JP7048505B2 - Pdgf-cc阻害剤および抗エストロゲン剤によるer陰性乳癌の処置 - Google Patents
Pdgf-cc阻害剤および抗エストロゲン剤によるer陰性乳癌の処置 Download PDFInfo
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- JP7048505B2 JP7048505B2 JP2018543455A JP2018543455A JP7048505B2 JP 7048505 B2 JP7048505 B2 JP 7048505B2 JP 2018543455 A JP2018543455 A JP 2018543455A JP 2018543455 A JP2018543455 A JP 2018543455A JP 7048505 B2 JP7048505 B2 JP 7048505B2
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- C07K16/18—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
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| WO2023172891A2 (en) * | 2022-03-07 | 2023-09-14 | Baylor College Of Medicine | Biomarkers for combination therapy for er+ breast cancer |
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| JP2015515487A (ja) | 2012-04-24 | 2015-05-28 | スロンボジェニックス エヌ.ブイ. | 抗pdgf−c抗体 |
Family Cites Families (64)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US2464203A (en) | 1943-05-21 | 1949-03-15 | Boots Pure Drug Co Ltd | Manufacture of dienoestrol |
| US2465505A (en) | 1944-12-05 | 1949-03-29 | Hoffmann La Roche | Process for the manufacture of 3, 4-di-(p-hydroxy-phenyl)-hexadiene-2, 4 |
| US2914562A (en) | 1957-08-06 | 1959-11-24 | Wm S Merrell Co | Amine derivatives of triphenylethanol |
| BE637389A (enExample) | 1962-09-13 | |||
| US3822287A (en) | 1969-04-17 | 1974-07-02 | Rexall Drug Chemical | Process for preparation of substituted 3,4-(diphenyl)chromans |
| US4133814A (en) | 1975-10-28 | 1979-01-09 | Eli Lilly And Company | 2-Phenyl-3-aroylbenzothiophenes useful as antifertility agents |
| US4230862A (en) | 1975-10-28 | 1980-10-28 | Eli Lilly And Company | Antifertility compounds |
| DE2658307C2 (de) | 1976-12-22 | 1979-03-15 | Klinge Pharma Gmbh & Co, 8000 Muenchen | Di-O'-hydroxyphenyD-alkanverbindungen, Verfahren zu ihrer Herstellung und ihre Verwendung als Arzneimittel |
| DE2860900D1 (en) | 1977-08-22 | 1981-11-05 | Ici Plc | Triphenylalkene derivatives, process for their preparation and pharmaceutical compositions containing them |
| DE3046719C2 (de) | 1980-12-11 | 1983-02-17 | Klinge Pharma GmbH, 8000 München | 1,1,2-Triphenyl-but-1-en-Derivate, Verfahren zu ihrer Herstellung und Arzneimittel |
| US4418068A (en) | 1981-04-03 | 1983-11-29 | Eli Lilly And Company | Antiestrogenic and antiandrugenic benzothiophenes |
| GB2126576B (en) | 1982-06-25 | 1985-06-19 | Farmos Group Limited | Alkane and alkene derivatives |
| US5491173A (en) | 1982-06-25 | 1996-02-13 | Orion-Yhtyma Oy | Tri-phenyl alkene derivatives and their preparation and use |
| GB8327256D0 (en) | 1983-10-12 | 1983-11-16 | Ici Plc | Steroid derivatives |
| IE58417B1 (en) | 1984-04-27 | 1993-09-22 | Ici Plc | Chemical derivatives |
| GB8517360D0 (en) | 1985-07-09 | 1985-08-14 | Erba Farmitalia | Substituted androsta-1,4-diene-3,17-diones |
| US5352795A (en) | 1986-03-07 | 1994-10-04 | Ciba-Geigy Corporation | Alpha-heterocycle substituted tolunitriles |
| EP0260066B1 (en) | 1986-09-11 | 1990-05-09 | National Research Development Corporation | Tamoxifen derivatives |
| GB8714013D0 (en) | 1987-06-16 | 1987-07-22 | Ici Plc | (substituted-aralkyl)heterocyclic compounds |
| US5395842A (en) | 1988-10-31 | 1995-03-07 | Endorecherche Inc. | Anti-estrogenic compounds and compositions |
| US6060503A (en) | 1991-12-02 | 2000-05-09 | Endorecherche, Inc. | Benzopyran-containing compounds and method for their use |
| AU665690B2 (en) | 1992-05-08 | 1996-01-11 | Otsuka Pharmaceutical Factory, Inc. | Indole derivative |
| TW366342B (en) | 1992-07-28 | 1999-08-11 | Lilly Co Eli | The use of 2-phenyl-3-aroylbenzothiophenes in inhibiting bone loss |
