O)N1CCC[C@H]1[C@H](OC)[C@@H](C)C(=O)N[C@H](C(O)=O)CC1=CC=CC=C1 LGNCNVVZCUVPOT-FUVGGWJZSA-N 0.000 description 2
- KQRHTCDQWJLLME-XUXIUFHCSA-N (2s)-2-[[(2s)-2-[[(2s)-2-[[(2s)-2-aminopropanoyl]amino]-4-methylpentanoyl]amino]propanoyl]amino]-4-methylpentanoic acid Chemical compound CC(C)C[C@@H](C(O)=O)NC(=O)[C@H](C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](C)N KQRHTCDQWJLLME-XUXIUFHCSA-N 0.000 description 2
- BLUGYPPOFIHFJS-UUFHNPECSA-N (2s)-n-[(2s)-1-[[(3r,4s,5s)-3-methoxy-1-[(2s)-2-[(1r,2r)-1-methoxy-2-methyl-3-oxo-3-[[(1s)-2-phenyl-1-(1,3-thiazol-2-yl)ethyl]amino]propyl]pyrrolidin-1-yl]-5-methyl-1-oxoheptan-4-yl]-methylamino]-3-methyl-1-oxobutan-2-yl]-3-methyl-2-(methylamino)butanamid Chemical compound CN[C@@H](C(C)C)C(=O)N[C@@H](C(C)C)C(=O)N(C)[C@@H]([C@@H](C)CC)[C@H](OC)CC(=O)N1CCC[C@H]1[C@H](OC)[C@@H](C)C(=O)N[C@H](C=1SC=CN=1)CC1=CC=CC=C1 BLUGYPPOFIHFJS-UUFHNPECSA-N 0.000 description 2
- GERXSZLDSOPHJV-UHFFFAOYSA-N (4-nitrophenyl) 2-iodoacetate Chemical compound [O-][N+](=O)C1=CC=C(OC(=O)CI)C=C1 GERXSZLDSOPHJV-UHFFFAOYSA-N 0.000 description 2
- OMRPLUKQNWNZAV-CONSDPRKSA-N (6as)-3-[3-[[(6as)-2-methoxy-8-(4-methoxyphenyl)-11-oxo-6a,7-dihydropyrrolo[2,1-c][1,4]benzodiazepin-3-yl]oxy]propoxy]-8-(4-aminophenyl)-2-methoxy-6a,7-dihydropyrrolo[2,1-c][1,4]benzodiazepin-11-one Chemical compound C1=CC(OC)=CC=C1C1=CN2C(=O)C3=CC(OC)=C(OCCCOC=4C(=CC=5C(=O)N6C=C(C[C@H]6C=NC=5C=4)C=4C=CC(N)=CC=4)OC)C=C3N=C[C@@H]2C1 OMRPLUKQNWNZAV-CONSDPRKSA-N 0.000 description 2
- WRIDQFICGBMAFQ-UHFFFAOYSA-N (E)-8-Octadecenoic acid Natural products CCCCCCCCCC=CCCCCCCC(O)=O WRIDQFICGBMAFQ-UHFFFAOYSA-N 0.000 description 2
- IAKHMKGGTNLKSZ-INIZCTEOSA-N (S)-colchicine Chemical compound C1([C@@H](NC(C)=O)CC2)=CC(=O)C(OC)=CC=C1C1=C2C=C(OC)C(OC)=C1OC IAKHMKGGTNLKSZ-INIZCTEOSA-N 0.000 description 2
- 102000040650 (ribonucleotides)n+m Human genes 0.000 description 2
- ZORQXIQZAOLNGE-UHFFFAOYSA-N 1,1-difluorocyclohexane Chemical compound FC1(F)CCCCC1 ZORQXIQZAOLNGE-UHFFFAOYSA-N 0.000 description 2
- NWHMETIBESABNA-UHFFFAOYSA-N 1-[2-(7-azido-4-methyl-2-oxochromen-3-yl)acetyl]oxy-2,5-dioxopyrrolidine-3-sulfonic acid Chemical compound O=C1OC=2C=C(N=[N+]=[N-])C=CC=2C(C)=C1CC(=O)ON1C(=O)CC(S(O)(=O)=O)C1=O NWHMETIBESABNA-UHFFFAOYSA-N 0.000 description 2
- WQQBUTMELIQJNY-UHFFFAOYSA-N 1-[4-(2,5-dioxo-3-sulfopyrrolidin-1-yl)oxy-2,3-dihydroxy-4-oxobutanoyl]oxy-2,5-dioxopyrrolidine-3-sulfonic acid Chemical compound O=C1CC(S(O)(=O)=O)C(=O)N1OC(=O)C(O)C(O)C(=O)ON1C(=O)CC(S(O)(=O)=O)C1=O WQQBUTMELIQJNY-UHFFFAOYSA-N 0.000 description 2
- SYEKJCKNTHYWOJ-UHFFFAOYSA-N 2-(2,5-dioxopyrrolidin-1-yl)-2-sulfobutanedioic acid;ethane-1,2-diol Chemical compound OCCO.OC(=O)CC(S(O)(=O)=O)(C(O)=O)N1C(=O)CCC1=O.OC(=O)CC(S(O)(=O)=O)(C(O)=O)N1C(=O)CCC1=O SYEKJCKNTHYWOJ-UHFFFAOYSA-N 0.000 description 2
- CALIYGMVBZRBLV-UHFFFAOYSA-N 2-(4-azidophenyl)-2-oxoacetaldehyde Chemical compound [N-]=[N+]=NC1=CC=C(C(=O)C=O)C=C1 CALIYGMVBZRBLV-UHFFFAOYSA-N 0.000 description 2
- HNLXNOZHXNSSPN-UHFFFAOYSA-N 2-[2-[2-[2-[2-[2-[2-[4-(2,4,4-trimethylpentan-2-yl)phenoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethanol Chemical compound CC(C)(C)CC(C)(C)C1=CC=C(OCCOCCOCCOCCOCCOCCOCCO)C=C1 HNLXNOZHXNSSPN-UHFFFAOYSA-N 0.000 description 2
- WEZDRVHTDXTVLT-GJZGRUSLSA-N 2-[[(2s)-2-[[(2s)-2-[(2-aminoacetyl)amino]-3-phenylpropanoyl]amino]-4-methylpentanoyl]amino]acetic acid Chemical compound OC(=O)CNC(=O)[C@H](CC(C)C)NC(=O)[C@@H](NC(=O)CN)CC1=CC=CC=C1 WEZDRVHTDXTVLT-GJZGRUSLSA-N 0.000 description 2
- HXUVTXPOZRFMOY-NSHDSACASA-N 2-[[(2s)-2-[[2-[(2-aminoacetyl)amino]acetyl]amino]-3-phenylpropanoyl]amino]acetic acid Chemical compound NCC(=O)NCC(=O)N[C@H](C(=O)NCC(O)=O)CC1=CC=CC=C1 HXUVTXPOZRFMOY-NSHDSACASA-N 0.000 description 2
- JRYMOPZHXMVHTA-DAGMQNCNSA-N 2-amino-7-[(2r,3r,4s,5r)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]-1h-pyrrolo[2,3-d]pyrimidin-4-one Chemical compound C1=CC=2C(=O)NC(N)=NC=2N1[C@@H]1O[C@H](CO)[C@@H](O)[C@H]1O JRYMOPZHXMVHTA-DAGMQNCNSA-N 0.000 description 2
- YHJZWYNRTYKWEC-UHFFFAOYSA-N 2-diazonio-3,3,3-trifluoro-1-(4-nitrophenoxy)prop-1-en-1-olate Chemical compound [O-][N+](=O)C1=CC=C(OC(=O)C(=[N+]=[N-])C(F)(F)F)C=C1 YHJZWYNRTYKWEC-UHFFFAOYSA-N 0.000 description 2
- LQJBNNIYVWPHFW-UHFFFAOYSA-N 20:1omega9c fatty acid Natural products CCCCCCCCCCC=CCCCCCCCC(O)=O LQJBNNIYVWPHFW-UHFFFAOYSA-N 0.000 description 2
- YRLKXQVDEQEYSN-UHFFFAOYSA-N 4-azidobenzohydrazide Chemical compound NNC(=O)C1=CC=C(N=[N+]=[N-])C=C1 YRLKXQVDEQEYSN-UHFFFAOYSA-N 0.000 description 2
- PZOUSPYUWWUPPK-UHFFFAOYSA-N 4-methyl-1h-indole Chemical compound CC1=CC=CC2=C1C=CN2 PZOUSPYUWWUPPK-UHFFFAOYSA-N 0.000 description 2
- XZIIFPSPUDAGJM-UHFFFAOYSA-N 6-chloro-2-n,2-n-diethylpyrimidine-2,4-diamine Polymers CCN(CC)C1=NC(N)=CC(Cl)=N1 XZIIFPSPUDAGJM-UHFFFAOYSA-N 0.000 description 2
- FHVDTGUDJYJELY-UHFFFAOYSA-N 6-{[2-carboxy-4,5-dihydroxy-6-(phosphanyloxy)oxan-3-yl]oxy}-4,5-dihydroxy-3-phosphanyloxane-2-carboxylic acid Chemical compound O1C(C(O)=O)C(P)C(O)C(O)C1OC1C(C(O)=O)OC(OP)C(O)C1O FHVDTGUDJYJELY-UHFFFAOYSA-N 0.000 description 2
- QSBYPNXLFMSGKH-UHFFFAOYSA-N 9-Heptadecensaeure Natural products CCCCCCCC=CCCCCCCCC(O)=O QSBYPNXLFMSGKH-UHFFFAOYSA-N 0.000 description 2
- LRFVTYWOQMYALW-UHFFFAOYSA-N 9H-xanthine Chemical compound O=C1NC(=O)NC2=C1NC=N2 LRFVTYWOQMYALW-UHFFFAOYSA-N 0.000 description 2
- HDZZVAMISRMYHH-UHFFFAOYSA-N 9beta-Ribofuranosyl-7-deazaadenin Natural products C1=CC=2C(N)=NC=NC=2N1C1OC(CO)C(O)C1O HDZZVAMISRMYHH-UHFFFAOYSA-N 0.000 description 2
- 229940126638 Akt inhibitor Drugs 0.000 description 2
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 2
- 108010063104 Apoptosis Regulatory Proteins Proteins 0.000 description 2
- 102000010565 Apoptosis Regulatory Proteins Human genes 0.000 description 2
- 108091023037 Aptamer Proteins 0.000 description 2
- 101100064317 Arabidopsis thaliana DTX41 gene Proteins 0.000 description 2
- DCXYFEDJOCDNAF-UHFFFAOYSA-N Asparagine Natural products OC(=O)C(N)CC(N)=O DCXYFEDJOCDNAF-UHFFFAOYSA-N 0.000 description 2
- 241000894006 Bacteria Species 0.000 description 2
- 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 2
- FERIUCNNQQJTOY-UHFFFAOYSA-M Butyrate Chemical compound CCCC([O-])=O FERIUCNNQQJTOY-UHFFFAOYSA-M 0.000 description 2
- FERIUCNNQQJTOY-UHFFFAOYSA-N Butyric acid Natural products CCCC(O)=O FERIUCNNQQJTOY-UHFFFAOYSA-N 0.000 description 2
- 102100032528 C-type lectin domain family 11 member A Human genes 0.000 description 2
- 101710167766 C-type lectin domain family 11 member A Proteins 0.000 description 2
- 238000011357 CAR T-cell therapy Methods 0.000 description 2
- 241000283707 Capra Species 0.000 description 2
- 229920002134 Carboxymethyl cellulose Polymers 0.000 description 2
- 101150015280 Cel gene Proteins 0.000 description 2
- 108010035563 Chloramphenicol O-acetyltransferase Proteins 0.000 description 2
- 108091026890 Coding region Proteins 0.000 description 2
- 108091035707 Consensus sequence Proteins 0.000 description 2
- MIKUYHXYGGJMLM-GIMIYPNGSA-N Crotonoside Natural products C1=NC2=C(N)NC(=O)N=C2N1[C@H]1O[C@@H](CO)[C@H](O)[C@@H]1O MIKUYHXYGGJMLM-GIMIYPNGSA-N 0.000 description 2
- PMATZTZNYRCHOR-CGLBZJNRSA-N Cyclosporin A Chemical compound CC[C@@H]1NC(=O)[C@H]([C@H](O)[C@H](C)C\C=C\C)N(C)C(=O)[C@H](C(C)C)N(C)C(=O)[C@H](CC(C)C)N(C)C(=O)[C@H](CC(C)C)N(C)C(=O)[C@@H](C)NC(=O)[C@H](C)NC(=O)[C@H](CC(C)C)N(C)C(=O)[C@H](C(C)C)NC(=O)[C@H](CC(C)C)N(C)C(=O)CN(C)C1=O PMATZTZNYRCHOR-CGLBZJNRSA-N 0.000 description 2
- 108010036949 Cyclosporine Proteins 0.000 description 2
- FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 2
- 150000008574 D-amino acids Chemical class 0.000 description 2
- FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 description 2
- 108091008102 DNA aptamers Proteins 0.000 description 2
- 108010092160 Dactinomycin Proteins 0.000 description 2
- 229920002307 Dextran Polymers 0.000 description 2
- 239000012591 Dulbecco’s Phosphate Buffered Saline Substances 0.000 description 2
- 239000006144 Dulbecco’s modified Eagle's medium Substances 0.000 description 2
- 108010087819 Fc receptors Proteins 0.000 description 2
- 102000009109 Fc receptors Human genes 0.000 description 2
- 108010070675 Glutathione transferase Proteins 0.000 description 2
- 102000005720 Glutathione transferase Human genes 0.000 description 2
- 108010009504 Gly-Phe-Leu-Gly Proteins 0.000 description 2
- YLEIWGJJBFBFHC-KBPBESRZSA-N Gly-Phe-Lys Chemical compound NCCCC[C@@H](C(O)=O)NC(=O)[C@@H](NC(=O)CN)CC1=CC=CC=C1 YLEIWGJJBFBFHC-KBPBESRZSA-N 0.000 description 2
- NYHBQMYGNKIUIF-UUOKFMHZSA-N Guanosine Chemical compound C1=NC=2C(=O)NC(N)=NC=2N1[C@@H]1O[C@H](CO)[C@@H](O)[C@H]1O NYHBQMYGNKIUIF-UUOKFMHZSA-N 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 2
- 239000004354 Hydroxyethyl cellulose Substances 0.000 description 2
- 229920000663 Hydroxyethyl cellulose Polymers 0.000 description 2
- 229920001612 Hydroxyethyl starch Polymers 0.000 description 2
- 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 2
- 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 2
- UGQMRVRMYYASKQ-KQYNXXCUSA-N Inosine Chemical compound O[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1N1C2=NC=NC(O)=C2N=C1 UGQMRVRMYYASKQ-KQYNXXCUSA-N 0.000 description 2
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 2
- 208000009164 Islet Cell Adenoma Diseases 0.000 description 2
- FADYJNXDPBKVCA-UHFFFAOYSA-N L-Phenylalanyl-L-lysin Natural products NCCCCC(C(O)=O)NC(=O)C(N)CC1=CC=CC=C1 FADYJNXDPBKVCA-UHFFFAOYSA-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
- AYFVYJQAPQTCCC-GBXIJSLDSA-N L-threonine Chemical compound C[C@@H](O)[C@H](N)C(O)=O AYFVYJQAPQTCCC-GBXIJSLDSA-N 0.000 description 2
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 2
- 108010000817 Leuprolide Proteins 0.000 description 2
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 2
- 101710175625 Maltose/maltodextrin-binding periplasmic protein Proteins 0.000 description 2
- 108700011259 MicroRNAs Proteins 0.000 description 2
- 229920000168 Microcrystalline cellulose Polymers 0.000 description 2
- 241000699660 Mus musculus Species 0.000 description 2
- 101100180399 Mus musculus Izumo1r gene Proteins 0.000 description 2
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 2
- WHNWPMSKXPGLAX-UHFFFAOYSA-N N-Vinyl-2-pyrrolidone Chemical compound C=CN1CCCC1=O WHNWPMSKXPGLAX-UHFFFAOYSA-N 0.000 description 2
- PXHVJJICTQNCMI-UHFFFAOYSA-N Nickel Chemical compound [Ni] PXHVJJICTQNCMI-UHFFFAOYSA-N 0.000 description 2
- 239000005642 Oleic acid Substances 0.000 description 2
- ZQPPMHVWECSIRJ-UHFFFAOYSA-N Oleic acid Natural products CCCCCCCCC=CCCCCCCCC(O)=O ZQPPMHVWECSIRJ-UHFFFAOYSA-N 0.000 description 2
- 229930012538 Paclitaxel Natural products 0.000 description 2
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 2
- 108091093037 Peptide nucleic acid Proteins 0.000 description 2
- MIDZLCFIAINOQN-WPRPVWTQSA-N Phe-Ala Chemical compound OC(=O)[C@H](C)NC(=O)[C@@H](N)CC1=CC=CC=C1 MIDZLCFIAINOQN-WPRPVWTQSA-N 0.000 description 2
- OZILORBBPKKGRI-RYUDHWBXSA-N Phe-Arg Chemical compound NC(N)=NCCC[C@@H](C(O)=O)NC(=O)[C@@H](N)CC1=CC=CC=C1 OZILORBBPKKGRI-RYUDHWBXSA-N 0.000 description 2
- FADYJNXDPBKVCA-STQMWFEESA-N Phe-Lys Chemical compound NCCCC[C@@H](C(O)=O)NC(=O)[C@@H](N)CC1=CC=CC=C1 FADYJNXDPBKVCA-STQMWFEESA-N 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- 206010035226 Plasma cell myeloma Diseases 0.000 description 2
- 229920000954 Polyglycolide Polymers 0.000 description 2
- 239000004743 Polypropylene Substances 0.000 description 2
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 2
- WCUXLLCKKVVCTQ-UHFFFAOYSA-M Potassium chloride Chemical compound [Cl-].[K+] WCUXLLCKKVVCTQ-UHFFFAOYSA-M 0.000 description 2
- 241000288906 Primates Species 0.000 description 2
- 108010076504 Protein Sorting Signals Proteins 0.000 description 2
- 108091008103 RNA aptamers Proteins 0.000 description 2
- 230000010799 Receptor Interactions Effects 0.000 description 2
- 241000283984 Rodentia Species 0.000 description 2
- KJTLSVCANCCWHF-UHFFFAOYSA-N Ruthenium Chemical compound [Ru] KJTLSVCANCCWHF-UHFFFAOYSA-N 0.000 description 2
- MTCFGRXMJLQNBG-UHFFFAOYSA-N Serine Natural products OCC(N)C(O)=O MTCFGRXMJLQNBG-UHFFFAOYSA-N 0.000 description 2
- 206010041067 Small cell lung cancer Diseases 0.000 description 2
- 108091027967 Small hairpin RNA Proteins 0.000 description 2
- 108020004459 Small interfering RNA Proteins 0.000 description 2
- VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 2
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 2
- 229920002125 Sokalan® Polymers 0.000 description 2
- 108091008874 T cell receptors Proteins 0.000 description 2
- 102000016266 T-Cell Antigen Receptors Human genes 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
- AYFVYJQAPQTCCC-UHFFFAOYSA-N Threonine Natural products CC(O)C(N)C(O)=O AYFVYJQAPQTCCC-UHFFFAOYSA-N 0.000 description 2
- 239000004473 Threonine Substances 0.000 description 2
- 102000006601 Thymidine Kinase Human genes 0.000 description 2
- 108020004440 Thymidine kinase Proteins 0.000 description 2
- 101710120037 Toxin CcdB Proteins 0.000 description 2
- DRTQHJPVMGBUCF-XVFCMESISA-N Uridine Chemical compound O[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1N1C(=O)NC(=O)C=C1 DRTQHJPVMGBUCF-XVFCMESISA-N 0.000 description 2
- IBIDRSSEHFLGSD-YUMQZZPRSA-N Val-Arg Chemical compound CC(C)[C@H](N)C(=O)N[C@H](C(O)=O)CCCN=C(N)N IBIDRSSEHFLGSD-YUMQZZPRSA-N 0.000 description 2
- JKHXYJKMNSSFFL-IUCAKERBSA-N Val-Lys Chemical compound CC(C)[C@H](N)C(=O)N[C@H](C(O)=O)CCCCN JKHXYJKMNSSFFL-IUCAKERBSA-N 0.000 description 2
- JXLYSJRDGCGARV-WWYNWVTFSA-N Vinblastine Natural products O=C(O[C@H]1[C@](O)(C(=O)OC)[C@@H]2N(C)c3c(cc(c(OC)c3)[C@]3(C(=O)OC)c4[nH]c5c(c4CCN4C[C@](O)(CC)C[C@H](C3)C4)cccc5)[C@@]32[C@H]2[C@@]1(CC)C=CCN2CC3)C JXLYSJRDGCGARV-WWYNWVTFSA-N 0.000 description 2
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 2
- PVNFMCBFDPTNQI-UIBOPQHZSA-N [(1S,2R,5S,6S,16E,18E,20R,21S)-11-chloro-21-hydroxy-12,20-dimethoxy-2,5,9,16-tetramethyl-8,23-dioxo-4,24-dioxa-9,22-diazatetracyclo[19.3.1.110,14.03,5]hexacosa-10,12,14(26),16,18-pentaen-6-yl] acetate [(1S,2R,5S,6S,16E,18E,20R,21S)-11-chloro-21-hydroxy-12,20-dimethoxy-2,5,9,16-tetramethyl-8,23-dioxo-4,24-dioxa-9,22-diazatetracyclo[19.3.1.110,14.03,5]hexacosa-10,12,14(26),16,18-pentaen-6-yl] 3-methylbutanoate [(1S,2R,5S,6S,16E,18E,20R,21S)-11-chloro-21-hydroxy-12,20-dimethoxy-2,5,9,16-tetramethyl-8,23-dioxo-4,24-dioxa-9,22-diazatetracyclo[19.3.1.110,14.03,5]hexacosa-10,12,14(26),16,18-pentaen-6-yl] 2-methylpropanoate [(1S,2R,5S,6S,16E,18E,20R,21S)-11-chloro-21-hydroxy-12,20-dimethoxy-2,5,9,16-tetramethyl-8,23-dioxo-4,24-dioxa-9,22-diazatetracyclo[19.3.1.110,14.03,5]hexacosa-10,12,14(26),16,18-pentaen-6-yl] propanoate Chemical compound CO[C@@H]1\C=C\C=C(C)\Cc2cc(OC)c(Cl)c(c2)N(C)C(=O)C[C@H](OC(C)=O)[C@]2(C)OC2[C@H](C)[C@@H]2C[C@@]1(O)NC(=O)O2.CCC(=O)O[C@H]1CC(=O)N(C)c2cc(C\C(C)=C\C=C\[C@@H](OC)[C@@]3(O)C[C@H](OC(=O)N3)[C@@H](C)C3O[C@@]13C)cc(OC)c2Cl.CO[C@@H]1\C=C\C=C(C)\Cc2cc(OC)c(Cl)c(c2)N(C)C(=O)C[C@H](OC(=O)C(C)C)[C@]2(C)OC2[C@H](C)[C@@H]2C[C@@]1(O)NC(=O)O2.CO[C@@H]1\C=C\C=C(C)\Cc2cc(OC)c(Cl)c(c2)N(C)C(=O)C[C@H](OC(=O)CC(C)C)[C@]2(C)OC2[C@H](C)[C@@H]2C[C@@]1(O)NC(=O)O2 PVNFMCBFDPTNQI-UIBOPQHZSA-N 0.000 description 2
- NLMBVBUNULOTNS-HOKPPMCLSA-N [4-[[(2s)-5-(carbamoylamino)-2-[[(2s)-2-[6-(2,5-dioxopyrrol-1-yl)hexanoylamino]-3-methylbutanoyl]amino]pentanoyl]amino]phenyl]methyl n-[(2s)-1-[[(2s)-1-[[(3r,4s,5s)-1-[(2s)-2-[(1r,2r)-3-[[(1s,2r)-1-hydroxy-1-phenylpropan-2-yl]amino]-1-methoxy-2-methyl-3-o Chemical compound C1([C@H](O)[C@@H](C)NC(=O)[C@H](C)[C@@H](OC)[C@@H]2CCCN2C(=O)C[C@H]([C@H]([C@@H](C)CC)N(C)C(=O)[C@@H](NC(=O)[C@H](C(C)C)N(C)C(=O)OCC=2C=CC(NC(=O)[C@H](CCCNC(N)=O)NC(=O)[C@@H](NC(=O)CCCCCN3C(C=CC3=O)=O)C(C)C)=CC=2)C(C)C)OC)=CC=CC=C1 NLMBVBUNULOTNS-HOKPPMCLSA-N 0.000 description 2
- 230000002159 abnormal effect Effects 0.000 description 2
- RJURFGZVJUQBHK-IIXSONLDSA-N actinomycin D Chemical compound C[C@H]1OC(=O)[C@H](C(C)C)N(C)C(=O)CN(C)C(=O)[C@@H]2CCCN2C(=O)[C@@H](C(C)C)NC(=O)[C@H]1NC(=O)C1=C(N)C(=O)C(C)=C2OC(C(C)=CC=C3C(=O)N[C@@H]4C(=O)N[C@@H](C(N5CCC[C@H]5C(=O)N(C)CC(=O)N(C)[C@@H](C(C)C)C(=O)O[C@@H]4C)=O)C(C)C)=C3N=C21 RJURFGZVJUQBHK-IIXSONLDSA-N 0.000 description 2
- 230000004913 activation Effects 0.000 description 2
- 238000007792 addition Methods 0.000 description 2
- 238000011467 adoptive cell therapy Methods 0.000 description 2
- 108010054982 alanyl-leucyl-alanyl-leucine Proteins 0.000 description 2
- 229940072056 alginate Drugs 0.000 description 2
- 239000000783 alginic acid Substances 0.000 description 2
- 229960001126 alginic acid Drugs 0.000 description 2
- 150000004781 alginic acids Chemical class 0.000 description 2
- 229910052782 aluminium Inorganic materials 0.000 description 2
- XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 description 2
- 239000003098 androgen Substances 0.000 description 2
- 230000000840 anti-viral effect Effects 0.000 description 2
- 229940125644 antibody drug Drugs 0.000 description 2
- 239000000611 antibody drug conjugate Substances 0.000 description 2
- 238000009175 antibody therapy Methods 0.000 description 2
- 239000013059 antihormonal agent Substances 0.000 description 2
- 230000006907 apoptotic process Effects 0.000 description 2
- 239000003886 aromatase inhibitor Substances 0.000 description 2
- 235000009582 asparagine Nutrition 0.000 description 2
- 229960001230 asparagine Drugs 0.000 description 2
- 230000001580 bacterial effect Effects 0.000 description 2
- 239000011324 bead Substances 0.000 description 2
- 239000000440 bentonite Substances 0.000 description 2
- 229910000278 bentonite Inorganic materials 0.000 description 2
- SVPXDRXYRYOSEX-UHFFFAOYSA-N bentoquatam Chemical compound O.O=[Si]=O.O=[Al]O[Al]=O SVPXDRXYRYOSEX-UHFFFAOYSA-N 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
- 210000000013 bile duct Anatomy 0.000 description 2
- 229920001400 block copolymer Polymers 0.000 description 2
- 210000004369 blood Anatomy 0.000 description 2
- 239000008280 blood Substances 0.000 description 2
- KGBXLFKZBHKPEV-UHFFFAOYSA-N boric acid Chemical compound OB(O)O KGBXLFKZBHKPEV-UHFFFAOYSA-N 0.000 description 2
- 239000004327 boric acid Substances 0.000 description 2
- 235000010338 boric acid Nutrition 0.000 description 2
- 229910052796 boron Inorganic materials 0.000 description 2
- HQABUPZFAYXKJW-UHFFFAOYSA-N butan-1-amine Chemical compound CCCCN HQABUPZFAYXKJW-UHFFFAOYSA-N 0.000 description 2
- 229910000019 calcium carbonate Inorganic materials 0.000 description 2
- 235000010216 calcium carbonate Nutrition 0.000 description 2
- FUFJGUQYACFECW-UHFFFAOYSA-L calcium hydrogenphosphate Chemical compound [Ca+2].OP([O-])([O-])=O FUFJGUQYACFECW-UHFFFAOYSA-L 0.000 description 2
- VSJKWCGYPAHWDS-FQEVSTJZSA-N camptothecin Chemical compound C1=CC=C2C=C(CN3C4=CC5=C(C3=O)COC(=O)[C@]5(O)CC)C4=NC2=C1 VSJKWCGYPAHWDS-FQEVSTJZSA-N 0.000 description 2
- 231100000504 carcinogenesis Toxicity 0.000 description 2
- 230000003833 cell viability Effects 0.000 description 2
- 238000012054 celltiter-glo Methods 0.000 description 2
- 238000002512 chemotherapy Methods 0.000 description 2
- 229910052804 chromium Inorganic materials 0.000 description 2
- 239000011651 chromium Substances 0.000 description 2
- 229960001265 ciclosporin 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
- 239000011248 coating agent Substances 0.000 description 2
- 238000000576 coating method Methods 0.000 description 2
- 230000002301 combined effect Effects 0.000 description 2
- 238000012875 competitive assay Methods 0.000 description 2
- 230000009137 competitive binding Effects 0.000 description 2
- 238000004590 computer program Methods 0.000 description 2
- 238000013270 controlled release Methods 0.000 description 2
- 229920001577 copolymer Polymers 0.000 description 2
- 230000009260 cross reactivity Effects 0.000 description 2
- 239000001767 crosslinked sodium carboxy methyl cellulose Substances 0.000 description 2
- 229930182912 cyclosporin Natural products 0.000 description 2
- 231100000599 cytotoxic agent Toxicity 0.000 description 2
- 239000002619 cytotoxin Substances 0.000 description 2
- 229960000640 dactinomycin Drugs 0.000 description 2
- 238000013461 design Methods 0.000 description 2
- 238000000502 dialysis Methods 0.000 description 2
- 235000019700 dicalcium phosphate Nutrition 0.000 description 2
- 229940095079 dicalcium phosphate anhydrous Drugs 0.000 description 2
- RBLGLDWTCZMLRW-UHFFFAOYSA-K dicalcium;phosphate;dihydrate Chemical compound O.O.[Ca+2].[Ca+2].[O-]P([O-])([O-])=O RBLGLDWTCZMLRW-UHFFFAOYSA-K 0.000 description 2
- 235000014113 dietary fatty acids Nutrition 0.000 description 2
- 230000029087 digestion Effects 0.000 description 2
- 238000010790 dilution Methods 0.000 description 2
