KR102655833B1 - T-세포 전림프구성 백혈병의 치료에 사용하기 위한 티노스타무스틴 - Google Patents
T-세포 전림프구성 백혈병의 치료에 사용하기 위한 티노스타무스틴 Download PDFInfo
- Publication number
- KR102655833B1 KR102655833B1 KR1020197037098A KR20197037098A KR102655833B1 KR 102655833 B1 KR102655833 B1 KR 102655833B1 KR 1020197037098 A KR1020197037098 A KR 1020197037098A KR 20197037098 A KR20197037098 A KR 20197037098A KR 102655833 B1 KR102655833 B1 KR 102655833B1
- Authority
- KR
- South Korea
- Prior art keywords
- cells
- pll
- treatment
- tinostamustine
- 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.)
- Active
Links
- 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 title claims abstract description 118
- 208000026651 T-cell prolymphocytic leukemia Diseases 0.000 title claims abstract description 93
- 208000033759 Prolymphocytic T-Cell Leukemia Diseases 0.000 title claims abstract description 92
- 238000011282 treatment Methods 0.000 title claims abstract description 74
- 229940070131 tinostamustine Drugs 0.000 title claims abstract description 47
- 150000003839 salts Chemical class 0.000 claims abstract description 61
- 238000001959 radiotherapy Methods 0.000 claims description 12
- 239000008194 pharmaceutical composition Substances 0.000 claims description 11
- 238000001802 infusion Methods 0.000 claims description 10
- 238000000034 method Methods 0.000 claims description 10
- 206010061289 metastatic neoplasm Diseases 0.000 claims description 4
- 230000001394 metastastic effect Effects 0.000 claims description 3
- 230000000750 progressive effect Effects 0.000 claims description 2
- 238000002648 combination therapy Methods 0.000 claims 2
- 238000002560 therapeutic procedure Methods 0.000 abstract description 3
- 210000004027 cell Anatomy 0.000 description 122
- 229960002707 bendamustine Drugs 0.000 description 61
- YTKUWDBFDASYHO-UHFFFAOYSA-N bendamustine Chemical compound ClCCN(CCCl)C1=CC=C2N(C)C(CCCC(O)=O)=NC2=C1 YTKUWDBFDASYHO-UHFFFAOYSA-N 0.000 description 61
- WAEXFXRVDQXREF-UHFFFAOYSA-N vorinostat Chemical compound ONC(=O)CCCCCCC(=O)NC1=CC=CC=C1 WAEXFXRVDQXREF-UHFFFAOYSA-N 0.000 description 46
- 229960000237 vorinostat Drugs 0.000 description 44
- 206010028980 Neoplasm Diseases 0.000 description 38
- 201000011510 cancer Diseases 0.000 description 33
- 241000699670 Mus sp. Species 0.000 description 22
- 150000001875 compounds Chemical class 0.000 description 19
- 229960000390 fludarabine Drugs 0.000 description 14
- 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 14
- 210000000265 leukocyte Anatomy 0.000 description 14
- 239000003814 drug Substances 0.000 description 13
- 230000004083 survival effect Effects 0.000 description 13
- 230000006907 apoptotic process Effects 0.000 description 12
- 230000000694 effects Effects 0.000 description 12
- 208000032839 leukemia Diseases 0.000 description 12
- 210000001744 T-lymphocyte Anatomy 0.000 description 11
- 231100000111 LD50 Toxicity 0.000 description 10
- 210000004369 blood Anatomy 0.000 description 10
- 239000008280 blood Substances 0.000 description 10
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 9
- 238000002474 experimental method Methods 0.000 description 9
- 239000000203 mixture Substances 0.000 description 9
- 230000028617 response to DNA damage stimulus Effects 0.000 description 9
- 210000004271 bone marrow stromal cell Anatomy 0.000 description 8
- 239000007788 liquid Substances 0.000 description 8
- 210000005259 peripheral blood Anatomy 0.000 description 8
- 239000011886 peripheral blood Substances 0.000 description 8
- 102000004121 Annexin A5 Human genes 0.000 description 7
- 108090000672 Annexin A5 Proteins 0.000 description 7
- 108020004414 DNA Proteins 0.000 description 7
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 7
- -1 amino acid salts Chemical class 0.000 description 7
- 238000002054 transplantation Methods 0.000 description 7
- 238000001262 western blot Methods 0.000 description 7
- 206010025323 Lymphomas Diseases 0.000 description 6
- 210000001185 bone marrow Anatomy 0.000 description 6
- 230000030833 cell death Effects 0.000 description 6
- 230000003833 cell viability Effects 0.000 description 6
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 6
- 238000000684 flow cytometry Methods 0.000 description 6
- 239000003276 histone deacetylase inhibitor Substances 0.000 description 6
- 230000001965 increasing effect Effects 0.000 description 6
- 102000004169 proteins and genes Human genes 0.000 description 6
- 108090000623 proteins and genes Proteins 0.000 description 6
- 210000001519 tissue Anatomy 0.000 description 6
- 108700012813 7-aminoactinomycin D Proteins 0.000 description 5
- YXHLJMWYDTXDHS-IRFLANFNSA-N 7-aminoactinomycin 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)=C(N)C=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 YXHLJMWYDTXDHS-IRFLANFNSA-N 0.000 description 5
- 102100025064 Cellular tumor antigen p53 Human genes 0.000 description 5
- 101000721661 Homo sapiens Cellular tumor antigen p53 Proteins 0.000 description 5
- 239000002253 acid Substances 0.000 description 5
- 229960000548 alemtuzumab Drugs 0.000 description 5
- 230000001640 apoptogenic effect Effects 0.000 description 5
- 239000003795 chemical substances by application Substances 0.000 description 5
- 238000002512 chemotherapy Methods 0.000 description 5
- 239000013068 control sample Substances 0.000 description 5
- 201000010099 disease Diseases 0.000 description 5
- 229940079593 drug Drugs 0.000 description 5
- 230000037361 pathway Effects 0.000 description 5
- 239000000243 solution Substances 0.000 description 5
