JP2020501513A - 治療用多標的コンストラクトおよびその使用 - Google Patents
治療用多標的コンストラクトおよびその使用 Download PDFInfo
- Publication number
- JP2020501513A JP2020501513A JP2019517069A JP2019517069A JP2020501513A JP 2020501513 A JP2020501513 A JP 2020501513A JP 2019517069 A JP2019517069 A JP 2019517069A JP 2019517069 A JP2019517069 A JP 2019517069A JP 2020501513 A JP2020501513 A JP 2020501513A
- Authority
- JP
- Japan
- Prior art keywords
- peptide
- seq
- toxin
- construct
- analog
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
Links
- 230000001225 therapeutic effect Effects 0.000 title description 10
- 108090000765 processed proteins & peptides Proteins 0.000 claims abstract description 774
- 239000003053 toxin Substances 0.000 claims abstract description 373
- 231100000765 toxin Toxicity 0.000 claims abstract description 371
- 108700012359 toxins Proteins 0.000 claims abstract description 371
- 102000004196 processed proteins & peptides Human genes 0.000 claims abstract description 231
- 206010028980 Neoplasm Diseases 0.000 claims abstract description 172
- 201000011510 cancer Diseases 0.000 claims abstract description 77
- 239000000427 antigen Substances 0.000 claims abstract description 73
- 108091007433 antigens Proteins 0.000 claims abstract description 73
- 102000036639 antigens Human genes 0.000 claims abstract description 73
- 230000008685 targeting Effects 0.000 claims abstract description 51
- 125000000885 organic scaffold group Chemical group 0.000 claims abstract description 8
- FWMNVWWHGCHHJJ-SKKKGAJSSA-N 4-amino-1-[(2r)-6-amino-2-[[(2r)-2-[[(2r)-2-[[(2r)-2-amino-3-phenylpropanoyl]amino]-3-phenylpropanoyl]amino]-4-methylpentanoyl]amino]hexanoyl]piperidine-4-carboxylic acid Chemical compound C([C@H](C(=O)N[C@H](CC(C)C)C(=O)N[C@H](CCCCN)C(=O)N1CCC(N)(CC1)C(O)=O)NC(=O)[C@H](N)CC=1C=CC=CC=1)C1=CC=CC=C1 FWMNVWWHGCHHJJ-SKKKGAJSSA-N 0.000 claims description 116
- 229920001223 polyethylene glycol Polymers 0.000 claims description 98
- 239000002202 Polyethylene glycol Substances 0.000 claims description 91
- 102000001301 EGF receptor Human genes 0.000 claims description 78
- 108060006698 EGF receptor Proteins 0.000 claims description 78
- 108010074708 B7-H1 Antigen Proteins 0.000 claims description 68
- 239000008194 pharmaceutical composition Substances 0.000 claims description 65
- 101710088791 Elongation factor 2 Proteins 0.000 claims description 47
- 125000003275 alpha amino acid group Chemical group 0.000 claims description 44
- 102000040430 polynucleotide Human genes 0.000 claims description 43
- 108091033319 polynucleotide Proteins 0.000 claims description 43
- 239000002157 polynucleotide Substances 0.000 claims description 43
- 238000000034 method Methods 0.000 claims description 41
- 230000000694 effects Effects 0.000 claims description 28
- 101710100963 Receptor tyrosine-protein kinase erbB-4 Proteins 0.000 claims description 26
- 102100029981 Receptor tyrosine-protein kinase erbB-4 Human genes 0.000 claims description 26
- 229920001184 polypeptide Polymers 0.000 claims description 23
- 230000030833 cell death Effects 0.000 claims description 19
- 150000007523 nucleic acids Chemical class 0.000 claims description 19
- 102000039446 nucleic acids Human genes 0.000 claims description 18
- 108020004707 nucleic acids Proteins 0.000 claims description 18
- 239000002246 antineoplastic agent Substances 0.000 claims description 17
- 125000004122 cyclic group Chemical group 0.000 claims description 16
- 102100032187 Androgen receptor Human genes 0.000 claims description 14
- 102100031650 C-X-C chemokine receptor type 4 Human genes 0.000 claims description 14
- 101000922348 Homo sapiens C-X-C chemokine receptor type 4 Proteins 0.000 claims description 14
- 101001012157 Homo sapiens Receptor tyrosine-protein kinase erbB-2 Proteins 0.000 claims description 14
- 102100030086 Receptor tyrosine-protein kinase erbB-2 Human genes 0.000 claims description 14
- 108010080146 androgen receptors Proteins 0.000 claims description 14
- 230000001939 inductive effect Effects 0.000 claims description 14
- 102100024222 B-lymphocyte antigen CD19 Human genes 0.000 claims description 13
- 108010021064 CTLA-4 Antigen Proteins 0.000 claims description 13
- 102000008203 CTLA-4 Antigen Human genes 0.000 claims description 13
- 229940045513 CTLA4 antagonist Drugs 0.000 claims description 13
- 102000000905 Cadherin Human genes 0.000 claims description 13
- 108050007957 Cadherin Proteins 0.000 claims description 13
- 102000010180 Endothelin receptor Human genes 0.000 claims description 13
- 108050001739 Endothelin receptor Proteins 0.000 claims description 13
- 108091008794 FGF receptors Proteins 0.000 claims description 13
- 102000004300 GABA-A Receptors Human genes 0.000 claims description 13
- 108090000839 GABA-A Receptors Proteins 0.000 claims description 13
- 102100022623 Hepatocyte growth factor receptor Human genes 0.000 claims description 13
- 101000980825 Homo sapiens B-lymphocyte antigen CD19 Proteins 0.000 claims description 13
- 101000972946 Homo sapiens Hepatocyte growth factor receptor Proteins 0.000 claims description 13
- 101000692455 Homo sapiens Platelet-derived growth factor receptor beta Proteins 0.000 claims description 13
- 101000934346 Homo sapiens T-cell surface antigen CD2 Proteins 0.000 claims description 13
- 108010008707 Mucin-1 Proteins 0.000 claims description 13
- 102000007298 Mucin-1 Human genes 0.000 claims description 13
- 101100407308 Mus musculus Pdcd1lg2 gene Proteins 0.000 claims description 13
- 101150042165 Ogfr gene Proteins 0.000 claims description 13
- 102100026949 Opioid growth factor receptor Human genes 0.000 claims description 13
- 102100026547 Platelet-derived growth factor receptor beta Human genes 0.000 claims description 13
- 108700030875 Programmed Cell Death 1 Ligand 2 Proteins 0.000 claims description 13
- 102100024213 Programmed cell death 1 ligand 2 Human genes 0.000 claims description 13
- 102100025237 T-cell surface antigen CD2 Human genes 0.000 claims description 13
- 108091008605 VEGF receptors Proteins 0.000 claims description 13
- 102100033177 Vascular endothelial growth factor receptor 2 Human genes 0.000 claims description 13
- 102000052178 fibroblast growth factor receptor activity proteins Human genes 0.000 claims description 13
- 101710089372 Programmed cell death protein 1 Proteins 0.000 claims description 12
- 241000589517 Pseudomonas aeruginosa Species 0.000 claims description 12
- 101000844259 Thrixopelma pruriens Beta/omega-theraphotoxin-Tp2a Proteins 0.000 claims description 12
- 230000002708 enhancing effect Effects 0.000 claims description 12
- 230000035699 permeability Effects 0.000 claims description 12
- XOAUGYVLRSCGBG-UHFFFAOYSA-N protx ii Chemical compound O=C1NC(CCC(N)=O)C(=O)NC(CCCCN)C(=O)NC(CC=2C3=CC=CC=C3NC=2)C(=O)NC(CCSC)C(=O)NC(CC=2C3=CC=CC=C3NC=2)C(=O)NC(C(C)O)C(=O)NC(C(NC(CC(O)=O)C(=O)NC(CO)C(=O)NC(CCC(O)=O)C(=O)NC(CCCNC(N)=N)C(=O)NC(CCCCN)C(=O)NC(CSSCC(NC(=O)C(CC=2C3=CC=CC=C3NC=2)NC(=O)C(CC(C)C)NC(=O)C(CCCNC(N)=N)NC2=O)C(=O)NC(CCCCN)C(=O)NC(CCCCN)C(=O)NC(CCCCN)C(=O)NC(CC(C)C)C(=O)NC(CC=3C4=CC=CC=C4NC=3)C(O)=O)C(=O)N3)=O)CSSCC2NC(=O)C(C(C)C)NC(=O)C(CCSC)NC(=O)CNC(=O)C(CCC(O)=O)NC(=O)C3CSSCC1NC(=O)C(N)CC1=CC=C(O)C=C1 XOAUGYVLRSCGBG-UHFFFAOYSA-N 0.000 claims description 12
- 239000003998 snake venom Substances 0.000 claims description 12
- OTLLEIBWKHEHGU-UHFFFAOYSA-N 2-[5-[[5-(6-aminopurin-9-yl)-3,4-dihydroxyoxolan-2-yl]methoxy]-3,4-dihydroxy-6-(hydroxymethyl)oxan-2-yl]oxy-3,5-dihydroxy-4-phosphonooxyhexanedioic acid Chemical compound C1=NC=2C(N)=NC=NC=2N1C(C(C1O)O)OC1COC1C(CO)OC(OC(C(O)C(OP(O)(O)=O)C(O)C(O)=O)C(O)=O)C(O)C1O OTLLEIBWKHEHGU-UHFFFAOYSA-N 0.000 claims description 11
- 241000193738 Bacillus anthracis Species 0.000 claims description 11
- 108030001720 Bontoxilysin Proteins 0.000 claims description 11
- 241000651013 Californiconus californicus Species 0.000 claims description 11
- 108010053187 Diphtheria Toxin Proteins 0.000 claims description 11
- 102000016607 Diphtheria Toxin Human genes 0.000 claims description 11
- 108700004714 Gelonium multiflorum GEL Proteins 0.000 claims description 11
- 108010039491 Ricin Proteins 0.000 claims description 11
- 108010084592 Saporins Proteins 0.000 claims description 11
- 101000844260 Thrixopelma pruriens Beta/omega-theraphotoxin-Tp1a Proteins 0.000 claims description 11
- 229940053031 botulinum toxin Drugs 0.000 claims description 11
- 231100000776 exotoxin Toxicity 0.000 claims description 11
- 239000002095 exotoxin Substances 0.000 claims description 11
- 239000009562 momordin Substances 0.000 claims description 11
- 108040000983 polyphosphate:AMP phosphotransferase activity proteins Proteins 0.000 claims description 11
- 125000006850 spacer group Chemical group 0.000 claims description 10
- ODJLBQGVINUMMR-HZXDTFASSA-N strophanthidin Chemical compound C1([C@H]2CC[C@]3(O)[C@H]4[C@@H]([C@]5(CC[C@H](O)C[C@@]5(O)CC4)C=O)CC[C@@]32C)=CC(=O)OC1 ODJLBQGVINUMMR-HZXDTFASSA-N 0.000 claims description 10
- 239000013598 vector Substances 0.000 claims description 10
- 101000851181 Homo sapiens Epidermal growth factor receptor Proteins 0.000 claims description 9
- 125000000539 amino acid group Chemical group 0.000 claims description 9
- 239000005557 antagonist Substances 0.000 claims description 9
- 101001117317 Homo sapiens Programmed cell death 1 ligand 1 Proteins 0.000 claims description 8
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 6
- 239000003937 drug carrier Substances 0.000 claims description 3
- 238000011269 treatment regimen Methods 0.000 claims description 3
- 231100000654 protein toxin Toxicity 0.000 claims description 2
- 102100024216 Programmed cell death 1 ligand 1 Human genes 0.000 claims 9
- 102100023990 60S ribosomal protein L17 Human genes 0.000 claims 1
- 102000010453 Folate receptor gamma Human genes 0.000 claims 1
- 108050001933 Folate receptor gamma Proteins 0.000 claims 1
- 238000011282 treatment Methods 0.000 abstract description 22
- 230000000259 anti-tumor effect Effects 0.000 abstract description 3
- 238000010586 diagram Methods 0.000 abstract description 2
- 210000004027 cell Anatomy 0.000 description 140
- 239000012634 fragment Substances 0.000 description 128
- 235000001014 amino acid Nutrition 0.000 description 74
- 229940024606 amino acid Drugs 0.000 description 72
- 150000001413 amino acids Chemical class 0.000 description 71
- 102000008096 B7-H1 Antigen Human genes 0.000 description 59
- 230000027455 binding Effects 0.000 description 35
- 108010069514 Cyclic Peptides Proteins 0.000 description 34
- 102000001189 Cyclic Peptides Human genes 0.000 description 34
- 239000000203 mixture Substances 0.000 description 34
- 239000000243 solution Substances 0.000 description 27
- 238000006467 substitution reaction Methods 0.000 description 26
- 101100153643 Phaeosphaeria nodorum (strain SN15 / ATCC MYA-4574 / FGSC 10173) Tox1 gene Proteins 0.000 description 22
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 21
- 239000003814 drug Substances 0.000 description 19
- -1 poly (ethylene) Polymers 0.000 description 17
- LOKCTEFSRHRXRJ-UHFFFAOYSA-I dipotassium trisodium dihydrogen phosphate hydrogen phosphate dichloride Chemical compound P(=O)(O)(O)[O-].[K+].P(=O)(O)([O-])[O-].[Na+].[Na+].[Cl-].[K+].[Cl-].[Na+] LOKCTEFSRHRXRJ-UHFFFAOYSA-I 0.000 description 16
- 239000002953 phosphate buffered saline Substances 0.000 description 16
- 238000012360 testing method Methods 0.000 description 14
- 150000001875 compounds Chemical class 0.000 description 13
- 208000035475 disorder Diseases 0.000 description 13
- 229940079593 drug Drugs 0.000 description 12
- 208000015914 Non-Hodgkin lymphomas Diseases 0.000 description 11
- 102100040678 Programmed cell death protein 1 Human genes 0.000 description 11
- 241000699670 Mus sp. Species 0.000 description 10
- 108090000623 proteins and genes Proteins 0.000 description 10
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 9
- 108020005243 folate receptor Proteins 0.000 description 9
- 102000006815 folate receptor Human genes 0.000 description 9
- 102000005962 receptors Human genes 0.000 description 9
- 108020003175 receptors Proteins 0.000 description 9
- 239000003795 chemical substances by application Substances 0.000 description 8
- 201000010099 disease Diseases 0.000 description 8
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 8
- 238000011534 incubation Methods 0.000 description 8
- 239000013612 plasmid Substances 0.000 description 8
- 231100000135 cytotoxicity Toxicity 0.000 description 7
- 230000003013 cytotoxicity Effects 0.000 description 7
- OVBPIULPVIDEAO-LBPRGKRZSA-N folic acid Chemical compound C=1N=C2NC(N)=NC(=O)C2=NC=1CNC1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 OVBPIULPVIDEAO-LBPRGKRZSA-N 0.000 description 7
- 230000002401 inhibitory effect Effects 0.000 description 7
- 238000002360 preparation method Methods 0.000 description 7
- 208000024891 symptom Diseases 0.000 description 7
- 231100000337 synergistic cytotoxicity Toxicity 0.000 description 7
- 231100000331 toxic Toxicity 0.000 description 7
- 230000002588 toxic effect Effects 0.000 description 7
- 108020004414 DNA Proteins 0.000 description 6
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 6
- 101800003838 Epidermal growth factor Proteins 0.000 description 6
- 102400001368 Epidermal growth factor Human genes 0.000 description 6
- 239000013543 active substance Substances 0.000 description 6
- 239000012888 bovine serum Substances 0.000 description 6
- 229940116977 epidermal growth factor Drugs 0.000 description 6
- 238000001727 in vivo Methods 0.000 description 6
- 230000005764 inhibitory process Effects 0.000 description 6
- 239000002609 medium Substances 0.000 description 6
- GETQZCLCWQTVFV-UHFFFAOYSA-N trimethylamine Chemical compound CN(C)C GETQZCLCWQTVFV-UHFFFAOYSA-N 0.000 description 6
- 210000004881 tumor cell Anatomy 0.000 description 6
- 238000002965 ELISA Methods 0.000 description 5
- QNAYBMKLOCPYGJ-REOHCLBHSA-N L-alanine Chemical compound C[C@H](N)C(O)=O QNAYBMKLOCPYGJ-REOHCLBHSA-N 0.000 description 5
- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 5
- 206010027476 Metastases Diseases 0.000 description 5
- NKANXQFJJICGDU-QPLCGJKRSA-N Tamoxifen Chemical compound C=1C=CC=CC=1C(/CC)=C(C=1C=CC(OCCN(C)C)=CC=1)/C1=CC=CC=C1 NKANXQFJJICGDU-QPLCGJKRSA-N 0.000 description 5
- 238000007792 addition Methods 0.000 description 5
- 235000004279 alanine Nutrition 0.000 description 5
- 230000000903 blocking effect Effects 0.000 description 5
- 235000019152 folic acid Nutrition 0.000 description 5
- 239000011724 folic acid Substances 0.000 description 5
- 238000009472 formulation Methods 0.000 description 5
- 208000020816 lung neoplasm Diseases 0.000 description 5
- 230000009401 metastasis Effects 0.000 description 5
- 230000002062 proliferating effect Effects 0.000 description 5
- 102000004169 proteins and genes Human genes 0.000 description 5
- 239000000126 substance Substances 0.000 description 5
- 230000004083 survival effect Effects 0.000 description 5
- 238000013518 transcription Methods 0.000 description 5
- 230000035897 transcription Effects 0.000 description 5
- VBEQCZHXXJYVRD-GACYYNSASA-N uroanthelone Chemical compound C([C@@H](C(=O)N[C@H](C(=O)N[C@@H](CS)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CS)C(=O)N[C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)NCC(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N[C@@H](CO)C(=O)NCC(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CS)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O)C(C)C)[C@@H](C)O)NC(=O)[C@H](CO)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CO)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@@H](NC(=O)[C@H](CC=1NC=NC=1)NC(=O)[C@H](CCSC)NC(=O)[C@H](CS)NC(=O)[C@@H](NC(=O)CNC(=O)CNC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CS)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)CNC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CO)NC(=O)[C@H](CO)NC(=O)[C@H]1N(CCC1)C(=O)[C@H](CS)NC(=O)CNC(=O)[C@H]1N(CCC1)C(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CO)NC(=O)[C@@H](N)CC(N)=O)C(C)C)[C@@H](C)CC)C1=CC=C(O)C=C1 VBEQCZHXXJYVRD-GACYYNSASA-N 0.000 description 5
