JP2019510005A - 急性骨髄性白血病の治療方法 - Google Patents
急性骨髄性白血病の治療方法 Download PDFInfo
- Publication number
- JP2019510005A JP2019510005A JP2018544337A JP2018544337A JP2019510005A JP 2019510005 A JP2019510005 A JP 2019510005A JP 2018544337 A JP2018544337 A JP 2018544337A JP 2018544337 A JP2018544337 A JP 2018544337A JP 2019510005 A JP2019510005 A JP 2019510005A
- Authority
- JP
- Japan
- Prior art keywords
- cxcr4
- subject
- antagonist
- aml
- chemotherapeutic agent
- 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
- 208000031261 Acute myeloid leukaemia Diseases 0.000 title claims abstract description 75
- 208000033776 Myeloid Acute Leukemia Diseases 0.000 title claims abstract description 66
- 229940121384 cxc chemokine receptor type 4 (cxcr4) antagonist Drugs 0.000 claims abstract description 104
- 239000002576 chemokine receptor CXCR4 antagonist Substances 0.000 claims abstract description 93
- 238000000034 method Methods 0.000 claims abstract description 77
- 239000002246 antineoplastic agent Substances 0.000 claims abstract description 65
- 229940127089 cytotoxic agent Drugs 0.000 claims abstract description 64
- 210000005259 peripheral blood Anatomy 0.000 claims abstract description 58
- 239000011886 peripheral blood Substances 0.000 claims abstract description 58
- 210000001185 bone marrow Anatomy 0.000 claims abstract description 42
- 210000000265 leukocyte Anatomy 0.000 claims abstract description 21
- 230000002093 peripheral effect Effects 0.000 claims abstract description 16
- 238000011282 treatment Methods 0.000 claims description 57
- 108090000765 processed proteins & peptides Proteins 0.000 claims description 53
- 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 24
- 102100031650 C-X-C chemokine receptor type 4 Human genes 0.000 claims description 17
- 101000922348 Homo sapiens C-X-C chemokine receptor type 4 Proteins 0.000 claims description 15
- 229960000684 cytarabine Drugs 0.000 claims description 12
- 230000037396 body weight Effects 0.000 claims description 8
- 230000004043 responsiveness Effects 0.000 claims description 7
- 239000003795 chemical substances by application Substances 0.000 claims description 6
- 238000002512 chemotherapy Methods 0.000 claims description 6
- 238000011284 combination treatment Methods 0.000 claims description 6
- 238000009097 single-agent therapy Methods 0.000 claims description 5
- 230000001747 exhibiting effect Effects 0.000 claims description 3
- 210000003969 blast cell Anatomy 0.000 claims description 2
- JJVZSYKFCOBILL-MKMRYRNGSA-N motixafortide Chemical compound NCCCC[C@@H]1NC(=O)[C@H](CCCNC(N)=O)NC(=O)[C@H](Cc2ccc(O)cc2)NC(=O)[C@H](CSSC[C@H](NC(=O)[C@H](CCCNC(N)=O)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](Cc2ccc(O)cc2)NC(=O)[C@@H]2CCCN2C(=O)[C@H](CCCCN)NC1=O)C(=O)N[C@@H](CCCNC(N)=N)C(N)=O)NC(=O)[C@H](Cc1ccc2ccccc2c1)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CCCNC(N)=N)NC(=O)c1ccc(F)cc1 JJVZSYKFCOBILL-MKMRYRNGSA-N 0.000 description 24
- 108010060188 4-fluorobenzoyl-TN-14003 Proteins 0.000 description 23
- 150000001413 amino acids Chemical class 0.000 description 23
- 239000004480 active ingredient Substances 0.000 description 16
- 239000000203 mixture Substances 0.000 description 15
- 239000008194 pharmaceutical composition Substances 0.000 description 15
- 210000004027 cell Anatomy 0.000 description 13
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 12
- 206010028980 Neoplasm Diseases 0.000 description 11
- 235000001014 amino acid Nutrition 0.000 description 10
- 201000010099 disease Diseases 0.000 description 10
- 239000003112 inhibitor Substances 0.000 description 10
- 102000004196 processed proteins & peptides Human genes 0.000 description 10
- 201000011510 cancer Diseases 0.000 description 9
- 229960002169 plerixafor Drugs 0.000 description 9
- 239000003814 drug Substances 0.000 description 8
- 239000004475 Arginine Substances 0.000 description 7
- ODKSFYDXXFIFQN-BYPYZUCNSA-P L-argininium(2+) Chemical compound NC(=[NH2+])NCCC[C@H]([NH3+])C(O)=O ODKSFYDXXFIFQN-BYPYZUCNSA-P 0.000 description 7
- RHGKLRLOHDJJDR-BYPYZUCNSA-N L-citrulline Chemical compound NC(=O)NCCC[C@H]([NH3+])C([O-])=O RHGKLRLOHDJJDR-BYPYZUCNSA-N 0.000 description 7
- ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 7
- 235000009697 arginine Nutrition 0.000 description 7
- 238000009472 formulation Methods 0.000 description 7
- 230000035772 mutation Effects 0.000 description 7
- 230000003285 pharmacodynamic effect Effects 0.000 description 7
- YIQPUIGJQJDJOS-UHFFFAOYSA-N plerixafor Chemical compound C=1C=C(CN2CCNCCCNCCNCCC2)C=CC=1CN1CCCNCCNCCCNCC1 YIQPUIGJQJDJOS-UHFFFAOYSA-N 0.000 description 7
- RHGKLRLOHDJJDR-UHFFFAOYSA-N Ndelta-carbamoyl-DL-ornithine Natural products OC(=O)C(N)CCCNC(N)=O RHGKLRLOHDJJDR-UHFFFAOYSA-N 0.000 description 6
- 235000013477 citrulline Nutrition 0.000 description 6
- 229960002173 citrulline Drugs 0.000 description 6
- 229940079593 drug Drugs 0.000 description 6
- 230000000694 effects Effects 0.000 description 6
- 125000000291 glutamic acid group Chemical group N[C@@H](CCC(O)=O)C(=O)* 0.000 description 6
- 238000002347 injection Methods 0.000 description 6
- 239000007924 injection Substances 0.000 description 6
- 239000000725 suspension Substances 0.000 description 6
- UEUPDYPUTTUXLJ-UHFFFAOYSA-N 1-[[4-(1,4,8,11-tetrazacyclotetradec-1-ylmethyl)phenyl]methyl]-1,4,8,11-tetrazacyclotetradecane;octahydrochloride Chemical compound Cl.Cl.Cl.Cl.Cl.Cl.Cl.Cl.C=1C=C(CN2CCNCCCNCCNCCC2)C=CC=1CN1CCCNCCNCCCNCC1 UEUPDYPUTTUXLJ-UHFFFAOYSA-N 0.000 description 5
- 101000932478 Homo sapiens Receptor-type tyrosine-protein kinase FLT3 Proteins 0.000 description 5
- QNAYBMKLOCPYGJ-REOHCLBHSA-N L-alanine Chemical compound C[C@H](N)C(O)=O QNAYBMKLOCPYGJ-REOHCLBHSA-N 0.000 description 5
- KDXKERNSBIXSRK-YFKPBYRVSA-N L-lysine Chemical compound NCCCC[C@H](N)C(O)=O KDXKERNSBIXSRK-YFKPBYRVSA-N 0.000 description 5
- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 5
- 239000004472 Lysine Substances 0.000 description 5
- 102100020718 Receptor-type tyrosine-protein kinase FLT3 Human genes 0.000 description 5
- 235000004279 alanine Nutrition 0.000 description 5
- 239000005557 antagonist Substances 0.000 description 5
- 235000018977 lysine Nutrition 0.000 description 5
- 239000000546 pharmaceutical excipient Substances 0.000 description 5
- 238000002360 preparation method Methods 0.000 description 5
- 238000011084 recovery Methods 0.000 description 5
- 230000010076 replication Effects 0.000 description 5
- 230000001225 therapeutic effect Effects 0.000 description 5
- -1 triethylene Chemical compound 0.000 description 5
- PTOAARAWEBMLNO-KVQBGUIXSA-N Cladribine Chemical compound C1=NC=2C(N)=NC(Cl)=NC=2N1[C@H]1C[C@H](O)[C@@H](CO)O1 PTOAARAWEBMLNO-KVQBGUIXSA-N 0.000 description 4
- AOJJSUZBOXZQNB-TZSSRYMLSA-N Doxorubicin Chemical compound O([C@H]1C[C@@](O)(CC=2C(O)=C3C(=O)C=4C=CC=C(C=4C(=O)C3=C(O)C=21)OC)C(=O)CO)[C@H]1C[C@H](N)[C@H](O)[C@H](C)O1 AOJJSUZBOXZQNB-TZSSRYMLSA-N 0.000 description 4
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 4
- AHLPHDHHMVZTML-BYPYZUCNSA-N L-Ornithine Chemical compound NCCC[C@H](N)C(O)=O AHLPHDHHMVZTML-BYPYZUCNSA-N 0.000 description 4
- AHLPHDHHMVZTML-UHFFFAOYSA-N Orn-delta-NH2 Natural products NCCCC(N)C(O)=O AHLPHDHHMVZTML-UHFFFAOYSA-N 0.000 description 4
- UTJLXEIPEHZYQJ-UHFFFAOYSA-N Ornithine Natural products OC(=O)C(C)CCCN UTJLXEIPEHZYQJ-UHFFFAOYSA-N 0.000 description 4
- 229930012538 Paclitaxel Natural products 0.000 description 4
- 238000003556 assay Methods 0.000 description 4
- 238000004113 cell culture Methods 0.000 description 4
- 208000032839 leukemia Diseases 0.000 description 4
- 239000000463 material Substances 0.000 description 4
- 238000005259 measurement Methods 0.000 description 4
- GLVAUDGFNGKCSF-UHFFFAOYSA-N mercaptopurine Chemical compound S=C1NC=NC2=C1NC=N2 GLVAUDGFNGKCSF-UHFFFAOYSA-N 0.000 description 4
- 229960003104 ornithine Drugs 0.000 description 4
- 229960001592 paclitaxel Drugs 0.000 description 4
- BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Chemical compound [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 description 4
- 230000004044 response Effects 0.000 description 4
- RCINICONZNJXQF-MZXODVADSA-N taxol Chemical compound O([C@@H]1[C@@]2(C[C@@H](C(C)=C(C2(C)C)[C@H](C([C@]2(C)[C@@H](O)C[C@H]3OC[C@]3([C@H]21)OC(C)=O)=O)OC(=O)C)OC(=O)[C@H](O)[C@@H](NC(=O)C=1C=CC=CC=1)C=1C=CC=CC=1)O)C(=O)C1=CC=CC=C1 RCINICONZNJXQF-MZXODVADSA-N 0.000 description 4
- WYWHKKSPHMUBEB-UHFFFAOYSA-N tioguanine Chemical compound N1C(N)=NC(=S)C2=C1N=CN2 WYWHKKSPHMUBEB-UHFFFAOYSA-N 0.000 description 4
- FDKXTQMXEQVLRF-ZHACJKMWSA-N (E)-dacarbazine Chemical compound CN(C)\N=N\c1[nH]cnc1C(N)=O FDKXTQMXEQVLRF-ZHACJKMWSA-N 0.000 description 3
- WVLHHLRVNDMIAR-IBGZPJMESA-N AMD 070 Chemical compound C1CCC2=CC=CN=C2[C@H]1N(CCCCN)CC1=NC2=CC=CC=C2N1 WVLHHLRVNDMIAR-IBGZPJMESA-N 0.000 description 3
- COVZYZSDYWQREU-UHFFFAOYSA-N Busulfan Chemical compound CS(=O)(=O)OCCCCOS(C)(=O)=O COVZYZSDYWQREU-UHFFFAOYSA-N 0.000 description 3
- 101710082513 C-X-C chemokine receptor type 4 Proteins 0.000 description 3
- 108010053045 CTCE-9908 Proteins 0.000 description 3
- 108010061299 CXCR4 Receptors Proteins 0.000 description 3
- 102000012000 CXCR4 Receptors Human genes 0.000 description 3
- DLGOEMSEDOSKAD-UHFFFAOYSA-N Carmustine Chemical compound ClCCNC(=O)N(N=O)CCCl DLGOEMSEDOSKAD-UHFFFAOYSA-N 0.000 description 3
- CMSMOCZEIVJLDB-UHFFFAOYSA-N Cyclophosphamide Chemical compound ClCCN(CCCl)P1(=O)NCCCO1 CMSMOCZEIVJLDB-UHFFFAOYSA-N 0.000 description 3
- GQYIWUVLTXOXAJ-UHFFFAOYSA-N Lomustine Chemical compound ClCCN(N=O)C(=O)NC1CCCCC1 GQYIWUVLTXOXAJ-UHFFFAOYSA-N 0.000 description 3
- 241001465754 Metazoa Species 0.000 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 description 3
- 230000001413 cellular effect Effects 0.000 description 3
- 230000000973 chemotherapeutic effect Effects 0.000 description 3
- 150000001875 compounds Chemical class 0.000 description 3
- VUYRSKROGTWHDC-HZGLMRDYSA-N ctce 9908 Chemical compound C([C@H](NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)CNC(=O)[C@@H](N)CCCCN)C(C)C)CC(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)NCCCC[C@H](NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CO)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)CNC(=O)[C@@H](N)CCCCN)C(C)C)C(N)=O)C1=CC=C(O)C=C1 VUYRSKROGTWHDC-HZGLMRDYSA-N 0.000 description 3
