CA2547196A1 - Combination of (a) n-{5-[4-(4-methyl-piperazino-methyl)-benzoylamido]-2methylphenyl}-4-(3-pyridyl)-2-pyrimidine-amine and (b) at least one hypusination inhibitor and the use thereof - Google Patents
Combination of (a) n-{5-[4-(4-methyl-piperazino-methyl)-benzoylamido]-2methylphenyl}-4-(3-pyridyl)-2-pyrimidine-amine and (b) at least one hypusination inhibitor and the use thereof Download PDFInfo
- Publication number
- CA2547196A1 CA2547196A1 CA002547196A CA2547196A CA2547196A1 CA 2547196 A1 CA2547196 A1 CA 2547196A1 CA 002547196 A CA002547196 A CA 002547196A CA 2547196 A CA2547196 A CA 2547196A CA 2547196 A1 CA2547196 A1 CA 2547196A1
- Authority
- CA
- Canada
- Prior art keywords
- combination
- leukemia
- methyl
- imatinib
- proliferative disease
- 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.)
- Abandoned
Links
- 239000003112 inhibitor Substances 0.000 title claims abstract description 40
- KTUFNOKKBVMGRW-UHFFFAOYSA-N imatinib Chemical compound C1CN(C)CCN1CC1=CC=C(C(=O)NC=2C=C(NC=3N=C(C=CN=3)C=3C=NC=CC=3)C(C)=CC=2)C=C1 KTUFNOKKBVMGRW-UHFFFAOYSA-N 0.000 claims abstract description 51
- 239000005517 L01XE01 - Imatinib Substances 0.000 claims abstract description 50
- 229960002411 imatinib Drugs 0.000 claims abstract description 50
- 208000032839 leukemia Diseases 0.000 claims abstract description 45
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 39
- 201000010099 disease Diseases 0.000 claims abstract description 38
- 230000002062 proliferating effect Effects 0.000 claims abstract description 30
- 238000000034 method Methods 0.000 claims abstract description 27
- 238000011282 treatment Methods 0.000 claims abstract description 25
- 239000003814 drug Substances 0.000 claims abstract description 19
- 241001465754 Metazoa Species 0.000 claims abstract description 16
- 238000002360 preparation method Methods 0.000 claims abstract description 14
- 239000003937 drug carrier Substances 0.000 claims abstract description 8
- SCKYRAXSEDYPSA-UHFFFAOYSA-N ciclopirox Chemical compound ON1C(=O)C=C(C)C=C1C1CCCCC1 SCKYRAXSEDYPSA-UHFFFAOYSA-N 0.000 claims description 24
- 229960003749 ciclopirox Drugs 0.000 claims description 23
- 150000003839 salts Chemical class 0.000 claims description 22
- 150000001875 compounds Chemical class 0.000 claims description 14
- 239000008194 pharmaceutical composition Substances 0.000 claims description 11
- 239000004480 active ingredient Substances 0.000 claims description 10
- 239000000203 mixture Substances 0.000 claims description 7
- UBQYURCVBFRUQT-UHFFFAOYSA-N N-benzoyl-Ferrioxamine B Chemical group CC(=O)N(O)CCCCCNC(=O)CCC(=O)N(O)CCCCCNC(=O)CCC(=O)N(O)CCCCCN UBQYURCVBFRUQT-UHFFFAOYSA-N 0.000 claims description 5
- 229960000958 deferoxamine Drugs 0.000 claims description 5
- TZXKOCQBRNJULO-UHFFFAOYSA-N Ferriprox Chemical compound CC1=C(O)C(=O)C=CN1C TZXKOCQBRNJULO-UHFFFAOYSA-N 0.000 claims description 3
- 229960003266 deferiprone Drugs 0.000 claims description 3
- 229960002706 gusperimus Drugs 0.000 claims description 3
- IDINUJSAMVOPCM-INIZCTEOSA-N n-[(1s)-2-[4-(3-aminopropylamino)butylamino]-1-hydroxy-2-oxoethyl]-7-(diaminomethylideneamino)heptanamide Chemical compound NCCCNCCCCNC(=O)[C@H](O)NC(=O)CCCCCCN=C(N)N IDINUJSAMVOPCM-INIZCTEOSA-N 0.000 claims description 3
- BOFQWVMAQOTZIW-UHFFFAOYSA-N deferasirox Chemical group C1=CC(C(=O)O)=CC=C1N1C(C=2C(=CC=CC=2)O)=NC(C=2C(=CC=CC=2)O)=N1 BOFQWVMAQOTZIW-UHFFFAOYSA-N 0.000 claims description 2
- 210000004027 cell Anatomy 0.000 description 42
- 108090000623 proteins and genes Proteins 0.000 description 33
- 102000004169 proteins and genes Human genes 0.000 description 32
- 235000018102 proteins Nutrition 0.000 description 27
- 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 18
- 230000000694 effects Effects 0.000 description 17
- 206010028980 Neoplasm Diseases 0.000 description 14
- 229940079593 drug Drugs 0.000 description 13
- 230000002195 synergetic effect Effects 0.000 description 13
- 239000000499 gel Substances 0.000 description 12
- 230000001225 therapeutic effect Effects 0.000 description 9
- 230000006907 apoptotic process Effects 0.000 description 7
- 238000012360 testing method Methods 0.000 description 7
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 6
- 208000032791 BCR-ABL1 positive chronic myelogenous leukemia Diseases 0.000 description 6
