JP2011507880A - 慢性リンパ性白血病の処置のためのニロチニブとナイトロジェンマスタードの組み合わせ剤 - Google Patents
慢性リンパ性白血病の処置のためのニロチニブとナイトロジェンマスタードの組み合わせ剤 Download PDFInfo
- Publication number
- JP2011507880A JP2011507880A JP2010539775A JP2010539775A JP2011507880A JP 2011507880 A JP2011507880 A JP 2011507880A JP 2010539775 A JP2010539775 A JP 2010539775A JP 2010539775 A JP2010539775 A JP 2010539775A JP 2011507880 A JP2011507880 A JP 2011507880A
- Authority
- JP
- Japan
- Prior art keywords
- combination
- combination according
- nilotinib
- nitrogen mustard
- cll
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
- 208000010839 B-cell chronic lymphocytic leukemia Diseases 0.000 title claims description 51
- 208000031422 Lymphocytic Chronic B-Cell Leukemia Diseases 0.000 title claims description 40
- 208000032852 chronic lymphocytic leukemia Diseases 0.000 title claims description 40
- 238000011282 treatment Methods 0.000 title claims description 23
- HAWPXGHAZFHHAD-UHFFFAOYSA-N mechlorethamine Chemical class ClCCN(C)CCCl HAWPXGHAZFHHAD-UHFFFAOYSA-N 0.000 title claims description 16
- 239000005536 L01XE08 - Nilotinib Substances 0.000 title abstract description 41
- 229960001346 nilotinib Drugs 0.000 title abstract description 41
- HHZIURLSWUIHRB-UHFFFAOYSA-N nilotinib Chemical compound C1=NC(C)=CN1C1=CC(NC(=O)C=2C=C(NC=3N=C(C=CN=3)C=3C=NC=CC=3)C(C)=CC=2)=CC(C(F)(F)F)=C1 HHZIURLSWUIHRB-UHFFFAOYSA-N 0.000 title abstract description 41
- 229960004961 mechlorethamine Drugs 0.000 title description 3
- KXDAEFPNCMNJSK-UHFFFAOYSA-N Benzamide Chemical compound NC(=O)C1=CC=CC=C1 KXDAEFPNCMNJSK-UHFFFAOYSA-N 0.000 claims abstract description 15
- 239000003814 drug Substances 0.000 claims abstract description 14
- 238000000034 method Methods 0.000 claims abstract description 12
- KPCZJLGGXRGYIE-UHFFFAOYSA-N [C]1=CC=CN=C1 Chemical group [C]1=CC=CN=C1 KPCZJLGGXRGYIE-UHFFFAOYSA-N 0.000 claims abstract description 10
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims abstract description 10
- 239000012623 DNA damaging agent Substances 0.000 claims abstract description 9
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 8
- 241001465754 Metazoa Species 0.000 claims abstract description 7
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims abstract description 7
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims abstract description 7
- 239000003937 drug carrier Substances 0.000 claims abstract description 6
- 238000004519 manufacturing process Methods 0.000 claims abstract description 6
- 229960004630 chlorambucil Drugs 0.000 claims description 59
- JCKYGMPEJWAADB-UHFFFAOYSA-N chlorambucil Chemical compound OC(=O)CCCC1=CC=C(N(CCCl)CCCl)C=C1 JCKYGMPEJWAADB-UHFFFAOYSA-N 0.000 claims description 59
- 239000004480 active ingredient Substances 0.000 claims description 18
- -1 chlornafazine Chemical compound 0.000 claims description 14
- 150000003839 salts Chemical group 0.000 claims description 14
- CMSMOCZEIVJLDB-UHFFFAOYSA-N Cyclophosphamide Chemical compound ClCCN(CCCl)P1(=O)NCCCO1 CMSMOCZEIVJLDB-UHFFFAOYSA-N 0.000 claims description 10
- IDPUKCWIGUEADI-UHFFFAOYSA-N 5-[bis(2-chloroethyl)amino]uracil Chemical compound ClCCN(CCCl)C1=CNC(=O)NC1=O IDPUKCWIGUEADI-UHFFFAOYSA-N 0.000 claims description 9
- 229960004397 cyclophosphamide Drugs 0.000 claims description 9
- 229960001055 uracil mustard Drugs 0.000 claims description 9
- 229960000390 fludarabine Drugs 0.000 claims description 7
- GIUYCYHIANZCFB-FJFJXFQQSA-N fludarabine phosphate Chemical group 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 claims description 7
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 5
