ES2884044T3 - Profármaco alquilante de fosforamidato para el tratamiento del cáncer - Google Patents
Profármaco alquilante de fosforamidato para el tratamiento del cáncer Download PDFInfo
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- ES2884044T3 ES2884044T3 ES07869800T ES07869800T ES2884044T3 ES 2884044 T3 ES2884044 T3 ES 2884044T3 ES 07869800 T ES07869800 T ES 07869800T ES 07869800 T ES07869800 T ES 07869800T ES 2884044 T3 ES2884044 T3 ES 2884044T3
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- A—HUMAN NECESSITIES
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- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
- A61K9/19—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles lyophilised, i.e. freeze-dried, solutions or dispersions
-
- 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)
- Engineering & Computer Science (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- Dermatology (AREA)
- Oil, Petroleum & Natural Gas (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicinal Preparation (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US87186506P | 2006-12-26 | 2006-12-26 | |
| PCT/US2007/088645 WO2008083101A1 (en) | 2006-12-26 | 2007-12-21 | Phosphoramidate alkylator prodrugs for the treatment of cancer |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| ES2884044T3 true ES2884044T3 (es) | 2021-12-10 |
Family
ID=39588979
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| ES07869800T Active ES2884044T3 (es) | 2006-12-26 | 2007-12-21 | Profármaco alquilante de fosforamidato para el tratamiento del cáncer |
Country Status (5)
| Country | Link |
|---|---|
| US (1) | US8552048B2 (cg-RX-API-DMAC7.html) |
| EP (1) | EP2114157B1 (cg-RX-API-DMAC7.html) |
| JP (1) | JP5357049B2 (cg-RX-API-DMAC7.html) |
| ES (1) | ES2884044T3 (cg-RX-API-DMAC7.html) |
| WO (1) | WO2008083101A1 (cg-RX-API-DMAC7.html) |
Families Citing this family (37)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| ZA200507752B (en) | 2003-03-28 | 2007-01-31 | Threshold Pharmaceuticals Inc | Compositions and methods for treating cancer |
| EP1896040B1 (en) | 2005-06-29 | 2012-08-01 | Threshold Pharmaceuticals, Inc. | Phosphoramidate alkylator prodrugs |
| EP2114157B1 (en) | 2006-12-26 | 2021-05-26 | ImmunoGenesis, Inc. | Phosphoramidate alkylator prodrug for the treatment of cancer |
| ES2884674T3 (es) * | 2008-10-21 | 2021-12-10 | Immunogenesis Inc | Tratamiento del cáncer con el profármaco activado por hipoxia TH-302 en combinación con docetaxel o pemetrexed |
| MX2012014416A (es) * | 2010-06-28 | 2013-02-27 | Threshold Pharmaceuticals Inc | Tratamiento de cancer de sangre. |
| MX2012014428A (es) | 2010-07-12 | 2013-03-05 | Threshold Pharmaceuticals Inc | Administracion de profarmacos activados por hipoxia y de agentes antiangiogenicos para el tratamiento de cancer. |
| KR20140038390A (ko) * | 2011-04-01 | 2014-03-28 | 쓰레솔드 파마슈티컬스, 인코포레이티드 | 암을 치료하는 방법 |
| WO2012142520A2 (en) * | 2011-04-15 | 2012-10-18 | Threshold Pharmaceuticals, Inc. | Unit dose form for oral administration |
| JP2015500885A (ja) * | 2011-12-22 | 2015-01-08 | スレッショルド ファーマシューティカルズ，インコーポレイテッド | 癌を治療するためのｃｈｋ１阻害剤と組み合わせた低酸素活性化プロドラッグの投与 |
| US20160045522A1 (en) * | 2012-02-21 | 2016-02-18 | Threshold Pharmaceuticals, Inc. | Treatment of Cancer |
