JP5650193B2 - 胸腺腫の治療のためのキナーゼ阻害剤の使用 - Google Patents
胸腺腫の治療のためのキナーゼ阻害剤の使用 Download PDFInfo
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- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
- 239000011976 maleic acid Substances 0.000 description 1
- 229940098895 maleic acid Drugs 0.000 description 1
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- 235000011090 malic acid Nutrition 0.000 description 1
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- 239000011159 matrix material Substances 0.000 description 1
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- 206010028417 myasthenia gravis Diseases 0.000 description 1
- RXZMYLDMFYNEIM-UHFFFAOYSA-N n,1,4,4-tetramethyl-8-[4-(4-methylpiperazin-1-yl)anilino]-5h-pyrazolo[4,3-h]quinazoline-3-carboxamide Chemical compound CNC(=O)C1=NN(C)C(C2=N3)=C1C(C)(C)CC2=CN=C3NC(C=C1)=CC=C1N1CCN(C)CC1 RXZMYLDMFYNEIM-UHFFFAOYSA-N 0.000 description 1
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- 229910052757 nitrogen Inorganic materials 0.000 description 1
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- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 1
- OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 235000005985 organic acids Nutrition 0.000 description 1
- 235000006408 oxalic acid Nutrition 0.000 description 1
- 229960001592 paclitaxel Drugs 0.000 description 1
- 238000002638 palliative care Methods 0.000 description 1
- FJKROLUGYXJWQN-UHFFFAOYSA-N papa-hydroxy-benzoic acid Natural products OC(=O)C1=CC=C(O)C=C1 FJKROLUGYXJWQN-UHFFFAOYSA-N 0.000 description 1
- 230000007170 pathology Effects 0.000 description 1
- 239000001814 pectin Substances 0.000 description 1
- 229920001277 pectin Polymers 0.000 description 1
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- 210000004303 peritoneum Anatomy 0.000 description 1
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- 150000003057 platinum Chemical class 0.000 description 1
- 210000004224 pleura Anatomy 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- 229950008882 polysorbate Drugs 0.000 description 1
- 229920000136 polysorbate Polymers 0.000 description 1
- 229920002451 polyvinyl alcohol Polymers 0.000 description 1
- 235000019422 polyvinyl alcohol Nutrition 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
- 229920001592 potato starch Polymers 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
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- 239000002599 prostaglandin synthase inhibitor Substances 0.000 description 1
- 239000003528 protein farnesyltransferase inhibitor Substances 0.000 description 1
- 239000000700 radioactive tracer Substances 0.000 description 1
- 102000005962 receptors Human genes 0.000 description 1
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- 235000010413 sodium alginate Nutrition 0.000 description 1
- 239000000661 sodium alginate Substances 0.000 description 1
- 229940005550 sodium alginate Drugs 0.000 description 1
- 229940023144 sodium glycolate Drugs 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 239000000600 sorbitol Substances 0.000 description 1
- 239000008117 stearic acid Substances 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- 238000009495 sugar coating Methods 0.000 description 1
- 239000003765 sweetening agent Substances 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- 235000012222 talc Nutrition 0.000 description 1