- STQGQHZAVUOBTE-VGBVRHCVSA-N daunorubicin Chemical compound O([C@H]1C[C@@](O)(CC=2C(O)=C3C(=O)C=4C=CC=C(C=4C(=O)C3=C(O)C=21)OC)C(C)=O)[C@H]1C[C@H](N)[C@H](O)[C@H](C)O1 STQGQHZAVUOBTE-VGBVRHCVSA-N 0.000 description 3
- 239000002552 dosage form Substances 0.000 description 3
- 210000003958 hematopoietic stem cell Anatomy 0.000 description 3
- YLMAHDNUQAMNNX-UHFFFAOYSA-N imatinib methanesulfonate Chemical compound CS(O)(=O)=O.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 YLMAHDNUQAMNNX-UHFFFAOYSA-N 0.000 description 3
- 238000000338 in vitro Methods 0.000 description 3
- 230000000670 limiting effect Effects 0.000 description 3
- 238000004519 manufacturing process Methods 0.000 description 3
- KKZJGLLVHKMTCM-UHFFFAOYSA-N mitoxantrone Chemical compound O=C1C2=C(O)C=CC(O)=C2C(=O)C2=C1C(NCCNCCO)=CC=C2NCCNCCO KKZJGLLVHKMTCM-UHFFFAOYSA-N 0.000 description 3
- 229960001156 mitoxantrone Drugs 0.000 description 3
- 238000010369 molecular cloning Methods 0.000 description 3
- 239000000243 solution Substances 0.000 description 3
- 239000000126 substance Substances 0.000 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 description 3
- FPVKHBSQESCIEP-UHFFFAOYSA-N (8S)-3-(2-deoxy-beta-D-erythro-pentofuranosyl)-3,6,7,8-tetrahydroimidazo[4,5-d][1,3]diazepin-8-ol Natural products C1C(O)C(CO)OC1N1C(NC=NCC2O)=C2N=C1 FPVKHBSQESCIEP-UHFFFAOYSA-N 0.000 description 2
- VMPSPJAKJZDOSU-UHFFFAOYSA-N 1-[(2,6-dichloropyridin-4-yl)methyl]-1,4,8,11-tetrazacyclotetradecane;trihydrochloride Chemical compound Cl.Cl.Cl.ClC1=NC(Cl)=CC(CN2CCNCCCNCCNCCC2)=C1 VMPSPJAKJZDOSU-UHFFFAOYSA-N 0.000 description 2
- OZRIBMWKRWFARD-UHFFFAOYSA-N 4-[[1h-benzimidazol-2-ylmethyl(5,6,7,8-tetrahydroquinolin-8-yl)amino]methyl]-n-pyridin-2-ylbenzamide Chemical compound C=1C=C(CN(CC=2NC3=CC=CC=C3N=2)C2C3=NC=CC=C3CCC2)C=CC=1C(=O)NC1=CC=CC=N1 OZRIBMWKRWFARD-UHFFFAOYSA-N 0.000 description 2
- NMUSYJAQQFHJEW-UHFFFAOYSA-N 5-Azacytidine Natural products O=C1N=C(N)N=CN1C1C(O)C(O)C(CO)O1 NMUSYJAQQFHJEW-UHFFFAOYSA-N 0.000 description 2
- NMUSYJAQQFHJEW-KVTDHHQDSA-N 5-azacytidine Chemical compound O=C1N=C(N)N=CN1[C@H]1[C@H](O)[C@H](O)[C@@H](CO)O1 NMUSYJAQQFHJEW-KVTDHHQDSA-N 0.000 description 2
- STQGQHZAVUOBTE-UHFFFAOYSA-N 7-Cyan-hept-2t-en-4,6-diinsaeure Natural products C1=2C(O)=C3C(=O)C=4C(OC)=CC=CC=4C(=O)C3=C(O)C=2CC(O)(C(C)=O)CC1OC1CC(N)C(O)C(C)O1 STQGQHZAVUOBTE-UHFFFAOYSA-N 0.000 description 2
- 108010006654 Bleomycin Proteins 0.000 description 2
- VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 description 2
- JWBOIMRXGHLCPP-UHFFFAOYSA-N Chloditan Chemical compound C=1C=CC=C(Cl)C=1C(C(Cl)Cl)C1=CC=C(Cl)C=C1 JWBOIMRXGHLCPP-UHFFFAOYSA-N 0.000 description 2
- 108010092160 Dactinomycin Proteins 0.000 description 2
- 102000004190 Enzymes Human genes 0.000 description 2
- 108090000790 Enzymes Proteins 0.000 description 2
- WHUUTDBJXJRKMK-UHFFFAOYSA-N Glutamic acid Natural products OC(=O)C(N)CCC(O)=O WHUUTDBJXJRKMK-UHFFFAOYSA-N 0.000 description 2
- 239000004471 Glycine Substances 0.000 description 2
- 101100335080 Homo sapiens FLT3 gene Proteins 0.000 description 2
- 241000713772 Human immunodeficiency virus 1 Species 0.000 description 2
- XDXDZDZNSLXDNA-TZNDIEGXSA-N Idarubicin Chemical compound C1[C@H](N)[C@H](O)[C@H](C)O[C@H]1O[C@@H]1C2=C(O)C(C(=O)C3=CC=CC=C3C3=O)=C3C(O)=C2C[C@@](O)(C(C)=O)C1 XDXDZDZNSLXDNA-TZNDIEGXSA-N 0.000 description 2
- XDXDZDZNSLXDNA-UHFFFAOYSA-N Idarubicin Natural products C1C(N)C(O)C(C)OC1OC1C2=C(O)C(C(=O)C3=CC=CC=C3C3=O)=C3C(O)=C2CC(O)(C(C)=O)C1 XDXDZDZNSLXDNA-UHFFFAOYSA-N 0.000 description 2
- 102000014150 Interferons Human genes 0.000 description 2
- 108010050904 Interferons Proteins 0.000 description 2
- ONIBWKKTOPOVIA-BYPYZUCNSA-N L-Proline Chemical compound OC(=O)[C@@H]1CCCN1 ONIBWKKTOPOVIA-BYPYZUCNSA-N 0.000 description 2
- WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 description 2
- FBOZXECLQNJBKD-ZDUSSCGKSA-N L-methotrexate Chemical compound C=1N=C2N=C(N)N=C(N)C2=NC=1CN(C)C1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 FBOZXECLQNJBKD-ZDUSSCGKSA-N 0.000 description 2
- NWIBSHFKIJFRCO-WUDYKRTCSA-N Mytomycin Chemical compound C1N2C(C(C(C)=C(N)C3=O)=O)=C3[C@@H](COC(N)=O)[C@@]2(OC)[C@@H]2[C@H]1N2 NWIBSHFKIJFRCO-WUDYKRTCSA-N 0.000 description 2
- ONIBWKKTOPOVIA-UHFFFAOYSA-N Proline Natural products OC(=O)C1CCCN1 ONIBWKKTOPOVIA-UHFFFAOYSA-N 0.000 description 2
- 108020004511 Recombinant DNA Proteins 0.000 description 2
- 102100021669 Stromal cell-derived factor 1 Human genes 0.000 description 2
- 108010025037 T140 peptide Proteins 0.000 description 2
- NKANXQFJJICGDU-QPLCGJKRSA-N Tamoxifen Chemical compound C=1C=CC=CC=1C(/CC)=C(C=1C=CC(OCCN(C)C)=CC=1)/C1=CC=CC=C1 NKANXQFJJICGDU-QPLCGJKRSA-N 0.000 description 2
- FOCVUCIESVLUNU-UHFFFAOYSA-N Thiotepa Chemical compound C1CN1P(N1CC1)(=S)N1CC1 FOCVUCIESVLUNU-UHFFFAOYSA-N 0.000 description 2
- 108060008682 Tumor Necrosis Factor Proteins 0.000 description 2
- RJURFGZVJUQBHK-UHFFFAOYSA-N actinomycin D Natural products CC1OC(=O)C(C(C)C)N(C)C(=O)CN(C)C(=O)C2CCCN2C(=O)C(C(C)C)NC(=O)C1NC(=O)C1=C(N)C(=O)C(C)=C2OC(C(C)=CC=C3C(=O)NC4C(=O)NC(C(N5CCCC5C(=O)N(C)CC(=O)N(C)C(C(C)C)C(=O)OC4C)=O)C(C)C)=C3N=C21 RJURFGZVJUQBHK-UHFFFAOYSA-N 0.000 description 2
- 229960003437 aminoglutethimide Drugs 0.000 description 2
- ROBVIMPUHSLWNV-UHFFFAOYSA-N aminoglutethimide Chemical compound C=1C=C(N)C=CC=1C1(CC)CCC(=O)NC1=O ROBVIMPUHSLWNV-UHFFFAOYSA-N 0.000 description 2
- 239000002870 angiogenesis inducing agent Substances 0.000 description 2
- 238000010171 animal model Methods 0.000 description 2
- 230000036436 anti-hiv Effects 0.000 description 2
- 239000007864 aqueous solution Substances 0.000 description 2
- 229960002756 azacitidine Drugs 0.000 description 2
- VSRXQHXAPYXROS-UHFFFAOYSA-N azanide;cyclobutane-1,1-dicarboxylic acid;platinum(2+) Chemical compound [NH2-].[NH2-].[Pt+2].OC(=O)C1(C(O)=O)CCC1 VSRXQHXAPYXROS-UHFFFAOYSA-N 0.000 description 2
- 230000004071 biological effect Effects 0.000 description 2
- 238000001574 biopsy Methods 0.000 description 2
- 229960001561 bleomycin Drugs 0.000 description 2
- OYVAGSVQBOHSSS-UAPAGMARSA-O bleomycin A2 Chemical compound N([C@H](C(=O)N[C@H](C)[C@@H](O)[C@H](C)C(=O)N[C@@H]([C@H](O)C)C(=O)NCCC=1SC=C(N=1)C=1SC=C(N=1)C(=O)NCCC[S+](C)C)[C@@H](O[C@H]1[C@H]([C@@H](O)[C@H](O)[C@H](CO)O1)O[C@@H]1[C@H]([C@@H](OC(N)=O)[C@H](O)[C@@H](CO)O1)O)C=1N=CNC=1)C(=O)C1=NC([C@H](CC(N)=O)NC[C@H](N)C(N)=O)=NC(N)=C1C OYVAGSVQBOHSSS-UAPAGMARSA-O 0.000 description 2
- 210000004369 blood Anatomy 0.000 description 2
- 239000008280 blood Substances 0.000 description 2
- 210000000601 blood cell Anatomy 0.000 description 2
- 239000000872 buffer Substances 0.000 description 2
- 229960002092 busulfan Drugs 0.000 description 2
- 229960004562 carboplatin Drugs 0.000 description 2
- 229960005243 carmustine Drugs 0.000 description 2
- 239000000969 carrier Substances 0.000 description 2
- 239000013043 chemical agent Substances 0.000 description 2
- 229960004630 chlorambucil Drugs 0.000 description 2
- JCKYGMPEJWAADB-UHFFFAOYSA-N chlorambucil Chemical compound OC(=O)CCCC1=CC=C(N(CCCl)CCCl)C=C1 JCKYGMPEJWAADB-UHFFFAOYSA-N 0.000 description 2
- DQLATGHUWYMOKM-UHFFFAOYSA-L cisplatin Chemical compound N[Pt](N)(Cl)Cl DQLATGHUWYMOKM-UHFFFAOYSA-L 0.000 description 2
- 229960004316 cisplatin Drugs 0.000 description 2
- 229960002436 cladribine Drugs 0.000 description 2
- VFLDPWHFBUODDF-FCXRPNKRSA-N curcumin Chemical compound C1=C(O)C(OC)=CC(\C=C\C(=O)CC(=O)\C=C\C=2C=C(OC)C(O)=CC=2)=C1 VFLDPWHFBUODDF-FCXRPNKRSA-N 0.000 description 2
- 229960004397 cyclophosphamide Drugs 0.000 description 2
- 125000000151 cysteine group Chemical group N[C@@H](CS)C(=O)* 0.000 description 2
- 231100000135 cytotoxicity Toxicity 0.000 description 2
- 230000003013 cytotoxicity Effects 0.000 description 2
- 229960003901 dacarbazine Drugs 0.000 description 2
- 229960000975 daunorubicin Drugs 0.000 description 2
- 230000001419 dependent effect Effects 0.000 description 2
- 208000035475 disorder Diseases 0.000 description 2
- 229960004679 doxorubicin Drugs 0.000 description 2
- 239000003937 drug carrier Substances 0.000 description 2
- 229940088598 enzyme Drugs 0.000 description 2
- VJJPUSNTGOMMGY-MRVIYFEKSA-N etoposide Chemical compound COC1=C(O)C(OC)=CC([C@@H]2C3=CC=4OCOC=4C=C3[C@@H](O[C@H]3[C@@H]([C@@H](O)[C@@H]4O[C@H](C)OC[C@H]4O3)O)[C@@H]3[C@@H]2C(OC3)=O)=C1 VJJPUSNTGOMMGY-MRVIYFEKSA-N 0.000 description 2
- 229960005420 etoposide Drugs 0.000 description 2
- GIUYCYHIANZCFB-FJFJXFQQSA-N fludarabine phosphate Chemical compound C1=NC=2C(N)=NC(F)=NC=2N1[C@@H]1O[C@H](COP(O)(O)=O)[C@@H](O)[C@@H]1O GIUYCYHIANZCFB-FJFJXFQQSA-N 0.000 description 2
- 229960002074 flutamide Drugs 0.000 description 2
- MKXKFYHWDHIYRV-UHFFFAOYSA-N flutamide Chemical compound CC(C)C(=O)NC1=CC=C([N+]([O-])=O)C(C(F)(F)F)=C1 MKXKFYHWDHIYRV-UHFFFAOYSA-N 0.000 description 2
- 235000013922 glutamic acid Nutrition 0.000 description 2
- 239000004220 glutamic acid Substances 0.000 description 2
- 230000012010 growth Effects 0.000 description 2
- UUVWYPNAQBNQJQ-UHFFFAOYSA-N hexamethylmelamine Chemical compound CN(C)C1=NC(N(C)C)=NC(N(C)C)=N1 UUVWYPNAQBNQJQ-UHFFFAOYSA-N 0.000 description 2
- 229940088597 hormone Drugs 0.000 description 2
- 239000005556 hormone Substances 0.000 description 2
- 229960000908 idarubicin Drugs 0.000 description 2
- 229960001101 ifosfamide Drugs 0.000 description 2
- HOMGKSMUEGBAAB-UHFFFAOYSA-N ifosfamide Chemical compound ClCCNP1(=O)OCCCN1CCCl HOMGKSMUEGBAAB-UHFFFAOYSA-N 0.000 description 2
- 229960003685 imatinib mesylate Drugs 0.000 description 2
- 239000004615 ingredient Substances 0.000 description 2
- 230000002401 inhibitory effect Effects 0.000 description 2
- 238000003780 insertion Methods 0.000 description 2
- 230000037431 insertion Effects 0.000 description 2
- 229940079322 interferon Drugs 0.000 description 2
- 239000003446 ligand Substances 0.000 description 2
- 229960002247 lomustine Drugs 0.000 description 2
- 229960001924 melphalan Drugs 0.000 description 2
- SGDBTWWWUNNDEQ-LBPRGKRZSA-N melphalan Chemical compound OC(=O)[C@@H](N)CC1=CC=C(N(CCCl)CCCl)C=C1 SGDBTWWWUNNDEQ-LBPRGKRZSA-N 0.000 description 2
- 229960001428 mercaptopurine Drugs 0.000 description 2
- 229960000485 methotrexate Drugs 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- HDZGCSFEDULWCS-UHFFFAOYSA-N monomethylhydrazine Chemical class CNN HDZGCSFEDULWCS-UHFFFAOYSA-N 0.000 description 2
- 210000001167 myeloblast Anatomy 0.000 description 2
- 208000025113 myeloid leukemia Diseases 0.000 description 2
