JP2021046446A - グルココルチコイド及びedo−s101を含む組合せ - Google Patents
グルココルチコイド及びedo−s101を含む組合せ Download PDFInfo
- Publication number
- JP2021046446A JP2021046446A JP2020215171A JP2020215171A JP2021046446A JP 2021046446 A JP2021046446 A JP 2021046446A JP 2020215171 A JP2020215171 A JP 2020215171A JP 2020215171 A JP2020215171 A JP 2020215171A JP 2021046446 A JP2021046446 A JP 2021046446A
- Authority
- JP
- Japan
- Prior art keywords
- combination
- compound
- formula
- patient
- pharmaceutically acceptable
- 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.)
- Pending
Links
- 239000003862 glucocorticoid Substances 0.000 title claims abstract description 59
- 206010028980 Neoplasm Diseases 0.000 claims abstract description 94
- 150000001875 compounds Chemical class 0.000 claims abstract description 92
- 239000000203 mixture Substances 0.000 claims abstract description 82
- 150000003839 salts Chemical class 0.000 claims abstract description 70
- 201000011510 cancer Diseases 0.000 claims abstract description 49
- 238000011282 treatment Methods 0.000 claims abstract description 42
- 206010035226 Plasma cell myeloma Diseases 0.000 claims abstract description 39
- 238000000034 method Methods 0.000 claims abstract description 35
- 206010006187 Breast cancer Diseases 0.000 claims abstract description 29
- 208000026310 Breast neoplasm Diseases 0.000 claims abstract description 29
- 208000032839 leukemia Diseases 0.000 claims abstract description 25
- 208000034578 Multiple myelomas Diseases 0.000 claims abstract description 23
- 206010025323 Lymphomas Diseases 0.000 claims abstract description 18
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 5
- 229940079156 Proteasome inhibitor Drugs 0.000 claims description 55
- 239000003207 proteasome inhibitor Substances 0.000 claims description 55
- 230000037396 body weight Effects 0.000 claims description 33
- 229960003957 dexamethasone Drugs 0.000 claims description 32
- 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 claims description 32
- 229960001467 bortezomib Drugs 0.000 claims description 20
- 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 claims description 18
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 claims description 17
- 208000015914 Non-Hodgkin lymphomas Diseases 0.000 claims description 13
- 201000000050 myeloid neoplasm Diseases 0.000 claims description 13
- 229960002438 carfilzomib Drugs 0.000 claims description 11
- 108010021331 carfilzomib Proteins 0.000 claims description 11
- BLMPQMFVWMYDKT-NZTKNTHTSA-N carfilzomib Chemical compound C([C@@H](C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CC(C)C)C(=O)[C@]1(C)OC1)NC(=O)CN1CCOCC1)CC1=CC=CC=C1 BLMPQMFVWMYDKT-NZTKNTHTSA-N 0.000 claims description 11
- 208000031261 Acute myeloid leukaemia Diseases 0.000 claims description 10
- 208000033776 Myeloid Acute Leukemia Diseases 0.000 claims description 10
- 239000013543 active substance Substances 0.000 claims description 10
- -1 glucronate Chemical compound 0.000 claims description 10
- 208000002250 Hematologic Neoplasms Diseases 0.000 claims description 8
- 208000017604 Hodgkin disease Diseases 0.000 claims description 8
- 208000021519 Hodgkin lymphoma Diseases 0.000 claims description 8
- 208000010747 Hodgkins lymphoma Diseases 0.000 claims description 8
- 201000009277 hairy cell leukemia Diseases 0.000 claims description 8
- 239000003085 diluting agent Substances 0.000 claims description 7
- 208000003721 Triple Negative Breast Neoplasms Diseases 0.000 claims description 6
- 230000002489 hematologic effect Effects 0.000 claims description 6
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 claims description 6
- 208000022679 triple-negative breast carcinoma Diseases 0.000 claims description 6
- 208000007452 Plasmacytoma Diseases 0.000 claims description 5
- 210000001744 T-lymphocyte Anatomy 0.000 claims description 5
- 208000024893 Acute lymphoblastic leukemia Diseases 0.000 claims description 4
- 208000010839 B-cell chronic lymphocytic leukemia Diseases 0.000 claims description 4
- 208000032791 BCR-ABL1 positive chronic myelogenous leukemia Diseases 0.000 claims description 4
- 101001012157 Homo sapiens Receptor tyrosine-protein kinase erbB-2 Proteins 0.000 claims description 4
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 4
- 102100030086 Receptor tyrosine-protein kinase erbB-2 Human genes 0.000 claims description 4
- 239000011885 synergistic combination Substances 0.000 claims description 4
- KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 claims description 3
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 claims description 3
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 claims description 3
- JVTAAEKCZFNVCJ-UHFFFAOYSA-M Lactate Chemical compound CC(O)C([O-])=O JVTAAEKCZFNVCJ-UHFFFAOYSA-M 0.000 claims description 3
- 229910019142 PO4 Inorganic materials 0.000 claims description 3
- 208000029052 T-cell acute lymphoblastic leukemia Diseases 0.000 claims description 3
- DTQVDTLACAAQTR-UHFFFAOYSA-M Trifluoroacetate Chemical compound [O-]C(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-M 0.000 claims description 3
- 229940049920 malate Drugs 0.000 claims description 3
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 claims description 3
- BJEPYKJPYRNKOW-UHFFFAOYSA-N malic acid Chemical compound OC(=O)C(O)CC(O)=O BJEPYKJPYRNKOW-UHFFFAOYSA-N 0.000 claims description 3
- PSZYNBSKGUBXEH-UHFFFAOYSA-M naphthalene-1-sulfonate Chemical compound C1=CC=C2C(S(=O)(=O)[O-])=CC=CC2=C1 PSZYNBSKGUBXEH-UHFFFAOYSA-M 0.000 claims description 3
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 claims description 3
- 239000010452 phosphate Substances 0.000 claims description 3
- 229960004618 prednisone Drugs 0.000 claims description 3
- 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 claims description 3
- YGSDEFSMJLZEOE-UHFFFAOYSA-M salicylate Chemical compound OC1=CC=CC=C1C([O-])=O YGSDEFSMJLZEOE-UHFFFAOYSA-M 0.000 claims description 3
- 229960001860 salicylate Drugs 0.000 claims description 3
- KDYFGRWQOYBRFD-UHFFFAOYSA-L succinate(2-) Chemical compound [O-]C(=O)CCC([O-])=O KDYFGRWQOYBRFD-UHFFFAOYSA-L 0.000 claims description 3
- 229940095064 tartrate Drugs 0.000 claims description 3
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 claims description 3
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 claims description 2
- WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 claims description 2
- 208000006404 Large Granular Lymphocytic Leukemia Diseases 0.000 claims description 2
- 229910002651 NO3 Inorganic materials 0.000 claims description 2
- NHNBFGGVMKEFGY-UHFFFAOYSA-N Nitrate Chemical compound [O-][N+]([O-])=O NHNBFGGVMKEFGY-UHFFFAOYSA-N 0.000 claims description 2
- 108010064641 ONX 0912 Proteins 0.000 claims description 2
- 201000008717 T-cell large granular lymphocyte leukemia Diseases 0.000 claims description 2
- 238000011260 co-administration Methods 0.000 claims description 2
- SJFBTAPEPRWNKH-CCKFTAQKSA-N delanzomib Chemical compound CC(C)C[C@@H](B(O)O)NC(=O)[C@H]([C@@H](C)O)NC(=O)C1=CC=CC(C=2C=CC=CC=2)=N1 SJFBTAPEPRWNKH-CCKFTAQKSA-N 0.000 claims description 2
- 230000008472 epithelial growth Effects 0.000 claims description 2
- 229960001347 fluocinolone acetonide Drugs 0.000 claims description 2
- FEBLZLNTKCEFIT-VSXGLTOVSA-N fluocinolone acetonide Chemical compound C1([C@@H](F)C2)=CC(=O)C=C[C@]1(C)[C@]1(F)[C@@H]2[C@@H]2C[C@H]3OC(C)(C)O[C@@]3(C(=O)CO)[C@@]2(C)C[C@@H]1O FEBLZLNTKCEFIT-VSXGLTOVSA-N 0.000 claims description 2
- 229930195712 glutamate Natural products 0.000 claims description 2
- JFCQEDHGNNZCLN-UHFFFAOYSA-N glutaric acid Chemical compound OC(=O)CCCC(O)=O JFCQEDHGNNZCLN-UHFFFAOYSA-N 0.000 claims description 2
- 239000008187 granular material Substances 0.000 claims description 2
- XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 claims description 2
- 229940079826 hydrogen sulfite Drugs 0.000 claims description 2
- QAOWNCQODCNURD-UHFFFAOYSA-M hydrogensulfate Chemical compound OS([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-M 0.000 claims description 2
- 229960003648 ixazomib Drugs 0.000 claims description 2
- MXAYKZJJDUDWDS-LBPRGKRZSA-N ixazomib Chemical compound CC(C)C[C@@H](B(O)O)NC(=O)CNC(=O)C1=CC(Cl)=CC=C1Cl MXAYKZJJDUDWDS-LBPRGKRZSA-N 0.000 claims description 2
- 208000003747 lymphoid leukemia Diseases 0.000 claims description 2
- 229950002736 marizomib Drugs 0.000 claims description 2
- SWZXEVABPLUDIO-WSZYKNRRSA-N n-[(2s)-3-methoxy-1-[[(2s)-3-methoxy-1-[[(2s)-1-[(2r)-2-methyloxiran-2-yl]-1-oxo-3-phenylpropan-2-yl]amino]-1-oxopropan-2-yl]amino]-1-oxopropan-2-yl]-2-methyl-1,3-thiazole-5-carboxamide Chemical compound N([C@@H](COC)C(=O)N[C@@H](COC)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)[C@]1(C)OC1)C(=O)C1=CN=C(C)S1 SWZXEVABPLUDIO-WSZYKNRRSA-N 0.000 claims description 2