| US9278124B2 (en) | 2012-10-16 | 2016-03-08 | Halozyme, Inc. | Hypoxia and hyaluronan and markers thereof for diagnosis and monitoring of diseases and conditions and related methods |
| US10037382B2 (en) | 2012-10-29 | 2018-07-31 | Kyocera Corporation | Surface acoustic wave sensor |
| WO2015013448A1 (en) | 2013-07-26 | 2015-01-29 | Threshold Pharmaceuticals, Inc. | Treatment of pancreatic cancer with a combination of a hypoxia-acti vated prodrug and a taxane |
| US10071109B2 (en) | 2013-11-06 | 2018-09-11 | Molecular Templates, Inc. | Predictive biomarker for hypoxia-activated prodrug therapy |
| US10131683B2 (en) | 2014-07-17 | 2018-11-20 | Molecular Templates, Inc. | TH-302 solid forms and methods related thereto |
| SG11201707293VA (en) | 2015-03-10 | 2017-10-30 | Ascenta Pharmaceuticals Ltd | Dna alkylating agents |
| BR112017021167A2 (pt) | 2015-04-02 | 2018-07-03 | Obi Pharma, Inc. | composto, método de tratamento de câncer, e processo para preparar o composto de fórmula i |
| PL412787A1 (pl) | 2015-06-22 | 2017-01-02 | Magdalena Król | Oparty na makrofagach celowany system dostarczania związków związanych z ferrytyną |
| WO2016210175A1 (en) | 2015-06-24 | 2016-12-29 | Threshold Pharmaceuticals, Inc. | Aziridine containing dna alkylating agents |
| JP2019527236A (ja) | 2016-08-01 | 2019-09-26 | モレキュラー テンプレーツ，インコーポレイティド | 癌を治療するための免疫調節剤と組み合わせた低酸素活性化型プロドラッグの投与 |
| US20210283139A1 (en) | 2018-06-13 | 2021-09-16 | Amphista Therapeutics Ltd | Bifunctional molecules for targeting uchl5 |
| WO2019238886A1 (en) | 2018-06-13 | 2019-12-19 | University Of Dundee | Bifunctional molecules for targeting usp14 |
| CA3103185A1 (en) | 2018-06-13 | 2019-12-19 | Amphista Therapeutics Ltd | Bifunctional molecules for targeting rpn11 |
| WO2020068347A1 (en) * | 2018-09-24 | 2020-04-02 | Sierra Oncology, Inc. | Methods of treatment of cancer comprising cdc7 inhibitors |
| EP3650046A1 (en) | 2018-11-08 | 2020-05-13 | Cellis AG | Mesenchymal stem cell based targeted active ingredient delivery system |
| US20230174624A1 (en) | 2020-03-18 | 2023-06-08 | Cellis Ag | Ferritin variants with increased stability, complexation ability and transferrin receptor affinity |
| CA3212386A1 (en) | 2021-03-18 | 2022-09-22 | Alessandro ARCOVITO | Ferritin variants with increased stability and complexation ability |
| US20240366640A1 (en) * | 2021-08-27 | 2024-11-07 | Ascentawits Pharmaceuticals, Ltd. | Lyophilized formulation solution and lyophilized formulation, and method and use thereof |
| JP7762796B2 (ja) * | 2021-08-27 | 2025-10-30 | アセンタウィッツ ファーマシューティカルズ リミテッド | Ｐａｒｐ阻害剤に耐性のある患者のｔｈ－３０２による治療 |
| CN118829436A (zh) | 2022-03-15 | 2024-10-22 | 深圳艾欣达伟医药科技有限公司 | 治疗brca突变癌症患者的方法 |
| US20250295677A1 (en) | 2022-04-15 | 2025-09-25 | Ascentawits Pharmaceuticals, Ltd. | Method for treating cancer by using th-302 alone or in combination with parp inhibitor |
| WO2023226959A1 (zh) | 2022-05-23 | 2023-11-30 | 深圳艾欣达伟医药科技有限公司 | 烷化剂前药与细胞周期抑制剂联用治疗癌症的方法 |
| JP2025532550A (ja) | 2022-09-13 | 2025-10-01 | セリス アーゲー | 神経膠腫の処置用の単離標的化送達系 |
| WO2024061346A1 (zh) | 2022-09-22 | 2024-03-28 | 深圳艾欣达伟医药科技有限公司 | 乏氧激活的化合物在制备治疗癌症患者的药物中的用途 |
| EP4637829A1 (en) | 2022-12-20 | 2025-10-29 | Cellis Sp. z o.o. ([Ltd.] | Isolated targeted delivery system for the treatment of ovarian cancer |
| WO2024179467A1 (zh) * | 2023-02-27 | 2024-09-06 | 深圳艾欣达伟医药科技有限公司 | 溶液、冻干制剂、冻干制剂单位包装、注射液及注射液配制方法 |