- 239000000725 suspension Substances 0.000 description 5
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 5
- 230000035899 viability Effects 0.000 description 5
- 230000005778 DNA damage Effects 0.000 description 4
- 231100000277 DNA damage Toxicity 0.000 description 4
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerol Natural products OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 4
- 108010033040 Histones Proteins 0.000 description 4
- 206010027476 Metastases Diseases 0.000 description 4
- 229920000776 Poly(Adenosine diphosphate-ribose) polymerase Polymers 0.000 description 4
- 230000021736 acetylation Effects 0.000 description 4
- 238000006640 acetylation reaction Methods 0.000 description 4
- 238000004458 analytical method Methods 0.000 description 4
- 238000004113 cell culture Methods 0.000 description 4
- 230000006378 damage Effects 0.000 description 4
- 231100000673 dose–response relationship Toxicity 0.000 description 4
- 230000001976 improved effect Effects 0.000 description 4
- 238000001727 in vivo Methods 0.000 description 4
- 230000006698 induction Effects 0.000 description 4
- 239000007924 injection Substances 0.000 description 4
- 238000002347 injection Methods 0.000 description 4
- 230000009401 metastasis Effects 0.000 description 4
- 208000037819 metastatic cancer Diseases 0.000 description 4
- 208000011575 metastatic malignant neoplasm Diseases 0.000 description 4
- 230000010076 replication Effects 0.000 description 4
- 238000010186 staining Methods 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
- 206010006187 Breast cancer Diseases 0.000 description 3
- 208000026310 Breast neoplasm Diseases 0.000 description 3
- 239000012624 DNA alkylating agent Substances 0.000 description 3
- 230000004543 DNA replication Effects 0.000 description 3
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 3
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 3
- 208000002250 Hematologic Neoplasms Diseases 0.000 description 3
- 102000003964 Histone deacetylase Human genes 0.000 description 3
- 108090000353 Histone deacetylase Proteins 0.000 description 3
- 102000006947 Histones Human genes 0.000 description 3
- 206010058467 Lung neoplasm malignant Diseases 0.000 description 3
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- 208000000389 T-cell leukemia Diseases 0.000 description 3
- 208000028530 T-cell lymphoblastic leukemia/lymphoma Diseases 0.000 description 3
- 239000002585 base Substances 0.000 description 3
- 239000013592 cell lysate Substances 0.000 description 3
- 230000034994 death Effects 0.000 description 3
- 235000005911 diet Nutrition 0.000 description 3
- 230000037213 diet Effects 0.000 description 3
- 230000004927 fusion Effects 0.000 description 3
- 230000036541 health Effects 0.000 description 3
- 229940121372 histone deacetylase inhibitor Drugs 0.000 description 3
- 238000000338 in vitro Methods 0.000 description 3
- 201000005202 lung cancer Diseases 0.000 description 3
- 208000020816 lung neoplasm Diseases 0.000 description 3
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 3
- 239000000463 material Substances 0.000 description 3
- 230000003389 potentiating effect Effects 0.000 description 3
- 230000008439 repair process Effects 0.000 description 3
- 239000011780 sodium chloride Substances 0.000 description 3
- 239000007787 solid Substances 0.000 description 3
- 210000000952 spleen Anatomy 0.000 description 3
- 238000001356 surgical procedure Methods 0.000 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 description 3
- HZAXFHJVJLSVMW-UHFFFAOYSA-N 2-Aminoethan-1-ol Chemical compound NCCO HZAXFHJVJLSVMW-UHFFFAOYSA-N 0.000 description 2
- 102000007469 Actins Human genes 0.000 description 2
- 108010085238 Actins Proteins 0.000 description 2
- 208000024893 Acute lymphoblastic leukemia Diseases 0.000 description 2
- 208000014697 Acute lymphocytic leukaemia Diseases 0.000 description 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- 208000010839 B-cell chronic lymphocytic leukemia Diseases 0.000 description 2
- 208000032791 BCR-ABL1 positive chronic myelogenous leukemia Diseases 0.000 description 2
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 2
- 208000010833 Chronic myeloid leukaemia Diseases 0.000 description 2
- KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 description 2
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 2
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 2
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 2
- 206010066476 Haematological malignancy Diseases 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 2
- 238000012404 In vitro experiment Methods 0.000 description 2
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 2
- JVTAAEKCZFNVCJ-UHFFFAOYSA-M Lactate Chemical compound CC(O)C([O-])=O JVTAAEKCZFNVCJ-UHFFFAOYSA-M 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
- 208000008771 Lymphadenopathy Diseases 0.000 description 2
- TWRXJAOTZQYOKJ-UHFFFAOYSA-L Magnesium chloride Chemical compound [Mg+2].[Cl-].[Cl-] TWRXJAOTZQYOKJ-UHFFFAOYSA-L 0.000 description 2
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 2
- 241000699666 Mus <mouse, genus> Species 0.000 description 2
- 208000033761 Myelogenous Chronic BCR-ABL Positive Leukemia Diseases 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
- 229910002651 NO3 Inorganic materials 0.000 description 2
- NHNBFGGVMKEFGY-UHFFFAOYSA-N Nitrate Chemical compound [O-][N+]([O-])=O NHNBFGGVMKEFGY-UHFFFAOYSA-N 0.000 description 2
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 2
- 229910019142 PO4 Inorganic materials 0.000 description 2
