JP2010047598A - 治療的ケモカイン受容体アンタゴニスト - Google Patents
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Abstract
【解決手段】T細胞によるインターフェロンγ産生の減少、自己免疫疾患の治療、多発性硬化症の治療、癌の治療、血管新生の阻害。該治療では、治療的な用量のCXCR4アンタゴニストが薬学的に許容される製剤に含まれて投与される。CXCR4アンタゴニストと、薬学的に許容される賦形剤又は担体とを含む治療用組成物であり、該CXCR4アンタゴニストは、SDF−1の実質的に精製されたペプチド断片、修飾された断片、類似体、又は薬学的に許容される塩を含むペプチド化合物。
【選択図】なし
Description
本発明は、癌および自己免疫疾患の治療に用いられるCXCケモカイン受容体4のペプチドアンタゴニストを含む、ケモカイン受容体アンタゴニストの治療的使用に関する。
サイトカインは、免疫応答を調節する単球およびリンパ球を含む多様な細胞によって分泌される可溶性蛋白質である。ケモカインは化学誘引性蛋白質のスーパーファミリーである。ケモカインは様々な生物反応を調節し、それらは多数の系列の白血球およびリンパ球の生体臓器組織への動員を促進する。ケモカインは蛋白質に存在する最初の2つのシステイン残基の相対的な位置により、2つのファミリーに分類されることがある。第一のファミリーでは、最初の2つのシステインが1つのアミノ酸残基を隔てて存在するCXCケモカインであり、もう一つのファミリーでは最初の2つのシステインが隣接するCCケモカインである。
本発明の様々な局面に従って、CXCR4アンタゴニストは、多様な自己免疫疾患を治療するため、または治療する薬物を生成するために用いてもよい。そのような疾患には、多発性硬化症、ギラン・バレー症候群(GBS)、筋萎縮性側索硬化症(ALS)、および神経系のその他の疾患、リウマチ性関節炎、乾癬、I型糖尿病、潰瘍性大腸炎、痛風、狼瘡、および移植の拒絶が含まれる。
この実施例は、マウスモデルを用いた腫瘍増殖に対するCXCR4アンタゴニストの阻害効果を示す。
本実施例は、活性化T細胞によるインターフェロンγ産生のCXCR4阻害剤による阻害を示す。
Claims (22)
- 哺乳動物においてT細胞によるインターフェロンγ産生を減少させる薬物を製造するためのCXCR4アンタゴニストの使用。
- 哺乳動物においてT細胞によるインターフェロンγ産生を減少させるためのCXCR4アンタゴニストの使用。
- 哺乳動物における自己免疫疾患を治療する薬物を製造するためのCXCR4アンタゴニストの使用。
- 哺乳動物における自己免疫疾患を治療するためのCXCR4アンタゴニストの使用。
- 哺乳動物における多発性硬化症を治療する薬物を製造するためのCXCR4アンタゴニストの使用。
- 哺乳動物における多発性硬化症を治療するためのCXCR4アンタゴニストの使用。
- 薬物がβインターフェロンを含む、請求項5記載のCXCR4アンタゴニストの使用。
- 哺乳動物がβインターフェロンによる治療を受けている、請求項5、6または7記載のCXCR4アンタゴニストの使用。
- 哺乳動物における癌を治療する薬物を製造するためのCXCR4アンタゴニストの使用。
- 哺乳動物における血管新生を阻害する薬物を製造するためのCXCR4アンタゴニストの使用。
- 哺乳動物における血管新生を阻害することによって癌を治療する薬物を製造するためのCXCR4アンタゴニストの使用。
- 薬物を製造するためのCXCR4アンタゴニストの使用。
- CXCR4アンタゴニストが、SDF-1の実質的に精製されたペプチド断片、修飾された断片、類似体または薬学的に許容される塩を含むペプチド化合物である、請求項1〜12のいずれか一項に記載のCXCR4アンタゴニストの使用。
- ペプチド化合物がN-末端アミノ酸配列KGVSLSYRC-R1(配列番号:2)を含み、R1が水素およびSDF-1の少なくとも一部と相同であるポリペプチドからなる群より選択される、請求項13記載のCXCR4アンタゴニストの使用。
- 哺乳動物がヒトである、請求項1〜14のいずれか一項に記載のCXCR4アンタゴニストの使用。
- CXCR4アンタゴニストが薬学的に許容される製剤において、治療的用量で哺乳動物に投与される、請求項1〜15のいずれか一項に記載のCXCR4アンタゴニストの使用を含む、薬物治療の方法。
- CXCR4アンタゴニストおよび薬学的に許容される賦形剤を含む治療的組成物。
- インターフェロンβをさらに含む、請求項17記載の治療的組成物。
- ポリマーCXCR4アンタゴニストが複数のN-末端を有するように架橋部分によって共有結合している複数のペプチドを含む、ポリマーCXCR4アンタゴニスト。
- ポリマーCXCR4アンタゴニストがSDF-1(1-9[P2G])2である、請求項21記載のポリマーCXCR4アンタゴニスト。
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CA002226391A CA2226391A1 (en) | 1998-03-13 | 1998-03-13 | N-terminal peptides of sdf-1 have functional activities mediated by cxcr4 |
CA002245224A CA2245224A1 (en) | 1998-08-14 | 1998-08-14 | Chemokine receptor antagonists and chemotherapeutics |
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JP2000536397A Division JP2002506830A (ja) | 1998-03-13 | 1999-03-12 | 治療的ケモカイン受容体アンタゴニスト |
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JP2010047598A true JP2010047598A (ja) | 2010-03-04 |
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Application Number | Title | Priority Date | Filing Date |
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JP2000536397A Pending JP2002506830A (ja) | 1998-03-13 | 1999-03-12 | 治療的ケモカイン受容体アンタゴニスト |
JP2009242544A Pending JP2010047598A (ja) | 1998-03-13 | 2009-10-21 | 治療的ケモカイン受容体アンタゴニスト |
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JP2000536397A Pending JP2002506830A (ja) | 1998-03-13 | 1999-03-12 | 治療的ケモカイン受容体アンタゴニスト |
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Country | Link |
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US (2) | US6946445B1 (ja) |
EP (1) | EP1061944B1 (ja) |
JP (2) | JP2002506830A (ja) |
AT (1) | ATE258444T1 (ja) |
AU (1) | AU762472B2 (ja) |
DE (1) | DE69914463T2 (ja) |
WO (1) | WO1999047158A2 (ja) |
Cited By (1)
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EP1061944A2 (en) | 2000-12-27 |
AU2821699A (en) | 1999-10-11 |
ATE258444T1 (de) | 2004-02-15 |
DE69914463D1 (en) | 2004-03-04 |
WO1999047158A3 (en) | 1999-11-25 |
WO1999047158A2 (en) | 1999-09-23 |
AU762472B2 (en) | 2003-06-26 |
DE69914463T2 (de) | 2004-11-11 |
US6946445B1 (en) | 2005-09-20 |
US20050265969A1 (en) | 2005-12-01 |
EP1061944B1 (en) | 2004-01-28 |
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