TW202342505A - IL-7Rαγc結合化合物 - Google Patents

Info

Publication number

TW202342505A

TW202342505A TW112126553A TW112126553A TW202342505A TW 202342505 A TW202342505 A TW 202342505A TW 112126553 A TW112126553 A TW 112126553A TW 112126553 A TW112126553 A TW 112126553A TW 202342505 A TW202342505 A TW 202342505A

Authority

TW

Taiwan

Prior art keywords

ligand

seq

7rαγc

amino acid

linker

Prior art date

2020-02-03

Links

• Espacenet
• Global Dossier
• Discuss

• 150000001875 compounds Chemical class 0.000 title claims abstract description 283
• 230000027455 binding Effects 0.000 title abstract description 287
• 206010028980 Neoplasm Diseases 0.000 claims abstract description 72
• 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 65
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 54
• 201000010099 disease Diseases 0.000 claims abstract description 47
• 201000011510 cancer Diseases 0.000 claims abstract description 34
• 208000023275 Autoimmune disease Diseases 0.000 claims abstract description 12
• 230000003612 virological effect Effects 0.000 claims abstract description 8
• 239000003446 ligand Substances 0.000 claims description 998
• 150000001413 amino acids Chemical class 0.000 claims description 258
• 125000003275 alpha amino acid group Chemical group 0.000 claims description 243
• 108090000765 processed proteins & peptides Proteins 0.000 claims description 113
• 108090000623 proteins and genes Proteins 0.000 claims description 75
• 102000004169 proteins and genes Human genes 0.000 claims description 70
• 229910052739 hydrogen Inorganic materials 0.000 claims description 52
• 238000006467 substitution reaction Methods 0.000 claims description 48
• 229910052721 tungsten Inorganic materials 0.000 claims description 47
• 229910052727 yttrium Inorganic materials 0.000 claims description 44
• 229910052731 fluorine Inorganic materials 0.000 claims description 41
• 108010091135 Immunoglobulin Fc Fragments Proteins 0.000 claims description 34
• 102000018071 Immunoglobulin Fc Fragments Human genes 0.000 claims description 34
• 239000003814 drug Substances 0.000 claims description 30
• 230000001225 therapeutic effect Effects 0.000 claims description 27
• 229910052698 phosphorus Inorganic materials 0.000 claims description 23
• 229910052700 potassium Inorganic materials 0.000 claims description 21
• 210000002865 immune cell Anatomy 0.000 claims description 18
• 102000008394 Immunoglobulin Fragments Human genes 0.000 claims description 14
• 108010021625 Immunoglobulin Fragments Proteins 0.000 claims description 14
• 229960005486 vaccine Drugs 0.000 claims description 14
• 229910052717 sulfur Inorganic materials 0.000 claims description 13
• 208000027866 inflammatory disease Diseases 0.000 claims description 10
• 230000028993 immune response Effects 0.000 claims description 8
• 150000007523 nucleic acids Chemical class 0.000 claims description 8
• 229940079593 drug Drugs 0.000 claims description 7
• 241000700605 Viruses Species 0.000 claims description 6
• 102000039446 nucleic acids Human genes 0.000 claims description 6
• 108020004707 nucleic acids Proteins 0.000 claims description 6
• 238000002360 preparation method Methods 0.000 claims description 6
• 230000001105 regulatory effect Effects 0.000 claims description 4
• 208000035473 Communicable disease Diseases 0.000 claims description 3
• 238000009566 cancer vaccine Methods 0.000 claims description 2
• 229940022399 cancer vaccine Drugs 0.000 claims description 2
• 229920000554 ionomer Polymers 0.000 claims 1
• 239000000556 agonist Substances 0.000 abstract description 40
• 208000037979 autoimmune inflammatory disease Diseases 0.000 abstract description 2
• 235000001014 amino acid Nutrition 0.000 description 303
• 229940024606 amino acid Drugs 0.000 description 261
• 125000005647 linker group Chemical group 0.000 description 240
• 210000004027 cell Anatomy 0.000 description 144
• 102000004196 processed proteins & peptides Human genes 0.000 description 74
• 239000000427 antigen Substances 0.000 description 72
• 108091007433 antigens Proteins 0.000 description 72
• 102000036639 antigens Human genes 0.000 description 72
• 235000018102 proteins Nutrition 0.000 description 67
• 108010002586 Interleukin-7 Proteins 0.000 description 53
• 102000000704 Interleukin-7 Human genes 0.000 description 53
• 229940100994 interleukin-7 Drugs 0.000 description 52
• 210000001744 T-lymphocyte Anatomy 0.000 description 47
• 229920001184 polypeptide Polymers 0.000 description 46
• 108020001507 fusion proteins Proteins 0.000 description 42
• 102000037865 fusion proteins Human genes 0.000 description 42
• 229910052720 vanadium Inorganic materials 0.000 description 42
• 230000004927 fusion Effects 0.000 description 41
• DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 36
• 229910052740 iodine Inorganic materials 0.000 description 34
• 125000001151 peptidyl group Chemical group 0.000 description 34
• 239000000126 substance Substances 0.000 description 34
• 241000282414 Homo sapiens Species 0.000 description 33
• 238000000034 method Methods 0.000 description 32
• 230000004913 activation Effects 0.000 description 30
• 108060003951 Immunoglobulin Proteins 0.000 description 29
• 102000018358 immunoglobulin Human genes 0.000 description 29
• 230000000694 effects Effects 0.000 description 28
• 230000002209 hydrophobic effect Effects 0.000 description 27
• 235000018417 cysteine Nutrition 0.000 description 26
• -1 hydrocarbon radical Chemical class 0.000 description 26
• 230000008685 targeting Effects 0.000 description 25
• KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 24
• 239000003112 inhibitor Substances 0.000 description 24
• 230000000144 pharmacologic effect Effects 0.000 description 22
• WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 description 21
• 229910052757 nitrogen Inorganic materials 0.000 description 21
• MTCFGRXMJLQNBG-REOHCLBHSA-N (2S)-2-Amino-3-hydroxypropansäure Chemical compound OC[C@H](N)C(O)=O MTCFGRXMJLQNBG-REOHCLBHSA-N 0.000 description 20
• MTCFGRXMJLQNBG-UHFFFAOYSA-N Serine Natural products OCC(N)C(O)=O MTCFGRXMJLQNBG-UHFFFAOYSA-N 0.000 description 20
• 102000005962 receptors Human genes 0.000 description 20
• 150000003839 salts Chemical class 0.000 description 20
• 231100000433 cytotoxic Toxicity 0.000 description 19
• 230000001472 cytotoxic effect Effects 0.000 description 19
• 108020003175 receptors Proteins 0.000 description 19
• OUYCCCASQSFEME-UHFFFAOYSA-N tyrosine Natural products OC(=O)C(N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-UHFFFAOYSA-N 0.000 description 19
• 239000004471 Glycine Substances 0.000 description 18
• OUYCCCASQSFEME-QMMMGPOBSA-N L-tyrosine Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-QMMMGPOBSA-N 0.000 description 18
• 235000004279 alanine Nutrition 0.000 description 18
• 230000014509 gene expression Effects 0.000 description 18
• 150000002333 glycines Chemical class 0.000 description 18
• XUJNEKJLAYXESH-REOHCLBHSA-N L-Cysteine Chemical compound SC[C@H](N)C(O)=O XUJNEKJLAYXESH-REOHCLBHSA-N 0.000 description 17
• QNAYBMKLOCPYGJ-REOHCLBHSA-N L-alanine Chemical compound C[C@H](N)C(O)=O QNAYBMKLOCPYGJ-REOHCLBHSA-N 0.000 description 17
• 239000004472 Lysine Substances 0.000 description 17
• 235000018977 lysine Nutrition 0.000 description 17
• 229940124597 therapeutic agent Drugs 0.000 description 17
• WHUUTDBJXJRKMK-UHFFFAOYSA-N Glutamic acid Natural products OC(=O)C(N)CCC(O)=O WHUUTDBJXJRKMK-UHFFFAOYSA-N 0.000 description 16
• AYFVYJQAPQTCCC-GBXIJSLDSA-N L-threonine Chemical compound C[C@@H](O)[C@H](N)C(O)=O AYFVYJQAPQTCCC-GBXIJSLDSA-N 0.000 description 15
• AYFVYJQAPQTCCC-UHFFFAOYSA-N Threonine Natural products CC(O)C(N)C(O)=O AYFVYJQAPQTCCC-UHFFFAOYSA-N 0.000 description 15
• 239000004473 Threonine Substances 0.000 description 15
• 229910052799 carbon Inorganic materials 0.000 description 15
• 235000013922 glutamic acid Nutrition 0.000 description 15
• 239000004220 glutamic acid Substances 0.000 description 15
• 229960002621 pembrolizumab Drugs 0.000 description 15
• 239000003795 chemical substances by application Substances 0.000 description 14
• XUJNEKJLAYXESH-UHFFFAOYSA-N cysteine Natural products SCC(N)C(O)=O XUJNEKJLAYXESH-UHFFFAOYSA-N 0.000 description 14
• 230000001965 increasing effect Effects 0.000 description 14
• 208000024891 symptom Diseases 0.000 description 14
• 210000001266 CD8-positive T-lymphocyte Anatomy 0.000 description 13
• 108020004414 DNA Proteins 0.000 description 13
• 229940076838 Immune checkpoint inhibitor Drugs 0.000 description 13
• ONIBWKKTOPOVIA-BYPYZUCNSA-N L-Proline Chemical compound OC(=O)[C@@H]1CCCN1 ONIBWKKTOPOVIA-BYPYZUCNSA-N 0.000 description 13
• HNDVDQJCIGZPNO-YFKPBYRVSA-N L-histidine Chemical compound OC(=O)[C@@H](N)CC1=CN=CN1 HNDVDQJCIGZPNO-YFKPBYRVSA-N 0.000 description 13
• ONIBWKKTOPOVIA-UHFFFAOYSA-N Proline Natural products OC(=O)C1CCCN1 ONIBWKKTOPOVIA-UHFFFAOYSA-N 0.000 description 13
• HNDVDQJCIGZPNO-UHFFFAOYSA-N histidine Natural products OC(=O)C(N)CC1=CN=CN1 HNDVDQJCIGZPNO-UHFFFAOYSA-N 0.000 description 13
• 239000012274 immune-checkpoint protein inhibitor Substances 0.000 description 13
• 230000026731 phosphorylation Effects 0.000 description 13
• 238000006366 phosphorylation reaction Methods 0.000 description 13
• 229920001223 polyethylene glycol Polymers 0.000 description 13
• 235000013930 proline Nutrition 0.000 description 13
• 229960002429 proline Drugs 0.000 description 13
• 210000001519 tissue Anatomy 0.000 description 13
• 239000002202 Polyethylene glycol Substances 0.000 description 12
• 230000002378 acidificating effect Effects 0.000 description 12
• 230000000975 bioactive effect Effects 0.000 description 12
• 150000001945 cysteines Chemical class 0.000 description 12
• RWSXRVCMGQZWBV-WDSKDSINSA-N glutathione Chemical compound OC(=O)[C@@H](N)CCC(=O)N[C@@H](CS)C(=O)NCC(O)=O RWSXRVCMGQZWBV-WDSKDSINSA-N 0.000 description 12
• 230000003993 interaction Effects 0.000 description 12
• 230000011664 signaling Effects 0.000 description 12
• 238000011282 treatment Methods 0.000 description 12
• 102000009027 Albumins Human genes 0.000 description 11
• 108010088751 Albumins Proteins 0.000 description 11
• 102000015696 Interleukins Human genes 0.000 description 11
• 108010063738 Interleukins Proteins 0.000 description 11
• KDXKERNSBIXSRK-YFKPBYRVSA-N L-lysine Chemical compound NCCCC[C@H](N)C(O)=O KDXKERNSBIXSRK-YFKPBYRVSA-N 0.000 description 11
• 102000001712 STAT5 Transcription Factor Human genes 0.000 description 11
• 108010029477 STAT5 Transcription Factor Proteins 0.000 description 11
• 125000000217 alkyl group Chemical group 0.000 description 11
• 239000005557 antagonist Substances 0.000 description 11
• 230000009977 dual effect Effects 0.000 description 11
• 239000012634 fragment Substances 0.000 description 11
• 125000000592 heterocycloalkyl group Chemical group 0.000 description 11
• 239000012216 imaging agent Substances 0.000 description 11
• 210000003289 regulatory T cell Anatomy 0.000 description 11
• 101001043809 Homo sapiens Interleukin-7 receptor subunit alpha Proteins 0.000 description 10
• 108091006905 Human Serum Albumin Proteins 0.000 description 10
• COLNVLDHVKWLRT-QMMMGPOBSA-N L-phenylalanine Chemical compound OC(=O)[C@@H](N)CC1=CC=CC=C1 COLNVLDHVKWLRT-QMMMGPOBSA-N 0.000 description 10
• 150000001412 amines Chemical class 0.000 description 10
• 125000003118 aryl group Chemical group 0.000 description 10
• 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 10
• COLNVLDHVKWLRT-UHFFFAOYSA-N phenylalanine Natural products OC(=O)C(N)CC1=CC=CC=C1 COLNVLDHVKWLRT-UHFFFAOYSA-N 0.000 description 10
• 229920000642 polymer Polymers 0.000 description 10
• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 10
• 102000008100 Human Serum Albumin Human genes 0.000 description 9
• 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 9
• QIVBCDIJIAJPQS-UHFFFAOYSA-N Tryptophan Natural products C1=CC=C2C(CC(N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-UHFFFAOYSA-N 0.000 description 9
• 125000002887 hydroxy group Chemical group [H]O* 0.000 description 9
• 238000001727 in vivo Methods 0.000 description 9
• 238000012986 modification Methods 0.000 description 9
• 230000004044 response Effects 0.000 description 9
• 108010038498 Interleukin-7 Receptors Proteins 0.000 description 8
• 150000001345 alkine derivatives Chemical class 0.000 description 8
• 210000004369 blood Anatomy 0.000 description 8
• 239000008280 blood Substances 0.000 description 8
• 125000004432 carbon atom Chemical group C* 0.000 description 8
• 125000005842 heteroatom Chemical group 0.000 description 8
• 210000003071 memory t lymphocyte Anatomy 0.000 description 8
• 239000000203 mixture Substances 0.000 description 8
• 230000004048 modification Effects 0.000 description 8
• 230000037361 pathway Effects 0.000 description 8
• 108091006020 Fc-tagged proteins Proteins 0.000 description 7
• 101001057504 Homo sapiens Interferon-stimulated gene 20 kDa protein Proteins 0.000 description 7
• 101001055144 Homo sapiens Interleukin-2 receptor subunit alpha Proteins 0.000 description 7
• 102100027268 Interferon-stimulated gene 20 kDa protein Human genes 0.000 description 7
• 102000010782 Interleukin-7 Receptors Human genes 0.000 description 7
• CKLJMWTZIZZHCS-REOHCLBHSA-N L-aspartic acid Chemical compound OC(=O)[C@@H](N)CC(O)=O CKLJMWTZIZZHCS-REOHCLBHSA-N 0.000 description 7
• ROHFNLRQFUQHCH-YFKPBYRVSA-N L-leucine Chemical compound CC(C)C[C@H](N)C(O)=O ROHFNLRQFUQHCH-YFKPBYRVSA-N 0.000 description 7
• ROHFNLRQFUQHCH-UHFFFAOYSA-N Leucine Natural products CC(C)CC(N)C(O)=O ROHFNLRQFUQHCH-UHFFFAOYSA-N 0.000 description 7
• 241000699670 Mus sp. Species 0.000 description 7
• 102000002669 Small Ubiquitin-Related Modifier Proteins Human genes 0.000 description 7
