DK2536414T3 - Fremgangsmåde til forebyggelse af cancermetastaser - Google Patents
Fremgangsmåde til forebyggelse af cancermetastaser Download PDFInfo
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- DK2536414T3 DK2536414T3 DK11703705.1T DK11703705T DK2536414T3 DK 2536414 T3 DK2536414 T3 DK 2536414T3 DK 11703705 T DK11703705 T DK 11703705T DK 2536414 T3 DK2536414 T3 DK 2536414T3
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Classifications
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- 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
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/7028—Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages
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- 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
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/7004—Monosaccharides having only carbon, hydrogen and oxygen atoms
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- 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
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/7008—Compounds having an amino group directly attached to a carbon atom of the saccharide radical, e.g. D-galactosamine, ranimustine
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- 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
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/7016—Disaccharides, e.g. lactose, lactulose
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- 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
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/702—Oligosaccharides, i.e. having three to five saccharide radicals attached to each other by glycosidic linkages
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
- A61P35/04—Antineoplastic agents specific for metastasis
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
- C07H11/00—Compounds containing saccharide radicals esterified by inorganic acids; Metal salts thereof
- C07H11/04—Phosphates; Phosphites; Polyphosphates
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
- C07H15/00—Compounds containing hydrocarbon or substituted hydrocarbon radicals directly attached to hetero atoms of saccharide radicals
- C07H15/02—Acyclic radicals, not substituted by cyclic structures
- C07H15/04—Acyclic radicals, not substituted by cyclic structures attached to an oxygen atom of the saccharide radical
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Molecular Biology (AREA)
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- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
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- Genetics & Genomics (AREA)
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- Biochemistry (AREA)
- Engineering & Computer Science (AREA)
- Crystallography & Structural Chemistry (AREA)
- Oncology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Saccharide Compounds (AREA)
Claims (12)
1. Glycerolipid med formel (I)
hvor: - Ri er en alkyl- eller alkenylgruppe med fra 16 til 18 carbonatomer, - R2 er en gruppe valgt fra gruppen bestående af: (a) en gruppe med formel (II):
hvor R21, R22 og R23, en uafhængigt fra hinanden, er valgt fra gruppen bestående af hydrogenatom og en alkylgruppe med 1 eller 2 carbonatomer, og (b) hydroxyl, og - R3 er valgt fra gruppen bestående af: - en monosaccharidgruppe eller en polysaccharidgruppe med fra 2 til 4 saccharidenheder, eller - en gruppe med formel (III)
hvor R4 er valgt fra gruppen bestående af en monosaccharidgruppe eller en polysaccharidgruppe med fra 2 til 4 saccharidenheder, til anvendelse i forebyggelse af cancermetastaser uden virkning på primær tumorvæksten.
2. Glycerolipidet med formel (I) til anvendelse ifølge krav 1, hvor Ri er en alkyl-eller alkenylgruppe med 16 eller 17 carbonatomer.
3. Glycerolipidet med formel (I) til anvendelse ifølge krav 1, hvor Ri er -(CH2)i5-CHs.
4. Glycerolipidet med formel (I) til anvendelse ifølge krav 1, hvor R2 er med formel (II) og R21, R22 og R23 hver er et hydrogenatom.
5. Glycerolipidet med formel (I) til anvendelse ifølge krav 1, hvor R3 eller R4 er et monosaccharid valgt fra gruppen bestående af pentosyl og hexosyl.
6. Glycerolipidet med formel (I) til anvendelse ifølge krav 1, hvor R3 eller R4 er hexosyl valgt fra gruppen bestående af D-glucosyl, D-mannosyl og D-galactosyl.