- 235000002906 tartaric acid Nutrition 0.000 description 1
- 239000011975 tartaric acid Substances 0.000 description 1
- 229960001367 tartaric acid Drugs 0.000 description 1
- RCINICONZNJXQF-MZXODVADSA-N taxol Chemical compound O([C@@H]1[C@@]2(C[C@@H](C(C)=C(C2(C)C)[C@H](C([C@]2(C)[C@@H](O)C[C@H]3OC[C@]3([C@H]21)OC(C)=O)=O)OC(=O)C)OC(=O)[C@H](O)[C@@H](NC(=O)C=1C=CC=CC=1)C=1C=CC=CC=1)O)C(=O)C1=CC=CC=C1 RCINICONZNJXQF-MZXODVADSA-N 0.000 description 1
- 239000003277 telomerase inhibitor Substances 0.000 description 1
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 1
- JEJAMASKDTUEBZ-UHFFFAOYSA-N tris(1,1,3-tribromo-2,2-dimethylpropyl) phosphate Chemical compound BrCC(C)(C)C(Br)(Br)OP(=O)(OC(Br)(Br)C(C)(C)CBr)OC(Br)(Br)C(C)(C)CBr JEJAMASKDTUEBZ-UHFFFAOYSA-N 0.000 description 1
- 229940121358 tyrosine kinase inhibitor Drugs 0.000 description 1
- 239000005483 tyrosine kinase inhibitor Substances 0.000 description 1
- 239000000080 wetting agent Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
- C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
- C07D487/04—Ortho-condensed systems
-
- 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
- A61K31/519—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
-
- 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
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Epidemiology (AREA)
- Pulmonology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
Description
本アッセイにより、試験化合物で得られる特定酵素のキナーゼ活性の阻害を調べることができる。異なるキナーゼを平行して試験することができる。
最初2002年5月に胸腺癌と診断され、2007年7月には肺への転移を伴う進行度3となり、2007年9月にフェーズI臨床トライアルに入った24才の女性患者で客観的腫瘍応答が得られた。4週サイクルで3週間の間4日間治療した後、残り3日間休薬する治療スケジュールで式(I)を有する化合物を150mgの1日用量で投与した。治療を10サイクル実施した後、患者は固形腫瘍のRECIST基準(Therasse P,Arbuck S,Eisenhauer EA,Wanders J,Kaplan RS,Rubinstein Lら,New guidelines to evaluate the response to treatment in solid tumors,J.Natl.Cancer Inst.,2000;92(3):205−216)により部分的な腫瘍応答(PR)を示し、基準と比較して標的病巣の合計が31.2%低下した。PRは1ヶ月後確認され、第13サイクルまでに基準と比較して標的病巣の合計が37.6%低下したことが立証された。臨床トライアルで治療を受ける前、患者は胸腺癌のために次のように他の治療を受けていた。2005年1月〜2005年6月の間はアドリアマイシン(登録商標)、シトキサン(登録商標)、シスプラチン;2006年2月〜2006年5月の間はイホスファミド;2006年10月〜2007年6月の間はタキソール(登録商標)、カルボプラチン;2007年6月〜2007年7月の間はアドリアマイシン(登録商標)、シトキサン(登録商標)、ビンクリスチン。患者はまた2002年5月に手術を受け、2002年7月及び2006年7月に放射線治療を受けていた。
最初2006年5月に胸腺癌と診断され、2007年10月には肺、骨及び腹膜に転移した62才の男性患者で別の客観的応答が得られた。この患者は2008年12月にフェーズI臨床トライアルの治療を始めた。4週サイクルで3週間の間4日間治療した後、残り3日間休薬する治療スケジュールで式(I)を有する化合物を150mgの1日用量で投与した。治療を6サイクル実施した後、患者はRECIST基準により部分的な腫瘍応答(PR)を示し、基準及び安定な非標的病巣と比較して標的病巣の合計が30%低下した。PRは1ヶ月後確認され、基準及び安定な非標的病巣と比較して標的病巣の合計が40%低下した。臨床トライアルで治療を受ける前、患者は2007年11月〜2008年3月の間に1ラインの化学療法(シスプラチン/ゲムシタビン)を受けた。2006年5月に手術を受け、2006年9月に放射線治療を受けた。
Claims (7)
- 胸腺腫が胸腺癌である、請求項1に記載の治療剤。
- (a)請求項1に定義されている式(I)の化合物及び(b)1つ以上の細胞傷害性または細胞増殖抑制性化学物質を含む、胸腺腫の治療用配合剤。
- 胸腺腫が胸腺癌である、請求項3に記載の治療用配合剤。
- 請求項1に定義されている式(I)の化合物を、医薬的に許容され得る担体、希釈剤または賦形剤と混合して含む、胸腺腫の治療に使用するための医薬組成物。
- 1つ以上の細胞傷害性または細胞増殖抑制性化学物質を更に含む、請求項5に記載の医薬組成物。
- 胸腺腫が胸腺癌である、請求項5または6に記載の医薬組成物。
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
EP09155745.4 | 2009-03-20 | ||
EP09155745 | 2009-03-20 | ||
PCT/EP2010/053311 WO2010106028A1 (en) | 2009-03-20 | 2010-03-15 | Use of a kinase inhibitor for the treatment of thymoma |
Publications (2)
Publication Number | Publication Date |
---|---|
JP2012520846A JP2012520846A (ja) | 2012-09-10 |