• 108010043401 Small Ubiquitin-Related Modifier Proteins Proteins 0.000 description 7
• 230000004071 biological effect Effects 0.000 description 7
• 208000035475 disorder Diseases 0.000 description 7
• 239000012636 effector Substances 0.000 description 7
• 230000006870 function Effects 0.000 description 7
• 210000004698 lymphocyte Anatomy 0.000 description 7
• 230000001404 mediated effect Effects 0.000 description 7
• 229930182817 methionine Natural products 0.000 description 7
• 239000000178 monomer Substances 0.000 description 7
• 229960003301 nivolumab Drugs 0.000 description 7
• SNOOUWRIMMFWNE-UHFFFAOYSA-M sodium;6-[(3,4,5-trimethoxybenzoyl)amino]hexanoate Chemical compound [Na+].COC1=CC(C(=O)NCCCCCC([O-])=O)=CC(OC)=C1OC SNOOUWRIMMFWNE-UHFFFAOYSA-M 0.000 description 7
• 238000003786 synthesis reaction Methods 0.000 description 7
• 239000004475 Arginine Substances 0.000 description 6
• DCXYFEDJOCDNAF-UHFFFAOYSA-N Asparagine Natural products OC(=O)C(N)CC(N)=O DCXYFEDJOCDNAF-UHFFFAOYSA-N 0.000 description 6
• 108010024636 Glutathione Proteins 0.000 description 6
• 102100026120 IgG receptor FcRn large subunit p51 Human genes 0.000 description 6
• 101710177940 IgG receptor FcRn large subunit p51 Proteins 0.000 description 6
• 241000712431 Influenza A virus Species 0.000 description 6
• 102100021593 Interleukin-7 receptor subunit alpha Human genes 0.000 description 6
• DCXYFEDJOCDNAF-REOHCLBHSA-N L-asparagine Chemical compound OC(=O)[C@@H](N)CC(N)=O DCXYFEDJOCDNAF-REOHCLBHSA-N 0.000 description 6
• AGPKZVBTJJNPAG-WHFBIAKZSA-N L-isoleucine Chemical compound CC[C@H](C)[C@H](N)C(O)=O AGPKZVBTJJNPAG-WHFBIAKZSA-N 0.000 description 6
• FFEARJCKVFRZRR-BYPYZUCNSA-N L-methionine Chemical compound CSCC[C@H](N)C(O)=O FFEARJCKVFRZRR-BYPYZUCNSA-N 0.000 description 6
• KZSNJWFQEVHDMF-BYPYZUCNSA-N L-valine Chemical compound CC(C)[C@H](N)C(O)=O KZSNJWFQEVHDMF-BYPYZUCNSA-N 0.000 description 6
• 102100033810 RAC-alpha serine/threonine-protein kinase Human genes 0.000 description 6
• 108010033576 Transferrin Receptors Proteins 0.000 description 6
• 102100026144 Transferrin receptor protein 1 Human genes 0.000 description 6
• KZSNJWFQEVHDMF-UHFFFAOYSA-N Valine Natural products CC(C)C(N)C(O)=O KZSNJWFQEVHDMF-UHFFFAOYSA-N 0.000 description 6
• 239000002253 acid Substances 0.000 description 6
• 230000002411 adverse Effects 0.000 description 6
• ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 6
• 235000009582 asparagine Nutrition 0.000 description 6
• 229960001230 asparagine Drugs 0.000 description 6
• 235000003704 aspartic acid Nutrition 0.000 description 6
• 150000001540 azides Chemical class 0.000 description 6
• OQFSQFPPLPISGP-UHFFFAOYSA-N beta-carboxyaspartic acid Natural products OC(=O)C(N)C(C(O)=O)C(O)=O OQFSQFPPLPISGP-UHFFFAOYSA-N 0.000 description 6
• 230000001413 cellular effect Effects 0.000 description 6
• 239000003937 drug carrier Substances 0.000 description 6
• 229960003180 glutathione Drugs 0.000 description 6
• 229940072221 immunoglobulins Drugs 0.000 description 6
• 229940047122 interleukins Drugs 0.000 description 6
• 229960005386 ipilimumab Drugs 0.000 description 6
• 229960000310 isoleucine Drugs 0.000 description 6
• AGPKZVBTJJNPAG-UHFFFAOYSA-N isoleucine Natural products CCC(C)C(N)C(O)=O AGPKZVBTJJNPAG-UHFFFAOYSA-N 0.000 description 6
• 230000007246 mechanism Effects 0.000 description 6
• 210000002966 serum Anatomy 0.000 description 6
• 230000009870 specific binding Effects 0.000 description 6
• 230000014616 translation Effects 0.000 description 6
• 239000004474 valine Substances 0.000 description 6
• GOJUJUVQIVIZAV-UHFFFAOYSA-N 2-amino-4,6-dichloropyrimidine-5-carbaldehyde Chemical group NC1=NC(Cl)=C(C=O)C(Cl)=N1 GOJUJUVQIVIZAV-UHFFFAOYSA-N 0.000 description 5
• 102000017420 CD3 protein, epsilon/gamma/delta subunit Human genes 0.000 description 5
• 108050005493 CD3 protein, epsilon/gamma/delta subunit Proteins 0.000 description 5
• 108010019670 Chimeric Antigen Receptors Proteins 0.000 description 5
• 206010018338 Glioma Diseases 0.000 description 5
• XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 5
• 108020004511 Recombinant DNA Proteins 0.000 description 5
• 230000005867 T cell response Effects 0.000 description 5
• 102000044159 Ubiquitin Human genes 0.000 description 5
• 108090000848 Ubiquitin Proteins 0.000 description 5
• 239000002671 adjuvant Substances 0.000 description 5
• 229960003852 atezolizumab Drugs 0.000 description 5
• 230000015572 biosynthetic process Effects 0.000 description 5
• 239000000539 dimer Substances 0.000 description 5
• 229930195712 glutamate Natural products 0.000 description 5
• 229940127121 immunoconjugate Drugs 0.000 description 5
• 230000002401 inhibitory effect Effects 0.000 description 5
• 230000003834 intracellular effect Effects 0.000 description 5
• 201000001441 melanoma Diseases 0.000 description 5
• 210000000822 natural killer cell Anatomy 0.000 description 5
• 230000036961 partial effect Effects 0.000 description 5
• 230000006320 pegylation Effects 0.000 description 5
• 230000004083 survival effect Effects 0.000 description 5
• 238000002560 therapeutic procedure Methods 0.000 description 5
• 238000013519 translation Methods 0.000 description 5
• 210000004881 tumor cell Anatomy 0.000 description 5
• 239000003981 vehicle Substances 0.000 description 5
• 108010022366 Carcinoembryonic Antigen Proteins 0.000 description 4
• 102100025475 Carcinoembryonic antigen-related cell adhesion molecule 5 Human genes 0.000 description 4
• 108010041986 DNA Vaccines Proteins 0.000 description 4
• 229940021995 DNA vaccine Drugs 0.000 description 4
• 101150029707 ERBB2 gene Proteins 0.000 description 4
• 102000004190 Enzymes Human genes 0.000 description 4
• 108090000790 Enzymes Proteins 0.000 description 4
• 102100027581 Forkhead box protein P3 Human genes 0.000 description 4
• 241000282412 Homo Species 0.000 description 4
• 101000861452 Homo sapiens Forkhead box protein P3 Proteins 0.000 description 4
• 108010002350 Interleukin-2 Proteins 0.000 description 4
• 102000000588 Interleukin-2 Human genes 0.000 description 4
• ZDXPYRJPNDTMRX-VKHMYHEASA-N L-glutamine Chemical compound OC(=O)[C@@H](N)CCC(N)=O ZDXPYRJPNDTMRX-VKHMYHEASA-N 0.000 description 4
• 206010027476 Metastases Diseases 0.000 description 4
• 239000012270 PD-1 inhibitor Substances 0.000 description 4
• 239000012668 PD-1-inhibitor Substances 0.000 description 4
• 206010035226 Plasma cell myeloma Diseases 0.000 description 4
• 206010060862 Prostate cancer Diseases 0.000 description 4
• 208000000236 Prostatic Neoplasms Diseases 0.000 description 4
• 108091008611 Protein Kinase B Proteins 0.000 description 4
• 125000000539 amino acid group Chemical group 0.000 description 4
• 125000003277 amino group Chemical group 0.000 description 4
• 238000004458 analytical method Methods 0.000 description 4
• 125000004429 atom Chemical group 0.000 description 4
• 239000002585 base Substances 0.000 description 4
• 210000004899 c-terminal region Anatomy 0.000 description 4
• 125000002843 carboxylic acid group Chemical group 0.000 description 4
• 125000000753 cycloalkyl group Chemical group 0.000 description 4
• 210000001151 cytotoxic T lymphocyte Anatomy 0.000 description 4
• 239000002552 dosage form Substances 0.000 description 4
• 238000005516 engineering process Methods 0.000 description 4
• 229940088598 enzyme Drugs 0.000 description 4
• 239000013604 expression vector Substances 0.000 description 4
• 208000005017 glioblastoma Diseases 0.000 description 4
• ZDXPYRJPNDTMRX-UHFFFAOYSA-N glutamine Natural products OC(=O)C(N)CCC(N)=O ZDXPYRJPNDTMRX-UHFFFAOYSA-N 0.000 description 4
• 125000003630 glycyl group Chemical group [H]N([H])C([H])([H])C(*)=O 0.000 description 4
• 230000013632 homeostatic process Effects 0.000 description 4
• 229940088597 hormone Drugs 0.000 description 4
• 239000005556 hormone Substances 0.000 description 4
• 239000001257 hydrogen Substances 0.000 description 4
• 125000004435 hydrogen atom Chemical group [H]* 0.000 description 4
• 230000007774 longterm Effects 0.000 description 4
• 108020004999 messenger RNA Proteins 0.000 description 4
• 230000009401 metastasis Effects 0.000 description 4
• 229910052760 oxygen Inorganic materials 0.000 description 4
• 229960001972 panitumumab Drugs 0.000 description 4
• 229940121655 pd-1 inhibitor Drugs 0.000 description 4
• 210000003819 peripheral blood mononuclear cell Anatomy 0.000 description 4
• 230000004962 physiological condition Effects 0.000 description 4
• 239000013612 plasmid Substances 0.000 description 4
• 102000040430 polynucleotide Human genes 0.000 description 4
• 108091033319 polynucleotide Proteins 0.000 description 4
• 239000002157 polynucleotide Substances 0.000 description 4
• 230000002035 prolonged effect Effects 0.000 description 4
• 230000012846 protein folding Effects 0.000 description 4
• 230000005855 radiation Effects 0.000 description 4
• 239000011347 resin Substances 0.000 description 4
• 229920005989 resin Polymers 0.000 description 4
• 229960004641 rituximab Drugs 0.000 description 4
• 230000035945 sensitivity Effects 0.000 description 4
• 239000002904 solvent Substances 0.000 description 4
• 125000006850 spacer group Chemical group 0.000 description 4
• 125000001424 substituent group Chemical group 0.000 description 4
• 238000013518 transcription Methods 0.000 description 4
• 230000035897 transcription Effects 0.000 description 4
• 229960000575 trastuzumab Drugs 0.000 description 4
• 150000003852 triazoles Chemical group 0.000 description 4
• 125000003088 (fluoren-9-ylmethoxy)carbonyl group Chemical group 0.000 description 3
• 108091032973 (ribonucleotides)n+m Proteins 0.000 description 3
• 102100033793 ALK tyrosine kinase receptor Human genes 0.000 description 3
• 101710168331 ALK tyrosine kinase receptor Proteins 0.000 description 3
• QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
• 206010003571 Astrocytoma Diseases 0.000 description 3
• 102100022005 B-lymphocyte antigen CD20 Human genes 0.000 description 3
• 206010006187 Breast cancer Diseases 0.000 description 3
• 208000026310 Breast neoplasm Diseases 0.000 description 3
• 101710149863 C-C chemokine receptor type 4 Proteins 0.000 description 3
• 102100035875 C-C chemokine receptor type 5 Human genes 0.000 description 3
• 101710149870 C-C chemokine receptor type 5 Proteins 0.000 description 3
• 102100032976 CCR4-NOT transcription complex subunit 6 Human genes 0.000 description 3
• 239000012275 CTLA-4 inhibitor Substances 0.000 description 3
• 229940045513 CTLA4 antagonist Drugs 0.000 description 3
• 102000019034 Chemokines Human genes 0.000 description 3
• 108010012236 Chemokines Proteins 0.000 description 3
• 102100028757 Chondroitin sulfate proteoglycan 4 Human genes 0.000 description 3
• 108091035707 Consensus sequence Proteins 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
• 108010087819 Fc receptors Proteins 0.000 description 3
• 102000009109 Fc receptors Human genes 0.000 description 3
• 102100040578 G antigen 7 Human genes 0.000 description 3
• 208000032612 Glial tumor Diseases 0.000 description 3
• 102000003886 Glycoproteins Human genes 0.000 description 3
• 108090000288 Glycoproteins Proteins 0.000 description 3
• 102000009465 Growth Factor Receptors Human genes 0.000 description 3
• 108010009202 Growth Factor Receptors Proteins 0.000 description 3
• 101000897405 Homo sapiens B-lymphocyte antigen CD20 Proteins 0.000 description 3
• 101000916489 Homo sapiens Chondroitin sulfate proteoglycan 4 Proteins 0.000 description 3
• 101000893968 Homo sapiens G antigen 7 Proteins 0.000 description 3
• 101001043807 Homo sapiens Interleukin-7 Proteins 0.000 description 3
• 208000009164 Islet Cell Adenoma Diseases 0.000 description 3
• 102100033467 L-selectin Human genes 0.000 description 3
• 206010025323 Lymphomas Diseases 0.000 description 3
• 206010025327 Lymphopenia Diseases 0.000 description 3
• OFOBLEOULBTSOW-UHFFFAOYSA-N Malonic acid Chemical compound OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 3
• 102000018697 Membrane Proteins Human genes 0.000 description 3
• 108010052285 Membrane Proteins Proteins 0.000 description 3
• 201000003793 Myelodysplastic syndrome Diseases 0.000 description 3
• 206010029113 Neovascularisation Diseases 0.000 description 3
• 101710160107 Outer membrane protein A Proteins 0.000 description 3
• 239000012271 PD-L1 inhibitor Substances 0.000 description 3
• RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 3
• 206010039491 Sarcoma Diseases 0.000 description 3
• 208000005718 Stomach Neoplasms Diseases 0.000 description 3
• 108010016672 Syk Kinase Proteins 0.000 description 3
• 102000000551 Syk Kinase Human genes 0.000 description 3
• 108091008874 T cell receptors Proteins 0.000 description 3
• 102000016266 T-Cell Antigen Receptors Human genes 0.000 description 3
• 102000007000 Tenascin Human genes 0.000 description 3
• 108010008125 Tenascin Proteins 0.000 description 3
• 102000004338 Transferrin Human genes 0.000 description 3
• 108090000901 Transferrin Proteins 0.000 description 3
• 108091008605 VEGF receptors Proteins 0.000 description 3
• 125000002777 acetyl group Chemical class [H]C([H])([H])C(*)=O 0.000 description 3
• 230000008484 agonism Effects 0.000 description 3
• 125000003545 alkoxy group Chemical group 0.000 description 3
• 230000008485 antagonism Effects 0.000 description 3
• 230000000890 antigenic effect Effects 0.000 description 3
• QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 3
• 229950002916 avelumab Drugs 0.000 description 3
• 210000003719 b-lymphocyte Anatomy 0.000 description 3
• 230000008901 benefit Effects 0.000 description 3
