NO332642B1 - Anvendelse av picropodophyllin for fremstilling av et medikament for profylakse eller behandling av Ewings sarkom, glioblastoma, prostatacarcinoma, brystcarcinoma, magekreft, pankreatisk carcinoma, ovariecancer og endometrisk carcinoma - Google Patents
Anvendelse av picropodophyllin for fremstilling av et medikament for profylakse eller behandling av Ewings sarkom, glioblastoma, prostatacarcinoma, brystcarcinoma, magekreft, pankreatisk carcinoma, ovariecancer og endometrisk carcinomaInfo
- Publication number
- NO332642B1 NO332642B1 NO20035648A NO20035648A NO332642B1 NO 332642 B1 NO332642 B1 NO 332642B1 NO 20035648 A NO20035648 A NO 20035648A NO 20035648 A NO20035648 A NO 20035648A NO 332642 B1 NO332642 B1 NO 332642B1
- Authority
- NO
- Norway
- Prior art keywords
- igf
- carcinoma
- cells
- picropodophyllin
- podophyllotoxin
- Prior art date
Links
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- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
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SE0102168A SE0102168D0 (sv) | 2001-06-19 | 2001-06-19 | New use and new compounds |
US30043101P | 2001-06-26 | 2001-06-26 | |
PCT/SE2002/001202 WO2002102804A1 (en) | 2001-06-19 | 2002-06-19 | New use of specific cyclolignans |
Publications (3)
Publication Number | Publication Date |
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NO20035648D0 NO20035648D0 (no) | 2003-12-17 |
NO20035648L NO20035648L (no) | 2004-02-18 |
NO332642B1 true NO332642B1 (no) | 2012-11-26 |
Family
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Application Number | Title | Priority Date | Filing Date |
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NO20035648A NO332642B1 (no) | 2001-06-19 | 2002-06-19 | Anvendelse av picropodophyllin for fremstilling av et medikament for profylakse eller behandling av Ewings sarkom, glioblastoma, prostatacarcinoma, brystcarcinoma, magekreft, pankreatisk carcinoma, ovariecancer og endometrisk carcinoma |
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Country | Link |
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US (7) | US20040167208A1 (da) |
EP (5) | EP1938818A3 (da) |
JP (2) | JP2004534078A (da) |
KR (1) | KR100940055B1 (da) |
CN (3) | CN1659171A (da) |
AT (1) | ATE441411T1 (da) |
AU (2) | AU2002311731B8 (da) |
CA (2) | CA2455328C (da) |
DK (1) | DK1498121T3 (da) |
ES (1) | ES2333014T3 (da) |
NO (1) | NO332642B1 (da) |
NZ (2) | NZ530290A (da) |
PT (1) | PT1498121E (da) |
SE (1) | SE0102168D0 (da) |
WO (2) | WO2002102804A1 (da) |
Families Citing this family (56)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
SE0102168D0 (sv) * | 2001-06-19 | 2001-06-19 | Karolinska Innovations Ab | New use and new compounds |
SE0203746D0 (sv) * | 2002-12-18 | 2002-12-18 | Karolinska Innovations Ab | New compounds |
SE0203747D0 (sv) * | 2002-12-18 | 2002-12-18 | Karolinska Innovations Ab | New use |
SE0301202D0 (sv) * | 2003-04-24 | 2003-04-24 | Orteca Ab C O Karolinska Innov | New use and new compounds |
US7342114B2 (en) | 2003-07-01 | 2008-03-11 | California Pacific Medical Center | Podophyllotoxin derivatives |
US20050075358A1 (en) * | 2003-10-06 | 2005-04-07 | Carboni Joan M. | Methods for treating IGF1R-inhibitor induced hyperglycemia |
AU2004282219C1 (en) | 2003-10-15 | 2009-12-17 | Osi Pharmaceuticals, Inc. | Imidazo [1, 5 - a] pyrazine tyrosine kinase inhibitors |
US7781393B2 (en) | 2004-02-25 | 2010-08-24 | Dana-Farber Cancer Institute, Inc. | Methods for inhibiting tumor cell growth |
CN100590118C (zh) | 2004-03-12 | 2010-02-17 | 阿纳里特康股份有限公司 | 作为类胰岛素生长因子第1类受体抑制剂的杂环化合物 |