JP5650193B2 true JP5650193B2 (ja) | 2015-01-07 |
Family
ID=42106701
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2012500209A Active JP5650193B2 (ja) | 2009-03-20 | 2010-03-15 | 胸腺腫の治療のためのキナーゼ阻害剤の使用 |
Country Status (7)
Country | Link |
---|---|
US (1) | US8580793B2 (ja) |
EP (1) | EP2408776B1 (ja) |
JP (1) | JP5650193B2 (ja) |
CN (1) | CN102356083B (ja) |
ES (1) | ES2445896T3 (ja) |
HK (1) | HK1166795A1 (ja) |
WO (1) | WO2010106028A1 (ja) |
Families Citing this family (6)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
ES2660146T3 (es) * | 2009-04-29 | 2018-03-21 | Nerviano Medical Sciences S.R.L. | Sales del inhibidor de cdk |
WO2012101029A1 (en) * | 2011-01-26 | 2012-08-02 | Nerviano Medical Sciences S.R.L. | Tricyclic derivatives, process for their preparation and their use as kinase inhibitors |
ES2602791T3 (es) * | 2011-01-26 | 2017-02-22 | Nerviano Medical Sciences S.R.L. | Derivados de pirrolo tricíclicos, proceso para su preparación y su uso como inhibidores de cinasa |
CN107383019B (zh) * | 2017-07-28 | 2019-10-15 | 江苏艾凡生物医药有限公司 | 吡唑并[4,3-h]喹唑啉类化合物及其用途 |
CN113811302B (zh) * | 2019-05-08 | 2023-12-29 | 山东轩竹医药科技有限公司 | 激酶抑制剂的用途 |
KR20220164125A (ko) | 2021-06-03 | 2022-12-13 | 한국과학기술원 | 흉선종의 진단, 예방, 또는 치료용 조성물 |
Family Cites Families (7)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
PL1636236T3 (pl) * | 2003-05-22 | 2014-02-28 | Nerviano Medical Sciences Srl | Pochodne pirazolochinazoliny, sposób ich wytwarzania oraz ich zastosowanie jako inhibitory kinaz |
JP2005006532A (ja) * | 2003-06-18 | 2005-01-13 | Pharma Design Inc | ヒトオーロラa蛋白質に対する抗体及びその応用 |
FR2857363B1 (fr) * | 2003-07-10 | 2007-09-07 | Aventis Pharma Sa | 4,5,6,7-tetrahydro-1h-pyrazolo[3,4-c] pyridines substituees compositions les contenant et utilisation |
JP2007137856A (ja) * | 2005-11-22 | 2007-06-07 | Univ Nagoya | オーロラaタンパク質の活性調節剤及びその利用 |
ES2390237T3 (es) | 2006-02-10 | 2012-11-07 | Nerviano Medical Sciences S.R.L. | Combinaciones que comprenden un inhibidor de cdk y un anticuerpo anti-factor de crecimiento o un agente antimitótico |
PE20080668A1 (es) * | 2006-08-30 | 2008-07-17 | Novartis Ag | Compuestos heterociclicos como inhibidores de la cinasa-2 de proteina activada por cinasa de proteina activada por mitogeno |
AU2008211172A1 (en) * | 2007-01-30 | 2008-08-07 | Biogen Idec Ma Inc. | 1-H-pyrazolo(3,4B)pyrimidine derivatives and their use as modulators of mitotic kinases |
-
2010
- 2010-03-15 WO PCT/EP2010/053311 patent/WO2010106028A1/en active Application Filing
- 2010-03-15 ES ES10708552.4T patent/ES2445896T3/es active Active
- 2010-03-15 CN CN201080012093.XA patent/CN102356083B/zh active Active
- 2010-03-15 US US13/256,467 patent/US8580793B2/en active Active
- 2010-03-15 EP EP10708552.4A patent/EP2408776B1/en active Active
- 2010-03-15 JP JP2012500209A patent/JP5650193B2/ja active Active
-
2012
- 2012-08-01 HK HK12107532.6A patent/HK1166795A1/xx unknown
Also Published As
Publication number | Publication date |
---|---|
US8580793B2 (en) | 2013-11-12 |
WO2010106028A1 (en) | 2010-09-23 |
ES2445896T3 (es) | 2014-03-05 |
EP2408776A1 (en) | 2012-01-25 |
EP2408776B1 (en) | 2014-01-08 |
CN102356083A (zh) | 2012-02-15 |
JP2012520846A (ja) | 2012-09-10 |
CN102356083B (zh) | 2014-10-15 |
US20120077819A1 (en) | 2012-03-29 |
HK1166795A1 (en) | 2012-11-09 |
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