JP2011517550A - 溶解ドメイン融合コンストラクト及びその生成及び使用方法 - Google Patents
溶解ドメイン融合コンストラクト及びその生成及び使用方法 Download PDFInfo
- Publication number
- JP2011517550A JP2011517550A JP2010544463A JP2010544463A JP2011517550A JP 2011517550 A JP2011517550 A JP 2011517550A JP 2010544463 A JP2010544463 A JP 2010544463A JP 2010544463 A JP2010544463 A JP 2010544463A JP 2011517550 A JP2011517550 A JP 2011517550A
- Authority
- JP
- Japan
- Prior art keywords
- cell
- tumor
- fusion construct
- cells
- hormone
- 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
- 230000004927 fusion Effects 0.000 title claims abstract description 320
- 238000000034 method Methods 0.000 title claims abstract description 212
- 230000009089 cytolysis Effects 0.000 title claims description 11
- 206010028980 Neoplasm Diseases 0.000 claims abstract description 366
- 201000011510 cancer Diseases 0.000 claims abstract description 265
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 76
- 201000010099 disease Diseases 0.000 claims abstract description 70
- 230000003463 hyperproliferative effect Effects 0.000 claims abstract description 48
- 230000004663 cell proliferation Effects 0.000 claims abstract description 27
- 210000004027 cell Anatomy 0.000 claims description 376
- 238000011282 treatment Methods 0.000 claims description 145
- 108090000765 processed proteins & peptides Proteins 0.000 claims description 119
- 210000004881 tumor cell Anatomy 0.000 claims description 101
- 230000027455 binding Effects 0.000 claims description 90
- 102000005962 receptors Human genes 0.000 claims description 90
- 108020003175 receptors Proteins 0.000 claims description 90
- 206010061289 metastatic neoplasm Diseases 0.000 claims description 88
- 150000007523 nucleic acids Chemical class 0.000 claims description 64
- 102000039446 nucleic acids Human genes 0.000 claims description 56
- 108020004707 nucleic acids Proteins 0.000 claims description 56
- 239000000579 Gonadotropin-Releasing Hormone Substances 0.000 claims description 52
- 239000000203 mixture Substances 0.000 claims description 51
- 108700012941 GNRH1 Proteins 0.000 claims description 50
- 239000000427 antigen Substances 0.000 claims description 50
- 108091007433 antigens Proteins 0.000 claims description 50
- 102000036639 antigens Human genes 0.000 claims description 50
- 239000003446 ligand Substances 0.000 claims description 49
- 230000001603 reducing effect Effects 0.000 claims description 47
- 230000000683 nonmetastatic effect Effects 0.000 claims description 41
- 230000035755 proliferation Effects 0.000 claims description 41
- 208000035269 cancer or benign tumor Diseases 0.000 claims description 40
- 230000001394 metastastic effect Effects 0.000 claims description 39
- 210000005170 neoplastic cell Anatomy 0.000 claims description 39
- 230000002401 inhibitory effect Effects 0.000 claims description 38
- 230000012010 growth Effects 0.000 claims description 35
- 102000004196 processed proteins & peptides Human genes 0.000 claims description 34
- 108090000623 proteins and genes Proteins 0.000 claims description 34
- 150000001413 amino acids Chemical class 0.000 claims description 33
- 125000003275 alpha amino acid group Chemical group 0.000 claims description 32
- 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 claims description 32
- 239000012634 fragment Substances 0.000 claims description 32
- 230000002949 hemolytic effect Effects 0.000 claims description 30
- 108010062540 Chorionic Gonadotropin Proteins 0.000 claims description 29
- 229940088597 hormone Drugs 0.000 claims description 29
- 239000005556 hormone Substances 0.000 claims description 29
- 102000011022 Chorionic Gonadotropin Human genes 0.000 claims description 28
- 229940015047 chorionic gonadotropin Drugs 0.000 claims description 28
- 206010027476 Metastases Diseases 0.000 claims description 27
- 239000013598 vector Substances 0.000 claims description 27
- 150000008574 D-amino acids Chemical class 0.000 claims description 25
- 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 claims description 24
- 230000009931 harmful effect Effects 0.000 claims description 24
- 208000024891 symptom Diseases 0.000 claims description 24
- 108010073521 Luteinizing Hormone Proteins 0.000 claims description 23
- 102000009151 Luteinizing Hormone Human genes 0.000 claims description 23
- 239000003102 growth factor Substances 0.000 claims description 23
- 102000006495 integrins Human genes 0.000 claims description 23
- 108010044426 integrins Proteins 0.000 claims description 23
- 229940040129 luteinizing hormone Drugs 0.000 claims description 23
- 102000012673 Follicle Stimulating Hormone Human genes 0.000 claims description 22
- 108010079345 Follicle Stimulating Hormone Proteins 0.000 claims description 22
- -1 LT) Proteins 0.000 claims description 22
- 108010072866 Prostate-Specific Antigen Proteins 0.000 claims description 22
- 108060008682 Tumor Necrosis Factor Proteins 0.000 claims description 22
- 229940028334 follicle stimulating hormone Drugs 0.000 claims description 22
- 102000004169 proteins and genes Human genes 0.000 claims description 22
- 238000002560 therapeutic procedure Methods 0.000 claims description 22
- 235000018102 proteins Nutrition 0.000 claims description 21
- 241001465754 Metazoa Species 0.000 claims description 20
- RJKFOVLPORLFTN-LEKSSAKUSA-N Progesterone Chemical compound 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 claims description 20
- MUMGGOZAMZWBJJ-DYKIIFRCSA-N Testostosterone Chemical compound O=C1CC[C@]2(C)[C@H]3CC[C@](C)([C@H](CC4)O)[C@@H]4[C@@H]3CCC2=C1 MUMGGOZAMZWBJJ-DYKIIFRCSA-N 0.000 claims description 20
- 102000000852 Tumor Necrosis Factor-alpha Human genes 0.000 claims description 20
- 230000010261 cell growth Effects 0.000 claims description 20
- VYFYYTLLBUKUHU-UHFFFAOYSA-N dopamine Chemical compound NCCC1=CC=C(O)C(O)=C1 VYFYYTLLBUKUHU-UHFFFAOYSA-N 0.000 claims description 20
- 239000003163 gonadal steroid hormone Substances 0.000 claims description 20
- 108010022366 Carcinoembryonic Antigen Proteins 0.000 claims description 19
- 102100025475 Carcinoembryonic antigen-related cell adhesion molecule 5 Human genes 0.000 claims description 19
- 230000002062 proliferating effect Effects 0.000 claims description 19
- 235000019152 folic acid Nutrition 0.000 claims description 18
- 239000011724 folic acid Substances 0.000 claims description 18
- 229940087857 lupron Drugs 0.000 claims description 18
- 230000009401 metastasis Effects 0.000 claims description 18
- 102000011923 Thyrotropin Human genes 0.000 claims description 17
- 108010061174 Thyrotropin Proteins 0.000 claims description 17
- 125000000539 amino acid group Chemical group 0.000 claims description 16
- 102100041003 Glutamate carboxypeptidase 2 Human genes 0.000 claims description 15
- 101000892862 Homo sapiens Glutamate carboxypeptidase 2 Proteins 0.000 claims description 15
- 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 claims description 15
- 229960000304 folic acid Drugs 0.000 claims description 15
- 208000037819 metastatic cancer Diseases 0.000 claims description 15
- 208000011575 metastatic malignant neoplasm Diseases 0.000 claims description 15
- 230000004083 survival effect Effects 0.000 claims description 15
- 108010051696 Growth Hormone Proteins 0.000 claims description 14
- 102100028389 Melanoma antigen recognized by T-cells 1 Human genes 0.000 claims description 14
- 102100038803 Somatotropin Human genes 0.000 claims description 14
- 230000000259 anti-tumor effect Effects 0.000 claims description 14
- 239000000122 growth hormone Substances 0.000 claims description 14
- NOESYZHRGYRDHS-UHFFFAOYSA-N insulin Chemical compound N1C(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(NC(=O)CN)C(C)CC)CSSCC(C(NC(CO)C(=O)NC(CC(C)C)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CCC(N)=O)C(=O)NC(CC(C)C)C(=O)NC(CCC(O)=O)C(=O)NC(CC(N)=O)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CSSCC(NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2C=CC(O)=CC=2)NC(=O)C(CC(C)C)NC(=O)C(C)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2NC=NC=2)NC(=O)C(CO)NC(=O)CNC2=O)C(=O)NCC(=O)NC(CCC(O)=O)C(=O)NC(CCCNC(N)=N)C(=O)NCC(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC(O)=CC=3)C(=O)NC(C(C)O)C(=O)N3C(CCC3)C(=O)NC(CCCCN)C(=O)NC(C)C(O)=O)C(=O)NC(CC(N)=O)C(O)=O)=O)NC(=O)C(C(C)CC)NC(=O)C(CO)NC(=O)C(C(C)O)NC(=O)C1CSSCC2NC(=O)C(CC(C)C)NC(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CC(N)=O)NC(=O)C(NC(=O)C(N)CC=1C=CC=CC=1)C(C)C)CC1=CN=CN1 NOESYZHRGYRDHS-UHFFFAOYSA-N 0.000 claims description 14
- 230000036210 malignancy Effects 0.000 claims description 14
- 108090000723 Insulin-Like Growth Factor I Proteins 0.000 claims description 13
- 102000004083 Lymphotoxin-alpha Human genes 0.000 claims description 13
- 108090000542 Lymphotoxin-alpha Proteins 0.000 claims description 13
- 230000000118 anti-neoplastic effect Effects 0.000 claims description 13
- 108091008039 hormone receptors Proteins 0.000 claims description 13
- 101150029707 ERBB2 gene Proteins 0.000 claims description 12
- 108700012411 TNFSF10 Proteins 0.000 claims description 12
- 108010026331 alpha-Fetoproteins Proteins 0.000 claims description 12
- 230000015572 biosynthetic process Effects 0.000 claims description 12
- 229960004679 doxorubicin Drugs 0.000 claims description 12
- 230000035558 fertility Effects 0.000 claims description 12
- 239000003862 glucocorticoid Substances 0.000 claims description 12
- 238000001959 radiotherapy Methods 0.000 claims description 12
- 102100022089 Acyl-[acyl-carrier-protein] hydrolase Human genes 0.000 claims description 11
- 108010039731 Fatty Acid Synthases Proteins 0.000 claims description 11
- 206010020843 Hyperthermia Diseases 0.000 claims description 11
- 102000004218 Insulin-Like Growth Factor I Human genes 0.000 claims description 11
- 108010002350 Interleukin-2 Proteins 0.000 claims description 11
- 102000000588 Interleukin-2 Human genes 0.000 claims description 11
- 239000003795 chemical substances by application Substances 0.000 claims description 11
- 230000036031 hyperthermia Effects 0.000 claims description 11
- 238000009169 immunotherapy Methods 0.000 claims description 11
- 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 claims description 11
- NVKAWKQGWWIWPM-ABEVXSGRSA-N 17-β-hydroxy-5-α-Androstan-3-one Chemical compound C1C(=O)CC[C@]2(C)[C@H]3CC[C@](C)([C@H](CC4)O)[C@@H]4[C@@H]3CC[C@H]21 NVKAWKQGWWIWPM-ABEVXSGRSA-N 0.000 claims description 10
- VOXZDWNPVJITMN-ZBRFXRBCSA-N 17β-estradiol Chemical compound OC1=CC=C2[C@H]3CC[C@](C)([C@H](CC4)O)[C@@H]4[C@@H]3CCC2=C1 VOXZDWNPVJITMN-ZBRFXRBCSA-N 0.000 claims description 10
- CERZMXAJYMMUDR-QBTAGHCHSA-N 5-amino-3,5-dideoxy-D-glycero-D-galacto-non-2-ulopyranosonic acid Chemical compound N[C@@H]1[C@@H](O)CC(O)(C(O)=O)O[C@H]1[C@H](O)[C@H](O)CO CERZMXAJYMMUDR-QBTAGHCHSA-N 0.000 claims description 10
- 102000004127 Cytokines Human genes 0.000 claims description 10
- 108090000695 Cytokines Proteins 0.000 claims description 10
- FMGSKLZLMKYGDP-UHFFFAOYSA-N Dehydroepiandrosterone Natural products C1C(O)CCC2(C)C3CCC(C)(C(CC4)=O)C4C3CC=C21 FMGSKLZLMKYGDP-UHFFFAOYSA-N 0.000 claims description 10
- 241000235789 Hyperoartia Species 0.000 claims description 10
- 241000124008 Mammalia Species 0.000 claims description 10
- 239000000637 Melanocyte-Stimulating Hormone Substances 0.000 claims description 10
- 108010007013 Melanocyte-Stimulating Hormones Proteins 0.000 claims description 10
- 206010033128 Ovarian cancer Diseases 0.000 claims description 10
- 102000005157 Somatostatin Human genes 0.000 claims description 10
- 108010056088 Somatostatin Proteins 0.000 claims description 10
- 101800004564 Transforming growth factor alpha Proteins 0.000 claims description 10
- 239000003098 androgen Substances 0.000 claims description 10
- AEMFNILZOJDQLW-QAGGRKNESA-N androst-4-ene-3,17-dione Chemical compound O=C1CC[C@]2(C)[C@H]3CC[C@](C)(C(CC4)=O)[C@@H]4[C@@H]3CCC2=C1 AEMFNILZOJDQLW-QAGGRKNESA-N 0.000 claims description 10
- 229960003473 androstanolone Drugs 0.000 claims description 10
- 229960005471 androstenedione Drugs 0.000 claims description 10
- AEMFNILZOJDQLW-UHFFFAOYSA-N androstenedione Natural products O=C1CCC2(C)C3CCC(C)(C(CC4)=O)C4C3CCC2=C1 AEMFNILZOJDQLW-UHFFFAOYSA-N 0.000 claims description 10
- 229940034982 antineoplastic agent Drugs 0.000 claims description 10
- 230000006907 apoptotic process Effects 0.000 claims description 10
- FMGSKLZLMKYGDP-USOAJAOKSA-N dehydroepiandrosterone Chemical compound C1[C@@H](O)CC[C@]2(C)[C@H]3CC[C@](C)(C(CC4)=O)[C@@H]4[C@@H]3CC=C21 FMGSKLZLMKYGDP-USOAJAOKSA-N 0.000 claims description 10
- RGLYKWWBQGJZGM-ISLYRVAYSA-N diethylstilbestrol Chemical compound C=1C=C(O)C=CC=1C(/CC)=C(\CC)C1=CC=C(O)C=C1 RGLYKWWBQGJZGM-ISLYRVAYSA-N 0.000 claims description 10
- 229960000452 diethylstilbestrol Drugs 0.000 claims description 10
- 229960003638 dopamine Drugs 0.000 claims description 10
- 229960005309 estradiol Drugs 0.000 claims description 10
- 229930182833 estradiol Natural products 0.000 claims description 10
- 229940011871 estrogen Drugs 0.000 claims description 10
- 239000000262 estrogen Substances 0.000 claims description 10
- XLXSAKCOAKORKW-AQJXLSMYSA-N gonadorelin Chemical group C([C@@H](C(=O)NCC(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N1[C@@H](CCC1)C(=O)NCC(N)=O)NC(=O)[C@H](CO)NC(=O)[C@H](CC=1C2=CC=CC=C2NC=1)NC(=O)[C@H](CC=1N=CNC=1)NC(=O)[C@H]1NC(=O)CC1)C1=CC=C(O)C=C1 XLXSAKCOAKORKW-AQJXLSMYSA-N 0.000 claims description 10
- 208000032839 leukemia Diseases 0.000 claims description 10
- 210000000056 organ Anatomy 0.000 claims description 10
- 229960002847 prasterone Drugs 0.000 claims description 10
- 229960003387 progesterone Drugs 0.000 claims description 10
- 239000000186 progesterone Substances 0.000 claims description 10
- NHXLMOGPVYXJNR-ATOGVRKGSA-N somatostatin Chemical compound C([C@H]1C(=O)N[C@H](C(N[C@@H](CO)C(=O)N[C@@H](CSSC[C@@H](C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC=2C=CC=CC=2)C(=O)N[C@@H](CC=2C=CC=CC=2)C(=O)N[C@@H](CC=2C3=CC=CC=C3NC=2)C(=O)N[C@@H](CCCCN)C(=O)N[C@H](C(=O)N1)[C@@H](C)O)NC(=O)CNC(=O)[C@H](C)N)C(O)=O)=O)[C@H](O)C)C1=CC=CC=C1 NHXLMOGPVYXJNR-ATOGVRKGSA-N 0.000 claims description 10
- 229960000553 somatostatin Drugs 0.000 claims description 10
- 102000005969 steroid hormone receptors Human genes 0.000 claims description 10
- 108020003113 steroid hormone receptors Proteins 0.000 claims description 10
- 229960003604 testosterone Drugs 0.000 claims description 10
- 102100024222 B-lymphocyte antigen CD19 Human genes 0.000 claims description 9
- 102100022005 B-lymphocyte antigen CD20 Human genes 0.000 claims description 9
- 101150013553 CD40 gene Proteins 0.000 claims description 9
- 102400000932 Gonadoliberin-1 Human genes 0.000 claims description 9
- 101710112034 Gonadoliberin-1 Proteins 0.000 claims description 9
- 101000980825 Homo sapiens B-lymphocyte antigen CD19 Proteins 0.000 claims description 9
- 101000897405 Homo sapiens B-lymphocyte antigen CD20 Proteins 0.000 claims description 9
- 101000623901 Homo sapiens Mucin-16 Proteins 0.000 claims description 9
- 206010025323 Lymphomas Diseases 0.000 claims description 9
- 102100023123 Mucin-16 Human genes 0.000 claims description 9
- 108010025020 Nerve Growth Factor Proteins 0.000 claims description 9
- 102000015336 Nerve Growth Factor Human genes 0.000 claims description 9
- 206010039491 Sarcoma Diseases 0.000 claims description 9
- 102000004338 Transferrin Human genes 0.000 claims description 9
- 108090000901 Transferrin Proteins 0.000 claims description 9
- 102000004887 Transforming Growth Factor beta Human genes 0.000 claims description 9
- 108090001012 Transforming Growth Factor beta Proteins 0.000 claims description 9
- 102400001320 Transforming growth factor alpha Human genes 0.000 claims description 9
- 102100040245 Tumor necrosis factor receptor superfamily member 5 Human genes 0.000 claims description 9
- 210000000170 cell membrane Anatomy 0.000 claims description 9
- 238000002512 chemotherapy Methods 0.000 claims description 9
- 230000005865 ionizing radiation Effects 0.000 claims description 9
- 229940053128 nerve growth factor Drugs 0.000 claims description 9
- 239000008194 pharmaceutical composition Substances 0.000 claims description 9
- 210000002307 prostate Anatomy 0.000 claims description 9
- 238000011127 radiochemotherapy Methods 0.000 claims description 9
- 239000012581 transferrin Substances 0.000 claims description 9
- 210000004291 uterus Anatomy 0.000 claims description 9
- 238000002255 vaccination Methods 0.000 claims description 9
- YBJHBAHKTGYVGT-ZKWXMUAHSA-N (+)-Biotin Chemical compound N1C(=O)N[C@@H]2[C@H](CCCCC(=O)O)SC[C@@H]21 YBJHBAHKTGYVGT-ZKWXMUAHSA-N 0.000 claims description 8
- MZOFCQQQCNRIBI-VMXHOPILSA-N (3s)-4-[[(2s)-1-[[(2s)-1-[[(1s)-1-carboxy-2-hydroxyethyl]amino]-4-methyl-1-oxopentan-2-yl]amino]-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-3-[[2-[[(2s)-2,6-diaminohexanoyl]amino]acetyl]amino]-4-oxobutanoic acid Chemical compound OC[C@@H](C(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCN=C(N)N)NC(=O)[C@H](CC(O)=O)NC(=O)CNC(=O)[C@@H](N)CCCCN MZOFCQQQCNRIBI-VMXHOPILSA-N 0.000 claims description 8
- NMWKYTGJWUAZPZ-WWHBDHEGSA-N (4S)-4-[[(4R,7S,10S,16S,19S,25S,28S,31R)-31-[[(2S)-2-[[(1R,6R,9S,12S,18S,21S,24S,27S,30S,33S,36S,39S,42R,47R,53S,56S,59S,62S,65S,68S,71S,76S,79S,85S)-47-[[(2S)-2-[[(2S)-4-amino-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-amino-3-methylbutanoyl]amino]-3-methylbutanoyl]amino]-3-hydroxypropanoyl]amino]-3-(1H-imidazol-4-yl)propanoyl]amino]-3-phenylpropanoyl]amino]-4-oxobutanoyl]amino]-3-carboxypropanoyl]amino]-18-(4-aminobutyl)-27,68-bis(3-amino-3-oxopropyl)-36,71,76-tribenzyl-39-(3-carbamimidamidopropyl)-24-(2-carboxyethyl)-21,56-bis(carboxymethyl)-65,85-bis[(1R)-1-hydroxyethyl]-59-(hydroxymethyl)-62,79-bis(1H-imidazol-4-ylmethyl)-9-methyl-33-(2-methylpropyl)-8,11,17,20,23,26,29,32,35,38,41,48,54,57,60,63,66,69,72,74,77,80,83,86-tetracosaoxo-30-propan-2-yl-3,4,44,45-tetrathia-7,10,16,19,22,25,28,31,34,37,40,49,55,58,61,64,67,70,73,75,78,81,84,87-tetracosazatetracyclo[40.31.14.012,16.049,53]heptaoctacontane-6-carbonyl]amino]-3-methylbutanoyl]amino]-7-(3-carbamimidamidopropyl)-25-(hydroxymethyl)-19-[(4-hydroxyphenyl)methyl]-28-(1H-imidazol-4-ylmethyl)-10-methyl-6,9,12,15,18,21,24,27,30-nonaoxo-16-propan-2-yl-1,2-dithia-5,8,11,14,17,20,23,26,29-nonazacyclodotriacontane-4-carbonyl]amino]-5-[[(2S)-1-[[(2S)-1-[[(2S)-3-carboxy-1-[[(2S)-1-[[(2S)-1-[[(1S)-1-carboxyethyl]amino]-4-methyl-1-oxopentan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-1-oxopropan-2-yl]amino]-1-oxopropan-2-yl]amino]-3-(1H-imidazol-4-yl)-1-oxopropan-2-yl]amino]-5-oxopentanoic acid Chemical compound CC(C)C[C@H](NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](C)NC(=O)[C@H](Cc1c[nH]cn1)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@@H]1CSSC[C@H](NC(=O)[C@@H](NC(=O)[C@@H]2CSSC[C@@H]3NC(=O)[C@H](Cc4ccccc4)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@@H](NC(=O)[C@H](Cc4c[nH]cn4)NC(=O)[C@H](CO)NC(=O)[C@H](CC(O)=O)NC(=O)[C@@H]4CCCN4C(=O)[C@H](CSSC[C@H](NC(=O)[C@@H](NC(=O)CNC(=O)[C@H](Cc4c[nH]cn4)NC(=O)[C@H](Cc4ccccc4)NC3=O)[C@@H](C)O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](Cc3ccccc3)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CCCCN)C(=O)N3CCC[C@H]3C(=O)N[C@@H](C)C(=O)N2)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](Cc2ccccc2)NC(=O)[C@H](Cc2c[nH]cn2)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@@H](N)C(C)C)C(C)C)[C@@H](C)O)C(C)C)C(=O)N[C@@H](Cc2c[nH]cn2)C(=O)N[C@@H](CO)C(=O)NCC(=O)N[C@@H](Cc2ccc(O)cc2)C(=O)N[C@@H](C(C)C)C(=O)NCC(=O)N[C@@H](C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N1)C(=O)N[C@@H](C)C(O)=O NMWKYTGJWUAZPZ-WWHBDHEGSA-N 0.000 claims description 8
- NMUSYJAQQFHJEW-UHFFFAOYSA-N 5-Azacytidine Natural products O=C1N=C(N)N=CN1C1C(O)C(O)C(CO)O1 NMUSYJAQQFHJEW-UHFFFAOYSA-N 0.000 claims description 8
- 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 claims description 8
- 108010051479 Bombesin Proteins 0.000 claims description 8
- 102000013585 Bombesin Human genes 0.000 claims description 8
- SHZGCJCMOBCMKK-UHFFFAOYSA-N D-mannomethylose Natural products CC1OC(O)C(O)C(O)C1O SHZGCJCMOBCMKK-UHFFFAOYSA-N 0.000 claims description 8
- WQZGKKKJIJFFOK-QTVWNMPRSA-N D-mannopyranose Chemical compound OC[C@H]1OC(O)[C@@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-QTVWNMPRSA-N 0.000 claims description 8
- 108050009340 Endothelin Proteins 0.000 claims description 8
- 102000002045 Endothelin Human genes 0.000 claims description 8
- PNNNRSAQSRJVSB-SLPGGIOYSA-N Fucose Natural products C[C@H](O)[C@@H](O)[C@H](O)[C@H](O)C=O PNNNRSAQSRJVSB-SLPGGIOYSA-N 0.000 claims description 8
- 101001103039 Homo sapiens Inactive tyrosine-protein kinase transmembrane receptor ROR1 Proteins 0.000 claims description 8
- 101001103036 Homo sapiens Nuclear receptor ROR-alpha Proteins 0.000 claims description 8
- 102100039615 Inactive tyrosine-protein kinase transmembrane receptor ROR1 Human genes 0.000 claims description 8
- SHZGCJCMOBCMKK-DHVFOXMCSA-N L-fucopyranose Chemical compound C[C@@H]1OC(O)[C@@H](O)[C@H](O)[C@@H]1O SHZGCJCMOBCMKK-DHVFOXMCSA-N 0.000 claims description 8
- 102100021669 Stromal cell-derived factor 1 Human genes 0.000 claims description 8
- 101710088580 Stromal cell-derived factor 1 Proteins 0.000 claims description 8
- 229930003756 Vitamin B7 Natural products 0.000 claims description 8
- KBGAYAKRZNYFFG-BOHATCBPSA-N aceneuramic acid Chemical compound OC(=O)C(=O)C[C@H](O)[C@@H](NC(=O)C)[C@@H](O)[C@H](O)[C@H](O)CO KBGAYAKRZNYFFG-BOHATCBPSA-N 0.000 claims description 8
- WQZGKKKJIJFFOK-PHYPRBDBSA-N alpha-D-galactose Chemical compound OC[C@H]1O[C@H](O)[C@H](O)[C@@H](O)[C@H]1O WQZGKKKJIJFFOK-PHYPRBDBSA-N 0.000 claims description 8
- 229960002756 azacitidine Drugs 0.000 claims description 8
- SQVRNKJHWKZAKO-UHFFFAOYSA-N beta-N-Acetyl-D-neuraminic acid Natural products CC(=O)NC1C(O)CC(O)(C(O)=O)OC1C(O)C(O)CO SQVRNKJHWKZAKO-UHFFFAOYSA-N 0.000 claims description 8
- 230000007423 decrease Effects 0.000 claims description 8
- ZUBDGKVDJUIMQQ-UBFCDGJISA-N endothelin-1 Chemical compound C([C@@H](C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(O)=O)NC(=O)[C@H]1NC(=O)[C@H](CC=2C=CC=CC=2)NC(=O)[C@@H](CC=2C=CC(O)=CC=2)NC(=O)[C@H](C(C)C)NC(=O)[C@H]2CSSC[C@@H](C(N[C@H](CO)C(=O)N[C@@H](CO)C(=O)N[C@H](CC(C)C)C(=O)N[C@@H](CCSC)C(=O)N[C@H](CC(O)=O)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCC(O)=O)C(=O)N2)=O)NC(=O)[C@@H](CO)NC(=O)[C@H](N)CSSC1)C1=CNC=N1 ZUBDGKVDJUIMQQ-UBFCDGJISA-N 0.000 claims description 8
- 229930182830 galactose Natural products 0.000 claims description 8
- 239000003668 hormone analog Substances 0.000 claims description 8
- 201000010260 leiomyoma Diseases 0.000 claims description 8
- 201000001441 melanoma Diseases 0.000 claims description 8
- 150000002772 monosaccharides Chemical class 0.000 claims description 8
- 229920001184 polypeptide Polymers 0.000 claims description 8
- SQVRNKJHWKZAKO-OQPLDHBCSA-N sialic acid Chemical compound CC(=O)N[C@@H]1[C@@H](O)C[C@@](O)(C(O)=O)OC1[C@H](O)[C@H](O)CO SQVRNKJHWKZAKO-OQPLDHBCSA-N 0.000 claims description 8
- ZRKFYGHZFMAOKI-QMGMOQQFSA-N tgfbeta Chemical compound C([C@H](NC(=O)[C@H](C(C)C)NC(=O)CNC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H]([C@@H](C)O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H]([C@@H](C)O)NC(=O)[C@H](CC(C)C)NC(=O)CNC(=O)[C@H](C)NC(=O)[C@H](CO)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@@H](NC(=O)[C@H](C)NC(=O)[C@H](C)NC(=O)[C@@H](NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](N)CCSC)C(C)C)[C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](C)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](C)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](C)C(=O)N[C@@H](CC(C)C)C(=O)N1[C@@H](CCC1)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(C)C)C(O)=O)C1=CC=C(O)C=C1 ZRKFYGHZFMAOKI-QMGMOQQFSA-N 0.000 claims description 8