• 125000004057 biotinyl group Chemical group [H]N1C(=O)N([H])[C@]2([H])[C@@]([H])(SC([H])([H])[C@]12[H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C(*)=O 0.000 description 3
• 230000037396 body weight Effects 0.000 description 3
• 210000004556 brain Anatomy 0.000 description 3
• 150000001721 carbon Chemical group 0.000 description 3
• 238000006243 chemical reaction Methods 0.000 description 3
• KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
• 230000001419 dependent effect Effects 0.000 description 3
• 238000011161 development Methods 0.000 description 3
• 230000018109 developmental process Effects 0.000 description 3
• 238000009826 distribution Methods 0.000 description 3
• 230000000857 drug effect Effects 0.000 description 3
• 229950009791 durvalumab Drugs 0.000 description 3
• 210000003162 effector t lymphocyte Anatomy 0.000 description 3
• 230000005670 electromagnetic radiation Effects 0.000 description 3
• 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 3
• 238000009472 formulation Methods 0.000 description 3
• 206010017758 gastric cancer Diseases 0.000 description 3
• 239000003102 growth factor Substances 0.000 description 3
• 230000036541 health Effects 0.000 description 3
• 206010073071 hepatocellular carcinoma Diseases 0.000 description 3
• 231100000844 hepatocellular carcinoma Toxicity 0.000 description 3
• FUZZWVXGSFPDMH-UHFFFAOYSA-N hexanoic acid Chemical compound CCCCCC(O)=O FUZZWVXGSFPDMH-UHFFFAOYSA-N 0.000 description 3
• 102000052622 human IL7 Human genes 0.000 description 3
• 230000002163 immunogen Effects 0.000 description 3
• 238000000338 in vitro Methods 0.000 description 3
• 238000000099 in vitro assay Methods 0.000 description 3
• 208000015181 infectious disease Diseases 0.000 description 3
• 238000001990 intravenous administration Methods 0.000 description 3
• 229910052742 iron Inorganic materials 0.000 description 3
• 208000032839 leukemia Diseases 0.000 description 3
• 208000012987 lip and oral cavity carcinoma Diseases 0.000 description 3
• 231100001023 lymphopenia Toxicity 0.000 description 3
• 238000012423 maintenance Methods 0.000 description 3
• 239000004570 mortar (masonry) Substances 0.000 description 3
• 230000007935 neutral effect Effects 0.000 description 3
• 208000002154 non-small cell lung carcinoma Diseases 0.000 description 3
• 239000001301 oxygen Substances 0.000 description 3
• 208000022102 pancreatic neuroendocrine neoplasm Diseases 0.000 description 3
• 229940121656 pd-l1 inhibitor Drugs 0.000 description 3
• 230000002093 peripheral effect Effects 0.000 description 3
• 239000002243 precursor Substances 0.000 description 3
• 239000000047 product Substances 0.000 description 3
• 230000001737 promoting effect Effects 0.000 description 3
• 238000010188 recombinant method Methods 0.000 description 3
• 238000004064 recycling Methods 0.000 description 3
• 210000002955 secretory cell Anatomy 0.000 description 3
• 239000012453 solvate Substances 0.000 description 3
• 230000000087 stabilizing effect Effects 0.000 description 3
• 201000011549 stomach cancer Diseases 0.000 description 3
• 229920001059 synthetic polymer Polymers 0.000 description 3
• 230000001839 systemic circulation Effects 0.000 description 3
• 230000009885 systemic effect Effects 0.000 description 3
• 210000001541 thymus gland Anatomy 0.000 description 3
• 230000001988 toxicity Effects 0.000 description 3
• 231100000419 toxicity Toxicity 0.000 description 3
• 239000012581 transferrin Substances 0.000 description 3
• 208000029729 tumor suppressor gene on chromosome 11 Diseases 0.000 description 3
• 239000013598 vector Substances 0.000 description 3
• YBJHBAHKTGYVGT-ZKWXMUAHSA-N (+)-Biotin Chemical compound N1C(=O)N[C@@H]2[C@H](CCCCC(=O)O)SC[C@@H]21 YBJHBAHKTGYVGT-ZKWXMUAHSA-N 0.000 description 2
• HZAXFHJVJLSVMW-UHFFFAOYSA-N 2-Aminoethan-1-ol Chemical compound NCCO HZAXFHJVJLSVMW-UHFFFAOYSA-N 0.000 description 2
• XMIIGOLPHOKFCH-UHFFFAOYSA-N 3-phenylpropionic acid Chemical compound OC(=O)CCC1=CC=CC=C1 XMIIGOLPHOKFCH-UHFFFAOYSA-N 0.000 description 2
• QCQCHGYLTSGIGX-GHXANHINSA-N 4-[[(3ar,5ar,5br,7ar,9s,11ar,11br,13as)-5a,5b,8,8,11a-pentamethyl-3a-[(5-methylpyridine-3-carbonyl)amino]-2-oxo-1-propan-2-yl-4,5,6,7,7a,9,10,11,11b,12,13,13a-dodecahydro-3h-cyclopenta[a]chrysen-9-yl]oxy]-2,2-dimethyl-4-oxobutanoic acid Chemical compound N([C@@]12CC[C@@]3(C)[C@]4(C)CC[C@H]5C(C)(C)[C@@H](OC(=O)CC(C)(C)C(O)=O)CC[C@]5(C)[C@H]4CC[C@@H]3C1=C(C(C2)=O)C(C)C)C(=O)C1=CN=CC(C)=C1 QCQCHGYLTSGIGX-GHXANHINSA-N 0.000 description 2
• 229940113178 5 Alpha reductase inhibitor Drugs 0.000 description 2
• 239000002677 5-alpha reductase inhibitor Substances 0.000 description 2
• 208000031261 Acute myeloid leukaemia Diseases 0.000 description 2
• IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical group N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
• 208000003174 Brain Neoplasms Diseases 0.000 description 2
• 102100025074 C-C chemokine receptor-like 2 Human genes 0.000 description 2
• 102100027207 CD27 antigen Human genes 0.000 description 2
• 208000025721 COVID-19 Diseases 0.000 description 2
• 108010001857 Cell Surface Receptors Proteins 0.000 description 2
• 102100036158 Ceramide kinase Human genes 0.000 description 2
• 108010017573 Ceramide kinase Proteins 0.000 description 2
• 102000011022 Chorionic Gonadotropin Human genes 0.000 description 2
• 108010062540 Chorionic Gonadotropin Proteins 0.000 description 2
• 102100026234 Cytokine receptor common subunit gamma Human genes 0.000 description 2
• RGHNJXZEOKUKBD-SQOUGZDYSA-N D-gluconic acid Chemical group OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C(O)=O RGHNJXZEOKUKBD-SQOUGZDYSA-N 0.000 description 2
• 102000053602 DNA Human genes 0.000 description 2
• 102100025012 Dipeptidyl peptidase 4 Human genes 0.000 description 2
• 102100023272 Dual specificity mitogen-activated protein kinase kinase 5 Human genes 0.000 description 2
• 241001481760 Erethizon dorsatum Species 0.000 description 2
• 208000000461 Esophageal Neoplasms Diseases 0.000 description 2
• LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 2
• 102000016359 Fibronectins Human genes 0.000 description 2
• 108010067306 Fibronectins Proteins 0.000 description 2
• ZHNUHDYFZUAESO-UHFFFAOYSA-N Formamide Chemical group NC=O ZHNUHDYFZUAESO-UHFFFAOYSA-N 0.000 description 2
• VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 2
• 101000766307 Gallus gallus Ovotransferrin Proteins 0.000 description 2
• 101000930822 Giardia intestinalis Dipeptidyl-peptidase 4 Proteins 0.000 description 2
• 102100041003 Glutamate carboxypeptidase 2 Human genes 0.000 description 2
• AEMRFAOFKBGASW-UHFFFAOYSA-N Glycolic acid Chemical compound OCC(O)=O AEMRFAOFKBGASW-UHFFFAOYSA-N 0.000 description 2
• 244000060234 Gmelina philippensis Species 0.000 description 2
• NTYJJOPFIAHURM-UHFFFAOYSA-N Histamine Chemical compound NCCC1=CN=CN1 NTYJJOPFIAHURM-UHFFFAOYSA-N 0.000 description 2
• 102100038970 Histone-lysine N-methyltransferase EZH2 Human genes 0.000 description 2
• 101710196274 Histone-lysine N-methyltransferase EZH2 Proteins 0.000 description 2
• 101000716068 Homo sapiens C-C chemokine receptor type 6 Proteins 0.000 description 2
• 101000914511 Homo sapiens CD27 antigen Proteins 0.000 description 2
• 101001115390 Homo sapiens Dual specificity mitogen-activated protein kinase kinase 5 Proteins 0.000 description 2
• 101000892862 Homo sapiens Glutamate carboxypeptidase 2 Proteins 0.000 description 2
• 101001114057 Homo sapiens P antigen family member 1 Proteins 0.000 description 2
• 101000914514 Homo sapiens T-cell-specific surface glycoprotein CD28 Proteins 0.000 description 2
• 101000851376 Homo sapiens Tumor necrosis factor receptor superfamily member 8 Proteins 0.000 description 2
• VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
• 102000006496 Immunoglobulin Heavy Chains Human genes 0.000 description 2
• 108010019476 Immunoglobulin Heavy Chains Proteins 0.000 description 2
• 102100020792 Interleukin-12 receptor subunit beta-2 Human genes 0.000 description 2
• 101710103840 Interleukin-12 receptor subunit beta-2 Proteins 0.000 description 2
• 102000010781 Interleukin-6 Receptors Human genes 0.000 description 2
• 108010038501 Interleukin-6 Receptors Proteins 0.000 description 2
• 108010024121 Janus Kinases Proteins 0.000 description 2
• 102000015617 Janus Kinases Human genes 0.000 description 2
• 150000007649 L alpha amino acids Chemical class 0.000 description 2
• 102000007547 Laminin Human genes 0.000 description 2
• 108010085895 Laminin Proteins 0.000 description 2
• 241000712899 Lymphocytic choriomeningitis mammarenavirus Species 0.000 description 2
• 102000043136 MAP kinase family Human genes 0.000 description 2
• 108091054455 MAP kinase family Proteins 0.000 description 2
• 230000037364 MAPK/ERK pathway Effects 0.000 description 2
• 241000124008 Mammalia Species 0.000 description 2
• 102100028389 Melanoma antigen recognized by T-cells 1 Human genes 0.000 description 2
• 241001465754 Metazoa Species 0.000 description 2
• AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 2
• 208000003445 Mouth Neoplasms Diseases 0.000 description 2
• 208000034578 Multiple myelomas Diseases 0.000 description 2
• 241001529936 Murinae Species 0.000 description 2
• 206010028729 Nasal cavity cancer Diseases 0.000 description 2
• 206010030155 Oesophageal carcinoma Diseases 0.000 description 2
• 108091034117 Oligonucleotide Proteins 0.000 description 2
• 102000015636 Oligopeptides Human genes 0.000 description 2
• 108010038807 Oligopeptides Proteins 0.000 description 2
• 102100023219 P antigen family member 1 Human genes 0.000 description 2
• 108091008606 PDGF receptors Proteins 0.000 description 2
• 206010061902 Pancreatic neoplasm Diseases 0.000 description 2
• 102000035195 Peptidases Human genes 0.000 description 2
• 108091005804 Peptidases Proteins 0.000 description 2
• 108091093037 Peptide nucleic acid Proteins 0.000 description 2
• NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
• 108091000080 Phosphotransferase Proteins 0.000 description 2
• NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 2
• 102000011653 Platelet-Derived Growth Factor Receptors Human genes 0.000 description 2
• 102000007066 Prostate-Specific Antigen Human genes 0.000 description 2
• 108010072866 Prostate-Specific Antigen Proteins 0.000 description 2
• 239000004365 Protease Substances 0.000 description 2
• JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
• LCTONWCANYUPML-UHFFFAOYSA-N Pyruvic acid Chemical compound CC(=O)C(O)=O LCTONWCANYUPML-UHFFFAOYSA-N 0.000 description 2
• 102000051619 SUMO-1 Human genes 0.000 description 2
• 108700038981 SUMO-1 Proteins 0.000 description 2
• 208000000453 Skin Neoplasms Diseases 0.000 description 2
• QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
• 230000006052 T cell proliferation Effects 0.000 description 2
• 102100027213 T-cell-specific surface glycoprotein CD28 Human genes 0.000 description 2
• 102100038126 Tenascin Human genes 0.000 description 2
• 208000003721 Triple Negative Breast Neoplasms Diseases 0.000 description 2
• 108060008682 Tumor Necrosis Factor Proteins 0.000 description 2
• 102100036857 Tumor necrosis factor receptor superfamily member 8 Human genes 0.000 description 2
• 102000009484 Vascular Endothelial Growth Factor Receptors Human genes 0.000 description 2
• 101001116872 Xenopus laevis Protein Pat Proteins 0.000 description 2
• 108010016200 Zinc Finger Protein GLI1 Proteins 0.000 description 2
• 102100035535 Zinc finger protein GLI1 Human genes 0.000 description 2
• 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 2
• DZBUGLKDJFMEHC-UHFFFAOYSA-N acridine Chemical compound C1=CC=CC2=CC3=CC=CC=C3N=C21 DZBUGLKDJFMEHC-UHFFFAOYSA-N 0.000 description 2
• 229960000548 alemtuzumab Drugs 0.000 description 2
• 150000001335 aliphatic alkanes Chemical class 0.000 description 2
• 125000002947 alkylene group Chemical group 0.000 description 2
• 238000010171 animal model Methods 0.000 description 2
• 230000000259 anti-tumor effect Effects 0.000 description 2
• 230000010056 antibody-dependent cellular cytotoxicity Effects 0.000 description 2
• 230000005888 antibody-dependent cellular phagocytosis Effects 0.000 description 2
• 210000000612 antigen-presenting cell Anatomy 0.000 description 2
• 238000003556 assay Methods 0.000 description 2
• WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 2
• UCMIRNVEIXFBKS-UHFFFAOYSA-N beta-alanine Chemical compound NCCC(O)=O UCMIRNVEIXFBKS-UHFFFAOYSA-N 0.000 description 2
• 229960000397 bevacizumab Drugs 0.000 description 2
• 230000003115 biocidal effect Effects 0.000 description 2
• 230000033228 biological regulation Effects 0.000 description 2
• 230000008512 biological response Effects 0.000 description 2
• 230000005540 biological transmission Effects 0.000 description 2
• 229960000455 brentuximab vedotin Drugs 0.000 description 2
• 239000011203 carbon fibre reinforced carbon Substances 0.000 description 2
• 230000004663 cell proliferation Effects 0.000 description 2
• 238000002659 cell therapy Methods 0.000 description 2
• 230000005754 cellular signaling Effects 0.000 description 2
• 229940015047 chorionic gonadotropin Drugs 0.000 description 2
• 238000004587 chromatography analysis Methods 0.000 description 2
• 230000001684 chronic effect Effects 0.000 description 2
• 238000002648 combination therapy Methods 0.000 description 2
• 238000012875 competitive assay Methods 0.000 description 2
• 230000000295 complement effect Effects 0.000 description 2
• 230000004540 complement-dependent cytotoxicity Effects 0.000 description 2
• 230000001276 controlling effect Effects 0.000 description 2
• 230000008878 coupling Effects 0.000 description 2
• 238000010168 coupling process Methods 0.000 description 2
• 238000005859 coupling reaction Methods 0.000 description 2