- 230000001965 increasing effect Effects 0.000 description 6
- 208000010833 Chronic myeloid leukaemia Diseases 0.000 description 5
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 5
- 208000033761 Myelogenous Chronic BCR-ABL Positive Leukemia Diseases 0.000 description 5
- 230000005889 cellular cytotoxicity Effects 0.000 description 5
- 230000000875 corresponding effect Effects 0.000 description 5
- 239000002552 dosage form Substances 0.000 description 5
- 230000005764 inhibitory process Effects 0.000 description 5
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 4
- 230000009286 beneficial effect Effects 0.000 description 4
- 238000002474 experimental method Methods 0.000 description 4
- 238000000338 in vitro Methods 0.000 description 4
- 239000012139 lysis buffer Substances 0.000 description 4
- 239000000463 material Substances 0.000 description 4
- 239000012528 membrane Substances 0.000 description 4
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 4
- 238000002560 therapeutic procedure Methods 0.000 description 4
- 208000032800 BCR-ABL1 positive blast phase chronic myelogenous leukemia Diseases 0.000 description 3
- 208000004860 Blast Crisis Diseases 0.000 description 3
- 102000004190 Enzymes Human genes 0.000 description 3
- 108090000790 Enzymes Proteins 0.000 description 3
- 206010051066 Gastrointestinal stromal tumour Diseases 0.000 description 3
- 239000000020 Nitrocellulose Substances 0.000 description 3
- DBMJMQXJHONAFJ-UHFFFAOYSA-M Sodium laurylsulphate Chemical compound [Na+].CCCCCCCCCCCCOS([O-])(=O)=O DBMJMQXJHONAFJ-UHFFFAOYSA-M 0.000 description 3
- 239000002253 acid Substances 0.000 description 3
- 230000009471 action Effects 0.000 description 3
- 239000000654 additive Substances 0.000 description 3
- 230000000996 additive effect Effects 0.000 description 3
- 230000001028 anti-proliverative effect Effects 0.000 description 3
- 230000008901 benefit Effects 0.000 description 3
- 230000004663 cell proliferation Effects 0.000 description 3
- 230000001413 cellular effect Effects 0.000 description 3
- 239000003153 chemical reaction reagent Substances 0.000 description 3
- 239000003795 chemical substances by application Substances 0.000 description 3
- 102000006735 deoxyhypusine hydroxylase Human genes 0.000 description 3
- 108010028753 deoxyhypusine hydroxylase Proteins 0.000 description 3
- 238000011161 development Methods 0.000 description 3
- 239000000284 extract Substances 0.000 description 3
- 238000000684 flow cytometry Methods 0.000 description 3
- 201000011243 gastrointestinal stromal tumor Diseases 0.000 description 3
- BZUIJMCJNWUGKQ-BDAKNGLRSA-N hypusine Chemical compound NCC[C@@H](O)CNCCCC[C@H](N)C(O)=O BZUIJMCJNWUGKQ-BDAKNGLRSA-N 0.000 description 3
- 230000006164 hypusine formation Effects 0.000 description 3
- 238000001727 in vivo Methods 0.000 description 3
- 230000007246 mechanism Effects 0.000 description 3
- 229920001220 nitrocellulos Polymers 0.000 description 3
- 210000004940 nucleus Anatomy 0.000 description 3
- 230000001105 regulatory effect Effects 0.000 description 3
- BOLDJAUMGUJJKM-LSDHHAIUSA-N renifolin D Natural products CC(=C)[C@@H]1Cc2c(O)c(O)ccc2[C@H]1CC(=O)c3ccc(O)cc3O BOLDJAUMGUJJKM-LSDHHAIUSA-N 0.000 description 3
- 238000002415 sodium dodecyl sulfate polyacrylamide gel electrophoresis Methods 0.000 description 3
- 239000000126 substance Substances 0.000 description 3
- 238000011269 treatment regimen Methods 0.000 description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 3
- AZKSAVLVSZKNRD-UHFFFAOYSA-M 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide Chemical compound [Br-].S1C(C)=C(C)N=C1[N+]1=NC(C=2C=CC=CC=2)=NN1C1=CC=CC=C1 AZKSAVLVSZKNRD-UHFFFAOYSA-M 0.000 description 2
- OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 2
- HRPVXLWXLXDGHG-UHFFFAOYSA-N Acrylamide Chemical compound NC(=O)C=C HRPVXLWXLXDGHG-UHFFFAOYSA-N 0.000 description 2
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 2
- 102000048231 Deoxyhypusine synthases Human genes 0.000 description 2
- 108700023218 Deoxyhypusine synthases Proteins 0.000 description 2
- 238000002965 ELISA Methods 0.000 description 2
- 102000006992 Interferon-alpha Human genes 0.000 description 2
- 108010047761 Interferon-alpha Proteins 0.000 description 2
- 231100000002 MTT assay Toxicity 0.000 description 2