7. Glycerolipidet med formel (I) til anvendelse ifølge krav 1, hvor forbindelsen med formel (I) er valgt fra gruppen bestående af forbindelserne (A) til (P) nedenfor: - forbindelse (A):
R= H eller CHsCO - forbindelse (B):
R= H eller CHsCO - forbindelse (C):
R= H eller CHsCO - forbindelse (D):
R= H eller CHsCO hvor R3 betegner en Gal-p-(l-4)-Glu-gruppe, også benævnt lactose - forbindelse (E):
R= H eller CHsCO hvor R3 betegner en Gal-a-(l-4)-Glu-gruppe - forbindelse (F):
R= H eller CHaCO hvor R3 betegner en Glu-p-(l-4)-Glu-gruppe, - forbindelse (G):
R= H eller CHaCO hvor R3 betegner en Glu-a-(l-4)-Glu-gruppe, også benævnt maltose, - forbindelse (H):
R= H eller CHaCO hvor R71 og R72 er uafhængigt valgt fra gruppen bestående af et hydrogenatom og en hydroxylgruppe eller acetylgruppe, der omfatter (i) Gal^-(l-6)-Glu når R71 er H og R72 er OH eller OAc og (ii) Glu^-(l-6)-Glu når R71 er OH eller OAc og R72 er H, - forbindelse (I):
R= H eller CHsCO hvor R71 og R72 er uafhængigt valgt fra gruppen bestående af et hydrogenatom og en hydroxylgruppe eller acetylgruppe, der omfatter (i) Gal-a-(l-6)-Glu når R71 er H og R72 er OH eller OAc ,også benævnt melibiose eller acetylmelibiose og (ii) Glu-a-(l-6)-Glu når R71 er OH eller OAc og R72 er H, - forbindelse (J):
R= H eller CHaCO hvor R71 og R72 er uafhængigt valgt fra gruppen bestående af et hydrogenatom og en hydroxylgruppe eller acetylgruppe, der omfatter (i) Gal^-(l-6)-Gal når R71 er H og R72 er OH eller OAc og (ii) Glu-p-(l-6)-Gal når R71 er OH eller OAc og R72 er H - forbindelse (K):
R= H eller CHaCO hvor R71 og R72 er uafhængigt valgt fra gruppen bestående af et hydrogenatom og en hydroxylgruppe eller acetylgruppe, der omfatter (i) Gal-a-(l-6)-Gal når R71 er H og R72 er OH eller OAc og (ii) Glu-a-(l-6)-Gal når R71 er OH eller OAc og R72 er H, - forbindelse (L):
R= H eller CHsCO hvor R81 og R82 er uafhængigt valgt fra gruppen bestående af et hydrogenatom og en hydroxylgruppe eller acetylgruppe, - forbindelse (M):
R= H eller CH3CO hvor R4 betegner en Gal-p-(l-4)-Glu-gruppe, også benævnt lactose eller acetyl lactose, - forbindelse (N):
R= H eller CHsCO hvor R4 betegner en Glu-a-(l-4)-Glu-gruppe, også benævnt maltose eller acetylmaltose, - forbindelse (O):
R= H eller CH3CO hvor R71 og R72 er uafhængigt valgt fra gruppen bestående af et hydrogenatom og en hydroxylgruppe eller acetyl, der omfatter (i) Gal-a-(l-6)-Glu når R71 er H og R72 er OH eller OAc ,også benævnt melibiose eller acetylmelibiose, og (ii) Glu-a-(l-6)-Glu når R71 er OH eller OAc og R72 er H, - forbindelse (P):
R= H eller CH3CO hvor R81 og R82 er uafhængigt valgt fra gruppen bestående af et hydrogenatom og en hydroxylgruppe eller acetylgruppe, der omfatter (i) lactose-p-eller acetyllactose-p-(l-6)-Gal når R81 er H og R82 er OH eller OAc og (ii) lactose-p-eller acetyllactose-β- (l-6)-Glu når R81 er OH eller OAc og R82 er H.
8. Glycerolipid med formel (I), ifølge krav i, hvor R3 består af en gruppe med formel (III)
og hvor R4 er valgt fra gruppen bestående af en monosaccharidgruppe eller en polysaccharidgruppe med fra 2 til 4 saccharidenheder til anvendelse som et medikament.
9. Forbindelse ifølge krav 8, valgt fra gruppen bestående af forbindelserne (M) til (P) nedenfor: - forbindelse (M):
R= H eller CHsCO hvor R4 betegner en Gal^-(l-4)-Glu-gruppe, også benævnt lactose eller acetyllactose, - forbindelse (N):
R= H eller CHsCO hvor R4 betegner en Glu-a-(l-4)-Glu-gruppe, også benævnt maltose eller acetylmaltose, - forbindelse (O):
R= H eller CHsCO hvor R71 og R72 er uafhængigt valgt fra gruppen bestående af et hydrogenatom og en hydroxylgruppe eller acetyl, der omfatter (i) Gal-a-(l-6)-Glu når R71 er H og R72 er OH eller OAc, også benævnt melibiose eller acetylmelibiose, og (ii) Glu-a-(l-6)-Glu når R71 er OH eller OAc og R72 er H, - forbindelse (P):
R= H eller CHaCO hvor R81 og R82 er uafhængigt valgt fra gruppen bestående af et hydrogenatom og en hydroxylgruppe eller acetylgruppe, der omfatter (i) lactose-β- eller acetyllactose-p-(l-6)-Glu når R81 er H og R82 er OH eller OAc og (ii) lactose-β- eller acetyllactose^-(l-6)-Gal når R81 er OH eller OAc og R82 er H, til anvendelse som et medikament.
10. Glycerolipid med formel (I), ifølge et hvilket som helst af kravene 8 eller 9.
11. Farmaceutisk sammensætning til forebyggelse af metastaser omfattende en forbindelse med formel (I) ifølge et hvilket som helst af kravene 8 eller 9, i kombination med ét eller flere farmaceutiske hjælpestoffer.
12. Glycerolipid med formel (I) til anvendelse ifølge kravene 8 eller 9, i forebyggelse af cancermetastaser med ingen virkning på primær tumorvæksten.
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EP10305169 | 2010-02-18 | ||
| PCT/EP2011/052351 WO2011101408A1 (en) | 2010-02-18 | 2011-02-17 | Method for preventing cancer metastasis |
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| EP (1) | EP2536414B1 (da) |
| JP (1) | JP2013519706A (da) |
| DK (1) | DK2536414T3 (da) |
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| WO (1) | WO2011101408A1 (da) |
Families Citing this family (39)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6795636B1 (en) | 2000-03-05 | 2004-09-21 | 3M Innovative Properties Company | Radiation-transmissive films on glass articles |
| RS53350B (sr) | 2008-09-22 | 2014-10-31 | Array Biopharma, Inc. | Supstituisana jedinjenja imidazo[1,2-b]piridazina kao inhibitori trk kinaze |
| PT2725028T (pt) | 2008-10-22 | 2016-08-31 | Array Biopharma Inc | Compostos de pirazolo[1,5-]pirimidina substituídos como intermediários na síntese de inibidores de cinase trk |
| AR077468A1 (es) | 2009-07-09 | 2011-08-31 | Array Biopharma Inc | Compuestos de pirazolo (1,5 -a) pirimidina sustituidos como inhibidores de trk- quinasa |
| WO2011146336A1 (en) | 2010-05-20 | 2011-11-24 | Array Biopharma Inc. | Macrocyclic compounds as trk kinase inhibitors |
| EP2747770A1 (en) | 2011-08-26 | 2014-07-02 | BIAL - Portela & Cª S.A. | Treatments involving eslicarbazepine acetate or eslicarbazepine |
| CN102286036A (zh) * | 2011-08-28 | 2011-12-21 | 武汉信嘉和诚药物化学有限公司 | 红景天苷的合成方法 |
| ES2941630T3 (es) | 2014-11-16 | 2023-05-24 | Array Biopharma Inc | Forma cristalina de sulfato de hidrógeno de (S)-N-(5-((R)-2-(2,5-difluorofenil)-pirrolidin-1-il)-pirazolo[1,5-a]pirimidin-3-il)-3-hidroxipirrolidin-1-carboxamida |
| JP6816100B2 (ja) | 2015-07-16 | 2021-01-20 | アレイ バイオファーマ、インコーポレイテッド | ＲＥＴキナーゼ阻害物質としての置換ピラゾロ［１，５−ａ］ピリジン化合物 |
| TN2019000271A1 (en) | 2015-10-26 | 2021-01-07 | Univ Colorado Regents | Point mutations in trk inhibitor-resistant cancer and methods relating to the same |
| MX386416B (es) | 2016-04-04 | 2025-03-18 | Loxo Oncology Inc | Formulaciones liquidas de (s)-n-(5-((r)-2-(2,5-difluorofenil)-pirrolidin-1-il)-pirazolo[1,5-a]pirimidin-3-il)-3-hidroxipirrolidina-1-carboxamida. |
| US10045991B2 (en) | 2016-04-04 | 2018-08-14 | Loxo Oncology, Inc. | Methods of treating pediatric cancers |
| PE20190437A1 (es) | 2016-05-18 | 2019-03-27 | Loxo Oncology Inc | Procesos para la preparacion de (s)-n-(5-((r)-2-(2,5-difluorofenil)pirrolidin-1-il)-pirazolo[1,5-a]pirimidin-3-il)-3-hidroxipirrolidin-1-carboxamida y sales del mismo |
| US10780907B1 (en) | 2016-06-02 | 2020-09-22 | Invententional Products, Llc | Attachable cart system and method |