- 230000035899 viability Effects 0.000 description 5
- 125000003088 (fluoren-9-ylmethoxy)carbonyl group Chemical group 0.000 description 4
- AOJJSUZBOXZQNB-TZSSRYMLSA-N Doxorubicin Chemical compound O([C@H]1C[C@@](O)(CC=2C(O)=C3C(=O)C=4C=CC=C(C=4C(=O)C3=C(O)C=21)OC)C(=O)CO)[C@H]1C[C@H](N)[C@H](O)[C@H](C)O1 AOJJSUZBOXZQNB-TZSSRYMLSA-N 0.000 description 4
- OAKJQQAXSVQMHS-UHFFFAOYSA-N Hydrazine Chemical compound NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 description 4
- 206010058467 Lung neoplasm malignant Diseases 0.000 description 4
- 241001465754 Metazoa Species 0.000 description 4
- 108091028043 Nucleic acid sequence Proteins 0.000 description 4
- 230000000118 anti-neoplastic effect Effects 0.000 description 4
- 229940034982 antineoplastic agent Drugs 0.000 description 4
- 239000000872 buffer Substances 0.000 description 4
- 239000000969 carrier Substances 0.000 description 4
- 231100000433 cytotoxic Toxicity 0.000 description 4
- 229940127089 cytotoxic agent Drugs 0.000 description 4
- 230000001472 cytotoxic effect Effects 0.000 description 4
- 230000012010 growth Effects 0.000 description 4
- 239000003112 inhibitor Substances 0.000 description 4
- 239000007924 injection Substances 0.000 description 4
- 238000002347 injection Methods 0.000 description 4
- 230000002147 killing effect Effects 0.000 description 4
- 239000003446 ligand Substances 0.000 description 4
- 230000000670 limiting effect Effects 0.000 description 4
- 210000004185 liver Anatomy 0.000 description 4
- 208000014018 liver neoplasm Diseases 0.000 description 4
- 201000005202 lung cancer Diseases 0.000 description 4
- 150000003141 primary amines Chemical class 0.000 description 4
- 235000018102 proteins Nutrition 0.000 description 4
- RCINICONZNJXQF-MZXODVADSA-N taxol Chemical compound O([C@@H]1[C@@]2(C[C@@H](C(C)=C(C2(C)C)[C@H](C([C@]2(C)[C@@H](O)C[C@H]3OC[C@]3([C@H]21)OC(C)=O)=O)OC(=O)C)OC(=O)[C@H](O)[C@@H](NC(=O)C=1C=CC=CC=1)C=1C=CC=CC=1)O)C(=O)C1=CC=CC=C1 RCINICONZNJXQF-MZXODVADSA-N 0.000 description 4
- 210000001519 tissue Anatomy 0.000 description 4
- 230000014616 translation Effects 0.000 description 4
- 229960005486 vaccine Drugs 0.000 description 4
- 241000894006 Bacteria Species 0.000 description 3
- 206010006187 Breast cancer Diseases 0.000 description 3
- 208000026310 Breast neoplasm Diseases 0.000 description 3
- 206010009944 Colon cancer Diseases 0.000 description 3
- 108010092160 Dactinomycin Proteins 0.000 description 3
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 3
- WHUUTDBJXJRKMK-UHFFFAOYSA-N Glutamic acid Natural products OC(=O)C(N)CCC(O)=O WHUUTDBJXJRKMK-UHFFFAOYSA-N 0.000 description 3
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 3
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 3
- DCXYFEDJOCDNAF-REOHCLBHSA-N L-asparagine Chemical compound OC(=O)[C@@H](N)CC(N)=O DCXYFEDJOCDNAF-REOHCLBHSA-N 0.000 description 3
- CKLJMWTZIZZHCS-REOHCLBHSA-N L-aspartic acid Chemical compound OC(=O)[C@@H](N)CC(O)=O CKLJMWTZIZZHCS-REOHCLBHSA-N 0.000 description 3
- AGPKZVBTJJNPAG-WHFBIAKZSA-N L-isoleucine Chemical compound CC[C@H](C)[C@H](N)C(O)=O AGPKZVBTJJNPAG-WHFBIAKZSA-N 0.000 description 3
- ROHFNLRQFUQHCH-YFKPBYRVSA-N L-leucine Chemical compound CC(C)C[C@H](N)C(O)=O ROHFNLRQFUQHCH-YFKPBYRVSA-N 0.000 description 3
- COLNVLDHVKWLRT-QMMMGPOBSA-N L-phenylalanine Chemical compound OC(=O)[C@@H](N)CC1=CC=CC=C1 COLNVLDHVKWLRT-QMMMGPOBSA-N 0.000 description 3
- OUYCCCASQSFEME-QMMMGPOBSA-N L-tyrosine Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-QMMMGPOBSA-N 0.000 description 3
- 239000004472 Lysine Substances 0.000 description 3
- NWIBSHFKIJFRCO-WUDYKRTCSA-N Mytomycin Chemical compound C1N2C(C(C(C)=C(N)C3=O)=O)=C3[C@@H](COC(N)=O)[C@@]2(OC)[C@@H]2[C@H]1N2 NWIBSHFKIJFRCO-WUDYKRTCSA-N 0.000 description 3
- 229930012538 Paclitaxel Natural products 0.000 description 3
- 102000007079 Peptide Fragments Human genes 0.000 description 3
- 108010033276 Peptide Fragments Proteins 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
- FOCVUCIESVLUNU-UHFFFAOYSA-N Thiotepa Chemical compound C1CN1P(N1CC1)(=S)N1CC1 FOCVUCIESVLUNU-UHFFFAOYSA-N 0.000 description 3
- 239000004473 Threonine Substances 0.000 description 3
- KZSNJWFQEVHDMF-UHFFFAOYSA-N Valine Natural products CC(C)C(N)C(O)=O KZSNJWFQEVHDMF-UHFFFAOYSA-N 0.000 description 3
- 238000009825 accumulation Methods 0.000 description 3
- 239000002253 acid Substances 0.000 description 3
- 238000003556 assay Methods 0.000 description 3
- 239000012911 assay medium Substances 0.000 description 3
- 230000035578 autophosphorylation Effects 0.000 description 3
- 230000037396 body weight Effects 0.000 description 3
- 238000004113 cell culture Methods 0.000 description 3
- 230000004663 cell proliferation Effects 0.000 description 3
- 230000006378 damage Effects 0.000 description 3
- 231100000673 dose–response relationship Toxicity 0.000 description 3
- 238000002474 experimental method Methods 0.000 description 3
- 239000013604 expression vector Substances 0.000 description 3
- 229940014144 folate Drugs 0.000 description 3
- BTCSSZJGUNDROE-UHFFFAOYSA-N gamma-aminobutyric acid Chemical compound NCCCC(O)=O BTCSSZJGUNDROE-UHFFFAOYSA-N 0.000 description 3
- 239000001963 growth medium Substances 0.000 description 3
- 206010073071 hepatocellular carcinoma Diseases 0.000 description 3
- 102000048776 human CD274 Human genes 0.000 description 3
- 102000045108 human EGFR Human genes 0.000 description 3
- 238000000338 in vitro Methods 0.000 description 3
- 230000001965 increasing effect Effects 0.000 description 3
- 210000003734 kidney Anatomy 0.000 description 3
- 201000007270 liver cancer Diseases 0.000 description 3
- HAWPXGHAZFHHAD-UHFFFAOYSA-N mechlorethamine Chemical class ClCCN(C)CCCl HAWPXGHAZFHHAD-UHFFFAOYSA-N 0.000 description 3
- 239000012528 membrane Substances 0.000 description 3
- 210000004379 membrane Anatomy 0.000 description 3
- 230000004048 modification Effects 0.000 description 3
- 238000012986 modification Methods 0.000 description 3
- 208000002154 non-small cell lung carcinoma Diseases 0.000 description 3
- 238000010899 nucleation Methods 0.000 description 3
- 229960001592 paclitaxel Drugs 0.000 description 3
- 230000037361 pathway Effects 0.000 description 3
- 238000010647 peptide synthesis reaction Methods 0.000 description 3
- BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Substances [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 description 3
- 229920000642 polymer Polymers 0.000 description 3
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 3
- 238000007363 ring formation reaction Methods 0.000 description 3
- HXCHCVDVKSCDHU-PJKCJEBCSA-N s-[(2r,3s,4s,6s)-6-[[(2r,3s,4s,5r,6r)-5-[(2s,4s,5s)-5-(ethylamino)-4-methoxyoxan-2-yl]oxy-4-hydroxy-6-[[(2s,5z,9r,13e)-9-hydroxy-12-(methoxycarbonylamino)-13-[2-(methyltrisulfanyl)ethylidene]-11-oxo-2-bicyclo[7.3.1]trideca-1(12),5-dien-3,7-diynyl]oxy]-2-m Chemical compound C1[C@H](OC)[C@@H](NCC)CO[C@H]1O[C@H]1[C@H](O[C@@H]2C\3=C(NC(=O)OC)C(=O)C[C@@](C/3=C/CSSSC)(O)C#C\C=C/C#C2)O[C@H](C)[C@@H](NO[C@@H]2O[C@H](C)[C@@H](SC(=O)C=3C(=C(OC)C(O[C@H]4[C@@H]([C@H](OC)[C@@H](O)[C@H](C)O4)O)=C(I)C=3C)OC)[C@@H](O)C2)[C@@H]1O HXCHCVDVKSCDHU-PJKCJEBCSA-N 0.000 description 3
- 150000003839 salts Chemical class 0.000 description 3
- 238000012216 screening Methods 0.000 description 3
- 239000007790 solid phase Substances 0.000 description 3
- 206010041823 squamous cell carcinoma Diseases 0.000 description 3
- 238000010189 synthetic method Methods 0.000 description 3
- 229940124597 therapeutic agent Drugs 0.000 description 3
- 230000004614 tumor growth Effects 0.000 description 3
- 208000029729 tumor suppressor gene on chromosome 11 Diseases 0.000 description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 3
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 2
- 239000004475 Arginine Substances 0.000 description 2
- BFYIZQONLCFLEV-DAELLWKTSA-N Aromasine Chemical compound O=C1C=C[C@]2(C)[C@H]3CC[C@](C)(C(CC4)=O)[C@@H]4[C@@H]3CC(=C)C2=C1 BFYIZQONLCFLEV-DAELLWKTSA-N 0.000 description 2
- DCXYFEDJOCDNAF-UHFFFAOYSA-N Asparagine Natural products OC(=O)C(N)CC(N)=O DCXYFEDJOCDNAF-UHFFFAOYSA-N 0.000 description 2
- 231100000699 Bacterial toxin Toxicity 0.000 description 2
- 201000009030 Carcinoma Diseases 0.000 description 2
- 108010078791 Carrier Proteins Proteins 0.000 description 2
- 102000014914 Carrier Proteins Human genes 0.000 description 2
- 108090000994 Catalytic RNA Proteins 0.000 description 2
- 102000053642 Catalytic RNA Human genes 0.000 description 2
- 208000001333 Colorectal Neoplasms Diseases 0.000 description 2
- CMSMOCZEIVJLDB-UHFFFAOYSA-N Cyclophosphamide Chemical compound ClCCN(CCCl)P1(=O)NCCCO1 CMSMOCZEIVJLDB-UHFFFAOYSA-N 0.000 description 2
- UHDGCWIWMRVCDJ-CCXZUQQUSA-N Cytarabine Chemical compound O=C1N=C(N)C=CN1[C@H]1[C@@H](O)[C@H](O)[C@@H](CO)O1 UHDGCWIWMRVCDJ-CCXZUQQUSA-N 0.000 description 2
- 108090000695 Cytokines Proteins 0.000 description 2
- 102000004127 Cytokines Human genes 0.000 description 2
- SRBFZHDQGSBBOR-IOVATXLUSA-N D-xylopyranose Chemical compound O[C@@H]1COC(O)[C@H](O)[C@H]1O SRBFZHDQGSBBOR-IOVATXLUSA-N 0.000 description 2
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 2
- GHASVSINZRGABV-UHFFFAOYSA-N Fluorouracil Chemical compound FC1=CNC(=O)NC1=O GHASVSINZRGABV-UHFFFAOYSA-N 0.000 description 2
- FFEARJCKVFRZRR-BYPYZUCNSA-N L-methionine Chemical compound CSCC[C@H](N)C(O)=O FFEARJCKVFRZRR-BYPYZUCNSA-N 0.000 description 2
- 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 2
- KZSNJWFQEVHDMF-BYPYZUCNSA-N L-valine Chemical compound CC(C)[C@H](N)C(O)=O KZSNJWFQEVHDMF-BYPYZUCNSA-N 0.000 description 2
- ROHFNLRQFUQHCH-UHFFFAOYSA-N Leucine Natural products CC(C)CC(N)C(O)=O ROHFNLRQFUQHCH-UHFFFAOYSA-N 0.000 description 2
- 206010025323 Lymphomas Diseases 0.000 description 2
- NQTADLQHYWFPDB-UHFFFAOYSA-N N-Hydroxysuccinimide Chemical compound ON1C(=O)CCC1=O NQTADLQHYWFPDB-UHFFFAOYSA-N 0.000 description 2
- OVBPIULPVIDEAO-UHFFFAOYSA-N N-Pteroyl-L-glutaminsaeure Natural products C=1N=C2NC(N)=NC(=O)C2=NC=1CNC1=CC=C(C(=O)NC(CCC(O)=O)C(O)=O)C=C1 OVBPIULPVIDEAO-UHFFFAOYSA-N 0.000 description 2
- 206010033128 Ovarian cancer Diseases 0.000 description 2
- 206010061535 Ovarian neoplasm Diseases 0.000 description 2
- 206010061902 Pancreatic neoplasm Diseases 0.000 description 2
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 2
- 229920001213 Polysorbate 20 Polymers 0.000 description 2
- 206010060862 Prostate cancer Diseases 0.000 description 2
- 208000000236 Prostatic Neoplasms Diseases 0.000 description 2
- 240000004808 Saccharomyces cerevisiae Species 0.000 description 2
- MTCFGRXMJLQNBG-UHFFFAOYSA-N Serine Natural products OCC(N)C(O)=O MTCFGRXMJLQNBG-UHFFFAOYSA-N 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- 208000005718 Stomach Neoplasms Diseases 0.000 description 2
- AYFVYJQAPQTCCC-UHFFFAOYSA-N Threonine Natural products CC(O)C(N)C(O)=O AYFVYJQAPQTCCC-UHFFFAOYSA-N 0.000 description 2
- QIVBCDIJIAJPQS-UHFFFAOYSA-N Tryptophan Natural products C1=CC=C2C(CC(N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-UHFFFAOYSA-N 0.000 description 2
- 102000003990 Urokinase-type plasminogen activator Human genes 0.000 description 2
- 108090000435 Urokinase-type plasminogen activator Proteins 0.000 description 2
- 230000005856 abnormality Effects 0.000 description 2
- 229930183665 actinomycin Natural products 0.000 description 2
- RJURFGZVJUQBHK-UHFFFAOYSA-N actinomycin D Natural products CC1OC(=O)C(C(C)C)N(C)C(=O)CN(C)C(=O)C2CCCN2C(=O)C(C(C)C)NC(=O)C1NC(=O)C1=C(N)C(=O)C(C)=C2OC(C(C)=CC=C3C(=O)NC4C(=O)NC(C(N5CCCC5C(=O)N(C)CC(=O)N(C)C(C(C)C)C(=O)OC4C)=O)C(C)C)=C3N=C21 RJURFGZVJUQBHK-UHFFFAOYSA-N 0.000 description 2
- 239000000556 agonist Substances 0.000 description 2
- 150000001412 amines Chemical class 0.000 description 2
- 125000003277 amino group Chemical group 0.000 description 2
- ROBVIMPUHSLWNV-UHFFFAOYSA-N aminoglutethimide Chemical compound C=1C=C(N)C=CC=1C1(CC)CCC(=O)NC1=O ROBVIMPUHSLWNV-UHFFFAOYSA-N 0.000 description 2
- 229960003437 aminoglutethimide Drugs 0.000 description 2
- AVKUERGKIZMTKX-NJBDSQKTSA-N ampicillin Chemical compound C1([C@@H](N)C(=O)N[C@H]2[C@H]3SC([C@@H](N3C2=O)C(O)=O)(C)C)=CC=CC=C1 AVKUERGKIZMTKX-NJBDSQKTSA-N 0.000 description 2
- 229960000723 ampicillin Drugs 0.000 description 2
- YBBLVLTVTVSKRW-UHFFFAOYSA-N anastrozole Chemical compound N#CC(C)(C)C1=CC(C(C)(C#N)C)=CC(CN2N=CN=C2)=C1 YBBLVLTVTVSKRW-UHFFFAOYSA-N 0.000 description 2
- 239000003098 androgen Substances 0.000 description 2
- 239000003242 anti bacterial agent Substances 0.000 description 2
- 229940088710 antibiotic agent Drugs 0.000 description 2
- 239000003963 antioxidant agent Substances 0.000 description 2
- ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 2
- 235000009582 asparagine Nutrition 0.000 description 2
- 229960001230 asparagine Drugs 0.000 description 2
- 235000003704 aspartic acid Nutrition 0.000 description 2
- 239000000688 bacterial toxin Substances 0.000 description 2
- 230000004888 barrier function Effects 0.000 description 2
- 239000011324 bead Substances 0.000 description 2
- 230000009286 beneficial effect Effects 0.000 description 2
- UCMIRNVEIXFBKS-UHFFFAOYSA-N beta-alanine Chemical compound NCCC(O)=O UCMIRNVEIXFBKS-UHFFFAOYSA-N 0.000 description 2
- 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 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 229930195731 calicheamicin Natural products 0.000 description 2
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 2
- 230000010261 cell growth Effects 0.000 description 2
- 210000000170 cell membrane Anatomy 0.000 description 2
- 229960004630 chlorambucil Drugs 0.000 description 2
- JCKYGMPEJWAADB-UHFFFAOYSA-N chlorambucil Chemical compound OC(=O)CCCC1=CC=C(N(CCCl)CCCl)C=C1 JCKYGMPEJWAADB-UHFFFAOYSA-N 0.000 description 2
- 238000013270 controlled release Methods 0.000 description 2
- 235000018417 cysteine Nutrition 0.000 description 2
- OPTASPLRGRRNAP-UHFFFAOYSA-N cytosine Chemical compound NC=1C=CNC(=O)N=1 OPTASPLRGRRNAP-UHFFFAOYSA-N 0.000 description 2
- 238000011161 development Methods 0.000 description 2
- 239000003085 diluting agent Substances 0.000 description 2
- 238000005516 engineering process Methods 0.000 description 2
- 230000007613 environmental effect Effects 0.000 description 2
- 239000000284 extract Substances 0.000 description 2
- 229960002949 fluorouracil Drugs 0.000 description 2
- 229960000304 folic acid Drugs 0.000 description 2
- 230000006870 function Effects 0.000 description 2
- CHPZKNULDCNCBW-UHFFFAOYSA-N gallium nitrate Chemical compound [Ga+3].[O-][N+]([O-])=O.[O-][N+]([O-])=O.[O-][N+]([O-])=O CHPZKNULDCNCBW-UHFFFAOYSA-N 0.000 description 2
- 229960003692 gamma aminobutyric acid Drugs 0.000 description 2
- 206010017758 gastric cancer Diseases 0.000 description 2
- SDUQYLNIPVEERB-QPPQHZFASA-N gemcitabine Chemical compound O=C1N=C(N)C=CN1[C@H]1C(F)(F)[C@H](O)[C@@H](CO)O1 SDUQYLNIPVEERB-QPPQHZFASA-N 0.000 description 2
- 208000005017 glioblastoma Diseases 0.000 description 2
- 235000013922 glutamic acid Nutrition 0.000 description 2
- 239000004220 glutamic acid Substances 0.000 description 2
- ZDXPYRJPNDTMRX-UHFFFAOYSA-N glutamine Natural products OC(=O)C(N)CCC(N)=O ZDXPYRJPNDTMRX-UHFFFAOYSA-N 0.000 description 2
- 230000009931 harmful effect Effects 0.000 description 2
- 201000010536 head and neck cancer Diseases 0.000 description 2
- 208000014829 head and neck neoplasm Diseases 0.000 description 2