- 229960002707 bendamustine Drugs 0.000 claims description 5
- YTKUWDBFDASYHO-UHFFFAOYSA-N bendamustine Chemical compound ClCCN(CCCl)C1=CC=C2N(C)C(CCCC(O)=O)=NC2=C1 YTKUWDBFDASYHO-UHFFFAOYSA-N 0.000 claims description 5
- FRPJXPJMRWBBIH-RBRWEJTLSA-N estramustine Chemical compound ClCCN(CCCl)C(=O)OC1=CC=C2[C@H]3CC[C@](C)([C@H](CC4)O)[C@@H]4[C@@H]3CCC2=C1 FRPJXPJMRWBBIH-RBRWEJTLSA-N 0.000 claims description 5
- 229960001842 estramustine Drugs 0.000 claims description 5
- 229960000875 trofosfamide Drugs 0.000 claims description 5
- UMKFEPPTGMDVMI-UHFFFAOYSA-N trofosfamide Chemical compound ClCCN(CCCl)P1(=O)OCCCN1CCCl UMKFEPPTGMDVMI-UHFFFAOYSA-N 0.000 claims description 5
- SPJCRMJCFSJKDE-ZWBUGVOYSA-N [(3s,8s,9s,10r,13r,14s,17r)-10,13-dimethyl-17-[(2r)-6-methylheptan-2-yl]-2,3,4,7,8,9,11,12,14,15,16,17-dodecahydro-1h-cyclopenta[a]phenanthren-3-yl] 2-[4-[bis(2-chloroethyl)amino]phenyl]acetate Chemical compound O([C@@H]1CC2=CC[C@H]3[C@@H]4CC[C@@H]([C@]4(CC[C@@H]3[C@@]2(C)CC1)C)[C@H](C)CCCC(C)C)C(=O)CC1=CC=C(N(CCCl)CCCl)C=C1 SPJCRMJCFSJKDE-ZWBUGVOYSA-N 0.000 claims description 4
- 150000001875 compounds Chemical class 0.000 claims description 4
- 229960001924 melphalan Drugs 0.000 claims description 4
- SGDBTWWWUNNDEQ-LBPRGKRZSA-N melphalan Chemical compound OC(=O)[C@@H](N)CC1=CC=C(N(CCCl)CCCl)C=C1 SGDBTWWWUNNDEQ-LBPRGKRZSA-N 0.000 claims description 4
- DKAGJZJALZXOOV-UHFFFAOYSA-N hydrate;hydrochloride Chemical compound O.Cl DKAGJZJALZXOOV-UHFFFAOYSA-N 0.000 claims description 2
- 230000037396 body weight Effects 0.000 claims 1
- 125000002962 imidazol-1-yl group Chemical group [*]N1C([H])=NC([H])=C1[H] 0.000 abstract description 4
- 208000006664 Precursor Cell Lymphoblastic Leukemia-Lymphoma Diseases 0.000 abstract 1
- 230000001684 chronic effect Effects 0.000 abstract 1
- 208000003747 lymphoid leukemia Diseases 0.000 abstract 1
- 238000004806 packaging method and process Methods 0.000 abstract 1
- 210000004698 lymphocyte Anatomy 0.000 description 21
- 239000005517 L01XE01 - Imatinib Substances 0.000 description 19
- KTUFNOKKBVMGRW-UHFFFAOYSA-N imatinib Chemical compound C1CN(C)CCN1CC1=CC=C(C(=O)NC=2C=C(NC=3N=C(C=CN=3)C=3C=NC=CC=3)C(C)=CC=2)C=C1 KTUFNOKKBVMGRW-UHFFFAOYSA-N 0.000 description 19
- 229960002411 imatinib Drugs 0.000 description 18
- 210000004027 cell Anatomy 0.000 description 11
- 230000000694 effects Effects 0.000 description 11
- 229940079593 drug Drugs 0.000 description 9
- 230000002195 synergetic effect Effects 0.000 description 8
- 230000003993 interaction Effects 0.000 description 6
- 231100000002 MTT assay Toxicity 0.000 description 5
- 238000000134 MTT assay Methods 0.000 description 5
- 230000009286 beneficial effect Effects 0.000 description 5
- 201000010099 disease Diseases 0.000 description 5
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 5
- 238000012360 testing method Methods 0.000 description 5
- XLSZMDLNRCVEIJ-UHFFFAOYSA-N 4-methylimidazole Chemical compound CC1=CNC=N1 XLSZMDLNRCVEIJ-UHFFFAOYSA-N 0.000 description 4
- 210000001744 T-lymphocyte Anatomy 0.000 description 4
- 210000003719 b-lymphocyte Anatomy 0.000 description 4
- 231100000135 cytotoxicity Toxicity 0.000 description 4
- 230000003013 cytotoxicity Effects 0.000 description 4
- 208000032839 leukemia Diseases 0.000 description 4
- 230000004083 survival effect Effects 0.000 description 4
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 3
- 230000000996 additive effect Effects 0.000 description 3
- 238000004458 analytical method Methods 0.000 description 3
- 230000000875 corresponding effect Effects 0.000 description 3
- 239000002552 dosage form Substances 0.000 description 3