| TWI704148B (zh) | 2016-10-10 | 2020-09-11 | 美商亞雷生物製藥股份有限公司 | 作為ｒｅｔ激酶抑制劑之經取代吡唑并[1,5-a]吡啶化合物 |
| JOP20190077A1 (ar) | 2016-10-10 | 2019-04-09 | Array Biopharma Inc | مركبات بيرازولو [1، 5-a]بيريدين بها استبدال كمثبطات كيناز ret |
| JOP20190092A1 (ar) | 2016-10-26 | 2019-04-25 | Array Biopharma Inc | عملية لتحضير مركبات بيرازولو[1، 5-a]بيريميدين وأملاح منها |
| CN110267960B (zh) | 2017-01-18 | 2022-04-26 | 阿雷生物药品公司 | 作为RET激酶抑制剂的取代的吡唑并[1,5-a]吡嗪化合物 |
| WO2018136663A1 (en) | 2017-01-18 | 2018-07-26 | Array Biopharma, Inc. | Ret inhibitors |
| JOP20190213A1 (ar) | 2017-03-16 | 2019-09-16 | Array Biopharma Inc | مركبات حلقية ضخمة كمثبطات لكيناز ros1 |
| TWI812649B (zh) | 2017-10-10 | 2023-08-21 | 美商絡速藥業公司 | 6-(2-羥基-2-甲基丙氧基)-4-(6-(6-((6-甲氧基吡啶-3-基)甲基)-3,6-二氮雜雙環[3.1.1]庚-3-基)吡啶-3-基)吡唑并[1,5-a]吡啶-3-甲腈之調配物 |
| TWI791053B (zh) | 2017-10-10 | 2023-02-01 | 美商亞雷生物製藥股份有限公司 | 6-(2-羥基-2-甲基丙氧基)-4-(6-(6-((6-甲氧基吡啶-3-基)甲基)-3,6-二氮雜雙環[3.1.1]庚-3-基)吡啶-3-基)吡唑并[1,5-a]吡啶-3-甲腈之結晶形式及其醫藥組合物 |
| EP3740486A1 (en) | 2018-01-18 | 2020-11-25 | Array Biopharma, Inc. | Substituted pyrazolyl[4,3-c]pyridinecompounds as ret kinase inhibitors |
| WO2019143977A1 (en) | 2018-01-18 | 2019-07-25 | Array Biopharma Inc. | Substituted pyrrolo[2,3-d]pyrimidines compounds as ret kinase inhibitors |
| CA3087578C (en) | 2018-01-18 | 2023-08-08 | Array Biopharma Inc. | Substituted pyrazolo[3,4-d]pyrimidine compounds as ret kinase inhibitors |
| EP3849986B1 (en) | 2018-09-10 | 2022-06-08 | Array Biopharma, Inc. | Fused heterocyclic compounds as ret kinase inhibitors |
| JP2022515197A (ja) | 2018-12-19 | 2022-02-17 | アレイ バイオファーマ インコーポレイテッド | がんを治療するためのｆｇｆｒ阻害剤としての７－（（３，５－ジメトキシフェニル）アミノ）キノキサリン誘導体 |
| US12180207B2 (en) | 2018-12-19 | 2024-12-31 | Array Biopharma Inc. | Substituted pyrazolo[1,5-a]pyridine compounds as inhibitors of FGFR tyrosine kinases |
| WO2021113492A1 (en) | 2019-12-06 | 2021-06-10 | Schrödinger, Inc. | Cyclic compounds and methods of using same |
| EP4081526A1 (en) | 2019-12-27 | 2022-11-02 | Schrödinger, Inc. | Cyclic compounds and methods of using same |
| US20230287031A1 (en) * | 2020-07-17 | 2023-09-14 | Université De Bretagne Occidentale | New glycolipids and use thereof as sk3 ion channel modulators |
| CN116490507A (zh) | 2020-09-10 | 2023-07-25 | 薛定谔公司 | 用于治疗癌症的杂环包缩合cdc7激酶抑制剂 |
| CN112321446A (zh) * | 2020-11-25 | 2021-02-05 | 华南理工大学 | 一种酰胺衍生物的合成方法 |
| EP4284804A1 (en) | 2021-01-26 | 2023-12-06 | Schrödinger, Inc. | Tricyclic compounds useful in the treatment of cancer, autoimmune and inflammatory disorders |
| TW202300150A (zh) | 2021-03-18 | 2023-01-01 | 美商薛定諤公司 | 環狀化合物及其使用方法 |
| WO2024126812A1 (en) | 2022-12-15 | 2024-06-20 | Lifesome Therapeutics, S.L. | Carrier as a multifunctional system |
| WO2025059027A1 (en) | 2023-09-11 | 2025-03-20 | Schrödinger, Inc. | Cyclopenta[e]pyrazolo[1,5-a]pyrimidine derivatives as malt1 inhibitors |
| WO2025235874A1 (en) | 2024-05-10 | 2025-11-13 | Schrödinger, Inc. | Heterocyclics as egfr inhibitors |
| WO2025235872A1 (en) | 2024-05-10 | 2025-11-13 | Schrödinger, Inc. | Heterocyclics as egfr inhibitors |