- 239000012895 dilution Substances 0.000 description 2
- ZLFRJHOBQVVTOJ-UHFFFAOYSA-N dimethyl hexanediimidate Chemical compound COC(=N)CCCCC(=N)OC ZLFRJHOBQVVTOJ-UHFFFAOYSA-N 0.000 description 2
- 238000010494 dissociation reaction Methods 0.000 description 2
- 230000005593 dissociations Effects 0.000 description 2
- 238000004090 dissolution Methods 0.000 description 2
- 239000003623 enhancer Substances 0.000 description 2
- 210000002919 epithelial cell Anatomy 0.000 description 2
- 229940011871 estrogen Drugs 0.000 description 2
- 239000000262 estrogen Substances 0.000 description 2
- 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 2
- 229960005420 etoposide Drugs 0.000 description 2
- 229930195729 fatty acid Natural products 0.000 description 2
- 239000000194 fatty acid Substances 0.000 description 2
- 239000000945 filler Substances 0.000 description 2
- 229960002074 flutamide Drugs 0.000 description 2
- MKXKFYHWDHIYRV-UHFFFAOYSA-N flutamide Chemical compound CC(C)C(=O)NC1=CC=C([N+]([O-])=O)C(C(F)(F)F)=C1 MKXKFYHWDHIYRV-UHFFFAOYSA-N 0.000 description 2
- 238000013467 fragmentation Methods 0.000 description 2
- 238000006062 fragmentation reaction Methods 0.000 description 2
- 229960003692 gamma aminobutyric acid Drugs 0.000 description 2
- 230000002068 genetic effect Effects 0.000 description 2
- 238000010353 genetic engineering Methods 0.000 description 2
- 229910052732 germanium Inorganic materials 0.000 description 2
- 239000011521 glass Substances 0.000 description 2
- 235000011187 glycerol Nutrition 0.000 description 2
- 229940075507 glyceryl monostearate Drugs 0.000 description 2
- PCHJSUWPFVWCPO-UHFFFAOYSA-N gold Chemical compound [Au] PCHJSUWPFVWCPO-UHFFFAOYSA-N 0.000 description 2
- XLXSAKCOAKORKW-AQJXLSMYSA-N gonadorelin Chemical compound C([C@@H](C(=O)NCC(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N1[C@@H](CCC1)C(=O)NCC(N)=O)NC(=O)[C@H](CO)NC(=O)[C@H](CC=1C2=CC=CC=C2NC=1)NC(=O)[C@H](CC=1N=CNC=1)NC(=O)[C@H]1NC(=O)CC1)C1=CC=C(O)C=C1 XLXSAKCOAKORKW-AQJXLSMYSA-N 0.000 description 2
- 230000012010 growth Effects 0.000 description 2
- 125000005843 halogen group Chemical group 0.000 description 2
- 238000004128 high performance liquid chromatography Methods 0.000 description 2
- 229960002885 histidine Drugs 0.000 description 2
- 238000009396 hybridization Methods 0.000 description 2
- 235000019447 hydroxyethyl cellulose Nutrition 0.000 description 2
- 229940071826 hydroxyethyl cellulose Drugs 0.000 description 2
- 229940050526 hydroxyethylstarch Drugs 0.000 description 2
- 229960000908 idarubicin Drugs 0.000 description 2
- 239000003018 immunosuppressive agent Substances 0.000 description 2
- 229940125721 immunosuppressive agent Drugs 0.000 description 2
- 108010074108 interleukin-21 Proteins 0.000 description 2
- 238000007918 intramuscular administration Methods 0.000 description 2
- 238000007912 intraperitoneal administration Methods 0.000 description 2
- 238000007914 intraventricular administration Methods 0.000 description 2
- 229960004768 irinotecan Drugs 0.000 description 2
- GURKHSYORGJETM-WAQYZQTGSA-N irinotecan hydrochloride (anhydrous) Chemical compound Cl.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 GURKHSYORGJETM-WAQYZQTGSA-N 0.000 description 2
- QXJSBBXBKPUZAA-UHFFFAOYSA-N isooleic acid Natural products CCCCCCCC=CCCCCCCCCC(O)=O QXJSBBXBKPUZAA-UHFFFAOYSA-N 0.000 description 2
- 238000002372 labelling Methods 0.000 description 2
- JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 2
- 239000000832 lactitol Substances 0.000 description 2
- 235000010448 lactitol Nutrition 0.000 description 2
- VQHSOMBJVWLPSR-JVCRWLNRSA-N lactitol Chemical compound OC[C@H](O)[C@@H](O)[C@@H]([C@H](O)CO)O[C@@H]1O[C@H](CO)[C@H](O)[C@H](O)[C@H]1O VQHSOMBJVWLPSR-JVCRWLNRSA-N 0.000 description 2
- 229960003451 lactitol Drugs 0.000 description 2
- 229960001375 lactose Drugs 0.000 description 2
- 239000008101 lactose Substances 0.000 description 2
- GFIJNRVAKGFPGQ-LIJARHBVSA-N leuprolide Chemical compound CCNC(=O)[C@@H]1CCCN1C(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](CC(C)C)NC(=O)[C@@H](NC(=O)[C@H](CO)NC(=O)[C@H](CC=1C2=CC=CC=C2NC=1)NC(=O)[C@H](CC=1N=CNC=1)NC(=O)[C@H]1NC(=O)CC1)CC1=CC=C(O)C=C1 GFIJNRVAKGFPGQ-LIJARHBVSA-N 0.000 description 2
- 229960004338 leuprorelin Drugs 0.000 description 2
- 230000000670 limiting effect Effects 0.000 description 2
- 238000012417 linear regression Methods 0.000 description 2
- 229910052749 magnesium Inorganic materials 0.000 description 2
- 239000011777 magnesium Substances 0.000 description 2
- 239000012528 membrane Substances 0.000 description 2
- 108020004999 messenger RNA Proteins 0.000 description 2
- 239000002082 metal nanoparticle Substances 0.000 description 2
- 239000002679 microRNA Substances 0.000 description 2
- 230000000813 microbial effect Effects 0.000 description 2
- 235000019813 microcrystalline cellulose Nutrition 0.000 description 2
- 239000008108 microcrystalline cellulose Substances 0.000 description 2
- 229940016286 microcrystalline cellulose Drugs 0.000 description 2
- 229960004857 mitomycin Drugs 0.000 description 2
- 239000001788 mono and diglycerides of fatty acids Substances 0.000 description 2
- 229940126619 mouse monoclonal antibody Drugs 0.000 description 2
- 201000000050 myeloid neoplasm Diseases 0.000 description 2
- 239000013642 negative control Substances 0.000 description 2
- IDBIFFKSXLYUOT-UHFFFAOYSA-N netropsin Chemical compound C1=C(C(=O)NCCC(N)=N)N(C)C=C1NC(=O)C1=CC(NC(=O)CN=C(N)N)=CN1C IDBIFFKSXLYUOT-UHFFFAOYSA-N 0.000 description 2
- 229960003301 nivolumab Drugs 0.000 description 2
- 108091008104 nucleic acid aptamers Proteins 0.000 description 2
- 239000002777 nucleoside Substances 0.000 description 2
- FDLYAMZZIXQODN-UHFFFAOYSA-N olaparib Chemical compound FC1=CC=C(CC=2C3=CC=CC=C3C(=O)NN=2)C=C1C(=O)N(CC1)CCN1C(=O)C1CC1 FDLYAMZZIXQODN-UHFFFAOYSA-N 0.000 description 2
- ZQPPMHVWECSIRJ-KTKRTIGZSA-N oleic acid Chemical compound CCCCCCCC\C=C/CCCCCCCC(O)=O ZQPPMHVWECSIRJ-KTKRTIGZSA-N 0.000 description 2
- 210000000056 organ Anatomy 0.000 description 2
- 230000002611 ovarian Effects 0.000 description 2
- 229960001756 oxaliplatin Drugs 0.000 description 2
- DWAFYCQODLXJNR-BNTLRKBRSA-L oxaliplatin Chemical compound O1C(=O)C(=O)O[Pt]11N[C@@H]2CCCC[C@H]2N1 DWAFYCQODLXJNR-BNTLRKBRSA-L 0.000 description 2
- 108010058266 p21-Activated Kinases Proteins 0.000 description 2
- 102000006271 p21-Activated Kinases Human genes 0.000 description 2
- 239000005022 packaging material Substances 0.000 description 2
- 229960001592 paclitaxel Drugs 0.000 description 2
- 210000000496 pancreas Anatomy 0.000 description 2
- 239000002245 particle Substances 0.000 description 2
- 230000008775 paternal effect Effects 0.000 description 2
- 229960002621 pembrolizumab Drugs 0.000 description 2
- 108010024607 phenylalanylalanine Proteins 0.000 description 2
- 108010018625 phenylalanylarginine Proteins 0.000 description 2
- 239000011574 phosphorus Substances 0.000 description 2
- 230000026731 phosphorylation Effects 0.000 description 2
- 238000006366 phosphorylation reaction Methods 0.000 description 2
- 230000000704 physical effect Effects 0.000 description 2
- 229910052697 platinum Inorganic materials 0.000 description 2
- 229920001983 poloxamer Polymers 0.000 description 2
- 229920000747 poly(lactic acid) Polymers 0.000 description 2
- 229920001155 polypropylene Polymers 0.000 description 2
- 229940068968 polysorbate 80 Drugs 0.000 description 2
- 239000011591 potassium Substances 0.000 description 2
- 238000012545 processing Methods 0.000 description 2
- QLNJFJADRCOGBJ-UHFFFAOYSA-N propionamide Chemical compound CCC(N)=O QLNJFJADRCOGBJ-UHFFFAOYSA-N 0.000 description 2
- 229940080818 propionamide Drugs 0.000 description 2
- 230000009257 reactivity Effects 0.000 description 2
- 230000010076 replication Effects 0.000 description 2
- 239000011347 resin Substances 0.000 description 2
- 229920005989 resin Polymers 0.000 description 2
- 230000004044 response Effects 0.000 description 2
- 230000002441 reversible effect Effects 0.000 description 2
- FGDZQCVHDSGLHJ-UHFFFAOYSA-M rubidium chloride Chemical compound [Cl-].[Rb+] FGDZQCVHDSGLHJ-UHFFFAOYSA-M 0.000 description 2
- 229910052707 ruthenium Inorganic materials 0.000 description 2
- 239000000523 sample Substances 0.000 description 2
- 229910052710 silicon Inorganic materials 0.000 description 2
- 239000010703 silicon Substances 0.000 description 2
- 208000000649 small cell carcinoma Diseases 0.000 description 2
- 208000000587 small cell lung carcinoma Diseases 0.000 description 2
- 239000001632 sodium acetate Substances 0.000 description 2
- 235000017281 sodium acetate Nutrition 0.000 description 2
- WXMKPNITSTVMEF-UHFFFAOYSA-M sodium benzoate Chemical compound [Na+].[O-]C(=O)C1=CC=CC=C1 WXMKPNITSTVMEF-UHFFFAOYSA-M 0.000 description 2
- 239000004299 sodium benzoate Substances 0.000 description 2
- 235000010234 sodium benzoate Nutrition 0.000 description 2
- HHSGWIABCIVPJT-UHFFFAOYSA-M sodium;1-[4-[(2-iodoacetyl)amino]benzoyl]oxy-2,5-dioxopyrrolidine-3-sulfonate Chemical compound [Na+].O=C1C(S(=O)(=O)[O-])CC(=O)N1OC(=O)C1=CC=C(NC(=O)CI)C=C1 HHSGWIABCIVPJT-UHFFFAOYSA-M 0.000 description 2
- 239000007790 solid phase Substances 0.000 description 2
- 235000011069 sorbitan monooleate Nutrition 0.000 description 2
- 239000001593 sorbitan monooleate Substances 0.000 description 2
- 229940035049 sorbitan monooleate Drugs 0.000 description 2
- 239000000600 sorbitol Substances 0.000 description 2
- 229960002920 sorbitol Drugs 0.000 description 2
- 235000010356 sorbitol Nutrition 0.000 description 2
- 210000000952 spleen Anatomy 0.000 description 2
- 206010041823 squamous cell carcinoma Diseases 0.000 description 2
- 239000003381 stabilizer Substances 0.000 description 2
- 238000010186 staining Methods 0.000 description 2
- UCSJYZPVAKXKNQ-HZYVHMACSA-N streptomycin Chemical compound CN[C@H]1[C@H](O)[C@@H](O)[C@H](CO)O[C@H]1O[C@@H]1[C@](C=O)(O)[C@H](C)O[C@H]1O[C@@H]1[C@@H](NC(N)=N)[C@H](O)[C@@H](NC(N)=N)[C@H](O)[C@H]1O UCSJYZPVAKXKNQ-HZYVHMACSA-N 0.000 description 2
- 150000008163 sugars Chemical class 0.000 description 2
- 239000000375 suspending agent Substances 0.000 description 2
- 239000000454 talc Substances 0.000 description 2
- 229910052623 talc Inorganic materials 0.000 description 2
- NRUKOCRGYNPUPR-QBPJDGROSA-N teniposide Chemical compound COC1=C(O)C(OC)=CC([C@@H]2C3=CC=4OCOC=4C=C3[C@@H](O[C@H]3[C@@H]([C@@H](O)[C@@H]4O[C@@H](OC[C@H]4O3)C=3SC=CC=3)O)[C@@H]3[C@@H]2C(OC3)=O)=C1 NRUKOCRGYNPUPR-QBPJDGROSA-N 0.000 description 2
- 229960001278 teniposide Drugs 0.000 description 2
- 231100001274 therapeutic index Toxicity 0.000 description 2
- 238000011285 therapeutic regimen Methods 0.000 description 2
- 125000003396 thiol group Chemical group [H]S* 0.000 description 2
- RYYWUUFWQRZTIU-UHFFFAOYSA-K thiophosphate Chemical compound [O-]P([O-])([O-])=S RYYWUUFWQRZTIU-UHFFFAOYSA-K 0.000 description 2
- 229940104230 thymidine Drugs 0.000 description 2
- 230000001988 toxicity Effects 0.000 description 2
- 231100000419 toxicity Toxicity 0.000 description 2
- 238000001890 transfection Methods 0.000 description 2
- 238000002054 transplantation Methods 0.000 description 2
- 235000019731 tricalcium phosphate Nutrition 0.000 description 2
- 229940078499 tricalcium phosphate Drugs 0.000 description 2
- 229910000391 tricalcium phosphate Inorganic materials 0.000 description 2
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 2
- HDZZVAMISRMYHH-KCGFPETGSA-N tubercidin Chemical compound C1=CC=2C(N)=NC=NC=2N1[C@@H]1O[C@H](CO)[C@@H](O)[C@H]1O HDZZVAMISRMYHH-KCGFPETGSA-N 0.000 description 2
- 210000004881 tumor cell Anatomy 0.000 description 2
- 102000003390 tumor necrosis factor Human genes 0.000 description 2
- 229960005486 vaccine Drugs 0.000 description 2
- IBIDRSSEHFLGSD-UHFFFAOYSA-N valinyl-arginine Natural products CC(C)C(N)C(=O)NC(C(O)=O)CCCN=C(N)N IBIDRSSEHFLGSD-UHFFFAOYSA-N 0.000 description 2
- 229960000653 valrubicin Drugs 0.000 description 2
- ZOCKGBMQLCSHFP-KQRAQHLDSA-N valrubicin Chemical compound O([C@H]1C[C@](CC2=C(O)C=3C(=O)C4=CC=CC(OC)=C4C(=O)C=3C(O)=C21)(O)C(=O)COC(=O)CCCC)[C@H]1C[C@H](NC(=O)C(F)(F)F)[C@H](O)[C@H](C)O1 ZOCKGBMQLCSHFP-KQRAQHLDSA-N 0.000 description 2
- 108010073969 valyllysine Proteins 0.000 description 2
- 235000015112 vegetable and seed oil Nutrition 0.000 description 2
- 239000008158 vegetable oil Substances 0.000 description 2
- 230000035899 viability Effects 0.000 description 2
- 229960003048 vinblastine Drugs 0.000 description 2
- JXLYSJRDGCGARV-XQKSVPLYSA-N vincaleukoblastine Chemical compound C([C@@H](C[C@]1(C(=O)OC)C=2C(=CC3=C([C@]45[C@H]([C@@]([C@H](OC(C)=O)[C@]6(CC)C=CCN([C@H]56)CC4)(O)C(=O)OC)N3C)C=2)OC)C[C@@](C2)(O)CC)N2CCC2=C1NC1=CC=CC=C21 JXLYSJRDGCGARV-XQKSVPLYSA-N 0.000 description 2
- OGWKCGZFUXNPDA-XQKSVPLYSA-N vincristine Chemical compound C([N@]1C[C@@H](C[C@]2(C(=O)OC)C=3C(=CC4=C([C@]56[C@H]([C@@]([C@H](OC(C)=O)[C@]7(CC)C=CCN([C@H]67)CC5)(O)C(=O)OC)N4C=O)C=3)OC)C[C@@](C1)(O)CC)CC1=C2NC2=CC=CC=C12 OGWKCGZFUXNPDA-XQKSVPLYSA-N 0.000 description 2
- 229960004528 vincristine Drugs 0.000 description 2
- OGWKCGZFUXNPDA-UHFFFAOYSA-N vincristine Natural products C1C(CC)(O)CC(CC2(C(=O)OC)C=3C(=CC4=C(C56C(C(C(OC(C)=O)C7(CC)C=CCN(C67)CC5)(O)C(=O)OC)N4C=O)C=3)OC)CN1CCC1=C2NC2=CC=CC=C12 OGWKCGZFUXNPDA-UHFFFAOYSA-N 0.000 description 2
- 238000005406 washing Methods 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- 235000010493 xanthan gum Nutrition 0.000 description 2
- 239000000230 xanthan gum Substances 0.000 description 2
- 229940082509 xanthan gum Drugs 0.000 description 2
- 229910052725 zinc Inorganic materials 0.000 description 2
- 239000011701 zinc Substances 0.000 description 2
- CMMLZMMKTYEOKV-LMBDXJSXSA-N (1R,4S,5'R,6'R,10S,11R,12R,14R,15R,16S,18R,19S,20R,25S,26R,27S,29S)-4-ethyl-11,15,19-trihydroxy-6'-[(2S)-2-hydroxypropyl]-5',10,12,14,16,18,20,26,29-nonamethylspiro[24,28-dioxabicyclo[23.3.1]nonacosa-5,7,21-triene-27,2'-oxane]-13,17,23-trione Polymers O([C@@H]1CC[C@@H](C=CC=CC[C@H](C)[C@@H](O)[C@@H](C)C(=O)[C@H](C)[C@@H](O)[C@H](C)C(=O)[C@H](C)[C@@H](O)[C@H](C)C=CC(=O)O[C@H]([C@H]2C)[C@H]1C)CC)[C@]12CC[C@@H](C)[C@@H](C[C@H](C)O)O1 CMMLZMMKTYEOKV-LMBDXJSXSA-N 0.000 description 1
- CMMLZMMKTYEOKV-HQCSJJBPSA-N (1r,4s,5e,5'r,6'r,7e,10s,11r,12r,14r,15r,16s,18r,19s,20r,21e,25s,26r,27s,29s)-4-ethyl-11,15,19-trihydroxy-6'-(2-hydroxypropyl)-5',10,12,14,16,18,20,26,29-nonamethylspiro[24,28-dioxabicyclo[23.3.1]nonacosa-5,7,21-triene-27,2'-oxane]-13,17,23-trione Polymers O([C@@H]1CC[C@@H](/C=C/C=C/C[C@H](C)[C@@H](O)[C@@H](C)C(=O)[C@H](C)[C@@H](O)[C@H](C)C(=O)[C@H](C)[C@@H](O)[C@H](C)/C=C/C(=O)O[C@H]([C@H]2C)[C@H]1C)CC)[C@]12CC[C@@H](C)[C@@H](CC(C)O)O1 CMMLZMMKTYEOKV-HQCSJJBPSA-N 0.000 description 1
- XSWBNALIBMCQED-UHFFFAOYSA-N (2,5-dioxopyrrolidin-1-yl) 2-phenyl-2-(pyridin-2-yldisulfanyl)propanoate Chemical compound O=C1CCC(=O)N1OC(=O)C(C=1C=CC=CC=1)(C)SSC1=CC=CC=N1 XSWBNALIBMCQED-UHFFFAOYSA-N 0.000 description 1
- FXYPGCIGRDZWNR-UHFFFAOYSA-N (2,5-dioxopyrrolidin-1-yl) 3-[[3-(2,5-dioxopyrrolidin-1-yl)oxy-3-oxopropyl]disulfanyl]propanoate Chemical compound O=C1CCC(=O)N1OC(=O)CCSSCCC(=O)ON1C(=O)CCC1=O FXYPGCIGRDZWNR-UHFFFAOYSA-N 0.000 description 1
- RBAFCMJBDZWZIV-UHFFFAOYSA-N (2,5-dioxopyrrolidin-1-yl) 4-azido-2-hydroxybenzoate Chemical compound OC1=CC(N=[N+]=[N-])=CC=C1C(=O)ON1C(=O)CCC1=O RBAFCMJBDZWZIV-UHFFFAOYSA-N 0.000 description 1
- CMMLZMMKTYEOKV-OWCJZXDLSA-N (27s)-4-ethyl-11,15,19-trihydroxy-6'-(2-hydroxypropyl)-5',10,12,14,16,18,20,26,29-nonamethylspiro[24,28-dioxabicyclo[23.3.1]nonacosa-5,7,21-triene-27,2'-oxane]-13,17,23-trione Polymers CC1C(C2C)OC(=O)C=CC(C)C(O)C(C)C(=O)C(C)C(O)C(C)C(=O)C(C)C(O)C(C)CC=CC=CC(CC)CCC2O[C@]21CCC(C)C(CC(C)O)O2 CMMLZMMKTYEOKV-OWCJZXDLSA-N 0.000 description 1
- DENYZIUJOTUUNY-MRXNPFEDSA-N (2R)-14-fluoro-2-methyl-6,9,10,19-tetrazapentacyclo[14.2.1.02,6.08,18.012,17]nonadeca-1(18),8,12(17),13,15-pentaen-11-one Chemical compound FC=1C=C2C=3C=4C(CN5[C@@](C4NC3C1)(CCC5)C)=NNC2=O DENYZIUJOTUUNY-MRXNPFEDSA-N 0.000 description 1
- GRZXWCHAXNAUHY-NSISKUIASA-N (2S)-2-(4-chlorophenyl)-1-[4-[(5R,7R)-7-hydroxy-5-methyl-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-yl]-1-piperazinyl]-3-(propan-2-ylamino)-1-propanone Chemical compound C1([C@H](C(=O)N2CCN(CC2)C=2C=3[C@H](C)C[C@@H](O)C=3N=CN=2)CNC(C)C)=CC=C(Cl)C=C1 GRZXWCHAXNAUHY-NSISKUIASA-N 0.000 description 1
- JNYAEWCLZODPBN-JGWLITMVSA-N (2r,3r,4s)-2-[(1r)-1,2-dihydroxyethyl]oxolane-3,4-diol Polymers OC[C@@H](O)[C@H]1OC[C@H](O)[C@H]1O JNYAEWCLZODPBN-JGWLITMVSA-N 0.000 description 1
- KYJLJOJCMUFWDY-UUOKFMHZSA-N (2r,3r,4s,5r)-2-(6-amino-8-azidopurin-9-yl)-5-(hydroxymethyl)oxolane-3,4-diol Chemical compound [N-]=[N+]=NC1=NC=2C(N)=NC=NC=2N1[C@@H]1O[C@H](CO)[C@@H](O)[C@H]1O KYJLJOJCMUFWDY-UUOKFMHZSA-N 0.000 description 1
- RIFDKYBNWNPCQK-IOSLPCCCSA-N (2r,3s,4r,5r)-2-(hydroxymethyl)-5-(6-imino-3-methylpurin-9-yl)oxolane-3,4-diol Chemical compound C1=2N(C)C=NC(=N)C=2N=CN1[C@@H]1O[C@H](CO)[C@@H](O)[C@H]1O RIFDKYBNWNPCQK-IOSLPCCCSA-N 0.000 description 1
- WJTCHBVEUFDSIK-NWDGAFQWSA-N (2r,5s)-1-benzyl-2,5-dimethylpiperazine Chemical compound C[C@@H]1CN[C@@H](C)CN1CC1=CC=CC=C1 WJTCHBVEUFDSIK-NWDGAFQWSA-N 0.000 description 1
- HSINOMROUCMIEA-FGVHQWLLSA-N (2s,4r)-4-[(3r,5s,6r,7r,8s,9s,10s,13r,14s,17r)-6-ethyl-3,7-dihydroxy-10,13-dimethyl-2,3,4,5,6,7,8,9,11,12,14,15,16,17-tetradecahydro-1h-cyclopenta[a]phenanthren-17-yl]-2-methylpentanoic acid Chemical class C([C@@]12C)C[C@@H](O)C[C@H]1[C@@H](CC)[C@@H](O)[C@@H]1[C@@H]2CC[C@]2(C)[C@@H]([C@H](C)C[C@H](C)C(O)=O)CC[C@H]21 HSINOMROUCMIEA-FGVHQWLLSA-N 0.000 description 1
- 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 1
- STGXGJRRAJKJRG-JDJSBBGDSA-N (3r,4r,5r)-5-(hydroxymethyl)-3-methoxyoxolane-2,4-diol Chemical compound CO[C@H]1C(O)O[C@H](CO)[C@H]1O STGXGJRRAJKJRG-JDJSBBGDSA-N 0.000 description 1
- MEJYDZQQVZJMPP-ULAWRXDQSA-N (3s,3ar,6r,6ar)-3,6-dimethoxy-2,3,3a,5,6,6a-hexahydrofuro[3,2-b]furan Chemical compound CO[C@H]1CO[C@@H]2[C@H](OC)CO[C@@H]21 MEJYDZQQVZJMPP-ULAWRXDQSA-N 0.000 description 1
- DEQANNDTNATYII-OULOTJBUSA-N (4r,7s,10s,13r,16s,19r)-10-(4-aminobutyl)-19-[[(2r)-2-amino-3-phenylpropanoyl]amino]-16-benzyl-n-[(2r,3r)-1,3-dihydroxybutan-2-yl]-7-[(1r)-1-hydroxyethyl]-13-(1h-indol-3-ylmethyl)-6,9,12,15,18-pentaoxo-1,2-dithia-5,8,11,14,17-pentazacycloicosane-4-carboxa Chemical compound C([C@@H](N)C(=O)N[C@H]1CSSC[C@H](NC(=O)[C@H]([C@@H](C)O)NC(=O)[C@H](CCCCN)NC(=O)[C@@H](CC=2C3=CC=CC=C3NC=2)NC(=O)[C@H](CC=2C=CC=CC=2)NC1=O)C(=O)N[C@H](CO)[C@H](O)C)C1=CC=CC=C1 DEQANNDTNATYII-OULOTJBUSA-N 0.000 description 1
- PXYUMIVMMHXGBH-OALUTQOASA-N (6as)-3-[3-[[(6as)-2-methoxy-11-oxo-6a,7,8,9-tetrahydropyrrolo[2,1-c][1,4]benzodiazepin-3-yl]oxy]propoxy]-2-methoxy-6a,7,8,9-tetrahydropyrrolo[2,1-c][1,4]benzodiazepin-11-one Chemical compound N1=C[C@@H]2CCCN2C(=O)C(C=C2OC)=C1C=C2OCCCOC1=CC(N=C[C@H]2N(CCC2)C2=O)=C2C=C1OC PXYUMIVMMHXGBH-OALUTQOASA-N 0.000 description 1
- SLURUCSFDHKXFR-WWMWMSKMSA-N (7s,9s)-7-[[(1s,3r,4as,9s,9ar,10as)-9-methoxy-1-methyl-3,4,4a,6,7,9,9a,10a-octahydro-1h-pyrano[1,2][1,3]oxazolo[3,4-b][1,4]oxazin-3-yl]oxy]-6,9,11-trihydroxy-9-(2-hydroxyacetyl)-4-methoxy-8,10-dihydro-7h-tetracene-5,12-dione Chemical compound O=C1C2=CC=CC(OC)=C2C(=O)C(C(O)=C23)=C1C(O)=C3C[C@@](O)(C(=O)CO)C[C@@H]2O[C@H]1C[C@@H]2N3CCO[C@H](OC)[C@H]3O[C@@H]2[C@H](C)O1 SLURUCSFDHKXFR-WWMWMSKMSA-N 0.000 description 1
- IEXUMDBQLIVNHZ-YOUGDJEHSA-N (8s,11r,13r,14s,17s)-11-[4-(dimethylamino)phenyl]-17-hydroxy-17-(3-hydroxypropyl)-13-methyl-1,2,6,7,8,11,12,14,15,16-decahydrocyclopenta[a]phenanthren-3-one Chemical compound C1=CC(N(C)C)=CC=C1[C@@H]1C2=C3CCC(=O)C=C3CC[C@H]2[C@H](CC[C@]2(O)CCCO)[C@@]2(C)C1 IEXUMDBQLIVNHZ-YOUGDJEHSA-N 0.000 description 1
- FDKXTQMXEQVLRF-ZHACJKMWSA-N (E)-dacarbazine Chemical compound CN(C)\N=N\c1[nH]cnc1C(N)=O FDKXTQMXEQVLRF-ZHACJKMWSA-N 0.000 description 1
- LKJPYSCBVHEWIU-KRWDZBQOSA-N (R)-bicalutamide Chemical compound C([C@@](O)(C)C(=O)NC=1C=C(C(C#N)=CC=1)C(F)(F)F)S(=O)(=O)C1=CC=C(F)C=C1 LKJPYSCBVHEWIU-KRWDZBQOSA-N 0.000 description 1
- ICLYJLBTOGPLMC-KVVVOXFISA-N (z)-octadec-9-enoate;tris(2-hydroxyethyl)azanium Chemical compound OCCN(CCO)CCO.CCCCCCCC\C=C/CCCCCCCC(O)=O ICLYJLBTOGPLMC-KVVVOXFISA-N 0.000 description 1
- LDVVTQMJQSCDMK-UHFFFAOYSA-N 1,3-dihydroxypropan-2-yl formate Chemical compound OCC(CO)OC=O LDVVTQMJQSCDMK-UHFFFAOYSA-N 0.000 description 1
- WDQFELCEOPFLCZ-UHFFFAOYSA-N 1-(2-hydroxyethyl)pyrrolidin-2-one Chemical compound OCCN1CCCC1=O WDQFELCEOPFLCZ-UHFFFAOYSA-N 0.000 description 1
- QWQORQURWIFIRD-UHFFFAOYSA-N 1-(4-benzoylphenyl)pyrrolidine-2,5-dione Chemical compound C=1C=C(N2C(CCC2=O)=O)C=CC=1C(=O)C1=CC=CC=C1 QWQORQURWIFIRD-UHFFFAOYSA-N 0.000 description 1