- 235000011912 vitamin B7 Nutrition 0.000 claims description 8
- 239000011735 vitamin B7 Substances 0.000 claims description 8
- 102000015735 Beta-catenin Human genes 0.000 claims description 7
- 108060000903 Beta-catenin Proteins 0.000 claims description 7
- 102100025570 Cancer/testis antigen 1 Human genes 0.000 claims description 7
- 108010075016 Ceruloplasmin Proteins 0.000 claims description 7
- 102100023321 Ceruloplasmin Human genes 0.000 claims description 7
- 201000009273 Endometriosis Diseases 0.000 claims description 7
- 102000003886 Glycoproteins Human genes 0.000 claims description 7
- 108090000288 Glycoproteins Proteins 0.000 claims description 7
- 101000856237 Homo sapiens Cancer/testis antigen 1 Proteins 0.000 claims description 7
- 101000578784 Homo sapiens Melanoma antigen recognized by T-cells 1 Proteins 0.000 claims description 7
- 108090001061 Insulin Proteins 0.000 claims description 7
- 102000004877 Insulin Human genes 0.000 claims description 7
- 108010063045 Lactoferrin Proteins 0.000 claims description 7
- 102000010445 Lactoferrin Human genes 0.000 claims description 7
- 108010010995 MART-1 Antigen Proteins 0.000 claims description 7
- 102100022430 Melanocyte protein PMEL Human genes 0.000 claims description 7
- 108010010424 Nuclear Factor 90 Proteins Proteins 0.000 claims description 7
- 102000015863 Nuclear Factor 90 Proteins Human genes 0.000 claims description 7
- 108010077077 Osteonectin Proteins 0.000 claims description 7
- 102000009890 Osteonectin Human genes 0.000 claims description 7
- 108060006580 PRAME Proteins 0.000 claims description 7
- 102000036673 PRAME Human genes 0.000 claims description 7
- 206010035226 Plasma cell myeloma Diseases 0.000 claims description 7
- 101800001271 Surface protein Proteins 0.000 claims description 7
- 108060008724 Tyrosinase Proteins 0.000 claims description 7
- 102000003425 Tyrosinase Human genes 0.000 claims description 7
- 206010046798 Uterine leiomyoma Diseases 0.000 claims description 7
- 108010003205 Vasoactive Intestinal Peptide Proteins 0.000 claims description 7
- 102400000015 Vasoactive intestinal peptide Human genes 0.000 claims description 7
- 108010048626 Y-Box-Binding Protein 1 Proteins 0.000 claims description 7
- 150000002016 disaccharides Chemical class 0.000 claims description 7
- 150000002224 folic acids Chemical class 0.000 claims description 7
- 229940125396 insulin Drugs 0.000 claims description 7
- VBUWHHLIZKOSMS-RIWXPGAOSA-N invicorp Chemical compound C([C@@H](C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CO)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(N)=O)C(O)=O)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CCCCN)NC(=O)[C@@H](NC(=O)[C@H](C)NC(=O)[C@H](CCSC)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@@H](NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(O)=O)NC(=O)[C@@H](NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@@H](NC(=O)[C@H](C)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CO)NC(=O)[C@@H](N)CC=1NC=NC=1)C(C)C)[C@@H](C)O)[C@@H](C)O)C(C)C)C1=CC=C(O)C=C1 VBUWHHLIZKOSMS-RIWXPGAOSA-N 0.000 claims description 7
- 210000003734 kidney Anatomy 0.000 claims description 7
- CSSYQJWUGATIHM-IKGCZBKSSA-N l-phenylalanyl-l-lysyl-l-cysteinyl-l-arginyl-l-arginyl-l-tryptophyl-l-glutaminyl-l-tryptophyl-l-arginyl-l-methionyl-l-lysyl-l-lysyl-l-leucylglycyl-l-alanyl-l-prolyl-l-seryl-l-isoleucyl-l-threonyl-l-cysteinyl-l-valyl-l-arginyl-l-arginyl-l-alanyl-l-phenylal Chemical compound C([C@H](N)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CS)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(C)C)C(=O)NCC(=O)N[C@@H](C)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CO)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CS)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](C)C(=O)N[C@@H](CC=1C=CC=CC=1)C(O)=O)C1=CC=CC=C1 CSSYQJWUGATIHM-IKGCZBKSSA-N 0.000 claims description 7
- 229940078795 lactoferrin Drugs 0.000 claims description 7
- 235000021242 lactoferrin Nutrition 0.000 claims description 7
- 210000004185 liver Anatomy 0.000 claims description 7
- 210000005075 mammary gland Anatomy 0.000 claims description 7
- 210000003739 neck Anatomy 0.000 claims description 7
- 229920001542 oligosaccharide Polymers 0.000 claims description 7
- 150000002482 oligosaccharides Chemical class 0.000 claims description 7
- 210000001672 ovary Anatomy 0.000 claims description 7
- 239000007787 solid Substances 0.000 claims description 7
- 210000001550 testis Anatomy 0.000 claims description 7
- 206010046811 uterine polyp Diseases 0.000 claims description 7
- 206010004446 Benign prostatic hyperplasia Diseases 0.000 claims description 6
- 102100036841 C-C motif chemokine 1 Human genes 0.000 claims description 6
- 102100023705 C-C motif chemokine 14 Human genes 0.000 claims description 6
- 102000019034 Chemokines Human genes 0.000 claims description 6
- 108010012236 Chemokines Proteins 0.000 claims description 6
- 101000978381 Homo sapiens C-C motif chemokine 14 Proteins 0.000 claims description 6
- 101001014223 Homo sapiens MAPK/MAK/MRK overlapping kinase Proteins 0.000 claims description 6
- 102100035304 Lymphotactin Human genes 0.000 claims description 6
- 102100031520 MAPK/MAK/MRK overlapping kinase Human genes 0.000 claims description 6
- 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 claims description 6
- 208000007571 Ovarian Epithelial Carcinoma Diseases 0.000 claims description 6
- 108050007154 PWWP domain-containing DNA repair factor 3A Proteins 0.000 claims description 6
- 102100034640 PWWP domain-containing DNA repair factor 3A Human genes 0.000 claims description 6
- 208000004403 Prostatic Hyperplasia Diseases 0.000 claims description 6
- RJURFGZVJUQBHK-UHFFFAOYSA-N actinomycin D Natural products CC1OC(=O)C(C(C)C)N(C)C(=O)CN(C)C(=O)C2CCCN2C(=O)C(C(C)C)NC(=O)C1NC(=O)C1=C(N)C(=O)C(C)=C2OC(C(C)=CC=C3C(=O)NC4C(=O)NC(C(N5CCCC5C(=O)N(C)CC(=O)N(C)C(C(C)C)C(=O)OC4C)=O)C(C)C)=C3N=C21 RJURFGZVJUQBHK-UHFFFAOYSA-N 0.000 claims description 6
- 230000001093 anti-cancer Effects 0.000 claims description 6
- 150000001720 carbohydrates Chemical class 0.000 claims description 6
- 230000002708 enhancing effect Effects 0.000 claims description 6
- 230000003308 immunostimulating effect Effects 0.000 claims description 6
- 210000004072 lung Anatomy 0.000 claims description 6
- 210000002751 lymph Anatomy 0.000 claims description 6
- GLVAUDGFNGKCSF-UHFFFAOYSA-N mercaptopurine Chemical compound S=C1NC=NC2=C1NC=N2 GLVAUDGFNGKCSF-UHFFFAOYSA-N 0.000 claims description 6
- 201000000050 myeloid neoplasm Diseases 0.000 claims description 6
- 125000003729 nucleotide group Chemical group 0.000 claims description 6
- 238000000015 thermotherapy Methods 0.000 claims description 6
- 210000001685 thyroid gland Anatomy 0.000 claims description 6
- 108010070875 Human Immunodeficiency Virus tat Gene Products Proteins 0.000 claims description 5
- 108010000817 Leuprolide Proteins 0.000 claims description 5
- 206010028851 Necrosis Diseases 0.000 claims description 5
- 102100022224 Y-box-binding protein 1 Human genes 0.000 claims description 5
- 230000002411 adverse Effects 0.000 claims description 5
- 210000003719 b-lymphocyte Anatomy 0.000 claims description 5
- 239000008280 blood Substances 0.000 claims description 5
- 230000024245 cell differentiation Effects 0.000 claims description 5
- DQLATGHUWYMOKM-UHFFFAOYSA-L cisplatin Chemical compound N[Pt](N)(Cl)Cl DQLATGHUWYMOKM-UHFFFAOYSA-L 0.000 claims description 5
- 229960004316 cisplatin Drugs 0.000 claims description 5
- 150000001875 compounds Chemical class 0.000 claims description 5
- 210000003128 head Anatomy 0.000 claims description 5
- 208000020816 lung neoplasm Diseases 0.000 claims description 5
- 230000017074 necrotic cell death Effects 0.000 claims description 5
- 210000000496 pancreas Anatomy 0.000 claims description 5
- 229910052700 potassium Inorganic materials 0.000 claims description 5
- 210000003932 urinary bladder Anatomy 0.000 claims description 5
- 102100036848 C-C motif chemokine 20 Human genes 0.000 claims description 4
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 4
- 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 claims description 4
- 208000002250 Hematologic Neoplasms Diseases 0.000 claims description 4
- 101000713099 Homo sapiens C-C motif chemokine 20 Proteins 0.000 claims description 4
- FBOZXECLQNJBKD-ZDUSSCGKSA-N L-methotrexate Chemical compound C=1N=C2N=C(N)N=C(N)C2=NC=1CN(C)C1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 FBOZXECLQNJBKD-ZDUSSCGKSA-N 0.000 claims description 4
- 206010028813 Nausea Diseases 0.000 claims description 4
- 208000015914 Non-Hodgkin lymphomas Diseases 0.000 claims description 4
- 210000004100 adrenal gland Anatomy 0.000 claims description 4
- 230000000340 anti-metabolite Effects 0.000 claims description 4
- 229940100197 antimetabolite Drugs 0.000 claims description 4
- 239000002256 antimetabolite Substances 0.000 claims description 4
- 210000003679 cervix uteri Anatomy 0.000 claims description 4
- 210000001072 colon Anatomy 0.000 claims description 4
- 230000002496 gastric effect Effects 0.000 claims description 4
- RGLRXNKKBLIBQS-XNHQSDQCSA-N leuprolide acetate Chemical compound CC(O)=O.CCNC(=O)[C@@H]1CCCN1C(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](CC(C)C)NC(=O)[C@@H](NC(=O)[C@H](CO)NC(=O)[C@H](CC=1C2=CC=CC=C2NC=1)NC(=O)[C@H](CC=1N=CNC=1)NC(=O)[C@H]1NC(=O)CC1)CC1=CC=C(O)C=C1 RGLRXNKKBLIBQS-XNHQSDQCSA-N 0.000 claims description 4
- 210000004698 lymphocyte Anatomy 0.000 claims description 4
- 210000002540 macrophage Anatomy 0.000 claims description 4
- 229960000485 methotrexate Drugs 0.000 claims description 4
- 230000008693 nausea Effects 0.000 claims description 4
- 210000003101 oviduct Anatomy 0.000 claims description 4
- 210000002784 stomach Anatomy 0.000 claims description 4
- WYWHKKSPHMUBEB-UHFFFAOYSA-N 6-Mercaptoguanine Natural products N1C(N)=NC(=S)C2=C1N=CN2 WYWHKKSPHMUBEB-UHFFFAOYSA-N 0.000 claims description 3
- 206010003571 Astrocytoma Diseases 0.000 claims description 3
- 108010006654 Bleomycin Proteins 0.000 claims description 3
- COVZYZSDYWQREU-UHFFFAOYSA-N Busulfan Chemical compound CS(=O)(=O)OCCCCOS(C)(=O)=O COVZYZSDYWQREU-UHFFFAOYSA-N 0.000 claims description 3
- 101710155835 C-C motif chemokine 1 Proteins 0.000 claims description 3
- 102100023702 C-C motif chemokine 13 Human genes 0.000 claims description 3
- 101710112613 C-C motif chemokine 13 Proteins 0.000 claims description 3
- 102100023703 C-C motif chemokine 15 Human genes 0.000 claims description 3
- 102100023698 C-C motif chemokine 17 Human genes 0.000 claims description 3
- 102100023701 C-C motif chemokine 18 Human genes 0.000 claims description 3
- 102100021943 C-C motif chemokine 2 Human genes 0.000 claims description 3
- 101710155857 C-C motif chemokine 2 Proteins 0.000 claims description 3
- 102100036849 C-C motif chemokine 24 Human genes 0.000 claims description 3
- 102100032367 C-C motif chemokine 5 Human genes 0.000 claims description 3
- 102100032366 C-C motif chemokine 7 Human genes 0.000 claims description 3
- 101710155834 C-C motif chemokine 7 Proteins 0.000 claims description 3
- 102100034871 C-C motif chemokine 8 Human genes 0.000 claims description 3
- 101710155833 C-C motif chemokine 8 Proteins 0.000 claims description 3
- 102100039398 C-X-C motif chemokine 2 Human genes 0.000 claims description 3
- 102100036153 C-X-C motif chemokine 6 Human genes 0.000 claims description 3
- 101710085504 C-X-C motif chemokine 6 Proteins 0.000 claims description 3
- FVLVBPDQNARYJU-XAHDHGMMSA-N C[C@H]1CCC(CC1)NC(=O)N(CCCl)N=O Chemical compound C[C@H]1CCC(CC1)NC(=O)N(CCCl)N=O FVLVBPDQNARYJU-XAHDHGMMSA-N 0.000 claims description 3
- DLGOEMSEDOSKAD-UHFFFAOYSA-N Carmustine Chemical compound ClCCNC(=O)N(N=O)CCCl DLGOEMSEDOSKAD-UHFFFAOYSA-N 0.000 claims description 3
- 108010083647 Chemokine CCL24 Proteins 0.000 claims description 3
- 108010055165 Chemokine CCL4 Proteins 0.000 claims description 3
- 102000001326 Chemokine CCL4 Human genes 0.000 claims description 3
- 108010055166 Chemokine CCL5 Proteins 0.000 claims description 3
- 108010014419 Chemokine CXCL1 Proteins 0.000 claims description 3
- 102000016950 Chemokine CXCL1 Human genes 0.000 claims description 3
- 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 claims description 3
- 208000005243 Chondrosarcoma Diseases 0.000 claims description 3
- CMSMOCZEIVJLDB-UHFFFAOYSA-N Cyclophosphamide Chemical group ClCCN(CCCl)P1(=O)NCCCO1 CMSMOCZEIVJLDB-UHFFFAOYSA-N 0.000 claims description 3
- 229930105110 Cyclosporin A Natural products 0.000 claims description 3
- PMATZTZNYRCHOR-CGLBZJNRSA-N Cyclosporin A Chemical compound CC[C@@H]1NC(=O)[C@H]([C@H](O)[C@H](C)C\C=C\C)N(C)C(=O)[C@H](C(C)C)N(C)C(=O)[C@H](CC(C)C)N(C)C(=O)[C@H](CC(C)C)N(C)C(=O)[C@@H](C)NC(=O)[C@H](C)NC(=O)[C@H](CC(C)C)N(C)C(=O)[C@H](C(C)C)NC(=O)[C@H](CC(C)C)N(C)C(=O)CN(C)C1=O PMATZTZNYRCHOR-CGLBZJNRSA-N 0.000 claims description 3
- 108010036949 Cyclosporine Proteins 0.000 claims description 3
- 108010092160 Dactinomycin Proteins 0.000 claims description 3
- 101710181478 Envelope glycoprotein GP350 Proteins 0.000 claims description 3
- 102100023688 Eotaxin Human genes 0.000 claims description 3
- 101710139422 Eotaxin Proteins 0.000 claims description 3
- 201000008808 Fibrosarcoma Diseases 0.000 claims description 3
- GHASVSINZRGABV-UHFFFAOYSA-N Fluorouracil Chemical compound FC1=CNC(=O)NC1=O GHASVSINZRGABV-UHFFFAOYSA-N 0.000 claims description 3
- 101710115997 Gamma-tubulin complex component 2 Proteins 0.000 claims description 3
- 206010018338 Glioma Diseases 0.000 claims description 3
- 101000728693 Homo sapiens 28S ribosomal protein S11, mitochondrial Proteins 0.000 claims description 3
- 101000713104 Homo sapiens C-C motif chemokine 1 Proteins 0.000 claims description 3
- 101000978376 Homo sapiens C-C motif chemokine 15 Proteins 0.000 claims description 3
- 101000978362 Homo sapiens C-C motif chemokine 17 Proteins 0.000 claims description 3
- 101000978371 Homo sapiens C-C motif chemokine 18 Proteins 0.000 claims description 3
- 101000889128 Homo sapiens C-X-C motif chemokine 2 Proteins 0.000 claims description 3
- 101000893764 Homo sapiens FUN14 domain-containing protein 2 Proteins 0.000 claims description 3
- 101000804764 Homo sapiens Lymphotactin Proteins 0.000 claims description 3
- 101000973997 Homo sapiens Nucleosome assembly protein 1-like 4 Proteins 0.000 claims description 3
- 101000947178 Homo sapiens Platelet basic protein Proteins 0.000 claims description 3
- 206010062767 Hypophysitis Diseases 0.000 claims description 3
- 102100037850 Interferon gamma Human genes 0.000 claims description 3
- 108010074328 Interferon-gamma Proteins 0.000 claims description 3
- 102000013462 Interleukin-12 Human genes 0.000 claims description 3
- 108010065805 Interleukin-12 Proteins 0.000 claims description 3
- 108010002386 Interleukin-3 Proteins 0.000 claims description 3
- 108090001005 Interleukin-6 Proteins 0.000 claims description 3
- 108010002586 Interleukin-7 Proteins 0.000 claims description 3
- 108090001007 Interleukin-8 Proteins 0.000 claims description 3
- 102000004890 Interleukin-8 Human genes 0.000 claims description 3
- 208000018142 Leiomyosarcoma Diseases 0.000 claims description 3
- GQYIWUVLTXOXAJ-UHFFFAOYSA-N Lomustine Chemical compound ClCCN(N=O)C(=O)NC1CCCCC1 GQYIWUVLTXOXAJ-UHFFFAOYSA-N 0.000 claims description 3
- 206010058467 Lung neoplasm malignant Diseases 0.000 claims description 3
- 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 claims description 3
- 101100441533 Mus musculus Cxcl9 gene Proteins 0.000 claims description 3
- 206010029260 Neuroblastoma Diseases 0.000 claims description 3
- 201000010133 Oligodendroglioma Diseases 0.000 claims description 3
- 229930012538 Paclitaxel Natural products 0.000 claims description 3
- 208000002193 Pain Diseases 0.000 claims description 3
- 102100036154 Platelet basic protein Human genes 0.000 claims description 3
- ZSJLQEPLLKMAKR-UHFFFAOYSA-N Streptozotocin Natural products O=NN(C)C(=O)NC1C(O)OC(CO)C(O)C1O ZSJLQEPLLKMAKR-UHFFFAOYSA-N 0.000 claims description 3
- JXLYSJRDGCGARV-WWYNWVTFSA-N Vinblastine Natural products O=C(O[C@H]1[C@](O)(C(=O)OC)[C@@H]2N(C)c3c(cc(c(OC)c3)[C@]3(C(=O)OC)c4[nH]c5c(c4CCN4C[C@](O)(CC)C[C@H](C3)C4)cccc5)[C@@]32[C@H]2[C@@]1(CC)C=CCN2CC3)C JXLYSJRDGCGARV-WWYNWVTFSA-N 0.000 claims description 3
- RJURFGZVJUQBHK-IIXSONLDSA-N actinomycin D Chemical compound C[C@H]1OC(=O)[C@H](C(C)C)N(C)C(=O)CN(C)C(=O)[C@@H]2CCCN2C(=O)[C@@H](C(C)C)NC(=O)[C@H]1NC(=O)C1=C(N)C(=O)C(C)=C2OC(C(C)=CC=C3C(=O)N[C@@H]4C(=O)N[C@@H](C(N5CCC[C@H]5C(=O)N(C)CC(=O)N(C)[C@@H](C(C)C)C(=O)O[C@@H]4C)=O)C(C)C)=C3N=C21 RJURFGZVJUQBHK-IIXSONLDSA-N 0.000 claims description 3
- 208000009956 adenocarcinoma Diseases 0.000 claims description 3
- 230000001919 adrenal effect Effects 0.000 claims description 3
- 229930013930 alkaloid Natural products 0.000 claims description 3
- 229940100198 alkylating agent Drugs 0.000 claims description 3
- 239000002168 alkylating agent Substances 0.000 claims description 3
- 230000036528 appetite Effects 0.000 claims description 3
- 235000019789 appetite Nutrition 0.000 claims description 3
- LMEKQMALGUDUQG-UHFFFAOYSA-N azathioprine Chemical compound CN1C=NC([N+]([O-])=O)=C1SC1=NC=NC2=C1NC=N2 LMEKQMALGUDUQG-UHFFFAOYSA-N 0.000 claims description 3
- 229960002170 azathioprine Drugs 0.000 claims description 3
- 229960001561 bleomycin Drugs 0.000 claims description 3
- 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 claims description 3
- 210000004369 blood Anatomy 0.000 claims description 3
- 210000000988 bone and bone Anatomy 0.000 claims description 3
- 210000001185 bone marrow Anatomy 0.000 claims description 3
- 210000004556 brain Anatomy 0.000 claims description 3
- 229960002092 busulfan Drugs 0.000 claims description 3
- 229960005243 carmustine Drugs 0.000 claims description 3
- JCKYGMPEJWAADB-UHFFFAOYSA-N chlorambucil Chemical compound OC(=O)CCCC1=CC=C(N(CCCl)CCCl)C=C1 JCKYGMPEJWAADB-UHFFFAOYSA-N 0.000 claims description 3
- 229960004630 chlorambucil Drugs 0.000 claims description 3
- 229960001265 ciclosporin Drugs 0.000 claims description 3
- 125000004122 cyclic group Chemical group 0.000 claims description 3
- 229960004397 cyclophosphamide Drugs 0.000 claims description 3
- 229960000640 dactinomycin Drugs 0.000 claims description 3
- 210000004443 dendritic cell Anatomy 0.000 claims description 3
- 210000001198 duodenum Anatomy 0.000 claims description 3
- 210000005168 endometrial cell Anatomy 0.000 claims description 3
- 210000004696 endometrium Anatomy 0.000 claims description 3
- 229960002949 fluorouracil Drugs 0.000 claims description 3
- 208000005017 glioblastoma Diseases 0.000 claims description 3
- 210000003714 granulocyte Anatomy 0.000 claims description 3
- 208000019691 hematopoietic and lymphoid cell neoplasm Diseases 0.000 claims description 3
- 210000003958 hematopoietic stem cell Anatomy 0.000 claims description 3
- 210000003405 ileum Anatomy 0.000 claims description 3
- 210000001630 jejunum Anatomy 0.000 claims description 3
- 206010024627 liposarcoma Diseases 0.000 claims description 3
- 229960002247 lomustine Drugs 0.000 claims description 3
- 201000005202 lung cancer Diseases 0.000 claims description 3
- 208000025036 lymphosarcoma Diseases 0.000 claims description 3
- 108010019677 lymphotactin Proteins 0.000 claims description 3
- 206010025482 malaise Diseases 0.000 claims description 3
- AEUKDPKXTPNBNY-XEYRWQBLSA-N mcp 2 Chemical compound C([C@@H](C(=O)N[C@@H](CS)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CCCNC(N)=N)C(=O)NCC(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CC=1NC=NC=1)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CS)C(=O)N[C@@H](CS)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O)NC(=O)CNC(=O)[C@H](C)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H]1N(CCC1)C(=O)[C@H](CC(C)C)NC(=O)[C@H](CS)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](C)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CS)NC(=O)[C@H](C)NC(=O)[C@H](CS)NC(=O)[C@@H](NC(=O)[C@@H](N)C(C)C)C(C)C)C1=CC=CC=C1 AEUKDPKXTPNBNY-XEYRWQBLSA-N 0.000 claims description 3
- HAWPXGHAZFHHAD-UHFFFAOYSA-N mechlorethamine Chemical compound ClCCN(C)CCCl HAWPXGHAZFHHAD-UHFFFAOYSA-N 0.000 claims description 3
- 229960004961 mechlorethamine Drugs 0.000 claims description 3
- SGDBTWWWUNNDEQ-LBPRGKRZSA-N melphalan Chemical compound OC(=O)[C@@H](N)CC1=CC=C(N(CCCl)CCCl)C=C1 SGDBTWWWUNNDEQ-LBPRGKRZSA-N 0.000 claims description 3
- 229960001924 melphalan Drugs 0.000 claims description 3
- 206010027191 meningioma Diseases 0.000 claims description 3
- 230000003340 mental effect Effects 0.000 claims description 3
- 229960001428 mercaptopurine Drugs 0.000 claims description 3
- 101150115039 mig gene Proteins 0.000 claims description 3
- CFCUWKMKBJTWLW-BKHRDMLASA-N mithramycin Chemical compound O([C@@H]1C[C@@H](O[C@H](C)[C@H]1O)OC=1C=C2C=C3C[C@H]([C@@H](C(=O)C3=C(O)C2=C(O)C=1C)O[C@@H]1O[C@H](C)[C@@H](O)[C@H](O[C@@H]2O[C@H](C)[C@H](O)[C@H](O[C@@H]3O[C@H](C)[C@@H](O)[C@@](C)(O)C3)C2)C1)[C@H](OC)C(=O)[C@@H](O)[C@@H](C)O)[C@H]1C[C@@H](O)[C@H](O)[C@@H](C)O1 CFCUWKMKBJTWLW-BKHRDMLASA-N 0.000 claims description 3
- 229960005485 mitobronitol Drugs 0.000 claims description 3
- 229960004857 mitomycin Drugs 0.000 claims description 3
- 229960000350 mitotane Drugs 0.000 claims description 3
- 230000037230 mobility Effects 0.000 claims description 3
- 210000003928 nasal cavity Anatomy 0.000 claims description 3
- 210000001989 nasopharynx Anatomy 0.000 claims description 3
- 210000000822 natural killer cell Anatomy 0.000 claims description 3
- 201000008968 osteosarcoma Diseases 0.000 claims description 3
- 229960001592 paclitaxel Drugs 0.000 claims description 3
- 210000003899 penis Anatomy 0.000 claims description 3
- 210000003800 pharynx Anatomy 0.000 claims description 3
- 230000001817 pituitary effect Effects 0.000 claims description 3
- 210000003635 pituitary gland Anatomy 0.000 claims description 3
- 239000000419 plant extract Substances 0.000 claims description 3
- 210000004180 plasmocyte Anatomy 0.000 claims description 3
- 229960003171 plicamycin Drugs 0.000 claims description 3
- OIGNJSKKLXVSLS-VWUMJDOOSA-N prednisolone Chemical compound O=C1C=C[C@]2(C)[C@H]3[C@@H](O)C[C@](C)([C@@](CC4)(O)C(=O)CO)[C@@H]4[C@@H]3CCC2=C1 OIGNJSKKLXVSLS-VWUMJDOOSA-N 0.000 claims description 3
- 229960005205 prednisolone Drugs 0.000 claims description 3
- CPTBDICYNRMXFX-UHFFFAOYSA-N procarbazine Chemical compound CNNCC1=CC=C(C(=O)NC(C)C)C=C1 CPTBDICYNRMXFX-UHFFFAOYSA-N 0.000 claims description 3
- 229960000624 procarbazine Drugs 0.000 claims description 3
- 210000005267 prostate cell Anatomy 0.000 claims description 3
- 210000000664 rectum Anatomy 0.000 claims description 3
- 238000002271 resection Methods 0.000 claims description 3
- 201000009410 rhabdomyosarcoma Diseases 0.000 claims description 3
- 229960003440 semustine Drugs 0.000 claims description 3
- 210000000813 small intestine Anatomy 0.000 claims description 3
- 210000000130 stem cell Anatomy 0.000 claims description 3
- 229960001052 streptozocin Drugs 0.000 claims description 3
- 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 claims description 3
- RCINICONZNJXQF-MZXODVADSA-N taxol Chemical compound O([C@@H]1[C@@]2(C[C@@H](C(C)=C(C2(C)C)[C@H](C([C@]2(C)[C@@H](O)C[C@H]3OC[C@]3([C@H]21)OC(C)=O)=O)OC(=O)C)OC(=O)[C@H](O)[C@@H](NC(=O)C=1C=CC=CC=1)C=1C=CC=CC=1)O)C(=O)C1=CC=CC=C1 RCINICONZNJXQF-MZXODVADSA-N 0.000 claims description 3
- 229960003087 tioguanine Drugs 0.000 claims description 3
- MNRILEROXIRVNJ-UHFFFAOYSA-N tioguanine Chemical compound N1C(N)=NC(=S)C2=NC=N[C]21 MNRILEROXIRVNJ-UHFFFAOYSA-N 0.000 claims description 3