- 239000003112 inhibitor Substances 0.000 description 3
- 239000000203 mixture Substances 0.000 description 3
- 230000003389 potentiating effect Effects 0.000 description 3
- 150000003212 purines Chemical class 0.000 description 3
- 238000007619 statistical method Methods 0.000 description 3
- 230000001225 therapeutic effect Effects 0.000 description 3
- 206010061818 Disease progression Diseases 0.000 description 2
- 238000000692 Student's t-test Methods 0.000 description 2
- 230000004913 activation Effects 0.000 description 2
- 239000000654 additive Substances 0.000 description 2
- 230000003042 antagnostic effect Effects 0.000 description 2
- 239000003795 chemical substances by application Substances 0.000 description 2
- 229940127089 cytotoxic agent Drugs 0.000 description 2
- 238000002784 cytotoxicity assay Methods 0.000 description 2
- 231100000263 cytotoxicity test Toxicity 0.000 description 2
- 238000009472 formulation Methods 0.000 description 2
- 229960003685 imatinib mesylate Drugs 0.000 description 2
- YLMAHDNUQAMNNX-UHFFFAOYSA-N imatinib methanesulfonate Chemical compound CS(O)(=O)=O.C1CN(C)CCN1CC1=CC=C(C(=O)NC=2C=C(NC=3N=C(C=CN=3)C=3C=NC=CC=3)C(C)=CC=2)C=C1 YLMAHDNUQAMNNX-UHFFFAOYSA-N 0.000 description 2
- 238000001727 in vivo Methods 0.000 description 2
- 210000005259 peripheral blood Anatomy 0.000 description 2
- 239000011886 peripheral blood Substances 0.000 description 2
- 238000002360 preparation method Methods 0.000 description 2
- 238000011160 research Methods 0.000 description 2
- 230000001235 sensitizing effect Effects 0.000 description 2
- 238000012353 t test Methods 0.000 description 2
- 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 1
- 102000003952 Caspase 3 Human genes 0.000 description 1
- 108090000397 Caspase 3 Proteins 0.000 description 1
- 108020004414 DNA Proteins 0.000 description 1
- 230000033616 DNA repair Effects 0.000 description 1
- 101100300807 Drosophila melanogaster spn-A gene Proteins 0.000 description 1
- 229920001917 Ficoll Polymers 0.000 description 1
- 238000012413 Fluorescence activated cell sorting analysis Methods 0.000 description 1
- 101000979342 Homo sapiens Nuclear factor NF-kappa-B p105 subunit Proteins 0.000 description 1
- 241000124008 Mammalia Species 0.000 description 1
- 206010028980 Neoplasm Diseases 0.000 description 1
- 102100023050 Nuclear factor NF-kappa-B p105 subunit Human genes 0.000 description 1
- 239000012979 RPMI medium Substances 0.000 description 1
- 239000012980 RPMI-1640 medium Substances 0.000 description 1
- 239000006146 Roswell Park Memorial Institute medium Substances 0.000 description 1
- 206010070834 Sensitisation Diseases 0.000 description 1
- 238000011481 absorbance measurement Methods 0.000 description 1
- 229940100198 alkylating agent Drugs 0.000 description 1
- 239000002168 alkylating agent Substances 0.000 description 1
- 238000000540 analysis of variance Methods 0.000 description 1
- 239000002246 antineoplastic agent Substances 0.000 description 1
- 230000005775 apoptotic pathway Effects 0.000 description 1
- 230000008901 benefit Effects 0.000 description 1
- 201000011510 cancer Diseases 0.000 description 1
- 238000004113 cell culture Methods 0.000 description 1
- 238000005119 centrifugation Methods 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 238000011109 contamination Methods 0.000 description 1
- 230000002596 correlated effect Effects 0.000 description 1
- 238000010219 correlation analysis Methods 0.000 description 1
- 231100000433 cytotoxic Toxicity 0.000 description 1
- 239000002254 cytotoxic agent Substances 0.000 description 1
- 231100000599 cytotoxic agent Toxicity 0.000 description 1