- RKSLVDIXBGWPIS-UAKXSSHOSA-N 1-[(2r,3r,4s,5r)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]-5-iodopyrimidine-2,4-dione Chemical compound O[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1N1C(=O)NC(=O)C(I)=C1 RKSLVDIXBGWPIS-UAKXSSHOSA-N 0.000 description 1
- QLOCVMVCRJOTTM-TURQNECASA-N 1-[(2r,3r,4s,5r)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]-5-prop-1-ynylpyrimidine-2,4-dione Chemical compound O=C1NC(=O)C(C#CC)=CN1[C@H]1[C@H](O)[C@H](O)[C@@H](CO)O1 QLOCVMVCRJOTTM-TURQNECASA-N 0.000 description 1
- PISWNSOQFZRVJK-XLPZGREQSA-N 1-[(2r,4s,5r)-4-hydroxy-5-(hydroxymethyl)oxolan-2-yl]-5-methyl-2-sulfanylidenepyrimidin-4-one Chemical compound S=C1NC(=O)C(C)=CN1[C@@H]1O[C@H](CO)[C@@H](O)C1 PISWNSOQFZRVJK-XLPZGREQSA-N 0.000 description 1
- AVKSPBJBGGHUMW-XLPZGREQSA-N 1-[(2r,4s,5r)-4-hydroxy-5-(hydroxymethyl)oxolan-2-yl]-5-methyl-4-sulfanylidenepyrimidin-2-one Chemical compound O=C1NC(=S)C(C)=CN1[C@@H]1O[C@H](CO)[C@@H](O)C1 AVKSPBJBGGHUMW-XLPZGREQSA-N 0.000 description 1
- VOTJUWBJENROFB-UHFFFAOYSA-N 1-[3-[[3-(2,5-dioxo-3-sulfopyrrolidin-1-yl)oxy-3-oxopropyl]disulfanyl]propanoyloxy]-2,5-dioxopyrrolidine-3-sulfonic acid Chemical compound O=C1C(S(=O)(=O)O)CC(=O)N1OC(=O)CCSSCCC(=O)ON1C(=O)C(S(O)(=O)=O)CC1=O VOTJUWBJENROFB-UHFFFAOYSA-N 0.000 description 1
- OKMWKBLSFKFYGZ-UHFFFAOYSA-N 1-behenoylglycerol Chemical compound CCCCCCCCCCCCCCCCCCCCCC(=O)OCC(O)CO OKMWKBLSFKFYGZ-UHFFFAOYSA-N 0.000 description 1
- UHDGCWIWMRVCDJ-UHFFFAOYSA-N 1-beta-D-Xylofuranosyl-NH-Cytosine Natural products O=C1N=C(N)C=CN1C1C(O)C(O)C(CO)O1 UHDGCWIWMRVCDJ-UHFFFAOYSA-N 0.000 description 1
- KHAWDEWNXJIVCJ-UHFFFAOYSA-N 1-fluoro-4-(4-fluoro-3-nitrophenyl)sulfonyl-2-nitrobenzene Chemical compound C1=C(F)C([N+](=O)[O-])=CC(S(=O)(=O)C=2C=C(C(F)=CC=2)[N+]([O-])=O)=C1 KHAWDEWNXJIVCJ-UHFFFAOYSA-N 0.000 description 1
- JLPULHDHAOZNQI-ZTIMHPMXSA-N 1-hexadecanoyl-2-(9Z,12Z-octadecadienoyl)-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCCCCCC\C=C/C\C=C/CCCCC JLPULHDHAOZNQI-ZTIMHPMXSA-N 0.000 description 1
- VSNHCAURESNICA-NJFSPNSNSA-N 1-oxidanylurea Chemical compound N[14C](=O)NO VSNHCAURESNICA-NJFSPNSNSA-N 0.000 description 1
- CTLOSZHDGZLOQE-UHFFFAOYSA-N 14-methoxy-9-[(4-methylpiperazin-1-yl)methyl]-9,19-diazapentacyclo[10.7.0.02,6.07,11.013,18]nonadeca-1(12),2(6),7(11),13(18),14,16-hexaene-8,10-dione Chemical compound O=C1C2=C3C=4C(OC)=CC=CC=4NC3=C3CCCC3=C2C(=O)N1CN1CCN(C)CC1 CTLOSZHDGZLOQE-UHFFFAOYSA-N 0.000 description 1
- VOXZDWNPVJITMN-ZBRFXRBCSA-N 17β-estradiol Chemical compound OC1=CC=C2[C@H]3CC[C@](C)([C@H](CC4)O)[C@@H]4[C@@H]3CCC2=C1 VOXZDWNPVJITMN-ZBRFXRBCSA-N 0.000 description 1
- YKBGVTZYEHREMT-KVQBGUIXSA-N 2'-deoxyguanosine Chemical compound C1=NC=2C(=O)NC(N)=NC=2N1[C@H]1C[C@H](O)[C@@H](CO)O1 YKBGVTZYEHREMT-KVQBGUIXSA-N 0.000 description 1
- CKTSBUTUHBMZGZ-SHYZEUOFSA-N 2'‐deoxycytidine Chemical compound O=C1N=C(N)C=CN1[C@@H]1O[C@H](CO)[C@@H](O)C1 CKTSBUTUHBMZGZ-SHYZEUOFSA-N 0.000 description 1
- KGRVJHAUYBGFFP-UHFFFAOYSA-N 2,2'-Methylenebis(4-methyl-6-tert-butylphenol) Chemical compound CC(C)(C)C1=CC(C)=CC(CC=2C(=C(C=C(C)C=2)C(C)(C)C)O)=C1O KGRVJHAUYBGFFP-UHFFFAOYSA-N 0.000 description 1
- ASNTZYQMIUCEBV-UHFFFAOYSA-N 2,5-dioxo-1-[6-[3-(pyridin-2-yldisulfanyl)propanoylamino]hexanoyloxy]pyrrolidine-3-sulfonic acid Chemical compound O=C1C(S(=O)(=O)O)CC(=O)N1OC(=O)CCCCCNC(=O)CCSSC1=CC=CC=N1 ASNTZYQMIUCEBV-UHFFFAOYSA-N 0.000 description 1
- YYDMSFVTLYEPOH-UHFFFAOYSA-N 2,5-dioxo-1-propanoyloxypyrrolidine-3-sulfonic acid Chemical compound CCC(=O)ON1C(=O)CC(S(O)(=O)=O)C1=O YYDMSFVTLYEPOH-UHFFFAOYSA-N 0.000 description 1
- JNYAEWCLZODPBN-UHFFFAOYSA-N 2-(1,2-dihydroxyethyl)oxolane-3,4-diol Polymers OCC(O)C1OCC(O)C1O JNYAEWCLZODPBN-UHFFFAOYSA-N 0.000 description 1
- BDPOCFDNTVUOKD-UHFFFAOYSA-N 2-(7-azido-4-methyl-2-oxochromen-3-yl)acetamide Chemical compound C1=C(N=[N+]=[N-])C=CC2=C1OC(=O)C(CC(N)=O)=C2C BDPOCFDNTVUOKD-UHFFFAOYSA-N 0.000 description 1
- ZDTFMPXQUSBYRL-UUOKFMHZSA-N 2-Aminoadenosine Chemical compound C12=NC(N)=NC(N)=C2N=CN1[C@@H]1O[C@H](CO)[C@@H](O)[C@H]1O ZDTFMPXQUSBYRL-UUOKFMHZSA-N 0.000 description 1
- SHKUUQIDMUMQQK-UHFFFAOYSA-N 2-[4-(oxiran-2-ylmethoxy)butoxymethyl]oxirane Chemical compound C1OC1COCCCCOCC1CO1 SHKUUQIDMUMQQK-UHFFFAOYSA-N 0.000 description 1
- BFFPVEVGHKMWLT-UHFFFAOYSA-N 2-amino-3,7-dihydropurin-6-one;3,7-dihydropurin-6-one Chemical compound O=C1NC=NC2=C1NC=N2.O=C1NC(N)=NC2=C1NC=N2 BFFPVEVGHKMWLT-UHFFFAOYSA-N 0.000 description 1
- MWBWWFOAEOYUST-UHFFFAOYSA-N 2-aminopurine Chemical compound NC1=NC=C2N=CNC2=N1 MWBWWFOAEOYUST-UHFFFAOYSA-N 0.000 description 1
- CODAYFPFZXWNLD-UHFFFAOYSA-N 2-hydroxypropanoyl octadecanoate Chemical compound CCCCCCCCCCCCCCCCCC(=O)OC(=O)C(C)O CODAYFPFZXWNLD-UHFFFAOYSA-N 0.000 description 1
- RLFPCLMBTQOMLI-UHFFFAOYSA-N 2-iodo-n-[2-[(2-iodoacetyl)amino]ethyl]acetamide Chemical compound ICC(=O)NCCNC(=O)CI RLFPCLMBTQOMLI-UHFFFAOYSA-N 0.000 description 1
- CQOQDQWUFQDJMK-SSTWWWIQSA-N 2-methoxy-17beta-estradiol Chemical compound C([C@@H]12)C[C@]3(C)[C@@H](O)CC[C@H]3[C@@H]1CCC1=C2C=C(OC)C(O)=C1 CQOQDQWUFQDJMK-SSTWWWIQSA-N 0.000 description 1
- XXUNIGZDNWWYED-UHFFFAOYSA-N 2-methylbenzamide Chemical compound CC1=CC=CC=C1C(N)=O XXUNIGZDNWWYED-UHFFFAOYSA-N 0.000 description 1
- GJTBSTBJLVYKAU-XVFCMESISA-N 2-thiouridine Chemical compound O[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1N1C(=S)NC(=O)C=C1 GJTBSTBJLVYKAU-XVFCMESISA-N 0.000 description 1
- NUIURNJTPRWVAP-UHFFFAOYSA-N 3,3'-Dimethylbenzidine Chemical compound C1=C(N)C(C)=CC(C=2C=C(C)C(N)=CC=2)=C1 NUIURNJTPRWVAP-UHFFFAOYSA-N 0.000 description 1
- JMUAKWNHKQBPGJ-UHFFFAOYSA-N 3-(pyridin-2-yldisulfanyl)-n-[4-[3-(pyridin-2-yldisulfanyl)propanoylamino]butyl]propanamide Chemical compound C=1C=CC=NC=1SSCCC(=O)NCCCCNC(=O)CCSSC1=CC=CC=N1 JMUAKWNHKQBPGJ-UHFFFAOYSA-N 0.000 description 1
- NITXODYAMWZEJY-UHFFFAOYSA-N 3-(pyridin-2-yldisulfanyl)propanehydrazide Chemical compound NNC(=O)CCSSC1=CC=CC=N1 NITXODYAMWZEJY-UHFFFAOYSA-N 0.000 description 1
- TVZRAEYQIKYCPH-UHFFFAOYSA-N 3-(trimethylsilyl)propane-1-sulfonic acid Chemical compound C[Si](C)(C)CCCS(O)(=O)=O TVZRAEYQIKYCPH-UHFFFAOYSA-N 0.000 description 1
- PBVAJRFEEOIAGW-UHFFFAOYSA-N 3-[bis(2-carboxyethyl)phosphanyl]propanoic acid;hydrochloride Chemical compound Cl.OC(=O)CCP(CCC(O)=O)CCC(O)=O PBVAJRFEEOIAGW-UHFFFAOYSA-N 0.000 description 1
- GSCPDZHWVNUUFI-UHFFFAOYSA-N 3-aminobenzamide Chemical compound NC(=O)C1=CC=CC(N)=C1 GSCPDZHWVNUUFI-UHFFFAOYSA-N 0.000 description 1
- LOJNBPNACKZWAI-UHFFFAOYSA-N 3-nitro-1h-pyrrole Chemical compound [O-][N+](=O)C=1C=CNC=1 LOJNBPNACKZWAI-UHFFFAOYSA-N 0.000 description 1
- CYDQOEWLBCCFJZ-UHFFFAOYSA-N 4-(4-fluorophenyl)oxane-4-carboxylic acid Chemical compound C=1C=C(F)C=CC=1C1(C(=O)O)CCOCC1 CYDQOEWLBCCFJZ-UHFFFAOYSA-N 0.000 description 1
- ZLOIGESWDJYCTF-UHFFFAOYSA-N 4-Thiouridine Natural products OC1C(O)C(CO)OC1N1C(=O)NC(=S)C=C1 ZLOIGESWDJYCTF-UHFFFAOYSA-N 0.000 description 1
- DODQJNMQWMSYGS-QPLCGJKRSA-N 4-[(z)-1-[4-[2-(dimethylamino)ethoxy]phenyl]-1-phenylbut-1-en-2-yl]phenol Chemical compound C=1C=C(O)C=CC=1C(/CC)=C(C=1C=CC(OCCN(C)C)=CC=1)/C1=CC=CC=C1 DODQJNMQWMSYGS-QPLCGJKRSA-N 0.000 description 1
- ZMRMMAOBSFSXLN-UHFFFAOYSA-N 4-[4-(2,5-dioxopyrrol-1-yl)phenyl]butanehydrazide Chemical compound C1=CC(CCCC(=O)NN)=CC=C1N1C(=O)C=CC1=O ZMRMMAOBSFSXLN-UHFFFAOYSA-N 0.000 description 1
- MDOJTZQKHMAPBK-UHFFFAOYSA-N 4-iodo-3-nitrobenzamide Chemical compound NC(=O)C1=CC=C(I)C([N+]([O-])=O)=C1 MDOJTZQKHMAPBK-UHFFFAOYSA-N 0.000 description 1
- ZLOIGESWDJYCTF-XVFCMESISA-N 4-thiouridine Chemical compound O[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1N1C(=O)NC(=S)C=C1 ZLOIGESWDJYCTF-XVFCMESISA-N 0.000 description 1
- LGZKGOGODCLQHG-CYBMUJFWSA-N 5-[(2r)-2-hydroxy-2-(3,4,5-trimethoxyphenyl)ethyl]-2-methoxyphenol Chemical compound C1=C(O)C(OC)=CC=C1C[C@@H](O)C1=CC(OC)=C(OC)C(OC)=C1 LGZKGOGODCLQHG-CYBMUJFWSA-N 0.000 description 1
- NMUSYJAQQFHJEW-KVTDHHQDSA-N 5-azacytidine Chemical compound O=C1N=C(N)N=CN1[C@H]1[C@H](O)[C@H](O)[C@@H](CO)O1 NMUSYJAQQFHJEW-KVTDHHQDSA-N 0.000 description 1
- AGFIRQJZCNVMCW-UAKXSSHOSA-N 5-bromouridine Chemical compound O[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1N1C(=O)NC(=O)C(Br)=C1 AGFIRQJZCNVMCW-UAKXSSHOSA-N 0.000 description 1
- FHIDNBAQOFJWCA-UAKXSSHOSA-N 5-fluorouridine Chemical compound O[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1N1C(=O)NC(=O)C(F)=C1 FHIDNBAQOFJWCA-UAKXSSHOSA-N 0.000 description 1
- ZKBQDFAWXLTYKS-UHFFFAOYSA-N 6-Chloro-1H-purine Chemical compound ClC1=NC=NC2=C1NC=N2 ZKBQDFAWXLTYKS-UHFFFAOYSA-N 0.000 description 1
- WYWHKKSPHMUBEB-UHFFFAOYSA-N 6-Mercaptoguanine Natural products N1C(N)=NC(=S)C2=C1N=CN2 WYWHKKSPHMUBEB-UHFFFAOYSA-N 0.000 description 1
- BXJHWYVXLGLDMZ-UHFFFAOYSA-N 6-O-methylguanine Chemical compound COC1=NC(N)=NC2=C1NC=N2 BXJHWYVXLGLDMZ-UHFFFAOYSA-N 0.000 description 1
- UEHOMUNTZPIBIL-UUOKFMHZSA-N 6-amino-9-[(2r,3r,4s,5r)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]-7h-purin-8-one Chemical compound O=C1NC=2C(N)=NC=NC=2N1[C@@H]1O[C@H](CO)[C@@H](O)[C@H]1O UEHOMUNTZPIBIL-UUOKFMHZSA-N 0.000 description 1
- WYXSYVWAUAUWLD-SHUUEZRQSA-N 6-azauridine Chemical compound O[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1N1C(=O)NC(=O)C=N1 WYXSYVWAUAUWLD-SHUUEZRQSA-N 0.000 description 1
- RYYIULNRIVUMTQ-UHFFFAOYSA-N 6-chloroguanine Chemical compound NC1=NC(Cl)=C2N=CNC2=N1 RYYIULNRIVUMTQ-UHFFFAOYSA-N 0.000 description 1
- OAUKGFJQZRGECT-UUOKFMHZSA-N 8-Azaadenosine Chemical compound N1=NC=2C(N)=NC=NC=2N1[C@@H]1O[C@H](CO)[C@@H](O)[C@H]1O OAUKGFJQZRGECT-UUOKFMHZSA-N 0.000 description 1
- HCAJQHYUCKICQH-VPENINKCSA-N 8-Oxo-7,8-dihydro-2'-deoxyguanosine Chemical compound C1=2NC(N)=NC(=O)C=2NC(=O)N1[C@H]1C[C@H](O)[C@@H](CO)O1 HCAJQHYUCKICQH-VPENINKCSA-N 0.000 description 1
- SHGAZHPCJJPHSC-ZVCIMWCZSA-N 9-cis-retinoic acid Chemical compound OC(=O)/C=C(\C)/C=C/C=C(/C)\C=C\C1=C(C)CCCC1(C)C SHGAZHPCJJPHSC-ZVCIMWCZSA-N 0.000 description 1
- MSSXOMSJDRHRMC-UHFFFAOYSA-N 9H-purine-2,6-diamine Chemical compound NC1=NC(N)=C2NC=NC2=N1 MSSXOMSJDRHRMC-UHFFFAOYSA-N 0.000 description 1
- GJCOSYZMQJWQCA-UHFFFAOYSA-N 9H-xanthene Chemical compound C1=CC=C2CC3=CC=CC=C3OC2=C1 GJCOSYZMQJWQCA-UHFFFAOYSA-N 0.000 description 1
- 240000005020 Acaciella glauca Species 0.000 description 1
- NIXOWILDQLNWCW-UHFFFAOYSA-N Acrylic acid Chemical compound OC(=O)C=C NIXOWILDQLNWCW-UHFFFAOYSA-N 0.000 description 1
- 208000010507 Adenocarcinoma of Lung Diseases 0.000 description 1
- 208000036764 Adenocarcinoma of the esophagus Diseases 0.000 description 1
- 229920001817 Agar Polymers 0.000 description 1
- QXRNAOYBCYVZCD-BQBZGAKWSA-N Ala-Lys Chemical compound C[C@H](N)C(=O)N[C@H](C(O)=O)CCCCN QXRNAOYBCYVZCD-BQBZGAKWSA-N 0.000 description 1
- 108010012934 Albumin-Bound Paclitaxel Proteins 0.000 description 1
- 239000005995 Aluminium silicate Substances 0.000 description 1
- 206010002199 Anaphylactic shock Diseases 0.000 description 1
- 102100021569 Apoptosis regulator Bcl-2 Human genes 0.000 description 1
- 101100463464 Arabidopsis thaliana PER73 gene Proteins 0.000 description 1
- 239000004475 Arginine Substances 0.000 description 1
- 229940122815 Aromatase inhibitor Drugs 0.000 description 1
- 101000669426 Aspergillus restrictus Ribonuclease mitogillin Proteins 0.000 description 1
- 241000416162 Astragalus gummifer Species 0.000 description 1
- 108090001008 Avidin Proteins 0.000 description 1
- 102000008096 B7-H1 Antigen Human genes 0.000 description 1
- 108010074708 B7-H1 Antigen Proteins 0.000 description 1
- 238000011729 BALB/c nude mouse Methods 0.000 description 1
- 229940125565 BMS-986016 Drugs 0.000 description 1
- 102100026189 Beta-galactosidase Human genes 0.000 description 1
- 206010004668 Biliary neoplasm Diseases 0.000 description 1
- 108010006654 Bleomycin Proteins 0.000 description 1
- 108030001720 Bontoxilysin Proteins 0.000 description 1
- ZOXJGFHDIHLPTG-UHFFFAOYSA-N Boron Chemical compound [B] ZOXJGFHDIHLPTG-UHFFFAOYSA-N 0.000 description 1
- 239000002126 C01EB10 - Adenosine Substances 0.000 description 1
- 102000008203 CTLA-4 Antigen Human genes 0.000 description 1
- 108010021064 CTLA-4 Antigen Proteins 0.000 description 1
- 229940045513 CTLA4 antagonist Drugs 0.000 description 1
- UXVMQQNJUSDDNG-UHFFFAOYSA-L Calcium chloride Chemical compound [Cl-].[Cl-].[Ca+2] UXVMQQNJUSDDNG-UHFFFAOYSA-L 0.000 description 1
- 239000001736 Calcium glycerylphosphate Substances 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
- 102100025570 Cancer/testis antigen 1 Human genes 0.000 description 1
- 241000282472 Canis lupus familiaris 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
- 208000005623 Carcinogenesis Diseases 0.000 description 1
- 102000014914 Carrier Proteins Human genes 0.000 description 1
- 108010078791 Carrier Proteins Proteins 0.000 description 1
- 102000011632 Caseins Human genes 0.000 description 1
- 108010076119 Caseins Proteins 0.000 description 1
- 102100026549 Caspase-10 Human genes 0.000 description 1
- 102100032616 Caspase-2 Human genes 0.000 description 1
- 102100026548 Caspase-8 Human genes 0.000 description 1
- 102100026550 Caspase-9 Human genes 0.000 description 1
- 108010076667 Caspases Proteins 0.000 description 1
- 102000011727 Caspases Human genes 0.000 description 1
- 240000008886 Ceratonia siliqua Species 0.000 description 1
- 235000013912 Ceratonia siliqua Nutrition 0.000 description 1
- 241000282693 Cercopithecidae Species 0.000 description 1
- DQFBYFPFKXHELB-UHFFFAOYSA-N Chalcone Natural products C=1C=CC=CC=1C(=O)C=CC1=CC=CC=C1 DQFBYFPFKXHELB-UHFFFAOYSA-N 0.000 description 1
- 229920001661 Chitosan Polymers 0.000 description 1
- 206010008631 Cholera Diseases 0.000 description 1
- VYZAMTAEIAYCRO-UHFFFAOYSA-N Chromium Chemical compound [Cr] VYZAMTAEIAYCRO-UHFFFAOYSA-N 0.000 description 1
- 241000207199 Citrus Species 0.000 description 1
- 102100038449 Claudin-6 Human genes 0.000 description 1
- 108090000229 Claudin-6 Proteins 0.000 description 1
- 241000193468 Clostridium perfringens Species 0.000 description 1
- 108700010070 Codon Usage Proteins 0.000 description 1
- 102000007644 Colony-Stimulating Factors Human genes 0.000 description 1
- 108010071942 Colony-Stimulating Factors Proteins 0.000 description 1
- RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 description 1
- 229920002261 Corn starch Polymers 0.000 description 1
- 239000004971 Cross linker Substances 0.000 description 1
- MIKUYHXYGGJMLM-UUOKFMHZSA-N Crotonoside Chemical compound C1=NC2=C(N)NC(=O)N=C2N1[C@@H]1O[C@H](CO)[C@@H](O)[C@H]1O MIKUYHXYGGJMLM-UUOKFMHZSA-N 0.000 description 1
- 229930188224 Cryptophycin Natural products 0.000 description 1
- 244000303965 Cyamopsis psoralioides Species 0.000 description 1
- 229930105110 Cyclosporin A Natural products 0.000 description 1
- UHDGCWIWMRVCDJ-PSQAKQOGSA-N Cytidine Natural products O=C1N=C(N)C=CN1[C@@H]1[C@@H](O)[C@@H](O)[C@H](CO)O1 UHDGCWIWMRVCDJ-PSQAKQOGSA-N 0.000 description 1
- 102000004127 Cytokines Human genes 0.000 description 1
- 108090000695 Cytokines Proteins 0.000 description 1
- 101710087047 Cytoskeleton-associated protein 4 Proteins 0.000 description 1
- NYHBQMYGNKIUIF-UHFFFAOYSA-N D-guanosine Natural products C1=2NC(N)=NC(=O)C=2N=CN1C1OC(CO)C(O)C1O NYHBQMYGNKIUIF-UHFFFAOYSA-N 0.000 description 1
- 230000000970 DNA cross-linking effect Effects 0.000 description 1
- 230000007018 DNA scission Effects 0.000 description 1
- 229940123780 DNA topoisomerase I inhibitor Drugs 0.000 description 1
- 229940124087 DNA topoisomerase II inhibitor Drugs 0.000 description 1
- MQJKPEGWNLWLTK-UHFFFAOYSA-N Dapsone Chemical compound C1=CC(N)=CC=C1S(=O)(=O)C1=CC=C(N)C=C1 MQJKPEGWNLWLTK-UHFFFAOYSA-N 0.000 description 1
- 229940122964 Deacetylase inhibitor Drugs 0.000 description 1
- CKTSBUTUHBMZGZ-UHFFFAOYSA-N Deoxycytidine Natural products O=C1N=C(N)C=CN1C1OC(CO)C(O)C1 CKTSBUTUHBMZGZ-UHFFFAOYSA-N 0.000 description 1
- BWGNESOTFCXPMA-UHFFFAOYSA-N Dihydrogen disulfide Chemical compound SS BWGNESOTFCXPMA-UHFFFAOYSA-N 0.000 description 1
- 108090000204 Dipeptidase 1 Proteins 0.000 description 1
- 108010053187 Diphtheria Toxin Proteins 0.000 description 1
- 102000016607 Diphtheria Toxin Human genes 0.000 description 1
- AZVARJHZBXHUSO-UHFFFAOYSA-N Duocarmycin A Natural products COC1=C(OC)C(OC)=C2NC(C(=O)N3CC4CC44C5=C(C(C=C43)=O)NC(C5=O)(C)C(=O)OC)=CC2=C1 AZVARJHZBXHUSO-UHFFFAOYSA-N 0.000 description 1
- FIZSMXNFUBCGCU-UHFFFAOYSA-N Duocarmycin C1 Natural products COC(=O)C1(C)NC2=C(C3CC(Cl)CN(C(=O)c4cc5cc(OC)c(OC)c(OC)c5[nH]4)C3=CC2=O)C1=O FIZSMXNFUBCGCU-UHFFFAOYSA-N 0.000 description 1
- WKODMLPZIYVYIR-UHFFFAOYSA-N Duocarmycin C2 Natural products COC(=O)C1(C)NC2=C(C3C(CCl)CN(C(=O)c4cc5cc(OC)c(OC)c(OC)c5[nH]4)C3=CC2=O)C1=O WKODMLPZIYVYIR-UHFFFAOYSA-N 0.000 description 1
- VQNATVDKACXKTF-UHFFFAOYSA-N Duocarmycin SA Natural products COC1=C(OC)C(OC)=C2NC(C(=O)N3C4=CC(=O)C5=C(C64CC6C3)C=C(N5)C(=O)OC)=CC2=C1 VQNATVDKACXKTF-UHFFFAOYSA-N 0.000 description 1
- LVGKNOAMLMIIKO-UHFFFAOYSA-N Elaidinsaeure-aethylester Natural products CCCCCCCCC=CCCCCCCCC(=O)OCC LVGKNOAMLMIIKO-UHFFFAOYSA-N 0.000 description 1
- 208000001976 Endocrine Gland Neoplasms Diseases 0.000 description 1
- 108010042407 Endonucleases Proteins 0.000 description 1
- 102000004533 Endonucleases Human genes 0.000 description 1
- 102100023882 Endoribonuclease ZC3H12A Human genes 0.000 description 1
- 101710112715 Endoribonuclease ZC3H12A Proteins 0.000 description 1
- 101710146739 Enterotoxin Proteins 0.000 description 1
- 108050004280 Epsilon toxin Proteins 0.000 description 1
- 241000588724 Escherichia coli Species 0.000 description 1
- 229930189413 Esperamicin Natural products 0.000 description 1
- 108010008165 Etanercept Proteins 0.000 description 1
- ZZSNKZQZMQGXPY-UHFFFAOYSA-N Ethyl cellulose Chemical compound CCOCC1OC(OC)C(OCC)C(OCC)C1OC1C(O)C(O)C(OC)C(CO)O1 ZZSNKZQZMQGXPY-UHFFFAOYSA-N 0.000 description 1
- 108060002716 Exonuclease Proteins 0.000 description 1
- GHASVSINZRGABV-UHFFFAOYSA-N Fluorouracil Chemical compound FC1=CNC(=O)NC1=O GHASVSINZRGABV-UHFFFAOYSA-N 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
- 108010010803 Gelatin Proteins 0.000 description 1
- 206010018404 Glucagonoma Diseases 0.000 description 1
- 239000000579 Gonadotropin-Releasing Hormone Substances 0.000 description 1
- 102000001398 Granzyme Human genes 0.000 description 1
- 108060005986 Granzyme Proteins 0.000 description 1
- 229920002907 Guar gum Polymers 0.000 description 1
- 101710154606 Hemagglutinin Proteins 0.000 description 1
- SQUHHTBVTRBESD-UHFFFAOYSA-N Hexa-Ac-myo-Inositol Natural products CC(=O)OC1C(OC(C)=O)C(OC(C)=O)C(OC(C)=O)C(OC(C)=O)C1OC(C)=O SQUHHTBVTRBESD-UHFFFAOYSA-N 0.000 description 1
- 101000971171 Homo sapiens Apoptosis regulator Bcl-2 Proteins 0.000 description 1
- 101000856237 Homo sapiens Cancer/testis antigen 1 Proteins 0.000 description 1
- 101000983518 Homo sapiens Caspase-10 Proteins 0.000 description 1
- 101000867612 Homo sapiens Caspase-2 Proteins 0.000 description 1
- 101000983528 Homo sapiens Caspase-8 Proteins 0.000 description 1
- 101000983523 Homo sapiens Caspase-9 Proteins 0.000 description 1
- 101000749329 Homo sapiens Claudin-18 Proteins 0.000 description 1
- 101000599852 Homo sapiens Intercellular adhesion molecule 1 Proteins 0.000 description 1
- 101000917858 Homo sapiens Low affinity immunoglobulin gamma Fc region receptor III-A Proteins 0.000 description 1
- 101001091194 Homo sapiens Peptidyl-prolyl cis-trans isomerase G Proteins 0.000 description 1
- 101001012157 Homo sapiens Receptor tyrosine-protein kinase erbB-2 Proteins 0.000 description 1
- 101000936922 Homo sapiens Sarcoplasmic/endoplasmic reticulum calcium ATPase 2 Proteins 0.000 description 1
- 101000801234 Homo sapiens Tumor necrosis factor receptor superfamily member 18 Proteins 0.000 description 1
- 229920002153 Hydroxypropyl cellulose Polymers 0.000 description 1
- NRSPOJRMDVHRCX-UHFFFAOYSA-N IC=1C(C(C=CC1C)(C)S(=O)(=O)O)I Chemical compound IC=1C(C(C=CC1C)(C)S(=O)(=O)O)I NRSPOJRMDVHRCX-UHFFFAOYSA-N 0.000 description 1
- 229940123309 Immune checkpoint modulator Drugs 0.000 description 1
- 108091008036 Immune checkpoint proteins Proteins 0.000 description 1
- 102000037982 Immune checkpoint proteins Human genes 0.000 description 1
- 108010009817 Immunoglobulin Constant Regions Proteins 0.000 description 1
- 102000009786 Immunoglobulin Constant Regions Human genes 0.000 description 1
- 102100037877 Intercellular adhesion molecule 1 Human genes 0.000 description 1
- 102000006992 Interferon-alpha Human genes 0.000 description 1
- 108010047761 Interferon-alpha Proteins 0.000 description 1
- 102000003996 Interferon-beta Human genes 0.000 description 1
- 108090000467 Interferon-beta Proteins 0.000 description 1
- 102000008070 Interferon-gamma Human genes 0.000 description 1
- 108010074328 Interferon-gamma Proteins 0.000 description 1
- 108010002352 Interleukin-1 Proteins 0.000 description 1
