ZA200304178B - Geldanamycin derivative and method of treating cancer using same. - Google Patents
Geldanamycin derivative and method of treating cancer using same. Download PDFInfo
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- ZA200304178B ZA200304178B ZA200304178A ZA200304178A ZA200304178B ZA 200304178 B ZA200304178 B ZA 200304178B ZA 200304178 A ZA200304178 A ZA 200304178A ZA 200304178 A ZA200304178 A ZA 200304178A ZA 200304178 B ZA200304178 B ZA 200304178B
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Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D225/00—Heterocyclic compounds containing rings of more than seven members having one nitrogen atom as the only ring hetero atom
- C07D225/04—Heterocyclic compounds containing rings of more than seven members having one nitrogen atom as the only ring hetero atom condensed with carbocyclic rings or ring systems
- C07D225/06—Heterocyclic compounds containing rings of more than seven members having one nitrogen atom as the only ring hetero atom condensed with carbocyclic rings or ring systems condensed with one six-membered ring
-
- 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
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Public Health (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Pharmacology & Pharmacy (AREA)
- Veterinary Medicine (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Saccharide Compounds (AREA)
- Other In-Based Heterocyclic Compounds (AREA)
- Addition Polymer Or Copolymer, Post-Treatments, Or Chemical Modifications (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Applications Claiming Priority (1)
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|---|---|---|---|
| US28007801P | 2001-03-30 | 2001-03-30 |
Publications (1)
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| ZA200304178B true ZA200304178B (en) | 2004-02-17 |
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| ZA200304178A ZA200304178B (en) | 2001-03-30 | 2003-05-29 | Geldanamycin derivative and method of treating cancer using same. |
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| US (1) | US6890917B2 (fr) |
| EP (1) | EP1373215B1 (fr) |
| JP (1) | JP4213472B2 (fr) |
| KR (1) | KR100831133B1 (fr) |
| CN (1) | CN1262542C (fr) |
| AT (1) | ATE334119T1 (fr) |
| AU (1) | AU2002307020B2 (fr) |
| CA (1) | CA2430692C (fr) |
| CY (1) | CY1107484T1 (fr) |
| DE (1) | DE60213386T2 (fr) |
| DK (1) | DK1373215T3 (fr) |
| ES (1) | ES2268068T3 (fr) |
| IL (2) | IL156122A0 (fr) |
| MX (1) | MXPA03007856A (fr) |
| NZ (1) | NZ526133A (fr) |
| PT (1) | PT1373215E (fr) |
| SI (1) | SI21369A (fr) |
| WO (1) | WO2002079167A1 (fr) |
| ZA (1) | ZA200304178B (fr) |
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| US6872715B2 (en) | 2001-08-06 | 2005-03-29 | Kosan Biosciences, Inc. | Benzoquinone ansamycins |
| US20060148776A1 (en) * | 2003-03-13 | 2006-07-06 | Conforma Therapeutics Corporation | Drug formulations having long and medium chain triglycerides |
| US20050054625A1 (en) * | 2003-05-30 | 2005-03-10 | Kosan Biosciences, Inc. | Method for treating diseases using HSP90-inhibiting agents in combination with nuclear export inhibitors |
| US7691838B2 (en) * | 2003-05-30 | 2010-04-06 | Kosan Biosciences Incorporated | Method for treating diseases using HSP90-inhibiting agents in combination with antimitotics |
| US20050020534A1 (en) * | 2003-05-30 | 2005-01-27 | Kosan Biosciences, Inc. | Method for treating diseases using HSP90-inhibiting agents in combination with antimetabolites |