- 229960001101 ifosfamide Drugs 0.000 description 2
- HOMGKSMUEGBAAB-UHFFFAOYSA-N ifosfamide Chemical compound ClCCNP1(=O)OCCCN1CCCl HOMGKSMUEGBAAB-UHFFFAOYSA-N 0.000 description 2
- AGPKZVBTJJNPAG-UHFFFAOYSA-N isoleucine Natural products CCC(C)C(N)C(O)=O AGPKZVBTJJNPAG-UHFFFAOYSA-N 0.000 description 2
- 229960000310 isoleucine Drugs 0.000 description 2
- HPJKCIUCZWXJDR-UHFFFAOYSA-N letrozole Chemical compound C1=CC(C#N)=CC=C1C(N1N=CN=C1)C1=CC=C(C#N)C=C1 HPJKCIUCZWXJDR-UHFFFAOYSA-N 0.000 description 2
- 239000002502 liposome Substances 0.000 description 2
- 208000015486 malignant pancreatic neoplasm Diseases 0.000 description 2
- 239000003550 marker Substances 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- 239000011159 matrix material Substances 0.000 description 2
- 229960004961 mechlorethamine Drugs 0.000 description 2
- GLVAUDGFNGKCSF-UHFFFAOYSA-N mercaptopurine Chemical compound S=C1NC=NC2=C1NC=N2 GLVAUDGFNGKCSF-UHFFFAOYSA-N 0.000 description 2
- 229930182817 methionine Natural products 0.000 description 2
- 229960004857 mitomycin Drugs 0.000 description 2
- KKZJGLLVHKMTCM-UHFFFAOYSA-N mitoxantrone Chemical compound O=C1C2=C(O)C=CC(O)=C2C(=O)C2=C1C(NCCNCCO)=CC=C2NCCNCCO KKZJGLLVHKMTCM-UHFFFAOYSA-N 0.000 description 2
- 239000000178 monomer Substances 0.000 description 2
- 230000035772 mutation Effects 0.000 description 2
- 239000002105 nanoparticle Substances 0.000 description 2
- 239000013642 negative control Substances 0.000 description 2
- 238000005457 optimization Methods 0.000 description 2
- 210000000056 organ Anatomy 0.000 description 2
- 210000003463 organelle Anatomy 0.000 description 2
- 201000002528 pancreatic cancer Diseases 0.000 description 2
- 208000008443 pancreatic carcinoma Diseases 0.000 description 2
- 230000000144 pharmacologic effect Effects 0.000 description 2
- 239000012071 phase Substances 0.000 description 2
- COLNVLDHVKWLRT-UHFFFAOYSA-N phenylalanine Natural products OC(=O)C(N)CC1=CC=CC=C1 COLNVLDHVKWLRT-UHFFFAOYSA-N 0.000 description 2
- 230000026731 phosphorylation Effects 0.000 description 2
- 238000006366 phosphorylation reaction Methods 0.000 description 2
- 239000000256 polyoxyethylene sorbitan monolaurate Substances 0.000 description 2
- 235000010486 polyoxyethylene sorbitan monolaurate Nutrition 0.000 description 2
- 239000013641 positive control Substances 0.000 description 2
- 230000001737 promoting effect Effects 0.000 description 2
- 238000001243 protein synthesis Methods 0.000 description 2
- 238000000746 purification Methods 0.000 description 2
- 239000011541 reaction mixture Substances 0.000 description 2
- 230000004044 response Effects 0.000 description 2
- 108091092562 ribozyme Proteins 0.000 description 2
- 229940095743 selective estrogen receptor modulator Drugs 0.000 description 2
- 239000000333 selective estrogen receptor modulator Substances 0.000 description 2
- 230000011664 signaling Effects 0.000 description 2
- 238000010532 solid phase synthesis reaction Methods 0.000 description 2
- 239000002904 solvent Substances 0.000 description 2
- 150000003431 steroids Chemical group 0.000 description 2
- 201000011549 stomach cancer Diseases 0.000 description 2
- PVYJZLYGTZKPJE-UHFFFAOYSA-N streptonigrin Chemical compound C=1C=C2C(=O)C(OC)=C(N)C(=O)C2=NC=1C(C=1N)=NC(C(O)=O)=C(C)C=1C1=CC=C(OC)C(OC)=C1O PVYJZLYGTZKPJE-UHFFFAOYSA-N 0.000 description 2
- 239000004094 surface-active agent Substances 0.000 description 2
- 239000000725 suspension Substances 0.000 description 2
- 230000002195 synergetic effect Effects 0.000 description 2
- 238000003786 synthesis reaction Methods 0.000 description 2
- 229960001603 tamoxifen Drugs 0.000 description 2
- 229960001196 thiotepa Drugs 0.000 description 2
- 230000001988 toxicity Effects 0.000 description 2
- 231100000419 toxicity Toxicity 0.000 description 2
- 238000013519 translation Methods 0.000 description 2
- 230000005748 tumor development Effects 0.000 description 2
- 229960004441 tyrosine Drugs 0.000 description 2
- OUYCCCASQSFEME-UHFFFAOYSA-N tyrosine Natural products OC(=O)C(N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-UHFFFAOYSA-N 0.000 description 2
- 241001515965 unidentified phage Species 0.000 description 2
- 229960005356 urokinase Drugs 0.000 description 2
- 239000004474 valine Substances 0.000 description 2
- 231100000747 viability assay Toxicity 0.000 description 2
- 238000003026 viability measurement method Methods 0.000 description 2
- 239000013603 viral vector Substances 0.000 description 2
- OGNSCSPNOLGXSM-UHFFFAOYSA-N (+/-)-DABA Natural products NCCC(N)C(O)=O OGNSCSPNOLGXSM-UHFFFAOYSA-N 0.000 description 1
- FDKWRPBBCBCIGA-REOHCLBHSA-N (2r)-2-azaniumyl-3-$l^{1}-selanylpropanoate Chemical compound [Se]C[C@H](N)C(O)=O FDKWRPBBCBCIGA-REOHCLBHSA-N 0.000 description 1
- WDQLRUYAYXDIFW-RWKIJVEZSA-N (2r,3r,4s,5r,6r)-4-[(2s,3r,4s,5r,6r)-3,5-dihydroxy-4-[(2r,3r,4s,5s,6r)-3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl]oxy-6-[[(2r,3r,4s,5s,6r)-3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl]oxymethyl]oxan-2-yl]oxy-6-(hydroxymethyl)oxane-2,3,5-triol Chemical compound O[C@@H]1[C@@H](CO)O[C@@H](O)[C@H](O)[C@H]1O[C@H]1[C@H](O)[C@@H](O[C@H]2[C@@H]([C@@H](O)[C@H](O)[C@@H](CO)O2)O)[C@H](O)[C@@H](CO[C@H]2[C@@H]([C@@H](O)[C@H](O)[C@@H](CO)O2)O)O1 WDQLRUYAYXDIFW-RWKIJVEZSA-N 0.000 description 1
- IYKLZBIWFXPUCS-VIFPVBQESA-N (2s)-2-(naphthalen-1-ylamino)propanoic acid Chemical compound C1=CC=C2C(N[C@@H](C)C(O)=O)=CC=CC2=C1 IYKLZBIWFXPUCS-VIFPVBQESA-N 0.000 description 1
- XHBJLKMBAFTWJD-JTQLQIEISA-N (2s)-2-amino-3-(3-ethynylphenyl)propanoic acid Chemical compound OC(=O)[C@@H](N)CC1=CC=CC(C#C)=C1 XHBJLKMBAFTWJD-JTQLQIEISA-N 0.000 description 1
- PEMUHKUIQHFMTH-QMMMGPOBSA-N (2s)-2-amino-3-(4-bromophenyl)propanoic acid Chemical compound OC(=O)[C@@H](N)CC1=CC=C(Br)C=C1 PEMUHKUIQHFMTH-QMMMGPOBSA-N 0.000 description 1
- PPDNGMUGVMESGE-JTQLQIEISA-N (2s)-2-amino-3-(4-ethynylphenyl)propanoic acid Chemical compound OC(=O)[C@@H](N)CC1=CC=C(C#C)C=C1 PPDNGMUGVMESGE-JTQLQIEISA-N 0.000 description 1
- FLHDTNWRXMTPMP-NSHDSACASA-N (2s)-2-amino-3-(5-ethynyl-1h-indol-3-yl)propanoic acid Chemical compound C1=C(C#C)C=C2C(C[C@H](N)C(O)=O)=CNC2=C1 FLHDTNWRXMTPMP-NSHDSACASA-N 0.000 description 1
- UIKHEWRXMDFLKN-NSHDSACASA-N (2s)-2-amino-3-(6-ethynyl-1h-indol-3-yl)propanoic acid Chemical compound C#CC1=CC=C2C(C[C@H](N)C(O)=O)=CNC2=C1 UIKHEWRXMDFLKN-NSHDSACASA-N 0.000 description 1
- HTFFMYRVHHNNBE-YFKPBYRVSA-N (2s)-2-amino-6-azidohexanoic acid Chemical compound OC(=O)[C@@H](N)CCCCN=[N+]=[N-] HTFFMYRVHHNNBE-YFKPBYRVSA-N 0.000 description 1
- NEMHIKRLROONTL-QMMMGPOBSA-N (2s)-2-azaniumyl-3-(4-azidophenyl)propanoate Chemical compound OC(=O)[C@@H](N)CC1=CC=C(N=[N+]=[N-])C=C1 NEMHIKRLROONTL-QMMMGPOBSA-N 0.000 description 1
- NNWQLZWAZSJGLY-VKHMYHEASA-N (2s)-2-azaniumyl-4-azidobutanoate Chemical compound OC(=O)[C@@H](N)CCN=[N+]=[N-] NNWQLZWAZSJGLY-VKHMYHEASA-N 0.000 description 1
- ZXSBHXZKWRIEIA-JTQLQIEISA-N (2s)-3-(4-acetylphenyl)-2-azaniumylpropanoate Chemical compound CC(=O)C1=CC=C(C[C@H](N)C(O)=O)C=C1 ZXSBHXZKWRIEIA-JTQLQIEISA-N 0.000 description 1
- CGMTUJFWROPELF-YPAAEMCBSA-N (3E,5S)-5-[(2S)-butan-2-yl]-3-(1-hydroxyethylidene)pyrrolidine-2,4-dione Chemical compound CC[C@H](C)[C@@H]1NC(=O)\C(=C(/C)O)C1=O CGMTUJFWROPELF-YPAAEMCBSA-N 0.000 description 1
- XRBSKUSTLXISAB-XVVDYKMHSA-N (5r,6r,7r,8r)-8-hydroxy-7-(hydroxymethyl)-5-(3,4,5-trimethoxyphenyl)-5,6,7,8-tetrahydrobenzo[f][1,3]benzodioxole-6-carboxylic acid Chemical compound COC1=C(OC)C(OC)=CC([C@@H]2C3=CC=4OCOC=4C=C3[C@H](O)[C@@H](CO)[C@@H]2C(O)=O)=C1 XRBSKUSTLXISAB-XVVDYKMHSA-N 0.000 description 1
- OMJKFYKNWZZKTK-POHAHGRESA-N (5z)-5-(dimethylaminohydrazinylidene)imidazole-4-carboxamide Chemical compound CN(C)N\N=C1/N=CN=C1C(N)=O OMJKFYKNWZZKTK-POHAHGRESA-N 0.000 description 1
- JXVAMODRWBNUSF-KZQKBALLSA-N (7s,9r,10r)-7-[(2r,4s,5s,6s)-5-[[(2s,4as,5as,7s,9s,9ar,10ar)-2,9-dimethyl-3-oxo-4,4a,5a,6,7,9,9a,10a-octahydrodipyrano[4,2-a:4',3'-e][1,4]dioxin-7-yl]oxy]-4-(dimethylamino)-6-methyloxan-2-yl]oxy-10-[(2s,4s,5s,6s)-4-(dimethylamino)-5-hydroxy-6-methyloxan-2 Chemical compound O([C@@H]1C2=C(O)C=3C(=O)C4=CC=CC(O)=C4C(=O)C=3C(O)=C2[C@@H](O[C@@H]2O[C@@H](C)[C@@H](O[C@@H]3O[C@@H](C)[C@H]4O[C@@H]5O[C@@H](C)C(=O)C[C@@H]5O[C@H]4C3)[C@H](C2)N(C)C)C[C@]1(O)CC)[C@H]1C[C@H](N(C)C)[C@H](O)[C@H](C)O1 JXVAMODRWBNUSF-KZQKBALLSA-N 0.000 description 1
- INAUWOVKEZHHDM-PEDBPRJASA-N (7s,9s)-6,9,11-trihydroxy-9-(2-hydroxyacetyl)-7-[(2r,4s,5s,6s)-5-hydroxy-6-methyl-4-morpholin-4-yloxan-2-yl]oxy-4-methoxy-8,10-dihydro-7h-tetracene-5,12-dione;hydrochloride Chemical compound Cl.N1([C@H]2C[C@@H](O[C@@H](C)[C@H]2O)O[C@H]2C[C@@](O)(CC=3C(O)=C4C(=O)C=5C=CC=C(C=5C(=O)C4=C(O)C=32)OC)C(=O)CO)CCOCC1 INAUWOVKEZHHDM-PEDBPRJASA-N 0.000 description 1
- NOPNWHSMQOXAEI-PUCKCBAPSA-N (7s,9s)-7-[(2r,4s,5s,6s)-4-(2,3-dihydropyrrol-1-yl)-5-hydroxy-6-methyloxan-2-yl]oxy-6,9,11-trihydroxy-9-(2-hydroxyacetyl)-4-methoxy-8,10-dihydro-7h-tetracene-5,12-dione Chemical compound N1([C@H]2C[C@@H](O[C@@H](C)[C@H]2O)O[C@H]2C[C@@](O)(CC=3C(O)=C4C(=O)C=5C=CC=C(C=5C(=O)C4=C(O)C=32)OC)C(=O)CO)CCC=C1 NOPNWHSMQOXAEI-PUCKCBAPSA-N 0.000 description 1
- FPVKHBSQESCIEP-UHFFFAOYSA-N (8S)-3-(2-deoxy-beta-D-erythro-pentofuranosyl)-3,6,7,8-tetrahydroimidazo[4,5-d][1,3]diazepin-8-ol Natural products C1C(O)C(CO)OC1N1C(NC=NCC2O)=C2N=C1 FPVKHBSQESCIEP-UHFFFAOYSA-N 0.000 description 1
- IEXUMDBQLIVNHZ-YOUGDJEHSA-N (8s,11r,13r,14s,17s)-11-[4-(dimethylamino)phenyl]-17-hydroxy-17-(3-hydroxypropyl)-13-methyl-1,2,6,7,8,11,12,14,15,16-decahydrocyclopenta[a]phenanthren-3-one Chemical compound C1=CC(N(C)C)=CC=C1[C@@H]1C2=C3CCC(=O)C=C3CC[C@H]2[C@H](CC[C@]2(O)CCCO)[C@@]2(C)C1 IEXUMDBQLIVNHZ-YOUGDJEHSA-N 0.000 description 1
- LKJPYSCBVHEWIU-KRWDZBQOSA-N (R)-bicalutamide Chemical compound C([C@@](O)(C)C(=O)NC=1C=C(C(C#N)=CC=1)C(F)(F)F)S(=O)(=O)C1=CC=C(F)C=C1 LKJPYSCBVHEWIU-KRWDZBQOSA-N 0.000 description 1
- AGNGYMCLFWQVGX-AGFFZDDWSA-N (e)-1-[(2s)-2-amino-2-carboxyethoxy]-2-diazonioethenolate Chemical compound OC(=O)[C@@H](N)CO\C([O-])=C\[N+]#N AGNGYMCLFWQVGX-AGFFZDDWSA-N 0.000 description 1
- 108091032973 (ribonucleotides)n+m Proteins 0.000 description 1
- WNXJIVFYUVYPPR-UHFFFAOYSA-N 1,3-dioxolane Chemical compound C1COCO1 WNXJIVFYUVYPPR-UHFFFAOYSA-N 0.000 description 1
- BLCJBICVQSYOIF-UHFFFAOYSA-N 2,2-diaminobutanoic acid Chemical compound CCC(N)(N)C(O)=O BLCJBICVQSYOIF-UHFFFAOYSA-N 0.000 description 1
- SKWCZPYWFRTSDD-UHFFFAOYSA-N 2,3-bis(azaniumyl)propanoate;chloride Chemical compound Cl.NCC(N)C(O)=O SKWCZPYWFRTSDD-UHFFFAOYSA-N 0.000 description 1
- BTOTXLJHDSNXMW-POYBYMJQSA-N 2,3-dideoxyuridine Chemical compound O1[C@H](CO)CC[C@@H]1N1C(=O)NC(=O)C=C1 BTOTXLJHDSNXMW-POYBYMJQSA-N 0.000 description 1
- BOMZMNZEXMAQQW-UHFFFAOYSA-N 2,5,11-trimethyl-6h-pyrido[4,3-b]carbazol-2-ium-9-ol;acetate Chemical compound CC([O-])=O.C[N+]1=CC=C2C(C)=C(NC=3C4=CC(O)=CC=3)C4=C(C)C2=C1 BOMZMNZEXMAQQW-UHFFFAOYSA-N 0.000 description 1
- OYIFNHCXNCRBQI-UHFFFAOYSA-N 2-aminoadipic acid Chemical compound OC(=O)C(N)CCCC(O)=O OYIFNHCXNCRBQI-UHFFFAOYSA-N 0.000 description 1
- AKVBCGQVQXPRLD-UHFFFAOYSA-N 2-aminooctanoic acid Chemical compound CCCCCCC(N)C(O)=O AKVBCGQVQXPRLD-UHFFFAOYSA-N 0.000 description 1
- OFYAYGJCPXRNBL-UHFFFAOYSA-N 2-azaniumyl-3-naphthalen-1-ylpropanoate Chemical compound C1=CC=C2C(CC(N)C(O)=O)=CC=CC2=C1 OFYAYGJCPXRNBL-UHFFFAOYSA-N 0.000 description 1
- FDAYLTPAFBGXAB-UHFFFAOYSA-N 2-chloro-n,n-bis(2-chloroethyl)ethanamine Chemical compound ClCCN(CCCl)CCCl FDAYLTPAFBGXAB-UHFFFAOYSA-N 0.000 description 1
- YIMDLWDNDGKDTJ-QLKYHASDSA-N 3'-deamino-3'-(3-cyanomorpholin-4-yl)doxorubicin Chemical compound N1([C@H]2C[C@@H](O[C@@H](C)[C@H]2O)O[C@H]2C[C@@](O)(CC=3C(O)=C4C(=O)C=5C=CC=C(C=5C(=O)C4=C(O)C=32)OC)C(=O)CO)CCOCC1C#N YIMDLWDNDGKDTJ-QLKYHASDSA-N 0.000 description 1
- NDMPLJNOPCLANR-UHFFFAOYSA-N 3,4-dihydroxy-15-(4-hydroxy-18-methoxycarbonyl-5,18-seco-ibogamin-18-yl)-16-methoxy-1-methyl-6,7-didehydro-aspidospermidine-3-carboxylic acid methyl ester Natural products C1C(CC)(O)CC(CC2(C(=O)OC)C=3C(=CC4=C(C56C(C(C(O)C7(CC)C=CCN(C67)CC5)(O)C(=O)OC)N4C)C=3)OC)CN1CCC1=C2NC2=CC=CC=C12 NDMPLJNOPCLANR-UHFFFAOYSA-N 0.000 description 1
- PWMYMKOUNYTVQN-UHFFFAOYSA-N 3-(8,8-diethyl-2-aza-8-germaspiro[4.5]decan-2-yl)-n,n-dimethylpropan-1-amine Chemical compound C1C[Ge](CC)(CC)CCC11CN(CCCN(C)C)CC1 PWMYMKOUNYTVQN-UHFFFAOYSA-N 0.000 description 1
- GSWYUZQBLVUEPH-UHFFFAOYSA-N 3-(azaniumylmethyl)benzoate Chemical compound NCC1=CC=CC(C(O)=O)=C1 GSWYUZQBLVUEPH-UHFFFAOYSA-N 0.000 description 1
- AOJJSUZBOXZQNB-VTZDEGQISA-N 4'-epidoxorubicin Chemical compound O([C@H]1C[C@@](O)(CC=2C(O)=C3C(=O)C=4C=CC=C(C=4C(=O)C3=C(O)C=21)OC)C(=O)CO)[C@H]1C[C@H](N)[C@@H](O)[C@H](C)O1 AOJJSUZBOXZQNB-VTZDEGQISA-N 0.000 description 1
- DODQJNMQWMSYGS-QPLCGJKRSA-N 4-[(z)-1-[4-[2-(dimethylamino)ethoxy]phenyl]-1-phenylbut-1-en-2-yl]phenol Chemical compound C=1C=C(O)C=CC=1C(/CC)=C(C=1C=CC(OCCN(C)C)=CC=1)/C1=CC=CC=C1 DODQJNMQWMSYGS-QPLCGJKRSA-N 0.000 description 1
- PZNQZSRPDOEBMS-QMMMGPOBSA-N 4-iodo-L-phenylalanine Chemical compound OC(=O)[C@@H](N)CC1=CC=C(I)C=C1 PZNQZSRPDOEBMS-QMMMGPOBSA-N 0.000 description 1
- NMUSYJAQQFHJEW-KVTDHHQDSA-N 5-azacytidine Chemical compound O=C1N=C(N)N=CN1[C@H]1[C@H](O)[C@H](O)[C@@H](CO)O1 NMUSYJAQQFHJEW-KVTDHHQDSA-N 0.000 description 1
- WYWHKKSPHMUBEB-UHFFFAOYSA-N 6-Mercaptoguanine Natural products N1C(N)=NC(=S)C2=C1N=CN2 WYWHKKSPHMUBEB-UHFFFAOYSA-N 0.000 description 1
- WYXSYVWAUAUWLD-SHUUEZRQSA-N 6-azauridine Chemical compound O[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1N1C(=O)NC(=O)C=N1 WYXSYVWAUAUWLD-SHUUEZRQSA-N 0.000 description 1
- STQGQHZAVUOBTE-UHFFFAOYSA-N 7-Cyan-hept-2t-en-4,6-diinsaeure Natural products C1=2C(O)=C3C(=O)C=4C(OC)=CC=CC=4C(=O)C3=C(O)C=2CC(O)(C(C)=O)CC1OC1CC(N)C(O)C(C)O1 STQGQHZAVUOBTE-UHFFFAOYSA-N 0.000 description 1
- ZGXJTSGNIOSYLO-UHFFFAOYSA-N 88755TAZ87 Chemical compound NCC(=O)CCC(O)=O ZGXJTSGNIOSYLO-UHFFFAOYSA-N 0.000 description 1
- HDZZVAMISRMYHH-UHFFFAOYSA-N 9beta-Ribofuranosyl-7-deazaadenin Natural products C1=CC=2C(N)=NC=NC=2N1C1OC(CO)C(O)C1O HDZZVAMISRMYHH-UHFFFAOYSA-N 0.000 description 1
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical group CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 1
- 208000024893 Acute lymphoblastic leukemia Diseases 0.000 description 1
- 108010012934 Albumin-Bound Paclitaxel Proteins 0.000 description 1
- CEIZFXOZIQNICU-UHFFFAOYSA-N Alternaria alternata Crofton-weed toxin Natural products CCC(C)C1NC(=O)C(C(C)=O)=C1O CEIZFXOZIQNICU-UHFFFAOYSA-N 0.000 description 1
- 206010002091 Anaesthesia Diseases 0.000 description 1
- 108090000644 Angiozyme Proteins 0.000 description 1
- 108020000948 Antisense Oligonucleotides Proteins 0.000 description 1
- 102000014654 Aromatase Human genes 0.000 description 1
- 108010078554 Aromatase Proteins 0.000 description 1
- 208000023275 Autoimmune disease Diseases 0.000 description 1
- NOWKCMXCCJGMRR-UHFFFAOYSA-N Aziridine Chemical compound C1CN1 NOWKCMXCCJGMRR-UHFFFAOYSA-N 0.000 description 1
- 208000010839 B-cell chronic lymphocytic leukemia Diseases 0.000 description 1
- 208000003950 B-cell lymphoma Diseases 0.000 description 1
- 108010077805 Bacterial Proteins Proteins 0.000 description 1
- VGGGPCQERPFHOB-MCIONIFRSA-N Bestatin Chemical compound CC(C)C[C@H](C(O)=O)NC(=O)[C@@H](O)[C@H](N)CC1=CC=CC=C1 VGGGPCQERPFHOB-MCIONIFRSA-N 0.000 description 1
- 229940122361 Bisphosphonate Drugs 0.000 description 1
- 206010005003 Bladder cancer Diseases 0.000 description 1
- 108010006654 Bleomycin Proteins 0.000 description 1
- 208000003174 Brain Neoplasms Diseases 0.000 description 1
- COVZYZSDYWQREU-UHFFFAOYSA-N Busulfan Chemical compound CS(=O)(=O)OCCCCOS(C)(=O)=O COVZYZSDYWQREU-UHFFFAOYSA-N 0.000 description 1
- 125000001433 C-terminal amino-acid group Chemical group 0.000 description 1