- 108090000172 Interleukin-15 Proteins 0.000 description 1
- 108010002386 Interleukin-3 Proteins 0.000 description 1
- 108090001005 Interleukin-6 Proteins 0.000 description 1
- 150000008575 L-amino acids Chemical class 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
- 125000000010 L-asparaginyl group Chemical group O=C([*])[C@](N([H])[H])([H])C([H])([H])C(=O)N([H])[H] 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
- FEWJPZIEWOKRBE-JCYAYHJZSA-L L-tartrate(2-) Chemical compound [O-]C(=O)[C@H](O)[C@@H](O)C([O-])=O FEWJPZIEWOKRBE-JCYAYHJZSA-L 0.000 description 1
- 239000005517 L01XE01 - Imatinib Substances 0.000 description 1
- 239000005411 L01XE02 - Gefitinib Substances 0.000 description 1
- JLERVPBPJHKRBJ-UHFFFAOYSA-N LY 117018 Chemical compound C1=CC(O)=CC=C1C1=C(C(=O)C=2C=CC(OCCN3CCCC3)=CC=2)C2=CC=C(O)C=C2S1 JLERVPBPJHKRBJ-UHFFFAOYSA-N 0.000 description 1
- 206010023774 Large cell lung cancer Diseases 0.000 description 1
- 239000012097 Lipofectamine 2000 Substances 0.000 description 1
- WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 1
- 102100029193 Low affinity immunoglobulin gamma Fc region receptor III-A Human genes 0.000 description 1
- 108060001084 Luciferase Proteins 0.000 description 1
- 239000005089 Luciferase Substances 0.000 description 1
- 102000009151 Luteinizing Hormone Human genes 0.000 description 1
- 108010073521 Luteinizing Hormone Proteins 0.000 description 1
- 208000007433 Lymphatic Metastasis Diseases 0.000 description 1
- 206010025323 Lymphomas Diseases 0.000 description 1
- 239000005913 Maltodextrin Substances 0.000 description 1
- 229920002774 Maltodextrin Polymers 0.000 description 1
- SGDBTWWWUNNDEQ-UHFFFAOYSA-N Merphalan Chemical compound OC(=O)C(N)CC1=CC=C(N(CCCl)CCCl)C=C1 SGDBTWWWUNNDEQ-UHFFFAOYSA-N 0.000 description 1
- 206010027476 Metastases Diseases 0.000 description 1
- ZOKXTWBITQBERF-UHFFFAOYSA-N Molybdenum Chemical compound [Mo] ZOKXTWBITQBERF-UHFFFAOYSA-N 0.000 description 1
- FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 description 1
- QPCDCPDFJACHGM-UHFFFAOYSA-N N,N-bis{2-[bis(carboxymethyl)amino]ethyl}glycine Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(=O)O)CCN(CC(O)=O)CC(O)=O QPCDCPDFJACHGM-UHFFFAOYSA-N 0.000 description 1
- SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 description 1
- 230000004988 N-glycosylation Effects 0.000 description 1
- 238000011794 NU/NU nude mouse Methods 0.000 description 1
- 108010042309 Netropsin Proteins 0.000 description 1
- 239000000020 Nitrocellulose Substances 0.000 description 1
- 238000000636 Northern blotting Methods 0.000 description 1
- 102000007399 Nuclear hormone receptor Human genes 0.000 description 1
- 108020005497 Nuclear hormone receptor Proteins 0.000 description 1
- 101710163270 Nuclease Proteins 0.000 description 1
- XEQLGWAGMYUVTR-UHFFFAOYSA-N O=C1NC=NC2=C1NC=N2.C1=CN=C2C(=O)NC(NN)=NC2=N1 Chemical compound O=C1NC=NC2=C1NC=N2.C1=CN=C2C(=O)NC(NN)=NC2=N1 XEQLGWAGMYUVTR-UHFFFAOYSA-N 0.000 description 1
- 108010016076 Octreotide Proteins 0.000 description 1
- 206010030113 Oedema Diseases 0.000 description 1
- CMMLZMMKTYEOKV-UHFFFAOYSA-N Oligomycin C Natural products CC1C(C2C)OC(=O)C=CC(C)C(O)C(C)C(=O)C(C)C(O)C(C)C(=O)C(C)C(O)C(C)CC=CC=CC(CC)CCC2OC21CCC(C)C(CC(C)O)O2 CMMLZMMKTYEOKV-UHFFFAOYSA-N 0.000 description 1
- 101710093908 Outer capsid protein VP4 Proteins 0.000 description 1
- 101710135467 Outer capsid protein sigma-1 Proteins 0.000 description 1
- 239000012661 PARP inhibitor Substances 0.000 description 1
- 229910019142 PO4 Inorganic materials 0.000 description 1
- 241000282320 Panthera leo Species 0.000 description 1
- 241000237988 Patellidae Species 0.000 description 1
- 229930182555 Penicillin Natural products 0.000 description 1
- JGSARLDLIJGVTE-MBNYWOFBSA-N Penicillin G Chemical compound N([C@H]1[C@H]2SC([C@@H](N2C1=O)C(O)=O)(C)C)C(=O)CC1=CC=CC=C1 JGSARLDLIJGVTE-MBNYWOFBSA-N 0.000 description 1
- 108091005804 Peptidases Proteins 0.000 description 1
- 108090000279 Peptidyltransferases Proteins 0.000 description 1
- 206010057249 Phagocytosis Diseases 0.000 description 1
- RBRNEFJTEHPDSL-ACRUOGEOSA-N Phe-Phe-Lys Chemical compound C([C@@H](C(=O)N[C@@H](CCCCN)C(O)=O)NC(=O)[C@@H](N)CC=1C=CC=CC=1)C1=CC=CC=C1 RBRNEFJTEHPDSL-ACRUOGEOSA-N 0.000 description 1
- 102000015439 Phospholipases Human genes 0.000 description 1
- 108010064785 Phospholipases Proteins 0.000 description 1
- OAICVXFJPJFONN-UHFFFAOYSA-N Phosphorus Chemical compound [P] OAICVXFJPJFONN-UHFFFAOYSA-N 0.000 description 1
- RVGRUAULSDPKGF-UHFFFAOYSA-N Poloxamer Chemical compound C1CO1.CC1CO1 RVGRUAULSDPKGF-UHFFFAOYSA-N 0.000 description 1
- 229940121906 Poly ADP ribose polymerase inhibitor Drugs 0.000 description 1
- 229920000081 Polyestradiol phosphate Polymers 0.000 description 1
- 239000004698 Polyethylene Substances 0.000 description 1
- 229920002534 Polyethylene Glycol 1450 Polymers 0.000 description 1
- 229920002556 Polyethylene Glycol 300 Polymers 0.000 description 1
- 229920002562 Polyethylene Glycol 3350 Polymers 0.000 description 1
- 229920002565 Polyethylene Glycol 400 Polymers 0.000 description 1
- 229920001030 Polyethylene Glycol 4000 Polymers 0.000 description 1
- 229920002582 Polyethylene Glycol 600 Polymers 0.000 description 1
- 229920002593 Polyethylene Glycol 800 Polymers 0.000 description 1
- 239000004642 Polyimide Substances 0.000 description 1
- 229920001213 Polysorbate 20 Polymers 0.000 description 1
- 229920001214 Polysorbate 60 Polymers 0.000 description 1
- 239000004793 Polystyrene Substances 0.000 description 1
- 239000004372 Polyvinyl alcohol Substances 0.000 description 1
- 208000026149 Primary peritoneal carcinoma Diseases 0.000 description 1
- 108091000054 Prion Proteins 0.000 description 1
- 102000029797 Prion Human genes 0.000 description 1
- GOOHAUXETOMSMM-UHFFFAOYSA-N Propylene oxide Chemical compound CC1CO1 GOOHAUXETOMSMM-UHFFFAOYSA-N 0.000 description 1
- 239000004365 Protease Substances 0.000 description 1
- 101710176177 Protein A56 Proteins 0.000 description 1
- 101900161471 Pseudomonas aeruginosa Exotoxin A Proteins 0.000 description 1
- 229930185560 Pseudouridine Natural products 0.000 description 1
- PTJWIQPHWPFNBW-UHFFFAOYSA-N Pseudouridine C Natural products OC1C(O)C(CO)OC1C1=CNC(=O)NC1=O PTJWIQPHWPFNBW-UHFFFAOYSA-N 0.000 description 1
- CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical class C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 description 1
- 229940125566 REGN3767 Drugs 0.000 description 1
- 102100030086 Receptor tyrosine-protein kinase erbB-2 Human genes 0.000 description 1
- 108020004511 Recombinant DNA Proteins 0.000 description 1
- 102000018779 Replication Protein C Human genes 0.000 description 1
- 108010027647 Replication Protein C Proteins 0.000 description 1
- 102100037486 Reverse transcriptase/ribonuclease H Human genes 0.000 description 1
- SKZKKFZAGNVIMN-UHFFFAOYSA-N Salicilamide Chemical compound NC(=O)C1=CC=CC=C1O SKZKKFZAGNVIMN-UHFFFAOYSA-N 0.000 description 1
- 102100027732 Sarcoplasmic/endoplasmic reticulum calcium ATPase 2 Human genes 0.000 description 1
- 241000239226 Scorpiones Species 0.000 description 1
- 238000012300 Sequence Analysis Methods 0.000 description 1
- 241000705082 Sialia Species 0.000 description 1
- XUIMIQQOPSSXEZ-UHFFFAOYSA-N Silicon Chemical compound [Si] XUIMIQQOPSSXEZ-UHFFFAOYSA-N 0.000 description 1
- BQCADISMDOOEFD-UHFFFAOYSA-N Silver Chemical compound [Ag] BQCADISMDOOEFD-UHFFFAOYSA-N 0.000 description 1
- DWAQJAXMDSEUJJ-UHFFFAOYSA-M Sodium bisulfite Chemical compound [Na+].OS([O-])=O DWAQJAXMDSEUJJ-UHFFFAOYSA-M 0.000 description 1
- BCKXLBQYZLBQEK-KVVVOXFISA-M Sodium oleate Chemical compound [Na+].CCCCCCCC\C=C/CCCCCCCC([O-])=O BCKXLBQYZLBQEK-KVVVOXFISA-M 0.000 description 1
- 235000019887 Solka-Floc® Nutrition 0.000 description 1
- 206010041329 Somatostatinoma Diseases 0.000 description 1
- 101000857870 Squalus acanthias Gonadoliberin Proteins 0.000 description 1
- 235000015125 Sterculia urens Nutrition 0.000 description 1
- 240000001058 Sterculia urens Species 0.000 description 1
- 108010090804 Streptavidin Proteins 0.000 description 1
- 241001495137 Streptomyces mobaraensis Species 0.000 description 1
- WBWWGRHZICKQGZ-UHFFFAOYSA-N Taurocholic acid Natural products OC1CC2CC(O)CCC2(C)C2C1C1CCC(C(CCC(=O)NCCS(O)(=O)=O)C)C1(C)C(O)C2 WBWWGRHZICKQGZ-UHFFFAOYSA-N 0.000 description 1
- 229940123237 Taxane Drugs 0.000 description 1
- 108010055044 Tetanus Toxin Proteins 0.000 description 1
- 102000000591 Tight Junction Proteins Human genes 0.000 description 1
- 108010002321 Tight Junction Proteins Proteins 0.000 description 1
- ATJFFYVFTNAWJD-UHFFFAOYSA-N Tin Chemical compound [Sn] ATJFFYVFTNAWJD-UHFFFAOYSA-N 0.000 description 1
- RTAQQCXQSZGOHL-UHFFFAOYSA-N Titanium Chemical compound [Ti] RTAQQCXQSZGOHL-UHFFFAOYSA-N 0.000 description 1
- 239000000365 Topoisomerase I Inhibitor Substances 0.000 description 1
- 239000000317 Topoisomerase II Inhibitor Substances 0.000 description 1
- 101150097193 Tp73 gene Proteins 0.000 description 1
- 229920001615 Tragacanth Polymers 0.000 description 1
- 108700009124 Transcription Initiation Site Proteins 0.000 description 1
- 108020004566 Transfer RNA Proteins 0.000 description 1
- 102000004357 Transferases Human genes 0.000 description 1
- 108090000992 Transferases Proteins 0.000 description 1
- 108060008539 Transglutaminase Proteins 0.000 description 1
- DOOTYTYQINUNNV-UHFFFAOYSA-N Triethyl citrate Chemical compound CCOC(=O)CC(O)(C(=O)OCC)CC(=O)OCC DOOTYTYQINUNNV-UHFFFAOYSA-N 0.000 description 1
- 239000007983 Tris buffer Substances 0.000 description 1
- 102000000852 Tumor Necrosis Factor-alpha Human genes 0.000 description 1
- 102100033728 Tumor necrosis factor receptor superfamily member 18 Human genes 0.000 description 1
- 102100022153 Tumor necrosis factor receptor superfamily member 4 Human genes 0.000 description 1
- 101710165473 Tumor necrosis factor receptor superfamily member 4 Proteins 0.000 description 1
- 102100027881 Tumor protein 63 Human genes 0.000 description 1
- 101710140697 Tumor protein 63 Proteins 0.000 description 1
- 102100030018 Tumor protein p73 Human genes 0.000 description 1
- VGQOVCHZGQWAOI-UHFFFAOYSA-N UNPD55612 Natural products N1C(O)C2CC(C=CC(N)=O)=CN2C(=O)C2=CC=C(C)C(O)=C12 VGQOVCHZGQWAOI-UHFFFAOYSA-N 0.000 description 1
- 241000251539 Vertebrata <Metazoa> Species 0.000 description 1
- 229940122803 Vinca alkaloid Drugs 0.000 description 1
- 108091008107 XNA aptamers Proteins 0.000 description 1
- TVXBFESIOXBWNM-UHFFFAOYSA-N Xylitol Natural products OCCC(O)C(O)C(O)CCO TVXBFESIOXBWNM-UHFFFAOYSA-N 0.000 description 1
- 240000008042 Zea mays Species 0.000 description 1
- 235000005824 Zea mays ssp. parviglumis Nutrition 0.000 description 1
- 235000002017 Zea mays subsp mays Nutrition 0.000 description 1
- QCWXUUIWCKQGHC-UHFFFAOYSA-N Zirconium Chemical compound [Zr] QCWXUUIWCKQGHC-UHFFFAOYSA-N 0.000 description 1
- RTJVUHUGTUDWRK-CSLCKUBZSA-N [(2r,4ar,6r,7r,8s,8ar)-6-[[(5s,5ar,8ar,9r)-9-(3,5-dimethoxy-4-phosphonooxyphenyl)-8-oxo-5a,6,8a,9-tetrahydro-5h-[2]benzofuro[6,5-f][1,3]benzodioxol-5-yl]oxy]-2-methyl-7-[2-(2,3,4,5,6-pentafluorophenoxy)acetyl]oxy-4,4a,6,7,8,8a-hexahydropyrano[3,2-d][1,3]d Chemical compound COC1=C(OP(O)(O)=O)C(OC)=CC([C@@H]2C3=CC=4OCOC=4C=C3[C@@H](O[C@H]3[C@@H]([C@@H](OC(=O)COC=4C(=C(F)C(F)=C(F)C=4F)F)[C@@H]4O[C@H](C)OC[C@H]4O3)OC(=O)COC=3C(=C(F)C(F)=C(F)C=3F)F)[C@@H]3[C@@H]2C(OC3)=O)=C1 RTJVUHUGTUDWRK-CSLCKUBZSA-N 0.000 description 1
- OKSSKVHGKYJNLL-LJRZAWCWSA-N [(3as,4r,9s,10as)-2,6-diamino-10,10-dihydroxy-9-sulfooxy-3a,4,8,9-tetrahydro-1h-pyrrolo[1,2-c]purin-4-yl]methoxycarbonylsulfamic acid Chemical compound OS(=O)(=O)NC(=O)OC[C@@H]1N=C(N)N2C[C@H](OS(O)(=O)=O)C(O)(O)[C@@]22N=C(N)N[C@H]21 OKSSKVHGKYJNLL-LJRZAWCWSA-N 0.000 description 1
- 238000002679 ablation Methods 0.000 description 1
- 229940028652 abraxane Drugs 0.000 description 1
- VJHCJDRQFCCTHL-UHFFFAOYSA-N acetic acid 2,3,4,5,6-pentahydroxyhexanal Chemical compound CC(O)=O.OCC(O)C(O)C(O)C(O)C=O VJHCJDRQFCCTHL-UHFFFAOYSA-N 0.000 description 1
- 230000021736 acetylation Effects 0.000 description 1
- 238000006640 acetylation reaction Methods 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 239000000654 additive Substances 0.000 description 1
- 229960005305 adenosine Drugs 0.000 description 1
- IBVAQQYNSHJXBV-UHFFFAOYSA-N adipic acid dihydrazide Chemical compound NNC(=O)CCCCC(=O)NN IBVAQQYNSHJXBV-UHFFFAOYSA-N 0.000 description 1
- 239000000443 aerosol Substances 0.000 description 1
- 238000001042 affinity chromatography Methods 0.000 description 1
- 238000001261 affinity purification Methods 0.000 description 1
- 239000008272 agar Substances 0.000 description 1
- 230000002776 aggregation Effects 0.000 description 1
- 238000004220 aggregation Methods 0.000 description 1
- 125000003172 aldehyde group Chemical group 0.000 description 1
- 150000001299 aldehydes Chemical class 0.000 description 1
- 229960001445 alitretinoin Drugs 0.000 description 1
- 239000003513 alkali Substances 0.000 description 1
- 229910052783 alkali metal Inorganic materials 0.000 description 1
- 150000001340 alkali metals Chemical class 0.000 description 1
- 229910052784 alkaline earth metal Inorganic materials 0.000 description 1
- 125000003342 alkenyl group Chemical group 0.000 description 1
- 125000003545 alkoxy group Chemical group 0.000 description 1
- 125000005262 alkoxyamine group Chemical group 0.000 description 1
- 150000005215 alkyl ethers Chemical class 0.000 description 1
- 229940100198 alkylating agent Drugs 0.000 description 1
- 239000002168 alkylating agent Substances 0.000 description 1
- 125000000304 alkynyl group Chemical group 0.000 description 1
- 239000000956 alloy Substances 0.000 description 1
- 229910045601 alloy Inorganic materials 0.000 description 1
- 125000005336 allyloxy group Chemical group 0.000 description 1
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
- 235000012211 aluminium silicate Nutrition 0.000 description 1
- 229940009868 aluminum magnesium silicate Drugs 0.000 description 1
- WMGSQTMJHBYJMQ-UHFFFAOYSA-N aluminum;magnesium;silicate Chemical compound [Mg+2].[Al+3].[O-][Si]([O-])([O-])[O-] WMGSQTMJHBYJMQ-UHFFFAOYSA-N 0.000 description 1
- 150000001408 amides Chemical group 0.000 description 1
- 235000019270 ammonium chloride Nutrition 0.000 description 1
- 150000003863 ammonium salts 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
- 208000003455 anaphylaxis Diseases 0.000 description 1
- 229960004977 anhydrous lactose Drugs 0.000 description 1
- 238000010171 animal model Methods 0.000 description 1
- 210000003423 ankle Anatomy 0.000 description 1
- VGQOVCHZGQWAOI-HYUHUPJXSA-N anthramycin Chemical compound N1[C@@H](O)[C@@H]2CC(\C=C\C(N)=O)=CN2C(=O)C2=CC=C(C)C(O)=C12 VGQOVCHZGQWAOI-HYUHUPJXSA-N 0.000 description 1
- 230000002280 anti-androgenic effect Effects 0.000 description 1
- 230000001093 anti-cancer Effects 0.000 description 1
- 230000002494 anti-cea effect Effects 0.000 description 1
- 230000003302 anti-idiotype Effects 0.000 description 1
- 239000000051 antiandrogen Substances 0.000 description 1
- 229940124691 antibody therapeutics Drugs 0.000 description 1
- 210000000628 antibody-producing cell Anatomy 0.000 description 1
- 230000000890 antigenic effect Effects 0.000 description 1
- 229910052787 antimony Inorganic materials 0.000 description 1
- WATWJIUSRGPENY-UHFFFAOYSA-N antimony atom Chemical compound [Sb] WATWJIUSRGPENY-UHFFFAOYSA-N 0.000 description 1
- 239000003963 antioxidant agent Substances 0.000 description 1
- 235000006708 antioxidants Nutrition 0.000 description 1
- PYMYPHUHKUWMLA-WDCZJNDASA-N arabinose Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)C=O PYMYPHUHKUWMLA-WDCZJNDASA-N 0.000 description 1
- PYMYPHUHKUWMLA-UHFFFAOYSA-N arabinose Natural products OCC(O)C(O)C(O)C=O PYMYPHUHKUWMLA-UHFFFAOYSA-N 0.000 description 1
- ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 1
- 230000010516 arginylation Effects 0.000 description 1
- 229940046844 aromatase inhibitors Drugs 0.000 description 1
- 229910052785 arsenic Inorganic materials 0.000 description 1
- RQNWIZPPADIBDY-UHFFFAOYSA-N arsenic atom Chemical compound [As] RQNWIZPPADIBDY-UHFFFAOYSA-N 0.000 description 1
- 235000010323 ascorbic acid Nutrition 0.000 description 1
- 125000003289 ascorbyl group Chemical class [H]O[C@@]([H])(C([H])([H])O*)[C@@]1([H])OC(=O)C(O*)=C1O* 0.000 description 1
- 239000012298 atmosphere Substances 0.000 description 1
- 125000004429 atom Chemical group 0.000 description 1
- 108010009065 auristatin PYE Proteins 0.000 description 1
- 229960002756 azacitidine Drugs 0.000 description 1
- 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 1
- 229960002170 azathioprine Drugs 0.000 description 1
- 229910052788 barium Inorganic materials 0.000 description 1
- DSAJWYNOEDNPEQ-UHFFFAOYSA-N barium atom Chemical compound [Ba] DSAJWYNOEDNPEQ-UHFFFAOYSA-N 0.000 description 1
- 230000004888 barrier function Effects 0.000 description 1
- 210000002469 basement membrane Anatomy 0.000 description 1
- 102000055102 bcl-2-Associated X Human genes 0.000 description 1
- 108700000707 bcl-2-Associated X Proteins 0.000 description 1
- 230000008901 benefit Effects 0.000 description 1
- 229940092782 bentonite Drugs 0.000 description 1
- HFACYLZERDEVSX-UHFFFAOYSA-N benzidine Chemical compound C1=CC(N)=CC=C1C1=CC=C(N)C=C1 HFACYLZERDEVSX-UHFFFAOYSA-N 0.000 description 1
- SRBFZHDQGSBBOR-UHFFFAOYSA-N beta-D-Pyranose-Lyxose Natural products OC1COC(O)C(O)C1O SRBFZHDQGSBBOR-UHFFFAOYSA-N 0.000 description 1
- 108010005774 beta-Galactosidase Proteins 0.000 description 1
- DRTQHJPVMGBUCF-PSQAKQOGSA-N beta-L-uridine Natural products O[C@H]1[C@@H](O)[C@H](CO)O[C@@H]1N1C(=O)NC(=O)C=C1 DRTQHJPVMGBUCF-PSQAKQOGSA-N 0.000 description 1
- WGDUUQDYDIIBKT-UHFFFAOYSA-N beta-Pseudouridine Natural products OC1OC(CN2C=CC(=O)NC2=O)C(O)C1O WGDUUQDYDIIBKT-UHFFFAOYSA-N 0.000 description 1
- 102000006635 beta-lactamase Human genes 0.000 description 1
- 229960000997 bicalutamide Drugs 0.000 description 1
- 208000026900 bile duct neoplasm Diseases 0.000 description 1
- 239000003833 bile salt Substances 0.000 description 1
- 210000003445 biliary tract Anatomy 0.000 description 1
- 239000011230 binding agent Substances 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
- 230000033228 biological regulation Effects 0.000 description 1
- 230000008512 biological response Effects 0.000 description 1
- 229910052797 bismuth Inorganic materials 0.000 description 1
- JCXGWMGPZLAOME-UHFFFAOYSA-N bismuth atom Chemical compound [Bi] JCXGWMGPZLAOME-UHFFFAOYSA-N 0.000 description 1
- OYVAGSVQBOHSSS-UAPAGMARSA-O bleomycin A2 Chemical compound N([C@H](C(=O)N[C@H](C)[C@@H](O)[C@H](C)C(=O)N[C@@H]([C@H](O)C)C(=O)NCCC=1SC=C(N=1)C=1SC=C(N=1)C(=O)NCCC[S+](C)C)[C@@H](O[C@H]1[C@H]([C@@H](O)[C@H](O)[C@H](CO)O1)O[C@@H]1[C@H]([C@@H](OC(N)=O)[C@H](O)[C@@H](CO)O1)O)C=1N=CNC=1)C(=O)C1=NC([C@H](CC(N)=O)NC[C@H](N)C(N)=O)=NC(N)=C1C OYVAGSVQBOHSSS-UAPAGMARSA-O 0.000 description 1
- 230000037396 body weight Effects 0.000 description 1
- 229910021538 borax Inorganic materials 0.000 description 1
- 150000001642 boronic acid derivatives Chemical class 0.000 description 1
- 231100001103 botulinum neurotoxin Toxicity 0.000 description 1
- 239000001273 butane Substances 0.000 description 1
- FCCCRBDJBTVFSJ-UHFFFAOYSA-N butanehydrazide Chemical compound CCCC(=O)NN FCCCRBDJBTVFSJ-UHFFFAOYSA-N 0.000 description 1
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 229910052793 cadmium Inorganic materials 0.000 description 1
- BDOSMKKIYDKNTQ-UHFFFAOYSA-N cadmium atom Chemical compound [Cd] BDOSMKKIYDKNTQ-UHFFFAOYSA-N 0.000 description 1
- 229960003563 calcium carbonate Drugs 0.000 description 1
- 239000001110 calcium chloride Substances 0.000 description 1
- 229910001628 calcium chloride Inorganic materials 0.000 description 1
- 239000001354 calcium citrate Substances 0.000 description 1
- AXCZMVOFGPJBDE-UHFFFAOYSA-L calcium dihydroxide Chemical compound [OH-].[OH-].[Ca+2] AXCZMVOFGPJBDE-UHFFFAOYSA-L 0.000 description 1
- 229940095618 calcium glycerophosphate Drugs 0.000 description 1
- UHHRFSOMMCWGSO-UHFFFAOYSA-L calcium glycerophosphate Chemical compound [Ca+2].OCC(CO)OP([O-])([O-])=O UHHRFSOMMCWGSO-UHFFFAOYSA-L 0.000 description 1
- 235000019299 calcium glycerylphosphate Nutrition 0.000 description 1
- 239000000920 calcium hydroxide Substances 0.000 description 1
- 229910001861 calcium hydroxide Inorganic materials 0.000 description 1
- MKJXYGKVIBWPFZ-UHFFFAOYSA-L calcium lactate Chemical compound [Ca+2].CC(O)C([O-])=O.CC(O)C([O-])=O MKJXYGKVIBWPFZ-UHFFFAOYSA-L 0.000 description 1
- 239000001527 calcium lactate Substances 0.000 description 1
- 235000011086 calcium lactate Nutrition 0.000 description 1
- 229960002401 calcium lactate Drugs 0.000 description 1