- 210000001215 vagina Anatomy 0.000 claims description 3
- 229960003048 vinblastine Drugs 0.000 claims description 3
- JXLYSJRDGCGARV-XQKSVPLYSA-N vincaleukoblastine Chemical compound C([C@@H](C[C@]1(C(=O)OC)C=2C(=CC3=C([C@]45[C@H]([C@@]([C@H](OC(C)=O)[C@]6(CC)C=CCN([C@H]56)CC4)(O)C(=O)OC)N3C)C=2)OC)C[C@@](C2)(O)CC)N2CCC2=C1NC1=CC=CC=C21 JXLYSJRDGCGARV-XQKSVPLYSA-N 0.000 claims description 3
- 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 claims description 3
- 229960004528 vincristine Drugs 0.000 claims description 3
- 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 claims description 3
- NOENHWMKHNSHGX-IZOOSHNJSA-N (2s)-1-[(2s)-2-[[(2s)-2-[[(2r)-2-[[(2r)-2-[[(2s)-2-[[(2r)-2-[[(2s)-2-[[(2r)-2-acetamido-3-naphthalen-2-ylpropanoyl]amino]-3-(4-chlorophenyl)propanoyl]amino]-3-pyridin-3-ylpropanoyl]amino]-3-hydroxypropanoyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]-6-(ca Chemical compound C([C@H](C(=O)N[C@H](CCCCNC(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)NC(=O)[C@H](CO)NC(=O)[C@@H](CC=1C=NC=CC=1)NC(=O)[C@H](CC=1C=CC(Cl)=CC=1)NC(=O)[C@@H](CC=1C=C2C=CC=CC2=CC=1)NC(C)=O)C1=CC=C(O)C=C1 NOENHWMKHNSHGX-IZOOSHNJSA-N 0.000 claims description 2
- FDKXTQMXEQVLRF-ZHACJKMWSA-N (E)-dacarbazine Chemical compound CN(C)\N=N\c1[nH]cnc1C(N)=O FDKXTQMXEQVLRF-ZHACJKMWSA-N 0.000 claims description 2
- VSNHCAURESNICA-NJFSPNSNSA-N 1-oxidanylurea Chemical compound N[14C](=O)NO VSNHCAURESNICA-NJFSPNSNSA-N 0.000 claims description 2
- 208000003200 Adenoma Diseases 0.000 claims description 2
- 206010001233 Adenoma benign Diseases 0.000 claims description 2
- 108010037003 Buserelin Proteins 0.000 claims description 2
- 208000032612 Glial tumor Diseases 0.000 claims description 2
- 108010069236 Goserelin Proteins 0.000 claims description 2
- 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 claims description 2
- 108010017080 Granulocyte Colony-Stimulating Factor Proteins 0.000 claims description 2
- 102000004269 Granulocyte Colony-Stimulating Factor Human genes 0.000 claims description 2
- 108010046938 Macrophage Colony-Stimulating Factor Proteins 0.000 claims description 2
- 102000007651 Macrophage Colony-Stimulating Factor Human genes 0.000 claims description 2
- 206010027406 Mesothelioma Diseases 0.000 claims description 2
- 206010041067 Small cell lung cancer Diseases 0.000 claims description 2
- 108010023617 abarelix Proteins 0.000 claims description 2
- 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 claims description 2
- 229960002184 abarelix Drugs 0.000 claims description 2
- 108010052004 acetyl-2-naphthylalanyl-3-chlorophenylalanyl-1-oxohexadecyl-seryl-4-aminophenylalanyl(hydroorotyl)-4-aminophenylalanyl(carbamoyl)-leucyl-ILys-prolyl-alaninamide Proteins 0.000 claims description 2
- 108010070670 antarelix Proteins 0.000 claims description 2
- WZPBZJONDBGPKJ-VEHQQRBSSA-N aztreonam Chemical compound O=C1N(S([O-])(=O)=O)[C@@H](C)[C@@H]1NC(=O)C(=N/OC(C)(C)C(O)=O)\C1=CSC([NH3+])=N1 WZPBZJONDBGPKJ-VEHQQRBSSA-N 0.000 claims description 2
- CUWODFFVMXJOKD-UVLQAERKSA-N buserelin Chemical compound CCNC(=O)[C@@H]1CCCN1C(=O)[C@H](CCCN=C(N)N)NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](COC(C)(C)C)NC(=O)[C@@H](NC(=O)[C@H](CO)NC(=O)[C@H](CC=1C2=CC=CC=C2NC=1)NC(=O)[C@H](CC=1NC=NC=1)NC(=O)[C@H]1NC(=O)CC1)CC1=CC=C(O)C=C1 CUWODFFVMXJOKD-UVLQAERKSA-N 0.000 claims description 2
- 229960002719 buserelin Drugs 0.000 claims description 2
- 108700008462 cetrorelix Proteins 0.000 claims description 2
- 229960003230 cetrorelix Drugs 0.000 claims description 2
- SBNPWPIBESPSIF-MHWMIDJBSA-N cetrorelix Chemical compound C([C@@H](C(=O)N[C@H](CCCNC(N)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N1[C@@H](CCC1)C(=O)N[C@H](C)C(N)=O)NC(=O)[C@H](CO)NC(=O)[C@@H](CC=1C=NC=CC=1)NC(=O)[C@@H](CC=1C=CC(Cl)=CC=1)NC(=O)[C@@H](CC=1C=C2C=CC=CC2=CC=1)NC(C)=O)C1=CC=C(O)C=C1 SBNPWPIBESPSIF-MHWMIDJBSA-N 0.000 claims description 2
- 229960003901 dacarbazine Drugs 0.000 claims description 2
- 229960002272 degarelix Drugs 0.000 claims description 2
- MEUCPCLKGZSHTA-XYAYPHGZSA-N degarelix Chemical compound C([C@H](C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCCNC(C)C)C(=O)N1[C@@H](CCC1)C(=O)N[C@H](C)C(N)=O)NC(=O)[C@H](CC=1C=CC(NC(=O)[C@H]2NC(=O)NC(=O)C2)=CC=1)NC(=O)[C@H](CO)NC(=O)[C@@H](CC=1C=NC=CC=1)NC(=O)[C@@H](CC=1C=CC(Cl)=CC=1)NC(=O)[C@@H](CC=1C=C2C=CC=CC2=CC=1)NC(C)=O)C1=CC=C(NC(N)=O)C=C1 MEUCPCLKGZSHTA-XYAYPHGZSA-N 0.000 claims description 2
- 230000001976 improved effect Effects 0.000 claims description 2
- 108010083551 iturelix Proteins 0.000 claims description 2
- QRYFGTULTGLGHU-NBERXCRTSA-N iturelix Chemical compound C([C@H](C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCCNC(C)C)C(=O)N1[C@@H](CCC1)C(=O)N[C@H](C)C(N)=O)NC(=O)[C@H](CCCCNC(=O)C=1C=NC=CC=1)NC(=O)[C@H](CO)NC(=O)[C@@H](CC=1C=NC=CC=1)NC(=O)[C@@H](CC=1C=CC(Cl)=CC=1)NC(=O)[C@@H](CC=1C=C2C=CC=CC2=CC=1)NC(C)=O)CCCNC(=O)C1=CC=CN=C1 QRYFGTULTGLGHU-NBERXCRTSA-N 0.000 claims description 2
- 208000019420 lymphoid neoplasm Diseases 0.000 claims description 2
- 229960003248 mifepristone Drugs 0.000 claims description 2
- VKHAHZOOUSRJNA-GCNJZUOMSA-N mifepristone Chemical compound C1([C@@H]2C3=C4CCC(=O)C=C4CC[C@H]3[C@@H]3CC[C@@]([C@]3(C2)C)(O)C#CC)=CC=C(N(C)C)C=C1 VKHAHZOOUSRJNA-GCNJZUOMSA-N 0.000 claims description 2
- 210000000214 mouth Anatomy 0.000 claims description 2
- OSTGTTZJOCZWJG-UHFFFAOYSA-N nitrosourea Chemical compound NC(=O)N=NO OSTGTTZJOCZWJG-UHFFFAOYSA-N 0.000 claims description 2
- 208000002154 non-small cell lung carcinoma Diseases 0.000 claims description 2
- 239000002773 nucleotide Substances 0.000 claims description 2
- LUYQYZLEHLTPBH-UHFFFAOYSA-N perfluorobutanesulfonyl fluoride Chemical compound FC(F)(F)C(F)(F)C(F)(F)C(F)(F)S(F)(=O)=O LUYQYZLEHLTPBH-UHFFFAOYSA-N 0.000 claims description 2
- 239000000018 receptor agonist Substances 0.000 claims description 2
- 229940044601 receptor agonist Drugs 0.000 claims description 2
- 239000002464 receptor antagonist Substances 0.000 claims description 2
- 229940044551 receptor antagonist Drugs 0.000 claims description 2
- 208000000587 small cell lung carcinoma Diseases 0.000 claims description 2
- 229950011372 teverelix Drugs 0.000 claims description 2
- 208000029729 tumor suppressor gene on chromosome 11 Diseases 0.000 claims description 2
- 229940033942 zoladex Drugs 0.000 claims description 2
- 102000007066 Prostate-Specific Antigen Human genes 0.000 claims 8
- 102000013529 alpha-Fetoproteins Human genes 0.000 claims 8
- 101710112050 Gonadoliberin-3 Proteins 0.000 claims 5
- DNDCVAGJPBKION-DOPDSADYSA-N bombesin Chemical compound C([C@@H](C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCSC)C(N)=O)NC(=O)CNC(=O)[C@@H](NC(=O)[C@H](C)NC(=O)[C@H](CC=1NC2=CC=CC=C2C=1)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CC(N)=O)NC(=O)CNC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H]1NC(=O)CC1)C(C)C)C1=CN=CN1 DNDCVAGJPBKION-DOPDSADYSA-N 0.000 claims 4
- 201000005787 hematologic cancer Diseases 0.000 claims 3
- 206010061187 Haematopoietic neoplasm Diseases 0.000 claims 2
- 208000002231 Muscle Neoplasms Diseases 0.000 claims 1
- 208000000453 Skin Neoplasms Diseases 0.000 claims 1
- 150000003797 alkaloid derivatives Chemical class 0.000 claims 1
- 201000000053 blastoma Diseases 0.000 claims 1
- 201000008184 embryoma Diseases 0.000 claims 1
- 108700032141 ganirelix Proteins 0.000 claims 1
- 229960003794 ganirelix Drugs 0.000 claims 1
- GJNXBNATEDXMAK-PFLSVRRQSA-N ganirelix Chemical compound C([C@@H](C(=O)N[C@H](CCCCN=C(NCC)NCC)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCCN=C(NCC)NCC)C(=O)N1[C@@H](CCC1)C(=O)N[C@H](C)C(N)=O)NC(=O)[C@H](CO)NC(=O)[C@@H](CC=1C=NC=CC=1)NC(=O)[C@@H](CC=1C=CC(Cl)=CC=1)NC(=O)[C@@H](CC=1C=C2C=CC=CC2=CC=1)NC(C)=O)C1=CC=C(O)C=C1 GJNXBNATEDXMAK-PFLSVRRQSA-N 0.000 claims 1
- 208000024200 hematopoietic and lymphoid system neoplasm Diseases 0.000 claims 1
- 208000037841 lung tumor Diseases 0.000 claims 1
- 210000003205 muscle Anatomy 0.000 claims 1
- 201000009368 muscle benign neoplasm Diseases 0.000 claims 1
- 208000017708 myomatous neoplasm Diseases 0.000 claims 1
- 210000001331 nose Anatomy 0.000 claims 1
- 210000001525 retina Anatomy 0.000 claims 1
- 201000010088 skin benign neoplasm Diseases 0.000 claims 1
- 208000010579 uterine corpus leiomyoma Diseases 0.000 claims 1
- 201000007954 uterine fibroid Diseases 0.000 claims 1
- 230000002159 abnormal effect Effects 0.000 abstract description 27
- 230000002939 deleterious effect Effects 0.000 abstract description 3
- 230000000694 effects Effects 0.000 description 73
- 235000001014 amino acid Nutrition 0.000 description 32
- 229940024606 amino acid Drugs 0.000 description 31
- 230000002101 lytic effect Effects 0.000 description 31
- 230000014509 gene expression Effects 0.000 description 30
- 239000003814 drug Substances 0.000 description 29
- 238000001727 in vivo Methods 0.000 description 24
- 230000002829 reductive effect Effects 0.000 description 24
- 241000699670 Mus sp. Species 0.000 description 22
- 229940124597 therapeutic agent Drugs 0.000 description 21
- 239000002246 antineoplastic agent Substances 0.000 description 20
- 210000001519 tissue Anatomy 0.000 description 18
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 17
- 238000002347 injection Methods 0.000 description 17
- 239000007924 injection Substances 0.000 description 17
- 239000000126 substance Substances 0.000 description 17
- 230000001965 increasing effect Effects 0.000 description 16
- 230000001225 therapeutic effect Effects 0.000 description 16
- 239000011780 sodium chloride Substances 0.000 description 15
- 102100038358 Prostate-specific antigen Human genes 0.000 description 14
- 238000011156 evaluation Methods 0.000 description 14
- 238000006467 substitution reaction Methods 0.000 description 14
- 206010006187 Breast cancer Diseases 0.000 description 13
- 230000003013 cytotoxicity Effects 0.000 description 13
- 231100000135 cytotoxicity Toxicity 0.000 description 13
- 229940079593 drug Drugs 0.000 description 12
- 238000000338 in vitro Methods 0.000 description 12
- 239000013604 expression vector Substances 0.000 description 11
- 125000006850 spacer group Chemical group 0.000 description 11
- 108010021290 LHRH Receptors Proteins 0.000 description 10
- 102000008238 LHRH Receptors Human genes 0.000 description 10
- 239000013612 plasmid Substances 0.000 description 10
- 208000026310 Breast neoplasm Diseases 0.000 description 9
- 229940127089 cytotoxic agent Drugs 0.000 description 9
- 238000002474 experimental method Methods 0.000 description 9
- 125000005647 linker group Chemical group 0.000 description 9
- 238000011269 treatment regimen Methods 0.000 description 9
- 102100023635 Alpha-fetoprotein Human genes 0.000 description 8
- QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 description 8
- 230000030833 cell death Effects 0.000 description 8
- 230000006872 improvement Effects 0.000 description 8
- 239000002609 medium Substances 0.000 description 8
- 230000003287 optical effect Effects 0.000 description 8
- 230000001988 toxicity Effects 0.000 description 8
- 231100000419 toxicity Toxicity 0.000 description 8
- 102000053602 DNA Human genes 0.000 description 7
- 108020004414 DNA Proteins 0.000 description 7
- 108091028043 Nucleic acid sequence Proteins 0.000 description 7
- 240000004808 Saccharomyces cerevisiae Species 0.000 description 7
- 230000001028 anti-proliverative effect Effects 0.000 description 7
- 230000001939 inductive effect Effects 0.000 description 7
- 230000009467 reduction Effects 0.000 description 7
- 231100000331 toxic Toxicity 0.000 description 7
- 230000002588 toxic effect Effects 0.000 description 7
- 238000013518 transcription Methods 0.000 description 7
- 230000035897 transcription Effects 0.000 description 7
- 102100032937 CD40 ligand Human genes 0.000 description 6
- 108010037362 Extracellular Matrix Proteins Proteins 0.000 description 6
- 102000010834 Extracellular Matrix Proteins Human genes 0.000 description 6
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 6
- 102000009465 Growth Factor Receptors Human genes 0.000 description 6
- 101000868215 Homo sapiens CD40 ligand Proteins 0.000 description 6
- 150000008575 L-amino acids Chemical group 0.000 description 6
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 6
- 230000002001 anti-metastasis Effects 0.000 description 6
- 230000006378 damage Effects 0.000 description 6
- 230000003247 decreasing effect Effects 0.000 description 6
- 208000035475 disorder Diseases 0.000 description 6
- 210000003743 erythrocyte Anatomy 0.000 description 6
- 210000002744 extracellular matrix Anatomy 0.000 description 6
- 230000003993 interaction Effects 0.000 description 6
- 238000005259 measurement Methods 0.000 description 6
- 239000012528 membrane Substances 0.000 description 6
- 239000005022 packaging material Substances 0.000 description 6
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 5
- 108060001084 Luciferase Proteins 0.000 description 5
- 108010073929 Vascular Endothelial Growth Factor A Proteins 0.000 description 5
- 102000005789 Vascular Endothelial Growth Factors Human genes 0.000 description 5
- 108010019530 Vascular Endothelial Growth Factors Proteins 0.000 description 5
- 238000004458 analytical method Methods 0.000 description 5
- 201000008274 breast adenocarcinoma Diseases 0.000 description 5
- 230000003833 cell viability Effects 0.000 description 5
- 230000008878 coupling Effects 0.000 description 5
- 238000010168 coupling process Methods 0.000 description 5
- 238000005859 coupling reaction Methods 0.000 description 5
- 229960001438 immunostimulant agent Drugs 0.000 description 5
- 239000003022 immunostimulating agent Substances 0.000 description 5
- 230000007774 longterm Effects 0.000 description 5
- 239000000463 material Substances 0.000 description 5
- 230000004048 modification Effects 0.000 description 5
- 238000012986 modification Methods 0.000 description 5
- 239000000546 pharmaceutical excipient Substances 0.000 description 5
- 102000040430 polynucleotide Human genes 0.000 description 5
- 108091033319 polynucleotide Proteins 0.000 description 5
- 239000002157 polynucleotide Substances 0.000 description 5
- 230000004044 response Effects 0.000 description 5
- 239000002904 solvent Substances 0.000 description 5
- 238000012360 testing method Methods 0.000 description 5
- QXZBMSIDSOZZHK-DOPDSADYSA-N 31362-50-2 Chemical compound C([C@@H](C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCSC)C(N)=O)NC(=O)CNC(=O)[C@@H](NC(=O)[C@H](C)NC(=O)[C@H](CC=1C2=CC=CC=C2NC=1)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CC(N)=O)NC(=O)CNC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H]1NC(=O)CC1)C(C)C)C1=CNC=N1 QXZBMSIDSOZZHK-DOPDSADYSA-N 0.000 description 4
- 208000024893 Acute lymphoblastic leukemia Diseases 0.000 description 4
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 4
- 102100024217 CAMPATH-1 antigen Human genes 0.000 description 4
- 102100027207 CD27 antigen Human genes 0.000 description 4
- 108010065524 CD52 Antigen Proteins 0.000 description 4
- 102100025221 CD70 antigen Human genes 0.000 description 4
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 4
- 241000196324 Embryophyta Species 0.000 description 4
- 102400001226 Gonadoliberin-2 Human genes 0.000 description 4
- 101710112036 Gonadoliberin-2 Proteins 0.000 description 4
- 108010009202 Growth Factor Receptors Proteins 0.000 description 4
- 102000003745 Hepatocyte Growth Factor Human genes 0.000 description 4
- 108090000100 Hepatocyte Growth Factor Proteins 0.000 description 4
- 101000914511 Homo sapiens CD27 antigen Proteins 0.000 description 4
- 101000934356 Homo sapiens CD70 antigen Proteins 0.000 description 4
- 101000878605 Homo sapiens Low affinity immunoglobulin epsilon Fc receptor Proteins 0.000 description 4
- 101000934338 Homo sapiens Myeloid cell surface antigen CD33 Proteins 0.000 description 4
- 101000581981 Homo sapiens Neural cell adhesion molecule 1 Proteins 0.000 description 4
- 101000914514 Homo sapiens T-cell-specific surface glycoprotein CD28 Proteins 0.000 description 4
- 101000851376 Homo sapiens Tumor necrosis factor receptor superfamily member 8 Proteins 0.000 description 4
- 239000002147 L01XE04 - Sunitinib Substances 0.000 description 4
- 239000002136 L01XE07 - Lapatinib Substances 0.000 description 4
- 102000023108 LH Receptors Human genes 0.000 description 4
- 108010011942 LH Receptors Proteins 0.000 description 4
- 102100038007 Low affinity immunoglobulin epsilon Fc receptor Human genes 0.000 description 4
- 239000005089 Luciferase Substances 0.000 description 4
- 241000699666 Mus <mouse, genus> Species 0.000 description 4
- 102100025243 Myeloid cell surface antigen CD33 Human genes 0.000 description 4
- 102100027347 Neural cell adhesion molecule 1 Human genes 0.000 description 4
- 206010061535 Ovarian neoplasm Diseases 0.000 description 4
- 208000007660 Residual Neoplasm Diseases 0.000 description 4
- 108010068542 Somatotropin Receptors Proteins 0.000 description 4
- 102100027213 T-cell-specific surface glycoprotein CD28 Human genes 0.000 description 4
- 102100036857 Tumor necrosis factor receptor superfamily member 8 Human genes 0.000 description 4
- 238000010521 absorption reaction Methods 0.000 description 4
- 230000001154 acute effect Effects 0.000 description 4
- 238000010171 animal model Methods 0.000 description 4
- 210000000481 breast Anatomy 0.000 description 4
- 210000004899 c-terminal region Anatomy 0.000 description 4
- 230000022534 cell killing Effects 0.000 description 4
- 238000006243 chemical reaction Methods 0.000 description 4
- 230000001086 cytosolic effect Effects 0.000 description 4
- 238000011161 development Methods 0.000 description 4
- 230000018109 developmental process Effects 0.000 description 4
- 238000002224 dissection Methods 0.000 description 4
- 206010020718 hyperplasia Diseases 0.000 description 4
- 230000002434 immunopotentiative effect Effects 0.000 description 4
- BCFGMOOMADDAQU-UHFFFAOYSA-N lapatinib Chemical compound O1C(CNCCS(=O)(=O)C)=CC=C1C1=CC=C(N=CN=C2NC=3C=C(Cl)C(OCC=4C=C(F)C=CC=4)=CC=3)C2=C1 BCFGMOOMADDAQU-UHFFFAOYSA-N 0.000 description 4
- 239000006166 lysate Substances 0.000 description 4
- 230000003211 malignant effect Effects 0.000 description 4
- 210000004962 mammalian cell Anatomy 0.000 description 4
- 230000007246 mechanism Effects 0.000 description 4
- 230000036961 partial effect Effects 0.000 description 4
- 229960004641 rituximab Drugs 0.000 description 4
- 229920002477 rna polymer Polymers 0.000 description 4
- 210000004927 skin cell Anatomy 0.000 description 4
- 238000003860 storage Methods 0.000 description 4
- 241000701161 unidentified adenovirus Species 0.000 description 4
- MTCFGRXMJLQNBG-REOHCLBHSA-N (2S)-2-Amino-3-hydroxypropansäure Chemical compound OC[C@H](N)C(O)=O MTCFGRXMJLQNBG-REOHCLBHSA-N 0.000 description 3
- 108091092568 Alarmone Proteins 0.000 description 3
- WVDDGKGOMKODPV-UHFFFAOYSA-N Benzyl alcohol Chemical compound OCC1=CC=CC=C1 WVDDGKGOMKODPV-UHFFFAOYSA-N 0.000 description 3
- 241000701822 Bovine papillomavirus Species 0.000 description 3
- 206010009944 Colon cancer Diseases 0.000 description 3
- 108010013369 Enteropeptidase Proteins 0.000 description 3
- 102100029727 Enteropeptidase Human genes 0.000 description 3
- 102100038595 Estrogen receptor Human genes 0.000 description 3
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 3
- 102000018233 Fibroblast Growth Factor Human genes 0.000 description 3
- 108050007372 Fibroblast Growth Factor Proteins 0.000 description 3
- 239000004471 Glycine Substances 0.000 description 3
- 241000238631 Hexapoda Species 0.000 description 3
- 108060003951 Immunoglobulin Proteins 0.000 description 3
- 108010021625 Immunoglobulin Fragments Proteins 0.000 description 3
- 102000008394 Immunoglobulin Fragments Human genes 0.000 description 3
- 108010050904 Interferons Proteins 0.000 description 3
- 102000014150 Interferons Human genes 0.000 description 3
- LRQKBLKVPFOOQJ-YFKPBYRVSA-N L-norleucine Chemical compound CCCC[C@H]([NH3+])C([O-])=O LRQKBLKVPFOOQJ-YFKPBYRVSA-N 0.000 description 3
- 239000005536 L01XE08 - Nilotinib Substances 0.000 description 3
- 229910019142 PO4 Inorganic materials 0.000 description 3
- 102000003982 Parathyroid hormone Human genes 0.000 description 3
- 108090000445 Parathyroid hormone Proteins 0.000 description 3
- 229920004890 Triton X-100 Polymers 0.000 description 3
- 241000700605 Viruses Species 0.000 description 3
- 230000009471 action Effects 0.000 description 3
- 230000000692 anti-sense effect Effects 0.000 description 3
- KBZOIRJILGZLEJ-LGYYRGKSSA-N argipressin Chemical compound C([C@H]1C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CSSC[C@@H](C(N[C@@H](CC=2C=CC(O)=CC=2)C(=O)N1)=O)N)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCCN=C(N)N)C(=O)NCC(N)=O)C1=CC=CC=C1 KBZOIRJILGZLEJ-LGYYRGKSSA-N 0.000 description 3
- 238000003556 assay Methods 0.000 description 3
- 210000000601 blood cell Anatomy 0.000 description 3
- 230000037396 body weight Effects 0.000 description 3
- 235000014633 carbohydrates Nutrition 0.000 description 3
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 3
- 230000008859 change Effects 0.000 description 3
- 210000004978 chinese hamster ovary cell Anatomy 0.000 description 3
- 238000012258 culturing Methods 0.000 description 3
- 208000031513 cyst Diseases 0.000 description 3
- 208000012106 cystic neoplasm Diseases 0.000 description 3
- 230000001472 cytotoxic effect Effects 0.000 description 3
- 230000034994 death Effects 0.000 description 3
- 230000006866 deterioration Effects 0.000 description 3
- 230000001627 detrimental effect Effects 0.000 description 3
- 239000003085 diluting agent Substances 0.000 description 3
- 239000002612 dispersion medium Substances 0.000 description 3
- 239000002552 dosage form Substances 0.000 description 3
- 239000003937 drug carrier Substances 0.000 description 3
- 229940126864 fibroblast growth factor Drugs 0.000 description 3
- 229940014144 folate Drugs 0.000 description 3
- 238000009472 formulation Methods 0.000 description 3
- 230000006870 function Effects 0.000 description 3
- 230000002209 hydrophobic effect Effects 0.000 description 3
- 102000018358 immunoglobulin Human genes 0.000 description 3
- 230000000091 immunopotentiator Effects 0.000 description 3
- 238000004519 manufacturing process Methods 0.000 description 3
- 239000003550 marker Substances 0.000 description 3
- 231100000682 maximum tolerated dose Toxicity 0.000 description 3
- 230000036457 multidrug resistance Effects 0.000 description 3
- 210000000663 muscle cell Anatomy 0.000 description 3
- VMGAPWLDMVPYIA-HIDZBRGKSA-N n'-amino-n-iminomethanimidamide Chemical compound N\N=C\N=N VMGAPWLDMVPYIA-HIDZBRGKSA-N 0.000 description 3
- 230000001613 neoplastic effect Effects 0.000 description 3
- 206010061311 nervous system neoplasm Diseases 0.000 description 3
- HHZIURLSWUIHRB-UHFFFAOYSA-N nilotinib Chemical compound C1=NC(C)=CN1C1=CC(NC(=O)C=2C=C(NC=3N=C(C=CN=3)C=3C=NC=CC=3)C(C)=CC=2)=CC(C(F)(F)F)=C1 HHZIURLSWUIHRB-UHFFFAOYSA-N 0.000 description 3
- GHLZUHZBBNDWHW-UHFFFAOYSA-N nonanamide Chemical compound CCCCCCCCC(N)=O GHLZUHZBBNDWHW-UHFFFAOYSA-N 0.000 description 3
- 238000004806 packaging method and process Methods 0.000 description 3
- 239000000199 parathyroid hormone Substances 0.000 description 3
- 229960001319 parathyroid hormone Drugs 0.000 description 3
- 239000012071 phase Substances 0.000 description 3
- 235000021317 phosphate Nutrition 0.000 description 3
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 3
- 238000000746 purification Methods 0.000 description 3
- 239000003488 releasing hormone Substances 0.000 description 3