- 238000000134 MTT assay Methods 0.000 description 2
- 241000283973 Oryctolagus cuniculus Species 0.000 description 2
- 108091008606 PDGF receptors Proteins 0.000 description 2
- 102000011653 Platelet-Derived Growth Factor Receptors Human genes 0.000 description 2
- 102000016971 Proto-Oncogene Proteins c-kit Human genes 0.000 description 2
- 108010014608 Proto-Oncogene Proteins c-kit Proteins 0.000 description 2
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 2
- 231100000230 acceptable toxicity Toxicity 0.000 description 2
- 230000001154 acute effect Effects 0.000 description 2
- 235000001014 amino acid Nutrition 0.000 description 2
- 150000001413 amino acids Chemical class 0.000 description 2
- 238000004458 analytical method Methods 0.000 description 2
- 230000001640 apoptogenic effect Effects 0.000 description 2
- 238000013459 approach Methods 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 230000000903 blocking effect Effects 0.000 description 2
- 201000011510 cancer Diseases 0.000 description 2
- 230000010261 cell growth Effects 0.000 description 2
- 239000002738 chelating agent Substances 0.000 description 2
- 230000007423 decrease Effects 0.000 description 2
- PGPFBXMCOQNMJO-VIFPVBQESA-N deoxyhypusine Chemical compound NCCCCNCCCC[C@H](N)C(O)=O PGPFBXMCOQNMJO-VIFPVBQESA-N 0.000 description 2
- 238000013461 design Methods 0.000 description 2
- 238000001962 electrophoresis Methods 0.000 description 2
- 238000011156 evaluation Methods 0.000 description 2
- 239000012894 fetal calf serum Substances 0.000 description 2
- 235000019253 formic acid Nutrition 0.000 description 2
- 239000012634 fragment Substances 0.000 description 2
- 238000001502 gel electrophoresis Methods 0.000 description 2
- 230000012010 growth Effects 0.000 description 2
- 239000000543 intermediate Substances 0.000 description 2
- 150000002500 ions Chemical class 0.000 description 2
- 229910052742 iron Inorganic materials 0.000 description 2
- 238000001155 isoelectric focusing Methods 0.000 description 2
- 210000004698 lymphocyte Anatomy 0.000 description 2
- 239000006166 lysate Substances 0.000 description 2
- 125000003588 lysine group Chemical group [H]N([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])(N([H])[H])C(*)=O 0.000 description 2
- 230000003211 malignant effect Effects 0.000 description 2
- 239000011159 matrix material Substances 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- VMGAPWLDMVPYIA-HIDZBRGKSA-N n'-amino-n-iminomethanimidamide Chemical compound N\N=C\N=N VMGAPWLDMVPYIA-HIDZBRGKSA-N 0.000 description 2
- 208000002154 non-small cell lung carcinoma Diseases 0.000 description 2
- 238000007911 parenteral administration Methods 0.000 description 2
- YBYRMVIVWMBXKQ-UHFFFAOYSA-N phenylmethanesulfonyl fluoride Chemical compound FS(=O)(=O)CC1=CC=CC=C1 YBYRMVIVWMBXKQ-UHFFFAOYSA-N 0.000 description 2
- 210000004214 philadelphia chromosome Anatomy 0.000 description 2
- 229920000136 polysorbate Polymers 0.000 description 2
- 238000010837 poor prognosis Methods 0.000 description 2
- 239000002243 precursor Substances 0.000 description 2
- 230000035755 proliferation Effects 0.000 description 2
- 230000022983 regulation of cell cycle Effects 0.000 description 2
- 238000012216 screening Methods 0.000 description 2
- 239000006228 supernatant Substances 0.000 description 2
- 238000010998 test method Methods 0.000 description 2
- 208000029729 tumor suppressor gene on chromosome 11 Diseases 0.000 description 2
- 238000005406 washing Methods 0.000 description 2
- QAPSNMNOIOSXSQ-YNEHKIRRSA-N 1-[(2r,4s,5r)-4-[tert-butyl(dimethyl)silyl]oxy-5-(hydroxymethyl)oxolan-2-yl]-5-methylpyrimidine-2,4-dione Chemical compound O=C1NC(=O)C(C)=CN1[C@@H]1O[C@H](CO)[C@@H](O[Si](C)(C)C(C)(C)C)C1 QAPSNMNOIOSXSQ-YNEHKIRRSA-N 0.000 description 1
- YAOAMZOGXBMLFQ-UHFFFAOYSA-N 2-(7-aminoheptyl)guanidine Chemical compound NCCCCCCCN=C(N)N YAOAMZOGXBMLFQ-UHFFFAOYSA-N 0.000 description 1
- KPKQWXGFEKRQQA-UHFFFAOYSA-N 3,5-diphenyl-1h-1,2,4-triazole Chemical class C1=CC=CC=C1C1=NNC(C=2C=CC=CC=2)=N1 KPKQWXGFEKRQQA-UHFFFAOYSA-N 0.000 description 1
- 125000004042 4-aminobutyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])N([H])[H] 0.000 description 1
- 229920000936 Agarose Polymers 0.000 description 1
- 201000001320 Atherosclerosis Diseases 0.000 description 1