- 235000011132 calcium sulphate Nutrition 0.000 description 1
- UBWYRXFZPXBISJ-UHFFFAOYSA-L calcium;2-hydroxypropanoate;trihydrate Chemical compound O.O.O.[Ca+2].CC(O)C([O-])=O.CC(O)C([O-])=O UBWYRXFZPXBISJ-UHFFFAOYSA-L 0.000 description 1
- ZHZFKLKREFECML-UHFFFAOYSA-L calcium;sulfate;hydrate Chemical compound O.[Ca+2].[O-]S([O-])(=O)=O ZHZFKLKREFECML-UHFFFAOYSA-L 0.000 description 1
- 229940127093 camptothecin Drugs 0.000 description 1
- 230000036952 cancer formation Effects 0.000 description 1
- 230000005773 cancer-related death Effects 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 229960001631 carbomer Drugs 0.000 description 1
- XEVRDFDBXJMZFG-UHFFFAOYSA-N carbonyl dihydrazine Chemical compound NNC(=O)NN XEVRDFDBXJMZFG-UHFFFAOYSA-N 0.000 description 1
- 229960004562 carboplatin Drugs 0.000 description 1
- 235000010948 carboxy methyl cellulose Nutrition 0.000 description 1
- 239000008112 carboxymethyl-cellulose Substances 0.000 description 1
- 229950008138 carmellose Drugs 0.000 description 1
- 235000010418 carrageenan Nutrition 0.000 description 1
- 239000000679 carrageenan Substances 0.000 description 1
- 229920001525 carrageenan Polymers 0.000 description 1
- 229940113118 carrageenan Drugs 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 239000004359 castor oil Substances 0.000 description 1
- 235000019438 castor oil Nutrition 0.000 description 1
- 230000015556 catabolic process Effects 0.000 description 1
- 239000003729 cation exchange resin Substances 0.000 description 1
- 229940023913 cation exchange resins Drugs 0.000 description 1
- 230000004663 cell proliferation Effects 0.000 description 1
- 238000003320 cell separation method Methods 0.000 description 1
- 230000005889 cellular cytotoxicity Effects 0.000 description 1
- 230000007541 cellular toxicity Effects 0.000 description 1
- 235000013339 cereals Nutrition 0.000 description 1
- 235000005513 chalcones Nutrition 0.000 description 1
- 239000003610 charcoal Substances 0.000 description 1
- 239000013522 chelant Substances 0.000 description 1
- HWGQMRYQVZSGDQ-HZPDHXFCSA-N chembl3137320 Chemical compound CN1N=CN=C1[C@H]([C@H](N1)C=2C=CC(F)=CC=2)C2=NNC(=O)C3=C2C1=CC(F)=C3 HWGQMRYQVZSGDQ-HZPDHXFCSA-N 0.000 description 1
- 238000007385 chemical modification Methods 0.000 description 1
- 150000001805 chlorine compounds Chemical class 0.000 description 1
- 208000006990 cholangiocarcinoma Diseases 0.000 description 1
- 150000001840 cholesterol esters Chemical class 0.000 description 1
- 238000004587 chromatography analysis Methods 0.000 description 1
- 150000001860 citric acid derivatives Chemical class 0.000 description 1
- 229960002173 citrulline Drugs 0.000 description 1
- 235000020971 citrus fruits Nutrition 0.000 description 1
- 238000003776 cleavage reaction Methods 0.000 description 1
- 229910017052 cobalt Inorganic materials 0.000 description 1
- 239000010941 cobalt Substances 0.000 description 1
- GUTLYIVDDKVIGB-UHFFFAOYSA-N cobalt atom Chemical compound [Co] GUTLYIVDDKVIGB-UHFFFAOYSA-N 0.000 description 1
- 229960001338 colchicine Drugs 0.000 description 1
- 229940075614 colloidal silicon dioxide Drugs 0.000 description 1
- 210000001072 colon Anatomy 0.000 description 1
- LGZKGOGODCLQHG-UHFFFAOYSA-N combretastatin Natural products C1=C(O)C(OC)=CC=C1CC(O)C1=CC(OC)=C(OC)C(OC)=C1 LGZKGOGODCLQHG-UHFFFAOYSA-N 0.000 description 1
- 230000000295 complement effect Effects 0.000 description 1
- 239000002299 complementary DNA Substances 0.000 description 1
- 239000002131 composite material Substances 0.000 description 1
- 238000007906 compression Methods 0.000 description 1
- 230000006835 compression Effects 0.000 description 1
- 238000005094 computer simulation Methods 0.000 description 1
- 239000000470 constituent Substances 0.000 description 1
- 238000010276 construction Methods 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 229910052802 copper Inorganic materials 0.000 description 1
- 239000010949 copper Substances 0.000 description 1
- 235000005822 corn Nutrition 0.000 description 1
- 239000008120 corn starch Substances 0.000 description 1
- POADTFBBIXOWFJ-VWLOTQADSA-N cositecan Chemical compound C1=CC=C2C(CC[Si](C)(C)C)=C(CN3C4=CC5=C(C3=O)COC(=O)[C@]5(O)CC)C4=NC2=C1 POADTFBBIXOWFJ-VWLOTQADSA-N 0.000 description 1
- 229950002415 cositecan Drugs 0.000 description 1
- 230000008878 coupling Effects 0.000 description 1
- 238000005859 coupling reaction Methods 0.000 description 1
- 229960005168 croscarmellose Drugs 0.000 description 1
- 229960000913 crospovidone Drugs 0.000 description 1
- 229920006037 cross link polymer Polymers 0.000 description 1
- 235000010947 crosslinked sodium carboxy methyl cellulose Nutrition 0.000 description 1
- 108010006226 cryptophycin Proteins 0.000 description 1
- PSNOPSMXOBPNNV-VVCTWANISA-N cryptophycin 1 Chemical compound C1=C(Cl)C(OC)=CC=C1C[C@@H]1C(=O)NC[C@@H](C)C(=O)O[C@@H](CC(C)C)C(=O)O[C@H]([C@H](C)[C@@H]2[C@H](O2)C=2C=CC=CC=2)C/C=C/C(=O)N1 PSNOPSMXOBPNNV-VVCTWANISA-N 0.000 description 1
- PSNOPSMXOBPNNV-UHFFFAOYSA-N cryptophycin-327 Natural products C1=C(Cl)C(OC)=CC=C1CC1C(=O)NCC(C)C(=O)OC(CC(C)C)C(=O)OC(C(C)C2C(O2)C=2C=CC=CC=2)CC=CC(=O)N1 PSNOPSMXOBPNNV-UHFFFAOYSA-N 0.000 description 1
- 125000004122 cyclic group Chemical group 0.000 description 1
- 208000002445 cystadenocarcinoma Diseases 0.000 description 1
- UHDGCWIWMRVCDJ-ZAKLUEHWSA-N cytidine Chemical compound O=C1N=C(N)C=CN1[C@H]1[C@H](O)[C@@H](O)[C@H](CO)O1 UHDGCWIWMRVCDJ-ZAKLUEHWSA-N 0.000 description 1
- 230000016396 cytokine production Effects 0.000 description 1
- 230000001461 cytolytic effect Effects 0.000 description 1
- 229940127096 cytoskeletal disruptor Drugs 0.000 description 1
- 239000003145 cytotoxic factor Substances 0.000 description 1
- 229960003901 dacarbazine Drugs 0.000 description 1
- POZRVZJJTULAOH-LHZXLZLDSA-N danazol Chemical compound C1[C@]2(C)[C@H]3CC[C@](C)([C@](CC4)(O)C#C)[C@@H]4[C@@H]3CCC2=CC2=C1C=NO2 POZRVZJJTULAOH-LHZXLZLDSA-N 0.000 description 1
- 229960000860 dapsone Drugs 0.000 description 1
- 230000009615 deamination Effects 0.000 description 1
- 238000006481 deamination reaction Methods 0.000 description 1
- 238000000354 decomposition reaction Methods 0.000 description 1
- 230000007812 deficiency Effects 0.000 description 1
- 238000006731 degradation reaction Methods 0.000 description 1
- 230000003111 delayed effect Effects 0.000 description 1
- 238000012217 deletion Methods 0.000 description 1
- 230000037430 deletion Effects 0.000 description 1
- 239000000412 dendrimer Substances 0.000 description 1
- 210000004443 dendritic cell Anatomy 0.000 description 1
- 229920000736 dendritic polymer Polymers 0.000 description 1
- LSXWFXONGKSEMY-UHFFFAOYSA-N di-tert-butyl peroxide Chemical compound CC(C)(C)OOC(C)(C)C LSXWFXONGKSEMY-UHFFFAOYSA-N 0.000 description 1
- 239000012969 di-tertiary-butyl peroxide Substances 0.000 description 1
- 229940039227 diagnostic agent Drugs 0.000 description 1
- 239000000032 diagnostic agent Substances 0.000 description 1
- RGLYKWWBQGJZGM-ISLYRVAYSA-N diethylstilbestrol Chemical compound C=1C=C(O)C=CC=1C(/CC)=C(\CC)C1=CC=C(O)C=C1 RGLYKWWBQGJZGM-ISLYRVAYSA-N 0.000 description 1
- KZNICNPSHKQLFF-UHFFFAOYSA-N dihydromaleimide Natural products O=C1CCC(=O)N1 KZNICNPSHKQLFF-UHFFFAOYSA-N 0.000 description 1
- 206010013023 diphtheria Diseases 0.000 description 1
- ZPWVASYFFYYZEW-UHFFFAOYSA-L dipotassium hydrogen phosphate Chemical compound [K+].[K+].OP([O-])([O-])=O ZPWVASYFFYYZEW-UHFFFAOYSA-L 0.000 description 1
- 235000019797 dipotassium phosphate Nutrition 0.000 description 1
- 229910000396 dipotassium phosphate Inorganic materials 0.000 description 1
- LOKCTEFSRHRXRJ-UHFFFAOYSA-I dipotassium trisodium dihydrogen phosphate hydrogen phosphate dichloride Chemical compound P(=O)(O)(O)[O-].[K+].P(=O)(O)([O-])[O-].[Na+].[Na+].[Cl-].[K+].[Cl-].[Na+] LOKCTEFSRHRXRJ-UHFFFAOYSA-I 0.000 description 1
- 235000021186 dishes Nutrition 0.000 description 1
- 208000035475 disorder Diseases 0.000 description 1
- 239000002270 dispersing agent Substances 0.000 description 1
- 238000002224 dissection Methods 0.000 description 1
- 238000009826 distribution Methods 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
- 239000003937 drug carrier Substances 0.000 description 1
- 238000012377 drug delivery Methods 0.000 description 1
- 230000009977 dual effect Effects 0.000 description 1
- 229960005519 duocarmycin A Drugs 0.000 description 1
- 229960005513 duocarmycin B1 Drugs 0.000 description 1
- NIADGRRCOZRRQF-UHFFFAOYSA-N duocarmycin B1 Natural products COC(=O)C1(C)NC2=C(C3CC(Br)CN(C(=O)c4cc5cc(OC)c(OC)c(OC)c5[nH]4)C3=CC2=O)C1=O NIADGRRCOZRRQF-UHFFFAOYSA-N 0.000 description 1
- 229960005514 duocarmycin B2 Drugs 0.000 description 1
- UQPQXFUURNIVNJ-UHFFFAOYSA-N duocarmycin B2 Natural products COC1=C(OC)C(OC)=C2NC(C(=O)N3CC(CBr)C=4C5=C(C(=CC=43)O)NC(C5=O)(C)C(=O)OC)=CC2=C1 UQPQXFUURNIVNJ-UHFFFAOYSA-N 0.000 description 1
- 229960005512 duocarmycin C1 Drugs 0.000 description 1
- 229960005511 duocarmycin C2 Drugs 0.000 description 1
- 229960005518 duocarmycin D Drugs 0.000 description 1
- OXYZQOYSQSPFMI-UHFFFAOYSA-N duocarmycin D Natural products COC1=C(OC)C(OC)=C2NC(C(=O)N3C=C(CO)C=4C5=C(C(=CC=43)O)NC(C5=O)(C)C(=O)OC)=CC2=C1 OXYZQOYSQSPFMI-UHFFFAOYSA-N 0.000 description 1
- 229960005510 duocarmycin SA Drugs 0.000 description 1
- 229950009791 durvalumab Drugs 0.000 description 1
- 101150058725 ecl1 gene Proteins 0.000 description 1
- 238000004520 electroporation Methods 0.000 description 1
- 238000010828 elution Methods 0.000 description 1
- 239000012149 elution buffer Substances 0.000 description 1
- 239000000839 emulsion Substances 0.000 description 1
- 238000005538 encapsulation Methods 0.000 description 1
- 201000011523 endocrine gland cancer Diseases 0.000 description 1
- 230000002121 endocytic effect Effects 0.000 description 1
- 239000000147 enterotoxin Substances 0.000 description 1
- 231100000655 enterotoxin Toxicity 0.000 description 1
- 229930013356 epothilone Natural products 0.000 description 1
- 150000003883 epothilone derivatives Chemical class 0.000 description 1
- 208000028653 esophageal adenocarcinoma Diseases 0.000 description 1
- 210000003238 esophagus Anatomy 0.000 description 1
- LJQQFQHBKUKHIS-WJHRIEJJSA-N esperamicin Chemical compound O1CC(NC(C)C)C(OC)CC1OC1C(O)C(NOC2OC(C)C(SC)C(O)C2)C(C)OC1OC1C(\C2=C/CSSSC)=C(NC(=O)OC)C(=O)C(OC3OC(C)C(O)C(OC(=O)C=4C(=CC(OC)=C(OC)C=4)NC(=O)C(=C)OC)C3)C2(O)C#C\C=C/C#C1 LJQQFQHBKUKHIS-WJHRIEJJSA-N 0.000 description 1
- 229940064258 estrace Drugs 0.000 description 1
- 239000000328 estrogen antagonist Substances 0.000 description 1
- 239000002834 estrogen receptor modulator Substances 0.000 description 1
- 229960000403 etanercept Drugs 0.000 description 1
- MVPICKVDHDWCJQ-UHFFFAOYSA-N ethyl 3-pyrrolidin-1-ylpropanoate Chemical compound CCOC(=O)CCN1CCCC1 MVPICKVDHDWCJQ-UHFFFAOYSA-N 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- LVGKNOAMLMIIKO-QXMHVHEDSA-N ethyl oleate Chemical compound CCCCCCCC\C=C/CCCCCCCC(=O)OCC LVGKNOAMLMIIKO-QXMHVHEDSA-N 0.000 description 1
- 229940093471 ethyl oleate Drugs 0.000 description 1
- 210000003527 eukaryotic cell Anatomy 0.000 description 1
- 238000011156 evaluation Methods 0.000 description 1
- 230000003203 everyday effect Effects 0.000 description 1
- ZVYVPGLRVWUPMP-FYSMJZIKSA-N exatecan Chemical compound C1C[C@H](N)C2=C(CN3C4=CC5=C(C3=O)COC(=O)[C@]5(O)CC)C4=NC3=CC(F)=C(C)C1=C32 ZVYVPGLRVWUPMP-FYSMJZIKSA-N 0.000 description 1
- 229950009429 exatecan Drugs 0.000 description 1
- 102000013165 exonuclease Human genes 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 150000004665 fatty acids Chemical class 0.000 description 1
- 239000007888 film coating Substances 0.000 description 1
- 238000009501 film coating Methods 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 239000012467 final product Substances 0.000 description 1
- 235000013312 flour Nutrition 0.000 description 1
- 239000012530 fluid Substances 0.000 description 1
- 239000007850 fluorescent dye Substances 0.000 description 1
- 229960002949 fluorouracil Drugs 0.000 description 1
- 229960001751 fluoxymesterone Drugs 0.000 description 1
- YLRFCQOZQXIBAB-RBZZARIASA-N fluoxymesterone Chemical compound C1CC2=CC(=O)CC[C@]2(C)[C@]2(F)[C@@H]1[C@@H]1CC[C@](C)(O)[C@@]1(C)C[C@@H]2O YLRFCQOZQXIBAB-RBZZARIASA-N 0.000 description 1
- 239000011888 foil Substances 0.000 description 1
- 125000002485 formyl group Chemical group [H]C(*)=O 0.000 description 1
- UIWYJDYFSGRHKR-UHFFFAOYSA-N gadolinium atom Chemical compound [Gd] UIWYJDYFSGRHKR-UHFFFAOYSA-N 0.000 description 1
- 210000000232 gallbladder Anatomy 0.000 description 1
- 229910052733 gallium Inorganic materials 0.000 description 1
- IRSCQMHQWWYFCW-UHFFFAOYSA-N ganciclovir Chemical compound O=C1NC(N)=NC2=C1N=CN2COC(CO)CO IRSCQMHQWWYFCW-UHFFFAOYSA-N 0.000 description 1
- 229960002963 ganciclovir Drugs 0.000 description 1
- 201000006585 gastric adenocarcinoma Diseases 0.000 description 1
- 201000011587 gastric lymphoma Diseases 0.000 description 1
- 210000001156 gastric mucosa Anatomy 0.000 description 1
- 208000015419 gastrin-producing neuroendocrine tumor Diseases 0.000 description 1
- 201000000052 gastrinoma Diseases 0.000 description 1
- 201000011243 gastrointestinal stromal tumor Diseases 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
- 229960002584 gefitinib Drugs 0.000 description 1
- 239000008273 gelatin Substances 0.000 description 1
- 229920000159 gelatin Polymers 0.000 description 1
- 229940014259 gelatin Drugs 0.000 description 1
- 235000019322 gelatine Nutrition 0.000 description 1
- 235000011852 gelatine desserts Nutrition 0.000 description 1
- 229960005277 gemcitabine Drugs 0.000 description 1
- SDUQYLNIPVEERB-QPPQHZFASA-N gemcitabine Chemical compound O=C1N=C(N)C=CN1[C@H]1C(F)(F)[C@H](O)[C@@H](CO)O1 SDUQYLNIPVEERB-QPPQHZFASA-N 0.000 description 1
- 238000009650 gentamicin protection assay Methods 0.000 description 1
- GNPVGFCGXDBREM-UHFFFAOYSA-N germanium atom Chemical compound [Ge] GNPVGFCGXDBREM-UHFFFAOYSA-N 0.000 description 1
- 239000003862 glucocorticoid Substances 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- 235000001727 glucose Nutrition 0.000 description 1
- JFCQEDHGNNZCLN-UHFFFAOYSA-N glutaric acid Chemical compound OC(=O)CCCC(O)=O JFCQEDHGNNZCLN-UHFFFAOYSA-N 0.000 description 1
- 229960005150 glycerol Drugs 0.000 description 1
- ZEMPKEQAKRGZGQ-XOQCFJPHSA-N glycerol triricinoleate Natural products CCCCCC[C@@H](O)CC=CCCCCCCCC(=O)OC[C@@H](COC(=O)CCCCCCCC=CC[C@@H](O)CCCCCC)OC(=O)CCCCCCCC=CC[C@H](O)CCCCCC ZEMPKEQAKRGZGQ-XOQCFJPHSA-N 0.000 description 1
- 229940049654 glyceryl behenate Drugs 0.000 description 1
- 229910052737 gold Inorganic materials 0.000 description 1
- 239000010931 gold Substances 0.000 description 1
- 229940035638 gonadotropin-releasing hormone Drugs 0.000 description 1
- ZWCXYZRRTRDGQE-SORVKSEFSA-N gramicidina Chemical compound C1=CC=C2C(C[C@H](NC(=O)[C@@H](CC(C)C)NC(=O)[C@H](CC=3C4=CC=CC=C4NC=3)NC(=O)[C@@H](CC(C)C)NC(=O)[C@H](CC=3C4=CC=CC=C4NC=3)NC(=O)[C@@H](CC(C)C)NC(=O)[C@H](CC=3C4=CC=CC=C4NC=3)NC(=O)[C@H](C(C)C)NC(=O)[C@H](C(C)C)NC(=O)[C@@H](C(C)C)NC(=O)[C@H](C)NC(=O)[C@H](NC(=O)[C@H](C)NC(=O)CNC(=O)[C@@H](NC=O)C(C)C)CC(C)C)C(=O)NCCO)=CNC2=C1 ZWCXYZRRTRDGQE-SORVKSEFSA-N 0.000 description 1
- 229940029575 guanosine Drugs 0.000 description 1
- 235000010417 guar gum Nutrition 0.000 description 1
- 239000000665 guar gum Substances 0.000 description 1
- 229960002154 guar gum Drugs 0.000 description 1
- 230000003394 haemopoietic effect Effects 0.000 description 1
- 229910052735 hafnium Inorganic materials 0.000 description 1
- VBJZVLUMGGDVMO-UHFFFAOYSA-N hafnium atom Chemical compound [Hf] VBJZVLUMGGDVMO-UHFFFAOYSA-N 0.000 description 1
- 150000004820 halides Chemical class 0.000 description 1
- 125000001475 halogen functional group Chemical group 0.000 description 1
- 239000000185 hemagglutinin Substances 0.000 description 1
- 210000003494 hepatocyte Anatomy 0.000 description 1
- 125000003104 hexanoyl group Chemical group O=C([*])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 210000000688 human artificial chromosome Anatomy 0.000 description 1
- 229930195733 hydrocarbon Natural products 0.000 description 1
- 150000002430 hydrocarbons Chemical class 0.000 description 1
- GYTMUNSNMBRSEW-UHFFFAOYSA-N hydrogen carbonate;1h-imidazol-1-ium Chemical compound OC(O)=O.C1=CNC=N1 GYTMUNSNMBRSEW-UHFFFAOYSA-N 0.000 description 1
- 230000007062 hydrolysis Effects 0.000 description 1
- 238000006460 hydrolysis reaction Methods 0.000 description 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 1
- 229920003063 hydroxymethyl cellulose Polymers 0.000 description 1
- 229940031574 hydroxymethyl cellulose Drugs 0.000 description 1
- 235000010977 hydroxypropyl cellulose Nutrition 0.000 description 1
- 239000001863 hydroxypropyl cellulose Substances 0.000 description 1
- 229920003132 hydroxypropyl methylcellulose phthalate Polymers 0.000 description 1
- 229940031704 hydroxypropyl methylcellulose phthalate Drugs 0.000 description 1
- 229940121569 ieramilimab Drugs 0.000 description 1
- KTUFNOKKBVMGRW-UHFFFAOYSA-N imatinib Chemical compound C1CN(C)CCN1CC1=CC=C(C(=O)NC=2C=C(NC=3N=C(C=CN=3)C=3C=NC=CC=3)C(C)=CC=2)C=C1 KTUFNOKKBVMGRW-UHFFFAOYSA-N 0.000 description 1
- 229960002411 imatinib Drugs 0.000 description 1
- 239000012729 immediate-release (IR) formulation Substances 0.000 description 1
- 230000014726 immortalization of host cell Effects 0.000 description 1
- 210000002865 immune cell Anatomy 0.000 description 1
- 230000001900 immune effect Effects 0.000 description 1
- 230000036039 immunity Effects 0.000 description 1
- 238000010166 immunofluorescence Methods 0.000 description 1
- 230000016784 immunoglobulin production Effects 0.000 description 1
- 238000013388 immunohistochemistry analysis Methods 0.000 description 1
- 229940121354 immunomodulator Drugs 0.000 description 1
- 230000003308 immunostimulating effect Effects 0.000 description 1
- 238000003017 in situ immunoassay Methods 0.000 description 1
- 229910052738 indium Inorganic materials 0.000 description 1
- APFVFJFRJDLVQX-UHFFFAOYSA-N indium atom Chemical compound [In] APFVFJFRJDLVQX-UHFFFAOYSA-N 0.000 description 1
- 239000012678 infectious agent Substances 0.000 description 1
- 208000015181 infectious disease Diseases 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 239000003999 initiator Substances 0.000 description 1
- 238000011081 inoculation Methods 0.000 description 1
- 229960000367 inositol Drugs 0.000 description 1
- CDAISMWEOUEBRE-GPIVLXJGSA-N inositol Chemical compound O[C@H]1[C@H](O)[C@@H](O)[C@H](O)[C@H](O)[C@@H]1O CDAISMWEOUEBRE-GPIVLXJGSA-N 0.000 description 1
- 206010022498 insulinoma Diseases 0.000 description 1
- 230000002452 interceptive effect Effects 0.000 description 1
- 229960003130 interferon gamma Drugs 0.000 description 1
- 229960001388 interferon-beta Drugs 0.000 description 1
- 238000001361 intraarterial administration Methods 0.000 description 1
- 201000007450 intrahepatic cholangiocarcinoma Diseases 0.000 description 1
- PGLTVOMIXTUURA-UHFFFAOYSA-N iodoacetamide Chemical compound NC(=O)CI PGLTVOMIXTUURA-UHFFFAOYSA-N 0.000 description 1
- 229910052741 iridium Inorganic materials 0.000 description 1
- GKOZUEZYRPOHIO-UHFFFAOYSA-N iridium atom Chemical compound [Ir] GKOZUEZYRPOHIO-UHFFFAOYSA-N 0.000 description 1
- 229910052742 iron Inorganic materials 0.000 description 1
- 238000006317 isomerization reaction Methods 0.000 description 1
- NLYAJNPCOHFWQQ-UHFFFAOYSA-N kaolin Chemical compound O.O.O=[Al]O[Si](=O)O[Si](=O)O[Al]=O NLYAJNPCOHFWQQ-UHFFFAOYSA-N 0.000 description 1
- 125000000468 ketone group Chemical group 0.000 description 1
- 230000002147 killing effect Effects 0.000 description 1
- 229940043355 kinase inhibitor Drugs 0.000 description 1
- 239000004310 lactic acid Substances 0.000 description 1
- 235000014655 lactic acid Nutrition 0.000 description 1
- 150000002596 lactones Chemical class 0.000 description 1
- 210000002429 large intestine Anatomy 0.000 description 1
- 150000002605 large molecules Chemical class 0.000 description 1
- 229920005610 lignin Polymers 0.000 description 1
- 230000029226 lipidation Effects 0.000 description 1
- 238000001638 lipofection Methods 0.000 description 1
- 239000002502 liposome Substances 0.000 description 1
- 238000002761 liquid phase assay Methods 0.000 description 1
- 229910052744 lithium Inorganic materials 0.000 description 1
- 210000004185 liver Anatomy 0.000 description 1
- 238000004020 luminiscence type Methods 0.000 description 1
- 201000005249 lung adenocarcinoma Diseases 0.000 description 1
- 201000009546 lung large cell carcinoma Diseases 0.000 description 1
- 201000005243 lung squamous cell carcinoma Diseases 0.000 description 1
