JP2008531589A5 - - Google Patents
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- JP2008531589A5 JP2008531589A5 JP2007557176A JP2007557176A JP2008531589A5 JP 2008531589 A5 JP2008531589 A5 JP 2008531589A5 JP 2007557176 A JP2007557176 A JP 2007557176A JP 2007557176 A JP2007557176 A JP 2007557176A JP 2008531589 A5 JP2008531589 A5 JP 2008531589A5
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- Prior art keywords
- minutes
- leucyl
- nle
- pmol
- cis
- Prior art date
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- 102400000686 Endothelin-1 Human genes 0.000 description 5
- 101800004490 Endothelin-1 Proteins 0.000 description 5
- 230000017531 blood circulation Effects 0.000 description 2
- 206010006187 Breast cancer Diseases 0.000 description 1
- 208000026310 Breast neoplasm Diseases 0.000 description 1
- 206010028980 Neoplasm Diseases 0.000 description 1
- 241000700159 Rattus Species 0.000 description 1
- 230000001404 mediated effect Effects 0.000 description 1
- 239000002504 physiological saline solution Substances 0.000 description 1
- 108090000765 processed proteins & peptides Proteins 0.000 description 1
- 239000002464 receptor antagonist Substances 0.000 description 1
- 229940044551 receptor antagonist Drugs 0.000 description 1
- 230000024883 vasodilation Effects 0.000 description 1
Description
（ｉ）生理食塩水処置ラットに、ＢＱ７８８（（Ｎ−シス２，６−ジメチルピペリジノカルボニル−Ｌ−ガンマ−メチル−ロイシル−Ｄ−１−メトキシカルボニルトリプトファニル−Ｄ−Ｎｌｅ）；Ａｍｅｒｉｃａｎ Ｐｅｐｔｉｄｅ Ｃｏｍｐａｎｙ Ｉｎｃ．（カリフォルニア州サニーベール）から入手、生理食塩水に０．５ｐｍｏｌ／ｋｇで溶解））を２０分間注入、次いでＥＴ−１（５０ｎｇ／ｋｇ／分）を３０分間注入（Ｎ＝５）；
（ii）ＭＮＵ（５０ｍｇ／ｋｇ、ｉ．ｐ．）処置ラットに、ＢＱ７８８（０．５ｐｍｏｌ／ｋｇ）を２０分間注入、次いでＥＴ−１（５０ｎｇ／ｋｇ／分）を３０分間注入（Ｎ＝５）。
(I) BQ788 ((N-cis 2,6-dimethylpiperidinocarbonyl-L-gamma-methyl- leucyl- D-1-methoxycarbonyltryptophanyl-D-Nle); American; Peptide Company Inc. (Sunnyvale, Calif., Dissolved in physiological saline at 0.5 pmol / kg)) for 20 minutes followed by ET-1 (50 ng / kg / minute) for 30 minutes (N = 5 );
(Ii) MNU (50 mg / kg, ip) treated rats were infused with BQ788 (0.5 pmol / kg) for 20 minutes, followed by ET-1 (50 ng / kg / min) for 30 minutes (N = 5 ).
さらに、ＥＴ−１に応答して観察された血流の増加は、ＥＴＢが媒介する血管拡張によるものであると理論化されている（それに頼らない）。研究によれば、ＥＴ−１及びＥＴＢ受容体の発現は乳がん組織で増大していることが示されている。Ａｌａｎｅｎら，Ｈｉｓｔｏｐａｔｈｏｌｏｇｙ，３６：１６１（２０００）；Ｙａｍａｓｈｉｔａら，Ｒｅｓ
Ｃｏｍｍｕｎ Ｃｈｅｍ Ｐａｔｈｏｌ Ｐｈａｒｍａｃｏｌ，７４：３６３（１９９１）。本発明よれば、ＢＱ７８８の投与はＥＴ−１が誘導する腫瘍組織への血流の増加を阻止することがわかった。ＢＱ７８８（すなわち、Ｎ−シス−２，６−ジメチルピペリジノカルボニル−Ｌ−ガンマ−メチル−ロイシル−Ｄ−１−メトキシカルボニルトリプトファニル−Ｄ−Ｎｌｅ）は、特異的なＥＴＢ受容体アンタゴニストである。ＢＱ７８８はＥＴＢ受容体への結合を１．２ｎＭのＩＣ５０値で阻害する。
Furthermore, it has been theorized that the increase in blood flow observed in response to ET-1 is due to ET B- mediated vasodilation (do not rely on it). Studies expression of ET-1 and ET B receptors have been shown to be increased in breast cancer tissue. Alanen et al., Histopathology, 36: 161 (2000); Yamashita et al., Res.