- 238000009020 BCA Protein Assay Kit Methods 0.000 description 1
- 206010005003 Bladder cancer Diseases 0.000 description 1
- 206010006187 Breast cancer Diseases 0.000 description 1
- 208000026310 Breast neoplasm Diseases 0.000 description 1
- 201000009030 Carcinoma Diseases 0.000 description 1
- UHDGCWIWMRVCDJ-CCXZUQQUSA-N Cytarabine Chemical compound O=C1N=C(N)C=CN1[C@H]1[C@@H](O)[C@H](O)[C@@H](CO)O1 UHDGCWIWMRVCDJ-CCXZUQQUSA-N 0.000 description 1
- KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 1
- 206010016654 Fibrosis Diseases 0.000 description 1
- 208000017604 Hodgkin disease Diseases 0.000 description 1
- 208000010747 Hodgkins lymphoma Diseases 0.000 description 1
- 101000716729 Homo sapiens Kit ligand Proteins 0.000 description 1
- 206010020843 Hyperthermia Diseases 0.000 description 1
- 238000012404 In vitro experiment Methods 0.000 description 1
- 206010065973 Iron Overload Diseases 0.000 description 1
- 208000007766 Kaposi sarcoma Diseases 0.000 description 1
- XUJNEKJLAYXESH-REOHCLBHSA-N L-Cysteine Chemical compound SC[C@H](N)C(O)=O XUJNEKJLAYXESH-REOHCLBHSA-N 0.000 description 1
- FFEARJCKVFRZRR-BYPYZUCNSA-N L-methionine Chemical compound CSCC[C@H](N)C(O)=O FFEARJCKVFRZRR-BYPYZUCNSA-N 0.000 description 1
- 206010058467 Lung neoplasm malignant Diseases 0.000 description 1
- 241000124008 Mammalia Species 0.000 description 1
- 208000031888 Mycoses Diseases 0.000 description 1
- 208000014767 Myeloproliferative disease Diseases 0.000 description 1
- 208000003788 Neoplasm Micrometastasis Diseases 0.000 description 1
- 108700020796 Oncogene Proteins 0.000 description 1
- 208000032721 Philadelphia Chromosome Diseases 0.000 description 1
- 101710164680 Platelet-derived growth factor receptor beta Proteins 0.000 description 1
- 206010060862 Prostate cancer Diseases 0.000 description 1
- 208000000236 Prostatic Neoplasms Diseases 0.000 description 1
- 102000001708 Protein Isoforms Human genes 0.000 description 1
- 108010029485 Protein Isoforms Proteins 0.000 description 1
- 102000004022 Protein-Tyrosine Kinases Human genes 0.000 description 1
- 108090000412 Protein-Tyrosine Kinases Proteins 0.000 description 1
- 201000004681 Psoriasis Diseases 0.000 description 1
- 239000012980 RPMI-1640 medium Substances 0.000 description 1
- 206010041067 Small cell lung cancer Diseases 0.000 description 1
- 208000007536 Thrombosis Diseases 0.000 description 1
- 102000004142 Trypsin Human genes 0.000 description 1
- 108090000631 Trypsin Proteins 0.000 description 1
- 208000007097 Urinary Bladder Neoplasms Diseases 0.000 description 1
- 208000008385 Urogenital Neoplasms Diseases 0.000 description 1
- 102000003970 Vinculin Human genes 0.000 description 1
- 108090000384 Vinculin Proteins 0.000 description 1
- 238000002835 absorbance Methods 0.000 description 1
- 230000001133 acceleration Effects 0.000 description 1
- 239000013543 active substance Substances 0.000 description 1
- 230000002411 adverse Effects 0.000 description 1
- 230000037354 amino acid metabolism Effects 0.000 description 1
- 230000001093 anti-cancer Effects 0.000 description 1
- 230000000843 anti-fungal effect Effects 0.000 description 1
- 229940121375 antifungal agent Drugs 0.000 description 1
- 239000003429 antifungal agent Substances 0.000 description 1
- 239000012298 atmosphere Substances 0.000 description 1
- 108010056708 bcr-abl Fusion Proteins Proteins 0.000 description 1
- 102000004441 bcr-abl Fusion Proteins Human genes 0.000 description 1
- 230000008827 biological function Effects 0.000 description 1
- 230000033228 biological regulation Effects 0.000 description 1
- 230000037396 body weight Effects 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 239000004202 carbamide Substances 0.000 description 1
- 238000004113 cell culture Methods 0.000 description 1
- 230000025084 cell cycle arrest Effects 0.000 description 1
- 230000006037 cell lysis Effects 0.000 description 1
- 230000003833 cell viability Effects 0.000 description 1
- 238000005119 centrifugation Methods 0.000 description 1
- 238000012512 characterization method Methods 0.000 description 1
- 210000000349 chromosome Anatomy 0.000 description 1
- 230000001684 chronic effect Effects 0.000 description 1
- 208000029742 colonic neoplasm Diseases 0.000 description 1
- 238000002648 combination therapy Methods 0.000 description 1