- CWJJHESJXJQCJA-UHFFFAOYSA-N n-(pyridin-2-ylmethyl)-1-[4-(1,4,8,11-tetrazacyclotetradec-1-ylmethyl)phenyl]methanamine Chemical compound C=1C=C(CN2CCNCCCNCCNCCC2)C=CC=1CNCC1=CC=CC=N1 CWJJHESJXJQCJA-UHFFFAOYSA-N 0.000 description 2
- PXZXYRKDDXKDTK-UHFFFAOYSA-N n-[[4-[(pyrimidin-2-ylamino)methyl]phenyl]methyl]pyrimidin-2-amine Chemical compound C=1C=C(CNC=2N=CC=CN=2)C=CC=1CNC1=NC=CC=N1 PXZXYRKDDXKDTK-UHFFFAOYSA-N 0.000 description 2
- 239000007800 oxidant agent Substances 0.000 description 2
- 229960002340 pentostatin Drugs 0.000 description 2
- FPVKHBSQESCIEP-JQCXWYLXSA-N pentostatin Chemical compound C1[C@H](O)[C@@H](CO)O[C@H]1N1C(N=CNC[C@H]2O)=C2N=C1 FPVKHBSQESCIEP-JQCXWYLXSA-N 0.000 description 2
- 229910052697 platinum Inorganic materials 0.000 description 2
- 229960004618 prednisone Drugs 0.000 description 2
- XOFYZVNMUHMLCC-ZPOLXVRWSA-N prednisone Chemical compound O=C1C=C[C@]2(C)[C@H]3C(=O)C[C@](C)([C@@](CC4)(O)C(=O)CO)[C@@H]4[C@@H]3CCC2=C1 XOFYZVNMUHMLCC-ZPOLXVRWSA-N 0.000 description 2
- 230000002265 prevention Effects 0.000 description 2
- 229960000624 procarbazine Drugs 0.000 description 2
- CPTBDICYNRMXFX-UHFFFAOYSA-N procarbazine Chemical compound CNNCC1=CC=C(C(=O)NC(C)C)C=C1 CPTBDICYNRMXFX-UHFFFAOYSA-N 0.000 description 2
- 230000008569 process Effects 0.000 description 2
- 230000002829 reductive effect Effects 0.000 description 2
- 229960004641 rituximab Drugs 0.000 description 2
- 150000003839 salts Chemical class 0.000 description 2
- 210000000130 stem cell Anatomy 0.000 description 2
- 238000007920 subcutaneous administration Methods 0.000 description 2
- 230000004083 survival effect Effects 0.000 description 2
- NRUKOCRGYNPUPR-QBPJDGROSA-N teniposide Chemical compound COC1=C(O)C(OC)=CC([C@@H]2C3=CC=4OCOC=4C=C3[C@@H](O[C@H]3[C@@H]([C@@H](O)[C@@H]4O[C@@H](OC[C@H]4O3)C=3SC=CC=3)O)[C@@H]3[C@@H]2C(OC3)=O)=C1 NRUKOCRGYNPUPR-QBPJDGROSA-N 0.000 description 2
- 229960001278 teniposide Drugs 0.000 description 2
- 229960001196 thiotepa Drugs 0.000 description 2
- 229960003087 tioguanine Drugs 0.000 description 2
- 238000011269 treatment regimen Methods 0.000 description 2
- IUCJMVBFZDHPDX-UHFFFAOYSA-N tretamine Chemical compound C1CN1C1=NC(N2CC2)=NC(N2CC2)=N1 IUCJMVBFZDHPDX-UHFFFAOYSA-N 0.000 description 2
- 229950001353 tretamine Drugs 0.000 description 2
- 102000003390 tumor necrosis factor Human genes 0.000 description 2
- 239000003981 vehicle Substances 0.000 description 2
- 229960003048 vinblastine Drugs 0.000 description 2
- 229960004528 vincristine Drugs 0.000 description 2
- OGWKCGZFUXNPDA-UHFFFAOYSA-N vincristine Natural products C1C(CC)(O)CC(CC2(C(=O)OC)C=3C(=CC4=C(C56C(C(C(OC(C)=O)C7(CC)C=CCN(C67)CC5)(O)C(=O)OC)N4C=O)C=3)OC)CN1CCC1=C2NC2=CC=CC=C12 OGWKCGZFUXNPDA-UHFFFAOYSA-N 0.000 description 2
- OGWKCGZFUXNPDA-XQKSVPLYSA-N vincristine Chemical compound C([N@]1C[C@@H](C[C@]2(C(=O)OC)C=3C(=CC4=C([C@]56[C@H]([C@@]([C@H](OC(C)=O)[C@]7(CC)C=CCN([C@H]67)CC5)(O)C(=O)OC)N4C=O)C=3)OC)C[C@@](C1)(O)CC)CC1=C2NC2=CC=CC=C12 OGWKCGZFUXNPDA-XQKSVPLYSA-N 0.000 description 2
- IYKLZBIWFXPUCS-VIFPVBQESA-N (2s)-2-(naphthalen-1-ylamino)propanoic acid Chemical compound C1=CC=C2C(N[C@@H](C)C(O)=O)=CC=CC2=C1 IYKLZBIWFXPUCS-VIFPVBQESA-N 0.000 description 1
- HJTAZXHBEBIQQX-UHFFFAOYSA-N 1,5-bis(chloromethyl)naphthalene Chemical compound C1=CC=C2C(CCl)=CC=CC2=C1CCl HJTAZXHBEBIQQX-UHFFFAOYSA-N 0.000 description 1
- USMXIXZBRZZOQH-UHFFFAOYSA-N 1-[[4-(1,4,8,11-tetrazacyclotetradec-1-ylmethyl)phenyl]methyl]-1,4,8,11-tetrazacyclotetradecane;dihydrate;octahydrochloride Chemical compound O.O.Cl.Cl.Cl.Cl.Cl.Cl.Cl.Cl.C=1C=C(CN2CCNCCCNCCNCCC2)C=CC=1CN1CCCNCCNCCCNCC1 USMXIXZBRZZOQH-UHFFFAOYSA-N 0.000 description 1
- 102100025573 1-alkyl-2-acetylglycerophosphocholine esterase Human genes 0.000 description 1
- VSNHCAURESNICA-NJFSPNSNSA-N 1-oxidanylurea Chemical compound N[14C](=O)NO VSNHCAURESNICA-NJFSPNSNSA-N 0.000 description 1
- BFPYWIDHMRZLRN-UHFFFAOYSA-N 17alpha-ethynyl estradiol Natural products OC1=CC=C2C3CCC(C)(C(CC4)(O)C#C)C4C3CCC2=C1 BFPYWIDHMRZLRN-UHFFFAOYSA-N 0.000 description 1
- YVPBVWICNJPHCW-UHFFFAOYSA-N 2-(4,5-dibromo-3-hydroxy-6-oxoxanthen-9-yl)benzoic acid Chemical compound OC(=O)C1=CC=CC=C1C1=C2C=CC(=O)C(Br)=C2OC2=C(Br)C(O)=CC=C21 YVPBVWICNJPHCW-UHFFFAOYSA-N 0.000 description 1
- CTRPRMNBTVRDFH-UHFFFAOYSA-N 2-n-methyl-1,3,5-triazine-2,4,6-triamine Chemical compound CNC1=NC(N)=NC(N)=N1 CTRPRMNBTVRDFH-UHFFFAOYSA-N 0.000 description 1
- FWMNVWWHGCHHJJ-SKKKGAJSSA-N 4-amino-1-[(2r)-6-amino-2-[[(2r)-2-[[(2r)-2-[[(2r)-2-amino-3-phenylpropanoyl]amino]-3-phenylpropanoyl]amino]-4-methylpentanoyl]amino]hexanoyl]piperidine-4-carboxylic acid Chemical compound C([C@H](C(=O)N[C@H](CC(C)C)C(=O)N[C@H](CCCCN)C(=O)N1CCC(N)(CC1)C(O)=O)NC(=O)[C@H](N)CC=1C=CC=CC=1)C1=CC=CC=C1 FWMNVWWHGCHHJJ-SKKKGAJSSA-N 0.000 description 1
- PTUYNGRETVWEER-UHFFFAOYSA-N 7-[[4-(4,7,10,17-tetrazabicyclo[11.3.1]heptadeca-1(17),13,15-trien-7-ylmethyl)phenyl]methyl]-4,7,10,17-tetrazabicyclo[11.3.1]heptadeca-1(17),13,15-triene;octahydrobromide Chemical compound [Br-].[Br-].[Br-].[Br-].[Br-].[Br-].[Br-].[Br-].C1C[NH2+]CCC([NH+]=2)=CC=CC=2CC[NH2+]CC[NH+]1CC(C=C1)=CC=C1C[NH+](CC[NH2+]CC1)CC[NH2+]CCC2=CC=CC1=[NH+]2 PTUYNGRETVWEER-UHFFFAOYSA-N 0.000 description 1
- 108010093192 ATI-2341 Proteins 0.000 description 1
- APKFDSVGJQXUKY-KKGHZKTASA-N Amphotericin-B Natural products O[C@H]1[C@@H](N)[C@H](O)[C@@H](C)O[C@H]1O[C@H]1C=CC=CC=CC=CC=CC=CC=C[C@H](C)[C@@H](O)[C@@H](C)[C@H](C)OC(=O)C[C@H](O)C[C@H](O)CC[C@@H](O)[C@H](O)C[C@H](O)C[C@](O)(C[C@H](O)[C@H]2C(O)=O)O[C@H]2C1 APKFDSVGJQXUKY-KKGHZKTASA-N 0.000 description 1
- 102400000068 Angiostatin Human genes 0.000 description 1
- 108010079709 Angiostatins Proteins 0.000 description 1
- 108010024976 Asparaginase Proteins 0.000 description 1
- 108010072524 BKT140 Proteins 0.000 description 1
- 208000003174 Brain Neoplasms Diseases 0.000 description 1
- 206010006187 Breast cancer Diseases 0.000 description 1
- 208000026310 Breast neoplasm Diseases 0.000 description 1
- 108010086884 CTCE-0021 Proteins 0.000 description 1
- 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 description 1
- 102000009410 Chemokine receptor Human genes 0.000 description 1
- 108050000299 Chemokine receptor Proteins 0.000 description 1
- 229940122444 Chemokine receptor antagonist Drugs 0.000 description 1
- 102000004127 Cytokines Human genes 0.000 description 1
- 108090000695 Cytokines Proteins 0.000 description 1
- FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 1
- FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 description 1
- WEAHRLBPCANXCN-UHFFFAOYSA-N Daunomycin Natural products CCC1(O)CC(OC2CC(N)C(O)C(C)O2)c3cc4C(=O)c5c(OC)cccc5C(=O)c4c(O)c3C1 WEAHRLBPCANXCN-UHFFFAOYSA-N 0.000 description 1
- 229920002307 Dextran Polymers 0.000 description 1
- 206010061818 Disease progression Diseases 0.000 description 1
- 102000001301 EGF receptor Human genes 0.000 description 1
- 108060006698 EGF receptor Proteins 0.000 description 1
- LVGKNOAMLMIIKO-UHFFFAOYSA-N Elaidinsaeure-aethylester Natural products CCCCCCCCC=CCCCCCCCC(=O)OCC LVGKNOAMLMIIKO-UHFFFAOYSA-N 0.000 description 1
- 102400001047 Endostatin Human genes 0.000 description 1
- 108010079505 Endostatins Proteins 0.000 description 1
- BFPYWIDHMRZLRN-SLHNCBLASA-N Ethinyl estradiol Chemical compound OC1=CC=C2[C@H]3CC[C@](C)([C@](CC4)(O)C#C)[C@@H]4[C@@H]3CCC2=C1 BFPYWIDHMRZLRN-SLHNCBLASA-N 0.000 description 1
- GHASVSINZRGABV-UHFFFAOYSA-N Fluorouracil Chemical compound FC1=CNC(=O)NC1=O GHASVSINZRGABV-UHFFFAOYSA-N 0.000 description 1
- 108010010803 Gelatin Proteins 0.000 description 1
- 239000000579 Gonadotropin-Releasing Hormone Substances 0.000 description 1
- 108010017213 Granulocyte-Macrophage Colony-Stimulating Factor Proteins 0.000 description 1
- 102100039620 Granulocyte-macrophage colony-stimulating factor Human genes 0.000 description 1
- 229940121710 HMGCoA reductase inhibitor Drugs 0.000 description 1
- 239000012981 Hank's balanced salt solution Substances 0.000 description 1
- 208000002250 Hematologic Neoplasms Diseases 0.000 description 1
- 102000001554 Hemoglobins Human genes 0.000 description 1
- 108010054147 Hemoglobins Proteins 0.000 description 1
- 108010033040 Histones Proteins 0.000 description 1
- 241000282412 Homo Species 0.000 description 1
- 101000617130 Homo sapiens Stromal cell-derived factor 1 Proteins 0.000 description 1
- DOMWKUIIPQCAJU-LJHIYBGHSA-N Hydroxyprogesterone caproate Chemical compound C1CC2=CC(=O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@@](C(C)=O)(OC(=O)CCCCC)[C@@]1(C)CC2 DOMWKUIIPQCAJU-LJHIYBGHSA-N 0.000 description 1
- VSNHCAURESNICA-UHFFFAOYSA-N Hydroxyurea Chemical compound NC(=O)NO VSNHCAURESNICA-UHFFFAOYSA-N 0.000 description 1
- 102000006992 Interferon-alpha Human genes 0.000 description 1
- 108010047761 Interferon-alpha Proteins 0.000 description 1
- 208000008839 Kidney Neoplasms Diseases 0.000 description 1
- COLNVLDHVKWLRT-QMMMGPOBSA-N L-phenylalanine Chemical compound OC(=O)[C@@H](N)CC1=CC=CC=C1 COLNVLDHVKWLRT-QMMMGPOBSA-N 0.000 description 1
- OUYCCCASQSFEME-QMMMGPOBSA-N L-tyrosine Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-QMMMGPOBSA-N 0.000 description 1
- 239000005551 L01XE03 - Erlotinib Substances 0.000 description 1
- UIARLYUEJFELEN-LROUJFHJSA-N LSM-1231 Chemical compound C12=C3N4C5=CC=CC=C5C3=C3C(=O)NCC3=C2C2=CC=CC=C2N1[C@]1(C)[C@](CO)(O)C[C@H]4O1 UIARLYUEJFELEN-LROUJFHJSA-N 0.000 description 1
- 108010000817 Leuprolide Proteins 0.000 description 1
- 102000004083 Lymphotoxin-alpha Human genes 0.000 description 1
- 108090000542 Lymphotoxin-alpha Proteins 0.000 description 1
- 241000124008 Mammalia Species 0.000 description 1
- 206010027476 Metastases Diseases 0.000 description 1
- ZDZOTLJHXYCWBA-VCVYQWHSSA-N N-debenzoyl-N-(tert-butoxycarbonyl)-10-deacetyltaxol Chemical compound O([C@H]1[C@H]2[C@@](C([C@H](O)C3=C(C)[C@@H](OC(=O)[C@H](O)[C@@H](NC(=O)OC(C)(C)C)C=4C=CC=CC=4)C[C@]1(O)C3(C)C)=O)(C)[C@@H](O)C[C@H]1OC[C@]12OC(=O)C)C(=O)C1=CC=CC=C1 ZDZOTLJHXYCWBA-VCVYQWHSSA-N 0.000 description 1
- 206010033128 Ovarian cancer Diseases 0.000 description 1
- 206010061535 Ovarian neoplasm Diseases 0.000 description 1
- 206010061902 Pancreatic neoplasm Diseases 0.000 description 1
- 229940083963 Peptide antagonist Drugs 0.000 description 1
- 108010043958 Peptoids Proteins 0.000 description 1
- 206010060862 Prostate cancer Diseases 0.000 description 1
- 208000000236 Prostatic Neoplasms Diseases 0.000 description 1
- 229940079156 Proteasome inhibitor Drugs 0.000 description 1