- 230000001472 cytotoxic effect Effects 0.000 description 1
- 238000013461 design Methods 0.000 description 1
- 238000003745 diagnosis Methods 0.000 description 1
- 230000005750 disease progression Effects 0.000 description 1
- 238000009826 distribution Methods 0.000 description 1
- 231100000673 dose–response relationship Toxicity 0.000 description 1
- 230000003828 downregulation Effects 0.000 description 1
- 238000011156 evaluation Methods 0.000 description 1
- 230000029142 excretion Effects 0.000 description 1
- 238000000684 flow cytometry Methods 0.000 description 1
- 230000006870 function Effects 0.000 description 1
- 229940080856 gleevec Drugs 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 230000005764 inhibitory process Effects 0.000 description 1
- 238000011221 initial treatment Methods 0.000 description 1
- 238000002955 isolation Methods 0.000 description 1
- 210000003734 kidney Anatomy 0.000 description 1
- 210000000265 leukocyte Anatomy 0.000 description 1
- 238000012417 linear regression Methods 0.000 description 1
- 210000004185 liver Anatomy 0.000 description 1
- 238000012423 maintenance Methods 0.000 description 1
- 230000003211 malignant effect Effects 0.000 description 1
- 230000001404 mediated effect Effects 0.000 description 1
- MIKKOBKEXMRYFQ-WZTVWXICSA-N meglumine amidotrizoate Chemical compound C[NH2+]C[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO.CC(=O)NC1=C(I)C(NC(C)=O)=C(I)C(C([O-])=O)=C1I MIKKOBKEXMRYFQ-WZTVWXICSA-N 0.000 description 1
- 239000000820 nonprescription drug Substances 0.000 description 1
- 125000003729 nucleotide group Chemical group 0.000 description 1
- 238000007911 parenteral administration Methods 0.000 description 1
- 230000037361 pathway Effects 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 238000007747 plating Methods 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- 229940002612 prodrug Drugs 0.000 description 1
- 239000000651 prodrug Substances 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 230000002062 proliferating effect Effects 0.000 description 1
- 150000003230 pyrimidines Chemical class 0.000 description 1
- 230000004044 response Effects 0.000 description 1
- 238000004062 sedimentation Methods 0.000 description 1
- 230000008313 sensitization Effects 0.000 description 1
- 238000009097 single-agent therapy Methods 0.000 description 1
- 241000894007 species Species 0.000 description 1
- 238000005728 strengthening Methods 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 239000013589 supplement Substances 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 238000010998 test method Methods 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 239000003981 vehicle Substances 0.000 description 1
- 238000005303 weighing Methods 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
- A61K31/495—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
- A61K31/506—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim not condensed and containing further heterocyclic rings
-
- 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
- A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
- A61K31/19—Carboxylic acids, e.g. valproic acid
- A61K31/195—Carboxylic acids, e.g. valproic acid having an amino group
- A61K31/196—Carboxylic acids, e.g. valproic acid having an amino group the amino group being directly attached to a ring, e.g. anthranilic acid, mefenamic acid, diclofenac, chlorambucil
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
- A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
- A61P35/02—Antineoplastic agents specific for leukemia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
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)
- General Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Oncology (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Hematology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US1570407P | 2007-12-21 | 2007-12-21 | |
| PCT/US2008/087336 WO2009082662A1 (en) | 2007-12-21 | 2008-12-18 | Combination of nilotinib and a nitrogen mustard analogue for the treatment of chronic lymphocytic leukemia |
Related Child Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2014115061A Division JP2014177487A (ja) | 2007-12-21 | 2014-06-03 | 慢性リンパ性白血病の処置のためのニロチニブとナイトロジェンマスタードの組み合わせ剤 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JP2011507880A true JP2011507880A (ja) | 2011-03-10 |
| JP2011507880A5 JP2011507880A5 (enExample) | 2012-01-26 |
Family
ID=40352369
Family Applications (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2010539775A Pending JP2011507880A (ja) | 2007-12-21 | 2008-12-18 | 慢性リンパ性白血病の処置のためのニロチニブとナイトロジェンマスタードの組み合わせ剤 |
| JP2014115061A Pending JP2014177487A (ja) | 2007-12-21 | 2014-06-03 | 慢性リンパ性白血病の処置のためのニロチニブとナイトロジェンマスタードの組み合わせ剤 |
Family Applications After (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2014115061A Pending JP2014177487A (ja) | 2007-12-21 | 2014-06-03 | 慢性リンパ性白血病の処置のためのニロチニブとナイトロジェンマスタードの組み合わせ剤 |
Country Status (7)
| Country | Link |
|---|---|
| US (2) | US20110028422A1 (enExample) |
| EP (1) | EP2240172B1 (enExample) |
| JP (2) | JP2011507880A (enExample) |
| ES (1) | ES2459877T3 (enExample) |
| PL (1) | PL2240172T3 (enExample) |
| PT (1) | PT2240172E (enExample) |
| WO (1) | WO2009082662A1 (enExample) |
Families Citing this family (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP2425830A1 (en) * | 2010-09-03 | 2012-03-07 | Max-Planck-Gesellschaft zur Förderung der Wissenschaften e.V. | Synergistic drug combination for the treatment of cancer |
| JP6280546B2 (ja) | 2012-06-26 | 2018-02-14 | デル マー ファーマシューティカルズ | ジアンヒドロガラクチトール、ジアセチルジアンヒドロガラクチトール、ジブロモズルシトール、又はこれらの類似体若しくは誘導体を用いた、遺伝子多型又はａｈｉ１の調節不全若しくは変異を有する患者におけるチロシンキナーゼインヒビター抵抗性悪性腫瘍を処置するための方法 |
| EP2983674A4 (en) | 2013-04-08 | 2017-05-10 | Dennis M. Brown | Therapeutic benefit of suboptimally administered chemical compounds |
| CN106102722A (zh) * | 2014-03-13 | 2016-11-09 | V·沃道里斯 | 苯达莫司汀固体分散体和连续输液 |
| US9777572B2 (en) * | 2014-11-17 | 2017-10-03 | Baker Hughes Incorporated | Multi-probe reservoir sampling device |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20060122186A1 (en) * | 2002-11-12 | 2006-06-08 | Panasci Lawrence C | Combination of a nitrogen mustard analogue and imatinib for the treatment of chronic lymphocytic leukemia |
Family Cites Families (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3046301A (en) | 1959-10-29 | 1962-07-24 | Burroughs Wellcome Co | Method of making chlorambucil |
| GB0215676D0 (en) | 2002-07-05 | 2002-08-14 | Novartis Ag | Organic compounds |
| GT200600315A (es) * | 2005-07-20 | 2007-03-19 | Formas cristalinas de 4-metilo-n-[3-(4-metilo-imidazol-1-ilo)-5-trifluorometilo-fenilo]-3-(4-pyridina-3-ilo-pirimidina-2-iloamino)-benzamida |
-
2008
- 2008-12-18 EP EP08864891.0A patent/EP2240172B1/en not_active Not-in-force
- 2008-12-18 JP JP2010539775A patent/JP2011507880A/ja active Pending
- 2008-12-18 US US12/809,805 patent/US20110028422A1/en not_active Abandoned
- 2008-12-18 ES ES08864891.0T patent/ES2459877T3/es active Active
- 2008-12-18 PT PT88648910T patent/PT2240172E/pt unknown
- 2008-12-18 PL PL08864891T patent/PL2240172T3/pl unknown
- 2008-12-18 WO PCT/US2008/087336 patent/WO2009082662A1/en not_active Ceased
-
2014