| US20050054589A1 (en) * | 2003-05-30 | 2005-03-10 | Kosan Biosciences, Inc. | Method for treating diseases using HSP90-inhibiting agents in combination with antibiotics |
| US20050020556A1 (en) * | 2003-05-30 | 2005-01-27 | Kosan Biosciences, Inc. | Method for treating diseases using HSP90-inhibiting agents in combination with platinum coordination complexes |
| US20050020557A1 (en) * | 2003-05-30 | 2005-01-27 | Kosan Biosciences, Inc. | Method for treating diseases using HSP90-inhibiting agents in combination with enzyme inhibitors |
| US20050026893A1 (en) * | 2003-05-30 | 2005-02-03 | Kosan Biosciences, Inc. | Method for treating diseases using HSP90-inhibiting agents in combination with immunosuppressants |
| WO2005009345A2 (fr) | 2003-06-13 | 2005-02-03 | Kosan Biosciences, Inc. | Composes de 2-desmethyl ansamycine |
| US6887993B1 (en) | 2003-11-12 | 2005-05-03 | Kosan Biosciences, Inc. | 11-O-methylgeldanamycin compounds |
| US6870049B1 (en) | 2003-11-12 | 2005-03-22 | Kosan Biosciences, Inc. | 11-O-methylgeldanamycin compounds |
| US6855705B1 (en) | 2003-11-12 | 2005-02-15 | Kosan Biosciences, Inc. | 11-O-methylgeldanamycin compounds |
| US6875863B1 (en) | 2003-11-12 | 2005-04-05 | Kosan Biosciences, Inc. | 11-O-methylgeldanamycin compounds |
| US20060019941A1 (en) * | 2003-12-23 | 2006-01-26 | Infinity Pharmaceuticals, Inc. | Analogs of benzoquinone-containing ansamycins and methods of use thereof |
| ES2409351T3 (es) | 2003-12-23 | 2013-06-26 | Infinity Discovery, Inc. | Análogos de ansamicinas que contienen benzoquinona para el tratamiento de cáncer |
| US20050256097A1 (en) * | 2004-05-11 | 2005-11-17 | Kosan Biosciences, Inc. | Pharmaceutical solution formulations containing 17-AAG |
| US7259156B2 (en) | 2004-05-20 | 2007-08-21 | Kosan Biosciences Incorporated | Geldanamycin compounds and method of use |
| US20060067953A1 (en) * | 2004-09-29 | 2006-03-30 | Conforma Therapeutics Corporation | Oral pharmaceutical formulations and methods for producing and using same |
| US7608611B2 (en) * | 2005-03-11 | 2009-10-27 | The Regents Of The University Of Colorado | Hsp90 inhibitors, methods of making and uses therefor |
| MX2007013499A (es) * | 2005-04-29 | 2008-01-24 | Kosan Biosciences Inc | Metodo para tratar mieloma multiple utilizando 17-aag o 17-ag o un profarmaco de ya sea 17-aag o 17-ag en combinacion con un inhibidor de proteasoma. |
| EP1906950A4 (fr) * | 2005-06-21 | 2008-09-24 | Infinity Discovery Inc | Formulations d'ansamycine et leurs procedes d'utilisation |
| WO2007059116A2 (fr) * | 2005-11-14 | 2007-05-24 | Abraxis Bioscience, Inc. | Derives de geldanamycine et compositions pharmaceutiques associees |
| US7648976B2 (en) * | 2005-11-23 | 2010-01-19 | Bristol-Myers Squibb Company | 17-allylamino-17-demethoxygeldanamycin polymorphs and formulations |
| US20090042847A1 (en) * | 2005-11-23 | 2009-02-12 | Kosan Biosciences Incorporated | 17-allylamino-17-demethoxygeldanamycin polymorphs and formulations |
| US20070167422A1 (en) * | 2006-01-18 | 2007-07-19 | Yu Kwok S | Pharmaceutical compositions comprising 17-allylamino-17-demethoxygeldanamycin |
| WO2007098229A2 (fr) * | 2006-02-21 | 2007-08-30 | Michigan State University | Derives de la geldanamycine et leur procede d'utilisation |
| CN100519536C (zh) * | 2006-03-21 | 2009-07-29 | 中国医学科学院医药生物技术研究所 | 一组连有核苷碱基的格尔德霉素衍生物 |