- 229940127361 Receptor Tyrosine Kinase Inhibitors Drugs 0.000 description 1
- 206010038389 Renal cancer Diseases 0.000 description 1
- 108010003723 Single-Domain Antibodies Proteins 0.000 description 1
- 101000857870 Squalus acanthias Gonadoliberin Proteins 0.000 description 1
- 229920002472 Starch Polymers 0.000 description 1
- 101710088580 Stromal cell-derived factor 1 Proteins 0.000 description 1
- 208000000389 T-cell leukemia Diseases 0.000 description 1
- 208000028530 T-cell lymphoblastic leukemia/lymphoma Diseases 0.000 description 1
- 210000001744 T-lymphocyte Anatomy 0.000 description 1
- 108010017842 Telomerase Proteins 0.000 description 1
- PDMMFKSKQVNJMI-BLQWBTBKSA-N Testosterone propionate Chemical compound C1CC2=CC(=O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H](OC(=O)CC)[C@@]1(C)CC2 PDMMFKSKQVNJMI-BLQWBTBKSA-N 0.000 description 1
- 229940127507 Ubiquitin Ligase Inhibitors Drugs 0.000 description 1
- 108091008605 VEGF receptors Proteins 0.000 description 1
- 102000009484 Vascular Endothelial Growth Factor Receptors Human genes 0.000 description 1
- 102000005789 Vascular Endothelial Growth Factors Human genes 0.000 description 1
- 108010019530 Vascular Endothelial Growth Factors Proteins 0.000 description 1
- 229940122803 Vinca alkaloid Drugs 0.000 description 1
- 230000002159 abnormal effect Effects 0.000 description 1
- DPXJVFZANSGRMM-UHFFFAOYSA-N acetic acid;2,3,4,5,6-pentahydroxyhexanal;sodium Chemical compound [Na].CC(O)=O.OCC(O)C(O)C(O)C(O)C=O DPXJVFZANSGRMM-UHFFFAOYSA-N 0.000 description 1
- 229930183665 actinomycin Natural products 0.000 description 1
- RJURFGZVJUQBHK-IIXSONLDSA-N actinomycin D Chemical compound C[C@H]1OC(=O)[C@H](C(C)C)N(C)C(=O)CN(C)C(=O)[C@@H]2CCCN2C(=O)[C@@H](C(C)C)NC(=O)[C@H]1NC(=O)C1=C(N)C(=O)C(C)=C2OC(C(C)=CC=C3C(=O)N[C@@H]4C(=O)N[C@@H](C(N5CCC[C@H]5C(=O)N(C)CC(=O)N(C)[C@@H](C(C)C)C(=O)O[C@@H]4C)=O)C(C)C)=C3N=C21 RJURFGZVJUQBHK-IIXSONLDSA-N 0.000 description 1
- 230000004913 activation Effects 0.000 description 1
- 239000002671 adjuvant Substances 0.000 description 1
- 210000004404 adrenal cortex Anatomy 0.000 description 1
- 239000000556 agonist Substances 0.000 description 1
- 229930013930 alkaloid Natural products 0.000 description 1
- 150000003797 alkaloid derivatives Chemical class 0.000 description 1
- 229940045714 alkyl sulfonate alkylating agent Drugs 0.000 description 1
- 150000008052 alkyl sulfonates Chemical class 0.000 description 1
- 229940100198 alkylating agent Drugs 0.000 description 1
- 239000002168 alkylating agent Substances 0.000 description 1
- 230000002152 alkylating effect Effects 0.000 description 1
- SHGAZHPCJJPHSC-YCNIQYBTSA-N all-trans-retinoic acid Chemical compound OC(=O)\C=C(/C)\C=C\C=C(/C)\C=C\C1=C(C)CCCC1(C)C SHGAZHPCJJPHSC-YCNIQYBTSA-N 0.000 description 1
- 229960000473 altretamine Drugs 0.000 description 1
- APKFDSVGJQXUKY-INPOYWNPSA-N amphotericin B Chemical compound O[C@H]1[C@@H](N)[C@H](O)[C@@H](C)O[C@H]1O[C@H]1/C=C/C=C/C=C/C=C/C=C/C=C/C=C/[C@H](C)[C@@H](O)[C@@H](C)[C@H](C)OC(=O)C[C@H](O)C[C@H](O)CC[C@@H](O)[C@H](O)C[C@H](O)C[C@](O)(C[C@H](O)[C@H]2C(O)=O)O[C@H]2C1 APKFDSVGJQXUKY-INPOYWNPSA-N 0.000 description 1
- 229960003942 amphotericin b Drugs 0.000 description 1
- 230000003698 anagen phase Effects 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 239000003098 androgen Substances 0.000 description 1
- 210000004102 animal cell Anatomy 0.000 description 1
- 230000003042 antagnostic effect Effects 0.000 description 1
- RGHILYZRVFRRNK-UHFFFAOYSA-N anthracene-1,2-dione Chemical compound C1=CC=C2C=C(C(C(=O)C=C3)=O)C3=CC2=C1 RGHILYZRVFRRNK-UHFFFAOYSA-N 0.000 description 1
- 239000003242 anti bacterial agent Substances 0.000 description 1
- 230000002280 anti-androgenic effect Effects 0.000 description 1
- 230000001772 anti-angiogenic effect Effects 0.000 description 1
- 229940046836 anti-estrogen Drugs 0.000 description 1
- 230000001833 anti-estrogenic effect Effects 0.000 description 1
- 230000000340 anti-metabolite Effects 0.000 description 1
- 230000002927 anti-mitotic effect Effects 0.000 description 1
- 239000000051 antiandrogen Substances 0.000 description 1
- 229940088710 antibiotic agent Drugs 0.000 description 1
- 229940100197 antimetabolite Drugs 0.000 description 1
- 239000002256 antimetabolite Substances 0.000 description 1
- 229940045686 antimetabolites antineoplastic purine analogs Drugs 0.000 description 1
- 229940045687 antimetabolites folic acid analogs Drugs 0.000 description 1
- 239000003080 antimitotic agent Substances 0.000 description 1
- 229940045719 antineoplastic alkylating agent nitrosoureas Drugs 0.000 description 1
- 229940045688 antineoplastic antimetabolites pyrimidine analogues Drugs 0.000 description 1
- 239000003963 antioxidant agent Substances 0.000 description 1
- 235000006708 antioxidants Nutrition 0.000 description 1
- 239000003443 antiviral agent Substances 0.000 description 1
- 230000006907 apoptotic process Effects 0.000 description 1
- 125000000637 arginyl group Chemical group N[C@@H](CCCNC(N)=N)C(=O)* 0.000 description 1
- GOLCXWYRSKYTSP-UHFFFAOYSA-N arsenic trioxide Inorganic materials O1[As]2O[As]1O2 GOLCXWYRSKYTSP-UHFFFAOYSA-N 0.000 description 1
- 229960002594 arsenic trioxide Drugs 0.000 description 1
- CKLJMWTZIZZHCS-REOHCLBHSA-N aspartic acid group Chemical group N[C@@H](CC(=O)O)C(=O)O CKLJMWTZIZZHCS-REOHCLBHSA-N 0.000 description 1
- FZCSTZYAHCUGEM-UHFFFAOYSA-N aspergillomarasmine B Natural products OC(=O)CNC(C(O)=O)CNC(C(O)=O)CC(O)=O FZCSTZYAHCUGEM-UHFFFAOYSA-N 0.000 description 1
- LMEKQMALGUDUQG-UHFFFAOYSA-N azathioprine Chemical compound CN1C=NC([N+]([O-])=O)=C1SC1=NC=NC2=C1NC=N2 LMEKQMALGUDUQG-UHFFFAOYSA-N 0.000 description 1
- 229960002170 azathioprine Drugs 0.000 description 1
- 230000008901 benefit Effects 0.000 description 1
- 238000002306 biochemical method Methods 0.000 description 1
- 239000003124 biologic agent Substances 0.000 description 1
- 230000000903 blocking effect Effects 0.000 description 1
- 238000004820 blood count Methods 0.000 description 1
- 210000004899 c-terminal region Anatomy 0.000 description 1
- 229910000019 calcium carbonate Inorganic materials 0.000 description 1
- 239000001506 calcium phosphate Substances 0.000 description 1
- 229910000389 calcium phosphate Inorganic materials 0.000 description 1
- 235000011010 calcium phosphates Nutrition 0.000 description 1
- 239000004202 carbamide Substances 0.000 description 1
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 1
- 239000001768 carboxy methyl cellulose Substances 0.000 description 1
- 230000030833 cell death Effects 0.000 description 1
- 239000001913 cellulose Substances 0.000 description 1
- 229920002678 cellulose Polymers 0.000 description 1
- 239000002559 chemokine receptor antagonist Substances 0.000 description 1
- 230000003399 chemotactic effect Effects 0.000 description 1
- 238000002648 combination therapy Methods 0.000 description 1
- 230000000052 comparative effect Effects 0.000 description 1
- 230000002860 competitive effect Effects 0.000 description 1
- 239000003246 corticosteroid Substances 0.000 description 1
- JLYVRXJEQTZZBE-UHFFFAOYSA-N ctk1c6083 Chemical compound NP(N)(N)=S JLYVRXJEQTZZBE-UHFFFAOYSA-N 0.000 description 1
- 239000004148 curcumin Substances 0.000 description 1
- 229940109262 curcumin Drugs 0.000 description 1
- 235000012754 curcumin Nutrition 0.000 description 1
- 229960000640 dactinomycin Drugs 0.000 description 1
- 230000034994 death Effects 0.000 description 1
- 239000007857 degradation product Substances 0.000 description 1
- 238000013461 design Methods 0.000 description 1
- 229960003957 dexamethasone Drugs 0.000 description 1
- UREBDLICKHMUKA-CXSFZGCWSA-N dexamethasone Chemical compound C1CC2=CC(=O)C=C[C@]2(C)[C@]2(F)[C@@H]1[C@@H]1C[C@@H](C)[C@@](C(=O)CO)(O)[C@@]1(C)C[C@@H]2O UREBDLICKHMUKA-CXSFZGCWSA-N 0.000 description 1
- 238000003745 diagnosis Methods 0.000 description 1
- 235000014113 dietary fatty acids Nutrition 0.000 description 1
- RGLYKWWBQGJZGM-ISLYRVAYSA-N diethylstilbestrol Chemical compound C=1C=C(O)C=CC=1C(/CC)=C(\CC)C1=CC=C(O)C=C1 RGLYKWWBQGJZGM-ISLYRVAYSA-N 0.000 description 1
- 229960000452 diethylstilbestrol Drugs 0.000 description 1
- VFLDPWHFBUODDF-UHFFFAOYSA-N diferuloylmethane Natural products C1=C(O)C(OC)=CC(C=CC(=O)CC(=O)C=CC=2C=C(OC)C(O)=CC=2)=C1 VFLDPWHFBUODDF-UHFFFAOYSA-N 0.000 description 1
- 239000003085 diluting agent Substances 0.000 description 1
- 230000005750 disease progression Effects 0.000 description 1
- GEJSZPYTUWHBIP-UHFFFAOYSA-L disodium;4-[(4-amino-1-methylpyrrole-2-carbonyl)amino]naphthalene-1,7-disulfonate Chemical compound [Na+].[Na+].CN1C=C(N)C=C1C(=O)NC1=CC=C(S([O-])(=O)=O)C2=CC(S([O-])(=O)=O)=CC=C12 GEJSZPYTUWHBIP-UHFFFAOYSA-L 0.000 description 1
- 239000008298 dragée Substances 0.000 description 1
- 239000013583 drug formulation Substances 0.000 description 1
- 230000001804 emulsifying effect Effects 0.000 description 1
- 229960001433 erlotinib Drugs 0.000 description 1
- AAKJLRGGTJKAMG-UHFFFAOYSA-N erlotinib Chemical compound C=12C=C(OCCOC)C(OCCOC)=CC2=NC=NC=1NC1=CC=CC(C#C)=C1 AAKJLRGGTJKAMG-UHFFFAOYSA-N 0.000 description 1
- 210000003743 erythrocyte Anatomy 0.000 description 1
- 229960001842 estramustine Drugs 0.000 description 1
- FRPJXPJMRWBBIH-RBRWEJTLSA-N estramustine Chemical compound ClCCN(CCCl)C(=O)OC1=CC=C2[C@H]3CC[C@](C)([C@H](CC4)O)[C@@H]4[C@@H]3CCC2=C1 FRPJXPJMRWBBIH-RBRWEJTLSA-N 0.000 description 1
- 229960004750 estramustine phosphate Drugs 0.000 description 1
- ADFOJJHRTBFFOF-RBRWEJTLSA-N estramustine phosphate Chemical compound ClCCN(CCCl)C(=O)OC1=CC=C2[C@H]3CC[C@](C)([C@H](CC4)OP(O)(O)=O)[C@@H]4[C@@H]3CCC2=C1 ADFOJJHRTBFFOF-RBRWEJTLSA-N 0.000 description 1
- 239000000262 estrogen Substances 0.000 description 1
- 229940011871 estrogen Drugs 0.000 description 1
- 239000000328 estrogen antagonist Substances 0.000 description 1
- 229960002568 ethinylestradiol Drugs 0.000 description 1
- LVGKNOAMLMIIKO-QXMHVHEDSA-N ethyl oleate Chemical compound CCCCCCCC\C=C/CCCCCCCC(=O)OCC LVGKNOAMLMIIKO-QXMHVHEDSA-N 0.000 description 1
- 229940093471 ethyl oleate Drugs 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 229930195729 fatty acid Natural products 0.000 description 1
- 239000000194 fatty acid Substances 0.000 description 1
- 239000010685 fatty oil Substances 0.000 description 1
- ODKNJVUHOIMIIZ-RRKCRQDMSA-N floxuridine Chemical compound C1[C@H](O)[C@@H](CO)O[C@H]1N1C(=O)NC(=O)C(F)=C1 ODKNJVUHOIMIIZ-RRKCRQDMSA-N 0.000 description 1