- 239000002202 Polyethylene glycol Substances 0.000 description 2
- 208000006664 Precursor Cell Lymphoblastic Leukemia-Lymphoma Diseases 0.000 description 2
- MTCFGRXMJLQNBG-UHFFFAOYSA-N Serine Natural products OCC(N)C(O)=O MTCFGRXMJLQNBG-UHFFFAOYSA-N 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
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 2
- 208000025317 T-cell and NK-cell neoplasm Diseases 0.000 description 2
- 101150091442 Trim28 gene Proteins 0.000 description 2
- 239000000090 biomarker Substances 0.000 description 2
- 210000000481 breast Anatomy 0.000 description 2
- 239000002775 capsule Substances 0.000 description 2
- 239000000969 carrier Substances 0.000 description 2
- 238000003501 co-culture Methods 0.000 description 2
- 239000003086 colorant Substances 0.000 description 2
- 238000011254 conventional chemotherapy Methods 0.000 description 2
- 231100000135 cytotoxicity Toxicity 0.000 description 2
- 230000003013 cytotoxicity Effects 0.000 description 2
- 230000006196 deacetylation Effects 0.000 description 2
- 238000003381 deacetylation reaction Methods 0.000 description 2
- 230000003111 delayed effect Effects 0.000 description 2
- 238000003745 diagnosis Methods 0.000 description 2
- 235000014113 dietary fatty acids Nutrition 0.000 description 2
- 239000003085 diluting agent Substances 0.000 description 2
- 239000002552 dosage form Substances 0.000 description 2
- 230000003203 everyday effect Effects 0.000 description 2
- 230000029142 excretion Effects 0.000 description 2
- 239000000194 fatty acid Substances 0.000 description 2
- 229930195729 fatty acid Natural products 0.000 description 2
- 239000012091 fetal bovine serum Substances 0.000 description 2
- 235000003599 food sweetener Nutrition 0.000 description 2
- 235000011187 glycerol Nutrition 0.000 description 2
- 206010019847 hepatosplenomegaly Diseases 0.000 description 2
- XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-M hydrogensulfate Chemical compound OS([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-M 0.000 description 2
- 230000001939 inductive effect Effects 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
- 150000002632 lipids Chemical class 0.000 description 2
- 210000004072 lung Anatomy 0.000 description 2
- 208000018555 lymphatic system disease Diseases 0.000 description 2
- 210000004698 lymphocyte 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
- IWYDHOAUDWTVEP-UHFFFAOYSA-M mandelate Chemical compound [O-]C(=O)C(O)C1=CC=CC=C1 IWYDHOAUDWTVEP-UHFFFAOYSA-M 0.000 description 2
- 239000003550 marker Substances 0.000 description 2
- 208000020968 mature T-cell and NK-cell non-Hodgkin lymphoma Diseases 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
- 150000007522 mineralic acids Chemical class 0.000 description 2
- PSZYNBSKGUBXEH-UHFFFAOYSA-M naphthalene-1-sulfonate Chemical compound C1=CC=C2C(S(=O)(=O)[O-])=CC=CC2=C1 PSZYNBSKGUBXEH-UHFFFAOYSA-M 0.000 description 2
- 229910052757 nitrogen Inorganic materials 0.000 description 2
- 150000007524 organic acids Chemical class 0.000 description 2
- 230000002093 peripheral effect Effects 0.000 description 2
- 239000000546 pharmaceutical excipient Substances 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 2
- 239000010452 phosphate Substances 0.000 description 2
- 239000002504 physiological saline solution Substances 0.000 description 2
- 229920001223 polyethylene glycol Polymers 0.000 description 2
- 229920000642 polymer Polymers 0.000 description 2
- 238000010837 poor prognosis Methods 0.000 description 2
- 239000003755 preservative agent Substances 0.000 description 2
- 230000004044 response Effects 0.000 description 2
- 230000000630 rising effect Effects 0.000 description 2
- YGSDEFSMJLZEOE-UHFFFAOYSA-M salicylate Chemical compound OC1=CC=CC=C1C([O-])=O YGSDEFSMJLZEOE-UHFFFAOYSA-M 0.000 description 2
- 229960001860 salicylate Drugs 0.000 description 2
- 239000008247 solid mixture Substances 0.000 description 2
- 230000006641 stabilisation Effects 0.000 description 2
- 238000011105 stabilization Methods 0.000 description 2
- UCSJYZPVAKXKNQ-HZYVHMACSA-N streptomycin Chemical compound CN[C@H]1[C@H](O)[C@@H](O)[C@H](CO)O[C@H]1O[C@@H]1[C@](C=O)(O)[C@H](C)O[C@H]1O[C@@H]1[C@@H](NC(N)=N)[C@H](O)[C@@H](NC(N)=N)[C@H](O)[C@H]1O UCSJYZPVAKXKNQ-HZYVHMACSA-N 0.000 description 2
- 210000002536 stromal cell Anatomy 0.000 description 2
- 238000007920 subcutaneous administration Methods 0.000 description 2
- KDYFGRWQOYBRFD-UHFFFAOYSA-L succinate(2-) Chemical compound [O-]C(=O)CCC([O-])=O KDYFGRWQOYBRFD-UHFFFAOYSA-L 0.000 description 2
- 239000005720 sucrose Substances 0.000 description 2
- 235000000346 sugar Nutrition 0.000 description 2
- 150000005846 sugar alcohols Polymers 0.000 description 2
- 150000008163 sugars Chemical class 0.000 description 2
- IIACRCGMVDHOTQ-UHFFFAOYSA-M sulfamate Chemical compound NS([O-])(=O)=O IIACRCGMVDHOTQ-UHFFFAOYSA-M 0.000 description 2
- 239000006228 supernatant Substances 0.000 description 2
- 238000004114 suspension culture Methods 0.000 description 2
- 239000003765 sweetening agent Substances 0.000 description 2
- 229940095064 tartrate Drugs 0.000 description 2
- 238000012360 testing method Methods 0.000 description 2
- 239000003981 vehicle Substances 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- ZQXCQTAELHSNAT-UHFFFAOYSA-N 1-chloro-3-nitro-5-(trifluoromethyl)benzene Chemical compound [O-][N+](=O)C1=CC(Cl)=CC(C(F)(F)F)=C1 ZQXCQTAELHSNAT-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
- 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
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