- KLWPJMFMVPTNCC-UHFFFAOYSA-N Camptothecin Natural products CCC1(O)C(=O)OCC2=C1C=C3C4Nc5ccccc5C=C4CN3C2=O KLWPJMFMVPTNCC-UHFFFAOYSA-N 0.000 description 1
- GAGWJHPBXLXJQN-UORFTKCHSA-N Capecitabine Chemical compound C1=C(F)C(NC(=O)OCCCCC)=NC(=O)N1[C@H]1[C@H](O)[C@H](O)[C@@H](C)O1 GAGWJHPBXLXJQN-UORFTKCHSA-N 0.000 description 1
- GAGWJHPBXLXJQN-UHFFFAOYSA-N Capecitabine Natural products C1=C(F)C(NC(=O)OCCCCC)=NC(=O)N1C1C(O)C(O)C(C)O1 GAGWJHPBXLXJQN-UHFFFAOYSA-N 0.000 description 1
- 208000010667 Carcinoma of liver and intrahepatic biliary tract Diseases 0.000 description 1
- AOCCBINRVIKJHY-UHFFFAOYSA-N Carmofur Chemical compound CCCCCCNC(=O)N1C=C(F)C(=O)NC1=O AOCCBINRVIKJHY-UHFFFAOYSA-N 0.000 description 1
- DLGOEMSEDOSKAD-UHFFFAOYSA-N Carmustine Chemical compound ClCCNC(=O)N(N=O)CCCl DLGOEMSEDOSKAD-UHFFFAOYSA-N 0.000 description 1
- 102000000844 Cell Surface Receptors Human genes 0.000 description 1
- 108010001857 Cell Surface Receptors Proteins 0.000 description 1
- 206010008342 Cervix carcinoma Diseases 0.000 description 1
- JWBOIMRXGHLCPP-UHFFFAOYSA-N Chloditan Chemical compound C=1C=CC=C(Cl)C=1C(C(Cl)Cl)C1=CC=C(Cl)C=C1 JWBOIMRXGHLCPP-UHFFFAOYSA-N 0.000 description 1
- MKQWTWSXVILIKJ-LXGUWJNJSA-N Chlorozotocin Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](C=O)NC(=O)N(N=O)CCCl MKQWTWSXVILIKJ-LXGUWJNJSA-N 0.000 description 1
- SRUWWOSWHXIIIA-UKPGNTDSSA-N Cyanoginosin Chemical compound N1C(=O)[C@H](CCCN=C(N)N)NC(=O)[C@@H](C)[C@H](C(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](C)NC(=O)C(=C)N(C)C(=O)CC[C@H](C(O)=O)N(C)C(=O)[C@@H](C)[C@@H]1\C=C\C(\C)=C\[C@H](C)[C@@H](O)CC1=CC=CC=C1 SRUWWOSWHXIIIA-UKPGNTDSSA-N 0.000 description 1
- FDKWRPBBCBCIGA-UWTATZPHSA-N D-Selenocysteine Natural products [Se]C[C@@H](N)C(O)=O FDKWRPBBCBCIGA-UWTATZPHSA-N 0.000 description 1
- 229940021995 DNA vaccine Drugs 0.000 description 1
- 102000004163 DNA-directed RNA polymerases Human genes 0.000 description 1
- 108090000626 DNA-directed RNA polymerases Proteins 0.000 description 1
- 108700021041 Disintegrin Proteins 0.000 description 1
- ZQZFYGIXNQKOAV-OCEACIFDSA-N Droloxifene Chemical compound C=1C=CC=CC=1C(/CC)=C(C=1C=C(O)C=CC=1)\C1=CC=C(OCCN(C)C)C=C1 ZQZFYGIXNQKOAV-OCEACIFDSA-N 0.000 description 1
- 229930193152 Dynemicin Natural products 0.000 description 1
- KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 1
- 206010014733 Endometrial cancer Diseases 0.000 description 1
- 206010014759 Endometrial neoplasm Diseases 0.000 description 1
- AFMYMMXSQGUCBK-UHFFFAOYSA-N Endynamicin A Natural products C1#CC=CC#CC2NC(C=3C(=O)C4=C(O)C=CC(O)=C4C(=O)C=3C(O)=C3)=C3C34OC32C(C)C(C(O)=O)=C(OC)C41 AFMYMMXSQGUCBK-UHFFFAOYSA-N 0.000 description 1
- SAMRUMKYXPVKPA-VFKOLLTISA-N Enocitabine Chemical compound O=C1N=C(NC(=O)CCCCCCCCCCCCCCCCCCCCC)C=CN1[C@H]1[C@@H](O)[C@H](O)[C@@H](CO)O1 SAMRUMKYXPVKPA-VFKOLLTISA-N 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- HTIJFSOGRVMCQR-UHFFFAOYSA-N Epirubicin Natural products COc1cccc2C(=O)c3c(O)c4CC(O)(CC(OC5CC(N)C(=O)C(C)O5)c4c(O)c3C(=O)c12)C(=O)CO HTIJFSOGRVMCQR-UHFFFAOYSA-N 0.000 description 1
- OBMLHUPNRURLOK-XGRAFVIBSA-N Epitiostanol Chemical compound C1[C@@H]2S[C@@H]2C[C@]2(C)[C@H]3CC[C@](C)([C@H](CC4)O)[C@@H]4[C@@H]3CC[C@H]21 OBMLHUPNRURLOK-XGRAFVIBSA-N 0.000 description 1
- 241001524679 Escherichia virus M13 Species 0.000 description 1
- 229930189413 Esperamicin Natural products 0.000 description 1
- NIGWMJHCCYYCSF-UHFFFAOYSA-N Fenclonine Chemical compound OC(=O)C(N)CC1=CC=C(Cl)C=C1 NIGWMJHCCYYCSF-UHFFFAOYSA-N 0.000 description 1
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 1
- 206010017993 Gastrointestinal neoplasms Diseases 0.000 description 1
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 1
- 239000004471 Glycine Substances 0.000 description 1
- BLCLNMBMMGCOAS-URPVMXJPSA-N Goserelin Chemical compound C([C@@H](C(=O)N[C@H](COC(C)(C)C)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCN=C(N)N)C(=O)N1[C@@H](CCC1)C(=O)NNC(N)=O)NC(=O)[C@H](CO)NC(=O)[C@H](CC=1C2=CC=CC=C2NC=1)NC(=O)[C@H](CC=1NC=NC=1)NC(=O)[C@H]1NC(=O)CC1)C1=CC=C(O)C=C1 BLCLNMBMMGCOAS-URPVMXJPSA-N 0.000 description 1
- 108010069236 Goserelin Proteins 0.000 description 1
- 206010073069 Hepatic cancer Diseases 0.000 description 1
- 101500025419 Homo sapiens Epidermal growth factor Proteins 0.000 description 1
- VSNHCAURESNICA-UHFFFAOYSA-N Hydroxyurea Chemical compound NC(=O)NO VSNHCAURESNICA-UHFFFAOYSA-N 0.000 description 1
- 208000019758 Hypergammaglobulinemia Diseases 0.000 description 1
- XDXDZDZNSLXDNA-TZNDIEGXSA-N Idarubicin Chemical compound C1[C@H](N)[C@H](O)[C@H](C)O[C@H]1O[C@@H]1C2=C(O)C(C(=O)C3=CC=CC=C3C3=O)=C3C(O)=C2C[C@@](O)(C(C)=O)C1 XDXDZDZNSLXDNA-TZNDIEGXSA-N 0.000 description 1
- XDXDZDZNSLXDNA-UHFFFAOYSA-N Idarubicin Natural products C1C(N)C(O)C(C)OC1OC1C2=C(O)C(C(=O)C3=CC=CC=C3C3=O)=C3C(O)=C2CC(O)(C(C)=O)C1 XDXDZDZNSLXDNA-UHFFFAOYSA-N 0.000 description 1
- 102000014150 Interferons Human genes 0.000 description 1
- 108010050904 Interferons Proteins 0.000 description 1
- 208000008839 Kidney Neoplasms Diseases 0.000 description 1
- AHLPHDHHMVZTML-BYPYZUCNSA-N L-Ornithine Chemical compound NCCC[C@H](N)C(O)=O AHLPHDHHMVZTML-BYPYZUCNSA-N 0.000 description 1
- JLERVPBPJHKRBJ-UHFFFAOYSA-N LY 117018 Chemical compound C1=CC(O)=CC=C1C1=C(C(=O)C=2C=CC(OCCN3CCCC3)=CC=2)C2=CC=C(O)C=C2S1 JLERVPBPJHKRBJ-UHFFFAOYSA-N 0.000 description 1
- 229920001491 Lentinan Polymers 0.000 description 1
- 108010000817 Leuprolide Proteins 0.000 description 1
- GQYIWUVLTXOXAJ-UHFFFAOYSA-N Lomustine Chemical compound ClCCN(N=O)C(=O)NC1CCCCC1 GQYIWUVLTXOXAJ-UHFFFAOYSA-N 0.000 description 1
- 208000030289 Lymphoproliferative disease Diseases 0.000 description 1
- 241000124008 Mammalia Species 0.000 description 1
- 208000025205 Mantle-Cell Lymphoma Diseases 0.000 description 1
- 206010027145 Melanocytic naevus Diseases 0.000 description 1
- 102000018697 Membrane Proteins Human genes 0.000 description 1
- 108010052285 Membrane Proteins Proteins 0.000 description 1
- 206010027406 Mesothelioma Diseases 0.000 description 1
- VFKZTMPDYBFSTM-KVTDHHQDSA-N Mitobronitol Chemical compound BrC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CBr VFKZTMPDYBFSTM-KVTDHHQDSA-N 0.000 description 1
- 229930192392 Mitomycin Natural products 0.000 description 1
- 208000034578 Multiple myelomas Diseases 0.000 description 1
- 102000016943 Muramidase Human genes 0.000 description 1
- 108010014251 Muramidase Proteins 0.000 description 1
- 241000699666 Mus <mouse, genus> Species 0.000 description 1
- 108010062010 N-Acetylmuramoyl-L-alanine Amidase Proteins 0.000 description 1
- ZDZOTLJHXYCWBA-VCVYQWHSSA-N N-debenzoyl-N-(tert-butoxycarbonyl)-10-deacetyltaxol Chemical compound O([C@H]1[C@H]2[C@@](C([C@H](O)C3=C(C)[C@@H](OC(=O)[C@H](O)[C@@H](NC(=O)OC(C)(C)C)C=4C=CC=CC=4)C[C@]1(O)C3(C)C)=O)(C)[C@@H](O)C[C@H]1OC[C@]12OC(=O)C)C(=O)C1=CC=CC=C1 ZDZOTLJHXYCWBA-VCVYQWHSSA-N 0.000 description 1
- 125000001429 N-terminal alpha-amino-acid group Chemical group 0.000 description 1
- 238000011887 Necropsy Methods 0.000 description 1
- 101710204212 Neocarzinostatin Proteins 0.000 description 1
- 102400001103 Neurotensin Human genes 0.000 description 1
- 101800001814 Neurotensin Proteins 0.000 description 1
- 208000007256 Nevus Diseases 0.000 description 1
- AFLXUQUGROGEFA-UHFFFAOYSA-N Nitrogen mustard N-oxide Chemical class ClCC[N+]([O-])(C)CCCl AFLXUQUGROGEFA-UHFFFAOYSA-N 0.000 description 1
- IXBQSRWSVIBXNC-HSKGSTCASA-N Nodularin Chemical compound C([C@H](OC)[C@@H](C)\C=C(/C)\C=C\[C@H]1[C@@H](C(=O)N[C@H](CCC(=O)N(C)C(=C\C)/C(=O)N[C@H]([C@H](C)C(=O)N[C@@H](CCCN=C(N)N)C(=O)N1)C(O)=O)C(O)=O)C)C1=CC=CC=C1 IXBQSRWSVIBXNC-HSKGSTCASA-N 0.000 description 1
- IXBQSRWSVIBXNC-UHFFFAOYSA-N Nodularin Natural products N1C(=O)C(CCCN=C(N)N)NC(=O)C(C)C(C(O)=O)NC(=O)C(=CC)N(C)C(=O)CCC(C(O)=O)NC(=O)C(C)C1C=CC(C)=CC(C)C(OC)CC1=CC=CC=C1 IXBQSRWSVIBXNC-UHFFFAOYSA-N 0.000 description 1
- GEYBMYRBIABFTA-VIFPVBQESA-N O-methyl-L-tyrosine Chemical compound COC1=CC=C(C[C@H](N)C(O)=O)C=C1 GEYBMYRBIABFTA-VIFPVBQESA-N 0.000 description 1
- 206010030113 Oedema Diseases 0.000 description 1
- 229930187135 Olivomycin Natural products 0.000 description 1
- AHLPHDHHMVZTML-UHFFFAOYSA-N Orn-delta-NH2 Natural products NCCCC(N)C(O)=O AHLPHDHHMVZTML-UHFFFAOYSA-N 0.000 description 1
- UTJLXEIPEHZYQJ-UHFFFAOYSA-N Ornithine Natural products OC(=O)C(C)CCCN UTJLXEIPEHZYQJ-UHFFFAOYSA-N 0.000 description 1
- 101100242312 Oryza sativa subsp. japonica OSK1 gene Proteins 0.000 description 1
- 101100533605 Oryza sativa subsp. japonica SKP1 gene Proteins 0.000 description 1
- 108010057150 Peplomycin Proteins 0.000 description 1
- 208000009565 Pharyngeal Neoplasms Diseases 0.000 description 1
- 206010034811 Pharyngeal cancer Diseases 0.000 description 1
- KMSKQZKKOZQFFG-HSUXVGOQSA-N Pirarubicin Chemical compound O([C@H]1[C@@H](N)C[C@@H](O[C@H]1C)O[C@H]1C[C@@](O)(CC=2C(O)=C3C(=O)C=4C=CC=C(C=4C(=O)C3=C(O)C=21)OC)C(=O)CO)[C@H]1CCCCO1 KMSKQZKKOZQFFG-HSUXVGOQSA-N 0.000 description 1
- 206010035226 Plasma cell myeloma Diseases 0.000 description 1
- 229920001054 Poly(ethylene‐co‐vinyl acetate) Polymers 0.000 description 1
- 229920002732 Polyanhydride Polymers 0.000 description 1
- 102400000745 Potential peptide Human genes 0.000 description 1
- 101800001357 Potential peptide Proteins 0.000 description 1
- HFVNWDWLWUCIHC-GUPDPFMOSA-N Prednimustine Chemical compound O=C([C@@]1(O)CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)[C@@H](O)C[C@@]21C)COC(=O)CCCC1=CC=C(N(CCCl)CCCl)C=C1 HFVNWDWLWUCIHC-GUPDPFMOSA-N 0.000 description 1
- RJKFOVLPORLFTN-LEKSSAKUSA-N Progesterone Chemical class C1CC2=CC(=O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H](C(=O)C)[C@@]1(C)CC2 RJKFOVLPORLFTN-LEKSSAKUSA-N 0.000 description 1
- ONIBWKKTOPOVIA-UHFFFAOYSA-N Proline Natural products OC(=O)C1CCCN1 ONIBWKKTOPOVIA-UHFFFAOYSA-N 0.000 description 1
- 102100024924 Protein kinase C alpha type Human genes 0.000 description 1
- 101710109947 Protein kinase C alpha type Proteins 0.000 description 1
- AHHFEZNOXOZZQA-ZEBDFXRSSA-N Ranimustine Chemical compound CO[C@H]1O[C@H](CNC(=O)N(CCCl)N=O)[C@@H](O)[C@H](O)[C@H]1O AHHFEZNOXOZZQA-ZEBDFXRSSA-N 0.000 description 1
- 108010008281 Recombinant Fusion Proteins Proteins 0.000 description 1
- 102000007056 Recombinant Fusion Proteins 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
- PLXBWHJQWKZRKG-UHFFFAOYSA-N Resazurin Chemical compound C1=CC(=O)C=C2OC3=CC(O)=CC=C3[N+]([O-])=C21 PLXBWHJQWKZRKG-UHFFFAOYSA-N 0.000 description 1
- OWPCHSCAPHNHAV-UHFFFAOYSA-N Rhizoxin Natural products C1C(O)C2(C)OC2C=CC(C)C(OC(=O)C2)CC2CC2OC2C(=O)OC1C(C)C(OC)C(C)=CC=CC(C)=CC1=COC(C)=N1 OWPCHSCAPHNHAV-UHFFFAOYSA-N 0.000 description 1
- 208000004337 Salivary Gland Neoplasms Diseases 0.000 description 1
- 206010061934 Salivary gland cancer Diseases 0.000 description 1
- 229920002305 Schizophyllan Polymers 0.000 description 1
- 206010041067 Small cell lung cancer Diseases 0.000 description 1
- 208000021712 Soft tissue sarcoma Diseases 0.000 description 1
- CGMTUJFWROPELF-UHFFFAOYSA-N Tenuazonic acid Natural products CCC(C)C1NC(=O)C(=C(C)/O)C1=O CGMTUJFWROPELF-UHFFFAOYSA-N 0.000 description 1
- 239000004098 Tetracycline Substances 0.000 description 1
- 208000024770 Thyroid neoplasm Diseases 0.000 description 1
- 101710183280 Topoisomerase Proteins 0.000 description 1
- IWEQQRMGNVVKQW-OQKDUQJOSA-N Toremifene citrate Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O.C1=CC(OCCN(C)C)=CC=C1C(\C=1C=CC=CC=1)=C(\CCCl)C1=CC=CC=C1 IWEQQRMGNVVKQW-OQKDUQJOSA-N 0.000 description 1
- FYAMXEPQQLNQDM-UHFFFAOYSA-N Tris(1-aziridinyl)phosphine oxide Chemical compound C1CN1P(N1CC1)(=O)N1CC1 FYAMXEPQQLNQDM-UHFFFAOYSA-N 0.000 description 1
- 102000004142 Trypsin Human genes 0.000 description 1
- 108090000631 Trypsin Proteins 0.000 description 1
- 208000007097 Urinary Bladder Neoplasms Diseases 0.000 description 1
- 208000006105 Uterine Cervical Neoplasms Diseases 0.000 description 1
- 208000002495 Uterine Neoplasms Diseases 0.000 description 1
- 102000005789 Vascular Endothelial Growth Factors Human genes 0.000 description 1
- 108010019530 Vascular Endothelial Growth Factors Proteins 0.000 description 1
- JXLYSJRDGCGARV-WWYNWVTFSA-N Vinblastine Natural products O=C(O[C@H]1[C@](O)(C(=O)OC)[C@@H]2N(C)c3c(cc(c(OC)c3)[C@]3(C(=O)OC)c4[nH]c5c(c4CCN4C[C@](O)(CC)C[C@H](C3)C4)cccc5)[C@@]32[C@H]2[C@@]1(CC)C=CCN2CC3)C JXLYSJRDGCGARV-WWYNWVTFSA-N 0.000 description 1
- 241000700605 Viruses Species 0.000 description 1
- 206010047741 Vulval cancer Diseases 0.000 description 1
- 208000004354 Vulvar Neoplasms Diseases 0.000 description 1
- AIWRTTMUVOZGPW-HSPKUQOVSA-N abarelix Chemical compound C([C@@H](C(=O)N[C@H](CC(N)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCCNC(C)C)C(=O)N1[C@@H](CCC1)C(=O)N[C@H](C)C(N)=O)N(C)C(=O)[C@H](CO)NC(=O)[C@@H](CC=1C=NC=CC=1)NC(=O)[C@@H](CC=1C=CC(Cl)=CC=1)NC(=O)[C@@H](CC=1C=C2C=CC=CC2=CC=1)NC(C)=O)C1=CC=C(O)C=C1 AIWRTTMUVOZGPW-HSPKUQOVSA-N 0.000 description 1
- 108010023617 abarelix Proteins 0.000 description 1
- 229960002184 abarelix Drugs 0.000 description 1
- 230000002159 abnormal effect Effects 0.000 description 1
- 229940028652 abraxane Drugs 0.000 description 1
- 239000003070 absorption delaying agent Substances 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- RJURFGZVJUQBHK-IIXSONLDSA-N actinomycin D Chemical compound C[C@H]1OC(=O)[C@H](C(C)C)N(C)C(=O)CN(C)C(=O)[C@@H]2CCCN2C(=O)[C@@H](C(C)C)NC(=O)[C@H]1NC(=O)C1=C(N)C(=O)C(C)=C2OC(C(C)=CC=C3C(=O)N[C@@H]4C(=O)N[C@@H](C(N5CCC[C@H]5C(=O)N(C)CC(=O)N(C)[C@@H](C(C)C)C(=O)O[C@@H]4C)=O)C(C)C)=C3N=C21 RJURFGZVJUQBHK-IIXSONLDSA-N 0.000 description 1
- 230000003213 activating effect Effects 0.000 description 1
- 239000004480 active ingredient Substances 0.000 description 1
- 230000001154 acute effect Effects 0.000 description 1
- 230000000996 additive effect Effects 0.000 description 1
- 210000004100 adrenal gland Anatomy 0.000 description 1
- 229940009456 adriamycin Drugs 0.000 description 1
- 230000002411 adverse Effects 0.000 description 1
- 239000000443 aerosol Substances 0.000 description 1
- 238000001042 affinity chromatography Methods 0.000 description 1
- 239000012996 alamarblue reagent Substances 0.000 description 1
- 125000003158 alcohol group Chemical group 0.000 description 1
- 235000013334 alcoholic beverage Nutrition 0.000 description 1
- 108700025316 aldesleukin Proteins 0.000 description 1
- 150000007824 aliphatic compounds Chemical class 0.000 description 1
- 125000001931 aliphatic group Chemical group 0.000 description 1
- 229940045714 alkyl sulfonate alkylating agent Drugs 0.000 description 1
- 150000008052 alkyl sulfonates Chemical class 0.000 description 1
- 229940100198 alkylating agent Drugs 0.000 description 1
- 239000002168 alkylating agent Substances 0.000 description 1
- SHGAZHPCJJPHSC-YCNIQYBTSA-N all-trans-retinoic acid Chemical compound OC(=O)\C=C(/C)\C=C\C=C(/C)\C=C\C1=C(C)CCCC1(C)C SHGAZHPCJJPHSC-YCNIQYBTSA-N 0.000 description 1
- 150000001408 amides Chemical class 0.000 description 1
- 229960002749 aminolevulinic acid Drugs 0.000 description 1
- 230000003321 amplification Effects 0.000 description 1
- 229960001220 amsacrine Drugs 0.000 description 1
- XCPGHVQEEXUHNC-UHFFFAOYSA-N amsacrine Chemical compound COC1=CC(NS(C)(=O)=O)=CC=C1NC1=C(C=CC=C2)C2=NC2=CC=CC=C12 XCPGHVQEEXUHNC-UHFFFAOYSA-N 0.000 description 1
- 230000037005 anaesthesia Effects 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 229960002932 anastrozole Drugs 0.000 description 1
- BBDAGFIXKZCXAH-CCXZUQQUSA-N ancitabine Chemical compound N=C1C=CN2[C@@H]3O[C@H](CO)[C@@H](O)[C@@H]3OC2=N1 BBDAGFIXKZCXAH-CCXZUQQUSA-N 0.000 description 1
- 229950000242 ancitabine Drugs 0.000 description 1
- 229940030486 androgens Drugs 0.000 description 1
- 238000010171 animal model Methods 0.000 description 1
- 230000002280 anti-androgenic effect Effects 0.000 description 1