- 229960000390 fludarabine Drugs 0.000 description 1
- 229960005304 fludarabine phosphate Drugs 0.000 description 1
- 229960002949 fluorouracil Drugs 0.000 description 1
- 229960001751 fluoxymesterone Drugs 0.000 description 1
- YLRFCQOZQXIBAB-RBZZARIASA-N fluoxymesterone Chemical compound C1CC2=CC(=O)CC[C@]2(C)[C@]2(F)[C@@H]1[C@@H]1CC[C@](C)(O)[C@@]1(C)C[C@@H]2O YLRFCQOZQXIBAB-RBZZARIASA-N 0.000 description 1
- 239000011888 foil Substances 0.000 description 1
- 150000002224 folic acids Chemical class 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
- XLXSAKCOAKORKW-AQJXLSMYSA-N gonadorelin Chemical compound C([C@@H](C(=O)NCC(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N1[C@@H](CCC1)C(=O)NCC(N)=O)NC(=O)[C@H](CO)NC(=O)[C@H](CC=1C2=CC=CC=C2NC=1)NC(=O)[C@H](CC=1N=CNC=1)NC(=O)[C@H]1NC(=O)CC1)C1=CC=C(O)C=C1 XLXSAKCOAKORKW-AQJXLSMYSA-N 0.000 description 1
- 229940035638 gonadotropin-releasing hormone Drugs 0.000 description 1
- 238000000227 grinding Methods 0.000 description 1
- 208000035474 group of disease Diseases 0.000 description 1
- 230000003394 haemopoietic effect Effects 0.000 description 1
- 230000009033 hematopoietic malignancy Effects 0.000 description 1
- 239000003668 hormone analog Substances 0.000 description 1
- 102000053523 human CXCR4 Human genes 0.000 description 1
- 229960001330 hydroxycarbamide Drugs 0.000 description 1
- 229950000801 hydroxyprogesterone caproate Drugs 0.000 description 1
- 210000001822 immobilized cell Anatomy 0.000 description 1
- 238000003018 immunoassay Methods 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 230000001939 inductive effect Effects 0.000 description 1
- 230000000977 initiatory effect Effects 0.000 description 1
- 229950000038 interferon alfa Drugs 0.000 description 1
- 230000007794 irritation Effects 0.000 description 1
- FZWBNHMXJMCXLU-BLAUPYHCSA-N isomaltotriose Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@@H]1OC[C@@H]1[C@@H](O)[C@H](O)[C@@H](O)[C@@H](OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C=O)O1 FZWBNHMXJMCXLU-BLAUPYHCSA-N 0.000 description 1
- 201000010982 kidney cancer Diseases 0.000 description 1
- 229940043355 kinase inhibitor Drugs 0.000 description 1
- GFIJNRVAKGFPGQ-LIJARHBVSA-N leuprolide Chemical compound CCNC(=O)[C@@H]1CCCN1C(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](CC(C)C)NC(=O)[C@@H](NC(=O)[C@H](CO)NC(=O)[C@H](CC=1C2=CC=CC=C2NC=1)NC(=O)[C@H](CC=1N=CNC=1)NC(=O)[C@H]1NC(=O)CC1)CC1=CC=C(O)C=C1 GFIJNRVAKGFPGQ-LIJARHBVSA-N 0.000 description 1
- 229960004338 leuprorelin Drugs 0.000 description 1
- 239000002502 liposome Substances 0.000 description 1
- 230000007774 longterm Effects 0.000 description 1
- 125000003588 lysine group Chemical group [H]N([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])(N([H])[H])C(*)=O 0.000 description 1
- 230000003211 malignant effect Effects 0.000 description 1
- 208000015486 malignant pancreatic neoplasm Diseases 0.000 description 1
- 229960004961 mechlorethamine Drugs 0.000 description 1
- HAWPXGHAZFHHAD-UHFFFAOYSA-N mechlorethamine Chemical class ClCCN(C)CCCl HAWPXGHAZFHHAD-UHFFFAOYSA-N 0.000 description 1
- 229960002985 medroxyprogesterone acetate Drugs 0.000 description 1
- PSGAAPLEWMOORI-PEINSRQWSA-N medroxyprogesterone acetate Chemical compound C([C@@]12C)CC(=O)C=C1[C@@H](C)C[C@@H]1[C@@H]2CC[C@]2(C)[C@@](OC(C)=O)(C(C)=O)CC[C@H]21 PSGAAPLEWMOORI-PEINSRQWSA-N 0.000 description 1
- 210000003593 megakaryocyte Anatomy 0.000 description 1
- 229960004296 megestrol acetate Drugs 0.000 description 1
- RQZAXGRLVPAYTJ-GQFGMJRRSA-N megestrol acetate Chemical compound C1=C(C)C2=CC(=O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@@](C(C)=O)(OC(=O)C)[C@@]1(C)CC2 RQZAXGRLVPAYTJ-GQFGMJRRSA-N 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- 230000011987 methylation Effects 0.000 description 1
- 238000007069 methylation reaction Methods 0.000 description 1
- 230000002906 microbiologic effect Effects 0.000 description 1
- BMGQWWVMWDBQGC-IIFHNQTCSA-N midostaurin Chemical compound CN([C@H]1[C@H]([C@]2(C)O[C@@H](N3C4=CC=CC=C4C4=C5C(=O)NCC5=C5C6=CC=CC=C6N2C5=C43)C1)OC)C(=O)C1=CC=CC=C1 BMGQWWVMWDBQGC-IIFHNQTCSA-N 0.000 description 1
- CFCUWKMKBJTWLW-BKHRDMLASA-N mithramycin Chemical compound O([C@@H]1C[C@@H](O[C@H](C)[C@H]1O)OC=1C=C2C=C3C[C@H]([C@@H](C(=O)C3=C(O)C2=C(O)C=1C)O[C@@H]1O[C@H](C)[C@@H](O)[C@H](O[C@@H]2O[C@H](C)[C@H](O)[C@H](O[C@@H]3O[C@H](C)[C@@H](O)[C@@](C)(O)C3)C2)C1)[C@H](OC)C(=O)[C@@H](O)[C@@H](C)O)[C@H]1C[C@@H](O)[C@H](O)[C@@H](C)O1 CFCUWKMKBJTWLW-BKHRDMLASA-N 0.000 description 1
- 229960004857 mitomycin Drugs 0.000 description 1
- 229960000350 mitotane Drugs 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 210000001616 monocyte Anatomy 0.000 description 1
- 201000000050 myeloid neoplasm Diseases 0.000 description 1
- 229940090009 myleran Drugs 0.000 description 1
- UYMDKKVILQGGBT-ZTOMLWHTSA-N n-[(2s)-5-(diaminomethylideneamino)-1-[[(1s)-1-naphthalen-1-ylethyl]amino]-1-oxopentan-2-yl]-4-[(pyridin-2-ylmethylamino)methyl]benzamide Chemical compound N([C@@H](CCCN=C(N)N)C(=O)N[C@@H](C)C=1C2=CC=CC=C2C=CC=1)C(=O)C(C=C1)=CC=C1CNCC1=CC=CC=N1 UYMDKKVILQGGBT-ZTOMLWHTSA-N 0.000 description 1
- 229930014626 natural product Natural products 0.000 description 1
- 208000002154 non-small cell lung carcinoma Diseases 0.000 description 1
- 230000036963 noncompetitive effect Effects 0.000 description 1
- 239000003956 nonsteroidal anti androgen Substances 0.000 description 1
- 238000007899 nucleic acid hybridization Methods 0.000 description 1
- 238000002515 oligonucleotide synthesis Methods 0.000 description 1
- 238000011275 oncology therapy Methods 0.000 description 1
- 210000000056 organ Anatomy 0.000 description 1
- 230000008520 organization Effects 0.000 description 1
- VSZGPKBBMSAYNT-RRFJBIMHSA-N oseltamivir Chemical compound CCOC(=O)C1=C[C@@H](OC(CC)CC)[C@H](NC(C)=O)[C@@H](N)C1 VSZGPKBBMSAYNT-RRFJBIMHSA-N 0.000 description 1
- 229960002194 oseltamivir phosphate Drugs 0.000 description 1
- 229950007318 ozogamicin Drugs 0.000 description 1
- 229960000402 palivizumab Drugs 0.000 description 1
- 201000002528 pancreatic cancer Diseases 0.000 description 1
- 208000008443 pancreatic carcinoma Diseases 0.000 description 1
- 230000007170 pathology Effects 0.000 description 1
- 239000000816 peptidomimetic Substances 0.000 description 1
- 239000000825 pharmaceutical preparation Substances 0.000 description 1
- 229940127557 pharmaceutical product Drugs 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- COLNVLDHVKWLRT-UHFFFAOYSA-N phenylalanine Natural products OC(=O)C(N)CC1=CC=CC=C1 COLNVLDHVKWLRT-UHFFFAOYSA-N 0.000 description 1
- 239000003757 phosphotransferase inhibitor Substances 0.000 description 1
- 239000004033 plastic Substances 0.000 description 1
- 229920003023 plastic Polymers 0.000 description 1
- 229960003171 plicamycin Drugs 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- 229920001184 polypeptide Polymers 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 229960005205 prednisolone Drugs 0.000 description 1
- 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 description 1
- 239000000955 prescription drug Substances 0.000 description 1
- 238000012545 processing Methods 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 239000000583 progesterone congener Substances 0.000 description 1
- 230000035755 proliferation Effects 0.000 description 1
- 230000000069 prophylactic effect Effects 0.000 description 1
- 239000003207 proteasome inhibitor Substances 0.000 description 1
- 238000012514 protein characterization Methods 0.000 description 1
- 238000001742 protein purification Methods 0.000 description 1
- 235000018102 proteins Nutrition 0.000 description 1
- 102000004169 proteins and genes Human genes 0.000 description 1
- 108090000623 proteins and genes Proteins 0.000 description 1
- 150000003212 purines Chemical class 0.000 description 1
- 150000003230 pyrimidines Chemical class 0.000 description 1
- 229940121896 radiopharmaceutical Drugs 0.000 description 1
- 239000012217 radiopharmaceutical Substances 0.000 description 1
- 230000002799 radiopharmaceutical effect Effects 0.000 description 1
- 102000005962 receptors Human genes 0.000 description 1
- 108020003175 receptors Proteins 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 208000037922 refractory disease Diseases 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 229930002330 retinoic acid Natural products 0.000 description 1
- HNMATTJJEPZZMM-BPKVFSPJSA-N s-[(2r,3s,4s,6s)-6-[[(2r,3s,4s,5r,6r)-5-[(2s,4s,5s)-5-[acetyl(ethyl)amino]-4-methoxyoxan-2-yl]oxy-6-[[(2s,5z,9r,13e)-13-[2-[[4-[(2e)-2-[1-[4-(4-amino-4-oxobutoxy)phenyl]ethylidene]hydrazinyl]-2-methyl-4-oxobutan-2-yl]disulfanyl]ethylidene]-9-hydroxy-12-(m Chemical compound C1[C@H](OC)[C@@H](N(CC)C(C)=O)CO[C@H]1O[C@H]1[C@H](O[C@@H]2C\3=C(NC(=O)OC)C(=O)C[C@@](C/3=C/CSSC(C)(C)CC(=O)N\N=C(/C)C=3C=CC(OCCCC(N)=O)=CC=3)(O)C#C\C=C/C#C2)O[C@H](C)[C@@H](NO[C@@H]2O[C@H](C)[C@@H](SC(=O)C=3C(=C(OC)C(O[C@H]4[C@@H]([C@H](OC)[C@@H](O)[C@H](C)O4)O)=C(I)C=3C)OC)[C@@H](O)C2)[C@@H]1O HNMATTJJEPZZMM-BPKVFSPJSA-N 0.000 description 1
- 229960003440 semustine Drugs 0.000 description 1
- 230000035945 sensitivity Effects 0.000 description 1
- UQDJGEHQDNVPGU-UHFFFAOYSA-N serine phosphoethanolamine Chemical compound [NH3+]CCOP([O-])(=O)OCC([NH3+])C([O-])=O UQDJGEHQDNVPGU-UHFFFAOYSA-N 0.000 description 1
- 235000011803 sesame oil Nutrition 0.000 description 1
- 239000008159 sesame oil Substances 0.000 description 1
- 150000003384 small molecules Chemical class 0.000 description 1
- 235000019812 sodium carboxymethyl cellulose Nutrition 0.000 description 1
- 229920001027 sodium carboxymethylcellulose Polymers 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- IVDHYUQIDRJSTI-UHFFFAOYSA-N sorafenib tosylate Chemical compound [H+].CC1=CC=C(S([O-])(=O)=O)C=C1.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 IVDHYUQIDRJSTI-UHFFFAOYSA-N 0.000 description 1
- 239000000600 sorbitol Substances 0.000 description 1
- 230000009870 specific binding Effects 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 230000000638 stimulation Effects 0.000 description 1
- 210000002536 stromal cell Anatomy 0.000 description 1
- 238000010254 subcutaneous injection Methods 0.000 description 1
- 239000007929 subcutaneous injection Substances 0.000 description 1
- 235000000346 sugar Nutrition 0.000 description 1
- 150000008163 sugars Chemical class 0.000 description 1