- BOLDJAUMGUJJKM-LSDHHAIUSA-N renifolin D Natural products CC(=C)[C@@H]1Cc2c(O)c(O)ccc2[C@H]1CC(=O)c3ccc(O)cc3O BOLDJAUMGUJJKM-LSDHHAIUSA-N 0.000 description 3
- 230000035945 sensitivity Effects 0.000 description 3
- 230000004936 stimulating effect Effects 0.000 description 3
- 239000000725 suspension Substances 0.000 description 3
- 230000008685 targeting Effects 0.000 description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 3
- RTQWWZBSTRGEAV-PKHIMPSTSA-N 2-[[(2s)-2-[bis(carboxymethyl)amino]-3-[4-(methylcarbamoylamino)phenyl]propyl]-[2-[bis(carboxymethyl)amino]propyl]amino]acetic acid Chemical compound CNC(=O)NC1=CC=C(C[C@@H](CN(CC(C)N(CC(O)=O)CC(O)=O)CC(O)=O)N(CC(O)=O)CC(O)=O)C=C1 RTQWWZBSTRGEAV-PKHIMPSTSA-N 0.000 description 2
- SLXKOJJOQWFEFD-UHFFFAOYSA-N 6-aminohexanoic acid Chemical compound NCCCCCC(O)=O SLXKOJJOQWFEFD-UHFFFAOYSA-N 0.000 description 2
- KDCGOANMDULRCW-UHFFFAOYSA-N 7H-purine Chemical compound N1=CNC2=NC=NC2=C1 KDCGOANMDULRCW-UHFFFAOYSA-N 0.000 description 2
- 208000014697 Acute lymphocytic leukaemia Diseases 0.000 description 2
- 208000036762 Acute promyelocytic leukaemia Diseases 0.000 description 2
- 108010064733 Angiotensins Proteins 0.000 description 2
- 102000015427 Angiotensins Human genes 0.000 description 2
- MLDQJTXFUGDVEO-UHFFFAOYSA-N BAY-43-9006 Chemical compound C1=NC(C(=O)NC)=CC(OC=2C=CC(NC(=O)NC=3C=C(C(Cl)=CC=3)C(F)(F)F)=CC=2)=C1 MLDQJTXFUGDVEO-UHFFFAOYSA-N 0.000 description 2
- 241000894006 Bacteria Species 0.000 description 2
- 208000003174 Brain Neoplasms Diseases 0.000 description 2
- 102100036150 C-X-C motif chemokine 5 Human genes 0.000 description 2
- 108091026890 Coding region Proteins 0.000 description 2
- QNAYBMKLOCPYGJ-UWTATZPHSA-N D-alanine Chemical compound C[C@@H](N)C(O)=O QNAYBMKLOCPYGJ-UWTATZPHSA-N 0.000 description 2
- ROHFNLRQFUQHCH-RXMQYKEDSA-N D-leucine Chemical compound CC(C)C[C@@H](N)C(O)=O ROHFNLRQFUQHCH-RXMQYKEDSA-N 0.000 description 2
- 102000001301 EGF receptor Human genes 0.000 description 2
- 108060006698 EGF receptor Proteins 0.000 description 2
- YQYJSBFKSSDGFO-UHFFFAOYSA-N Epihygromycin Natural products OC1C(O)C(C(=O)C)OC1OC(C(=C1)O)=CC=C1C=C(C)C(=O)NC1C(O)C(O)C2OCOC2C1O YQYJSBFKSSDGFO-UHFFFAOYSA-N 0.000 description 2
- 108010007005 Estrogen Receptor alpha Proteins 0.000 description 2
- 102000008857 Ferritin Human genes 0.000 description 2
- 108050000784 Ferritin Proteins 0.000 description 2
- 238000008416 Ferritin Methods 0.000 description 2
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 2
- SXRSQZLOMIGNAQ-UHFFFAOYSA-N Glutaraldehyde Chemical compound O=CCCCC=O SXRSQZLOMIGNAQ-UHFFFAOYSA-N 0.000 description 2
- 206010018910 Haemolysis Diseases 0.000 description 2
- 101000947186 Homo sapiens C-X-C motif chemokine 5 Proteins 0.000 description 2
- 101000856395 Homo sapiens Cullin-9 Proteins 0.000 description 2
- SIKJAQJRHWYJAI-UHFFFAOYSA-N Indole Chemical compound C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 description 2
- 108090001117 Insulin-Like Growth Factor II Proteins 0.000 description 2
- 102000048143 Insulin-Like Growth Factor II Human genes 0.000 description 2
- 108010070716 Intercellular Signaling Peptides and Proteins Proteins 0.000 description 2
- 102000013691 Interleukin-17 Human genes 0.000 description 2
- 108050003558 Interleukin-17 Proteins 0.000 description 2
- 102000015696 Interleukins Human genes 0.000 description 2
- 108010063738 Interleukins Proteins 0.000 description 2
- QNAYBMKLOCPYGJ-REOHCLBHSA-N L-alanine Chemical compound C[C@H](N)C(O)=O QNAYBMKLOCPYGJ-REOHCLBHSA-N 0.000 description 2
- 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
- 231100000002 MTT assay Toxicity 0.000 description 2
- 238000000134 MTT assay Methods 0.000 description 2
- PEEHTFAAVSWFBL-UHFFFAOYSA-N Maleimide Chemical compound O=C1NC(=O)C=C1 PEEHTFAAVSWFBL-UHFFFAOYSA-N 0.000 description 2
- YJPIGAIKUZMOQA-UHFFFAOYSA-N Melatonin Natural products COC1=CC=C2N(C(C)=O)C=C(CCN)C2=C1 YJPIGAIKUZMOQA-UHFFFAOYSA-N 0.000 description 2
- NQTADLQHYWFPDB-UHFFFAOYSA-N N-Hydroxysuccinimide Chemical compound ON1C(=O)CCC1=O NQTADLQHYWFPDB-UHFFFAOYSA-N 0.000 description 2
- 206010029096 Neoplasm prostate Diseases 0.000 description 2
- 102000052812 Ornithine decarboxylases Human genes 0.000 description 2
- 108700005126 Ornithine decarboxylases Proteins 0.000 description 2
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 2
- 108010038512 Platelet-Derived Growth Factor Proteins 0.000 description 2
- 102000010780 Platelet-Derived Growth Factor Human genes 0.000 description 2
- 239000002202 Polyethylene glycol Substances 0.000 description 2
- 208000037062 Polyps Diseases 0.000 description 2
- 208000006664 Precursor Cell Lymphoblastic Leukemia-Lymphoma Diseases 0.000 description 2
- 108010057464 Prolactin Proteins 0.000 description 2
- 102000003946 Prolactin Human genes 0.000 description 2
- 108010087786 Prolactin-Releasing Hormone Proteins 0.000 description 2
- 102100028850 Prolactin-releasing peptide Human genes 0.000 description 2
- 208000033766 Prolymphocytic Leukemia Diseases 0.000 description 2
- 208000033826 Promyelocytic Acute Leukemia Diseases 0.000 description 2
- 206010060862 Prostate cancer Diseases 0.000 description 2
- 208000000236 Prostatic Neoplasms Diseases 0.000 description 2
- CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 description 2
- 101710100968 Receptor tyrosine-protein kinase erbB-2 Proteins 0.000 description 2
- 102100030086 Receptor tyrosine-protein kinase erbB-2 Human genes 0.000 description 2
- 108090000103 Relaxin Proteins 0.000 description 2
- 102000003743 Relaxin Human genes 0.000 description 2
- 102100028255 Renin Human genes 0.000 description 2
- 108090000783 Renin Proteins 0.000 description 2
- 201000000582 Retinoblastoma Diseases 0.000 description 2
- 108010086019 Secretin Proteins 0.000 description 2
- 102100037505 Secretin Human genes 0.000 description 2
- MTCFGRXMJLQNBG-UHFFFAOYSA-N Serine Natural products OCC(N)C(O)=O MTCFGRXMJLQNBG-UHFFFAOYSA-N 0.000 description 2
- 241000700584 Simplexvirus Species 0.000 description 2
- 102000013275 Somatomedins Human genes 0.000 description 2
- 208000031673 T-Cell Cutaneous Lymphoma Diseases 0.000 description 2
- 210000001744 T-lymphocyte Anatomy 0.000 description 2
- 241000723873 Tobacco mosaic virus Species 0.000 description 2
- 239000013504 Triton X-100 Substances 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
- KZSNJWFQEVHDMF-UHFFFAOYSA-N Valine Natural products CC(C)C(N)C(O)=O KZSNJWFQEVHDMF-UHFFFAOYSA-N 0.000 description 2
- 108010004977 Vasopressins Proteins 0.000 description 2
- 102000002852 Vasopressins Human genes 0.000 description 2
- 238000007792 addition Methods 0.000 description 2
- WNLRTRBMVRJNCN-UHFFFAOYSA-N adipic acid Chemical compound OC(=O)CCCCC(O)=O WNLRTRBMVRJNCN-UHFFFAOYSA-N 0.000 description 2
- 210000004404 adrenal cortex Anatomy 0.000 description 2
- 235000004279 alanine Nutrition 0.000 description 2
- 229960000548 alemtuzumab Drugs 0.000 description 2
- 150000001336 alkenes Chemical class 0.000 description 2
- 229940093740 amino acid and derivative Drugs 0.000 description 2
- 229960002684 aminocaproic acid Drugs 0.000 description 2
- 102000001307 androgen receptors Human genes 0.000 description 2
- 108010080146 androgen receptors Proteins 0.000 description 2
- 208000007502 anemia Diseases 0.000 description 2
- 210000004102 animal cell Anatomy 0.000 description 2
- 239000003242 anti bacterial agent Substances 0.000 description 2
- 238000011394 anticancer treatment Methods 0.000 description 2
- 230000009876 antimalignant effect Effects 0.000 description 2
- 238000013459 approach Methods 0.000 description 2
- 210000001106 artificial yeast chromosome Anatomy 0.000 description 2
- 235000010323 ascorbic acid Nutrition 0.000 description 2
- 229960005070 ascorbic acid Drugs 0.000 description 2
- 239000011668 ascorbic acid Substances 0.000 description 2
- 229940120638 avastin Drugs 0.000 description 2
- 108010042362 beta-Lipotropin Proteins 0.000 description 2
- 229960000397 bevacizumab Drugs 0.000 description 2
- 230000001588 bifunctional effect Effects 0.000 description 2
- 229960000074 biopharmaceutical Drugs 0.000 description 2
- 238000004820 blood count Methods 0.000 description 2
- GXJABQQUPOEUTA-RDJZCZTQSA-N bortezomib Chemical compound C([C@@H](C(=O)N[C@@H](CC(C)C)B(O)O)NC(=O)C=1N=CC=NC=1)C1=CC=CC=C1 GXJABQQUPOEUTA-RDJZCZTQSA-N 0.000 description 2
- 239000002775 capsule Substances 0.000 description 2
- 229910052799 carbon Inorganic materials 0.000 description 2
- 239000011111 cardboard Substances 0.000 description 2
- 239000000969 carrier Substances 0.000 description 2
- 150000003943 catecholamines Chemical class 0.000 description 2
- 229960005395 cetuximab Drugs 0.000 description 2
- 238000003776 cleavage reaction Methods 0.000 description 2
- 238000000576 coating method Methods 0.000 description 2
- 208000029742 colonic neoplasm Diseases 0.000 description 2
- 238000002648 combination therapy Methods 0.000 description 2
- 230000000295 complement effect Effects 0.000 description 2
- 239000002299 complementary DNA Substances 0.000 description 2
- 230000002596 correlated effect Effects 0.000 description 2
- 230000000875 corresponding effect Effects 0.000 description 2
- 201000007241 cutaneous T cell lymphoma Diseases 0.000 description 2
- 230000000445 cytocidal effect Effects 0.000 description 2
- 102000003675 cytokine receptors Human genes 0.000 description 2
- 231100000433 cytotoxic Toxicity 0.000 description 2
- 238000012217 deletion Methods 0.000 description 2
- 230000037430 deletion Effects 0.000 description 2
- 230000001419 dependent effect Effects 0.000 description 2
- 235000014113 dietary fatty acids Nutrition 0.000 description 2
- 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 2
- 239000006185 dispersion Substances 0.000 description 2
- 238000004090 dissolution Methods 0.000 description 2
- VLCYCQAOQCDTCN-UHFFFAOYSA-N eflornithine Chemical compound NCCCC(N)(C(F)F)C(O)=O VLCYCQAOQCDTCN-UHFFFAOYSA-N 0.000 description 2
- 239000000839 emulsion Substances 0.000 description 2
- 230000002124 endocrine Effects 0.000 description 2
- 239000003623 enhancer Substances 0.000 description 2
- 230000007613 environmental effect Effects 0.000 description 2
- 210000003527 eukaryotic cell Anatomy 0.000 description 2
- 229930195729 fatty acid Natural products 0.000 description 2
- 239000000194 fatty acid Substances 0.000 description 2
- 150000004665 fatty acids Chemical class 0.000 description 2
- 210000002950 fibroblast Anatomy 0.000 description 2
- XGALLCVXEZPNRQ-UHFFFAOYSA-N gefitinib Chemical compound C=12C=C(OCCCN3CCOCC3)C(OC)=CC2=NC=NC=1NC1=CC=C(F)C(Cl)=C1 XGALLCVXEZPNRQ-UHFFFAOYSA-N 0.000 description 2
- 230000002068 genetic effect Effects 0.000 description 2
- 238000010353 genetic engineering Methods 0.000 description 2
- ZDXPYRJPNDTMRX-UHFFFAOYSA-N glutamine Natural products OC(=O)C(N)CCC(N)=O ZDXPYRJPNDTMRX-UHFFFAOYSA-N 0.000 description 2
- 235000011187 glycerol Nutrition 0.000 description 2
- 208000014829 head and neck neoplasm Diseases 0.000 description 2
- 230000004217 heart function Effects 0.000 description 2
- 230000008588 hemolysis Effects 0.000 description 2
- 229940022353 herceptin Drugs 0.000 description 2
- 231100000171 higher toxicity Toxicity 0.000 description 2
- HNDVDQJCIGZPNO-UHFFFAOYSA-N histidine Natural products OC(=O)C(N)CC1=CN=CN1 HNDVDQJCIGZPNO-UHFFFAOYSA-N 0.000 description 2
- 125000000487 histidyl group Chemical group [H]N([H])C(C(=O)O*)C([H])([H])C1=C([H])N([H])C([H])=N1 0.000 description 2
- 125000001165 hydrophobic group Chemical group 0.000 description 2
- 229960001001 ibritumomab tiuxetan Drugs 0.000 description 2
- KTUFNOKKBVMGRW-UHFFFAOYSA-N imatinib Chemical compound C1CN(C)CCN1CC1=CC=C(C(=O)NC=2C=C(NC=3N=C(C=CN=3)C=3C=NC=CC=3)C(C)=CC=2)C=C1 KTUFNOKKBVMGRW-UHFFFAOYSA-N 0.000 description 2
- 229940079322 interferon Drugs 0.000 description 2
- 238000002955 isolation Methods 0.000 description 2
- 230000003907 kidney function Effects 0.000 description 2
- 229960004891 lapatinib Drugs 0.000 description 2
- 210000000265 leukocyte Anatomy 0.000 description 2
- 150000002632 lipids Chemical class 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- 230000003908 liver function Effects 0.000 description 2
- 244000144972 livestock Species 0.000 description 2
- 108010082117 matrigel Proteins 0.000 description 2
- 229960003987 melatonin Drugs 0.000 description 2
- DRLFMBDRBRZALE-UHFFFAOYSA-N melatonin Chemical compound COC1=CC=C2NC=C(CCNC(C)=O)C2=C1 DRLFMBDRBRZALE-UHFFFAOYSA-N 0.000 description 2
- 229910052751 metal Inorganic materials 0.000 description 2
- 239000002184 metal Substances 0.000 description 2
- LXCFILQKKLGQFO-UHFFFAOYSA-N methylparaben Chemical compound COC(=O)C1=CC=C(O)C=C1 LXCFILQKKLGQFO-UHFFFAOYSA-N 0.000 description 2
- 244000005700 microbiome Species 0.000 description 2
- 201000005962 mycosis fungoides Diseases 0.000 description 2
- LBWFXVZLPYTWQI-IPOVEDGCSA-N n-[2-(diethylamino)ethyl]-5-[(z)-(5-fluoro-2-oxo-1h-indol-3-ylidene)methyl]-2,4-dimethyl-1h-pyrrole-3-carboxamide;(2s)-2-hydroxybutanedioic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O.CCN(CC)CCNC(=O)C1=C(C)NC(\C=C/2C3=CC(F)=CC=C3NC\2=O)=C1C LBWFXVZLPYTWQI-IPOVEDGCSA-N 0.000 description 2
- 230000009826 neoplastic cell growth Effects 0.000 description 2
- 229960001346 nilotinib Drugs 0.000 description 2
- 238000010899 nucleation Methods 0.000 description 2
- JRZJOMJEPLMPRA-UHFFFAOYSA-N olefin Natural products CCCCCCCC=C JRZJOMJEPLMPRA-UHFFFAOYSA-N 0.000 description 2
- 230000002611 ovarian Effects 0.000 description 2
- 229960001972 panitumumab Drugs 0.000 description 2
- 238000010647 peptide synthesis reaction Methods 0.000 description 2
- 239000000816 peptidomimetic Substances 0.000 description 2
- 230000000144 pharmacologic effect Effects 0.000 description 2
- 239000010452 phosphate Substances 0.000 description 2
- 239000002953 phosphate buffered saline Substances 0.000 description 2
- 230000003863 physical function Effects 0.000 description 2
- 239000004033 plastic Substances 0.000 description 2
- 229920003023 plastic Polymers 0.000 description 2
- 229920001223 polyethylene glycol Polymers 0.000 description 2
- 229920000642 polymer Polymers 0.000 description 2
- 239000000843 powder Substances 0.000 description 2
- 208000025638 primary cutaneous T-cell non-Hodgkin lymphoma Diseases 0.000 description 2
- 229940097325 prolactin Drugs 0.000 description 2
- 239000002877 prolactin releasing hormone Substances 0.000 description 2
- 230000004043 responsiveness Effects 0.000 description 2
- 230000003307 reticuloendothelial effect Effects 0.000 description 2
- 230000001177 retroviral effect Effects 0.000 description 2
- 230000007017 scission Effects 0.000 description 2
- 238000012216 screening Methods 0.000 description 2
- 229960002101 secretin Drugs 0.000 description 2
- OWMZNFCDEHGFEP-NFBCVYDUSA-N secretin human Chemical compound C([C@@H](C(=O)N[C@H](C(=O)N[C@@H](CO)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCC(O)=O)C(=O)NCC(=O)N[C@@H](C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(N)=O)C(=O)NCC(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](C(C)C)C(N)=O)[C@@H](C)O)NC(=O)[C@@H](NC(=O)CNC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CO)NC(=O)[C@@H](N)CC=1NC=NC=1)[C@@H](C)O)C1=CC=CC=C1 OWMZNFCDEHGFEP-NFBCVYDUSA-N 0.000 description 2
- 230000019491 signal transduction Effects 0.000 description 2
- 239000000243 solution Substances 0.000 description 2
- 230000000087 stabilizing effect Effects 0.000 description 2
- 238000011272 standard treatment Methods 0.000 description 2
- UCSJYZPVAKXKNQ-HZYVHMACSA-N streptomycin Chemical compound CN[C@H]1[C@H](O)[C@@H](O)[C@H](CO)O[C@H]1O[C@@H]1[C@](C=O)(O)[C@H](C)O[C@H]1O[C@@H]1[C@@H](NC(N)=N)[C@H](O)[C@@H](NC(N)=N)[C@H](O)[C@H]1O UCSJYZPVAKXKNQ-HZYVHMACSA-N 0.000 description 2
- WINHZLLDWRZWRT-ATVHPVEESA-N sunitinib Chemical compound CCN(CC)CCNC(=O)C1=C(C)NC(\C=C/2C3=CC(F)=CC=C3NC\2=O)=C1C WINHZLLDWRZWRT-ATVHPVEESA-N 0.000 description 2
- 229960001796 sunitinib Drugs 0.000 description 2
- 229940034785 sutent Drugs 0.000 description 2
- 238000003786 synthesis reaction Methods 0.000 description 2
- 150000003568 thioethers Chemical class 0.000 description 2
- 230000001052 transient effect Effects 0.000 description 2
- 230000014616 translation Effects 0.000 description 2
- 229960000575 trastuzumab Drugs 0.000 description 2
- 230000004614 tumor growth Effects 0.000 description 2
- 102000003390 tumor necrosis factor Human genes 0.000 description 2
- 229940094060 tykerb Drugs 0.000 description 2
- 229960003726 vasopressin Drugs 0.000 description 2
- 230000003612 virological effect Effects 0.000 description 2
- 238000001262 western blot Methods 0.000 description 2
- 238000012447 xenograft mouse model Methods 0.000 description 2
- PORPENFLTBBHSG-MGBGTMOVSA-N 1,2-dihexadecanoyl-sn-glycerol-3-phosphate Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP(O)(O)=O)OC(=O)CCCCCCCCCCCCCCC PORPENFLTBBHSG-MGBGTMOVSA-N 0.000 description 1
- BDNKZNFMNDZQMI-UHFFFAOYSA-N 1,3-diisopropylcarbodiimide Chemical compound CC(C)N=C=NC(C)C BDNKZNFMNDZQMI-UHFFFAOYSA-N 0.000 description 1
- RTBFRGCFXZNCOE-UHFFFAOYSA-N 1-methylsulfonylpiperidin-4-one Chemical compound CS(=O)(=O)N1CCC(=O)CC1 RTBFRGCFXZNCOE-UHFFFAOYSA-N 0.000 description 1
- IIZPXYDJLKNOIY-JXPKJXOSSA-N 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCC\C=C/C\C=C/C\C=C/C\C=C/CCCCC IIZPXYDJLKNOIY-JXPKJXOSSA-N 0.000 description 1
- SEAXAKYIBMDIRL-ARORVFOUSA-N 4-amino-1-[(2r,3r,4s,5r)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]-1,3,5-triazin-2-one;4-amino-1-[(2r,4s,5r)-4-hydroxy-5-(hydroxymethyl)oxolan-2-yl]-1,3,5-triazin-2-one Chemical compound O=C1N=C(N)N=CN1[C@@H]1O[C@H](CO)[C@@H](O)C1.O=C1N=C(N)N=CN1[C@H]1[C@H](O)[C@H](O)[C@@H](CO)O1 SEAXAKYIBMDIRL-ARORVFOUSA-N 0.000 description 1
- XAUDJQYHKZQPEU-KVQBGUIXSA-N 5-aza-2'-deoxycytidine Chemical compound O=C1N=C(N)N=CN1[C@@H]1O[C@H](CO)[C@@H](O)C1 XAUDJQYHKZQPEU-KVQBGUIXSA-N 0.000 description 1
- LJIRBXZDQGQUOO-KVTDHHQDSA-N 6-amino-3-[(2r,3r,4s,5r)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]-1,4-dihydro-1,3,5-triazin-2-one Chemical compound C1NC(N)=NC(=O)N1[C@H]1[C@H](O)[C@H](O)[C@@H](CO)O1 LJIRBXZDQGQUOO-KVTDHHQDSA-N 0.000 description 1
- 101150094949 APRT gene Proteins 0.000 description 1
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
- 208000031261 Acute myeloid leukaemia Diseases 0.000 description 1
- 108010024223 Adenine phosphoribosyltransferase Proteins 0.000 description 1
- 208000016683 Adult T-cell leukemia/lymphoma Diseases 0.000 description 1
- 108020004491 Antisense DNA Proteins 0.000 description 1
- 108020005544 Antisense RNA Proteins 0.000 description 1
- 239000004475 Arginine Substances 0.000 description 1
- DCXYFEDJOCDNAF-UHFFFAOYSA-N Asparagine Natural products OC(=O)C(N)CC(N)=O DCXYFEDJOCDNAF-UHFFFAOYSA-N 0.000 description 1
- 208000023275 Autoimmune disease Diseases 0.000 description 1
- 208000010839 B-cell chronic lymphocytic leukemia Diseases 0.000 description 1
- 208000032791 BCR-ABL1 positive chronic myelogenous leukemia Diseases 0.000 description 1
- 101150072950 BRCA1 gene Proteins 0.000 description 1
- 102100026189 Beta-galactosidase Human genes 0.000 description 1
- 241000283690 Bos taurus Species 0.000 description 1
- 101001011741 Bos taurus Insulin Proteins 0.000 description 1
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 1
- 108700012434 CCL3 Proteins 0.000 description 1
- 108060001064 Calcitonin Proteins 0.000 description 1
- 102000055006 Calcitonin Human genes 0.000 description 1
- 241000282472 Canis lupus familiaris Species 0.000 description 1
- 241000283707 Capra Species 0.000 description 1
- 201000000274 Carcinosarcoma Diseases 0.000 description 1
- 241000701489 Cauliflower mosaic virus Species 0.000 description 1
- 241000700199 Cavia porcellus Species 0.000 description 1
- 102000016289 Cell Adhesion Molecules Human genes 0.000 description 1
- 108010067225 Cell Adhesion Molecules Proteins 0.000 description 1
- 102000000013 Chemokine CCL3 Human genes 0.000 description 1
- 102000009410 Chemokine receptor Human genes 0.000 description 1
- 108050000299 Chemokine receptor Proteins 0.000 description 1
- 101800001982 Cholecystokinin Proteins 0.000 description 1
- 102100025841 Cholecystokinin Human genes 0.000 description 1
- 102100031196 Choriogonadotropin subunit beta 3 Human genes 0.000 description 1
- 208000001333 Colorectal Neoplasms Diseases 0.000 description 1
- 241000699802 Cricetulus griseus Species 0.000 description 1
- 101150074155 DHFR gene Proteins 0.000 description 1
- 238000012270 DNA recombination Methods 0.000 description 1
- 241000238557 Decapoda Species 0.000 description 1
- 102000015554 Dopamine receptor Human genes 0.000 description 1
- 108050004812 Dopamine receptor Proteins 0.000 description 1
- 208000000471 Dysplastic Nevus Syndrome Diseases 0.000 description 1
- 206010062805 Dysplastic naevus Diseases 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
- UPEZCKBFRMILAV-JNEQICEOSA-N Ecdysone Natural products O=C1[C@H]2[C@@](C)([C@@H]3C([C@@]4(O)[C@@](C)([C@H]([C@H]([C@@H](O)CCC(O)(C)C)C)CC4)CC3)=C1)C[C@H](O)[C@H](O)C2 UPEZCKBFRMILAV-JNEQICEOSA-N 0.000 description 1
- 241000283086 Equidae Species 0.000 description 1
- 241000701959 Escherichia virus Lambda Species 0.000 description 1
- 108010085330 Estradiol Receptors Proteins 0.000 description 1
- VGGSQFUCUMXWEO-UHFFFAOYSA-N Ethene Chemical compound C=C VGGSQFUCUMXWEO-UHFFFAOYSA-N 0.000 description 1
- 239000005977 Ethylene Substances 0.000 description 1
- 108010074860 Factor Xa Proteins 0.000 description 1
- 201000006107 Familial adenomatous polyposis Diseases 0.000 description 1
- 108010008177 Fd immunoglobulins Proteins 0.000 description 1
- 241000282326 Felis catus Species 0.000 description 1
- 102400000921 Gastrin Human genes 0.000 description 1
- 108010052343 Gastrins Proteins 0.000 description 1
- 108010010803 Gelatin Proteins 0.000 description 1
- 206010064571 Gene mutation Diseases 0.000 description 1
- 208000034826 Genetic Predisposition to Disease Diseases 0.000 description 1
- 101800001586 Ghrelin Proteins 0.000 description 1
- 102400000442 Ghrelin-28 Human genes 0.000 description 1
- 102000051325 Glucagon Human genes 0.000 description 1
- 108060003199 Glucagon Proteins 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
- WHUUTDBJXJRKMK-UHFFFAOYSA-N Glutamic acid Natural products OC(=O)C(N)CCC(O)=O WHUUTDBJXJRKMK-UHFFFAOYSA-N 0.000 description 1
- 239000000095 Growth Hormone-Releasing Hormone Substances 0.000 description 1
- 208000017604 Hodgkin disease Diseases 0.000 description 1
- 208000021519 Hodgkin lymphoma Diseases 0.000 description 1
- 208000010747 Hodgkins lymphoma Diseases 0.000 description 1
- 241001272567 Hominoidea Species 0.000 description 1
- 241000282412 Homo Species 0.000 description 1
- 101000776619 Homo sapiens Choriogonadotropin subunit beta 3 Proteins 0.000 description 1
- 101001091205 Homo sapiens KiSS-1 receptor Proteins 0.000 description 1
- VSNHCAURESNICA-UHFFFAOYSA-N Hydroxyurea Chemical compound NC(=O)NO VSNHCAURESNICA-UHFFFAOYSA-N 0.000 description 1
- 241000282596 Hylobatidae Species 0.000 description 1
- 108010091358 Hypoxanthine Phosphoribosyltransferase Proteins 0.000 description 1
- 108010054477 Immunoglobulin Fab Fragments Proteins 0.000 description 1
- 102000001706 Immunoglobulin Fab Fragments Human genes 0.000 description 1
- 108010091135 Immunoglobulin Fc Fragments Proteins 0.000 description 1
- 102000018071 Immunoglobulin Fc Fragments Human genes 0.000 description 1
- 102000017727 Immunoglobulin Variable Region Human genes 0.000 description 1
- 108010067060 Immunoglobulin Variable Region Proteins 0.000 description 1
- 102000005755 Intercellular Signaling Peptides and Proteins Human genes 0.000 description 1