• 125000006165 cyclic alkyl group Chemical group 0.000 description 2
• 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 2
• 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 2
• 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 2
• 230000003013 cytotoxicity Effects 0.000 description 2
• 231100000135 cytotoxicity Toxicity 0.000 description 2
• 229960002806 daclizumab Drugs 0.000 description 2
• 230000007423 decrease Effects 0.000 description 2
• 230000007812 deficiency Effects 0.000 description 2
• 229960001251 denosumab Drugs 0.000 description 2
• 238000001212 derivatisation Methods 0.000 description 2
• 238000013461 design Methods 0.000 description 2
• 238000001514 detection method Methods 0.000 description 2
• XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 2
• 230000002255 enzymatic effect Effects 0.000 description 2
• 201000004101 esophageal cancer Diseases 0.000 description 2
• 230000001747 exhibiting effect Effects 0.000 description 2
• 230000005714 functional activity Effects 0.000 description 2
• 238000002825 functional assay Methods 0.000 description 2
• BTCSSZJGUNDROE-UHFFFAOYSA-N gamma-aminobutyric acid Chemical compound NCCCC(O)=O BTCSSZJGUNDROE-UHFFFAOYSA-N 0.000 description 2
• 230000013595 glycosylation Effects 0.000 description 2
• 238000006206 glycosylation reaction Methods 0.000 description 2
• 201000010536 head and neck cancer Diseases 0.000 description 2
• 208000014829 head and neck neoplasm Diseases 0.000 description 2
• 210000002443 helper t lymphocyte Anatomy 0.000 description 2
• 201000005787 hematologic cancer Diseases 0.000 description 2
• 208000024200 hematopoietic and lymphoid system neoplasm Diseases 0.000 description 2
• 230000007062 hydrolysis Effects 0.000 description 2
• 238000006460 hydrolysis reaction Methods 0.000 description 2
• 230000002267 hypothalamic effect Effects 0.000 description 2
• 230000036039 immunity Effects 0.000 description 2
• 230000005847 immunogenicity Effects 0.000 description 2
• 230000006698 induction Effects 0.000 description 2
• 230000005764 inhibitory process Effects 0.000 description 2
• 102000006495 integrins Human genes 0.000 description 2
• 108010044426 integrins Proteins 0.000 description 2
• SUMDYPCJJOFFON-UHFFFAOYSA-N isethionic acid Chemical compound OCCS(O)(=O)=O SUMDYPCJJOFFON-UHFFFAOYSA-N 0.000 description 2
• 201000002529 islet cell tumor Diseases 0.000 description 2
• KQNPFQTWMSNSAP-UHFFFAOYSA-N isobutyric acid Chemical compound CC(C)C(O)=O KQNPFQTWMSNSAP-UHFFFAOYSA-N 0.000 description 2
• JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 2
• 201000007270 liver cancer Diseases 0.000 description 2
• 210000002540 macrophage Anatomy 0.000 description 2
• 230000003211 malignant effect Effects 0.000 description 2
• 238000004519 manufacturing process Methods 0.000 description 2
• 239000012528 membrane Substances 0.000 description 2
• 230000015654 memory Effects 0.000 description 2
• 230000004060 metabolic process Effects 0.000 description 2
• 229910052751 metal Inorganic materials 0.000 description 2
• 239000002184 metal Substances 0.000 description 2
• 150000007522 mineralic acids Chemical class 0.000 description 2
• 238000010172 mouse model Methods 0.000 description 2
• TXXHDPDFNKHHGW-UHFFFAOYSA-N muconic acid Chemical group OC(=O)C=CC=CC(O)=O TXXHDPDFNKHHGW-UHFFFAOYSA-N 0.000 description 2
• 201000005962 mycosis fungoides Diseases 0.000 description 2
• 201000000050 myeloid neoplasm Diseases 0.000 description 2
• 230000006780 non-homologous end joining Effects 0.000 description 2
• 229960002450 ofatumumab Drugs 0.000 description 2
• 201000002528 pancreatic cancer Diseases 0.000 description 2
• 239000004031 partial agonist Substances 0.000 description 2
• 244000052769 pathogen Species 0.000 description 2
• 239000000816 peptidomimetic Substances 0.000 description 2
• 229960002087 pertuzumab Drugs 0.000 description 2
• 230000003285 pharmacodynamic effect Effects 0.000 description 2
• 102000020233 phosphotransferase Human genes 0.000 description 2
• 238000002600 positron emission tomography Methods 0.000 description 2
• 230000035935 pregnancy Effects 0.000 description 2
• 230000002265 prevention Effects 0.000 description 2
• 230000002062 proliferating effect Effects 0.000 description 2
• 230000000069 prophylactic effect Effects 0.000 description 2
• 108020001580 protein domains Proteins 0.000 description 2
• 230000007026 protein scission Effects 0.000 description 2
• 230000002285 radioactive effect Effects 0.000 description 2
• 108091008598 receptor tyrosine kinases Proteins 0.000 description 2
• 102000027426 receptor tyrosine kinases Human genes 0.000 description 2
• 230000009467 reduction Effects 0.000 description 2
• 230000002829 reductive effect Effects 0.000 description 2
• 230000002441 reversible effect Effects 0.000 description 2
• 238000007363 ring formation reaction Methods 0.000 description 2
• YGSDEFSMJLZEOE-UHFFFAOYSA-N salicylic acid Chemical group OC(=O)C1=CC=CC=C1O YGSDEFSMJLZEOE-UHFFFAOYSA-N 0.000 description 2
• 229920006395 saturated elastomer Polymers 0.000 description 2
• 238000002603 single-photon emission computed tomography Methods 0.000 description 2
• 201000000849 skin cancer Diseases 0.000 description 2
• 238000010532 solid phase synthesis reaction Methods 0.000 description 2
• 241000894007 species Species 0.000 description 2
• 238000010561 standard procedure Methods 0.000 description 2
• 230000004936 stimulating effect Effects 0.000 description 2
• 238000007920 subcutaneous administration Methods 0.000 description 2
• 201000008205 supratentorial primitive neuroectodermal tumor Diseases 0.000 description 2
• 230000002195 synergetic effect Effects 0.000 description 2
• 231100001274 therapeutic index Toxicity 0.000 description 2
• VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 2
• 230000032258 transport Effects 0.000 description 2
• 239000013638 trimer Substances 0.000 description 2
• 208000022679 triple-negative breast carcinoma Diseases 0.000 description 2
• APJYDQYYACXCRM-UHFFFAOYSA-N tryptamine Chemical compound C1=CC=C2C(CCN)=CNC2=C1 APJYDQYYACXCRM-UHFFFAOYSA-N 0.000 description 2
• 238000002255 vaccination Methods 0.000 description 2
• 229940124676 vascular endothelial growth factor receptor Drugs 0.000 description 2
• OGNSCSPNOLGXSM-UHFFFAOYSA-N (+/-)-DABA Natural products NCCC(N)C(O)=O OGNSCSPNOLGXSM-UHFFFAOYSA-N 0.000 description 1
• QBYIENPQHBMVBV-HFEGYEGKSA-N (2R)-2-hydroxy-2-phenylacetic acid Chemical compound O[C@@H](C(O)=O)c1ccccc1.O[C@@H](C(O)=O)c1ccccc1 QBYIENPQHBMVBV-HFEGYEGKSA-N 0.000 description 1
• KIUKXJAPPMFGSW-DNGZLQJQSA-N (2S,3S,4S,5R,6R)-6-[(2S,3R,4R,5S,6R)-3-Acetamido-2-[(2S,3S,4R,5R,6R)-6-[(2R,3R,4R,5S,6R)-3-acetamido-2,5-dihydroxy-6-(hydroxymethyl)oxan-4-yl]oxy-2-carboxy-4,5-dihydroxyoxan-3-yl]oxy-5-hydroxy-6-(hydroxymethyl)oxan-4-yl]oxy-3,4,5-trihydroxyoxane-2-carboxylic acid Chemical compound CC(=O)N[C@H]1[C@H](O)O[C@H](CO)[C@@H](O)[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@H](O[C@H]2[C@@H]([C@@H](O[C@H]3[C@@H]([C@@H](O)[C@H](O)[C@H](O3)C(O)=O)O)[C@H](O)[C@@H](CO)O2)NC(C)=O)[C@@H](C(O)=O)O1 KIUKXJAPPMFGSW-DNGZLQJQSA-N 0.000 description 1
• LDDMACCNBZAMSG-BDVNFPICSA-N (2r,3r,4s,5r)-3,4,5,6-tetrahydroxy-2-(methylamino)hexanal Chemical compound CN[C@@H](C=O)[C@@H](O)[C@H](O)[C@H](O)CO LDDMACCNBZAMSG-BDVNFPICSA-N 0.000 description 1
• KWMLJOLKUYYJFJ-GASJEMHNSA-N (2xi)-D-gluco-heptonic acid Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C(O)C(O)=O KWMLJOLKUYYJFJ-GASJEMHNSA-N 0.000 description 1
• MZOFCQQQCNRIBI-VMXHOPILSA-N (3s)-4-[[(2s)-1-[[(2s)-1-[[(1s)-1-carboxy-2-hydroxyethyl]amino]-4-methyl-1-oxopentan-2-yl]amino]-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-3-[[2-[[(2s)-2,6-diaminohexanoyl]amino]acetyl]amino]-4-oxobutanoic acid Chemical compound OC[C@@H](C(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCN=C(N)N)NC(=O)[C@H](CC(O)=O)NC(=O)CNC(=O)[C@@H](N)CCCCN MZOFCQQQCNRIBI-VMXHOPILSA-N 0.000 description 1
• 125000004169 (C1-C6) alkyl group Chemical group 0.000 description 1
• 125000006555 (C3-C5) cycloalkyl group Chemical group 0.000 description 1
• 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 description 1
• 125000006552 (C3-C8) cycloalkyl group Chemical group 0.000 description 1
• 125000006704 (C5-C6) cycloalkyl group Chemical group 0.000 description 1
• MIOPJNTWMNEORI-GMSGAONNSA-N (S)-camphorsulfonic acid Chemical compound C1C[C@@]2(CS(O)(=O)=O)C(=O)C[C@@H]1C2(C)C MIOPJNTWMNEORI-GMSGAONNSA-N 0.000 description 1
• BJEPYKJPYRNKOW-REOHCLBHSA-N (S)-malic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O BJEPYKJPYRNKOW-REOHCLBHSA-N 0.000 description 1
• WBYWAXJHAXSJNI-VOTSOKGWSA-M .beta-Phenylacrylic acid Natural products [O-]C(=O)\C=C\C1=CC=CC=C1 WBYWAXJHAXSJNI-VOTSOKGWSA-M 0.000 description 1
• WEYNBWVKOYCCQT-UHFFFAOYSA-N 1-(3-chloro-4-methylphenyl)-3-{2-[({5-[(dimethylamino)methyl]-2-furyl}methyl)thio]ethyl}urea Chemical compound O1C(CN(C)C)=CC=C1CSCCNC(=O)NC1=CC=C(C)C(Cl)=C1 WEYNBWVKOYCCQT-UHFFFAOYSA-N 0.000 description 1
• AMMPLVWPWSYRDR-UHFFFAOYSA-N 1-methylbicyclo[2.2.2]oct-2-ene-4-carboxylic acid Chemical compound C1CC2(C(O)=O)CCC1(C)C=C2 AMMPLVWPWSYRDR-UHFFFAOYSA-N 0.000 description 1
• NFGXHKASABOEEW-UHFFFAOYSA-N 1-methylethyl 11-methoxy-3,7,11-trimethyl-2,4-dodecadienoate Chemical compound COC(C)(C)CCCC(C)CC=CC(C)=CC(=O)OC(C)C NFGXHKASABOEEW-UHFFFAOYSA-N 0.000 description 1
• RTQWWZBSTRGEAV-PKHIMPSTSA-N 2-[[(2s)-2-[bis(carboxymethyl)amino]-3-[4-(methylcarbamoylamino)phenyl]propyl]-[2-[bis(carboxymethyl)amino]propyl]amino]acetic acid Chemical compound CNC(=O)NC1=CC=C(C[C@@H](CN(CC(C)N(CC(O)=O)CC(O)=O)CC(O)=O)N(CC(O)=O)CC(O)=O)C=C1 RTQWWZBSTRGEAV-PKHIMPSTSA-N 0.000 description 1
• UPHOPMSGKZNELG-UHFFFAOYSA-N 2-hydroxynaphthalene-1-carboxylic acid Chemical group C1=CC=C2C(C(=O)O)=C(O)C=CC2=C1 UPHOPMSGKZNELG-UHFFFAOYSA-N 0.000 description 1
• OJDZHBWEGLIKRW-UHFFFAOYSA-N 3-[(4-hydroxyphenyl)methyl]benzoic acid Chemical compound OC(=O)C1=CC=CC(CC=2C=CC(O)=CC=2)=C1 OJDZHBWEGLIKRW-UHFFFAOYSA-N 0.000 description 1
• BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 1
• ZRPLANDPDWYOMZ-UHFFFAOYSA-N 3-cyclopentylpropionic acid Chemical compound OC(=O)CCC1CCCC1 ZRPLANDPDWYOMZ-UHFFFAOYSA-N 0.000 description 1
• RJWBTWIBUIGANW-UHFFFAOYSA-N 4-chlorobenzenesulfonic acid Chemical compound OS(=O)(=O)C1=CC=C(Cl)C=C1 RJWBTWIBUIGANW-UHFFFAOYSA-N 0.000 description 1
• 101710169336 5'-deoxyadenosine deaminase Proteins 0.000 description 1
• MJZJYWCQPMNPRM-UHFFFAOYSA-N 6,6-dimethyl-1-[3-(2,4,5-trichlorophenoxy)propoxy]-1,6-dihydro-1,3,5-triazine-2,4-diamine Chemical compound CC1(C)N=C(N)N=C(N)N1OCCCOC1=CC(Cl)=C(Cl)C=C1Cl MJZJYWCQPMNPRM-UHFFFAOYSA-N 0.000 description 1
• 208000024893 Acute lymphoblastic leukemia Diseases 0.000 description 1
• 208000014697 Acute lymphocytic leukaemia Diseases 0.000 description 1
• 101710137115 Adenylyl cyclase-associated protein 1 Proteins 0.000 description 1
• 102100021879 Adenylyl cyclase-associated protein 2 Human genes 0.000 description 1
• 101710137132 Adenylyl cyclase-associated protein 2 Proteins 0.000 description 1
• 208000006468 Adrenal Cortex Neoplasms Diseases 0.000 description 1
• 108020004774 Alkaline Phosphatase Proteins 0.000 description 1
• 102000002260 Alkaline Phosphatase Human genes 0.000 description 1
• 102000003730 Alpha-catenin Human genes 0.000 description 1
• 108090000020 Alpha-catenin Proteins 0.000 description 1
• 102100023635 Alpha-fetoprotein Human genes 0.000 description 1
• 108090000915 Aminopeptidases Proteins 0.000 description 1
• 102000004400 Aminopeptidases Human genes 0.000 description 1
• 240000003291 Armoracia rusticana Species 0.000 description 1
• 235000011330 Armoracia rusticana Nutrition 0.000 description 1
• 206010060971 Astrocytoma malignant Diseases 0.000 description 1
• 102100022718 Atypical chemokine receptor 2 Human genes 0.000 description 1
• 201000008271 Atypical teratoid rhabdoid tumor Diseases 0.000 description 1
• 108091008875 B cell receptors Proteins 0.000 description 1
• 102100035526 B melanoma antigen 1 Human genes 0.000 description 1
• 208000003950 B-cell lymphoma Diseases 0.000 description 1
• 102100038080 B-cell receptor CD22 Human genes 0.000 description 1
• 102100024222 B-lymphocyte antigen CD19 Human genes 0.000 description 1
• 108010074708 B7-H1 Antigen Proteins 0.000 description 1
• 208000032791 BCR-ABL1 positive chronic myelogenous leukemia Diseases 0.000 description 1
• 241000894006 Bacteria Species 0.000 description 1
• 208000035143 Bacterial infection Diseases 0.000 description 1
• 206010004146 Basal cell carcinoma Diseases 0.000 description 1
• 239000005711 Benzoic acid Substances 0.000 description 1
• 102100026189 Beta-galactosidase Human genes 0.000 description 1
• 206010005003 Bladder cancer Diseases 0.000 description 1
• 206010005949 Bone cancer Diseases 0.000 description 1
• 208000018084 Bone neoplasm Diseases 0.000 description 1
• 102000001805 Bromodomains Human genes 0.000 description 1
• 108050009021 Bromodomains Proteins 0.000 description 1
• 208000011691 Burkitt lymphomas Diseases 0.000 description 1
• 102100024167 C-C chemokine receptor type 3 Human genes 0.000 description 1
• 101710149862 C-C chemokine receptor type 3 Proteins 0.000 description 1
• 102100036301 C-C chemokine receptor type 7 Human genes 0.000 description 1
• 101710149858 C-C chemokine receptor type 7 Proteins 0.000 description 1
• 102100028990 C-X-C chemokine receptor type 3 Human genes 0.000 description 1
• 102100031658 C-X-C chemokine receptor type 5 Human genes 0.000 description 1
• 108010029697 CD40 Ligand Proteins 0.000 description 1
• 101150013553 CD40 gene Proteins 0.000 description 1
• 102100032937 CD40 ligand Human genes 0.000 description 1