- 229960000894 sulindac Drugs 0.000 description 1
- MLKXDPUZXIRXEP-MFOYZWKCSA-N sulindac Chemical compound CC1=C(CC(O)=O)C2=CC(F)=CC=C2\C1=C/C1=CC=C(S(C)=O)C=C1 MLKXDPUZXIRXEP-MFOYZWKCSA-N 0.000 description 1
- 238000013268 sustained release Methods 0.000 description 1
- 239000012730 sustained-release form Substances 0.000 description 1
- 229960001603 tamoxifen Drugs 0.000 description 1
- 229940063683 taxotere Drugs 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- 229960001712 testosterone propionate Drugs 0.000 description 1
- ABDIWGRATHZIPB-UHFFFAOYSA-J tetrasodium;4-[[4-[[4-[[5-[[5-[(4,8-disulfonatonaphthalen-1-yl)carbamoyl]-1-methylpyrrol-3-yl]carbamoyl]-1h-pyrrol-3-yl]carbamoylamino]-1h-pyrrole-2-carbonyl]amino]-1-methylpyrrole-2-carbonyl]amino]naphthalene-1,5-disulfonate Chemical compound [Na+].[Na+].[Na+].[Na+].C1=CC(S([O-])(=O)=O)=C2C(NC(=O)C3=CC(NC(=O)C=4NC=C(NC(=O)NC=5C=C(NC=5)C(=O)NC5=CN(C)C(C(=O)NC=6C7=C(C=CC=C7C(=CC=6)S([O-])(=O)=O)S([O-])(=O)=O)=C5)C=4)=CN3C)=CC=C(S([O-])(=O)=O)C2=C1 ABDIWGRATHZIPB-UHFFFAOYSA-J 0.000 description 1
- 238000002560 therapeutic procedure Methods 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
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 238000013518 transcription Methods 0.000 description 1
- 230000035897 transcription Effects 0.000 description 1
- 238000013519 translation Methods 0.000 description 1
- 150000003626 triacylglycerols Chemical class 0.000 description 1
- 150000003918 triazines Chemical class 0.000 description 1
- QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 description 1
- 229960001099 trimetrexate Drugs 0.000 description 1
- NOYPYLRCIDNJJB-UHFFFAOYSA-N trimetrexate Chemical compound COC1=C(OC)C(OC)=CC(NCC=2C(=C3C(N)=NC(N)=NC3=CC=2)C)=C1 NOYPYLRCIDNJJB-UHFFFAOYSA-N 0.000 description 1
- 208000029729 tumor suppressor gene on chromosome 11 Diseases 0.000 description 1
- OUYCCCASQSFEME-UHFFFAOYSA-N tyrosine Natural products OC(=O)C(N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-UHFFFAOYSA-N 0.000 description 1
- 150000003672 ureas Chemical class 0.000 description 1
- 235000015112 vegetable and seed oil Nutrition 0.000 description 1
- 239000008158 vegetable oil Substances 0.000 description 1
- GBABOYUKABKIAF-GHYRFKGUSA-N vinorelbine Chemical compound C1N(CC=2C3=CC=CC=C3NC=22)CC(CC)=C[C@H]1C[C@]2(C(=O)OC)C1=CC([C@]23[C@H]([C@]([C@H](OC(C)=O)[C@]4(CC)C=CCN([C@H]34)CC2)(O)C(=O)OC)N2C)=C2C=C1OC GBABOYUKABKIAF-GHYRFKGUSA-N 0.000 description 1
- 229960002066 vinorelbine Drugs 0.000 description 1
- 230000003612 virological effect Effects 0.000 description 1
Images
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/04—Peptides having up to 20 amino acids in a fully defined sequence; Derivatives thereof
- A61K38/10—Peptides having 12 to 20 amino acids
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/7042—Compounds having saccharide radicals and heterocyclic rings
- A61K31/7052—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides
- A61K31/706—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom
- A61K31/7064—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom containing condensed or non-condensed pyrimidines
- A61K31/7068—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom containing condensed or non-condensed pyrimidines having oxo groups directly attached to the pyrimidine ring, e.g. cytidine, cytidylic acid
-
- 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
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0019—Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner
- A61K9/0021—Intradermal administration, e.g. through microneedle arrays, needleless injectors
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
- A61P35/02—Antineoplastic agents specific for leukemia
-
- 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
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
- G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
- G01N33/53—Immunoassay; Biospecific binding assay; Materials therefor
- G01N33/569—Immunoassay; Biospecific binding assay; Materials therefor for microorganisms, e.g. protozoa, bacteria, viruses
- G01N33/56966—Animal cells
- G01N33/56972—White blood cells
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
- G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
- G01N33/53—Immunoassay; Biospecific binding assay; Materials therefor
- G01N33/574—Immunoassay; Biospecific binding assay; Materials therefor for cancer
- G01N33/57407—Specifically defined cancers
- G01N33/57426—Specifically defined cancers leukemia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K2300/00—Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N2333/00—Assays involving biological materials from specific organisms or of a specific nature
- G01N2333/435—Assays involving biological materials from specific organisms or of a specific nature from animals; from humans
- G01N2333/705—Assays involving receptors, cell surface antigens or cell surface determinants
- G01N2333/715—Assays involving receptors, cell surface antigens or cell surface determinants for cytokines; for lymphokines; for interferons
- G01N2333/7158—Assays involving receptors, cell surface antigens or cell surface determinants for cytokines; for lymphokines; for interferons for chemokines
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N2800/00—Detection or diagnosis of diseases
- G01N2800/52—Predicting or monitoring the response to treatment, e.g. for selection of therapy based on assay results in personalised medicine; Prognosis
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Engineering & Computer Science (AREA)
- Immunology (AREA)
- General Health & Medical Sciences (AREA)
- Hematology (AREA)
- Medicinal Chemistry (AREA)
- Molecular Biology (AREA)
- Animal Behavior & Ethology (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Pharmacology & Pharmacy (AREA)
- Urology & Nephrology (AREA)
- Cell Biology (AREA)
- Biomedical Technology (AREA)
- Epidemiology (AREA)
- Biochemistry (AREA)
- Organic Chemistry (AREA)
- Biotechnology (AREA)
- Pathology (AREA)
- Microbiology (AREA)
- Food Science & Technology (AREA)
- Physics & Mathematics (AREA)
- Analytical Chemistry (AREA)
- General Physics & Mathematics (AREA)
- Oncology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Gastroenterology & Hepatology (AREA)
- Tropical Medicine & Parasitology (AREA)
- Virology (AREA)
- Zoology (AREA)
- Hospice & Palliative Care (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Genetics & Genomics (AREA)
- Biophysics (AREA)
- Dermatology (AREA)
Abstract
Description
(i)全末梢白血球の10%未満であり;
(ii)前記骨髄中の前記芽細胞密度よりも少なくとも5倍低い;および/または
(iii)前記CXCR4アンタゴニストでの処置の1日以上後、少なくとも2倍高い、とき、
前記被験者は、前記CXCR4と化学療法剤との併用治療のために選択される。
(a)AMLを有する被験者の末梢血および骨髄における芽細胞の密度を測定する工程と、
(b)該被験者にCXCR4アンタゴニストを投与する工程と、
(c)末梢血中の前記芽細胞密度が
(i)全末梢白血球の10%未満であり;
(ii)前記骨髄中の前記芽細胞密度よりも少なくとも5倍低い;および/または
(iii)工程(b)の1日以上後、少なくとも2倍高い;
場合、治療有効量の前記CXCR4アンタゴニストおよび治療有効量の化学療法剤を前記被験者に投与する工程とを含み、
それにより、AML治療に対する前記被験者の応答を最大限にしている。
(a)末梢血中の全白血球の10%未満である芽細胞の密度を有するAMLと被験者を特定(分類)する工程と;
(b)治療有効量のCXCR4−アンタゴニストおよび治療有効量の化学療法剤を前記被験者に投与し、それによりAMLを治療する工程とを含む。
(a)骨髄中の芽細胞の密度よりも少なくとも5倍低い末梢血中の芽細胞の密度を有するAMLと被験者を特定する工程と;
(b)治療有効量のCXCR4−アンタゴニストおよび治療有効量の化学療法剤を前記被験者に投与し、それによりAMLを治療する工程とを含む。
(a)被験者へのCXCR4アンタゴニストの投与の少なくとも1日後に、末梢血中の芽細胞の密度の少なくとも2倍の増加を示すAMLと被験者を特定する工程と;
(b)段階(a)で同定された前記被験者に、治療有効量の前記CXCR4−アンタゴニストおよび治療有効量の化学療法薬を投与し、それにより前記AMLを治療する工程と、を含む。
(i)全末梢白血球の10%未満であり;
(ii)前記骨髄中の前記芽細胞密度よりも少なくとも5倍低い;および/または
(iii)前記CXCR4アンタゴニストでの処置の1日以上後、少なくとも2倍高い。
(i)全末梢白血球の10%未満であり;
(ii)前記骨髄中の前記芽細胞密度よりも少なくとも5倍低い;および/または
(iii)前記CXCR4アンタゴニストでの処置の1日以上後、少なくとも2倍高い、とき、
前記被験者は、前記CXCR4と化学療法剤との併用治療のために選択される。
(a)AMLを有する被験者の末梢血および骨髄における芽細胞の密度を測定する工程と、
(b)該被験者にCXCR4アンタゴニストを投与する工程と、
(c)末梢血中の前記芽細胞密度が、
(i)全末梢白血球の10%未満であり;
(ii)前記骨髄中の前記芽細胞密度よりも少なくとも5倍低い;および/または
(iii)工程(b)の1日以上後に少なくとも2倍高い場合、治療有効量の前記CXCR4アンタゴニストおよび治療有効量の化学療法剤を前記被験者に投与する工程とを含み、
それにより、AML治療に対する前記被験者の応答性を最大化している。
(a)末梢血中の全白血球の10%未満である芽細胞の密度を有するAMLと被験者を特定する工程と、
(b)治療有効量のCXCR4−アンタゴニストおよび治療有効量の化学療法剤を前記被験者に投与し、それによりAMLを治療する工程とを含む。
(a)骨髄中の芽細胞の密度よりも少なくとも5倍低い末梢血中の芽細胞の密度を有するAMLと被験者を特定する工程と;
(b)治療有効量のCXCR4−アンタゴニストおよび治療有効量の化学療法剤を前記被験者に投与し、それによってAMLを治療する工程とを含む。
(a)被験者へのCXCR4アンタゴニストの投与の少なくとも1日後に、末梢血中の芽細胞の密度の少なくとも2倍の増加を示すAMLと被験者を特定する工程と、
(b)段階(a)で同定された前記被験者に、治療有効量の前記CXCR4−アンタゴニストおよび治療有効量の化学療法薬を投与し、それにより前記AMLを治療する工程と、を含む。
(i)全末梢白血球の10%未満であり;
(ii)前記骨髄中の前記芽細胞密度よりも少なくとも5倍低い;および/または
(iii)前記CXCR4アンタゴニストでの処置の1日以上後、少なくとも2倍高い。
1 2 3 4 5 6 7 8 9 10 11 12 13 14
A1−A2−A3−Cys−Tyr−A4−A5−A6−A7−A8−A9−A10−Cys−A11 (I)
A2は、A1が存在する場合、アルギニンまたはグルタミン酸残基を表す。またはA2は、A1が存在しない場合、アルギニンまたはグルタミン酸残基またはこれらのアミノ酸のN-α-置換誘導体を表す。
A3は、芳香族アミノ酸残基を表す。
A4、A5およびA9は、それぞれ独立に、アルギニン、リシン、オルニチン、シトルリン、アラニンまたはグルタミン酸残基を表す。
A6は、プロリン、グリシン、オルニチン、リシン、アラニン、シトルリン、アルギニンまたはグルタミン酸残基を表す。
A7は、プロリン、グリシン、オルニチン、リジン、アラニン、シトルリンまたはアルギニン残基を表す。
A8は、チロシン、フェニルアラニン、アラニン、ナフチルアラニン、シトルリンまたはグルタミン酸残基を表す。
A10は、シトルリン、グルタミン酸、アルギニンまたはリジン残基を表す。
A11は、アルギニン、グルタミン酸、リジンまたはシトルリン残基を表し、C末端カルボキシルは誘導体化されていてもよい。
4位または13位のシステイン残基は、ジスルフィド結合を形成することができる。そして、アミノ酸は、L体またはD体のいずれであってもよい。
Kwon Y-U、Kodadek T. ペプトイドおよびペプチドの相対細胞透過性の定量的評価。J Am Chem Soc, 2007; 129:1508を参照。
Miller S, Simon R, Ng S, Zuckermann R, Kerr J, Moos W. 同族L−アミノ酸、D−アミノ酸、N−置換グリシンペプチドおよびペプトイドオリゴマーのタンパク質分解感受性の比較。Drug Dev Res. 1995; 35:20-32を参照。
Yoshikawa Y, Kobayashi K, Oishi S, Fujii N, Furuya T. 環状ペンタペプチドCXCR4アンタゴニストの分子モデリング研究:CXCR4−FC131相互作用の新しい知見。Bioorg Med Chem Lett. 2012; 22:2146-50を参照。
Jaahnichen S, Blanchetot C, Maussang D, Gonzalez-Pajuelo M, Chow KY, Bosch L, De Vrieze S, Serruys B, Ulrichts H, Vandevelde W. CXCR4ナノ体(VHHベースの単一可変ドメイン)は、走化性およびHIV−1複製を強力に阻害し、幹細胞を強く結集させる。Proc Natl Acad Sci USA. 2010; 107:20565-70を参照。
(i)全末梢白血球の10%未満または5%未満または3%未満、
(ii)前記骨髄中の前記芽細胞密度よりも少なくとも5倍低い、少なくとも4倍低い、少なくとも3倍低い、または少なくとも2倍低い、および/または
(iii)前記CXCR4アンタゴニスト(化学療法剤なし)での治療の1日以上(例えば、1〜4、2〜4、2〜3日)後、少なくとも2倍高い、少なくとも3倍高い、少なくとも4倍高い、または少なくとも5倍高い
(i)全末梢白血球の10%未満または5%未満または3%未満、および
(ii)前記骨髄中の前記芽細胞密度よりも少なくとも5倍低い、少なくとも4倍低い、少なくとも3倍低い、または少なくとも2倍低い
(i)全末梢白血球の10%未満または5%未満または3%未満、および
(ii)前記CXCR4アンタゴニスト(化学療法剤なし)での治療の1日以上(例えば、1〜4、2〜4、2〜3日)後、少なくとも2倍高い、少なくとも3倍高い、少なくとも4倍高い、または少なくとも5倍高い
(i)前記骨髄中の前記芽細胞密度よりも少なくとも5倍低い、少なくとも4倍低い、少なくとも3倍低い、または少なくとも2倍低い、および
(ii)前記CXCR4アンタゴニスト(化学療法剤なし)での治療の1日以上(例えば、1〜4、2〜4、2〜3日)の後、少なくとも2倍高い、少なくとも3倍高い、少なくとも4倍高い、または少なくとも5倍高い
一実施形態では、化学療法剤は、キザチニブ(AC220)である。
薬物
凍結乾燥された4F−ベンゾイル−TN14003(BL−8040)は、MSD/N.V.(Organon, Kloosterstraat 6, 5349 AB, Oss, Netherlands)によって、cGMPに従って製造された。
シタラビン(シトシンアラビノシド;ARA−C)は、Hadassah cytotoxica pharmacy(イスラエル)から購入された。