- 238000010835 comparative analysis Methods 0.000 description 1
- 230000006552 constitutive activation Effects 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 238000002425 crystallisation Methods 0.000 description 1
- 230000008025 crystallization Effects 0.000 description 1
- 235000018417 cysteine Nutrition 0.000 description 1
- XUJNEKJLAYXESH-UHFFFAOYSA-N cysteine Natural products SCC(N)C(O)=O XUJNEKJLAYXESH-UHFFFAOYSA-N 0.000 description 1
- 230000003436 cytoskeletal effect Effects 0.000 description 1
- 230000001419 dependent effect Effects 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 230000029087 digestion Effects 0.000 description 1
- 239000008298 dragée Substances 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 238000001378 electrochemiluminescence detection Methods 0.000 description 1
- 238000000132 electrospray ionisation Methods 0.000 description 1
- 238000002101 electrospray ionisation tandem mass spectrometry Methods 0.000 description 1
- 230000002708 enhancing effect Effects 0.000 description 1
- 238000011067 equilibration Methods 0.000 description 1
- 238000010195 expression analysis Methods 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 230000004761 fibrosis Effects 0.000 description 1
- 210000001650 focal adhesion Anatomy 0.000 description 1
- 230000006870 function Effects 0.000 description 1
- 210000001035 gastrointestinal tract Anatomy 0.000 description 1
- 229940080856 gleevec Drugs 0.000 description 1
- PCHJSUWPFVWCPO-UHFFFAOYSA-N gold Chemical compound [Au] PCHJSUWPFVWCPO-UHFFFAOYSA-N 0.000 description 1
- 230000009036 growth inhibition Effects 0.000 description 1
- 201000010536 head and neck cancer Diseases 0.000 description 1
- 208000014829 head and neck neoplasm Diseases 0.000 description 1
- 102000055151 human KITLG Human genes 0.000 description 1
- 230000033444 hydroxylation Effects 0.000 description 1
- 238000005805 hydroxylation reaction Methods 0.000 description 1
- 230000036031 hyperthermia Effects 0.000 description 1
- 238000003119 immunoblot Methods 0.000 description 1
- 238000011534 incubation Methods 0.000 description 1
- 230000006882 induction of apoptosis Effects 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 230000000977 initiatory effect Effects 0.000 description 1
- 230000003993 interaction Effects 0.000 description 1
- 239000002050 international nonproprietary name Substances 0.000 description 1
- 230000004068 intracellular signaling Effects 0.000 description 1
- 230000003907 kidney function Effects 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 230000003908 liver function Effects 0.000 description 1
- 201000005202 lung cancer Diseases 0.000 description 1
- 208000020816 lung neoplasm Diseases 0.000 description 1
- 230000002934 lysing effect Effects 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 238000004949 mass spectrometry Methods 0.000 description 1
- 238000001819 mass spectrum Methods 0.000 description 1
- 238000001906 matrix-assisted laser desorption--ionisation mass spectrometry Methods 0.000 description 1
- 238000001840 matrix-assisted laser desorption--ionisation time-of-flight mass spectrometry Methods 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 201000001441 melanoma Diseases 0.000 description 1
- 108020004999 messenger RNA Proteins 0.000 description 1
- 230000001394 metastastic effect Effects 0.000 description 1
- 206010061289 metastatic neoplasm Diseases 0.000 description 1
- 229930182817 methionine Natural products 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 238000010369 molecular cloning Methods 0.000 description 1
- 125000000896 monocarboxylic acid group Chemical group 0.000 description 1
- 208000025113 myeloid leukemia Diseases 0.000 description 1
- 230000030147 nuclear export Effects 0.000 description 1
- 230000012223 nuclear import Effects 0.000 description 1
- 230000008520 organization Effects 0.000 description 1
- 230000002611 ovarian Effects 0.000 description 1
- 230000003647 oxidation Effects 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- 238000000955 peptide mass fingerprinting Methods 0.000 description 1
- 239000000825 pharmaceutical preparation Substances 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 230000026731 phosphorylation Effects 0.000 description 1
- 238000006366 phosphorylation reaction Methods 0.000 description 1