| WO2025083276A1 (en) | 2023-10-19 | 2025-04-24 | Cellis Ag | Improved isolated targeted delivery system |
Family Cites Families (45)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3652579A (en) * | 1969-06-26 | 1972-03-28 | Hoffmann La Roche | 1-methyl-2-substituted 5-nitroimidazoles |
| DE2229248C3 (de) | 1971-07-30 | 1980-03-27 | Gruppo Lepetit S.P.A., Mailand (Italien) | 5-Iminomethyl-2-nitroimidazoI-Derivate und Verfahren zu deren Herstellung |
| US4921963A (en) * | 1987-04-13 | 1990-05-01 | British Columbia Cancer Foundation | Platinum complexes with one radiosensitizing ligand |
| JPH0819111B2 (ja) * | 1987-10-22 | 1996-02-28 | ポーラ化成工業株式会社 | ２―ニトロイミダゾール誘導体及びこれを有効成分とする放射線増感剤 |
| US4908356A (en) * | 1988-05-25 | 1990-03-13 | Research Corporation Technologies, Inc. | Aldophosphamide derivatives useful as antitumor agents |
| US5403932A (en) * | 1988-05-25 | 1995-04-04 | Research Corporation Technologies, Inc. | Phosphoramidates useful as antitumor agents |
| US5190929A (en) * | 1988-05-25 | 1993-03-02 | Research Corporation Technologies, Inc. | Cyclophosphamide analogs useful as anti-tumor agents |
| DE3835772A1 (de) * | 1988-10-20 | 1990-04-26 | Deutsches Krebsforsch | Tumorhemmende saccharid-konjugate |
| JP2626727B2 (ja) * | 1990-01-26 | 1997-07-02 | ポーラ化成工業株式会社 | ２―ニトロイミダゾール誘導体、その製造法及びこれを有効成分とする放射線増感剤 |
| US5233031A (en) * | 1991-09-23 | 1993-08-03 | University Of Rochester | Phosphoramidate analogs of 2'-deoxyuridine |
| WO1993008288A1 (en) * | 1991-10-23 | 1993-04-29 | Cancer Research Campaign Technology Limited | Bacterial nitroreductase for the reduction of cb 1954 and analogues thereof to a cytotoxic form |
| US5750782A (en) * | 1992-11-27 | 1998-05-12 | Cancer Research Campaign Technology Limited | Nitroaniline derivatives and their use as anti-tumour agents |
| US5306727A (en) | 1993-04-30 | 1994-04-26 | Research Corporation Technologies, Inc. | Phosphoramidates useful as antitumor agents |
| JPH08510469A (ja) * | 1993-05-25 | 1996-11-05 | オークランド ユニサービシーズ リミテッド | ニトロベンジルマスタード四級塩およびその低酸素選択性細胞毒剤としての利用 |
| EP0648503B1 (en) | 1993-09-22 | 2000-07-26 | Hoechst Aktiengesellschaft | Pro-prodrugs, their production and use |
| JPH07309761A (ja) * | 1994-05-20 | 1995-11-28 | Kyowa Hakko Kogyo Co Ltd | デュオカルマイシン誘導体の安定化法 |
| US5659061A (en) | 1995-04-20 | 1997-08-19 | Drug Innovation & Design, Inc. | Tumor protease activated prodrugs of phosphoramide mustard analogs with toxification and detoxification functionalities |
| GB9516943D0 (en) * | 1995-08-18 | 1995-10-18 | Cancer Soc Auckland Div Nz Inc | Novel cyclopropylindoles and their secoprecursors,and their use as prodrugs |
| US6218519B1 (en) * | 1996-04-12 | 2001-04-17 | Pro-Neuron, Inc. | Compounds and methods for the selective treatment of cancer and bacterial infections |
| US6130237A (en) * | 1996-09-12 | 2000-10-10 | Cancer Research Campaign Technology Limited | Condensed N-aclyindoles as antitumor agents |
| US6251933B1 (en) * | 1996-12-13 | 2001-06-26 | The Cancer Research Campaign Technology Limited | Seco precursors of cyclopropylindolines and their use as prodrugs |
| DE19720312A1 (de) * | 1997-05-15 | 1998-11-19 | Hoechst Ag | Zubereitung mit erhöhter in vivo Verträglichkeit |
| US6240925B1 (en) * | 1999-03-23 | 2001-06-05 | Cynosure, Inc. | Photothermal vascular targeting with bioreductive agents |