- 229950005750 oprozomib Drugs 0.000 claims description 2
- NGWSFRIPKNWYAO-SHTIJGAHSA-N salinosporamide A Chemical compound C([C@@H]1[C@H](O)[C@]23C(=O)O[C@]2([C@H](C(=O)N3)CCCl)C)CCC=C1 NGWSFRIPKNWYAO-SHTIJGAHSA-N 0.000 claims description 2
- NGWSFRIPKNWYAO-UHFFFAOYSA-N salinosporamide A Natural products N1C(=O)C(CCCl)C2(C)OC(=O)C21C(O)C1CCCC=C1 NGWSFRIPKNWYAO-UHFFFAOYSA-N 0.000 claims description 2
- IIACRCGMVDHOTQ-UHFFFAOYSA-M sulfamate Chemical compound NS([O-])(=O)=O IIACRCGMVDHOTQ-UHFFFAOYSA-M 0.000 claims description 2
- 102000002029 Claudin Human genes 0.000 claims 2
- 108050009302 Claudin Proteins 0.000 claims 2
- 208000026651 T-cell prolymphocytic leukemia Diseases 0.000 claims 2
- 102000009465 Growth Factor Receptors Human genes 0.000 claims 1
- 108010009202 Growth Factor Receptors Proteins 0.000 claims 1
- 208000028018 Lymphocytic leukaemia Diseases 0.000 claims 1
- AFVFQIVMOAPDHO-UHFFFAOYSA-M methanesulfonate group Chemical group CS(=O)(=O)[O-] AFVFQIVMOAPDHO-UHFFFAOYSA-M 0.000 claims 1
- 201000005787 hematologic cancer Diseases 0.000 abstract description 4
- 210000004027 cell Anatomy 0.000 description 27
- 230000000694 effects Effects 0.000 description 16
- GISXTRIGVCKQBX-UHFFFAOYSA-N 7-[5-[bis(2-chloroethyl)amino]-1-methylbenzimidazol-2-yl]-n-hydroxyheptanamide Chemical compound ClCCN(CCCl)C1=CC=C2N(C)C(CCCCCCC(=O)NO)=NC2=C1 GISXTRIGVCKQBX-UHFFFAOYSA-N 0.000 description 13
- 239000003814 drug Substances 0.000 description 11
- 239000007788 liquid Substances 0.000 description 11
- 229940037128 systemic glucocorticoids Drugs 0.000 description 11
- 239000000243 solution Substances 0.000 description 10
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 9
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 9
- 229940079593 drug Drugs 0.000 description 9
- 238000000338 in vitro Methods 0.000 description 9
- 239000003112 inhibitor Substances 0.000 description 9
- 230000034994 death Effects 0.000 description 8
- 231100000517 death Toxicity 0.000 description 8
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 8
- 230000004083 survival effect Effects 0.000 description 8
- 239000002253 acid Substances 0.000 description 7
- 238000002347 injection Methods 0.000 description 7
- 239000007924 injection Substances 0.000 description 7
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 7
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 6
- 230000001154 acute effect Effects 0.000 description 6
- 239000003795 chemical substances by application Substances 0.000 description 6
- 210000000265 leukocyte Anatomy 0.000 description 6
- 239000000725 suspension Substances 0.000 description 6
- 238000012360 testing method Methods 0.000 description 6
- 210000004369 blood Anatomy 0.000 description 5
- 239000008280 blood Substances 0.000 description 5
- 210000001185 bone marrow Anatomy 0.000 description 5
- 210000000481 breast Anatomy 0.000 description 5
- 238000002512 chemotherapy Methods 0.000 description 5
- 201000010099 disease Diseases 0.000 description 5
- 230000002195 synergetic effect Effects 0.000 description 5
- 210000001519 tissue Anatomy 0.000 description 5
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Chemical compound OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 4
- 102000003964 Histone deacetylase Human genes 0.000 description 4
- 108090000353 Histone deacetylase Proteins 0.000 description 4
- 241001465754 Metazoa Species 0.000 description 4
- 239000005557 antagonist Substances 0.000 description 4
- 239000002775 capsule Substances 0.000 description 4
- 235000005911 diet Nutrition 0.000 description 4
- 230000037213 diet Effects 0.000 description 4
- 239000003937 drug carrier Substances 0.000 description 4
- 238000002474 experimental method Methods 0.000 description 4
- 238000001727 in vivo Methods 0.000 description 4
- 210000004324 lymphatic system Anatomy 0.000 description 4
- VMGAPWLDMVPYIA-HIDZBRGKSA-N n'-amino-n-iminomethanimidamide Chemical compound N\N=C\N=N VMGAPWLDMVPYIA-HIDZBRGKSA-N 0.000 description 4
- 239000000843 powder Substances 0.000 description 4
- 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 4
- 239000011780 sodium chloride Substances 0.000 description 4
- 239000003826 tablet Substances 0.000 description 4
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
- WVDDGKGOMKODPV-UHFFFAOYSA-N Benzyl alcohol Chemical compound OCC1=CC=CC=C1 WVDDGKGOMKODPV-UHFFFAOYSA-N 0.000 description 3
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 3
- 102000004190 Enzymes Human genes 0.000 description 3
- 108090000790 Enzymes Proteins 0.000 description 3
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 3
- 108010010803 Gelatin Proteins 0.000 description 3
- 241000282412 Homo Species 0.000 description 3
- 239000002202 Polyethylene glycol Substances 0.000 description 3
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 3
- 229920002472 Starch Polymers 0.000 description 3
- 230000002159 abnormal effect Effects 0.000 description 3
- 239000000443 aerosol Substances 0.000 description 3
- 239000003242 anti bacterial agent Substances 0.000 description 3
- 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 3
- 239000000969 carrier Substances 0.000 description 3
- 239000003086 colorant Substances 0.000 description 3
- 208000035475 disorder Diseases 0.000 description 3
- 239000000839 emulsion Substances 0.000 description 3
- 230000029142 excretion Effects 0.000 description 3
- 238000009472 formulation Methods 0.000 description 3
- 239000008273 gelatin Substances 0.000 description 3
- 229920000159 gelatin Polymers 0.000 description 3
- 235000019322 gelatine Nutrition 0.000 description 3
- 235000011852 gelatine desserts Nutrition 0.000 description 3
- 235000011187 glycerol Nutrition 0.000 description 3
- 230000036541 health Effects 0.000 description 3
- 208000024200 hematopoietic and lymphoid system neoplasm Diseases 0.000 description 3
- 238000011534 incubation Methods 0.000 description 3
- 208000015181 infectious disease Diseases 0.000 description 3
- 210000004698 lymphocyte Anatomy 0.000 description 3
- 239000000463 material Substances 0.000 description 3
- 239000000546 pharmaceutical excipient Substances 0.000 description 3
- 210000004180 plasmocyte Anatomy 0.000 description 3
- 229920001223 polyethylene glycol Polymers 0.000 description 3
- 239000007787 solid Substances 0.000 description 3
- 239000008247 solid mixture Substances 0.000 description 3
- 239000008107 starch Substances 0.000 description 3
- 235000019698 starch Nutrition 0.000 description 3
- 239000004094 surface-active agent Substances 0.000 description 3
- 238000001356 surgical procedure Methods 0.000 description 3
- 230000004614 tumor growth Effects 0.000 description 3
- HZAXFHJVJLSVMW-UHFFFAOYSA-N 2-Aminoethan-1-ol Chemical compound NCCO HZAXFHJVJLSVMW-UHFFFAOYSA-N 0.000 description 2
- XTWYTFMLZFPYCI-KQYNXXCUSA-N 5'-adenylphosphoric acid Chemical compound C1=NC=2C(N)=NC=NC=2N1[C@@H]1O[C@H](COP(O)(=O)OP(O)(O)=O)[C@@H](O)[C@H]1O XTWYTFMLZFPYCI-KQYNXXCUSA-N 0.000 description 2
- 208000003950 B-cell lymphoma Diseases 0.000 description 2
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 2
- 206010059866 Drug resistance Diseases 0.000 description 2
- 241000196324 Embryophyta Species 0.000 description 2
- 102000003893 Histone acetyltransferases Human genes 0.000 description 2
- 108090000246 Histone acetyltransferases Proteins 0.000 description 2
- OAKJQQAXSVQMHS-UHFFFAOYSA-N Hydrazine Chemical compound NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 description 2
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 2
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 2
- 206010058467 Lung neoplasm malignant Diseases 0.000 description 2
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 2
- 102000015094 Paraproteins Human genes 0.000 description 2
- 108010064255 Paraproteins Proteins 0.000 description 2
- 238000011579 SCID mouse model Methods 0.000 description 2
- 229930006000 Sucrose Natural products 0.000 description 2
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 2
- 206010042971 T-cell lymphoma Diseases 0.000 description 2
- 208000027585 T-cell non-Hodgkin lymphoma Diseases 0.000 description 2
- 208000024313 Testicular Neoplasms Diseases 0.000 description 2
- 206010057644 Testis cancer Diseases 0.000 description 2
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 2
- 210000001015 abdomen Anatomy 0.000 description 2
- 230000000996 additive effect Effects 0.000 description 2
- 230000000259 anti-tumor effect Effects 0.000 description 2
- 229940088710 antibiotic agent Drugs 0.000 description 2
- 239000002246 antineoplastic agent Substances 0.000 description 2
- 239000011230 binding agent Substances 0.000 description 2
- 239000013078 crystal Substances 0.000 description 2
- 238000011161 development Methods 0.000 description 2
- 230000018109 developmental process Effects 0.000 description 2
- 239000008121 dextrose Substances 0.000 description 2
- 239000002270 dispersing agent Substances 0.000 description 2
- 239000003534 dna topoisomerase inhibitor Substances 0.000 description 2
- 235000003599 food sweetener Nutrition 0.000 description 2
- 238000007918 intramuscular administration Methods 0.000 description 2
- 238000001990 intravenous administration Methods 0.000 description 2
- 239000008101 lactose Substances 0.000 description 2
- 239000000314 lubricant Substances 0.000 description 2
- 201000005202 lung cancer Diseases 0.000 description 2
- 208000020816 lung neoplasm Diseases 0.000 description 2
- 210000001165 lymph node Anatomy 0.000 description 2
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
- 238000004519 manufacturing process Methods 0.000 description 2
- 230000004060 metabolic process Effects 0.000 description 2
- OSWPMRLSEDHDFF-UHFFFAOYSA-N methyl salicylate Chemical compound COC(=O)C1=CC=CC=C1O OSWPMRLSEDHDFF-UHFFFAOYSA-N 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
- 235000013336 milk Nutrition 0.000 description 2
- 239000008267 milk Substances 0.000 description 2
- 210000004080 milk Anatomy 0.000 description 2
- 208000025113 myeloid leukemia Diseases 0.000 description 2
- 150000007524 organic acids Chemical class 0.000 description 2
- 238000007911 parenteral administration Methods 0.000 description 2
- 239000002504 physiological saline solution Substances 0.000 description 2
- 239000006187 pill Substances 0.000 description 2
- BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Chemical compound [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 description 2
- 239000003755 preservative agent Substances 0.000 description 2
- 238000001959 radiotherapy Methods 0.000 description 2
- 210000001350 reed-sternberg cell Anatomy 0.000 description 2
- 239000003381 stabilizer Substances 0.000 description 2
- 238000007920 subcutaneous administration Methods 0.000 description 2
- 239000005720 sucrose Substances 0.000 description 2
- 239000000829 suppository Substances 0.000 description 2
- 239000003765 sweetening agent Substances 0.000 description 2
- 239000006188 syrup Substances 0.000 description 2
- 235000020357 syrup Nutrition 0.000 description 2
- 239000000454 talc Substances 0.000 description 2
- 229910052623 talc Inorganic materials 0.000 description 2
- 201000003120 testicular cancer Diseases 0.000 description 2
- 230000001225 therapeutic effect Effects 0.000 description 2
- 229940044693 topoisomerase inhibitor Drugs 0.000 description 2
- 210000004881 tumor cell Anatomy 0.000 description 2
- 230000035899 viability Effects 0.000 description 2
- 239000000080 wetting agent Substances 0.000 description 2
- MZOFCQQQCNRIBI-VMXHOPILSA-N (3s)-4-[[(2s)-1-[[(2s)-1-[[(1s)-1-carboxy-2-hydroxyethyl]amino]-4-methyl-1-oxopentan-2-yl]amino]-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-3-[[2-[[(2s)-2,6-diaminohexanoyl]amino]acetyl]amino]-4-oxobutanoic acid Chemical compound OC[C@@H](C(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCN=C(N)N)NC(=O)[C@H](CC(O)=O)NC(=O)CNC(=O)[C@@H](N)CCCCN MZOFCQQQCNRIBI-VMXHOPILSA-N 0.000 description 1
- JYEUMXHLPRZUAT-UHFFFAOYSA-N 1,2,3-triazine Chemical compound C1=CN=NN=C1 JYEUMXHLPRZUAT-UHFFFAOYSA-N 0.000 description 1
- LDVVTQMJQSCDMK-UHFFFAOYSA-N 1,3-dihydroxypropan-2-yl formate Chemical compound OCC(CO)OC=O LDVVTQMJQSCDMK-UHFFFAOYSA-N 0.000 description 1
- IXPNQXFRVYWDDI-UHFFFAOYSA-N 1-methyl-2,4-dioxo-1,3-diazinane-5-carboximidamide Chemical compound CN1CC(C(N)=N)C(=O)NC1=O IXPNQXFRVYWDDI-UHFFFAOYSA-N 0.000 description 1
- VBICKXHEKHSIBG-UHFFFAOYSA-N 1-monostearoylglycerol Chemical compound CCCCCCCCCCCCCCCCCC(=O)OCC(O)CO VBICKXHEKHSIBG-UHFFFAOYSA-N 0.000 description 1
- ASJSXUWOFZATJM-UHFFFAOYSA-N 2-(3,5-diphenyl-1h-tetrazol-2-yl)-4,5-dimethyl-1,3-thiazole Chemical compound S1C(C)=C(C)N=C1N1N(C=2C=CC=CC=2)NC(C=2C=CC=CC=2)=N1 ASJSXUWOFZATJM-UHFFFAOYSA-N 0.000 description 1
- WEVYNIUIFUYDGI-UHFFFAOYSA-N 3-[6-[4-(trifluoromethoxy)anilino]-4-pyrimidinyl]benzamide Chemical compound NC(=O)C1=CC=CC(C=2N=CN=C(NC=3C=CC(OC(F)(F)F)=CC=3)C=2)=C1 WEVYNIUIFUYDGI-UHFFFAOYSA-N 0.000 description 1
- 244000215068 Acacia senegal Species 0.000 description 1
- 208000003200 Adenoma Diseases 0.000 description 1
- XTWYTFMLZFPYCI-UHFFFAOYSA-N Adenosine diphosphate Natural products C1=NC=2C(N)=NC=NC=2N1C1OC(COP(O)(=O)OP(O)(O)=O)C(O)C1O XTWYTFMLZFPYCI-UHFFFAOYSA-N 0.000 description 1
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 1
- NOWKCMXCCJGMRR-UHFFFAOYSA-N Aziridine Chemical compound C1CN1 NOWKCMXCCJGMRR-UHFFFAOYSA-N 0.000 description 1
- 102100022005 B-lymphocyte antigen CD20 Human genes 0.000 description 1
- 208000005440 Basal Cell Neoplasms Diseases 0.000 description 1
- 206010004146 Basal cell carcinoma Diseases 0.000 description 1
- 206010005003 Bladder cancer Diseases 0.000 description 1
- 108010006654 Bleomycin Proteins 0.000 description 1
- 241000283690 Bos taurus Species 0.000 description 1
- CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 1
- 0 CCCCCN(CCC1CC1)c1ccc2[n](C)c(CCCCCCC(*O)=O)nc2c1 Chemical compound CCCCCN(CCC1CC1)c1ccc2[n](C)c(CCCCCCC(*O)=O)nc2c1 0.000 description 1
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
- 241000282472 Canis lupus familiaris Species 0.000 description 1
- 241000283707 Capra Species 0.000 description 1
- 229920002134 Carboxymethyl cellulose Polymers 0.000 description 1
- 201000009030 Carcinoma Diseases 0.000 description 1
- 241000282994 Cervidae Species 0.000 description 1
- 206010008342 Cervix carcinoma Diseases 0.000 description 1
- 229920002261 Corn starch Polymers 0.000 description 1
- 229920000858 Cyclodextrin Polymers 0.000 description 1
- 239000012623 DNA damaging agent Substances 0.000 description 1
- 229940123780 DNA topoisomerase I inhibitor Drugs 0.000 description 1
- 229940124087 DNA topoisomerase II inhibitor Drugs 0.000 description 1
- 239000004375 Dextrin Substances 0.000 description 1
- 229920001353 Dextrin Polymers 0.000 description 1
- 239000004097 EU approved flavor enhancer Substances 0.000 description 1
- 241000283086 Equidae Species 0.000 description 1
- 208000000461 Esophageal Neoplasms Diseases 0.000 description 1
- 229940102550 Estrogen receptor antagonist Drugs 0.000 description 1
- 239000001856 Ethyl cellulose Substances 0.000 description 1
- ZZSNKZQZMQGXPY-UHFFFAOYSA-N Ethyl cellulose Chemical compound CCOCC1OC(OC)C(OCC)C(OCC)C1OC1C(O)C(O)C(OC)C(CO)O1 ZZSNKZQZMQGXPY-UHFFFAOYSA-N 0.000 description 1
- PIICEJLVQHRZGT-UHFFFAOYSA-N Ethylenediamine Chemical compound NCCN PIICEJLVQHRZGT-UHFFFAOYSA-N 0.000 description 1
- 102000007317 Farnesyltranstransferase Human genes 0.000 description 1
- 108010007508 Farnesyltranstransferase Proteins 0.000 description 1
- 241000282326 Felis catus Species 0.000 description 1
- YCKRFDGAMUMZLT-UHFFFAOYSA-N Fluorine atom Chemical compound [F] YCKRFDGAMUMZLT-UHFFFAOYSA-N 0.000 description 1
- 206010051066 Gastrointestinal stromal tumour Diseases 0.000 description 1
- 208000032612 Glial tumor Diseases 0.000 description 1
- 206010018338 Glioma Diseases 0.000 description 1
- 244000060234 Gmelina philippensis Species 0.000 description 1
- 229920000084 Gum arabic Polymers 0.000 description 1
- 229940125497 HER2 kinase inhibitor Drugs 0.000 description 1
- 102000002812 Heat-Shock Proteins Human genes 0.000 description 1
- 108010004889 Heat-Shock Proteins Proteins 0.000 description 1
- 102100039996 Histone deacetylase 1 Human genes 0.000 description 1
- 101000897405 Homo sapiens B-lymphocyte antigen CD20 Proteins 0.000 description 1
- 101001035024 Homo sapiens Histone deacetylase 1 Proteins 0.000 description 1
- 101000599862 Homo sapiens Intercellular adhesion molecule 3 Proteins 0.000 description 1
- 101000934338 Homo sapiens Myeloid cell surface antigen CD33 Proteins 0.000 description 1
- 101000692455 Homo sapiens Platelet-derived growth factor receptor beta Proteins 0.000 description 1
- 101000984753 Homo sapiens Serine/threonine-protein kinase B-raf Proteins 0.000 description 1
- 101000851376 Homo sapiens Tumor necrosis factor receptor superfamily member 8 Proteins 0.000 description 1
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
- 108060003951 Immunoglobulin Proteins 0.000 description 1
- 102100037871 Intercellular adhesion molecule 3 Human genes 0.000 description 1
- 102000000588 Interleukin-2 Human genes 0.000 description 1
- 108010002350 Interleukin-2 Proteins 0.000 description 1
- 208000037396 Intraductal Noninfiltrating Carcinoma Diseases 0.000 description 1