- 108091092195 Intron Proteins 0.000 description 1
- 102100034845 KiSS-1 receptor Human genes 0.000 description 1
- 108010012048 Kisspeptins Proteins 0.000 description 1
- 102000013599 Kisspeptins Human genes 0.000 description 1
- AGPKZVBTJJNPAG-WHFBIAKZSA-N L-isoleucine Chemical compound CC[C@H](C)[C@H](N)C(O)=O AGPKZVBTJJNPAG-WHFBIAKZSA-N 0.000 description 1
- ROHFNLRQFUQHCH-YFKPBYRVSA-N L-leucine Chemical compound CC(C)C[C@H](N)C(O)=O ROHFNLRQFUQHCH-YFKPBYRVSA-N 0.000 description 1
- FFEARJCKVFRZRR-BYPYZUCNSA-N L-methionine Chemical compound CSCC[C@H](N)C(O)=O FFEARJCKVFRZRR-BYPYZUCNSA-N 0.000 description 1
- KZSNJWFQEVHDMF-BYPYZUCNSA-N L-valine Chemical compound CC(C)[C@H](N)C(O)=O KZSNJWFQEVHDMF-BYPYZUCNSA-N 0.000 description 1
- 208000006404 Large Granular Lymphocytic Leukemia Diseases 0.000 description 1
- 108090001090 Lectins Proteins 0.000 description 1
- 102000004856 Lectins Human genes 0.000 description 1
- ROHFNLRQFUQHCH-UHFFFAOYSA-N Leucine Natural products CC(C)CC(N)C(O)=O ROHFNLRQFUQHCH-UHFFFAOYSA-N 0.000 description 1
- 239000004472 Lysine Substances 0.000 description 1
- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 1
- 108010000410 MSH receptor Proteins 0.000 description 1
- 241000282553 Macaca Species 0.000 description 1
- 208000035490 Megakaryoblastic Acute Leukemia Diseases 0.000 description 1
- 102100034216 Melanocyte-stimulating hormone receptor Human genes 0.000 description 1
- 206010027145 Melanocytic naevus Diseases 0.000 description 1
- 102000003792 Metallothionein Human genes 0.000 description 1
- 108090000157 Metallothionein Proteins 0.000 description 1
- 101100261636 Methanothermobacter marburgensis (strain ATCC BAA-927 / DSM 2133 / JCM 14651 / NBRC 100331 / OCM 82 / Marburg) trpB2 gene Proteins 0.000 description 1
- 102000029749 Microtubule Human genes 0.000 description 1
- 108091022875 Microtubule Proteins 0.000 description 1
- 241000713333 Mouse mammary tumor virus Species 0.000 description 1
- 208000034578 Multiple myelomas Diseases 0.000 description 1
- 229930193140 Neomycin Natural products 0.000 description 1
- 208000007256 Nevus Diseases 0.000 description 1
- 108091034117 Oligonucleotide Proteins 0.000 description 1
- 102000002512 Orexin Human genes 0.000 description 1
- 229940122060 Ornithine decarboxylase inhibitor Drugs 0.000 description 1
- 241000283973 Oryctolagus cuniculus Species 0.000 description 1
- 102000016979 Other receptors Human genes 0.000 description 1
- 241000282579 Pan Species 0.000 description 1
- 206010061902 Pancreatic neoplasm Diseases 0.000 description 1
- 241001494479 Pecora Species 0.000 description 1
- 229930182555 Penicillin Natural products 0.000 description 1
- JGSARLDLIJGVTE-MBNYWOFBSA-N Penicillin G Chemical compound N([C@H]1[C@H]2SC([C@@H](N2C1=O)C(O)=O)(C)C)C(=O)CC1=CC=CC=C1 JGSARLDLIJGVTE-MBNYWOFBSA-N 0.000 description 1
- 208000027190 Peripheral T-cell lymphomas Diseases 0.000 description 1
- 101000622060 Photinus pyralis Luciferin 4-monooxygenase Proteins 0.000 description 1
- 101100124346 Photorhabdus laumondii subsp. laumondii (strain DSM 15139 / CIP 105565 / TT01) hisCD gene Proteins 0.000 description 1
- 229920002685 Polyoxyl 35CastorOil Polymers 0.000 description 1
- 241000282405 Pongo abelii Species 0.000 description 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
- 241000288906 Primates Species 0.000 description 1
- 108010001267 Protein Subunits Proteins 0.000 description 1
- 102000002067 Protein Subunits Human genes 0.000 description 1
- 241000700159 Rattus Species 0.000 description 1
- 201000010208 Seminoma Diseases 0.000 description 1
- 102220497176 Small vasohibin-binding protein_T47D_mutation Human genes 0.000 description 1
- DWAQJAXMDSEUJJ-UHFFFAOYSA-M Sodium bisulfite Chemical compound [Na+].OS([O-])=O DWAQJAXMDSEUJJ-UHFFFAOYSA-M 0.000 description 1
- 102100022831 Somatoliberin Human genes 0.000 description 1
- 101710142969 Somatoliberin Proteins 0.000 description 1
- 108050001286 Somatostatin Receptor Proteins 0.000 description 1
- 102000011096 Somatostatin receptor Human genes 0.000 description 1
- 101000857870 Squalus acanthias Gonadoliberin Proteins 0.000 description 1
- 108091081024 Start codon Proteins 0.000 description 1
- 208000005718 Stomach Neoplasms Diseases 0.000 description 1
- KDYFGRWQOYBRFD-UHFFFAOYSA-N Succinic acid Natural products OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 description 1
- 241000282887 Suidae Species 0.000 description 1
- 208000031672 T-Cell Peripheral Lymphoma Diseases 0.000 description 1
- 201000008717 T-cell large granular lymphocyte leukemia Diseases 0.000 description 1
- 208000024313 Testicular Neoplasms Diseases 0.000 description 1
- 206010057644 Testis cancer Diseases 0.000 description 1
- FZWLAAWBMGSTSO-UHFFFAOYSA-N Thiazole Chemical compound C1=CSC=N1 FZWLAAWBMGSTSO-UHFFFAOYSA-N 0.000 description 1
- 102100036407 Thioredoxin Human genes 0.000 description 1
- AYFVYJQAPQTCCC-UHFFFAOYSA-N Threonine Natural products CC(O)C(N)C(O)=O AYFVYJQAPQTCCC-UHFFFAOYSA-N 0.000 description 1
- 239000004473 Threonine Substances 0.000 description 1
- 108020004440 Thymidine kinase Proteins 0.000 description 1
- 108010033576 Transferrin Receptors Proteins 0.000 description 1
- 102100026144 Transferrin receptor protein 1 Human genes 0.000 description 1
- 102000006747 Transforming Growth Factor alpha Human genes 0.000 description 1
- 108010050144 Triptorelin Pamoate Proteins 0.000 description 1
- 108060008683 Tumor Necrosis Factor Receptor Proteins 0.000 description 1
- 102000044209 Tumor Suppressor Genes Human genes 0.000 description 1
- 108700025716 Tumor Suppressor Genes Proteins 0.000 description 1
- 102100031988 Tumor necrosis factor ligand superfamily member 6 Human genes 0.000 description 1
- 108050002568 Tumor necrosis factor ligand superfamily member 6 Proteins 0.000 description 1
- 208000002495 Uterine Neoplasms Diseases 0.000 description 1
- 241000700618 Vaccinia virus Species 0.000 description 1
- 102100026383 Vasopressin-neurophysin 2-copeptin Human genes 0.000 description 1
- 208000033559 Waldenström macroglobulinemia Diseases 0.000 description 1
- JLCPHMBAVCMARE-UHFFFAOYSA-N [3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-[[3-[[3-[[3-[[3-[[3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-hydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methyl [5-(6-aminopurin-9-yl)-2-(hydroxymethyl)oxolan-3-yl] hydrogen phosphate Polymers Cc1cn(C2CC(OP(O)(=O)OCC3OC(CC3OP(O)(=O)OCC3OC(CC3O)n3cnc4c3nc(N)[nH]c4=O)n3cnc4c3nc(N)[nH]c4=O)C(COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3CO)n3cnc4c(N)ncnc34)n3ccc(N)nc3=O)n3cnc4c(N)ncnc34)n3ccc(N)nc3=O)n3ccc(N)nc3=O)n3ccc(N)nc3=O)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cc(C)c(=O)[nH]c3=O)n3cc(C)c(=O)[nH]c3=O)n3ccc(N)nc3=O)n3cc(C)c(=O)[nH]c3=O)n3cnc4c3nc(N)[nH]c4=O)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)O2)c(=O)[nH]c1=O JLCPHMBAVCMARE-UHFFFAOYSA-N 0.000 description 1
- 239000003070 absorption delaying agent Substances 0.000 description 1
- 230000003213 activating effect Effects 0.000 description 1
- 230000004913 activation Effects 0.000 description 1
- 239000004480 active ingredient Substances 0.000 description 1
- 208000021841 acute erythroid leukemia Diseases 0.000 description 1
- 208000013593 acute megakaryoblastic leukemia Diseases 0.000 description 1
- 208000020700 acute megakaryocytic leukemia Diseases 0.000 description 1
- 208000036676 acute undifferentiated leukemia Diseases 0.000 description 1
- 239000001361 adipic acid Substances 0.000 description 1
- 235000011037 adipic acid Nutrition 0.000 description 1
- 201000005188 adrenal gland cancer Diseases 0.000 description 1
- 208000024447 adrenal gland neoplasm Diseases 0.000 description 1
- 201000006966 adult T-cell leukemia Diseases 0.000 description 1
- 238000001261 affinity purification Methods 0.000 description 1
- 230000002776 aggregation Effects 0.000 description 1
- 238000004220 aggregation Methods 0.000 description 1
- UPEZCKBFRMILAV-UHFFFAOYSA-N alpha-Ecdysone Natural products C1C(O)C(O)CC2(C)C(CCC3(C(C(C(O)CCC(C)(C)O)C)CCC33O)C)C3=CC(=O)C21 UPEZCKBFRMILAV-UHFFFAOYSA-N 0.000 description 1
- 150000003862 amino acid derivatives Chemical class 0.000 description 1
- 125000006295 amino methylene group Chemical group [H]N(*)C([H])([H])* 0.000 description 1
- 229940126575 aminoglycoside Drugs 0.000 description 1
- JFCQEDHGNNZCLN-UHFFFAOYSA-N anhydrous glutaric acid Natural products OC(=O)CCCC(O)=O JFCQEDHGNNZCLN-UHFFFAOYSA-N 0.000 description 1
- 208000022531 anorexia Diseases 0.000 description 1
- 230000000844 anti-bacterial effect Effects 0.000 description 1
- 238000011319 anticancer therapy Methods 0.000 description 1
- 229940121375 antifungal agent Drugs 0.000 description 1
- 239000003429 antifungal agent Substances 0.000 description 1
- 229940045719 antineoplastic alkylating agent nitrosoureas Drugs 0.000 description 1
- 239000003963 antioxidant agent Substances 0.000 description 1
- 235000006708 antioxidants Nutrition 0.000 description 1
- 239000003816 antisense DNA Substances 0.000 description 1
- 238000003782 apoptosis assay Methods 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 1
- 235000009582 asparagine Nutrition 0.000 description 1
- 229960001230 asparagine Drugs 0.000 description 1
- 150000001507 asparagine derivatives Chemical class 0.000 description 1
- 235000003704 aspartic acid Nutrition 0.000 description 1
- CKLJMWTZIZZHCS-REOHCLBHSA-N aspartic acid group Chemical class N[C@@H](CC(=O)O)C(=O)O CKLJMWTZIZZHCS-REOHCLBHSA-N 0.000 description 1
- 230000003416 augmentation Effects 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
- 230000001580 bacterial effect Effects 0.000 description 1
- 230000003385 bacteriostatic effect Effects 0.000 description 1
- 230000008901 benefit Effects 0.000 description 1
- 235000019445 benzyl alcohol Nutrition 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
- 108010005774 beta-Galactosidase Proteins 0.000 description 1
- OQFSQFPPLPISGP-UHFFFAOYSA-N beta-carboxyaspartic acid Natural products OC(=O)C(N)C(C(O)=O)C(O)=O OQFSQFPPLPISGP-UHFFFAOYSA-N 0.000 description 1
- GAQNUGISBQJMKO-YFKPBYRVSA-N beta-citrylglutamic acid Chemical compound OC(=O)CC[C@@H](C(O)=O)NC(=O)C(O)(CC(O)=O)CC(O)=O GAQNUGISBQJMKO-YFKPBYRVSA-N 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
- 210000004204 blood vessel Anatomy 0.000 description 1
- 208000015322 bone marrow disease Diseases 0.000 description 1
- IXIBAKNTJSCKJM-BUBXBXGNSA-N bovine insulin Chemical compound C([C@@H](C(=O)N[C@@H](CC(C)C)C(=O)N[C@H]1CSSC[C@H]2C(=O)N[C@@H](C)C(=O)N[C@@H](CO)C(=O)N[C@H](C(=O)N[C@H](C(N[C@@H](CO)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC=3C=CC(O)=CC=3)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC=3C=CC(O)=CC=3)C(=O)N[C@@H](CSSC[C@H](NC(=O)[C@H](C(C)C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC=3C=CC(O)=CC=3)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](C)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C(C)C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC=3NC=NC=3)NC(=O)[C@H](CO)NC(=O)CNC1=O)C(=O)NCC(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)NCC(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N[C@@H]([C@@H](C)O)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](C)C(O)=O)C(=O)N[C@@H](CC(N)=O)C(O)=O)=O)CSSC[C@@H](C(N2)=O)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C(C)C)NC(=O)[C@@H](NC(=O)CN)[C@@H](C)CC)C(C)C)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CC(N)=O)NC(=O)[C@@H](NC(=O)[C@@H](N)CC=1C=CC=CC=1)C(C)C)C1=CN=CN1 IXIBAKNTJSCKJM-BUBXBXGNSA-N 0.000 description 1
- 239000000872 buffer Substances 0.000 description 1
- KDYFGRWQOYBRFD-NUQCWPJISA-N butanedioic acid Chemical compound O[14C](=O)CC[14C](O)=O KDYFGRWQOYBRFD-NUQCWPJISA-N 0.000 description 1
- BBBFJLBPOGFECG-VJVYQDLKSA-N calcitonin Chemical compound N([C@H](C(=O)N[C@@H](CC(C)C)C(=O)NCC(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC=1NC=NC=1)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(=O)NCC(=O)N[C@@H](CO)C(=O)NCC(=O)N[C@@H]([C@@H](C)O)C(=O)N1[C@@H](CCC1)C(N)=O)C(C)C)C(=O)[C@@H]1CSSC[C@H](N)C(=O)N[C@@H](CO)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CO)C(=O)N[C@@H]([C@@H](C)O)C(=O)N1 BBBFJLBPOGFECG-VJVYQDLKSA-N 0.000 description 1
- 229960004015 calcitonin Drugs 0.000 description 1
- 229960004562 carboplatin Drugs 0.000 description 1
- 150000001735 carboxylic acids Chemical class 0.000 description 1
- 231100000357 carcinogen Toxicity 0.000 description 1
- 239000003183 carcinogenic agent Substances 0.000 description 1
- 125000002091 cationic group Chemical group 0.000 description 1
- 150000001768 cations Chemical class 0.000 description 1
- 238000004113 cell culture Methods 0.000 description 1
- 230000006369 cell cycle progression Effects 0.000 description 1
- 230000032823 cell division Effects 0.000 description 1
- 238000002659 cell therapy Methods 0.000 description 1
- 238000003570 cell viability assay Methods 0.000 description 1
- 230000001413 cellular effect Effects 0.000 description 1
- 230000007541 cellular toxicity Effects 0.000 description 1
- 239000002738 chelating agent Substances 0.000 description 1
- AOXOCDRNSPFDPE-UKEONUMOSA-N chembl413654 Chemical compound C([C@H](C(=O)NCC(=O)N[C@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@H](CCSC)C(=O)N[C@H](CC(O)=O)C(=O)N[C@H](CC=1C=CC=CC=1)C(N)=O)NC(=O)[C@@H](C)NC(=O)[C@@H](CCC(O)=O)NC(=O)[C@@H](CCC(O)=O)NC(=O)[C@@H](CCC(O)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC=1C2=CC=CC=C2NC=1)NC(=O)[C@H]1N(CCC1)C(=O)CNC(=O)[C@@H](N)CCC(O)=O)C1=CC=C(O)C=C1 AOXOCDRNSPFDPE-UKEONUMOSA-N 0.000 description 1
- 238000001311 chemical methods and process Methods 0.000 description 1
- 238000007385 chemical modification Methods 0.000 description 1
- 229940107137 cholecystokinin Drugs 0.000 description 1
- 210000000349 chromosome Anatomy 0.000 description 1
- 230000001684 chronic effect Effects 0.000 description 1
- 150000001860 citric acid derivatives Chemical class 0.000 description 1
- 208000029664 classic familial adenomatous polyposis Diseases 0.000 description 1
- 238000010367 cloning Methods 0.000 description 1
- 239000011248 coating agent Substances 0.000 description 1
- 238000004891 communication Methods 0.000 description 1
- 230000001609 comparable effect Effects 0.000 description 1
- 230000000052 comparative effect Effects 0.000 description 1
- 239000003184 complementary RNA Substances 0.000 description 1
- 238000004590 computer program Methods 0.000 description 1
- 239000000470 constituent Substances 0.000 description 1
- 239000013078 crystal Substances 0.000 description 1
- 229960000684 cytarabine Drugs 0.000 description 1
- 108010057085 cytokine receptors Proteins 0.000 description 1
- 230000001461 cytolytic effect Effects 0.000 description 1
- 229960003603 decitabine Drugs 0.000 description 1
- 206010061428 decreased appetite Diseases 0.000 description 1
- 230000002950 deficient Effects 0.000 description 1
- 230000003218 derepressive effect Effects 0.000 description 1
- 238000013461 design Methods 0.000 description 1
- 230000000368 destabilizing effect Effects 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 239000003599 detergent Substances 0.000 description 1
- 206010012601 diabetes mellitus Diseases 0.000 description 1
- 150000001991 dicarboxylic acids Chemical class 0.000 description 1
- 230000004069 differentiation Effects 0.000 description 1
- 230000001079 digestive effect Effects 0.000 description 1
- UGMCXQCYOVCMTB-UHFFFAOYSA-K dihydroxy(stearato)aluminium Chemical compound CCCCCCCCCCCCCCCCCC(=O)O[Al](O)O UGMCXQCYOVCMTB-UHFFFAOYSA-K 0.000 description 1
- 239000003534 dna topoisomerase inhibitor Substances 0.000 description 1
- 238000012377 drug delivery Methods 0.000 description 1
- 230000009977 dual effect Effects 0.000 description 1
- UPEZCKBFRMILAV-JMZLNJERSA-N ecdysone Chemical compound C1[C@@H](O)[C@@H](O)C[C@]2(C)[C@@H](CC[C@@]3([C@@H]([C@@H]([C@H](O)CCC(C)(C)O)C)CC[C@]33O)C)C3=CC(=O)[C@@H]21 UPEZCKBFRMILAV-JMZLNJERSA-N 0.000 description 1
- 230000008030 elimination Effects 0.000 description 1
- 238000003379 elimination reaction Methods 0.000 description 1
- 230000008451 emotion Effects 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 210000002919 epithelial cell Anatomy 0.000 description 1
- 210000000981 epithelium Anatomy 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- 102000015694 estrogen receptors Human genes 0.000 description 1
- 108010038795 estrogen receptors Proteins 0.000 description 1
- AEOCXXJPGCBFJA-UHFFFAOYSA-N ethionamide Chemical compound CCC1=CC(C(N)=S)=CC=N1 AEOCXXJPGCBFJA-UHFFFAOYSA-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
- 229960005420 etoposide Drugs 0.000 description 1
- 230000005713 exacerbation Effects 0.000 description 1
- NMUSYJAQQFHJEW-ARQDHWQXSA-N fazarabine Chemical compound O=C1N=C(N)N=CN1[C@H]1[C@@H](O)[C@H](O)[C@@H](CO)O1 NMUSYJAQQFHJEW-ARQDHWQXSA-N 0.000 description 1
- 239000012894 fetal calf serum Substances 0.000 description 1
- 230000001605 fetal effect Effects 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
- 239000011888 foil Substances 0.000 description 1
- 206010017758 gastric cancer Diseases 0.000 description 1
- 210000001035 gastrointestinal tract Anatomy 0.000 description 1
- 238000001502 gel electrophoresis Methods 0.000 description 1
- 239000008273 gelatin Substances 0.000 description 1
- 229920000159 gelatin Polymers 0.000 description 1
- 235000019322 gelatine Nutrition 0.000 description 1
- 235000011852 gelatine desserts Nutrition 0.000 description 1
- 229960005277 gemcitabine Drugs 0.000 description 1
- SDUQYLNIPVEERB-QPPQHZFASA-N gemcitabine Chemical compound O=C1N=C(N)C=CN1[C@H]1C(F)(F)[C@H](O)[C@@H](CO)O1 SDUQYLNIPVEERB-QPPQHZFASA-N 0.000 description 1
- 238000012224 gene deletion Methods 0.000 description 1
- BGHSOEHUOOAYMY-JTZMCQEISA-N ghrelin Chemical compound C([C@@H](C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CO)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC=1N=CNC=1)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCCCN)C(=O)N1[C@@H](CCC1)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](C)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(N)=O)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O)NC(=O)[C@H](CO)NC(=O)[C@H](CO)NC(=O)CN)C1=CC=CC=C1 BGHSOEHUOOAYMY-JTZMCQEISA-N 0.000 description 1
- 230000000762 glandular Effects 0.000 description 1
- 239000011521 glass Substances 0.000 description 1
- MASNOZXLGMXCHN-ZLPAWPGGSA-N glucagon Chemical compound C([C@@H](C(=O)N[C@H](C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(O)=O)C(C)C)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](C)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CO)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CO)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@@H](NC(=O)CNC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CO)NC(=O)[C@@H](N)CC=1NC=NC=1)[C@@H](C)O)[C@@H](C)O)C1=CC=CC=C1 MASNOZXLGMXCHN-ZLPAWPGGSA-N 0.000 description 1
- 229960004666 glucagon Drugs 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- 235000013922 glutamic acid Nutrition 0.000 description 1
- 239000004220 glutamic acid Substances 0.000 description 1
- 239000002434 gonadorelin derivative Substances 0.000 description 1
- 229940035638 gonadotropin-releasing hormone Drugs 0.000 description 1
- 239000008187 granular material Substances 0.000 description 1
- 210000002768 hair cell Anatomy 0.000 description 1
- 230000035876 healing Effects 0.000 description 1
- 210000002216 heart Anatomy 0.000 description 1
- 101150113423 hisD gene Proteins 0.000 description 1
- 238000002744 homologous recombination Methods 0.000 description 1
- 230000006801 homologous recombination Effects 0.000 description 1
- 229960001330 hydroxycarbamide Drugs 0.000 description 1
- 238000003365 immunocytochemistry Methods 0.000 description 1
- 230000002163 immunogen Effects 0.000 description 1
- 229940072221 immunoglobulins Drugs 0.000 description 1
- 239000007943 implant Substances 0.000 description 1
- PZOUSPYUWWUPPK-UHFFFAOYSA-N indole Natural products CC1=CC=CC2=C1C=CN2 PZOUSPYUWWUPPK-UHFFFAOYSA-N 0.000 description 1
- RKJUIXBNRJVNHR-UHFFFAOYSA-N indolenine Natural products C1=CC=C2CC=NC2=C1 RKJUIXBNRJVNHR-UHFFFAOYSA-N 0.000 description 1
- 239000004615 ingredient Substances 0.000 description 1
- 239000000893 inhibin Substances 0.000 description 1
- 239000003112 inhibitor Substances 0.000 description 1
- 230000005764 inhibitory process Effects 0.000 description 1
- ZPNFWUPYTFPOJU-LPYSRVMUSA-N iniprol Chemical compound C([C@H]1C(=O)NCC(=O)NCC(=O)N[C@H]2CSSC[C@H]3C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@H](C(N[C@H](C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC=4C=CC(O)=CC=4)C(=O)N[C@@H](CC=4C=CC=CC=4)C(=O)N[C@@H](CC=4C=CC(O)=CC=4)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](C)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](C)C(=O)NCC(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CSSC[C@H](NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C)NC(=O)[C@H](CO)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CC=4C=CC=CC=4)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CCCCN)NC(=O)[C@H](C)NC(=O)[C@H](CCCNC(N)=N)NC2=O)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CSSC[C@H](NC(=O)[C@H](CC=2C=CC=CC=2)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H]2N(CCC2)C(=O)[C@@H](N)CCCNC(N)=N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(O)=O)C(=O)N2[C@@H](CCC2)C(=O)N2[C@@H](CCC2)C(=O)N[C@@H](CC=2C=CC(O)=CC=2)C(=O)N[C@@H]([C@@H](C)O)C(=O)NCC(=O)N2[C@@H](CCC2)C(=O)N3)C(=O)NCC(=O)NCC(=O)N[C@@H](C)C(O)=O)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@H](C(=O)N[C@@H](CC=2C=CC=CC=2)C(=O)N[C@H](C(=O)N1)C(C)C)[C@@H](C)O)[C@@H](C)CC)=O)[C@@H](C)CC)C1=CC=C(O)C=C1 ZPNFWUPYTFPOJU-LPYSRVMUSA-N 0.000 description 1
- 229940102223 injectable solution Drugs 0.000 description 1
- 238000003780 insertion Methods 0.000 description 1
- 230000037431 insertion Effects 0.000 description 1
- 238000007689 inspection Methods 0.000 description 1
- 230000002608 insulinlike Effects 0.000 description 1
- 230000010354 integration Effects 0.000 description 1
- 229940047124 interferons Drugs 0.000 description 1
- 229940047122 interleukins Drugs 0.000 description 1
- 230000003834 intracellular effect Effects 0.000 description 1
- 238000007917 intracranial administration Methods 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- 229960004768 irinotecan Drugs 0.000 description 1
- UWKQSNNFCGGAFS-XIFFEERXSA-N irinotecan Chemical compound C1=C2C(CC)=C3CN(C(C4=C([C@@](C(=O)OC4)(O)CC)C=4)=O)C=4C3=NC2=CC=C1OC(=O)N(CC1)CCC1N1CCCCC1 UWKQSNNFCGGAFS-XIFFEERXSA-N 0.000 description 1
- AGPKZVBTJJNPAG-UHFFFAOYSA-N isoleucine Natural products CCC(C)C(N)C(O)=O AGPKZVBTJJNPAG-UHFFFAOYSA-N 0.000 description 1
- 229960000310 isoleucine Drugs 0.000 description 1
- 239000007951 isotonicity adjuster Substances 0.000 description 1
- KAHDONZOCXSKII-NJVVDGNHSA-N kisspeptin Chemical compound C([C@@H](C(=O)N[C@@H](CO)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](C)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCC(N)=O)C(=O)NCC(=O)N[C@@H](C)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CO)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)NCC(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC=1C=CC=CC=1)C(N)=O)NC(=O)[C@H]1N(CCC1)C(=O)[C@H](C)NC(=O)[C@H](CO)NC(=O)[C@H](CC(C)C)NC(=O)CNC(=O)[C@H]1N(CCC1)C(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CO)NC(=O)CNC(=O)[C@H](CO)NC(=O)[C@H](CO)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H]1N(CCC1)C(=O)[C@H]1N(CCC1)C(=O)[C@H]1N(CCC1)C(=O)[C@H](CO)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)CN)[C@@H](C)O)C1=CN=CN1 KAHDONZOCXSKII-NJVVDGNHSA-N 0.000 description 1
- 229940067606 lecithin Drugs 0.000 description 1
- 239000000787 lecithin Substances 0.000 description 1
- 235000010445 lecithin Nutrition 0.000 description 1
- 239000002523 lectin Substances 0.000 description 1
- 231100001231 less toxic Toxicity 0.000 description 1
- 201000007270 liver cancer Diseases 0.000 description 1
- 210000005229 liver cell Anatomy 0.000 description 1
- 208000014018 liver neoplasm Diseases 0.000 description 1
- 238000003670 luciferase enzyme activity assay Methods 0.000 description 1
- 210000001365 lymphatic vessel Anatomy 0.000 description 1
- 150000002668 lysine derivatives Chemical class 0.000 description 1
- 125000003588 lysine group Chemical class [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
- 230000002934 lysing effect Effects 0.000 description 1
- 201000000564 macroglobulinemia Diseases 0.000 description 1
- 208000015486 malignant pancreatic neoplasm Diseases 0.000 description 1
- 208000026037 malignant tumor of neck Diseases 0.000 description 1
- 210000004216 mammary stem cell Anatomy 0.000 description 1
- 238000013507 mapping Methods 0.000 description 1
- 239000011159 matrix material Substances 0.000 description 1
- 208000020968 mature T-cell and NK-cell non-Hodgkin lymphoma Diseases 0.000 description 1
- 235000012054 meals Nutrition 0.000 description 1
- 102000006240 membrane receptors Human genes 0.000 description 1
- 108020004084 membrane receptors Proteins 0.000 description 1
- 108020004999 messenger RNA Proteins 0.000 description 1
- 229930182817 methionine Natural products 0.000 description 1
- 239000004292 methyl p-hydroxybenzoate Substances 0.000 description 1
- 235000010270 methyl p-hydroxybenzoate Nutrition 0.000 description 1
- 229960002216 methylparaben Drugs 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
- 239000011325 microbead Substances 0.000 description 1
- 210000004688 microtubule Anatomy 0.000 description 1
- 230000003278 mimic effect Effects 0.000 description 1
- ZAHQPTJLOCWVPG-UHFFFAOYSA-N mitoxantrone dihydrochloride Chemical compound Cl.Cl.O=C1C2=C(O)C=CC(O)=C2C(=O)C2=C1C(NCCNCCO)=CC=C2NCCNCCO ZAHQPTJLOCWVPG-UHFFFAOYSA-N 0.000 description 1
- 108091005601 modified peptides Proteins 0.000 description 1
- 239000000178 monomer Substances 0.000 description 1
- 230000035772 mutation Effects 0.000 description 1
- 229960000951 mycophenolic acid Drugs 0.000 description 1
- HPNSFSBZBAHARI-RUDMXATFSA-N mycophenolic acid Chemical compound OC1=C(C\C=C(/C)CCC(O)=O)C(OC)=C(C)C2=C1C(=O)OC2 HPNSFSBZBAHARI-RUDMXATFSA-N 0.000 description 1
- 230000001338 necrotic effect Effects 0.000 description 1
- 229960004927 neomycin Drugs 0.000 description 1
- 210000000653 nervous system Anatomy 0.000 description 1
- 230000007935 neutral effect Effects 0.000 description 1
- 208000004649 neutrophil actin dysfunction Diseases 0.000 description 1
- 239000000346 nonvolatile oil Substances 0.000 description 1
- 238000001668 nucleic acid synthesis Methods 0.000 description 1
- 239000002777 nucleoside Substances 0.000 description 1
- 125000003835 nucleoside group Chemical group 0.000 description 1
- 108060005714 orexin Proteins 0.000 description 1
- 239000002818 ornithine decarboxylase inhibitor Substances 0.000 description 1
- DWAFYCQODLXJNR-BNTLRKBRSA-L oxaliplatin Chemical compound O1C(=O)C(=O)O[Pt]11N[C@@H]2CCCC[C@H]2N1 DWAFYCQODLXJNR-BNTLRKBRSA-L 0.000 description 1
- 229960001756 oxaliplatin Drugs 0.000 description 1
- QUANRIQJNFHVEU-UHFFFAOYSA-N oxirane;propane-1,2,3-triol Chemical compound C1CO1.OCC(O)CO QUANRIQJNFHVEU-UHFFFAOYSA-N 0.000 description 1
- 201000002528 pancreatic cancer Diseases 0.000 description 1
- 208000008443 pancreatic carcinoma Diseases 0.000 description 1
- 239000000123 paper Substances 0.000 description 1
- 239000011087 paperboard Substances 0.000 description 1
- 230000007170 pathology Effects 0.000 description 1
- 230000037361 pathway Effects 0.000 description 1
- WBXPDJSOTKVWSJ-ZDUSSCGKSA-N pemetrexed Chemical compound C=1NC=2NC(N)=NC(=O)C=2C=1CCC1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 WBXPDJSOTKVWSJ-ZDUSSCGKSA-N 0.000 description 1
- 229960005079 pemetrexed Drugs 0.000 description 1
- 229940049954 penicillin Drugs 0.000 description 1
- 229960003742 phenol Drugs 0.000 description 1
- 125000002467 phosphate group Chemical group [H]OP(=O)(O[H])O[*] 0.000 description 1
- 150000003013 phosphoric acid derivatives Chemical class 0.000 description 1
- 239000002504 physiological saline solution Substances 0.000 description 1
- 239000008389 polyethoxylated castor oil Substances 0.000 description 1
- 229920002704 polyhistidine Polymers 0.000 description 1
- 229920005862 polyol Polymers 0.000 description 1
- 150000003077 polyols Chemical class 0.000 description 1
- 230000008092 positive effect Effects 0.000 description 1
- 230000016833 positive regulation of signal transduction Effects 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 230000035935 pregnancy Effects 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- 238000012545 processing Methods 0.000 description 1
- 102000003998 progesterone receptors Human genes 0.000 description 1
- 230000005522 programmed cell death Effects 0.000 description 1
- 230000000750 progressive effect Effects 0.000 description 1
- 210000001236 prokaryotic cell Anatomy 0.000 description 1
- 230000001737 promoting effect Effects 0.000 description 1
- 230000000644 propagated effect Effects 0.000 description 1
- 230000000069 prophylactic effect Effects 0.000 description 1
- 238000011321 prophylaxis Methods 0.000 description 1
- 208000023958 prostate neoplasm Diseases 0.000 description 1
- 230000022558 protein metabolic process Effects 0.000 description 1
- 238000001243 protein synthesis Methods 0.000 description 1
- 150000003212 purines Chemical class 0.000 description 1
- 238000011002 quantification Methods 0.000 description 1
- 238000010188 recombinant method Methods 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 230000010076 replication Effects 0.000 description 1
- 230000000241 respiratory effect Effects 0.000 description 1
- 230000002441 reversible effect Effects 0.000 description 1
- 239000000523 sample Substances 0.000 description 1
- 238000010845 search algorithm Methods 0.000 description 1
- 238000012163 sequencing technique Methods 0.000 description 1
- 238000013207 serial dilution Methods 0.000 description 1
- 230000035939 shock Effects 0.000 description 1
- 230000003584 silencer Effects 0.000 description 1
- IZTQOLKUZKXIRV-YRVFCXMDSA-N sincalide Chemical compound C([C@@H](C(=O)N[C@@H](CCSC)C(=O)NCC(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC=1C=CC=CC=1)C(N)=O)NC(=O)[C@@H](N)CC(O)=O)C1=CC=C(OS(O)(=O)=O)C=C1 IZTQOLKUZKXIRV-YRVFCXMDSA-N 0.000 description 1
- 238000002741 site-directed mutagenesis Methods 0.000 description 1
- 210000003491 skin Anatomy 0.000 description 1
- 150000003384 small molecules Chemical class 0.000 description 1
- 230000000391 smoking effect Effects 0.000 description 1
- 235000010267 sodium hydrogen sulphite Nutrition 0.000 description 1
- 239000007909 solid dosage form Substances 0.000 description 1
- 239000007790 solid phase Substances 0.000 description 1
- 238000010532 solid phase synthesis reaction Methods 0.000 description 1
- 210000000952 spleen Anatomy 0.000 description 1
- 238000003892 spreading Methods 0.000 description 1
- 230000007480 spreading Effects 0.000 description 1
- 238000003153 stable transfection Methods 0.000 description 1
- 238000007619 statistical method Methods 0.000 description 1
- 230000000638 stimulation Effects 0.000 description 1
- 201000011549 stomach cancer Diseases 0.000 description 1
- 229960005322 streptomycin Drugs 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- 230000036561 sun exposure Effects 0.000 description 1
- 239000004094 surface-active agent Substances 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
- 229940069905 tasigna 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
- 230000002381 testicular Effects 0.000 description 1
- 201000003120 testicular cancer Diseases 0.000 description 1
- 150000003536 tetrazoles Chemical class 0.000 description 1
- RTKIYNMVFMVABJ-UHFFFAOYSA-L thimerosal Chemical compound [Na+].CC[Hg]SC1=CC=CC=C1C([O-])=O RTKIYNMVFMVABJ-UHFFFAOYSA-L 0.000 description 1
- 229940033663 thimerosal Drugs 0.000 description 1
- 108060008226 thioredoxin Proteins 0.000 description 1
- 229940094937 thioredoxin Drugs 0.000 description 1
- 150000003587 threonine derivatives Chemical class 0.000 description 1
- 239000008181 tonicity modifier Substances 0.000 description 1
- 230000000699 topical effect Effects 0.000 description 1
- 229940044693 topoisomerase inhibitor Drugs 0.000 description 1
- 229960000303 topotecan Drugs 0.000 description 1
- UCFGDBYHRUNTLO-QHCPKHFHSA-N topotecan Chemical compound C1=C(O)C(CN(C)C)=C2C=C(CN3C4=CC5=C(C3=O)COC(=O)[C@]5(O)CC)C4=NC2=C1 UCFGDBYHRUNTLO-QHCPKHFHSA-N 0.000 description 1
- 229960005267 tositumomab Drugs 0.000 description 1
- 238000012546 transfer Methods 0.000 description 1
- 230000009466 transformation Effects 0.000 description 1
- 238000000844 transformation Methods 0.000 description 1
- 238000013519 translation Methods 0.000 description 1
- VXKHXGOKWPXYNA-PGBVPBMZSA-N triptorelin Chemical compound C([C@@H](C(=O)N[C@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N1[C@@H](CCC1)C(=O)NCC(N)=O)NC(=O)[C@H](CO)NC(=O)[C@H](CC=1C2=CC=CC=C2NC=1)NC(=O)[C@H](CC=1N=CNC=1)NC(=O)[C@H]1NC(=O)CC1)C1=CC=C(O)C=C1 VXKHXGOKWPXYNA-PGBVPBMZSA-N 0.000 description 1
- 229960004824 triptorelin Drugs 0.000 description 1
- GPRLSGONYQIRFK-MNYXATJNSA-N triton Chemical compound [3H+] GPRLSGONYQIRFK-MNYXATJNSA-N 0.000 description 1
- 101150081616 trpB gene Proteins 0.000 description 1
- 101150111232 trpB-1 gene Proteins 0.000 description 1
- 230000010304 tumor cell viability Effects 0.000 description 1
- 102000003298 tumor necrosis factor receptor Human genes 0.000 description 1
- 238000000870 ultraviolet spectroscopy Methods 0.000 description 1
- 241000701447 unidentified baculovirus Species 0.000 description 1
- 241001430294 unidentified retrovirus Species 0.000 description 1
- 238000011144 upstream manufacturing Methods 0.000 description 1
- 210000002229 urogenital system Anatomy 0.000 description 1
- 206010046766 uterine cancer Diseases 0.000 description 1
- 239000004474 valine Substances 0.000 description 1
- 230000009278 visceral effect Effects 0.000 description 1
- 210000005253 yeast cell Anatomy 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K19/00—Hybrid peptides, i.e. peptides covalently bound to nucleic acids, or non-covalently bound protein-protein complexes
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- A61K38/22—Hormones
- A61K38/24—Follicle-stimulating hormone [FSH]; Chorionic gonadotropins, e.g. HCG; Luteinising hormone [LH]; Thyroid-stimulating hormone [TSH]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
- A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/08—Drugs for disorders of the alimentary tract or the digestive system for nausea, cinetosis or vertigo; Antiemetics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P13/00—Drugs for disorders of the urinary system
- A61P13/08—Drugs for disorders of the urinary system of the prostate
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P15/00—Drugs for genital or sexual disorders; Contraceptives
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/04—Centrally acting analgesics, e.g. opioids
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/02—Nutrients, e.g. vitamins, minerals
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- 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
- C07K14/575—Hormones
- C07K14/59—Follicle-stimulating hormone [FSH]; Chorionic gonadotropins, e.g.hCG [human chorionic gonadotropin]; Luteinising hormone [LH]; Thyroid-stimulating hormone [TSH]
-
- 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
- C07K14/575—Hormones
- C07K14/59—Follicle-stimulating hormone [FSH]; Chorionic gonadotropins, e.g.hCG [human chorionic gonadotropin]; Luteinising hormone [LH]; Thyroid-stimulating hormone [TSH]
- C07K14/592—Follicle-stimulating hormone [FSH]; Chorionic gonadotropins, e.g.hCG [human chorionic gonadotropin]; Luteinising hormone [LH]; Thyroid-stimulating hormone [TSH] at least 1 amino acid in D-form
-
- 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
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
- C12N15/09—Recombinant DNA-technology
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
- C12N15/09—Recombinant DNA-technology
- C12N15/11—DNA or RNA fragments; Modified forms thereof; Non-coding nucleic acids having a biological activity
- C12N15/62—DNA sequences coding for fusion proteins
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2319/00—Fusion polypeptide
- C07K2319/01—Fusion polypeptide containing a localisation/targetting motif
- C07K2319/03—Fusion polypeptide containing a localisation/targetting motif containing a transmembrane segment
-
- 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2319/00—Fusion polypeptide
- C07K2319/70—Fusion polypeptide containing domain for protein-protein interaction
- C07K2319/74—Fusion polypeptide containing domain for protein-protein interaction containing a fusion for binding to a cell surface receptor
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Organic Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Genetics & Genomics (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Molecular Biology (AREA)
- Biochemistry (AREA)
- Endocrinology (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Pharmacology & Pharmacy (AREA)
- Zoology (AREA)
- Biophysics (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Biomedical Technology (AREA)
- Reproductive Health (AREA)
- Wood Science & Technology (AREA)
- Gastroenterology & Hepatology (AREA)
- Biotechnology (AREA)
- General Engineering & Computer Science (AREA)
- Toxicology (AREA)
- Epidemiology (AREA)
- Physics & Mathematics (AREA)
- Plant Pathology (AREA)
- Microbiology (AREA)
- Immunology (AREA)
- Nutrition Science (AREA)
- Pain & Pain Management (AREA)
- Diabetes (AREA)
- Hematology (AREA)
- Obesity (AREA)
- Hospice & Palliative Care (AREA)
Abstract
Description
cell)が含まれる。レセプタ、リガンド、又は抗原を発現し、又は、本発明の方法に従って標的とされる細胞には、乳腺細胞、卵巣細胞、子宮細胞、頸部細胞、前立腺細胞、精巣細胞、膵臓細胞、皮膚細胞、血液細胞、副腎細胞、下垂体細胞及び子宮内膜細胞も含まれる。細胞において発現される結合部の種類の例には、ホルモンレセプタ、サイトカイン、成長因子(例えば、EGFレセプタ、Her2/neu、ROR1)、フェリチン、トランスフェリン受容体、細胞接着分子等が含まれる。増殖細胞において発現され、又は、抗体もしくはその断片の標的となる抗原の例には、CD19、CD20、CD23、CD27、CD28、CD30、CD33、CD40、CD52、CD56、CD70、CD154、免疫グロブリン様レセプタ等が含まれる。また、抗原には、例えば、前立腺特異抗原(PSA)、前立腺特異的膜抗原(PSMA)、癌胎児性抗原(CEA)、αフェトプロテイン(AFP)、前立腺特異抗原(PSA)、癌抗原125(CA−125)及び本明細書において開示されるリガンドに結合する他のレセプタ分子が含まれる。
Proteins, Vol. 7, pp 267-357 (1983), “Peptide and Backbone Modifications,”
Marcel Decker, NYを参照。)。
Mol Biol. 132:185 (2000)、及びSmith et al., J. Mol. Biol. 147:195 (1981)を参照。)。タンパク質構造の類似性を定量化するためには、ドロネー位相マッピングを用いたプログラムが開発されている(Bostick et al., Biochem Biophys Res Commun. 304:320 (2003)参照。)。
Peptides and Proteins, Vol. 7, pp 267-357, “Peptide and Backbone Modifications,”
Marcel Decker, NYを参照。)。
(1980)及び Banga, A.K., Therapeutic Peptides and Proteins, Formulation,
Processing and Delivery Systems (1995) Technomic Publishing Co., Lancaster, PAを参照。)。ペプチド合成は、様々な固相法を用いて行うことができ(例えば、Roberge Science 269:202 (1995)、及び、Merrifield, Methods Enzymol.
289:3(1997)を参照。)、例えば、ABI431ペプチドシンセサイザ( ABI 431A peptide Synthesizer(Perkin Elmer))を取扱説明書に従って使用することにより、ペプチド合成を自動化することができる。ペプチド及びペプチド模倣体は、組み合わされた手法を用いて実現することもできる。模倣体を含んでいる合成残基及びポリペプチドは、本発明の技術分野において知られている様々な手法及び手段を用いて合成される(例えば、Organic Syntheses Collective Volumes, Gilman, et al. (Eds) John
Wiley & Sons, Inc., NYを参照)。修飾されたペプチドは、化学的な修飾によって生成される(例えば、Belousov, Nucleic Acids Res. 25:3440 (1997)、Frenkel, Free
Radic. Biol. Med. 19:373 (1995)、及びBlommers, Biochemistry 33:7886 (1994)を参照。)。
及びその他のウイルスプロモータ、又は、哺乳類細胞のゲノム由来の誘導性プロモータ(例えば、メタロチオネインIIAプロモータや熱ショックプロモータ)、又は、哺乳類ウイルス由来のプロモータ(例えば、アデノウイルス後期プロモータや誘導性のマウス乳癌ウイルスの長い末端反復)が含まれる。また、レトロウイルスゲノムは遺伝子的に修飾されて、適当な宿主細胞において融合コンストラクトの発現を導入し指令することができる。
ed., Greene Publish. Assoc. & WILey Interscience, 1988、Grant et al.
Methods in Enzymology, 153:516 (1987), eds. Wu & Grossman、 Bitter Methods in
Enzymology, 152:673 (1987) , eds. Berger & Kimmel, Acad. Press, N.Y.、及びStrathern et al.,
The Molecular Biology of the Yeast Saccharomyces (1982) eds. Cold Spring Harbor
Press, Vols. I and IIを参照。)。ADHやLEU2等の構成的イーストプロモータ、又は、GAL等の誘導性プロモータが用いられる(R. Rothstein In: DNA Cloning, A Practical Approach, Vol.11, Ch. 3, ed.
D.M. Glover, IRL Press, Wash., D.C., 1986を参照)。相同的組み換えによって外来核酸配列のイースト染色体への組み込みを促進するベクターが、本発明の技術分野において知られている。イースト人工染色体(YAC)が用いられるのは、典型的には、挿入されたポリヌクレオチドが従来のベクター(例えば、約12Kbよりも大きい場合)にとって大きすぎる場合である。
(1988))、グルタミンシンターゼ系;オルニチンデカルボキシラーゼ阻害剤である2−(ジフルオロメチル)−DL−オルニチン(DFMO)に対する耐性を与えるODC(オルニチンデカルボキシラーゼ)(McConlogue (1987) In: Current Communications in Molecular Biology,
Cold Spring Harbor Laborator)が含まれる。
(IL−2)レセプタ、RAGE−1、チロシナーゼ、MAGE−1、MAGE−2、NY−ESO−1、Melan−A/MART−1、糖タンパク質(gp)75、gp100、βカテニン、PRAME、MUM−1、ZEP161、ユビキリン−1、HOX−B6、YB−1、オステオネクチン、及びILF3を発現させる細胞が、増殖を減少させ又は阻害する標的細胞に含まれる。増殖を減少させ又は阻害する標的細胞には、非選択的又は選択的に、次の物質を発現させる細胞がさらに含まれる。すなわち、トランスフェリン、葉酸及び葉酸誘導体(例えば、葉酸塩)、及びTNF−α、TNF−β(リンフォトキシン、LT)等の腫瘍壊死因子(TNF)ファミリーメンバー、腫瘍壊死因子関連アポトーシス誘導リガンド(TRAIL)、脂肪酸合成酵素(FAS)、LIGHT、及び41BB、及びこれらのためのレセプタを発現させる細胞が、増殖を減少させ又は阻害する標的細胞に含まれる。
融合コンストラクト及び方法とともに用いることができる追加剤が、本発明の技術分野において知られており、利用可能である。例えば、抗体、細胞成長因子、細胞生存因子、細胞分化因子、サイトカイン及びケモカイン等の生物製剤を投与することができる。モノクロナール抗体の例には、リツキシマブ(リツキサン(登録商標))、トラスツズマブ(ハーセプチン)、ベバシズマブ(アバスチン)、セツキシマブ(アービタックス)、アレムツズマブ(キャンパス)、パニツムマブ(ベクチビックス)、イブリツモマブ・チウキセタン(ゼヴァリン)、トシツモマブ(ベクザー)等が含まれる。これらの例示されたモノクロナール抗体は、例えば、本発明の融合コンストラクトと組み合わせて用いることができる。本発明の融合コンストラクトとともに用いることができる他の標的薬は、イマチニブ(グリベック)、ゲフィチニブ(イレッサ)、ボルテゾミブ(ベルケイド)、ラパチニブ(Tykerb)、スニチニブ(スーテント)、ソラフェニブ(ネクサバール)、ニロチニブ(Tasigna)等である。細胞成長因子、細胞生存因子、細胞分化因子、サイトカイン及びケモカインの例には、IL−2、IL−1α、IL−1β、IL−3、IL−6、IL−7、顆粒球・マクロファージ・コロニー刺激因子(GMCSF)、IFN−γ、IL−12、TNF−α、TNFβ、MIP−1α , MIP−1β、RANTES、SDF−1、MCP−1、MCP−2、MCP−3、MCP−4、エオタキシン、エオタキシン−2、I−309/TCA3、ATAC、HCC−1、HCC−2、HCC−3、LARC/MIP−3a、PARC、TARC、CKβ、CKβ6、CKβ7、CKβ8、CKβ9、CKβ11、CKβ12、C10、IL−8、GROα、GROβ、ENA−78、GCP−2、PBP/CTAPIIIβ−TG/NAP−2、Mig、PBSF/SDF−1及びリンフォタクチン(lymphotactin)が含まれる。
壊死、溶解もしくはアポトーシスを活性化、促進もしくは増加させ、新生物、腫瘍、癌又は悪性腫瘍の体積、サイズ、細胞質量を減少させ、新生物、腫瘍、癌又は悪性腫瘍の体積、質量、サイズもしくは細胞数の増加もしくは進行を抑制もしくは防止し、過剰増殖細胞(例えば、転移癌)が被験者の他の(二次的な)部位、位置、組織又は臓器へ拡散又は播種すること、又は、過剰増殖細胞(例えば、転移癌)が被験者の他の(二次的な)部位、位置、組織において形成されることを阻害し減少させ、被験者の寿命を延ばす。追加的な実施形態における治療方法は、転移性又は非転移性の腫瘍、癌、悪性腫瘍又は新生物に関連する又はこれらによって引き起こされる有害な症状や合併症の重症度、継続時間もしくは頻度を減少させる。
Co., Easton, PA、The Merck Index (1996) 12th ed., Merck Publishing Group, Whitehouse,
NJ、Pharmaceutical
Principles of Solid Dosage Forms, Technonic Publishing Co., Inc., Lancaster,
Pa., (1993)、及びPoznansky, et al., Drug Delivery Systems, R. L. Juliano, ed.,
Oxford, N.Y. (1980), pp. 253-315を参照。)。
Biochemistry 36:9540 (1997)、Leuschner and Hansel, Current Pharmaceutical Design, 10:2299 (2004)、及びLeuschner and Hansel,
Biol Reprod 73:255 (2005))。C末端においてβCG−alaに結合された溶解ペプチドは、コンストラクトの長さの増加によって毒性が増加することを示した。様々な長さを有するペプチドのIC50は次の通りであった。すなわち、14アミノ酸(Phor14)については5.74μM、15アミノ酸(Phor15)については1.92μM、18アミノ酸(Phor18=CLIP71)については1.09μM、21アミノ酸(Phor21)については2.31μM、28アミノ酸(Phor28)については1.36μMであった(表3−1及び3−2)。
(338983)、D−ala−Phor18−LHRH(339385)、及び(KKKFAFA)3−LHRH(338984)は、全く溶血活性を示さなかった。D−アミノ酸光学異性体は、測定可能な溶血活性を示さなかった。
ASAASβ−CG−ala(337471)、D−ala−Phor21−LHRH(338611)、及びPhor18−ASAAS−LHRH(338612)であった。
割り付けられたポイント:1 2 3
インビボ活性 1x 2x 3x
HA50 <50 50−100>100
IC50/HA50
<0.03<0.006<0.004
インビボでの有効性
33との比較 同等 より良い
33と比較されたMTD 同等 より良い
1) 33のIC50は2.31μM、33のIC50/IC50ペプチドとして表現された値
2) HA50[μM]として表現された溶血活性
3) インビボパフォーマンスは、ペプチド33の同じパラメータと比較される基準値と対比した腫瘍質量の減少及び生存腫瘍細胞の減少における有意性を意味する。
4) 注射された投与薬によって66.6%生存(急性及び注射後8−14日経過時)
ペプチドコード
33 = Phor21βCG−ala
76 = Phor18−βCG−ala
81 = D ala Phor21−βCG−ala
85 = D ala Phor18−LHRH
47 = Phor18−ルプロン
13 = Phor18−LHRH
11 = D ala Phor21−LHRH
12 = Phor18−ASAAS−LHRH
71 = Phor15−βCG−ala
74 = Phor15−C6−βCG−ala
intercalation)や微小管相互作用を通じて相互作用し、又はシグナル変換経路の阻害剤である。したがって、これらの作用メカニズムが標的細胞を破壊するための所要時間を定める。MDA−MB−435S等のヒト乳腺癌細胞を破壊するドキソルビシンインビトロの反応速度は4時間程度の速さであるが、これ以外の標準的な治療方法についてはより長い時間が必要との報告がなされている。癌細胞を破壊する最も一般的なメカニズムはアポトーシスである。可逆的なプロセスとして、また、多剤耐性(MDR)の発生や、MDR癌細胞内の薬剤分子を排出するPgpポンプの働きによって、標準的な治療方法の効果がなくなる可能性がある。
Prismのバージョン5.01において、様々な傾きを有するシグモイド型容量反応のためのプログラムを使用し、0%及び100%の制約値を用いて行った。2つの96ウェルプレートの各セットの4ウェルを比較及び分析した。有意性に関する統計分析はスチューデントの両側T検定によって決定した。
のIC50値が得られた。Phor18−LHRH(338613)は、機能的LHRHレセプタを発現させないため、SKOV−3細胞にとって適切な標的ではない。
mg/kg (N=10))、生理食塩水のシスプラチン/CP(Calbiochem社、Cat232120、D0005495)(10mg/kg、3qd(N=10))、基準値(N=9)が含まれる。
mg/kgのPhor18−LHRH(338613)を投与したグループにおいて見られた。治療開始時と比較した腫瘍の退行として観測される治療反応は、Phor18−LHRH(338613)を0.2mg/kg(p<0.03対基準値)投与して治療したマウスにおいて最も大きかった。シスプラチン及び非結合Phor18=CLIP71には、腫瘍質量を減少させる効果がなかった。
Claims (108)
- 第1のドメイン及び第2のドメインを含む融合コンストラクトであって、前記第1のドメインは、KFAKFAKKFAKFAKK、KFAKFAKKFAKFAKKF、KFAKFAKKFAKFAKKFA、KFAKFAKKFAKFAKKFAK、KFAKFAKKFAKFAKKFAKF及びKFAKFAKKFAKFAKKFAKFAから選択されるペプチドを含む12から28のアミノ酸配列、又は、KFAKFAKKFAKFAKK、KFAKFAKKFAKFAKKF、KFAKFAKKFAKFAKKFA、KFAKFAKKFAKFAKKFAK、KFAKFAKKFAKFAKKFAKF及びKFAKFAKKFAKFAKKFAKFAから選択されるペプチドを含む12から25のアミノ酸配列であって単数もしくは複数の前記K残基をF残基又はL残基のいずれかで、単数もしくは複数の前記F残基をK残基、A残基もしくはL残基のいずれかで、もしくは、単数もしくは複数の前記A残基をK残基、F残基もしくはL残基のいずれかで置換させたものからなり、前記第2のドメインは結合部を含む、融合コンストラクト。
- 第1のドメイン及び第2のドメインを含む融合コンストラクトであって、前記第1のドメインは、KFAKFAKKFAKFAKK、KFAKFAKKFAKFAKKF、KFAKFAKKFAKFAKKFA、KFAKFAKKFAKFAKKFAK、KFAKFAKKFAKFAKKFAKF及びKFAKFAKKFAKFAKKFAKFAから選択されるアミノ酸配列、又は、KFAKFAKKFAKFAKK、KFAKFAKKFAKFAKKF、KFAKFAKKFAKFAKKFA、KFAKFAKKFAKFAKKFAK、KFAKFAKKFAKFAKKFAKF及びKFAKFAKKFAKFAKKFAKFAから選択されるアミノ酸配列であって、単数又は複数の前記K残基をF残基又はL残基のいずれかで、単数又は複数の前記F残基をK残基、A残基又はL残基のいずれかで、もしくは、単数又は複数の前記A残基をK残基、F残基又はL残基のいずれかで置換させたものからなり、前記第2のドメインは結合部を含む、融合コンストラクト。
- 前記結合部がレセプタ、リガンド又は抗原と結合する請求項1又は2に記載の融合コンストラクト。
- 前記リガンドがレセプタアゴニスト又はアンタゴニストを含む請求項3に記載の融合コンストラクト。
- 前記結合部が細胞で発現するレセプタ、リガンド又は抗原と結合する請求項1又は2に記載の融合コンストラクト。
- 前記細胞が過剰増殖細胞である請求項5に記載の融合コンストラクト。
- 前記細胞が乳腺細胞、卵巣細胞、子宮細胞、頸部細胞、前立腺細胞、精巣細胞、副腎細胞、下垂体細胞又は子宮内膜細胞である請求項5に記載の融合コンストラクト。
- 前記結合部がリガンド、レセプタ又は抗体を含む請求項1又は2に記載の融合コンストラクト。
- 前記結合部が、ペプチド、ポリペプチド、タンパク質、核酸又は炭水化物を含む請求項1又は2に記載の融合コンストラクト。
- 前記結合部が、ホルモン、ホルモンアナログ、ホルモンレセプタに結合するホルモンもしくはホルモンアナログの断片、ホルモンレセプタ、又はホルモンもしくはホルモンレセプタに結合する作用物質である請求項1又は2に記載の融合コンストラクト。
- 前記結合部が線形の又は環状の構造を有する請求項1又は2に記載の融合コンストラクト。
- 前記結合部が、ホルモン又はホルモンレセプタに結合する請求項1又は2に記載の融合コンストラクト。
- 前記ホルモンが、ゴナドトロピン放出ホルモンI、ゴナドトロピン放出ホルモンIII、ヤツメウナギIII黄体形成ホルモン放出ホルモン、黄体形成ホルモンβ鎖、黄体形成ホルモン、絨毛性ゴナドトロピン、絨毛性ゴナドトロピンβサブユニット、メラニン細胞刺激ホルモン、エストラジオール、ジエチルスチルベストロール、ドーパミン、ソマトスタチン、卵胞刺激ホルモン(FSH)、グルココルチコイド、エストロゲン、テストステロン、アンドロステンジオン、ジヒドロテストステロン、デヒドロエピアンドロステロン、プロゲステロン、又はアンドロゲンから選択される請求項12に記載の融合コンストラクト。
- 前記第2のドメインがアミノ酸配列からなり、又はアミノ酸配列を含む請求項1又は2に記載の融合コンストラクト。
- 前記第1又は第2のドメインが、約1から10、10から20、15から20、20から30、30から40、40から50、60から70、70から80、80から90、90から100又はそれ以上のアミノ酸のアミノ酸配列からなり、又は当該アミノ酸配列を含む請求項1又は2に記載の融合コンストラクト。
- 前記第1のドメインが、約15から20のアミノ酸を持つ配列からなる請求項1又は2に記載の融合コンストラクト。
- 前記第1のドメインが、15、16、17、18、19又は20のアミノ酸を持つ配列からなる請求項1又は2に記載の融合コンストラクト。
- 前記第2のドメインが、SYAVALSAQAALARRで表されるアミノ酸配列からなり、又は当該アミノ酸配列を含む請求項1又は2に記載の融合コンストラクト。
- 前記第2のドメインが、QHWSYGLRPGで表されるアミノ酸配列からなり、又は当該アミノ酸配列を含む請求項1又は2に記載の融合コンストラクト。
- 前記第1のドメインが、前記第2のドメインに対してNH2末端に位置する請求項1又は2に記載の融合コンストラクト。
- 前記第2のドメインが、前記第1のドメインに対してNH2末端に位置する請求項1又は2に記載の融合コンストラクト。
- 前記第1のドメイン又は前記第2のドメインが単数又は複数のD−アミノ酸を有する請求項1又は2に記載の融合コンストラクト。
- 前記第1のドメインが、K、F又はA残基にD−アミノ酸を有する請求項1又は2に記載の融合コンストラクト。
- 前記第1のドメインが両親媒性αヘリックスを形成する請求項1又は2に記載の融合コンストラクト。
- 前記第1及び第2のドメインが共有結合によって結合される請求項1又は2に記載の融合コンストラクト。
- 前記第1及び第2のドメインが、ペプチド又は非ペプチドリンカーによって結合される請求項1又は2に記載の融合コンストラクト。
- 前記第1及び第2のドメインが、1から25のアミノ酸残基又は線状炭素鎖を有するペプチド配列によって結合される請求項1又は2に記載の融合コンストラクト。
- 前記第1及び第2のドメインが、単数又は複数のA、S又はGアミノ酸残基を含むペプチド配列によって結合される請求項1又は2に記載の融合コンストラクト。
- 前記第1及び第2のドメインが、GSGGS、ASAASもしくはCCCCCCを含み、又は、GSGGS、ASAASもしくはCCCCCCからなるペプチド配列によって結合される請求項1又は2に記載の融合コンストラクト。
- 第3のドメイン、第4のドメイン、第5のドメイン、第6のドメイン、又は第7のドメインをさらに含む請求項1又は2に記載の融合コンストラクト。
- 前記融合コンストラクトが単離され又は精製される請求項1又は2に記載の融合コンストラクト。
- 前記融合コンストラクトが混合物を含む請求項1又は2に記載の融合コンストラクト。
- 請求項1又は2に記載の融合コンストラクトを含む組成物。.