オープンラベル単一アームフェーズ1/2試験で、再発性または難治性疾患を有するAMLと診断された患者は、1〜2日目で単独療法として、1日1回の皮下(SC)用量のBL−8040を投与され、続いて3〜7日目で、同じ用量のBL−8040プラスAra−C(60歳以上の患者では1.5g/m2;60歳より下の患者では3g/m2)を投与された。BL−8040(0.5〜2.0mg/kg)の6用量レベルは、増殖フェーズのために選択された1.5mg/kgで、用量漸増フェーズで試験された。モビリゼーションの程度などの広範な薬力学(PD)パラメータは、研究中に評価された。治療に対する臨床的応答性は、30日目のBM生検によって決定された。治療に対する臨床的応答性は、30日目のBM生検によって決定された。
骨髄芽細胞数は、Lee et al.(Int. Jnl. Lab. Hem. 30:349-364, 2008)によって記載されているような手順を本質的に使用して実行された。
ANL治療に対する臨床的応答性は、AMLの国際ワーキンググループの基準に従って決定された(Cheson et al., J. Clin. Oncol. 21: 4642-4649, 2003;Dohner et al., Blood 115: 453-474, 2010;およびde Greef et al., British Journal of Hematology 128: 184-91, 2005)。これらを下記の表4にまとめた。
完全寛解(CR)、または、不完全な回復を伴う完全寛解(CRiまたはCRp)を達成した治療患者は、応答性があると考えられた。少なくとも1mg/kgのBL−8040を投与されている全ての患者の中で、ベースラインBM芽細胞密度において、応答性患者と、非応答性患者との間に本質的に差はなかった(それぞれ、37.8%および40.8%:図1)。測定は、シタラビンを有する配列番号1の併用治療の前に行われた。
Claims (14)
- 急性骨髄性白血病(AML)を有する被験者の治療計画を選択する方法であって、
前記方法は、前記被験者の末梢血および所望により骨髄における芽細胞の密度を測定する工程を含み、
前記被験者は、CXCR4アンタゴニストで処置されており、
前記末梢血中の前記芽細胞密度が次の(i)、(ii)および/または(iii)の時、
(i)全末梢白血球の10%未満
(ii)前記骨髄中の前記芽細胞密度よりも少なくとも5倍低い
(iii)前記CXCR4アンタゴニストでの処置の1日以上後、少なくとも2倍高い
前記被験者は、前記CXCR4と化学療法剤との併用治療のために選択されることを特徴とする治療計画を選択する方法。 - 急性骨髄性白血病(AML)の治療に対する応答性を最大化する方法であって、前記方法は、
(a)前記AMLを有する被験者の末梢血および骨髄における芽細胞の密度を測定する工程と、
(b)前記被験者にCXCR4アンタゴニストを投与する工程と、
(c)前記末梢血中の前記芽細胞密度が以下の(i)、(ii)および/または(iii)場合、前記CXCR4アンタゴニストの治療有効量と、化学療法剤の治療有効量とを前記被験者に投与する工程と、を含み、
(i)全末梢白血球の10%未満
(ii)前記骨髄中の前記芽細胞密度よりも少なくとも5倍低い
(iii)前記工程(b)の1日以上後、少なくとも2倍高い
前記AMLの治療に対する前記被験者の応答性を最大化することを特徴とする方法。 - AMLを治療する方法であって、前記方法は、
(a)末梢血中の全白血球の10%未満である芽細胞の密度を有するAMLと被験者を特定する工程と、
(b)治療有効量のCXCR4−アンタゴニストと、治療有効量の化学療法剤とを前記被験者に投与し、それにより前記AMLを治療する工程と、を含むことを特徴とするAMLを治療する方法。 - AMLを治療する方法であって、前記方法は、
(a)骨髄中の芽細胞の密度よりも少なくとも5倍低い末梢血中の芽細胞の密度を有するAMLと被験者を特定する工程と、
(b)治療有効量のCXCR4−アンタゴニストと、治療有効量の化学療法剤とを前記被験者に投与し、それにより前記AMLを治療する工程と、を含むことを特徴とするAMLを治療する方法。 - AMLを治療する方法であって、前記方法は、
(a)被験者へのCXCR4アンタゴニストの投与の少なくとも1日後に、末梢血中の芽細胞の密度の少なくとも2倍の増加を示す前記AMLと前記被験者を特定する工程と、
(b)治療有効量の前記CXCR4−アンタゴニストと、治療有効量の化学療法薬とを前記工程(a)で特定された前記被験者に投与し、それにより前記AMLを治療する工程と、を含むことを特徴とするAMLを治療する方法。 - 被験者のAMLの治療におけるCXCR4アンタゴニストおよび化学療法剤であって、
前記被験者は、選択され、前記CXCR4アンタゴニストで治療され、次の(i)、(ii)および/または(iii)である末梢血中の芽細胞密度を示すことを特徴とするCXCR4アンタゴニストおよび化学療法剤。
(i)全末梢白血球の10%未満
(ii)骨髄中の前記芽細胞密度よりも少なくとも5倍低い
(iii)前記CXCR4アンタゴニストでの処置の1日以上後、少なくとも2倍高い - 前記CXCR4アンタゴニストは、CXCR4−アンタゴニストペプチドである請求項1ないし6のいずれか1項に記載の方法またはCXCR4アンタゴニストおよび化学療法剤。
- 前記CXCR4−アンタゴニストペプチドは、配列番号1に記載のものである請求項7に記載の方法またはCXCR4アンタゴニストおよび化学療法剤。
- 前記末梢血中の前記芽細胞の密度は、5%未満である請求項1ないし8のいずれか1項に記載の方法またはCXCR4アンタゴニストおよび化学療法剤。
- 前記CXCR4−アンタゴニストペプチドは、体重1kg当たり0.1〜5mgの1日用量で前記被験者に投与される請求項8または9に記載の方法またはCXCR4アンタゴニストおよび化学療法剤。
- 前記CXCR4アンタゴニスト−ペプチドは、皮下投与される請求項7ないし10のいずれか1項に記載の方法またはCXCR4アンタゴニストおよび化学療法剤。
- 前記CXCR4−アンタゴニストは、前記化学療法剤の投与の少なくとも1日前に、単独療法として前記被験者に投与される請求項1ないし11のいずれか1項に記載の方法またはCXCR4アンタゴニストおよび化学療法剤。
- 前記CXCR4−アンタゴニストは、前記化学療法剤の投与の少なくとも1時間前に、前記被験者に投与される請求項1ないし12のいずれか1項に記載の方法またはCXCR4アンタゴニストおよび化学療法剤。
- 前記化学療法剤は、シタラビン(ARA−C)を含む請求項1ないし13のいずれか1項に記載の方法またはCXCR4アンタゴニストおよび化学療法剤。
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US201662298563P | 2016-02-23 | 2016-02-23 | |
US62/298,563 | 2016-02-23 | ||
PCT/IL2017/050232 WO2017145161A1 (en) | 2016-02-23 | 2017-02-23 | Methods of treating acute myeloid leukemia |
Publications (2)
Publication Number | Publication Date |
---|---|
JP2019510005A true JP2019510005A (ja) | 2019-04-11 |
JP6676182B2 JP6676182B2 (ja) | 2020-04-08 |
Family
ID=59684875
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2018544337A Active JP6676182B2 (ja) | 2016-02-23 | 2017-02-23 | 急性骨髄性白血病の治療方法 |
Country Status (12)
Country | Link |
---|---|
US (1) | US10993985B2 (ja) |
EP (1) | EP3419645B1 (ja) |
JP (1) | JP6676182B2 (ja) |
KR (1) | KR102033920B1 (ja) |
CN (1) | CN109310733A (ja) |
AU (1) | AU2017222495B2 (ja) |
BR (1) | BR112018016924A2 (ja) |
CA (1) | CA3014530A1 (ja) |
ES (1) | ES2830726T3 (ja) |
IL (1) | IL261160B (ja) |
MX (1) | MX2018010125A (ja) |
WO (1) | WO2017145161A1 (ja) |
Families Citing this family (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2017009843A2 (en) | 2015-07-16 | 2017-01-19 | Biokine Therapeutics Ltd. | Compositions, articles of manufacture and methods for treating cancer |
BR112018016924A2 (pt) | 2016-02-23 | 2019-01-02 | Biokine Therapeutics Ltd | método de seleção de regime de tratamento para indivíduo que tem leucemia mieloide aguda (lma), método de maximização de resposta ao tratamento de leucemia mieloide aguda (lma), método de tratamento de lma, antagonista de cxcr4 e agente quimioterápico no tratamento de lma |
WO2024107891A2 (en) * | 2022-11-16 | 2024-05-23 | Nkarta, Inc. | Dosing regimens for combination therapies |
Family Cites Families (95)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US4179337A (en) | 1973-07-20 | 1979-12-18 | Davis Frank F | Non-immunogenic polypeptides |
JPS552602A (en) | 1978-06-20 | 1980-01-10 | Yamasa Shoyu Co Ltd | 1-beta-d-arabinofranosylcytosine-5'-phosphoric acid oleyl ester |
US5206018A (en) | 1978-11-03 | 1993-04-27 | Ayerst, Mckenna & Harrison, Inc. | Use of rapamycin in treatment of tumors |
US4342828A (en) | 1979-07-20 | 1982-08-03 | Morinaga Milk Industry Co., Ltd. | Method for producing substance capable of stimulating differentiation and proliferation of human granulopoietic stem cells |
JPS61227526A (ja) | 1984-07-25 | 1986-10-09 | Chugai Pharmaceut Co Ltd | 新規なコロニー刺激因子 |
WO1986004605A1 (en) | 1985-02-08 | 1986-08-14 | Chugai Seiyaku Kabushiki Kaisha | Human granulocyte colony stimulating factor |
US4810643A (en) | 1985-08-23 | 1989-03-07 | Kirin- Amgen Inc. | Production of pluripotent granulocyte colony-stimulating factor |
EP0396158A1 (en) | 1985-08-23 | 1990-11-07 | Kirin-Amgen, Inc. | Production of pluripotent granulocyte colony-stimulating factor |
DE3681551D1 (de) | 1985-09-30 | 1991-10-24 | Chugai Pharmaceutical Co Ltd | Menschlicher granulozyten-colony stimulierender faktor. |
JPH0618778B2 (ja) | 1985-10-04 | 1994-03-16 | 中外製薬株式会社 | 白血球減少症治療剤 |
ES2039209T5 (es) | 1986-01-22 | 1996-07-16 | Chugai Pharmaceutical Co Ltd | Compuesto farmaceutico que promueve el restablecimiento de la capacidad hemopoyetica. |
ES2036530T3 (es) | 1986-01-22 | 1993-06-01 | Chugai Seiyaku Kabushiki Kaisha | Utilizacion de un factor estimulante de las colonias granulociticas humano para preparar una composicion farmaceutica para el tratamiento de la leucemia mielogena. |
DK203187A (da) | 1986-04-22 | 1987-10-23 | Immunex Corp | Human g-csf proteinekspression |
GR871067B (en) | 1986-07-18 | 1987-11-19 | Chugai Pharmaceutical Co Ltd | Process for producing stable pharmaceutical preparation containing granulocyte colony stimulating factor |
JPH0725689B2 (ja) | 1986-10-07 | 1995-03-22 | 中外製薬株式会社 | 顆粒球コロニ−刺激因子を含有する徐放性製剤 |
DK174044B1 (da) | 1986-12-23 | 2002-05-06 | Kyowa Hakko Kogyo Kk | Polypeptid afledt fra human granulocytkolonistimulerende faktor, og fremgangsmåde til fremstilling deraf, DNA kodende for nævnte polypeptid, rekombinant plasmid indeholdende nævnte DNA, og mikroorganismer indeholdende nævnte rekombinante plasmid....... |
JP2618618B2 (ja) | 1988-03-04 | 1997-06-11 | 協和醗酵工業株式会社 | 抗g−csf誘導体、nd28モノクローナル抗体 |
CA1340810C (en) | 1988-03-31 | 1999-11-02 | Motoo Yamasaki | Polypeptide derivatives of human granulocyte colony stimulating factor |
EP0344796B1 (en) | 1988-06-03 | 1994-09-21 | Chugai Seiyaku Kabushiki Kaisha | Crystalline human granulocyte colony stimulating factor and process for preparing the same |
CA1339071C (en) | 1988-08-24 | 1997-07-29 | Koichiro Tsuji | Thrombus control agent |
US5218092A (en) | 1988-09-29 | 1993-06-08 | Kyowa Hakko Kogyo Co., Ltd. | Modified granulocyte-colony stimulating factor polypeptide with added carbohydrate chains |
US5104651A (en) | 1988-12-16 | 1992-04-14 | Amgen Inc. | Stabilized hydrophobic protein formulations of g-csf |
CA2006596C (en) | 1988-12-22 | 2000-09-05 | Rika Ishikawa | Chemically-modified g-csf |
IL96477A0 (en) | 1989-12-01 | 1991-08-16 | Amgen Inc | Megakaryocyte production |
GB9107846D0 (en) | 1990-04-30 | 1991-05-29 | Ici Plc | Polypeptides |
JP3249147B2 (ja) | 1990-06-01 | 2002-01-21 | キリン−アムジエン・インコーポレーテツド | 生理活性蛋白含有経口製剤 |
EP0459516A1 (en) | 1990-06-01 | 1991-12-04 | Kirin-Amgen, Inc. | Oral dosage form of biologically active proteins |
IE912365A1 (en) | 1990-07-23 | 1992-01-29 | Zeneca Ltd | Continuous release pharmaceutical compositions |
US5250732A (en) | 1991-07-18 | 1993-10-05 | Genentech, Inc. | Ketamine analogues for treatment of thrombocytopenia |
FR2686900B1 (fr) | 1992-01-31 | 1995-07-21 | Rhone Poulenc Rorer Sa | Nouveaux polypeptides ayant une activite de stimulation des colonies de granulocytes, leur preparation et compositions pharmaceutiques les contenant. |
DE69416824T2 (de) | 1993-10-14 | 1999-07-08 | Seikagaku Corp., Tokio/Tokyo | Polypeptide und daraus hergestellte, gegen hiv wirksame substanzen |
US5595756A (en) | 1993-12-22 | 1997-01-21 | Inex Pharmaceuticals Corporation | Liposomal compositions for enhanced retention of bioactive agents |
US5492126A (en) | 1994-05-02 | 1996-02-20 | Focal Surgery | Probe for medical imaging and therapy using ultrasound |
JP4562815B2 (ja) | 1997-05-21 | 2010-10-13 | ジェネンテック, インコーポレイテッド | トロンボポエチンの新規な投与 |
WO1998052465A1 (en) | 1997-05-23 | 1998-11-26 | Transurgical, Inc. | Mri-guided therapeutic unit and methods |
US6569418B1 (en) | 1997-12-11 | 2003-05-27 | University Of Maryland Biotechnology Institute | Immuno-modulating effects of chemokines in DNA vaccination |
CA2305787A1 (en) | 2000-05-09 | 2001-11-09 | The University Of British Columbia | Cxcr4 antagonist treatment of hematopoietic cells |
CA2245224A1 (en) | 1998-08-14 | 2000-02-14 | Jiang-Hong Giong | Chemokine receptor antagonists and chemotherapeutics |
WO2000009152A1 (en) | 1998-08-14 | 2000-02-24 | The University Of British Columbia | Therapeutic chemokine receptor antagonists |
US6946445B1 (en) | 1998-03-13 | 2005-09-20 | The University Of British Columbia | Therapeutic chemokine receptor antagonists |
AU5241099A (en) | 1998-07-31 | 2000-02-21 | Trustees Of Columbia University In The City Of New York, The | Use of inhibitors of the activation of cxcr4 receptor by sdf-1 in treating rheumatoid arthritis |
US6294459B1 (en) | 1998-09-03 | 2001-09-25 | Micron Technology, Inc. | Anti-reflective coatings and methods for forming and using same |
MXPA01003503A (es) | 1998-10-05 | 2005-01-14 | Pharmexa As | Nuevos metodos terapeuticos de vacunacion. |
EP1124614A1 (de) | 1998-10-27 | 2001-08-22 | Fraunhofer-Gesellschaft Zur Förderung Der Angewandten Forschung E.V. | Verfahren und vorrichtung zur regelung einer gezielten wärmedeponierung in ein material |