- 239000000902 placebo Substances 0.000 description 1
- 229940068196 placebo Drugs 0.000 description 1
- 229920002401 polyacrylamide Polymers 0.000 description 1
- 230000004481 post-translational protein modification Effects 0.000 description 1
- 230000001323 posttranslational effect Effects 0.000 description 1
- 238000011533 pre-incubation Methods 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- 108090000765 processed proteins & peptides Proteins 0.000 description 1
- 239000000651 prodrug Substances 0.000 description 1
- 229940002612 prodrug Drugs 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 230000002035 prolonged effect Effects 0.000 description 1
- XJMOSONTPMZWPB-UHFFFAOYSA-M propidium iodide Chemical compound [I-].[I-].C12=CC(N)=CC=C2C2=CC=C(N)C=C2[N+](CCC[N+](C)(CC)CC)=C1C1=CC=CC=C1 XJMOSONTPMZWPB-UHFFFAOYSA-M 0.000 description 1
- 210000002307 prostate Anatomy 0.000 description 1
- 238000000751 protein extraction Methods 0.000 description 1
- 238000001799 protein solubilization Methods 0.000 description 1
- 230000007925 protein solubilization Effects 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 239000008213 purified water Substances 0.000 description 1
- 230000004144 purine metabolism Effects 0.000 description 1
- GGOZGYRTNQBSSA-UHFFFAOYSA-N pyridine-2,3-diol Chemical class OC1=CC=CN=C1O GGOZGYRTNQBSSA-UHFFFAOYSA-N 0.000 description 1
- 230000008707 rearrangement Effects 0.000 description 1
- 102000005962 receptors Human genes 0.000 description 1
- 108020003175 receptors Proteins 0.000 description 1
- 230000011514 reflex Effects 0.000 description 1
- 230000004044 response Effects 0.000 description 1
- 208000037803 restenosis Diseases 0.000 description 1
- 239000000523 sample Substances 0.000 description 1
- 239000012723 sample buffer Substances 0.000 description 1
- 238000012163 sequencing technique Methods 0.000 description 1
- 230000011664 signaling Effects 0.000 description 1
- 238000009097 single-agent therapy Methods 0.000 description 1
- 208000000587 small cell lung carcinoma Diseases 0.000 description 1
- NLJMYIDDQXHKNR-UHFFFAOYSA-K sodium citrate Chemical compound O.O.[Na+].[Na+].[Na+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O NLJMYIDDQXHKNR-UHFFFAOYSA-K 0.000 description 1
- 239000001509 sodium citrate Substances 0.000 description 1
- 239000000243 solution Substances 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 239000011550 stock solution Substances 0.000 description 1
- 239000007940 sugar coated tablet Substances 0.000 description 1
- 238000009495 sugar coating Methods 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 238000011477 surgical intervention Methods 0.000 description 1
- 230000004083 survival effect Effects 0.000 description 1
- 230000002459 sustained effect Effects 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- 238000004885 tandem mass spectrometry Methods 0.000 description 1
- 210000001550 testis Anatomy 0.000 description 1
- 125000003831 tetrazolyl group Chemical group 0.000 description 1
- 210000001519 tissue Anatomy 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 238000012546 transfer Methods 0.000 description 1
- 238000013519 translation Methods 0.000 description 1
- 230000032258 transport Effects 0.000 description 1
- 239000012588 trypsin Substances 0.000 description 1
- 229940121358 tyrosine kinase inhibitor Drugs 0.000 description 1
- 239000005483 tyrosine kinase inhibitor Substances 0.000 description 1
- 150000004917 tyrosine kinase inhibitor derivatives Chemical class 0.000 description 1
- 125000001493 tyrosinyl group Chemical group [H]OC1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])(N([H])[H])C(*)=O 0.000 description 1
- 230000003827 upregulation Effects 0.000 description 1
- 201000005112 urinary bladder cancer Diseases 0.000 description 1
- 238000012795 verification Methods 0.000 description 1
- 238000001262 western blot Methods 0.000 description 1
- AFVLVVWMAFSXCK-UHFFFAOYSA-N α-cyano-4-hydroxycinnamic acid Chemical compound OC(=O)C(C#N)=CC1=CC=C(O)C=C1 AFVLVVWMAFSXCK-UHFFFAOYSA-N 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
- A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- 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
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
-