• 102100032912 CD44 antigen Human genes 0.000 description 1
• 102000013135 CD52 Antigen Human genes 0.000 description 1
• 108010065524 CD52 Antigen Proteins 0.000 description 1
• 102000000905 Cadherin Human genes 0.000 description 1
• 108050007957 Cadherin Proteins 0.000 description 1
• 101100455063 Caenorhabditis elegans lmp-1 gene Proteins 0.000 description 1
• 241000070928 Calligonum comosum Species 0.000 description 1
• 108090000565 Capsid Proteins Proteins 0.000 description 1
• 101710132601 Capsid protein Proteins 0.000 description 1
• 239000004215 Carbon black (E152) Substances 0.000 description 1
• 101800005309 Carboxy-terminal peptide Proteins 0.000 description 1
• 108010006303 Carboxypeptidases Proteins 0.000 description 1
• 102000005367 Carboxypeptidases Human genes 0.000 description 1
• 206010007275 Carcinoid tumour Diseases 0.000 description 1
• 206010007279 Carcinoid tumour of the gastrointestinal tract Diseases 0.000 description 1
• 102000014914 Carrier Proteins Human genes 0.000 description 1
• 102000011632 Caseins Human genes 0.000 description 1
• 108010076119 Caseins Proteins 0.000 description 1
• 102100028906 Catenin delta-1 Human genes 0.000 description 1
• 102000000844 Cell Surface Receptors Human genes 0.000 description 1
• 206010007953 Central nervous system lymphoma Diseases 0.000 description 1
• 102100023321 Ceruloplasmin Human genes 0.000 description 1
• 206010008342 Cervix carcinoma Diseases 0.000 description 1
• 108091007741 Chimeric antigen receptor T cells Proteins 0.000 description 1
• 201000009047 Chordoma Diseases 0.000 description 1
• 206010008761 Choriomeningitis lymphocytic Diseases 0.000 description 1
• 208000010833 Chronic myeloid leukaemia Diseases 0.000 description 1
• WBYWAXJHAXSJNI-SREVYHEPSA-N Cinnamic acid Chemical compound OC(=O)\C=C/C1=CC=CC=C1 WBYWAXJHAXSJNI-SREVYHEPSA-N 0.000 description 1
• 208000005443 Circulating Neoplastic Cells Diseases 0.000 description 1
• 206010009944 Colon cancer Diseases 0.000 description 1
• 208000001333 Colorectal Neoplasms Diseases 0.000 description 1
• 208000009798 Craniopharyngioma Diseases 0.000 description 1
• 108010025464 Cyclin-Dependent Kinase 4 Proteins 0.000 description 1
• 102100036252 Cyclin-dependent kinase 4 Human genes 0.000 description 1
• 102100032218 Cytokine-inducible SH2-containing protein Human genes 0.000 description 1
• 150000007650 D alpha amino acids Chemical class 0.000 description 1
• 150000008574 D-amino acids Chemical class 0.000 description 1
• LEVWYRKDKASIDU-QWWZWVQMSA-N D-cystine Chemical compound OC(=O)[C@H](N)CSSC[C@@H](N)C(O)=O LEVWYRKDKASIDU-QWWZWVQMSA-N 0.000 description 1
• RGHNJXZEOKUKBD-UHFFFAOYSA-N D-gluconic acid Chemical group OCC(O)C(O)C(O)C(O)C(O)=O RGHNJXZEOKUKBD-UHFFFAOYSA-N 0.000 description 1
• KDXKERNSBIXSRK-RXMQYKEDSA-N D-lysine Chemical compound NCCCC[C@@H](N)C(O)=O KDXKERNSBIXSRK-RXMQYKEDSA-N 0.000 description 1
• 230000005778 DNA damage Effects 0.000 description 1
• 231100000277 DNA damage Toxicity 0.000 description 1
• 239000012626 DNA minor groove binder Substances 0.000 description 1
• 230000006820 DNA synthesis Effects 0.000 description 1
• 208000008743 Desmoplastic Small Round Cell Tumor Diseases 0.000 description 1
• 206010064581 Desmoplastic small round cell tumour Diseases 0.000 description 1
• FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 1
• 101100216227 Dictyostelium discoideum anapc3 gene Proteins 0.000 description 1
• BWGNESOTFCXPMA-UHFFFAOYSA-N Dihydrogen disulfide Chemical compound SS BWGNESOTFCXPMA-UHFFFAOYSA-N 0.000 description 1
• 108010016626 Dipeptides Proteins 0.000 description 1
• 102100023266 Dual specificity mitogen-activated protein kinase kinase 2 Human genes 0.000 description 1
• 101710146529 Dual specificity mitogen-activated protein kinase kinase 2 Proteins 0.000 description 1
• 238000012286 ELISA Assay Methods 0.000 description 1
• 102100025137 Early activation antigen CD69 Human genes 0.000 description 1
• 206010014733 Endometrial cancer Diseases 0.000 description 1
• 206010014759 Endometrial neoplasm Diseases 0.000 description 1
• 201000008228 Ependymoblastoma Diseases 0.000 description 1
• 206010014968 Ependymoma malignant Diseases 0.000 description 1
• 108010069621 Epstein-Barr virus EBV-associated membrane antigen Proteins 0.000 description 1
• 241000588724 Escherichia coli Species 0.000 description 1
• 208000012468 Ewing sarcoma/peripheral primitive neuroectodermal tumor Diseases 0.000 description 1
• 102000010834 Extracellular Matrix Proteins Human genes 0.000 description 1
• 108010037362 Extracellular Matrix Proteins Proteins 0.000 description 1
• 108010067715 Focal Adhesion Protein-Tyrosine Kinases Proteins 0.000 description 1
• 102000016621 Focal Adhesion Protein-Tyrosine Kinases Human genes 0.000 description 1
• 241000710198 Foot-and-mouth disease virus Species 0.000 description 1
• 101100484380 Fowlpox virus (strain NVSL) FPV061 gene Proteins 0.000 description 1
• 102100039699 G antigen 4 Human genes 0.000 description 1
• 101710092267 G antigen 5 Proteins 0.000 description 1
• 102100039698 G antigen 5 Human genes 0.000 description 1
• 101710092269 G antigen 6 Proteins 0.000 description 1
• 102100039713 G antigen 6 Human genes 0.000 description 1
• 102000040452 GAGE family Human genes 0.000 description 1
• 108091072337 GAGE family Proteins 0.000 description 1
• 229940116409 GLI1 inhibitor Drugs 0.000 description 1
• 102100029974 GTPase HRas Human genes 0.000 description 1
• 101710091881 GTPase HRas Proteins 0.000 description 1
• 102100021260 Galactosylgalactosylxylosylprotein 3-beta-glucuronosyltransferase 1 Human genes 0.000 description 1
• 208000022072 Gallbladder Neoplasms Diseases 0.000 description 1
• 102100030525 Gap junction alpha-4 protein Human genes 0.000 description 1
• 201000003741 Gastrointestinal carcinoma Diseases 0.000 description 1
• 206010051066 Gastrointestinal stromal tumour Diseases 0.000 description 1
• 102000007390 Glycogen Phosphorylase Human genes 0.000 description 1
• 108010046163 Glycogen Phosphorylase Proteins 0.000 description 1
• 239000007821 HATU Substances 0.000 description 1
• 101710154606 Hemagglutinin Proteins 0.000 description 1
• 108010022901 Heparin Lyase Proteins 0.000 description 1
• 108010073141 Hepatitis C virus glycoprotein E2 Proteins 0.000 description 1
• 102000018713 Histocompatibility Antigens Class II Human genes 0.000 description 1
• 208000017604 Hodgkin disease Diseases 0.000 description 1
• 208000021519 Hodgkin lymphoma Diseases 0.000 description 1
• 208000010747 Hodgkins lymphoma Diseases 0.000 description 1
• 101000678892 Homo sapiens Atypical chemokine receptor 2 Proteins 0.000 description 1
• 101000874316 Homo sapiens B melanoma antigen 1 Proteins 0.000 description 1
• 101000884305 Homo sapiens B-cell receptor CD22 Proteins 0.000 description 1
• 101000980825 Homo sapiens B-lymphocyte antigen CD19 Proteins 0.000 description 1
• 101000777558 Homo sapiens C-C chemokine receptor type 10 Proteins 0.000 description 1
• 101000916050 Homo sapiens C-X-C chemokine receptor type 3 Proteins 0.000 description 1
• 101000922405 Homo sapiens C-X-C chemokine receptor type 5 Proteins 0.000 description 1
• 101000868273 Homo sapiens CD44 antigen Proteins 0.000 description 1
• 101000943420 Homo sapiens Cytokine-inducible SH2-containing protein Proteins 0.000 description 1
• 101000934374 Homo sapiens Early activation antigen CD69 Proteins 0.000 description 1
• 101000886678 Homo sapiens G antigen 2D Proteins 0.000 description 1
• 101000886136 Homo sapiens G antigen 4 Proteins 0.000 description 1
• 101000894906 Homo sapiens Galactosylgalactosylxylosylprotein 3-beta-glucuronosyltransferase 1 Proteins 0.000 description 1
• 101000840258 Homo sapiens Immunoglobulin J chain Proteins 0.000 description 1
• 101000878605 Homo sapiens Low affinity immunoglobulin epsilon Fc receptor Proteins 0.000 description 1
• 101000578784 Homo sapiens Melanoma antigen recognized by T-cells 1 Proteins 0.000 description 1
• 101001005719 Homo sapiens Melanoma-associated antigen 3 Proteins 0.000 description 1
• 101001057156 Homo sapiens Melanoma-associated antigen C2 Proteins 0.000 description 1
• 101001057159 Homo sapiens Melanoma-associated antigen C3 Proteins 0.000 description 1
• 101000950687 Homo sapiens Mitogen-activated protein kinase 7 Proteins 0.000 description 1
• 101000934338 Homo sapiens Myeloid cell surface antigen CD33 Proteins 0.000 description 1
• 101000622137 Homo sapiens P-selectin Proteins 0.000 description 1
• 101000880770 Homo sapiens Protein SSX2 Proteins 0.000 description 1
• 101000779418 Homo sapiens RAC-alpha serine/threonine-protein kinase Proteins 0.000 description 1
• 101001062222 Homo sapiens Receptor-binding cancer antigen expressed on SiSo cells Proteins 0.000 description 1
• 101000884271 Homo sapiens Signal transducer CD24 Proteins 0.000 description 1
• 101001074042 Homo sapiens Transcriptional activator GLI3 Proteins 0.000 description 1
• 102000003839 Human Proteins Human genes 0.000 description 1
• 108090000144 Human Proteins Proteins 0.000 description 1
• 241000701074 Human alphaherpesvirus 2 Species 0.000 description 1
• 241000701806 Human papillomavirus Species 0.000 description 1
• UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 1
• 206010021042 Hypopharyngeal cancer Diseases 0.000 description 1
• 206010056305 Hypopharyngeal neoplasm Diseases 0.000 description 1
• 108010073816 IgE Receptors Proteins 0.000 description 1
• 102000009438 IgE Receptors Human genes 0.000 description 1
• WRYCSMQKUKOKBP-UHFFFAOYSA-N Imidazolidine Chemical compound C1CNCN1 WRYCSMQKUKOKBP-UHFFFAOYSA-N 0.000 description 1
• 229940123776 Immuno-oncology therapy Drugs 0.000 description 1
• 208000029462 Immunodeficiency disease Diseases 0.000 description 1
• 108010043496 Immunoglobulin Idiotypes Proteins 0.000 description 1
• 102100029571 Immunoglobulin J chain Human genes 0.000 description 1
• 108010067060 Immunoglobulin Variable Region Proteins 0.000 description 1
• 102000017727 Immunoglobulin Variable Region Human genes 0.000 description 1
• 102000008070 Interferon-gamma Human genes 0.000 description 1
• 108010074328 Interferon-gamma Proteins 0.000 description 1
• 108010050904 Interferons Proteins 0.000 description 1
• 102000014150 Interferons Human genes 0.000 description 1
• 108010066719 Interleukin Receptor Common gamma Subunit Proteins 0.000 description 1
• 102000018682 Interleukin Receptor Common gamma Subunit Human genes 0.000 description 1
• 102000003812 Interleukin-15 Human genes 0.000 description 1
• 108090000172 Interleukin-15 Proteins 0.000 description 1
• 102100030703 Interleukin-22 Human genes 0.000 description 1
• 102000004388 Interleukin-4 Human genes 0.000 description 1
• 108090000978 Interleukin-4 Proteins 0.000 description 1
• 108090001005 Interleukin-6 Proteins 0.000 description 1
• 102000004889 Interleukin-6 Human genes 0.000 description 1
• 101710131799 Interleukin-7 receptor subunit alpha Proteins 0.000 description 1
• 108010002335 Interleukin-9 Proteins 0.000 description 1
• 102000000585 Interleukin-9 Human genes 0.000 description 1
• 206010061252 Intraocular melanoma Diseases 0.000 description 1
• 229940122245 Janus kinase inhibitor Drugs 0.000 description 1
• 229940123830 K-Ras inhibitor Drugs 0.000 description 1
• 208000007766 Kaposi sarcoma Diseases 0.000 description 1
• 108010044023 Ki-1 Antigen Proteins 0.000 description 1
• 108010092694 L-Selectin Proteins 0.000 description 1
• 150000008575 L-amino acids Chemical class 0.000 description 1
• 201000005099 Langerhans cell histiocytosis Diseases 0.000 description 1
• 206010023774 Large cell lung cancer Diseases 0.000 description 1
• 206010023825 Laryngeal cancer Diseases 0.000 description 1
• 108090001090 Lectins Proteins 0.000 description 1
• 102000004856 Lectins Human genes 0.000 description 1
• 102100038007 Low affinity immunoglobulin epsilon Fc receptor Human genes 0.000 description 1
• 108060001084 Luciferase Proteins 0.000 description 1
• 239000005089 Luciferase Substances 0.000 description 1
• 206010058467 Lung neoplasm malignant Diseases 0.000 description 1
• 102000019149 MAP kinase activity proteins Human genes 0.000 description 1
• 108040008097 MAP kinase activity proteins Proteins 0.000 description 1
• 108010010995 MART-1 Antigen Proteins 0.000 description 1
• 229940124647 MEK inhibitor Drugs 0.000 description 1
• 239000012820 MEK1 Inhibitor Substances 0.000 description 1
• 108091054438 MHC class II family Proteins 0.000 description 1
• 208000004059 Male Breast Neoplasms Diseases 0.000 description 1
• 208000006644 Malignant Fibrous Histiocytoma Diseases 0.000 description 1
• 208000030070 Malignant epithelial tumor of ovary Diseases 0.000 description 1
• 208000032271 Malignant tumor of penis Diseases 0.000 description 1
• 102000002274 Matrix Metalloproteinases Human genes 0.000 description 1
• 108010000684 Matrix Metalloproteinases Proteins 0.000 description 1
• 102000000440 Melanoma-associated antigen Human genes 0.000 description 1
• 108050008953 Melanoma-associated antigen Proteins 0.000 description 1
• 102100025082 Melanoma-associated antigen 3 Human genes 0.000 description 1
• 102100027252 Melanoma-associated antigen C2 Human genes 0.000 description 1
• 102100027248 Melanoma-associated antigen C3 Human genes 0.000 description 1
• 208000002030 Merkel cell carcinoma Diseases 0.000 description 1
• 206010027406 Mesothelioma Diseases 0.000 description 1
• 102100037805 Mitogen-activated protein kinase 7 Human genes 0.000 description 1
• TXXHDPDFNKHHGW-CCAGOZQPSA-N Muconic acid Chemical group OC(=O)\C=C/C=C\C(O)=O TXXHDPDFNKHHGW-CCAGOZQPSA-N 0.000 description 1
• 101001043808 Mus musculus Interleukin-7 Proteins 0.000 description 1
• 241000187479 Mycobacterium tuberculosis Species 0.000 description 1