US20060079492A1 (en) | 1999-10-25 | 2006-04-13 | Ahlem Clarence N | Compositions and treatment methods |
US6365583B1 (en) | 1999-02-02 | 2002-04-02 | Anormed, Inc. | Methods to enhance white blood cell count |
SK13822001A3 (sk) | 1999-03-29 | 2002-02-05 | Shire Biochem Inc. | Použitie zlúčenín podľa vynálezu na prípravu farmaceutických prostriedkov na liečenie leukémie |
MXPA02005199A (es) | 1999-11-24 | 2002-11-07 | Schering Corp | Metodos para inhibir metastasis. |
AU2001236065A1 (en) | 2000-03-03 | 2001-09-12 | Nobutaka Fujii | Antiviral compounds |
ATE265219T1 (de) | 2000-05-09 | 2004-05-15 | Univ British Columbia | Verwendung von cxcr4 antagonisten zur behandlung von krebs und autoimmunkrankheiten |
US8435939B2 (en) | 2000-09-05 | 2013-05-07 | Biokine Therapeutics Ltd. | Polypeptide anti-HIV agent containing the same |
US7138488B2 (en) | 2000-09-05 | 2006-11-21 | Biokine Therapeutics Ltd. | Polypeptides having anti-HIV activity and compositions comprising same |
US20020159996A1 (en) | 2001-01-31 | 2002-10-31 | Kandasamy Hariharan | Use of CD23 antagonists for the treatment of neoplastic disorders |
US7630750B2 (en) | 2001-02-05 | 2009-12-08 | The Research Foundation For The State University Of New York | Computer aided treatment planning |
JP3374917B2 (ja) | 2001-02-16 | 2003-02-10 | サンケン電気株式会社 | スイッチング電源装置 |
US7169750B2 (en) | 2001-07-31 | 2007-01-30 | Anormed, Inc. | Methods to mobilize progenitor/stem cells |
US20030221931A1 (en) | 2002-02-28 | 2003-12-04 | Steve Marsh | Sliding device |
US8774913B2 (en) | 2002-04-08 | 2014-07-08 | Medtronic Ardian Luxembourg S.A.R.L. | Methods and apparatus for intravasculary-induced neuromodulation |
JP4781621B2 (ja) | 2002-08-27 | 2011-09-28 | バイオカイン セラピューティックス リミテッド | Cxcr4拮抗薬およびその用途 |
WO2004020462A1 (ja) | 2002-08-27 | 2004-03-11 | Fujii, Nobutaka | Cxcr4拮抗薬およびその用途 |
DE10240064A1 (de) | 2002-08-30 | 2004-03-11 | Universitätsklinikum Freiburg | CXCR4-Rezeptor-Antagonisten |
WO2004052862A1 (ja) | 2002-12-10 | 2004-06-24 | Ono Pharmaceutical Co., Ltd. | 含窒素複素環化合物およびその医薬用途 |
US20050002939A1 (en) | 2002-12-23 | 2005-01-06 | Albert Zlotnik | Tumor killing/tumor regression using CXCR4 antagonists |
EP1608318A4 (en) | 2003-03-27 | 2009-07-29 | Univ Emory | CXCR4 ANTAGONISTS AND METHODS OF USE |
CA2520259A1 (en) | 2003-04-11 | 2004-10-28 | Anormed Inc. | Cxcr4 chemokine receptor binding compounds |
US8012136B2 (en) | 2003-05-20 | 2011-09-06 | Optimyst Systems, Inc. | Ophthalmic fluid delivery device and method of operation |
US7419667B2 (en) | 2004-03-19 | 2008-09-02 | Morinaga Milk Industry Co. Ltd. | Drug for cancer therapy |
CN101094684A (zh) | 2004-08-13 | 2007-12-26 | 阿诺麦德股份有限公司 | 用趋化因子的组合活化祖细胞/干细胞 |
US20080233053A1 (en) | 2005-02-07 | 2008-09-25 | Pharmalight Inc. | Method and Device for Ophthalmic Administration of Active Pharmaceutical Ingredients |
EP1898943B1 (en) | 2005-05-25 | 2012-10-10 | Hadasit Medical Research Services & Development Ltd. | Cxcr4 antagonists for wound healing and re-epithelialization |
JP2009504788A (ja) | 2005-08-19 | 2009-02-05 | ジェンザイム・コーポレーション | 化学療法の強化方法 |
EP1974018A4 (en) | 2005-12-08 | 2010-01-27 | Univ Louisville Res Found | VSEL (VERY SMALL EMBRYONIC LIKE) STEM CELLS AND METHOD OF ISOLATING AND USE THEREOF |
EP2032691A2 (en) | 2006-06-15 | 2009-03-11 | Neostem, Inc | Processing procedure for peripheral blood stem cells |
RU2009107030A (ru) | 2006-08-02 | 2010-09-10 | Джензим Корпорейшн (Us) | Комбинированная терапия |
US7968098B2 (en) | 2006-08-04 | 2011-06-28 | Kurume University | HLA-A24-binding KIF-derived peptide |
CA2673719C (en) | 2006-12-21 | 2018-07-24 | Biokine Therapeutics Ltd. | T-140 peptide analogs having cxcr4 super-agonist activity for bone marrow recovery |
WO2009091826A2 (en) | 2008-01-14 | 2009-07-23 | The Board Of Regents Of The University Of Texas System | Compositions and methods related to a human cd19-specific chimeric antigen receptor (h-car) |
ES2681529T3 (es) | 2009-03-23 | 2018-09-13 | Ambit Biosciences Corporation | Métodos de tratamiento utilizando terapia de combinación |
EP2243833A1 (en) | 2009-04-22 | 2010-10-27 | Erasmus University Medical Center Rotterdam | Method for the treatment of acute myeloid leukemia |
US9427456B2 (en) | 2009-06-14 | 2016-08-30 | Biokine Therapeutics Ltd. | Peptide therapy for increasing platelet levels |
EP2443137B1 (en) | 2009-06-15 | 2015-05-20 | Biokine Therapeutics Ltd. | Novel chemokine binding polypeptides capable of inhibiting the course of autoimmunity, inflammation and cancer |
WO2011069121A1 (en) | 2009-12-04 | 2011-06-09 | Neostem, Inc. | Mesenchymal stem cells (mscs) isolated from mobilized peripheral blood |
US20120082687A1 (en) | 2010-10-04 | 2012-04-05 | Alex Wah Hin Yeung | Use of cell adhesion inhibitor for the mobilization of antigen presenting cells and immune cells in a cell mixture (AIM) from the peripheral blood and methods of use |
EP2663320A1 (en) | 2011-01-10 | 2013-11-20 | Biokine Therapeutics Ltd. | Peptides and compositions for the treatment of neuroectodermal derived tumors and retinoblastoma |
KR102024957B1 (ko) * | 2011-11-09 | 2019-09-24 | 브리스톨-마이어스 스큅 컴퍼니 | 항-cxcr4 항체를 이용한 혈액 악성종양의 치료 |
WO2013160895A1 (en) | 2012-04-24 | 2013-10-31 | Biokine Therapeutics Ltd. | Peptides and use thereof in the treatment of large cell lung cancer |
US20140147411A1 (en) | 2012-11-14 | 2014-05-29 | U.S. GOVERNMENT represented by the UNITED STATES DEPARTMENT OF VETERANS AFFAIRS | Methods of treating cancer and testing mutation zygosity related thereto |
CN105163749B (zh) | 2013-03-24 | 2018-03-27 | 拜欧肯治疗有限公司 | 治疗骨髓性白血病的方法 |
MX2016000750A (es) | 2013-08-02 | 2016-08-05 | Aduro Biotech Holdings Europe B V | Combinacion de agonistas de cd27 e inhibicion del punto de control inmunologico para estimulacion del sistema inmunologico. |
CA2920377A1 (en) | 2013-08-05 | 2015-02-12 | Cambridge Enterprise Limited | Inhibition of cxcr4 signaling in cancer immunotherapy |
CN106029084A (zh) | 2013-10-31 | 2016-10-12 | 百欧肯治疗有限公司 | 治疗具有类fms酪氨酸激酶3突变的急性骨髓性白血病的方法 |
IL292510A (en) | 2013-11-05 | 2022-06-01 | Cognate Bioservices Inc | Combinations of checkpoint inhibitors and cancer drugs |
WO2016185476A1 (en) | 2015-05-20 | 2016-11-24 | Biokine Therapeutics Ltd. | Methods of obtaining mononuclear blood cells and uses thereof |
WO2017009843A2 (en) | 2015-07-16 | 2017-01-19 | Biokine Therapeutics Ltd. | Compositions, articles of manufacture and methods for treating cancer |
BR112018016924A2 (pt) | 2016-02-23 | 2019-01-02 | Biokine Therapeutics Ltd | método de seleção de regime de tratamento para indivíduo que tem leucemia mieloide aguda (lma), método de maximização de resposta ao tratamento de leucemia mieloide aguda (lma), método de tratamento de lma, antagonista de cxcr4 e agente quimioterápico no tratamento de lma |
-
2017
- 2017-02-23 BR BR112018016924A patent/BR112018016924A2/pt unknown
- 2017-02-23 US US16/078,696 patent/US10993985B2/en active Active
- 2017-02-23 KR KR1020187027178A patent/KR102033920B1/ko active IP Right Grant
- 2017-02-23 CN CN201780026678.9A patent/CN109310733A/zh active Pending
- 2017-02-23 MX MX2018010125A patent/MX2018010125A/es unknown
- 2017-02-23 AU AU2017222495A patent/AU2017222495B2/en active Active
- 2017-02-23 JP JP2018544337A patent/JP6676182B2/ja active Active
- 2017-02-23 CA CA3014530A patent/CA3014530A1/en not_active Abandoned
- 2017-02-23 ES ES17755946T patent/ES2830726T3/es active Active
- 2017-02-23 EP EP17755946.5A patent/EP3419645B1/en active Active
- 2017-02-23 WO PCT/IL2017/050232 patent/WO2017145161A1/en active Application Filing
-
2018
- 2018-08-15 IL IL261160A patent/IL261160B/en active IP Right Grant
Also Published As
Publication number | Publication date |
---|---|
CN109310733A (zh) | 2019-02-05 |
IL261160B (en) | 2019-12-31 |
IL261160A (en) | 2018-10-31 |
CA3014530A1 (en) | 2017-08-31 |
WO2017145161A1 (en) | 2017-08-31 |
AU2017222495A1 (en) | 2018-09-27 |
KR20180115757A (ko) | 2018-10-23 |
JP6676182B2 (ja) | 2020-04-08 |
BR112018016924A2 (pt) | 2019-01-02 |
EP3419645A4 (en) | 2019-10-16 |
EP3419645B1 (en) | 2020-09-02 |
US20190046602A1 (en) | 2019-02-14 |
EP3419645A1 (en) | 2019-01-02 |
AU2017222495B2 (en) | 2019-08-08 |
KR102033920B1 (ko) | 2019-10-18 |
ES2830726T3 (es) | 2021-06-04 |
MX2018010125A (es) | 2019-03-28 |
US10993985B2 (en) | 2021-05-04 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
JP6759402B2 (ja) | Flt3変異を有する急性骨髄性白血病の治療用の医薬組成物 | |
US20180344801A1 (en) | Methods of treating myeloid leukemia | |
EP3804758A1 (en) | Biomarker for judging efficacy of immune checkpoint inhibitor | |
JP6676182B2 (ja) | 急性骨髄性白血病の治療方法 | |
US20210338767A1 (en) | Methods of selecting treatment for cxcr4-associated cancer |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A821 Effective date: 20180905 Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20181127 |
|
A621 | Written request for application examination |
Free format text: JAPANESE INTERMEDIATE CODE: A621 Effective date: 20181127 |
|
A871 | Explanation of circumstances concerning accelerated examination |
Free format text: JAPANESE INTERMEDIATE CODE: A871 Effective date: 20181127 |
|
RD01 | Notification of change of attorney |
Free format text: JAPANESE INTERMEDIATE CODE: A7426 Effective date: 20180905 |
|
A975 | Report on accelerated examination |
Free format text: JAPANESE INTERMEDIATE CODE: A971005 Effective date: 20181227 |
|
A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20190115 |
|
A601 | Written request for extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A601 Effective date: 20190412 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20190423 |
|
A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20190611 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20190719 |
|
A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20190806 |
|
A601 | Written request for extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A601 Effective date: 20191023 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20200117 |
|
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: 20200218 |
|
A61 | First payment of annual fees (during grant procedure) |
Free format text: JAPANESE INTERMEDIATE CODE: A61 Effective date: 20200311 |
|
R150 | Certificate of patent or registration of utility model |
Ref document number: 6676182 Country of ref document: JP Free format text: JAPANESE INTERMEDIATE CODE: R150 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |