CA2460713A1 - Valproic acid and derivatives for the combinatorial therapeutic treatment of human cancers and for the treatment of tumor metastasis and minimal residual disease - Google Patents
Valproic acid and derivatives for the combinatorial therapeutic treatment of human cancers and for the treatment of tumor metastasis and minimal residual disease Download PDFInfo
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- CA2460713A1 CA2460713A1 CA002460713A CA2460713A CA2460713A1 CA 2460713 A1 CA2460713 A1 CA 2460713A1 CA 002460713 A CA002460713 A CA 002460713A CA 2460713 A CA2460713 A CA 2460713A CA 2460713 A1 CA2460713 A1 CA 2460713A1
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- A61K31/28—Compounds containing heavy metals
-
- 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
- A61K31/59—Compounds containing 9, 10- seco- cyclopenta[a]hydrophenanthrene ring systems
-
- 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
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- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Epidemiology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
- Investigating Or Analysing Biological Materials (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EP01121722A EP1293205A1 (en) | 2001-09-18 | 2001-09-18 | Valproic acid and derivatives thereof for the combination therapy of human cancers, for the treatment of tumour metastasis and minimal residual disease |
| EP01121722.1 | 2001-09-18 | ||
| PCT/EP2002/010419 WO2003024442A2 (en) | 2001-09-18 | 2002-09-17 | Valproic acid and derivatives for the combinatorial therapeutic treatment of human cancers and for the treatment of tumor metastasis and minimal residual disease |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA2460713A1 true CA2460713A1 (en) | 2003-03-27 |
Family
ID=8178602
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA002460713A Abandoned CA2460713A1 (en) | 2001-09-18 | 2002-09-17 | Valproic acid and derivatives for the combinatorial therapeutic treatment of human cancers and for the treatment of tumor metastasis and minimal residual disease |
Country Status (11)
| Country | Link |
|---|---|
| US (1) | US20050038113A1 (https=) |
| EP (4) | EP1293205A1 (https=) |
| JP (1) | JP2005512961A (https=) |
| AT (1) | ATE314063T1 (https=) |
| AU (1) | AU2002338716B2 (https=) |
| CA (1) | CA2460713A1 (https=) |
| CY (1) | CY1105552T1 (https=) |
| DE (1) | DE60208397T2 (https=) |
| DK (1) | DK1427403T3 (https=) |
| ES (1) | ES2252519T3 (https=) |
| WO (1) | WO2003024442A2 (https=) |
Families Citing this family (42)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US7154002B1 (en) | 2002-10-08 | 2006-12-26 | Takeda San Diego, Inc. | Histone deacetylase inhibitors |
| US7250514B1 (en) | 2002-10-21 | 2007-07-31 | Takeda San Diego, Inc. | Histone deacetylase inhibitors |
| US7381825B2 (en) * | 2003-03-17 | 2008-06-03 | Takeda San Diego, Inc. | Histone deacetylase inhibitors |
| MXPA05012464A (es) * | 2003-05-21 | 2006-01-30 | Novartis Ag | Combinacion de inhibidores de deacetilasa de histona con agentes quimioterapeuticos. |
| EP1491188A1 (en) * | 2003-06-25 | 2004-12-29 | G2M Cancer Drugs AG | Topical use of valproic acid for the prevention or treatment of skin disorders |
| CN102349927A (zh) * | 2003-08-29 | 2012-02-15 | Hdac默克研究有限责任公司 | 联合治疗癌症的方法 |
| US20050159470A1 (en) * | 2003-12-19 | 2005-07-21 | Syrrx, Inc. | Histone deacetylase inhibitors |
| US20050137234A1 (en) * | 2003-12-19 | 2005-06-23 | Syrrx, Inc. | Histone deacetylase inhibitors |
| US7951780B2 (en) | 2004-02-25 | 2011-05-31 | Astellas Pharma Inc. | Antitumor agent |
| EP1824831A2 (en) * | 2004-12-16 | 2007-08-29 | Takeda San Diego, Inc. | Histone deacetylase inhibitors |
| JP5156392B2 (ja) * | 2005-02-03 | 2013-03-06 | トポターゲット ユーケー リミテッド | Ｈｄａｃ阻害剤を用いる併用療法 |
| US7869590B2 (en) * | 2005-04-12 | 2011-01-11 | Broadcom Corporation | Method and system for hardware accelerator for implementing f9 integrity algorithm in WCDMA compliant handsets |
| EP1896436A2 (en) * | 2005-05-11 | 2008-03-12 | Takeda San Diego, Inc. | Histone deacetylase inhibitors |
| ATE542527T1 (de) | 2005-05-13 | 2012-02-15 | Topotarget Uk Ltd | Pharmazeutische formulierungen von hdac-hemmern |
| EA200800321A1 (ru) * | 2005-07-14 | 2008-06-30 | Такеда Сан Диего, Инк. | Ингибиторы гистондеацетилазы |
| WO2007054719A2 (en) | 2005-11-10 | 2007-05-18 | Topotarget Uk Limited | Histone deacetylase (hdac) inhibitors (pxdlol) for the treatment of cancer alone or in combination with chemotherapeutic agent |
| US9186339B2 (en) * | 2005-11-16 | 2015-11-17 | Universidad Nacional Autonoma De Mexico | Use of transcriptome modifying agents and chemotherapy or radiotherapy against cancer |
| RU2389484C2 (ru) * | 2005-11-18 | 2010-05-20 | Универсидад Насиональ Аутонома Де Мексико | Применение модифицирующих транскриптом агентов и химиотерапии или радиотерапии против рака |
| JP2009525955A (ja) * | 2006-01-13 | 2009-07-16 | タケダ サン ディエゴ インコーポレイテッド | ヒストンデアセチラーゼ阻害剤 |
| JP5113038B2 (ja) * | 2006-03-23 | 2013-01-09 | テムリック株式会社 | 癌治療用キットおよび癌治療用医薬組成物 |
| EP2012801A4 (en) | 2006-04-24 | 2009-08-05 | Gloucester Pharmaceuticals Inc | GEMCITABINE COMBINATION THERAPY |
| DE102006022877B4 (de) * | 2006-05-15 | 2009-01-29 | Sartorius Stedim Biotech Gmbh | Verfahren zur Bestimmung der Viabilität von Zellen in Zellkulturen |
| US8957027B2 (en) | 2006-06-08 | 2015-02-17 | Celgene Corporation | Deacetylase inhibitor therapy |
| EP2056808A4 (en) * | 2006-08-28 | 2009-12-23 | Univ California | Small molecule potentiator of hormonal therapy for breast cancer |
| CA2671649A1 (en) * | 2006-12-06 | 2008-06-12 | Sapporo Medical University | Potentiation of cellular immunity using histone deacetylase (hdac) inhibitors |
| GB0625283D0 (en) * | 2006-12-19 | 2007-01-24 | Cyclacel Ltd | Combination |
| AU2007342028B2 (en) | 2006-12-29 | 2013-06-13 | Celgene Corporation | Purifiction of romidepsin |
| GB2454118B (en) * | 2007-06-06 | 2010-06-02 | Univ Maryland | Hdac inhibitors and hormone targeted drugs for the treatment of cancer |
| US8642809B2 (en) | 2007-09-25 | 2014-02-04 | Topotarget Uk Ltd. | Methods of synthesis of certain hydroxamic acid compounds |
| WO2010064422A1 (ja) * | 2008-12-02 | 2010-06-10 | 静岡県公立大学法人 | ヒストン高アセチル化状態における光増感処理による腫瘍殺傷法 |
| US8491927B2 (en) | 2009-12-02 | 2013-07-23 | Nimble Epitech, Llc | Pharmaceutical composition containing a hypomethylating agent and a histone deacetylase inhibitor |
| NZ605526A (en) | 2010-07-12 | 2015-04-24 | Celgene Corp | Romidepsin solid forms and uses thereof |
| US8859502B2 (en) | 2010-09-13 | 2014-10-14 | Celgene Corporation | Therapy for MLL-rearranged leukemia |
| KR101733189B1 (ko) * | 2010-10-06 | 2017-05-08 | (주)아모레퍼시픽 | 손톱 또는 발톱 성장 촉진용 조성물 |
| CA2829263C (en) * | 2011-03-21 | 2020-05-12 | Valcuria Ab | A pharmaceutical composition comprising a hdac inhibitor and a steroid and the use thereof. |
| AU2013202506B2 (en) | 2012-09-07 | 2015-06-18 | Celgene Corporation | Resistance biomarkers for hdac inhibitors |
| AU2013202507B9 (en) | 2012-11-14 | 2015-08-13 | Celgene Corporation | Inhibition of drug resistant cancer cells |
| NZ630311A (en) | 2013-12-27 | 2016-03-31 | Celgene Corp | Romidepsin formulations and uses thereof |
| JP6551963B2 (ja) * | 2014-05-14 | 2019-07-31 | 国立大学法人京都大学 | 巨核球前駆細胞の製造方法 |
| MX388409B (es) | 2014-06-12 | 2025-03-19 | Cedars Sinai Medical Center | Composiciones y metodos para tratar canceres. |
| GB202102606D0 (en) * | 2021-02-24 | 2021-04-07 | Univ Oxford Innovation Ltd | Treatment of ovarian cancer minimal residual disease |
| CN117693363A (zh) * | 2021-07-27 | 2024-03-12 | 东丽株式会社 | 用于癌的治疗和/或预防的药品 |
Family Cites Families (17)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4935450A (en) * | 1982-09-17 | 1990-06-19 | Therapeutical Systems Corporation | Cancer therapy system for effecting oncolysis of malignant neoplasms |
| CA1339034C (en) * | 1988-08-22 | 1997-04-01 | Paul A. Tremblay | Platinum complexes of single isomer neoalkyl acids |
| JPH0279969A (ja) * | 1988-09-19 | 1990-03-20 | Shigeyoshi Fujimoto | 細胞障害性ｔ細胞誘導及び活性化の方法 |