- 206010073094 Intraductal proliferative breast lesion Diseases 0.000 description 1
- 108010076876 Keratins Proteins 0.000 description 1
- 102000011782 Keratins Human genes 0.000 description 1
- 208000008839 Kidney Neoplasms Diseases 0.000 description 1
- 238000000134 MTT assay Methods 0.000 description 1
- 231100000002 MTT assay Toxicity 0.000 description 1
- 241000124008 Mammalia Species 0.000 description 1
- 102000002274 Matrix Metalloproteinases Human genes 0.000 description 1
- 108010000684 Matrix Metalloproteinases Proteins 0.000 description 1
- 244000246386 Mentha pulegium Species 0.000 description 1
- 235000016257 Mentha pulegium Nutrition 0.000 description 1
- 235000004357 Mentha x piperita Nutrition 0.000 description 1
- 108060004795 Methyltransferase Proteins 0.000 description 1
- 102000016397 Methyltransferase Human genes 0.000 description 1
- 229920000168 Microcrystalline cellulose Polymers 0.000 description 1
- 229930192392 Mitomycin Natural products 0.000 description 1
- 241000699670 Mus sp. Species 0.000 description 1
- 102100025243 Myeloid cell surface antigen CD33 Human genes 0.000 description 1
- 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 1
- GXCLVBGFBYZDAG-UHFFFAOYSA-N N-[2-(1H-indol-3-yl)ethyl]-N-methylprop-2-en-1-amine Chemical compound CN(CCC1=CNC2=C1C=CC=C2)CC=C GXCLVBGFBYZDAG-UHFFFAOYSA-N 0.000 description 1
- 102000014736 Notch Human genes 0.000 description 1
- 108010070047 Notch Receptors Proteins 0.000 description 1
- 206010030155 Oesophageal carcinoma Diseases 0.000 description 1
- 241000283973 Oryctolagus cuniculus Species 0.000 description 1
- 240000007594 Oryza sativa Species 0.000 description 1
- 235000007164 Oryza sativa Nutrition 0.000 description 1
- 206010033128 Ovarian cancer Diseases 0.000 description 1
- 206010061535 Ovarian neoplasm Diseases 0.000 description 1
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 1
- 239000012661 PARP inhibitor Substances 0.000 description 1
- 206010061902 Pancreatic neoplasm Diseases 0.000 description 1
- 235000019483 Peanut oil Nutrition 0.000 description 1
- 241001494479 Pecora Species 0.000 description 1
- 102100026547 Platelet-derived growth factor receptor beta Human genes 0.000 description 1
- 229940121906 Poly ADP ribose polymerase inhibitor Drugs 0.000 description 1
- 229920002565 Polyethylene Glycol 400 Polymers 0.000 description 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
- 208000006664 Precursor Cell Lymphoblastic Leukemia-Lymphoma Diseases 0.000 description 1
- 206010060862 Prostate cancer Diseases 0.000 description 1
- 208000000236 Prostatic Neoplasms Diseases 0.000 description 1
- 102000001253 Protein Kinase Human genes 0.000 description 1
- 108091030071 RNAI Proteins 0.000 description 1
- 239000012980 RPMI-1640 medium Substances 0.000 description 1
- 208000015634 Rectal Neoplasms Diseases 0.000 description 1
- 206010038389 Renal cancer Diseases 0.000 description 1
- 229940127395 Ribonucleotide Reductase Inhibitors Drugs 0.000 description 1
- 239000012891 Ringer solution Substances 0.000 description 1
- 206010039491 Sarcoma Diseases 0.000 description 1
- 102100027103 Serine/threonine-protein kinase B-raf Human genes 0.000 description 1
- 208000005718 Stomach Neoplasms Diseases 0.000 description 1
- 102000019259 Succinate Dehydrogenase Human genes 0.000 description 1
- 108010012901 Succinate Dehydrogenase Proteins 0.000 description 1
- 241000282887 Suidae Species 0.000 description 1
- LSNNMFCWUKXFEE-UHFFFAOYSA-N Sulfurous acid Chemical class OS(O)=O LSNNMFCWUKXFEE-UHFFFAOYSA-N 0.000 description 1
- 208000000389 T-cell leukemia Diseases 0.000 description 1
- AUYYCJSJGJYCDS-LBPRGKRZSA-N Thyrolar Chemical class IC1=CC(C[C@H](N)C(O)=O)=CC(I)=C1OC1=CC=C(O)C(I)=C1 AUYYCJSJGJYCDS-LBPRGKRZSA-N 0.000 description 1
- 239000000365 Topoisomerase I Inhibitor Substances 0.000 description 1
- 239000000317 Topoisomerase II Inhibitor Substances 0.000 description 1
- GSEJCLTVZPLZKY-UHFFFAOYSA-N Triethanolamine Chemical compound OCCN(CCO)CCO GSEJCLTVZPLZKY-UHFFFAOYSA-N 0.000 description 1
- 108060008682 Tumor Necrosis Factor Proteins 0.000 description 1
- 102000000852 Tumor Necrosis Factor-alpha Human genes 0.000 description 1
- 102100036857 Tumor necrosis factor receptor superfamily member 8 Human genes 0.000 description 1
- 208000007097 Urinary Bladder Neoplasms Diseases 0.000 description 1
- 208000006105 Uterine Cervical Neoplasms Diseases 0.000 description 1
- 208000002495 Uterine Neoplasms Diseases 0.000 description 1
- 229940091171 VEGFR-2 tyrosine kinase inhibitor Drugs 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
- 238000002835 absorbance Methods 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 235000010489 acacia gum Nutrition 0.000 description 1
- 239000000205 acacia gum Substances 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 239000002487 adenosine deaminase inhibitor Substances 0.000 description 1
- 239000002671 adjuvant Substances 0.000 description 1
- 235000010443 alginic acid Nutrition 0.000 description 1
- 239000000783 alginic acid Substances 0.000 description 1
- 229920000615 alginic acid Polymers 0.000 description 1
- 229960001126 alginic acid Drugs 0.000 description 1
- 150000004781 alginic acids Chemical class 0.000 description 1
- 229930013930 alkaloid Natural products 0.000 description 1
- 150000008052 alkyl sulfonates Chemical class 0.000 description 1
- 150000003863 ammonium salts Chemical class 0.000 description 1
- 229940045799 anthracyclines and related substance Drugs 0.000 description 1
- 229940034982 antineoplastic agent Drugs 0.000 description 1
- 230000005775 apoptotic pathway Effects 0.000 description 1
- 239000003886 aromatase inhibitor Substances 0.000 description 1
- 229940046844 aromatase inhibitors Drugs 0.000 description 1
- 239000012298 atmosphere Substances 0.000 description 1
- 239000012752 auxiliary agent Substances 0.000 description 1
- 210000003719 b-lymphocyte Anatomy 0.000 description 1
- YTKUWDBFDASYHO-UHFFFAOYSA-N bendamustine Chemical compound ClCCN(CCCl)C1=CC=C2N(C)C(CCCC(O)=O)=NC2=C1 YTKUWDBFDASYHO-UHFFFAOYSA-N 0.000 description 1
- 229960002707 bendamustine Drugs 0.000 description 1
- 235000019445 benzyl alcohol Nutrition 0.000 description 1
- 230000001588 bifunctional effect Effects 0.000 description 1
- 201000009036 biliary tract cancer Diseases 0.000 description 1
- 208000020790 biliary tract neoplasm Diseases 0.000 description 1
- 238000004166 bioassay Methods 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 229960001561 bleomycin Drugs 0.000 description 1
- OYVAGSVQBOHSSS-UAPAGMARSA-O bleomycin A2 Chemical compound N([C@H](C(=O)N[C@H](C)[C@@H](O)[C@H](C)C(=O)N[C@@H]([C@H](O)C)C(=O)NCCC=1SC=C(N=1)C=1SC=C(N=1)C(=O)NCCC[S+](C)C)[C@@H](O[C@H]1[C@H]([C@@H](O)[C@H](O)[C@H](CO)O1)O[C@@H]1[C@H]([C@@H](OC(N)=O)[C@H](O)[C@@H](CO)O1)O)C=1N=CNC=1)C(=O)C1=NC([C@H](CC(N)=O)NC[C@H](N)C(N)=O)=NC(N)=C1C OYVAGSVQBOHSSS-UAPAGMARSA-O 0.000 description 1
- 210000002798 bone marrow cell Anatomy 0.000 description 1
- 239000000872 buffer Substances 0.000 description 1
- 239000011575 calcium Substances 0.000 description 1
- 229910052791 calcium Inorganic materials 0.000 description 1
- 238000002619 cancer immunotherapy Methods 0.000 description 1
- 208000035269 cancer or benign tumor Diseases 0.000 description 1
- 229940022399 cancer vaccine Drugs 0.000 description 1
- 238000009566 cancer vaccine Methods 0.000 description 1
- 239000004202 carbamide Substances 0.000 description 1
- 239000001768 carboxy methyl cellulose Substances 0.000 description 1
- 235000010948 carboxy methyl cellulose Nutrition 0.000 description 1
- 239000008112 carboxymethyl-cellulose Substances 0.000 description 1
- 230000019522 cellular metabolic process Effects 0.000 description 1
- 201000010881 cervical cancer Diseases 0.000 description 1
- 229940124444 chemoprotective agent Drugs 0.000 description 1
- 235000015218 chewing gum Nutrition 0.000 description 1
- ZYVSOIYQKUDENJ-WKSBCEQHSA-N chromomycin A3 Chemical compound O([C@@H]1C[C@@H](O[C@H](C)[C@@H]1OC(C)=O)OC=1C=C2C=C3C[C@H]([C@@H](C(=O)C3=C(O)C2=C(O)C=1C)O[C@@H]1O[C@H](C)[C@@H](O)[C@H](O[C@@H]2O[C@H](C)[C@@H](O)[C@H](O[C@@H]3O[C@@H](C)[C@H](OC(C)=O)[C@@](C)(O)C3)C2)C1)[C@H](OC)C(=O)[C@@H](O)[C@@H](C)O)[C@@H]1C[C@@H](O)[C@@H](OC)[C@@H](C)O1 ZYVSOIYQKUDENJ-WKSBCEQHSA-N 0.000 description 1
- 239000008119 colloidal silica Substances 0.000 description 1
- 229940075614 colloidal silicon dioxide Drugs 0.000 description 1
- 210000001072 colon Anatomy 0.000 description 1
- 230000000112 colonic effect Effects 0.000 description 1
- 239000007891 compressed tablet Substances 0.000 description 1
- 239000008120 corn starch Substances 0.000 description 1