- 229940040129 luteinizing hormone Drugs 0.000 description 1
- 230000001320 lysogenic effect Effects 0.000 description 1
- 229920002521 macromolecule Polymers 0.000 description 1
- 229940037627 magnesium lauryl sulfate Drugs 0.000 description 1
- HCWCAKKEBCNQJP-UHFFFAOYSA-N magnesium orthosilicate Chemical compound [Mg+2].[Mg+2].[O-][Si]([O-])([O-])[O-] HCWCAKKEBCNQJP-UHFFFAOYSA-N 0.000 description 1
- 239000000391 magnesium silicate Substances 0.000 description 1
- 235000019792 magnesium silicate Nutrition 0.000 description 1
- 229910052919 magnesium silicate Inorganic materials 0.000 description 1
- 229960002366 magnesium silicate Drugs 0.000 description 1
- HBNDBUATLJAUQM-UHFFFAOYSA-L magnesium;dodecyl sulfate Chemical compound [Mg+2].CCCCCCCCCCCCOS([O-])(=O)=O.CCCCCCCCCCCCOS([O-])(=O)=O HBNDBUATLJAUQM-UHFFFAOYSA-L 0.000 description 1
- 230000005291 magnetic effect Effects 0.000 description 1
- 238000012423 maintenance Methods 0.000 description 1
- 230000014759 maintenance of location Effects 0.000 description 1
- 229940035034 maltodextrin Drugs 0.000 description 1
- 210000004962 mammalian cell Anatomy 0.000 description 1
- 238000007726 management method Methods 0.000 description 1
- WPBNNNQJVZRUHP-UHFFFAOYSA-L manganese(2+);methyl n-[[2-(methoxycarbonylcarbamothioylamino)phenyl]carbamothioyl]carbamate;n-[2-(sulfidocarbothioylamino)ethyl]carbamodithioate Chemical compound [Mn+2].[S-]C(=S)NCCNC([S-])=S.COC(=O)NC(=S)NC1=CC=CC=C1NC(=S)NC(=O)OC WPBNNNQJVZRUHP-UHFFFAOYSA-L 0.000 description 1
- 229960001855 mannitol Drugs 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- 229940126601 medicinal product Drugs 0.000 description 1
- 229960002985 medroxyprogesterone acetate Drugs 0.000 description 1
- PSGAAPLEWMOORI-PEINSRQWSA-N medroxyprogesterone acetate Chemical compound C([C@@]12C)CC(=O)C=C1[C@@H](C)C[C@@H]1[C@@H]2CC[C@]2(C)[C@@](OC(C)=O)(C(C)=O)CC[C@H]21 PSGAAPLEWMOORI-PEINSRQWSA-N 0.000 description 1
- 229960004296 megestrol acetate Drugs 0.000 description 1
- RQZAXGRLVPAYTJ-GQFGMJRRSA-N megestrol acetate Chemical compound C1=C(C)C2=CC(=O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@@](C(C)=O)(OC(=O)C)[C@@]1(C)CC2 RQZAXGRLVPAYTJ-GQFGMJRRSA-N 0.000 description 1
- 210000004379 membrane Anatomy 0.000 description 1
- GLVAUDGFNGKCSF-UHFFFAOYSA-N mercaptopurine Chemical compound S=C1NC=NC2=C1NC=N2 GLVAUDGFNGKCSF-UHFFFAOYSA-N 0.000 description 1
- 229960001428 mercaptopurine Drugs 0.000 description 1
- HEBKCHPVOIAQTA-UHFFFAOYSA-N meso ribitol Natural products OCC(O)C(O)C(O)CO HEBKCHPVOIAQTA-UHFFFAOYSA-N 0.000 description 1
- 150000002739 metals Chemical class 0.000 description 1
- TWXDDNPPQUTEOV-FVGYRXGTSA-N methamphetamine hydrochloride Chemical compound Cl.CN[C@@H](C)CC1=CC=CC=C1 TWXDDNPPQUTEOV-FVGYRXGTSA-N 0.000 description 1
- WSFSSNUMVMOOMR-NJFSPNSNSA-N methanone Chemical compound O=[14CH2] WSFSSNUMVMOOMR-NJFSPNSNSA-N 0.000 description 1
- 229960000485 methotrexate Drugs 0.000 description 1
- AZVARJHZBXHUSO-DZQVEHCYSA-N methyl (1R,4R,12S)-4-methyl-3,7-dioxo-10-(5,6,7-trimethoxy-1H-indole-2-carbonyl)-5,10-diazatetracyclo[7.4.0.01,12.02,6]trideca-2(6),8-diene-4-carboxylate Chemical compound COC1=C(OC)C(OC)=C2NC(C(=O)N3C[C@H]4C[C@]44C5=C(C(C=C43)=O)N[C@@](C5=O)(C)C(=O)OC)=CC2=C1 AZVARJHZBXHUSO-DZQVEHCYSA-N 0.000 description 1
- ILRQRCTVPANBBE-GWQKEKGPSA-N methyl (2R,8S)-8-chloro-4-hydroxy-2-methyl-1-oxo-6-(5,6,7-trimethoxy-1H-indole-2-carbonyl)-3,7,8,9-tetrahydropyrrolo[3,2-f]quinoline-2-carboxylate Chemical compound COC(=O)[C@]1(C)Nc2c(C1=O)c1C[C@H](Cl)CN(C(=O)c3cc4cc(OC)c(OC)c(OC)c4[nH]3)c1cc2O ILRQRCTVPANBBE-GWQKEKGPSA-N 0.000 description 1
- OXYZQOYSQSPFMI-AREMUKBSSA-N methyl (2r)-4-hydroxy-8-(hydroxymethyl)-2-methyl-1-oxo-6-(5,6,7-trimethoxy-1h-indole-2-carbonyl)-3h-pyrrolo[3,2-e]indole-2-carboxylate Chemical compound COC1=C(OC)C(OC)=C2NC(C(=O)N3C=C(CO)C=4C5=C(C(=CC=43)O)N[C@@](C5=O)(C)C(=O)OC)=CC2=C1 OXYZQOYSQSPFMI-AREMUKBSSA-N 0.000 description 1
- UQPQXFUURNIVNJ-MZHQLVBMSA-N methyl (2r,8s)-8-(bromomethyl)-4-hydroxy-2-methyl-1-oxo-6-(5,6,7-trimethoxy-1h-indole-2-carbonyl)-7,8-dihydro-3h-pyrrolo[3,2-e]indole-2-carboxylate Chemical compound COC1=C(OC)C(OC)=C2NC(C(=O)N3C[C@@H](CBr)C=4C5=C(C(=CC=43)O)N[C@@](C5=O)(C)C(=O)OC)=CC2=C1 UQPQXFUURNIVNJ-MZHQLVBMSA-N 0.000 description 1
- BOGFADYROAVVTF-MZHQLVBMSA-N methyl (2r,8s)-8-(chloromethyl)-4-hydroxy-2-methyl-1-oxo-6-(5,6,7-trimethoxy-1h-indole-2-carbonyl)-7,8-dihydro-3h-pyrrolo[3,2-e]indole-2-carboxylate Chemical compound COC1=C(OC)C(OC)=C2NC(C(=O)N3C[C@@H](CCl)C=4C5=C(C(=CC=43)O)N[C@@](C5=O)(C)C(=O)OC)=CC2=C1 BOGFADYROAVVTF-MZHQLVBMSA-N 0.000 description 1
- SUWUAMDOMCWKCL-GWQKEKGPSA-N methyl (2r,8s)-8-bromo-4-hydroxy-2-methyl-1-oxo-6-(5,6,7-trimethoxy-1h-indole-2-carbonyl)-3,7,8,9-tetrahydropyrrolo[3,2-f]quinoline-2-carboxylate Chemical compound COC1=C(OC)C(OC)=C2NC(C(=O)N3C[C@@H](Br)CC=4C5=C(C(=CC=43)O)N[C@@](C5=O)(C)C(=O)OC)=CC2=C1 SUWUAMDOMCWKCL-GWQKEKGPSA-N 0.000 description 1
- 229920012128 methyl methacrylate acrylonitrile butadiene styrene Polymers 0.000 description 1
- 230000011987 methylation Effects 0.000 description 1
- 238000007069 methylation reaction Methods 0.000 description 1
- YACKEPLHDIMKIO-UHFFFAOYSA-N methylphosphonic acid Chemical class CP(O)(O)=O YACKEPLHDIMKIO-UHFFFAOYSA-N 0.000 description 1
- HPNSFSBZBAHARI-UHFFFAOYSA-N micophenolic acid Natural products OC1=C(CC=C(C)CCC(O)=O)C(OC)=C(C)C2=C1C(=O)OC2 HPNSFSBZBAHARI-UHFFFAOYSA-N 0.000 description 1
- 238000001471 micro-filtration Methods 0.000 description 1
- 239000002480 mineral oil Substances 0.000 description 1
- 231100000324 minimal toxicity Toxicity 0.000 description 1
- CFCUWKMKBJTWLW-BKHRDMLASA-N mithramycin Chemical compound O([C@@H]1C[C@@H](O[C@H](C)[C@H]1O)OC=1C=C2C=C3C[C@H]([C@@H](C(=O)C3=C(O)C2=C(O)C=1C)O[C@@H]1O[C@H](C)[C@@H](O)[C@H](O[C@@H]2O[C@H](C)[C@H](O)[C@H](O[C@@H]3O[C@H](C)[C@@H](O)[C@@](C)(O)C3)C2)C1)[C@H](OC)C(=O)[C@@H](O)[C@@H](C)O)[C@H]1C[C@@H](O)[C@H](O)[C@@H](C)O1 CFCUWKMKBJTWLW-BKHRDMLASA-N 0.000 description 1
- 229960001156 mitoxantrone 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
- 238000002715 modification method Methods 0.000 description 1
- 238000010369 molecular cloning Methods 0.000 description 1
- 229910052750 molybdenum Inorganic materials 0.000 description 1
- 239000011733 molybdenum Substances 0.000 description 1
- 238000004264 monolayer culture Methods 0.000 description 1
- 125000004573 morpholin-4-yl group Chemical group N1(CCOCC1)* 0.000 description 1
- 238000010172 mouse model Methods 0.000 description 1
- 208000022669 mucinous neoplasm Diseases 0.000 description 1
- 229940014456 mycophenolate Drugs 0.000 description 1
- HPNSFSBZBAHARI-RUDMXATFSA-N mycophenolic acid Chemical compound OC1=C(C\C=C(/C)CCC(O)=O)C(OC)=C(C)C2=C1C(=O)OC2 HPNSFSBZBAHARI-RUDMXATFSA-N 0.000 description 1
- 239000002636 mycotoxin Substances 0.000 description 1
- 230000002107 myocardial effect Effects 0.000 description 1
- SENLDUJVTGGYIH-UHFFFAOYSA-N n-(2-aminoethyl)-3-[[3-(2-aminoethylamino)-3-oxopropyl]-[2-[bis[3-(2-aminoethylamino)-3-oxopropyl]amino]ethyl]amino]propanamide Chemical compound NCCNC(=O)CCN(CCC(=O)NCCN)CCN(CCC(=O)NCCN)CCC(=O)NCCN SENLDUJVTGGYIH-UHFFFAOYSA-N 0.000 description 1
- ODTZGFFHYPHJNS-UHFFFAOYSA-N n-(4-benzoylphenyl)-2-iodoacetamide Chemical compound C1=CC(NC(=O)CI)=CC=C1C(=O)C1=CC=CC=C1 ODTZGFFHYPHJNS-UHFFFAOYSA-N 0.000 description 1
- IJDNQMDRQITEOD-UHFFFAOYSA-N n-butane Chemical compound CCCC IJDNQMDRQITEOD-UHFFFAOYSA-N 0.000 description 1
- OFBQJSOFQDEBGM-UHFFFAOYSA-N n-pentane Natural products CCCCC OFBQJSOFQDEBGM-UHFFFAOYSA-N 0.000 description 1
- 239000002121 nanofiber Substances 0.000 description 1
- 239000002073 nanorod Substances 0.000 description 1
- 239000002072 nanorope Substances 0.000 description 1
- 239000002071 nanotube Substances 0.000 description 1
- 210000000822 natural killer cell Anatomy 0.000 description 1
- 229920005615 natural polymer Polymers 0.000 description 1
- 229950010159 nemorubicin Drugs 0.000 description 1
- CTMCWCONSULRHO-UHQPFXKFSA-N nemorubicin Chemical compound C1CO[C@H](OC)CN1[C@@H]1[C@H](O)[C@H](C)O[C@@H](O[C@@H]2C3=C(O)C=4C(=O)C5=C(OC)C=CC=C5C(=O)C=4C(O)=C3C[C@](O)(C2)C(=O)CO)C1 CTMCWCONSULRHO-UHQPFXKFSA-N 0.000 description 1
- 230000009826 neoplastic cell growth Effects 0.000 description 1
- 210000005036 nerve Anatomy 0.000 description 1
- 238000006386 neutralization reaction Methods 0.000 description 1
- 229910052759 nickel Inorganic materials 0.000 description 1
- 229910052758 niobium Inorganic materials 0.000 description 1
- 239000010955 niobium Substances 0.000 description 1
- GUCVJGMIXFAOAE-UHFFFAOYSA-N niobium atom Chemical compound [Nb] GUCVJGMIXFAOAE-UHFFFAOYSA-N 0.000 description 1
- PCHKPVIQAHNQLW-CQSZACIVSA-N niraparib Chemical compound N1=C2C(C(=O)N)=CC=CC2=CN1C(C=C1)=CC=C1[C@@H]1CCCNC1 PCHKPVIQAHNQLW-CQSZACIVSA-N 0.000 description 1
- 229920001220 nitrocellulos Polymers 0.000 description 1
- IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 1
- 230000009871 nonspecific binding Effects 0.000 description 1
- 238000010899 nucleation Methods 0.000 description 1
- 238000007826 nucleic acid assay Methods 0.000 description 1
- 150000003833 nucleoside derivatives Chemical class 0.000 description 1
- 210000004940 nucleus Anatomy 0.000 description 1
- 235000015097 nutrients Nutrition 0.000 description 1
- QYSGYZVSCZSLHT-UHFFFAOYSA-N octafluoropropane Chemical compound FC(F)(F)C(F)(F)C(F)(F)F QYSGYZVSCZSLHT-UHFFFAOYSA-N 0.000 description 1
- YYZUSRORWSJGET-UHFFFAOYSA-N octanoic acid ethyl ester Natural products CCCCCCCC(=O)OCC YYZUSRORWSJGET-UHFFFAOYSA-N 0.000 description 1
- 229950004053 octoxinol Drugs 0.000 description 1
- 229960002700 octreotide Drugs 0.000 description 1
- 239000003921 oil Substances 0.000 description 1
- 235000019198 oils Nutrition 0.000 description 1
- 229960000572 olaparib Drugs 0.000 description 1
- 229960002969 oleic acid Drugs 0.000 description 1
- CMMLZMMKTYEOKV-RDKHTNMBSA-N oligomycin C Polymers O([C@H]1CC[C@H](/C=C/C=C/C[C@@H](C)[C@H](O)[C@H](C)C(=O)[C@@H](C)[C@H](O)[C@@H](C)C(=O)[C@@H](C)[C@H](O)[C@@H](C)/C=C/C(=O)O[C@@H]([C@@H]2C)[C@@H]1C)CC)[C@@]12CC[C@H](C)[C@H](C[C@@H](C)O)O1 CMMLZMMKTYEOKV-RDKHTNMBSA-N 0.000 description 1
- CMMLZMMKTYEOKV-JEKNLLRFSA-N oligomycin c Polymers O([C@@H]1CC[C@@H](/C=C/C=C/C[C@H](C)[C@@H](O)[C@@H](C)C(=O)[C@H](C)[C@@H](O)[C@H](C)C(=O)[C@H](C)[C@@H](O)[C@H](C)/C=C/C(=O)O[C@H]([C@H]2C)[C@H]1C)CC)[C@]12CC[C@@H](C)[C@@H](C[C@H](C)O)O1 CMMLZMMKTYEOKV-JEKNLLRFSA-N 0.000 description 1
- 229950011093 onapristone Drugs 0.000 description 1
- 230000003287 optical effect Effects 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 229910052762 osmium Inorganic materials 0.000 description 1
- SYQBFIAQOQZEGI-UHFFFAOYSA-N osmium atom Chemical compound [Os] SYQBFIAQOQZEGI-UHFFFAOYSA-N 0.000 description 1
- 230000003204 osmotic effect Effects 0.000 description 1
- 208000021284 ovarian germ cell tumor Diseases 0.000 description 1
- 239000003002 pH adjusting agent Substances 0.000 description 1
- 238000004806 packaging method and process Methods 0.000 description 1
- 229910052763 palladium Inorganic materials 0.000 description 1
- 230000009996 pancreatic endocrine effect Effects 0.000 description 1
- 208000021255 pancreatic insulinoma Diseases 0.000 description 1
- 230000005298 paramagnetic effect Effects 0.000 description 1
- 238000010827 pathological analysis Methods 0.000 description 1
- 235000010987 pectin Nutrition 0.000 description 1
- 239000001814 pectin Substances 0.000 description 1
- 229920001277 pectin Polymers 0.000 description 1
- 229960000292 pectin Drugs 0.000 description 1
- QGVYYLZOAMMKAH-UHFFFAOYSA-N pegnivacogin Chemical compound COCCOC(=O)NCCCCC(NC(=O)OCCOC)C(=O)NCCCCCCOP(=O)(O)O QGVYYLZOAMMKAH-UHFFFAOYSA-N 0.000 description 1
- 229940049954 penicillin Drugs 0.000 description 1
- JLFNLZLINWHATN-UHFFFAOYSA-N pentaethylene glycol Chemical compound OCCOCCOCCOCCOCCO JLFNLZLINWHATN-UHFFFAOYSA-N 0.000 description 1
- 210000005105 peripheral blood lymphocyte Anatomy 0.000 description 1
- 230000008782 phagocytosis Effects 0.000 description 1
- 239000011129 pharmaceutical packaging material Substances 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 235000021317 phosphate Nutrition 0.000 description 1
- 125000002467 phosphate group Chemical group [H]OP(=O)(O[H])O[*] 0.000 description 1
- 150000003013 phosphoric acid derivatives Chemical class 0.000 description 1
- 239000003757 phosphotransferase inhibitor Substances 0.000 description 1
- 239000006187 pill Substances 0.000 description 1
- 229960004403 pixantrone Drugs 0.000 description 1
- PEZPMAYDXJQYRV-UHFFFAOYSA-N pixantrone Chemical compound O=C1C2=CN=CC=C2C(=O)C2=C1C(NCCN)=CC=C2NCCN PEZPMAYDXJQYRV-UHFFFAOYSA-N 0.000 description 1
- 229960003171 plicamycin Drugs 0.000 description 1
- 229960000502 poloxamer Drugs 0.000 description 1
- 229920000962 poly(amidoamine) Polymers 0.000 description 1
- 229920001481 poly(stearyl methacrylate) Polymers 0.000 description 1
- 239000004584 polyacrylic acid Substances 0.000 description 1
- 230000008488 polyadenylation Effects 0.000 description 1
- 229920002721 polycyanoacrylate Polymers 0.000 description 1
- 229960001298 polyestradiol phosphate Drugs 0.000 description 1
- 229920000573 polyethylene Polymers 0.000 description 1
- 229920005644 polyethylene terephthalate glycol copolymer Polymers 0.000 description 1
- 229920001721 polyimide Polymers 0.000 description 1
- 235000010486 polyoxyethylene sorbitan monolaurate Nutrition 0.000 description 1
- 239000000256 polyoxyethylene sorbitan monolaurate Substances 0.000 description 1
- 229920001282 polysaccharide Polymers 0.000 description 1
- 239000005017 polysaccharide Substances 0.000 description 1
- 150000004804 polysaccharides Chemical class 0.000 description 1
- 229920000136 polysorbate Polymers 0.000 description 1
- 229950008882 polysorbate Drugs 0.000 description 1
- 229920002223 polystyrene Polymers 0.000 description 1
- 239000004814 polyurethane Substances 0.000 description 1
- 229920002635 polyurethane Polymers 0.000 description 1
- 229920002451 polyvinyl alcohol Polymers 0.000 description 1
- 229940068984 polyvinyl alcohol Drugs 0.000 description 1
- 235000019422 polyvinyl alcohol Nutrition 0.000 description 1
- 235000013809 polyvinylpolypyrrolidone Nutrition 0.000 description 1
- 229920000523 polyvinylpolypyrrolidone Polymers 0.000 description 1
- 229920006316 polyvinylpyrrolidine Polymers 0.000 description 1
- 239000013641 positive control Substances 0.000 description 1
- 239000001103 potassium chloride Substances 0.000 description 1
- 235000011164 potassium chloride Nutrition 0.000 description 1
- LWIHDJKSTIGBAC-UHFFFAOYSA-K potassium phosphate Substances [K+].[K+].[K+].[O-]P([O-])([O-])=O LWIHDJKSTIGBAC-UHFFFAOYSA-K 0.000 description 1
- 229920001592 potato starch Polymers 0.000 description 1
- 229940069328 povidone Drugs 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 229920003124 powdered cellulose Polymers 0.000 description 1
- 235000019814 powdered cellulose Nutrition 0.000 description 1
- 238000001556 precipitation Methods 0.000 description 1
- 239000002243 precursor Chemical class 0.000 description 1
- 230000013823 prenylation Effects 0.000 description 1
- 239000000955 prescription drug Substances 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 150000003141 primary amines Chemical class 0.000 description 1
- 210000001236 prokaryotic cell Anatomy 0.000 description 1
- 230000035755 proliferation Effects 0.000 description 1
- 230000002035 prolonged effect Effects 0.000 description 1
- 230000001737 promoting effect Effects 0.000 description 1
- 238000002731 protein assay Methods 0.000 description 1
- 238000000734 protein sequencing Methods 0.000 description 1
- 230000003161 proteinsynthetic effect Effects 0.000 description 1
- 230000017854 proteolysis Effects 0.000 description 1
- PTJWIQPHWPFNBW-GBNDHIKLSA-N pseudouridine Chemical compound O[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1C1=CNC(=O)NC1=O PTJWIQPHWPFNBW-GBNDHIKLSA-N 0.000 description 1
- 235000021251 pulses Nutrition 0.000 description 1
- BOGFADYROAVVTF-UHFFFAOYSA-N pyrindamycin A Natural products COC1=C(OC)C(OC)=C2NC(C(=O)N3CC(CCl)C=4C5=C(C(=CC=43)O)NC(C5=O)(C)C(=O)OC)=CC2=C1 BOGFADYROAVVTF-UHFFFAOYSA-N 0.000 description 1
- ILRQRCTVPANBBE-UHFFFAOYSA-N pyrindamycin B Natural products COC1=C(OC)C(OC)=C2NC(C(=O)N3CC(Cl)CC=4C5=C(C(=CC=43)O)NC(C5=O)(C)C(=O)OC)=CC2=C1 ILRQRCTVPANBBE-UHFFFAOYSA-N 0.000 description 1
- 230000006340 racemization Effects 0.000 description 1
- 230000002285 radioactive effect Effects 0.000 description 1
- 238000000163 radioactive labelling Methods 0.000 description 1
- 238000003127 radioimmunoassay Methods 0.000 description 1
- 238000001959 radiotherapy Methods 0.000 description 1
- 229960004622 raloxifene Drugs 0.000 description 1
- GZUITABIAKMVPG-UHFFFAOYSA-N raloxifene Chemical compound C1=CC(O)=CC=C1C1=C(C(=O)C=2C=CC(OCCN3CCCCC3)=CC=2)C2=CC=C(O)C=C2S1 GZUITABIAKMVPG-UHFFFAOYSA-N 0.000 description 1
- 210000000664 rectum Anatomy 0.000 description 1
- 235000003499 redwood Nutrition 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 229910052703 rhodium Inorganic materials 0.000 description 1
- 239000010948 rhodium Substances 0.000 description 1
- MHOVAHRLVXNVSD-UHFFFAOYSA-N rhodium atom Chemical compound [Rh] MHOVAHRLVXNVSD-UHFFFAOYSA-N 0.000 description 1
- 102200004932 rs76764689 Human genes 0.000 description 1
- 229940102127 rubidium chloride Drugs 0.000 description 1
- VHXNKPBCCMUMSW-FQEVSTJZSA-N rubitecan Chemical compound C1=CC([N+]([O-])=O)=C2C=C(CN3C4=CC5=C(C3=O)COC(=O)[C@]5(O)CC)C4=NC2=C1 VHXNKPBCCMUMSW-FQEVSTJZSA-N 0.000 description 1
- 229950009213 rubitecan Drugs 0.000 description 1
- CVHZOJJKTDOEJC-UHFFFAOYSA-N saccharin Chemical compound C1=CC=C2C(=O)NS(=O)(=O)C2=C1 CVHZOJJKTDOEJC-UHFFFAOYSA-N 0.000 description 1
- 235000002020 sage Nutrition 0.000 description 1
- 229960000581 salicylamide Drugs 0.000 description 1
- 229920006395 saturated elastomer Polymers 0.000 description 1
- 229910052706 scandium Inorganic materials 0.000 description 1
- SIXSYDAISGFNSX-UHFFFAOYSA-N scandium atom Chemical compound [Sc] SIXSYDAISGFNSX-UHFFFAOYSA-N 0.000 description 1
- 230000007017 scission Effects 0.000 description 1
- CDAISMWEOUEBRE-UHFFFAOYSA-N scyllo-inosotol Natural products OC1C(O)C(O)C(O)C(O)C1O CDAISMWEOUEBRE-UHFFFAOYSA-N 0.000 description 1
- 239000000333 selective estrogen receptor modulator Substances 0.000 description 1
- 229910052711 selenium Inorganic materials 0.000 description 1
- 239000011669 selenium Substances 0.000 description 1
- 239000004065 semiconductor Substances 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 238000002864 sequence alignment Methods 0.000 description 1
- 238000012163 sequencing technique Methods 0.000 description 1
- 238000004904 shortening Methods 0.000 description 1
- 239000000377 silicon dioxide Substances 0.000 description 1
- 229920002545 silicone oil Polymers 0.000 description 1
- 229910052709 silver Inorganic materials 0.000 description 1
- 239000004332 silver Substances 0.000 description 1
- 210000000813 small intestine Anatomy 0.000 description 1
- 210000002460 smooth muscle Anatomy 0.000 description 1
- 108010047846 soblidotin Proteins 0.000 description 1
- DZMVCVHATYROOS-ZBFGKEHZSA-N soblidotin Chemical compound CC(C)[C@H](N(C)C)C(=O)N[C@@H](C(C)C)C(=O)N(C)[C@@H]([C@@H](C)CC)[C@H](OC)CC(=O)N1CCC[C@H]1[C@H](OC)[C@@H](C)C(=O)NCCC1=CC=CC=C1 DZMVCVHATYROOS-ZBFGKEHZSA-N 0.000 description 1
- 229960003885 sodium benzoate Drugs 0.000 description 1
- 235000017557 sodium bicarbonate Nutrition 0.000 description 1
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
- 229940080237 sodium caseinate Drugs 0.000 description 1
- 239000001509 sodium citrate Substances 0.000 description 1
- NLJMYIDDQXHKNR-UHFFFAOYSA-K sodium citrate Chemical compound O.O.[Na+].[Na+].[Na+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O NLJMYIDDQXHKNR-UHFFFAOYSA-K 0.000 description 1
- 235000011083 sodium citrates Nutrition 0.000 description 1
- 238000002415 sodium dodecyl sulfate polyacrylamide gel electrophoresis Methods 0.000 description 1
- 235000010267 sodium hydrogen sulphite Nutrition 0.000 description 1
- 235000011121 sodium hydroxide Nutrition 0.000 description 1
- 239000001540 sodium lactate Substances 0.000 description 1
- 235000011088 sodium lactate Nutrition 0.000 description 1
- 229940005581 sodium lactate Drugs 0.000 description 1
- RYYKJJJTJZKILX-UHFFFAOYSA-M sodium octadecanoate Chemical compound [Na+].CCCCCCCCCCCCCCCCCC([O-])=O RYYKJJJTJZKILX-UHFFFAOYSA-M 0.000 description 1
- 239000001488 sodium phosphate Substances 0.000 description 1
- 229910000162 sodium phosphate Inorganic materials 0.000 description 1