| US6756388B1 (en) | 1993-10-12 | 2004-06-29 | Pfizer Inc. | Benzothiophenes and related compounds as estrogen agonists |
| GB9326332D0 (en) | 1993-12-23 | 1994-02-23 | Karo Bio | Indole derivatives |
| US5681835A (en) | 1994-04-25 | 1997-10-28 | Glaxo Wellcome Inc. | Non-steroidal ligands for the estrogen receptor |
| DE4426625A1 (de) | 1994-07-27 | 1996-03-14 | Schering Ag | 2-Phenylindole, Verfahren zu deren Herstellung, diese enthaltende pharmazeutische Präparate sowie deren Verwendung zur Herstellung von Arzneimitteln |
| US5552412A (en) | 1995-01-09 | 1996-09-03 | Pfizer Inc | 5-substitued-6-cyclic-5,6,7,8-tetrahydronaphthalen2-ol compounds which are useful for treating osteoporosis |
| US5883118A (en) | 1996-01-11 | 1999-03-16 | Nova Nordisk A/S | Prostatic carcinoma |
| CZ217298A3 (cs) | 1996-01-11 | 1999-01-13 | Novo Nordisk A/S | Použití 3,4-difenyl chromanů pro výrobu farm. prostředku |
| PL328135A1 (en) | 1996-01-11 | 1999-01-18 | Novo Nordisk As | Application of 1-centchromane enantiomer in production of a pharmaceutic agent for preventing or treating mammary cancers |
| US5726202A (en) | 1996-01-11 | 1998-03-10 | Novo Nordisk A/S | Benign prostatic hypertrophy |
| US5780497A (en) | 1996-04-19 | 1998-07-14 | American Home Products Corporation | 2-phenyl-1- 4-(amino-1-yl-alk-1-ynyl)-benzyl!-1H-indol-5-ols as estrogenic agents |
| US5998402A (en) | 1996-04-19 | 1999-12-07 | American Home Products Corporation | 2-phenyl-1-[4-(2-aminoethoxy)-benzyl]-indoles as estrogenic agents |
| US5985910A (en) | 1996-04-19 | 1999-11-16 | American Home Products Corporation | 3- [4- (2- Phenyl-Indole-1-ylmethyl) Phenyl]- Acrylamides as estrogenic agents |
| US5880137A (en) | 1996-04-19 | 1999-03-09 | American Home Products Corporation | 2-phenyl-1- 4-(amino-1-yl-alk-1-ynyl)-benzyl!-1H-indol-5-ols as estrogenic agents |
| DE19635525A1 (de) | 1996-08-20 | 1998-02-26 | Schering Ag | 7alpha-(xi-Aminoalkyl)-estratriene, Verfahren zu deren Herstellung, pharmazeutische Präparate, die diese 7alpha(xi-Aminoalkyl-estratriene enthalten sowie deren Verwendung zur Herstellung von Arzneimitteln |
| ZA982819B (en) | 1997-04-09 | 1999-10-04 | Lilly Co Eli | Treatment or prophylaxis of prostatic cancer and benign prostatic hyperplasia with selective estrogn receptor modulators. |
| ZA982877B (en) | 1997-04-09 | 1999-10-04 | Lilly Co Eli | Treatment of central nervous system disorders with selective estrogen receptor modulators. |
| ZA982818B (en) | 1997-04-09 | 1999-10-04 | Lilly Co Eli | Prevention of breast cancer using selective estrogen receptor modulators. |
| ATE295834T1 (de) | 1997-08-07 | 2005-06-15 | Lilly Co Eli | 1-(4-substituierte alkoxy)benzylnaphthalinderivate als östrogeninhibitoren |
| AR015500A1 (es) | 1997-12-23 | 2001-05-02 | Schering Ag | 11 BETA-HALoGENO-ESTRATRIENOS SUSTITUIDOS EN 7 ALFA, PROCEDIMIENTO PARA ELABORAR PREPARADOS FARMACEUTICOS QUE CONTIENEN TALES 11 BETA-HALOGENO-ESTRATRIENOSSUSTITUIDOS EN 7 ALFA, ASI COMO SU UTILIZACION EN LA ELABORACION DE MEDICAMENTOS. |
| US6054446A (en) | 1997-12-24 | 2000-04-25 | Sri International | Anti-estrogenic steroids, and associated pharmaceutical compositions and methods of use |
| US6548491B2 (en) | 1997-12-24 | 2003-04-15 | Sri International | Anti-estrogenic steroids, and associated pharmaceutical compositions and methods of use |
| US6069153A (en) | 1998-05-12 | 2000-05-30 | American Home Products Corporation | Indenoindoles and benzocarbazoles as estrogenic agents |
| JP2002522425A (ja) | 1998-08-07 | 2002-07-23 | カイロン コーポレイション | エストロゲンレセプターモジュレーターとしての置換イソオキサゾール |