Commun Chem Pathol Pharmacol, 74: 363 (1991). According to the present invention, it was found that administration of BQ788 prevents the increase in blood flow to tumor tissue induced by ET-1. BQ788 (i.e., N- cis-2,6-dimethyl-piperidinocarbonyl -L- gamma - methyl - leucyl -D-1-methoxycarbonyl-tryptophanyl -D-Nle) is a specific ET B receptor antagonist It is. BQ788 inhibits binding to the ET B receptor with an IC 50 value of 1.2 nM.
Applications Claiming Priority (4)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US65565405P | 2005-02-22 | 2005-02-22 | |
| US65564305P | 2005-02-22 | 2005-02-22 | |
| US65565605P | 2005-02-22 | 2005-02-22 | |
| PCT/US2006/006513 WO2006091767A2 (en) | 2005-02-22 | 2006-02-22 | Methods, compositions and articles of manufacture for contributing to the treatment of solid tumors |
Related Child Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2012179596A Division JP2012214519A (en) | 2005-02-22 | 2012-08-13 | Method, composition and product for contributing to treatment of solid tumors |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JP2008531589A JP2008531589A (en) | 2008-08-14 |
| JP2008531589A5 true JP2008531589A5 (en) | 2012-10-18 |
Family
ID=36617185
Family Applications (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2007557176A Withdrawn JP2008531589A (en) | 2005-02-22 | 2006-02-22 | Methods, compositions and products for contributing to the treatment of solid tumors |
| JP2012179596A Pending JP2012214519A (en) | 2005-02-22 | 2012-08-13 | Method, composition and product for contributing to treatment of solid tumors |
Family Applications After (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2012179596A Pending JP2012214519A (en) | 2005-02-22 | 2012-08-13 | Method, composition and product for contributing to treatment of solid tumors |
Country Status (4)
| Country | Link |
|---|---|
| EP (1) | EP1858539A2 (en) |
| JP (2) | JP2008531589A (en) |
| CA (1) | CA2598439A1 (en) |
| WO (1) | WO2006091767A2 (en) |
Families Citing this family (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US8217010B2 (en) | 2002-10-24 | 2012-07-10 | The Board Of Trustees Of The University Of Illinois | Methods, compositions and articles of manufacture for contributing to the treatment of solid tumors |
| US8026216B2 (en) | 2002-10-24 | 2011-09-27 | Spectrum Pharmaceuticals, Inc. | Methods and compositions for contributing to the treatment of cancers |
| US20070032422A1 (en) | 2002-10-24 | 2007-02-08 | Spectrum Pharmaceuticals, Inc. | Methods, compositions and articles of manufacture for contributing to the treatment of cancers |
| EP2059254B1 (en) | 2006-08-31 | 2015-04-08 | Spectrum Pharmaceuticals, Inc. | Sensitization of tumor cells to radiation therapy through the administration of endothelin agonists |
| DK2144607T3 (en) * | 2007-04-13 | 2014-04-07 | Spectrum Pharmaceuticals Inc | Compositions for contributions to the treatment of cancer |
| US9308235B2 (en) | 2012-05-09 | 2016-04-12 | Spectrum Pharmaceuticals, Inc. | Treatment of primary and metastatic carcinoma |
Family Cites Families (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2004037235A2 (en) * | 2002-10-24 | 2004-05-06 | The Board Of Trustees Of The University Of Illinois | Method and composition for preventing and treating solid tumors |
-
2006
- 2006-02-22 WO PCT/US2006/006513 patent/WO2006091767A2/en active Application Filing
- 2006-02-22 CA CA002598439A patent/CA2598439A1/en not_active Abandoned
- 2006-02-22 EP EP06748250A patent/EP1858539A2/en not_active Withdrawn
- 2006-02-22 JP JP2007557176A patent/JP2008531589A/en not_active Withdrawn
-
2012
- 2012-08-13 JP JP2012179596A patent/JP2012214519A/en active Pending
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