- 235000011008 sodium phosphates Nutrition 0.000 description 1
- 229940045902 sodium stearyl fumarate Drugs 0.000 description 1
- 235000010339 sodium tetraborate Nutrition 0.000 description 1
- AKHNMLFCWUSKQB-UHFFFAOYSA-L sodium thiosulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=S AKHNMLFCWUSKQB-UHFFFAOYSA-L 0.000 description 1
- 235000019345 sodium thiosulphate Nutrition 0.000 description 1
- 239000008279 sol Substances 0.000 description 1
- 239000007909 solid dosage form Substances 0.000 description 1
- 238000002764 solid phase assay Methods 0.000 description 1
- 239000006104 solid solution Substances 0.000 description 1
- 238000005063 solubilization Methods 0.000 description 1
- 230000007928 solubilization Effects 0.000 description 1
- NHXLMOGPVYXJNR-ATOGVRKGSA-N somatostatin Chemical class C([C@H]1C(=O)N[C@H](C(N[C@@H](CO)C(=O)N[C@@H](CSSC[C@@H](C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC=2C=CC=CC=2)C(=O)N[C@@H](CC=2C=CC=CC=2)C(=O)N[C@@H](CC=2C3=CC=CC=C3NC=2)C(=O)N[C@@H](CCCCN)C(=O)N[C@H](C(=O)N1)[C@@H](C)O)NC(=O)CNC(=O)[C@H](C)N)C(O)=O)=O)[C@H](O)C)C1=CC=CC=C1 NHXLMOGPVYXJNR-ATOGVRKGSA-N 0.000 description 1
- JNYAEWCLZODPBN-CTQIIAAMSA-N sorbitan Polymers OCC(O)C1OCC(O)[C@@H]1O JNYAEWCLZODPBN-CTQIIAAMSA-N 0.000 description 1
- 229940035044 sorbitan monolaurate Drugs 0.000 description 1
- 229940083466 soybean lecithin Drugs 0.000 description 1
- 235000012424 soybean oil Nutrition 0.000 description 1
- 239000003549 soybean oil Substances 0.000 description 1
- 229950007213 spartalizumab Drugs 0.000 description 1
- 241000894007 species Species 0.000 description 1
- 238000003153 stable transfection Methods 0.000 description 1
- 238000010561 standard procedure Methods 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 150000003431 steroids Chemical class 0.000 description 1
- 229960005322 streptomycin Drugs 0.000 description 1
- 229910052712 strontium Inorganic materials 0.000 description 1
- CIOAGBVUUVVLOB-UHFFFAOYSA-N strontium atom Chemical compound [Sr] CIOAGBVUUVVLOB-UHFFFAOYSA-N 0.000 description 1
- 229960002317 succinimide Drugs 0.000 description 1
- 230000019635 sulfation Effects 0.000 description 1
- 238000005670 sulfation reaction Methods 0.000 description 1
- 125000000020 sulfo group Chemical group O=S(=O)([*])O[H] 0.000 description 1
- 239000011593 sulfur Substances 0.000 description 1
- 150000003467 sulfuric acid derivatives Chemical class 0.000 description 1
- 239000013595 supernatant sample Substances 0.000 description 1
- 238000013268 sustained release Methods 0.000 description 1
- 239000012730 sustained-release form Substances 0.000 description 1
- 230000008961 swelling Effects 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 229920001059 synthetic polymer Polymers 0.000 description 1
- 229940037128 systemic glucocorticoids Drugs 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- 229950003999 tafluposide Drugs 0.000 description 1
- 229960001603 tamoxifen Drugs 0.000 description 1
- 229910052715 tantalum Inorganic materials 0.000 description 1
- GUVRBAGPIYLISA-UHFFFAOYSA-N tantalum atom Chemical compound [Ta] GUVRBAGPIYLISA-UHFFFAOYSA-N 0.000 description 1
- 229940095064 tartrate Drugs 0.000 description 1
- WBWWGRHZICKQGZ-GIHLXUJPSA-N taurocholic acid 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)NCCS(O)(=O)=O)C)[C@@]2(C)[C@H](O)C1 WBWWGRHZICKQGZ-GIHLXUJPSA-N 0.000 description 1
- 229940126625 tavolimab Drugs 0.000 description 1
- 229940063683 taxotere Drugs 0.000 description 1
- 150000003573 thiols Chemical class 0.000 description 1
- 150000004764 thiosulfuric acid derivatives Chemical class 0.000 description 1
- 210000001578 tight junction Anatomy 0.000 description 1
- 229910052718 tin Inorganic materials 0.000 description 1
- MNRILEROXIRVNJ-UHFFFAOYSA-N tioguanine Chemical compound N1C(N)=NC(=S)C2=NC=N[C]21 MNRILEROXIRVNJ-UHFFFAOYSA-N 0.000 description 1
- 229960003087 tioguanine Drugs 0.000 description 1
- 229910052719 titanium Inorganic materials 0.000 description 1
- 239000010936 titanium Substances 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
- 229960005026 toremifene Drugs 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- 235000010487 tragacanth Nutrition 0.000 description 1
- 239000000196 tragacanth Substances 0.000 description 1
- 229940116362 tragacanth Drugs 0.000 description 1
- DQFBYFPFKXHELB-VAWYXSNFSA-N trans-chalcone Chemical compound C=1C=CC=CC=1C(=O)\C=C\C1=CC=CC=C1 DQFBYFPFKXHELB-VAWYXSNFSA-N 0.000 description 1
- 238000012546 transfer Methods 0.000 description 1
- 230000001131 transforming effect Effects 0.000 description 1
- 230000009261 transgenic effect Effects 0.000 description 1
- 102000003601 transglutaminase Human genes 0.000 description 1
- 238000013519 translation Methods 0.000 description 1
- 230000014621 translational initiation Effects 0.000 description 1
- 229940117013 triethanolamine oleate Drugs 0.000 description 1
- 239000001069 triethyl citrate Substances 0.000 description 1
- VMYFZRTXGLUXMZ-UHFFFAOYSA-N triethyl citrate Natural products CCOC(=O)C(O)(C(=O)OCC)C(=O)OCC VMYFZRTXGLUXMZ-UHFFFAOYSA-N 0.000 description 1
- 235000013769 triethyl citrate Nutrition 0.000 description 1
- PHYFQTYBJUILEZ-IUPFWZBJSA-N triolein Chemical compound CCCCCCCC\C=C/CCCCCCCC(=O)OCC(OC(=O)CCCCCCC\C=C/CCCCCCCC)COC(=O)CCCCCCC\C=C/CCCCCCCC PHYFQTYBJUILEZ-IUPFWZBJSA-N 0.000 description 1
- BSVBQGMMJUBVOD-UHFFFAOYSA-N trisodium borate Chemical compound [Na+].[Na+].[Na+].[O-]B([O-])[O-] BSVBQGMMJUBVOD-UHFFFAOYSA-N 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
- 230000005748 tumor development Effects 0.000 description 1
- 230000002100 tumorsuppressive effect Effects 0.000 description 1
- WFKWXMTUELFFGS-UHFFFAOYSA-N tungsten Chemical compound [W] WFKWXMTUELFFGS-UHFFFAOYSA-N 0.000 description 1
- 229910052721 tungsten Inorganic materials 0.000 description 1
- 239000010937 tungsten Substances 0.000 description 1
- 238000010798 ubiquitination Methods 0.000 description 1
- 230000034512 ubiquitination Effects 0.000 description 1
- 241000712461 unidentified influenza virus Species 0.000 description 1
- DRTQHJPVMGBUCF-UHFFFAOYSA-N uracil arabinoside Natural products OC1C(O)C(CO)OC1N1C(=O)NC(=O)C=C1 DRTQHJPVMGBUCF-UHFFFAOYSA-N 0.000 description 1
- 229940045145 uridine Drugs 0.000 description 1
- GPPXJZIENCGNKB-UHFFFAOYSA-N vanadium Chemical compound [V]#[V] GPPXJZIENCGNKB-UHFFFAOYSA-N 0.000 description 1
- 239000003981 vehicle Substances 0.000 description 1
- JNAHVYVRKWKWKQ-CYBMUJFWSA-N veliparib Chemical compound N=1C2=CC=CC(C(N)=O)=C2NC=1[C@@]1(C)CCCN1 JNAHVYVRKWKWKQ-CYBMUJFWSA-N 0.000 description 1
- 239000001993 wax Substances 0.000 description 1
- 230000003442 weekly effect Effects 0.000 description 1
- 230000004580 weight loss Effects 0.000 description 1
- 238000001262 western blot Methods 0.000 description 1
- 239000002023 wood Substances 0.000 description 1
- 239000000811 xylitol Substances 0.000 description 1
- 235000010447 xylitol Nutrition 0.000 description 1
- HEBKCHPVOIAQTA-SCDXWVJYSA-N xylitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)CO HEBKCHPVOIAQTA-SCDXWVJYSA-N 0.000 description 1
- 229960002675 xylitol Drugs 0.000 description 1
- 229940055760 yervoy Drugs 0.000 description 1
- UHVMMEOXYDMDKI-JKYCWFKZSA-L zinc;1-(5-cyanopyridin-2-yl)-3-[(1s,2s)-2-(6-fluoro-2-hydroxy-3-propanoylphenyl)cyclopropyl]urea;diacetate Chemical compound [Zn+2].CC([O-])=O.CC([O-])=O.CCC(=O)C1=CC=C(F)C([C@H]2[C@H](C2)NC(=O)NC=2N=CC(=CC=2)C#N)=C1O UHVMMEOXYDMDKI-JKYCWFKZSA-L 0.000 description 1
- 229910052726 zirconium Inorganic materials 0.000 description 1
Images
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
- C07K16/18—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
- C07K16/28—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
- A61K31/513—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim having oxo groups directly attached to the heterocyclic ring, e.g. cytosine
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/555—Heterocyclic compounds containing heavy metals, e.g. hemin, hematin, melarsoprol
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/7028—Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages
- A61K31/7034—Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages attached to a carbocyclic compound, e.g. phloridzin
- A61K31/704—Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages attached to a carbocyclic compound, e.g. phloridzin attached to a condensed carbocyclic ring system, e.g. sennosides, thiocolchicosides, escin, daunorubicin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K39/395—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K2039/505—Medicinal preparations containing antigens or antibodies comprising antibodies
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/20—Immunoglobulins specific features characterized by taxonomic origin
- C07K2317/24—Immunoglobulins specific features characterized by taxonomic origin containing regions, domains or residues from different species, e.g. chimeric, humanized or veneered
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/30—Immunoglobulins specific features characterized by aspects of specificity or valency
- C07K2317/33—Crossreactivity, e.g. for species or epitope, or lack of said crossreactivity
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/50—Immunoglobulins specific features characterized by immunoglobulin fragments
- C07K2317/52—Constant or Fc region; Isotype
- C07K2317/524—CH2 domain
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/50—Immunoglobulins specific features characterized by immunoglobulin fragments
- C07K2317/52—Constant or Fc region; Isotype
- C07K2317/526—CH3 domain
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/50—Immunoglobulins specific features characterized by immunoglobulin fragments
- C07K2317/56—Immunoglobulins specific features characterized by immunoglobulin fragments variable (Fv) region, i.e. VH and/or VL
- C07K2317/565—Complementarity determining region [CDR]
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/50—Immunoglobulins specific features characterized by immunoglobulin fragments
- C07K2317/56—Immunoglobulins specific features characterized by immunoglobulin fragments variable (Fv) region, i.e. VH and/or VL
- C07K2317/567—Framework region [FR]
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/70—Immunoglobulins specific features characterized by effect upon binding to a cell or to an antigen
- C07K2317/72—Increased effector function due to an Fc-modification
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/70—Immunoglobulins specific features characterized by effect upon binding to a cell or to an antigen
- C07K2317/73—Inducing cell death, e.g. apoptosis, necrosis or inhibition of cell proliferation
- C07K2317/732—Antibody-dependent cellular cytotoxicity [ADCC]
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/70—Immunoglobulins specific features characterized by effect upon binding to a cell or to an antigen
- C07K2317/73—Inducing cell death, e.g. apoptosis, necrosis or inhibition of cell proliferation
- C07K2317/734—Complement-dependent cytotoxicity [CDC]
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/70—Immunoglobulins specific features characterized by effect upon binding to a cell or to an antigen
- C07K2317/77—Internalization into the cell
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/90—Immunoglobulins specific features characterized by (pharmaco)kinetic aspects or by stability of the immunoglobulin
- C07K2317/92—Affinity (KD), association rate (Ka), dissociation rate (Kd) or EC50 value
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Medicinal Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Organic Chemistry (AREA)
- Immunology (AREA)
- Public Health (AREA)
- Animal Behavior & Ethology (AREA)
- Veterinary Medicine (AREA)
- Pharmacology & Pharmacy (AREA)
- Molecular Biology (AREA)
- Epidemiology (AREA)
- Genetics & Genomics (AREA)
- Biophysics (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Biochemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Microbiology (AREA)
- Mycology (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
- Peptides Or Proteins (AREA)
- Medicinal Preparation (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Abstract
Description
本出願は、2018年12月7日に出願された特許協力条約出願第PCT/CN2018/119797号の優先権を主張する。当該出願は、参照することにより、すべての目的のため、全体として本明細書に組み込まれる。
ある特定の実施形態では、本明細書に開示するのは、抗クローディン18.2(抗CLDN18.2)抗体である。いくつかの例では、抗CLDN18.2抗体は、CLDN18.2の細胞外ドメインに結合する。場合によっては、該抗CLDN18.2抗体は、CLDN18.2の第一の細胞外ドメインに結合する。場合によっては、該抗CLDN18.2抗体は、該CLDN18.2の第一の細胞外ドメイン内の8残基領域、例えば、ヒトCLDN18.2(UniProtKB識別子P56856-2)の残基32~41に結合する。いくつかの実施形態では、参照抗CLDN18.2抗体とは異なる機能特性を有する、及び/またはCLDN18.2のアイソフォームに対する選択性を有する1つ以上の突然変異を翻訳後修飾部位に含む抗CLDN18.2抗体もまた本明細書に記載する。
いくつかの実施形態では、抗CLDN18.2抗体は、産生動物に抗原組成物を注射することによる標準的な方法で産生される。例えば、Harlow and Lane,Antibodies:A Laboratory Manual,Cold Spring Harbor Laboratory,1988を参照されたい。タンパク質全体、または該タンパク質の大部分を使用する場合、抗体は、該産生動物に、該タンパク質及び適切なアジュバント(例えば、フロイントアジュバント、完全フロイントアジュバント、水中油エマルション等)で免疫付与することによって産生され得る。小さいペプチドを使用する場合、該ペプチドを大きな分子とコンジュゲートさせ、免疫賦活コンジュゲートを作製することが有利である。かかる使用のための市販の一般的に使用されているコンジュゲートタンパク質としては、ウシ血清アルブミン(BSA)及びキーホールリンペットヘモシアニン(KLH)が挙げられる。特定のエピトープに対する抗体を産生するために、完全な配列に由来するペプチドを使用することができる。別の方法として、タンパク質標的の比較的短いペプチド部分に対する抗体を産生するためには、ポリペプチドが卵白アルブミン、BSAまたはKLH等の担体タンパク質に結合されている場合に優れた免疫応答が誘発され得る。
いくつかの実施形態では、本開示は、本明細書に開示する抗CLDN18.2抗体のいずれかをコードする単離された核酸を提供する。別の実施形態では、本開示は、本明細書に開示する任意の抗CLDN18.2抗体をコードする核酸配列を含むベクターを提供する。いくつかの実施形態では、本発明は、本明細書に開示する抗CLDN18.2抗体の軽鎖CDR及び重鎖CDRをコードする単離された核酸を提供する。
いくつかの実施形態では、本開示は、本明細書に開示する抗CLDN18.2抗体のいずれか1つを発現する宿主細胞を提供する。対象の宿主細胞は、通常、本明細書に開示する抗CLDN18.2抗体のいずれか1つをコードする核酸を含む。
いくつかの実施形態では、本明細書に記載の抗CLDN18.2抗体は、さらにペイロードにコンジュゲートされる。いくつかの例では、該ペイロードは、該抗CLDN18.2抗体に直接コンジュゲートされる。他の例では、該ペイロードは、該抗CLDN18.2抗体にリンカーを介して間接的にコンジュゲートされる。場合によっては、該ペイロードは、小分子、タンパク質もしくはその機能的断片、ペプチド、または核酸ポリマーを含む。
いくつかの例では、該ペイロードは、ネイティブライゲーションによって本明細書に記載の抗CLDN18.2抗体にコンジュゲートされる。いくつかの例では、該コンジュゲーションは、以下に記載のものである:Dawson,et al.“Synthesis of proteins by native chemical ligation,”Science 1994,266,776-779、Dawson,et al.“Modulation of Reactivity in Native Chemical Ligation through the Use of Thiol Additives,”J.Am.Chem.Soc.1997,119,4325-4329、Hackeng,et al.“Protein synthesis by native chemical ligation:Expanded scope by using straightforward methodology.,”Proc.Natl.Acad.Sci.USA 1999, 96, 10068-10073、またはWu,et al.“Building complex glycopeptides:Development of a cysteine-free native chemical ligation protocol,”Angew.Chem.Int.Ed.2006, 45, 4116-4125。いくつかの例では、該コンジュゲーションは、米国特許第8,936,910号に記載のものである。
いくつかの例では、上記のリンカーは、分岐もしくは非分岐モノマーの長鎖、及び/または二次元もしくは三次元のモノマーの架橋ネットワークからなる天然または合成ポリマーを含む。いくつかの例では、該リンカーは、多糖類、リグニン、ゴム、またはポリアルキレンオキシド(例えば、ポリエチレングリコール)を含む。
ある特定の実施形態では、本明細書に開示するのは、CLDN18.2タンパク質の過剰発現を特徴とするがんを有する対象の治療方法である。場合によっては、該方法は、該対象に対して、本明細書に記載の抗CLDN18.2抗体、または抗CLDN18.2抗体を含む医薬組成物を投与し、該対象における該がんを治療することを含む。場合によっては、該がんは消化管癌である。例示的な消化管癌としては、食道、胆嚢及び胆道、肝臓、膵臓、胃、小腸、大腸、結腸、直腸、及び/または肛門の癌が挙げられる。
いくつかの実施形態では、抗CLDN18.2抗体は、さらに、医薬組成物として製剤化される。いくつかの例では、該医薬組成物は、非経口(例えば、静脈内、皮下、筋肉内、動脈内、皮内、腹腔内、硝子体内、脳内、もしくは脳室内)、経口、鼻腔内、口腔内、直腸、または経皮投与経路が挙げられるが、これらに限定されない複数の投与経路での対象への投与用に製剤化される。いくつかの例では、本明細書に記載の医薬組成物は、非経口(例えば、静脈内、皮下、筋肉内、動脈内、皮内、腹腔内、硝子体内、脳内、もしくは脳室内)投与用に製剤化される。他の例では、本明細書に記載の医薬組成物は、経口投与用に製剤化される。さらに他の例では、本明細書に記載の医薬組成物は、鼻腔内投与用に製剤化される。
いくつかの実施形態では、本明細書に記載の医薬組成物は、治療への応用のために投与される。いくつかの実施形態では、該医薬組成物は、1日1回、1日2回、1日3回、またはそれを超えて投与される。該医薬組成物は、毎日(daily)、毎日(every day)、1日おき、週5日、週1回、1週おき、月2週間、月3週間、月1回、月2回、月3回、またはそれを超えて投与される。該医薬組成物は、少なくとも1ヶ月、2ヶ月、3ヶ月、4ヶ月、5ヶ月、6ヶ月、7ヶ月、8ヶ月、9ヶ月、10ヶ月、11ヶ月、12ヶ月、18ヶ月、2年、3年、またはそれを超えて投与される。
ある特定の実施形態では、本明細書に開示するのは、本明細書に記載の組成物及び方法のうちの1つ以上とともに用いるキット及び製品である。かかるキットは、担体、包装、または容器を含み、これは、バイアル、チューブ等の1つ以上の容器を受けるように区切られ、該容器(複数可)の各々は、本明細書に記載の方法に用いられる別々の要素のうちの1つを含む。適切な容器としては、例えば、ボトル、バイアル、シリンジ、及び試験管が挙げられる。1つの実施形態では、該容器は、ガラスまたはプラスチック等の多様な材料から形成される。
特に定義されない限り、本明細書で使用されるすべての技術用語及び科学用語は、特許請求の範囲に記載された対象が属する当業者が通常理解するものと同じ意味を有する。前述の一般的な説明及び以下の詳細な説明は、例示的かつ説明的なものであるにすぎず、特許請求の範囲に記載された対象を限定するものではないと理解するべきである。本出願では、単数形の使用は、別途明確に記述されない限り、複数形を含む。本明細書及び添付の特許請求の範囲で使用される、単数形「a」、「an」、及び「the」は、文脈上別途明確に指示されない限り、複数の指示対象を含むことに留意されなければならない。本出願では、「または」の使用は、別途記載のない限り、「及び/または」を意味する。更に、「含むこと(including)」という用語、ならびに他の形態、例えば、「含む(include)」、「含む(includes)」、及び「含まれる(included)」の使用は、限定的でない。
CLDN18.2を過剰発現するHEK293及びCHO細胞は、免疫付与及びスクリーニング目的で、NovoBioSci及びGenomeditechで生成された。CLDN18.2を発現するHEK293細胞は、IRESによってGFPと共発現させた。GFP及びCLDN18.2の発現は、CLDN18(ab203563)に対する市販の蛍光標識抗体で染色することにより実証した(図1)。CHO細胞でのCLDN18.2の発現は、DNAシーケンシングによって確認した。
抗体を産生するためのラットの免疫付与は、以下の免疫付与スケジュールを使用して実施した(表10)。簡潔には、最初の2回の免疫付与では、2種類のDNA構築物、すなわち、細胞外ループ1(ECL1、図3)のみまたは完全長CLDN18.2(図2)DNAのいずれかを使用した。3回目の免疫付与は、CLDN18.2を過剰発現するHEK293細胞で行い、4回目の免疫付与は、対応するDNAを使用して、またはDNAとCLDN18.2を過剰発現する細胞を使用して行った。最終ブーストは、CLDN18.2を過剰発現するHEK293細胞で行った。4匹のラットを融合に使用した。
ハイブリドーマの上清は、CHO-CLDN18.2に特異的に結合した。合計80枚の96ウェルプレートに播種し、これらを、細胞ベースのELISAによって免疫付与動物のハイブリドーマからスクリーニングした。194個のクローンを、OD値>0.3に基づいて陽性と識別した。CLDN18.2に特異的に結合したがCLDN18.1には結合しなかった抗体を得るため、ラットまたは/及びマウスの改変細胞株、すなわち、CHO-CLDN18.1及びCHO-CLDN18.2での免疫付与由来のハイブリドーマをスクリーニングした。簡潔には、50μLのCHO-CLDN18.1またはCHO-CLDN18.2細胞(細胞密度:2×106細胞/mL、生存率>90%)を、等量のハイブリドーマ上清とともに96ウェルプレートにて4℃で1時間インキュベートした。FACS緩衝液(2%FBSを含むDPBS)で洗浄した後、その細胞/抗体混合物を二次抗体(ヤギ抗ラットIgG(H+L)iFlour647、Genscript、またはAlexa Flour(登録商標)647コンジュゲートウサギ抗マウスIgG、Jackson ImmunoResearch)で染色した。最後に、その混合物を洗浄し、FACS緩衝液に再懸濁し、BD FACSCelestaでFACS分析に供した。その生データを、FlowJoソフトウェアで分析した。
精製抗体を、上清からプロテインGアフィニティー精製によって生成した。簡潔には、ハイブリドーマ上清を8000rpm及び4℃にて30分間遠心分離した。次に、その上清を0.22μmの精密ろ過膜でろ過した。NaClをその上清に、10mLの上清に対して1gのNaClの比で加えた。この上清サンプルを4℃で毎分3mLの速度で精製カラムにロードした。プロテインGレジンを4~5カラム容量の1xPBSで平衡化し、その後溶出緩衝液(0.1MのTris、pH12)で洗浄した。中和緩衝液を、次に、溶出した抗体を含む収集チューブに直ちに加え、そのpHを中和した。次に、溶出した抗体を1xPBSに対して室温で2時間透析した。この抗体を、その後分析用に保存した。
ハイブリドーマ抗体の結合親和性をランク付けするために結合曲線を作成した。簡潔には、各ウェルに対して、合計1×105のCHO-CLDN18.2細胞を96ウェルプレートに播種し、FACS緩衝液(2%FBSを含むDPBS)で2回洗浄した。細胞を、連続希釈した精製ハイブリドーマ抗体で1時間インキュベートした。一次抗体のインキュベーション後、細胞をFACS緩衝液で2回洗浄した。次いで、細胞を、二次抗体(Alexa Flour(登録商標)647コンジュゲートウサギ抗マウスIgG、Jackson ImmunoResearch)で染色した。染色した細胞のAlexa Fluor647シグナルを、BD FACS Celestaで検出し、幾何平均蛍光シグナルを特定した。FlowJoソフトウェアを分析に使用した。データを、平均蛍光シグナルに対する抗体濃度の対数としてプロットした。非線形回帰分析を、GraphPad Prism 6(GraphPad Software)で行い、EC50値を計算した。
胃癌細胞株SNU601及びSNU620はCLDN18.2の内因性発現を有する。SNU601及びSNU620細胞でのCLDN18.2の発現を、CLDN18.2特異的プライマー及びDNAシーケンシングを使用したRT-PCRで確認した。高レベルのCLDN18.2を発現するSNU601及びSNU620細胞を結合アッセイのために選別した。結合アッセイは、前述のように行った。ラット産生クローン282A12及び101C6ならびに参照抗体175D10はすべて、胃癌株SNU601に結合したが、クローン282A12及び101C6は、SU620にも結合した(図5A及び図5B)。
マウス及びラットの抗体は、ヒトIgG1のシグナル配列及び定常領域のアミノ酸をコードするDNA配列を含むpCDNA3.1(+)プラスミドにおいて、マウス及びラットの軽鎖可変領域を発現させることによってキメラ化した。ヒトIgG1の重鎖及び軽鎖定常領域(CH及びCL)の配列を表4に示す。
時として、不均一性の増加、生物活性の低下、安定性の低下、免疫原性、断片化及び凝集等、治療用タンパク質の開発中に問題を引き起こす翻訳後修飾(PTM)について、ハイブリドーマ技術によって生成された抗体の配列を分析した。PTMの潜在的な影響は、PTMの場所によって決まり、場合によっては、溶剤への暴露によって決まる。すべての配列のCDRを、アスパラギンの脱アミノ化、アスパラギン酸の異性化、遊離システインのチオール基、N-グリコシル化、酸化、及び潜在的な加水分解部位による断片化について分析した。
CLDN18.2結合抗体のエピトープ結合基を調べるため、4つのキメラ抗体の競合的結合活性を、CHO-CLDN18.2細胞を使用して試験した。各抗体の作用濃度は、CHO-CLDN18.2細胞ベースの結合アッセイによって特定した。細胞を収集し、PBSで洗浄した後、1×105細胞を含む50μLのPBSを96ウェルプレートに加えた。試験抗体を、PBSにより、60μg/mLから3倍で12段階に連続希釈し、50μLの希釈抗体を細胞と混合し、4℃で120分間インキュベートした。その後、ウェルをPBSで洗浄した。競合結合アッセイでは、100μLのビオチン標識抗CLDN18.2抗体を作用濃度(それぞれ、5、1、0.5及び1μg/mLのxi175D10、282A12F3(T62A)、413H9F8-VL-S32V、及び364D1A7-VL-S32V)で加えた。ビオチン標識ヤギ抗ヒトIgGのFcを、1:800希釈で、100μL/ウェルにて対照として加えた。これらのプレートを4℃で40分間インキュベートした。ストレプトアビジン-APC(1:1700)を使用し、ビオチン標識抗体を検出した。フローサイトメトリーを実施し、結合を測定した。
種間交差反応性により、薬理学モデル(マウス)及び毒性モデル(カニクイザル)での臨床候補の評価が可能である。抗ヒトCLDN18.2抗体の種間交差反応性を、細胞ベースの結合アッセイによって特定した。同定されたモノクローナル抗体のマウス及びカニクイザルCLDN18.2への結合をフローサイトメトリーで分析した。HEK293細胞を、蛍光マーカーならびにマウスCLDN18.2及びカニクイザルCLDN18.2で一過性コトランスフェクトした。簡潔には、ディッシュあたり2.5×106のHEK-293細胞を、各ディッシュに対して10mLのDMEM培地を用いて、2枚の10cm2ディッシュに播種した。播種の24時間後、細胞をマウスGFP-CLDN18.2及びカニクイザルGFP-CLDN18.2プラスミドでトランスフェクトした。ディッシュあたり全プラスミド質量10μgを、20μLのLipofectamine2000(Life Technologies)を使用してトランスフェクトした。トランスフェクションの5時間後に培地を交換した。トランスフェクションの48時間後、細胞を解離させ、結合親和性検出用に調製した。ヒトCLDN18.2を発現する安定細胞株HEK293-GFP-CLDN18.2を使用し、ヒトGFP-CLDN18.2を検出した。
キメラ抗CLDN18.2抗体は、CHO-CLDN18.2細胞に対して特異的なADCCを誘導した。
いくつかの例では、腫瘍特異的mAbは、補体依存性細胞傷害(CDC)によってもそれらの効果を発揮する。ヒト血清及びCHO-CLDN18.2細胞株を使用して、キメラ抗体のCDC機能を検証した。3×104のCHO-CLDN18.2細胞50μLを、25μLの連続希釈キメラ抗ヒトCLDN18.2mAbと混合した。室温で15~30分間インキュベートした。25μLの40%ヒト血清を加え、最終血清濃度10%を得た。37℃、5%CO2にて30分間のインキュベーション後、1μg/mLのPI(Invitrogen)を加え、フローサイトメトリー(BD FACS Celesta)により分析した。
抗体282A12F3のヒト化
ヒト化抗体の結合親和性及び特異性を、FACS分析により、上記のCHO-CLDN18.1及びCHO-CLDN18.2細胞を用いて親抗体のものと比較した。図18~図18Bに示すように、hz282-3、hz282-4、hz282-8、hz282-10、hz282-11、hz282-12、hz282-15、hz282-19、及びhz282-10を含むヒト化282A12F3(T62A)クローンは、282A12F3(T62A)と同様の結合親和性をCHO-CLDN18.2に対して示した。CHO-CLDN18.1に結合したヒト化クローンはなかった。このデータは、ヒト化282A12F3(T62A)抗体が、CLDN18.2への結合特異性及び親和性を保持していたことを示している。
ヒト化抗体のCLDN18.2特異的ADCC活性を、上記のようにCHO-CLDN18.1及びCHO-CLDN18.2細胞株で検証した。図14A~図14Bに示すように、ヒト化抗体413H9F8-H1L1及び364D1A7-H1L1は、ADCC媒介性のCHO-CLDN18.2の溶解を誘導したが、CHO-CLDN18.1の溶解は誘導しなかった。これにより、ヒト化抗体が、それらの親抗体の標的特異性を保持していたことが示された。
*1ドナー由来のデータ。他のデータは3ドナーの平均である