- 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
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
- A61P17/02—Drugs for dermatological disorders for treating wounds, ulcers, burns, scars, keloids, or the like
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
- A61P17/06—Antipsoriatics
-
- 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
-
- 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
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
- A61P7/02—Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Medicinal Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Chemical & Material Sciences (AREA)
- Public Health (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Organic Chemistry (AREA)
- Epidemiology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Dermatology (AREA)
- Oncology (AREA)
- Hematology (AREA)
- Heart & Thoracic Surgery (AREA)
- Diabetes (AREA)
- Cardiology (AREA)
- Vascular Medicine (AREA)
- Urology & Nephrology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Plural Heterocyclic Compounds (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US53156303P | 2003-12-19 | 2003-12-19 | |
| US60/531,563 | 2003-12-19 | ||
| PCT/EP2004/014439 WO2005058320A1 (en) | 2003-12-19 | 2004-12-17 | COMBINATION OF (a) N-{5-[4-(4-METHYL-PIPERAZINO-METHYL)-BENZOYLAMIDO]-2METHYLPHENYL}-4-(3-PYRIDYL)-2-PYRIMIDINE-AMINE AND (b) AT LEAST ONE HYPUSINATION INHIBITOR AND THE USE THEREOF |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA2547196A1 true CA2547196A1 (en) | 2005-06-30 |
Family
ID=34700180
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA002547196A Abandoned CA2547196A1 (en) | 2003-12-19 | 2004-12-17 | Combination of (a) n-{5-[4-(4-methyl-piperazino-methyl)-benzoylamido]-2methylphenyl}-4-(3-pyridyl)-2-pyrimidine-amine and (b) at least one hypusination inhibitor and the use thereof |
Country Status (17)
| Country | Link |
|---|---|
| US (1) | US20080139480A1 (enExample) |
| EP (1) | EP1696917A1 (enExample) |
| JP (1) | JP2007514699A (enExample) |
| KR (1) | KR20060125810A (enExample) |
| CN (1) | CN1889952A (enExample) |
| AU (2) | AU2004298761A1 (enExample) |
| BR (1) | BRPI0417759A (enExample) |
| CA (1) | CA2547196A1 (enExample) |
| EC (1) | ECSP066656A (enExample) |
| IL (1) | IL176070A0 (enExample) |
| MA (1) | MA28240A1 (enExample) |
| MX (1) | MXPA06006925A (enExample) |
| NO (1) | NO20063326L (enExample) |
| RU (1) | RU2006125741A (enExample) |
| TN (1) | TNSN06182A1 (enExample) |
| WO (1) | WO2005058320A1 (enExample) |
| ZA (1) | ZA200603904B (enExample) |
Families Citing this family (10)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| PL2197440T3 (pl) | 2007-08-31 | 2013-05-31 | Janssen Pharmaceutica Nv | Kombinacje imazalilu i hydroksypirydonów |
| WO2009036753A2 (de) * | 2007-09-20 | 2009-03-26 | Schebo Biotech Ag | Neue pharmazeutika, verfahren zu ihrer herstellung und ihre verwendung in der medizinischen therapie |
| WO2009098243A1 (en) * | 2008-02-06 | 2009-08-13 | Janssen Pharmaceutica Nv | Combinations of anilinopyrimidines and pyrion compounds |
| WO2009098245A2 (en) | 2008-02-06 | 2009-08-13 | Janssen Pharmaceutica Nv | Combinations of phenylpyrroles and pyrion compounds |
| WO2010048712A1 (en) * | 2008-10-31 | 2010-05-06 | University Health Network | Ciclopirox and cytarabine for the treatment of leukemic disorders |
| CN104926722A (zh) * | 2010-06-01 | 2015-09-23 | 拜欧赛里克斯公司 | 羟基吡啶酮衍生物、其药物组合物及其用于治疗增生性疾病的治疗用途 |
| MX342465B (es) * | 2010-06-01 | 2016-09-30 | Biotheryx Inc * | Metodos para tratar enfermedades hematologicas usando 6-ciclohexil-1-hidroxi-4-metil-2(1h)-piridona. |
| EP2579718B1 (en) | 2010-06-10 | 2014-10-01 | Janssen Pharmaceutica, N.V. | Combinations of pyrimethanil and monoterpenes |
| JP5870101B2 (ja) | 2010-07-01 | 2016-02-24 | ジヤンセン・フアーマシユーチカ・ナームローゼ・フエンノートシヤツプＪａｎｓｓｅｎ Ｐｈａｒｍａｃｅｕｔｉｃａ Ｎａａｍｌｏｚｅ Ｖｅｎｎｏｏｔｓｃｈａｐ | ピリオン化合物とポリエチレンイミンとの抗微生物性組み合わせ |
| CN103191110A (zh) * | 2013-03-28 | 2013-07-10 | 中国科学院昆明植物研究所 | 环吡酮及环吡酮胺在制备防治黑色素瘤的药物中的应用 |
Family Cites Families (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB8528983D0 (en) * | 1985-11-25 | 1986-01-02 | Ciba Geigy Ag | Use of chelating agents |
| EP0227593A1 (en) * | 1985-11-25 | 1987-07-01 | The Hospital For Sick Children | Use of chelating agents |
| TW533205B (en) * | 1996-06-25 | 2003-05-21 | Novartis Ag | Substituted 3,5-diphenyl-l,2,4-triazoles and their pharmaceutical composition |