PT1740591E (pt) * | 2004-04-02 | 2009-09-24 | Osi Pharm Inc | Inibidores da proteína quinase heterobicíclicos em substituição de anel bicíclico 6,6 |
AR053090A1 (es) | 2004-07-20 | 2007-04-25 | Osi Pharm Inc | Imidazotriazinas como inhibidores de proteina quinasas y su uso para la preparacion de medicamentos |
US7566721B2 (en) * | 2005-08-08 | 2009-07-28 | Osi Pharmaceuticals, Inc. | Substituted thienol[2,3-d]pyrimidines as kinase inhibitors |
EP1926996B1 (en) | 2005-09-20 | 2011-11-09 | OSI Pharmaceuticals, Inc. | Biological markers predictive of anti-cancer response to insulin-like growth factor-1 receptor kinase inhibitors |
AR057960A1 (es) | 2005-12-02 | 2007-12-26 | Osi Pharm Inc | Inhibidores de proteina quinasa biciclicos |
US8575164B2 (en) * | 2005-12-19 | 2013-11-05 | OSI Pharmaceuticals, LLC | Combination cancer therapy |
CA2638124A1 (en) * | 2006-02-24 | 2007-08-30 | Axelar Ab | Use of cyclolignans for the treatment of type 2 diabetes and as contraceptives |
EP2056808A4 (en) * | 2006-08-28 | 2009-12-23 | Univ California | SMALL MOLECULAR AMPLIFIER OF HORMONTHERAPY FOR BREAST CANCER |
EP2250173A1 (en) * | 2008-01-18 | 2010-11-17 | OSI Pharmaceuticals, Inc. | Imidazopyrazinol derivatives for the treatment of cancers |
WO2009100349A1 (en) * | 2008-02-09 | 2009-08-13 | The Trustees Of Columbia University In The City Of New York | Analogues of (-)-picropodophyllin, synthesis and uses thereof |
WO2009108857A2 (en) * | 2008-02-27 | 2009-09-03 | Combithera, Inc. | Combination therapy for prostate cancer |
JP2011522515A (ja) * | 2008-04-10 | 2011-08-04 | マサチューセッツ インスティテュート オブ テクノロジー | 癌幹細胞を標的とする薬剤を同定する方法およびその使用 |
EP2283020B8 (en) * | 2008-05-19 | 2012-12-12 | OSI Pharmaceuticals, LLC | Substituted imidazopyr-and imidazotri-azines |
MX2011004824A (es) | 2008-11-07 | 2012-01-12 | Triact Therapeutics Inc | Uso de derivados de butano catecólico en terapia contra el cáncer. |
US20120189641A1 (en) | 2009-02-25 | 2012-07-26 | OSI Pharmaceuticals, LLC | Combination anti-cancer therapy |
US20110171124A1 (en) | 2009-02-26 | 2011-07-14 | Osi Pharmaceuticals, Inc. | In situ methods for monitoring the EMT status of tumor cells in vivo |
US8642834B2 (en) | 2009-02-27 | 2014-02-04 | OSI Pharmaceuticals, LLC | Methods for the identification of agents that inhibit mesenchymal-like tumor cells or their formation |
WO2010099138A2 (en) | 2009-02-27 | 2010-09-02 | Osi Pharmaceuticals, Inc. | Methods for the identification of agents that inhibit mesenchymal-like tumor cells or their formation |
JP2012519282A (ja) | 2009-02-27 | 2012-08-23 | オーエスアイ・ファーマシューティカルズ,エルエルシー | 間葉様腫瘍細胞またはその生成を阻害する薬剤を同定するための方法 |
JP2012524119A (ja) | 2009-04-20 | 2012-10-11 | オーエスアイ・ファーマシューティカルズ,エルエルシー | C−ピラジン−メチルアミンの調製 |
WO2010129740A1 (en) * | 2009-05-07 | 2010-11-11 | Osi Pharmaceuticals, Inc. | Use of osi-906 for treating adrenocortical carcinoma |
WO2010138686A1 (en) * | 2009-05-29 | 2010-12-02 | The United States Of America, As Represented By The Secretary, Department Of Health And Human Services | Mdri-inverse agents |
US7924203B2 (en) * | 2009-06-12 | 2011-04-12 | Analog Devices, Inc. | Most significant bits analog to digital converter, and an analog to digital converter including a most significant bits analog to digital converter |
US20100316639A1 (en) | 2009-06-16 | 2010-12-16 | Genentech, Inc. | Biomarkers for igf-1r inhibitor therapy |
EP2542893A2 (en) | 2010-03-03 | 2013-01-09 | OSI Pharmaceuticals, LLC | Biological markers predictive of anti-cancer response to insulin-like growth factor-1 receptor kinase inhibitors |