• 208000033761 Myelogenous Chronic BCR-ABL Positive Leukemia Diseases 0.000 description 1
• 208000033776 Myeloid Acute Leukemia Diseases 0.000 description 1
• 102100025243 Myeloid cell surface antigen CD33 Human genes 0.000 description 1
• 201000007224 Myeloproliferative neoplasm Diseases 0.000 description 1
• 208000001894 Nasopharyngeal Neoplasms Diseases 0.000 description 1
• 206010061306 Nasopharyngeal cancer Diseases 0.000 description 1
• 208000034176 Neoplasms, Germ Cell and Embryonal Diseases 0.000 description 1
• 206010029260 Neuroblastoma Diseases 0.000 description 1
• 206010029266 Neuroendocrine carcinoma of the skin Diseases 0.000 description 1
• GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 1
• 208000015914 Non-Hodgkin lymphomas Diseases 0.000 description 1
• 102000014736 Notch Human genes 0.000 description 1
• 108010070047 Notch Receptors Proteins 0.000 description 1
• 108010051791 Nuclear Antigens Proteins 0.000 description 1
• 102000019040 Nuclear Antigens Human genes 0.000 description 1
• 108091028043 Nucleic acid sequence Proteins 0.000 description 1
• 208000000160 Olfactory Esthesioneuroblastoma Diseases 0.000 description 1
• 206010031096 Oropharyngeal cancer Diseases 0.000 description 1
• 206010057444 Oropharyngeal neoplasm Diseases 0.000 description 1
• 102000004264 Osteopontin Human genes 0.000 description 1
• 108010081689 Osteopontin Proteins 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
• 208000007571 Ovarian Epithelial Carcinoma Diseases 0.000 description 1
• 206010033128 Ovarian cancer Diseases 0.000 description 1
• 206010061328 Ovarian epithelial cancer Diseases 0.000 description 1
• 206010061535 Ovarian neoplasm Diseases 0.000 description 1
• 102000004316 Oxidoreductases Human genes 0.000 description 1
• 108090000854 Oxidoreductases Proteins 0.000 description 1
• 102100023472 P-selectin Human genes 0.000 description 1
• 239000012272 PD-L2 inhibitor Substances 0.000 description 1
• 238000012879 PET imaging Methods 0.000 description 1
• 229910019142 PO4 Inorganic materials 0.000 description 1
• 108060006580 PRAME Proteins 0.000 description 1
• 102000036673 PRAME Human genes 0.000 description 1
• 102100034640 PWWP domain-containing DNA repair factor 3A Human genes 0.000 description 1
• 108050007154 PWWP domain-containing DNA repair factor 3A Proteins 0.000 description 1
• 206010061332 Paraganglion neoplasm Diseases 0.000 description 1
• 208000000821 Parathyroid Neoplasms Diseases 0.000 description 1
• 208000002471 Penile Neoplasms Diseases 0.000 description 1
• 206010034299 Penile cancer Diseases 0.000 description 1
• 102100040283 Peptidyl-prolyl cis-trans isomerase B Human genes 0.000 description 1
• 208000009565 Pharyngeal Neoplasms Diseases 0.000 description 1
• 206010034811 Pharyngeal cancer Diseases 0.000 description 1
• 206010050487 Pinealoblastoma Diseases 0.000 description 1
• 208000007641 Pinealoma Diseases 0.000 description 1
• 208000007913 Pituitary Neoplasms Diseases 0.000 description 1
• 208000007452 Plasmacytoma Diseases 0.000 description 1
• 201000008199 Pleuropulmonary blastoma Diseases 0.000 description 1
• 229920003171 Poly (ethylene oxide) Polymers 0.000 description 1
• 208000006664 Precursor Cell Lymphoblastic Leukemia-Lymphoma Diseases 0.000 description 1
• 102100033237 Pro-epidermal growth factor Human genes 0.000 description 1
• 101710098940 Pro-epidermal growth factor Proteins 0.000 description 1
• 102100024216 Programmed cell death 1 ligand 1 Human genes 0.000 description 1
• 101710176177 Protein A56 Proteins 0.000 description 1
• 102100037686 Protein SSX2 Human genes 0.000 description 1
• IWYDHOAUDWTVEP-UHFFFAOYSA-N R-2-phenyl-2-hydroxyacetic acid Natural products OC(=O)C(O)C1=CC=CC=C1 IWYDHOAUDWTVEP-UHFFFAOYSA-N 0.000 description 1
• 101710113459 RAC-alpha serine/threonine-protein kinase Proteins 0.000 description 1
• 102100029165 Receptor-binding cancer antigen expressed on SiSo cells Human genes 0.000 description 1
• 208000015634 Rectal Neoplasms Diseases 0.000 description 1
• 206010038389 Renal cancer Diseases 0.000 description 1
• 208000006265 Renal cell carcinoma Diseases 0.000 description 1
• 201000000582 Retinoblastoma Diseases 0.000 description 1
• 208000004337 Salivary Gland Neoplasms Diseases 0.000 description 1
• 206010061934 Salivary gland cancer Diseases 0.000 description 1
• 206010040047 Sepsis Diseases 0.000 description 1
• 206010040070 Septic Shock Diseases 0.000 description 1
• 102100023085 Serine/threonine-protein kinase mTOR Human genes 0.000 description 1
• 102000007562 Serum Albumin Human genes 0.000 description 1
• 108010071390 Serum Albumin Proteins 0.000 description 1
• 208000009359 Sezary Syndrome Diseases 0.000 description 1
• 102100038081 Signal transducer CD24 Human genes 0.000 description 1
• 206010041067 Small cell lung cancer Diseases 0.000 description 1
• 108010052164 Sodium Channels Proteins 0.000 description 1
• 102000018674 Sodium Channels Human genes 0.000 description 1
• 208000021712 Soft tissue sarcoma Diseases 0.000 description 1
• 235000021355 Stearic acid Nutrition 0.000 description 1
• 108010090804 Streptavidin Proteins 0.000 description 1
• KDYFGRWQOYBRFD-UHFFFAOYSA-N Succinic acid Natural products OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 description 1
• NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 1
• 102100036234 Synaptonemal complex protein 1 Human genes 0.000 description 1
• 101710143177 Synaptonemal complex protein 1 Proteins 0.000 description 1
• 102000019361 Syndecan Human genes 0.000 description 1
• 108050006774 Syndecan Proteins 0.000 description 1
• 230000006044 T cell activation Effects 0.000 description 1
• 208000031673 T-Cell Cutaneous Lymphoma Diseases 0.000 description 1
• 206010042971 T-cell lymphoma Diseases 0.000 description 1
• 208000027585 T-cell non-Hodgkin lymphoma Diseases 0.000 description 1
• 102100033082 TNF receptor-associated factor 3 Human genes 0.000 description 1
• 108010065917 TOR Serine-Threonine Kinases Proteins 0.000 description 1
• FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 1
• 208000024313 Testicular Neoplasms Diseases 0.000 description 1
• 206010057644 Testis cancer Diseases 0.000 description 1
• 210000000447 Th1 cell Anatomy 0.000 description 1
• 210000000068 Th17 cell Anatomy 0.000 description 1
• 210000004241 Th2 cell Anatomy 0.000 description 1
• 206010043515 Throat cancer Diseases 0.000 description 1
• 208000000728 Thymus Neoplasms Diseases 0.000 description 1
• 208000024770 Thyroid neoplasm Diseases 0.000 description 1
• 101710120037 Toxin CcdB Proteins 0.000 description 1
• 102100035559 Transcriptional activator GLI3 Human genes 0.000 description 1
• 108010009583 Transforming Growth Factors Proteins 0.000 description 1
• 102000009618 Transforming Growth Factors Human genes 0.000 description 1
• GSEJCLTVZPLZKY-UHFFFAOYSA-N Triethanolamine Chemical compound OCCN(CCO)CCO GSEJCLTVZPLZKY-UHFFFAOYSA-N 0.000 description 1
• 108060008683 Tumor Necrosis Factor Receptor Proteins 0.000 description 1
• 102000000852 Tumor Necrosis Factor-alpha Human genes 0.000 description 1
• 102100040245 Tumor necrosis factor receptor superfamily member 5 Human genes 0.000 description 1
• 102100039094 Tyrosinase Human genes 0.000 description 1
• 108060008724 Tyrosinase Proteins 0.000 description 1
• 208000015778 Undifferentiated pleomorphic sarcoma Diseases 0.000 description 1
• 208000023915 Ureteral Neoplasms Diseases 0.000 description 1
• 206010046392 Ureteric cancer Diseases 0.000 description 1
• 206010046431 Urethral cancer Diseases 0.000 description 1
• 206010046458 Urethral neoplasms Diseases 0.000 description 1
• 208000007097 Urinary Bladder Neoplasms Diseases 0.000 description 1
• 208000006105 Uterine Cervical Neoplasms Diseases 0.000 description 1
• 201000005969 Uveal melanoma Diseases 0.000 description 1
• 238000005411 Van der Waals force Methods 0.000 description 1
• 102100033177 Vascular endothelial growth factor receptor 2 Human genes 0.000 description 1
• 108020000999 Viral RNA Proteins 0.000 description 1
• 208000036142 Viral infection Diseases 0.000 description 1
• 206010047741 Vulval cancer Diseases 0.000 description 1
• 208000004354 Vulvar Neoplasms Diseases 0.000 description 1
• 208000033559 Waldenström macroglobulinemia Diseases 0.000 description 1
• 208000008383 Wilms tumor Diseases 0.000 description 1
• 108010088665 Zinc Finger Protein Gli2 Proteins 0.000 description 1
• 102100035558 Zinc finger protein GLI2 Human genes 0.000 description 1
• 229960000446 abciximab Drugs 0.000 description 1
• 238000010521 absorption reaction Methods 0.000 description 1
• 229960000583 acetic acid Drugs 0.000 description 1
• 230000021736 acetylation Effects 0.000 description 1
• 238000006640 acetylation reaction Methods 0.000 description 1
• 150000007513 acids Chemical class 0.000 description 1
• 230000003213 activating effect Effects 0.000 description 1
• 239000012190 activator Substances 0.000 description 1
• 239000013543 active substance Substances 0.000 description 1
• 229960002964 adalimumab Drugs 0.000 description 1
• 238000001042 affinity chromatography Methods 0.000 description 1
• 230000032683 aging Effects 0.000 description 1
• 150000001294 alanine derivatives Chemical class 0.000 description 1
• 125000003295 alanine group Chemical group N[C@@H](C)C(=O)* 0.000 description 1
• 229960002459 alefacept Drugs 0.000 description 1
• 125000001931 aliphatic group Chemical group 0.000 description 1
• 229910001413 alkali metal ion Inorganic materials 0.000 description 1
• 229910001420 alkaline earth metal ion Inorganic materials 0.000 description 1
• 150000001336 alkenes Chemical class 0.000 description 1
• 239000002168 alkylating agent Substances 0.000 description 1
• 229940100198 alkylating agent Drugs 0.000 description 1
• 108010026331 alpha-Fetoproteins Proteins 0.000 description 1
• BJEPYKJPYRNKOW-UHFFFAOYSA-N alpha-hydroxysuccinic acid Natural products OC(=O)C(O)CC(O)=O BJEPYKJPYRNKOW-UHFFFAOYSA-N 0.000 description 1
• 229910052782 aluminium Inorganic materials 0.000 description 1
• 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
• 230000009435 amidation Effects 0.000 description 1
• 238000007112 amidation reaction Methods 0.000 description 1
• 150000001408 amides Chemical class 0.000 description 1
• 230000003321 amplification Effects 0.000 description 1
• 150000008064 anhydrides Chemical class 0.000 description 1
• 239000003242 anti bacterial agent Substances 0.000 description 1
• 230000002424 anti-apoptotic effect Effects 0.000 description 1
• 229940121363 anti-inflammatory agent Drugs 0.000 description 1
• 239000002260 anti-inflammatory agent Substances 0.000 description 1
• 230000000340 anti-metabolite Effects 0.000 description 1
• 229940044684 anti-microtubule agent Drugs 0.000 description 1
• 230000001188 anti-phage Effects 0.000 description 1
• 230000006023 anti-tumor response Effects 0.000 description 1
• 230000005875 antibody response Effects 0.000 description 1
• 229940100197 antimetabolite Drugs 0.000 description 1
• 239000002256 antimetabolite Substances 0.000 description 1
• 239000004599 antimicrobial Substances 0.000 description 1
• 239000002246 antineoplastic agent Substances 0.000 description 1
• 229940034982 antineoplastic agent Drugs 0.000 description 1
• 238000003782 apoptosis assay Methods 0.000 description 1
• 230000006907 apoptotic process Effects 0.000 description 1
• 208000021780 appendiceal neoplasm Diseases 0.000 description 1
• 238000013459 approach Methods 0.000 description 1
• 239000007864 aqueous solution Substances 0.000 description 1
• 230000008267 autocrine signaling Effects 0.000 description 1
• 230000001363 autoimmune Effects 0.000 description 1
• 230000005784 autoimmunity Effects 0.000 description 1
• IVRMZWNICZWHMI-UHFFFAOYSA-N azide group Chemical group [N-]=[N+]=[N-] IVRMZWNICZWHMI-UHFFFAOYSA-N 0.000 description 1
• 208000022362 bacterial infectious disease Diseases 0.000 description 1
• 229960004669 basiliximab Drugs 0.000 description 1
• 229960003270 belimumab Drugs 0.000 description 1
• SRSXLGNVWSONIS-UHFFFAOYSA-N benzenesulfonic acid Chemical compound OS(=O)(=O)C1=CC=CC=C1 SRSXLGNVWSONIS-UHFFFAOYSA-N 0.000 description 1
• 229940092714 benzenesulfonic acid Drugs 0.000 description 1
• 235000010233 benzoic acid Nutrition 0.000 description 1
• 108010005774 beta-Galactosidase Proteins 0.000 description 1
• 229940000635 beta-alanine Drugs 0.000 description 1
• 150000001576 beta-amino acids Chemical class 0.000 description 1
• 230000001588 bifunctional effect Effects 0.000 description 1
• 108091008324 binding proteins Proteins 0.000 description 1
• 239000003124 biologic agent Substances 0.000 description 1
• 239000012472 biological sample Substances 0.000 description 1
• 229960002685 biotin Drugs 0.000 description 1
• 235000020958 biotin Nutrition 0.000 description 1
• 239000011616 biotin Substances 0.000 description 1
• 210000003969 blast cell Anatomy 0.000 description 1
• 229960003008 blinatumomab Drugs 0.000 description 1
• 230000000903 blocking effect Effects 0.000 description 1
• 230000008499 blood brain barrier function Effects 0.000 description 1
• 210000001218 blood-brain barrier Anatomy 0.000 description 1
• 238000006664 bond formation reaction Methods 0.000 description 1
• 210000001185 bone marrow Anatomy 0.000 description 1
• 201000000220 brain stem cancer Diseases 0.000 description 1
• 210000000481 breast Anatomy 0.000 description 1
• 201000010983 breast ductal carcinoma Diseases 0.000 description 1
• KDYFGRWQOYBRFD-NUQCWPJISA-N butanedioic acid Chemical compound O[14C](=O)CC[14C](O)=O KDYFGRWQOYBRFD-NUQCWPJISA-N 0.000 description 1
• 238000004364 calculation method Methods 0.000 description 1