- 208000031261 Acute myeloid leukaemia Diseases 0.000 description 1
- 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
- 241000283690 Bos taurus Species 0.000 description 1
- 206010055113 Breast cancer metastatic Diseases 0.000 description 1
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
- UXVMQQNJUSDDNG-UHFFFAOYSA-L Calcium chloride Chemical compound [Cl-].[Cl-].[Ca+2] UXVMQQNJUSDDNG-UHFFFAOYSA-L 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
- 241000282994 Cervidae Species 0.000 description 1
- 229920002261 Corn starch Polymers 0.000 description 1
- 229920000858 Cyclodextrin Polymers 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-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-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
- AEMOLEFTQBMNLQ-AQKNRBDQSA-N D-glucopyranuronic acid Chemical compound OC1O[C@H](C(O)=O)[C@@H](O)[C@H](O)[C@H]1O AEMOLEFTQBMNLQ-AQKNRBDQSA-N 0.000 description 1
- 229940126161 DNA alkylating agent Drugs 0.000 description 1
- 230000007118 DNA alkylation Effects 0.000 description 1
- 229920002307 Dextran Polymers 0.000 description 1
- 239000004375 Dextrin Substances 0.000 description 1
- 229920001353 Dextrin Polymers 0.000 description 1
- 206010061818 Disease progression Diseases 0.000 description 1
- 206010061819 Disease recurrence Diseases 0.000 description 1
- 206010059866 Drug resistance Diseases 0.000 description 1
- 239000004097 EU approved flavor enhancer Substances 0.000 description 1
- 241000283086 Equidae Species 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
- 241000282326 Felis catus Species 0.000 description 1
- 108010010803 Gelatin Proteins 0.000 description 1
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 1
- 229930186217 Glycolipid Natural products 0.000 description 1
- 102100039996 Histone deacetylase 1 Human genes 0.000 description 1
- 241000282412 Homo Species 0.000 description 1
- 101000711004 Homo sapiens Cx9C motif-containing protein 4 Proteins 0.000 description 1
- 101001035024 Homo sapiens Histone deacetylase 1 Proteins 0.000 description 1
- 101001006782 Homo sapiens Kinesin-associated protein 3 Proteins 0.000 description 1
- 101001014035 Homo sapiens Protein p13 MTCP-1 Proteins 0.000 description 1
- 101000650863 Homo sapiens SH2 domain-containing protein 1A Proteins 0.000 description 1
- 101000837401 Homo sapiens T-cell leukemia/lymphoma protein 1A Proteins 0.000 description 1
- 101000753286 Homo sapiens Transcription intermediary factor 1-beta Proteins 0.000 description 1
- 101000997835 Homo sapiens Tyrosine-protein kinase JAK1 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
- WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 description 1
- ZDXPYRJPNDTMRX-VKHMYHEASA-N L-glutamine Chemical compound OC(=O)[C@@H](N)CCC(N)=O ZDXPYRJPNDTMRX-VKHMYHEASA-N 0.000 description 1
- 229930182816 L-glutamine Natural products 0.000 description 1
- 208000031422 Lymphocytic Chronic B-Cell Leukemia Diseases 0.000 description 1
- 231100000002 MTT assay Toxicity 0.000 description 1
- 238000000134 MTT assay Methods 0.000 description 1
- 241000124008 Mammalia Species 0.000 description 1
- 229930195725 Mannitol Natural products 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
- 229920000168 Microcrystalline cellulose Polymers 0.000 description 1
- 208000034578 Multiple myelomas Diseases 0.000 description 1
- 241000204031 Mycoplasma Species 0.000 description 1
- 241000283973 Oryctolagus cuniculus Species 0.000 description 1
- 241001494479 Pecora Species 0.000 description 1
- 229930182555 Penicillin Natural products 0.000 description 1
- JGSARLDLIJGVTE-MBNYWOFBSA-N Penicillin G Chemical compound N([C@H]1[C@H]2SC([C@@H](N2C1=O)C(O)=O)(C)C)C(=O)CC1=CC=CC=C1 JGSARLDLIJGVTE-MBNYWOFBSA-N 0.000 description 1
- 206010035226 Plasma cell myeloma Diseases 0.000 description 1
- RVGRUAULSDPKGF-UHFFFAOYSA-N Poloxamer Chemical compound C1CO1.CC1CO1 RVGRUAULSDPKGF-UHFFFAOYSA-N 0.000 description 1
- 229920003171 Poly (ethylene oxide) Polymers 0.000 description 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
- 102100031352 Protein p13 MTCP-1 Human genes 0.000 description 1
- 239000012980 RPMI-1640 medium Substances 0.000 description 1
- 208000009359 Sezary Syndrome Diseases 0.000 description 1
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 1
- 229920002472 Starch Polymers 0.000 description 1
- 241000282887 Suidae Species 0.000 description 1
- 102100028676 T-cell leukemia/lymphoma protein 1A Human genes 0.000 description 1
- 206010042971 T-cell lymphoma Diseases 0.000 description 1
- 208000027585 T-cell non-Hodgkin lymphoma Diseases 0.000 description 1
- 208000024313 Testicular Neoplasms Diseases 0.000 description 1
- 206010057644 Testis cancer Diseases 0.000 description 1
- 102100022012 Transcription intermediary factor 1-beta Human genes 0.000 description 1
- GSEJCLTVZPLZKY-UHFFFAOYSA-N Triethanolamine Chemical compound OCCN(CCO)CCO GSEJCLTVZPLZKY-UHFFFAOYSA-N 0.000 description 1
- DTQVDTLACAAQTR-UHFFFAOYSA-M Trifluoroacetate Chemical compound [O-]C(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-M 0.000 description 1
- 102100033438 Tyrosine-protein kinase JAK1 Human genes 0.000 description 1
- 230000002159 abnormal effect Effects 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 238000009825 accumulation Methods 0.000 description 1
- 159000000021 acetate salts Chemical class 0.000 description 1
- 230000001154 acute effect Effects 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
- 239000003513 alkali Substances 0.000 description 1