- 230000001093 anti-cancer Effects 0.000 description 1
- 229940046836 anti-estrogen Drugs 0.000 description 1
- 230000001833 anti-estrogenic effect Effects 0.000 description 1
- 230000003388 anti-hormonal effect Effects 0.000 description 1
- 230000000340 anti-metabolite Effects 0.000 description 1
- 230000001028 anti-proliverative effect Effects 0.000 description 1
- 239000000051 antiandrogen Substances 0.000 description 1
- 229940030495 antiandrogen sex hormone and modulator of the genital system Drugs 0.000 description 1
- 239000012635 anticancer drug combination Substances 0.000 description 1
- 229940100197 antimetabolite Drugs 0.000 description 1
- 239000002256 antimetabolite Substances 0.000 description 1
- 229940045719 antineoplastic alkylating agent nitrosoureas Drugs 0.000 description 1
- 229940041181 antineoplastic drug Drugs 0.000 description 1
- 239000000074 antisense oligonucleotide Substances 0.000 description 1
- 238000012230 antisense oligonucleotides Methods 0.000 description 1
- 230000006907 apoptotic process Effects 0.000 description 1
- PYMYPHUHKUWMLA-UHFFFAOYSA-N arabinose Natural products OCC(O)C(O)C(O)C=O PYMYPHUHKUWMLA-UHFFFAOYSA-N 0.000 description 1
- 150000008209 arabinosides Chemical class 0.000 description 1
- 229940078010 arimidex Drugs 0.000 description 1
- 229940087620 aromasin Drugs 0.000 description 1
- 239000003886 aromatase inhibitor Substances 0.000 description 1
- 229940046844 aromatase inhibitors Drugs 0.000 description 1
- 150000001491 aromatic compounds Chemical class 0.000 description 1
- 210000004507 artificial chromosome Anatomy 0.000 description 1
- 125000003118 aryl group Chemical group 0.000 description 1
- 229960002756 azacitidine Drugs 0.000 description 1
- VSRXQHXAPYXROS-UHFFFAOYSA-N azanide;cyclobutane-1,1-dicarboxylic acid;platinum(2+) Chemical compound [NH2-].[NH2-].[Pt+2].OC(=O)C1(C(O)=O)CCC1 VSRXQHXAPYXROS-UHFFFAOYSA-N 0.000 description 1
- 229950011321 azaserine Drugs 0.000 description 1
- 150000001541 aziridines Chemical class 0.000 description 1
- SRBFZHDQGSBBOR-UHFFFAOYSA-N beta-D-Pyranose-Lyxose Natural products OC1COC(O)C(O)C1O SRBFZHDQGSBBOR-UHFFFAOYSA-N 0.000 description 1
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 1
- 229940000635 beta-alanine Drugs 0.000 description 1
- 229960000997 bicalutamide Drugs 0.000 description 1
- 239000011230 binding agent Substances 0.000 description 1
- 108091008324 binding proteins Proteins 0.000 description 1
- 230000003115 biocidal effect Effects 0.000 description 1
- 229920000249 biocompatible polymer Polymers 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
- 229950008548 bisantrene Drugs 0.000 description 1
- 150000004663 bisphosphonates Chemical class 0.000 description 1
- 201000000053 blastoma Diseases 0.000 description 1
- 229960001561 bleomycin Drugs 0.000 description 1
- OYVAGSVQBOHSSS-UAPAGMARSA-O bleomycin A2 Chemical compound N([C@H](C(=O)N[C@H](C)[C@@H](O)[C@H](C)C(=O)N[C@@H]([C@H](O)C)C(=O)NCCC=1SC=C(N=1)C=1SC=C(N=1)C(=O)NCCC[S+](C)C)[C@@H](O[C@H]1[C@H]([C@@H](O)[C@H](O)[C@H](CO)O1)O[C@@H]1[C@H]([C@@H](OC(N)=O)[C@H](O)[C@@H](CO)O1)O)C=1N=CNC=1)C(=O)C1=NC([C@H](CC(N)=O)NC[C@H](N)C(N)=O)=NC(N)=C1C OYVAGSVQBOHSSS-UAPAGMARSA-O 0.000 description 1
- 229920001400 block copolymer Polymers 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 210000000481 breast Anatomy 0.000 description 1
- 229960005520 bryostatin Drugs 0.000 description 1
- MJQUEDHRCUIRLF-TVIXENOKSA-N bryostatin 1 Chemical compound C([C@@H]1CC(/[C@@H]([C@@](C(C)(C)/C=C/2)(O)O1)OC(=O)/C=C/C=C/CCC)=C\C(=O)OC)[C@H]([C@@H](C)O)OC(=O)C[C@H](O)C[C@@H](O1)C[C@H](OC(C)=O)C(C)(C)[C@]1(O)C[C@@H]1C\C(=C\C(=O)OC)C[C@H]\2O1 MJQUEDHRCUIRLF-TVIXENOKSA-N 0.000 description 1
- MUIWQCKLQMOUAT-AKUNNTHJSA-N bryostatin 20 Natural products COC(=O)C=C1C[C@@]2(C)C[C@]3(O)O[C@](C)(C[C@@H](O)CC(=O)O[C@](C)(C[C@@]4(C)O[C@](O)(CC5=CC(=O)O[C@]45C)C(C)(C)C=C[C@@](C)(C1)O2)[C@@H](C)O)C[C@H](OC(=O)C(C)(C)C)C3(C)C MUIWQCKLQMOUAT-AKUNNTHJSA-N 0.000 description 1
- 229960002092 busulfan Drugs 0.000 description 1
- VSJKWCGYPAHWDS-FQEVSTJZSA-N camptothecin Chemical compound C1=CC=C2C=C(CN3C4=CC5=C(C3=O)COC(=O)[C@]5(O)CC)C4=NC2=C1 VSJKWCGYPAHWDS-FQEVSTJZSA-N 0.000 description 1
- 229940127093 camptothecin Drugs 0.000 description 1
- 230000004611 cancer cell death Effects 0.000 description 1
- 239000012830 cancer therapeutic Substances 0.000 description 1
- 229960004117 capecitabine Drugs 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 150000001720 carbohydrates Chemical group 0.000 description 1
- 229960004562 carboplatin Drugs 0.000 description 1
- 150000001732 carboxylic acid derivatives Chemical group 0.000 description 1
- 208000002458 carcinoid tumor Diseases 0.000 description 1
- XREUEWVEMYWFFA-CSKJXFQVSA-N carminomycin Chemical compound C1[C@H](N)[C@H](O)[C@H](C)O[C@H]1O[C@@H]1C2=C(O)C(C(=O)C3=C(O)C=CC=C3C3=O)=C3C(O)=C2C[C@@](O)(C(C)=O)C1 XREUEWVEMYWFFA-CSKJXFQVSA-N 0.000 description 1
- 229930188550 carminomycin Natural products 0.000 description 1
- XREUEWVEMYWFFA-UHFFFAOYSA-N carminomycin I Natural products C1C(N)C(O)C(C)OC1OC1C2=C(O)C(C(=O)C3=C(O)C=CC=C3C3=O)=C3C(O)=C2CC(O)(C(C)=O)C1 XREUEWVEMYWFFA-UHFFFAOYSA-N 0.000 description 1
- 229960003261 carmofur Drugs 0.000 description 1
- 229960005243 carmustine Drugs 0.000 description 1
- 229950001725 carubicin Drugs 0.000 description 1
- 230000006727 cell loss Effects 0.000 description 1
- 238000001516 cell proliferation assay Methods 0.000 description 1
- 239000006285 cell suspension Substances 0.000 description 1
- 230000003833 cell viability Effects 0.000 description 1
- 230000001413 cellular effect Effects 0.000 description 1
- 201000010881 cervical cancer Diseases 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 238000012512 characterization method Methods 0.000 description 1
- 238000007385 chemical modification Methods 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 231100000481 chemical toxicant Toxicity 0.000 description 1
- 229940044683 chemotherapy drug Drugs 0.000 description 1
- 229960001480 chlorozotocin Drugs 0.000 description 1
- 238000004587 chromatography analysis Methods 0.000 description 1
- ZYVSOIYQKUDENJ-WKSBCEQHSA-N chromomycin A3 Chemical compound O([C@@H]1C[C@@H](O[C@H](C)[C@@H]1OC(C)=O)OC=1C=C2C=C3C[C@H]([C@@H](C(=O)C3=C(O)C2=C(O)C=1C)O[C@@H]1O[C@H](C)[C@@H](O)[C@H](O[C@@H]2O[C@H](C)[C@@H](O)[C@H](O[C@@H]3O[C@@H](C)[C@H](OC(C)=O)[C@@](C)(O)C3)C2)C1)[C@H](OC)C(=O)[C@@H](O)[C@@H](C)O)[C@@H]1C[C@@H](O)[C@@H](OC)[C@@H](C)O1 ZYVSOIYQKUDENJ-WKSBCEQHSA-N 0.000 description 1
- 230000001684 chronic effect Effects 0.000 description 1
- ACSIXWWBWUQEHA-UHFFFAOYSA-N clodronic acid Chemical compound OP(O)(=O)C(Cl)(Cl)P(O)(O)=O ACSIXWWBWUQEHA-UHFFFAOYSA-N 0.000 description 1
- 229960002286 clodronic acid Drugs 0.000 description 1
- 239000011248 coating agent Substances 0.000 description 1
- 210000001072 colon Anatomy 0.000 description 1
- 208000029742 colonic neoplasm Diseases 0.000 description 1
- 238000009833 condensation Methods 0.000 description 1
- 230000005494 condensation Effects 0.000 description 1
- 238000010276 construction Methods 0.000 description 1
- 239000006071 cream Substances 0.000 description 1
- 125000004093 cyano group Chemical group *C#N 0.000 description 1
- 229960004397 cyclophosphamide Drugs 0.000 description 1
- XUJNEKJLAYXESH-UHFFFAOYSA-N cysteine Natural products SCC(N)C(O)=O XUJNEKJLAYXESH-UHFFFAOYSA-N 0.000 description 1
- 150000001945 cysteines Chemical class 0.000 description 1
- 229960000684 cytarabine Drugs 0.000 description 1
- 102000003675 cytokine receptors Human genes 0.000 description 1
- 108010057085 cytokine receptors Proteins 0.000 description 1
- 229940104302 cytosine Drugs 0.000 description 1
- 210000000172 cytosol Anatomy 0.000 description 1
- 229960003901 dacarbazine Drugs 0.000 description 1
- 229960000640 dactinomycin Drugs 0.000 description 1
- STQGQHZAVUOBTE-VGBVRHCVSA-N daunorubicin Chemical compound O([C@H]1C[C@@](O)(CC=2C(O)=C3C(=O)C=4C=CC=C(C=4C(=O)C3=C(O)C=21)OC)C(C)=O)[C@H]1C[C@H](N)[C@H](O)[C@H](C)O1 STQGQHZAVUOBTE-VGBVRHCVSA-N 0.000 description 1
- 229960000975 daunorubicin Drugs 0.000 description 1
- 230000003111 delayed effect Effects 0.000 description 1
- 238000012217 deletion Methods 0.000 description 1
- 230000037430 deletion Effects 0.000 description 1
- 230000001419 dependent effect Effects 0.000 description 1
- 230000001627 detrimental effect Effects 0.000 description 1
- 230000018109 developmental process Effects 0.000 description 1
- 239000008121 dextrose Substances 0.000 description 1
- 238000003745 diagnosis Methods 0.000 description 1
- 235000014113 dietary fatty acids Nutrition 0.000 description 1
- 239000007884 disintegrant Substances 0.000 description 1
- 239000002612 dispersion medium Substances 0.000 description 1
- VSJKWCGYPAHWDS-UHFFFAOYSA-N dl-camptothecin Natural products C1=CC=C2C=C(CN3C4=CC5=C(C3=O)COC(=O)C5(O)CC)C4=NC2=C1 VSJKWCGYPAHWDS-UHFFFAOYSA-N 0.000 description 1
- AMRJKAQTDDKMCE-UHFFFAOYSA-N dolastatin Chemical compound CC(C)C(N(C)C)C(=O)NC(C(C)C)C(=O)N(C)C(C(C)C)C(OC)CC(=O)N1CCCC1C(OC)C(C)C(=O)NC(C=1SC=CN=1)CC1=CC=CC=C1 AMRJKAQTDDKMCE-UHFFFAOYSA-N 0.000 description 1
- 229930188854 dolastatin Natural products 0.000 description 1
- 229960004679 doxorubicin Drugs 0.000 description 1
- 229950004203 droloxifene Drugs 0.000 description 1
- NOTIQUSPUUHHEH-UXOVVSIBSA-N dromostanolone propionate Chemical compound C([C@@H]1CC2)C(=O)[C@H](C)C[C@]1(C)[C@@H]1[C@@H]2[C@@H]2CC[C@H](OC(=O)CC)[C@@]2(C)CC1 NOTIQUSPUUHHEH-UXOVVSIBSA-N 0.000 description 1
- 229950004683 drostanolone propionate Drugs 0.000 description 1
- 238000012377 drug delivery Methods 0.000 description 1
- 229960005501 duocarmycin Drugs 0.000 description 1
- VQNATVDKACXKTF-XELLLNAOSA-N duocarmycin Chemical compound COC1=C(OC)C(OC)=C2NC(C(=O)N3C4=CC(=O)C5=C([C@@]64C[C@@H]6C3)C=C(N5)C(=O)OC)=CC2=C1 VQNATVDKACXKTF-XELLLNAOSA-N 0.000 description 1
- 229930184221 duocarmycin Natural products 0.000 description 1
- 239000000975 dye Substances 0.000 description 1
- AFMYMMXSQGUCBK-AKMKHHNQSA-N dynemicin a Chemical compound C1#C\C=C/C#C[C@@H]2NC(C=3C(=O)C4=C(O)C=CC(O)=C4C(=O)C=3C(O)=C3)=C3[C@@]34O[C@]32[C@@H](C)C(C(O)=O)=C(OC)[C@H]41 AFMYMMXSQGUCBK-AKMKHHNQSA-N 0.000 description 1
- VLCYCQAOQCDTCN-UHFFFAOYSA-N eflornithine Chemical compound NCCCC(N)(C(F)F)C(O)=O VLCYCQAOQCDTCN-UHFFFAOYSA-N 0.000 description 1
- 238000001962 electrophoresis Methods 0.000 description 1
- 230000008030 elimination Effects 0.000 description 1
- 238000003379 elimination reaction Methods 0.000 description 1
- 229950000549 elliptinium acetate Drugs 0.000 description 1
- 230000013020 embryo development Effects 0.000 description 1
- 201000008184 embryoma Diseases 0.000 description 1
- 239000000839 emulsion Substances 0.000 description 1
- 230000002357 endometrial effect Effects 0.000 description 1
- 239000003623 enhancer Substances 0.000 description 1
- 229950011487 enocitabine Drugs 0.000 description 1
- 229940088598 enzyme Drugs 0.000 description 1
- 229960001904 epirubicin Drugs 0.000 description 1
- 230000010502 episomal replication Effects 0.000 description 1
- 229950002973 epitiostanol Drugs 0.000 description 1
- 229930013356 epothilone Natural products 0.000 description 1
- 150000003883 epothilone derivatives Chemical class 0.000 description 1
- ITSGNOIFAJAQHJ-BMFNZSJVSA-N esorubicin Chemical compound O([C@H]1C[C@@](O)(CC=2C(O)=C3C(=O)C=4C=CC=C(C=4C(=O)C3=C(O)C=21)OC)C(=O)CO)[C@H]1C[C@H](N)C[C@H](C)O1 ITSGNOIFAJAQHJ-BMFNZSJVSA-N 0.000 description 1
- 229950002017 esorubicin Drugs 0.000 description 1
- LJQQFQHBKUKHIS-WJHRIEJJSA-N esperamicin Chemical compound O1CC(NC(C)C)C(OC)CC1OC1C(O)C(NOC2OC(C)C(SC)C(O)C2)C(C)OC1OC1C(\C2=C/CSSSC)=C(NC(=O)OC)C(=O)C(OC3OC(C)C(O)C(OC(=O)C=4C(=CC(OC)=C(OC)C=4)NC(=O)C(=C)OC)C3)C2(O)C#C\C=C/C#C1 LJQQFQHBKUKHIS-WJHRIEJJSA-N 0.000 description 1
- 229960001842 estramustine Drugs 0.000 description 1
- FRPJXPJMRWBBIH-RBRWEJTLSA-N estramustine Chemical compound ClCCN(CCCl)C(=O)OC1=CC=C2[C@H]3CC[C@](C)([C@H](CC4)O)[C@@H]4[C@@H]3CCC2=C1 FRPJXPJMRWBBIH-RBRWEJTLSA-N 0.000 description 1
- 229940011871 estrogen Drugs 0.000 description 1
- 239000000262 estrogen Substances 0.000 description 1
- 239000000328 estrogen antagonist Substances 0.000 description 1
- QSRLNKCNOLVZIR-KRWDZBQOSA-N ethyl (2s)-2-[[2-[4-[bis(2-chloroethyl)amino]phenyl]acetyl]amino]-4-methylsulfanylbutanoate Chemical compound CCOC(=O)[C@H](CCSC)NC(=O)CC1=CC=C(N(CCCl)CCCl)C=C1 QSRLNKCNOLVZIR-KRWDZBQOSA-N 0.000 description 1
- VJJPUSNTGOMMGY-MRVIYFEKSA-N etoposide Chemical compound COC1=C(O)C(OC)=CC([C@@H]2C3=CC=4OCOC=4C=C3[C@@H](O[C@H]3[C@@H]([C@@H](O)[C@@H]4O[C@H](C)OC[C@H]4O3)O)[C@@H]3[C@@H]2C(OC3)=O)=C1 VJJPUSNTGOMMGY-MRVIYFEKSA-N 0.000 description 1
- 238000011156 evaluation Methods 0.000 description 1
- 230000005713 exacerbation Effects 0.000 description 1
- 229960000255 exemestane Drugs 0.000 description 1
- 210000000416 exudates and transudate Anatomy 0.000 description 1
- 239000003885 eye ointment Substances 0.000 description 1
- 229940043168 fareston Drugs 0.000 description 1
- 229930195729 fatty acid Natural products 0.000 description 1
- 239000000194 fatty acid Substances 0.000 description 1
- 150000004665 fatty acids Chemical group 0.000 description 1
- 229940087476 femara Drugs 0.000 description 1
- 239000000945 filler Substances 0.000 description 1
- 238000013100 final test Methods 0.000 description 1
- 239000000834 fixative Substances 0.000 description 1
- 229960000961 floxuridine Drugs 0.000 description 1
- ODKNJVUHOIMIIZ-RRKCRQDMSA-N floxuridine Chemical compound C1[C@H](O)[C@@H](CO)O[C@H]1N1C(=O)NC(=O)C(F)=C1 ODKNJVUHOIMIIZ-RRKCRQDMSA-N 0.000 description 1
- 229960000390 fludarabine Drugs 0.000 description 1
- GIUYCYHIANZCFB-FJFJXFQQSA-N fludarabine phosphate Chemical compound C1=NC=2C(N)=NC(F)=NC=2N1[C@@H]1O[C@H](COP(O)(O)=O)[C@@H](O)[C@@H]1O GIUYCYHIANZCFB-FJFJXFQQSA-N 0.000 description 1
- 239000012530 fluid Substances 0.000 description 1
- GNBHRKFJIUUOQI-UHFFFAOYSA-N fluorescein Chemical compound O1C(=O)C2=CC=CC=C2C21C1=CC=C(O)C=C1OC1=CC(O)=CC=C21 GNBHRKFJIUUOQI-UHFFFAOYSA-N 0.000 description 1
- 102000034287 fluorescent proteins Human genes 0.000 description 1
- 108091006047 fluorescent proteins Proteins 0.000 description 1
- 229960002074 flutamide Drugs 0.000 description 1
- MKXKFYHWDHIYRV-UHFFFAOYSA-N flutamide Chemical compound CC(C)C(=O)NC1=CC=C([N+]([O-])=O)C(C(F)(F)F)=C1 MKXKFYHWDHIYRV-UHFFFAOYSA-N 0.000 description 1
- 230000003325 follicular Effects 0.000 description 1
- 201000003444 follicular lymphoma Diseases 0.000 description 1
- 230000037406 food intake Effects 0.000 description 1
- 239000008098 formaldehyde solution Substances 0.000 description 1
- 229960004421 formestane Drugs 0.000 description 1
- 229960004783 fotemustine Drugs 0.000 description 1
- YAKWPXVTIGTRJH-UHFFFAOYSA-N fotemustine Chemical compound CCOP(=O)(OCC)C(C)NC(=O)N(CCCl)N=O YAKWPXVTIGTRJH-UHFFFAOYSA-N 0.000 description 1
- 125000000524 functional group Chemical group 0.000 description 1
- 108020001507 fusion proteins Proteins 0.000 description 1
- 102000037865 fusion proteins Human genes 0.000 description 1
- 229940044658 gallium nitrate Drugs 0.000 description 1
- 230000002496 gastric effect Effects 0.000 description 1
- 239000000499 gel Substances 0.000 description 1
- 239000007903 gelatin capsule Substances 0.000 description 1
- 229960005277 gemcitabine Drugs 0.000 description 1
- 229940020967 gemzar Drugs 0.000 description 1
- 238000001415 gene therapy Methods 0.000 description 1
- 229930182470 glycoside Natural products 0.000 description 1
- XLXSAKCOAKORKW-UHFFFAOYSA-N gonadorelin Chemical group C1CCC(C(=O)NCC(N)=O)N1C(=O)C(CCCN=C(N)N)NC(=O)C(CC(C)C)NC(=O)CNC(=O)C(NC(=O)C(CO)NC(=O)C(CC=1C2=CC=CC=C2NC=1)NC(=O)C(CC=1NC=NC=1)NC(=O)C1NC(=O)CC1)CC1=CC=C(O)C=C1 XLXSAKCOAKORKW-UHFFFAOYSA-N 0.000 description 1
