JP2013539778A - 癌の治療／転移の阻害 - Google Patents
癌の治療／転移の阻害 Download PDFInfo
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- JP2013539778A JP2013539778A JP2013533265A JP2013533265A JP2013539778A JP 2013539778 A JP2013539778 A JP 2013539778A JP 2013533265 A JP2013533265 A JP 2013533265A JP 2013533265 A JP2013533265 A JP 2013533265A JP 2013539778 A JP2013539778 A JP 2013539778A
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- Prior art keywords
- cells
- ranolazine
- cancer
- cell
- riluzole
- 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.)
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Classifications
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- C07D295/00—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms
- C07D295/04—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms
- C07D295/14—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
- C07D295/145—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals with the ring nitrogen atoms and the carbon atoms with three bonds to hetero atoms attached to the same carbon chain, which is not interrupted by carbocyclic rings
- C07D295/15—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals with the ring nitrogen atoms and the carbon atoms with three bonds to hetero atoms attached to the same carbon chain, which is not interrupted by carbocyclic rings to an acyclic saturated chain
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- A61K31/16—Amides, e.g. hydroxamic acids
- A61K31/165—Amides, e.g. hydroxamic acids having aromatic rings, e.g. colchicine, atenolol, progabide
- A61K31/167—Amides, e.g. hydroxamic acids having aromatic rings, e.g. colchicine, atenolol, progabide having the nitrogen of a carboxamide group directly attached to the aromatic ring, e.g. lidocaine, paracetamol
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- 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
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- A—HUMAN NECESSITIES
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- 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
- A61K31/425—Thiazoles
- A61K31/428—Thiazoles condensed with carbocyclic rings
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- 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
- A61K31/445—Non condensed piperidines, e.g. piperocaine
- A61K31/4458—Non condensed piperidines, e.g. piperocaine only substituted in position 2, e.g. methylphenidate
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- 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
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- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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- A61P13/08—Drugs for disorders of the urinary system of the prostate
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- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D241/00—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings
- C07D241/02—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings not condensed with other rings
- C07D241/04—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings not condensed with other rings having no double bonds between ring members or between ring members and non-ring members
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D277/00—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings
- C07D277/60—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings condensed with carbocyclic rings or ring systems
- C07D277/62—Benzothiazoles
- C07D277/68—Benzothiazoles with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached in position 2
- C07D277/82—Nitrogen atoms
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)
- Animal Behavior & Ethology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pain & Pain Management (AREA)
- Endocrinology (AREA)
- Reproductive Health (AREA)
- Urology & Nephrology (AREA)
- Oncology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| PCT/GB2010/001908 WO2012049440A1 (en) | 2010-10-13 | 2010-10-13 | Treatment of cancer/inhibition of metastasis |
Related Child Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2016019817A Division JP6465306B2 (ja) | 2016-02-04 | 2016-02-04 | 癌の治療／転移の阻害 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JP2013539778A true JP2013539778A (ja) | 2013-10-28 |
| JP2013539778A5 JP2013539778A5 (https=) | 2013-12-05 |
Family
ID=44022817
Family Applications (1)
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| JP2013533265A Pending JP2013539778A (ja) | 2010-10-13 | 2010-10-13 | 癌の治療／転移の阻害 |
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| US (5) | US20130203764A1 (https=) |
| EP (4) | EP2627321A1 (https=) |
| JP (1) | JP2013539778A (https=) |
| KR (1) | KR20140032346A (https=) |
| CN (2) | CN112755029A (https=) |
| AU (2) | AU2010362412A1 (https=) |
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| CA (1) | CA2851694C (https=) |
| DK (1) | DK3132791T3 (https=) |
| IL (1) | IL225689A0 (https=) |
| RU (1) | RU2013121744A (https=) |
| SG (1) | SG189352A1 (https=) |
| WO (1) | WO2012049440A1 (https=) |
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2016128490A (ja) * | 2016-02-04 | 2016-07-14 | ムスタファ・ビルギン・アリ・ジャムゴズ | 癌の治療／転移の阻害 |
| JP2022554201A (ja) * | 2019-10-24 | 2022-12-28 | セレックス・オンコロジー・イノヴェーションズ・リミテッド | がんのための組合せ処置 |
| US11634398B2 (en) | 2010-10-13 | 2023-04-25 | Celex Oncology Limited | Treatment of cancer/inhibition of metastasis |
| JP2023540425A (ja) * | 2020-07-01 | 2023-09-25 | ニュー キャンサー キュア－バイオ カンパニー リミテッド | ３－ケトアシルｃｏａタイオレース阻害剤とカルニチンアシルカルニチンキャリア阻害剤を含む癌の予防または治療のための医薬組成物 |
Families Citing this family (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2013123403A1 (en) * | 2012-02-15 | 2013-08-22 | Sanford-Burnham Medical Research Institute | Theranostics platform and methods of use |
| WO2017091574A1 (en) * | 2015-11-25 | 2017-06-01 | Health Research, Inc. | Riluzole and riluzole drug combinations for the treatment of prostate cancer |
| LT3458053T (lt) * | 2016-05-20 | 2022-02-25 | Biohaven Pharmaceutical Holding Company Ltd. | Riluzolo, rilizolo provaistų arba riluzolo analogų panaudojimas kartu su imunoterapijomis vėžio formų gydymui |
| AU2018218341B2 (en) * | 2017-02-10 | 2023-07-06 | Celex Oncology Innovations Limited | Treatment of cancer and inhibition of metastasis |
| US20200123544A1 (en) * | 2018-10-22 | 2020-04-23 | Celex Oncology Innovations Limited | Gene therapy targeting the neonatal form of nav1.5 for treating cancer |
| US20230062361A1 (en) | 2020-01-21 | 2023-03-02 | Celex Oncology Innovations Limited | Monoclonal antibodies against neonatal nav1.5 |
| US20230139204A1 (en) | 2020-03-09 | 2023-05-04 | Celex Oncology Innovations Limited | Measuring electric activity of cells for the evaluation of metastatic potential of cancer cells |
| AU2024357729A1 (en) | 2023-10-12 | 2026-04-09 | Celex Oncology Innovations Limited | Treatment of metastatic or invasive brain cancer |
| WO2025252860A1 (en) | 2024-06-04 | 2025-12-11 | Celex Oncology Innovations Limited | Ranolazine enantiomer for use in cancer treatment |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2005523314A (ja) * | 2002-04-18 | 2005-08-04 | ユニバーシティ オブ バージニア パテント ファウンデーション | 新規ナトリウムチャンネル遮断化合物 |
| WO2010033581A1 (en) * | 2008-09-16 | 2010-03-25 | University Of Washington | Molecular modulators of the wnt/beta-catenin pathway |
| US20100221246A1 (en) * | 2004-04-16 | 2010-09-02 | University Of Medicine And Dentistry Of New Jersey | Methods and compositions for treating cancer |
Family Cites Families (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2004062604A2 (en) * | 2003-01-10 | 2004-07-29 | Threshold Pharmaceuticals, Inc. | Treatment of cancer with 2-deoxyglucose |
| ES2691411T3 (es) | 2006-03-27 | 2018-11-27 | Wex Medical Limited | Uso de bloqueadores de los canales de sodio para el tratamiento del dolor neuropático que se desarrolla como consecuencia de la quimioterapia |
| CA2716321A1 (en) * | 2008-02-21 | 2009-08-27 | The Regents Of The University Of Colorado | Methods for treating cancer using combination therapy |
| US20090247535A1 (en) * | 2008-03-26 | 2009-10-01 | Duke University | Use of ranolazine for non-cardiovascular disorders |
| BR112013009086A2 (pt) * | 2010-10-13 | 2016-07-26 | Mustafa Bilgin Ali Djamgoz | tratamento de câncer/inibição de metástase |
-
2010
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- 2010-10-13 EP EP10776791.5A patent/EP2627321A1/en not_active Withdrawn
- 2010-10-13 CN CN202110087549.9A patent/CN112755029A/zh active Pending
- 2010-10-13 EP EP19211429.6A patent/EP3653206A1/en not_active Ceased
- 2010-10-13 CN CN2010800703488A patent/CN103370060A/zh active Pending
- 2010-10-13 EP EP25174138.5A patent/EP4640281A3/en active Pending