- 2014-06-03 JP JP2014115061A patent/JP2014177487A/ja active Pending
- 2014-10-27 US US14/524,493 patent/US20150051236A1/en not_active Abandoned
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20060122186A1 (en) * | 2002-11-12 | 2006-06-08 | Panasci Lawrence C | Combination of a nitrogen mustard analogue and imatinib for the treatment of chronic lymphocytic leukemia |
Non-Patent Citations (3)
| Title |
|---|
| JPN6013028084; Ｎ ＥＮＧＬ Ｊ ＭＥＤ Ｖｏｌ．３５４，Ｎｏ．２４, 2006, ｐ．２５４２-２５５１ * |
| JPN6013028086; 医学のあゆみ Ｖｏｌ．２２０，Ｎｏ．９, 200703, ｐ．６７５-６８０ * |
| JPN6013028088; 血液・腫瘍科 Ｖｏｌ．５５，Ｎｏ．５, 200711, ｐ．５２１-５２９ * |
Also Published As
| Publication number | Publication date |
|---|---|
| WO2009082662A1 (en) | 2009-07-02 |
| EP2240172A1 (en) | 2010-10-20 |
| ES2459877T3 (es) | 2014-05-12 |
| JP2014177487A (ja) | 2014-09-25 |
| PL2240172T3 (pl) | 2014-08-29 |
| US20150051236A1 (en) | 2015-02-19 |
| PT2240172E (pt) | 2014-05-28 |
| EP2240172B1 (en) | 2014-03-19 |
| US20110028422A1 (en) | 2011-02-03 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| JP2023515817A (ja) | ダブラフェニブ、ｅｒｋ阻害剤及びｓｈｐ２阻害剤を含む三重の医薬品の組合せ | |
| US8492383B2 (en) | Combination of a nitrogen mustard analogue and imatinib for treatment of chronic lymphocytic leukemia | |
| US20020156023A1 (en) | Lometrexol combination therapy | |
| EP4297750A1 (en) | Use of a bet inhibitor alone or in combination with fedratinib or ruxolitinib for treating a hematological malignancy such as myelofibrosis | |
| JP2014177487A (ja) | 慢性リンパ性白血病の処置のためのニロチニブとナイトロジェンマスタードの組み合わせ剤 | |
| US20190290627A1 (en) | Pim kinase inhibitor combinations | |
| EP3010505A1 (en) | Pharmaceutical combinations | |
| US20100008923A1 (en) | Organic Compounds | |
| KR20200036880A (ko) | 3세대 EGFR 타이로신 키나아제 억제제 및 Raf 억제제의 치료적 조합물 | |
| JP2022514056A (ja) | 癌の治療に使用するためのＲａｆ阻害剤及びＣＤＫ４／６阻害剤による組み合わせ療法 | |
| JP2023524789A (ja) | Ｔｎｏ１５５及びナザルチニブを含む医薬組合せ | |
| JP2022518974A (ja) | ブルトン型チロシンキナーゼ阻害剤の投薬 | |
| EP1496908B1 (en) | Combination of glivec(sti571) with a cyclin-dependent kinase inhibitor, especially flavopiridol in the treatment of cancer | |
| JP2006504727A (ja) | 多発性骨髄腫の処置のためのラクトン誘導体 | |
| EA050366B1 (ru) | Применение ингибиторов bet отдельно или в комбинации с федратинибом или с руксолитинибом для лечения гематологического злокачественного новообразования, такого как миелофиброз | |
| EA040521B1 (ru) | Комбинированная терапия с применением иметельстата и abt-199 для лечения острого миелоидного лейкоза, набор и фармацевтическая композиция для её реализации, способ in vitro индукции апоптоза в клетке острого миелоидного лейкоза |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20111201 |
|
| A621 | Written request for application examination |
Free format text: JAPANESE INTERMEDIATE CODE: A621 Effective date: 20111201 |
|
| A601 | Written request for extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A601 Effective date: 20130911 |
|
| A602 | Written permission of extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A602 Effective date: 20130919 |
|
| A601 | Written request for extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A601 Effective date: 20131011 |
|
| A602 | Written permission of extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A602 Effective date: 20131021 |
|
| A601 | Written request for extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A601 Effective date: 20131111 |
|
| A602 | Written permission of extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A602 Effective date: 20131118 |
|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20131211 |
|
| A02 | Decision of refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A02 Effective date: 20140204 |