重鎖が異なるG1m1(D356/L358)、G1m-1(E356/M358)、G1m3(R214)、及びG1m17(K214)を含むヒトIgG1の4つの主要なアロタイプがある。アロタイプは共優性のメンデルの法則で遺伝し、アフリカ人、白人、及びモンゴロイドの集団では様々な組み合わせが見られる(PMID:25368619、26685205)。これらの試験に含まれる抗CLDN18.2抗体は、D356/L358またはE356/M358のFcバリアントを有する。例えば、参照抗体Xi175D10には、D356/L358のFcバリアントを有する。D356/L358及びE356/M358のFcバリアントを有する抗体が同様のADCC活性を有することは注目に値する(データは示さず)。該FcのD356/L358を有する抗体を示すために「DL」の名称接尾辞を付加したが、E356/M358バリアントのものに関しては、特定の名称接尾辞を付加しなかった。S239D/I332E及びF243L/R292P/Y300L/V305I/P396Lの突然変異を含む様々なFcの改変法を開発し、抗体のエフェクター機能を高めている(PMID:29070978)。
ヒト化抗体バリアントのCDC活性を分析し、それらのCDC機能を上記のように親抗体と比較した。図26A~図26B及び表24に示すように、調べたヒト化413H9F8-VL-S32V及び364D1A7-VL-S32Vクローンのほとんどすべてが、それらの親抗体と比較して、それぞれ同様のCDC活性を示した。
腫瘍細胞による抗体の内在化を、37℃でインキュベートして抗体の内在化を誘導した後の抗体の細胞表面保持を検出することによって間接的に特定した。簡潔には、NUGC4-CLDN18.2及びNCI-N87-CLDN18.2細胞を収集し、洗浄緩衝液(1%FBSを含むPBS)で洗浄し、1×105細胞/50μLに調整した。抗体を20μg/mLに希釈し、50μLの希釈抗体を体積比1:1で細胞と混合した後、氷浴で30分間インキュベートした。細胞を予冷洗浄緩衝液で2回洗浄し、800μLの予冷洗浄緩衝液に再懸濁した。100μLの細胞懸濁液を96ウェルプレートに異なる時点で加え、37℃でインキュベートした。200μLの予冷洗浄緩衝液を加え、すべてのサンプルのエンドサイトーシス温度条件を終了した。氷浴でインキュベートしたサンプルを、内在化がないまたは最小限の対照として設定した。1回洗浄した後、100μL/ウェルの二次抗体(AF647-ヤギ抗ヒトIgGFcγ、Jackson、#109-606-170、1:800希釈)を加え、氷浴で30分間インキュベートした。細胞を予冷洗浄緩衝液で2回洗浄し、200μLの予冷洗浄緩衝液に再懸濁し、フローサイトメトリー(BD FACS Celesta)で分析した。
裸抗体175D10(xi175D10)、282A12F3(T62A)及びアイソタイプ対照抗体ヒトIgG1を、mc-vc-PAB-MMAE、すなわち、開裂可能なバリン-シトルリン(vc)リンカーを含むモノメチルアウリスタチンE(MMAE)誘導体にコンジュゲートした(図27)。簡潔には、抗体を4時間かけて4℃の冷蔵庫で解凍し、コンジュゲーション緩衝液(25mMのNa2B4O7、25mMのNaCl、1mMのDTPA、pH7.4)に対して4℃で終夜透析した。新たに調製したTCEP使用液(5mMのTCEPを含むシステイン-マレイミドコンジュゲーション緩衝液、TCEP-HCl)を加え、25℃の水浴で2時間インキュベートすることによって抗体を還元した。抗体は、新たに調製したmc-vc-PAB-MMAE(XDCExplorer)のDMSO(10mM)使用液で、6の比にて、10%v/vの有機溶媒(DMSO)の存在下、その混合物を25℃の水浴で2時間インキュベートしてコンジュゲートした。この抗体薬物コンジュゲーションを、L-ヒスチジン透析緩衝液(20mMのL-ヒスチジン、pH5.5)に対して4℃にて終夜透析した。透析緩衝液の交換を4時間後に1回行った。最終生成物を取り出し、0.2mフィルターでろ過し、品質をHIC-HPLCで分析した。HIC-HPLCの結果、すべてのコンジュゲートの薬物対抗体比(DAR)値が3.5~4.0の範囲であることが示された(表25)。TCEPのモル比の増加に伴い、ADCのDAR値も増加した。
xi-175D10-vcMMAE、282A12F3(T62A)-vcMMAE、及びhuIgG1-vcMMAE(3つの異なるDARを有する)ならびに対応する裸抗体の細胞毒性を、CLDN18.2を過剰発現するHEK29(HK293-CLDN18.2)細胞株で調べた。簡潔には、HK293-CLDN18.2細胞を、96ウェルプレートに播種し、37℃、5%CO2にて終夜増殖させた。裸抗体及びADCを4倍濃度(60μg/mL、400nM)で調製し、細胞増殖培地にて5倍連続希釈した。100μLの一次希釈液を100μLの培地と混合して2倍濃度にした。各複合希釈液50μLを、三連で細胞に加えた。細胞を37℃、5%CO2にて5日間インキュベートした。細胞毒性は、CellTiter Glo発光細胞生存アッセイキット(Promega)で特定した。100μl/ウェルのCellTiter Glo試薬を加え、細胞生存を読み取った。シェーカー上で室温にて10分間インキュベートし、Envisionで発光を記録した。
CLDN18.2を過剰発現する2つ胃癌細胞株、すなわち、NCI-N87-CLDN18.2及びNUGC4-CLDN18.2細胞を使用して、上記のようにADCの殺細胞活性を調べた。図29A~図29Bに示すように、細胞生存率は、ADC 282A12F3(T62A)-vcMMAE及びxi175D10-vcMMAEで処理した場合、濃度依存的に低下した。さらに、282A12(T62A)-vcMMAEのADCは、xi175D10-vcMMAEよりも高い殺細胞を誘導した。NUGC4-CLDN18.2は、NCI-N87-CLDN18.2細胞と比較して、ADCが誘導する細胞死に対する感受性が低かった。
CLDN18.2で安定にトランスフェクトし、キメラ282A12F3(T62A)が媒介するADCC効果に対する感受性が低いことが分かった(図30A)膵臓癌細胞株PANC-1-CLDN18.2を、ADC依存性殺細胞アッセイに使用した。図30Bに示すように、282A12F3(T62A)-vcMMAE及びxi175D10-vcMMAEの両方がPANC-1-CLDN18.2細胞の生存を濃度依存的に阻害し、282A12F3(T62A)-vcMMAEは、PANC-1-CLDN18.2細胞の細胞死の誘導において、xi175D10-vcMMAEよりも強力であった。
抗CLDN18.2抗体のインビボ効果を、ヌードマウスの患者由来異種移植(PDX)モデルで調べた。GA0006は、腺癌型、すなわち、多コピーERBB2の病理学的診断をされたアジア人の胃癌患者の胃から得た。GA0006でのCLDN18.2の高発現は、抗CLDN18.2抗体を用いたIHC及びFACS分析によって確認した(データは示さず)。BALB/cヌードマウスに、約3mm×3mm×3mmのサイズの腫瘍を右足首から皮下移植した。平均腫瘍サイズが約100mm3に達した時点で、マウスをランダムに8群(1群あたり8匹):PBS、hIgG1アイソタイプ(100mg/kg)、xi175D10-V2、413H9F8-H2L2-V2-DL及び413H9F8-cp2-V2-DL(50及び100mg/kg)に分けた。腫瘍体積の変動係数は40%未満であった。これは次式により計算した:CV=SD/MTV×100%。ランダム化の当日を0日目として記録した。マウスの処理を0日目に開始した。抗体を週3回、3週間にわたり、交互に静脈内注射と腹腔内注射で投与した。腫瘍サイズを週2回観察した。
抗CLDN18.2抗体のインビボ効果を、Nu/Nuマウスの膵臓癌の皮下異種移植モデルで調べた。CLDN18.2を過剰発現する膵臓癌細胞株MIA Paca-2(MIA Paca-2-CLDN18.2)を、10%ウシ胎児血清、2.5%馬血清、1%ペニシリン/ストレプトマイシン、5μg/mLのブラストサイジンを添加したDMEM培地中、37℃にて、5%CO2を含む空気の雰囲気中、単層培養としてインビトロで維持した。MIA Paca-2-CLDN18.2細胞を、トリプシン-EDTA処理により週2回定期的に継代培養した。指数増殖期に増殖中のMIA Paca-2-CLDN18.2細胞を回収し、腫瘍接種用に計数した。4~6週齢のNu/Nuヌードマウスの雌に、5×106のMIA Paca-2-CLDN18.2細胞を含む0.2mlのPBS(Matrigelを補充、PBS:Matrigel=1:1)を右脇腹から皮下移植し、腫瘍を成長させた。Paca-2-CLDN18.2担腫瘍Nu/Nuマウス(1群あたり10匹)の処理を腫瘍移植の3日後に開始した。抗CLDN18.2抗体(10及び40mg/kg)を、週2回、5週間にわたり、交互に静脈内注射と腹腔内注射で投与した。PBSまたはアイソタイプ(hIgG1、40mg/kg)で処理した担腫瘍Nu/Nuマウスを陰性対照として設定した。
PDXマウスモデルを上記のように確立した。マウスの処理を0日目に開始した。担腫瘍マウスをPBS、EOF(1.25mg/kgのエピルビシン、3.25mg/kgのオキサリプラチン及び56.25mg/kgの5-フルオロウラシル)、xi175D10-V2(40mg/kg)とEOFの組み合わせまたは413H9F8-H2L2-V2-DL(40mg/kg)とEOFの組み合わせで処理した。EOFは、週1回腹腔内に投与した。抗体を、週3回、交互に静脈内注射と腹腔内注射で投与した。腫瘍サイズを週2回観察した。合計で5回のEOF投与及び14回の抗体処理を行った。
Claims (97)
- 半数効果濃度(EC50)が、参照抗体175D10のEC50より低い抗クローディン18.2(抗CLDN18.2)抗体であって、前記参照抗体175D10は、配列番号98に記載の重鎖(HC)配列及び配列番号99に記載の軽鎖(LC)配列を含む、前記抗体。
- 翻訳後修飾部位に少なくとも1つの突然変異を含む抗クローディン18.2(抗CLDN18.2)抗体。
- Fc領域において抗体依存性細胞媒介性細胞傷害(ADCC)の向上をもたらす少なくとも1つの突然変異を含む抗クローディン18.2(抗CLDN18.2)抗体であって、前記ADCCの向上は、配列番号98に記載の重鎖(HC)配列及び配列番号99に記載の軽鎖(LC)配列を含む参照抗体175D10と比較される、前記抗体。
- 前記抗CLDN18.2抗体の前記EC50が、約5nM以下である、請求項1に記載の抗CLDN18.2抗体。
- 前記抗CLDN18.2抗体の前記EC50が、約5nM、約4nM、約3nM、約2nM、約1nM、約0.5nM、またはそれより低い、請求項1に記載の抗CLDN18.2抗体。
- CLDN18.2に対する結合親和性が、参照抗体175D10の結合親和性と比較して高い抗クローディン18.2(抗CLDN18.2)抗体であって、前記参照抗体175D10は、配列番号98に記載の重鎖(HC)配列及び配列番号99に記載の軽鎖(LC)配列を含む、前記抗体。
- 可変重鎖(VH)領域及び可変軽鎖(VL)領域を含む請求項1~6のいずれか1項に記載の抗CLDN18.2抗体であって、前記VH領域が、以下を含む、前記抗体:
CDR1配列GFSLTSYX1VX2、
ここで、X1は、NまたはGから選択され、X2は、YまたはHから選択されるもの、
CDR2配列VIWX3X4GX5TX6YX7X8X9LX10S、
ここで、X3は、NまたはPから選択され、X4は、TまたはGから選択され、X5は、AまたはNから選択され、X6は、RまたはNから選択され、X7は、N、Q、またはEから選択され、X8は、SまたはIから選択され、X9は、TまたはAから選択され、X10は、KまたはMから選択されるもの、及び
CDR3配列DX11X12X13X14X15X16X17X18X19X20、
ここで、X11は、SまたはRから選択され、X12は、AまたはRから選択され、X13は、MまたはLから選択され、X14は、PまたはAから選択され、X15は、AまたはMから選択され、X16は、IまたはDから選択され、X17は、PまたはYから選択され、X18は、存在するかまたは存在せず、存在する場合、Fであり、X19は、存在するかまたは存在せず、存在する場合、Aであり、X20は、存在するかまたは存在せず、存在する場合、Yであるもの。 - 前記VH領域が、以下を含む、請求項1~6のいずれか1項に記載の抗CLDN18.2抗体:
CDR1配列X21X22X23X24X25SFGMH、
ここで、X21は、存在するかまたは存在せず、存在する場合、Gであり、X22は、存在するかまたは存在せず、存在する場合、Fであり、X23は、存在するかまたは存在せず、存在する場合、Tであり、X24は、存在するかまたは存在せず、存在する場合、Fであり、X25は、存在するかまたは存在せず、存在する場合、Sであるもの、
CDR2配列YISSGSX26X27IYYX28DX29X30KG、
ここで、X26は、SまたはGから選択され、X27は、PまたはSから選択され、X28は、VまたはAから選択され、X29は、KまたはTから選択され、X30は、LまたはVから選択されるもの、及び
CDR3配列AX31X32X33X34X35X36X37X38X39X40X41、
ここで、X31は、GまたはTから選択され、X32は、YまたはSから選択され、X33は、AまたはYから選択され、X34は、VまたはYから選択され、X35は、RまたはYから選択され、X36は、NまたはGから選択され、X37は、AまたはNから選択され、X38は、LまたはAから選択され、X39は、DまたはLから選択され、X40は、YまたはEから選択され、X41は、存在するかまたは存在せず、存在する場合、Yであるもの。 - 前記VH領域が、配列番号1からなるCDR1配列、CDR2配列VIWNTGATRYX7SX9LKS、及び配列番号3からなるCDR3配列を含み、ここで、X7は、N、Q、またはEから選択され、X9は、TまたはAから選択される、請求項1~8のいずれか1項に記載の抗CLDN18.2抗体。
- 前記VH領域が、配列番号13からなるCDR1配列、CDR2配列VIWPGGNTNYX7X8ALMS、及び配列番号15からなるCDR3配列を含み、ここで、X7は、NまたはEから選択され、X8は、SまたはIから選択される、請求項1~8のいずれか1項に記載の抗CLDN18.2抗体。
- 前記VH領域が、配列番号1、7、10、または13から選択されるCDR1配列、配列番号2、4、5、6、8、11、14、16、または17から選択されるCDR2配列、及び配列番号3、9、12、または15から選択されるCDR3配列を含む、請求項1~10のいずれか1項に記載の抗CLDN18.2抗体。
- 前記VH領域が、配列番号1からなるCDR1配列、配列番号2、4、5、または6から選択されるCDR2配列、及び配列番号3からなるCDR3配列を含む、請求項1~10のいずれか1項に記載の抗CLDN18.2抗体。
- 前記VH領域が、配列番号13からなるCDR1配列、配列番号14、16、または17から選択されるCDR2配列、及び配列番号15からなるCDR3配列を含む、請求項1~10のいずれか1項に記載の抗CLDN18.2抗体。
- 前記VH領域が、配列番号7からなるCDR1配列、配列番号8からなるCDR2配列、及び配列番号9からなるCDR3配列を含む、請求項1~10のいずれか1項に記載の抗CLDN18.2抗体。
- 前記VH領域が、配列番号10からなるCDR1配列、配列番号11からなるCDR2配列、及び配列番号12からなるCDR3配列を含む、請求項1~10のいずれか1項に記載の抗CLDN18.2抗体。
- 前記VL領域が、配列番号18、21、24~28、31~35、38、または39から選択されるCDR1配列、配列番号19、22、29、または36から選択されるCDR2配列、及び配列番号20、23、30、または37から選択されるCDR3配列を含む、請求項1~15のいずれか1項に記載の抗CLDN18.2抗体。
- 前記VL領域が、配列番号21または24~27から選択されるCDR1配列、配列番号22からなるCDR2配列、及び配列番号23からなるCDR3配列を含む、請求項1~15のいずれか1項に記載の抗CLDN18.2抗体。
- 前記VL領域が、配列番号28または31~34から選択されるCDR1配列、配列番号29からなるCDR2配列、及び配列番号30からなるCDR3配列を含む、請求項1~15のいずれか1項に記載の抗CLDN18.2抗体。
- 前記VL領域が、配列番号35、38、または39から選択されるCDR1配列、配列番号36からなるCDR2配列、及び配列番号37からなるCDR3配列を含む、請求項1~15のいずれか1項に記載の抗CLDN18.2抗体。
- 前記VL領域が、配列番号18からなるCDR1配列、配列番号19からなるCDR2配列、及び配列番号20からなるCDR3配列を含む、請求項1~15のいずれか1項に記載の抗CLDN18.2抗体。
- 完全長抗体である、請求項1~20のいずれか1項に記載の抗CLDN18.2抗体。
- 結合断片である、請求項1~20のいずれか1項に記載の抗CLDN18.2抗体。
- 一価のFab’、二価のFab2、一本鎖可変断片(scFv)、ダイアボディ、ミニボディ、ナノボディ、単一ドメイン抗体(sdAb)、またはラクダ科動物抗体もしくはその結合断片を含む、請求項1~22のいずれか1項に記載の抗CLDN18.2抗体。
- ヒト化抗体もしくはその結合断片、キメラ抗体もしくはその結合断片、モノクローナル抗体もしくはその結合断片、または二重特異性抗体もしくはその結合断片を含む、請求項1~22のいずれか1項に記載の抗CLDN18.2抗体。
- 翻訳後修飾部位に突然変異を含む、請求項1~24のいずれか1項に記載の抗CLDN18.2抗体。
- 前記突然変異が、VH領域のアミノ酸位置60、61、または62にあり、前記アミノ酸位置が、配列番号40の60、61、または62位に対応する、請求項25に記載の抗CLDN18.2抗体。
- 前記突然変異が、配列番号40のアミノ酸位置60または62にある、請求項26に記載の抗CLDN18.2抗体。
- 前記突然変異が、配列番号57のアミノ酸位置60または61にある、請求項26に記載の抗CLDN18.2抗体。
- アミノ酸残基N60での前記突然変異が、グルタミンまたはグルタミン酸への突然変異である、請求項26~28のいずれか1項に記載の抗CLDN18.2抗体。
- アミノ酸残基S61での前記突然変異が、イソロイシンへの突然変異である、請求項26~28のいずれか1項に記載の抗CLDN18.2抗体。
- アミノ酸残基T62での前記突然変異が、アラニンへの突然変異である、請求項26~28のいずれか1項に記載の抗CLDN18.2抗体。
- 前記突然変異が、VL領域のアミノ酸位置31または32にあり、前記アミノ酸位置が、配列番号46、52、または60の31または32位に対応する、請求項25に記載の抗CLDN18.2抗体。
- 前記突然変異が、配列番号46、52、または60のアミノ酸位置31または32にある、請求項32に記載の抗CLDN18.2抗体。
- アミノ酸残基N31での前記突然変異が、アスパラギン酸またはグルタミン酸への突然変異である、請求項32または33に記載の抗CLDN18.2抗体。
- アミノ酸残基S32での前記突然変異が、ロイシン、バリン、またはイソロイシンへの突然変異である、請求項32または33に記載の抗CLDN18.2抗体。
- 前記突然変異が、修飾抗CLDN18.2抗体の結合親和性を、前記参照抗体175D10と比較して高める、請求項25~35のいずれか1項に記載の抗CLDN18.2抗体。
- キメラ抗体またはその結合断片を含む、請求項1~36のいずれか1項に記載の抗CLDN18.2抗体。
- 前記キメラ抗体またはその結合断片が、配列番号40~43に対して、少なくとも80%、85%、90%、95%、または100%の配列同一性からなるVH領域及び配列番号44に対して、少なくとも80%、85%、90%、95%、または100%の配列同一性からなるVL領域を含む、請求項37に記載の抗CLDN18.2抗体。
- 前記キメラ抗体またはその結合断片が、配列番号45に対して、少なくとも80%、85%、90%、95%、または100%の配列同一性からなるVH領域及び配列番号46~50に対して、少なくとも80%、85%、90%、95%、または100%の配列同一性からなるVL領域を含む、請求項37に記載の抗CLDN18.2抗体。
- 前記キメラ抗体またはその結合断片が、配列番号51に対して、少なくとも80%、85%、90%、95%、または100%の配列同一性からなるVH領域及び配列番号52~56に対して、少なくとも80%、85%、90%、95%、または100%の配列同一性からなるVL領域を含む、請求項37に記載の抗CLDN18.2抗体。
- 前記キメラ抗体またはその結合断片が、配列番号57~59に対して、少なくとも80%、85%、90%、95%、または100%の配列同一性からなるVH領域及び配列番号60~62に対して、少なくとも80%、85%、90%、95%、または100%の配列同一性からなるVL領域を含む、請求項37に記載の抗CLDN18.2抗体。
- 前記キメラ抗体またはその結合断片が、配列番号63に対して、少なくとも80%、85%、90%、95%、または100%の配列同一性からなるCH領域及び配列番号64に対して、少なくとも80%、85%、90%、95%、または100%の配列同一性からなるCL領域を含む、請求項37~41のいずれか1項に記載の抗CLDN18.2抗体。
- ヒト化抗体またはその結合断片を含む、請求項1~36のいずれか1項に記載の抗CLDN18.2抗体。
- 前記ヒト化抗体またはその結合断片が、配列番号65~68に対して、少なくとも80%、85%、90%、95%、または100%の配列同一性からなるVH領域及び配列番号69~73に対して、少なくとも80%、85%、90%、95%、または100%の配列同一性からなるVL領域を含む、請求項43に記載の抗CLDN18.2抗体。
- 前記ヒト化抗体またはその結合断片が、配列番号74~76に対して、少なくとも80%、85%、90%、95%、または100%の配列同一性からなるVH領域及び配列番号77~80に対して、少なくとも80%、85%、90%、95%、または100%の配列同一性からなるVL領域を含む、請求項43に記載の抗CLDN18.2抗体。
- 前記ヒト化抗体またはその結合断片が、配列番号81~84に対して、少なくとも80%、85%、90%、95%、または100%の配列同一性からなるVH領域及び配列番号85~88に対して、少なくとも80%、85%、90%、95%、または100%の配列同一性からなるVL領域を含む、請求項43に記載の抗CLDN18.2抗体。
- 前記ヒト化抗体またはその結合断片が、配列番号89~92に対して、少なくとも80%、85%、90%、95%、または100%の配列同一性からなるVH領域及び配列番号93~97に対して、少なくとも80%、85%、90%、95%、または100%の配列同一性からなるVL領域を含む、請求項43に記載の抗CLDN18.2抗体。
- IgMのフレームワークを含む、請求項1~47のいずれか1項に記載の抗CLDN18.2抗体。
- IgG2のフレームワークを含む、請求項1~47のいずれか1項に記載の抗CLDN18.2抗体。
- IgG1のフレームワークを含む、請求項1~47のいずれか1項に記載の抗CLDN18.2抗体。
- 前記Fc領域に1つ以上の突然変異を含む、請求項1~50のいずれか1項に記載の抗CLDN18.2抗体。
- 前記1つ以上の突然変異が、アミノ酸位置S239、アミノ酸位置I332、アミノ酸位置F243、アミノ酸位置R292、アミノ酸位置Y300、アミノ酸位置V305、アミノ酸位置P396またはそれらの組み合わせでの突然変異を含む、請求項51に記載の抗CLDN18.2抗体。
- 前記Fc領域での1つ以上の突然変異が、前記参照抗体175D10に対して向上したADCCを与える、請求項51または52に記載の抗CLDN18.2抗体。
- 前記参照抗体175D10と比較して補体依存性細胞傷害(CDC)活性を有する、請求項1~53のいずれか1項に記載の抗CLDN18.2抗体。
- さらにペイロードにコンジュゲートされる、請求項1~54のいずれか1項に記載の抗CLDN18.2抗体。
- 前記ペイロードが、アウリスタチンまたはその誘導体である、請求項55に記載の抗CLDN18.2抗体。
- 前記アウリスタチン誘導体が、モノメチルアウリスタチンE(MMAE)である、請求項56に記載の抗CLDN18.2抗体。
- 前記アウリスタチン誘導体が、モノメチルアウリスタチンF(MMAF)である、請求項56に記載の抗CLDN18.2抗体。
- 薬物対抗体比(DAR)が、約2、約3、または約4である、請求項55~58のいずれか1項に記載の抗CLDN18.2抗体。
- 前記参照抗体175D10と結合エピトープを共有する、請求項1~59のいずれか1項に記載の抗CLDN18.2抗体。
- マウス及びカニクイザルCLDN18.2タンパク質に対して交差結合活性を有する、請求項1~60のいずれか1項に記載の抗CLDN18.2抗体。
- CLDN18.2のアイソフォームに特異的に結合する抗クローディン18.2(抗CLDN18.2)抗体。
- 前記CLDN18.2のアイソフォームが、細胞株SNU620で発現されるアイソフォームである、請求項62に記載の抗CLDN18.2抗体。
- 請求項1~63に記載の抗CLDN18.2抗体をコードする核酸ポリマー。
- 請求項64に記載の核酸ポリマーを含むベクター。
- 請求項1~63に記載の抗CLDN18.2抗体、及び
医薬的に許容される賦形剤を含む医薬組成物。 - 全身投与用に製剤化される、請求項66に記載の医薬組成物。
- 非経口投与用に製剤化される、請求項66または67に記載の医薬組成物。
- CLDN18.2タンパク質の過剰発現を特徴とするがんを有する対象の治療方法であって、
請求項1~63に記載の抗CLDN18.2抗体または請求項66~68に記載の医薬組成物を前記対象に投与し、それにより、前記対象における前記がんを治療することを含む、前記方法。 - 前記がんが消化管癌である、請求項69に記載の方法。
- 前記消化管癌が胃癌である、請求項70に記載の方法。
- 前記消化管癌が膵臓癌である、請求項70に記載の方法。
- 前記消化管癌が、食道癌または胆管細胞癌である、請求項70に記載の方法。
- 前記がんが、肺癌または卵巣癌である、請求項69に記載の方法。
- さらに、前記対象に対して、さらなる治療薬を投与することを含む、請求項69に記載の方法。
- 前記さらなる治療薬が、化学療法剤、免疫療法薬、標的治療薬、ホルモン系治療薬、幹細胞系治療薬、または放射線を含む、請求項75に記載の方法。
- 前記さらなる治療薬及び前記抗CLDN18.2抗体が、同時に投与される、請求項75または76に記載の方法。
- 前記さらなる治療薬及び前記抗CLDN18.2抗体が、連続して投与される、請求項75または76に記載の方法。
- 前記さらなる治療薬が、前記抗CLDN18.2抗体に先立って投与される、請求項78に記載の方法。
- 前記さらなる治療薬が、前記抗CLDN18.2抗体の投与後に投与される、請求項78に記載の方法。
- 前記さらなる治療薬及び前記抗CLDN18.2抗体が、異なる投与として製剤化される、請求項75~80のいずれか1項に記載の方法。
- 殺細胞効果を誘導する方法であって、
複数の細胞を、ペイロードを含む抗CLDN18.2抗体と、前記抗CLDN18.2抗体を内在化するのに十分な時間接触させ、それにより、前記殺細胞効果を誘導することを含む、前記方法。 - 前記抗CLDN18.2抗体が、請求項1~54に記載の抗CLDN18.2抗体を含む、請求項82に記載の方法。
- 前記ペイロードが、メイタンシノイド、アウリスタチン、タキソイド、カリケアマイシン、デュオカルマイシン、アマトキシン、またはそれらの誘導体を含む、請求項83に記載の方法。
- 前記ペイロードが、アウリスタチンまたはその誘導体を含む、請求項83に記載の方法。
- 前記ペイロードが、モノメチルアウリスタチンE(MMAE)である、請求項85に記載の方法。
- 前記ペイロードが、モノメチルアウリスタチンF(MMAF)である、請求項85に記載の方法。
- 前記細胞が、がん細胞である、請求項82に記載の方法。
- 前記細胞が消化管癌に由来する、請求項88に記載の方法。
- 前記消化管癌が胃癌である、請求項89に記載の方法。
- 前記消化管癌が膵臓癌である、請求項89に記載の方法。
- 前記消化管癌が、食道癌または胆管細胞癌である、請求項89に記載の方法。
- 前記細胞が、肺癌または卵巣癌に由来する、請求項88に記載の方法。
- インビトロ法である、請求項82~93のいずれか1項に記載の方法。
- インビボ法である、請求項82~93のいずれか1項に記載の方法。
- 前記対象がヒトである、先行請求項のいずれか1項に記載の方法。
- 請求項1~63に記載の抗CLDN18.2抗体、請求項65に記載のベクター、または請求項66~68に記載の医薬組成物を含むキット。
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CNPCT/CN2018/119797 | 2018-12-07 | ||
CNPCT/CN2018/119797 | 2018-12-07 | ||
PCT/CN2019/123588 WO2020114480A1 (en) | 2018-12-07 | 2019-12-06 | Anti-claudin antibodies and uses thereof |
Publications (3)
Publication Number | Publication Date |
---|---|
JP2022512132A true JP2022512132A (ja) | 2022-02-02 |
JPWO2020114480A5 JPWO2020114480A5 (ja) | 2022-12-13 |
JP7458399B2 JP7458399B2 (ja) | 2024-03-29 |
Family
ID=70975310
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2021532180A Active JP7458399B2 (ja) | 2018-12-07 | 2019-12-06 | 抗クローディン抗体及びそれらの使用 |
Country Status (12)
Country | Link |
---|---|
US (1) | US20210380680A1 (ja) |
EP (1) | EP3891183A4 (ja) |
JP (1) | JP7458399B2 (ja) |
KR (1) | KR20210100655A (ja) |
CN (1) | CN113423735B (ja) |
AU (1) | AU2019391204A1 (ja) |
BR (1) | BR112021011014A2 (ja) |
CA (1) | CA3122135A1 (ja) |
IL (1) | IL283754A (ja) |
MX (1) | MX2021006681A (ja) |
SG (1) | SG11202105885WA (ja) |
WO (1) | WO2020114480A1 (ja) |
Families Citing this family (12)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
EP3917564A4 (en) | 2019-02-01 | 2022-12-21 | NovaRock Biotherapeutics, Ltd. | ANTI-CLAUDINE 18 ANTIBODIES AND THEIR METHODS OF USE |
CN113929780A (zh) * | 2020-07-13 | 2022-01-14 | 北京凯因科技股份有限公司 | 一种结合密蛋白的用于治疗癌症的人源化抗体 |
AU2021354827A1 (en) * | 2020-09-30 | 2023-06-01 | Jiangsu Hengrui Pharmaceuticals Co., Ltd. | Pharmaceutical composition comprising antibody-drug conjugate, and use of pharmaceutical composition |
WO2022068854A1 (en) * | 2020-09-30 | 2022-04-07 | Nanjing GenScript Biotech Co., Ltd. | Antibodies targeting human claudin 18.2 and uses thereof |
CN115109154A (zh) * | 2021-03-17 | 2022-09-27 | 三优生物医药(上海)有限公司 | 一种靶向cldn18.2的抗体或其抗原结合片段及其应用 |
CN115611983A (zh) * | 2021-07-14 | 2023-01-17 | 三优生物医药(上海)有限公司 | Cldn18.2结合分子及其用途 |
CN114044822B (zh) * | 2021-10-28 | 2023-06-27 | 杭州博茵生物技术有限公司 | 血清淀粉样蛋白a抗体的重链和轻链可变区、抗体及运用 |
WO2023078386A1 (zh) * | 2021-11-05 | 2023-05-11 | 正大天晴药业集团股份有限公司 | 抗cldn18.2抗体及其用途 |
CN114395040B (zh) * | 2022-02-09 | 2023-12-15 | 东南大学附属中大医院 | 再生蛋白reg1a单克隆抗体及其应用 |
WO2023196882A1 (en) | 2022-04-06 | 2023-10-12 | Zai Lab (Us) Llc | Claudin 18.2 immunohistochemistry assay and use thereof |
WO2024011186A2 (en) * | 2022-07-08 | 2024-01-11 | Imaginab, Inc. | Antibodies and methods of making and using same |
WO2024131683A1 (zh) * | 2022-12-19 | 2024-06-27 | 华润生物医药有限公司 | 结合cldn18.2的抗体和抗体药物偶联物及其用途 |
Citations (6)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2009517354A (ja) * | 2005-11-24 | 2009-04-30 | ガニメド ファーマシューティカルズ アーゲー | 癌の治療のためのクローディン18に対するモノクローナル抗体 |
JP2010528075A (ja) * | 2007-05-29 | 2010-08-19 | ガニメド ファーマシューティカルズ アーゲー | 癌の治療のためのクローディン18に対するモノクローナル抗体 |
JP2015518838A (ja) * | 2012-05-23 | 2015-07-06 | ガニメド ファーマシューティカルズ アーゲー | がんを処置するためのクローディン18.2に対する抗体を伴う併用療法 |
JP2016517447A (ja) * | 2013-03-18 | 2016-06-16 | ガニメド ファーマシューティカルズ アーゲー | 癌の治療のためのクローディン18.2に対する抗体を含む治療法 |
WO2018006882A1 (zh) * | 2016-07-08 | 2018-01-11 | 科济生物医药(上海)有限公司 | 抗密蛋白18a2的抗体及其应用 |
JP2018513146A (ja) * | 2015-04-15 | 2018-05-24 | ガニメド ファーマシューティカルズ ゲーエムベーハー | クローディン18.2に対する抗体を含む薬物コンジュゲート |
Family Cites Families (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
DE102004024617A1 (de) * | 2004-05-18 | 2005-12-29 | Ganymed Pharmaceuticals Ag | Differentiell in Tumoren exprimierte Genprodukte und deren Verwendung |
WO2013167153A1 (en) * | 2012-05-09 | 2013-11-14 | Ganymed Pharmaceuticals Ag | Antibodies useful in cancer diagnosis |
WO2018054484A1 (en) * | 2016-09-23 | 2018-03-29 | Biontech Ag | Bispecific trivalent antibodies binding to claudin 6 or claudin18.2 and cd3 for treatment of claudin expressing cancer diseases |
-
2019
- 2019-12-06 SG SG11202105885WA patent/SG11202105885WA/en unknown
- 2019-12-06 EP EP19893031.5A patent/EP3891183A4/en active Pending
- 2019-12-06 JP JP2021532180A patent/JP7458399B2/ja active Active
- 2019-12-06 BR BR112021011014-3A patent/BR112021011014A2/pt unknown
- 2019-12-06 MX MX2021006681A patent/MX2021006681A/es unknown
- 2019-12-06 CN CN201980088317.6A patent/CN113423735B/zh active Active
- 2019-12-06 AU AU2019391204A patent/AU2019391204A1/en active Pending
- 2019-12-06 CA CA3122135A patent/CA3122135A1/en active Pending
- 2019-12-06 WO PCT/CN2019/123588 patent/WO2020114480A1/en unknown
- 2019-12-06 KR KR1020217020208A patent/KR20210100655A/ko unknown
- 2019-12-06 US US17/311,307 patent/US20210380680A1/en active Pending
-
2021
- 2021-06-06 IL IL283754A patent/IL283754A/en unknown
Patent Citations (6)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2009517354A (ja) * | 2005-11-24 | 2009-04-30 | ガニメド ファーマシューティカルズ アーゲー | 癌の治療のためのクローディン18に対するモノクローナル抗体 |
JP2010528075A (ja) * | 2007-05-29 | 2010-08-19 | ガニメド ファーマシューティカルズ アーゲー | 癌の治療のためのクローディン18に対するモノクローナル抗体 |
JP2015518838A (ja) * | 2012-05-23 | 2015-07-06 | ガニメド ファーマシューティカルズ アーゲー | がんを処置するためのクローディン18.2に対する抗体を伴う併用療法 |
JP2016517447A (ja) * | 2013-03-18 | 2016-06-16 | ガニメド ファーマシューティカルズ アーゲー | 癌の治療のためのクローディン18.2に対する抗体を含む治療法 |
JP2018513146A (ja) * | 2015-04-15 | 2018-05-24 | ガニメド ファーマシューティカルズ ゲーエムベーハー | クローディン18.2に対する抗体を含む薬物コンジュゲート |
WO2018006882A1 (zh) * | 2016-07-08 | 2018-01-11 | 科济生物医药(上海)有限公司 | 抗密蛋白18a2的抗体及其应用 |
Non-Patent Citations (1)
Title |
---|
LAZAR, G. A. ET AL.: ""Engineered antibody Fc variants with enhanced effector function"", PROC. NATL. ACAD. SCI. U. S. A., vol. 103, JPN6023046746, 2006, pages 4005 - 4010, ISSN: 0005196073 * |
Also Published As
Publication number | Publication date |
---|---|
JP7458399B2 (ja) | 2024-03-29 |
KR20210100655A (ko) | 2021-08-17 |
CA3122135A1 (en) | 2020-06-11 |
AU2019391204A1 (en) | 2021-06-24 |
IL283754A (en) | 2021-07-29 |
CN113423735B (zh) | 2024-02-13 |
US20210380680A1 (en) | 2021-12-09 |
SG11202105885WA (en) | 2021-07-29 |
MX2021006681A (es) | 2021-11-17 |
BR112021011014A2 (pt) | 2021-08-31 |
EP3891183A1 (en) | 2021-10-13 |
WO2020114480A1 (en) | 2020-06-11 |
CN113423735A (zh) | 2021-09-21 |
EP3891183A4 (en) | 2022-08-31 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
JP7458399B2 (ja) | 抗クローディン抗体及びそれらの使用 | |
JP7084569B2 (ja) | Vista及びその結合パートナーの相互作用を遮断することによる癌治療 | |
CN109963591B (zh) | B7h3抗体-药物偶联物及其医药用途 | |
JP7323102B2 (ja) | 抗psma抗体およびその使用 | |
CN116063505B (zh) | 抗gal3抗体及其用途 | |
JP2020529863A (ja) | 抗ror1抗体とその作製及び使用方法 | |
JP2017500028A (ja) | 新規の抗dpep3抗体および使用方法 | |
EP3717007A1 (en) | Ildr2 antagonists and combinations thereof | |
JP2022507485A (ja) | Cd38抗体とicam1抗体およびそれらの使用 | |
CN111630069A (zh) | 针对Thomsen-nouvelle(Tn)抗原的人抗体 | |
CN110799538A (zh) | 抗cd3抗体及其制备和使用方法 | |
TW201605480A (zh) | 抗efna4抗體-藥物結合物 | |
RU2815926C2 (ru) | Антитела против клаудина и их применение | |
CN112533948A (zh) | 与双触角Lewis B以及Lewis Y抗原结合的治疗性抗体 | |
US20240166768A1 (en) | Anti-matrix metalloproteinase-14 antibodies for the treatment of cancer | |
US20220185911A1 (en) | Therapeutic antibodies for treating lung cancer | |
EP4363456A1 (en) | Anti-alk antibodies & uses thereof | |
IL285313A (en) | Antibodies for cancer treatment | |
CN114630841A (zh) | 抗体以及阻断vista及其结合配偶体的相互作用 |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20221205 |
|
A621 | Written request for application examination |
Free format text: JAPANESE INTERMEDIATE CODE: A621 Effective date: 20221205 |
|
A977 | Report on retrieval |
Free format text: JAPANESE INTERMEDIATE CODE: A971007 Effective date: 20231108 |
|
A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20231114 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20240213 |
|
TRDD | Decision of grant or rejection written | ||
A01 | Written decision to grant a patent or to grant a registration (utility model) |
Free format text: JAPANESE INTERMEDIATE CODE: A01 Effective date: 20240311 |
|
A61 | First payment of annual fees (during grant procedure) |
Free format text: JAPANESE INTERMEDIATE CODE: A61 Effective date: 20240318 |
|
R150 | Certificate of patent or registration of utility model |
Ref document number: 7458399 Country of ref document: JP Free format text: JAPANESE INTERMEDIATE CODE: R150 |