- 150000001447 alkali salts 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
- 150000003863 ammonium salts Chemical class 0.000 description 1
- 239000003242 anti bacterial agent Substances 0.000 description 1
- 230000008901 benefit Effects 0.000 description 1
- 235000019445 benzyl alcohol Nutrition 0.000 description 1
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 1
- 239000011230 binding agent Substances 0.000 description 1
- 238000004166 bioassay Methods 0.000 description 1
- 210000000601 blood cell Anatomy 0.000 description 1
- 238000004820 blood count Methods 0.000 description 1
- 239000006172 buffering agent Substances 0.000 description 1
- 239000011575 calcium Substances 0.000 description 1
- 229910052791 calcium Inorganic materials 0.000 description 1
- 239000001110 calcium chloride Substances 0.000 description 1
- 229910001628 calcium chloride Inorganic materials 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
- 239000006285 cell suspension Substances 0.000 description 1
- 230000001413 cellular effect Effects 0.000 description 1
- 230000019522 cellular metabolic process Effects 0.000 description 1
- 238000011342 chemoimmunotherapy Methods 0.000 description 1
- 238000009104 chemotherapy regimen Methods 0.000 description 1
- 229940112822 chewing gum Drugs 0.000 description 1
- 235000015218 chewing gum Nutrition 0.000 description 1
- 208000032852 chronic lymphocytic leukemia Diseases 0.000 description 1
- 238000003776 cleavage reaction Methods 0.000 description 1
- 229940075614 colloidal silicon dioxide Drugs 0.000 description 1
- 210000001072 colon Anatomy 0.000 description 1
- 238000004040 coloring Methods 0.000 description 1
- 238000011284 combination treatment Methods 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
- 230000002596 correlated effect Effects 0.000 description 1
- 229960004397 cyclophosphamide Drugs 0.000 description 1
- 230000002950 deficient Effects 0.000 description 1
- 230000001419 dependent effect Effects 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 235000019425 dextrin Nutrition 0.000 description 1
- 239000008121 dextrose Substances 0.000 description 1
- 230000005750 disease progression Effects 0.000 description 1
- 239000007884 disintegrant Substances 0.000 description 1
- 208000035475 disorder Diseases 0.000 description 1
- 239000002270 dispersing agent Substances 0.000 description 1
- 238000012137 double-staining Methods 0.000 description 1
- 239000003937 drug carrier Substances 0.000 description 1
- 239000000839 emulsion Substances 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 235000019325 ethyl cellulose Nutrition 0.000 description 1
- 229920001249 ethyl cellulose Polymers 0.000 description 1
- 150000004665 fatty acids Chemical class 0.000 description 1
- 239000010685 fatty oil Substances 0.000 description 1
- 239000000796 flavoring agent Substances 0.000 description 1
- 235000013355 food flavoring agent Nutrition 0.000 description 1
- 235000019264 food flavour enhancer Nutrition 0.000 description 1
- 239000000499 gel Substances 0.000 description 1
- 239000008273 gelatin Substances 0.000 description 1
- 229920000159 gelatin Polymers 0.000 description 1
- 239000007903 gelatin capsule Substances 0.000 description 1
- 235000019322 gelatine Nutrition 0.000 description 1
- 235000011852 gelatine desserts Nutrition 0.000 description 1
- 239000011521 glass Substances 0.000 description 1
- 229940097042 glucuronate Drugs 0.000 description 1
- 229930195712 glutamate Natural products 0.000 description 1
- JFCQEDHGNNZCLN-UHFFFAOYSA-N glutaric acid Chemical compound OC(=O)CCCC(O)=O JFCQEDHGNNZCLN-UHFFFAOYSA-N 0.000 description 1
- 239000008187 granular material Substances 0.000 description 1
- 230000012010 growth Effects 0.000 description 1
- 208000019622 heart disease Diseases 0.000 description 1
- 201000005787 hematologic cancer Diseases 0.000 description 1
- 208000024200 hematopoietic and lymphoid system neoplasm Diseases 0.000 description 1
- 235000001050 hortel pimenta Nutrition 0.000 description 1
- 238000011534 incubation Methods 0.000 description 1
- 239000000411 inducer Substances 0.000 description 1
- 230000006882 induction of apoptosis Effects 0.000 description 1
- 239000003701 inert diluent Substances 0.000 description 1
- 230000005764 inhibitory process Effects 0.000 description 1
- 150000007529 inorganic bases Chemical class 0.000 description 1
- 238000002743 insertional mutagenesis Methods 0.000 description 1
- 238000000185 intracerebroventricular administration Methods 0.000 description 1
- 238000007912 intraperitoneal administration Methods 0.000 description 1
- 239000007928 intraperitoneal injection Substances 0.000 description 1
- 238000007913 intrathecal administration Methods 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
- 230000007774 longterm Effects 0.000 description 1
- 239000000314 lubricant Substances 0.000 description 1
- 210000001165 lymph node Anatomy 0.000 description 1
- 210000004324 lymphatic system Anatomy 0.000 description 1
- 229910001629 magnesium chloride Inorganic materials 0.000 description 1
- 235000019359 magnesium stearate Nutrition 0.000 description 1
- 229940049920 malate Drugs 0.000 description 1
- BJEPYKJPYRNKOW-UHFFFAOYSA-N malic acid Chemical compound OC(=O)C(O)CC(O)=O BJEPYKJPYRNKOW-UHFFFAOYSA-N 0.000 description 1
- 239000000594 mannitol Substances 0.000 description 1
- 235000010355 mannitol Nutrition 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 230000001404 mediated effect Effects 0.000 description 1
- STZCRXQWRGQSJD-GEEYTBSJSA-M methyl orange Chemical compound [Na+].C1=CC(N(C)C)=CC=C1\N=N\C1=CC=C(S([O-])(=O)=O)C=C1 STZCRXQWRGQSJD-GEEYTBSJSA-M 0.000 description 1