| US20070293451A1 (en) * | 2006-05-02 | 2007-12-20 | University Of Pittsburgh | Regulation ao ApoB by Hsp110 proteins and related compositions and methods |
| KR100796637B1 (ko) * | 2006-09-29 | 2008-01-22 | 한국생명공학연구원 | 젤다나마이신 유도체, 이의 약학적으로 허용가능한 염,이의 제조방법 및 이를 유효성분으로 함유하는 암 예방 및치료제 |
| CN100500668C (zh) * | 2006-12-19 | 2009-06-17 | 中国人民解放军军事医学科学院毒物药物研究所 | 格尔德霉素衍生物及其制备方法和制备药物的用途 |
| WO2008094438A1 (fr) | 2007-01-26 | 2008-08-07 | Kosan Biosciences Incorporated | Macrolactames obtenus par biosynthèse modifiée |
| US8303960B2 (en) * | 2007-02-27 | 2012-11-06 | The United States Of America, As Represented By The Secretary, Department Of Health And Human Services | Radiolabeled affibody molecules |
| WO2008116216A1 (fr) * | 2007-03-22 | 2008-09-25 | Medical College Of Georgia Research Institute, Inc. | Compositions et procédés permettant d'inhiber les métastases |
| WO2008128063A1 (fr) * | 2007-04-12 | 2008-10-23 | Infinity Discovery, Inc. | Formulations d'ansamycine hydroquinone |
| EP2190291B1 (fr) | 2007-08-23 | 2015-10-14 | The Regents of The University of Colorado, A Body Corporate | Inhibiteurs de hsp90 avec toxicité modifiée |
| JP2011501731A (ja) | 2007-09-10 | 2011-01-13 | ユニバーシティ オブ マサチューセッツ | ミトコンドリア標的化抗腫瘍剤 |
| US20090186039A1 (en) * | 2008-01-18 | 2009-07-23 | Jang Sung-Key | Novel use of grp 94 in virus infection |
| US20090258869A1 (en) * | 2008-02-08 | 2009-10-15 | The Regents Of The University Of California | Methods and compounds for treatment or prevention of substance-related disorders |
| KR20110090925A (ko) | 2008-10-15 | 2011-08-10 | 인피니티 파마슈티컬스, 인코포레이티드 | 안사마이신 하이드로퀴논 조성물 |
| DE102008060549A1 (de) | 2008-12-04 | 2010-06-10 | MAX-PLANCK-Gesellschaft zur Förderung der Wissenschaften e.V. | Wirkstoff-Peptid-Konstrukt zur extrazellulären Anreicherung |
| US20120283120A1 (en) | 2009-09-29 | 2012-11-08 | Takeda Pharmaceutical Company Limited | Screening method |
| CN102030764B (zh) * | 2010-11-12 | 2012-07-04 | 中国医学科学院医药生物技术研究所 | 4，5双氢噻嗪酮格尔德霉素及其制备方法 |
| WO2012082765A2 (fr) | 2010-12-16 | 2012-06-21 | The United State Of America. As Represented By The Secretary Department Of Health And Human Services | Méthodes pour réduire le poids corporel et traiter le diabète |
| CN102603635B (zh) * | 2011-01-21 | 2016-08-03 | 杭州华东医药集团生物工程研究所有限公司 | 格尔德霉素衍生物及其制备方法和用途 |
| US8921533B2 (en) | 2011-07-25 | 2014-12-30 | Chromatin Technologies | Glycosylated valproic acid analogs and uses thereof |
| WO2013074695A1 (fr) | 2011-11-14 | 2013-05-23 | The Regents Of The University Of Colorado, A Body Corporate | Inhibiteurs de hsp90 ayant une toxicité modifiée |
| CN102552150B (zh) * | 2012-03-02 | 2013-10-30 | 首都医科大学 | 一种格尔德霉素脂质体的制备及应用 |
| WO2018160772A1 (fr) | 2017-02-28 | 2018-09-07 | The United State Of America, As Represented By The Secretary, Department Of Health & Human Services | Procédé de traitement de l'obésité, de la résistance à l'insuline, d'une stéatose hépatique non alcoolique comprenant une stéatohépatite non alcoolique |
Family Cites Families (12)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS55111470A (en) | 1979-02-19 | 1980-08-28 | Kaken Pharmaceut Co Ltd | Geldanamycin derivative, its preparation, antitumor drug comprising it as active ingredient |
| JPS55111469A (en) | 1979-02-19 | 1980-08-28 | Kaken Pharmaceut Co Ltd | Novel geldanamycin derivative, its preparation, and antitumor drug comprising it as active ingredient |
| US4261989A (en) * | 1979-02-19 | 1981-04-14 | Kaken Chemical Co. Ltd. | Geldanamycin derivatives and antitumor drug |