- 2010-10-13 CA CA2851694A patent/CA2851694C/en active Active
- 2010-10-13 SG SG2013026968A patent/SG189352A1/en unknown
- 2010-10-13 EP EP16020321.2A patent/EP3132791B1/en active Active
- 2010-10-13 KR KR1020137012365A patent/KR20140032346A/ko not_active Withdrawn
- 2010-10-13 RU RU2013121744/15A patent/RU2013121744A/ru not_active Application Discontinuation
- 2010-10-13 DK DK16020321.2T patent/DK3132791T3/da active
- 2010-10-13 US US13/879,146 patent/US20130203764A1/en not_active Abandoned
- 2010-10-13 AU AU2010362412A patent/AU2010362412A1/en not_active Abandoned
- 2010-10-13 JP JP2013533265A patent/JP2013539778A/ja active Pending
- 2010-10-13 WO PCT/GB2010/001908 patent/WO2012049440A1/en not_active Ceased
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2013
- 2013-04-10 IL IL225689A patent/IL225689A0/en unknown
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2015
- 2015-10-13 US US14/881,952 patent/US20160096812A1/en not_active Abandoned
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2017
- 2017-04-06 AU AU2017202267A patent/AU2017202267B2/en active Active
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2018
- 2018-06-07 US US16/002,555 patent/US20180346431A1/en not_active Abandoned
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2019
- 2019-09-19 US US16/576,178 patent/US11634398B2/en active Active
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2022
- 2022-12-19 US US18/068,263 patent/US12534444B2/en active Active
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2005523314A (ja) * | 2002-04-18 | 2005-08-04 | ユニバーシティ オブ バージニア パテント ファウンデーション | 新規ナトリウムチャンネル遮断化合物 |
| US20100221246A1 (en) * | 2004-04-16 | 2010-09-02 | University Of Medicine And Dentistry Of New Jersey | Methods and compositions for treating cancer |
| WO2010033581A1 (en) * | 2008-09-16 | 2010-03-25 | University Of Washington | Molecular modulators of the wnt/beta-catenin pathway |
Non-Patent Citations (5)
| Title |
|---|
| ABDUL M, ANTICANCER RESEARCH, vol. V22 N3, JPN5006003385, 2002, GR, pages 1727 - 1730, ISSN: 0002922737 * |
| EUR J NEUROSCI. 2000 OCT;12(10):3567-74, JPN6015039222, ISSN: 0003165086 * |
| EUROPEAN JOURNAL OF PHARMACOLOGY, vol. 625, JPN6014044268, 2009, pages 206 - 219, ISSN: 0002922738 * |
| HEART, vol. 92, JPN6014044270, 2006, pages 6 - 14, ISSN: 0002922740 * |
| PHARMACY IN PRACTICE, vol. 17, no. 2, JPN6014044272, 2007, pages 60 - 62, ISSN: 0002922739 * |
Cited By (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US11634398B2 (en) | 2010-10-13 | 2023-04-25 | Celex Oncology Limited | Treatment of cancer/inhibition of metastasis |
| US12534444B2 (en) | 2010-10-13 | 2026-01-27 | Celex Oncology Innovations Limited | Treatment of cancer/inhibition of metastasis |
| JP2016128490A (ja) * | 2016-02-04 | 2016-07-14 | ムスタファ・ビルギン・アリ・ジャムゴズ | 癌の治療／転移の阻害 |
| JP2022554201A (ja) * | 2019-10-24 | 2022-12-28 | セレックス・オンコロジー・イノヴェーションズ・リミテッド | がんのための組合せ処置 |
| JP7783630B2 (ja) | 2019-10-24 | 2025-12-10 | セレックス・オンコロジー・イノヴェーションズ・リミテッド | がんのための組合せ処置 |
| JP2023540425A (ja) * | 2020-07-01 | 2023-09-25 | ニュー キャンサー キュア－バイオ カンパニー リミテッド | ３－ケトアシルｃｏａタイオレース阻害剤とカルニチンアシルカルニチンキャリア阻害剤を含む癌の予防または治療のための医薬組成物 |
| JP7669053B2 (ja) | 2020-07-01 | 2025-04-28 | ニュー キャンサー キュア－バイオ カンパニー リミテッド | ３－ケトアシルｃｏａタイオレース阻害剤とカルニチンアシルカルニチンキャリア阻害剤を含む癌の予防または治療のための医薬組成物 |
Also Published As
| Publication number | Publication date |
|---|---|
| WO2012049440A1 (en) | 2012-04-19 |
| US20160096812A1 (en) | 2016-04-07 |
| CA2851694C (en) | 2019-02-26 |
| AU2017202267A1 (en) | 2017-04-27 |
| US20200017457A1 (en) | 2020-01-16 |
| IL225689A0 (en) | 2013-06-27 |
| US20130203764A1 (en) | 2013-08-08 |
| EP3653206A1 (en) | 2020-05-20 |
| EP2627321A1 (en) | 2013-08-21 |
| BR112013009086A2 (pt) | 2016-07-26 |
| EP3132791B1 (en) | 2019-11-27 |
| EP3132791A1 (en) | 2017-02-22 |
| US11634398B2 (en) | 2023-04-25 |
| AU2010362412A1 (en) | 2013-05-30 |
| US20230202994A1 (en) | 2023-06-29 |
| EP4640281A3 (en) | 2026-01-07 |
| US12534444B2 (en) | 2026-01-27 |
| AU2017202267B2 (en) | 2019-01-24 |
| DK3132791T3 (da) | 2020-03-09 |
| CN112755029A (zh) | 2021-05-07 |
| RU2013121744A (ru) | 2014-11-20 |
| US20180346431A1 (en) | 2018-12-06 |
| CN103370060A (zh) | 2013-10-23 |
| EP4640281A2 (en) | 2025-10-29 |
| SG189352A1 (en) | 2013-05-31 |
| KR20140032346A (ko) | 2014-03-14 |
| CA2851694A1 (en) | 2012-04-19 |
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