- 229940012189 methyl orange Drugs 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
- 239000008108 microcrystalline cellulose Substances 0.000 description 1
- 229940016286 microcrystalline cellulose Drugs 0.000 description 1
- 235000019813 microcrystalline cellulose Nutrition 0.000 description 1
- 229960004857 mitomycin Drugs 0.000 description 1
- 238000007479 molecular analysis Methods 0.000 description 1
- 238000009343 monoculture Methods 0.000 description 1
- 238000010172 mouse model Methods 0.000 description 1
- 238000011395 multi-agent chemotherapy Methods 0.000 description 1
- 230000001338 necrotic effect Effects 0.000 description 1
- 239000013642 negative control Substances 0.000 description 1
- 239000012457 nonaqueous media Substances 0.000 description 1
- 239000000346 nonvolatile oil Substances 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
- 230000008520 organization Effects 0.000 description 1
- 238000002638 palliative care Methods 0.000 description 1
- 238000007911 parenteral administration Methods 0.000 description 1
- 239000013610 patient sample Substances 0.000 description 1
- 229940049954 penicillin Drugs 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 150000003904 phospholipids Chemical class 0.000 description 1
- 230000026731 phosphorylation Effects 0.000 description 1
- 238000006366 phosphorylation reaction Methods 0.000 description 1
- 239000006187 pill Substances 0.000 description 1
- 239000004033 plastic Substances 0.000 description 1
- 229920003023 plastic Polymers 0.000 description 1
- 229960000502 poloxamer Drugs 0.000 description 1
- 229920001983 poloxamer Polymers 0.000 description 1
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 1
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
- 230000008092 positive effect Effects 0.000 description 1
- 230000004481 post-translational protein modification Effects 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- 230000001737 promoting effect Effects 0.000 description 1
- 230000001681 protective effect Effects 0.000 description 1
- 230000005180 public health Effects 0.000 description 1
- 150000003212 purines Chemical class 0.000 description 1
- 230000005855 radiation Effects 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 238000012552 review Methods 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
- 239000000523 sample 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
- 230000007017 scission Effects 0.000 description 1
- 230000035945 sensitivity Effects 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
- 239000002904 solvent Substances 0.000 description 1
- 239000000600 sorbitol Substances 0.000 description 1
- 230000003393 splenic effect Effects 0.000 description 1
- 230000007480 spreading Effects 0.000 description 1
- 238000003892 spreading Methods 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 238000010561 standard procedure Methods 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 238000003860 storage Methods 0.000 description 1
- 229960005322 streptomycin Drugs 0.000 description 1
- 239000004094 surface-active agent Substances 0.000 description 1
- 239000000375 suspending agent Substances 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 201000003120 testicular cancer Diseases 0.000 description 1
- 238000010257 thawing Methods 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 238000004448 titration Methods 0.000 description 1
- 230000000699 topical effect Effects 0.000 description 1
- 230000004222 uncontrolled growth Effects 0.000 description 1
- 238000009827 uniform distribution Methods 0.000 description 1
- 238000010200 validation analysis Methods 0.000 description 1
- 235000012431 wafers Nutrition 0.000 description 1
- 239000008215 water for injection Substances 0.000 description 1
- 239000000080 wetting agent Substances 0.000 description 1
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
- A61K31/33—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
- 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
-
- 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
- A61P35/00—Antineoplastic agents
- A61P35/04—Antineoplastic agents specific for metastasis
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Veterinary Medicine (AREA)
- Chemical & Material Sciences (AREA)
- Public Health (AREA)
- Medicinal Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Organic Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Oncology (AREA)
- Hematology (AREA)
- Dermatology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GB1709402.0 | 2017-06-13 | ||
| GBGB1709402.0A GB201709402D0 (en) | 2017-06-13 | 2017-06-13 | Compounds for treating t-pll |
| PCT/EP2018/065664 WO2018229132A1 (en) | 2017-06-13 | 2018-06-13 | Tinostamustine for use in the treatment of t-cell prolymphocytic leukaemia |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| KR20200015563A KR20200015563A (ko) | 2020-02-12 |
| KR102655833B1 true KR102655833B1 (ko) | 2024-04-08 |
Family
ID=59358363
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| KR1020197037098A Active KR102655833B1 (ko) | 2017-06-13 | 2018-06-13 | T-세포 전림프구성 백혈병의 치료에 사용하기 위한 티노스타무스틴 |
Country Status (14)
| Country | Link |
|---|---|
| US (3) | US11318117B2 (enExample) |
| EP (1) | EP3638231B1 (enExample) |
| JP (1) | JP7195283B2 (enExample) |
| KR (1) | KR102655833B1 (enExample) |
| AR (1) | AR112101A1 (enExample) |
| AU (1) | AU2018285821B2 (enExample) |
| BR (1) | BR112019026484A2 (enExample) |
| CA (1) | CA3067276A1 (enExample) |