- 請求項1又は2に記載の融合コンストラクトを含む医薬組成物。
- 有害な細胞増殖又は過増殖疾患を有する被験者を治療するために効果のある量の請求項1又は2に記載の融合コンストラクトを含む投与ユニット。
- 新生物、腫瘍又は癌を有する被験者を治療するために効果のある量の請求項1又は2に記載の融合コンストラクトを含む投与ユニット。
- 被験者の生殖能力を減少させるために効果のある量の請求項1又は2に記載の融合コンストラクトを含む投与ユニット。
- 細胞増殖を減少させもしくは阻害し、過剰増殖細胞の増殖を減少させもしくは阻害し、新生物細胞、腫瘍細胞もしくは癌細胞の増殖を減少させもしくは阻害し、treating a 過増殖疾患を有する被験者を治療し、新生物、腫瘍もしくは癌を有する被験者を治療し、又は動物の生殖能力を減少させるための請求項1又は2に記載の融合コンストラクト及び説明書を含むキット。
- 請求項1又は2に記載の融合コンストラクト、及び、抗細胞増殖又は免疫刺激剤を含む組成物。
- 請求項9の融合コンストラクトをコードする核酸分子。
- 請求項40の核酸分子を含むベクター。
- 請求項41のベクターで形質転換される宿主細胞。
- 請求項1又は2に記載の融合コンストラクトを発現する細胞。
- 細胞を、当該細胞の増殖を減少させ又は阻害するために十分な量の請求項1又は2のいずれか1項に記載の融合コンストラクトに接触させる、細胞の増殖を減少させ又は阻害する方法。
- 細胞を、当該細胞の増殖を減少させ又は阻害するために十分な量の請求項1又は2のいずれか1項に記載の融合コンストラクトに接触させる、細胞増殖を減少させ又は阻害する方法。
- 過剰増殖細胞の増殖を減少させ又は阻害する方法であって、細胞を、当該過剰増殖細胞の増殖を減少させ又は阻害するために十分な量の請求項1又は2のいずれか1項に記載の融合コンストラクトに接触させる方法。
- 新生物細胞、腫瘍細胞、癌細胞又は悪性腫瘍細胞の増殖を減少させ又は阻害する方法であって、細胞を、当該新生物細胞、腫瘍細胞、癌細胞又は悪性腫瘍細胞の増殖を減少させ又は阻害するために十分な量の請求項1又は2のいずれか1項に記載の融合コンストラクトに接触させる方法。
- 前記細胞が、レセプタ、リガンド、又は抗原を発現する請求項45から47のいずれか1項に記載の方法。
- 前記細胞が、ホルモン又はホルモンレセプタを発現する請求項45から47のいずれか1項に記載の方法。
- 前記細胞が、性ステロイドホルモンもしくは性腺ステロイドホルモン又は性ステロイドホルモンレセプタもしくは性腺ステロイドホルモンレセプタを発現する請求項45から47のいずれか1項に記載の方法。
- 前記細胞が、ゴナドトロピン放出ホルモンI、ゴナドトロピン放出ホルモンIII、ヤツメウナギIII黄体形成ホルモン放出ホルモン、黄体形成ホルモンβ鎖、黄体形成ホルモン、絨毛性ゴナドトロピン、絨毛性ゴナドトロピンβサブユニット、メラニン細胞刺激ホルモン、エストラジオール、ジエチルスチルベストロール、ドーパミン、ソマトスタチン、卵胞刺激ホルモン(FSH)、グルココルチコイド、エストロゲン、テストステロン、アンドロステンジオン、ジヒドロテストステロン、デヒドロエピアンドロステロン、プロゲステロン、アンドロゲン、上皮細胞増殖因子(EGF)、成長ホルモン(GH)、Her2/neu、ビタミンH、葉酸、トランスフェリン、甲状腺刺激ホルモン(TSH)、エンドセリン、ボンベシン、成長ホルモン、血管作動性腸管ペプチド、ラクトフェリン、インテグリン、神経成長因子、CD−8、CD−33、CD19、CD20、CD40、ROR1、IGF−1、癌胎児性抗原(CEA)、αフェトプロテイン(AFP)、前立腺特異抗原(PSA)、前立腺特異細胞膜抗原(PSAM)、CA125(残存上皮性卵巣癌)、可溶性インターロイキン−2(IL−2)レセプタ、RAGE−1、チロシナーゼ、MAGE−1、MAGE−2、NY−ESO−1、Melan−A/MART−1、糖タンパク質(gp)75、gp100、βカテニン、PRAME、MUM−1、ZEP161、ユビキチン−1、HOX−B6、YB−1、オステオネクチン、ILF3、葉酸又は葉酸誘導体、腫瘍壊死因子(TNF)ファミリーメンバー、TNF−α、TNF−β(リンフォトキシン、LT)、腫瘍壊死因子関連アポトーシス誘導リガンド(TRAIL)、脂肪酸合成酵素(FAS)、LIGHT、41BB、形質転換成長因子α、形質転換成長因子β、インスリン、セルロプラスミン、HIV−tat、RGD配列モチーフを含むペプチド又はタンパク質、単糖、二糖、オリゴ糖、シアル酸、ガラクトース、マンノース、フコース、又はアセチルノイラミン酸と結合するレセプタを発現する請求項45から47のいずれか1項に記載の方法。
- 前記インテグリンはα5β1インテグリンから選択される請求項51に記載のの方法。
- 前記細胞が、ゴナドトロピン放出ホルモンI、ゴナドトロピン放出ホルモンIII、ヤツメウナギIII黄体形成ホルモン放出ホルモン、黄体形成ホルモンβ鎖、黄体形成ホルモン、絨毛性ゴナドトロピン、絨毛性ゴナドトロピンβサブユニット、メラニン細胞刺激ホルモン、エストラジオール、ジエチルスチルベストロール、ドーパミン、ソマトスタチン、卵胞刺激ホルモン(FSH)、グルココルチコイド、エストロゲン、テストステロン、アンドロステンジオン、ジヒドロテストステロン、デヒドロエピアンドロステロン、プロゲステロン、アンドロゲン、上皮細胞増殖因子(EGF)、成長ホルモン(GH)、Her2/neu、ビタミンH、葉酸、トランスフェリン、甲状腺刺激ホルモン(TSH)、エンドセリン、ボンベシン、成長ホルモン、血管作動性腸管ペプチド、ラクトフェリン、インテグリン、神経成長因子、CD−8、CD−33、CD19、CD20、CD40、ROR1、IGF−1、癌胎児性抗原(CEA)、αフェトプロテイン(AFP)、前立腺特異抗原(PSA)、前立腺特異的膜抗原(PSMA)、CA125(残存上皮性卵巣癌)、可溶性インターロイキン−2(IL−2)レセプタ、RAGE−1、チロシナーゼ、MAGE−1、MAGE−2、NY−ESO−1、Melan−A/MART−1、糖タンパク質(gp)75、gp100、βカテニン、PRAME、MUM−1、ZEP161、ユビキリン−1、HOX−B6、YB−1、オステオネクチン、及びILF3と結合するレセプタを発現する請求項45から47のいずれか1項に記載の方法。
- 前記類似体が、ミフェプリストン、フルタミンド、ルプロン、ゾラデックス、サプレリン、シナテルトリプトレリン、ブセレリン、セトロレリクス、ガニレリクス、アバレリクス、アンチド、テベレリクス及びデガレリクス(Fe200486)から選択される請求項53に記載の方法。
- レセプタ又は抗原を発現する細胞の増殖を選択的に減少させ又は阻害する方法であって、当該方法は、前記細胞を、細胞の増殖を減少させ又は阻害するために十分な量の請求項1又は2のいずれか1項に記載の融合コンストラクトに接触させることを含み、前記ペプチドの前記結合部が前記細胞によって発現される前記レセプタ、リガンド又は抗原に結合する方法。
- レセプタや抗原を発現する過剰増殖細胞の増殖を選択的に減少させ又は阻害する方法であって、当該方法は、前記細胞を、過剰増殖細胞の増殖を減少させ又は阻害するために十分な量の請求項1又は2のいずれか1項に記載の融合コンストラクトに接触させることを含み、前記ペプチドの結合部が、過剰増殖細胞によって発現される前記レセプタ、リガンド又は抗原に結合する方法。
- レセプタや抗原を発現する新生物細胞、腫瘍細胞、癌細胞又は悪性腫瘍細胞の増殖を減少させ又は阻害する方法であって、当該方法は、前記細胞を、新生物細胞、腫瘍細胞、癌細胞又は悪性腫瘍細胞の増殖を減少させ又は阻害するために十分な量の請求項1又は2のいずれか1項に記載の融合コンストラクトに接触させることを含み、前記融合コンストラクトの前記結合部が、前記レセプタ、リガンド又は抗原に結合する方法。
- 前記細胞がレセプタ又は抗原を発現する請求項55から57のいずれか1項に記載の方法。
- 前記細胞がホルモン又はホルモンレセプタを発現する請求項55から57のいずれか1項に記載の方法。
- 前記細胞が性ステロイドホルモンもしくは性腺ステロイドホルモン又は性ステロイドホルモンレセプタもしくは性腺ステロイドホルモンレセプタを発現する請求項55から57のいずれか1項に記載の方法。
- 前記細胞が、ゴナドトロピン放出ホルモンI、ゴナドトロピン放出ホルモンIII、ヤツメウナギIII黄体形成ホルモン放出ホルモン、黄体形成ホルモンβ鎖、黄体形成ホルモン、絨毛性ゴナドトロピン、絨毛性ゴナドトロピンβサブユニット、メラニン細胞刺激ホルモン、エストラジオール、ジエチルスチルベストロール、ドーパミン、ソマトスタチン、卵胞刺激ホルモン(FSH)、グルココルチコイド、エストロゲン、テストステロン、アンドロステンジオン、ジヒドロテストステロン、デヒドロエピアンドロステロン、プロゲステロン、アンドロゲン、上皮細胞増殖因子(EGF)、成長ホルモン(GH)、Her2/neu、ビタミンH、葉酸、トランスフェリン、甲状腺 刺激ホルモン(TSH)、エンドセリン、ボンベシン、成長ホルモン、血管作動性腸管ペプチド、ラクトフェリン、インテグリン、神経成長因子、CD−8、CD−33、CD19、CD20、CD40、ROR1、IGF−1、癌胎児性抗原(CEA)、αフェトプロテイン(AFP)、前立腺特異抗原(PSA)、前立腺特異細胞膜抗原(PSAM)、CA125 (残存上皮性卵巣癌)、可溶性インターロイキン−2(IL−2)レセプタ、RAGE−1、チロシナーゼ、MAGE−1、MAGE−2、NY−ESO−1、Melan−A/MART−1、糖タンパク質(gp)75、gp100、βカテニン、PRAME、MUM−1、ZEP161、ユビキチン−1、HOX−B6、YB−1、オステオネクチン、ILF3、葉酸又は葉酸誘導体、腫瘍壊死因子(TNF)ファミリーメンバー、TNF−α、TNF−β(リンフォトキシン、LT)、腫瘍壊死因子関連アポトーシス誘導リガンド(TRAIL)、脂肪酸合成酵素(FAS)、LIGHT、41BB、形質転換成長因子α、形質転換成長因子β、インスリン、セルロプラスミン、HIV−tat、RGD配列モチーフを含むペプチドもしくはタンパク質、単糖、二糖、オリゴ糖、シアル酸、ガラクトース、マンノース、フコース、又はアセチルノイラミン酸と結合するレセプタを発現する請求項55から57のいずれか1項に記載の方法。
- 前記細胞が、ゴナドトロピン放出ホルモンI、ゴナドトロピン放出ホルモンIII、ヤツメウナギIII黄体形成ホルモン放出ホルモン、黄体形成ホルモンβ鎖、黄体形成ホルモン、絨毛性ゴナドトロピン、絨毛性ゴナドトロピンβサブユニット、メラニン細胞刺激ホルモン、エストラジオール、ジエチルスチルベストロール、ドーパミン、ソマトスタチン、卵胞刺激ホルモン(FSH)、グルココルチコイド、エストロゲン、テストステロン、アンドロステンジオン、ジヒドロテストステロン、デヒドロエピアンドロステロン、プロゲステロン、アンドロゲン、上皮細胞増殖因子(EGF)、成長ホルモン(GH)、Her2/neu、ビタミンH、葉酸、トランスフェリン、甲状腺刺激ホルモン(TSH)、エンドセリン、ボンベシン、成長ホルモン、血管作動性腸管ペプチド、ラクトフェリン、インテグリン、神経成長因子、CD−8、CD−33、CD19、CD20、CD40、ROR1、IGF−1、癌胎児性抗原(CEA)、αフェトプロテイン(AFP)、前立腺特異抗原(PSA)、前立腺特異的膜抗原(PSMA)、CA125(残存上皮性卵巣癌)、可溶性インターロイキン−2(IL−2)レセプタ、RAGE−1、チロシナーゼ、MAGE−1、MAGE−2、NY−ESO−1、Melan−A/MART−1、糖タンパク質(gp)75、gp100、βカテニン、PRAME、MUM−1、ZEP161、ユビキチン−1、HOX−B6、YB−1、オステオネクチン、ILF3、葉酸又は葉酸誘導体、腫瘍壊死因子(TNF)ファミリーメンバー、TNF−α、TNF−β(リンフォトキシン、LT)、腫瘍壊死因子関連アポトーシス誘導リガンド(TRAIL)、脂肪酸合成酵素(FAS)、LIGHT、41BB、形質転換成長因子α、形質転換成長因子β、インスリン、セルロプラスミン、HIV−tat、RGD配列モチーフを含むペプチドもしくはタンパク質、単糖、二糖、オリゴ糖、シアル酸、ガラクトース、マンノース、フコース、アセチルノイラミン酸、又はこれらの類似体と結合するレセプタを発現する請求項55から57のいずれか1項に記載の方法。
- 過増殖疾患を有する被験者を治療する方法であって、前記過増殖疾患を治療するために十分な量の請求項1又は2のいずれか1項に記載の融合コンストラクトを被験者に投与することを含む方法。
- 新生物、腫瘍、癌又は悪性腫瘍を有する被験者を治療する方法であって、前記新生物、腫瘍、癌又は悪性腫瘍の増殖を減少させ又は阻害するために十分な量の請求項1又は2のいずれか1項に記載の融合コンストラクトを被験者に投与することを含む方法。
- 新生物、腫瘍、癌もしくは悪性腫瘍の他部位への転移、又は、原発性の新生物、腫瘍、癌又は悪性腫瘍から遠位にある他部位における転移性の新生物、腫瘍、癌又は悪性腫瘍の形成を減少させ又は阻害する方法であって、前記新生物、腫瘍、癌又は悪性腫瘍の他部位への転移、又は、前記原発性の新生物、腫瘍、癌又は悪性腫瘍から遠位にある他部位における転移性の新生物、腫瘍、癌又は悪性腫瘍の形成を減少させ又は阻害するために十分な量の請求項1又は2のいずれか1項に記載の融合コンストラクトを、前記被験者に投与する方法。
- 前記新生物、腫瘍、癌又は悪性腫瘍が転移性、非転移性、又は良性である請求項64又は65のいずれか1項に記載の方法。
- 前記新生物、腫瘍、癌又は悪性腫瘍が固形細胞塊を含む請求項64又は65のいずれか1項に記載の方法。
- 前記新生物、腫瘍、癌又は悪性腫瘍が造血細胞を含む請求項64又は65のいずれか1項に記載の方法。
- 前記新生物、腫瘍、癌又は悪性腫瘍が、上皮性悪性腫瘍、肉腫、リンパ腫、白血病、腺腫、腺癌、黒色腫、神経膠腫、膠芽細胞腫、髄膜腫、神経芽細胞腫、網膜芽細胞腫、星状細胞腫、オリゴデンドログリオーマ、中皮腫、網内系・リンパ系・造血系の新生物、腫瘍、癌又は悪性腫瘍を含む請求項64又は65のいずれか1項に記載の方法。
- 前記肉腫が、リンパ肉腫、脂肪肉腫、骨肉腫、軟骨肉腫、平滑筋肉腫、横紋筋肉腫又は線維肉腫を含む請求項64又は65のいずれか1項に記載の方法。
- 前記造血系の新生物、腫瘍、癌又は悪性腫瘍が、骨髄腫、リンパ腫又は白血病を含む請求項68に記載の方法。
- 前記新生物、腫瘍、癌又は悪性腫瘍が、肺、甲状腺、頭部もしくは頸部、鼻咽頭、咽喉部、鼻部もしくは鼻腔部、脳、脊椎、乳腺、副腎、下垂体、甲状腺、リンパ液、胃腸(口腔、食堂、胃、十二指腸、回腸、空腸(小腸)、結腸、直腸)、泌尿生殖器(子宮、卵巣、頸部、子宮内膜、膀胱、睾丸、陰茎、前立腺)、腎臓、膵臓、肝臓、骨、骨髄、リンパ液、血液、筋肉、又は皮膚の新生物、腫瘍もしくは癌を含む請求項64又は65のいずれか1項に記載の方法。
- 前記肺の新生物、腫瘍、癌又は悪性腫瘍が、肺小細胞癌又は非小細胞肺癌を含む請求項72に記載の方法。
- 前記新生物、腫瘍、癌又は悪性腫瘍が、幹細胞の新生物、腫瘍、癌又は悪性腫瘍を含む請求項64又は65のいずれか1項に記載の方法。
- 前記方法が、前記新生物、腫瘍、癌又は悪性腫瘍の再発又は進行を阻害し又は減少させる請求項64又は65のいずれか1項に記載の方法。
- 抗細胞増殖、抗新生物、抗腫瘍、抗癌もしくは免疫増強の治療又は療法を実施することをさらに含む請求項63又は64のいずれか1項に記載の方法。
- 前記治療又は療法が、外科的切除、放射線治療、電離放射線治療もしくは化学放射線治療、化学療法、免疫療法、局部的もしくは局所的温熱療法(温熱療法)、又はワクチン接種を含む請求項76に記載の方法。
- 前記治療又は療法が、アルキル化剤、代謝拮抗剤、植物エキス、植物性アルカロイド、ニトロソウレア、ホルモン、ヌクレオチド又はヌクレオチド類似体を投与することを含む請求項76に記載の方法。
- 前記治療又は療法が、シクロホスファミド、アザチオプリン、シクロスポリンA、プレドニゾロン、メルファラン、クロラムブシル、メクロレタミン、ブスルファン、メトトレキサート、6−メルカプトプリン、チオグアニン、5−フルオロウラシル、シトシンアラビノシド、AZT、5−アザシチジン(5−AZC)及び5−アザシチジン関連化合物、ブレオマイシン、アクチノマイシンD、ミトラマイシン、マイトマイシンC、カルムスチン、ロムスチン、セムスチン、ストレプトゾトシン、ヒドロキシウレア、シスプラチン、ミトタン、プロカルバジン、ダカルバジン、タクソール、ビンブラスチン、ビンクリスチン、ドキソルビシン、又はジブロモマンニトールを投与することを含む請求項76に記載の方法。
- 前記治療又は療法が、リンパ球、形質細胞、マクロファージ、樹枝状細胞、NK細胞、又はB−細胞を投与することを含む請求項76に記載の方法。
- 前記治療又は療法が、抗体、細胞成長因子、細胞生存因子、細胞分化因子、サイトカイン、又はケモカインを投与することを含む請求項76に記載の方法。
- 前記治療又は療法が、IL−2、IL−1a、IL−1β、IL−3、IL−6、IL−7、顆粒球・マクロファージ・コロニー刺激因子(GMCSF)、IFN−γ、IL−12、TNF−α、TNF−β、MIP−1a, MIP−1β、RANTES、SDF−1、MCP−1、MCP−2、MCP−3、MCP−4、エオタキシン、エオタキシン−2、I−309/TCA3、ATAC、HCC−1、HCC−2、HCC−3、LARC/MIP−3α、PARC、TARC、CKβ、CKβ6、CKβ7、CKβ8、CKβ9、CKβ11、CKβ12、C10、IL−8、GROα、GROβ、ENA−78、GCP−2、PBP/CTAPIIIβ−TG/NAP−2、Mig、PBSF/SDF−1、又はリンフォタクチン(lymphotactin)を投与することを含む請求項76に記載の方法。
- 抗細胞増殖、抗新生物、抗腫瘍、抗癌もしくは免疫増強の治療又は療法を実施する前に、この実施と同時に、又は、この実施の後に、前記融合コンストラクトが投与される請求項76に記載の方法。
- 前記被験者が、外科的切除、化学療法、免疫療法、電離放射線治療もしくは化学放射線治療、局部的もしくは局所的温熱療法(温熱療法)、又はワクチン接種を受ける請求項64又は65のいずれか1項に記載の方法。
- 前記被験者が、外科的切除、化学療法、免疫療法、電離放射線治療もしくは化学放射線治療、局部的もしくは局所的温熱療法(温熱療法)、又はワクチン接種の候補である請求項64又は65のいずれか1項に記載の方法。
- 前記被験者が、外科的切除、化学療法、免疫療法、電離放射線治療もしくは化学放射線治療、局部的もしくは局所的温熱療法(温熱療法)、又はワクチン接種の候補ではない請求項64又は65のいずれか1項に記載の方法。
- 前記治療が、前記新生物細胞、腫瘍細胞、癌細胞もしくは悪性腫瘍細胞の質量、体積、サイズ又は細胞数を部分的に又は完全に破壊し、新生物細胞、腫瘍細胞、癌細胞もしくは悪性腫瘍細胞の壊死、溶解又はアポトーシスを刺激、誘導又は増強し、新生物、腫瘍、癌又は悪性腫瘍の体積、細胞質量を減少させ、新生物、腫瘍、癌又は悪性腫瘍の体積、質量、サイズもしくは細胞数の進行又は増加を阻害又は抑制し、寿命を延ばす請求項64又は65のいずれか1項に記載の方法。
- 前記治療が、前記新生物、腫瘍、癌又は悪性腫瘍に関連する又はこれらによって引き起こされる有害な症状や合併症の重症度、継続時間もしくは頻度を減少させる請求項64又は65のいずれか1項に記載の方法。
- 前記治療が、痛み、不快感、吐き気、衰弱又は倦怠感を減少させる請求項64又は65のいずれか1項に記載の方法。
- 前記治療が、活力、食欲、移動度の改善又は精神的充足感をもたらす請求項64又は65のいずれか1項に記載の方法。
- 前記被験者が哺乳類である請求項64又は65のいずれか1項に記載の方法。
- 前記被験者がヒトである請求項64又は65のいずれか1項に記載の方法。
- 受胎能力を減少させるために十分な量の請求項1又は2のいずれか1項に記載の融合コンストラクトを投与することを含む動物の生殖能力を減少させる方法。
- 前記動物が哺乳類である請求項93に記載の方法。
- 前記動物がヒトである請求項93に記載の方法。
- 動物の子宮内膜症を治療する方法であって、前記子宮内膜症を治療するために十分な量の請求項1又は2のいずれか1項に記載の融合コンストラクトを前記動物に投与することを含む方法。
- 良性の前立腺過形成を治療する方法であって、前記良性の前立腺過形成を治療するために十分な量の請求項1又は2のいずれか1項に記載の融合コンストラクトを前記動物に投与することを含む方法。
- 子宮筋腫又はポリープを治療する方法であって、前記子宮筋腫又はポリープを治療するために十分な量の請求項1又は2のいずれか1項に記載の融合コンストラクトを前記動物に投与することを含む方法。
- 前記子宮筋腫又は子宮ポリープが、乳腺、子宮、膣、頸部又は卵管に存在する請求項98に記載の方法。
- 前記融合コンストラクトが、Phor21−βCG−ala、Phor21−GSGGS−βCG−ala、Phor21−ASAAS−βCG−ala、又はPhor14−βCG−alaよりも優れた抗細胞増殖性を有し、この優れた抗細胞増殖性を有することがより小さなIC50値によって確認される請求項1又は2に記載の融合コンストラクト。
- 前記融合コンストラクトが、Phor21−βCG−ala、Phor21−GSGGS−βCG−ala、Phor21−ASAAS−βCG−ala、又はPhor14−βCG−alaより小さなIC50/HA50(溶血活性)比を有する請求項1又は2に記載の融合コンストラクト。
- 前記融合コンストラクトが、約0.02、0.01、又は0.005よりも小さなIC50/HA50(溶血活性)を有する請求項1又は2に記載の融合コンストラクト。
- KFAKFAKKFAKFAKK、KFAKFAKKFAKFAKKF、KFAKFAKKFAKFAKKFA、KFAKFAKKFAKFAKKFAK、KFAKFAKKFAKFAKKFAKF及びKFAKFAKKFAKFAKKFAKFAから選択される単離され又は精製されたペプチド。
- KFAKFAKKFAKFAKK、KFAKFAKKFAKFAKKF、KFAKFAKKFAKFAKKFA、KFAKFAKKFAKFAKKFAK、KFAKFAKKFAKFAKKFAKF及びKFAKFAKKFAKFAKKFAKFAから選択される単離され又は精製されたペプチドであって、単数又は複数の前記K残基をF残基又はL残基のいずれかで、単数又は複数の前記F残基をK残基、A残基又はL残基のいずれかで、単数又は複数の前記A残基をK残基、F残基又はL残基のいずれかで置換させたペプチド。
- 請求項103又は104のペプチドをコードする核酸。
- 請求項103又は104のペプチドをコードする核酸を含むベクター。
- 請求項103又は104のペプチドをコードする核酸を含むベクターで形質転換される宿主細胞。
- 請求項103又は104のペプチドを発現する細胞。
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US2337708P | 2008-01-24 | 2008-01-24 | |
US61/023,377 | 2008-01-24 | ||
PCT/US2009/031999 WO2009094634A1 (en) | 2008-01-24 | 2009-01-26 | Lytic domain fusion constructs and methods of making and using same |
Publications (2)
Publication Number | Publication Date |
---|---|
JP2011517550A true JP2011517550A (ja) | 2011-06-16 |
JP5616233B2 JP5616233B2 (ja) | 2014-10-29 |
Family
ID=40671139
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2010544463A Expired - Fee Related JP5616233B2 (ja) | 2008-01-24 | 2009-01-26 | 溶解ドメイン融合コンストラクト及びその生成及び使用方法 |
Country Status (13)
Country | Link |
---|---|
US (4) | US8318899B2 (ja) |
EP (1) | EP2252627B1 (ja) |
JP (1) | JP5616233B2 (ja) |
KR (2) | KR101863136B1 (ja) |
CN (1) | CN102089320B (ja) |
AU (1) | AU2009206212B2 (ja) |
BR (1) | BRPI0906404B8 (ja) |
CA (1) | CA2713126C (ja) |
DK (1) | DK2252627T3 (ja) |
ES (1) | ES2633453T3 (ja) |
IL (2) | IL207181A (ja) |
PT (1) | PT2252627T (ja) |
WO (1) | WO2009094634A1 (ja) |
Cited By (6)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2014061419A1 (ja) | 2012-10-17 | 2014-04-24 | 公立大学法人奈良県立医科大学 | 新規癌マーカーおよびその利用 |
JP2015504052A (ja) * | 2011-12-28 | 2015-02-05 | アダムド エスピー.ゼット オー.オー.Adamed Sp.Z O.O. | 抗がん融合タンパク質 |
JP2015514134A (ja) * | 2012-04-12 | 2015-05-18 | ステルス ペプチドズ インターナショナル インコーポレイテッド | 芳香族カチオン性ペプチド及びその使用 |
JP2016501839A (ja) * | 2012-10-30 | 2016-01-21 | エスペランス ファーマシューティカルズ, インコーポレイテッド | 抗体/薬剤結合体及び使用方法 |
JP2016506373A (ja) * | 2012-11-15 | 2016-03-03 | エスペランス ファーマシューティカルズ, インコーポレイテッド | 卵胞刺激ホルモン(fsh)/溶解ドメイン融合コンストラクト及びその作製及び使用の方法 |
JP2019507749A (ja) * | 2016-02-12 | 2019-03-22 | ボード オブ スーパーバイザーズ オブ ルイジアナ ステイト ユニバーシティ アンド アグリカルチュラル アンド メカニカル カレッジBoard Of Supervisors Of Louisiana State University And Agricultural And Mechanical College | がん処置組合せ組成物、方法及び使用 |
Families Citing this family (15)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2011031477A2 (en) * | 2009-08-25 | 2011-03-17 | Esperance Pharmaceuticals, Inc. | Nucleolin-binding peptides, nucleolin-binding lytic peptides, fusion constructs and methods of making and using same |
US10093961B2 (en) * | 2009-12-22 | 2018-10-09 | Esperance Pharmaceuticals | Methods for diagnosis of and predicting treatment efficacy of hormone receptor expressing tumors, cancers and neoplasias |
CN104177501A (zh) * | 2010-02-09 | 2014-12-03 | 沈阳药科大学 | 蝎镇痛抗肿瘤缬精甘肽融合体及其获得方法 |
US9150663B2 (en) | 2010-04-20 | 2015-10-06 | Genmab A/S | Heterodimeric antibody Fc-containing proteins and methods for production thereof |
WO2011137245A2 (en) * | 2010-04-30 | 2011-11-03 | Esperance Pharmaceuticals, Inc. | Lytic-peptide-her2/neu (human epidermal growth factor receptor 2) ligand conjugates and methods of use |
WO2012050892A2 (en) * | 2010-09-29 | 2012-04-19 | Esperance Pharmaceuticals, Inc. | Methods for stimulating, increasing or enhancing killing of a cell that expresses luteinizing hormone releasing hormone (lhrh) receptors |
US8461118B2 (en) * | 2011-07-07 | 2013-06-11 | Tuskegee University | Lytic peptides having anti-proliferative activity against prostate cancer cells |
PT2771364T (pt) | 2011-10-27 | 2019-09-10 | Genmab As | Produção de proteínas heterodiméricas |
PL397167A1 (pl) * | 2011-11-28 | 2013-06-10 | Adamed Spólka Z Ograniczona Odpowiedzialnoscia | Przeciwnowotworowe bialko fuzyjne |
WO2016054153A1 (en) | 2014-10-02 | 2016-04-07 | The Wistar Institute Of Anatomy And Biology | Methods and compositions for treating cancer |
GB2543550A (en) * | 2015-10-21 | 2017-04-26 | Hox Therapeutics Ltd | Peptides |
CN105963687A (zh) * | 2016-04-27 | 2016-09-28 | 张金凤 | 一种用于治疗慢性盆腔疼痛的复方制剂及其制备方法 |
CN107955061B (zh) * | 2017-11-15 | 2021-07-30 | 连云港恒运药业有限公司 | 地加瑞克关键中间体的制备方法 |
BR112022018994A2 (pt) * | 2020-03-26 | 2022-11-29 | A28 Therapeutics Inc | Construtos de fusão de domínio lítico, inibidores de via de sinalização e métodos de produzir e usar os mesmos |