- 229960002913 goserelin Drugs 0.000 description 1
- 239000008187 granular material Substances 0.000 description 1
- 201000009277 hairy cell leukemia Diseases 0.000 description 1
- 230000036541 health Effects 0.000 description 1
- 231100000844 hepatocellular carcinoma Toxicity 0.000 description 1
- 238000004128 high performance liquid chromatography Methods 0.000 description 1
- HNDVDQJCIGZPNO-UHFFFAOYSA-N histidine Natural products OC(=O)C(N)CC1=CN=CN1 HNDVDQJCIGZPNO-UHFFFAOYSA-N 0.000 description 1
- 230000003054 hormonal effect Effects 0.000 description 1
- 231100000508 hormonal effect Toxicity 0.000 description 1
- 210000005260 human cell Anatomy 0.000 description 1
- 229940116978 human epidermal growth factor Drugs 0.000 description 1
- 239000000017 hydrogel Substances 0.000 description 1
- 230000002209 hydrophobic effect Effects 0.000 description 1
- WGCNASOHLSPBMP-UHFFFAOYSA-N hydroxyacetaldehyde Natural products OCC=O WGCNASOHLSPBMP-UHFFFAOYSA-N 0.000 description 1
- 229960001330 hydroxycarbamide Drugs 0.000 description 1
- 229920003063 hydroxymethyl cellulose Polymers 0.000 description 1
- 229940031574 hydroxymethyl cellulose Drugs 0.000 description 1
- 229960000908 idarubicin Drugs 0.000 description 1
- 210000000987 immune system Anatomy 0.000 description 1
- DBIGHPPNXATHOF-UHFFFAOYSA-N improsulfan Chemical compound CS(=O)(=O)OCCCNCCCOS(C)(=O)=O DBIGHPPNXATHOF-UHFFFAOYSA-N 0.000 description 1
- 229950008097 improsulfan Drugs 0.000 description 1
- 230000001976 improved effect Effects 0.000 description 1
- 238000001802 infusion Methods 0.000 description 1
- 230000003993 interaction Effects 0.000 description 1
- 229940047124 interferons Drugs 0.000 description 1
- 238000001361 intraarterial administration Methods 0.000 description 1
- 238000007918 intramuscular administration Methods 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- BPHPUYQFMNQIOC-NXRLNHOXSA-N isopropyl beta-D-thiogalactopyranoside Chemical compound CC(C)S[C@@H]1O[C@H](CO)[C@H](O)[C@H](O)[C@H]1O BPHPUYQFMNQIOC-NXRLNHOXSA-N 0.000 description 1
- 239000007951 isotonicity adjuster Substances 0.000 description 1
- 201000010982 kidney cancer Diseases 0.000 description 1
- 150000002596 lactones Chemical class 0.000 description 1
- 235000015122 lemonade Nutrition 0.000 description 1
- 229940115286 lentinan Drugs 0.000 description 1
- 230000003902 lesion Effects 0.000 description 1
- 229960003881 letrozole Drugs 0.000 description 1
- 208000032839 leukemia Diseases 0.000 description 1
- GFIJNRVAKGFPGQ-LIJARHBVSA-N leuprolide Chemical compound CCNC(=O)[C@@H]1CCCN1C(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](CC(C)C)NC(=O)[C@@H](NC(=O)[C@H](CO)NC(=O)[C@H](CC=1C2=CC=CC=C2NC=1)NC(=O)[C@H](CC=1N=CNC=1)NC(=O)[C@H]1NC(=O)CC1)CC1=CC=C(O)C=C1 GFIJNRVAKGFPGQ-LIJARHBVSA-N 0.000 description 1
- 229960004338 leuprorelin Drugs 0.000 description 1
- 239000000865 liniment Substances 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 201000002250 liver carcinoma Diseases 0.000 description 1
- 229960002247 lomustine Drugs 0.000 description 1
- 239000006210 lotion Substances 0.000 description 1
- 239000000314 lubricant Substances 0.000 description 1
- 201000005249 lung adenocarcinoma Diseases 0.000 description 1
- 201000005243 lung squamous cell carcinoma Diseases 0.000 description 1
- 208000037841 lung tumor Diseases 0.000 description 1
- RVFGKBWWUQOIOU-NDEPHWFRSA-N lurtotecan Chemical compound O=C([C@]1(O)CC)OCC(C(N2CC3=4)=O)=C1C=C2C3=NC1=CC=2OCCOC=2C=C1C=4CN1CCN(C)CC1 RVFGKBWWUQOIOU-NDEPHWFRSA-N 0.000 description 1
- 229950002654 lurtotecan Drugs 0.000 description 1
- 230000000527 lymphocytic effect Effects 0.000 description 1
- 239000006166 lysate Substances 0.000 description 1
- 125000003588 lysine group Chemical group [H]N([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])(N([H])[H])C(*)=O 0.000 description 1
- 239000004325 lysozyme Substances 0.000 description 1
- 229960000274 lysozyme Drugs 0.000 description 1
- 235000010335 lysozyme Nutrition 0.000 description 1
- 229920002521 macromolecule Polymers 0.000 description 1
- 230000036210 malignancy Effects 0.000 description 1
- 210000004962 mammalian cell Anatomy 0.000 description 1
- MQXVYODZCMMZEM-ZYUZMQFOSA-N mannomustine Chemical compound ClCCNC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CNCCCl MQXVYODZCMMZEM-ZYUZMQFOSA-N 0.000 description 1
- 229950008612 mannomustine Drugs 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- RQZAXGRLVPAYTJ-GQFGMJRRSA-N megestrol acetate Chemical compound C1=C(C)C2=CC(=O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@@](C(C)=O)(OC(=O)C)[C@@]1(C)CC2 RQZAXGRLVPAYTJ-GQFGMJRRSA-N 0.000 description 1
- 229960004296 megestrol acetate Drugs 0.000 description 1
- 201000001441 melanoma Diseases 0.000 description 1
- 229960001428 mercaptopurine Drugs 0.000 description 1
- 208000037819 metastatic cancer Diseases 0.000 description 1
- 208000011575 metastatic malignant neoplasm Diseases 0.000 description 1
- HPNSFSBZBAHARI-UHFFFAOYSA-N micophenolic acid Natural products OC1=C(CC=C(C)CCC(O)=O)C(OC)=C(C)C2=C1C(=O)OC2 HPNSFSBZBAHARI-UHFFFAOYSA-N 0.000 description 1
- 239000004530 micro-emulsion Substances 0.000 description 1
- 244000005700 microbiome Species 0.000 description 1
- 239000003094 microcapsule Substances 0.000 description 1
- 108010067094 microcystin Proteins 0.000 description 1
- 239000004005 microsphere Substances 0.000 description 1
- 229960005485 mitobronitol Drugs 0.000 description 1
- VFKZTMPDYBFSTM-GUCUJZIJSA-N mitolactol Chemical compound BrC[C@H](O)[C@@H](O)[C@@H](O)[C@H](O)CBr VFKZTMPDYBFSTM-GUCUJZIJSA-N 0.000 description 1
- 229950010913 mitolactol Drugs 0.000 description 1
- 229960000350 mitotane Drugs 0.000 description 1
- 229960001156 mitoxantrone Drugs 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 238000001823 molecular biology technique Methods 0.000 description 1
- 201000006417 multiple sclerosis Diseases 0.000 description 1
- HPNSFSBZBAHARI-RUDMXATFSA-N mycophenolic acid Chemical compound OC1=C(C\C=C(/C)CCC(O)=O)C(OC)=C(C)C2=C1C(=O)OC2 HPNSFSBZBAHARI-RUDMXATFSA-N 0.000 description 1
- 229960000951 mycophenolic acid Drugs 0.000 description 1
- 208000025113 myeloid leukemia Diseases 0.000 description 1
- NJSMWLQOCQIOPE-OCHFTUDZSA-N n-[(e)-[10-[(e)-(4,5-dihydro-1h-imidazol-2-ylhydrazinylidene)methyl]anthracen-9-yl]methylideneamino]-4,5-dihydro-1h-imidazol-2-amine Chemical compound N1CCN=C1N\N=C\C(C1=CC=CC=C11)=C(C=CC=C2)C2=C1\C=N\NC1=NCCN1 NJSMWLQOCQIOPE-OCHFTUDZSA-N 0.000 description 1
- 229940086322 navelbine Drugs 0.000 description 1
- 230000017074 necrotic cell death Effects 0.000 description 1
- QZGIWPZCWHMVQL-UIYAJPBUSA-N neocarzinostatin chromophore Chemical compound O1[C@H](C)[C@H](O)[C@H](O)[C@@H](NC)[C@H]1O[C@@H]1C/2=C/C#C[C@H]3O[C@@]3([C@@H]3OC(=O)OC3)C#CC\2=C[C@H]1OC(=O)C1=C(O)C=CC2=C(C)C=C(OC)C=C12 QZGIWPZCWHMVQL-UIYAJPBUSA-N 0.000 description 1
- GVUGOAYIVIDWIO-UFWWTJHBSA-N nepidermin Chemical compound C([C@@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)NCC(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CS)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O)NC(=O)CNC(=O)[C@@H](NC(=O)[C@@H](NC(=O)[C@H](CS)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CS)NC(=O)[C@H](C)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](C)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@@H](NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CCSC)NC(=O)[C@H](CS)NC(=O)[C@@H](NC(=O)CNC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC=1NC=NC=1)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CS)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)CNC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC=1NC=NC=1)NC(=O)[C@H](CO)NC(=O)[C@H](CC(C)C)NC(=O)[C@H]1N(CCC1)C(=O)[C@H](CS)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CO)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CO)NC(=O)[C@@H](N)CC(N)=O)C(C)C)[C@@H](C)CC)C(C)C)C(C)C)C1=CC=C(O)C=C1 GVUGOAYIVIDWIO-UFWWTJHBSA-N 0.000 description 1
- PCJGZPGTCUMMOT-ISULXFBGSA-N neurotensin Chemical compound C([C@@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CC(C)C)C(O)=O)NC(=O)[C@H]1N(CCC1)C(=O)[C@H](CCCN=C(N)N)NC(=O)[C@H](CCCN=C(N)N)NC(=O)[C@H]1N(CCC1)C(=O)[C@H](CCCCN)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CC(C)C)NC(=O)[C@H]1NC(=O)CC1)C1=CC=C(O)C=C1 PCJGZPGTCUMMOT-ISULXFBGSA-N 0.000 description 1
- 229960002653 nilutamide Drugs 0.000 description 1
- XWXYUMMDTVBTOU-UHFFFAOYSA-N nilutamide Chemical compound O=C1C(C)(C)NC(=O)N1C1=CC=C([N+]([O-])=O)C(C(F)(F)F)=C1 XWXYUMMDTVBTOU-UHFFFAOYSA-N 0.000 description 1
- 229960001420 nimustine Drugs 0.000 description 1
- VFEDRRNHLBGPNN-UHFFFAOYSA-N nimustine Chemical compound CC1=NC=C(CNC(=O)N(CCCl)N=O)C(N)=N1 VFEDRRNHLBGPNN-UHFFFAOYSA-N 0.000 description 1
- 108010065793 nodularin Proteins 0.000 description 1
- 229940085033 nolvadex Drugs 0.000 description 1
- 238000003199 nucleic acid amplification method Methods 0.000 description 1
- 239000002777 nucleoside Substances 0.000 description 1
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical class CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 1
- 239000002674 ointment Substances 0.000 description 1
- CZDBNBLGZNWKMC-MWQNXGTOSA-N olivomycin Chemical compound O([C@@H]1C[C@@H](O[C@H](C)[C@@H]1O)OC=1C=C2C=C3C[C@H]([C@@H](C(=O)C3=C(O)C2=C(O)C=1)O[C@H]1O[C@@H](C)[C@H](O)[C@@H](OC2O[C@@H](C)[C@H](O)[C@@H](O)C2)C1)[C@H](OC)C(=O)[C@@H](O)[C@@H](C)O)[C@H]1C[C@H](O)[C@H](OC)[C@H](C)O1 CZDBNBLGZNWKMC-MWQNXGTOSA-N 0.000 description 1
- 229950005848 olivomycin Drugs 0.000 description 1
- 229950011093 onapristone Drugs 0.000 description 1
- 239000002997 ophthalmic solution Substances 0.000 description 1
- 150000002894 organic compounds Chemical class 0.000 description 1
- 239000011368 organic material Substances 0.000 description 1
- 229960003104 ornithine Drugs 0.000 description 1
- 230000002611 ovarian Effects 0.000 description 1
- 230000036961 partial effect Effects 0.000 description 1
- 239000002245 particle Substances 0.000 description 1
- 239000008188 pellet Substances 0.000 description 1
- 229960002340 pentostatin Drugs 0.000 description 1
- FPVKHBSQESCIEP-JQCXWYLXSA-N pentostatin Chemical compound C1[C@H](O)[C@@H](CO)O[C@H]1N1C(N=CNC[C@H]2O)=C2N=C1 FPVKHBSQESCIEP-JQCXWYLXSA-N 0.000 description 1
- QIMGFXOHTOXMQP-GFAGFCTOSA-N peplomycin Chemical compound N([C@H](C(=O)N[C@H](C)[C@@H](O)[C@H](C)C(=O)N[C@@H]([C@H](O)C)C(=O)NCCC=1SC=C(N=1)C=1SC=C(N=1)C(=O)NCCCN[C@@H](C)C=1C=CC=CC=1)[C@@H](O[C@H]1[C@H]([C@@H](O)[C@H](O)[C@H](CO)O1)O[C@@H]1[C@H]([C@@H](OC(N)=O)[C@H](O)[C@@H](CO)O1)O)C=1NC=NC=1)C(=O)C1=NC([C@H](CC(N)=O)NC[C@H](N)C(N)=O)=NC(N)=C1C QIMGFXOHTOXMQP-GFAGFCTOSA-N 0.000 description 1
- 229950003180 peplomycin Drugs 0.000 description 1
- 201000002628 peritoneum cancer Diseases 0.000 description 1
- 238000002823 phage display Methods 0.000 description 1
- 239000006187 pill Substances 0.000 description 1
- NJBFOOCLYDNZJN-UHFFFAOYSA-N pipobroman Chemical compound BrCCC(=O)N1CCN(C(=O)CCBr)CC1 NJBFOOCLYDNZJN-UHFFFAOYSA-N 0.000 description 1
- 229960000952 pipobroman Drugs 0.000 description 1
- NUKCGLDCWQXYOQ-UHFFFAOYSA-N piposulfan Chemical compound CS(=O)(=O)OCCC(=O)N1CCN(C(=O)CCOS(C)(=O)=O)CC1 NUKCGLDCWQXYOQ-UHFFFAOYSA-N 0.000 description 1
- 229950001100 piposulfan Drugs 0.000 description 1
- 229960001221 pirarubicin Drugs 0.000 description 1
- 229910052697 platinum Inorganic materials 0.000 description 1
- 229920001200 poly(ethylene-vinyl acetate) Polymers 0.000 description 1
- 108010005636 polypeptide C Proteins 0.000 description 1
- 229920001282 polysaccharide Polymers 0.000 description 1
- 239000005017 polysaccharide Substances 0.000 description 1
- 230000003389 potentiating effect Effects 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 229960004694 prednimustine Drugs 0.000 description 1
- 238000002953 preparative HPLC Methods 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- CPTBDICYNRMXFX-UHFFFAOYSA-N procarbazine Chemical compound CNNCC1=CC=C(C(=O)NC(C)C)C=C1 CPTBDICYNRMXFX-UHFFFAOYSA-N 0.000 description 1
- 229960000624 procarbazine Drugs 0.000 description 1
- 238000012545 processing Methods 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 239000000583 progesterone congener Substances 0.000 description 1
- 229940087463 proleukin Drugs 0.000 description 1
- 230000035755 proliferation Effects 0.000 description 1
- 230000002035 prolonged effect Effects 0.000 description 1
- 125000006239 protecting group Chemical group 0.000 description 1
- 238000002731 protein assay Methods 0.000 description 1
- 238000000751 protein extraction Methods 0.000 description 1
- 239000012474 protein marker Substances 0.000 description 1
- 150000003212 purines Chemical class 0.000 description 1
- 150000003230 pyrimidines Chemical class 0.000 description 1
- 230000002285 radioactive effect Effects 0.000 description 1
- 239000000941 radioactive substance Substances 0.000 description 1
- 229960004622 raloxifene Drugs 0.000 description 1
- GZUITABIAKMVPG-UHFFFAOYSA-N raloxifene Chemical compound C1=CC(O)=CC=C1C1=C(C(=O)C=2C=CC(OCCN3CCCCC3)=CC=2)C2=CC=C(O)C=C2S1 GZUITABIAKMVPG-UHFFFAOYSA-N 0.000 description 1
- 229960002185 ranimustine Drugs 0.000 description 1
- 230000008707 rearrangement Effects 0.000 description 1
- 229940044551 receptor antagonist Drugs 0.000 description 1
- 239000002464 receptor antagonist Substances 0.000 description 1
- 206010038038 rectal cancer Diseases 0.000 description 1
- 201000001275 rectum cancer Diseases 0.000 description 1
- 230000002829 reductive effect Effects 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 239000003488 releasing hormone Substances 0.000 description 1
- 230000003362 replicative effect Effects 0.000 description 1
- 229930002330 retinoic acid Natural products 0.000 description 1
- 230000002441 reversible effect Effects 0.000 description 1
- OWPCHSCAPHNHAV-LMONGJCWSA-N rhizoxin Chemical compound C/C([C@H](OC)[C@@H](C)[C@@H]1C[C@H](O)[C@]2(C)O[C@@H]2/C=C/[C@@H](C)[C@]2([H])OC(=O)C[C@@](C2)(C[C@@H]2O[C@H]2C(=O)O1)[H])=C\C=C\C(\C)=C\C1=COC(C)=N1 OWPCHSCAPHNHAV-LMONGJCWSA-N 0.000 description 1
- 229950004892 rodorubicin Drugs 0.000 description 1
- VHXNKPBCCMUMSW-FQEVSTJZSA-N rubitecan Chemical compound C1=CC([N+]([O-])=O)=C2C=C(CN3C4=CC5=C(C3=O)COC(=O)[C@]5(O)CC)C4=NC2=C1 VHXNKPBCCMUMSW-FQEVSTJZSA-N 0.000 description 1
- 229930182947 sarcodictyin Natural products 0.000 description 1
- ZKZBPNGNEQAJSX-UHFFFAOYSA-N selenocysteine Natural products [SeH]CC(N)C(O)=O ZKZBPNGNEQAJSX-UHFFFAOYSA-N 0.000 description 1
- 235000016491 selenocysteine Nutrition 0.000 description 1
- 229940055619 selenocysteine Drugs 0.000 description 1
- 238000012163 sequencing technique Methods 0.000 description 1
- 230000019491 signal transduction Effects 0.000 description 1
- 208000000587 small cell lung carcinoma Diseases 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 230000009870 specific binding Effects 0.000 description 1
- 229950006315 spirogermanium Drugs 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 230000004936 stimulating effect Effects 0.000 description 1
- 229960001052 streptozocin Drugs 0.000 description 1
- ZSJLQEPLLKMAKR-GKHCUFPYSA-N streptozocin Chemical compound O=NN(C)C(=O)N[C@H]1[C@@H](O)O[C@H](CO)[C@@H](O)[C@@H]1O ZSJLQEPLLKMAKR-GKHCUFPYSA-N 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- 235000000346 sugar Nutrition 0.000 description 1
- 150000008163 sugars Chemical class 0.000 description 1
- 239000013589 supplement Substances 0.000 description 1
- 230000000153 supplemental effect Effects 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 208000011580 syndromic disease Diseases 0.000 description 1