| ES (1) | ES2966954T3 (enExample) |
| GB (1) | GB201709402D0 (enExample) |
| IL (1) | IL271017A (enExample) |
| MX (1) | MX392103B (enExample) |
| TW (1) | TW201919616A (enExample) |
| WO (1) | WO2018229132A1 (enExample) |
Families Citing this family (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| 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 |
| US11266631B2 (en) | 2016-10-11 | 2022-03-08 | Purdue Pharmaceutical Products L.P. | Hodgkin lymphoma therapy |
| GB201709406D0 (en) | 2017-06-13 | 2017-07-26 | Euro-Cletique S A | Compounds for treating TNBC |
| GB201709405D0 (en) | 2017-06-13 | 2017-07-26 | Euro Celtique Sa | Compounds for treating ovarian cancer |
| 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 |
| WO2020128912A1 (en) * | 2018-12-18 | 2020-06-25 | Mundipharma International Corporation Limited | Compounds for treating lymphoma or a t-cell malignant disease |
| EP4007585A4 (en) * | 2019-08-02 | 2023-11-08 | OneHealthCompany, Inc. | TREATMENT OF CANINE CANCERS |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2015181157A1 (en) | 2014-05-28 | 2015-12-03 | Euro-Celtique S.A. | Combination comprising a glucocorticoid and edo-s101 |
| WO2015180865A1 (en) | 2014-05-28 | 2015-12-03 | Euro-Celtique S.A. | Compounds for treating brain cancer |
| WO2015181154A1 (en) | 2014-05-28 | 2015-12-03 | Euro-Celtique S.A | Pharmaceutical combination comprising a class iii receptor tyrosine kinase inhibitor and the alkylating histone-deacetylase inhibitor fusion molecule edo-s101 together with its use in the treatment of cancer |
Family Cites Families (62)
| 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 |
| DE69819721T2 (de) | 1997-06-13 | 2004-09-23 | Cydex Inc., Overland Park | Zusammensetzung mit erhöhter lagerstabilität enthaltend cyclodextrin und wirkstoffe oder wirkstoff-vorstufen, die in wasserunlösliche komponenten zersetzt werden |
| US6040321A (en) | 1997-11-12 | 2000-03-21 | Bristol-Myers Squibb Company | Aminothiazole inhibitors of cyclin dependent kinases |
| 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 |
| US20020076409A1 (en) | 2000-07-12 | 2002-06-20 | March Carl J. | Method for treating cancer |
| PE20020354A1 (es) | 2000-09-01 | 2002-06-12 | Novartis Ag | Compuestos de hidroxamato como inhibidores de histona-desacetilasa (hda) |
| EP2083005A1 (en) | 2000-09-29 | 2009-07-29 | TopoTarget UK Limited | Carbamic acid compounds comprising an amide linkage as HDAC inhibitors |
| AU2002243231A1 (en) | 2000-11-21 | 2002-07-24 | 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 |
| AU2004215624B2 (en) | 2003-02-25 | 2011-06-02 | Topotarget Uk Limited | Hydroxamic acid compounds comprising a bicyclic heteroaryl group as HDAC inhibitors |
| JP2007501775A (ja) | 2003-08-07 | 2007-02-01 | ノバルティス アクチエンゲゼルシャフト | 免疫抑制剤としてのヒストンデアセチラーゼ阻害剤 |
| US7223745B2 (en) | 2003-08-14 | 2007-05-29 | Cephalon, Inc. | Proteasome inhibitors and methods of using the same |
| US8227636B2 (en) | 2004-04-05 | 2012-07-24 | 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 |
| ES2380887T3 (es) | 2005-05-13 | 2012-05-21 | Topotarget Uk Limited | Formulaciones farmacéuticas de inhibidores de la HDAC |
| EA200900571A1 (ru) | 2006-10-20 | 2009-12-30 | Айкос Корпорейшн | Композиции chk1 ингибиторов |
| GB0621160D0 (en) | 2006-10-24 | 2006-12-06 | Imp College Innovations Ltd | Compounds and uses thereof |
| EP2086525B1 (en) | 2006-11-20 | 2010-10-06 | Cephalon, Inc. | Method of radio-sensitizing tumors using a radio-sensitizing agent |
| 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 |
| JP5670335B2 (ja) | 2008-09-25 | 2015-02-18 | セファロン、インク. | ベンダムスチン液体製剤 |
| JP5773874B2 (ja) | 2008-10-08 | 2015-09-02 | セファロン、インク. | ベンダムスチンの調製方法 |
| WO2010075542A1 (en) | 2008-12-23 | 2010-07-01 | Curis, Inc. | Cdk inhibitors |
| ME02254B (me) | 2009-01-23 | 2015-12-31 | Euro Celtique Sa | Derivati hidroksamske kiseline |
| AU2010217297A1 (en) | 2009-02-25 | 2011-10-20 | Supratek Pharma, Inc. | Bendamustine cyclopolysaccharide compositions |
| 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 |
| US20130030237A1 (en) | 2010-04-15 | 2013-01-31 | Charles Theuer | Potentiation of anti-cancer activity through combination therapy with ber pathway inhibitors |
| JP5727000B2 (ja) | 2010-04-16 | 2015-06-03 | ツェルアクト ファーマ ゲーエムベーハー | 腫瘍の処置のためのエポトシドのアナログ |
| 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 |
| EP2755648B1 (en) | 2011-09-13 | 2017-03-08 | Pharmacyclics LLC | Formulations of histone deacetylase inhibitor in combination with bendamustine and uses thereof |
| 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 |
| JP2014526512A (ja) | 2011-09-18 | 2014-10-06 | ユーロ−セルティーク エス.エイ. | 医薬組成物 |
| SI2760860T1 (sl) | 2011-09-28 | 2017-04-26 | Euro-Celtique S.A. | Derivati dušikove gorčice |
| 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 |
| 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 |
| US11266631B2 (en) | 2016-10-11 | 2022-03-08 | Purdue Pharmaceutical Products L.P. | Hodgkin lymphoma therapy |
| US20180098969A1 (en) | 2016-10-11 | 2018-04-12 | Purdue Pharmaceutical Products L.P. | Hodgkin lymphoma therapy |
| GB201709405D0 (en) | 2017-06-13 | 2017-07-26 | Euro Celtique Sa | Compounds for treating ovarian cancer |
| GB201709403D0 (en) | 2017-06-13 | 2017-07-26 | Euro Celtique Sa | Compounds for treating sarcoma |
| 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 |
| WO2020128912A1 (en) | 2018-12-18 | 2020-06-25 | Mundipharma International Corporation Limited | Compounds for treating lymphoma or a t-cell malignant disease |
-
2017