| ES2331562T3 (es) * | 2001-03-23 | 2010-01-08 | Enzon, Inc. | Profarmacos de agentes anticancerigenos que emplean acidos aromaticos sustituidos. |
| WO2004007676A2 (en) * | 2002-07-15 | 2004-01-22 | Combinatorx, Incorporated | Combination therapy for the treatment of neoplasms |
-
2004
- 2004-12-17 JP JP2006544368A patent/JP2007514699A/ja active Pending
- 2004-12-17 CN CNA2004800362740A patent/CN1889952A/zh active Pending
- 2004-12-17 US US10/583,107 patent/US20080139480A1/en not_active Abandoned
- 2004-12-17 BR BRPI0417759-2A patent/BRPI0417759A/pt not_active IP Right Cessation
- 2004-12-17 EP EP04804040A patent/EP1696917A1/en not_active Withdrawn
- 2004-12-17 RU RU2006125741/14A patent/RU2006125741A/ru not_active Application Discontinuation
- 2004-12-17 AU AU2004298761A patent/AU2004298761A1/en not_active Abandoned
- 2004-12-17 KR KR1020067012061A patent/KR20060125810A/ko not_active Withdrawn
- 2004-12-17 MX MXPA06006925A patent/MXPA06006925A/es not_active Application Discontinuation
- 2004-12-17 CA CA002547196A patent/CA2547196A1/en not_active Abandoned
- 2004-12-17 WO PCT/EP2004/014439 patent/WO2005058320A1/en not_active Ceased
-
2006
- 2006-05-16 ZA ZA200603904A patent/ZA200603904B/en unknown
- 2006-05-31 IL IL176070A patent/IL176070A0/en unknown
- 2006-06-15 TN TNP2006000182A patent/TNSN06182A1/en unknown
- 2006-06-19 EC EC2006006656A patent/ECSP066656A/es unknown
- 2006-06-26 MA MA29141A patent/MA28240A1/fr unknown
- 2006-07-18 NO NO20063326A patent/NO20063326L/no not_active Application Discontinuation
-
2009
- 2009-04-28 AU AU2009201694A patent/AU2009201694A1/en not_active Abandoned
Also Published As
| Publication number | Publication date |
|---|---|
| AU2009201694A1 (en) | 2009-05-28 |
| WO2005058320A1 (en) | 2005-06-30 |
| MA28240A1 (fr) | 2006-10-02 |
| IL176070A0 (en) | 2006-10-05 |
| BRPI0417759A (pt) | 2007-04-10 |
| NO20063326L (no) | 2006-09-19 |
| ECSP066656A (es) | 2006-10-25 |
| ZA200603904B (en) | 2007-09-26 |
| MXPA06006925A (es) | 2006-08-23 |
| TNSN06182A1 (en) | 2007-11-15 |
| RU2006125741A (ru) | 2008-01-27 |
| EP1696917A1 (en) | 2006-09-06 |
| JP2007514699A (ja) | 2007-06-07 |
| KR20060125810A (ko) | 2006-12-06 |
| AU2004298761A1 (en) | 2005-06-30 |
| CN1889952A (zh) | 2007-01-03 |
| US20080139480A1 (en) | 2008-06-12 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| AU2009201694A1 (en) | Combination of (a) N-{5-[4-(4-methyl-piperazino-methyl)-benzoylamido]-2-methylphenyl}-4-(3-pyridyl)-2-pyrimidine-amine and (b) at least one hypusination inhibitor and the use thereof | |
| Cicenas et al. | Roscovitine in cancer and other diseases | |
| US11938124B2 (en) | Combination therapy for treatment of cancer | |
| JP6532878B2 (ja) | 組合せ医薬 | |
| EP1250140B1 (en) | Combination ofan abl-, pdgf-receptor- and/or kit receptor-tyrosine kinase inhibitor with an organic compound capable of binding to alpha1-acidic glycoprotein | |
| US11786500B2 (en) | Glutaminase inhibitor therapy | |
| Lara Jr et al. | The cyclin-dependent kinase inhibitor UCN-01 plus cisplatin in advanced solid tumors: a California cancer consortium phase I pharmacokinetic and molecular correlative trial | |
| CN116019921A (zh) | 用于治疗癌症的组合疗法 | |
| Patel et al. | Albendazole sensitizes cancer cells to ionizing radiation | |
| WO2013152342A1 (en) | Anti-cancer mtor inhibitor and anti-androgen combination | |
| US20220098196A1 (en) | Trapping-free parp inhibitors | |
| US20190000850A1 (en) | Combination cancer therapy | |
| CN114246864B (zh) | Csf1r激酶抑制剂及其用途 | |
| JP2025098099A (ja) | ブルトン型チロシンキナーゼ阻害剤の投薬 | |
| KR20240004548A (ko) | 암 치료를 위한 pcna 억제제 및 egfr 억제제 | |
| JP2008542253A (ja) | Ｄｎａ損傷癌療法に対してａｔｍ欠損癌を感作するためのｄｎａ−ｐｋ阻害の使用 | |
| US7045523B2 (en) | Combination comprising N-{5-[4-(4-methyl-piperazino-methyl)-benzoylamido]-2-methylphenyl}-4-(3-pyridyl)-2-pyrimidine-amine and telomerase inhibitor | |
| US12383557B2 (en) | Treatment of cancer using combination therapies comprising GDC-6036 and GDC-0077 | |
| JP2009504674A (ja) | 有機化合物の組合せ | |
| Ahmad et al. | Venetoclax (Venclexta): A BCL‐2 Antagonist for Treating Chronic Lymphocytic Leukemia | |
| HK40007742A (en) | Pharmaceutical combinations for the treatment of cancer |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| FZDE | Discontinued |