| TW593256B (en) | 1999-11-16 | 2004-06-21 | Hormos Medical Oy Ltd | Triphenylalkene derivatives and their use as selective estrogen receptor modulators |
| US6340774B1 (en) | 2000-01-31 | 2002-01-22 | The Board Of Trustees Of The Leland Stanford Junior University | Non-steroidal estrogen-receptor antagonists |
| DE10013782A1 (de) | 2000-03-15 | 2001-10-18 | Schering Ag | 4-Fluoralkyl-2H-benzopyrane mit antiestrogener Wirksamkeit, Verfahren zu ihrer Herstellung, pharmazeutische Präparate, die diese enthalten sowie deren Verwendung zur Herstellung von Arzneimitteln |
| US7041839B2 (en) | 2000-06-22 | 2006-05-09 | Northeastern University | Steroidal antiestrogens and antiandrogens and uses thereof |
| US6750213B2 (en) | 2000-10-19 | 2004-06-15 | Merck & Co., Inc. | Estrogen receptor modulators |
| ES2405944T3 (es) | 2000-11-30 | 2013-06-04 | Medarex, Inc. | Ácidos nucleicos que codifican las secuencias de inmunoglobulina humana reorganizadas a partir de ratones transcromoscómicos transgénicos zadas |
| US6599921B2 (en) | 2001-02-22 | 2003-07-29 | Nanodesign, Inc. | Non-steroidal estrogen receptor ligands |
| US6927224B2 (en) | 2001-08-11 | 2005-08-09 | Bristol Myers Squibb Company | Selective estrogen receptor modulators |
| WO2003015761A1 (en) | 2001-08-13 | 2003-02-27 | Merck & Co., Inc. | Selective estrogen receptor modulators |
| US7138426B2 (en) | 2002-04-24 | 2006-11-21 | Merck & Co., Inc. | Estrogen receptor modulators |
| WO2005087812A1 (en) | 2004-03-05 | 2005-09-22 | Ludwig Institute For Cancer Research | Multivalent antibody materials and methods for vegf/pdgf family of growth factors |
| AR051597A1 (es) | 2004-11-01 | 2007-01-24 | Merck & Co Inc | Moduladores de los receptores de estrogeno |
| AU2007240429A1 (en) | 2006-04-17 | 2007-11-01 | Ludwig Institute For Cancer Research Ltd | Methods and compositions for modulation of blood-neural barrier |
| EP2068911A4 (en) * | 2006-09-13 | 2011-08-03 | Arca Biopharma Inc | METHOD FOR THE TREATMENT OF CANCER |
| US7504530B2 (en) | 2007-02-14 | 2009-03-17 | Hormos Medical Ltd. | Methods for the preparation of fispemifene from ospemifene |
| NZ586125A (en) * | 2007-11-12 | 2012-12-21 | Bipar Sciences Inc | Treatment of breast cancer with a parp inhibitor alone or in combination with anti-tumor agents |
| EP2558098A2 (en) | 2010-04-16 | 2013-02-20 | Novartis AG | Treatment of endocrine resistant breast cancer |
| HK1216502A1 (zh) | 2012-11-02 | 2016-11-18 | Repros Therapeutics Inc. | 用於癌症治療的反式-克羅米芬 |
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| JP2015515487A (ja) | 2012-04-24 | 2015-05-28 | スロンボジェニックス エヌ.ブイ. | 抗pdgf−c抗体 |
Non-Patent Citations (9)
| Title |
|---|
| Am. J. Pathol. (2013) vol.182, no.6, p.2037-2047 |
| Br. J. Cancer (2008) vol.99, issue 7, p.1056-1063 |
| Cancer Lett. (2009) vol.275, issue 2, p.178-184 |
| Eur. J. Cancer (2005) vol.41, issue 13, p.1980-1989 |
| Int. J. Mol. Sci. (2014) vol.15, issue 11, p.20306-20320 |
| Int. J. Oncol. (2014) vol.45, issue 5, p.2167-2175 |
| J. Cancer Res. Ther. (2014) vol.10, issue 14, p.1107-1108 |
| J. Cell. Biochem. (1997) vol.67, issue 1, p.55-65 |
| Oncogene (2013) vol.32, no.5, p.554-563 |
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| US20230310385A1 (en) | 2023-10-05 |
| US11633382B2 (en) | 2023-04-25 |
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| EP3373967B1 (en) | 2023-06-07 |
| WO2017081171A1 (en) | 2017-05-18 |
| EP3373967A1 (en) | 2018-09-19 |
| JP2019501957A (ja) | 2019-01-24 |
| EP3373967B9 (en) | 2023-10-04 |
| AU2016352592B2 (en) | 2023-04-27 |
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