| FR2697752B1 (fr) * | 1992-11-10 | 1995-04-14 | Rhone Poulenc Rorer Sa | Compositions antitumorales contenant des dérivés du taxane. |
| EP0632008B1 (en) * | 1993-06-01 | 1998-02-04 | Ono Pharmaceutical Co., Ltd. | Pentanoic acid derivatives |
| US5672746A (en) * | 1994-08-30 | 1997-09-30 | American Biogenetic Sciences, Inc. | Antiproliferative and neurotrophic molecules |
| US6300373B1 (en) * | 1993-09-10 | 2001-10-09 | American Biogenetic Sciences, Inc. | Antiproliferative and neurotrophic molecules |
| US5786344A (en) * | 1994-07-05 | 1998-07-28 | Arch Development Corporation | Camptothecin drug combinations and methods with reduced side effects |
| ATE229810T1 (de) * | 1996-10-11 | 2003-01-15 | Univ California | Krebs immuntherapie unter verwendung von tumorzellen kombiniert mit lymphozytmischungen |
| US6110955A (en) * | 1997-03-11 | 2000-08-29 | Beacon Laboratories, Inc. | Metabolically stabilized oxyalkylene esters and uses thereof |
| US6110970A (en) * | 1997-03-11 | 2000-08-29 | Beacon Laboratories, Inc. | Nitrogen-containing oxyalkylene esters and uses thereof |
| US6124495A (en) * | 1997-03-11 | 2000-09-26 | Beacon Laboratories, Inc. | Unsaturated oxyalkylene esters and uses thereof |
| US6043389A (en) * | 1997-03-11 | 2000-03-28 | Mor Research Applications, Ltd. | Hydroxy and ether-containing oxyalkylene esters and uses thereof |
| US5939455A (en) * | 1997-03-11 | 1999-08-17 | Beacon Laboratories, Inc. | Therapeutic augmentation of oxyalkylene diesters and butyric acid derivatives |
| US6028102A (en) * | 1998-02-24 | 2000-02-22 | Yissum Research Development Company Of The Hebrew University Of Jerusalem | Anticonvulsant drugs and pharmaceutical compositions thereof |
| AU2337601A (en) * | 1999-12-23 | 2001-07-09 | Ontario Cancer Institute, The | Inhibition of gsk-3beta |
| EP1170008A1 (en) * | 2000-07-07 | 2002-01-09 | Chemotherapeutisches Forschungsinstitut Georg-Speyer-Haus | Valproic acid and derivatives thereof as histone deacetylase inhibitors |
-
2001
- 2001-09-18 EP EP01121722A patent/EP1293205A1/en not_active Withdrawn
-
2002
- 2002-09-17 DE DE60208397T patent/DE60208397T2/de not_active Expired - Lifetime
- 2002-09-17 ES ES02777129T patent/ES2252519T3/es not_active Expired - Lifetime
- 2002-09-17 EP EP02777129A patent/EP1427403B8/en not_active Expired - Lifetime
- 2002-09-17 AU AU2002338716A patent/AU2002338716B2/en not_active Ceased
- 2002-09-17 CA CA002460713A patent/CA2460713A1/en not_active Abandoned
- 2002-09-17 US US10/489,770 patent/US20050038113A1/en not_active Abandoned
- 2002-09-17 WO PCT/EP2002/010419 patent/WO2003024442A2/en not_active Ceased
- 2002-09-17 AT AT02777129T patent/ATE314063T1/de active
- 2002-09-17 DK DK02777129T patent/DK1427403T3/da active
- 2002-09-17 EP EP05101081A patent/EP1529527A3/en not_active Withdrawn
- 2002-09-17 JP JP2003528538A patent/JP2005512961A/ja active Pending
- 2002-09-17 EP EP05019659A patent/EP1602371A3/en not_active Withdrawn
-
2006
- 2006-02-28 CY CY20061100277T patent/CY1105552T1/el unknown
Also Published As
| Publication number | Publication date |
|---|---|
| WO2003024442A2 (en) | 2003-03-27 |
| EP1602371A2 (en) | 2005-12-07 |
| DK1427403T3 (da) | 2006-04-03 |
| WO2003024442A3 (en) | 2003-09-18 |
| EP1602371A3 (en) | 2006-11-15 |
| EP1427403B1 (en) | 2005-12-28 |
| CY1105552T1 (el) | 2010-07-28 |
| AU2002338716B2 (en) | 2007-08-16 |
| DE60208397D1 (de) | 2006-02-02 |
| ATE314063T1 (de) | 2006-01-15 |
| DE60208397T2 (de) | 2006-07-13 |
| EP1427403A2 (en) | 2004-06-16 |
| EP1293205A1 (en) | 2003-03-19 |
| JP2005512961A (ja) | 2005-05-12 |
| ES2252519T3 (es) | 2006-05-16 |
| EP1529527A3 (en) | 2005-05-25 |
| EP1427403B8 (en) | 2006-03-22 |
| EP1529527A2 (en) | 2005-05-11 |
| US20050038113A1 (en) | 2005-02-17 |
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Legal Events
| Date | Code | Title | Description |
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| EEER | Examination request | ||
| FZDE | Discontinued |
Effective date: 20130917 |