- 2017-06-13 GB GBGB1709402.0A patent/GB201709402D0/en not_active Ceased
-
2018
- 2018-06-13 ES ES18733527T patent/ES2966954T3/es active Active
- 2018-06-13 WO PCT/EP2018/065664 patent/WO2018229132A1/en not_active Ceased
- 2018-06-13 KR KR1020197037098A patent/KR102655833B1/ko active Active
- 2018-06-13 AR ARP180101622A patent/AR112101A1/es unknown
- 2018-06-13 CA CA3067276A patent/CA3067276A1/en active Pending
- 2018-06-13 JP JP2019568675A patent/JP7195283B2/ja active Active
- 2018-06-13 TW TW107120389A patent/TW201919616A/zh unknown
- 2018-06-13 US US16/621,898 patent/US11318117B2/en active Active
- 2018-06-13 AU AU2018285821A patent/AU2018285821B2/en active Active
- 2018-06-13 BR BR112019026484-1A patent/BR112019026484A2/pt not_active Application Discontinuation
- 2018-06-13 MX MX2019015208A patent/MX392103B/es unknown
- 2018-06-13 EP EP18733527.8A patent/EP3638231B1/en active Active
-
2019
- 2019-11-28 IL IL271017A patent/IL271017A/en unknown
-
2022
- 2022-04-27 US US17/730,276 patent/US11918558B2/en active Active
-
2024
- 2024-01-25 US US18/422,118 patent/US12370178B2/en active Active
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2015181157A1 (en) | 2014-05-28 | 2015-12-03 | Euro-Celtique S.A. | Combination comprising a glucocorticoid and edo-s101 |
| WO2015180865A1 (en) | 2014-05-28 | 2015-12-03 | Euro-Celtique S.A. | Compounds for treating brain cancer |
| WO2015181154A1 (en) | 2014-05-28 | 2015-12-03 | Euro-Celtique S.A | Pharmaceutical combination comprising a class iii receptor tyrosine kinase inhibitor and the alkylating histone-deacetylase inhibitor fusion molecule edo-s101 together with its use in the treatment of cancer |
Also Published As
| Publication number | Publication date |
|---|---|
| TW201919616A (zh) | 2019-06-01 |
| AU2018285821A1 (en) | 2019-12-19 |
| WO2018229132A1 (en) | 2018-12-20 |
| KR20200015563A (ko) | 2020-02-12 |
| US12370178B2 (en) | 2025-07-29 |
| US20220401417A1 (en) | 2022-12-22 |
| JP2020523359A (ja) | 2020-08-06 |
| EP3638231B1 (en) | 2023-12-20 |
| MX2019015208A (es) | 2022-05-03 |
| BR112019026484A2 (pt) | 2020-07-14 |
| JP7195283B2 (ja) | 2022-12-23 |
| ES2966954T3 (es) | 2024-04-25 |
| MX392103B (es) | 2025-03-21 |
| IL271017A (en) | 2020-01-30 |
| AR112101A1 (es) | 2019-09-18 |
| US20240316009A1 (en) | 2024-09-26 |
| GB201709402D0 (en) | 2017-07-26 |
| EP3638231A1 (en) | 2020-04-22 |
| AU2018285821B2 (en) | 2024-07-04 |
| US11318117B2 (en) | 2022-05-03 |
| US11918558B2 (en) | 2024-03-05 |
| US20200113871A1 (en) | 2020-04-16 |
| EP3638231C0 (en) | 2023-12-20 |
| CA3067276A1 (en) | 2018-12-20 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| KR102655833B1 (ko) | T-세포 전림프구성 백혈병의 치료에 사용하기 위한 티노스타무스틴 | |
| KR101938431B1 (ko) | 뇌 종양의 치료를 위한 csf-1r 억제제 | |
| CN107106580B (zh) | 治疗癌症干细胞的组合物 | |
| KR20200014790A (ko) | 난소암의 치료에 사용되는 티노스타무스틴 | |
| BR112019017851A2 (pt) | método para tratar câncer em um indivíduo que precisa do mesmo, método para identificar um indivíduo que tem um câncer como um candidato para o tratamento com um antagonista de smarca2, método para identificar uma célula cancerosa como sensível ao tratamento com um antagonista de smarca2, antagonista de smarca2 para uso no tratamento de câncer em um indivíduo que precisa do mesmo, antagonista de smarca2 para uso como um medicamento no tratamento de câncer em um indivíduo que precisa do mesmo e uso do antagonista de smarca2 na fabricação de um medicamento no tratamento de câncer em um indivíduo que precisa do mesmo | |
| US20180207168A1 (en) | Dactinomycin compositions and methods for the treatment of acute myeloid leukemia | |
| US12121565B2 (en) | Methods of treatment of specific cancers with NLRP3 inhibitors and anti-PD1/PD-L1 antibodies | |
| KR20200014789A (ko) | Tnbc 치료용 화합물 | |
| EP3220908B1 (en) | Compositions and methods for treating endometriosis | |
| JP7586835B2 (ja) | ミトコンドリア標的化及び抗癌治療のためのアルキルtpp化合物 | |
| KR101401891B1 (ko) | 테모졸로미드 및 발프로산을 함께 이용하는 항암적 용도 | |
| CN111132672A (zh) | 抗药性胶质瘤的治疗 | |
| US20250352555A1 (en) | Method of increasing immune cell activation and/or treating cancer using dibenzoxazepinones | |
| US10213449B2 (en) | Compositions and methods for treating medulloblastoma | |
| WO2025059216A1 (en) | Treatment of high-grade serous carcinoma | |
| US20220273752A1 (en) | Modulation of dendritic cell function by the phospholipid messenger lpa | |
| JP2022518143A (ja) | ビタミンeならびにがん治療用組成物および方法 | |
| TW201808278A (zh) | 二氫異丹蔘酮i於治療癌症之用途 |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PA0105 | International application |
Patent event date: 20191216 Patent event code: PA01051R01D Comment text: International Patent Application |
|
| PG1501 | Laying open of application | ||
| PA0201 | Request for examination |
Patent event code: PA02012R01D Patent event date: 20210528 Comment text: Request for Examination of Application |
|
| E902 | Notification of reason for refusal | ||
| PE0902 | Notice of grounds for rejection |
Comment text: Notification of reason for refusal Patent event date: 20230829 Patent event code: PE09021S01D |
|
| E701 | Decision to grant or registration of patent right | ||
| PE0701 | Decision of registration |
Patent event code: PE07011S01D Comment text: Decision to Grant Registration Patent event date: 20240202 |
|
| GRNT | Written decision to grant | ||
| PR0701 | Registration of establishment |
Comment text: Registration of Establishment Patent event date: 20240403 Patent event code: PR07011E01D |
|
| PR1002 | Payment of registration fee |
Payment date: 20240404 End annual number: 3 Start annual number: 1 |
|
| PG1601 | Publication of registration |