• 229960001838 canakinumab Drugs 0.000 description 1
• 150000004657 carbamic acid derivatives Chemical class 0.000 description 1
• 208000002458 carcinoid tumor Diseases 0.000 description 1
• 229940021722 caseins Drugs 0.000 description 1
• 235000021240 caseins Nutrition 0.000 description 1
• 230000015556 catabolic process Effects 0.000 description 1
• 238000006555 catalytic reaction Methods 0.000 description 1
• 238000004113 cell culture Methods 0.000 description 1
• 230000025084 cell cycle arrest Effects 0.000 description 1
• 230000012820 cell cycle checkpoint Effects 0.000 description 1
• 230000011712 cell development Effects 0.000 description 1
• 239000002771 cell marker Substances 0.000 description 1
• 230000006800 cellular catabolic process Effects 0.000 description 1
• 230000010001 cellular homeostasis Effects 0.000 description 1
• 230000008614 cellular interaction Effects 0.000 description 1
• 230000019522 cellular metabolic process Effects 0.000 description 1
• 230000033077 cellular process Effects 0.000 description 1
• 229940121420 cemiplimab Drugs 0.000 description 1
• 210000003169 central nervous system Anatomy 0.000 description 1
• 201000007455 central nervous system cancer Diseases 0.000 description 1
• 238000005119 centrifugation Methods 0.000 description 1
• 201000007335 cerebellar astrocytoma Diseases 0.000 description 1
• 208000030239 cerebral astrocytoma Diseases 0.000 description 1
• 229960003115 certolizumab pegol Drugs 0.000 description 1
• 201000010881 cervical cancer Diseases 0.000 description 1
• 229960005395 cetuximab Drugs 0.000 description 1
• 230000003196 chaotropic effect Effects 0.000 description 1
• 239000002738 chelating agent Substances 0.000 description 1
• 238000001311 chemical methods and process Methods 0.000 description 1
• 208000006990 cholangiocarcinoma Diseases 0.000 description 1
• 208000037976 chronic inflammation Diseases 0.000 description 1
• 208000037893 chronic inflammatory disorder Diseases 0.000 description 1
• 235000013985 cinnamic acid Nutrition 0.000 description 1
• 229930016911 cinnamic acid Natural products 0.000 description 1
• 230000004087 circulation Effects 0.000 description 1
• 235000015165 citric acid Nutrition 0.000 description 1
• 238000003776 cleavage reaction Methods 0.000 description 1
• 210000001072 colon Anatomy 0.000 description 1
• 238000004737 colorimetric analysis Methods 0.000 description 1
• 238000004891 communication Methods 0.000 description 1
• 230000006854 communication Effects 0.000 description 1
• 230000002860 competitive effect Effects 0.000 description 1
• 239000012141 concentrate Substances 0.000 description 1
• 108010015408 connexin 37 Proteins 0.000 description 1
• 238000010276 construction Methods 0.000 description 1
• 230000001186 cumulative effect Effects 0.000 description 1
• 201000007241 cutaneous T cell lymphoma Diseases 0.000 description 1
• 208000017763 cutaneous neuroendocrine carcinoma Diseases 0.000 description 1
• 125000004122 cyclic group Chemical group 0.000 description 1
• 125000000392 cycloalkenyl group Chemical group 0.000 description 1
• 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
• 108010048032 cyclophilin B Proteins 0.000 description 1
• 229960003067 cystine Drugs 0.000 description 1
• 230000034994 death Effects 0.000 description 1
• 230000003412 degenerative effect Effects 0.000 description 1
• 238000006731 degradation reaction Methods 0.000 description 1
• 108010031971 delta catenin Proteins 0.000 description 1
• 238000003745 diagnosis Methods 0.000 description 1
• 239000000032 diagnostic agent Substances 0.000 description 1
• 229940039227 diagnostic agent Drugs 0.000 description 1
• ZBCBWPMODOFKDW-UHFFFAOYSA-N diethanolamine Chemical compound OCCNCCO ZBCBWPMODOFKDW-UHFFFAOYSA-N 0.000 description 1
• 230000004069 differentiation Effects 0.000 description 1
• 230000029087 digestion Effects 0.000 description 1
• 239000003085 diluting agent Substances 0.000 description 1
• 238000006073 displacement reaction Methods 0.000 description 1
• 125000005883 dithianyl group Chemical group 0.000 description 1
• 239000003534 dna topoisomerase inhibitor Substances 0.000 description 1
• MOTZDAYCYVMXPC-UHFFFAOYSA-N dodecyl hydrogen sulfate Chemical group CCCCCCCCCCCCOS(O)(=O)=O MOTZDAYCYVMXPC-UHFFFAOYSA-N 0.000 description 1
• 229940043264 dodecyl sulfate Drugs 0.000 description 1
• 239000000975 dye Substances 0.000 description 1
• 229960000284 efalizumab Drugs 0.000 description 1
• 238000001962 electrophoresis Methods 0.000 description 1
• 208000014616 embryonal neoplasm Diseases 0.000 description 1
• 230000002124 endocrine Effects 0.000 description 1
• 210000001163 endosome Anatomy 0.000 description 1
• 210000003989 endothelium vascular Anatomy 0.000 description 1
• 230000002708 enhancing effect Effects 0.000 description 1
• 102000052116 epidermal growth factor receptor activity proteins Human genes 0.000 description 1
• 108700015053 epidermal growth factor receptor activity proteins Proteins 0.000 description 1
• AFAXGSQYZLGZPG-UHFFFAOYSA-N ethanedisulfonic acid Chemical compound OS(=O)(=O)CCS(O)(=O)=O AFAXGSQYZLGZPG-UHFFFAOYSA-N 0.000 description 1
• CCIVGXIOQKPBKL-UHFFFAOYSA-M ethanesulfonate Chemical compound CCS([O-])(=O)=O CCIVGXIOQKPBKL-UHFFFAOYSA-M 0.000 description 1
• 150000002170 ethers Chemical class 0.000 description 1
• 230000029142 excretion Effects 0.000 description 1
• 210000002744 extracellular matrix Anatomy 0.000 description 1
• 230000002349 favourable effect Effects 0.000 description 1
• 210000002950 fibroblast Anatomy 0.000 description 1
• 238000000684 flow cytometry Methods 0.000 description 1
• MHMNJMPURVTYEJ-UHFFFAOYSA-N fluorescein-5-isothiocyanate Chemical compound O1C(=O)C2=CC(N=C=S)=CC=C2C21C1=CC=C(O)C=C1OC1=CC(O)=CC=C21 MHMNJMPURVTYEJ-UHFFFAOYSA-N 0.000 description 1
• 239000007850 fluorescent dye Substances 0.000 description 1
• 238000001215 fluorescent labelling Methods 0.000 description 1
• 108010006620 fodrin Proteins 0.000 description 1
• 150000004675 formic acid derivatives Chemical class 0.000 description 1
• 239000001530 fumaric acid Substances 0.000 description 1
• 125000000524 functional group Chemical group 0.000 description 1
• 201000010175 gallbladder cancer Diseases 0.000 description 1
• 108010084448 gamma Catenin Proteins 0.000 description 1
• 102000054078 gamma Catenin Human genes 0.000 description 1
• 229960003692 gamma aminobutyric acid Drugs 0.000 description 1
• 150000002270 gangliosides Chemical class 0.000 description 1
• 201000011243 gastrointestinal stromal tumor Diseases 0.000 description 1
• 230000024924 glomerular filtration Effects 0.000 description 1
• 239000000174 gluconic acid Chemical group 0.000 description 1
• 235000012208 gluconic acid Nutrition 0.000 description 1
• 150000002332 glycine derivatives Chemical class 0.000 description 1
• 229960001743 golimumab Drugs 0.000 description 1
• 229940093915 gynecological organic acid Drugs 0.000 description 1
• 230000003394 haemopoietic effect Effects 0.000 description 1
• 201000009277 hairy cell leukemia Diseases 0.000 description 1
• 230000003862 health status Effects 0.000 description 1
• 208000024348 heart neoplasm Diseases 0.000 description 1
• 239000000185 hemagglutinin Substances 0.000 description 1
• 125000000623 heterocyclic group Chemical group 0.000 description 1
• 238000005734 heterodimerization reaction Methods 0.000 description 1
• 229920000140 heteropolymer Polymers 0.000 description 1
• 208000029824 high grade glioma Diseases 0.000 description 1
• 229960001340 histamine Drugs 0.000 description 1
• 150000002410 histidine derivatives Chemical class 0.000 description 1
• 108091008039 hormone receptors Proteins 0.000 description 1
• 229920002674 hyaluronan Polymers 0.000 description 1
• 229960003160 hyaluronic acid Drugs 0.000 description 1
• 150000004677 hydrates Chemical class 0.000 description 1
• 229930195733 hydrocarbon Natural products 0.000 description 1
• WGCNASOHLSPBMP-UHFFFAOYSA-N hydroxyacetaldehyde Natural products OCC=O WGCNASOHLSPBMP-UHFFFAOYSA-N 0.000 description 1
• 201000006866 hypopharynx cancer Diseases 0.000 description 1
• 229960001001 ibritumomab tiuxetan Drugs 0.000 description 1
• 238000003384 imaging method Methods 0.000 description 1
• 125000002632 imidazolidinyl group Chemical group 0.000 description 1
• 125000002883 imidazolyl group Chemical group 0.000 description 1
• 150000002466 imines Chemical class 0.000 description 1
• 230000002519 immonomodulatory effect Effects 0.000 description 1
• 230000007124 immune defense Effects 0.000 description 1
• 210000000987 immune system Anatomy 0.000 description 1
• 239000002955 immunomodulating agent Substances 0.000 description 1
• 229940121354 immunomodulator Drugs 0.000 description 1
• 238000009169 immunotherapy Methods 0.000 description 1
• 230000001976 improved effect Effects 0.000 description 1
• 238000005462 in vivo assay Methods 0.000 description 1
• 238000010348 incorporation Methods 0.000 description 1
• 230000001939 inductive effect Effects 0.000 description 1
• 229940037993 inflectra Drugs 0.000 description 1
• 239000007972 injectable composition Substances 0.000 description 1
• 210000005007 innate immune system Anatomy 0.000 description 1
• 230000002452 interceptive effect Effects 0.000 description 1
• 229960003130 interferon gamma Drugs 0.000 description 1
• 229940047124 interferons Drugs 0.000 description 1
• 102000002467 interleukin receptors Human genes 0.000 description 1
• 108010093036 interleukin receptors Proteins 0.000 description 1
• 108010074108 interleukin-21 Proteins 0.000 description 1
• 201000002313 intestinal cancer Diseases 0.000 description 1
• 230000031146 intracellular signal transduction Effects 0.000 description 1
• 238000007918 intramuscular administration Methods 0.000 description 1
• 238000007912 intraperitoneal administration Methods 0.000 description 1
• 150000002500 ions Chemical class 0.000 description 1
• 229960005435 ixekizumab Drugs 0.000 description 1
• 210000003734 kidney Anatomy 0.000 description 1
• 210000000244 kidney pelvis Anatomy 0.000 description 1
• 229940043355 kinase inhibitor Drugs 0.000 description 1
• 238000002372 labelling Methods 0.000 description 1
• 239000004310 lactic acid Substances 0.000 description 1
• 235000014655 lactic acid Nutrition 0.000 description 1
• 229910052747 lanthanoid Inorganic materials 0.000 description 1
• 150000002602 lanthanoids Chemical class 0.000 description 1
• 206010023841 laryngeal neoplasm Diseases 0.000 description 1
• 239000002523 lectin Substances 0.000 description 1
• 210000000265 leukocyte Anatomy 0.000 description 1
• 230000000670 limiting effect Effects 0.000 description 1
• 208000014018 liver neoplasm Diseases 0.000 description 1
• 210000004072 lung Anatomy 0.000 description 1
• 201000005202 lung cancer Diseases 0.000 description 1
• 201000009546 lung large cell carcinoma Diseases 0.000 description 1
• 208000020816 lung neoplasm Diseases 0.000 description 1
• 208000001419 lymphocytic choriomeningitis Diseases 0.000 description 1
• 230000000527 lymphocytic effect Effects 0.000 description 1
• 230000000329 lymphopenic effect Effects 0.000 description 1
• 229940124302 mTOR inhibitor Drugs 0.000 description 1
• 201000003175 male breast cancer Diseases 0.000 description 1
• 208000010907 male breast carcinoma Diseases 0.000 description 1
• VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
• 239000011976 maleic acid Substances 0.000 description 1
• 239000001630 malic acid Substances 0.000 description 1
• 235000011090 malic acid Nutrition 0.000 description 1
• 208000030883 malignant astrocytoma Diseases 0.000 description 1
• 208000016848 malignant germ cell tumor Diseases 0.000 description 1
• 201000011614 malignant glioma Diseases 0.000 description 1
• 208000006178 malignant mesothelioma Diseases 0.000 description 1
• 208000015486 malignant pancreatic neoplasm Diseases 0.000 description 1
• 208000020984 malignant renal pelvis neoplasm Diseases 0.000 description 1
• 208000026045 malignant tumor of parathyroid gland Diseases 0.000 description 1
• 239000003628 mammalian target of rapamycin inhibitor Substances 0.000 description 1
• 229960002510 mandelic acid Drugs 0.000 description 1
• 230000000873 masking effect Effects 0.000 description 1
• 238000002483 medication Methods 0.000 description 1
• 230000002503 metabolic effect Effects 0.000 description 1
• 229910021645 metal ion Inorganic materials 0.000 description 1
• 208000037970 metastatic squamous neck cancer Diseases 0.000 description 1
• 229940098779 methanesulfonic acid Drugs 0.000 description 1
• 150000002741 methionine derivatives Chemical class 0.000 description 1
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
• WBYWAXJHAXSJNI-UHFFFAOYSA-N methyl p-hydroxycinnamate Natural products OC(=O)C=CC1=CC=CC=C1 WBYWAXJHAXSJNI-UHFFFAOYSA-N 0.000 description 1
• 125000000250 methylamino group Chemical group [H]N(*)C([H])([H])[H] 0.000 description 1
• 238000012737 microarray-based gene expression Methods 0.000 description 1
• 231100000324 minimal toxicity Toxicity 0.000 description 1
• 230000000394 mitotic effect Effects 0.000 description 1
• 239000003607 modifier Substances 0.000 description 1
• 210000001616 monocyte Anatomy 0.000 description 1
• 206010051747 multiple endocrine neoplasia Diseases 0.000 description 1
• 238000012243 multiplex automated genomic engineering Methods 0.000 description 1
• 230000035772 mutation Effects 0.000 description 1
• 210000000066 myeloid cell Anatomy 0.000 description 1
• PUPNJSIFIXXJCH-UHFFFAOYSA-N n-(4-hydroxyphenyl)-2-(1,1,3-trioxo-1,2-benzothiazol-2-yl)acetamide Chemical compound C1=CC(O)=CC=C1NC(=O)CN1S(=O)(=O)C2=CC=CC=C2C1=O PUPNJSIFIXXJCH-UHFFFAOYSA-N 0.000 description 1