- 229940099112 cornstarch Drugs 0.000 description 1
- 239000003246 corticosteroid Substances 0.000 description 1
- 229940084953 dexamethasone 0.5 mg Drugs 0.000 description 1
- 235000019425 dextrin Nutrition 0.000 description 1
- 239000012895 dilution Substances 0.000 description 1
- 238000010790 dilution Methods 0.000 description 1
- 239000007884 disintegrant Substances 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 230000009977 dual effect Effects 0.000 description 1
- 208000028715 ductal breast carcinoma in situ Diseases 0.000 description 1
- 201000007273 ductal carcinoma in situ Diseases 0.000 description 1
- 229940121647 egfr inhibitor Drugs 0.000 description 1
- 239000003995 emulsifying agent Substances 0.000 description 1
- 102000052116 epidermal growth factor receptor activity proteins Human genes 0.000 description 1
- 108700015053 epidermal growth factor receptor activity proteins Proteins 0.000 description 1
- 230000001973 epigenetic effect Effects 0.000 description 1
- 201000004101 esophageal cancer Diseases 0.000 description 1
- 235000019325 ethyl cellulose Nutrition 0.000 description 1
- 229920001249 ethyl cellulose Polymers 0.000 description 1
- 239000010685 fatty oil Substances 0.000 description 1
- 239000000796 flavoring agent Substances 0.000 description 1
- 235000013312 flour Nutrition 0.000 description 1
- 239000012530 fluid Substances 0.000 description 1
- 239000011737 fluorine Substances 0.000 description 1
- 229910052731 fluorine Inorganic materials 0.000 description 1
- 239000004052 folic acid antagonist Substances 0.000 description 1
- 235000013355 food flavoring agent Nutrition 0.000 description 1
- 235000019264 food flavour enhancer Nutrition 0.000 description 1
- 230000004927 fusion Effects 0.000 description 1
- 206010017758 gastric cancer Diseases 0.000 description 1
- 201000011243 gastrointestinal stromal tumor Diseases 0.000 description 1
- 239000000499 gel Substances 0.000 description 1
- 239000007903 gelatin capsule Substances 0.000 description 1
- 230000009368 gene silencing by RNA Effects 0.000 description 1
- 238000001415 gene therapy Methods 0.000 description 1
- 239000011521 glass Substances 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- 159000000011 group IA salts Chemical class 0.000 description 1
- 208000035474 group of disease Diseases 0.000 description 1
- 239000003102 growth factor Substances 0.000 description 1
- 230000003394 haemopoietic effect Effects 0.000 description 1
- 208000019622 heart disease Diseases 0.000 description 1
- 239000003481 heat shock protein 90 inhibitor Substances 0.000 description 1
- 235000001050 hortel pimenta Nutrition 0.000 description 1
- 150000003840 hydrochlorides Chemical class 0.000 description 1
- 229940127121 immunoconjugate Drugs 0.000 description 1
- 102000018358 immunoglobulin Human genes 0.000 description 1
- 229940072221 immunoglobulins Drugs 0.000 description 1
- 239000000411 inducer Substances 0.000 description 1
- 239000003701 inert diluent Substances 0.000 description 1
- 238000001802 infusion Methods 0.000 description 1
- 229940102223 injectable solution Drugs 0.000 description 1
- 150000007529 inorganic bases Chemical class 0.000 description 1
- 229910052500 inorganic mineral Inorganic materials 0.000 description 1
- 238000007912 intraperitoneal administration Methods 0.000 description 1
- 238000007913 intrathecal administration Methods 0.000 description 1
- 238000007914 intraventricular administration Methods 0.000 description 1
- 208000030776 invasive breast carcinoma Diseases 0.000 description 1
- 230000005865 ionizing radiation Effects 0.000 description 1
- 230000002427 irreversible effect Effects 0.000 description 1
- 239000007951 isotonicity adjuster Substances 0.000 description 1
- 201000010982 kidney cancer Diseases 0.000 description 1
- 239000002502 liposome Substances 0.000 description 1
- 201000007270 liver cancer Diseases 0.000 description 1
- 208000014018 liver neoplasm Diseases 0.000 description 1
- 230000007774 longterm Effects 0.000 description 1
- 210000004072 lung Anatomy 0.000 description 1
- 239000003580 lung surfactant Substances 0.000 description 1
- 235000019359 magnesium stearate Nutrition 0.000 description 1
- 208000015486 malignant pancreatic neoplasm Diseases 0.000 description 1
- 210000005075 mammary gland Anatomy 0.000 description 1
- IWYDHOAUDWTVEP-UHFFFAOYSA-M mandelate Chemical compound [O-]C(=O)C(O)C1=CC=CC=C1 IWYDHOAUDWTVEP-UHFFFAOYSA-M 0.000 description 1
- 108010082117 matrigel Proteins 0.000 description 1
- 201000001441 melanoma Diseases 0.000 description 1
- 230000002503 metabolic effect Effects 0.000 description 1
- 235000010270 methyl p-hydroxybenzoate Nutrition 0.000 description 1
- 239000004292 methyl p-hydroxybenzoate Substances 0.000 description 1
- 229960001047 methyl salicylate Drugs 0.000 description 1
- 229960002216 methylparaben Drugs 0.000 description 1
- 239000000693 micelle Substances 0.000 description 1
- 235000019813 microcrystalline cellulose Nutrition 0.000 description 1
- 239000008108 microcrystalline cellulose Substances 0.000 description 1
- 229940016286 microcrystalline cellulose Drugs 0.000 description 1
- 231100000782 microtubule inhibitor Toxicity 0.000 description 1
- 239000011707 mineral Substances 0.000 description 1
- 239000002480 mineral oil Substances 0.000 description 1
- 235000010446 mineral oil Nutrition 0.000 description 1
- 150000007522 mineralic acids Chemical class 0.000 description 1
- 230000002438 mitochondrial effect Effects 0.000 description 1
- 230000004898 mitochondrial function Effects 0.000 description 1
- 229960004857 mitomycin Drugs 0.000 description 1
- 239000011259 mixed solution Substances 0.000 description 1
- YOHYSYJDKVYCJI-UHFFFAOYSA-N n-[3-[[6-[3-(trifluoromethyl)anilino]pyrimidin-4-yl]amino]phenyl]cyclopropanecarboxamide Chemical compound FC(F)(F)C1=CC=CC(NC=2N=CN=C(NC=3C=C(NC(=O)C4CC4)C=CC=3)C=2)=C1 YOHYSYJDKVYCJI-UHFFFAOYSA-N 0.000 description 1
- 239000002105 nanoparticle Substances 0.000 description 1
- 239000006199 nebulizer Substances 0.000 description 1
- 210000002445 nipple Anatomy 0.000 description 1
- 150000002823 nitrates Chemical class 0.000 description 1
- 239000012457 nonaqueous media Substances 0.000 description 1
- 239000000346 nonvolatile oil Substances 0.000 description 1
- 239000003921 oil Substances 0.000 description 1
- 235000019198 oils Nutrition 0.000 description 1
- 210000000056 organ Anatomy 0.000 description 1
- 235000005985 organic acids Nutrition 0.000 description 1
- 150000007530 organic bases Chemical class 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 239000006179 pH buffering agent Substances 0.000 description 1
- 201000002528 pancreatic cancer Diseases 0.000 description 1
- 208000008443 pancreatic carcinoma Diseases 0.000 description 1
- 230000037361 pathway Effects 0.000 description 1
- 239000000312 peanut oil Substances 0.000 description 1
- 239000008188 pellet Substances 0.000 description 1
- JLFNLZLINWHATN-UHFFFAOYSA-N pentaethylene glycol Chemical compound OCCOCCOCCOCCOCCO JLFNLZLINWHATN-UHFFFAOYSA-N 0.000 description 1
- 230000010412 perfusion Effects 0.000 description 1
- 239000003208 petroleum Substances 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 239000000049 pigment Substances 0.000 description 1
- 239000004033 plastic Substances 0.000 description 1
- 229920003023 plastic Polymers 0.000 description 1
- 229910052697 platinum Inorganic materials 0.000 description 1
- 239000008389 polyethoxylated castor oil Substances 0.000 description 1
- 229920000642 polymer Polymers 0.000 description 1
- 229920001282 polysaccharide Polymers 0.000 description 1
- 239000005017 polysaccharide Substances 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 239000002243 precursor Substances 0.000 description 1
- 230000001855 preneoplastic effect Effects 0.000 description 1
- 238000004393 prognosis Methods 0.000 description 1
- 230000002062 proliferating effect Effects 0.000 description 1
- 108060006633 protein kinase Proteins 0.000 description 1
- 230000005180 public health Effects 0.000 description 1
- 230000002685 pulmonary effect Effects 0.000 description 1
- 239000000649 purine antagonist Substances 0.000 description 1
- 239000003790 pyrimidine antagonist Substances 0.000 description 1
- 230000005855 radiation Effects 0.000 description 1
- 102000005962 receptors Human genes 0.000 description 1
- 108020003175 receptors Proteins 0.000 description 1
- 206010038038 rectal cancer Diseases 0.000 description 1
- 201000001275 rectum cancer Diseases 0.000 description 1
- 230000000306 recurrent effect Effects 0.000 description 1
- 230000002829 reductive effect Effects 0.000 description 1