CA2783656A1 (en) | 2010-03-03 | 2011-09-09 | OSI Pharmaceuticals, LLC | Biological markers predictive of anti-cancer response to insulin-like growth factor-1 receptor kinase inhibitors |
US20130005733A1 (en) | 2010-03-09 | 2013-01-03 | OSI Pharmaceuticals, LLC | Combination anti-cancer therapy |
PL2611811T3 (pl) | 2010-08-31 | 2017-07-31 | Axelar Ab | Nowy sposób wytwarzania cyklolignanów |
RU2013120990A (ru) | 2010-10-08 | 2014-11-20 | Акселар Аб | Полиморфы в или с пикроподофиллина для использования в противораковой терапии |
US20120214830A1 (en) | 2011-02-22 | 2012-08-23 | OSI Pharmaceuticals, LLC | Biological markers predictive of anti-cancer response to insulin-like growth factor-1 receptor kinase inhibitors in hepatocellular carcinoma |
US9896730B2 (en) | 2011-04-25 | 2018-02-20 | OSI Pharmaceuticals, LLC | Use of EMT gene signatures in cancer drug discovery, diagnostics, and treatment |
JP5892508B2 (ja) * | 2011-05-23 | 2016-03-23 | 国立大学法人 鹿児島大学 | 抗腫瘍剤及びその製造方法 |
WO2013124382A1 (en) * | 2012-02-24 | 2013-08-29 | Nestec S.A. | Peltatin for use in the treatment of cardiovascular disorders |
WO2013132262A1 (en) | 2012-03-09 | 2013-09-12 | Axelar Ab | Picropodophyllin derivatives |
WO2013132263A1 (en) | 2012-03-09 | 2013-09-12 | Axelar Ab | Picropodophyllin derivatives for use in therapy |
WO2013152252A1 (en) | 2012-04-06 | 2013-10-10 | OSI Pharmaceuticals, LLC | Combination anti-cancer therapy |
JP5923375B2 (ja) * | 2012-04-24 | 2016-05-24 | 花王株式会社 | Cgrp応答性促進剤 |
WO2014102889A1 (ja) * | 2012-12-25 | 2014-07-03 | 国立大学法人鹿児島大学 | 抗腫瘍剤及びその製造方法 |
CA2941010A1 (en) | 2013-02-26 | 2014-09-04 | Triact Therapeutics, Inc. | Cancer therapy |
WO2014183055A1 (en) | 2013-05-10 | 2014-11-13 | M. Alphabet 2, L.L.C. | Methods of treating skin conditions using cyclolignan compounds |
CA2923667A1 (en) | 2013-09-09 | 2015-03-12 | Triact Therapeutics, Inc. | Cancer therapy |
CN104434909A (zh) * | 2013-09-12 | 2015-03-25 | 中国药科大学 | 一种去氧鬼臼毒素作为胰岛素样生长因子受体拮抗剂用途 |
WO2015168255A1 (en) | 2014-04-29 | 2015-11-05 | Whitehead Institute For Biomedical Research | Methods and compositions for targeting cancer stem cells |
US10087194B2 (en) | 2015-10-27 | 2018-10-02 | California Pacific Medical Center | Podophyllotoxin derivatives and their use |
JP6550538B2 (ja) | 2015-10-27 | 2019-07-24 | カリフォルニア パシフィック メディカル センター | ポドフィロトキシン誘導体およびそれらの使用 |
CN110669054B (zh) * | 2018-07-03 | 2022-04-26 | 南京药石科技股份有限公司 | 胰岛素样生长因子-1受体酪氨酸激酶抑制剂及其用途 |
KR102378151B1 (ko) * | 2020-05-11 | 2022-03-24 | 주식회사 제이앤씨사이언스 | 베타-아포피크로포도필린의 신규한 유도체 |
Family Cites Families (18)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US2825730A (en) * | 1953-02-04 | 1958-03-04 | Thompson Boyce Plant Res | Organic compounds |
US4342777A (en) * | 1979-03-29 | 1982-08-03 | The United States Of America As Represented By The Secretary Of Agriculture | Polybutylbenzylphenols and benzyl-3,4-methylenedioxybenzenes in insect population control |
DE3584370D1 (de) | 1984-12-28 | 1991-11-14 | Conpharm Ab | Verwendung von podophyllotoxin und dessen derivaten. |
NO170760C (no) | 1985-01-10 | 1992-12-02 | Tanabe Seiyaku Co | Analogifremgangsmaate for fremstilling av terapeutisk aktive nafthalenderivater |
SE468213B (sv) * | 1986-06-27 | 1992-11-23 | Conpharm Ab | Anvaendning av podophyllotoxin eller ett derivat daerav till framstaellning av en farmakologisk beredning foer behandling av kollagenoser, saerskilt reumatoid artrit |
WO1988003800A1 (en) * | 1986-11-19 | 1988-06-02 | Chemex Pharmaceuticals, Inc. | Lipoxygenase inhibitors |