- 230000002194 synthesizing effect Effects 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- 229940063683 taxotere Drugs 0.000 description 1
- NRUKOCRGYNPUPR-QBPJDGROSA-N teniposide Chemical compound COC1=C(O)C(OC)=CC([C@@H]2C3=CC=4OCOC=4C=C3[C@@H](O[C@H]3[C@@H]([C@@H](O)[C@@H]4O[C@@H](OC[C@H]4O3)C=3SC=CC=3)O)[C@@H]3[C@@H]2C(OC3)=O)=C1 NRUKOCRGYNPUPR-QBPJDGROSA-N 0.000 description 1
- 229960001278 teniposide Drugs 0.000 description 1
- 229960002180 tetracycline Drugs 0.000 description 1
- 229930101283 tetracycline Natural products 0.000 description 1
- 235000019364 tetracycline Nutrition 0.000 description 1
- 150000003522 tetracyclines Chemical class 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 201000002510 thyroid cancer Diseases 0.000 description 1
- MNRILEROXIRVNJ-UHFFFAOYSA-N tioguanine Chemical compound N1C(N)=NC(=S)C2=NC=N[C]21 MNRILEROXIRVNJ-UHFFFAOYSA-N 0.000 description 1
- 229960003087 tioguanine Drugs 0.000 description 1
- UCFGDBYHRUNTLO-QHCPKHFHSA-N topotecan Chemical compound C1=C(O)C(CN(C)C)=C2C=C(CN3C4=CC5=C(C3=O)COC(=O)[C@]5(O)CC)C4=NC2=C1 UCFGDBYHRUNTLO-QHCPKHFHSA-N 0.000 description 1
- 229960000303 topotecan Drugs 0.000 description 1
- 229960005026 toremifene Drugs 0.000 description 1
- XFCLJVABOIYOMF-QPLCGJKRSA-N toremifene Chemical compound C1=CC(OCCN(C)C)=CC=C1C(\C=1C=CC=CC=1)=C(\CCCl)C1=CC=CC=C1 XFCLJVABOIYOMF-QPLCGJKRSA-N 0.000 description 1
- 239000003440 toxic substance Substances 0.000 description 1
- 230000001131 transforming effect Effects 0.000 description 1
- 238000002054 transplantation Methods 0.000 description 1
- IUCJMVBFZDHPDX-UHFFFAOYSA-N tretamine Chemical compound C1CN1C1=NC(N2CC2)=NC(N2CC2)=N1 IUCJMVBFZDHPDX-UHFFFAOYSA-N 0.000 description 1
- 229950001353 tretamine Drugs 0.000 description 1
- 229960001727 tretinoin Drugs 0.000 description 1
- PXSOHRWMIRDKMP-UHFFFAOYSA-N triaziquone Chemical compound O=C1C(N2CC2)=C(N2CC2)C(=O)C=C1N1CC1 PXSOHRWMIRDKMP-UHFFFAOYSA-N 0.000 description 1
- 229960004560 triaziquone Drugs 0.000 description 1
- KVJXBPDAXMEYOA-CXANFOAXSA-N trilostane Chemical compound OC1=C(C#N)C[C@]2(C)[C@H]3CC[C@](C)([C@H](CC4)O)[C@@H]4[C@@H]3CC[C@@]32O[C@@H]31 KVJXBPDAXMEYOA-CXANFOAXSA-N 0.000 description 1
- 229960001670 trilostane Drugs 0.000 description 1
- GPRLSGONYQIRFK-MNYXATJNSA-N triton Chemical compound [3H+] GPRLSGONYQIRFK-MNYXATJNSA-N 0.000 description 1
- 229960000875 trofosfamide Drugs 0.000 description 1
- UMKFEPPTGMDVMI-UHFFFAOYSA-N trofosfamide Chemical compound ClCCN(CCCl)P1(=O)OCCCN1CCCl UMKFEPPTGMDVMI-UHFFFAOYSA-N 0.000 description 1
- 229950010147 troxacitabine Drugs 0.000 description 1
- RXRGZNYSEHTMHC-BQBZGAKWSA-N troxacitabine Chemical compound O=C1N=C(N)C=CN1[C@H]1O[C@@H](CO)OC1 RXRGZNYSEHTMHC-BQBZGAKWSA-N 0.000 description 1
- 239000012588 trypsin Substances 0.000 description 1
- HDZZVAMISRMYHH-LITAXDCLSA-N tubercidin Chemical compound C1=CC=2C(N)=NC=NC=2N1[C@@H]1O[C@@H](CO)[C@H](O)[C@H]1O HDZZVAMISRMYHH-LITAXDCLSA-N 0.000 description 1
- 230000005747 tumor angiogenesis Effects 0.000 description 1
- 229950009811 ubenimex Drugs 0.000 description 1
- 238000000108 ultra-filtration Methods 0.000 description 1
- 241001430294 unidentified retrovirus Species 0.000 description 1
- 201000005112 urinary bladder cancer Diseases 0.000 description 1
- 102000009816 urokinase plasminogen activator receptor activity proteins Human genes 0.000 description 1
- 108040001269 urokinase plasminogen activator receptor activity proteins Proteins 0.000 description 1
- 206010046766 uterine cancer Diseases 0.000 description 1
- 230000006444 vascular growth Effects 0.000 description 1
- 239000003981 vehicle Substances 0.000 description 1
- 210000003462 vein Anatomy 0.000 description 1
- 229960003048 vinblastine Drugs 0.000 description 1
- JXLYSJRDGCGARV-XQKSVPLYSA-N vincaleukoblastine Chemical compound C([C@@H](C[C@]1(C(=O)OC)C=2C(=CC3=C([C@]45[C@H]([C@@]([C@H](OC(C)=O)[C@]6(CC)C=CCN([C@H]56)CC4)(O)C(=O)OC)N3C)C=2)OC)C[C@@](C2)(O)CC)N2CCC2=C1NC1=CC=CC=C21 JXLYSJRDGCGARV-XQKSVPLYSA-N 0.000 description 1
- 229960004528 vincristine Drugs 0.000 description 1
- OGWKCGZFUXNPDA-XQKSVPLYSA-N vincristine Chemical compound C([N@]1C[C@@H](C[C@]2(C(=O)OC)C=3C(=CC4=C([C@]56[C@H]([C@@]([C@H](OC(C)=O)[C@]7(CC)C=CCN([C@H]67)CC5)(O)C(=O)OC)N4C=O)C=3)OC)C[C@@](C1)(O)CC)CC1=C2NC2=CC=CC=C12 OGWKCGZFUXNPDA-XQKSVPLYSA-N 0.000 description 1
- OGWKCGZFUXNPDA-UHFFFAOYSA-N vincristine Natural products C1C(CC)(O)CC(CC2(C(=O)OC)C=3C(=CC4=C(C56C(C(C(OC(C)=O)C7(CC)C=CCN(C67)CC5)(O)C(=O)OC)N4C=O)C=3)OC)CN1CCC1=C2NC2=CC=CC=C12 OGWKCGZFUXNPDA-UHFFFAOYSA-N 0.000 description 1
- UGGWPQSBPIFKDZ-KOTLKJBCSA-N vindesine Chemical compound C([C@@H](C[C@]1(C(=O)OC)C=2C(=CC3=C([C@]45[C@H]([C@@]([C@H](O)[C@]6(CC)C=CCN([C@H]56)CC4)(O)C(N)=O)N3C)C=2)OC)C[C@@](C2)(O)CC)N2CCC2=C1N=C1[C]2C=CC=C1 UGGWPQSBPIFKDZ-KOTLKJBCSA-N 0.000 description 1
- 229960004355 vindesine Drugs 0.000 description 1
- GBABOYUKABKIAF-IELIFDKJSA-N vinorelbine Chemical compound C1N(CC=2C3=CC=CC=C3NC=22)CC(CC)=C[C@H]1C[C@]2(C(=O)OC)C1=CC([C@]23[C@H]([C@@]([C@H](OC(C)=O)[C@]4(CC)C=CCN([C@H]34)CC2)(O)C(=O)OC)N2C)=C2C=C1OC GBABOYUKABKIAF-IELIFDKJSA-N 0.000 description 1
- 229960002066 vinorelbine Drugs 0.000 description 1
- CILBMBUYJCWATM-PYGJLNRPSA-N vinorelbine ditartrate Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O.OC(=O)[C@H](O)[C@@H](O)C(O)=O.C1N(CC=2C3=CC=CC=C3NC=22)CC(CC)=C[C@H]1C[C@]2(C(=O)OC)C1=CC([C@]23[C@H]([C@@]([C@H](OC(C)=O)[C@]4(CC)C=CCN([C@H]34)CC2)(O)C(=O)OC)N2C)=C2C=C1OC CILBMBUYJCWATM-PYGJLNRPSA-N 0.000 description 1
- 229940088594 vitamin Drugs 0.000 description 1
- 235000013343 vitamin Nutrition 0.000 description 1
- 239000011782 vitamin Substances 0.000 description 1
- 229930003231 vitamin Natural products 0.000 description 1
- 229960001771 vorozole Drugs 0.000 description 1
- XLMPPFTZALNBFS-INIZCTEOSA-N vorozole Chemical compound C1([C@@H](C2=CC=C3N=NN(C3=C2)C)N2N=CN=C2)=CC=C(Cl)C=C1 XLMPPFTZALNBFS-INIZCTEOSA-N 0.000 description 1
- 201000005102 vulva cancer Diseases 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
- 239000000080 wetting agent Substances 0.000 description 1
- 229950009268 zinostatin Drugs 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
Images
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K17/00—Carrier-bound or immobilised peptides; Preparation thereof
- C07K17/02—Peptides being immobilised on, or in, an organic carrier
- C07K17/08—Peptides being immobilised on, or in, an organic carrier the carrier being a synthetic polymer
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
- A61K47/51—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
- A61K47/56—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic macromolecular compound, e.g. an oligomeric, polymeric or dendrimeric molecule
- A61K47/59—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic macromolecular compound, e.g. an oligomeric, polymeric or dendrimeric molecule obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyureas or polyurethanes
- A61K47/60—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic macromolecular compound, e.g. an oligomeric, polymeric or dendrimeric molecule obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyureas or polyurethanes the organic macromolecular compound being a polyoxyalkylene oligomer, polymer or dendrimer, e.g. PEG, PPG, PEO or polyglycerol
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
- A61K47/51—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
- A61K47/62—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being a protein, peptide or polyamino acid
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
- A61K47/51—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
- A61K47/62—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being a protein, peptide or polyamino acid
- A61K47/64—Drug-peptide, drug-protein or drug-polyamino acid conjugates, i.e. the modifying agent being a peptide, protein or polyamino acid which is covalently bonded or complexed to a therapeutically active agent
- A61K47/6415—Toxins or lectins, e.g. clostridial toxins or Pseudomonas exotoxins
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/195—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from bacteria
- C07K14/33—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from bacteria from Clostridium (G)
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- C07K14/46—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates
- C07K14/47—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates from mammals
- C07K14/4701—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates from mammals not used
- C07K14/4748—Tumour specific antigens; Tumour rejection antigen precursors [TRAP], e.g. MAGE
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- C07K14/705—Receptors; Cell surface antigens; Cell surface determinants
- C07K14/70503—Immunoglobulin superfamily
- C07K14/70532—B7 molecules, e.g. CD80, CD86
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/82—Translation products from oncogenes
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K7/00—Peptides having 5 to 20 amino acids in a fully defined sequence; Derivatives thereof
- C07K7/04—Linear peptides containing only normal peptide links
- C07K7/08—Linear peptides containing only normal peptide links having 12 to 20 amino acids
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2319/00—Fusion polypeptide
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2319/00—Fusion polypeptide
- C07K2319/33—Fusion polypeptide fusions for targeting to specific cell types, e.g. tissue specific targeting, targeting of a bacterial subspecies
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2319/00—Fusion polypeptide
- C07K2319/40—Fusion polypeptide containing a tag for immunodetection, or an epitope for immunisation
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2319/00—Fusion polypeptide
- C07K2319/55—Fusion polypeptide containing a fusion with a toxin, e.g. diphteria toxin
Abstract
Description
(式中、Xは、カルボキシ酸(carboxy acid)、アミドまたはアルコール基および場合によってはリンカーまたはスペーサーから選択されるペプチドのおよび/または毒素のC末端に相当し、ペプチドは、本発明による、例えば細胞−標的に結合可能な7〜20個のアミノ酸を有するペプチドを示す)。それぞれの可能性は、本発明の別個の実施形態に相当する。
実施例1.コンストラクトのライブラリ
分岐状PEG、毒素ペプチドおよび2個の標的−結合ペプチドを含むコンストラクトのライブラリ。各コンストラクトは、8個の連結アームがあり、それぞれが、ペプチドのアミノ部分が連結されるNHS(N−ヒドロキシスクシンイミド)末端を有する分岐状PEGを含む。各足場に、8個のペプチドが連結される:ペプチド毒素の6コピーおよび2つの標的−結合ペプチドのそれぞれの1コピー。
国際公開第2007/010525号パンフレットに記載の技術を使用して、ヒト真核細胞伸長因子2(eEF2)に結合するシクロペプチド(毒素またはシクロトキシンTox1およびTox2と呼ぶ)を作製し、試験した。Tox1(配列番号3からなる)およびTox2(配列番号4からなる)として示される環状ペプチドの配列を表2で提供する。
リガンドとしてeEF2またはBSAを使用するELISAによってeEF2へのTox1およびTox2の結合を試験した。
0.25μgの標的タンパク質、eEF2(ヒト;酵母由来)またはBSA(陰性対照)を、50μL PBS中でmaxisorpプレート(NUNC)のいくつかのウェルに適用し、4℃で一晩インキュベートした。溶液を除去し、各ウェルに280μLのブロッキング溶液(BSA 2mg/mL)を追加した。プレートを25℃で1時間インキュベートした。
Tox1およびTox2の効果を、HeLa Lysate system 1−Step Human Coupled IVT Kit−DNA(ThermoFisher Scientific)を使用してインビトロ転写/翻訳系で試験した。次のペプチド:GW(Tox1)、DRB RB、TB2(Tox2)およびBWを試験した。さらに、非eEF2−結合対照ペプチド、GRも試験した。
2つの異なる癌−標的化部分および2つの異なる毒素部分が共有結合された分岐状PEG分子のコンストラクトを設計し、合成した(足場の略図を図1で示す)。この実施例のコンストラクトに含まれる標的化部分は、環状ペプチドE13.3(配列番号1からなる)およびPD−L1−GR(配列番号2からなる)であり、毒素部分は環状ペプチドTox1(配列番号からなる3)およびTox2(配列番号4からなる)であった。
2.4μmoleの標的化ペプチドまたは7.3μmoleの毒素ペプチドをDMSO中に溶解した。
分岐状PEG−ペプチド溶液:PEG−E13.3、PEG−PD−L1−GR、PEG−Tox1およびPEG−Tox2を1:1:1:3:3のPEG−NHS:PEG−E13.3:PEG−PD−L1−GR:PEG−Tox1:PEG−Tox2の化学量論的モル比で20mM PEG−NHS溶液と一緒に混合し、Rotamix上、30rpmで室温にて2時間インキュベートし、続いて5%の最終濃度まで80%ヒドラジンをゆっくりと添加した。E13.3部分からdde保護基を除去するためにヒドラジンを使用した。混合物をRotamix上、30rpmで、室温にて2時間インキュベートした。得られたコンストラクトは、56個の標的化/毒素部分:E13.3ペプチドの7コピー、PD−L1−GRペプチドの7コピー、Tox1の21コピーおよびTox2の21コピーとカップリングされた多分岐状PEGである。反応終了時に、穏やかに混合しながらPBSを添加した。
Vivaspin 20濃縮器(30K MWCO PES)を使用して20mL PBSを2回添加して試料を限外ろ過し、PEG−E13.3−(PD−L1−GR)−Tox1−Tox2として表示される、搭載される多アーム型PEGの濃度を〜206μMにし、緩衝液をPBSに置換した。
配列番号1(CHPGDKQEDPNCLQADK)を有するE13.3標的化ペプチドに結合される多アーム型PEG足場配列およびBIMBH3(BIMとも呼ばれ、配列 配列番号5 MRPEIWIAQELRRIGDEFNAを有する)またはTox1およびTox2の組み合わせから選択される毒素を含むコンストラクトを作製した。足場を実施例5に記載のように調製し、したがってPEG−E13.3−Tox1−Tox2およびPEG−13.3−BIMとして表示する。
A431細胞(各細胞上で約100,000コピーのEGFRを発現するヒト扁平上皮癌)およびMCF−7細胞(各細胞上でEGFR約3,000コピーを発現する乳癌細胞)を凍結融解し、培養して、指数関数的増殖培養に到達させた。細胞を収集し、計数し、96ウェル組織培養プレート中でそれぞれ細胞7,000個/ウェルおよび細胞5,000個/ウェルの密度で播種した。
Alamar Blue生存能アッセイを使用してA549細胞の細胞生存能を試験した。播種後翌日に、増殖培地を、2%FBSおよび様々なコンストラクトの濃度の(1、3および8μM)の試験品またはビヒクル対照(PBS;濃度−0)を含有した200μLのアッセイ培地に置き換えた。プレートを37±1℃、加湿5±0.5%CO2/空気でインキュベートした。インキュベーションの48時間後に、細胞処理の画像を顕微鏡下で撮影した(図4〜7参照)。
実施例5および6と同様の条件において、PEG−PD−L1−GR−BIM、PEG−E13.3−BIMおよびPEG−E13.3−PD−L1−GR−BIMコンストラクトを調製し、コンストラクト濃度を10nMから1μMに変化させて、A431細胞およびAlamar Blue Blue生存能アッセイを用いて細胞毒性について試験した。インキュベーションの48時間後に、細胞処理の画像を顕微鏡下で撮影した。
材料および方法
実施例5に記載のように試験品PEG−E13.3−(PD−L1−GR)−Tox1−Tox2およびPEG−E13.3−(PD−L1−GR)−BIMを調製し、10μMの濃度で使用した。リン酸緩衝食塩水(PBS)を対照として使用する。
播種後翌日に、アッセイ培地(2%fFBS)中で調製した試験品溶液に増殖培地を置き換えた。試験品溶液を200μL/ウェルの体積で慎重に適用して(細胞上に直接ではなく、ウェルの側面に)、最終濃度が次のようになるようにした:PEG−E13.3−(PD−L1−GR)−Tox1−Tox2:3または10μMおよびPEG−E13.3−(PD−L1−GR)−BIM−10μM。
図9から明らかに分かり得るように、PEG−E13.3−(PD−L1−GR)−Tox1−Tox2は、3および10μMの両濃度でA549細胞の死滅において効果的であった。興味深いことに、3μMの濃度でのPEG−E13.3−(PD−L1−GR)−Tox1−Tox2は、周知のBIM毒素を含む10μM PEG−E13.3−(PD−L1−GR)−BIMコンストラクトよりもかなり効率的であった。
実施例5に記載のようにPEG−E13.3−(PD−L1−GR)−Tox1−Tox2を調製し、表3に記載のレジメント(regiment)に従い、4mL/kg用量を使用して3匹の雌Hsd:ICR(CD−1(登録商標))マウス、7週齢に静脈内注射した。
材料および方法
動物:3群(1群の対照および2群の試験品群)に分けた18匹の6〜7週齢胸腺欠損ヌード雌マウスを少なくとも5日間にわたり累積させた(accumulate)。累積(accumulation)後、各マウスの右フラン(flan)領域にA431腫瘍細胞を皮下注射し、その注射日を第0日とする。
スクリーニング
国際公開第2007/010525号明細書に記載の技術を使用して、ヒト上皮増殖因子受容体(EGFR)に結合する一連の新しいペプチド(シクロペプチド)を作製し、使用した。いくつかの可能性のあるペプチドの同定後、数回のさらなる最適化サイクルを行った。E13.3と表示され、CHPGDKQEDPNCLQADK(配列番号1)の配列を有する、ペプチドの1つは、その結合部位での受容体への高い親和性を示した。
同定したペプチドE7.1、E10.2、E10.3、E13.3、E15.1.3−T、E14.1.1、E14.1.4、E23I3、E23I5およびA4.3.12−Tの発現のためのプラスミドを含む細菌を、アンピシリン入りの5mLの2YT培地中で適切なペプチドのプラスミドを含む2.5μLの細胞で開始し、350rpmで一晩、38℃にて増殖させた。2mLの各開始物を50mLの2YT中、37℃で増殖させ;発現をOD1.5〜2.5で3時間にわたりIPTG、0.43mMにより誘導し、その後、細胞を遠心分離し、−20℃で維持した。
ヒト類表皮癌細胞株A431におけるヒトEGFRのリン酸化レベルに対するいくつかのペプチドの効果を、ELISA試験によって評価した。簡潔に述べると、指数関数に増殖するA431細胞培養物を0.25%トリプシン/EDTA溶液を用いてフラスコから剥離させ、200μLの細胞懸濁液を細胞2x105個/mLの濃度で96ウェルプレートに移し、約3日間増殖させた。培地交換後、50μLのEGF希釈液およびEGF+ペプチド(それぞれ50ng/mLおよび0.2mg/mL)を添加した。プレートを37℃で7.5分間インキュベートした。EGF含有培地を除去し、細胞を150μLの固定液により固定し、室温で20分間インキュベートした後、プレートをtriton洗浄溶液で2回洗浄した。リン酸化レベルを、一次抗体としてホスホ−EGFR(Tyr1045)抗体および二次抗体として抗ウサギIgGとインキュベートすることにより評価した。様々なペプチドのEGFR自己リン酸化阻害能を、図2で与える。(EGFR自己リン酸化の正規化した阻害パーセントを図11および表4で与える。正規化した阻害パーセントは、試験品の蛍光シグナルを、同じEGF濃度で、試験品を含有しない対照の蛍光シグナルで除したものとして計算する。
ウシ血清中での選択されたペプチドの安定性を、ウシ血清との本ペプチドのインキュベーション後の本ペプチドの阻害活性の測定によって評価した。阻害活性を実施例12に記載のように測定した。本ペプチドの阻害活性を、37℃で様々な時間にわたるウシ血清との本ペプチドのインキュベーション後に評価した。試料中のEGF濃度は50ng/mLであった。結果を図12で与える。全てのペプチドがウシ血清中で同様の安定性を有し、t0.5が約1.5時間であったことが明らかに分かり得る。
様々な濃度の選択ペプチドの有効性を、実施例12と同様にELISAによって評価した。結果を図13で与える。全ペプチドのIC50は約0.5〜1μMであった。
9.8mgのE13.3(fmoc)Lysを水中で20mg/mLの最終濃度に溶解した。11.3mgの8本アーム型PEGスクシンイミジルカルボキシメチルエステル、MW73,000(JENKEM TECHNOLOGY USA INC)を565μLのジオキサンとともに37℃で加熱して、完全に溶解させた。E13.3およびPEG溶液を50μLのTEAの存在下で混合し、室温で一晩インキュベートした。得られた溶液に、50μLピペリジンを添加し、室温で0.5インキュベートした。この溶液に、1mLの酢酸エチルを添加して懸濁液を得て、次に(than)これを遠心分離し、上相を除去した。酢酸エチルでの洗浄のこれらの段階を4〜5回反復した。最後に、上相を完全に除去し、残留ペレットを200μL PBS中で溶解させた。酢酸エチルの痕跡を全て除くために、Vivaspin20mL濃縮器を使用して、緩衝液をPBSにさらに交換した。
蛍光で印を付したペプチドE13.3単独または8本アーム型PEGに結合されたものの安定性を、マウスの尾静脈に本化合物を注射することによりインビボで評価した。動物の血液を、様々な時間間隔でペプチド(蛍光)の存在について分析した。図14で示される結果から、遊離ペプチドのt0.5が、PEG結合ペプチド(t0.5約3.5時間)よりも大幅に短い(約数分)ことが明らかに分かり得る。
E13.3の抗癌活性を、いくつかの癌細胞株(A549−ヒト肺癌細胞株およびFaDu−ヒト咽頭癌細胞株)を使用して評価した。細胞培養物を、E13.3の(様々な濃度での)存在下または非存在下でインキュベートし、alamarBlue試薬を使用して生存能について試験した。結果を図15で与える。PEGに結合されたE13.3が試験した全濃度において癌細胞の生存能を首尾よく低下させ得ることが分かり得る。
E13.3−PEGをフルオレセインで標識し、皮下NCI−H1650腫瘍(肺癌)を有する異種移植マウスにIV注射した。麻酔後、腎臓、肝臓および腫瘍を特定の時間点で収集し、蛍光を測定した。結果を図16および17で与える。
スクリーニング
国際公開第2007/010525号パンフレットに記載の技術を使用して、ヒトPD−L1に対する結合に結合する一連の新しいペプチド(シクロペプチド)を作製し、試験した。いくつかの候補ペプチドの同定後に、さらに数回の最適化のサイクルを行った。PD−L1−GRとして表されCysGluGlyLeuProAlaAspTrpAlaAlaAlaCys(配列番号2)の配列を有するペプチドの1つは、その結合部位で受容体に対する高い親和性を示した。
(i)PD−L1−GR環状ペプチドおよびBIM−BH3(PEG−(PD−L1−GR)−BIMとして示される)、(ii)E13.3標的化ペプチド(配列番号1)およびBIM−BH3毒素(PEG−E13.3−BIMとして示される)および(iii)E13.3、PD−L1−GRおよびBIM−BH3毒素(PEG−E13.3−(PD−L1−GR)−BIMとして示される)を含む多アーム型PEGコンストラクトを実施例5に記載のように調製した。
Claims (72)
- 少なくとも2つの異なる細胞外腫瘍抗原に結合する少なくとも2つの異なるペプチドと、少なくとも1つの毒素とを含むコンストラクトであって、前記ペプチドおよび前記毒素が直接共有結合されるかまたは担体を通じて共有結合される、コンストラクト。
- 前記ペプチドの少なくとも1つが、ヒト上皮増殖因子受容体(EGFR)およびヒトプログラム死リガンド1(PD−L1)から選択される細胞外腫瘍抗原に特異的に結合する、請求項1に記載のコンストラクト。
- 前記少なくとも2つのペプチドの別の1つが、EGFR、PD−L1、HER2、アンドロゲン受容体、ベンゾジアゼピン受容体、カドヘリン、CXCR4、CTLA−4、CD2、CD19、エンドセリン受容体、ERBB4、FGFR、葉酸受容体、HER4、HGFR、ムチン1、OGFR、PD−1、PD−L2、PDGFR、およびVEGFRからなる群から選択される細胞外腫瘍抗原に特異的に結合する、請求項2に記載のコンストラクト。
- 前記ペプチドのそれぞれが、5〜30個または10〜25個のアミノ酸残基からなる、請求項1〜3の何れか1項に記載のコンストラクト。
- 前記コンストラクトが、3〜10個の異なるペプチドを含む、請求項1〜4の何れか1項に記載のコンストラクト。
- 前記ペプチドの少なくとも1つが、EGFRに特異的に結合する、請求項1〜5の何れか1項に記載のコンストラクト。
- 前記ペプチドが、配列番号1で示されるアミノ酸配列またはその類似体を含む、請求項6に記載のコンストラクト。
- 前記類似体が、配列番号1に対して少なくとも70%の同一性を有する、請求項7に記載のコンストラクト。
- 前記ペプチドの少なくとも1つが、PD−L1に特異的に結合する、請求項1〜5の何れか1項に記載のコンストラクト。
- 前記ペプチドが、配列番号2で示されるアミノ酸配列またはその類似体を含む、請求項9に記載のコンストラクト。
- 前記類似体が、配列番号2に対して少なくとも70%の同一性を有する、請求項10に記載のコンストラクト。
- 前記ペプチドの1つが、EGFRに特異的に結合しかつ前記ペプチドの1つが、PD−L1に特異的に結合する、請求項1〜5の何れか1項に記載のコンストラクト。
- EGFRに特異的に結合するペプチドが、配列番号1を有するペプチドまたはその類似体であり、かつPD−L1に特異的に結合するペプチドが、配列番号2を有するペプチドまたはその類似体である、請求項12に記載のコンストラクト。
- 前記コンストラクトが、前記ペプチドの少なくとも1つの複数コピーを含む、請求項1〜13の何れか1項に記載のコンストラクト。
- 前記コンストラクトが、前記ペプチドの少なくとも1つの2〜50コピーを含む、請求項14に記載のコンストラクト。
- 前記毒素が、ペプチド、ポリペプチドまたはタンパク質毒素である、請求項1〜15の何れか1項に記載のコンストラクト。
- 前記毒素が、真核細胞伸長因子2に特異的に結合する毒素、配列番号5のBIM−BH3、ジフテリア毒素、緑膿菌外毒素、炭疽毒素、ボツリヌス毒素、リシン、PAP、サポリン、ゲロニン、モモルジン、ProTx−I ProTx−II、コヌス・カリフォルニクス(Conus californicus)毒素、ヘビ毒毒素、およびシアノトキシンからなる群から選択される、請求項16に記載のコンストラクト。
- 真核細胞伸長因子2に結合する毒素が、配列番号3、4またはその類似体から選択されるアミノ酸配列を含む毒素である、請求項17に記載のコンストラクト。
- 前記毒素が、配列番号3、4および5から選択されるアミノ酸配列を含む、請求項17または18に記載のコンストラクト。
- 前記コンストラクトが、2〜10個の異なる毒素を含む、請求項16〜19の何れか1項に記載のコンストラクト。
- 前記コンストラクトが、配列番号3を有する毒素および配列番号4を有する毒素を含む、請求項20に記載のコンストラクト。
- 前記コンストラクトが、前記毒素の少なくとも1つの複数コピーを含む、請求項16〜21の何れか1項に記載のコンストラクト。
- 前記コンストラクトが、前記毒素の少なくとも1つの2〜50コピーを含む、請求項22に記載のコンストラクト。
- 前記コンストラクトが、配列番号3を有する毒素の2〜50コピーおよび配列番号4を有する毒素の2〜50コピーを含む、請求項23に記載のコンストラクト。
- 前記ペプチドの1つが、EGFRに特異的に結合しかつ前記ペプチドの1つが、PD−L1に特異的に結合しかつ前記毒素が、真核細胞伸長因子2に結合する毒素および配列番号5を有する毒素から選択される、請求項1に記載のコンストラクト。
- 配列番号1を有するペプチドまたはその類似体、配列番号2を有するペプチドまたはその類似体、および配列番号3、4および5から選択されるアミノ酸配列を有する少なくとも1つの毒素を含む、請求項25に記載のコンストラクト。
- 配列番号1を含むペプチドまたはその類似体、配列番号2を含むペプチドまたはその類似体、配列番号3を含む毒素、および配列番号4を含む毒素を含む、請求項26に記載のコンストラクト。
- 前記ペプチドのそれぞれ1つおよび前記毒素の複数コピーを含む、請求項25〜27の何れか1項に記載のコンストラクト。
- 前記ペプチドの少なくとも1つおよび/または少なくとも1つの毒素が、担体を通じて共有結合され、前記担体が、有機足場である、請求項1〜28の何れか1項に記載のコンストラクト。
- 前記ペプチドのそれぞれ1つおよび前記毒素が、担体に結合されかつ前記担体が、有機足場である、請求項1〜29の何れか1項に記載のコンストラクト。
- 前記有機足場が、ポリエチレングリコール(PEG)分子または修飾PEG分子を含む、請求項29または30に記載のコンストラクト。
- 前記PEG分子が、前記ペプチドおよび前記毒素を結合するために利用可能な8〜56個の部位を含む、請求項31に記載のコンストラクト。
- 前記ペプチドのそれぞれ1つの複数コピーおよび少なくとも1つの毒素の複数コピーが、前記担体に結合されかつ前記ペプチドの少なくとも1つが、EGFRまたはPD−L1に特異的に結合する、請求項29〜32の何れか1項に記載のコンストラクト。
- 前記ペプチドの1つが、EGFRに特異的に結合しかつ前記ペプチドの1つが、PD−L1に特異的に結合する、請求項33に記載のコンストラクト。
- EGFRに特異的に結合するペプチドが、配列番号1を有するペプチドまたはその類似体であり、かつPD−L1に特異的に結合するペプチドが、配列番号2を有するペプチドまたはその類似体である、請求項34に記載のコンストラクト。
- 前記毒素が、配列番号3、4および5から選択されるアミノ酸配列、またはその類似体を含む、請求項34または35に記載のコンストラクト。
- 前記コンストラクトが、(i)配列番号1を有するペプチド、(ii)配列番号2を有するペプチド、(iii)配列番号3を有する毒素および(iv)配列番号4を有する毒素:の複数コピーを含み、前記ペプチドのそれぞれ1つおよび前記毒素が、前記足場に結合される、請求項33に記載のコンストラクト。
- 前記コンストラクトが、(i)配列番号1からなるペプチド(ii)配列番号2からなるペプチドおよび(iii)配列番号3からなる毒素、および(iv)配列番号4からなる毒素:の複数コピーを含み、前記ペプチドのそれぞれ1つおよび前記毒素が、前記足場に結合される、請求項33に記載のコンストラクト。
- 配列番号1を有するかまたはそれからなるペプチド、配列番号2を有するかまたはそれからなるペプチド、配列番号3を有するかまたはそれからなる毒素および配列番号4を有するかまたはそれからなる毒素の間の化学量論的分子比が、1:1:3:3である、請求項37または38に記載のコンストラクト。
- 前記ペプチドまたは前記毒素の少なくとも1つが、リンカーまたはスペーサーを通じて前記足場に連結される、請求項1〜39の何れか1項に記載のコンストラクト。
- 透過性促進部分をさらに含む、請求項1〜40の何れか1項に記載のコンストラクト。
- 請求項1〜41の何れか1項に記載のコンストラクトと、薬学的に許容可能な賦形剤とを含む医薬組成物。
- 癌を処置することにおける使用のための、請求項42に記載の医薬組成物。
- 請求項42に記載の医薬組成物を対象に投与することを含むそれを必要とする前記対象において癌を処置する方法。
- 前記医薬組成物が、少なくとも1つの抗癌剤と組み合わせて処置計画の一部として投与される、請求項44に記載の方法。
- ヒト真核細胞伸長因子2(eEF2)に特異的に結合するペプチドであって、配列番号3、配列番号4またはその類似体から選択されるアミノ酸配列を含む、ペプチド。
- 前記類似体が、前記ペプチドに対して少なくとも70%、少なくとも80%、または少なくとも90%の配列同一性を有する、請求項46に記載のペプチド。
- 前記ペプチドまたはその類似体が、環状である、請求項46または47に記載のペプチド。
- eEF2活性を増強する、請求項46〜48の何れか1項に記載のペプチド。
- 細胞死を誘導することにおける使用のための、請求項46〜49の何れか1項に記載のペプチド。
- 前記細胞が、癌細胞である、請求項50に記載のペプチド。
- 配列番号3および配列番号4から選択されるアミノ酸配列からなる、請求項46〜50の何れか1項に記載のペプチド。
- 配列番号1で示されるアミノ酸配列またはその類似体を含むペプチド。
- ヒト上皮増殖因子受容体(EGFR)のアンタゴニストである、請求項53に記載のペプチド。
- 前記類似体が、配列番号1に対して少なくとも70%、少なくとも80%、または少なくとも90%の配列同一性を有する、請求項53または54に記載のペプチド。
- 前記ペプチドまたはその類似体が、環状である、請求項53〜55の何れか1項に記載のペプチド。
- 配列番号1で示されるアミノ酸配列からなる、請求項53〜56の何れか1項に記載のペプチド。
- 配列番号2で示されるアミノ酸配列を含むペプチドまたはその類似体。
- 前記ペプチドまたはその類似体が、ヒトプログラム死リガンド1(PD−L1)のアンタゴニストである、請求項58に記載のペプチド。
- 前記類似体が、配列番号2に対して少なくとも70%、少なくとも80%、または少なくとも90%の配列同一性を有する、請求項58または59に記載のペプチド。
- 前記ペプチドが、環状である、請求項58〜60の何れか1項に記載のペプチド。
- 前記ペプチドが、配列番号2で示されるアミノ酸配列からなる、請求項58〜61の何れか1項に記載のペプチド。
- 癌細胞への標的化における使用のための、請求項58〜62の何れか1項に記載のペプチド。
- 請求項46〜63の何れか1項に記載の少なくとも1つのペプチドを含む抱合体。
- 請求項46〜63の何れか1項に記載のペプチドまたは請求項64に記載の抱合体と、薬学的に許容可能な担体とを含む医薬組成物。
- 複数の前記ペプチドまたは前記抱合体を含む、請求項65に記載の医薬組成物。
- 癌を処置することにおける使用のための、請求項65または66に記載の医薬組成物。
- 請求項46〜63の何れか1項に記載のペプチドまたは請求項64に記載の抱合体の治療的有効量を投与することを含むそれを必要とする対象において癌を処置する方法。
- 請求項46〜63の何れか1項に記載のペプチドまたはその類似体をコードする配列を含む単離ポリヌクレオチド。
- (i)配列番号1の少なくとも1コピー;(ii)配列番号2の少なくとも1コピー;(iii)配列番号3の少なくとも1コピー、および/または配列番号4の少なくとも1コピーを含むポリペプチドをコードする配列を含む単離ポリヌクレオチド。
- プロモーターに操作可能に連結される、請求項69または70に記載のポリヌクレオチドを含む、核酸コンストラクト。
- 請求項70に記載の少なくとも1つのポリヌクレオチドを含むベクター。
Applications Claiming Priority (5)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US201662401192P | 2016-09-29 | 2016-09-29 | |
US201662401195P | 2016-09-29 | 2016-09-29 | |
US62/401,192 | 2016-09-29 | ||
US62/401,195 | 2016-09-29 | ||
PCT/IL2017/051094 WO2018061004A1 (en) | 2016-09-29 | 2017-09-27 | Therapeutic multi-targeting constructs and uses thereof |
Publications (3)
Publication Number | Publication Date |
---|---|
JP2020501513A true JP2020501513A (ja) | 2020-01-23 |
JP2020501513A5 JP2020501513A5 (ja) | 2020-11-12 |
JP7133225B2 JP7133225B2 (ja) | 2022-09-08 |
Family
ID=61763358
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2019517069A Active JP7133225B2 (ja) | 2016-09-29 | 2017-09-27 | 治療用多標的コンストラクトおよびその使用 |
Country Status (8)
Country | Link |
---|---|
US (2) | US11739163B2 (ja) |
EP (1) | EP3518953A4 (ja) |
JP (1) | JP7133225B2 (ja) |
CN (1) | CN109789183A (ja) |
AU (2) | AU2017333442A1 (ja) |
CA (1) | CA3037261A1 (ja) |
IL (1) | IL265236B2 (ja) |
WO (1) | WO2018061004A1 (ja) |
Families Citing this family (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US20210198319A1 (en) * | 2017-09-27 | 2021-07-01 | Aebi Ltd. | Cytotoxic peptides and conjugates thereof |
KR102268983B1 (ko) | 2019-09-11 | 2021-06-24 | 경북대학교 산학협력단 | 엔도테린 수용체 억제제에 의한 엑소좀 분비 억제 또는 pd-l1 발현 억제 용도 |
CN112252362A (zh) * | 2020-10-10 | 2021-01-22 | 无锡市市政设施建设工程有限公司 | 基于bim实现地铁车站主体结构盘扣支架搭设的方法 |
Citations (9)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2007524598A (ja) * | 2003-03-03 | 2007-08-30 | ダイアックス、コープ | HGFレセプター(cMet)を特異的に結合するペプチドおよびその使用 |
JP2009518025A (ja) * | 2005-12-06 | 2009-05-07 | ドマンティス リミテッド | 細胞表面標的に対して結合特異性を有する二重特異性リガンドおよびその使用方法 |
US20100151003A1 (en) * | 2006-12-21 | 2010-06-17 | Mohit Trikha | Egfr binding peptides and uses thereof |
JP2010154842A (ja) * | 2008-12-03 | 2010-07-15 | Koji Kawakami | Egfrを標的にした新規抗がんキメラペプチド |
JP2011517314A (ja) * | 2008-02-14 | 2011-06-02 | ブリストル−マイヤーズ スクイブ カンパニー | Egfrに結合する操作されたタンパク質に基づく標的化された治療薬 |
JP2015509501A (ja) * | 2012-02-23 | 2015-03-30 | プレジデント・アンド・フェロウズ・オブ・ハーバード・カレッジ | 剤を細胞へ送達するための改変型微生物毒素受容体 |
WO2015195721A1 (en) * | 2014-06-16 | 2015-12-23 | Purdue Research Foundation | Compositions and methods for treating cancer |
JP2016512508A (ja) * | 2013-03-12 | 2016-04-28 | バイオコン・リミテッド | 融合免疫調節タンパク質及びその生産方法 |
JP2016526892A (ja) * | 2013-07-18 | 2016-09-08 | ユートロピクス ファーマシューティカルズ, インコーポレイテッド | 示差的bh3ミトコンドリアプロファイリング |
Family Cites Families (17)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US20040058865A1 (en) | 2001-11-26 | 2004-03-25 | Danishefsky Samuel J | Homing peptide multimers, their preparation and uses |
WO2005090393A2 (en) | 2004-02-09 | 2005-09-29 | The Government Of The United States, As Represented By The Secretary Of Health And Human Services | Multimeric protein toxins to target cells having multiple identifying characteristics |
EP1915617B1 (en) | 2005-07-21 | 2011-09-14 | Aebi Ltd. | Methods and compositions for identifying a peptide having an intermolecular interaction with a target of interest |
ES2544954T3 (es) | 2006-02-14 | 2015-09-07 | Universita' Degli Studi Di Siena | Péptidos multiméricos ramificados para diagnóstico y terapia de tumores |
US20080131428A1 (en) * | 2006-02-24 | 2008-06-05 | Arius Research, Inc. | Cytotoxicity mediation of cells evidencing surface expression of TROP-2 |
US7803769B2 (en) | 2006-10-25 | 2010-09-28 | Amgen Inc. | OSK1 peptide analogs and pharmaceutical compositions |
CN101842116A (zh) | 2007-08-28 | 2010-09-22 | 比奥根艾迪克Ma公司 | 结合igf-1r多个表位的组合物 |
JP2012507581A (ja) | 2008-11-06 | 2012-03-29 | ユニヴァーシティ オブ ワシントン | 二重特異性細胞内送達媒体 |
WO2010083495A2 (en) | 2009-01-18 | 2010-07-22 | The Board Of Trustees Of The Leland Stanford Junior University | Polypeptides targeting vascular endothelial growth factor receptor-2 and alpha v beta 3 integrin |
WO2011047135A2 (en) | 2009-10-14 | 2011-04-21 | The Regents Of The University Of Colorado, A Body Corporate | Compositions and methods for treating bladder cancer |
CN103025345B (zh) | 2010-03-19 | 2016-01-20 | 巴克斯特国际公司 | Tfpi抑制剂及使用方法 |
CA2837169C (en) * | 2011-05-24 | 2021-11-09 | Zyngenia, Inc. | Multispecific complexes comprising angiopoietin-2-binding peptide and their uses |
DK3489254T3 (da) | 2012-04-30 | 2022-11-07 | Biocon Ltd | Målrettede/immunmodulatoriske fusionsproteiner og fremgangsmåder til fremstilling deraf |
JP6103832B2 (ja) | 2012-06-25 | 2017-03-29 | Hoya株式会社 | Egfr結合性ペプチド |
US10786497B2 (en) | 2013-08-16 | 2020-09-29 | Equip, Llc | Discrete PEG constructs |
US20210198319A1 (en) | 2017-09-27 | 2021-07-01 | Aebi Ltd. | Cytotoxic peptides and conjugates thereof |
US20200339629A1 (en) | 2019-04-24 | 2020-10-29 | Aebi Ltd. | Therapeutic constructs comprising cmet binding peptides |
-
2017
- 2017-09-27 CN CN201780060289.8A patent/CN109789183A/zh active Pending
- 2017-09-27 EP EP17855166.9A patent/EP3518953A4/en active Pending
- 2017-09-27 WO PCT/IL2017/051094 patent/WO2018061004A1/en unknown
- 2017-09-27 AU AU2017333442A patent/AU2017333442A1/en not_active Abandoned
- 2017-09-27 IL IL265236A patent/IL265236B2/en unknown
- 2017-09-27 US US16/337,163 patent/US11739163B2/en active Active
- 2017-09-27 CA CA3037261A patent/CA3037261A1/en active Pending
- 2017-09-27 JP JP2019517069A patent/JP7133225B2/ja active Active
-
2022
- 2022-08-24 AU AU2022221434A patent/AU2022221434A1/en active Pending
-
2023
- 2023-07-06 US US18/348,229 patent/US20240002547A1/en active Pending
Patent Citations (9)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2007524598A (ja) * | 2003-03-03 | 2007-08-30 | ダイアックス、コープ | HGFレセプター(cMet)を特異的に結合するペプチドおよびその使用 |
JP2009518025A (ja) * | 2005-12-06 | 2009-05-07 | ドマンティス リミテッド | 細胞表面標的に対して結合特異性を有する二重特異性リガンドおよびその使用方法 |
US20100151003A1 (en) * | 2006-12-21 | 2010-06-17 | Mohit Trikha | Egfr binding peptides and uses thereof |
JP2011517314A (ja) * | 2008-02-14 | 2011-06-02 | ブリストル−マイヤーズ スクイブ カンパニー | Egfrに結合する操作されたタンパク質に基づく標的化された治療薬 |
JP2010154842A (ja) * | 2008-12-03 | 2010-07-15 | Koji Kawakami | Egfrを標的にした新規抗がんキメラペプチド |
JP2015509501A (ja) * | 2012-02-23 | 2015-03-30 | プレジデント・アンド・フェロウズ・オブ・ハーバード・カレッジ | 剤を細胞へ送達するための改変型微生物毒素受容体 |
JP2016512508A (ja) * | 2013-03-12 | 2016-04-28 | バイオコン・リミテッド | 融合免疫調節タンパク質及びその生産方法 |
JP2016526892A (ja) * | 2013-07-18 | 2016-09-08 | ユートロピクス ファーマシューティカルズ, インコーポレイテッド | 示差的bh3ミトコンドリアプロファイリング |
WO2015195721A1 (en) * | 2014-06-16 | 2015-12-23 | Purdue Research Foundation | Compositions and methods for treating cancer |
Non-Patent Citations (5)
Title |
---|
ANGEW. CHEM. INT. ED., 2015, VOL.54, PP.11760-11764, JPN6021033329, ISSN: 0004778909 * |
ASIAN J. PHARM. SCI., AVAILABLE ONLINE 2015.09.14, VOL.11, PP.337-348, JPN6021033325, ISSN: 0004778911 * |
CANCER LETT., 2014, VOL.351, PP.13-22, JPN6021033327, ISSN: 0004778910 * |
EUR. J. CANCER, 2011, VOL.47, PP.773-783, JPN6021033330, ISSN: 0004778908 * |
ファルマシア, 2009, VOL.45, NO.9, PP.923-924, JPN6021033324, ISSN: 0004778912 * |
Also Published As
Publication number | Publication date |
---|---|
AU2022221434A1 (en) | 2022-10-06 |
CA3037261A1 (en) | 2018-04-05 |
EP3518953A4 (en) | 2020-10-28 |
IL265236B1 (en) | 2023-07-01 |
AU2017333442A1 (en) | 2019-04-04 |
JP7133225B2 (ja) | 2022-09-08 |
CN109789183A (zh) | 2019-05-21 |
US11739163B2 (en) | 2023-08-29 |
US20240002547A1 (en) | 2024-01-04 |
WO2018061004A1 (en) | 2018-04-05 |
US20190225711A1 (en) | 2019-07-25 |
IL265236B2 (en) | 2023-11-01 |
IL265236A (en) | 2019-05-30 |
EP3518953A1 (en) | 2019-08-07 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
JP6722134B2 (ja) | セリンプロテアーゼ分子および療法 | |
US20240002547A1 (en) | Therapeutic multi-targeting constructs and uses thereof | |
AU2021201085B2 (en) | Peptide compounds and peptide conjugates for the treatment of cancer through receptor-mediated chemotherapy | |
CN103347514B (zh) | Fgfr1胞外域组合疗法 | |
JP2015533838A (ja) | rTRAIL突然変異体およびそのモノメチルアウリスタチンEコンジュゲート | |
KR20160064726A (ko) | 세포 투과 펩타이드-항암제 접합체 및 이를 포함하는 암 치료용 조성물 | |
KR20220015375A (ko) | Sephb4-hsa 융합 단백질을 이용한 암의 치료 | |
JP2024016040A (ja) | 去勢抵抗性前立腺癌 | |
JP2023145635A (ja) | 免疫調節特性を有するペプチド | |
US20210054047A1 (en) | Novel anticancer fusion protein and use thereof | |
JP2021514661A (ja) | サイトカインに連結させたecm親和性ペプチドを用いてがんを処置するための方法および組成物 | |
CN115666645A (zh) | 用于脑瘤治疗的TNFα免疫缀合物疗法 | |
JP2010509241A (ja) | 膜貫通ペプチドからなる自己凝集性ナノ粒子および抗癌剤の特異的腫瘍内送達のためのその利用 | |
US20200339629A1 (en) | Therapeutic constructs comprising cmet binding peptides | |
EP3068797A1 (en) | Epha3 and multi-valent targeting of tumors | |
KR101732380B1 (ko) | 상피성장인자 수용체를 표적으로 하는 신규 항암제 | |
US20210198319A1 (en) | Cytotoxic peptides and conjugates thereof | |
US20220177547A1 (en) | Ferritin nanocage for multi-displaying trail trimer and cancer-targeting peptide and use thereof as anticancer agent | |
WO2013140317A2 (en) | Peptides | |
KR20200107842A (ko) | 트레일 트라이머와 암표적 펩타이드를 멀티디스플레이하는 페리틴 나노케이지 및 이의 항암제로서의 용도 | |
US20220298225A1 (en) | Methods and compositions for treating cancer with collagen binding drug carriers | |
WO2023097111A2 (en) | Methods and compositions for treating calcinosis associated conditions | |
KR20220151333A (ko) | 가시광선에 의해 활성화되는 항암 면역치료용 나노입자 및 이의 용도 | |
KR20220053848A (ko) | Pd-l1 결합 펩타이드 1을 융합한 페리틴 나노케이지 및 이의 항암면역치료제로서의 용도 |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20190527 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20200928 |
|
A621 | Written request for application examination |
Free format text: JAPANESE INTERMEDIATE CODE: A621 Effective date: 20200928 |
|
A977 | Report on retrieval |
Free format text: JAPANESE INTERMEDIATE CODE: A971007 Effective date: 20210728 |
|
A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20210831 |
|
A601 | Written request for extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A601 Effective date: 20211124 |
|
A601 | Written request for extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A601 Effective date: 20220127 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20220225 |
|
A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20220524 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20220712 |
|
TRDD | Decision of grant or rejection written | ||
A01 | Written decision to grant a patent or to grant a registration (utility model) |
Free format text: JAPANESE INTERMEDIATE CODE: A01 Effective date: 20220802 |
|
A61 | First payment of annual fees (during grant procedure) |
Free format text: JAPANESE INTERMEDIATE CODE: A61 Effective date: 20220822 |
|
R150 | Certificate of patent or registration of utility model |
Ref document number: 7133225 Country of ref document: JP Free format text: JAPANESE INTERMEDIATE CODE: R150 |