• YOHYSYJDKVYCJI-UHFFFAOYSA-N n-[3-[[6-[3-(trifluoromethyl)anilino]pyrimidin-4-yl]amino]phenyl]cyclopropanecarboxamide Chemical compound FC(F)(F)C1=CC=CC(NC=2N=CN=C(NC=3C=C(NC(=O)C4CC4)C=CC=3)C=2)=C1 YOHYSYJDKVYCJI-UHFFFAOYSA-N 0.000 description 1
• DIOQZVSQGTUSAI-UHFFFAOYSA-N n-butylhexane Natural products CCCCCCCCCC DIOQZVSQGTUSAI-UHFFFAOYSA-N 0.000 description 1
• OFYAYGJCPXRNBL-LBPRGKRZSA-N naphthalen-2-yl-3-alanine Chemical compound C1=CC=C2C(C[C@H](N)C(O)=O)=CC=CC2=C1 OFYAYGJCPXRNBL-LBPRGKRZSA-N 0.000 description 1
• KVBGVZZKJNLNJU-UHFFFAOYSA-N naphthalene-2-sulfonic acid Chemical compound C1=CC=CC2=CC(S(=O)(=O)O)=CC=C21 KVBGVZZKJNLNJU-UHFFFAOYSA-N 0.000 description 1
• 210000003928 nasal cavity Anatomy 0.000 description 1
• 201000008026 nephroblastoma Diseases 0.000 description 1
• 210000000276 neural tube Anatomy 0.000 description 1
• 210000000440 neutrophil Anatomy 0.000 description 1
• 229910017604 nitric acid Inorganic materials 0.000 description 1
• 231100000252 nontoxic Toxicity 0.000 description 1
• 230000003000 nontoxic effect Effects 0.000 description 1
• 230000005937 nuclear translocation Effects 0.000 description 1
• 230000025308 nuclear transport Effects 0.000 description 1
• 238000003199 nucleic acid amplification method Methods 0.000 description 1
• 239000002777 nucleoside Substances 0.000 description 1
• 150000003833 nucleoside derivatives Chemical class 0.000 description 1
• 229960003347 obinutuzumab Drugs 0.000 description 1
• QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical group CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 1
• OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Chemical group CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 1
• 201000002575 ocular melanoma Diseases 0.000 description 1
• 229950008516 olaratumab Drugs 0.000 description 1
• 201000008859 olfactory neuroblastoma Diseases 0.000 description 1
• 208000022982 optic pathway glioma Diseases 0.000 description 1
• 230000003287 optical effect Effects 0.000 description 1
• 239000006186 oral dosage form Substances 0.000 description 1
• 210000000056 organ Anatomy 0.000 description 1
• 150000007524 organic acids Chemical class 0.000 description 1
• 235000005985 organic acids Nutrition 0.000 description 1
• 150000007530 organic bases Chemical class 0.000 description 1
• 201000006958 oropharynx cancer Diseases 0.000 description 1
• 150000002905 orthoesters Chemical class 0.000 description 1
• 201000008968 osteosarcoma Diseases 0.000 description 1
• 230000002611 ovarian Effects 0.000 description 1
• 208000021284 ovarian germ cell tumor Diseases 0.000 description 1
• 230000002018 overexpression Effects 0.000 description 1
• 150000002924 oxiranes Chemical class 0.000 description 1
• 229960000402 palivizumab Drugs 0.000 description 1
• 208000008443 pancreatic carcinoma Diseases 0.000 description 1
• 208000021010 pancreatic neuroendocrine tumor Diseases 0.000 description 1
• FJKROLUGYXJWQN-UHFFFAOYSA-N papa-hydroxy-benzoic acid Chemical group OC(=O)C1=CC=C(O)C=C1 FJKROLUGYXJWQN-UHFFFAOYSA-N 0.000 description 1
• 208000003154 papilloma Diseases 0.000 description 1
• 208000029211 papillomatosis Diseases 0.000 description 1
• 230000014306 paracrine signaling Effects 0.000 description 1
• 208000007312 paraganglioma Diseases 0.000 description 1
• 208000022775 paranasal sinus carcinoma Diseases 0.000 description 1
• 239000002245 particle Substances 0.000 description 1
• 230000001575 pathological effect Effects 0.000 description 1
• 229940121654 pd-l2 inhibitor Drugs 0.000 description 1
• 238000010647 peptide synthesis reaction Methods 0.000 description 1
• 108010044156 peptidyl-prolyl cis-trans isomerase b Proteins 0.000 description 1
• 230000008823 permeabilization Effects 0.000 description 1
• 239000000546 pharmaceutical excipient Substances 0.000 description 1
• 239000012071 phase Substances 0.000 description 1
• 208000028591 pheochromocytoma Diseases 0.000 description 1
• 235000021317 phosphate Nutrition 0.000 description 1
• 150000004713 phosphodiesters Chemical class 0.000 description 1
• 150000003013 phosphoric acid derivatives Chemical class 0.000 description 1
• 238000003566 phosphorylation assay Methods 0.000 description 1
• 239000003757 phosphotransferase inhibitor Substances 0.000 description 1
• 230000035790 physiological processes and functions Effects 0.000 description 1
• 125000003386 piperidinyl group Chemical group 0.000 description 1
• 125000005936 piperidyl group Chemical group 0.000 description 1
• IUGYQRQAERSCNH-UHFFFAOYSA-N pivalic acid Chemical compound CC(C)(C)C(O)=O IUGYQRQAERSCNH-UHFFFAOYSA-N 0.000 description 1
• 210000002706 plastid Anatomy 0.000 description 1
• 239000002798 polar solvent Substances 0.000 description 1
• 208000015768 polyposis Diseases 0.000 description 1
• 230000006267 polysialylation Effects 0.000 description 1
• 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 1
• 208000016800 primary central nervous system lymphoma Diseases 0.000 description 1
• 208000025638 primary cutaneous T-cell non-Hodgkin lymphoma Diseases 0.000 description 1
• 238000011809 primate model Methods 0.000 description 1
• 208000029340 primitive neuroectodermal tumor Diseases 0.000 description 1
• 230000000861 pro-apoptotic effect Effects 0.000 description 1
• 230000008569 process Effects 0.000 description 1
• 230000005522 programmed cell death Effects 0.000 description 1
• 235000019260 propionic acid Nutrition 0.000 description 1
• 239000004405 propyl p-hydroxybenzoate Substances 0.000 description 1
• 235000019419 proteases Nutrition 0.000 description 1
• 230000001681 protective effect Effects 0.000 description 1
• 230000006916 protein interaction Effects 0.000 description 1
• 230000009145 protein modification Effects 0.000 description 1
• 230000029983 protein stabilization Effects 0.000 description 1
• 238000001243 protein synthesis Methods 0.000 description 1
• 230000017854 proteolysis Effects 0.000 description 1
• 230000002797 proteolythic effect Effects 0.000 description 1
• 230000005588 protonation Effects 0.000 description 1
• 238000000746 purification Methods 0.000 description 1
• 230000006825 purine synthesis Effects 0.000 description 1
• USPWKWBDZOARPV-UHFFFAOYSA-N pyrazolidine Chemical compound C1CNNC1 USPWKWBDZOARPV-UHFFFAOYSA-N 0.000 description 1
• UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
• 125000000719 pyrrolidinyl group Chemical group 0.000 description 1
• 229940107700 pyruvic acid Drugs 0.000 description 1
• 150000004728 pyruvic acid derivatives Chemical class 0.000 description 1
• IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical compound O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 0.000 description 1
• 108010014186 ras Proteins Proteins 0.000 description 1
• 102000016914 ras Proteins Human genes 0.000 description 1
• 230000007420 reactivation Effects 0.000 description 1
• 230000009257 reactivity Effects 0.000 description 1
• 230000010837 receptor-mediated endocytosis Effects 0.000 description 1
• 238000011084 recovery Methods 0.000 description 1
• 206010038038 rectal cancer Diseases 0.000 description 1
• 201000001275 rectum cancer Diseases 0.000 description 1
• 201000010174 renal carcinoma Diseases 0.000 description 1
• 201000007444 renal pelvis carcinoma Diseases 0.000 description 1
• 201000010384 renal tubular acidosis Diseases 0.000 description 1
• 230000010076 replication Effects 0.000 description 1
• 210000002345 respiratory system Anatomy 0.000 description 1
• 108091008146 restriction endonucleases Proteins 0.000 description 1
• 201000009410 rhabdomyosarcoma Diseases 0.000 description 1
• 229920002477 rna polymer Polymers 0.000 description 1
• 229940081623 rose bengal Drugs 0.000 description 1
• AZJPTIGZZTZIDR-UHFFFAOYSA-L rose bengal Chemical compound [K+].[K+].[O-]C(=O)C1=C(Cl)C(Cl)=C(Cl)C(Cl)=C1C1=C2C=C(I)C(=O)C(I)=C2OC2=C(I)C([O-])=C(I)C=C21 AZJPTIGZZTZIDR-UHFFFAOYSA-L 0.000 description 1
• 229930187593 rose bengal Natural products 0.000 description 1
• STRXNPAVPKGJQR-UHFFFAOYSA-N rose bengal A Natural products O1C(=O)C(C(=CC=C2Cl)Cl)=C2C21C1=CC(I)=C(O)C(I)=C1OC1=C(I)C(O)=C(I)C=C21 STRXNPAVPKGJQR-UHFFFAOYSA-N 0.000 description 1
• 229960004889 salicylic acid Drugs 0.000 description 1
• 230000007017 scission Effects 0.000 description 1
• 150000003335 secondary amines Chemical class 0.000 description 1
• 230000003248 secreting effect Effects 0.000 description 1
• 229960004540 secukinumab Drugs 0.000 description 1
• 230000036303 septic shock Effects 0.000 description 1
• 229910052710 silicon Inorganic materials 0.000 description 1
• 208000037968 sinus cancer Diseases 0.000 description 1
• 238000001542 size-exclusion chromatography Methods 0.000 description 1
• 208000000587 small cell lung carcinoma Diseases 0.000 description 1
• 150000003384 small molecules Chemical class 0.000 description 1
• 159000000000 sodium salts Chemical class 0.000 description 1
• 239000007790 solid phase Substances 0.000 description 1
• 230000003381 solubilizing effect Effects 0.000 description 1
• 239000000243 solution Substances 0.000 description 1
• 230000009295 sperm incapacitation Effects 0.000 description 1
• 206010062261 spinal cord neoplasm Diseases 0.000 description 1
• 206010041823 squamous cell carcinoma Diseases 0.000 description 1
• 108010087686 src-Family Kinases Proteins 0.000 description 1
• 102000009076 src-Family Kinases Human genes 0.000 description 1
• 238000010186 staining Methods 0.000 description 1
• 239000008117 stearic acid Chemical group 0.000 description 1
• 230000000638 stimulation Effects 0.000 description 1
• 210000002536 stromal cell Anatomy 0.000 description 1
• 239000000758 substrate Substances 0.000 description 1
• WPLOVIFNBMNBPD-ATHMIXSHSA-N subtilin Chemical compound CC1SCC(NC2=O)C(=O)NC(CC(N)=O)C(=O)NC(C(=O)NC(CCCCN)C(=O)NC(C(C)CC)C(=O)NC(=C)C(=O)NC(CCCCN)C(O)=O)CSC(C)C2NC(=O)C(CC(C)C)NC(=O)C1NC(=O)C(CCC(N)=O)NC(=O)C(CC(C)C)NC(=O)C(NC(=O)C1NC(=O)C(=C/C)/NC(=O)C(CCC(N)=O)NC(=O)C(CC(C)C)NC(=O)C(C)NC(=O)CNC(=O)C(NC(=O)C(NC(=O)C2NC(=O)CNC(=O)C3CCCN3C(=O)C(NC(=O)C3NC(=O)C(CC(C)C)NC(=O)C(=C)NC(=O)C(CCC(O)=O)NC(=O)C(NC(=O)C(CCCCN)NC(=O)C(N)CC=4C5=CC=CC=C5NC=4)CSC3)C(C)SC2)C(C)C)C(C)SC1)CC1=CC=CC=C1 WPLOVIFNBMNBPD-ATHMIXSHSA-N 0.000 description 1
• 239000011593 sulfur Chemical group 0.000 description 1
• 230000002459 sustained effect Effects 0.000 description 1
• 238000010189 synthetic method Methods 0.000 description 1
• 238000007910 systemic administration Methods 0.000 description 1
• 239000011975 tartaric acid Substances 0.000 description 1
• 235000002906 tartaric acid Nutrition 0.000 description 1
• 238000011191 terminal modification Methods 0.000 description 1
• 150000003512 tertiary amines Chemical class 0.000 description 1
• 201000003120 testicular cancer Diseases 0.000 description 1
• 125000003718 tetrahydrofuranyl group Chemical group 0.000 description 1
• 125000001412 tetrahydropyranyl group Chemical group 0.000 description 1
• 125000005958 tetrahydrothienyl group Chemical group 0.000 description 1
• 125000001984 thiazolidinyl group Chemical group 0.000 description 1
• VOVUARRWDCVURC-UHFFFAOYSA-N thiirane Chemical compound C1CS1 VOVUARRWDCVURC-UHFFFAOYSA-N 0.000 description 1
• 208000008732 thymoma Diseases 0.000 description 1
• 201000009377 thymus cancer Diseases 0.000 description 1
• 201000002510 thyroid cancer Diseases 0.000 description 1
• 229960003989 tocilizumab Drugs 0.000 description 1
• JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 1
• 229940044693 topoisomerase inhibitor Drugs 0.000 description 1
• 231100000331 toxic Toxicity 0.000 description 1
• 230000002588 toxic effect Effects 0.000 description 1
• 108091006106 transcriptional activators Proteins 0.000 description 1
• 238000012546 transfer Methods 0.000 description 1
• 230000009466 transformation Effects 0.000 description 1
• 206010044412 transitional cell carcinoma Diseases 0.000 description 1
• 238000002054 transplantation Methods 0.000 description 1
• 229960001612 trastuzumab emtansine Drugs 0.000 description 1
• 238000011269 treatment regimen Methods 0.000 description 1
• 208000029387 trophoblastic neoplasm Diseases 0.000 description 1
• 230000004614 tumor growth Effects 0.000 description 1
• 102000003390 tumor necrosis factor Human genes 0.000 description 1
• 102000003298 tumor necrosis factor receptor Human genes 0.000 description 1
• 241000712461 unidentified influenza virus Species 0.000 description 1
• 241001515965 unidentified phage Species 0.000 description 1
• 201000011294 ureter cancer Diseases 0.000 description 1
• 201000005112 urinary bladder cancer Diseases 0.000 description 1
• 229960003824 ustekinumab Drugs 0.000 description 1
• 208000037965 uterine sarcoma Diseases 0.000 description 1
• 239000012646 vaccine adjuvant Substances 0.000 description 1
• 229940124931 vaccine adjuvant Drugs 0.000 description 1
• 206010046885 vaginal cancer Diseases 0.000 description 1
• 208000013139 vaginal neoplasm Diseases 0.000 description 1
• 230000029812 viral genome replication Effects 0.000 description 1
• 230000009385 viral infection Effects 0.000 description 1
• 229960004854 viral vaccine Drugs 0.000 description 1
• 230000007810 virus-infected cell apoptotic process Effects 0.000 description 1
• 230000004400 visual pathway Effects 0.000 description 1
• 210000000239 visual pathway Anatomy 0.000 description 1
• 201000005102 vulva cancer Diseases 0.000 description 1
• JPZXHKDZASGCLU-LBPRGKRZSA-N β-(2-naphthyl)-alanine Chemical compound C1=CC=CC2=CC(C[C@H](N)C(O)=O)=CC=C21 JPZXHKDZASGCLU-LBPRGKRZSA-N 0.000 description 1
• ORQXBVXKBGUSBA-QMMMGPOBSA-N β-cyclohexyl-alanine Chemical compound OC(=O)[C@@H](N)CC1CCCCC1 ORQXBVXKBGUSBA-QMMMGPOBSA-N 0.000 description 1