SE464167B (sv) * | 1989-07-31 | 1991-03-18 | Analytecon Sa | Topisk farmaceutisk beredning av podophyllotoxin |
CN1075316A (zh) | 1992-10-22 | 1993-08-18 | 布里斯托尔-米尔斯·斯奎布公司 | 表鬼臼毒中间体的制备方法 |
GB9422947D0 (en) | 1994-11-14 | 1995-01-04 | Univ Salamanca | Immunosuppressive cyclolignan derivatives |
JPH09194368A (ja) * | 1996-01-11 | 1997-07-29 | Pola Chem Ind Inc | ポドフィロトキシン誘導体及びそれからなる新規細胞分化誘導剤 |
US5726027A (en) | 1996-03-08 | 1998-03-10 | The Regents Of The University Of California | Method for treatment of insulin resistance |
DE69834828T2 (de) * | 1997-11-27 | 2007-01-04 | Commonwealth Scientific And Industrial Research Organisation | Verfahren zur konstruktion von agonisten und antagonisten des igf-rezeptors (1-462) |
WO2000000238A1 (en) | 1998-06-26 | 2000-01-06 | Quanam Medical Corporation | Topoisomerase inhibitors for prevention of restenosis |
AU2001225432A1 (en) | 2000-01-20 | 2001-07-31 | Supratek Pharma, Inc. | Novel podophyllotoxin compositions |
JP4024148B2 (ja) * | 2000-11-20 | 2007-12-19 | ソンベ キム | 新規な4’−デメチル−4’−o−置換−1−デオキシポドフィロトキシン誘導体及びその幾何異性体、その製造方法及びそれを含んでなる抗癌剤組成物 |
SE0102168D0 (sv) * | 2001-06-19 | 2001-06-19 | Karolinska Innovations Ab | New use and new compounds |
EP2260846B1 (en) | 2003-03-27 | 2018-11-28 | Lankenau Institute for Medical Research | Novel methods for the treatment of cancer |
SE0301202D0 (sv) * | 2003-04-24 | 2003-04-24 | Orteca Ab C O Karolinska Innov | New use and new compounds |
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2001
- 2001-06-19 SE SE0102168A patent/SE0102168D0/xx unknown
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2002
- 2002-06-19 EP EP08150436A patent/EP1938818A3/en not_active Withdrawn
- 2002-06-19 EP EP10153209A patent/EP2186513A1/en not_active Withdrawn
- 2002-06-19 EP EP04024370A patent/EP1498121B1/en not_active Expired - Lifetime
- 2002-06-19 WO PCT/SE2002/001202 patent/WO2002102804A1/en active IP Right Grant
- 2002-06-19 NO NO20035648A patent/NO332642B1/no not_active IP Right Cessation
- 2002-06-19 CN CN028162404A patent/CN1659171A/zh active Pending
- 2002-06-19 JP JP2003506278A patent/JP2004534078A/ja active Pending
- 2002-06-19 DK DK04024370T patent/DK1498121T3/da active
- 2002-06-19 CA CA2455328A patent/CA2455328C/en not_active Expired - Fee Related
- 2002-06-19 PT PT04024370T patent/PT1498121E/pt unknown
- 2002-06-19 AU AU2002311731A patent/AU2002311731B8/en not_active Ceased
- 2002-06-19 US US10/480,800 patent/US20040167208A1/en not_active Abandoned
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- 2002-06-19 CN CNA2009101347598A patent/CN101606929A/zh active Pending
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- 2002-06-19 KR KR1020037016630A patent/KR100940055B1/ko active IP Right Grant
- 2002-06-19 NZ NZ530290A patent/NZ530290A/en not_active IP Right Cessation
- 2002-06-19 ES ES04024370T patent/ES2333014T3/es not_active Expired - Lifetime
- 2002-06-19 AT AT04024370T patent/ATE441411T1/de active
- 2002-06-19 CN CNB028161904A patent/CN100503611C/zh not_active Expired - Fee Related
- 2002-06-19 JP JP2003506277A patent/JP5071910B2/ja not_active Expired - Fee Related
- 2002-06-19 EP EP08150437A patent/EP1938819A3/en not_active Withdrawn
- 2002-06-19 EP EP02741588A patent/EP1397369A1/en not_active Ceased
- 2002-06-19 NZ NZ53017202A patent/NZ530172A/xx unknown
- 2002-06-19 CA CA2451047A patent/CA2451047C/en not_active Expired - Fee Related
- 2002-06-19 WO PCT/SE2002/001223 patent/WO2002102805A1/en not_active Application Discontinuation
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