| JPS55111419A (en) | 1979-02-20 | 1980-08-28 | Kaken Pharmaceut Co Ltd | Antitumorigenic agent |
| JP2794342B2 (ja) * | 1993-06-29 | 1998-09-03 | ファイザー・インク． | 抗癌遺伝子剤および抗癌剤としてのアンサマイシン誘導体 |
| ATE202571T1 (de) * | 1993-09-14 | 2001-07-15 | Merck & Co Inc | Humane protein-tyrosinphosphatase decodierende cdna |
| US5932566A (en) * | 1994-06-16 | 1999-08-03 | Pfizer Inc. | Ansamycin derivatives as antioncogene and anticancer agents |
| WO1996034525A1 (fr) * | 1995-05-02 | 1996-11-07 | The Regents Of The University Of California | Induction de la thermotolerance a l'aide d'ansamycines benzoquinonoides |
| US5958892A (en) * | 1996-07-30 | 1999-09-28 | Board Of Regents, The University Of Texas System | 2-methoxyestradiol-induced apoptosis in cancer cells |
| US5948814A (en) * | 1997-02-20 | 1999-09-07 | The Curators Of The University Of Missouri | Genistein for the treatment of cystic fibrosis |
| US5952175A (en) * | 1997-10-09 | 1999-09-14 | Incyte Pharmaceuticals, Inc. | DNA encoding a human progesterone receptor complex p23-like protein |
| US5968921A (en) * | 1997-10-24 | 1999-10-19 | Orgegon Health Sciences University | Compositions and methods for promoting nerve regeneration |
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2002
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- 2002-03-28 JP JP2002577794A patent/JP4213472B2/ja not_active Expired - Lifetime
- 2002-03-28 WO PCT/US2002/010097 patent/WO2002079167A1/fr active IP Right Grant
- 2002-03-28 IL IL15612202A patent/IL156122A0/xx unknown
- 2002-03-28 US US10/432,581 patent/US6890917B2/en not_active Expired - Lifetime
- 2002-03-28 KR KR1020037008551A patent/KR100831133B1/ko active IP Right Grant
- 2002-03-28 DK DK02757908T patent/DK1373215T3/da active
- 2002-03-28 EP EP02757908A patent/EP1373215B1/fr not_active Expired - Lifetime
- 2002-03-28 CA CA2430692A patent/CA2430692C/fr not_active Expired - Lifetime
- 2002-03-28 AT AT02757908T patent/ATE334119T1/de active
- 2002-03-28 AU AU2002307020A patent/AU2002307020B2/en not_active Expired
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- 2002-03-28 MX MXPA03007856A patent/MXPA03007856A/es active IP Right Grant
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- 2002-03-28 ES ES02757908T patent/ES2268068T3/es not_active Expired - Lifetime
- 2002-03-28 CN CNB028034651A patent/CN1262542C/zh not_active Expired - Lifetime
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Also Published As
| Publication number | Publication date |
|---|---|
| AU2002307020B2 (en) | 2007-06-28 |
| MXPA03007856A (es) | 2003-12-04 |
| DE60213386D1 (de) | 2006-09-07 |
| JP4213472B2 (ja) | 2009-01-21 |
| ATE334119T1 (de) | 2006-08-15 |
| KR100831133B1 (ko) | 2008-05-20 |
| JP2004519514A (ja) | 2004-07-02 |
| CA2430692C (fr) | 2011-05-31 |
| US6890917B2 (en) | 2005-05-10 |
| US20040053909A1 (en) | 2004-03-18 |
| EP1373215A1 (fr) | 2004-01-02 |
| CA2430692A1 (fr) | 2002-10-10 |
| NZ526133A (en) | 2005-08-26 |
| CY1107484T1 (el) | 2013-03-13 |
| SI21369A (sl) | 2004-06-30 |
| PT1373215E (pt) | 2006-12-29 |
| CN1484639A (zh) | 2004-03-24 |
| IL156122A (en) | 2010-11-30 |
| WO2002079167A1 (fr) | 2002-10-10 |
| IL156122A0 (en) | 2003-12-23 |
| DE60213386T2 (de) | 2006-11-23 |
| ES2268068T3 (es) | 2007-03-16 |
| DK1373215T3 (da) | 2006-11-13 |
| EP1373215B1 (fr) | 2006-07-26 |
| KR20040023581A (ko) | 2004-03-18 |
| CN1262542C (zh) | 2006-07-05 |
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