- 230000010076 replication Effects 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 230000000284 resting effect Effects 0.000 description 1
- 235000009566 rice Nutrition 0.000 description 1
- CVHZOJJKTDOEJC-UHFFFAOYSA-N saccharin Chemical compound C1=CC=C2C(=O)NS(=O)(=O)C2=C1 CVHZOJJKTDOEJC-UHFFFAOYSA-N 0.000 description 1
- 229940081974 saccharin Drugs 0.000 description 1
- 235000019204 saccharin Nutrition 0.000 description 1
- 239000000901 saccharin and its Na,K and Ca salt Substances 0.000 description 1
- HFHDHCJBZVLPGP-UHFFFAOYSA-N schardinger α-dextrin Chemical compound O1C(C(C2O)O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC(C(O)C2O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC2C(O)C(O)C1OC2CO HFHDHCJBZVLPGP-UHFFFAOYSA-N 0.000 description 1
- 210000002966 serum Anatomy 0.000 description 1
- 239000008159 sesame oil Substances 0.000 description 1
- 235000011803 sesame oil Nutrition 0.000 description 1
- 230000001568 sexual effect Effects 0.000 description 1
- 102000034285 signal transducing proteins Human genes 0.000 description 1
- 108091006024 signal transducing proteins Proteins 0.000 description 1
- 239000000741 silica gel Substances 0.000 description 1
- 229910002027 silica gel Inorganic materials 0.000 description 1
- 210000003491 skin Anatomy 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 235000010413 sodium alginate Nutrition 0.000 description 1
- 239000000661 sodium alginate Substances 0.000 description 1
- 229940005550 sodium alginate Drugs 0.000 description 1
- RYYKJJJTJZKILX-UHFFFAOYSA-M sodium octadecanoate Chemical compound [Na+].CCCCCCCCCCCCCCCCCC([O-])=O RYYKJJJTJZKILX-UHFFFAOYSA-M 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 239000003549 soybean oil Substances 0.000 description 1
- 235000012424 soybean oil Nutrition 0.000 description 1
- 210000000952 spleen Anatomy 0.000 description 1
- 239000007921 spray Substances 0.000 description 1
- 201000011549 stomach cancer Diseases 0.000 description 1
- 238000010254 subcutaneous injection Methods 0.000 description 1
- 239000007929 subcutaneous injection Substances 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- IIACRCGMVDHOTQ-UHFFFAOYSA-N sulfamic acid Chemical class NS(O)(=O)=O IIACRCGMVDHOTQ-UHFFFAOYSA-N 0.000 description 1
- 229940097346 sulfobutylether-beta-cyclodextrin Drugs 0.000 description 1
- 150000003467 sulfuric acid derivatives Chemical class 0.000 description 1
- 239000000375 suspending agent Substances 0.000 description 1
- 238000013268 sustained release Methods 0.000 description 1
- 239000012730 sustained-release form Substances 0.000 description 1
- 208000011580 syndromic disease Diseases 0.000 description 1
- 239000002562 thickening agent Substances 0.000 description 1
- 210000000115 thoracic cavity Anatomy 0.000 description 1
- 210000001685 thyroid gland Anatomy 0.000 description 1
- 239000005495 thyroid hormone Substances 0.000 description 1
- 229940036555 thyroid hormone Drugs 0.000 description 1
- 230000000699 topical effect Effects 0.000 description 1
- 125000002088 tosyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1C([H])([H])[H])S(*)(=O)=O 0.000 description 1
- ODLHGICHYURWBS-LKONHMLTSA-N trappsol cyclo Chemical compound CC(O)COC[C@H]([C@H]([C@@H]([C@H]1O)O)O[C@H]2O[C@@H]([C@@H](O[C@H]3O[C@H](COCC(C)O)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](COCC(C)O)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](COCC(C)O)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](COCC(C)O)[C@H]([C@@H]([C@H]3O)O)O3)[C@H](O)[C@H]2O)COCC(O)C)O[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@@H]3O[C@@H]1COCC(C)O ODLHGICHYURWBS-LKONHMLTSA-N 0.000 description 1
- 150000003626 triacylglycerols Chemical class 0.000 description 1
- 201000005112 urinary bladder cancer Diseases 0.000 description 1
- 210000002700 urine Anatomy 0.000 description 1
- 206010046766 uterine cancer Diseases 0.000 description 1
- 239000004066 vascular targeting agent Substances 0.000 description 1
- 239000003981 vehicle Substances 0.000 description 1
- 235000012431 wafers Nutrition 0.000 description 1
- 239000008215 water for injection Substances 0.000 description 1
- 230000003442 weekly effect Effects 0.000 description 1
- 238000009736 wetting Methods 0.000 description 1
Images
Classifications
-
- 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
- A61K31/56—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids
- A61K31/57—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids substituted in position 17 beta by a chain of two carbon atoms, e.g. pregnane or progesterone
- A61K31/573—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids substituted in position 17 beta by a chain of two carbon atoms, e.g. pregnane or progesterone substituted in position 21, e.g. cortisone, dexamethasone, prednisone or aldosterone
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
- A61K31/4164—1,3-Diazoles
- A61K31/4184—1,3-Diazoles condensed with carbocyclic rings, e.g. benzimidazoles
-
- 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
- A61K31/69—Boron compounds
-
- 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
- A61P35/00—Antineoplastic agents
-
- 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
-
- 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
-
- 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
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- Hematology (AREA)
- Oncology (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Peptides Or Proteins (AREA)
Abstract
Description
CI 1>1:アンタゴニスト効果、CI=1:相加効果、及びCI<1相乗効果。
EDO-S101を、in vitroで、多発性骨髄腫MM1S細胞系(LGC Standards S.a.r.l.、6、rue Alfred Kastler、BP 83076、F-67123 Molsheim Cedex、Franceから入手)において、デキサメタゾン及びボルテゾミブと組み合わせた。活性を、ミトコンドリアの酵素であるスクシネートデヒドロゲナーゼによって生成され、ホルマザンと呼ばれる青色化合物に変わる、3-(4,5-ジメチルチアゾール-2-イル)-2,5-ジフェニルテトラゾール(MTT)からの臭化物の還元代謝に基づくMTTアッセイにより測定した。次いで、処理した細胞のミトコンドリアの機能を決定する。この方法は、細胞の増殖及び生存の能力を測定するのに広く用いられている。残存する生存細胞は、生成されたホルマザンの量に比例する。
- ウエル1個あたりMM1S細胞30000個を、96ウエルマイクロタイタープレート中にプレーティングした。
- EDO-S101及びPIの希釈を、エタノール中のDMSO及びデキサメタゾンにおいて調製し、実験で指摘する最終濃度までウエル中に加えた。
- プレートを、5%CO2/95%空気の存在下、湿潤雰囲気中、37℃のインキュベータで24〜48〜72時間インキュベートした。
- インキュベート後、MTT溶液10μLを各ウエルに加え、2時間インキュベートしてホルマザン結晶を形成させた。
- SDSとの混合溶液プラスHCl(SDS各12mlに対してHCl10μL) 100μlを加えて、ホルマザン結晶を溶解させた。
- 570nmODの吸光度を読み取り、650nmの基準波長を用いる。
- 細胞の生存度(パーセント値)を以下の通り得た:%生存度=処理細胞のOD×100/対照細胞のOD。
- 各用量を4回ずつ試験し、各実験を少なくとも2回ずつ行った。
CI 1>1:アンタゴニスト効果、CI=1:相加効果、及びCI<1相乗効果。
CB17-SCIDマウス(The Jackson Laboratory社、Bar Harbor、MEより入手)の右側腹部中に、RPMI1640培地100μL及びMatrigel (BD Biosciences社) 100μL中、多発性骨髄腫MM1S細胞(LGC Standards S.a.r.l.、6、rue Alfred Kastler、BP 83076、F-67123 Molsheim Cedex、Franceより入手)3×106個を皮下接種した。腫瘍が触診可能になったら、マウスを各群5匹の8つの処置群に無作為化した。
- 対照(ビヒクル単独で処置した群)
- ボルテゾミブ1mg/kg腹腔内を週2回、3週間
- デキサメタゾン0,5mg静脈内を週2回、3週間
- EDO-S101 30mg/kg用量の静脈内を週1回、3用量
- ボルテゾミブ プラス デキサメタゾン
- ボルテゾミブ プラスEDO-S101
- EDO-S101 プラス デキサメタゾン
- EDO-S101プラス ボルテゾミブ、及びデキサメタゾンの三重組合せ。
Claims (56)
- 式Iの化合物の薬学的に許容される塩が、塩酸塩、臭化水素酸塩、ヨウ化水素酸塩、硫酸塩、亜硫酸水素塩、スルファミン酸塩、硝酸塩、リン酸塩、クエン酸塩、メタンスルホン酸塩、トリフルオロ酢酸塩、グルタミン酸塩、グルクロン酸塩、グルタル酸塩、リンゴ酸塩、マレイン酸塩、コハク酸塩、フマル酸塩、酒石酸塩、トシル酸塩、サリチル酸塩、乳酸塩、ナフタレンスルホン酸塩、又は酢酸塩である、請求項1に記載の組合せ物。
- グルココルチコイドが、デキサメタゾン、フルオシノロンアセトニド、及びプレドニゾンからなる群から選択される、請求項1又は請求項2に記載の組合せ物。
- グルココルチコイドがデキサメタゾンである、請求項1又は請求項2に記載の組合せ物。
- プロテアソームインヒビターを更に含む、請求項1から4のいずれか一項に記載の組合せ物。
- プロテアソームインヒビターが、ボルテゾミブ、カルフィルゾミブ、マリゾミブ、デランゾミブ(CEP-18770)、オプロゾミブ(ONX0912)、イキサゾミブ(MLN-9708)、及びLU-102又は薬学的に許容されるこれらの塩からなる群から選択される、請求項5に記載の組合せ物。
- プロテアソームインヒビターが、ボルテゾミブ、カルフィルゾミブ、及びLU-102から選択される、請求項5に記載の組合せ物。
- 1つ又は複数の追加の薬学的に活性な薬剤を更に含む、請求項1から7のいずれか一項に記載の組合せ物。
- 式Iの化合物又は薬学的に許容されるその塩、グルココルチコイド、及び存在する場合にはプロテアソームインヒビターが、同時、逐次的、又は別々の投与に適合される、請求項1から8のいずれか一項に記載の組合せ物。
- 式Iの化合物又は薬学的に許容されるその塩、グルココルチコイド、及び存在する場合にはプロテアソームインヒビターが、同時投与に適合される、請求項9に記載の組合せ物。
- 前記組合せ物中のグルココルチコイド対式Iの化合物又は薬学的に許容されるその塩のモル比が1:500から500:1までである、請求項1から10のいずれか一項に記載の組合せ物。
- 前記組合せ物中のグルココルチコイド対式Iの化合物又は薬学的に許容されるその塩のモル比が1:500から1:100までである、請求項11に記載の組合せ物。
- 前記組合せ物中のグルココルチコイド対式Iの化合物又は薬学的に許容されるその塩のモル比が1:300から1:100までである、請求項11に記載の組合せ物。
- 前記組合せ物中のグルココルチコイド対式Iの化合物又は薬学的に許容されるその塩のモル比が1:250から1:150までである、請求項11に記載の組合せ物。
- 式Iの化合物又はその酢酸塩及びデキサメタゾンを含み、前記組合せ物中のデキサメタゾン対式Iの化合物又はその酢酸塩のモル比が1:250から1:150までである、請求項11に記載の組合せ物。
- グルココルチコイド及び式Iの化合物又は薬学的に許容されるその塩が相乗的な組合せである、請求項1から15のいずれか一項に記載の組合せ物。
- プロテアソームインヒビターを更に含み、前記組合せ物中のプロテアソームインヒビター対式Iの化合物又は薬学的に許容されるその塩対グルココルチコイドのモル比が1:1000:10から1000:1:20までである、請求項1から16のいずれか一項に記載の組合せ物。
- 前記組合せ物中のプロテアソームインヒビター対式Iの化合物又は薬学的に許容されるその塩対グルココルチコイドのモル比が1:1000:10から1:100:2までである、請求項17に記載の組合せ物。
- 前記組合せ物中のプロテアソームインヒビター対式Iの化合物又は薬学的に許容されるその塩対グルココルチコイドのモル比が1:700:4から1:400:3までである、請求項17に記載の組合せ物。
- ボルテゾミブ及びカルフィルゾミブから選択されるプロテアソームインヒビター、式Iの化合物又はその酢酸塩、並びにデキサメタゾンを含み、前記組合せ物中のボルテゾミブ及びカルフィルゾミブから選択されるプロテアソームインヒビター対式Iの化合物又はその酢酸塩対デキサメタゾンのモル比が1:700:4から1:400:3までである、請求項17に記載の組合せ物。
- LU-102から選択されるプロテアソームインヒビター、式Iの化合物又はその酢酸塩、及びデキサメタゾンを含み、前記組合せ物中のLU-102対式Iの化合物又はその酢酸塩対デキサメタゾンのモル比が1:3:4から1:0.5:3までである、請求項17に記載の組合せ物。