CN112225821B (zh) * | 2020-10-21 | 2021-05-21 | 徐州医科大学 | 一种具有抗肿瘤作用的多肽及其应用 |
Citations (6)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JPH08507749A (ja) * | 1992-12-03 | 1996-08-20 | マガイニン ファーマシューティカルズ,インク. | 皮膚悪性疾患の生物学的活性を有するペプチドによる治療 |
JP2000514836A (ja) * | 1997-03-27 | 2000-11-07 | ボード オブ スーパーバイザーズ オブ ルイジアナ ステイト ユニバーシティー アンド アグリカルチュラル アンド メカニカル カレッジ | リガンド/細胞溶解ペプチド組成物及びその使用方法 |
JP2002514605A (ja) * | 1998-05-08 | 2002-05-21 | ザ レジェンツ オブ ザ ユニヴァースティ オブ カリフォルニア | 血管形成を検出および阻害する方法 |
JP2006516546A (ja) * | 2002-11-15 | 2006-07-06 | サングスタット メディカル コーポレイション | 間質性膀胱炎の治療用細胞調節性ペプチド |
JP2007500744A (ja) * | 2003-05-06 | 2007-01-18 | シントニックス・ファーマシューティカルズ・インコーポレーテッド | 免疫グロブリンキメラ単量体−二量体ハイブリッド |
WO2007115033A2 (en) * | 2006-03-31 | 2007-10-11 | Board Of Supervisors Of Louisiana State University And Agricultural And Mechanical College | Layered nanoparticles for sustained release of small molecules |
Family Cites Families (48)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
DE3854476T2 (de) | 1987-07-06 | 1996-04-04 | Univ Louisiana State | Inhibierung von eukaryotischen pathogenen und neoplasmen mit lytischen peptiden. |
CA1327311C (en) | 1987-07-06 | 1994-03-01 | Jesse M. Jaynes | Therapeutic antimicrobial polypeptides, their use and methods for preparation |
US5861478A (en) | 1987-07-06 | 1999-01-19 | Helix Biomedix, Inc. | Lytic peptides |
US5792831A (en) | 1990-02-08 | 1998-08-11 | Magainin Pharmaceuticals Inc. | Analogues of magainin peptides containing D-amino acids |
US5459237A (en) | 1990-02-08 | 1995-10-17 | Magainin Pharmaceuticals Inc. | Peptide compositions and uses therefor |
JPH07504152A (ja) | 1990-02-08 | 1995-05-11 | マゲイニン ファーマスーティカルズ, インコーポレーテッド | 生物活性ペプチドおよび標的細胞、ウイルス、あるいはウイルス感染細胞の成長を抑制する方法 |
WO1992022317A1 (en) | 1991-06-12 | 1992-12-23 | Magainin Pharmaceuticals, Inc. | Composition and treatment with biologically active peptides having c-terminal substitutions |
AU3236293A (en) | 1991-12-09 | 1993-07-19 | Magainin Pharmaceuticals, Inc. | Composition and treatment with biologically active peptides and chelating agents |
CA2137087A1 (en) | 1992-06-01 | 1993-12-09 | U. Prasad Kari | Biologically active peptides having n-terminal substitutions |
US6348445B1 (en) | 1992-06-01 | 2002-02-19 | Magainin Pharmaceuticals, Inc. | Biologically active peptides with reduced toxicity in animals and a method for preparing same |
AU5081193A (en) | 1992-08-31 | 1994-03-29 | Magainin Pharmaceuticals, Inc. | Treatment of gynecological malignancies with biologically active peptides |
AU5741794A (en) | 1992-12-07 | 1994-07-04 | Magainin Pharmaceuticals, Inc. | Treatment of septic shock with conjugated biologically active peptides |
AU6251594A (en) | 1993-02-26 | 1994-09-14 | Magainin Pharmaceuticals, Inc. | Treatment of cancerous growths with biologically active peptides and protease inhibitors |
JPH09500102A (ja) | 1993-04-28 | 1997-01-07 | ウォーセスター ファウンデーション フォー エクスペリメンタル バイオロジー | 細胞指向性溶解孔形成剤 |
US5773413A (en) | 1993-06-04 | 1998-06-30 | Demeter Biotechnologies, Ltd. | Method of combating mammalian neoplasias, and lytic peptides therefor |
US5955573A (en) | 1993-06-04 | 1999-09-21 | Demegen, Inc. | Ubiquitin-lytic peptide fusion gene constructs, protein products deriving therefrom, and methods of making and using same |
US5561107A (en) | 1993-06-04 | 1996-10-01 | Demeter Biotechnologies, Ltd. | Method of enhancing wound healing by stimulating fibroblast and keratinocyte growth in vivo, utilizing amphipathic peptides |
AU7050294A (en) | 1993-06-04 | 1995-01-03 | Demeter Biotechnologies, Ltd. | Method of treating pulmonary disease states with non-naturally occurring amphipathic peptides |
US5968904A (en) | 1993-06-04 | 1999-10-19 | Demegen, Inc. | Modified arginine containing lytic peptides and method of making the same by glyoxylation |
WO1995013085A1 (en) | 1993-11-08 | 1995-05-18 | Demeter Biotechnologies Ltd. | Methylated lysine-rich lytic peptides and method of making same by reductive alkylation |
US5789542A (en) * | 1994-04-22 | 1998-08-04 | Board Of Supervisors Of Louisiana State University And Agricultural And Mechanical College | Amphipathic peptides |
IL114697A0 (en) | 1994-07-22 | 1995-11-27 | Demeter Biotech Ltd | Polypeptides comprising ubiquitin-lytic peptide fusion protein products deriving therefrom their preparation and use |
JP2001501620A (ja) | 1996-10-04 | 2001-02-06 | デメジェン インコーポレイテッド | 免疫不全ウイルス感染の治療方法 |
WO2000053755A2 (en) | 1999-03-08 | 2000-09-14 | Genentech, Inc. | Compositions and methods for the treatment of tumor |
US6566334B1 (en) | 1997-02-06 | 2003-05-20 | Board Of Supervisors Of Louisiana State University And Agricultural And Mechanical College | Short amphipathic peptides with activity against bacteria and intracellular pathogens |
US6635740B1 (en) * | 1997-03-27 | 2003-10-21 | Board Of Supervisors Of Louisiana State University And Agricultural And Mechanical College | Ligand/lytic peptide compositions and methods of use |
GB9711115D0 (en) * | 1997-05-29 | 1997-07-23 | Inst Of Child Health | Integrin-targeting vectors having enhanced transfection activity |
WO1999003488A2 (en) | 1997-07-15 | 1999-01-28 | Magainin Pharmaceuticals Inc. | Biologically active peptides with reduced toxicity in animals and a method for preparing same |
US6680058B1 (en) | 1997-09-03 | 2004-01-20 | Board Of Supervisors Of Louisiana State University And Agricultural And Mechanical College | Compositions and methods for contraception in or sterilization of mammals |
US6461813B2 (en) * | 1998-09-21 | 2002-10-08 | Rigel Pharmaceuticals, Inc. | Multiparameter FACS assays to detect alterations in cell cycle regulation |
US6656906B1 (en) * | 1998-05-20 | 2003-12-02 | Trimeris, Inc. | Hybrid polypeptides with enhanced pharmacokinetic properties |
GB0005702D0 (en) | 2000-03-09 | 2000-05-03 | Alpharma As | Method |
PL201898B1 (pl) | 1999-09-23 | 2009-05-29 | Zentaris Gmbh | Zastosowanie antagonisty LH-RH w leczeniu endometriozy |
PL357999A1 (en) | 2000-03-14 | 2004-08-09 | Zentaris Gmbh | Lhrh-antagonists, production and use thereof as medicament |
EP1285081A2 (en) * | 2000-05-30 | 2003-02-26 | ICH Productions Limited | Improved methods of transfection |
US6875744B2 (en) | 2001-03-28 | 2005-04-05 | Helix Biomedix, Inc. | Short bioactive peptides |
CA2467237C (en) | 2001-11-15 | 2011-09-20 | Herman Jan Tijmen Coelingh Bennink | Method of preventing or treating benign gynaecological disorders |
CA2482995C (en) | 2002-04-22 | 2013-01-29 | Dow Global Technologies Inc. | Low-cost production of peptides |
AU2003287950B2 (en) | 2002-09-27 | 2009-01-29 | Zentaris Gmbh | Administration form for pharmaceutically active peptides with sustained release and method for the production thereof |
US7091185B2 (en) | 2003-02-24 | 2006-08-15 | Dow Global Technologies Inc. | Periodic antimicrobial peptides |
CN1894277A (zh) | 2003-02-24 | 2007-01-10 | 陶氏环球技术公司 | 周期性抗微生物肽 |
GB0307777D0 (en) | 2003-04-04 | 2003-05-07 | Medical Res Council | Conjugate compounds |
NO20031818D0 (no) | 2003-04-23 | 2003-04-23 | Uni I Tromsoe | Fremgangsmåte av bioaktiv peptid forberedelse |
GB0320806D0 (en) | 2003-09-05 | 2003-10-08 | Astrazeneca Ab | Therapeutic treatment |
WO2005062881A2 (en) | 2003-12-24 | 2005-07-14 | Transgenrx, Inc. | Gene therapy using transposon-based vectors |
GB0506759D0 (en) | 2005-04-02 | 2005-05-11 | Medical Res Council | Combination treatment methods |
US7288622B1 (en) | 2006-09-19 | 2007-10-30 | Issar Pharmaceuticals Pvt Ltd | Composition for treatment of burns and wounds |
US7803755B2 (en) | 2006-12-21 | 2010-09-28 | Jesse Jaynes | Molecules for the treatment and prevention of fungal diseases |
-
2009
- 2009-01-26 CN CN200980111383.7A patent/CN102089320B/zh active Active
- 2009-01-26 ES ES09704677.5T patent/ES2633453T3/es active Active
- 2009-01-26 EP EP09704677.5A patent/EP2252627B1/en active Active
- 2009-01-26 WO PCT/US2009/031999 patent/WO2009094634A1/en active Application Filing
- 2009-01-26 JP JP2010544463A patent/JP5616233B2/ja not_active Expired - Fee Related
- 2009-01-26 US US12/359,906 patent/US8318899B2/en active Active
- 2009-01-26 AU AU2009206212A patent/AU2009206212B2/en active Active
- 2009-01-26 KR KR1020167023712A patent/KR101863136B1/ko active IP Right Grant
- 2009-01-26 PT PT97046775T patent/PT2252627T/pt unknown
- 2009-01-26 CA CA2713126A patent/CA2713126C/en not_active Expired - Fee Related
- 2009-01-26 BR BRPI0906404A patent/BRPI0906404B8/pt active IP Right Grant
- 2009-01-26 KR KR1020107018765A patent/KR101749310B1/ko active IP Right Grant
- 2009-01-26 DK DK09704677.5T patent/DK2252627T3/en active
- 2009-03-05 US US12/398,965 patent/US8546535B2/en active Active
- 2009-03-05 US US12/398,958 patent/US20090233860A1/en not_active Abandoned
-
2010
- 2010-07-25 IL IL207181A patent/IL207181A/en active IP Right Grant
-
2013
- 2013-09-26 US US14/038,631 patent/US9255134B2/en active Active
-
2016
- 2016-01-03 IL IL243446A patent/IL243446B/en unknown
Patent Citations (6)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JPH08507749A (ja) * | 1992-12-03 | 1996-08-20 | マガイニン ファーマシューティカルズ,インク. | 皮膚悪性疾患の生物学的活性を有するペプチドによる治療 |
JP2000514836A (ja) * | 1997-03-27 | 2000-11-07 | ボード オブ スーパーバイザーズ オブ ルイジアナ ステイト ユニバーシティー アンド アグリカルチュラル アンド メカニカル カレッジ | リガンド/細胞溶解ペプチド組成物及びその使用方法 |
JP2002514605A (ja) * | 1998-05-08 | 2002-05-21 | ザ レジェンツ オブ ザ ユニヴァースティ オブ カリフォルニア | 血管形成を検出および阻害する方法 |
JP2006516546A (ja) * | 2002-11-15 | 2006-07-06 | サングスタット メディカル コーポレイション | 間質性膀胱炎の治療用細胞調節性ペプチド |
JP2007500744A (ja) * | 2003-05-06 | 2007-01-18 | シントニックス・ファーマシューティカルズ・インコーポレーテッド | 免疫グロブリンキメラ単量体−二量体ハイブリッド |
WO2007115033A2 (en) * | 2006-03-31 | 2007-10-11 | Board Of Supervisors Of Louisiana State University And Agricultural And Mechanical College | Layered nanoparticles for sustained release of small molecules |
Non-Patent Citations (2)
Title |
---|
BODEK GABRIEL: "A NOVEL APPROACH OF TARGETED ABLATION OF MAMMARY CARCINOMA CELLS THROUGH LUTEINIZING HORMONE RECEPTO", BREAST CANCER RESEARCH AND TREATMENT, vol. V79 N1, JPN5012000114, May 2003 (2003-05-01), pages 1 - 10, ISSN: 0002605666 * |
MOLECULAR AND CELLULAR ENDOCRINOLOGY, vol. vol.260-262, JPN6013039873, 2007, pages 183 - 189, ISSN: 0002605667 * |
Cited By (8)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2015504052A (ja) * | 2011-12-28 | 2015-02-05 | アダムド エスピー.ゼット オー.オー.Adamed Sp.Z O.O. | 抗がん融合タンパク質 |
JP2015514134A (ja) * | 2012-04-12 | 2015-05-18 | ステルス ペプチドズ インターナショナル インコーポレイテッド | 芳香族カチオン性ペプチド及びその使用 |
JP2017203036A (ja) * | 2012-04-12 | 2017-11-16 | ステルス ペプチドズ インターナショナル インコーポレイテッド | 芳香族カチオン性ペプチド及びその使用 |
WO2014061419A1 (ja) | 2012-10-17 | 2014-04-24 | 公立大学法人奈良県立医科大学 | 新規癌マーカーおよびその利用 |
US9857375B2 (en) | 2012-10-17 | 2018-01-02 | Public University Corporation Nara Medical University | Cancer marker and utilization thereof |
JP2016501839A (ja) * | 2012-10-30 | 2016-01-21 | エスペランス ファーマシューティカルズ, インコーポレイテッド | 抗体/薬剤結合体及び使用方法 |
JP2016506373A (ja) * | 2012-11-15 | 2016-03-03 | エスペランス ファーマシューティカルズ, インコーポレイテッド | 卵胞刺激ホルモン(fsh)/溶解ドメイン融合コンストラクト及びその作製及び使用の方法 |
JP2019507749A (ja) * | 2016-02-12 | 2019-03-22 | ボード オブ スーパーバイザーズ オブ ルイジアナ ステイト ユニバーシティ アンド アグリカルチュラル アンド メカニカル カレッジBoard Of Supervisors Of Louisiana State University And Agricultural And Mechanical College | がん処置組合せ組成物、方法及び使用 |
Also Published As
Publication number | Publication date |
---|---|
CN102089320A (zh) | 2011-06-08 |
WO2009094634A1 (en) | 2009-07-30 |
ES2633453T3 (es) | 2017-09-21 |
EP2252627B1 (en) | 2017-04-19 |
IL207181A (en) | 2016-09-29 |
BRPI0906404B1 (pt) | 2021-04-06 |
CN102089320B (zh) | 2015-11-25 |
CA2713126C (en) | 2017-08-15 |
KR20100127212A (ko) | 2010-12-03 |
AU2009206212A1 (en) | 2009-07-30 |
BRPI0906404A2 (pt) | 2015-11-24 |
US8318899B2 (en) | 2012-11-27 |
US9255134B2 (en) | 2016-02-09 |
KR101863136B1 (ko) | 2018-05-31 |
IL207181A0 (en) | 2010-12-30 |
KR20160106191A (ko) | 2016-09-09 |
AU2009206212B2 (en) | 2014-01-16 |
BRPI0906404B8 (pt) | 2021-05-25 |
IL243446B (en) | 2021-08-31 |
DK2252627T3 (en) | 2017-08-14 |
US20090233861A1 (en) | 2009-09-17 |
US8546535B2 (en) | 2013-10-01 |
IL243446A0 (en) | 2016-02-29 |
JP5616233B2 (ja) | 2014-10-29 |
PT2252627T (pt) | 2017-07-24 |
CA2713126A1 (en) | 2009-07-30 |
US20140255513A1 (en) | 2014-09-11 |
KR101749310B1 (ko) | 2017-06-21 |
EP2252627A1 (en) | 2010-11-24 |
US20090233860A1 (en) | 2009-09-17 |
US20090269341A1 (en) | 2009-10-29 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
JP5616233B2 (ja) | 溶解ドメイン融合コンストラクト及びその生成及び使用方法 | |
JP2016506373A (ja) | 卵胞刺激ホルモン(fsh)/溶解ドメイン融合コンストラクト及びその作製及び使用の方法 | |
JP6509169B2 (ja) | 溶解性ペプチド−Her2/neu(ヒト上皮成長因子レセプター2)リガンド結合体およびその使用方法 | |
JP2016501839A (ja) | 抗体/薬剤結合体及び使用方法 | |
WO2012050892A2 (en) | Methods for stimulating, increasing or enhancing killing of a cell that expresses luteinizing hormone releasing hormone (lhrh) receptors | |
JP2010508020A (ja) | Lightを介する抗細胞増殖性組成物および方法 | |
JP2023518977A (ja) | 溶解性ドメイン融合構築物、チェックポイント阻害剤、およびそれらを作出し、使用する方法 |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
A621 | Written request for application examination |
Free format text: JAPANESE INTERMEDIATE CODE: A621 Effective date: 20120120 |
|
A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20130813 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20131112 |
|
A02 | Decision of refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A02 Effective date: 20140114 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20140428 |
|
A911 | Transfer to examiner for re-examination before appeal (zenchi) |
Free format text: JAPANESE INTERMEDIATE CODE: A911 Effective date: 20140616 |
|
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: 20140819 |
|
A61 | First payment of annual fees (during grant procedure) |
Free format text: JAPANESE INTERMEDIATE CODE: A61 Effective date: 20140911 |
|
R150 | Certificate of patent or registration of utility model |
Ref document number: 5616233 Country of ref document: JP Free format text: JAPANESE INTERMEDIATE CODE: R150 |
|
LAPS | Cancellation because of no payment of annual fees |