Family Cites Families (17)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4275588A (en) | 1979-12-31 | 1981-06-30 | Texaco Inc. | Heavy duty dynamic high-torque-measurement coupling unit |
| US5385685A (en) | 1991-12-31 | 1995-01-31 | Lever Brothers Company, Division Of Conopco, Inc. | Compositions comprising glyceroglycolipids having an ether linkage as a surfactant or cosurfactant |
| PT785773E (pt) | 1994-10-14 | 2001-05-31 | Liposome Co Inc | Lipossomas de eteres lipidicos e sua utilizacao terapeutica |
| US6153736A (en) * | 1995-09-27 | 2000-11-28 | The Liposome Company, Inc. | Modified ether glyceroglycolipids |
| CA2246568C (en) | 1996-02-16 | 2007-08-07 | Hans-Jorg Eibl | Phosphatidyl oligoglycerols |
| DE19634020A1 (de) | 1996-08-23 | 1998-02-26 | Beiersdorf Ag | Herstellung von Glycoglycerolipiden, deren Verwendung als Tenside sowie kosmetische oder dermatologische Zubereitungen, solche Glycoglycerolipide enthaltend |
| DE19634021A1 (de) * | 1996-08-23 | 1998-02-26 | Beiersdorf Ag | Antiadhäsive Glycoglycerolipide |
| US5932242A (en) | 1996-10-15 | 1999-08-03 | The Liposome Company, Inc. | Ether lipid-containing pharmaceutical compositions and therapeutic uses thereof |
| AU4427199A (en) * | 1998-06-26 | 2000-01-17 | Georgetown University | Inhibitors of phosphatidyl (myo)-inositol cycle |
| DE69924146D1 (de) | 1998-12-21 | 2005-04-14 | Inkeysa Sa | Etherlysophospholipide zur behandlung von chronischen entzündlichen erkrankungen |
| DE60032470T2 (de) | 1999-02-26 | 2007-10-11 | Toyo Suisan Kaisha, Ltd. | Heilmittel die sulfopyranosylacylglycerolderivate enthalten |
| WO2001062206A2 (en) | 2000-02-22 | 2001-08-30 | Mount Sinai School Of Medicine Of New York University | N-cadherin modulated migration, invasion, and metastasis |
| EP1341800A2 (en) * | 2000-12-11 | 2003-09-10 | The Research Foundation Of the City university of New York | C-glucosyl ether lipids |
| EP1583552A2 (en) * | 2003-01-09 | 2005-10-12 | Zeneus Pharma Limited | Antineoplastic ether lipid compounds |
| CN1326823C (zh) * | 2006-05-26 | 2007-07-18 | 中国科学院南海海洋研究所 | 一种环醇衍生物角质海绵醇及其制备方法和应用 |
| EP1884774A1 (en) | 2006-08-03 | 2008-02-06 | INSERM (Institut National de la Santé et de la Recherche Medicale) | A method for the in vitro screening of anti-cancer compounds that inhibits SK3 activity, and said anti-cancer compounds |
| WO2009092170A1 (en) * | 2008-01-24 | 2009-07-30 | University Of Manitoba | The use of glycosylated antitumor ether lipids to induce and/or enhance autophagy for treatment of diseases |
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- 2011-02-17 JP JP2012553317A patent/JP2013519706A/ja not_active Withdrawn
- 2011-02-17 WO PCT/EP2011/052351 patent/WO2011101408A1/en not_active Ceased
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Also Published As
| Publication number | Publication date |
|---|---|
| ES2594927T3 (es) | 2016-12-23 |
| WO2011101408A1 (en) | 2011-08-25 |
| US20130029925A1 (en) | 2013-01-31 |
| EP2536414A1 (en) | 2012-12-26 |
| JP2013519706A (ja) | 2013-05-30 |
| EP2536414B1 (en) | 2016-07-13 |
| US9161944B2 (en) | 2015-10-20 |
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