- 式Iの化合物又は薬学的に許容されるその塩、グルココルチコイド、及びプロテアソームインヒビターを含み、式Iの化合物又は薬学的に許容されるその塩、グルココルチコイド、及びプロテアソームインヒビターが相乗的な組合せである、請求項17から21のいずれか一項に記載の組合せ物。
- 薬学的に許容される希釈剤又は担体、及び請求項1から22のいずれか一項に記載の組合せ物を含む医薬組成物。
- 請求項1から22のいずれか一項に記載の組合せ物、及び場合により、患者を処置するための指示書を含むキット。
- 癌の処置における使用のための、請求項1から22のいずれか一項に記載の組合せ物、請求項23に記載の組成物、又は請求項24に記載のキット。
- 前記癌が血液癌及び乳癌から選択される、請求項25に記載の使用のための組合せ物、組成物、又はキット。
- 前記血液癌が、多発性骨髄腫、リンパ腫、及び白血病から選択される、請求項26に記載の使用のための組合せ物、組成物、又はキット。
- 前記多発性骨髄腫が、活動型骨髄腫、形質細胞腫、軽鎖骨髄腫、及び非分泌型骨髄腫から選択される、請求項27に記載の使用のための組合せ物、組成物、又はキット。
- 前記リンパ腫が、ホジキンリンパ腫及び非ホジキンリンパ腫から選択される、請求項27に記載の使用のための組合せ物、組成物、又はキット。
- 前記白血病が、急性リンパ芽球性白血病(ALL)、慢性リンパ性白血病(CLL)、急性骨髄性白血病(AML)、慢性骨髄性白血病(CML)、ヘアリー細胞白血病(HCL)、T細胞前リンパ球性白血病(T-PLL)、大顆粒リンパ球性白血病、及びT細胞急性リンパ芽球性白血病から選択される、請求項27に記載の使用のための組合せ物、組成物、又はキット。
- 前記乳癌が、低クローディン腫瘍、基底細胞様腫瘍、ヒト上皮成長因子受容体2(HER2)陽性腫瘍、管腔A腫瘍、及び管腔B腫瘍から選択される、請求項26に記載の使用のための組合せ物、組成物、又はキット。
- 前記乳癌がトリプルネガティブ乳癌である、請求項26に記載の使用のための組合せ物、組成物、又はキット。
- 前記処置において、グルココルチコイド、式Iの化合物又は薬学的に許容されるその塩、及び存在する場合にはプロテアソームインヒビターを、同時に、逐次的に、又は別々に投与する、請求項25から32のいずれか一項に記載の使用のための組合せ物、組成物、又はキット。
- 前記処置において、グルココルチコイド、式Iの化合物又は薬学的に許容されるその塩、及び存在する場合にはプロテアソームインヒビターを同時に投与する、請求項33に記載の使用のための組合せ物、組成物、又はキット。
- 前記処置において、患者の体重1kgあたり10から100mgの用量範囲の式Iの化合物又は薬学的に許容されるその塩を、それを必要とする患者に投与する、請求項25から34のいずれか一項に記載の使用のための組合せ物、組成物、又はキット。
- 前記処置において、患者の体重1kgあたり40から80mgの用量範囲の式Iの化合物又は薬学的に許容されるその塩を、それを必要とする患者に投与する、請求項35に記載の使用のための組合せ物、組成物、又はキット。
- 前記処置において、患者の体重1kgあたり0.1から1mgの用量範囲のグルココルチコイドを投与する、請求項25から36のいずれか一項に記載の使用のための組合せ物、組成物、又はキット。
- 前記処置において、患者の体重1kgあたり0.3から0.5mgの用量範囲のグルココルチコイドを投与する、請求項37に記載の使用のための組合せ物、組成物、又はキット。
- 存在する場合には、患者の体重1kgあたり0.01から0.3mgの用量範囲のプロテアソームインヒビターを患者に投与する、請求項25から38のいずれか一項に記載の使用のための組合せ物、組成物、又はキット。
- 患者の体重1kgあたり0.05から0.15mgの用量範囲のプロテアソームインヒビターを患者に投与する、請求項39に記載の使用のための組合せ物、組成物、又はキット。
- 請求項1から22のいずれか一項に記載の組合せ物、請求項23に記載の組成物、又は請求項24に記載のキットをそれを必要とする患者に投与する工程を含む、前記患者における癌を処置する方法。
- 前記癌が血液癌及び乳癌から選択される、請求項41に記載の方法。
- 前記血液癌が、多発性骨髄腫、リンパ腫、及び白血病から選択される、請求項42に記載の方法。
- 前記多発性骨髄腫が、活動型骨髄腫、形質細胞腫、軽鎖骨髄腫、及び非分泌型骨髄腫から選択される、請求項43に記載の方法。
- 前記リンパ腫が、ホジキンリンパ腫及び非ホジキンリンパ腫から選択される、請求項43に記載の方法。
- 前記白血病が、急性リンパ芽球性白血病(ALL)、慢性リンパ性白血病(CLL)、急性骨髄性白血病(AML)、慢性骨髄性白血病(CML)、ヘアリー細胞白血病(HCL)、T細胞前リンパ球性白血病(T-PLL)、大顆粒リンパ球性白血病、及びT細胞急性リンパ芽球性白血病から選択される、請求項43に記載の方法。
- 前記乳癌が、低クローディン腫瘍、基底細胞様腫瘍、ヒト上皮成長因子受容体2(HER2)陽性腫瘍、管腔A腫瘍、及び管腔B腫瘍から選択される、請求項42に記載の方法。
- 前記乳癌がトリプルネガティブ乳癌から選択される、請求項42に記載の方法。
- 前記方法において、グルココルチコイド、式Iの化合物又は薬学的に許容されるその塩、及び存在する場合にはプロテアソームインヒビターを、同時に、逐次的に、又は別々に投与する、請求項41から48のいずれか一項に記載の方法。
- 前記方法において、グルココルチコイド、式Iの化合物又は薬学的に許容されるその塩、及び存在する場合にはプロテアソームインヒビターを同時に投与する、請求項49に記載の方法。
- 患者の体重1kgあたり10から100mgの用量範囲の式Iの化合物又は薬学的に許容されるその塩を、それを必要とする患者に投与する、請求項41から50のいずれか一項に記載の方法。
- 患者の体重1kgあたり40から80mgの用量範囲の式Iの化合物又は薬学的に許容されるその塩を、それを必要とする患者に投与する、請求項51に記載の方法。
- 患者の体重1kgあたり0.1から1.0mgの用量範囲のグルココルチコイドを患者に投与する、請求項41から52のいずれか一項に記載の方法。
- 患者の体重1kgあたり0.3から0.5mgの用量範囲のグルココルチコイドを投与する、請求項53に記載の方法。
- 存在する場合には患者の体重1kgあたり0.01から0.3mgの用量範囲のプロテアソームインヒビターを患者に投与する、請求項41から54のいずれか一項に記載の方法。
- 患者の体重1kgあたり0.05から0.15mgの用量範囲のプロテアソームインヒビターを患者に投与する、請求項55に記載の方法。
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
GBGB1409485.8A GB201409485D0 (en) | 2014-05-28 | 2014-05-28 | Pharmaceutical composition |
GB1409485.8 | 2014-05-28 |
Related Parent Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2016569598A Division JP2017518292A (ja) | 2014-05-28 | 2015-05-26 | グルココルチコイド及びedo−s101を含む組合せ |
Publications (2)
Publication Number | Publication Date |
---|---|
JP2021046446A true JP2021046446A (ja) | 2021-03-25 |
JP2021046446A5 JP2021046446A5 (ja) | 2021-06-17 |
Family
ID=51177587
Family Applications (2)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2016569598A Pending JP2017518292A (ja) | 2014-05-28 | 2015-05-26 | グルココルチコイド及びedo−s101を含む組合せ |
JP2020215171A Pending JP2021046446A (ja) | 2014-05-28 | 2020-12-24 | グルココルチコイド及びedo−s101を含む組合せ |
Family Applications Before (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2016569598A Pending JP2017518292A (ja) | 2014-05-28 | 2015-05-26 | グルココルチコイド及びedo−s101を含む組合せ |
Country Status (19)
Country | Link |
---|---|
US (3) | US10744120B2 (ja) |
EP (1) | EP3148584B1 (ja) |
JP (2) | JP2017518292A (ja) |
KR (1) | KR20170008846A (ja) |
CN (1) | CN106488776B (ja) |
AU (1) | AU2015266053B2 (ja) |
BR (1) | BR112016027043B1 (ja) |
CA (1) | CA2950340C (ja) |
DK (1) | DK3148584T3 (ja) |
EA (1) | EA038323B1 (ja) |
ES (1) | ES2885429T3 (ja) |
GB (1) | GB201409485D0 (ja) |
IL (1) | IL249230A0 (ja) |
MX (1) | MX2016015437A (ja) |
PH (1) | PH12016502352A1 (ja) |
SG (2) | SG10201810404XA (ja) |
TW (1) | TWI731837B (ja) |
UA (1) | UA121392C2 (ja) |
WO (1) | WO2015181157A1 (ja) |
Families Citing this family (10)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
TWI573792B (zh) | 2012-02-01 | 2017-03-11 | 歐陸斯迪公司 | 新穎治療劑 |
GB201409485D0 (en) * | 2014-05-28 | 2014-07-09 | Euro Celtique Sa | Pharmaceutical composition |
GB201409471D0 (en) | 2014-05-28 | 2014-07-09 | Euro Celtique Sa | Pharmaceutical composition |
GB201409488D0 (en) | 2014-05-28 | 2014-07-09 | Euro Celtique Sa | Pharmaceutical composition |
AU2016426574B2 (en) * | 2016-10-11 | 2023-07-13 | Euro-Celtique S.A. | Hodgkin lymphoma therapy |
GB201709403D0 (en) | 2017-06-13 | 2017-07-26 | Euro Celtique Sa | Compounds for treating sarcoma |
GB201709402D0 (en) | 2017-06-13 | 2017-07-26 | Euro Celtique Sa | Compounds for treating t-pll |
GB201709405D0 (en) | 2017-06-13 | 2017-07-26 | Euro Celtique Sa | Compounds for treating ovarian cancer |
GB201709406D0 (en) | 2017-06-13 | 2017-07-26 | Euro-Cletique S A | Compounds for treating TNBC |
AU2019402158A1 (en) * | 2018-12-18 | 2021-06-10 | Mundipharma International Corporation Limited | Compounds for treating lymphoma or a T-cell malignant disease |
Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2012515776A (ja) * | 2009-01-23 | 2012-07-12 | ノースレイク インターナショナル エルエルシー | ヒドロキサム酸誘導体 |
WO2013040286A2 (en) * | 2011-09-18 | 2013-03-21 | Euro-Celtique S.A. | Pharmaceutical compositions |
Family Cites Families (60)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
DE34727C (de) | Ch. H. TH. HAVEMANN in Paris, 16 rue Bleue | Verfahren zur direkten Gewinnung metallischen Bleis | ||
US4522811A (en) | 1982-07-08 | 1985-06-11 | Syntex (U.S.A.) Inc. | Serial injection of muramyldipeptides and liposomes enhances the anti-infective activity of muramyldipeptides |
US6407079B1 (en) | 1985-07-03 | 2002-06-18 | Janssen Pharmaceutica N.V. | Pharmaceutical compositions containing drugs which are instable or sparingly soluble in water and methods for their preparation |
KR0166088B1 (ko) | 1990-01-23 | 1999-01-15 | . | 수용해도가 증가된 시클로덱스트린 유도체 및 이의 용도 |
US5376645A (en) | 1990-01-23 | 1994-12-27 | University Of Kansas | Derivatives of cyclodextrins exhibiting enhanced aqueous solubility and the use thereof |
US5369108A (en) | 1991-10-04 | 1994-11-29 | Sloan-Kettering Institute For Cancer Research | Potent inducers of terminal differentiation and methods of use thereof |
GB9126209D0 (en) | 1991-12-10 | 1992-02-12 | Orion Yhtymae Oy | Drug formulations for parenteral use |
US5602112A (en) | 1992-06-19 | 1997-02-11 | Supergen, Inc. | Pharmaceutical formulation |
US5882941A (en) | 1994-05-04 | 1999-03-16 | Massachusette Institute Of Technology | Programmable genotoxic agents and uses therefor |
US6046177A (en) | 1997-05-05 | 2000-04-04 | Cydex, Inc. | Sulfoalkyl ether cyclodextrin based controlled release solid pharmaceutical formulations |
US5874418A (en) | 1997-05-05 | 1999-02-23 | Cydex, Inc. | Sulfoalkyl ether cyclodextrin based solid pharmaceutical formulations and their use |
AU750207B2 (en) | 1997-06-13 | 2002-07-11 | Cydex Pharmaceuticals, Inc. | Polar drug or prodrug compositions with extended shelf-life storage and a method of making thereof |
US6214852B1 (en) | 1998-10-21 | 2001-04-10 | Bristol-Myers Squibb Company | N-[5-[[[5-alkyl-2-oxazolyl]methyl]thio]-2-thiazolyl]-carboxamide inhibitors of cyclin dependent kinases |
US6392053B2 (en) | 1999-12-15 | 2002-05-21 | Bristol-Myers Squibb Company | Process for preparing arylacetylaminothiazoles |
AU2001273413A1 (en) | 2000-07-12 | 2002-01-21 | Immunex Corporation | Method for treating cancer using an interleukin- 4 antagonist |
PE20020354A1 (es) | 2000-09-01 | 2002-06-12 | Novartis Ag | Compuestos de hidroxamato como inhibidores de histona-desacetilasa (hda) |
JP2004509941A (ja) | 2000-09-29 | 2004-04-02 | プロリフィクス リミテッド | Hdacインヒビターとしてのアミド結合を含むカルバミン酸化合物 |
WO2002055017A2 (en) | 2000-11-21 | 2002-07-18 | Wake Forest University | Method of treating autoimmune diseases |
CN1764648A (zh) | 2003-01-13 | 2006-04-26 | 安斯泰来制药有限公司 | 作为组蛋白脱乙酰酶(hdac)抑制剂的异羟肟酸衍生物 |
US7652036B2 (en) | 2003-02-25 | 2010-01-26 | Topotarget Uk Limited | Carbamic acid compounds comprising a bicyclic heteroaryl group as HDAC inhibitors |