| GB9909612D0 (en) | 1999-04-26 | 1999-06-23 | Cancer Res Campaign Tech | N-protected amines and their use as prodrugs |
| JP4629238B2 (ja) * | 1999-05-24 | 2011-02-09 | サザン・リサーチ・インスティテュート | イソホスホアミドマスタード・アナログ及びその使用 |
| WO2001004130A1 (en) * | 1999-07-14 | 2001-01-18 | Purdue Research Foundation | Phosphoramide compounds |
| ATE317846T1 (de) * | 2000-03-31 | 2006-03-15 | Purdue Research Foundation | Phosphoramidat-prodrugs |
| EP1243276A1 (en) | 2001-03-23 | 2002-09-25 | Franciscus Marinus Hendrikus De Groot | Elongated and multiple spacers containing activatible prodrugs |
| US6506739B1 (en) * | 2001-05-01 | 2003-01-14 | Telik, Inc. | Bis-(N,N'-bis-(2-haloethyl)amino)phosphoramidates as antitumor agents |
| US7087600B2 (en) | 2001-05-31 | 2006-08-08 | Medarex, Inc. | Peptidyl prodrugs and linkers and stabilizers useful therefor |
| FR2825926A1 (fr) | 2001-06-14 | 2002-12-20 | Sod Conseils Rech Applic | Derives d'imidazoles modulant les canaux sodiques |
| US7091186B2 (en) * | 2001-09-24 | 2006-08-15 | Seattle Genetics, Inc. | p-Amidobenzylethers in drug delivery agents |
| KR20030067275A (ko) | 2002-02-07 | 2003-08-14 | 주식회사 하이폭시 | 니트로이미다졸 및 위상 이성질화 효소 저해제를유효성분으로 포함하는 항암제 |
| GB0306907D0 (en) | 2003-03-26 | 2003-04-30 | Angiogene Pharm Ltd | Boireductively-activated prodrugs |
| GB0306908D0 (en) | 2003-03-26 | 2003-04-30 | Angiogene Pharm Ltd | Bioreductively activated stilbene prodrugs |
| ZA200507752B (en) | 2003-03-28 | 2007-01-31 | Threshold Pharmaceuticals Inc | Compositions and methods for treating cancer |
| US6855695B2 (en) * | 2003-06-13 | 2005-02-15 | Vion Pharmaceuticals, Inc. | Water-soluble SHPs as novel alkylating agents |
| BRPI0416085A (pt) | 2003-10-31 | 2007-01-02 | Auckland Uniservices Ltd | álcoois de nitrofenil mostarda e nitrofenilaziridina e seus fosfatos correspondentes e seu uso como agentes citotóxicos alvo-dirigidos |
| EP1711188B1 (en) | 2004-02-06 | 2012-06-06 | Threshold Pharmaceuticals, Inc. | Anti-cancer therapies |
| AU2005309761A1 (en) | 2004-11-22 | 2006-06-01 | Threshold Pharmaceuticals, Inc. | Tubulin binding anti cancer agents and prodrugs thereof |
| EP1896040B1 (en) * | 2005-06-29 | 2012-08-01 | Threshold Pharmaceuticals, Inc. | Phosphoramidate alkylator prodrugs |
| KR100755435B1 (ko) * | 2005-10-04 | 2007-09-04 | 삼성전자주식회사 | 디지털 방송 제한 수신 단말기 및 그 방법 |
| WO2008011588A2 (en) | 2006-07-20 | 2008-01-24 | Threshold Pharmaceuticals, Inc. | Glycoconjugates of phosphoramidate alkylators for treatment of cancer |
| WO2008076826A1 (en) | 2006-12-13 | 2008-06-26 | Threshold Pharmaceuticals, Inc. | Pyrophosphoramide alkylators |
| EP2114157B1 (en) | 2006-12-26 | 2021-05-26 | ImmunoGenesis, Inc. | Phosphoramidate alkylator prodrug for the treatment of cancer |
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- 2007-12-21 ES ES07869800T patent/ES2884044T3/es active Active
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- 2007-12-21 WO PCT/US2007/088645 patent/WO2008083101A1/en not_active Ceased
Also Published As
| Publication number | Publication date |
|---|---|
| EP2114157A1 (en) | 2009-11-11 |
| US20100183742A1 (en) | 2010-07-22 |
| US8552048B2 (en) | 2013-10-08 |
| WO2008083101A1 (en) | 2008-07-10 |
| EP2114157A4 (en) | 2013-01-23 |
| EP2114157B1 (en) | 2021-05-26 |
| JP5357049B2 (ja) | 2013-12-04 |
| JP2010514787A (ja) | 2010-05-06 |
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