US20060270730A1 (en) | 2003-08-07 | 2006-11-30 | Andreas Katopodis | Histone deacetylase inhibitors as immunosuppressants |
AU2005230682B2 (en) | 2004-04-05 | 2010-10-21 | Merck Hdac Research, Llc | Histone deacetylase inhibitor prodrugs |
WO2007134169A2 (en) | 2006-05-10 | 2007-11-22 | Nuada, Llc | Indole, benzimidazole, and benzolactam boronic acid compounds, analogs thereof and methods of use thereof |
US8436190B2 (en) | 2005-01-14 | 2013-05-07 | Cephalon, Inc. | Bendamustine pharmaceutical compositions |
KR101329437B1 (ko) | 2005-05-13 | 2013-11-14 | 토포타겟 유케이 리미티드 | Hdac 억제제의 약학 제형 |
BRPI0717460A2 (pt) | 2006-10-20 | 2013-12-24 | Icos Corp | Composições de inibidores de chk1 |
GB0621160D0 (en) | 2006-10-24 | 2006-12-06 | Imp College Innovations Ltd | Compounds and uses thereof |
CN101784268B (zh) | 2006-11-20 | 2013-06-19 | 赛福伦公司 | 使用辐射敏化剂使肿瘤对辐射敏化的方法 |
CN101084876A (zh) | 2007-07-11 | 2007-12-12 | 济南康泉医药科技有限公司 | 一种含苯达莫司汀的抗癌组合物 |
TW200922564A (en) | 2007-09-10 | 2009-06-01 | Curis Inc | CDK inhibitors containing a zinc binding moiety |
WO2009067453A1 (en) | 2007-11-19 | 2009-05-28 | Syndax Pharmaceuticals, Inc. | Combinations of hdac inhibitors and proteasome inhibitors |
WO2009100045A1 (en) | 2008-02-04 | 2009-08-13 | Translational Genomics Research Institute | Compounds, pharmaceutical compositions and methods of use of hydroxamic acid derivatives |
MX2011002936A (es) | 2008-09-25 | 2011-04-11 | Cephalon Inc | Formulaciones liquidas de bendamustina. |
AU2009302493B2 (en) | 2008-10-08 | 2015-04-09 | Cephalon Llc | Processes for the preparation of bendamustine |
WO2010075542A1 (en) | 2008-12-23 | 2010-07-01 | Curis, Inc. | Cdk inhibitors |
NO2792369T3 (ja) | 2009-02-25 | 2018-09-15 | ||
US8603521B2 (en) | 2009-04-17 | 2013-12-10 | Pharmacyclics, Inc. | Formulations of histone deacetylase inhibitor and uses thereof |
WO2011017448A1 (en) | 2009-08-05 | 2011-02-10 | The Trustees Of The University Of Pennsylvania | Use of histone deacetylase inhibitors for treatment of autoimmune diseases |
CN101928234B (zh) | 2010-01-15 | 2012-12-12 | 北京欧凯纳斯科技有限公司 | 6/7-(杂)芳基-n-羟基己/庚酰胺化合物及其制备方法 |
EP2558866B1 (en) | 2010-04-15 | 2016-08-17 | Tracon Pharmaceuticals, Inc. | Potentiation of anti-cancer activity through combination therapy with ber pathway inhibitors |
WO2011127948A1 (en) | 2010-04-16 | 2011-10-20 | Cellact Pharma Gmbh | Analogues of etoposide for the treatment of tumours |
JO3659B1 (ar) | 2010-06-02 | 2020-08-27 | Astellas Deutschland Gmbh | أشكال جرعات بينداموستين عن طريق الفم وإستخداماته العلاجية |
US8748470B2 (en) | 2011-03-17 | 2014-06-10 | The University Of Chicago | Methods for treating ovarian cancer by inhibiting fatty acid binding proteins |
ES2627820T3 (es) | 2011-09-13 | 2017-07-31 | Pharmacyclics, Inc. | Formulaciones de inhibidor de histona desacetilasa en combinación con bendamustina y usos de las mismas |
CN102993102B (zh) | 2011-09-16 | 2016-08-24 | 杭州民生药业有限公司 | [1-甲基-2-(7’-庚异羟肟酸基)-5-n,n-二(2’-氯乙基)]-1h-苯并咪唑的合成方法 |
PT2760860T (pt) | 2011-09-28 | 2017-02-21 | Euro Celtique Sa | Derivados de mostarda de azoto |
TWI573792B (zh) | 2012-02-01 | 2017-03-11 | 歐陸斯迪公司 | 新穎治療劑 |
US10335494B2 (en) | 2013-12-06 | 2019-07-02 | Millennium Pharmaceuticals, Inc. | Combination of aurora kinase inhibitors and anti-CD30 antibodies |
NZ630314A (en) | 2014-02-18 | 2016-03-31 | Celgene Corp | Combination therapy for hematological malignancies |
GB201409488D0 (en) | 2014-05-28 | 2014-07-09 | Euro Celtique Sa | Pharmaceutical composition |
GB201409471D0 (en) | 2014-05-28 | 2014-07-09 | Euro Celtique Sa | Pharmaceutical composition |
GB201409485D0 (en) * | 2014-05-28 | 2014-07-09 | Euro Celtique Sa | Pharmaceutical composition |
AU2015356779A1 (en) | 2014-12-05 | 2017-07-13 | University of Modena and Reggio Emilia | Combinations of histone deacetylase inhibitors and bendamustine for use in the treatment of lymphoma |
CN106580971B (zh) | 2015-10-20 | 2019-11-12 | 杭州梯诺医药科技有限公司 | 一种药物组合物及其制备方法 |
US20180098969A1 (en) | 2016-10-11 | 2018-04-12 | Purdue Pharmaceutical Products L.P. | Hodgkin lymphoma therapy |
AU2016426574B2 (en) | 2016-10-11 | 2023-07-13 | Euro-Celtique S.A. | Hodgkin lymphoma therapy |
GB201709406D0 (en) | 2017-06-13 | 2017-07-26 | Euro-Cletique S A | Compounds for treating TNBC |
GB201709402D0 (en) | 2017-06-13 | 2017-07-26 | Euro Celtique Sa | Compounds for treating t-pll |
GB201709403D0 (en) | 2017-06-13 | 2017-07-26 | Euro Celtique Sa | Compounds for treating sarcoma |
GB201709405D0 (en) | 2017-06-13 | 2017-07-26 | Euro Celtique Sa | Compounds for treating ovarian cancer |
-
2014
- 2014-05-28 GB GBGB1409485.8A patent/GB201409485D0/en not_active Ceased
-
2015
- 2015-05-26 WO PCT/EP2015/061572 patent/WO2015181157A1/en active Application Filing
- 2015-05-26 MX MX2016015437A patent/MX2016015437A/es unknown
- 2015-05-26 KR KR1020167035845A patent/KR20170008846A/ko not_active Application Discontinuation
- 2015-05-26 US US15/314,180 patent/US10744120B2/en active Active
- 2015-05-26 EP EP15724308.0A patent/EP3148584B1/en active Active
- 2015-05-26 BR BR112016027043-6A patent/BR112016027043B1/pt active IP Right Grant
- 2015-05-26 CA CA2950340A patent/CA2950340C/en active Active
- 2015-05-26 AU AU2015266053A patent/AU2015266053B2/en active Active
- 2015-05-26 SG SG10201810404XA patent/SG10201810404XA/en unknown
- 2015-05-26 ES ES15724308T patent/ES2885429T3/es active Active
- 2015-05-26 SG SG11201609362YA patent/SG11201609362YA/en unknown
- 2015-05-26 EA EA201692481A patent/EA038323B1/ru unknown
- 2015-05-26 TW TW104116781A patent/TWI731837B/zh active
- 2015-05-26 DK DK15724308.0T patent/DK3148584T3/da active
- 2015-05-26 JP JP2016569598A patent/JP2017518292A/ja active Pending
- 2015-05-26 CN CN201580027933.2A patent/CN106488776B/zh active Active
- 2015-05-26 UA UAA201613346A patent/UA121392C2/uk unknown
-
2016
- 2016-11-25 PH PH12016502352A patent/PH12016502352A1/en unknown
- 2016-11-27 IL IL249230A patent/IL249230A0/en unknown
-
2020
- 2020-08-14 US US16/994,154 patent/US11541038B2/en active Active
- 2020-12-24 JP JP2020215171A patent/JP2021046446A/ja active Pending
-
2022
- 2022-12-19 US US18/083,651 patent/US20230285363A1/en active Pending
Patent Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2012515776A (ja) * | 2009-01-23 | 2012-07-12 | ノースレイク インターナショナル エルエルシー | ヒドロキサム酸誘導体 |
WO2013040286A2 (en) * | 2011-09-18 | 2013-03-21 | Euro-Celtique S.A. | Pharmaceutical compositions |
Non-Patent Citations (3)
Title |
---|
BLOOD CANCER JOURNAL, vol. 3, JPN6019011680, 2013, pages 162, ISSN: 0005025738 * |
BLOOD, vol. 122, JPN6020004360, 2013, pages 2331 - 2337, ISSN: 0005025740 * |
MOLECULAR CANCER THERAPEUTICS, vol. 10, JPN6020004359, 2011, pages 2034 - 2042, ISSN: 0005025739 * |
Also Published As
Publication number | Publication date |
---|---|
BR112016027043A2 (pt) | 2017-08-15 |
UA121392C2 (uk) | 2020-05-25 |
CA2950340A1 (en) | 2015-12-03 |
IL249230A0 (en) | 2017-02-28 |
US11541038B2 (en) | 2023-01-03 |
TW201613577A (en) | 2016-04-16 |
GB201409485D0 (en) | 2014-07-09 |
AU2015266053B2 (en) | 2020-07-02 |
ES2885429T3 (es) | 2021-12-13 |
SG10201810404XA (en) | 2018-12-28 |
US20230285363A1 (en) | 2023-09-14 |
AU2015266053A1 (en) | 2016-11-17 |
TWI731837B (zh) | 2021-07-01 |
EA038323B1 (ru) | 2021-08-10 |
DK3148584T3 (da) | 2021-08-30 |
CN106488776B (zh) | 2021-01-22 |
PH12016502352A1 (en) | 2017-02-13 |
CA2950340C (en) | 2023-10-17 |
EA201692481A1 (ru) | 2017-04-28 |
US20170296513A1 (en) | 2017-10-19 |
CN106488776A (zh) | 2017-03-08 |
EP3148584A1 (en) | 2017-04-05 |
JP2017518292A (ja) | 2017-07-06 |
US20210059989A1 (en) | 2021-03-04 |
SG11201609362YA (en) | 2016-12-29 |
BR112016027043A8 (pt) | 2021-07-20 |
MX2016015437A (es) | 2017-06-23 |
BR112016027043B1 (pt) | 2023-01-31 |
KR20170008846A (ko) | 2017-01-24 |
EP3148584B1 (en) | 2021-05-26 |
WO2015181157A1 (en) | 2015-12-03 |
US10744120B2 (en) | 2020-08-18 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
JP2021059579A (ja) | 癌を処置するための医薬組合せ | |
JP2021046446A (ja) | グルココルチコイド及びedo−s101を含む組合せ | |
JP2017519736A (ja) | クラスiii受容体チロシンキナーゼインヒビター及びアルキル化ヒストンデアセチラーゼインヒビター融合分子edo−s101を含む医薬組合せ、並びに癌の処置におけるその使用 |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20210125 |
|
A621 | Written request for application examination |
Free format text: JAPANESE INTERMEDIATE CODE: A621 Effective date: 20210125 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20210428 |
|
A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20220117 |
|
A601 | Written request for extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A601 Effective date: 20220418 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20220610 |
|
A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20220905 |
|
A02 | Decision of refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A02 Effective date: 20230403 |